The advent of endovascular aortic aneurysm repair (EVAR) has steadily become the standard of care in the management of infrarenal abdominal aortic aneurysms (AAAs). In fact, it has now surpassed open surgical repair and is the predominant therapeutic modality in managing this disease entity. Clearly, there are specific anatomic and technical factors that may preclude the use of traditional EVAR – most notably, challenging proximal neck anatomy, be it insufficient length or severe angulation.
It is estimated that up to 30%-40% of patients are unsuitable candidates because of these concerns.1 Such patients are thus relegated to traditional open repair with the associated concerns for supravisceral clamping, including dramatic changes in hemodynamics and prolonged ICU and hospital stays.
Dr. Nicholas J. MouawadHowever, with increasing surgeon experience and volume, complex endovascular strategies are being championed and performed, including use of traditional infrarenal devices outside the instructions-for-use indications, “back-table” physician modified devices, chimney/snorkel barreled parallel covered grafts (Ch-EVAR), custom built fenestrated endografts (FEVAR), and use of adjunctive techniques such as endoanchors.
Open surgical repair of pararenal, juxtarenal, and suprarenal AAAs is tried, tested, and durable. Knott and the group from Mayo Clinic reviewed their repair of 126 consecutive elective juxtarenal AAAs requiring suprarenal aortic clamping noting a 30-day mortality of .8%.2 More recent data from Kabbani and the Henry Ford group involved their 27-year clinical experience suggesting that open repair of complex proximal aortic aneurysms can be performed with clinical outcomes that are similar to those of open infrarenal repair.3 I respectfully accept this traditional – and historic – treatment modality.
However, we vascular surgeons are progressive and resilient in our quest to innovate and modernize – some of us even modified the traditional endografts on the back table. We charged forward despite the initial paucity of data on infrarenal EVAR compared to traditional open repair of aneurysms in the past. Now, a large percentage of infrarenal AAA repairs are performed via EVAR. In fact, our steadfast progression to advanced endovascular techniques has raised the concern that our graduating trainees are no longer proficient, competent, or even capable, in open complex aneurysm repair!
Tsilimparis and colleagues reported the first outcomes comparing open repair and FEVAR.4 They queried the NSQIP database comparing 1,091 patients undergoing open repair with 264 in the FEVAR group. There was an increased risk of morbidity in all combined endpoints including pulmonary and cardiovascular complications as well as length of stay in patients undergoing the open repair group. A larger comprehensive review pooled the results from 8 FEVAR and 12 open repair series. Analysis of the data found the groups to be identical. Open repair, however, was found to have an increased 30-day mortality when compared to FEVAR (relative risk 1.03, 2% increased absolute mortality).5
Gupta and colleagues reported the latest multi-institutional data noting that open repair was associated with higher risk than FEVAR for 30-day mortality, cardiac and pulmonary complications, renal failure requiring dialysis, return to the operating room, and in this age of cost-containment, length of stay (2 days vs. 7 days; P less than .0001).6
A further study by Donas and colleagues evaluated 90 consecutive patients with primary degenerative juxtarenal AAAs to different operative strategies based on morphologic and clinical characteristics – 29 FEVAR, 30 chEVAR, and 31 open repair.7 Early procedure-related and all-cause 30-day mortality was 0% in the endovascular group and 6.4% in the open group.
Although open repair for juxtarenal AAAs is the gold standard, short- and mid-term data on the outcomes for complex endovascular repair are excellent. Data on long-term durability, graft fixation/migration as well as the integrity of the graft and concerns for endoleaks and branch vessel patency, however, are limited. We do not have long-term data because we have not been doing these newer procedures for that long – but the data thus far show great promise.
We need to continue to challenge the status quo, particularly when the current data are satisfactory and the procedure feasible. With our continued appraisal of the data we publish as vascular surgeons, we can then identify if these innovations and techniques will withstand the test of time. After all, we are vascular surgeons (particularly those of us who have trained extensively in open repair) – and if open repair is necessary, then we will be ready.
But, if I can avoid a thoracoabdominal incision for a few percutaneous access sites, then sign me up!
Dr. Mouawad is chief of vascular and endovascular surgery, medical director of the vascular laboratory, and vice-chair of the department of surgery at McLaren Bay Region, Bay City, Mich. He is assistant professor of surgery at Michigan State University and Central Michigan University.
Over the past 3 decades, EVAR, with its very low periprocedural morbidity and mortality, and satisfactory long-term results, has become the primary treatment modality for the majority of infrarenal AAAs. The success of stent grafts for the repair of AAA relies heavily on satisfactory proximal and distal seal zones. Each commercially available standard EVAR graft has a manufacturer’s instructions for use requiring a proximal landing zone length of between 10 and 15 mm. Patients with less than this required length are considered to have “short necks.” Evaluation of this group of patients has demonstrated that this is not an uncommon finding and that EVAR performed outside the instructions for use has been associated with an increased risk of intraoperative failure, aneurysm expansion, and later complications.1-3
Current treatment options for patients with short necks include open surgical repair (OSR), FEVAR, and EVAR with the chimney graft technique (Ch-EVAR).
Dr. Mitchell WeaverThe Ch-EVAR technique currently lacks any significant long term follow-up, and with the availability of more proven commercially available devices is presently a lower tier endovascular treatment option. There are no head-to-head trials available between FEVAR and OSR of short neck aneurysms to guide our treatment choice.
Thus, current knowledge acquired from case series, registries, and clinical experience must be used in deciding which therapeutic option to offer patients. Relevant factors influencing this decision include the availability and adaptability of the technique, early outcomes including technical success, morbidity and mortality, and late outcomes including survival, need for reintervention, and other late morbidity. Finally, in an era of value-based medical care, cost also must be considered.
Currently there is only one Food and Drug Administration–approved fenestrated graft. When used in properly selected patients, excellent periprocedural results have been reported approaching those of standard EVAR. However, there are limitations in both the availability and adaptability of FEVAR. These grafts are custom made for each patient, often requiring several weeks of lead time. Adaptability also has its limitations, including access vessels, severe neck angulation, calcification, mural thrombus, and branch vessel size, number, location, and associated arterial disease. Any of these factors may preclude the use of this technology. Open repair, on the other hand, is not limited by graft availability and allows for custom modification for each patient’s specific disease morphology. The essential limitation for open repair is the patient’s physiological ability to withstand the operation.
Several studies attempting to compare the early outcomes of FEVAR versus comparable patients undergoing OSR of similar aneurysms have reported significantly lower 30-day mortality and major morbidity rates for FEVAR.4,5 However, Rao et al., in a recent systematic review and meta-analysis that included data on 2,326 patients from 35 case series reporting on elective repair of juxtarenal aneurysms by either OSR or FEVAR, found perioperative mortality to not be significantly different (4.1% for both). Also, no significant difference was found between the two groups when evaluating postoperative renal insufficiency and need for permanent dialysis. However, OSR did have significantly higher major complication rates (25% vs. 15.7%).6 These findings suggest that both modalities can be performed successfully, but that long term outcomes need to be considered to determine if the increased initial morbidity of OSR is justified by differences in long term results between the two modalities.
Open surgical repair of juxtarenal AAA has been shown to be a durable repair.7 While early and even intermediate results of FEVAR appear to be satisfactory, long-term durability has yet to be determined.4,8 Along with continuing to exclude the aneurysm sac, as with standard EVAR, there is the additional concern regarding the outcome of the organs supplied by the fenestrated/stent-grafted branches with FEVAR. Longer-term follow-up in the same review by Rao et al. showed that significantly more FEVAR patients developed renal failure compared with OSR patients (19.7% vs. 7.7%). FEVAR patients also had a higher rate of reintervention.
And finally, long-term survival was significantly greater in OSR patients compared to FEVAR at 3 and 5 years (80% vs. 74% vs. 73% vs. 55%). These authors concluded that open repair remains the gold standard while FEVAR is a favorable option for high risk patients.6
These new and innovative stent graft devices come at considerable expense. While this aspect of FEVAR has not been extensively studied, Michel et al., in their report from the multicenter prospective Windows registry, attempted to evaluate the economic aspect of FEVAR. They compared a group of patients who underwent FEVAR to patients from a large national hospital discharge database who underwent OSR. No difference in 30-day mortality was noted between these two groups; however, there was a significantly greater cost with FEVAR. The authors concluded that FEVAR did not appear to be justified for patients fit for open surgery with juxtarenal AAA.9
For now, the roles of OSR and FEVAR would appear to be complementary. Current evidence suggests that OSR is the most appropriate intervention for good risk patients with an anticipated longer life expectancy. Patients with appropriate anatomy for FEVAR and who are at higher risk for open repair would benefit from FEVAR. As further experience and outcomes are accumulated, our ability to select the appropriate therapy for individual patients should improve.
Dr. Weaver is an assistant clinical professor for surgery at Wayne State School of Medicine, Detroit, and an attending in the division of vascular surgery, Henry Ford Hospital.
The advent of endovascular aortic aneurysm repair (EVAR) has steadily become the standard of care in the management of infrarenal abdominal aortic aneurysms (AAAs). In fact, it has now surpassed open surgical repair and is the predominant therapeutic modality in managing this disease entity. Clearly, there are specific anatomic and technical factors that may preclude the use of traditional EVAR – most notably, challenging proximal neck anatomy, be it insufficient length or severe angulation.
It is estimated that up to 30%-40% of patients are unsuitable candidates because of these concerns.1 Such patients are thus relegated to traditional open repair with the associated concerns for supravisceral clamping, including dramatic changes in hemodynamics and prolonged ICU and hospital stays.
Dr. Nicholas J. MouawadHowever, with increasing surgeon experience and volume, complex endovascular strategies are being championed and performed, including use of traditional infrarenal devices outside the instructions-for-use indications, “back-table” physician modified devices, chimney/snorkel barreled parallel covered grafts (Ch-EVAR), custom built fenestrated endografts (FEVAR), and use of adjunctive techniques such as endoanchors.
Open surgical repair of pararenal, juxtarenal, and suprarenal AAAs is tried, tested, and durable. Knott and the group from Mayo Clinic reviewed their repair of 126 consecutive elective juxtarenal AAAs requiring suprarenal aortic clamping noting a 30-day mortality of .8%.2 More recent data from Kabbani and the Henry Ford group involved their 27-year clinical experience suggesting that open repair of complex proximal aortic aneurysms can be performed with clinical outcomes that are similar to those of open infrarenal repair.3 I respectfully accept this traditional – and historic – treatment modality.
However, we vascular surgeons are progressive and resilient in our quest to innovate and modernize – some of us even modified the traditional endografts on the back table. We charged forward despite the initial paucity of data on infrarenal EVAR compared to traditional open repair of aneurysms in the past. Now, a large percentage of infrarenal AAA repairs are performed via EVAR. In fact, our steadfast progression to advanced endovascular techniques has raised the concern that our graduating trainees are no longer proficient, competent, or even capable, in open complex aneurysm repair!
Tsilimparis and colleagues reported the first outcomes comparing open repair and FEVAR.4 They queried the NSQIP database comparing 1,091 patients undergoing open repair with 264 in the FEVAR group. There was an increased risk of morbidity in all combined endpoints including pulmonary and cardiovascular complications as well as length of stay in patients undergoing the open repair group. A larger comprehensive review pooled the results from 8 FEVAR and 12 open repair series. Analysis of the data found the groups to be identical. Open repair, however, was found to have an increased 30-day mortality when compared to FEVAR (relative risk 1.03, 2% increased absolute mortality).5
Gupta and colleagues reported the latest multi-institutional data noting that open repair was associated with higher risk than FEVAR for 30-day mortality, cardiac and pulmonary complications, renal failure requiring dialysis, return to the operating room, and in this age of cost-containment, length of stay (2 days vs. 7 days; P less than .0001).6
A further study by Donas and colleagues evaluated 90 consecutive patients with primary degenerative juxtarenal AAAs to different operative strategies based on morphologic and clinical characteristics – 29 FEVAR, 30 chEVAR, and 31 open repair.7 Early procedure-related and all-cause 30-day mortality was 0% in the endovascular group and 6.4% in the open group.
Although open repair for juxtarenal AAAs is the gold standard, short- and mid-term data on the outcomes for complex endovascular repair are excellent. Data on long-term durability, graft fixation/migration as well as the integrity of the graft and concerns for endoleaks and branch vessel patency, however, are limited. We do not have long-term data because we have not been doing these newer procedures for that long – but the data thus far show great promise.
We need to continue to challenge the status quo, particularly when the current data are satisfactory and the procedure feasible. With our continued appraisal of the data we publish as vascular surgeons, we can then identify if these innovations and techniques will withstand the test of time. After all, we are vascular surgeons (particularly those of us who have trained extensively in open repair) – and if open repair is necessary, then we will be ready.
But, if I can avoid a thoracoabdominal incision for a few percutaneous access sites, then sign me up!
Dr. Mouawad is chief of vascular and endovascular surgery, medical director of the vascular laboratory, and vice-chair of the department of surgery at McLaren Bay Region, Bay City, Mich. He is assistant professor of surgery at Michigan State University and Central Michigan University.
Over the past 3 decades, EVAR, with its very low periprocedural morbidity and mortality, and satisfactory long-term results, has become the primary treatment modality for the majority of infrarenal AAAs. The success of stent grafts for the repair of AAA relies heavily on satisfactory proximal and distal seal zones. Each commercially available standard EVAR graft has a manufacturer’s instructions for use requiring a proximal landing zone length of between 10 and 15 mm. Patients with less than this required length are considered to have “short necks.” Evaluation of this group of patients has demonstrated that this is not an uncommon finding and that EVAR performed outside the instructions for use has been associated with an increased risk of intraoperative failure, aneurysm expansion, and later complications.1-3
Current treatment options for patients with short necks include open surgical repair (OSR), FEVAR, and EVAR with the chimney graft technique (Ch-EVAR).
Dr. Mitchell WeaverThe Ch-EVAR technique currently lacks any significant long term follow-up, and with the availability of more proven commercially available devices is presently a lower tier endovascular treatment option. There are no head-to-head trials available between FEVAR and OSR of short neck aneurysms to guide our treatment choice.
Thus, current knowledge acquired from case series, registries, and clinical experience must be used in deciding which therapeutic option to offer patients. Relevant factors influencing this decision include the availability and adaptability of the technique, early outcomes including technical success, morbidity and mortality, and late outcomes including survival, need for reintervention, and other late morbidity. Finally, in an era of value-based medical care, cost also must be considered.
Currently there is only one Food and Drug Administration–approved fenestrated graft. When used in properly selected patients, excellent periprocedural results have been reported approaching those of standard EVAR. However, there are limitations in both the availability and adaptability of FEVAR. These grafts are custom made for each patient, often requiring several weeks of lead time. Adaptability also has its limitations, including access vessels, severe neck angulation, calcification, mural thrombus, and branch vessel size, number, location, and associated arterial disease. Any of these factors may preclude the use of this technology. Open repair, on the other hand, is not limited by graft availability and allows for custom modification for each patient’s specific disease morphology. The essential limitation for open repair is the patient’s physiological ability to withstand the operation.
Several studies attempting to compare the early outcomes of FEVAR versus comparable patients undergoing OSR of similar aneurysms have reported significantly lower 30-day mortality and major morbidity rates for FEVAR.4,5 However, Rao et al., in a recent systematic review and meta-analysis that included data on 2,326 patients from 35 case series reporting on elective repair of juxtarenal aneurysms by either OSR or FEVAR, found perioperative mortality to not be significantly different (4.1% for both). Also, no significant difference was found between the two groups when evaluating postoperative renal insufficiency and need for permanent dialysis. However, OSR did have significantly higher major complication rates (25% vs. 15.7%).6 These findings suggest that both modalities can be performed successfully, but that long term outcomes need to be considered to determine if the increased initial morbidity of OSR is justified by differences in long term results between the two modalities.
Open surgical repair of juxtarenal AAA has been shown to be a durable repair.7 While early and even intermediate results of FEVAR appear to be satisfactory, long-term durability has yet to be determined.4,8 Along with continuing to exclude the aneurysm sac, as with standard EVAR, there is the additional concern regarding the outcome of the organs supplied by the fenestrated/stent-grafted branches with FEVAR. Longer-term follow-up in the same review by Rao et al. showed that significantly more FEVAR patients developed renal failure compared with OSR patients (19.7% vs. 7.7%). FEVAR patients also had a higher rate of reintervention.
And finally, long-term survival was significantly greater in OSR patients compared to FEVAR at 3 and 5 years (80% vs. 74% vs. 73% vs. 55%). These authors concluded that open repair remains the gold standard while FEVAR is a favorable option for high risk patients.6
These new and innovative stent graft devices come at considerable expense. While this aspect of FEVAR has not been extensively studied, Michel et al., in their report from the multicenter prospective Windows registry, attempted to evaluate the economic aspect of FEVAR. They compared a group of patients who underwent FEVAR to patients from a large national hospital discharge database who underwent OSR. No difference in 30-day mortality was noted between these two groups; however, there was a significantly greater cost with FEVAR. The authors concluded that FEVAR did not appear to be justified for patients fit for open surgery with juxtarenal AAA.9
For now, the roles of OSR and FEVAR would appear to be complementary. Current evidence suggests that OSR is the most appropriate intervention for good risk patients with an anticipated longer life expectancy. Patients with appropriate anatomy for FEVAR and who are at higher risk for open repair would benefit from FEVAR. As further experience and outcomes are accumulated, our ability to select the appropriate therapy for individual patients should improve.
Dr. Weaver is an assistant clinical professor for surgery at Wayne State School of Medicine, Detroit, and an attending in the division of vascular surgery, Henry Ford Hospital.
The advent of endovascular aortic aneurysm repair (EVAR) has steadily become the standard of care in the management of infrarenal abdominal aortic aneurysms (AAAs). In fact, it has now surpassed open surgical repair and is the predominant therapeutic modality in managing this disease entity. Clearly, there are specific anatomic and technical factors that may preclude the use of traditional EVAR – most notably, challenging proximal neck anatomy, be it insufficient length or severe angulation.
It is estimated that up to 30%-40% of patients are unsuitable candidates because of these concerns.1 Such patients are thus relegated to traditional open repair with the associated concerns for supravisceral clamping, including dramatic changes in hemodynamics and prolonged ICU and hospital stays.
Dr. Nicholas J. MouawadHowever, with increasing surgeon experience and volume, complex endovascular strategies are being championed and performed, including use of traditional infrarenal devices outside the instructions-for-use indications, “back-table” physician modified devices, chimney/snorkel barreled parallel covered grafts (Ch-EVAR), custom built fenestrated endografts (FEVAR), and use of adjunctive techniques such as endoanchors.
Open surgical repair of pararenal, juxtarenal, and suprarenal AAAs is tried, tested, and durable. Knott and the group from Mayo Clinic reviewed their repair of 126 consecutive elective juxtarenal AAAs requiring suprarenal aortic clamping noting a 30-day mortality of .8%.2 More recent data from Kabbani and the Henry Ford group involved their 27-year clinical experience suggesting that open repair of complex proximal aortic aneurysms can be performed with clinical outcomes that are similar to those of open infrarenal repair.3 I respectfully accept this traditional – and historic – treatment modality.
However, we vascular surgeons are progressive and resilient in our quest to innovate and modernize – some of us even modified the traditional endografts on the back table. We charged forward despite the initial paucity of data on infrarenal EVAR compared to traditional open repair of aneurysms in the past. Now, a large percentage of infrarenal AAA repairs are performed via EVAR. In fact, our steadfast progression to advanced endovascular techniques has raised the concern that our graduating trainees are no longer proficient, competent, or even capable, in open complex aneurysm repair!
Tsilimparis and colleagues reported the first outcomes comparing open repair and FEVAR.4 They queried the NSQIP database comparing 1,091 patients undergoing open repair with 264 in the FEVAR group. There was an increased risk of morbidity in all combined endpoints including pulmonary and cardiovascular complications as well as length of stay in patients undergoing the open repair group. A larger comprehensive review pooled the results from 8 FEVAR and 12 open repair series. Analysis of the data found the groups to be identical. Open repair, however, was found to have an increased 30-day mortality when compared to FEVAR (relative risk 1.03, 2% increased absolute mortality).5
Gupta and colleagues reported the latest multi-institutional data noting that open repair was associated with higher risk than FEVAR for 30-day mortality, cardiac and pulmonary complications, renal failure requiring dialysis, return to the operating room, and in this age of cost-containment, length of stay (2 days vs. 7 days; P less than .0001).6
A further study by Donas and colleagues evaluated 90 consecutive patients with primary degenerative juxtarenal AAAs to different operative strategies based on morphologic and clinical characteristics – 29 FEVAR, 30 chEVAR, and 31 open repair.7 Early procedure-related and all-cause 30-day mortality was 0% in the endovascular group and 6.4% in the open group.
Although open repair for juxtarenal AAAs is the gold standard, short- and mid-term data on the outcomes for complex endovascular repair are excellent. Data on long-term durability, graft fixation/migration as well as the integrity of the graft and concerns for endoleaks and branch vessel patency, however, are limited. We do not have long-term data because we have not been doing these newer procedures for that long – but the data thus far show great promise.
We need to continue to challenge the status quo, particularly when the current data are satisfactory and the procedure feasible. With our continued appraisal of the data we publish as vascular surgeons, we can then identify if these innovations and techniques will withstand the test of time. After all, we are vascular surgeons (particularly those of us who have trained extensively in open repair) – and if open repair is necessary, then we will be ready.
But, if I can avoid a thoracoabdominal incision for a few percutaneous access sites, then sign me up!
Dr. Mouawad is chief of vascular and endovascular surgery, medical director of the vascular laboratory, and vice-chair of the department of surgery at McLaren Bay Region, Bay City, Mich. He is assistant professor of surgery at Michigan State University and Central Michigan University.
Over the past 3 decades, EVAR, with its very low periprocedural morbidity and mortality, and satisfactory long-term results, has become the primary treatment modality for the majority of infrarenal AAAs. The success of stent grafts for the repair of AAA relies heavily on satisfactory proximal and distal seal zones. Each commercially available standard EVAR graft has a manufacturer’s instructions for use requiring a proximal landing zone length of between 10 and 15 mm. Patients with less than this required length are considered to have “short necks.” Evaluation of this group of patients has demonstrated that this is not an uncommon finding and that EVAR performed outside the instructions for use has been associated with an increased risk of intraoperative failure, aneurysm expansion, and later complications.1-3
Current treatment options for patients with short necks include open surgical repair (OSR), FEVAR, and EVAR with the chimney graft technique (Ch-EVAR).
Dr. Mitchell WeaverThe Ch-EVAR technique currently lacks any significant long term follow-up, and with the availability of more proven commercially available devices is presently a lower tier endovascular treatment option. There are no head-to-head trials available between FEVAR and OSR of short neck aneurysms to guide our treatment choice.
Thus, current knowledge acquired from case series, registries, and clinical experience must be used in deciding which therapeutic option to offer patients. Relevant factors influencing this decision include the availability and adaptability of the technique, early outcomes including technical success, morbidity and mortality, and late outcomes including survival, need for reintervention, and other late morbidity. Finally, in an era of value-based medical care, cost also must be considered.
Currently there is only one Food and Drug Administration–approved fenestrated graft. When used in properly selected patients, excellent periprocedural results have been reported approaching those of standard EVAR. However, there are limitations in both the availability and adaptability of FEVAR. These grafts are custom made for each patient, often requiring several weeks of lead time. Adaptability also has its limitations, including access vessels, severe neck angulation, calcification, mural thrombus, and branch vessel size, number, location, and associated arterial disease. Any of these factors may preclude the use of this technology. Open repair, on the other hand, is not limited by graft availability and allows for custom modification for each patient’s specific disease morphology. The essential limitation for open repair is the patient’s physiological ability to withstand the operation.
Several studies attempting to compare the early outcomes of FEVAR versus comparable patients undergoing OSR of similar aneurysms have reported significantly lower 30-day mortality and major morbidity rates for FEVAR.4,5 However, Rao et al., in a recent systematic review and meta-analysis that included data on 2,326 patients from 35 case series reporting on elective repair of juxtarenal aneurysms by either OSR or FEVAR, found perioperative mortality to not be significantly different (4.1% for both). Also, no significant difference was found between the two groups when evaluating postoperative renal insufficiency and need for permanent dialysis. However, OSR did have significantly higher major complication rates (25% vs. 15.7%).6 These findings suggest that both modalities can be performed successfully, but that long term outcomes need to be considered to determine if the increased initial morbidity of OSR is justified by differences in long term results between the two modalities.
Open surgical repair of juxtarenal AAA has been shown to be a durable repair.7 While early and even intermediate results of FEVAR appear to be satisfactory, long-term durability has yet to be determined.4,8 Along with continuing to exclude the aneurysm sac, as with standard EVAR, there is the additional concern regarding the outcome of the organs supplied by the fenestrated/stent-grafted branches with FEVAR. Longer-term follow-up in the same review by Rao et al. showed that significantly more FEVAR patients developed renal failure compared with OSR patients (19.7% vs. 7.7%). FEVAR patients also had a higher rate of reintervention.
And finally, long-term survival was significantly greater in OSR patients compared to FEVAR at 3 and 5 years (80% vs. 74% vs. 73% vs. 55%). These authors concluded that open repair remains the gold standard while FEVAR is a favorable option for high risk patients.6
These new and innovative stent graft devices come at considerable expense. While this aspect of FEVAR has not been extensively studied, Michel et al., in their report from the multicenter prospective Windows registry, attempted to evaluate the economic aspect of FEVAR. They compared a group of patients who underwent FEVAR to patients from a large national hospital discharge database who underwent OSR. No difference in 30-day mortality was noted between these two groups; however, there was a significantly greater cost with FEVAR. The authors concluded that FEVAR did not appear to be justified for patients fit for open surgery with juxtarenal AAA.9
For now, the roles of OSR and FEVAR would appear to be complementary. Current evidence suggests that OSR is the most appropriate intervention for good risk patients with an anticipated longer life expectancy. Patients with appropriate anatomy for FEVAR and who are at higher risk for open repair would benefit from FEVAR. As further experience and outcomes are accumulated, our ability to select the appropriate therapy for individual patients should improve.
Dr. Weaver is an assistant clinical professor for surgery at Wayne State School of Medicine, Detroit, and an attending in the division of vascular surgery, Henry Ford Hospital.
SAN DIEGO – A new class of anticoagulants competing with or replacing warfarin and heparin is now commonly seen in patients and can require new strategies for management in the surgical setting. New drugs to reverse anticoagulation agents now need to be routinely considered in advance of surgery.
“They’re all over the place. It feels like everyone I see is on an anticoagulant, especially the new anticoagulants,” said Carlos V.R. Brown, MD, FACS, associate professor of surgery and chief of the division of acute care surgery at the University of Texas at Austin. “There’s a lot more learning that has to take place into how these medications work and how to take care of patients who use them.”
Dr. Carlos V.R. BrownDr. Brown spoke about management of anticoagulants at the annual clinical congress of the American College of Surgeons and in a follow-up interview. He offered some details during his San Diego presentation about the significant limitations of the traditional blood thinners.
“Warfarin is slow, unpredictable, and requires monitoring and dose adjustment,” he said. In addition, interactions with food and other medications can be problematic, he said. The injectable drug heparin, meanwhile, requires monitoring and frequent dose adjustments, he said. “We’re in search of the ideal anticoagulant – one that’s oral, has a wide therapeutic window, is very predictable with rapid onset, and has minimal interaction with other food or drugs.”
Here’s the hitch, he said: “It probably doesn’t exist.”
There are now several alternatives to the old standbys on the market. One class, the direct thrombin inhibitor, is led by dabigatran etexilate (Pradaxa). Another class, the factor Xa inhibitors, includes rivaroxaban (Xarelto), apixaban (Eliquis), and edoxaban (Savaysa). From an elective surgery standpoint, Dr. Brown said in an interview, it has become important to understand how to reverse the effects of anticoagulants before a procedure.
To determine levels of the drugs, a TT (thrombin time) screening test is recommended for dabigatran and an anti-Xa test for rivaroxaban, apixaban, and edoxaban said Dr. Brown, referring to a 2017 study published in Critical Care Clinics. The paper summarized the available evidence and provided the optimal reversal strategy for bleeding patients with trauma on novel oral anticoagulants. The report also noted that newer blood thinners have a half-life of 7 or 12 hours and reach peak plasma level at 1-4 hours, depending on the medication (Crit Care Clin. 2017;33[1]135-52).
There may be no time to determine blood thinner levels in emergency situations. In those cases, patient or caregiver history about recent doses can be crucial, Dr. Brown said. “Knowing the patient’s history is going to be a key component,” he said.
Surgeons can turn to a variety of options to reverse the newer anticoagulants in an emergent setting, but only dabigatran has a Food and Drug Administration–approved reversal agent. Activated charcoal, PCC (Kcentra) and aPCC (FEIBA) can reverse dabigatran and oral factor Xa inhibitors, Dr. Brown said. Dialysis is also an option for dabigatran.
Another option to reverse dabigatran may be idarucizumab (Praxbind), a reversal agent. A 2017 industry-funded, open-label study reported successful results. It has been shown to work rapidly, Dr. Brown said, and the drug is now FDA approved (N Engl J Med. 2017 Aug 3;377[5]:431-41).
For oral factor Xa inhibitors, Dr. Brown said, andexanet alfa is now in a trial and doesn’t yet have FDA approval. “Presumably, it will provide a benefit over PCC because it’s directed at that specific medication,” he said.
Dr. Brown cautioned about the risks of reversing anticoagulants. “Any time you’re reversing an anticoagulant, the side effect is going to be clotting,” boosting the likelihood of events such as heart attack or stroke, he said. “You’re always weighing the risk versus the benefit of reversing.”
SAN DIEGO – A new class of anticoagulants competing with or replacing warfarin and heparin is now commonly seen in patients and can require new strategies for management in the surgical setting. New drugs to reverse anticoagulation agents now need to be routinely considered in advance of surgery.
“They’re all over the place. It feels like everyone I see is on an anticoagulant, especially the new anticoagulants,” said Carlos V.R. Brown, MD, FACS, associate professor of surgery and chief of the division of acute care surgery at the University of Texas at Austin. “There’s a lot more learning that has to take place into how these medications work and how to take care of patients who use them.”
Dr. Carlos V.R. BrownDr. Brown spoke about management of anticoagulants at the annual clinical congress of the American College of Surgeons and in a follow-up interview. He offered some details during his San Diego presentation about the significant limitations of the traditional blood thinners.
“Warfarin is slow, unpredictable, and requires monitoring and dose adjustment,” he said. In addition, interactions with food and other medications can be problematic, he said. The injectable drug heparin, meanwhile, requires monitoring and frequent dose adjustments, he said. “We’re in search of the ideal anticoagulant – one that’s oral, has a wide therapeutic window, is very predictable with rapid onset, and has minimal interaction with other food or drugs.”
Here’s the hitch, he said: “It probably doesn’t exist.”
There are now several alternatives to the old standbys on the market. One class, the direct thrombin inhibitor, is led by dabigatran etexilate (Pradaxa). Another class, the factor Xa inhibitors, includes rivaroxaban (Xarelto), apixaban (Eliquis), and edoxaban (Savaysa). From an elective surgery standpoint, Dr. Brown said in an interview, it has become important to understand how to reverse the effects of anticoagulants before a procedure.
To determine levels of the drugs, a TT (thrombin time) screening test is recommended for dabigatran and an anti-Xa test for rivaroxaban, apixaban, and edoxaban said Dr. Brown, referring to a 2017 study published in Critical Care Clinics. The paper summarized the available evidence and provided the optimal reversal strategy for bleeding patients with trauma on novel oral anticoagulants. The report also noted that newer blood thinners have a half-life of 7 or 12 hours and reach peak plasma level at 1-4 hours, depending on the medication (Crit Care Clin. 2017;33[1]135-52).
There may be no time to determine blood thinner levels in emergency situations. In those cases, patient or caregiver history about recent doses can be crucial, Dr. Brown said. “Knowing the patient’s history is going to be a key component,” he said.
Surgeons can turn to a variety of options to reverse the newer anticoagulants in an emergent setting, but only dabigatran has a Food and Drug Administration–approved reversal agent. Activated charcoal, PCC (Kcentra) and aPCC (FEIBA) can reverse dabigatran and oral factor Xa inhibitors, Dr. Brown said. Dialysis is also an option for dabigatran.
Another option to reverse dabigatran may be idarucizumab (Praxbind), a reversal agent. A 2017 industry-funded, open-label study reported successful results. It has been shown to work rapidly, Dr. Brown said, and the drug is now FDA approved (N Engl J Med. 2017 Aug 3;377[5]:431-41).
For oral factor Xa inhibitors, Dr. Brown said, andexanet alfa is now in a trial and doesn’t yet have FDA approval. “Presumably, it will provide a benefit over PCC because it’s directed at that specific medication,” he said.
Dr. Brown cautioned about the risks of reversing anticoagulants. “Any time you’re reversing an anticoagulant, the side effect is going to be clotting,” boosting the likelihood of events such as heart attack or stroke, he said. “You’re always weighing the risk versus the benefit of reversing.”
Dr. Brown has no relevant disclosures.
SAN DIEGO – A new class of anticoagulants competing with or replacing warfarin and heparin is now commonly seen in patients and can require new strategies for management in the surgical setting. New drugs to reverse anticoagulation agents now need to be routinely considered in advance of surgery.
“They’re all over the place. It feels like everyone I see is on an anticoagulant, especially the new anticoagulants,” said Carlos V.R. Brown, MD, FACS, associate professor of surgery and chief of the division of acute care surgery at the University of Texas at Austin. “There’s a lot more learning that has to take place into how these medications work and how to take care of patients who use them.”
Dr. Carlos V.R. BrownDr. Brown spoke about management of anticoagulants at the annual clinical congress of the American College of Surgeons and in a follow-up interview. He offered some details during his San Diego presentation about the significant limitations of the traditional blood thinners.
“Warfarin is slow, unpredictable, and requires monitoring and dose adjustment,” he said. In addition, interactions with food and other medications can be problematic, he said. The injectable drug heparin, meanwhile, requires monitoring and frequent dose adjustments, he said. “We’re in search of the ideal anticoagulant – one that’s oral, has a wide therapeutic window, is very predictable with rapid onset, and has minimal interaction with other food or drugs.”
Here’s the hitch, he said: “It probably doesn’t exist.”
There are now several alternatives to the old standbys on the market. One class, the direct thrombin inhibitor, is led by dabigatran etexilate (Pradaxa). Another class, the factor Xa inhibitors, includes rivaroxaban (Xarelto), apixaban (Eliquis), and edoxaban (Savaysa). From an elective surgery standpoint, Dr. Brown said in an interview, it has become important to understand how to reverse the effects of anticoagulants before a procedure.
To determine levels of the drugs, a TT (thrombin time) screening test is recommended for dabigatran and an anti-Xa test for rivaroxaban, apixaban, and edoxaban said Dr. Brown, referring to a 2017 study published in Critical Care Clinics. The paper summarized the available evidence and provided the optimal reversal strategy for bleeding patients with trauma on novel oral anticoagulants. The report also noted that newer blood thinners have a half-life of 7 or 12 hours and reach peak plasma level at 1-4 hours, depending on the medication (Crit Care Clin. 2017;33[1]135-52).
There may be no time to determine blood thinner levels in emergency situations. In those cases, patient or caregiver history about recent doses can be crucial, Dr. Brown said. “Knowing the patient’s history is going to be a key component,” he said.
Surgeons can turn to a variety of options to reverse the newer anticoagulants in an emergent setting, but only dabigatran has a Food and Drug Administration–approved reversal agent. Activated charcoal, PCC (Kcentra) and aPCC (FEIBA) can reverse dabigatran and oral factor Xa inhibitors, Dr. Brown said. Dialysis is also an option for dabigatran.
Another option to reverse dabigatran may be idarucizumab (Praxbind), a reversal agent. A 2017 industry-funded, open-label study reported successful results. It has been shown to work rapidly, Dr. Brown said, and the drug is now FDA approved (N Engl J Med. 2017 Aug 3;377[5]:431-41).
For oral factor Xa inhibitors, Dr. Brown said, andexanet alfa is now in a trial and doesn’t yet have FDA approval. “Presumably, it will provide a benefit over PCC because it’s directed at that specific medication,” he said.
Dr. Brown cautioned about the risks of reversing anticoagulants. “Any time you’re reversing an anticoagulant, the side effect is going to be clotting,” boosting the likelihood of events such as heart attack or stroke, he said. “You’re always weighing the risk versus the benefit of reversing.”
Although uncommon, major venous injury during surgery for aortic reconstruction can result in massive blood loss resulting in increased morbidity and mortality, according to the results of a retrospective review conducted by Sachinder S. Hans, MD, and colleagues, and reported online in the Annals of Vascular Surgery.
Of 945 patients undergoing major aortic reconstruction, 723 (76.5%) underwent open abdominal aortic aneurysm (AAA) repair/iliac aneurysm repair; 222 patients (23.5%) underwent aortofemoral grafting (AFG). The number of units of packed red blood cells transfused, location of injured vessel, type of repair, postoperative morbidity, and mortality were collected in a vascular registry on a continuous basis. All patients identified with iliac vein/inferior vena cava/femoral vein injury had follow-up noninvasive venous examination of the lower extremities.
A total of 17 of 945 patients (1.9%) suffered 18 major venous injuries during aortic reconstruction according to Dr. Hans and his colleagues at St. John Macomb Hospital, Warren, Mich. These injuries comprised four inferior vena cava injuries, 10 iliac vein injuries, and four left renal vein injuries (Ann Vasc Surg. 2017. doi: 10.1016/j.avsg.2017.08.004).
Overall, 16 of the 18 injuries occurred during open AAA repair (7 for ruptured AAA, and 9 for intact). Two of the patients with venous injury died (11.8%), one from uncontrolled bleeding from a tear in the right iliac during repair of a ruptured AAA, and the second from disseminated intravascular complication following repair of ruptured AAA. The remaining two major venous injuries occurred during redo AFG (1 out of 6 total) and primary AFG (1 out of 216 total).
The following risk factors were also observed: The majority of the patients experiencing major venous injury were men (83%; P = .002), and the presence of periarterial inflammation (P = .006) and associated iliac aneurysm (P = .05) were significantly associated with major venous injury among the AAA patients.
The researchers suggested the following tips to lessen the likelihood of major venous injury: “Prevention of major venous injury is not always possible; however, keeping dissection plane close to arterial wall, avoiding passage of vessel loops or tapes around the neck of the aorta and iliac bifurcation, particularly in patients with surrounding inflammation and ligating venous tributaries crossing the aorta as they are joining the inferior vena cava may help reduce incidence of such injuries.”
They also suggested that surgeons should be cognizant of the serious complication that major venous injury was for patients undergoing aortic reconstruction, and to be aware that “the incidence of such injury is higher during the repair of ruptured AAA and redo aortofemoral grafting.”
The authors received no study funding and reported that they had no conflicts.
Although uncommon, major venous injury during surgery for aortic reconstruction can result in massive blood loss resulting in increased morbidity and mortality, according to the results of a retrospective review conducted by Sachinder S. Hans, MD, and colleagues, and reported online in the Annals of Vascular Surgery.
Of 945 patients undergoing major aortic reconstruction, 723 (76.5%) underwent open abdominal aortic aneurysm (AAA) repair/iliac aneurysm repair; 222 patients (23.5%) underwent aortofemoral grafting (AFG). The number of units of packed red blood cells transfused, location of injured vessel, type of repair, postoperative morbidity, and mortality were collected in a vascular registry on a continuous basis. All patients identified with iliac vein/inferior vena cava/femoral vein injury had follow-up noninvasive venous examination of the lower extremities.
A total of 17 of 945 patients (1.9%) suffered 18 major venous injuries during aortic reconstruction according to Dr. Hans and his colleagues at St. John Macomb Hospital, Warren, Mich. These injuries comprised four inferior vena cava injuries, 10 iliac vein injuries, and four left renal vein injuries (Ann Vasc Surg. 2017. doi: 10.1016/j.avsg.2017.08.004).
Overall, 16 of the 18 injuries occurred during open AAA repair (7 for ruptured AAA, and 9 for intact). Two of the patients with venous injury died (11.8%), one from uncontrolled bleeding from a tear in the right iliac during repair of a ruptured AAA, and the second from disseminated intravascular complication following repair of ruptured AAA. The remaining two major venous injuries occurred during redo AFG (1 out of 6 total) and primary AFG (1 out of 216 total).
The following risk factors were also observed: The majority of the patients experiencing major venous injury were men (83%; P = .002), and the presence of periarterial inflammation (P = .006) and associated iliac aneurysm (P = .05) were significantly associated with major venous injury among the AAA patients.
The researchers suggested the following tips to lessen the likelihood of major venous injury: “Prevention of major venous injury is not always possible; however, keeping dissection plane close to arterial wall, avoiding passage of vessel loops or tapes around the neck of the aorta and iliac bifurcation, particularly in patients with surrounding inflammation and ligating venous tributaries crossing the aorta as they are joining the inferior vena cava may help reduce incidence of such injuries.”
They also suggested that surgeons should be cognizant of the serious complication that major venous injury was for patients undergoing aortic reconstruction, and to be aware that “the incidence of such injury is higher during the repair of ruptured AAA and redo aortofemoral grafting.”
The authors received no study funding and reported that they had no conflicts.
Although uncommon, major venous injury during surgery for aortic reconstruction can result in massive blood loss resulting in increased morbidity and mortality, according to the results of a retrospective review conducted by Sachinder S. Hans, MD, and colleagues, and reported online in the Annals of Vascular Surgery.
Of 945 patients undergoing major aortic reconstruction, 723 (76.5%) underwent open abdominal aortic aneurysm (AAA) repair/iliac aneurysm repair; 222 patients (23.5%) underwent aortofemoral grafting (AFG). The number of units of packed red blood cells transfused, location of injured vessel, type of repair, postoperative morbidity, and mortality were collected in a vascular registry on a continuous basis. All patients identified with iliac vein/inferior vena cava/femoral vein injury had follow-up noninvasive venous examination of the lower extremities.
A total of 17 of 945 patients (1.9%) suffered 18 major venous injuries during aortic reconstruction according to Dr. Hans and his colleagues at St. John Macomb Hospital, Warren, Mich. These injuries comprised four inferior vena cava injuries, 10 iliac vein injuries, and four left renal vein injuries (Ann Vasc Surg. 2017. doi: 10.1016/j.avsg.2017.08.004).
Overall, 16 of the 18 injuries occurred during open AAA repair (7 for ruptured AAA, and 9 for intact). Two of the patients with venous injury died (11.8%), one from uncontrolled bleeding from a tear in the right iliac during repair of a ruptured AAA, and the second from disseminated intravascular complication following repair of ruptured AAA. The remaining two major venous injuries occurred during redo AFG (1 out of 6 total) and primary AFG (1 out of 216 total).
The following risk factors were also observed: The majority of the patients experiencing major venous injury were men (83%; P = .002), and the presence of periarterial inflammation (P = .006) and associated iliac aneurysm (P = .05) were significantly associated with major venous injury among the AAA patients.
The researchers suggested the following tips to lessen the likelihood of major venous injury: “Prevention of major venous injury is not always possible; however, keeping dissection plane close to arterial wall, avoiding passage of vessel loops or tapes around the neck of the aorta and iliac bifurcation, particularly in patients with surrounding inflammation and ligating venous tributaries crossing the aorta as they are joining the inferior vena cava may help reduce incidence of such injuries.”
They also suggested that surgeons should be cognizant of the serious complication that major venous injury was for patients undergoing aortic reconstruction, and to be aware that “the incidence of such injury is higher during the repair of ruptured AAA and redo aortofemoral grafting.”
The authors received no study funding and reported that they had no conflicts.
Older and younger patients benefited from varicose vein procedures, a finding that calls into question the use of compression therapy as the primary treatment for patients aged 65 years and older, according to the results of a prospectively maintained database study of all patients in the Vascular Quality Initiative Varicose Vein Registry–participating centers.
Procedures for varicose veins in 1,068 patients aged 65 years or older showed similar improvement in Clinical, Etiology, Anatomy, and Pathophysiology class and Venous Clinical Severity Score, compared with a group of 2,691 younger patients, according to a report published in Journal of Vascular Surgery: Venous and Lymphatic Disorders. Among patients younger than 65 years, 57.4% had an improvement, compared with 52% of patients aged 65 years or older.
copyright iStock /Thinkstock
However, the younger patients had more improvement in patient-reported outcomes, according to Danielle C. Sutzko, MD, of the University of Michigan, Ann Arbor, and her colleagues (J Vasc Surg Venous Lymphat Disord. 2017 Sep;5[5]:647-57).
One of the main limitations of the study was the fact that only 62% of procedures within the Vascular Quality Initiative Varicose Vein Registry had follow-up.
“Patients older than 65 years appear to benefit from appropriate varicose vein procedures and should not be denied interventions on their varicose veins and venous insufficiency on the basis of their age only,” the researchers concluded.
Dr. Sutzko and her colleagues reported having no conflicts of interest.
Older and younger patients benefited from varicose vein procedures, a finding that calls into question the use of compression therapy as the primary treatment for patients aged 65 years and older, according to the results of a prospectively maintained database study of all patients in the Vascular Quality Initiative Varicose Vein Registry–participating centers.
Procedures for varicose veins in 1,068 patients aged 65 years or older showed similar improvement in Clinical, Etiology, Anatomy, and Pathophysiology class and Venous Clinical Severity Score, compared with a group of 2,691 younger patients, according to a report published in Journal of Vascular Surgery: Venous and Lymphatic Disorders. Among patients younger than 65 years, 57.4% had an improvement, compared with 52% of patients aged 65 years or older.
copyright iStock /Thinkstock
However, the younger patients had more improvement in patient-reported outcomes, according to Danielle C. Sutzko, MD, of the University of Michigan, Ann Arbor, and her colleagues (J Vasc Surg Venous Lymphat Disord. 2017 Sep;5[5]:647-57).
One of the main limitations of the study was the fact that only 62% of procedures within the Vascular Quality Initiative Varicose Vein Registry had follow-up.
“Patients older than 65 years appear to benefit from appropriate varicose vein procedures and should not be denied interventions on their varicose veins and venous insufficiency on the basis of their age only,” the researchers concluded.
Dr. Sutzko and her colleagues reported having no conflicts of interest.
Older and younger patients benefited from varicose vein procedures, a finding that calls into question the use of compression therapy as the primary treatment for patients aged 65 years and older, according to the results of a prospectively maintained database study of all patients in the Vascular Quality Initiative Varicose Vein Registry–participating centers.
Procedures for varicose veins in 1,068 patients aged 65 years or older showed similar improvement in Clinical, Etiology, Anatomy, and Pathophysiology class and Venous Clinical Severity Score, compared with a group of 2,691 younger patients, according to a report published in Journal of Vascular Surgery: Venous and Lymphatic Disorders. Among patients younger than 65 years, 57.4% had an improvement, compared with 52% of patients aged 65 years or older.
copyright iStock /Thinkstock
However, the younger patients had more improvement in patient-reported outcomes, according to Danielle C. Sutzko, MD, of the University of Michigan, Ann Arbor, and her colleagues (J Vasc Surg Venous Lymphat Disord. 2017 Sep;5[5]:647-57).
One of the main limitations of the study was the fact that only 62% of procedures within the Vascular Quality Initiative Varicose Vein Registry had follow-up.
“Patients older than 65 years appear to benefit from appropriate varicose vein procedures and should not be denied interventions on their varicose veins and venous insufficiency on the basis of their age only,” the researchers concluded.
Dr. Sutzko and her colleagues reported having no conflicts of interest.
Venous training during vascular residency programs is perceived to be lacking in both case volume and didactic education, based on the results of a national survey of vascular trainees.
The majority of respondents (82%) believed that treating venous disease is part of a standard vascular practice, and 75% indicated a desire for increased venous training, according to article in press published online in the Journal of Vascular Surgery: Venous and Lymphatic Disorders.
Dmitrii Kotin/Thinkstock
A 13-question survey was distributed to all 464 vascular surgery residents in the United States. Of these, 104 (22%) responded. The majority (80%) of the responders were aged 25-34 years, 40% were women, 72% were white, 91% reported that they were in an academic training program, and 57% were enrolled in an integrated vascular surgery residency program. There was good representation of the various postgraduate years (PGY 1, 14%; PGY 2, 8%; PGY 3, 14%; PGY 4, 12%; PGY 5, 9%; PGY 6, 18%; and PGY 7, 25%), according to Caitlin W. Hicks, MD, of the department of vascular surgery and endovascular therapy at Johns Hopkins Hospital, Baltimore, and her colleagues (J Vasc Surg Venous Lymphat Disord. 2017. doi: 10.1016/j.jvsv.2017.06.014).
In terms of case loads, the responders reported the following:
63% had performed fewer than 10 inferior vena cava stents.
64% had performed fewer than 10 vein stripping/ligation procedures.
50% had performed fewer than 10 iliac stents.
92% had performed fewer than 10 venous bypasses.
In contrast, 74% of responders reported having performed as many as 20 cases of endothermal ablation.
Although integrated and traditional vascular surgery trainees showed no overall differences in reported venous procedure volumes (P less than or equal to .28), integrated students reported receiving significantly more didactic education than their traditionally trained peers (P less than or equal to .01).
Both integrated and traditional vascular surgery trainees recognized a need for a more comprehensive educational curriculum in venous disease in terms of both didactic education and case exposure, the authors reported.
“Our data suggest that expansion of the venous training curriculum with clear training standards is warranted and that trainees would welcome such a change,” wrote Dr. Hicks and her colleagues.
“Further study will be required to determine if the perceived deficits affect recent graduates’ experiences with venous disease in their developing practice and if increasing training in venous disease during vascular residency will increase the venous work performed by practicing vascular surgeons,” they concluded.
The authors reported that they had no conflicts of interest.
Venous training during vascular residency programs is perceived to be lacking in both case volume and didactic education, based on the results of a national survey of vascular trainees.
The majority of respondents (82%) believed that treating venous disease is part of a standard vascular practice, and 75% indicated a desire for increased venous training, according to article in press published online in the Journal of Vascular Surgery: Venous and Lymphatic Disorders.
Dmitrii Kotin/Thinkstock
A 13-question survey was distributed to all 464 vascular surgery residents in the United States. Of these, 104 (22%) responded. The majority (80%) of the responders were aged 25-34 years, 40% were women, 72% were white, 91% reported that they were in an academic training program, and 57% were enrolled in an integrated vascular surgery residency program. There was good representation of the various postgraduate years (PGY 1, 14%; PGY 2, 8%; PGY 3, 14%; PGY 4, 12%; PGY 5, 9%; PGY 6, 18%; and PGY 7, 25%), according to Caitlin W. Hicks, MD, of the department of vascular surgery and endovascular therapy at Johns Hopkins Hospital, Baltimore, and her colleagues (J Vasc Surg Venous Lymphat Disord. 2017. doi: 10.1016/j.jvsv.2017.06.014).
In terms of case loads, the responders reported the following:
63% had performed fewer than 10 inferior vena cava stents.
64% had performed fewer than 10 vein stripping/ligation procedures.
50% had performed fewer than 10 iliac stents.
92% had performed fewer than 10 venous bypasses.
In contrast, 74% of responders reported having performed as many as 20 cases of endothermal ablation.
Although integrated and traditional vascular surgery trainees showed no overall differences in reported venous procedure volumes (P less than or equal to .28), integrated students reported receiving significantly more didactic education than their traditionally trained peers (P less than or equal to .01).
Both integrated and traditional vascular surgery trainees recognized a need for a more comprehensive educational curriculum in venous disease in terms of both didactic education and case exposure, the authors reported.
“Our data suggest that expansion of the venous training curriculum with clear training standards is warranted and that trainees would welcome such a change,” wrote Dr. Hicks and her colleagues.
“Further study will be required to determine if the perceived deficits affect recent graduates’ experiences with venous disease in their developing practice and if increasing training in venous disease during vascular residency will increase the venous work performed by practicing vascular surgeons,” they concluded.
The authors reported that they had no conflicts of interest.
Venous training during vascular residency programs is perceived to be lacking in both case volume and didactic education, based on the results of a national survey of vascular trainees.
The majority of respondents (82%) believed that treating venous disease is part of a standard vascular practice, and 75% indicated a desire for increased venous training, according to article in press published online in the Journal of Vascular Surgery: Venous and Lymphatic Disorders.
Dmitrii Kotin/Thinkstock
A 13-question survey was distributed to all 464 vascular surgery residents in the United States. Of these, 104 (22%) responded. The majority (80%) of the responders were aged 25-34 years, 40% were women, 72% were white, 91% reported that they were in an academic training program, and 57% were enrolled in an integrated vascular surgery residency program. There was good representation of the various postgraduate years (PGY 1, 14%; PGY 2, 8%; PGY 3, 14%; PGY 4, 12%; PGY 5, 9%; PGY 6, 18%; and PGY 7, 25%), according to Caitlin W. Hicks, MD, of the department of vascular surgery and endovascular therapy at Johns Hopkins Hospital, Baltimore, and her colleagues (J Vasc Surg Venous Lymphat Disord. 2017. doi: 10.1016/j.jvsv.2017.06.014).
In terms of case loads, the responders reported the following:
63% had performed fewer than 10 inferior vena cava stents.
64% had performed fewer than 10 vein stripping/ligation procedures.
50% had performed fewer than 10 iliac stents.
92% had performed fewer than 10 venous bypasses.
In contrast, 74% of responders reported having performed as many as 20 cases of endothermal ablation.
Although integrated and traditional vascular surgery trainees showed no overall differences in reported venous procedure volumes (P less than or equal to .28), integrated students reported receiving significantly more didactic education than their traditionally trained peers (P less than or equal to .01).
Both integrated and traditional vascular surgery trainees recognized a need for a more comprehensive educational curriculum in venous disease in terms of both didactic education and case exposure, the authors reported.
“Our data suggest that expansion of the venous training curriculum with clear training standards is warranted and that trainees would welcome such a change,” wrote Dr. Hicks and her colleagues.
“Further study will be required to determine if the perceived deficits affect recent graduates’ experiences with venous disease in their developing practice and if increasing training in venous disease during vascular residency will increase the venous work performed by practicing vascular surgeons,” they concluded.
The authors reported that they had no conflicts of interest.
BALTIMORE – Prehospital tourniquet use on injured civilians in trauma situations was associated with a nearly sixfold decrease in mortality, according to a study presented at the annual meeting of the American Association for Surgery of Trauma.
While tourniquets have been an effective tool in military settings, data on successful applications in civilian settings have been scarce.
Wikimedia Creative Commons License/INDNAM
“Our data support a more aggressive prehospital push to the application of extremity tourniquets in civilian trauma patients with severe hemorrhage and traumatic amputation,” said presenter Pedro G. Teixeira, MD, a vascular surgeon and associate trauma director at Seton Medical Center, Austin, Tex.
Dr. Teixeira and his coinvestigators conducted a multicenter, retrospective study of 1,026 peripheral–vascular injury patients admitted to level I trauma centers between January 2011 and December 2016. Among the patients studied, 181 (17.6%) received a tourniquet prior to hospital admission.
A majority of tourniquets were applied to the limbs, with the most common application sites on the arm (49%) and the thigh (29%).Tourniquets were held in place for an average 77 minutes.
Of the patients in the study, 98 (9.6%) underwent an amputation; 35 of these patients had received a tourniquet.
After adjusting for confounding factors, such as age and mechanism of injury, investigators found patients who received tourniquets were nearly six times more likely to survive than were their nontourniquet counterparts (odds ratio, 5.86; 95% confidence interval, 1.41-24.47; P = .015).
While the overall mortality rate among those with a tourniquet – compared with those without a tourniquet – was significantly lower, the comparative mortality rate among amputee patients was not significant, which investigators hypothesized could be because of the smaller number of patients in this subgroup.
Additionally, patients who did not receive a tourniquet had lower injury severity scores, had better vital signs, and needed less blood, according to investigators.
The findings of this study mirror what many military medical professionals have historically, and adamantly, supported, according to discussant Jay J. Doucet, MD, FACS, medical director for the surgical intensive care unit at the University of California San Diego Medical Center and a former combat surgeon.
“The medical lessons on our battlefields that hold such great promise have to be carefully relearned, brought home, and fearlessly applied here,” said Dr. Doucet. “I have yet to meet an employed military surgeon who does not believe the tourniquet is an indispensable tool.” While Dr. Doucet did acknowledge the benefit of tourniquets outside military use and addressed the need for increased implementation among civilian hospitals, he did pose a query about the mortality rate that investigators had found.
“The no-tourniquet group has an adjusted odds of death at a rate that is 5.86 times higher, yet they had better vitals, needed less blood, had lower [injury severity scores], had less head injury, fewer traumatic amputations, and fewer complications,” said Dr. Doucet. “So why do they die?”
Investigators were not able to pinpoint the cause of death among patients because of the limitations of their study; however, Dr. Teixeira and his colleagues were able to determine the presence of cardiac complications, pulmonary complications, and acute kidney injury, none of which had a significantly different presence between the two study groups.
The data gathered from this study are strong enough to support the use of tourniquets in civilian situations, asserted Dr. Teixeira, which means the next hurdle is to integrate it into the health system.
“What’s important from our perspective as leaders of this issue is what we are doing to increase the rate [of tourniquet use],” said Dr. Teixeira. “I think one of the important things is the Stop the Bleed program, [in which] we are actually teaching the Austin police department, and we are trying to increase the use of the tourniquet and demonstrate its importance.”
Investigators reported no relevant financial disclosures.
BALTIMORE – Prehospital tourniquet use on injured civilians in trauma situations was associated with a nearly sixfold decrease in mortality, according to a study presented at the annual meeting of the American Association for Surgery of Trauma.
While tourniquets have been an effective tool in military settings, data on successful applications in civilian settings have been scarce.
Wikimedia Creative Commons License/INDNAM
“Our data support a more aggressive prehospital push to the application of extremity tourniquets in civilian trauma patients with severe hemorrhage and traumatic amputation,” said presenter Pedro G. Teixeira, MD, a vascular surgeon and associate trauma director at Seton Medical Center, Austin, Tex.
Dr. Teixeira and his coinvestigators conducted a multicenter, retrospective study of 1,026 peripheral–vascular injury patients admitted to level I trauma centers between January 2011 and December 2016. Among the patients studied, 181 (17.6%) received a tourniquet prior to hospital admission.
A majority of tourniquets were applied to the limbs, with the most common application sites on the arm (49%) and the thigh (29%).Tourniquets were held in place for an average 77 minutes.
Of the patients in the study, 98 (9.6%) underwent an amputation; 35 of these patients had received a tourniquet.
After adjusting for confounding factors, such as age and mechanism of injury, investigators found patients who received tourniquets were nearly six times more likely to survive than were their nontourniquet counterparts (odds ratio, 5.86; 95% confidence interval, 1.41-24.47; P = .015).
While the overall mortality rate among those with a tourniquet – compared with those without a tourniquet – was significantly lower, the comparative mortality rate among amputee patients was not significant, which investigators hypothesized could be because of the smaller number of patients in this subgroup.
Additionally, patients who did not receive a tourniquet had lower injury severity scores, had better vital signs, and needed less blood, according to investigators.
The findings of this study mirror what many military medical professionals have historically, and adamantly, supported, according to discussant Jay J. Doucet, MD, FACS, medical director for the surgical intensive care unit at the University of California San Diego Medical Center and a former combat surgeon.
“The medical lessons on our battlefields that hold such great promise have to be carefully relearned, brought home, and fearlessly applied here,” said Dr. Doucet. “I have yet to meet an employed military surgeon who does not believe the tourniquet is an indispensable tool.” While Dr. Doucet did acknowledge the benefit of tourniquets outside military use and addressed the need for increased implementation among civilian hospitals, he did pose a query about the mortality rate that investigators had found.
“The no-tourniquet group has an adjusted odds of death at a rate that is 5.86 times higher, yet they had better vitals, needed less blood, had lower [injury severity scores], had less head injury, fewer traumatic amputations, and fewer complications,” said Dr. Doucet. “So why do they die?”
Investigators were not able to pinpoint the cause of death among patients because of the limitations of their study; however, Dr. Teixeira and his colleagues were able to determine the presence of cardiac complications, pulmonary complications, and acute kidney injury, none of which had a significantly different presence between the two study groups.
The data gathered from this study are strong enough to support the use of tourniquets in civilian situations, asserted Dr. Teixeira, which means the next hurdle is to integrate it into the health system.
“What’s important from our perspective as leaders of this issue is what we are doing to increase the rate [of tourniquet use],” said Dr. Teixeira. “I think one of the important things is the Stop the Bleed program, [in which] we are actually teaching the Austin police department, and we are trying to increase the use of the tourniquet and demonstrate its importance.”
Investigators reported no relevant financial disclosures.
BALTIMORE – Prehospital tourniquet use on injured civilians in trauma situations was associated with a nearly sixfold decrease in mortality, according to a study presented at the annual meeting of the American Association for Surgery of Trauma.
While tourniquets have been an effective tool in military settings, data on successful applications in civilian settings have been scarce.
Wikimedia Creative Commons License/INDNAM
“Our data support a more aggressive prehospital push to the application of extremity tourniquets in civilian trauma patients with severe hemorrhage and traumatic amputation,” said presenter Pedro G. Teixeira, MD, a vascular surgeon and associate trauma director at Seton Medical Center, Austin, Tex.
Dr. Teixeira and his coinvestigators conducted a multicenter, retrospective study of 1,026 peripheral–vascular injury patients admitted to level I trauma centers between January 2011 and December 2016. Among the patients studied, 181 (17.6%) received a tourniquet prior to hospital admission.
A majority of tourniquets were applied to the limbs, with the most common application sites on the arm (49%) and the thigh (29%).Tourniquets were held in place for an average 77 minutes.
Of the patients in the study, 98 (9.6%) underwent an amputation; 35 of these patients had received a tourniquet.
After adjusting for confounding factors, such as age and mechanism of injury, investigators found patients who received tourniquets were nearly six times more likely to survive than were their nontourniquet counterparts (odds ratio, 5.86; 95% confidence interval, 1.41-24.47; P = .015).
While the overall mortality rate among those with a tourniquet – compared with those without a tourniquet – was significantly lower, the comparative mortality rate among amputee patients was not significant, which investigators hypothesized could be because of the smaller number of patients in this subgroup.
Additionally, patients who did not receive a tourniquet had lower injury severity scores, had better vital signs, and needed less blood, according to investigators.
The findings of this study mirror what many military medical professionals have historically, and adamantly, supported, according to discussant Jay J. Doucet, MD, FACS, medical director for the surgical intensive care unit at the University of California San Diego Medical Center and a former combat surgeon.
“The medical lessons on our battlefields that hold such great promise have to be carefully relearned, brought home, and fearlessly applied here,” said Dr. Doucet. “I have yet to meet an employed military surgeon who does not believe the tourniquet is an indispensable tool.” While Dr. Doucet did acknowledge the benefit of tourniquets outside military use and addressed the need for increased implementation among civilian hospitals, he did pose a query about the mortality rate that investigators had found.
“The no-tourniquet group has an adjusted odds of death at a rate that is 5.86 times higher, yet they had better vitals, needed less blood, had lower [injury severity scores], had less head injury, fewer traumatic amputations, and fewer complications,” said Dr. Doucet. “So why do they die?”
Investigators were not able to pinpoint the cause of death among patients because of the limitations of their study; however, Dr. Teixeira and his colleagues were able to determine the presence of cardiac complications, pulmonary complications, and acute kidney injury, none of which had a significantly different presence between the two study groups.
The data gathered from this study are strong enough to support the use of tourniquets in civilian situations, asserted Dr. Teixeira, which means the next hurdle is to integrate it into the health system.
“What’s important from our perspective as leaders of this issue is what we are doing to increase the rate [of tourniquet use],” said Dr. Teixeira. “I think one of the important things is the Stop the Bleed program, [in which] we are actually teaching the Austin police department, and we are trying to increase the use of the tourniquet and demonstrate its importance.”
Investigators reported no relevant financial disclosures.
Key clinical point: Prehospital tourniquets are associated with dramatic decrease in peripheral–vascular injury mortality.
Major finding: Patients who were given a prehospital tourniquet were associated with a survival odds ratio nearly sixfold higher than those without (odds ratio, 5.86; 95% confidence interval, 1.41-24.47; P = .015).
Data source: Multicenter retrospective study of 1,026 patients with peripheral vascular injuries admitted to a level I trauma facility between January 2011 and December 2016.
Disclosures: Investigators reported no relevant financial disclosures.
An 83-year-old man presented to the emergency department with acute, painless loss of vision in his left eye. His vision in that eye had been normal in the middle of the night when he woke to use the restroom, but on awakening 6 hours later he could perceive only light or darkness.
He denied headache, scalp tenderness, jaw claudication, fever, weight loss, myalgia, or other neurologic symptoms. He had not experienced any recent change in his vision before this presentation, including halos around lights, floaters, eye pain, or redness. However, 6 months ago he had undergone left cataract surgery (left phacoemulsification with intraocular implant) without complications. And he said that when he was 3 years old, he had sustained a serious injury to his right eye.
His medical history included ischemic heart disease and hypertension. His medications included losartan, furosemide, amlodipine, atorvastatin, and aspirin.
CAUSES OF ACUTE MONOCULAR VISION LOSS
1. Which of the following is the least likely cause of this patient’s acute monocular vision loss?
Optic neuritis
Retinal vein occlusion
Retinal artery occlusion
Pituitary apoplexy
Retinal detachment
Acute vision loss is often so distressing to the patient that the emergency department may be the first step in evaluation. While its diagnosis and management often require an interdisciplinary effort, early evaluation and triage of this potential medical emergency is often done by clinicians without specialized training in ophthalmology.
The physiology of vision is complex and the list of possible causes of vision loss is long, but the differential diagnosis can be narrowed quickly by considering the time course of vision loss and the anatomic localization.1
The time course (including onset and tempo) of vision loss can classified as:
Transient (ie, vision returned to normal by the time seen by clinician)
Acute (instantaneous onset, ie, within seconds to minutes)
Subacute (progression over days to weeks)
Chronic (insidious progression over months to years).
Although acute vision loss is usually dramatic, insidious vision loss may occasionally be unnoticed for a surprisingly long time until the normal eye is inadvertently shielded.
Figure 1. Common causes of monocular vision loss can arise in the media (cornea, anterior chamber, or lens), retina, or optic nerve.
Anatomic localization. Lesions anterior to the optic chiasm cause monocular vision loss, whereas lesions at or posterior to the chiasm lead to bilateral visual field defects. Problems leading to monocular blindness can be broadly divided into 3 anatomic categories (Figure 1):
Ocular medial (including the cornea, anterior chamber, and lens)
Retinal
Neurologic (including the optic nerve and chiasm).
Clues from the history
A careful ophthalmic history is an essential initial step in the evaluation (Table 1). In addition, nonvisual symptoms can help narrow the differential diagnosis.
Nausea and vomiting often accompany acute elevation of intraocular pressure.
Focal neurologic deficits or other neurologic symptoms can point to a demyelinating disease such as multiple sclerosis.
Risk factors for vascular atherosclerotic disease such as diabetes, hypertension, and coronary artery disease raise concern for retinal, optic nerve, or cerebral ischemia.
Medications with anticholinergic and adrenergic properties can also precipitate monocular vision loss with acute angle-closure glaucoma.
Can we rule out anything yet?
Our patient presented with painless monocular vision loss. As discussed, causes of monocular vision loss can be localized to ocular abnormalities and prechiasmatic neurologic ones. Retinal detachment, occlusion of a retinal artery or vein, and optic neuritis are all important potential causes of acute monocular vision loss.
Pituitary apoplexy, on the other hand, is characterized by an acute increase in pituitary volume, often leading to compression of the optic chiasm resulting in a visual-field defect. It is most often characterized by binocular deficits (eg, bitemporal hemianopia) but is less likely to cause monocular vision loss.1
CASE CONTINUED: EXAMINATION
On examination, the patient appeared comfortable. His temperature was 97.6°F (36.4°C), pulse 59 beats per minute, respiratory rate 18 per minute, and blood pressure 153/56 mm Hg.
Heart and lung examinations were notable for a grade 3 of 6 midsystolic, low-pitched murmur in the aortic area radiating to the neck, bilateral carotid bruits, and clear lungs. The cardiac impulse was normal in location and character. There was no evidence of aortic insufficiency (including auscultation during exhalation phase while sitting upright).
Eye examination. Visual acuity in the right eye was 20/200 with correction (owing to his eye injury at age 3). With the left eye, he could see only light or darkness. The conjunctiva and sclera were normal.
The right pupil was irregular and measured 3 mm (baseline from his previous eye injury). The left pupil was 3.5 mm. The direct pupillary response was preserved, but a relative afferent pupillary defect was present: on the swinging flashlight test, the left pupil dilated when the flashlight was passed from the right to the left pupil. Extraocular movements were full and intact bilaterally. The rest of the neurologic examination was normal.
Figure 2. The patient’s funduscopic examination revealed a cherry red spot (arrow), a characteristic finding in central retinal artery occlusion.
An ophthalmologist was urgently consulted. A dilated funduscopic examination of the left eye revealed peripapillary atrophy, tortuous vessels, a cherry red macular spot, and flame hemorrhages, but no disc edema or pallor (Figure 2).
FURTHER WORKUP
2. Which of the following investigations would be least useful and not indicated at this point for this patient?
Carotid ultrasonography
Electrocardiography and echocardiography
Magnetic resonance angiography of the brain
Computed tomographic (CT) angiography of the head and neck
Testing for the factor V Leiden and prothrombin gene mutations
A systematic ocular physical examination can offer important diagnostic information (Table 2). Ophthalmoscopy directly examines the optic disc, macula, and retinal vasculature. To interpret the funduscopic examination, we need a basic understanding of the vascular supply to the eye (Figure 3).
Information from references 4 and 5.
Figure 3. Vascular supply to the eye. The internal carotid artery’s first major branch is the ophthalmic artery. Four major vessels break off from the ophthalmic artery: Central retinal artery: large-diameter vessel that supplies the retina (vulnerable to embolic disease); short and long posterior ciliary arteries: small vessels that supply the optic nerve and macula (susceptible to small-vessel disease); anterior ciliary arteries supply the iris and ciliary body.
For example, the cherry red spot within the macula in our patient is characteristic of central retinal artery occlusion and highlights the relationship between anatomy and pathophysiology. The retina’s blood supply is compromised, leading to an ischemic, white background (secondary to edema of the inner third of the retina), but the macula continues to be nourished by the posterior ciliary arteries. This contrast in color is accentuated by the underlying structures composing the fovea, which lacks the nerve fiber layer and ganglion cell layer, making the vascular bed more visible.2,3
Also in our patient, the marked reduction in visual acuity and relative afferent pupillary defect in the left eye point to unilateral optic nerve (or retinal ganglion cell) dysfunction. The findings on direct funduscopy were consistent with acute central retinal artery ischemia or occlusion. Central retinal artery occlusion can be either arteritic (due to inflammation, most often giant cell arteritis) or nonarteritic (due to atherosclerotic vascular disease).
Thus, carotid ultrasonography, electrocardiography, and transthoracic and transesophageal echocardiography are important components of the further workup. In addition, urgent brain imaging including either CT angiography or magnetic resonance angiography of the head and neck is indicated in all patients with central retinal artery occlusion.
Thrombophilia testing, including tests for the factor V Leiden and prothrombin gene mutations, is indicated in specific cases when a hypercoagulable state is suggested by components of the history, physical examination, and laboratory and radiologic testing. Thrombophilia testing would be low-yield and should not be part of the first-line testing in elderly patients with several atherosclerotic risk factors, such as our patient.
CASE CONTINUED: LABORATORY AND IMAGING EVIDENCE
Initial laboratory work showed:
Mild microcytic anemia
Erythrocyte sedimentation rate 77 mm/hour (reference range 1–10)
C-reactive protein 4.0 mg/dL (reference range < 0.9).
The rest of the complete blood cell count and metabolic profile were unremarkable. His hemoglobin A1c value was 5.3% (reference range 4.8%–6.2%).
A neurologist was urgently consulted.
Magnetic resonance imaging of the brain without contrast revealed nonspecific white-matter disease with no evidence of ischemic stroke.
Magnetic resonance angiography of the head and neck with contrast demonstrated 20% to 40% stenosis in both carotid arteries with otherwise patent anterior and posterior circulation.
Continuous monitoring of the left carotid artery with transcranial Doppler ultrasonography was also ordered, and the study concluded there were no undetected microembolic events.
Transthoracic echocardiography showed aortic sclerosis with no other abnormalities.
Ophthalmic fluorescein angiography was performed and showed patchy choroidal hypoperfusion, severe delayed filling, and extensive pruning of the arterial circulation with no involvement of the posterior ciliary arteries.
Given the elevated inflammatory markers, pulse-dose intravenous methylprednisolone was started, and a temporal artery biopsy was planned.
CENTRAL RETINAL ARTERY OCCLUSION: NONARTERITIC VS ARTERITIC CAUSES
3. Which of the following is least useful to differentiate arteritic from nonarteritic causes of central retinal artery occlusion?
Finding emboli in the retinal vasculature on funduscopy
Temporal artery biopsy
Measuring the C-reactive protein level and the erythrocyte sedimentation rate
Echocardiography
Positron-emission tomography (PET)
Retinal fluorescein angiography
In patients diagnosed with central retinal artery occlusion, the next step is to differentiate between nonarteritic and arteritic causes, since separating them has therapeutic relevance.
The carotid artery is the main culprit for embolic disease affecting the central retinal artery, leading to the nonarteritic subtype. Thus, evaluation of acute retinal ischemia secondary to nonarteritic central retinal artery occlusion is similar to the evaluation of patients with an acute cerebral stroke.4 Studies have shown that 25% of patients diagnosed with central retinal artery occlusion have an additional ischemic insult in the cerebrovascular system, and these patients are at high risk of recurrent ocular or cerebral infarction. Workup includes diffusion-weighted MRI, angiography, echocardiography, and telemetry.5
Arteritic central retinal artery occlusion is most often caused by giant cell arteritis. The American College of Rheumatology classification criteria for giant cell arteritis include 3 of the following 5:
Age 50 or older
New onset of localized headache
Temporal artery tenderness or decreased temporal artery pulse
Erythrocyte sedimentation rate 50 mm/hour or greater
Positive biopsy findings.6
Temporal artery biopsy is the gold standard for the diagnosis of giant cell arteritis and should be done whenever the disease is suspected.7,8 However, the test is invasive and imperfect, as a negative result does not completely rule out giant cell arteritis.9
Although a unilateral temporal artery biopsy can be falsely negative, several studies evaluating the efficacy of bilateral biopsies did not show significant improvement in the diagnostic yield.10,11
Ophthalmic fluorescein angiography is another helpful test for distinguishing nonarteritic from arteritic central retinal artery occlusion.12 Involvement of the posterior ciliary arteries usually occurs in giant cell arteritis, and this leads to choroidal malperfusion with or without retinal involvement. The optic nerve may also be infarcted by closure of the paraoptic vessels fed by the posterior ciliary vessels.12,13 Such involvement of multiple vessels would not be typical with nonarteritic central retinal artery occlusion. Thus, this finding is helpful in making the final diagnosis along with supplying possible prognostic information.13
PET-CT is emerging as a test for early inflammation in extracranial disease, but its utility for diagnosing intracranial disease is limited by high uptake of the tracer fluorodeoxyglucose by the brain and low resolution.14 Currently, it has no established role in the evaluation of patients with central retinal artery occlusion and would have no utility in differentiating arteritic vs nonarteritic causes of central retinal artery occlusion.
If giant cell arteritis is suspected, it is essential to start intravenous pulse-dose methylprednisolone early to prevent further vision loss in the contralateral eye. Treatment should not be delayed for invasive testing or temporal artery biopsy. Improvement in headache, jaw claudication, or scalp tenderness once steroids are initiated also helps support the diagnosis of giant cell arteritis.7
Unfortunately, visual symptoms may be irreversible despite treatment.
Our patient’s central retinal artery occlusion
This case highlights how difficult it is in practice to distinguish nonarteritic from arteritic central retinal artery occlusion.
Our patient had numerous cardiovascular risk factors, including known carotid and coronary artery disease, favoring a nonarteritic diagnosis.
On the other hand, his elevated inflammatory markers suggested an underlying inflammatory response. He lacked the characteristic headache and other systemic signs of giant cell arteritis, but this has been described in about 25% of patients.15 If emboli are seen on funduscopy, further workup for arteritic central retinal artery occlusion is not warranted, but emboli are not always present. Then again, absence of posterior ciliary artery involvement on fluorescein angiography pointed away from giant cell arteritis.
CASE CONTINUED: FINAL DIAGNOSIS
Biopsy of the left temporal artery showed intimal thickening with focal destruction of the internal elastic lamina by dystrophic calcification with no evidence of inflammatory infiltrates, giant cells, or granulomata in the adventitia, media, or intima. Based on the results of biopsy study and fluorescein angiography, we concluded that this was nonarteritic central retinal artery occlusion related to atherosclerotic disease.
Methylprednisolone was discontinued. The patient was discharged on aspirin, losartan, furosemide, amlodipine, and high-dose atorvastatin for standard stroke prevention. He was followed by the medical team and the ophthalmology department. At 6 weeks, there was only marginal improvement in the visual acuity of the left eye.
MANAGEMENT
4. Management of nonarteritic central retinal artery occlusion could include all of the following except which one?
Ocular massage
Intravenous thrombolysis
Intra-arterial thrombolysis
Risk-factor modification
Intraocular steroid injection
In patients with acute vision loss from nonarteritic central retinal artery occlusion, acute strategies to restore retinal perfusion include noninvasive “standard” therapies and thrombolysis (intravenous or intra-arterial). Unfortunately, consensus and guidelines are lacking.
Traditional therapies include sublingual isosorbide dinitrate, systemic pentoxifylline, inhalation of a carbogen, hyperbaric oxygen, ocular massage, intravenous acetazolamide and mannitol, anterior chamber paracentesis, and systemic steroids. However, none of these have been shown to be more effective than placebo.16
Thrombolytic therapy, analogous to the treatment of patients with ischemic stroke or myocardial infarction, is more controversial in acute central retinal artery occlusion.13 Data from small case-series suggested that intra-arterial or intravenous thrombolysis might improve visual acuity with reasonable safety.17 On the other hand, a randomized study from the United Kingdom that compared intra-arterial thrombolysis within a 24-hour window and conservative measures concluded that thrombolysis should not be used.18
Thrombolysis is thus used only in selected patients on a case-specific basis with involvement of a multispecialty team including stroke neurologists, especially if patients present within hours of onset and have concomitant neurologic symptoms.
Treatment beyond the acute phase focuses on preventing complications of the eye ischemia and aggressively managing systemic atherosclerotic risk factors to decrease the incidence of further ischemic events. Other interventions include endarterectomy for significant carotid stenosis and anticoagulation to prevent cardioembolic embolization (such as atrial fibrillation). Most experts agree on the addition of an antiplatelet agent.13,19
Intraocular steroid injection can be used in the management of some retinal disorders but has no value in nonarteritic central retinal artery occlusion.
Vision recovery in nonarteritic central retinal artery occlusion is variable, but the prognosis is generally poor. The visual acuity on presentation, the onset of the symptoms, and collateral vessels are major factors influencing long-term recovery. Most of the recovery occurs within 7 days and involves peripheral vision rather than central vision. Several studies report some recovery in peripheral vision in approximately 30% to 35% of affected eyes.20–22
PROMPT ACTION MAY SAVE SIGHT
Vision loss is a common presenting symptom in the emergency setting. A meticulous history and systematic physical examination can narrow the differential diagnosis of this neuro-ophthalmologic emergency. Acute retinal ischemia from central retinal artery occlusion is the ocular equivalent of an ischemic stroke, and they share risk factors, diagnostic workup, and management approaches.
Both etiologic subtypes (ie, arteritic and nonarteritic) require prompt intervention by front-line physicians. If giant cell arteritis is suspected, corticosteroid therapy must be initiated to save the contralateral retina from ischemia. Suspicion of central retinal artery occlusion warrants immediate evaluation by a neurologist to consider thrombolysis. Prompt action and interdisciplinary care involving an ophthalmologist, neurologist, and emergency or internal medicine physician may save a patient from permanent visual disability.
KEY POINTS
Monocular vision loss requires urgent evaluation with a multidisciplinary management approach.
There are no consensus treatment guidelines for nonarteritic central retinal artery occlusion, but the workup includes a comprehensive stroke evaluation.
Arteritic central retinal artery occlusion is most often due to giant cell arteritis, and when it is suspected, the patient should be empirically treated with steroids.
References
Glezer A, Bronstein MD. Pituitary apoplexy: pathophysiology, diagnosis and management. Arch Endocrinol Metab 2015; 59:259–264.
Campbell WW. DeJong’s The Neurologic Examination. 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2013.
Biller J. Practical Neurology. 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2012.
Biousse V. Acute retinal arterial ischemia: an emergency often ignored. Am J Ophthalmol 2014; 157:1119–1121.
Hunder GG, Bloch DA, Michel BA, et al. American College of Rheumatology 1990 criteria for the classification of giant cell arteritis. Arthritis Rheum 1990; 33:1122–1128.
Smith JH, Swanson JW. Giant cell arteritis. Headache 2014; 54:1273–1289.
Hall S, Persellin S, Lie JT, O’Brien PC, Kurland LT, Hunder GG. The therapeutic impact of temporal artery biopsy. Lancet 1983; 2:1217–1220.
Gabriel SE, O’Fallon WM, Achkar AA, Lie JT, Hunder GG. The use of clinical characteristics to predict the results of temporal artery biopsy among patients with suspected giant cell arteritis. J Rheumatol 1995; 22:93–96.
Boyev LR, Miller NR, Green WR. Efficacy of unilateral versus bilateral temporal artery biopsies for the diagnosis of giant cell arteritis. Am J Ophthalmol 1999; 128:211–215.
Danesh-Meyer HV, Savino PJ, Eagle RC Jr, Kubis KC, Sergott RC. Low diagnostic yield with second biopsies in suspected giant cell arteritis. J Neuroophthalmol 2000; 20:213–215.
Khan A, Dasgupta B. Imaging in giant cell arteritis. Curr Rheumatol Rep 2015; 17:52.
Biousse V, Newman N. Retinal and optic nerve ischemia. Continuum (Minneap Minn) 2014; 20:838–856.
Fraser SG, Adams W. Interventions for acute non-arteritic central retinal artery occlusion. Cochrane Database Syst Rev 2009; 1:CD001989.
Beatty S, Au Eong KG. Local intra-arterial fibrinolysis for acute occlusion of the central retinal artery: a meta-analysis of the published data. Br J Ophthalmol 2000; 84:914–916.
Schumacher M, Schmidt D, Jurklies B, et al; EAGLE-Study Group. Central retinal artery occlusion: local intra-arterial fibrinolysis versus conservative treatment, a multicenter randomized trial. Ophthalmology 2010; 117:1367–1375.e1.
Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002; 324:71–86.
Hayreh SS, Zimmerman MB. Central retinal artery occlusion: visual outcome. Am J Ophthalmol 2005; 140:376–391.
Augsburger JJ, Magargal LE. Visual prognosis following treatment of acute central retinal artery obstruction. Br J Ophthalmol 1980; 64:913–917.
Brown GC, Shields JA. Cilioretinal arteries and retinal arterial occlusion. Arch Ophthalmol 1979; 97:84–92.
Justin R. Abbatemarco, MD Neurology Resident, Cleveland Clinic
Rushad Patell, MD Internal Medicine Resident, Cleveland Clinic
Janet Buccola, MD Department of Hospital Medicine, Medicine Institute, Cleveland Clinic; Clinical Assistant Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH
Mary Alissa Willis, MD Mellen Center for Multiple Sclerosis Treatment and Research, Neurological Institute, Cleveland Clinic; Assistant Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH
Address: Mary Alissa Willis, MD, Mellen Center for Multiple Sclerosis, U10, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; Willism@ccf.org
Justin R. Abbatemarco, MD Neurology Resident, Cleveland Clinic
Rushad Patell, MD Internal Medicine Resident, Cleveland Clinic
Janet Buccola, MD Department of Hospital Medicine, Medicine Institute, Cleveland Clinic; Clinical Assistant Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH
Mary Alissa Willis, MD Mellen Center for Multiple Sclerosis Treatment and Research, Neurological Institute, Cleveland Clinic; Assistant Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH
Address: Mary Alissa Willis, MD, Mellen Center for Multiple Sclerosis, U10, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; Willism@ccf.org
Author and Disclosure Information
Justin R. Abbatemarco, MD Neurology Resident, Cleveland Clinic
Rushad Patell, MD Internal Medicine Resident, Cleveland Clinic
Janet Buccola, MD Department of Hospital Medicine, Medicine Institute, Cleveland Clinic; Clinical Assistant Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH
Mary Alissa Willis, MD Mellen Center for Multiple Sclerosis Treatment and Research, Neurological Institute, Cleveland Clinic; Assistant Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH
Address: Mary Alissa Willis, MD, Mellen Center for Multiple Sclerosis, U10, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; Willism@ccf.org
An 83-year-old man presented to the emergency department with acute, painless loss of vision in his left eye. His vision in that eye had been normal in the middle of the night when he woke to use the restroom, but on awakening 6 hours later he could perceive only light or darkness.
He denied headache, scalp tenderness, jaw claudication, fever, weight loss, myalgia, or other neurologic symptoms. He had not experienced any recent change in his vision before this presentation, including halos around lights, floaters, eye pain, or redness. However, 6 months ago he had undergone left cataract surgery (left phacoemulsification with intraocular implant) without complications. And he said that when he was 3 years old, he had sustained a serious injury to his right eye.
His medical history included ischemic heart disease and hypertension. His medications included losartan, furosemide, amlodipine, atorvastatin, and aspirin.
CAUSES OF ACUTE MONOCULAR VISION LOSS
1. Which of the following is the least likely cause of this patient’s acute monocular vision loss?
Optic neuritis
Retinal vein occlusion
Retinal artery occlusion
Pituitary apoplexy
Retinal detachment
Acute vision loss is often so distressing to the patient that the emergency department may be the first step in evaluation. While its diagnosis and management often require an interdisciplinary effort, early evaluation and triage of this potential medical emergency is often done by clinicians without specialized training in ophthalmology.
The physiology of vision is complex and the list of possible causes of vision loss is long, but the differential diagnosis can be narrowed quickly by considering the time course of vision loss and the anatomic localization.1
The time course (including onset and tempo) of vision loss can classified as:
Transient (ie, vision returned to normal by the time seen by clinician)
Acute (instantaneous onset, ie, within seconds to minutes)
Subacute (progression over days to weeks)
Chronic (insidious progression over months to years).
Although acute vision loss is usually dramatic, insidious vision loss may occasionally be unnoticed for a surprisingly long time until the normal eye is inadvertently shielded.
Figure 1. Common causes of monocular vision loss can arise in the media (cornea, anterior chamber, or lens), retina, or optic nerve.
Anatomic localization. Lesions anterior to the optic chiasm cause monocular vision loss, whereas lesions at or posterior to the chiasm lead to bilateral visual field defects. Problems leading to monocular blindness can be broadly divided into 3 anatomic categories (Figure 1):
Ocular medial (including the cornea, anterior chamber, and lens)
Retinal
Neurologic (including the optic nerve and chiasm).
Clues from the history
A careful ophthalmic history is an essential initial step in the evaluation (Table 1). In addition, nonvisual symptoms can help narrow the differential diagnosis.
Nausea and vomiting often accompany acute elevation of intraocular pressure.
Focal neurologic deficits or other neurologic symptoms can point to a demyelinating disease such as multiple sclerosis.
Risk factors for vascular atherosclerotic disease such as diabetes, hypertension, and coronary artery disease raise concern for retinal, optic nerve, or cerebral ischemia.
Medications with anticholinergic and adrenergic properties can also precipitate monocular vision loss with acute angle-closure glaucoma.
Can we rule out anything yet?
Our patient presented with painless monocular vision loss. As discussed, causes of monocular vision loss can be localized to ocular abnormalities and prechiasmatic neurologic ones. Retinal detachment, occlusion of a retinal artery or vein, and optic neuritis are all important potential causes of acute monocular vision loss.
Pituitary apoplexy, on the other hand, is characterized by an acute increase in pituitary volume, often leading to compression of the optic chiasm resulting in a visual-field defect. It is most often characterized by binocular deficits (eg, bitemporal hemianopia) but is less likely to cause monocular vision loss.1
CASE CONTINUED: EXAMINATION
On examination, the patient appeared comfortable. His temperature was 97.6°F (36.4°C), pulse 59 beats per minute, respiratory rate 18 per minute, and blood pressure 153/56 mm Hg.
Heart and lung examinations were notable for a grade 3 of 6 midsystolic, low-pitched murmur in the aortic area radiating to the neck, bilateral carotid bruits, and clear lungs. The cardiac impulse was normal in location and character. There was no evidence of aortic insufficiency (including auscultation during exhalation phase while sitting upright).
Eye examination. Visual acuity in the right eye was 20/200 with correction (owing to his eye injury at age 3). With the left eye, he could see only light or darkness. The conjunctiva and sclera were normal.
The right pupil was irregular and measured 3 mm (baseline from his previous eye injury). The left pupil was 3.5 mm. The direct pupillary response was preserved, but a relative afferent pupillary defect was present: on the swinging flashlight test, the left pupil dilated when the flashlight was passed from the right to the left pupil. Extraocular movements were full and intact bilaterally. The rest of the neurologic examination was normal.
Figure 2. The patient’s funduscopic examination revealed a cherry red spot (arrow), a characteristic finding in central retinal artery occlusion.
An ophthalmologist was urgently consulted. A dilated funduscopic examination of the left eye revealed peripapillary atrophy, tortuous vessels, a cherry red macular spot, and flame hemorrhages, but no disc edema or pallor (Figure 2).
FURTHER WORKUP
2. Which of the following investigations would be least useful and not indicated at this point for this patient?
Carotid ultrasonography
Electrocardiography and echocardiography
Magnetic resonance angiography of the brain
Computed tomographic (CT) angiography of the head and neck
Testing for the factor V Leiden and prothrombin gene mutations
A systematic ocular physical examination can offer important diagnostic information (Table 2). Ophthalmoscopy directly examines the optic disc, macula, and retinal vasculature. To interpret the funduscopic examination, we need a basic understanding of the vascular supply to the eye (Figure 3).
Information from references 4 and 5.
Figure 3. Vascular supply to the eye. The internal carotid artery’s first major branch is the ophthalmic artery. Four major vessels break off from the ophthalmic artery: Central retinal artery: large-diameter vessel that supplies the retina (vulnerable to embolic disease); short and long posterior ciliary arteries: small vessels that supply the optic nerve and macula (susceptible to small-vessel disease); anterior ciliary arteries supply the iris and ciliary body.
For example, the cherry red spot within the macula in our patient is characteristic of central retinal artery occlusion and highlights the relationship between anatomy and pathophysiology. The retina’s blood supply is compromised, leading to an ischemic, white background (secondary to edema of the inner third of the retina), but the macula continues to be nourished by the posterior ciliary arteries. This contrast in color is accentuated by the underlying structures composing the fovea, which lacks the nerve fiber layer and ganglion cell layer, making the vascular bed more visible.2,3
Also in our patient, the marked reduction in visual acuity and relative afferent pupillary defect in the left eye point to unilateral optic nerve (or retinal ganglion cell) dysfunction. The findings on direct funduscopy were consistent with acute central retinal artery ischemia or occlusion. Central retinal artery occlusion can be either arteritic (due to inflammation, most often giant cell arteritis) or nonarteritic (due to atherosclerotic vascular disease).
Thus, carotid ultrasonography, electrocardiography, and transthoracic and transesophageal echocardiography are important components of the further workup. In addition, urgent brain imaging including either CT angiography or magnetic resonance angiography of the head and neck is indicated in all patients with central retinal artery occlusion.
Thrombophilia testing, including tests for the factor V Leiden and prothrombin gene mutations, is indicated in specific cases when a hypercoagulable state is suggested by components of the history, physical examination, and laboratory and radiologic testing. Thrombophilia testing would be low-yield and should not be part of the first-line testing in elderly patients with several atherosclerotic risk factors, such as our patient.
CASE CONTINUED: LABORATORY AND IMAGING EVIDENCE
Initial laboratory work showed:
Mild microcytic anemia
Erythrocyte sedimentation rate 77 mm/hour (reference range 1–10)
C-reactive protein 4.0 mg/dL (reference range < 0.9).
The rest of the complete blood cell count and metabolic profile were unremarkable. His hemoglobin A1c value was 5.3% (reference range 4.8%–6.2%).
A neurologist was urgently consulted.
Magnetic resonance imaging of the brain without contrast revealed nonspecific white-matter disease with no evidence of ischemic stroke.
Magnetic resonance angiography of the head and neck with contrast demonstrated 20% to 40% stenosis in both carotid arteries with otherwise patent anterior and posterior circulation.
Continuous monitoring of the left carotid artery with transcranial Doppler ultrasonography was also ordered, and the study concluded there were no undetected microembolic events.
Transthoracic echocardiography showed aortic sclerosis with no other abnormalities.
Ophthalmic fluorescein angiography was performed and showed patchy choroidal hypoperfusion, severe delayed filling, and extensive pruning of the arterial circulation with no involvement of the posterior ciliary arteries.
Given the elevated inflammatory markers, pulse-dose intravenous methylprednisolone was started, and a temporal artery biopsy was planned.
CENTRAL RETINAL ARTERY OCCLUSION: NONARTERITIC VS ARTERITIC CAUSES
3. Which of the following is least useful to differentiate arteritic from nonarteritic causes of central retinal artery occlusion?
Finding emboli in the retinal vasculature on funduscopy
Temporal artery biopsy
Measuring the C-reactive protein level and the erythrocyte sedimentation rate
Echocardiography
Positron-emission tomography (PET)
Retinal fluorescein angiography
In patients diagnosed with central retinal artery occlusion, the next step is to differentiate between nonarteritic and arteritic causes, since separating them has therapeutic relevance.
The carotid artery is the main culprit for embolic disease affecting the central retinal artery, leading to the nonarteritic subtype. Thus, evaluation of acute retinal ischemia secondary to nonarteritic central retinal artery occlusion is similar to the evaluation of patients with an acute cerebral stroke.4 Studies have shown that 25% of patients diagnosed with central retinal artery occlusion have an additional ischemic insult in the cerebrovascular system, and these patients are at high risk of recurrent ocular or cerebral infarction. Workup includes diffusion-weighted MRI, angiography, echocardiography, and telemetry.5
Arteritic central retinal artery occlusion is most often caused by giant cell arteritis. The American College of Rheumatology classification criteria for giant cell arteritis include 3 of the following 5:
Age 50 or older
New onset of localized headache
Temporal artery tenderness or decreased temporal artery pulse
Erythrocyte sedimentation rate 50 mm/hour or greater
Positive biopsy findings.6
Temporal artery biopsy is the gold standard for the diagnosis of giant cell arteritis and should be done whenever the disease is suspected.7,8 However, the test is invasive and imperfect, as a negative result does not completely rule out giant cell arteritis.9
Although a unilateral temporal artery biopsy can be falsely negative, several studies evaluating the efficacy of bilateral biopsies did not show significant improvement in the diagnostic yield.10,11
Ophthalmic fluorescein angiography is another helpful test for distinguishing nonarteritic from arteritic central retinal artery occlusion.12 Involvement of the posterior ciliary arteries usually occurs in giant cell arteritis, and this leads to choroidal malperfusion with or without retinal involvement. The optic nerve may also be infarcted by closure of the paraoptic vessels fed by the posterior ciliary vessels.12,13 Such involvement of multiple vessels would not be typical with nonarteritic central retinal artery occlusion. Thus, this finding is helpful in making the final diagnosis along with supplying possible prognostic information.13
PET-CT is emerging as a test for early inflammation in extracranial disease, but its utility for diagnosing intracranial disease is limited by high uptake of the tracer fluorodeoxyglucose by the brain and low resolution.14 Currently, it has no established role in the evaluation of patients with central retinal artery occlusion and would have no utility in differentiating arteritic vs nonarteritic causes of central retinal artery occlusion.
If giant cell arteritis is suspected, it is essential to start intravenous pulse-dose methylprednisolone early to prevent further vision loss in the contralateral eye. Treatment should not be delayed for invasive testing or temporal artery biopsy. Improvement in headache, jaw claudication, or scalp tenderness once steroids are initiated also helps support the diagnosis of giant cell arteritis.7
Unfortunately, visual symptoms may be irreversible despite treatment.
Our patient’s central retinal artery occlusion
This case highlights how difficult it is in practice to distinguish nonarteritic from arteritic central retinal artery occlusion.
Our patient had numerous cardiovascular risk factors, including known carotid and coronary artery disease, favoring a nonarteritic diagnosis.
On the other hand, his elevated inflammatory markers suggested an underlying inflammatory response. He lacked the characteristic headache and other systemic signs of giant cell arteritis, but this has been described in about 25% of patients.15 If emboli are seen on funduscopy, further workup for arteritic central retinal artery occlusion is not warranted, but emboli are not always present. Then again, absence of posterior ciliary artery involvement on fluorescein angiography pointed away from giant cell arteritis.
CASE CONTINUED: FINAL DIAGNOSIS
Biopsy of the left temporal artery showed intimal thickening with focal destruction of the internal elastic lamina by dystrophic calcification with no evidence of inflammatory infiltrates, giant cells, or granulomata in the adventitia, media, or intima. Based on the results of biopsy study and fluorescein angiography, we concluded that this was nonarteritic central retinal artery occlusion related to atherosclerotic disease.
Methylprednisolone was discontinued. The patient was discharged on aspirin, losartan, furosemide, amlodipine, and high-dose atorvastatin for standard stroke prevention. He was followed by the medical team and the ophthalmology department. At 6 weeks, there was only marginal improvement in the visual acuity of the left eye.
MANAGEMENT
4. Management of nonarteritic central retinal artery occlusion could include all of the following except which one?
Ocular massage
Intravenous thrombolysis
Intra-arterial thrombolysis
Risk-factor modification
Intraocular steroid injection
In patients with acute vision loss from nonarteritic central retinal artery occlusion, acute strategies to restore retinal perfusion include noninvasive “standard” therapies and thrombolysis (intravenous or intra-arterial). Unfortunately, consensus and guidelines are lacking.
Traditional therapies include sublingual isosorbide dinitrate, systemic pentoxifylline, inhalation of a carbogen, hyperbaric oxygen, ocular massage, intravenous acetazolamide and mannitol, anterior chamber paracentesis, and systemic steroids. However, none of these have been shown to be more effective than placebo.16
Thrombolytic therapy, analogous to the treatment of patients with ischemic stroke or myocardial infarction, is more controversial in acute central retinal artery occlusion.13 Data from small case-series suggested that intra-arterial or intravenous thrombolysis might improve visual acuity with reasonable safety.17 On the other hand, a randomized study from the United Kingdom that compared intra-arterial thrombolysis within a 24-hour window and conservative measures concluded that thrombolysis should not be used.18
Thrombolysis is thus used only in selected patients on a case-specific basis with involvement of a multispecialty team including stroke neurologists, especially if patients present within hours of onset and have concomitant neurologic symptoms.
Treatment beyond the acute phase focuses on preventing complications of the eye ischemia and aggressively managing systemic atherosclerotic risk factors to decrease the incidence of further ischemic events. Other interventions include endarterectomy for significant carotid stenosis and anticoagulation to prevent cardioembolic embolization (such as atrial fibrillation). Most experts agree on the addition of an antiplatelet agent.13,19
Intraocular steroid injection can be used in the management of some retinal disorders but has no value in nonarteritic central retinal artery occlusion.
Vision recovery in nonarteritic central retinal artery occlusion is variable, but the prognosis is generally poor. The visual acuity on presentation, the onset of the symptoms, and collateral vessels are major factors influencing long-term recovery. Most of the recovery occurs within 7 days and involves peripheral vision rather than central vision. Several studies report some recovery in peripheral vision in approximately 30% to 35% of affected eyes.20–22
PROMPT ACTION MAY SAVE SIGHT
Vision loss is a common presenting symptom in the emergency setting. A meticulous history and systematic physical examination can narrow the differential diagnosis of this neuro-ophthalmologic emergency. Acute retinal ischemia from central retinal artery occlusion is the ocular equivalent of an ischemic stroke, and they share risk factors, diagnostic workup, and management approaches.
Both etiologic subtypes (ie, arteritic and nonarteritic) require prompt intervention by front-line physicians. If giant cell arteritis is suspected, corticosteroid therapy must be initiated to save the contralateral retina from ischemia. Suspicion of central retinal artery occlusion warrants immediate evaluation by a neurologist to consider thrombolysis. Prompt action and interdisciplinary care involving an ophthalmologist, neurologist, and emergency or internal medicine physician may save a patient from permanent visual disability.
KEY POINTS
Monocular vision loss requires urgent evaluation with a multidisciplinary management approach.
There are no consensus treatment guidelines for nonarteritic central retinal artery occlusion, but the workup includes a comprehensive stroke evaluation.
Arteritic central retinal artery occlusion is most often due to giant cell arteritis, and when it is suspected, the patient should be empirically treated with steroids.
An 83-year-old man presented to the emergency department with acute, painless loss of vision in his left eye. His vision in that eye had been normal in the middle of the night when he woke to use the restroom, but on awakening 6 hours later he could perceive only light or darkness.
He denied headache, scalp tenderness, jaw claudication, fever, weight loss, myalgia, or other neurologic symptoms. He had not experienced any recent change in his vision before this presentation, including halos around lights, floaters, eye pain, or redness. However, 6 months ago he had undergone left cataract surgery (left phacoemulsification with intraocular implant) without complications. And he said that when he was 3 years old, he had sustained a serious injury to his right eye.
His medical history included ischemic heart disease and hypertension. His medications included losartan, furosemide, amlodipine, atorvastatin, and aspirin.
CAUSES OF ACUTE MONOCULAR VISION LOSS
1. Which of the following is the least likely cause of this patient’s acute monocular vision loss?
Optic neuritis
Retinal vein occlusion
Retinal artery occlusion
Pituitary apoplexy
Retinal detachment
Acute vision loss is often so distressing to the patient that the emergency department may be the first step in evaluation. While its diagnosis and management often require an interdisciplinary effort, early evaluation and triage of this potential medical emergency is often done by clinicians without specialized training in ophthalmology.
The physiology of vision is complex and the list of possible causes of vision loss is long, but the differential diagnosis can be narrowed quickly by considering the time course of vision loss and the anatomic localization.1
The time course (including onset and tempo) of vision loss can classified as:
Transient (ie, vision returned to normal by the time seen by clinician)
Acute (instantaneous onset, ie, within seconds to minutes)
Subacute (progression over days to weeks)
Chronic (insidious progression over months to years).
Although acute vision loss is usually dramatic, insidious vision loss may occasionally be unnoticed for a surprisingly long time until the normal eye is inadvertently shielded.
Figure 1. Common causes of monocular vision loss can arise in the media (cornea, anterior chamber, or lens), retina, or optic nerve.
Anatomic localization. Lesions anterior to the optic chiasm cause monocular vision loss, whereas lesions at or posterior to the chiasm lead to bilateral visual field defects. Problems leading to monocular blindness can be broadly divided into 3 anatomic categories (Figure 1):
Ocular medial (including the cornea, anterior chamber, and lens)
Retinal
Neurologic (including the optic nerve and chiasm).
Clues from the history
A careful ophthalmic history is an essential initial step in the evaluation (Table 1). In addition, nonvisual symptoms can help narrow the differential diagnosis.
Nausea and vomiting often accompany acute elevation of intraocular pressure.
Focal neurologic deficits or other neurologic symptoms can point to a demyelinating disease such as multiple sclerosis.
Risk factors for vascular atherosclerotic disease such as diabetes, hypertension, and coronary artery disease raise concern for retinal, optic nerve, or cerebral ischemia.
Medications with anticholinergic and adrenergic properties can also precipitate monocular vision loss with acute angle-closure glaucoma.
Can we rule out anything yet?
Our patient presented with painless monocular vision loss. As discussed, causes of monocular vision loss can be localized to ocular abnormalities and prechiasmatic neurologic ones. Retinal detachment, occlusion of a retinal artery or vein, and optic neuritis are all important potential causes of acute monocular vision loss.
Pituitary apoplexy, on the other hand, is characterized by an acute increase in pituitary volume, often leading to compression of the optic chiasm resulting in a visual-field defect. It is most often characterized by binocular deficits (eg, bitemporal hemianopia) but is less likely to cause monocular vision loss.1
CASE CONTINUED: EXAMINATION
On examination, the patient appeared comfortable. His temperature was 97.6°F (36.4°C), pulse 59 beats per minute, respiratory rate 18 per minute, and blood pressure 153/56 mm Hg.
Heart and lung examinations were notable for a grade 3 of 6 midsystolic, low-pitched murmur in the aortic area radiating to the neck, bilateral carotid bruits, and clear lungs. The cardiac impulse was normal in location and character. There was no evidence of aortic insufficiency (including auscultation during exhalation phase while sitting upright).
Eye examination. Visual acuity in the right eye was 20/200 with correction (owing to his eye injury at age 3). With the left eye, he could see only light or darkness. The conjunctiva and sclera were normal.
The right pupil was irregular and measured 3 mm (baseline from his previous eye injury). The left pupil was 3.5 mm. The direct pupillary response was preserved, but a relative afferent pupillary defect was present: on the swinging flashlight test, the left pupil dilated when the flashlight was passed from the right to the left pupil. Extraocular movements were full and intact bilaterally. The rest of the neurologic examination was normal.
Figure 2. The patient’s funduscopic examination revealed a cherry red spot (arrow), a characteristic finding in central retinal artery occlusion.
An ophthalmologist was urgently consulted. A dilated funduscopic examination of the left eye revealed peripapillary atrophy, tortuous vessels, a cherry red macular spot, and flame hemorrhages, but no disc edema or pallor (Figure 2).
FURTHER WORKUP
2. Which of the following investigations would be least useful and not indicated at this point for this patient?
Carotid ultrasonography
Electrocardiography and echocardiography
Magnetic resonance angiography of the brain
Computed tomographic (CT) angiography of the head and neck
Testing for the factor V Leiden and prothrombin gene mutations
A systematic ocular physical examination can offer important diagnostic information (Table 2). Ophthalmoscopy directly examines the optic disc, macula, and retinal vasculature. To interpret the funduscopic examination, we need a basic understanding of the vascular supply to the eye (Figure 3).
Information from references 4 and 5.
Figure 3. Vascular supply to the eye. The internal carotid artery’s first major branch is the ophthalmic artery. Four major vessels break off from the ophthalmic artery: Central retinal artery: large-diameter vessel that supplies the retina (vulnerable to embolic disease); short and long posterior ciliary arteries: small vessels that supply the optic nerve and macula (susceptible to small-vessel disease); anterior ciliary arteries supply the iris and ciliary body.
For example, the cherry red spot within the macula in our patient is characteristic of central retinal artery occlusion and highlights the relationship between anatomy and pathophysiology. The retina’s blood supply is compromised, leading to an ischemic, white background (secondary to edema of the inner third of the retina), but the macula continues to be nourished by the posterior ciliary arteries. This contrast in color is accentuated by the underlying structures composing the fovea, which lacks the nerve fiber layer and ganglion cell layer, making the vascular bed more visible.2,3
Also in our patient, the marked reduction in visual acuity and relative afferent pupillary defect in the left eye point to unilateral optic nerve (or retinal ganglion cell) dysfunction. The findings on direct funduscopy were consistent with acute central retinal artery ischemia or occlusion. Central retinal artery occlusion can be either arteritic (due to inflammation, most often giant cell arteritis) or nonarteritic (due to atherosclerotic vascular disease).
Thus, carotid ultrasonography, electrocardiography, and transthoracic and transesophageal echocardiography are important components of the further workup. In addition, urgent brain imaging including either CT angiography or magnetic resonance angiography of the head and neck is indicated in all patients with central retinal artery occlusion.
Thrombophilia testing, including tests for the factor V Leiden and prothrombin gene mutations, is indicated in specific cases when a hypercoagulable state is suggested by components of the history, physical examination, and laboratory and radiologic testing. Thrombophilia testing would be low-yield and should not be part of the first-line testing in elderly patients with several atherosclerotic risk factors, such as our patient.
CASE CONTINUED: LABORATORY AND IMAGING EVIDENCE
Initial laboratory work showed:
Mild microcytic anemia
Erythrocyte sedimentation rate 77 mm/hour (reference range 1–10)
C-reactive protein 4.0 mg/dL (reference range < 0.9).
The rest of the complete blood cell count and metabolic profile were unremarkable. His hemoglobin A1c value was 5.3% (reference range 4.8%–6.2%).
A neurologist was urgently consulted.
Magnetic resonance imaging of the brain without contrast revealed nonspecific white-matter disease with no evidence of ischemic stroke.
Magnetic resonance angiography of the head and neck with contrast demonstrated 20% to 40% stenosis in both carotid arteries with otherwise patent anterior and posterior circulation.
Continuous monitoring of the left carotid artery with transcranial Doppler ultrasonography was also ordered, and the study concluded there were no undetected microembolic events.
Transthoracic echocardiography showed aortic sclerosis with no other abnormalities.
Ophthalmic fluorescein angiography was performed and showed patchy choroidal hypoperfusion, severe delayed filling, and extensive pruning of the arterial circulation with no involvement of the posterior ciliary arteries.
Given the elevated inflammatory markers, pulse-dose intravenous methylprednisolone was started, and a temporal artery biopsy was planned.
CENTRAL RETINAL ARTERY OCCLUSION: NONARTERITIC VS ARTERITIC CAUSES
3. Which of the following is least useful to differentiate arteritic from nonarteritic causes of central retinal artery occlusion?
Finding emboli in the retinal vasculature on funduscopy
Temporal artery biopsy
Measuring the C-reactive protein level and the erythrocyte sedimentation rate
Echocardiography
Positron-emission tomography (PET)
Retinal fluorescein angiography
In patients diagnosed with central retinal artery occlusion, the next step is to differentiate between nonarteritic and arteritic causes, since separating them has therapeutic relevance.
The carotid artery is the main culprit for embolic disease affecting the central retinal artery, leading to the nonarteritic subtype. Thus, evaluation of acute retinal ischemia secondary to nonarteritic central retinal artery occlusion is similar to the evaluation of patients with an acute cerebral stroke.4 Studies have shown that 25% of patients diagnosed with central retinal artery occlusion have an additional ischemic insult in the cerebrovascular system, and these patients are at high risk of recurrent ocular or cerebral infarction. Workup includes diffusion-weighted MRI, angiography, echocardiography, and telemetry.5
Arteritic central retinal artery occlusion is most often caused by giant cell arteritis. The American College of Rheumatology classification criteria for giant cell arteritis include 3 of the following 5:
Age 50 or older
New onset of localized headache
Temporal artery tenderness or decreased temporal artery pulse
Erythrocyte sedimentation rate 50 mm/hour or greater
Positive biopsy findings.6
Temporal artery biopsy is the gold standard for the diagnosis of giant cell arteritis and should be done whenever the disease is suspected.7,8 However, the test is invasive and imperfect, as a negative result does not completely rule out giant cell arteritis.9
Although a unilateral temporal artery biopsy can be falsely negative, several studies evaluating the efficacy of bilateral biopsies did not show significant improvement in the diagnostic yield.10,11
Ophthalmic fluorescein angiography is another helpful test for distinguishing nonarteritic from arteritic central retinal artery occlusion.12 Involvement of the posterior ciliary arteries usually occurs in giant cell arteritis, and this leads to choroidal malperfusion with or without retinal involvement. The optic nerve may also be infarcted by closure of the paraoptic vessels fed by the posterior ciliary vessels.12,13 Such involvement of multiple vessels would not be typical with nonarteritic central retinal artery occlusion. Thus, this finding is helpful in making the final diagnosis along with supplying possible prognostic information.13
PET-CT is emerging as a test for early inflammation in extracranial disease, but its utility for diagnosing intracranial disease is limited by high uptake of the tracer fluorodeoxyglucose by the brain and low resolution.14 Currently, it has no established role in the evaluation of patients with central retinal artery occlusion and would have no utility in differentiating arteritic vs nonarteritic causes of central retinal artery occlusion.
If giant cell arteritis is suspected, it is essential to start intravenous pulse-dose methylprednisolone early to prevent further vision loss in the contralateral eye. Treatment should not be delayed for invasive testing or temporal artery biopsy. Improvement in headache, jaw claudication, or scalp tenderness once steroids are initiated also helps support the diagnosis of giant cell arteritis.7
Unfortunately, visual symptoms may be irreversible despite treatment.
Our patient’s central retinal artery occlusion
This case highlights how difficult it is in practice to distinguish nonarteritic from arteritic central retinal artery occlusion.
Our patient had numerous cardiovascular risk factors, including known carotid and coronary artery disease, favoring a nonarteritic diagnosis.
On the other hand, his elevated inflammatory markers suggested an underlying inflammatory response. He lacked the characteristic headache and other systemic signs of giant cell arteritis, but this has been described in about 25% of patients.15 If emboli are seen on funduscopy, further workup for arteritic central retinal artery occlusion is not warranted, but emboli are not always present. Then again, absence of posterior ciliary artery involvement on fluorescein angiography pointed away from giant cell arteritis.
CASE CONTINUED: FINAL DIAGNOSIS
Biopsy of the left temporal artery showed intimal thickening with focal destruction of the internal elastic lamina by dystrophic calcification with no evidence of inflammatory infiltrates, giant cells, or granulomata in the adventitia, media, or intima. Based on the results of biopsy study and fluorescein angiography, we concluded that this was nonarteritic central retinal artery occlusion related to atherosclerotic disease.
Methylprednisolone was discontinued. The patient was discharged on aspirin, losartan, furosemide, amlodipine, and high-dose atorvastatin for standard stroke prevention. He was followed by the medical team and the ophthalmology department. At 6 weeks, there was only marginal improvement in the visual acuity of the left eye.
MANAGEMENT
4. Management of nonarteritic central retinal artery occlusion could include all of the following except which one?
Ocular massage
Intravenous thrombolysis
Intra-arterial thrombolysis
Risk-factor modification
Intraocular steroid injection
In patients with acute vision loss from nonarteritic central retinal artery occlusion, acute strategies to restore retinal perfusion include noninvasive “standard” therapies and thrombolysis (intravenous or intra-arterial). Unfortunately, consensus and guidelines are lacking.
Traditional therapies include sublingual isosorbide dinitrate, systemic pentoxifylline, inhalation of a carbogen, hyperbaric oxygen, ocular massage, intravenous acetazolamide and mannitol, anterior chamber paracentesis, and systemic steroids. However, none of these have been shown to be more effective than placebo.16
Thrombolytic therapy, analogous to the treatment of patients with ischemic stroke or myocardial infarction, is more controversial in acute central retinal artery occlusion.13 Data from small case-series suggested that intra-arterial or intravenous thrombolysis might improve visual acuity with reasonable safety.17 On the other hand, a randomized study from the United Kingdom that compared intra-arterial thrombolysis within a 24-hour window and conservative measures concluded that thrombolysis should not be used.18
Thrombolysis is thus used only in selected patients on a case-specific basis with involvement of a multispecialty team including stroke neurologists, especially if patients present within hours of onset and have concomitant neurologic symptoms.
Treatment beyond the acute phase focuses on preventing complications of the eye ischemia and aggressively managing systemic atherosclerotic risk factors to decrease the incidence of further ischemic events. Other interventions include endarterectomy for significant carotid stenosis and anticoagulation to prevent cardioembolic embolization (such as atrial fibrillation). Most experts agree on the addition of an antiplatelet agent.13,19
Intraocular steroid injection can be used in the management of some retinal disorders but has no value in nonarteritic central retinal artery occlusion.
Vision recovery in nonarteritic central retinal artery occlusion is variable, but the prognosis is generally poor. The visual acuity on presentation, the onset of the symptoms, and collateral vessels are major factors influencing long-term recovery. Most of the recovery occurs within 7 days and involves peripheral vision rather than central vision. Several studies report some recovery in peripheral vision in approximately 30% to 35% of affected eyes.20–22
PROMPT ACTION MAY SAVE SIGHT
Vision loss is a common presenting symptom in the emergency setting. A meticulous history and systematic physical examination can narrow the differential diagnosis of this neuro-ophthalmologic emergency. Acute retinal ischemia from central retinal artery occlusion is the ocular equivalent of an ischemic stroke, and they share risk factors, diagnostic workup, and management approaches.
Both etiologic subtypes (ie, arteritic and nonarteritic) require prompt intervention by front-line physicians. If giant cell arteritis is suspected, corticosteroid therapy must be initiated to save the contralateral retina from ischemia. Suspicion of central retinal artery occlusion warrants immediate evaluation by a neurologist to consider thrombolysis. Prompt action and interdisciplinary care involving an ophthalmologist, neurologist, and emergency or internal medicine physician may save a patient from permanent visual disability.
KEY POINTS
Monocular vision loss requires urgent evaluation with a multidisciplinary management approach.
There are no consensus treatment guidelines for nonarteritic central retinal artery occlusion, but the workup includes a comprehensive stroke evaluation.
Arteritic central retinal artery occlusion is most often due to giant cell arteritis, and when it is suspected, the patient should be empirically treated with steroids.
References
Glezer A, Bronstein MD. Pituitary apoplexy: pathophysiology, diagnosis and management. Arch Endocrinol Metab 2015; 59:259–264.
Campbell WW. DeJong’s The Neurologic Examination. 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2013.
Biller J. Practical Neurology. 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2012.
Biousse V. Acute retinal arterial ischemia: an emergency often ignored. Am J Ophthalmol 2014; 157:1119–1121.
Hunder GG, Bloch DA, Michel BA, et al. American College of Rheumatology 1990 criteria for the classification of giant cell arteritis. Arthritis Rheum 1990; 33:1122–1128.
Smith JH, Swanson JW. Giant cell arteritis. Headache 2014; 54:1273–1289.
Hall S, Persellin S, Lie JT, O’Brien PC, Kurland LT, Hunder GG. The therapeutic impact of temporal artery biopsy. Lancet 1983; 2:1217–1220.
Gabriel SE, O’Fallon WM, Achkar AA, Lie JT, Hunder GG. The use of clinical characteristics to predict the results of temporal artery biopsy among patients with suspected giant cell arteritis. J Rheumatol 1995; 22:93–96.
Boyev LR, Miller NR, Green WR. Efficacy of unilateral versus bilateral temporal artery biopsies for the diagnosis of giant cell arteritis. Am J Ophthalmol 1999; 128:211–215.
Danesh-Meyer HV, Savino PJ, Eagle RC Jr, Kubis KC, Sergott RC. Low diagnostic yield with second biopsies in suspected giant cell arteritis. J Neuroophthalmol 2000; 20:213–215.
Khan A, Dasgupta B. Imaging in giant cell arteritis. Curr Rheumatol Rep 2015; 17:52.
Biousse V, Newman N. Retinal and optic nerve ischemia. Continuum (Minneap Minn) 2014; 20:838–856.
Fraser SG, Adams W. Interventions for acute non-arteritic central retinal artery occlusion. Cochrane Database Syst Rev 2009; 1:CD001989.
Beatty S, Au Eong KG. Local intra-arterial fibrinolysis for acute occlusion of the central retinal artery: a meta-analysis of the published data. Br J Ophthalmol 2000; 84:914–916.
Schumacher M, Schmidt D, Jurklies B, et al; EAGLE-Study Group. Central retinal artery occlusion: local intra-arterial fibrinolysis versus conservative treatment, a multicenter randomized trial. Ophthalmology 2010; 117:1367–1375.e1.
Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002; 324:71–86.
Hayreh SS, Zimmerman MB. Central retinal artery occlusion: visual outcome. Am J Ophthalmol 2005; 140:376–391.
Augsburger JJ, Magargal LE. Visual prognosis following treatment of acute central retinal artery obstruction. Br J Ophthalmol 1980; 64:913–917.
Brown GC, Shields JA. Cilioretinal arteries and retinal arterial occlusion. Arch Ophthalmol 1979; 97:84–92.
References
Glezer A, Bronstein MD. Pituitary apoplexy: pathophysiology, diagnosis and management. Arch Endocrinol Metab 2015; 59:259–264.
Campbell WW. DeJong’s The Neurologic Examination. 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2013.
Biller J. Practical Neurology. 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2012.
Biousse V. Acute retinal arterial ischemia: an emergency often ignored. Am J Ophthalmol 2014; 157:1119–1121.
Hunder GG, Bloch DA, Michel BA, et al. American College of Rheumatology 1990 criteria for the classification of giant cell arteritis. Arthritis Rheum 1990; 33:1122–1128.
Smith JH, Swanson JW. Giant cell arteritis. Headache 2014; 54:1273–1289.
Hall S, Persellin S, Lie JT, O’Brien PC, Kurland LT, Hunder GG. The therapeutic impact of temporal artery biopsy. Lancet 1983; 2:1217–1220.
Gabriel SE, O’Fallon WM, Achkar AA, Lie JT, Hunder GG. The use of clinical characteristics to predict the results of temporal artery biopsy among patients with suspected giant cell arteritis. J Rheumatol 1995; 22:93–96.
Boyev LR, Miller NR, Green WR. Efficacy of unilateral versus bilateral temporal artery biopsies for the diagnosis of giant cell arteritis. Am J Ophthalmol 1999; 128:211–215.
Danesh-Meyer HV, Savino PJ, Eagle RC Jr, Kubis KC, Sergott RC. Low diagnostic yield with second biopsies in suspected giant cell arteritis. J Neuroophthalmol 2000; 20:213–215.
Khan A, Dasgupta B. Imaging in giant cell arteritis. Curr Rheumatol Rep 2015; 17:52.
Biousse V, Newman N. Retinal and optic nerve ischemia. Continuum (Minneap Minn) 2014; 20:838–856.
Fraser SG, Adams W. Interventions for acute non-arteritic central retinal artery occlusion. Cochrane Database Syst Rev 2009; 1:CD001989.
Beatty S, Au Eong KG. Local intra-arterial fibrinolysis for acute occlusion of the central retinal artery: a meta-analysis of the published data. Br J Ophthalmol 2000; 84:914–916.
Schumacher M, Schmidt D, Jurklies B, et al; EAGLE-Study Group. Central retinal artery occlusion: local intra-arterial fibrinolysis versus conservative treatment, a multicenter randomized trial. Ophthalmology 2010; 117:1367–1375.e1.
Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002; 324:71–86.
Hayreh SS, Zimmerman MB. Central retinal artery occlusion: visual outcome. Am J Ophthalmol 2005; 140:376–391.
Augsburger JJ, Magargal LE. Visual prognosis following treatment of acute central retinal artery obstruction. Br J Ophthalmol 1980; 64:913–917.
Brown GC, Shields JA. Cilioretinal arteries and retinal arterial occlusion. Arch Ophthalmol 1979; 97:84–92.
Raynaud phenomenon is an overactive vascular response to cold and emotional stress that results in cutaneous color changes and sensory symptoms of the digits (Figure 1). It can occur in isolation as primary Raynaud phenomenon or secondary to another disease process. It is thought to be triggered by a heightened sympathetic vasoconstrictive response of small arteriovenous anastomoses in the fingers, toes, ears, and tip of the nose. These structures play a key role in maintaining a stable core body temperature by cutaneous thermoregulation.1
Figure 1. (A) White digits with intense vasoconstriction in Raynaud phenomenon; (B) blue digits with
hypoxemic venous stasis; (C) red digits with hyperemic reperfusion.
Secondary Raynaud phenomenon can be seen with a wide array of systemic conditions as well as environmental and drug exposures. It is a frequent feature of autoimmune rheumatic conditions such as systemic sclerosis, mixed connective tissue disease, systemic lupus erythematosus, and dermatomyositis. Less commonly, cryoproteinemias, paraneoplastic syndromes, hypothyroidism, and carpal tunnel syndrome can be associated with or cause Raynaud phenomenon. Vibratory trauma (eg, from using a jackhammer) and drugs (eg, vasopressors, stimulants, ergots, chemotherapeutic agents) can also cause Raynaud phenomenon.1
A variety of disorders that cause vasospasm or vascular occlusion of the peripheral circulation can mimic typical Raynaud phenomenon, including peripheral nerve injury,2 complex regional pain syndrome,3 occlusive vascular disease, vasculitis, acrocyanosis,4 and thoracic outlet syndrome.
The prevalence of Raynaud phenomenon is not exactly known, in part due to geographic differences in climate and variation in methods of assessment. However, a 2015 systematic review and meta-analysis of primary Raynaud phenomenon determined a pooled prevalence of 4.85% (95% confidence interval [CI] 2.08%–8.71%) in the general population.5 Accordingly, accurate identification and management of this condition is a useful skill for the internist.
COLD SENSITIVITY AND COLOR CHANGES
Because there are no confirmatory diagnostic tests for this condition, there are no formal diagnostic criteria. However, many experts agree that Raynaud phenomenon can be diagnosed clinically when patients report:
Unusual sensitivity of the fingers to cold, manifesting as pain or paresthesia (eg, tingling, pricking, numbness), and
Color changes of the fingers when exposed to cold, specifically pale white or blue-black, or both.6
Provocative testing such as submerging patients’ hands in cold water is not recommended, as it is distressing to the patient and inconsistent in triggering an event.
Pain is a symptom of critical digital ischemia.
The skin color changes are due to rapid alterations in blood flow in digital skin. The pale white is due to markedly reduced or absent flow secondary to intense vasoconstriction, the blue-black is due to hypoxemic venous stasis, and the red blush is due to hyperemic reperfusion (Figure 1). However, not all patients have all 3 phases of the classic triphasic color changes, and color changes may not follow a set sequence.
Raynaud phenomenon can also occur in other areas of the body that have thermoregulatory vessels, such as the toes, ears, nipples, tongue, and nose. While some patients with Raynaud phenomenon have a finger that is more sensitive than the others, repeated isolated single-digit or asymmetric events without typical progression to all fingers suggest a secondary local structural disease requiring further investigation (see below).
Symptoms related to Raynaud often mimic sensory changes including paresthesias, numbness, aching, and clumsiness of the hand. Abnormal vascular reactivity has been implicated as a causative factor in several disorders, such as migraine headache, preeclampsia, and variant angina. While case reports, case series, and some controlled studies have linked Raynaud phenomenon and these conditions, there is no solid evidence of a systemic vasospastic disorder in patients with primary Raynaud phenomenon.
Raynaud phenomenon is triggered by more than just a cold ambient temperature. Provocation can occur during movement from warmer to relatively cooler temperatures, as well as during episodes of elevated sympathetic activity (eg, emotional distress or fear). In fact, maintaining full body warmth as well as emotional equilibrium are the most important strategies to reduce the frequency of attacks.
PRIMARY VS SECONDARY RAYNAUD PHENOMENON
To distinguish between primary and secondary Raynaud phenomenon, a careful history and physical examination are paramount.
Primary Raynaud phenomenon
In uncomplicated primary Raynaud phenomenon, the episodes typically last 15 to 20 minutes after rewarming and usually start in a single finger and spread to other digits symmetrically and bilaterally.7 The thumb is often spared, and ischemic digital ulcers do not occur. Vasoconstrictive episodes are mild.
Females under age 20 are most commonly affected. In our experience, a young woman with the above clinical picture, no signs or symptoms suggestive of connective tissue disease (see below), and normal nailfold capillaries can be diagnosed as having primary Raynaud phenomenon without any further workup.
Careful clinical follow-up is recommended, because if an occult secondary process is indeed present, most patients will begin to show additional symptoms or signs of it within 2 years of the onset of Raynaud phenomenon.
Should a clinician be unfamiliar with nailfold capillary examination, or if symptoms (eg, fatigue or arthralgia) or signs (eg, rash, arthritis) suggestive of connective tissue disease are present, referral to a rheumatologist for further evaluation is appropriate. Results of further diagnostic testing dictated by the history and physical such as a screening antinuclear antibody test can be sent before referral.
Secondary Raynaud phenomenon
Several clinical features suggest secondary Raynaud phenomenon and warrant referral to a rheumatologist:
Age 20 or older at onset
Frequent severe vasoconstrictive episodes
Male sex
Thumb involvement
Figure 2. (A) Dilated nailfold capillaries in a patient with scleroderma (blue arrow); (B) dilation and dropout of nailfold capillaries (white arrow) viewed with a magnifier.Signs of an autoimmune rheumatic disease, eg, sclerodactyly, cutaneous or mucosal matted telangiectasia, inflammatory arthritis, an abnormal lung examination, severe digital ischemia with ulceration or gangrene, or nailfold capillary dilation or dropout (Figure 2)8
Isolated single-limb or 1-finger ischemic events, seen in macrovascular occlusive disease or inflammatory disease mimicking Raynaud phenomenon (eg, atherosclerosis, vasculitis); when isolated acute ischemic events occur in the upper or lower extremity, a further workup is necessary.
Figure 3 shows our approach to evaluation.
NONPHARMACOLOGIC THERAPY
Figure 3. Our approach to diagnosis of Raynaud phenomenon and differentiating primary from secondary Raynaud phenomenon.
Cold avoidance and stress management are first-line therapies for preventing Raynaud attacks and must be part of any treatment strategy. Digital arteries and thermoregulatory vessels of the skin are predominantly under sympathetic adrenergic control, so temperature changes and emotional stressors trigger vasoconstriction. Patients should be counseled to:
Keep the whole body warm. Patients should wear multiple layers of clothing, a hat, warm gloves, and warm socks. Commercially available hand-warmers can help, especially for patients who live in cold climates.
Learn to avoid or manage stress. Good communication, attention to the patient’s needs, and regular follow-up for reassurance are paramount. For some patients, psychotropic medications to manage mood may help. Behavioral approaches have been suggested for acute stress management. One approach, autogenic training, is a form of relaxation with temperature biofeedback in which finger temperature data are provided to patients to help them learn to relax by monitoring their internal states and changes in temperature. However, there are no strong data to support the routine use of this technique or the use of one behavioral approach over another. Trials have generally been of low quality and limited by small sample size.9
Stop smoking!10
Stop a Raynaud attack should one occur, eg, place the hands under warm water or in a warm part of the body, such as under legs when sitting. This can help speed recovery.
In addition, the physician should:
Eliminate vasoconstricting agents such as nonselective beta-blockers, ergots, triptans, and amphetamines.
PHARMACOLOGIC THERAPY
For many patients, nonpharmacologic interventions are enough to decrease the severity and frequency of attacks. However, if Raynaud phenomenon continues to negatively affect quality of life, drug therapy can be added (Table 1).
Calcium channel blockers
Calcium channel blockers are first-line agents for both primary and secondary Raynaud phenomenon that does not adequately respond to nonpharmacologic interventions. These agents are effective, available, and reasonably inexpensive.
Dihydropyridine calcium channel blockers such as nifedipine and amlodipine are commonly used. Both drugs are acceptable options, though some patients may respond better to one than the other in terms of symptoms and side effects. Nondihydropyridines such as diltiazem can also be used, but they have less potent vasodilatory effects because they are less selective for vascular smooth muscle.
These medications should be started at the lowest dose and titrated up over several weeks as tolerated to achieve their maximal effect. Intermittent therapy (eg, during the winter months only) is reasonable for primary Raynaud without risk of digital ulceration, as relief of symptoms and improvement in quality of life are the main indications for therapy in this circumstance.
A 2016 Cochrane review and meta-analysis of the use of calcium channel blockers to treat primary Raynaud phenomenon included 7 randomized controlled trials with 296 patients treated with either nifedipine or nicardipine.11 There was moderate-quality evidence that these drugs minimally decreased the frequency of attacks (standardized mean difference of 0.23; 95% CI 0.08–0.38, P = .003). This translated to 1.72 fewer attacks per week with treatment than with no pharmacologic therapy (95% CI 0.60–2.84). When analyzed individually, only nifedipine was effective; nicardipine did not decrease the frequency of attacks.
Unfortunately, calcium channel blockers failed to decrease the severity of attacks (according to unvalidated severity scoring systems) or make any differences in physiologic measurement outcomes. Attacks were not completely eliminated, just less frequent than before treatment.11
Most commonly reported side effects included headache, flushing, hypotension, edema, and, rarely, gastrointestinal reflux. Use of these medications may be limited by hypotension.
The review was limited by the small sample size, short duration of treatment, and relatively low doses of calcium channel blockers used in the available studies.11
A 2005 meta-analysis also indicated a statistically significant decrease of 2.8 to 5 attacks per week with nifedipine treatment, though this study also included some patients with secondary Raynaud phenomenon.12
Phosphodiesterase type 5 inhibitors
When calcium channel blockers do not adequately control symptoms, phosphodiesterase type 5 (PDE5) inhibitors can be added or substituted. These medications work by preventing breakdown of cyclic guanosine monophosphate, which induces relaxation in vascular smooth muscle and vasodilation.
Sildenafil can be started at a low dose (20 mg daily) and up-titrated to the maximum dose (20 mg 3 times daily) as tolerated.
A 2014 meta-analysis of 6 randomized controlled trials included 244 patients with secondary Raynaud phenomenon treated with sildenafil, tadalafil, or vardenafil.13 These drugs decreased the daily frequency of attacks by about 0.5 per day vs placebo (–0.49, 95% CI –0.71 to –0.28, P < .0001). PDE5 inhibitors also decreased the severity of attacks (based on the Raynaud’s Condition Score, a popular scoring system) and the duration of attacks by a statistically significant amount.
Almost all patients in these 6 trials were on PDE5 monotherapy. Data on the cumulative benefit of calcium channel blocker and PDE5 inhibitor combination therapy are not yet available. Not all patients tolerate combination therapy, as it can cause symptomatic hypotension, but it can be a successful option in some.
There are also no data showing that either calcium channel blockers or PDE5 inhibitors are superior, though the former are less expensive. A small double-blind, randomized, crossover study of udenafil vs amlodipine in the treatment of secondary Raynaud phenomenon showed that both medications significantly decreased the frequency of attacks and had comparable efficacy.14
Cost and insurance coverage. We have generally been successful in obtaining coverage for this off-label use of PDE5 inhibitors, though additional effort may be required. No drug (not even a calcium channel blocker) is approved by the US Food and Drug Administration for use in Raynaud phenomenon. In our experience, a letter of appeal outlining the rationale for use and citing supporting publications can lead to successful coverage of a medication. If the drug is still not approved, the patient either pays for it out of pocket or another agent is selected. In certain circumstances, pharmaceutical companies may provide prescription assistance for compassionate use of these drugs in Raynaud phenomenon, although this also takes letter-writing, phone calls, or both on the part of the physician.
Topical nitrates
Patients who have an unsatisfactory response to calcium channel blockers with or without PDE5 inhibitors can try topical nitrates, available as sustained-release transdermal patches, tapes, creams, gels, and ointments.
Small trials have noted slight improvement in the Raynaud Condition Score15 and finger temperature16 with these therapies. Another trial noted decreased frequency of attacks and symptoms with the use of sustained-release glyceryl trinitrate patches, but use was limited by intolerable headache.17
In our experience, topical nitrates are most helpful for patients who have 1 or a few digits that are more severely affected than the others, and we reserve these drugs for this indication. Localized vasodilation can provide targeted rapid relief of more ischemic areas.
Topical nitroglycerin can be applied to the base of the ischemic digit for 6 to 12 hours. Preparations vary, and patients should be closely monitored for dose response and tolerance.
Combining a topical nitrate with a calcium channel blocker is safe, but the use of a nitrate with a PDE5 inhibitor is contraindicated due to the risk of hypotension. The use of topical nitrates may be limited by systemic side effects such as headache and flushing and a lack of benefit over time.
Other therapies
If the aforementioned agents are not tolerated or not effective, there is limited evidence that other therapies reduce the frequency and sometimes the severity of attacks. These are not first-line agents but may be tried when other options have been exhausted and symptoms persist. There are no data to support combining these therapies, but in our experience doing so may help some patients in whom drug-drug interactions are not prohibitive.
Prazosin, an alpha-1-adrenergic receptor antagonist, was reported to improve Raynaud phenomenon in 2 small studies in the 1980s, but we do not use it since better options are available. In addition, the vasoactive blood vessels involved do not have alpha-1 receptors, so there is no theoretical basis for using prazosin.18,19
Fluoxetine, a selective serotonin reuptake inhibitor, reduced the frequency and severity of attacks in a 6-week crossover study with nifedipine.20
Losartan, an angiotensin II receptor blocker, also reduced the severity and frequency of attacks when compared with nifedipine.21
Pentoxifylline, a nonselective phosphodiesterase inhibitor, showed some benefit in a trial in 11 patients with primary Raynaud.22
Atorvastatin, a lipid-lowering drug, reduced the number of digital ulcers in patients with secondary Raynaud already on first-line vasodilatory therapy, and might be added in this situation.23
Botulinum toxin A injections have some data to support their use, but evidence is based on uncontrolled case series.24 A controlled trial in scleroderma patients with severe Raynaud phenomenon found botulinum toxin to be no better than placebo.25
Prostacyclin preparations are available. Intermittent intravenous doses of prostacyclin analogues over several days can be used in resistant cases. Oral prostacyclin agents have not shown consistent benefit. New prostacyclin receptor agonists are under investigation.
Overall, we move to other options only in patients with persistent symptoms that impair quality of life, or in patients with recurrent digital ischemic lesions that have not responded to calcium channel blockers and PDE5 inhibitors or nitrates, either alone or in combination.
DIGITAL ULCERATION AND ACUTE DIGITAL ISCHEMIC CRISIS
Patients with secondary Raynaud phenomenon may be at risk of recurrent digital ulceration and acute digital ischemia with gangrene. These patients should be comanaged with a rheumatologist so that the underlying disease process is fully addressed. Digital ulcers should be inspected closely for signs of infection, which may require treatment with antibiotics.
Acute digital ischemia is a medical emergency and should prompt inpatient admission with warming, emotional regulation, and pain control (often with narcotics) to decrease sympathetic vasoconstriction. These patients require aggressive vasodilatory therapy to reverse the ischemic event.
A short-acting calcium channel blocker or combination therapy with a calcium channel blocker and a PDE5 inhibitor or topical nitrate should be started. If there is no benefit, then transient intravenous vasodilatory therapy with a prostacyclin (epoprostenol) or localized digital sympathectomy is used to prevent digital loss.
The endothelin receptor inhibitor bosentan has been shown to decrease recurrent digital ulcers in patients with scleroderma, and while bosentan does not decrease the frequency of Raynaud attacks, it can be used in this select group to prevent new digital ulcers.
Treatment options may be limited by insurance coverage or access to intravenous infusions.
TAKE-HOME RECOMMENDATIONS
For many patients with primary or secondary Raynaud phenomenon, nonpharmacologic interventions are all that are required to decrease the frequency of attacks and improve quality of life. The goal should not be to eliminate attacks completely, as aggressive drug treatment may cause more harm than benefit. From our perspective, the goals of treatment should be to improve quality of life and prevent ischemic complications.
Pharmacologic therapies should be added only if attacks remain poorly controlled with incapacitating symptoms, or if the patient has digital ischemic ulcers. Calcium channel blockers are first-line therapy, given proven efficacy and low cost, and should be titrated to the maximum tolerated dose before adding or substituting other agents.
References
Wigley FM, Flavahan NA. Raynaud’s phenomenon. N Engl J Med 2016; 375:556–565.
Irwin MS, Gilbert SE, Terenghi G, Smith RW, Green CJ. Cold intolerance following peripheral nerve injury. Natural history and factors predicting severity of symptoms. J Hand Surg Br 1997; 22:308–316.
Wasner G. Vasomotor disturbances in complex regional pain syndrome—a review. Pain Med 2010; 11:1267–1273.
Kurklinsky AK, Miller VM, Rooke TW. Acrocyanosis: the Flying Dutchman. Vasc Med 2011; 16:288–301.
Garner R, Kumari R, Lanyon P, Doherty M, Zhang W. Prevalence, risk factors and associations of primary Raynaud’s phenomenon: systematic review and meta-analysis of observational studies. BMJ Open 2015; 5:e006389.
Wigley FM. Clinical practice. Raynaud’s phenomenon. N Engl J Med 2002; 347:1001–1008.
Chikura B, Moore TL, Manning JB, Vail A, Herrick AL. Sparing of the thumb in Raynaud’s phenomenon. Rheumatology (Oxford) 2008; 47:219–221.
Kallenerg CG. Early detection of connective tissue disease in patients with Raynaud’s phenomenon. Rheum Dis Clin North Am 1990; 16:11–30.
Kwakkenbos L, Thombs BD. Non-drug approaches to treating Raynaud’s phenomenon. In: Wigley FM, Herrick AL, Flavahan NA, editors. Raynaud’s Phenomenon. A Guide to Pathogenesis and Treatment. New York: Springer Science+Business Media, 2015:299–313.
Goodfield MJ, Hume A, Rowell NR. The acute effects of cigarette smoking on cutaneous blood flow in smoking and non-smoking subjects with and without Raynaud’s phenomenon. Br J Rheumatol 1990; 29:89–91.
Ennis H, Hughes M, Anderson ME, Wilkinson J, Herrick AL. Calcium channel blockers for primary Raynaud’s phenomenon. Cochrane Database Sys Review 2016; 2:CD002069.
Thompson AE, Pope JE. Calcium channel blockers for primary Raynaud’s phenomenon: a meta-analysis. Rheumatology (Oxford) 2005; 44:145–150.
Roustit M, Blaise S, Allanore Y, Carpentier P, Caglayan E, Cracowski J. Phosphodiesterase-5 inhibitors for the treatment of secondary Raynaud’s phenomenon: systematic review and meta-analysis of randomized trials. Ann Rheum Dis 2013; 72:1696–1699.
Lee EY, Park JK, Lee W, et al. Head-to-head comparison of udenafil vs amlodipine in the treatment of secondary Raynaud's phenomenon: a double-blind, randomized, cross-over study. Rheumatology (Oxford) 2014; 53:658–664.
Chung L, Shapiro L, Fiorentino D, et al. MQX-503, a novel formulation of nitroglycerin, improves the severity of Raynaud’s phenomenon: a randomized, controlled trial. Arthritis Rheum 2009; 60:870–877.
Kan C, Akimoto S, Abe M, Okada K, Ishikawa O. Preliminary thermographic evaluation of a new nitroglycerine tape on the peripheral circulatory disturbance in systemic sclerosis. Ann Rheum Dis 2002; 61:177–179.
Teh LS, Manning J, Moore T, Tully MP, O’Reilly D, Jayson MI. Sustained-release transdermal glyceryl trinitrate patches as a treatment for primary and secondary Raynaud’s phenomenon. Br J Rheumatol 1995; 34:636–641.
Russell IJ, Lessard JA. Prazosin treatment of Raynaud’s phenomenon: a double blind single crossover study. J Rheumatol 1985; 12:94–98.
Wollersheim H, Thien T, Fennis J, van Elteren P, van ‘t Laar A. Double-blind, placebo-controlled study of prazosin in Raynaud’s phenomenon. Clin Pharmacol Ther 1986; 40:219–225.
Coleiro B, Marshall SE, Denton CP, et al. Treatment of Raynaud’s phenomenon with the selective serotonin reuptake inhibitor fluoxetine. Rheumatology (Oxford) 2001; 40:1038–1043.
Didazio M, Denton CP, Smith R, et al. Losartan therapy for Raynaud’s phenomenon and scleroderma: clinical and biochemical findings in a fifteen-week randomized, parallel-group, controlled trial. Arthritis Rheum 1999; 42:2646–2655.
Neirotti M, Longo F, Molaschi M, Macchione C, Pernigotti L. Functional vascular disorders: treatment with pentoxifylline. Angiology 1987; 38:575–580.
Abou-Raya A, Abou-Raya S, Helmii M. Statins: potentially useful in therapy of systemic sclerosis-related Raynaud’s phenomenon and digital ulcers. J Rheumatol 2008; 35:1801–1808.
Iorio ML, Masden DL, Higgins JP. Botulinum toxin A treatment of Raynaud’s phenomenon: a review. Semin Arthritis Rheum 2012; 41: 599–603.
Bello RJ, Cooney CM, Melamed E, et al. The therapeutic efficacy of botulinum toxin in treating scleroderma-associated Raynaud’s phenomenon: a randomized, double-blind, placebo-controlled clinical trial. Arthritis Rheumatol 2017. Epub ahead of print.
Samantha C. Shapiro, MD Department of Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine; Postdoctoral Fellow, Johns Hopkins Division of Rheumatology, Baltimore, MD
Fredrick M. Wigley, MD Department of Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine; Martha McCrory Professor of Medicine, Johns Hopkins Division of Rheumatology, Baltimore, MD
Address: Samantha C. Shapiro, MD, Department of Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine; 5200 Eastern Avenue, Suite 4100, Mason F. Lord Building, Center Tower, Baltimore, MD 21224; sshapi28@jhmi.edu
Samantha C. Shapiro, MD Department of Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine; Postdoctoral Fellow, Johns Hopkins Division of Rheumatology, Baltimore, MD
Fredrick M. Wigley, MD Department of Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine; Martha McCrory Professor of Medicine, Johns Hopkins Division of Rheumatology, Baltimore, MD
Address: Samantha C. Shapiro, MD, Department of Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine; 5200 Eastern Avenue, Suite 4100, Mason F. Lord Building, Center Tower, Baltimore, MD 21224; sshapi28@jhmi.edu
Author and Disclosure Information
Samantha C. Shapiro, MD Department of Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine; Postdoctoral Fellow, Johns Hopkins Division of Rheumatology, Baltimore, MD
Fredrick M. Wigley, MD Department of Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine; Martha McCrory Professor of Medicine, Johns Hopkins Division of Rheumatology, Baltimore, MD
Address: Samantha C. Shapiro, MD, Department of Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine; 5200 Eastern Avenue, Suite 4100, Mason F. Lord Building, Center Tower, Baltimore, MD 21224; sshapi28@jhmi.edu
Raynaud phenomenon is an overactive vascular response to cold and emotional stress that results in cutaneous color changes and sensory symptoms of the digits (Figure 1). It can occur in isolation as primary Raynaud phenomenon or secondary to another disease process. It is thought to be triggered by a heightened sympathetic vasoconstrictive response of small arteriovenous anastomoses in the fingers, toes, ears, and tip of the nose. These structures play a key role in maintaining a stable core body temperature by cutaneous thermoregulation.1
Figure 1. (A) White digits with intense vasoconstriction in Raynaud phenomenon; (B) blue digits with
hypoxemic venous stasis; (C) red digits with hyperemic reperfusion.
Secondary Raynaud phenomenon can be seen with a wide array of systemic conditions as well as environmental and drug exposures. It is a frequent feature of autoimmune rheumatic conditions such as systemic sclerosis, mixed connective tissue disease, systemic lupus erythematosus, and dermatomyositis. Less commonly, cryoproteinemias, paraneoplastic syndromes, hypothyroidism, and carpal tunnel syndrome can be associated with or cause Raynaud phenomenon. Vibratory trauma (eg, from using a jackhammer) and drugs (eg, vasopressors, stimulants, ergots, chemotherapeutic agents) can also cause Raynaud phenomenon.1
A variety of disorders that cause vasospasm or vascular occlusion of the peripheral circulation can mimic typical Raynaud phenomenon, including peripheral nerve injury,2 complex regional pain syndrome,3 occlusive vascular disease, vasculitis, acrocyanosis,4 and thoracic outlet syndrome.
The prevalence of Raynaud phenomenon is not exactly known, in part due to geographic differences in climate and variation in methods of assessment. However, a 2015 systematic review and meta-analysis of primary Raynaud phenomenon determined a pooled prevalence of 4.85% (95% confidence interval [CI] 2.08%–8.71%) in the general population.5 Accordingly, accurate identification and management of this condition is a useful skill for the internist.
COLD SENSITIVITY AND COLOR CHANGES
Because there are no confirmatory diagnostic tests for this condition, there are no formal diagnostic criteria. However, many experts agree that Raynaud phenomenon can be diagnosed clinically when patients report:
Unusual sensitivity of the fingers to cold, manifesting as pain or paresthesia (eg, tingling, pricking, numbness), and
Color changes of the fingers when exposed to cold, specifically pale white or blue-black, or both.6
Provocative testing such as submerging patients’ hands in cold water is not recommended, as it is distressing to the patient and inconsistent in triggering an event.
Pain is a symptom of critical digital ischemia.
The skin color changes are due to rapid alterations in blood flow in digital skin. The pale white is due to markedly reduced or absent flow secondary to intense vasoconstriction, the blue-black is due to hypoxemic venous stasis, and the red blush is due to hyperemic reperfusion (Figure 1). However, not all patients have all 3 phases of the classic triphasic color changes, and color changes may not follow a set sequence.
Raynaud phenomenon can also occur in other areas of the body that have thermoregulatory vessels, such as the toes, ears, nipples, tongue, and nose. While some patients with Raynaud phenomenon have a finger that is more sensitive than the others, repeated isolated single-digit or asymmetric events without typical progression to all fingers suggest a secondary local structural disease requiring further investigation (see below).
Symptoms related to Raynaud often mimic sensory changes including paresthesias, numbness, aching, and clumsiness of the hand. Abnormal vascular reactivity has been implicated as a causative factor in several disorders, such as migraine headache, preeclampsia, and variant angina. While case reports, case series, and some controlled studies have linked Raynaud phenomenon and these conditions, there is no solid evidence of a systemic vasospastic disorder in patients with primary Raynaud phenomenon.
Raynaud phenomenon is triggered by more than just a cold ambient temperature. Provocation can occur during movement from warmer to relatively cooler temperatures, as well as during episodes of elevated sympathetic activity (eg, emotional distress or fear). In fact, maintaining full body warmth as well as emotional equilibrium are the most important strategies to reduce the frequency of attacks.
PRIMARY VS SECONDARY RAYNAUD PHENOMENON
To distinguish between primary and secondary Raynaud phenomenon, a careful history and physical examination are paramount.
Primary Raynaud phenomenon
In uncomplicated primary Raynaud phenomenon, the episodes typically last 15 to 20 minutes after rewarming and usually start in a single finger and spread to other digits symmetrically and bilaterally.7 The thumb is often spared, and ischemic digital ulcers do not occur. Vasoconstrictive episodes are mild.
Females under age 20 are most commonly affected. In our experience, a young woman with the above clinical picture, no signs or symptoms suggestive of connective tissue disease (see below), and normal nailfold capillaries can be diagnosed as having primary Raynaud phenomenon without any further workup.
Careful clinical follow-up is recommended, because if an occult secondary process is indeed present, most patients will begin to show additional symptoms or signs of it within 2 years of the onset of Raynaud phenomenon.
Should a clinician be unfamiliar with nailfold capillary examination, or if symptoms (eg, fatigue or arthralgia) or signs (eg, rash, arthritis) suggestive of connective tissue disease are present, referral to a rheumatologist for further evaluation is appropriate. Results of further diagnostic testing dictated by the history and physical such as a screening antinuclear antibody test can be sent before referral.
Secondary Raynaud phenomenon
Several clinical features suggest secondary Raynaud phenomenon and warrant referral to a rheumatologist:
Age 20 or older at onset
Frequent severe vasoconstrictive episodes
Male sex
Thumb involvement
Figure 2. (A) Dilated nailfold capillaries in a patient with scleroderma (blue arrow); (B) dilation and dropout of nailfold capillaries (white arrow) viewed with a magnifier.Signs of an autoimmune rheumatic disease, eg, sclerodactyly, cutaneous or mucosal matted telangiectasia, inflammatory arthritis, an abnormal lung examination, severe digital ischemia with ulceration or gangrene, or nailfold capillary dilation or dropout (Figure 2)8
Isolated single-limb or 1-finger ischemic events, seen in macrovascular occlusive disease or inflammatory disease mimicking Raynaud phenomenon (eg, atherosclerosis, vasculitis); when isolated acute ischemic events occur in the upper or lower extremity, a further workup is necessary.
Figure 3 shows our approach to evaluation.
NONPHARMACOLOGIC THERAPY
Figure 3. Our approach to diagnosis of Raynaud phenomenon and differentiating primary from secondary Raynaud phenomenon.
Cold avoidance and stress management are first-line therapies for preventing Raynaud attacks and must be part of any treatment strategy. Digital arteries and thermoregulatory vessels of the skin are predominantly under sympathetic adrenergic control, so temperature changes and emotional stressors trigger vasoconstriction. Patients should be counseled to:
Keep the whole body warm. Patients should wear multiple layers of clothing, a hat, warm gloves, and warm socks. Commercially available hand-warmers can help, especially for patients who live in cold climates.
Learn to avoid or manage stress. Good communication, attention to the patient’s needs, and regular follow-up for reassurance are paramount. For some patients, psychotropic medications to manage mood may help. Behavioral approaches have been suggested for acute stress management. One approach, autogenic training, is a form of relaxation with temperature biofeedback in which finger temperature data are provided to patients to help them learn to relax by monitoring their internal states and changes in temperature. However, there are no strong data to support the routine use of this technique or the use of one behavioral approach over another. Trials have generally been of low quality and limited by small sample size.9
Stop smoking!10
Stop a Raynaud attack should one occur, eg, place the hands under warm water or in a warm part of the body, such as under legs when sitting. This can help speed recovery.
In addition, the physician should:
Eliminate vasoconstricting agents such as nonselective beta-blockers, ergots, triptans, and amphetamines.
PHARMACOLOGIC THERAPY
For many patients, nonpharmacologic interventions are enough to decrease the severity and frequency of attacks. However, if Raynaud phenomenon continues to negatively affect quality of life, drug therapy can be added (Table 1).
Calcium channel blockers
Calcium channel blockers are first-line agents for both primary and secondary Raynaud phenomenon that does not adequately respond to nonpharmacologic interventions. These agents are effective, available, and reasonably inexpensive.
Dihydropyridine calcium channel blockers such as nifedipine and amlodipine are commonly used. Both drugs are acceptable options, though some patients may respond better to one than the other in terms of symptoms and side effects. Nondihydropyridines such as diltiazem can also be used, but they have less potent vasodilatory effects because they are less selective for vascular smooth muscle.
These medications should be started at the lowest dose and titrated up over several weeks as tolerated to achieve their maximal effect. Intermittent therapy (eg, during the winter months only) is reasonable for primary Raynaud without risk of digital ulceration, as relief of symptoms and improvement in quality of life are the main indications for therapy in this circumstance.
A 2016 Cochrane review and meta-analysis of the use of calcium channel blockers to treat primary Raynaud phenomenon included 7 randomized controlled trials with 296 patients treated with either nifedipine or nicardipine.11 There was moderate-quality evidence that these drugs minimally decreased the frequency of attacks (standardized mean difference of 0.23; 95% CI 0.08–0.38, P = .003). This translated to 1.72 fewer attacks per week with treatment than with no pharmacologic therapy (95% CI 0.60–2.84). When analyzed individually, only nifedipine was effective; nicardipine did not decrease the frequency of attacks.
Unfortunately, calcium channel blockers failed to decrease the severity of attacks (according to unvalidated severity scoring systems) or make any differences in physiologic measurement outcomes. Attacks were not completely eliminated, just less frequent than before treatment.11
Most commonly reported side effects included headache, flushing, hypotension, edema, and, rarely, gastrointestinal reflux. Use of these medications may be limited by hypotension.
The review was limited by the small sample size, short duration of treatment, and relatively low doses of calcium channel blockers used in the available studies.11
A 2005 meta-analysis also indicated a statistically significant decrease of 2.8 to 5 attacks per week with nifedipine treatment, though this study also included some patients with secondary Raynaud phenomenon.12
Phosphodiesterase type 5 inhibitors
When calcium channel blockers do not adequately control symptoms, phosphodiesterase type 5 (PDE5) inhibitors can be added or substituted. These medications work by preventing breakdown of cyclic guanosine monophosphate, which induces relaxation in vascular smooth muscle and vasodilation.
Sildenafil can be started at a low dose (20 mg daily) and up-titrated to the maximum dose (20 mg 3 times daily) as tolerated.
A 2014 meta-analysis of 6 randomized controlled trials included 244 patients with secondary Raynaud phenomenon treated with sildenafil, tadalafil, or vardenafil.13 These drugs decreased the daily frequency of attacks by about 0.5 per day vs placebo (–0.49, 95% CI –0.71 to –0.28, P < .0001). PDE5 inhibitors also decreased the severity of attacks (based on the Raynaud’s Condition Score, a popular scoring system) and the duration of attacks by a statistically significant amount.
Almost all patients in these 6 trials were on PDE5 monotherapy. Data on the cumulative benefit of calcium channel blocker and PDE5 inhibitor combination therapy are not yet available. Not all patients tolerate combination therapy, as it can cause symptomatic hypotension, but it can be a successful option in some.
There are also no data showing that either calcium channel blockers or PDE5 inhibitors are superior, though the former are less expensive. A small double-blind, randomized, crossover study of udenafil vs amlodipine in the treatment of secondary Raynaud phenomenon showed that both medications significantly decreased the frequency of attacks and had comparable efficacy.14
Cost and insurance coverage. We have generally been successful in obtaining coverage for this off-label use of PDE5 inhibitors, though additional effort may be required. No drug (not even a calcium channel blocker) is approved by the US Food and Drug Administration for use in Raynaud phenomenon. In our experience, a letter of appeal outlining the rationale for use and citing supporting publications can lead to successful coverage of a medication. If the drug is still not approved, the patient either pays for it out of pocket or another agent is selected. In certain circumstances, pharmaceutical companies may provide prescription assistance for compassionate use of these drugs in Raynaud phenomenon, although this also takes letter-writing, phone calls, or both on the part of the physician.
Topical nitrates
Patients who have an unsatisfactory response to calcium channel blockers with or without PDE5 inhibitors can try topical nitrates, available as sustained-release transdermal patches, tapes, creams, gels, and ointments.
Small trials have noted slight improvement in the Raynaud Condition Score15 and finger temperature16 with these therapies. Another trial noted decreased frequency of attacks and symptoms with the use of sustained-release glyceryl trinitrate patches, but use was limited by intolerable headache.17
In our experience, topical nitrates are most helpful for patients who have 1 or a few digits that are more severely affected than the others, and we reserve these drugs for this indication. Localized vasodilation can provide targeted rapid relief of more ischemic areas.
Topical nitroglycerin can be applied to the base of the ischemic digit for 6 to 12 hours. Preparations vary, and patients should be closely monitored for dose response and tolerance.
Combining a topical nitrate with a calcium channel blocker is safe, but the use of a nitrate with a PDE5 inhibitor is contraindicated due to the risk of hypotension. The use of topical nitrates may be limited by systemic side effects such as headache and flushing and a lack of benefit over time.
Other therapies
If the aforementioned agents are not tolerated or not effective, there is limited evidence that other therapies reduce the frequency and sometimes the severity of attacks. These are not first-line agents but may be tried when other options have been exhausted and symptoms persist. There are no data to support combining these therapies, but in our experience doing so may help some patients in whom drug-drug interactions are not prohibitive.
Prazosin, an alpha-1-adrenergic receptor antagonist, was reported to improve Raynaud phenomenon in 2 small studies in the 1980s, but we do not use it since better options are available. In addition, the vasoactive blood vessels involved do not have alpha-1 receptors, so there is no theoretical basis for using prazosin.18,19
Fluoxetine, a selective serotonin reuptake inhibitor, reduced the frequency and severity of attacks in a 6-week crossover study with nifedipine.20
Losartan, an angiotensin II receptor blocker, also reduced the severity and frequency of attacks when compared with nifedipine.21
Pentoxifylline, a nonselective phosphodiesterase inhibitor, showed some benefit in a trial in 11 patients with primary Raynaud.22
Atorvastatin, a lipid-lowering drug, reduced the number of digital ulcers in patients with secondary Raynaud already on first-line vasodilatory therapy, and might be added in this situation.23
Botulinum toxin A injections have some data to support their use, but evidence is based on uncontrolled case series.24 A controlled trial in scleroderma patients with severe Raynaud phenomenon found botulinum toxin to be no better than placebo.25
Prostacyclin preparations are available. Intermittent intravenous doses of prostacyclin analogues over several days can be used in resistant cases. Oral prostacyclin agents have not shown consistent benefit. New prostacyclin receptor agonists are under investigation.
Overall, we move to other options only in patients with persistent symptoms that impair quality of life, or in patients with recurrent digital ischemic lesions that have not responded to calcium channel blockers and PDE5 inhibitors or nitrates, either alone or in combination.
DIGITAL ULCERATION AND ACUTE DIGITAL ISCHEMIC CRISIS
Patients with secondary Raynaud phenomenon may be at risk of recurrent digital ulceration and acute digital ischemia with gangrene. These patients should be comanaged with a rheumatologist so that the underlying disease process is fully addressed. Digital ulcers should be inspected closely for signs of infection, which may require treatment with antibiotics.
Acute digital ischemia is a medical emergency and should prompt inpatient admission with warming, emotional regulation, and pain control (often with narcotics) to decrease sympathetic vasoconstriction. These patients require aggressive vasodilatory therapy to reverse the ischemic event.
A short-acting calcium channel blocker or combination therapy with a calcium channel blocker and a PDE5 inhibitor or topical nitrate should be started. If there is no benefit, then transient intravenous vasodilatory therapy with a prostacyclin (epoprostenol) or localized digital sympathectomy is used to prevent digital loss.
The endothelin receptor inhibitor bosentan has been shown to decrease recurrent digital ulcers in patients with scleroderma, and while bosentan does not decrease the frequency of Raynaud attacks, it can be used in this select group to prevent new digital ulcers.
Treatment options may be limited by insurance coverage or access to intravenous infusions.
TAKE-HOME RECOMMENDATIONS
For many patients with primary or secondary Raynaud phenomenon, nonpharmacologic interventions are all that are required to decrease the frequency of attacks and improve quality of life. The goal should not be to eliminate attacks completely, as aggressive drug treatment may cause more harm than benefit. From our perspective, the goals of treatment should be to improve quality of life and prevent ischemic complications.
Pharmacologic therapies should be added only if attacks remain poorly controlled with incapacitating symptoms, or if the patient has digital ischemic ulcers. Calcium channel blockers are first-line therapy, given proven efficacy and low cost, and should be titrated to the maximum tolerated dose before adding or substituting other agents.
Raynaud phenomenon is an overactive vascular response to cold and emotional stress that results in cutaneous color changes and sensory symptoms of the digits (Figure 1). It can occur in isolation as primary Raynaud phenomenon or secondary to another disease process. It is thought to be triggered by a heightened sympathetic vasoconstrictive response of small arteriovenous anastomoses in the fingers, toes, ears, and tip of the nose. These structures play a key role in maintaining a stable core body temperature by cutaneous thermoregulation.1
Figure 1. (A) White digits with intense vasoconstriction in Raynaud phenomenon; (B) blue digits with
hypoxemic venous stasis; (C) red digits with hyperemic reperfusion.
Secondary Raynaud phenomenon can be seen with a wide array of systemic conditions as well as environmental and drug exposures. It is a frequent feature of autoimmune rheumatic conditions such as systemic sclerosis, mixed connective tissue disease, systemic lupus erythematosus, and dermatomyositis. Less commonly, cryoproteinemias, paraneoplastic syndromes, hypothyroidism, and carpal tunnel syndrome can be associated with or cause Raynaud phenomenon. Vibratory trauma (eg, from using a jackhammer) and drugs (eg, vasopressors, stimulants, ergots, chemotherapeutic agents) can also cause Raynaud phenomenon.1
A variety of disorders that cause vasospasm or vascular occlusion of the peripheral circulation can mimic typical Raynaud phenomenon, including peripheral nerve injury,2 complex regional pain syndrome,3 occlusive vascular disease, vasculitis, acrocyanosis,4 and thoracic outlet syndrome.
The prevalence of Raynaud phenomenon is not exactly known, in part due to geographic differences in climate and variation in methods of assessment. However, a 2015 systematic review and meta-analysis of primary Raynaud phenomenon determined a pooled prevalence of 4.85% (95% confidence interval [CI] 2.08%–8.71%) in the general population.5 Accordingly, accurate identification and management of this condition is a useful skill for the internist.
COLD SENSITIVITY AND COLOR CHANGES
Because there are no confirmatory diagnostic tests for this condition, there are no formal diagnostic criteria. However, many experts agree that Raynaud phenomenon can be diagnosed clinically when patients report:
Unusual sensitivity of the fingers to cold, manifesting as pain or paresthesia (eg, tingling, pricking, numbness), and
Color changes of the fingers when exposed to cold, specifically pale white or blue-black, or both.6
Provocative testing such as submerging patients’ hands in cold water is not recommended, as it is distressing to the patient and inconsistent in triggering an event.
Pain is a symptom of critical digital ischemia.
The skin color changes are due to rapid alterations in blood flow in digital skin. The pale white is due to markedly reduced or absent flow secondary to intense vasoconstriction, the blue-black is due to hypoxemic venous stasis, and the red blush is due to hyperemic reperfusion (Figure 1). However, not all patients have all 3 phases of the classic triphasic color changes, and color changes may not follow a set sequence.
Raynaud phenomenon can also occur in other areas of the body that have thermoregulatory vessels, such as the toes, ears, nipples, tongue, and nose. While some patients with Raynaud phenomenon have a finger that is more sensitive than the others, repeated isolated single-digit or asymmetric events without typical progression to all fingers suggest a secondary local structural disease requiring further investigation (see below).
Symptoms related to Raynaud often mimic sensory changes including paresthesias, numbness, aching, and clumsiness of the hand. Abnormal vascular reactivity has been implicated as a causative factor in several disorders, such as migraine headache, preeclampsia, and variant angina. While case reports, case series, and some controlled studies have linked Raynaud phenomenon and these conditions, there is no solid evidence of a systemic vasospastic disorder in patients with primary Raynaud phenomenon.
Raynaud phenomenon is triggered by more than just a cold ambient temperature. Provocation can occur during movement from warmer to relatively cooler temperatures, as well as during episodes of elevated sympathetic activity (eg, emotional distress or fear). In fact, maintaining full body warmth as well as emotional equilibrium are the most important strategies to reduce the frequency of attacks.
PRIMARY VS SECONDARY RAYNAUD PHENOMENON
To distinguish between primary and secondary Raynaud phenomenon, a careful history and physical examination are paramount.
Primary Raynaud phenomenon
In uncomplicated primary Raynaud phenomenon, the episodes typically last 15 to 20 minutes after rewarming and usually start in a single finger and spread to other digits symmetrically and bilaterally.7 The thumb is often spared, and ischemic digital ulcers do not occur. Vasoconstrictive episodes are mild.
Females under age 20 are most commonly affected. In our experience, a young woman with the above clinical picture, no signs or symptoms suggestive of connective tissue disease (see below), and normal nailfold capillaries can be diagnosed as having primary Raynaud phenomenon without any further workup.
Careful clinical follow-up is recommended, because if an occult secondary process is indeed present, most patients will begin to show additional symptoms or signs of it within 2 years of the onset of Raynaud phenomenon.
Should a clinician be unfamiliar with nailfold capillary examination, or if symptoms (eg, fatigue or arthralgia) or signs (eg, rash, arthritis) suggestive of connective tissue disease are present, referral to a rheumatologist for further evaluation is appropriate. Results of further diagnostic testing dictated by the history and physical such as a screening antinuclear antibody test can be sent before referral.
Secondary Raynaud phenomenon
Several clinical features suggest secondary Raynaud phenomenon and warrant referral to a rheumatologist:
Age 20 or older at onset
Frequent severe vasoconstrictive episodes
Male sex
Thumb involvement
Figure 2. (A) Dilated nailfold capillaries in a patient with scleroderma (blue arrow); (B) dilation and dropout of nailfold capillaries (white arrow) viewed with a magnifier.Signs of an autoimmune rheumatic disease, eg, sclerodactyly, cutaneous or mucosal matted telangiectasia, inflammatory arthritis, an abnormal lung examination, severe digital ischemia with ulceration or gangrene, or nailfold capillary dilation or dropout (Figure 2)8
Isolated single-limb or 1-finger ischemic events, seen in macrovascular occlusive disease or inflammatory disease mimicking Raynaud phenomenon (eg, atherosclerosis, vasculitis); when isolated acute ischemic events occur in the upper or lower extremity, a further workup is necessary.
Figure 3 shows our approach to evaluation.
NONPHARMACOLOGIC THERAPY
Figure 3. Our approach to diagnosis of Raynaud phenomenon and differentiating primary from secondary Raynaud phenomenon.
Cold avoidance and stress management are first-line therapies for preventing Raynaud attacks and must be part of any treatment strategy. Digital arteries and thermoregulatory vessels of the skin are predominantly under sympathetic adrenergic control, so temperature changes and emotional stressors trigger vasoconstriction. Patients should be counseled to:
Keep the whole body warm. Patients should wear multiple layers of clothing, a hat, warm gloves, and warm socks. Commercially available hand-warmers can help, especially for patients who live in cold climates.
Learn to avoid or manage stress. Good communication, attention to the patient’s needs, and regular follow-up for reassurance are paramount. For some patients, psychotropic medications to manage mood may help. Behavioral approaches have been suggested for acute stress management. One approach, autogenic training, is a form of relaxation with temperature biofeedback in which finger temperature data are provided to patients to help them learn to relax by monitoring their internal states and changes in temperature. However, there are no strong data to support the routine use of this technique or the use of one behavioral approach over another. Trials have generally been of low quality and limited by small sample size.9
Stop smoking!10
Stop a Raynaud attack should one occur, eg, place the hands under warm water or in a warm part of the body, such as under legs when sitting. This can help speed recovery.
In addition, the physician should:
Eliminate vasoconstricting agents such as nonselective beta-blockers, ergots, triptans, and amphetamines.
PHARMACOLOGIC THERAPY
For many patients, nonpharmacologic interventions are enough to decrease the severity and frequency of attacks. However, if Raynaud phenomenon continues to negatively affect quality of life, drug therapy can be added (Table 1).
Calcium channel blockers
Calcium channel blockers are first-line agents for both primary and secondary Raynaud phenomenon that does not adequately respond to nonpharmacologic interventions. These agents are effective, available, and reasonably inexpensive.
Dihydropyridine calcium channel blockers such as nifedipine and amlodipine are commonly used. Both drugs are acceptable options, though some patients may respond better to one than the other in terms of symptoms and side effects. Nondihydropyridines such as diltiazem can also be used, but they have less potent vasodilatory effects because they are less selective for vascular smooth muscle.
These medications should be started at the lowest dose and titrated up over several weeks as tolerated to achieve their maximal effect. Intermittent therapy (eg, during the winter months only) is reasonable for primary Raynaud without risk of digital ulceration, as relief of symptoms and improvement in quality of life are the main indications for therapy in this circumstance.
A 2016 Cochrane review and meta-analysis of the use of calcium channel blockers to treat primary Raynaud phenomenon included 7 randomized controlled trials with 296 patients treated with either nifedipine or nicardipine.11 There was moderate-quality evidence that these drugs minimally decreased the frequency of attacks (standardized mean difference of 0.23; 95% CI 0.08–0.38, P = .003). This translated to 1.72 fewer attacks per week with treatment than with no pharmacologic therapy (95% CI 0.60–2.84). When analyzed individually, only nifedipine was effective; nicardipine did not decrease the frequency of attacks.
Unfortunately, calcium channel blockers failed to decrease the severity of attacks (according to unvalidated severity scoring systems) or make any differences in physiologic measurement outcomes. Attacks were not completely eliminated, just less frequent than before treatment.11
Most commonly reported side effects included headache, flushing, hypotension, edema, and, rarely, gastrointestinal reflux. Use of these medications may be limited by hypotension.
The review was limited by the small sample size, short duration of treatment, and relatively low doses of calcium channel blockers used in the available studies.11
A 2005 meta-analysis also indicated a statistically significant decrease of 2.8 to 5 attacks per week with nifedipine treatment, though this study also included some patients with secondary Raynaud phenomenon.12
Phosphodiesterase type 5 inhibitors
When calcium channel blockers do not adequately control symptoms, phosphodiesterase type 5 (PDE5) inhibitors can be added or substituted. These medications work by preventing breakdown of cyclic guanosine monophosphate, which induces relaxation in vascular smooth muscle and vasodilation.
Sildenafil can be started at a low dose (20 mg daily) and up-titrated to the maximum dose (20 mg 3 times daily) as tolerated.
A 2014 meta-analysis of 6 randomized controlled trials included 244 patients with secondary Raynaud phenomenon treated with sildenafil, tadalafil, or vardenafil.13 These drugs decreased the daily frequency of attacks by about 0.5 per day vs placebo (–0.49, 95% CI –0.71 to –0.28, P < .0001). PDE5 inhibitors also decreased the severity of attacks (based on the Raynaud’s Condition Score, a popular scoring system) and the duration of attacks by a statistically significant amount.
Almost all patients in these 6 trials were on PDE5 monotherapy. Data on the cumulative benefit of calcium channel blocker and PDE5 inhibitor combination therapy are not yet available. Not all patients tolerate combination therapy, as it can cause symptomatic hypotension, but it can be a successful option in some.
There are also no data showing that either calcium channel blockers or PDE5 inhibitors are superior, though the former are less expensive. A small double-blind, randomized, crossover study of udenafil vs amlodipine in the treatment of secondary Raynaud phenomenon showed that both medications significantly decreased the frequency of attacks and had comparable efficacy.14
Cost and insurance coverage. We have generally been successful in obtaining coverage for this off-label use of PDE5 inhibitors, though additional effort may be required. No drug (not even a calcium channel blocker) is approved by the US Food and Drug Administration for use in Raynaud phenomenon. In our experience, a letter of appeal outlining the rationale for use and citing supporting publications can lead to successful coverage of a medication. If the drug is still not approved, the patient either pays for it out of pocket or another agent is selected. In certain circumstances, pharmaceutical companies may provide prescription assistance for compassionate use of these drugs in Raynaud phenomenon, although this also takes letter-writing, phone calls, or both on the part of the physician.
Topical nitrates
Patients who have an unsatisfactory response to calcium channel blockers with or without PDE5 inhibitors can try topical nitrates, available as sustained-release transdermal patches, tapes, creams, gels, and ointments.
Small trials have noted slight improvement in the Raynaud Condition Score15 and finger temperature16 with these therapies. Another trial noted decreased frequency of attacks and symptoms with the use of sustained-release glyceryl trinitrate patches, but use was limited by intolerable headache.17
In our experience, topical nitrates are most helpful for patients who have 1 or a few digits that are more severely affected than the others, and we reserve these drugs for this indication. Localized vasodilation can provide targeted rapid relief of more ischemic areas.
Topical nitroglycerin can be applied to the base of the ischemic digit for 6 to 12 hours. Preparations vary, and patients should be closely monitored for dose response and tolerance.
Combining a topical nitrate with a calcium channel blocker is safe, but the use of a nitrate with a PDE5 inhibitor is contraindicated due to the risk of hypotension. The use of topical nitrates may be limited by systemic side effects such as headache and flushing and a lack of benefit over time.
Other therapies
If the aforementioned agents are not tolerated or not effective, there is limited evidence that other therapies reduce the frequency and sometimes the severity of attacks. These are not first-line agents but may be tried when other options have been exhausted and symptoms persist. There are no data to support combining these therapies, but in our experience doing so may help some patients in whom drug-drug interactions are not prohibitive.
Prazosin, an alpha-1-adrenergic receptor antagonist, was reported to improve Raynaud phenomenon in 2 small studies in the 1980s, but we do not use it since better options are available. In addition, the vasoactive blood vessels involved do not have alpha-1 receptors, so there is no theoretical basis for using prazosin.18,19
Fluoxetine, a selective serotonin reuptake inhibitor, reduced the frequency and severity of attacks in a 6-week crossover study with nifedipine.20
Losartan, an angiotensin II receptor blocker, also reduced the severity and frequency of attacks when compared with nifedipine.21
Pentoxifylline, a nonselective phosphodiesterase inhibitor, showed some benefit in a trial in 11 patients with primary Raynaud.22
Atorvastatin, a lipid-lowering drug, reduced the number of digital ulcers in patients with secondary Raynaud already on first-line vasodilatory therapy, and might be added in this situation.23
Botulinum toxin A injections have some data to support their use, but evidence is based on uncontrolled case series.24 A controlled trial in scleroderma patients with severe Raynaud phenomenon found botulinum toxin to be no better than placebo.25
Prostacyclin preparations are available. Intermittent intravenous doses of prostacyclin analogues over several days can be used in resistant cases. Oral prostacyclin agents have not shown consistent benefit. New prostacyclin receptor agonists are under investigation.
Overall, we move to other options only in patients with persistent symptoms that impair quality of life, or in patients with recurrent digital ischemic lesions that have not responded to calcium channel blockers and PDE5 inhibitors or nitrates, either alone or in combination.
DIGITAL ULCERATION AND ACUTE DIGITAL ISCHEMIC CRISIS
Patients with secondary Raynaud phenomenon may be at risk of recurrent digital ulceration and acute digital ischemia with gangrene. These patients should be comanaged with a rheumatologist so that the underlying disease process is fully addressed. Digital ulcers should be inspected closely for signs of infection, which may require treatment with antibiotics.
Acute digital ischemia is a medical emergency and should prompt inpatient admission with warming, emotional regulation, and pain control (often with narcotics) to decrease sympathetic vasoconstriction. These patients require aggressive vasodilatory therapy to reverse the ischemic event.
A short-acting calcium channel blocker or combination therapy with a calcium channel blocker and a PDE5 inhibitor or topical nitrate should be started. If there is no benefit, then transient intravenous vasodilatory therapy with a prostacyclin (epoprostenol) or localized digital sympathectomy is used to prevent digital loss.
The endothelin receptor inhibitor bosentan has been shown to decrease recurrent digital ulcers in patients with scleroderma, and while bosentan does not decrease the frequency of Raynaud attacks, it can be used in this select group to prevent new digital ulcers.
Treatment options may be limited by insurance coverage or access to intravenous infusions.
TAKE-HOME RECOMMENDATIONS
For many patients with primary or secondary Raynaud phenomenon, nonpharmacologic interventions are all that are required to decrease the frequency of attacks and improve quality of life. The goal should not be to eliminate attacks completely, as aggressive drug treatment may cause more harm than benefit. From our perspective, the goals of treatment should be to improve quality of life and prevent ischemic complications.
Pharmacologic therapies should be added only if attacks remain poorly controlled with incapacitating symptoms, or if the patient has digital ischemic ulcers. Calcium channel blockers are first-line therapy, given proven efficacy and low cost, and should be titrated to the maximum tolerated dose before adding or substituting other agents.
References
Wigley FM, Flavahan NA. Raynaud’s phenomenon. N Engl J Med 2016; 375:556–565.
Irwin MS, Gilbert SE, Terenghi G, Smith RW, Green CJ. Cold intolerance following peripheral nerve injury. Natural history and factors predicting severity of symptoms. J Hand Surg Br 1997; 22:308–316.
Wasner G. Vasomotor disturbances in complex regional pain syndrome—a review. Pain Med 2010; 11:1267–1273.
Kurklinsky AK, Miller VM, Rooke TW. Acrocyanosis: the Flying Dutchman. Vasc Med 2011; 16:288–301.
Garner R, Kumari R, Lanyon P, Doherty M, Zhang W. Prevalence, risk factors and associations of primary Raynaud’s phenomenon: systematic review and meta-analysis of observational studies. BMJ Open 2015; 5:e006389.
Wigley FM. Clinical practice. Raynaud’s phenomenon. N Engl J Med 2002; 347:1001–1008.
Chikura B, Moore TL, Manning JB, Vail A, Herrick AL. Sparing of the thumb in Raynaud’s phenomenon. Rheumatology (Oxford) 2008; 47:219–221.
Kallenerg CG. Early detection of connective tissue disease in patients with Raynaud’s phenomenon. Rheum Dis Clin North Am 1990; 16:11–30.
Kwakkenbos L, Thombs BD. Non-drug approaches to treating Raynaud’s phenomenon. In: Wigley FM, Herrick AL, Flavahan NA, editors. Raynaud’s Phenomenon. A Guide to Pathogenesis and Treatment. New York: Springer Science+Business Media, 2015:299–313.
Goodfield MJ, Hume A, Rowell NR. The acute effects of cigarette smoking on cutaneous blood flow in smoking and non-smoking subjects with and without Raynaud’s phenomenon. Br J Rheumatol 1990; 29:89–91.
Ennis H, Hughes M, Anderson ME, Wilkinson J, Herrick AL. Calcium channel blockers for primary Raynaud’s phenomenon. Cochrane Database Sys Review 2016; 2:CD002069.
Thompson AE, Pope JE. Calcium channel blockers for primary Raynaud’s phenomenon: a meta-analysis. Rheumatology (Oxford) 2005; 44:145–150.
Roustit M, Blaise S, Allanore Y, Carpentier P, Caglayan E, Cracowski J. Phosphodiesterase-5 inhibitors for the treatment of secondary Raynaud’s phenomenon: systematic review and meta-analysis of randomized trials. Ann Rheum Dis 2013; 72:1696–1699.
Lee EY, Park JK, Lee W, et al. Head-to-head comparison of udenafil vs amlodipine in the treatment of secondary Raynaud's phenomenon: a double-blind, randomized, cross-over study. Rheumatology (Oxford) 2014; 53:658–664.
Chung L, Shapiro L, Fiorentino D, et al. MQX-503, a novel formulation of nitroglycerin, improves the severity of Raynaud’s phenomenon: a randomized, controlled trial. Arthritis Rheum 2009; 60:870–877.
Kan C, Akimoto S, Abe M, Okada K, Ishikawa O. Preliminary thermographic evaluation of a new nitroglycerine tape on the peripheral circulatory disturbance in systemic sclerosis. Ann Rheum Dis 2002; 61:177–179.
Teh LS, Manning J, Moore T, Tully MP, O’Reilly D, Jayson MI. Sustained-release transdermal glyceryl trinitrate patches as a treatment for primary and secondary Raynaud’s phenomenon. Br J Rheumatol 1995; 34:636–641.
Russell IJ, Lessard JA. Prazosin treatment of Raynaud’s phenomenon: a double blind single crossover study. J Rheumatol 1985; 12:94–98.
Wollersheim H, Thien T, Fennis J, van Elteren P, van ‘t Laar A. Double-blind, placebo-controlled study of prazosin in Raynaud’s phenomenon. Clin Pharmacol Ther 1986; 40:219–225.
Coleiro B, Marshall SE, Denton CP, et al. Treatment of Raynaud’s phenomenon with the selective serotonin reuptake inhibitor fluoxetine. Rheumatology (Oxford) 2001; 40:1038–1043.
Didazio M, Denton CP, Smith R, et al. Losartan therapy for Raynaud’s phenomenon and scleroderma: clinical and biochemical findings in a fifteen-week randomized, parallel-group, controlled trial. Arthritis Rheum 1999; 42:2646–2655.
Neirotti M, Longo F, Molaschi M, Macchione C, Pernigotti L. Functional vascular disorders: treatment with pentoxifylline. Angiology 1987; 38:575–580.
Abou-Raya A, Abou-Raya S, Helmii M. Statins: potentially useful in therapy of systemic sclerosis-related Raynaud’s phenomenon and digital ulcers. J Rheumatol 2008; 35:1801–1808.
Iorio ML, Masden DL, Higgins JP. Botulinum toxin A treatment of Raynaud’s phenomenon: a review. Semin Arthritis Rheum 2012; 41: 599–603.
Bello RJ, Cooney CM, Melamed E, et al. The therapeutic efficacy of botulinum toxin in treating scleroderma-associated Raynaud’s phenomenon: a randomized, double-blind, placebo-controlled clinical trial. Arthritis Rheumatol 2017. Epub ahead of print.
References
Wigley FM, Flavahan NA. Raynaud’s phenomenon. N Engl J Med 2016; 375:556–565.
Irwin MS, Gilbert SE, Terenghi G, Smith RW, Green CJ. Cold intolerance following peripheral nerve injury. Natural history and factors predicting severity of symptoms. J Hand Surg Br 1997; 22:308–316.
Wasner G. Vasomotor disturbances in complex regional pain syndrome—a review. Pain Med 2010; 11:1267–1273.
Kurklinsky AK, Miller VM, Rooke TW. Acrocyanosis: the Flying Dutchman. Vasc Med 2011; 16:288–301.
Garner R, Kumari R, Lanyon P, Doherty M, Zhang W. Prevalence, risk factors and associations of primary Raynaud’s phenomenon: systematic review and meta-analysis of observational studies. BMJ Open 2015; 5:e006389.
Wigley FM. Clinical practice. Raynaud’s phenomenon. N Engl J Med 2002; 347:1001–1008.
Chikura B, Moore TL, Manning JB, Vail A, Herrick AL. Sparing of the thumb in Raynaud’s phenomenon. Rheumatology (Oxford) 2008; 47:219–221.
Kallenerg CG. Early detection of connective tissue disease in patients with Raynaud’s phenomenon. Rheum Dis Clin North Am 1990; 16:11–30.
Kwakkenbos L, Thombs BD. Non-drug approaches to treating Raynaud’s phenomenon. In: Wigley FM, Herrick AL, Flavahan NA, editors. Raynaud’s Phenomenon. A Guide to Pathogenesis and Treatment. New York: Springer Science+Business Media, 2015:299–313.
Goodfield MJ, Hume A, Rowell NR. The acute effects of cigarette smoking on cutaneous blood flow in smoking and non-smoking subjects with and without Raynaud’s phenomenon. Br J Rheumatol 1990; 29:89–91.
Ennis H, Hughes M, Anderson ME, Wilkinson J, Herrick AL. Calcium channel blockers for primary Raynaud’s phenomenon. Cochrane Database Sys Review 2016; 2:CD002069.
Thompson AE, Pope JE. Calcium channel blockers for primary Raynaud’s phenomenon: a meta-analysis. Rheumatology (Oxford) 2005; 44:145–150.
Roustit M, Blaise S, Allanore Y, Carpentier P, Caglayan E, Cracowski J. Phosphodiesterase-5 inhibitors for the treatment of secondary Raynaud’s phenomenon: systematic review and meta-analysis of randomized trials. Ann Rheum Dis 2013; 72:1696–1699.
Lee EY, Park JK, Lee W, et al. Head-to-head comparison of udenafil vs amlodipine in the treatment of secondary Raynaud's phenomenon: a double-blind, randomized, cross-over study. Rheumatology (Oxford) 2014; 53:658–664.
Chung L, Shapiro L, Fiorentino D, et al. MQX-503, a novel formulation of nitroglycerin, improves the severity of Raynaud’s phenomenon: a randomized, controlled trial. Arthritis Rheum 2009; 60:870–877.
Kan C, Akimoto S, Abe M, Okada K, Ishikawa O. Preliminary thermographic evaluation of a new nitroglycerine tape on the peripheral circulatory disturbance in systemic sclerosis. Ann Rheum Dis 2002; 61:177–179.
Teh LS, Manning J, Moore T, Tully MP, O’Reilly D, Jayson MI. Sustained-release transdermal glyceryl trinitrate patches as a treatment for primary and secondary Raynaud’s phenomenon. Br J Rheumatol 1995; 34:636–641.
Russell IJ, Lessard JA. Prazosin treatment of Raynaud’s phenomenon: a double blind single crossover study. J Rheumatol 1985; 12:94–98.
Wollersheim H, Thien T, Fennis J, van Elteren P, van ‘t Laar A. Double-blind, placebo-controlled study of prazosin in Raynaud’s phenomenon. Clin Pharmacol Ther 1986; 40:219–225.
Coleiro B, Marshall SE, Denton CP, et al. Treatment of Raynaud’s phenomenon with the selective serotonin reuptake inhibitor fluoxetine. Rheumatology (Oxford) 2001; 40:1038–1043.
Didazio M, Denton CP, Smith R, et al. Losartan therapy for Raynaud’s phenomenon and scleroderma: clinical and biochemical findings in a fifteen-week randomized, parallel-group, controlled trial. Arthritis Rheum 1999; 42:2646–2655.
Neirotti M, Longo F, Molaschi M, Macchione C, Pernigotti L. Functional vascular disorders: treatment with pentoxifylline. Angiology 1987; 38:575–580.
Abou-Raya A, Abou-Raya S, Helmii M. Statins: potentially useful in therapy of systemic sclerosis-related Raynaud’s phenomenon and digital ulcers. J Rheumatol 2008; 35:1801–1808.
Iorio ML, Masden DL, Higgins JP. Botulinum toxin A treatment of Raynaud’s phenomenon: a review. Semin Arthritis Rheum 2012; 41: 599–603.
Bello RJ, Cooney CM, Melamed E, et al. The therapeutic efficacy of botulinum toxin in treating scleroderma-associated Raynaud’s phenomenon: a randomized, double-blind, placebo-controlled clinical trial. Arthritis Rheumatol 2017. Epub ahead of print.
Primary Raynaud phenomenon occurs in the absence of any underlying disease process. Secondary Raynaud phenomenon occurs in concert with another disease, frequently rheumatic.
Young patients with mild Raynaud phenomenon, normal nailfold capillaries, and no additional symptoms or signs to suggest a rheumatic or other underlying disease can be followed carefully by the primary care doctor and do not require further serologic workup or referral to a specialist.
Nonpharmacologic interventions, ie, cold avoidance and stress management, are first-line for all patients.
Calcium channel blockers are first-line drugs and should be titrated to the maximum tolerated dose before adding or switching to other agents.
The goal of treatment should not be to eliminate Raynaud attacks completely but to improve quality of life and prevent ischemic complications.
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For practitioners who see a lot of patients, particularly a lot of young women, patients describing cold-induced color changes of the fingers sometimes accompanied by tingling or burning are common. For most patients it is mild, but for some the discoloration or dysesthesia may be striking and disconcerting. For a minority, this reversible vasoconstrictive phenomenon (Raynaud “disease” if it occurs in isolation, without any associated underlying condition) may be the presenting sign of a systemic disorder.
For many patients, Raynaud symptoms are mild enough to not even mention to their primary care provider, and conversely, there is little reason for most clinicians to routinely inquire about such symptoms. So it may surprise some readers to read about the nuances of diagnosis and treatment discussed by Shapiro and Wigley in this issue of the Journal.
To a rheumatologist, Raynaud phenomenon, particularly of recent onset in an adult, raises the specter of an underlying systemic inflammatory disease. The phenomenon is not linked to a specific diagnosis; it is associated with lupus, rheumatoid arthritis, cryoglobulinemia, inflammatory myopathy, Sjögren syndrome, and, in its severe form, with the scleroderma syndromes. We focus on differentiating between these rheumatic disorders once we have discarded nonrheumatic causes such as atherosclerotic arterial disease, carcinoma, embolism, Buerger disease, medications, smoking, or thrombosis.
But rheumatologists are toward the bottom of the diagnostic funnel—we see these patients when an underlying disease is already suspected. The real challenge is for the primary care providers who first recognize the digital vasospasm on examination or are told of the symptoms by their patient. These clinicians need to know which initial reflexive actions are warranted and which can wait, for, as noted by Shapiro and Wigley, there are several options.
The first action is to try to determine the timeline, although Raynaud disease often has an insidious onset or the patient doesn’t recall the onset. New and sudden onset likely has a stronger association with an underlying disease. A focused physical examination should look for digital stigmata of ischemic damage; the presence of digital ulcers or healed digital pits indicates a possible vascular occlusive component in addition to the vascular spasm. This strongly suggests scleroderma or Buerger disease, as tissue damage doesn’t occur in (primary) Raynaud disease or generally even with Raynaud phenomenon associated with lupus or other rheumatic disorders. Sclerodactyly should be looked for: diffuse finger puffiness, skin-tightening, or early signs such as loss of the usual finger skin creases. Telangiectasia (not vascular spiders or cherry angiomata) should be searched for, particularly on the palms, face, and inner lips, as these vascular lesions are common in patients with limited scleroderma. Careful auscultation for basilar lung crackles should be done. Distal pulses should all be assessed, and bruits in the neck, abdomen and inguinal areas should be carefully sought.
Patients should be questioned about any symptom-associated reduction in exercise tolerance and particularly about trouble swallowing, “heartburn,” and symptoms of reflux. Although patients with Raynaud disease may have demonstrable esophageal dysmotility, the presence of significant, new, or worsened symptoms raises the concern of scleroderma. Patients should be asked about symptoms of malabsorption. Specific questioning should be directed at eliciting a history of joint stiffness and especially muscle weakness. The latter can be approached by inquiring about new or progressive difficulty in specific tasks such as walking up steps, brushing hair, and arising from low chairs or the toilet. Distinguishing muscle weakness from general fatigue is not always easy, but it is important.
Shapiro and Wigley discuss the extremely useful evaluation of nailfold capillaries, which can be done with a standard magnifier or ophthalmoscope. This is very valuable to help predict the development or current presence of a systemic rheumatic disease. But this is not a technique that most clinicians are familiar with. A potentially useful surrogate or adjunctive test, especially in the setting of new-onset Raynaud, is the antinuclear antibody (ANA) test; I prefer the immunofluorescent assay. While a positive test alone (with Raynaud) does not define the presence of any rheumatic disease, several older studies suggest that patients with a new onset of Raynaud phenomenon and a positive ANA test are more likely to develop a systemic autoimmune disorder than if the test is negative. Those who do so (and this is far from all) are most likely to have the disease manifest within a few years. Hence, if the ANA test is positive but the history, physical examination, and limited laboratory testing (complete blood cell count with differential, complete metabolic panel, creatine kinase, and urinalysis) are normal, it is reasonable to reexamine the patient in 3 months and then every 6 months for 2 to 3 years, repeating the focused history and physical examination. It is also reasonable at some point to refer these patients to a rheumatologist.
Since Raynaud phenomenon is common, and the associated severe rheumatic disorders associated with it are rare, it is easy to not recognize Raynaud phenomenon as a clue to the onset of a potentially severe systemic disease. Yet with a few simple questions, a focused examination, and minimal laboratory testing, patients who are more likely to harbor a systemic disease can usually be treated symptomatically if necessary, and appropriately triaged to observation or for subspecialty referral.
For practitioners who see a lot of patients, particularly a lot of young women, patients describing cold-induced color changes of the fingers sometimes accompanied by tingling or burning are common. For most patients it is mild, but for some the discoloration or dysesthesia may be striking and disconcerting. For a minority, this reversible vasoconstrictive phenomenon (Raynaud “disease” if it occurs in isolation, without any associated underlying condition) may be the presenting sign of a systemic disorder.
For many patients, Raynaud symptoms are mild enough to not even mention to their primary care provider, and conversely, there is little reason for most clinicians to routinely inquire about such symptoms. So it may surprise some readers to read about the nuances of diagnosis and treatment discussed by Shapiro and Wigley in this issue of the Journal.
To a rheumatologist, Raynaud phenomenon, particularly of recent onset in an adult, raises the specter of an underlying systemic inflammatory disease. The phenomenon is not linked to a specific diagnosis; it is associated with lupus, rheumatoid arthritis, cryoglobulinemia, inflammatory myopathy, Sjögren syndrome, and, in its severe form, with the scleroderma syndromes. We focus on differentiating between these rheumatic disorders once we have discarded nonrheumatic causes such as atherosclerotic arterial disease, carcinoma, embolism, Buerger disease, medications, smoking, or thrombosis.
But rheumatologists are toward the bottom of the diagnostic funnel—we see these patients when an underlying disease is already suspected. The real challenge is for the primary care providers who first recognize the digital vasospasm on examination or are told of the symptoms by their patient. These clinicians need to know which initial reflexive actions are warranted and which can wait, for, as noted by Shapiro and Wigley, there are several options.
The first action is to try to determine the timeline, although Raynaud disease often has an insidious onset or the patient doesn’t recall the onset. New and sudden onset likely has a stronger association with an underlying disease. A focused physical examination should look for digital stigmata of ischemic damage; the presence of digital ulcers or healed digital pits indicates a possible vascular occlusive component in addition to the vascular spasm. This strongly suggests scleroderma or Buerger disease, as tissue damage doesn’t occur in (primary) Raynaud disease or generally even with Raynaud phenomenon associated with lupus or other rheumatic disorders. Sclerodactyly should be looked for: diffuse finger puffiness, skin-tightening, or early signs such as loss of the usual finger skin creases. Telangiectasia (not vascular spiders or cherry angiomata) should be searched for, particularly on the palms, face, and inner lips, as these vascular lesions are common in patients with limited scleroderma. Careful auscultation for basilar lung crackles should be done. Distal pulses should all be assessed, and bruits in the neck, abdomen and inguinal areas should be carefully sought.
Patients should be questioned about any symptom-associated reduction in exercise tolerance and particularly about trouble swallowing, “heartburn,” and symptoms of reflux. Although patients with Raynaud disease may have demonstrable esophageal dysmotility, the presence of significant, new, or worsened symptoms raises the concern of scleroderma. Patients should be asked about symptoms of malabsorption. Specific questioning should be directed at eliciting a history of joint stiffness and especially muscle weakness. The latter can be approached by inquiring about new or progressive difficulty in specific tasks such as walking up steps, brushing hair, and arising from low chairs or the toilet. Distinguishing muscle weakness from general fatigue is not always easy, but it is important.
Shapiro and Wigley discuss the extremely useful evaluation of nailfold capillaries, which can be done with a standard magnifier or ophthalmoscope. This is very valuable to help predict the development or current presence of a systemic rheumatic disease. But this is not a technique that most clinicians are familiar with. A potentially useful surrogate or adjunctive test, especially in the setting of new-onset Raynaud, is the antinuclear antibody (ANA) test; I prefer the immunofluorescent assay. While a positive test alone (with Raynaud) does not define the presence of any rheumatic disease, several older studies suggest that patients with a new onset of Raynaud phenomenon and a positive ANA test are more likely to develop a systemic autoimmune disorder than if the test is negative. Those who do so (and this is far from all) are most likely to have the disease manifest within a few years. Hence, if the ANA test is positive but the history, physical examination, and limited laboratory testing (complete blood cell count with differential, complete metabolic panel, creatine kinase, and urinalysis) are normal, it is reasonable to reexamine the patient in 3 months and then every 6 months for 2 to 3 years, repeating the focused history and physical examination. It is also reasonable at some point to refer these patients to a rheumatologist.
Since Raynaud phenomenon is common, and the associated severe rheumatic disorders associated with it are rare, it is easy to not recognize Raynaud phenomenon as a clue to the onset of a potentially severe systemic disease. Yet with a few simple questions, a focused examination, and minimal laboratory testing, patients who are more likely to harbor a systemic disease can usually be treated symptomatically if necessary, and appropriately triaged to observation or for subspecialty referral.
For practitioners who see a lot of patients, particularly a lot of young women, patients describing cold-induced color changes of the fingers sometimes accompanied by tingling or burning are common. For most patients it is mild, but for some the discoloration or dysesthesia may be striking and disconcerting. For a minority, this reversible vasoconstrictive phenomenon (Raynaud “disease” if it occurs in isolation, without any associated underlying condition) may be the presenting sign of a systemic disorder.
For many patients, Raynaud symptoms are mild enough to not even mention to their primary care provider, and conversely, there is little reason for most clinicians to routinely inquire about such symptoms. So it may surprise some readers to read about the nuances of diagnosis and treatment discussed by Shapiro and Wigley in this issue of the Journal.
To a rheumatologist, Raynaud phenomenon, particularly of recent onset in an adult, raises the specter of an underlying systemic inflammatory disease. The phenomenon is not linked to a specific diagnosis; it is associated with lupus, rheumatoid arthritis, cryoglobulinemia, inflammatory myopathy, Sjögren syndrome, and, in its severe form, with the scleroderma syndromes. We focus on differentiating between these rheumatic disorders once we have discarded nonrheumatic causes such as atherosclerotic arterial disease, carcinoma, embolism, Buerger disease, medications, smoking, or thrombosis.
But rheumatologists are toward the bottom of the diagnostic funnel—we see these patients when an underlying disease is already suspected. The real challenge is for the primary care providers who first recognize the digital vasospasm on examination or are told of the symptoms by their patient. These clinicians need to know which initial reflexive actions are warranted and which can wait, for, as noted by Shapiro and Wigley, there are several options.
The first action is to try to determine the timeline, although Raynaud disease often has an insidious onset or the patient doesn’t recall the onset. New and sudden onset likely has a stronger association with an underlying disease. A focused physical examination should look for digital stigmata of ischemic damage; the presence of digital ulcers or healed digital pits indicates a possible vascular occlusive component in addition to the vascular spasm. This strongly suggests scleroderma or Buerger disease, as tissue damage doesn’t occur in (primary) Raynaud disease or generally even with Raynaud phenomenon associated with lupus or other rheumatic disorders. Sclerodactyly should be looked for: diffuse finger puffiness, skin-tightening, or early signs such as loss of the usual finger skin creases. Telangiectasia (not vascular spiders or cherry angiomata) should be searched for, particularly on the palms, face, and inner lips, as these vascular lesions are common in patients with limited scleroderma. Careful auscultation for basilar lung crackles should be done. Distal pulses should all be assessed, and bruits in the neck, abdomen and inguinal areas should be carefully sought.
Patients should be questioned about any symptom-associated reduction in exercise tolerance and particularly about trouble swallowing, “heartburn,” and symptoms of reflux. Although patients with Raynaud disease may have demonstrable esophageal dysmotility, the presence of significant, new, or worsened symptoms raises the concern of scleroderma. Patients should be asked about symptoms of malabsorption. Specific questioning should be directed at eliciting a history of joint stiffness and especially muscle weakness. The latter can be approached by inquiring about new or progressive difficulty in specific tasks such as walking up steps, brushing hair, and arising from low chairs or the toilet. Distinguishing muscle weakness from general fatigue is not always easy, but it is important.
Shapiro and Wigley discuss the extremely useful evaluation of nailfold capillaries, which can be done with a standard magnifier or ophthalmoscope. This is very valuable to help predict the development or current presence of a systemic rheumatic disease. But this is not a technique that most clinicians are familiar with. A potentially useful surrogate or adjunctive test, especially in the setting of new-onset Raynaud, is the antinuclear antibody (ANA) test; I prefer the immunofluorescent assay. While a positive test alone (with Raynaud) does not define the presence of any rheumatic disease, several older studies suggest that patients with a new onset of Raynaud phenomenon and a positive ANA test are more likely to develop a systemic autoimmune disorder than if the test is negative. Those who do so (and this is far from all) are most likely to have the disease manifest within a few years. Hence, if the ANA test is positive but the history, physical examination, and limited laboratory testing (complete blood cell count with differential, complete metabolic panel, creatine kinase, and urinalysis) are normal, it is reasonable to reexamine the patient in 3 months and then every 6 months for 2 to 3 years, repeating the focused history and physical examination. It is also reasonable at some point to refer these patients to a rheumatologist.
Since Raynaud phenomenon is common, and the associated severe rheumatic disorders associated with it are rare, it is easy to not recognize Raynaud phenomenon as a clue to the onset of a potentially severe systemic disease. Yet with a few simple questions, a focused examination, and minimal laboratory testing, patients who are more likely to harbor a systemic disease can usually be treated symptomatically if necessary, and appropriately triaged to observation or for subspecialty referral.
The Food and Drug Administration has reported an apparent increase in device-related adverse events from the use of endovascular graft repair (EVAR) to treat abdominal aortic aneurysms (AAA).
In a Letter to Health Care Providers issued on Sept. 28, the FDA indicated that “recent information from several sources, including FDA’s Medical Device Reporting system and Annual Clinical Updates to Physicians by the manufacturers, suggests an increase in the occurrence of Type III endoleaks.”
A Type III endoleak is defined by the failure to completely exclude the AAA from blood flow, thereby allowing a systematic arterial pressurization of the aneurysm sac, increasing the risk of rupture, which is a life-threatening event.
The FDA stated that predictors of Type III endoleaks included treatment with early-generation graft materials, the presence of calcified plaque, and inadequate overlap between graft components.
Secondary interventions to treat Type III endoleaks carry their own risk of adverse events.
It is recommended that health care providers should do the following:
Consider lifelong surveillance of patients who have been treated with EVAR.
Consider type III endoleaks in the differential diagnosis of patients who present with symptoms of potential aneurysm expansion or rupture.
Discuss all treatment options in depth with patients before deciding on the best treatment for Type III endoleaks.
Report any early or late device-related adverse events, including Type IIIa and Type IIIb endoleaks, associated with EVAR, as well as any device-related adverse events that occur as the result of a secondary intervention to treat Type III endoleaks.
These events should be reported to MedWatch, using the FDA’s Safety Information and Adverse Event Reporting Program Online Voluntary Reporting Form. A form also can be requested by calling 800-332-1088.
The FDA stated that it “continues to work with all manufacturers of endovascular graft systems to better understand this issue,” and that the agency would keep the public informed when significant new information becomes available.
The Food and Drug Administration has reported an apparent increase in device-related adverse events from the use of endovascular graft repair (EVAR) to treat abdominal aortic aneurysms (AAA).
In a Letter to Health Care Providers issued on Sept. 28, the FDA indicated that “recent information from several sources, including FDA’s Medical Device Reporting system and Annual Clinical Updates to Physicians by the manufacturers, suggests an increase in the occurrence of Type III endoleaks.”
A Type III endoleak is defined by the failure to completely exclude the AAA from blood flow, thereby allowing a systematic arterial pressurization of the aneurysm sac, increasing the risk of rupture, which is a life-threatening event.
The FDA stated that predictors of Type III endoleaks included treatment with early-generation graft materials, the presence of calcified plaque, and inadequate overlap between graft components.
Secondary interventions to treat Type III endoleaks carry their own risk of adverse events.
It is recommended that health care providers should do the following:
Consider lifelong surveillance of patients who have been treated with EVAR.
Consider type III endoleaks in the differential diagnosis of patients who present with symptoms of potential aneurysm expansion or rupture.
Discuss all treatment options in depth with patients before deciding on the best treatment for Type III endoleaks.
Report any early or late device-related adverse events, including Type IIIa and Type IIIb endoleaks, associated with EVAR, as well as any device-related adverse events that occur as the result of a secondary intervention to treat Type III endoleaks.
These events should be reported to MedWatch, using the FDA’s Safety Information and Adverse Event Reporting Program Online Voluntary Reporting Form. A form also can be requested by calling 800-332-1088.
The FDA stated that it “continues to work with all manufacturers of endovascular graft systems to better understand this issue,” and that the agency would keep the public informed when significant new information becomes available.
The Food and Drug Administration has reported an apparent increase in device-related adverse events from the use of endovascular graft repair (EVAR) to treat abdominal aortic aneurysms (AAA).
In a Letter to Health Care Providers issued on Sept. 28, the FDA indicated that “recent information from several sources, including FDA’s Medical Device Reporting system and Annual Clinical Updates to Physicians by the manufacturers, suggests an increase in the occurrence of Type III endoleaks.”
A Type III endoleak is defined by the failure to completely exclude the AAA from blood flow, thereby allowing a systematic arterial pressurization of the aneurysm sac, increasing the risk of rupture, which is a life-threatening event.
The FDA stated that predictors of Type III endoleaks included treatment with early-generation graft materials, the presence of calcified plaque, and inadequate overlap between graft components.
Secondary interventions to treat Type III endoleaks carry their own risk of adverse events.
It is recommended that health care providers should do the following:
Consider lifelong surveillance of patients who have been treated with EVAR.
Consider type III endoleaks in the differential diagnosis of patients who present with symptoms of potential aneurysm expansion or rupture.
Discuss all treatment options in depth with patients before deciding on the best treatment for Type III endoleaks.
Report any early or late device-related adverse events, including Type IIIa and Type IIIb endoleaks, associated with EVAR, as well as any device-related adverse events that occur as the result of a secondary intervention to treat Type III endoleaks.
These events should be reported to MedWatch, using the FDA’s Safety Information and Adverse Event Reporting Program Online Voluntary Reporting Form. A form also can be requested by calling 800-332-1088.
The FDA stated that it “continues to work with all manufacturers of endovascular graft systems to better understand this issue,” and that the agency would keep the public informed when significant new information becomes available.
