User login
What is the best test to detect herpes in skin lesions?
Polymerase chain reaction (PCR) techniques appear to be more sensitive and specific in detecting herpes simplex virus (HSV) in genital lesions (strength of recommendation [SOR]: A, based on 2 diagnostic cohort studies); however, viral culture remains the gold standard (SOR: C, based on expert opinion). Studies of serologic and antibody detection tests report higher sensitivities than viral culture (SOR: C, based on consensus guidelines). Cytologic tests such as the Tzanck smear and Papanicolaou (Pap) smear have poor sensitivities and specificities and should not be relied upon for a diagnosis of genital herpes (SOR: C, based on expert opinion).
Test ulcers with culture or PCR
James Holt, MD
Department of Family Medicine, East Tennessee State University, Johnson City
Genital and oral lesions consistent with herpes simplex lesions are relatively common in my practice. Before PCR testing was available, ulcers could be tested via culture—which took too long to be immediately useful—or via Tzanck smear, which helped greatly if multinucleated giant cells were seen. However, both tests were relatively insensitive. As this Clinical Inquiry demonstrates, ulcers currently should be tested either with culture or with PCR. Herpes culture is most sensitive if vesicles are still intact for unroofing.
Evidence summary
More than 50 million individuals in the United States have genital herpes. The diagnosis of genital herpes based on clinical history and physical examination is often inaccurate.1 Clinical suspicion needs to be confirmed by laboratory testing because it has a direct impact on counseling and prognosis.2
Viral culture is still the gold standard test for the detection of HSV; however, the rate of positive cultures depends on the stage of the lesion, the quality of the specimen, and the transport conditions. A British study3 found the rate of virus recovery for early vesicles to be 52% to 93%. This dropped to 41% to 72% if midstage ulcers were present. Finally, the detection for late-stage crusted lesions was only 19% to 27%. Another disadvantage is that culture is labor-intensive. A positive culture takes an average of 3 days to grow, whereas a negative culture must incubate for 10 days.3
PCR techniques are more sensitive and results can be available in less than 4 hours.3 In 110 clinical samples from dermal or genital lesions of patients with suspected HSV infection, the sensitivity of PCR was 98% (positive likelihood ratio [LR+]=∞; negative likelihood ratio [LR–]=0.02) compared with 73% (LR+ = ∞; LR– = 0.27) for culture. The specificities of both were 100%.4 In London, 233 samples from patients at a genitourinary medicine clinic were tested with both viral culture and PCR. HSV was detected in 79 samples by culture and 132 samples by PCR. The detection by PCR was higher in early as well as late stages of infection and in both first and recurrent episodes.3 The reference standard for these studies was not an independent standard, but a positive result on both tests or modified versions of the PCR test. The use of a version of the test of interest (PCR) as part of the reference standard, while probably unavoidable in this situation, will tend inflate the sensitivity and specificity.
In another study, daily sampling of lesions in patients with known HSV infections detected HSV DNA on 15 of 17 days with PCR and only 3 of 17 days with culture.1 This suggests that PCR is more effective in detecting early, as well as late, stages of infection. Currently PCR is more expensive, but it may become cheaper because of decreased labor expense when compared with culture.
Genital herpes may also be detected with enzyme immunoassay testing in as little as 5 hours. In a study5 using 275 samples from genital lesions, HSV was detected in 65% of the antigen tests and 53% of the viral cultures. The sensitivity of this method is equal to culture for early lesions, but much higher in late-stage lesions (58% vs 26%).5
Serologic tests are often used to detect HSV because they can differentiate between HSV-1 and HSV-2. There is an FDA-approved point-of-care test called POCkit that gives results from capillary blood or serum during an office visit. These tests are 80% to 98% sensitive and more than 96% specific. Unfortunately, they are not readily available in all countries.2
Other detection methods include the Tzanck smear, which is only 40% to 50% sensitive compared with culture, and the Pap smear, which is 60% to 70% sensitive.6 These tests should not be the sole method for the diagnosis of HSV. They cannot differentiate between HSV 1 and HSV 2; furthermore, the Tzanck prep will give a positive result if varicella zoster virus is present.6 If these tests are positive, confirmatory testing specific for HSV should be performed.
Recommendations from others
The Centers for Disease Control and Prevention7 recommends screening with a viral culture when a genital lesion is present, however, the sensitivity declines rapidly within a few days as the lesion begins to heal. To collect a sample the lesion must be unroofed using a Dacron swab, which is then placed in a viral transport medium and processed within 24 hours. Swabs containing calcium agglutinate are toxic to HSV.6 Type-specific antibodies develop during the first several weeks and can be detected with serologic tests; however, these may be falsely negative in the early stages of a primary infection.7
The US Preventative Services Task Force8 recommends against routine serologic screening for HSV in asymptomatic adolescents and adults. They also recommend against routine screening of asymptomatic pregnant women at any time during pregnancy as a way to decrease neonatal transmission.8
1. Albrecht MA. Clinical manifestations and diagnosis of genital herpes simplex virus infection. UpToDate [database online]. Available at: www.uptodate.com.
2. Centers for Disease Control and Prevention. Diseases characterized by genital ulcers. Sexually transmitted diseases treatment guidelines. MMWR Recomm Rep 2002;51(RR-6):11-25.
3. Ramaswamy M, McDonald C, Smith M, et al. Diagnosis of genital herpes by real time PCR in routine clinical practice. Sex Trasm Infect 2004;80:406-410.
4. Schmutzhard J, Riedel H, Wirgart B, Grillner L. Detection of herpes simplex virus type 1, herpes simplex virus type 2 and varicella-zoster virus in skin lesions. Comparison of real-time PCR, nested PCR and virus isolation. J Clin Virol 2004;29:120-126.
5. Cone RW, Swenson PD, Hobson AC, Remington M, Corey L. Herpes simplex virus detection from genital lesions: a comparative study using antigen detection (HerpChek) and culture. J Clin Microbiol 1993;31:1774-1776.
6. Herpes, genital. InfoPOEMS [online database]. Available at www.infopoems.com.
7. Centers for Disease Control and Prevention. Sexually Transmitted Diseases Treatment Guidelines 2002. Diseases Characterized by Genital Ulcers. Available at: www.cdc.gov/STD/treatment/2-2002TG.htm. Accessed on March 13, 2006.
8. United States Preventative Services Task Force. Screening for Genital Herpes. March 2005. Available at: www.ahrq.gov/clinic/uspstf/uspsherp.htm. Accessed on March 13, 2006.
Polymerase chain reaction (PCR) techniques appear to be more sensitive and specific in detecting herpes simplex virus (HSV) in genital lesions (strength of recommendation [SOR]: A, based on 2 diagnostic cohort studies); however, viral culture remains the gold standard (SOR: C, based on expert opinion). Studies of serologic and antibody detection tests report higher sensitivities than viral culture (SOR: C, based on consensus guidelines). Cytologic tests such as the Tzanck smear and Papanicolaou (Pap) smear have poor sensitivities and specificities and should not be relied upon for a diagnosis of genital herpes (SOR: C, based on expert opinion).
Test ulcers with culture or PCR
James Holt, MD
Department of Family Medicine, East Tennessee State University, Johnson City
Genital and oral lesions consistent with herpes simplex lesions are relatively common in my practice. Before PCR testing was available, ulcers could be tested via culture—which took too long to be immediately useful—or via Tzanck smear, which helped greatly if multinucleated giant cells were seen. However, both tests were relatively insensitive. As this Clinical Inquiry demonstrates, ulcers currently should be tested either with culture or with PCR. Herpes culture is most sensitive if vesicles are still intact for unroofing.
Evidence summary
More than 50 million individuals in the United States have genital herpes. The diagnosis of genital herpes based on clinical history and physical examination is often inaccurate.1 Clinical suspicion needs to be confirmed by laboratory testing because it has a direct impact on counseling and prognosis.2
Viral culture is still the gold standard test for the detection of HSV; however, the rate of positive cultures depends on the stage of the lesion, the quality of the specimen, and the transport conditions. A British study3 found the rate of virus recovery for early vesicles to be 52% to 93%. This dropped to 41% to 72% if midstage ulcers were present. Finally, the detection for late-stage crusted lesions was only 19% to 27%. Another disadvantage is that culture is labor-intensive. A positive culture takes an average of 3 days to grow, whereas a negative culture must incubate for 10 days.3
PCR techniques are more sensitive and results can be available in less than 4 hours.3 In 110 clinical samples from dermal or genital lesions of patients with suspected HSV infection, the sensitivity of PCR was 98% (positive likelihood ratio [LR+]=∞; negative likelihood ratio [LR–]=0.02) compared with 73% (LR+ = ∞; LR– = 0.27) for culture. The specificities of both were 100%.4 In London, 233 samples from patients at a genitourinary medicine clinic were tested with both viral culture and PCR. HSV was detected in 79 samples by culture and 132 samples by PCR. The detection by PCR was higher in early as well as late stages of infection and in both first and recurrent episodes.3 The reference standard for these studies was not an independent standard, but a positive result on both tests or modified versions of the PCR test. The use of a version of the test of interest (PCR) as part of the reference standard, while probably unavoidable in this situation, will tend inflate the sensitivity and specificity.
In another study, daily sampling of lesions in patients with known HSV infections detected HSV DNA on 15 of 17 days with PCR and only 3 of 17 days with culture.1 This suggests that PCR is more effective in detecting early, as well as late, stages of infection. Currently PCR is more expensive, but it may become cheaper because of decreased labor expense when compared with culture.
Genital herpes may also be detected with enzyme immunoassay testing in as little as 5 hours. In a study5 using 275 samples from genital lesions, HSV was detected in 65% of the antigen tests and 53% of the viral cultures. The sensitivity of this method is equal to culture for early lesions, but much higher in late-stage lesions (58% vs 26%).5
Serologic tests are often used to detect HSV because they can differentiate between HSV-1 and HSV-2. There is an FDA-approved point-of-care test called POCkit that gives results from capillary blood or serum during an office visit. These tests are 80% to 98% sensitive and more than 96% specific. Unfortunately, they are not readily available in all countries.2
Other detection methods include the Tzanck smear, which is only 40% to 50% sensitive compared with culture, and the Pap smear, which is 60% to 70% sensitive.6 These tests should not be the sole method for the diagnosis of HSV. They cannot differentiate between HSV 1 and HSV 2; furthermore, the Tzanck prep will give a positive result if varicella zoster virus is present.6 If these tests are positive, confirmatory testing specific for HSV should be performed.
Recommendations from others
The Centers for Disease Control and Prevention7 recommends screening with a viral culture when a genital lesion is present, however, the sensitivity declines rapidly within a few days as the lesion begins to heal. To collect a sample the lesion must be unroofed using a Dacron swab, which is then placed in a viral transport medium and processed within 24 hours. Swabs containing calcium agglutinate are toxic to HSV.6 Type-specific antibodies develop during the first several weeks and can be detected with serologic tests; however, these may be falsely negative in the early stages of a primary infection.7
The US Preventative Services Task Force8 recommends against routine serologic screening for HSV in asymptomatic adolescents and adults. They also recommend against routine screening of asymptomatic pregnant women at any time during pregnancy as a way to decrease neonatal transmission.8
Polymerase chain reaction (PCR) techniques appear to be more sensitive and specific in detecting herpes simplex virus (HSV) in genital lesions (strength of recommendation [SOR]: A, based on 2 diagnostic cohort studies); however, viral culture remains the gold standard (SOR: C, based on expert opinion). Studies of serologic and antibody detection tests report higher sensitivities than viral culture (SOR: C, based on consensus guidelines). Cytologic tests such as the Tzanck smear and Papanicolaou (Pap) smear have poor sensitivities and specificities and should not be relied upon for a diagnosis of genital herpes (SOR: C, based on expert opinion).
Test ulcers with culture or PCR
James Holt, MD
Department of Family Medicine, East Tennessee State University, Johnson City
Genital and oral lesions consistent with herpes simplex lesions are relatively common in my practice. Before PCR testing was available, ulcers could be tested via culture—which took too long to be immediately useful—or via Tzanck smear, which helped greatly if multinucleated giant cells were seen. However, both tests were relatively insensitive. As this Clinical Inquiry demonstrates, ulcers currently should be tested either with culture or with PCR. Herpes culture is most sensitive if vesicles are still intact for unroofing.
Evidence summary
More than 50 million individuals in the United States have genital herpes. The diagnosis of genital herpes based on clinical history and physical examination is often inaccurate.1 Clinical suspicion needs to be confirmed by laboratory testing because it has a direct impact on counseling and prognosis.2
Viral culture is still the gold standard test for the detection of HSV; however, the rate of positive cultures depends on the stage of the lesion, the quality of the specimen, and the transport conditions. A British study3 found the rate of virus recovery for early vesicles to be 52% to 93%. This dropped to 41% to 72% if midstage ulcers were present. Finally, the detection for late-stage crusted lesions was only 19% to 27%. Another disadvantage is that culture is labor-intensive. A positive culture takes an average of 3 days to grow, whereas a negative culture must incubate for 10 days.3
PCR techniques are more sensitive and results can be available in less than 4 hours.3 In 110 clinical samples from dermal or genital lesions of patients with suspected HSV infection, the sensitivity of PCR was 98% (positive likelihood ratio [LR+]=∞; negative likelihood ratio [LR–]=0.02) compared with 73% (LR+ = ∞; LR– = 0.27) for culture. The specificities of both were 100%.4 In London, 233 samples from patients at a genitourinary medicine clinic were tested with both viral culture and PCR. HSV was detected in 79 samples by culture and 132 samples by PCR. The detection by PCR was higher in early as well as late stages of infection and in both first and recurrent episodes.3 The reference standard for these studies was not an independent standard, but a positive result on both tests or modified versions of the PCR test. The use of a version of the test of interest (PCR) as part of the reference standard, while probably unavoidable in this situation, will tend inflate the sensitivity and specificity.
In another study, daily sampling of lesions in patients with known HSV infections detected HSV DNA on 15 of 17 days with PCR and only 3 of 17 days with culture.1 This suggests that PCR is more effective in detecting early, as well as late, stages of infection. Currently PCR is more expensive, but it may become cheaper because of decreased labor expense when compared with culture.
Genital herpes may also be detected with enzyme immunoassay testing in as little as 5 hours. In a study5 using 275 samples from genital lesions, HSV was detected in 65% of the antigen tests and 53% of the viral cultures. The sensitivity of this method is equal to culture for early lesions, but much higher in late-stage lesions (58% vs 26%).5
Serologic tests are often used to detect HSV because they can differentiate between HSV-1 and HSV-2. There is an FDA-approved point-of-care test called POCkit that gives results from capillary blood or serum during an office visit. These tests are 80% to 98% sensitive and more than 96% specific. Unfortunately, they are not readily available in all countries.2
Other detection methods include the Tzanck smear, which is only 40% to 50% sensitive compared with culture, and the Pap smear, which is 60% to 70% sensitive.6 These tests should not be the sole method for the diagnosis of HSV. They cannot differentiate between HSV 1 and HSV 2; furthermore, the Tzanck prep will give a positive result if varicella zoster virus is present.6 If these tests are positive, confirmatory testing specific for HSV should be performed.
Recommendations from others
The Centers for Disease Control and Prevention7 recommends screening with a viral culture when a genital lesion is present, however, the sensitivity declines rapidly within a few days as the lesion begins to heal. To collect a sample the lesion must be unroofed using a Dacron swab, which is then placed in a viral transport medium and processed within 24 hours. Swabs containing calcium agglutinate are toxic to HSV.6 Type-specific antibodies develop during the first several weeks and can be detected with serologic tests; however, these may be falsely negative in the early stages of a primary infection.7
The US Preventative Services Task Force8 recommends against routine serologic screening for HSV in asymptomatic adolescents and adults. They also recommend against routine screening of asymptomatic pregnant women at any time during pregnancy as a way to decrease neonatal transmission.8
1. Albrecht MA. Clinical manifestations and diagnosis of genital herpes simplex virus infection. UpToDate [database online]. Available at: www.uptodate.com.
2. Centers for Disease Control and Prevention. Diseases characterized by genital ulcers. Sexually transmitted diseases treatment guidelines. MMWR Recomm Rep 2002;51(RR-6):11-25.
3. Ramaswamy M, McDonald C, Smith M, et al. Diagnosis of genital herpes by real time PCR in routine clinical practice. Sex Trasm Infect 2004;80:406-410.
4. Schmutzhard J, Riedel H, Wirgart B, Grillner L. Detection of herpes simplex virus type 1, herpes simplex virus type 2 and varicella-zoster virus in skin lesions. Comparison of real-time PCR, nested PCR and virus isolation. J Clin Virol 2004;29:120-126.
5. Cone RW, Swenson PD, Hobson AC, Remington M, Corey L. Herpes simplex virus detection from genital lesions: a comparative study using antigen detection (HerpChek) and culture. J Clin Microbiol 1993;31:1774-1776.
6. Herpes, genital. InfoPOEMS [online database]. Available at www.infopoems.com.
7. Centers for Disease Control and Prevention. Sexually Transmitted Diseases Treatment Guidelines 2002. Diseases Characterized by Genital Ulcers. Available at: www.cdc.gov/STD/treatment/2-2002TG.htm. Accessed on March 13, 2006.
8. United States Preventative Services Task Force. Screening for Genital Herpes. March 2005. Available at: www.ahrq.gov/clinic/uspstf/uspsherp.htm. Accessed on March 13, 2006.
1. Albrecht MA. Clinical manifestations and diagnosis of genital herpes simplex virus infection. UpToDate [database online]. Available at: www.uptodate.com.
2. Centers for Disease Control and Prevention. Diseases characterized by genital ulcers. Sexually transmitted diseases treatment guidelines. MMWR Recomm Rep 2002;51(RR-6):11-25.
3. Ramaswamy M, McDonald C, Smith M, et al. Diagnosis of genital herpes by real time PCR in routine clinical practice. Sex Trasm Infect 2004;80:406-410.
4. Schmutzhard J, Riedel H, Wirgart B, Grillner L. Detection of herpes simplex virus type 1, herpes simplex virus type 2 and varicella-zoster virus in skin lesions. Comparison of real-time PCR, nested PCR and virus isolation. J Clin Virol 2004;29:120-126.
5. Cone RW, Swenson PD, Hobson AC, Remington M, Corey L. Herpes simplex virus detection from genital lesions: a comparative study using antigen detection (HerpChek) and culture. J Clin Microbiol 1993;31:1774-1776.
6. Herpes, genital. InfoPOEMS [online database]. Available at www.infopoems.com.
7. Centers for Disease Control and Prevention. Sexually Transmitted Diseases Treatment Guidelines 2002. Diseases Characterized by Genital Ulcers. Available at: www.cdc.gov/STD/treatment/2-2002TG.htm. Accessed on March 13, 2006.
8. United States Preventative Services Task Force. Screening for Genital Herpes. March 2005. Available at: www.ahrq.gov/clinic/uspstf/uspsherp.htm. Accessed on March 13, 2006.
Evidence-based answers from the Family Physicians Inquiries Network
Should people with a first-degree relative who died from subarachnoid hemorrhage be screened for aneurysms?
Patients whose family history includes 1 first-degree relative with subarachnoid hemorrhage caused by intracranial aneurysm (ICA) need not be screened for ICAs (strength of recommendation [SOR]: B, based on a single case series).
Hypertension, hyperlipidemia, ethanol use, and tobacco use do not increase the risk of ICA for patients whose primary family member had an ICA (SOR: B, based on case series). Screening for intracranial aneurysms is not cost-effective (SOR: C, mathematical modeling/expert opinion).
In studies using mathematic modeling, harms associated with screening (functional impairment, severe morbidity, or death) would outweigh benefits of screening, even for individuals having 2 or more relatives with ICA (SOR: C). Patients experience varying levels of psychological distress when offered screening for ICA (SOR: B).
Although the risk of screening may outweigh the benefit, it may be worth it for a worried patient
Frances Biagioli, MD
Department of Family Medicine, Oregon Health and Science University, Portland
The answer to the question, “Is screening for ICA appropriate?” depends on who asked it. If you asked it, prompted by the family history, then the evidence-based answer may be the most appropriate one. However, if the patient poses the question unsolicited—and is worried sick that they too will succumb to this abrupt, unpredictable end, leaving their family behind—then applying the “common-sense” answer may be most appropriate. The MRI/MRA, in this case, is being used more to treat the anxiety than to screen for the disease. Although the risk of screening may outweigh the harm from ICA in the general population, the benefit may be worth it for the patient who is losing sleep and has somatic symptoms as a result of the worry.
Evidence summary
In a systematic review of 23 studies involving 56,304 patients, the prevalence of ICA varied by the number of family members affected; 2.3% in general population, 4% for 1 primary family member affected, and 8% for 2 or more primary family members affected.1 The annual rate of rupture in a retrospective study of 1449 patients was 0.5%.2 Rate of rupture varied based on size of aneurysm, location, and gender. In a more recent case series of relatives of people who suffered an subarachnoid hemorrhage, the absolute lifetime risk of subarachnoid hemorrhage was 4.7% (95% confidence interval [CI], 3.1–6.3%).2
In a case series of 626 patients having 1 primary relative with ICA, screening with magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) backup resulted in 0.9 months increased life expectancy per person screened, at the cost of 19 years of decreased function.3 A mathematical model applied to this study showed that surgery improved life expectancy by an average of 2.5 years; a 6-month postoperative functional assessment found functional impairment in 11 of 18 surgical patients (number needed to harm [NNH]=1.6). In a separate study using data from the same population, being a sibling of an ICA sufferer increased risk of ICA (relative risk=3.8, though with a wide 95% CI of 1.1–29.3).4 Neither hypertension nor hypercholesterolemia conferred increased risk of ICA, and the risk conferred by smoking and use of alcohol was statistically insignificant.4
In a study of MRA with digital subtraction angiography backup, conducted using theoretical models, screening individuals having 2 or more first-degree relatives with aneurysm would result in severe morbidity or death in 26 individuals per 1000 patients screened, vs 15 per 1000 unscreened individuals over a 30-year period.5 These results were achieved assuming an ICA prevalence estimate of 9.8%, as determined from an earlier population study of individuals with at least 2 first-degree relatives with ICA. The lower ICA prevalence rate of 4% for patients with only 1 primary affected relative would yield an even more favorable result for not screening.
A mathematical model for evaluating cost effectiveness of screening for asymptomatic intracranial aneurysms in the general population determined there is a quality-adjusted life-year reduction for presumed ICA prevalence rates as high as 10%, given an annual rate of rupture of 0.05%.6 The average cost was $1121 for those who underwent screening vs $147 for those who did not. The presumed variables of prevalence, annual rates of ICA rupture, and surgical mortality and morbidity greatly influenced cost-effectiveness. Screening could be reasonable in populations with higher rupture rates, and if surgical morbidity and mortality decline.
Recently, the psychosocial aspects of screening for ICA have been studied. In 1 case series of 105 patients, 35 screen-positive patients scored lower for quality of life than 70 screen-negative patients. However, only 3 patients regretted participating in screening.7 An observational study of 980 first-degree relatives of patients with subarachnoid hemorrhage determined that offering screening for ICA did not provoke anxiety or depression.8 Providing thorough counseling before screening can help to alleviate the patient’s anxiety.
Recommendations from others
In 2000, the Stroke Council of the American Heart Association concluded that screening is not efficacious in populations having a single first-degree relative with aneurismal subarachnoid hemorrhage or intracranial aneurysm.9
1. Rinkel GJE, Djibuti M. Prevalence and risk of rupture of intracranial aneurysms. A systematic review. Stroke 1998;29:251-256.
2. The International Study of Unruptured Intracranial Aneurysms Investigators. Unruptured intracranial aneurysms—risk of rupture and risks of surgical intervention. N Engl J Med 1998;339:1725-1733.
3. Raaymakers TWM, for the Magnetic Resonance Angiography in Relatives of Patients with Subarachnoid Hemorrhage Study Group. Risks and benefits of screening for intracranial aneurysms in first-degree relatives of patients with sporadic subarachnoid hemorrhage. N Engl J Med 1999;341:1344-1350.
4. Raaymakers TWM, and the MARS Study Group. Aneurysms in relatives of patients with subarachnoid hemorrhage. Frequency and risk factors. Neurology 1999;53:982-988.
5. Crawley F, Clifton A, Brown MM. Should we screen for familial intracranial aneurysm? Stroke 1999;30:312-316.
6. Yoshimoto Y, Wakai S. Cost-effectiveness analysis of screening for asymptomatic, unruptured intracranial aneurysms. A mathematical model. Stroke 1999;30:1621-1627.
7. Bederson JB, Awad IA. Recommendations for the management of patients with unruptured intracranial aneurysms. A statement for healthcare professionals from the stroke council of the American Heart Association. Circulation 2000;102:2300-2308.
8. Bossuyt PM, Raaymakers TW. Screening families for intracranial aneurysms: Anxiety, perceived risk, and informed choice. Prev Med 2005;41:795-799.
9. Bederson JB, Awad IA. Recommendations for the Management of patients With Unruptured Intracranial Aneurysms. A Statement for Healthcare Professionals From the Stroke Council of the American Heart Association. Circulation 2000;102:2300-2308.
Patients whose family history includes 1 first-degree relative with subarachnoid hemorrhage caused by intracranial aneurysm (ICA) need not be screened for ICAs (strength of recommendation [SOR]: B, based on a single case series).
Hypertension, hyperlipidemia, ethanol use, and tobacco use do not increase the risk of ICA for patients whose primary family member had an ICA (SOR: B, based on case series). Screening for intracranial aneurysms is not cost-effective (SOR: C, mathematical modeling/expert opinion).
In studies using mathematic modeling, harms associated with screening (functional impairment, severe morbidity, or death) would outweigh benefits of screening, even for individuals having 2 or more relatives with ICA (SOR: C). Patients experience varying levels of psychological distress when offered screening for ICA (SOR: B).
Although the risk of screening may outweigh the benefit, it may be worth it for a worried patient
Frances Biagioli, MD
Department of Family Medicine, Oregon Health and Science University, Portland
The answer to the question, “Is screening for ICA appropriate?” depends on who asked it. If you asked it, prompted by the family history, then the evidence-based answer may be the most appropriate one. However, if the patient poses the question unsolicited—and is worried sick that they too will succumb to this abrupt, unpredictable end, leaving their family behind—then applying the “common-sense” answer may be most appropriate. The MRI/MRA, in this case, is being used more to treat the anxiety than to screen for the disease. Although the risk of screening may outweigh the harm from ICA in the general population, the benefit may be worth it for the patient who is losing sleep and has somatic symptoms as a result of the worry.
Evidence summary
In a systematic review of 23 studies involving 56,304 patients, the prevalence of ICA varied by the number of family members affected; 2.3% in general population, 4% for 1 primary family member affected, and 8% for 2 or more primary family members affected.1 The annual rate of rupture in a retrospective study of 1449 patients was 0.5%.2 Rate of rupture varied based on size of aneurysm, location, and gender. In a more recent case series of relatives of people who suffered an subarachnoid hemorrhage, the absolute lifetime risk of subarachnoid hemorrhage was 4.7% (95% confidence interval [CI], 3.1–6.3%).2
In a case series of 626 patients having 1 primary relative with ICA, screening with magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) backup resulted in 0.9 months increased life expectancy per person screened, at the cost of 19 years of decreased function.3 A mathematical model applied to this study showed that surgery improved life expectancy by an average of 2.5 years; a 6-month postoperative functional assessment found functional impairment in 11 of 18 surgical patients (number needed to harm [NNH]=1.6). In a separate study using data from the same population, being a sibling of an ICA sufferer increased risk of ICA (relative risk=3.8, though with a wide 95% CI of 1.1–29.3).4 Neither hypertension nor hypercholesterolemia conferred increased risk of ICA, and the risk conferred by smoking and use of alcohol was statistically insignificant.4
In a study of MRA with digital subtraction angiography backup, conducted using theoretical models, screening individuals having 2 or more first-degree relatives with aneurysm would result in severe morbidity or death in 26 individuals per 1000 patients screened, vs 15 per 1000 unscreened individuals over a 30-year period.5 These results were achieved assuming an ICA prevalence estimate of 9.8%, as determined from an earlier population study of individuals with at least 2 first-degree relatives with ICA. The lower ICA prevalence rate of 4% for patients with only 1 primary affected relative would yield an even more favorable result for not screening.
A mathematical model for evaluating cost effectiveness of screening for asymptomatic intracranial aneurysms in the general population determined there is a quality-adjusted life-year reduction for presumed ICA prevalence rates as high as 10%, given an annual rate of rupture of 0.05%.6 The average cost was $1121 for those who underwent screening vs $147 for those who did not. The presumed variables of prevalence, annual rates of ICA rupture, and surgical mortality and morbidity greatly influenced cost-effectiveness. Screening could be reasonable in populations with higher rupture rates, and if surgical morbidity and mortality decline.
Recently, the psychosocial aspects of screening for ICA have been studied. In 1 case series of 105 patients, 35 screen-positive patients scored lower for quality of life than 70 screen-negative patients. However, only 3 patients regretted participating in screening.7 An observational study of 980 first-degree relatives of patients with subarachnoid hemorrhage determined that offering screening for ICA did not provoke anxiety or depression.8 Providing thorough counseling before screening can help to alleviate the patient’s anxiety.
Recommendations from others
In 2000, the Stroke Council of the American Heart Association concluded that screening is not efficacious in populations having a single first-degree relative with aneurismal subarachnoid hemorrhage or intracranial aneurysm.9
Patients whose family history includes 1 first-degree relative with subarachnoid hemorrhage caused by intracranial aneurysm (ICA) need not be screened for ICAs (strength of recommendation [SOR]: B, based on a single case series).
Hypertension, hyperlipidemia, ethanol use, and tobacco use do not increase the risk of ICA for patients whose primary family member had an ICA (SOR: B, based on case series). Screening for intracranial aneurysms is not cost-effective (SOR: C, mathematical modeling/expert opinion).
In studies using mathematic modeling, harms associated with screening (functional impairment, severe morbidity, or death) would outweigh benefits of screening, even for individuals having 2 or more relatives with ICA (SOR: C). Patients experience varying levels of psychological distress when offered screening for ICA (SOR: B).
Although the risk of screening may outweigh the benefit, it may be worth it for a worried patient
Frances Biagioli, MD
Department of Family Medicine, Oregon Health and Science University, Portland
The answer to the question, “Is screening for ICA appropriate?” depends on who asked it. If you asked it, prompted by the family history, then the evidence-based answer may be the most appropriate one. However, if the patient poses the question unsolicited—and is worried sick that they too will succumb to this abrupt, unpredictable end, leaving their family behind—then applying the “common-sense” answer may be most appropriate. The MRI/MRA, in this case, is being used more to treat the anxiety than to screen for the disease. Although the risk of screening may outweigh the harm from ICA in the general population, the benefit may be worth it for the patient who is losing sleep and has somatic symptoms as a result of the worry.
Evidence summary
In a systematic review of 23 studies involving 56,304 patients, the prevalence of ICA varied by the number of family members affected; 2.3% in general population, 4% for 1 primary family member affected, and 8% for 2 or more primary family members affected.1 The annual rate of rupture in a retrospective study of 1449 patients was 0.5%.2 Rate of rupture varied based on size of aneurysm, location, and gender. In a more recent case series of relatives of people who suffered an subarachnoid hemorrhage, the absolute lifetime risk of subarachnoid hemorrhage was 4.7% (95% confidence interval [CI], 3.1–6.3%).2
In a case series of 626 patients having 1 primary relative with ICA, screening with magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) backup resulted in 0.9 months increased life expectancy per person screened, at the cost of 19 years of decreased function.3 A mathematical model applied to this study showed that surgery improved life expectancy by an average of 2.5 years; a 6-month postoperative functional assessment found functional impairment in 11 of 18 surgical patients (number needed to harm [NNH]=1.6). In a separate study using data from the same population, being a sibling of an ICA sufferer increased risk of ICA (relative risk=3.8, though with a wide 95% CI of 1.1–29.3).4 Neither hypertension nor hypercholesterolemia conferred increased risk of ICA, and the risk conferred by smoking and use of alcohol was statistically insignificant.4
In a study of MRA with digital subtraction angiography backup, conducted using theoretical models, screening individuals having 2 or more first-degree relatives with aneurysm would result in severe morbidity or death in 26 individuals per 1000 patients screened, vs 15 per 1000 unscreened individuals over a 30-year period.5 These results were achieved assuming an ICA prevalence estimate of 9.8%, as determined from an earlier population study of individuals with at least 2 first-degree relatives with ICA. The lower ICA prevalence rate of 4% for patients with only 1 primary affected relative would yield an even more favorable result for not screening.
A mathematical model for evaluating cost effectiveness of screening for asymptomatic intracranial aneurysms in the general population determined there is a quality-adjusted life-year reduction for presumed ICA prevalence rates as high as 10%, given an annual rate of rupture of 0.05%.6 The average cost was $1121 for those who underwent screening vs $147 for those who did not. The presumed variables of prevalence, annual rates of ICA rupture, and surgical mortality and morbidity greatly influenced cost-effectiveness. Screening could be reasonable in populations with higher rupture rates, and if surgical morbidity and mortality decline.
Recently, the psychosocial aspects of screening for ICA have been studied. In 1 case series of 105 patients, 35 screen-positive patients scored lower for quality of life than 70 screen-negative patients. However, only 3 patients regretted participating in screening.7 An observational study of 980 first-degree relatives of patients with subarachnoid hemorrhage determined that offering screening for ICA did not provoke anxiety or depression.8 Providing thorough counseling before screening can help to alleviate the patient’s anxiety.
Recommendations from others
In 2000, the Stroke Council of the American Heart Association concluded that screening is not efficacious in populations having a single first-degree relative with aneurismal subarachnoid hemorrhage or intracranial aneurysm.9
1. Rinkel GJE, Djibuti M. Prevalence and risk of rupture of intracranial aneurysms. A systematic review. Stroke 1998;29:251-256.
2. The International Study of Unruptured Intracranial Aneurysms Investigators. Unruptured intracranial aneurysms—risk of rupture and risks of surgical intervention. N Engl J Med 1998;339:1725-1733.
3. Raaymakers TWM, for the Magnetic Resonance Angiography in Relatives of Patients with Subarachnoid Hemorrhage Study Group. Risks and benefits of screening for intracranial aneurysms in first-degree relatives of patients with sporadic subarachnoid hemorrhage. N Engl J Med 1999;341:1344-1350.
4. Raaymakers TWM, and the MARS Study Group. Aneurysms in relatives of patients with subarachnoid hemorrhage. Frequency and risk factors. Neurology 1999;53:982-988.
5. Crawley F, Clifton A, Brown MM. Should we screen for familial intracranial aneurysm? Stroke 1999;30:312-316.
6. Yoshimoto Y, Wakai S. Cost-effectiveness analysis of screening for asymptomatic, unruptured intracranial aneurysms. A mathematical model. Stroke 1999;30:1621-1627.
7. Bederson JB, Awad IA. Recommendations for the management of patients with unruptured intracranial aneurysms. A statement for healthcare professionals from the stroke council of the American Heart Association. Circulation 2000;102:2300-2308.
8. Bossuyt PM, Raaymakers TW. Screening families for intracranial aneurysms: Anxiety, perceived risk, and informed choice. Prev Med 2005;41:795-799.
9. Bederson JB, Awad IA. Recommendations for the Management of patients With Unruptured Intracranial Aneurysms. A Statement for Healthcare Professionals From the Stroke Council of the American Heart Association. Circulation 2000;102:2300-2308.
1. Rinkel GJE, Djibuti M. Prevalence and risk of rupture of intracranial aneurysms. A systematic review. Stroke 1998;29:251-256.
2. The International Study of Unruptured Intracranial Aneurysms Investigators. Unruptured intracranial aneurysms—risk of rupture and risks of surgical intervention. N Engl J Med 1998;339:1725-1733.
3. Raaymakers TWM, for the Magnetic Resonance Angiography in Relatives of Patients with Subarachnoid Hemorrhage Study Group. Risks and benefits of screening for intracranial aneurysms in first-degree relatives of patients with sporadic subarachnoid hemorrhage. N Engl J Med 1999;341:1344-1350.
4. Raaymakers TWM, and the MARS Study Group. Aneurysms in relatives of patients with subarachnoid hemorrhage. Frequency and risk factors. Neurology 1999;53:982-988.
5. Crawley F, Clifton A, Brown MM. Should we screen for familial intracranial aneurysm? Stroke 1999;30:312-316.
6. Yoshimoto Y, Wakai S. Cost-effectiveness analysis of screening for asymptomatic, unruptured intracranial aneurysms. A mathematical model. Stroke 1999;30:1621-1627.
7. Bederson JB, Awad IA. Recommendations for the management of patients with unruptured intracranial aneurysms. A statement for healthcare professionals from the stroke council of the American Heart Association. Circulation 2000;102:2300-2308.
8. Bossuyt PM, Raaymakers TW. Screening families for intracranial aneurysms: Anxiety, perceived risk, and informed choice. Prev Med 2005;41:795-799.
9. Bederson JB, Awad IA. Recommendations for the Management of patients With Unruptured Intracranial Aneurysms. A Statement for Healthcare Professionals From the Stroke Council of the American Heart Association. Circulation 2000;102:2300-2308.
Evidence-based answers from the Family Physicians Inquiries Network