A 46-year-old man comes to clinic for evaluation of night sweats. He has been having drenching night sweats for the past 3 months. He has to change his night shirt at least once per night. He has had a 10-pound weight gain over the past 6 months. No chest pain, nausea, or fatigue. He has had a cough for the past 6 months.

Which is the most likely diagnosis?

A. Gastroesophageal reflux disease.

B. Tuberculosis.

C. Lymphoma.

D. Multiple myeloma.

Night sweats are a common symptom in the general population, estimated to occur in about 10% of people. They can range in frequency and severity. We become most concerned when the patient is concerned, usually when they report drenching night sweats.

Lea et al. described the prevalence of night sweats among different inpatient populations, with a range from 33% in surgical and medicine patients, to 60% on obstetrics service.²

Night sweats are common, and don’t appear to be correlated with worse prognosis. So, what are the likely common causes?

There just aren’t good studies on causes of night sweats, but there are studies that suggest that they are seen in some very common diseases. It is always good to look at medication lists as a start when evaluating unexplained symptoms.

Dr. Mold, along with Barbara J. Holtzclaw, PhD, reported higher odds ratios for night sweats for patients on SSRIs (OR, 3.01), angiotensin receptor blockers (OR, 3.44) and thyroid hormone supplements (OR, 2.53).³ W.A. Reynolds, MD, looked at the prevalence of night sweats in a GI practice.⁴ A total of 41% of the patients reported night sweats, and 12 of 12 patients with GERD who had night sweats had resolution of the night sweats with effective treatment of the GERD.

Dr. Mold and his colleagues found that night sweats were associated with several sleep-related symptoms, including waking up with a bitter taste in the mouth (OR, 1.94), daytime tiredness (OR, 1.99), and legs jerking during sleep (OR, 1.87).⁵

Erna Arnardottir, PhD, and her colleagues found that obstructive sleep apnea was associated with frequent nocturnal sweating.⁶ They found that 31% of men and 33% of women with OSA had nocturnal sweating, compared with about 10% of the general population. When the OSA patients were treated with positive airway pressure, the prevalence of nocturnal sweating decreased to 11.5%, similar to general population numbers.

Pearl: Night sweats are associated with common conditions: medications, GERD, and sleep disorders. These are more likely than lymphoma and tuberculosis.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.

References

1. J Am Board Fam Med. 2010 Jan-Feb;23(1):97-103.

2. South Med J. 1985 Sep;78(9):1065-7.

3. Drugs Real World Outcomes. 2015 Mar;2(1):29-33.

4. J Clin Gastroenterol. 1989 Oct;11(5):590-1.

5. Ann Fam Med. 2006 Sep-Oct;4(5):423-6.

6. BMJ Open. 2013 May 14;3(5).

A 46-year-old man comes to clinic for evaluation of night sweats. He has been having drenching night sweats for the past 3 months. He has to change his night shirt at least once per night. He has had a 10-pound weight gain over the past 6 months. No chest pain, nausea, or fatigue. He has had a cough for the past 6 months.

Which is the most likely diagnosis?

A. Gastroesophageal reflux disease.

B. Tuberculosis.

C. Lymphoma.

D. Multiple myeloma.

Night sweats are a common symptom in the general population, estimated to occur in about 10% of people. They can range in frequency and severity. We become most concerned when the patient is concerned, usually when they report drenching night sweats.

Lea et al. described the prevalence of night sweats among different inpatient populations, with a range from 33% in surgical and medicine patients, to 60% on obstetrics service.²

Night sweats are common, and don’t appear to be correlated with worse prognosis. So, what are the likely common causes?

There just aren’t good studies on causes of night sweats, but there are studies that suggest that they are seen in some very common diseases. It is always good to look at medication lists as a start when evaluating unexplained symptoms.

Dr. Mold, along with Barbara J. Holtzclaw, PhD, reported higher odds ratios for night sweats for patients on SSRIs (OR, 3.01), angiotensin receptor blockers (OR, 3.44) and thyroid hormone supplements (OR, 2.53).³ W.A. Reynolds, MD, looked at the prevalence of night sweats in a GI practice.⁴ A total of 41% of the patients reported night sweats, and 12 of 12 patients with GERD who had night sweats had resolution of the night sweats with effective treatment of the GERD.

Dr. Mold and his colleagues found that night sweats were associated with several sleep-related symptoms, including waking up with a bitter taste in the mouth (OR, 1.94), daytime tiredness (OR, 1.99), and legs jerking during sleep (OR, 1.87).⁵

Erna Arnardottir, PhD, and her colleagues found that obstructive sleep apnea was associated with frequent nocturnal sweating.⁶ They found that 31% of men and 33% of women with OSA had nocturnal sweating, compared with about 10% of the general population. When the OSA patients were treated with positive airway pressure, the prevalence of nocturnal sweating decreased to 11.5%, similar to general population numbers.

Pearl: Night sweats are associated with common conditions: medications, GERD, and sleep disorders. These are more likely than lymphoma and tuberculosis.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.

References

1. J Am Board Fam Med. 2010 Jan-Feb;23(1):97-103.

2. South Med J. 1985 Sep;78(9):1065-7.

3. Drugs Real World Outcomes. 2015 Mar;2(1):29-33.

4. J Clin Gastroenterol. 1989 Oct;11(5):590-1.

5. Ann Fam Med. 2006 Sep-Oct;4(5):423-6.

6. BMJ Open. 2013 May 14;3(5).

A 46-year-old man comes to clinic for evaluation of night sweats. He has been having drenching night sweats for the past 3 months. He has to change his night shirt at least once per night. He has had a 10-pound weight gain over the past 6 months. No chest pain, nausea, or fatigue. He has had a cough for the past 6 months.

Which is the most likely diagnosis?

A. Gastroesophageal reflux disease.

B. Tuberculosis.

C. Lymphoma.

D. Multiple myeloma.

Night sweats are a common symptom in the general population, estimated to occur in about 10% of people. They can range in frequency and severity. We become most concerned when the patient is concerned, usually when they report drenching night sweats.

Lea et al. described the prevalence of night sweats among different inpatient populations, with a range from 33% in surgical and medicine patients, to 60% on obstetrics service.²

Night sweats are common, and don’t appear to be correlated with worse prognosis. So, what are the likely common causes?

There just aren’t good studies on causes of night sweats, but there are studies that suggest that they are seen in some very common diseases. It is always good to look at medication lists as a start when evaluating unexplained symptoms.

Dr. Mold, along with Barbara J. Holtzclaw, PhD, reported higher odds ratios for night sweats for patients on SSRIs (OR, 3.01), angiotensin receptor blockers (OR, 3.44) and thyroid hormone supplements (OR, 2.53).³ W.A. Reynolds, MD, looked at the prevalence of night sweats in a GI practice.⁴ A total of 41% of the patients reported night sweats, and 12 of 12 patients with GERD who had night sweats had resolution of the night sweats with effective treatment of the GERD.

Dr. Mold and his colleagues found that night sweats were associated with several sleep-related symptoms, including waking up with a bitter taste in the mouth (OR, 1.94), daytime tiredness (OR, 1.99), and legs jerking during sleep (OR, 1.87).⁵

Erna Arnardottir, PhD, and her colleagues found that obstructive sleep apnea was associated with frequent nocturnal sweating.⁶ They found that 31% of men and 33% of women with OSA had nocturnal sweating, compared with about 10% of the general population. When the OSA patients were treated with positive airway pressure, the prevalence of nocturnal sweating decreased to 11.5%, similar to general population numbers.

Pearl: Night sweats are associated with common conditions: medications, GERD, and sleep disorders. These are more likely than lymphoma and tuberculosis.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.

References

1. J Am Board Fam Med. 2010 Jan-Feb;23(1):97-103.

2. South Med J. 1985 Sep;78(9):1065-7.

3. Drugs Real World Outcomes. 2015 Mar;2(1):29-33.

4. J Clin Gastroenterol. 1989 Oct;11(5):590-1.

5. Ann Fam Med. 2006 Sep-Oct;4(5):423-6.

6. BMJ Open. 2013 May 14;3(5).

To the Editor:

Mycetoma is a noncontagious chronic infection of the skin and subcutaneous tissue caused by exogenous fungi or bacteria that can involve deeper structures such as the fasciae, muscles, and bones. Clinically it is characterized by increased swelling of the affected area, fibrosis, nodules, tumefaction, formation of draining sinuses, and abscesses that drain pus-containing grains through fistulae.¹ The initiation of the infection is related to local trauma and can involve muscle, underlying bone, and adjacent organs. The feet are the most commonly affected region, and the incubation period is variable. Patients rarely report prior trauma to the affected area and only seek medical consultation when the nodules and draining sinuses become evident. The etiopathogenesis of mycetoma is associated with aerobic actinomycetes (ie, Nocardia, Actinomadura, Streptomyces), known as actinomycetoma, and fungal infections, known as eumycetomas.¹

We report the case of a 57-year-old Albanian man who was referred to the outpatient clinic of our dermatology department for diagnosis and treatment of a chronic, suppurative, subcutaneous infection on the right foot presenting as abscesses and draining sinuses. The patient was a farmer and reported that the condition appeared 4 years prior following a laceration he sustained while at work. Dermatologic examination revealed local tumefaction, fistulated nodules, and abscesses discharging a serohemorrhagic fluid on the right foot (Figure 1). Perilesional erythema and subcutaneous swelling were evident. There was no regional lymph­adenopathy. Standard laboratory examination was normal. Radiography of the right foot showed no osteolytic lesions or evidence of osteomyelitis.

A skin biopsy from a lesion on the right foot was performed, and identification of the possible etiologic agent was based on direct microscopic examination of the granules, culture isolation of the agent, and fungal microscopic morphology.² Granules were studied under direct examination with potassium hydroxide solution 20% and showed septate branching hyphae (Figure 2). The culture produced colonies that were white, yellow, and brown. Colonies were comprised of dense mycelium with melanin pigment and were grown at 37°C. A lactose tolerance test was positive.² Therefore, the strain was identified as Madurella mycetomatis, and a diagnosis of eumycetoma pedis was made.

The patient was hospitalized for 2 weeks and treated with intravenous fluconazole, then treatment with oral itraconazole 200 mg once daily was initiated. At 4-month follow-up, he had self-discontinued treatment but demonstrated partial improvement of the tumefaction, healing of sinus tracts, and functional recovery of the right foot.

One year following the initial presentation, the patient’s clinical condition worsened (Figure 3A). Radiography of the right foot showed osteolytic lesions on bones in the right foot (Figure 3B), and a repeat culture showed the presence of Staphylococcus aureus; thus, treatment with itraconazole 200 mg once daily along with antibiotics (cefuroxime and gentamicin) was started immediately. Surgical treatment was recommended, but the patient refused treatment.

Mycetomas are rare in Albania but are common in countries of tropical and subtropical regions. Known as “Madura foot” by the native people, mycetoma was recognized as a disease entity in 1842.¹ In 1860, Carter³ (who established the fungal etiology of this disorder) first proposed the term mycetoma and further proposed the terms melanoid mycetoma and ochroid mycetoma in an attempt to classify the disease into 2 varieties on the basis of the black or pale-colored granules (ie, grains, sclerotia) on histology produced by the etiologic agents.^2-4

Clinical features of eumycetoma include lesions with clear margins, few sinuses, black grains, slow progression, and long-term involvement of bone. The grains represent an aggregate of hyphae produced by fungi; thus, the characteristic feature of eumycetoma is the formation of large granules that can involve bone.¹ A critical diagnostic step is to distinguish between eumycetoma and actinomycetoma. If possible, it is important to culture the organism because treatment varies depending on the cause of the infection.

Fungal identification is crucial in the diagnosis of mycetoma. In our case, diagnosis of eumycetoma pedis was based on clinical examination and detection of fungal species by microscopic examination and culture. The color of small granules (black grains) is a parameter used to identify different pathogens on histology but is not sufficient for diagnosis.⁵ The examination by potassium hydroxide preparation is helpful to identify the hyphae; however, culture is necessary.²

Therapeutic management of eumycetoma needs a combined strategy that includes systemic treatment and surgical therapy. Eumycetomas generally are more difficult to treat then actinomycetomas. Some authors recommend a high dose of amphotericin B as the treatment of choice for eumycetoma,^6,7 but there are some that emphasize that amphotericin B is partially effective.^8,9 There also is evidence in the literature of resistance of eumycetoma to ketoconazole treatment^10,11 and successful treatment with fluconazole and itraconazole.^10-13 For this reason, we treated our patient with the latter agents. In cases of osteolysis, amputation often is required.

In conclusion, eumycetoma pedis is a rare deep fungal infection that can cause considerable morbidity. Patients should be well educated about this condition and be made aware of the risk of environmental exposure (eg, contact of broken skin with contaminated soil and water) and the need to wear protective footwear in potentially contaminated environments. Early diagnosis, correct treatment, and regular follow-up can reduce the risk of osteolytic complications and increase the possibility of complete recovery.

To the Editor:

Mycetoma is a noncontagious chronic infection of the skin and subcutaneous tissue caused by exogenous fungi or bacteria that can involve deeper structures such as the fasciae, muscles, and bones. Clinically it is characterized by increased swelling of the affected area, fibrosis, nodules, tumefaction, formation of draining sinuses, and abscesses that drain pus-containing grains through fistulae.¹ The initiation of the infection is related to local trauma and can involve muscle, underlying bone, and adjacent organs. The feet are the most commonly affected region, and the incubation period is variable. Patients rarely report prior trauma to the affected area and only seek medical consultation when the nodules and draining sinuses become evident. The etiopathogenesis of mycetoma is associated with aerobic actinomycetes (ie, Nocardia, Actinomadura, Streptomyces), known as actinomycetoma, and fungal infections, known as eumycetomas.¹

We report the case of a 57-year-old Albanian man who was referred to the outpatient clinic of our dermatology department for diagnosis and treatment of a chronic, suppurative, subcutaneous infection on the right foot presenting as abscesses and draining sinuses. The patient was a farmer and reported that the condition appeared 4 years prior following a laceration he sustained while at work. Dermatologic examination revealed local tumefaction, fistulated nodules, and abscesses discharging a serohemorrhagic fluid on the right foot (Figure 1). Perilesional erythema and subcutaneous swelling were evident. There was no regional lymph­adenopathy. Standard laboratory examination was normal. Radiography of the right foot showed no osteolytic lesions or evidence of osteomyelitis.

A skin biopsy from a lesion on the right foot was performed, and identification of the possible etiologic agent was based on direct microscopic examination of the granules, culture isolation of the agent, and fungal microscopic morphology.² Granules were studied under direct examination with potassium hydroxide solution 20% and showed septate branching hyphae (Figure 2). The culture produced colonies that were white, yellow, and brown. Colonies were comprised of dense mycelium with melanin pigment and were grown at 37°C. A lactose tolerance test was positive.² Therefore, the strain was identified as Madurella mycetomatis, and a diagnosis of eumycetoma pedis was made.

The patient was hospitalized for 2 weeks and treated with intravenous fluconazole, then treatment with oral itraconazole 200 mg once daily was initiated. At 4-month follow-up, he had self-discontinued treatment but demonstrated partial improvement of the tumefaction, healing of sinus tracts, and functional recovery of the right foot.

One year following the initial presentation, the patient’s clinical condition worsened (Figure 3A). Radiography of the right foot showed osteolytic lesions on bones in the right foot (Figure 3B), and a repeat culture showed the presence of Staphylococcus aureus; thus, treatment with itraconazole 200 mg once daily along with antibiotics (cefuroxime and gentamicin) was started immediately. Surgical treatment was recommended, but the patient refused treatment.

Mycetomas are rare in Albania but are common in countries of tropical and subtropical regions. Known as “Madura foot” by the native people, mycetoma was recognized as a disease entity in 1842.¹ In 1860, Carter³ (who established the fungal etiology of this disorder) first proposed the term mycetoma and further proposed the terms melanoid mycetoma and ochroid mycetoma in an attempt to classify the disease into 2 varieties on the basis of the black or pale-colored granules (ie, grains, sclerotia) on histology produced by the etiologic agents.^2-4

Clinical features of eumycetoma include lesions with clear margins, few sinuses, black grains, slow progression, and long-term involvement of bone. The grains represent an aggregate of hyphae produced by fungi; thus, the characteristic feature of eumycetoma is the formation of large granules that can involve bone.¹ A critical diagnostic step is to distinguish between eumycetoma and actinomycetoma. If possible, it is important to culture the organism because treatment varies depending on the cause of the infection.

Fungal identification is crucial in the diagnosis of mycetoma. In our case, diagnosis of eumycetoma pedis was based on clinical examination and detection of fungal species by microscopic examination and culture. The color of small granules (black grains) is a parameter used to identify different pathogens on histology but is not sufficient for diagnosis.⁵ The examination by potassium hydroxide preparation is helpful to identify the hyphae; however, culture is necessary.²

Therapeutic management of eumycetoma needs a combined strategy that includes systemic treatment and surgical therapy. Eumycetomas generally are more difficult to treat then actinomycetomas. Some authors recommend a high dose of amphotericin B as the treatment of choice for eumycetoma,^6,7 but there are some that emphasize that amphotericin B is partially effective.^8,9 There also is evidence in the literature of resistance of eumycetoma to ketoconazole treatment^10,11 and successful treatment with fluconazole and itraconazole.^10-13 For this reason, we treated our patient with the latter agents. In cases of osteolysis, amputation often is required.

In conclusion, eumycetoma pedis is a rare deep fungal infection that can cause considerable morbidity. Patients should be well educated about this condition and be made aware of the risk of environmental exposure (eg, contact of broken skin with contaminated soil and water) and the need to wear protective footwear in potentially contaminated environments. Early diagnosis, correct treatment, and regular follow-up can reduce the risk of osteolytic complications and increase the possibility of complete recovery.

To the Editor:

Mycetoma is a noncontagious chronic infection of the skin and subcutaneous tissue caused by exogenous fungi or bacteria that can involve deeper structures such as the fasciae, muscles, and bones. Clinically it is characterized by increased swelling of the affected area, fibrosis, nodules, tumefaction, formation of draining sinuses, and abscesses that drain pus-containing grains through fistulae.¹ The initiation of the infection is related to local trauma and can involve muscle, underlying bone, and adjacent organs. The feet are the most commonly affected region, and the incubation period is variable. Patients rarely report prior trauma to the affected area and only seek medical consultation when the nodules and draining sinuses become evident. The etiopathogenesis of mycetoma is associated with aerobic actinomycetes (ie, Nocardia, Actinomadura, Streptomyces), known as actinomycetoma, and fungal infections, known as eumycetomas.¹

We report the case of a 57-year-old Albanian man who was referred to the outpatient clinic of our dermatology department for diagnosis and treatment of a chronic, suppurative, subcutaneous infection on the right foot presenting as abscesses and draining sinuses. The patient was a farmer and reported that the condition appeared 4 years prior following a laceration he sustained while at work. Dermatologic examination revealed local tumefaction, fistulated nodules, and abscesses discharging a serohemorrhagic fluid on the right foot (Figure 1). Perilesional erythema and subcutaneous swelling were evident. There was no regional lymph­adenopathy. Standard laboratory examination was normal. Radiography of the right foot showed no osteolytic lesions or evidence of osteomyelitis.

A skin biopsy from a lesion on the right foot was performed, and identification of the possible etiologic agent was based on direct microscopic examination of the granules, culture isolation of the agent, and fungal microscopic morphology.² Granules were studied under direct examination with potassium hydroxide solution 20% and showed septate branching hyphae (Figure 2). The culture produced colonies that were white, yellow, and brown. Colonies were comprised of dense mycelium with melanin pigment and were grown at 37°C. A lactose tolerance test was positive.² Therefore, the strain was identified as Madurella mycetomatis, and a diagnosis of eumycetoma pedis was made.

The patient was hospitalized for 2 weeks and treated with intravenous fluconazole, then treatment with oral itraconazole 200 mg once daily was initiated. At 4-month follow-up, he had self-discontinued treatment but demonstrated partial improvement of the tumefaction, healing of sinus tracts, and functional recovery of the right foot.

One year following the initial presentation, the patient’s clinical condition worsened (Figure 3A). Radiography of the right foot showed osteolytic lesions on bones in the right foot (Figure 3B), and a repeat culture showed the presence of Staphylococcus aureus; thus, treatment with itraconazole 200 mg once daily along with antibiotics (cefuroxime and gentamicin) was started immediately. Surgical treatment was recommended, but the patient refused treatment.

Mycetomas are rare in Albania but are common in countries of tropical and subtropical regions. Known as “Madura foot” by the native people, mycetoma was recognized as a disease entity in 1842.¹ In 1860, Carter³ (who established the fungal etiology of this disorder) first proposed the term mycetoma and further proposed the terms melanoid mycetoma and ochroid mycetoma in an attempt to classify the disease into 2 varieties on the basis of the black or pale-colored granules (ie, grains, sclerotia) on histology produced by the etiologic agents.^2-4

Clinical features of eumycetoma include lesions with clear margins, few sinuses, black grains, slow progression, and long-term involvement of bone. The grains represent an aggregate of hyphae produced by fungi; thus, the characteristic feature of eumycetoma is the formation of large granules that can involve bone.¹ A critical diagnostic step is to distinguish between eumycetoma and actinomycetoma. If possible, it is important to culture the organism because treatment varies depending on the cause of the infection.

Fungal identification is crucial in the diagnosis of mycetoma. In our case, diagnosis of eumycetoma pedis was based on clinical examination and detection of fungal species by microscopic examination and culture. The color of small granules (black grains) is a parameter used to identify different pathogens on histology but is not sufficient for diagnosis.⁵ The examination by potassium hydroxide preparation is helpful to identify the hyphae; however, culture is necessary.²

Therapeutic management of eumycetoma needs a combined strategy that includes systemic treatment and surgical therapy. Eumycetomas generally are more difficult to treat then actinomycetomas. Some authors recommend a high dose of amphotericin B as the treatment of choice for eumycetoma,^6,7 but there are some that emphasize that amphotericin B is partially effective.^8,9 There also is evidence in the literature of resistance of eumycetoma to ketoconazole treatment^10,11 and successful treatment with fluconazole and itraconazole.^10-13 For this reason, we treated our patient with the latter agents. In cases of osteolysis, amputation often is required.

In conclusion, eumycetoma pedis is a rare deep fungal infection that can cause considerable morbidity. Patients should be well educated about this condition and be made aware of the risk of environmental exposure (eg, contact of broken skin with contaminated soil and water) and the need to wear protective footwear in potentially contaminated environments. Early diagnosis, correct treatment, and regular follow-up can reduce the risk of osteolytic complications and increase the possibility of complete recovery.

Pre-exposure prophylaxis (PrEP) for HIV is valuable enough for the federal government to mandate insurance coverage, a group of experts told the personal finance website WalletHub, but individuals who are at risk for infection may be missing out for other reasons.

The effectiveness of PrEP is clear, those experts said, but 34% of primary care physicians and nurses in the United States are unaware of the preventive regimen, according to the WalletHub report, which also noted that the majority of Americans with AIDS (61%) are not seeing a specialist.

“Even among [men who have sex with men] in the U.S., coverage is only about 10%, which is abysmal. We can and need to do better. If we don’t pay now, we’ll pay later,” Steffanie Strathdee, PhD, associate dean of global health sciences and Harold Simon Professor at the University of California, San Diego, told WalletHub.

Those taking PrEP have a 90% chance of avoiding HIV infection, the report noted.

“Making PrEP available to all is a giant step forward in the fight against HIV. Mandating this critical prevention be covered by all insurance plans makes it part of mainstream medicine and will only increase its use and help prevent HIV acquisition in exposed populations. I can’t think of other low-risk, high-reward prophylaxis for a lifelong disease,” said Sharon Nachman, MD, professor of pediatrics and associate dean for research at the State University of New York at Stony Brook.

To get PrEP covered, the U.S. Preventive Services Task Force needs to act, explained Gerald M. Oppenheimer, PhD, MPH, of the department of health policy and management at the City University of New York.

“Under the Affordable Care Act, if the [USPSTF] finds that PrEP serves as an effective prevention to disease and gives it a grade of A or B, all insurers must offer it free. That, of course, may lead to an increase in premiums. This is another example of pharmaceutical companies charging high prices in the U.S., compared to what other countries pay, and cries out for an amendment to Medicare Part D, allowing the federal government to negotiate lower drug prices,” he said.

rfranki@mdedge.com

Pre-exposure prophylaxis (PrEP) for HIV is valuable enough for the federal government to mandate insurance coverage, a group of experts told the personal finance website WalletHub, but individuals who are at risk for infection may be missing out for other reasons.

The effectiveness of PrEP is clear, those experts said, but 34% of primary care physicians and nurses in the United States are unaware of the preventive regimen, according to the WalletHub report, which also noted that the majority of Americans with AIDS (61%) are not seeing a specialist.

“Even among [men who have sex with men] in the U.S., coverage is only about 10%, which is abysmal. We can and need to do better. If we don’t pay now, we’ll pay later,” Steffanie Strathdee, PhD, associate dean of global health sciences and Harold Simon Professor at the University of California, San Diego, told WalletHub.

Those taking PrEP have a 90% chance of avoiding HIV infection, the report noted.

“Making PrEP available to all is a giant step forward in the fight against HIV. Mandating this critical prevention be covered by all insurance plans makes it part of mainstream medicine and will only increase its use and help prevent HIV acquisition in exposed populations. I can’t think of other low-risk, high-reward prophylaxis for a lifelong disease,” said Sharon Nachman, MD, professor of pediatrics and associate dean for research at the State University of New York at Stony Brook.

To get PrEP covered, the U.S. Preventive Services Task Force needs to act, explained Gerald M. Oppenheimer, PhD, MPH, of the department of health policy and management at the City University of New York.

“Under the Affordable Care Act, if the [USPSTF] finds that PrEP serves as an effective prevention to disease and gives it a grade of A or B, all insurers must offer it free. That, of course, may lead to an increase in premiums. This is another example of pharmaceutical companies charging high prices in the U.S., compared to what other countries pay, and cries out for an amendment to Medicare Part D, allowing the federal government to negotiate lower drug prices,” he said.

rfranki@mdedge.com

Pre-exposure prophylaxis (PrEP) for HIV is valuable enough for the federal government to mandate insurance coverage, a group of experts told the personal finance website WalletHub, but individuals who are at risk for infection may be missing out for other reasons.

The effectiveness of PrEP is clear, those experts said, but 34% of primary care physicians and nurses in the United States are unaware of the preventive regimen, according to the WalletHub report, which also noted that the majority of Americans with AIDS (61%) are not seeing a specialist.

“Even among [men who have sex with men] in the U.S., coverage is only about 10%, which is abysmal. We can and need to do better. If we don’t pay now, we’ll pay later,” Steffanie Strathdee, PhD, associate dean of global health sciences and Harold Simon Professor at the University of California, San Diego, told WalletHub.

Those taking PrEP have a 90% chance of avoiding HIV infection, the report noted.

“Making PrEP available to all is a giant step forward in the fight against HIV. Mandating this critical prevention be covered by all insurance plans makes it part of mainstream medicine and will only increase its use and help prevent HIV acquisition in exposed populations. I can’t think of other low-risk, high-reward prophylaxis for a lifelong disease,” said Sharon Nachman, MD, professor of pediatrics and associate dean for research at the State University of New York at Stony Brook.

To get PrEP covered, the U.S. Preventive Services Task Force needs to act, explained Gerald M. Oppenheimer, PhD, MPH, of the department of health policy and management at the City University of New York.

“Under the Affordable Care Act, if the [USPSTF] finds that PrEP serves as an effective prevention to disease and gives it a grade of A or B, all insurers must offer it free. That, of course, may lead to an increase in premiums. This is another example of pharmaceutical companies charging high prices in the U.S., compared to what other countries pay, and cries out for an amendment to Medicare Part D, allowing the federal government to negotiate lower drug prices,” he said.

rfranki@mdedge.com

To the Editor:

Postirradiation morphea (PIM) is a rare but well-documented phenomenon that primarily occurs in breast cancer patients who have received radiation therapy; however, it also has been reported in patients who have received radiation therapy for lymphoma as well as endocervical, endometrial, and gastric carcinomas.¹ Importantly, clinicians must be able to recognize and differentiate this condition from other causes of new-onset induration and erythema of the breast, such as cancer recurrence, a new primary malignancy, or inflammatory etiologies (eg, radiation or contact dermatitis). Typically, PIM presents months to years after radiation therapy as an erythematous patch within the irradiated area that progressively becomes indurated. We report an unusual case of PIM with a reticulated appearance occurring 3 weeks after radiotherapy, chemotherapy, and surgery for an infiltrating ductal carcinoma of the left breast.

A 62-year-old woman presented to the dermatology department with a stage IIA, lymph node–negative, estrogen and progesterone receptor–negative, human epidermal growth factor receptor 2–negative infiltrating ductal carcinoma of the left breast. She was treated with a partial mastectomy of the left breast followed by external beam radiotherapy to the entire left breast in combination with chemotherapy (doxorubicin, cyclophosphamide, paclitaxel). The patient received 15 fractions of 270 cGy (4050 cGy total) with a weekly 600-cGy boost over 21 days without any complications.

Three weeks after finishing radiation therapy, the patient developed redness and swelling of the left breast that did not encompass the entire radiation field. There was no associated pain or pruritus. She was treated by her surgical oncologist with topical calendula and 3 courses of cephalexin for suspected mastitis with only modest improvement, then was referred to dermatology 3 months later.

At the initial dermatology evaluation, the patient reported little improvement after antibiotics and topical calendula. On physical examination, there were erythematous, reticulated, dusky, indurated patches on the entire left breast. The area of most pronounced induration surrounded the surgical scar on the left superior breast. Punch biopsy for hematoxylin and eosin staining and tissue cultures was obtained at this appointment. The patient was started on doxycycline 100 mg twice daily and was instructed to apply triamcinolone ointment 0.1% twice daily to the affected area. After 1 month of therapy, she reported slight improvement in the degree of erythema with this regimen, but the involved area continued to extend outside of the radiation field to the central chest wall and medial right breast (Figure 1). Two additional biopsies—one from the central chest and another from the right breast—were then taken over the course of 4 months, given the consistently inconclusive clinicopathologic nature and failure of the eruption to respond to antibiotics plus topical corticosteroids.

Punch biopsy from the central chest revealed a sparse perivascular infiltrate comprised predominantly of lymphocytes with occasional eosinophils (Figure 2). There were foci suggestive of early dermal sclerosis, an increased number of small blood vessels in the dermis, and scattered enlarged fibroblasts. Metastatic carcinoma was not identified. Although the histologic findings were not entirely specific, the changes were most suggestive of PIM, for which the patient was started on pentoxifylline (400 mg 3 times daily) and oral vitamin E supplementation (400 IU daily). At subsequent follow-up appointments, she showed markedly decreased skin erythema and induration.

Morphea, also known as localized scleroderma, is an inflammatory skin condition characterized by sclerosis of the dermis and subcutis leading to scarlike tissue formation. Worldwide incidence ranges from 0.4 to 2.7 cases per 100,000 individuals with a predilection for white women.² Unlike systemic scleroderma, morphea patients lack Raynaud phenomenon and visceral involvement.^3,4

There are several clinical subtypes of morphea, including plaque, linear, generalized, and pansclerotic morphea. Lesions may vary in appearance based on configuration, stage of development, and depth of involvement.⁴ During the earliest phases, morphea lesions are asymptomatic, asymmetrically distributed, erythematous to violaceous patches or subtly indurated plaques expanding centrifugally with a lilac ring. Central sclerosis with loss of follicles and sweat glands is a later finding associated with advanced disease. Moreover, some reports of early-stage morphea have suggested a reticulated or geographic vascular morphology that may be misdiagnosed for other conditions such as a port-wine stain.⁵

Local skin exposures have long been hypothesized to contribute to development of morphea, including infection, especially Borrelia burgdorferi; trauma; chronic venous insufficiency; cosmetic surgery; medications; and exposure to toxic cooking oils, silicones, silica, pesticides, organic solvents, and vinyl chloride.^2,6,7

Radiation therapy is an often overlooked cause of morphea. It was first described in 1905 but then rarely discussed until a 1989 case series of 9 patients, 7 of whom had received irradiation for breast cancer.^8,9 Today, the increasing popularity of lumpectomy plus radiation therapy for treatment of early-stage breast cancer has led to a rise in PIM incidence.¹⁰Estimates have indicated an incidence among previously irradiated breast cancer patients as high as 1 in 500 individuals, appreciably higher than that seen in the general population.¹¹ Tissue changes occur as early as weeks or as late as 32 years after radiation treatment and are commonly mistaken for mastitis, such as in our case, as well as radiation dermatitis, radiation fibrosis, or malignant conditions.^1,11

In contrast to other radiation-induced skin conditions, development of PIM is independent of the presence or absence of adjuvant chemotherapy, type of radiation therapy, or the total radiation dose or fractionation number, with reported doses ranging from less than 20.0 Gy to up to 59.4 Gy and dose fractions ranging from 10 to 30. In 20% to 30% of cases, PIM extends beyond the radiation field, sometimes involving distant sites never exposed to high-energy rays.^1,10,11 This observation suggests a mechanism reliant on more widespread cascade rather than solely local tissue damage.

Prominent culture-negative, lymphoplasmacytic inflammation is another important diagnostic clue. Radiation dermatitis and fibrosis do not have the marked erythematous to violaceous hue seen in early morphea plaques. This color seen in early morphea plaques may be intense enough and in a geographic pattern, emulating a vascular lesion. However, a PubMed search of articles indexed for MEDLINE using the terms reticulate radiation morphea and livedo radiation morphea yielded no reports linking the reticulate erythema seen in our patient with early PIM. It is important to note that the histopathology findings in our patient were not entirely specific, and although there were some background changes that may have represented a sequela of radiation to the area (ie, the enlarged fibroblasts and increased number of vessels), there were foci suggestive of early sclerosing dermatitis. With clinical correlation, including the extension beyond the radiation field, these changes were best interpreted as early PIM. Therefore, our case demonstrated a novel presentation of a frequently underrecognized trigger for morphea. Although we favored a diagnosis of PIM, a fibrosing chronic radiation dermatitis could not be entirely excluded based on the clinical and histologic features.

There is no standardized treatment of PIM, but traditional therapies for morphea may provide some benefit. Several randomized controlled clinical trials have shown success with pentoxifylline and oral vitamin E supplementation to treat or prevent radiation-induced breast fibrosis.¹² Extrapolating from this data, our patient was started on this combination therapy and showed marked improvement in skin color and texture.

To the Editor:

Postirradiation morphea (PIM) is a rare but well-documented phenomenon that primarily occurs in breast cancer patients who have received radiation therapy; however, it also has been reported in patients who have received radiation therapy for lymphoma as well as endocervical, endometrial, and gastric carcinomas.¹ Importantly, clinicians must be able to recognize and differentiate this condition from other causes of new-onset induration and erythema of the breast, such as cancer recurrence, a new primary malignancy, or inflammatory etiologies (eg, radiation or contact dermatitis). Typically, PIM presents months to years after radiation therapy as an erythematous patch within the irradiated area that progressively becomes indurated. We report an unusual case of PIM with a reticulated appearance occurring 3 weeks after radiotherapy, chemotherapy, and surgery for an infiltrating ductal carcinoma of the left breast.

A 62-year-old woman presented to the dermatology department with a stage IIA, lymph node–negative, estrogen and progesterone receptor–negative, human epidermal growth factor receptor 2–negative infiltrating ductal carcinoma of the left breast. She was treated with a partial mastectomy of the left breast followed by external beam radiotherapy to the entire left breast in combination with chemotherapy (doxorubicin, cyclophosphamide, paclitaxel). The patient received 15 fractions of 270 cGy (4050 cGy total) with a weekly 600-cGy boost over 21 days without any complications.

Three weeks after finishing radiation therapy, the patient developed redness and swelling of the left breast that did not encompass the entire radiation field. There was no associated pain or pruritus. She was treated by her surgical oncologist with topical calendula and 3 courses of cephalexin for suspected mastitis with only modest improvement, then was referred to dermatology 3 months later.

At the initial dermatology evaluation, the patient reported little improvement after antibiotics and topical calendula. On physical examination, there were erythematous, reticulated, dusky, indurated patches on the entire left breast. The area of most pronounced induration surrounded the surgical scar on the left superior breast. Punch biopsy for hematoxylin and eosin staining and tissue cultures was obtained at this appointment. The patient was started on doxycycline 100 mg twice daily and was instructed to apply triamcinolone ointment 0.1% twice daily to the affected area. After 1 month of therapy, she reported slight improvement in the degree of erythema with this regimen, but the involved area continued to extend outside of the radiation field to the central chest wall and medial right breast (Figure 1). Two additional biopsies—one from the central chest and another from the right breast—were then taken over the course of 4 months, given the consistently inconclusive clinicopathologic nature and failure of the eruption to respond to antibiotics plus topical corticosteroids.

Punch biopsy from the central chest revealed a sparse perivascular infiltrate comprised predominantly of lymphocytes with occasional eosinophils (Figure 2). There were foci suggestive of early dermal sclerosis, an increased number of small blood vessels in the dermis, and scattered enlarged fibroblasts. Metastatic carcinoma was not identified. Although the histologic findings were not entirely specific, the changes were most suggestive of PIM, for which the patient was started on pentoxifylline (400 mg 3 times daily) and oral vitamin E supplementation (400 IU daily). At subsequent follow-up appointments, she showed markedly decreased skin erythema and induration.

Morphea, also known as localized scleroderma, is an inflammatory skin condition characterized by sclerosis of the dermis and subcutis leading to scarlike tissue formation. Worldwide incidence ranges from 0.4 to 2.7 cases per 100,000 individuals with a predilection for white women.² Unlike systemic scleroderma, morphea patients lack Raynaud phenomenon and visceral involvement.^3,4

There are several clinical subtypes of morphea, including plaque, linear, generalized, and pansclerotic morphea. Lesions may vary in appearance based on configuration, stage of development, and depth of involvement.⁴ During the earliest phases, morphea lesions are asymptomatic, asymmetrically distributed, erythematous to violaceous patches or subtly indurated plaques expanding centrifugally with a lilac ring. Central sclerosis with loss of follicles and sweat glands is a later finding associated with advanced disease. Moreover, some reports of early-stage morphea have suggested a reticulated or geographic vascular morphology that may be misdiagnosed for other conditions such as a port-wine stain.⁵

Local skin exposures have long been hypothesized to contribute to development of morphea, including infection, especially Borrelia burgdorferi; trauma; chronic venous insufficiency; cosmetic surgery; medications; and exposure to toxic cooking oils, silicones, silica, pesticides, organic solvents, and vinyl chloride.^2,6,7

Radiation therapy is an often overlooked cause of morphea. It was first described in 1905 but then rarely discussed until a 1989 case series of 9 patients, 7 of whom had received irradiation for breast cancer.^8,9 Today, the increasing popularity of lumpectomy plus radiation therapy for treatment of early-stage breast cancer has led to a rise in PIM incidence.¹⁰Estimates have indicated an incidence among previously irradiated breast cancer patients as high as 1 in 500 individuals, appreciably higher than that seen in the general population.¹¹ Tissue changes occur as early as weeks or as late as 32 years after radiation treatment and are commonly mistaken for mastitis, such as in our case, as well as radiation dermatitis, radiation fibrosis, or malignant conditions.^1,11

In contrast to other radiation-induced skin conditions, development of PIM is independent of the presence or absence of adjuvant chemotherapy, type of radiation therapy, or the total radiation dose or fractionation number, with reported doses ranging from less than 20.0 Gy to up to 59.4 Gy and dose fractions ranging from 10 to 30. In 20% to 30% of cases, PIM extends beyond the radiation field, sometimes involving distant sites never exposed to high-energy rays.^1,10,11 This observation suggests a mechanism reliant on more widespread cascade rather than solely local tissue damage.

Prominent culture-negative, lymphoplasmacytic inflammation is another important diagnostic clue. Radiation dermatitis and fibrosis do not have the marked erythematous to violaceous hue seen in early morphea plaques. This color seen in early morphea plaques may be intense enough and in a geographic pattern, emulating a vascular lesion. However, a PubMed search of articles indexed for MEDLINE using the terms reticulate radiation morphea and livedo radiation morphea yielded no reports linking the reticulate erythema seen in our patient with early PIM. It is important to note that the histopathology findings in our patient were not entirely specific, and although there were some background changes that may have represented a sequela of radiation to the area (ie, the enlarged fibroblasts and increased number of vessels), there were foci suggestive of early sclerosing dermatitis. With clinical correlation, including the extension beyond the radiation field, these changes were best interpreted as early PIM. Therefore, our case demonstrated a novel presentation of a frequently underrecognized trigger for morphea. Although we favored a diagnosis of PIM, a fibrosing chronic radiation dermatitis could not be entirely excluded based on the clinical and histologic features.

There is no standardized treatment of PIM, but traditional therapies for morphea may provide some benefit. Several randomized controlled clinical trials have shown success with pentoxifylline and oral vitamin E supplementation to treat or prevent radiation-induced breast fibrosis.¹² Extrapolating from this data, our patient was started on this combination therapy and showed marked improvement in skin color and texture.

To the Editor:

Postirradiation morphea (PIM) is a rare but well-documented phenomenon that primarily occurs in breast cancer patients who have received radiation therapy; however, it also has been reported in patients who have received radiation therapy for lymphoma as well as endocervical, endometrial, and gastric carcinomas.¹ Importantly, clinicians must be able to recognize and differentiate this condition from other causes of new-onset induration and erythema of the breast, such as cancer recurrence, a new primary malignancy, or inflammatory etiologies (eg, radiation or contact dermatitis). Typically, PIM presents months to years after radiation therapy as an erythematous patch within the irradiated area that progressively becomes indurated. We report an unusual case of PIM with a reticulated appearance occurring 3 weeks after radiotherapy, chemotherapy, and surgery for an infiltrating ductal carcinoma of the left breast.

A 62-year-old woman presented to the dermatology department with a stage IIA, lymph node–negative, estrogen and progesterone receptor–negative, human epidermal growth factor receptor 2–negative infiltrating ductal carcinoma of the left breast. She was treated with a partial mastectomy of the left breast followed by external beam radiotherapy to the entire left breast in combination with chemotherapy (doxorubicin, cyclophosphamide, paclitaxel). The patient received 15 fractions of 270 cGy (4050 cGy total) with a weekly 600-cGy boost over 21 days without any complications.

Three weeks after finishing radiation therapy, the patient developed redness and swelling of the left breast that did not encompass the entire radiation field. There was no associated pain or pruritus. She was treated by her surgical oncologist with topical calendula and 3 courses of cephalexin for suspected mastitis with only modest improvement, then was referred to dermatology 3 months later.

At the initial dermatology evaluation, the patient reported little improvement after antibiotics and topical calendula. On physical examination, there were erythematous, reticulated, dusky, indurated patches on the entire left breast. The area of most pronounced induration surrounded the surgical scar on the left superior breast. Punch biopsy for hematoxylin and eosin staining and tissue cultures was obtained at this appointment. The patient was started on doxycycline 100 mg twice daily and was instructed to apply triamcinolone ointment 0.1% twice daily to the affected area. After 1 month of therapy, she reported slight improvement in the degree of erythema with this regimen, but the involved area continued to extend outside of the radiation field to the central chest wall and medial right breast (Figure 1). Two additional biopsies—one from the central chest and another from the right breast—were then taken over the course of 4 months, given the consistently inconclusive clinicopathologic nature and failure of the eruption to respond to antibiotics plus topical corticosteroids.

Punch biopsy from the central chest revealed a sparse perivascular infiltrate comprised predominantly of lymphocytes with occasional eosinophils (Figure 2). There were foci suggestive of early dermal sclerosis, an increased number of small blood vessels in the dermis, and scattered enlarged fibroblasts. Metastatic carcinoma was not identified. Although the histologic findings were not entirely specific, the changes were most suggestive of PIM, for which the patient was started on pentoxifylline (400 mg 3 times daily) and oral vitamin E supplementation (400 IU daily). At subsequent follow-up appointments, she showed markedly decreased skin erythema and induration.

Morphea, also known as localized scleroderma, is an inflammatory skin condition characterized by sclerosis of the dermis and subcutis leading to scarlike tissue formation. Worldwide incidence ranges from 0.4 to 2.7 cases per 100,000 individuals with a predilection for white women.² Unlike systemic scleroderma, morphea patients lack Raynaud phenomenon and visceral involvement.^3,4

There are several clinical subtypes of morphea, including plaque, linear, generalized, and pansclerotic morphea. Lesions may vary in appearance based on configuration, stage of development, and depth of involvement.⁴ During the earliest phases, morphea lesions are asymptomatic, asymmetrically distributed, erythematous to violaceous patches or subtly indurated plaques expanding centrifugally with a lilac ring. Central sclerosis with loss of follicles and sweat glands is a later finding associated with advanced disease. Moreover, some reports of early-stage morphea have suggested a reticulated or geographic vascular morphology that may be misdiagnosed for other conditions such as a port-wine stain.⁵

Local skin exposures have long been hypothesized to contribute to development of morphea, including infection, especially Borrelia burgdorferi; trauma; chronic venous insufficiency; cosmetic surgery; medications; and exposure to toxic cooking oils, silicones, silica, pesticides, organic solvents, and vinyl chloride.^2,6,7

Radiation therapy is an often overlooked cause of morphea. It was first described in 1905 but then rarely discussed until a 1989 case series of 9 patients, 7 of whom had received irradiation for breast cancer.^8,9 Today, the increasing popularity of lumpectomy plus radiation therapy for treatment of early-stage breast cancer has led to a rise in PIM incidence.¹⁰Estimates have indicated an incidence among previously irradiated breast cancer patients as high as 1 in 500 individuals, appreciably higher than that seen in the general population.¹¹ Tissue changes occur as early as weeks or as late as 32 years after radiation treatment and are commonly mistaken for mastitis, such as in our case, as well as radiation dermatitis, radiation fibrosis, or malignant conditions.^1,11

In contrast to other radiation-induced skin conditions, development of PIM is independent of the presence or absence of adjuvant chemotherapy, type of radiation therapy, or the total radiation dose or fractionation number, with reported doses ranging from less than 20.0 Gy to up to 59.4 Gy and dose fractions ranging from 10 to 30. In 20% to 30% of cases, PIM extends beyond the radiation field, sometimes involving distant sites never exposed to high-energy rays.^1,10,11 This observation suggests a mechanism reliant on more widespread cascade rather than solely local tissue damage.

Prominent culture-negative, lymphoplasmacytic inflammation is another important diagnostic clue. Radiation dermatitis and fibrosis do not have the marked erythematous to violaceous hue seen in early morphea plaques. This color seen in early morphea plaques may be intense enough and in a geographic pattern, emulating a vascular lesion. However, a PubMed search of articles indexed for MEDLINE using the terms reticulate radiation morphea and livedo radiation morphea yielded no reports linking the reticulate erythema seen in our patient with early PIM. It is important to note that the histopathology findings in our patient were not entirely specific, and although there were some background changes that may have represented a sequela of radiation to the area (ie, the enlarged fibroblasts and increased number of vessels), there were foci suggestive of early sclerosing dermatitis. With clinical correlation, including the extension beyond the radiation field, these changes were best interpreted as early PIM. Therefore, our case demonstrated a novel presentation of a frequently underrecognized trigger for morphea. Although we favored a diagnosis of PIM, a fibrosing chronic radiation dermatitis could not be entirely excluded based on the clinical and histologic features.

There is no standardized treatment of PIM, but traditional therapies for morphea may provide some benefit. Several randomized controlled clinical trials have shown success with pentoxifylline and oral vitamin E supplementation to treat or prevent radiation-induced breast fibrosis.¹² Extrapolating from this data, our patient was started on this combination therapy and showed marked improvement in skin color and texture.

CHICAGO – The big news regarding Lyme disease at the annual meeting of the American College of Rheumatology was a report that hamstring tendon calcification is extremely common among patients who have persistent Lyme arthritis despite having undergone appropriate antibiotic therapy.

“This is a fascinating study,” Robert A. Kalish, MD, a Lyme disease expert not involved in the research, said regarding the report by Sheila L. Arvikar, MD, and her coworkers at Massachusetts General Hospital, Boston.

One implication of this finding by a renowned group of Lyme disease researchers is that persistent posttreatment Lyme arthritis may in many cases be due to ongoing immunostimulation by spirochete remains located in hamstring tendons, a privileged, relatively avascular site where the foreign material may be able to evade immune clearance.

Also, as Dr. Arvikar pointed out in her presentation, calcific tendinopathy implies prior inflammation or degenerative changes. Thus, these calcific hamstring abnormalities implicate the hamstring tendons as a potential initial site of infection by hematogenously-spread Borrelia burgdorferi during the prearthritis phase of Lyme disease.

A further implication of the study is the possibility that hamstring tendon calcification could serve as a useful diagnostic aid in distinguishing Lyme arthritis from arthritis due to other causes. In the study, hamstring calcific tendinopathy was found in 28 of 31 adults and children with Lyme arthritis, 3 of 22 with knee osteoarthritis, and 1 of 14 patients with inflammatory arthritis, Dr. Arvikar noted.

She and her coinvestigators evaluated tendon pathology in their retrospective study of patients at the Massachusetts General Hospital Rheumatology Musculoskeletal Ultrasound Clinic. They used ultrasound because they have found it offers far better spatial resolution of calcification than does MRI or x-rays. The semimembranosus tendon was the hamstring tendon that most commonly exhibited calcification, although 11 patients with Lyme arthritis also had involvement of the semitendinosus tendon, compared with none of the controls with osteoarthritis or inflammatory arthritis.

In the eight patients with serial ultrasound evaluations over a period of up to 12 months, the calcification persisted but the symptoms of tendinitis and synovitis improved.

Dr. Arvikar and her colleagues are expanding the scope of their ongoing study by examining patients whose Lyme arthritis is milder than that of the initial population, including patients who haven’t yet received antibiotics. They are also evaluating more controls with inflammatory arthritis.

In a separate presentation, Dr. Kalish noted that Lyme arthritis, the manifestation of Lyme disease of greatest interest to rheumatologists, occurs in about 60% of untreated patients, with onset a mean of 6 months after the tick bite. It typically entails recurrent mono- or oligoarthritis of large joints. The knee is involved in roughly 95% of cases.

The natural history of untreated Lyme arthritis is a spontaneous resolution rate of 10%-20% per year. Since the 1980s, however, 4 weeks of oral doxycycline or amoxicillin has been the treatment of choice. About 10% of patients with Lyme arthritis continue to have active synovitis 3 months after their course of antibiotics.

“There are some patients you give the treatment to and their arthritis just melts away in a month, but some, no matter what you do with antibiotics, continue to have synovitis, often developing a highly proliferative palpable synovitis that is really gunked up and features obliterative microvascular lesions,” observed Dr. Kalish, a rheumatologist at Tufts University in Boston.

Dr. Kalish said that persistent posttreatment Lyme arthritis is most often due to a self-perpetuating immune response after the spirochete has been killed by antibiotics. He noted that patients with certain HLA-DRB1 haplotypes are more likely to experience persistent Lyme arthritis after standard recommended courses of antibiotics, and these DRB1 alleles correlate closely with the shared epitope associated with increased susceptibility to rheumatoid arthritis. Several candidate autoantigens have already been identified.

He noted that the Massachusetts General group, in an earlier study, demonstrated that the presence of B. burgdorferi DNA by PCR in synovial fluid from patients with persistent Lyme arthritis after antibiotic therapy was not a reliable indicator of active joint infection (Arthritis Rheum. 2011 Aug;63[8]:2238-47).

“This was a paradigm change for me in seeing this study, because prior to that I had used PCR somewhat to guide treatment and make management decisions,” Dr. Kalish said.

What’s a reasonable treatment strategy in patients with persistent Lyme arthritis despite 30 days of oral antibiotics? Dr. Kalish favors an algorithm similar to one published by Dr. Arvikar and Allen C. Steere, MD (Infect Dis Clin North Am. 2015 Jun;29[2]:269-80). In the case of mild persistent arthritis, he opts for another 30 days of oral doxycycline. If the arthritis is moderate or severe, he goes with either another 30 days of doxycycline or 30 days of intravenous ceftriaxone.

If the arthritis still hasn’t resolved despite two 30-day rounds of antibiotic therapy, he prescribes an NSAID or hydroxychloroquine if the persistent arthritis is mild, or methotrexate if it’s moderate to severe. And if the arthritis still persists after 3-6 months of disease-modifying antirheumatic drug therapy, he’ll consider synovectomy, which has a good success rate.

Neither Dr. Arvikar nor Dr. Kalish reported having any financial conflicts regarding their presentations.

bjancin@mdedge.com

SOURCE: Arvikar SL et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 950.

CHICAGO – The big news regarding Lyme disease at the annual meeting of the American College of Rheumatology was a report that hamstring tendon calcification is extremely common among patients who have persistent Lyme arthritis despite having undergone appropriate antibiotic therapy.

“This is a fascinating study,” Robert A. Kalish, MD, a Lyme disease expert not involved in the research, said regarding the report by Sheila L. Arvikar, MD, and her coworkers at Massachusetts General Hospital, Boston.

One implication of this finding by a renowned group of Lyme disease researchers is that persistent posttreatment Lyme arthritis may in many cases be due to ongoing immunostimulation by spirochete remains located in hamstring tendons, a privileged, relatively avascular site where the foreign material may be able to evade immune clearance.

Also, as Dr. Arvikar pointed out in her presentation, calcific tendinopathy implies prior inflammation or degenerative changes. Thus, these calcific hamstring abnormalities implicate the hamstring tendons as a potential initial site of infection by hematogenously-spread Borrelia burgdorferi during the prearthritis phase of Lyme disease.

A further implication of the study is the possibility that hamstring tendon calcification could serve as a useful diagnostic aid in distinguishing Lyme arthritis from arthritis due to other causes. In the study, hamstring calcific tendinopathy was found in 28 of 31 adults and children with Lyme arthritis, 3 of 22 with knee osteoarthritis, and 1 of 14 patients with inflammatory arthritis, Dr. Arvikar noted.

She and her coinvestigators evaluated tendon pathology in their retrospective study of patients at the Massachusetts General Hospital Rheumatology Musculoskeletal Ultrasound Clinic. They used ultrasound because they have found it offers far better spatial resolution of calcification than does MRI or x-rays. The semimembranosus tendon was the hamstring tendon that most commonly exhibited calcification, although 11 patients with Lyme arthritis also had involvement of the semitendinosus tendon, compared with none of the controls with osteoarthritis or inflammatory arthritis.

In the eight patients with serial ultrasound evaluations over a period of up to 12 months, the calcification persisted but the symptoms of tendinitis and synovitis improved.

Dr. Arvikar and her colleagues are expanding the scope of their ongoing study by examining patients whose Lyme arthritis is milder than that of the initial population, including patients who haven’t yet received antibiotics. They are also evaluating more controls with inflammatory arthritis.

In a separate presentation, Dr. Kalish noted that Lyme arthritis, the manifestation of Lyme disease of greatest interest to rheumatologists, occurs in about 60% of untreated patients, with onset a mean of 6 months after the tick bite. It typically entails recurrent mono- or oligoarthritis of large joints. The knee is involved in roughly 95% of cases.

The natural history of untreated Lyme arthritis is a spontaneous resolution rate of 10%-20% per year. Since the 1980s, however, 4 weeks of oral doxycycline or amoxicillin has been the treatment of choice. About 10% of patients with Lyme arthritis continue to have active synovitis 3 months after their course of antibiotics.

“There are some patients you give the treatment to and their arthritis just melts away in a month, but some, no matter what you do with antibiotics, continue to have synovitis, often developing a highly proliferative palpable synovitis that is really gunked up and features obliterative microvascular lesions,” observed Dr. Kalish, a rheumatologist at Tufts University in Boston.

Dr. Kalish said that persistent posttreatment Lyme arthritis is most often due to a self-perpetuating immune response after the spirochete has been killed by antibiotics. He noted that patients with certain HLA-DRB1 haplotypes are more likely to experience persistent Lyme arthritis after standard recommended courses of antibiotics, and these DRB1 alleles correlate closely with the shared epitope associated with increased susceptibility to rheumatoid arthritis. Several candidate autoantigens have already been identified.

He noted that the Massachusetts General group, in an earlier study, demonstrated that the presence of B. burgdorferi DNA by PCR in synovial fluid from patients with persistent Lyme arthritis after antibiotic therapy was not a reliable indicator of active joint infection (Arthritis Rheum. 2011 Aug;63[8]:2238-47).

“This was a paradigm change for me in seeing this study, because prior to that I had used PCR somewhat to guide treatment and make management decisions,” Dr. Kalish said.

What’s a reasonable treatment strategy in patients with persistent Lyme arthritis despite 30 days of oral antibiotics? Dr. Kalish favors an algorithm similar to one published by Dr. Arvikar and Allen C. Steere, MD (Infect Dis Clin North Am. 2015 Jun;29[2]:269-80). In the case of mild persistent arthritis, he opts for another 30 days of oral doxycycline. If the arthritis is moderate or severe, he goes with either another 30 days of doxycycline or 30 days of intravenous ceftriaxone.

If the arthritis still hasn’t resolved despite two 30-day rounds of antibiotic therapy, he prescribes an NSAID or hydroxychloroquine if the persistent arthritis is mild, or methotrexate if it’s moderate to severe. And if the arthritis still persists after 3-6 months of disease-modifying antirheumatic drug therapy, he’ll consider synovectomy, which has a good success rate.

Neither Dr. Arvikar nor Dr. Kalish reported having any financial conflicts regarding their presentations.

bjancin@mdedge.com

SOURCE: Arvikar SL et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 950.

CHICAGO – The big news regarding Lyme disease at the annual meeting of the American College of Rheumatology was a report that hamstring tendon calcification is extremely common among patients who have persistent Lyme arthritis despite having undergone appropriate antibiotic therapy.

“This is a fascinating study,” Robert A. Kalish, MD, a Lyme disease expert not involved in the research, said regarding the report by Sheila L. Arvikar, MD, and her coworkers at Massachusetts General Hospital, Boston.

One implication of this finding by a renowned group of Lyme disease researchers is that persistent posttreatment Lyme arthritis may in many cases be due to ongoing immunostimulation by spirochete remains located in hamstring tendons, a privileged, relatively avascular site where the foreign material may be able to evade immune clearance.

Also, as Dr. Arvikar pointed out in her presentation, calcific tendinopathy implies prior inflammation or degenerative changes. Thus, these calcific hamstring abnormalities implicate the hamstring tendons as a potential initial site of infection by hematogenously-spread Borrelia burgdorferi during the prearthritis phase of Lyme disease.

A further implication of the study is the possibility that hamstring tendon calcification could serve as a useful diagnostic aid in distinguishing Lyme arthritis from arthritis due to other causes. In the study, hamstring calcific tendinopathy was found in 28 of 31 adults and children with Lyme arthritis, 3 of 22 with knee osteoarthritis, and 1 of 14 patients with inflammatory arthritis, Dr. Arvikar noted.

She and her coinvestigators evaluated tendon pathology in their retrospective study of patients at the Massachusetts General Hospital Rheumatology Musculoskeletal Ultrasound Clinic. They used ultrasound because they have found it offers far better spatial resolution of calcification than does MRI or x-rays. The semimembranosus tendon was the hamstring tendon that most commonly exhibited calcification, although 11 patients with Lyme arthritis also had involvement of the semitendinosus tendon, compared with none of the controls with osteoarthritis or inflammatory arthritis.

In the eight patients with serial ultrasound evaluations over a period of up to 12 months, the calcification persisted but the symptoms of tendinitis and synovitis improved.

Dr. Arvikar and her colleagues are expanding the scope of their ongoing study by examining patients whose Lyme arthritis is milder than that of the initial population, including patients who haven’t yet received antibiotics. They are also evaluating more controls with inflammatory arthritis.

In a separate presentation, Dr. Kalish noted that Lyme arthritis, the manifestation of Lyme disease of greatest interest to rheumatologists, occurs in about 60% of untreated patients, with onset a mean of 6 months after the tick bite. It typically entails recurrent mono- or oligoarthritis of large joints. The knee is involved in roughly 95% of cases.

The natural history of untreated Lyme arthritis is a spontaneous resolution rate of 10%-20% per year. Since the 1980s, however, 4 weeks of oral doxycycline or amoxicillin has been the treatment of choice. About 10% of patients with Lyme arthritis continue to have active synovitis 3 months after their course of antibiotics.

“There are some patients you give the treatment to and their arthritis just melts away in a month, but some, no matter what you do with antibiotics, continue to have synovitis, often developing a highly proliferative palpable synovitis that is really gunked up and features obliterative microvascular lesions,” observed Dr. Kalish, a rheumatologist at Tufts University in Boston.

Dr. Kalish said that persistent posttreatment Lyme arthritis is most often due to a self-perpetuating immune response after the spirochete has been killed by antibiotics. He noted that patients with certain HLA-DRB1 haplotypes are more likely to experience persistent Lyme arthritis after standard recommended courses of antibiotics, and these DRB1 alleles correlate closely with the shared epitope associated with increased susceptibility to rheumatoid arthritis. Several candidate autoantigens have already been identified.

He noted that the Massachusetts General group, in an earlier study, demonstrated that the presence of B. burgdorferi DNA by PCR in synovial fluid from patients with persistent Lyme arthritis after antibiotic therapy was not a reliable indicator of active joint infection (Arthritis Rheum. 2011 Aug;63[8]:2238-47).

“This was a paradigm change for me in seeing this study, because prior to that I had used PCR somewhat to guide treatment and make management decisions,” Dr. Kalish said.

What’s a reasonable treatment strategy in patients with persistent Lyme arthritis despite 30 days of oral antibiotics? Dr. Kalish favors an algorithm similar to one published by Dr. Arvikar and Allen C. Steere, MD (Infect Dis Clin North Am. 2015 Jun;29[2]:269-80). In the case of mild persistent arthritis, he opts for another 30 days of oral doxycycline. If the arthritis is moderate or severe, he goes with either another 30 days of doxycycline or 30 days of intravenous ceftriaxone.

If the arthritis still hasn’t resolved despite two 30-day rounds of antibiotic therapy, he prescribes an NSAID or hydroxychloroquine if the persistent arthritis is mild, or methotrexate if it’s moderate to severe. And if the arthritis still persists after 3-6 months of disease-modifying antirheumatic drug therapy, he’ll consider synovectomy, which has a good success rate.

Neither Dr. Arvikar nor Dr. Kalish reported having any financial conflicts regarding their presentations.

bjancin@mdedge.com

SOURCE: Arvikar SL et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 950.

The NIH and DoD are working on a new database that aims to establish the number of people in the US living with limb loss and to provide insight on their challenges and needs.

The Limb Loss and Preservation Registry, expected to be operational in 2020, will address a “significant public health knowledge gap,” said Dr. Alison Cernich, director of the National Center for Medical Rehabilitation Research. She says the information housed in the database will be vital to preventing limb loss, improving amputation surgeries, refining rehabilitation approaches, and guiding the development of devices for people who have lost limbs. Researchers will be able to sort the data by age, gender, and type of limb loss.

The National Institute of Child Health and Human Development has awarded a 5-year contract, capped at $5 million, to the Mayo Clinic to develop and launch the registry.

The NIH and DoD chose to join resources because there are not enough amputations within the DoD alone to provide a suitable sample for statistically valid conclusions, Dr. Cernich said. Moreover, data available from the DoD and the VA do not include service members who leave the military and seek care in the private sector. Cernich says the partnership between federal agencies will allow them to collect data that will “inform research and improve the lives of all citizens coping with limb loss.”

The NIH and DoD are working on a new database that aims to establish the number of people in the US living with limb loss and to provide insight on their challenges and needs.

The Limb Loss and Preservation Registry, expected to be operational in 2020, will address a “significant public health knowledge gap,” said Dr. Alison Cernich, director of the National Center for Medical Rehabilitation Research. She says the information housed in the database will be vital to preventing limb loss, improving amputation surgeries, refining rehabilitation approaches, and guiding the development of devices for people who have lost limbs. Researchers will be able to sort the data by age, gender, and type of limb loss.

The National Institute of Child Health and Human Development has awarded a 5-year contract, capped at $5 million, to the Mayo Clinic to develop and launch the registry.

The NIH and DoD chose to join resources because there are not enough amputations within the DoD alone to provide a suitable sample for statistically valid conclusions, Dr. Cernich said. Moreover, data available from the DoD and the VA do not include service members who leave the military and seek care in the private sector. Cernich says the partnership between federal agencies will allow them to collect data that will “inform research and improve the lives of all citizens coping with limb loss.”

The NIH and DoD are working on a new database that aims to establish the number of people in the US living with limb loss and to provide insight on their challenges and needs.

The Limb Loss and Preservation Registry, expected to be operational in 2020, will address a “significant public health knowledge gap,” said Dr. Alison Cernich, director of the National Center for Medical Rehabilitation Research. She says the information housed in the database will be vital to preventing limb loss, improving amputation surgeries, refining rehabilitation approaches, and guiding the development of devices for people who have lost limbs. Researchers will be able to sort the data by age, gender, and type of limb loss.

The National Institute of Child Health and Human Development has awarded a 5-year contract, capped at $5 million, to the Mayo Clinic to develop and launch the registry.

The NIH and DoD chose to join resources because there are not enough amputations within the DoD alone to provide a suitable sample for statistically valid conclusions, Dr. Cernich said. Moreover, data available from the DoD and the VA do not include service members who leave the military and seek care in the private sector. Cernich says the partnership between federal agencies will allow them to collect data that will “inform research and improve the lives of all citizens coping with limb loss.”

U.S. life expectancy is down while drug overdose and suicide are up sharply. Also today, an increase of less-distressed patients is driving an increase in outpatient services, the American Society of Hematology releases new guidelines on VTE ahead of ASH 2018 and commentary from Francis Collins, MD, denouncing reports from China on CRISPR-cas9 editing on embryos.
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U.S. life expectancy is down while drug overdose and suicide are up sharply. Also today, an increase of less-distressed patients is driving an increase in outpatient services, the American Society of Hematology releases new guidelines on VTE ahead of ASH 2018 and commentary from Francis Collins, MD, denouncing reports from China on CRISPR-cas9 editing on embryos.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

U.S. life expectancy is down while drug overdose and suicide are up sharply. Also today, an increase of less-distressed patients is driving an increase in outpatient services, the American Society of Hematology releases new guidelines on VTE ahead of ASH 2018 and commentary from Francis Collins, MD, denouncing reports from China on CRISPR-cas9 editing on embryos.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

Photo from Business Wire

The U.S. Food and Drug Administration (FDA) has released a safety communication warning that cases of  differentiation syndrome are going unnoticed in patients treated with the IDH2 inhibitor enasidenib (Idhifa).

Enasidenib is FDA-approved to treat adults with relapsed or refractory acute myeloid leukemia (AML) and an IDH2 mutation.

The drug is known to be associated with differentiation syndrome, and the prescribing information contains a boxed warning about this life-threatening condition.

However, the FDA has found that patients and healthcare providers are missing the signs and symptoms of differentiation syndrome, and some patients are not receiving the necessary treatment in time.

The FDA is also warning that differentiation syndrome has been observed in AML patients taking the IDH1 inhibitor ivosidenib (Tibsovo).

However, the agency has not provided many details on cases related to this drug, which is FDA-approved to treat adults with relapsed or refractory AML who have an IDH1 mutation.

Recognizing differentiation syndrome

The FDA says differentiation syndrome may occur anywhere from 10 days to 5 months after starting enasidenib.

The agency is advising healthcare providers to describe the symptoms of differentiation syndrome to patients, both when starting them on enasidenib and at follow-up visits.

Symptoms of differentiation syndrome include:

• Acute respiratory distress represented by dyspnea and/or hypoxia and a need for supplemental oxygen
• Pulmonary infiltrates and pleural effusion
• Fever
• Lymphadenopathy
• Bone pain
• Peripheral edema with rapid weight gain
• Pericardial effusion
• Hepatic, renal, and multiorgan dysfunction.

The FDA notes that differentiation syndrome may be mistaken for cardiogenic pulmonary edema, pneumonia, or sepsis.

Treatment

If healthcare providers suspect differentiation syndrome, they should promptly administer oral or intravenous corticosteroids, such as dexamethasone at 10 mg every 12 hours, according to the FDA.

Providers should also monitor hemodynamics until improvement and provide supportive care as necessary.

If patients continue to experience renal dysfunction or severe pulmonary symptoms requiring intubation or ventilator support for more than 48 hours after starting corticosteroids, enasidenib should be stopped until signs and symptoms of differentiation syndrome are no longer severe.

Corticosteroids should be tapered only after the symptoms resolve completely, as differentiation syndrome may recur if treatment is stopped too soon.

Cases of differentiation syndrome

The FDA notes that, in the phase 1/2 trial that supported the U.S. approval of enasidenib, at least 14% of patients experienced differentiation syndrome.

The manufacturer’s latest safety report includes 5 deaths (from May 1, 2018, to July 31, 2018) associated with differentiation syndrome in patients taking enasidenib.

Differentiation syndrome was listed as the only cause of death in two cases. In the remaining three cases, patients also had hemorrhagic stroke, pneumonia and sepsis, and sepsis alone.

One patient received systemic corticosteroids promptly but may have died of sepsis during hospitalization. In another patient, differentiation syndrome was not diagnosed or treated promptly. Treatment details are not available for the remaining three patients, according to the FDA.

The FDA has also performed a systematic analysis of differentiation syndrome in 293 patients treated with enasidenib (n=214) or ivosidenib (n=179).

With both drugs, the incidence of differentiation syndrome was 19%. The condition was fatal in 6% (n=2) of ivosidenib-treated patients and 5% (n=2) of enasidenib-treated patients.

Additional results from this analysis are scheduled to be presented at the 2018 ASH Annual Meeting (abstract 288).

Photo from Business Wire

The U.S. Food and Drug Administration (FDA) has released a safety communication warning that cases of  differentiation syndrome are going unnoticed in patients treated with the IDH2 inhibitor enasidenib (Idhifa).

Enasidenib is FDA-approved to treat adults with relapsed or refractory acute myeloid leukemia (AML) and an IDH2 mutation.

The drug is known to be associated with differentiation syndrome, and the prescribing information contains a boxed warning about this life-threatening condition.

However, the FDA has found that patients and healthcare providers are missing the signs and symptoms of differentiation syndrome, and some patients are not receiving the necessary treatment in time.

The FDA is also warning that differentiation syndrome has been observed in AML patients taking the IDH1 inhibitor ivosidenib (Tibsovo).

However, the agency has not provided many details on cases related to this drug, which is FDA-approved to treat adults with relapsed or refractory AML who have an IDH1 mutation.

Recognizing differentiation syndrome

The FDA says differentiation syndrome may occur anywhere from 10 days to 5 months after starting enasidenib.

The agency is advising healthcare providers to describe the symptoms of differentiation syndrome to patients, both when starting them on enasidenib and at follow-up visits.

Symptoms of differentiation syndrome include:

• Acute respiratory distress represented by dyspnea and/or hypoxia and a need for supplemental oxygen
• Pulmonary infiltrates and pleural effusion
• Fever
• Lymphadenopathy
• Bone pain
• Peripheral edema with rapid weight gain
• Pericardial effusion
• Hepatic, renal, and multiorgan dysfunction.

The FDA notes that differentiation syndrome may be mistaken for cardiogenic pulmonary edema, pneumonia, or sepsis.

Treatment

If healthcare providers suspect differentiation syndrome, they should promptly administer oral or intravenous corticosteroids, such as dexamethasone at 10 mg every 12 hours, according to the FDA.

Providers should also monitor hemodynamics until improvement and provide supportive care as necessary.

If patients continue to experience renal dysfunction or severe pulmonary symptoms requiring intubation or ventilator support for more than 48 hours after starting corticosteroids, enasidenib should be stopped until signs and symptoms of differentiation syndrome are no longer severe.

Corticosteroids should be tapered only after the symptoms resolve completely, as differentiation syndrome may recur if treatment is stopped too soon.

Cases of differentiation syndrome

The FDA notes that, in the phase 1/2 trial that supported the U.S. approval of enasidenib, at least 14% of patients experienced differentiation syndrome.

The manufacturer’s latest safety report includes 5 deaths (from May 1, 2018, to July 31, 2018) associated with differentiation syndrome in patients taking enasidenib.

Differentiation syndrome was listed as the only cause of death in two cases. In the remaining three cases, patients also had hemorrhagic stroke, pneumonia and sepsis, and sepsis alone.

One patient received systemic corticosteroids promptly but may have died of sepsis during hospitalization. In another patient, differentiation syndrome was not diagnosed or treated promptly. Treatment details are not available for the remaining three patients, according to the FDA.

The FDA has also performed a systematic analysis of differentiation syndrome in 293 patients treated with enasidenib (n=214) or ivosidenib (n=179).

With both drugs, the incidence of differentiation syndrome was 19%. The condition was fatal in 6% (n=2) of ivosidenib-treated patients and 5% (n=2) of enasidenib-treated patients.

Additional results from this analysis are scheduled to be presented at the 2018 ASH Annual Meeting (abstract 288).

Photo from Business Wire

The U.S. Food and Drug Administration (FDA) has released a safety communication warning that cases of  differentiation syndrome are going unnoticed in patients treated with the IDH2 inhibitor enasidenib (Idhifa).

Enasidenib is FDA-approved to treat adults with relapsed or refractory acute myeloid leukemia (AML) and an IDH2 mutation.

The drug is known to be associated with differentiation syndrome, and the prescribing information contains a boxed warning about this life-threatening condition.

However, the FDA has found that patients and healthcare providers are missing the signs and symptoms of differentiation syndrome, and some patients are not receiving the necessary treatment in time.

The FDA is also warning that differentiation syndrome has been observed in AML patients taking the IDH1 inhibitor ivosidenib (Tibsovo).

However, the agency has not provided many details on cases related to this drug, which is FDA-approved to treat adults with relapsed or refractory AML who have an IDH1 mutation.

Recognizing differentiation syndrome

The FDA says differentiation syndrome may occur anywhere from 10 days to 5 months after starting enasidenib.

The agency is advising healthcare providers to describe the symptoms of differentiation syndrome to patients, both when starting them on enasidenib and at follow-up visits.

Symptoms of differentiation syndrome include:

• Acute respiratory distress represented by dyspnea and/or hypoxia and a need for supplemental oxygen
• Pulmonary infiltrates and pleural effusion
• Fever
• Lymphadenopathy
• Bone pain
• Peripheral edema with rapid weight gain
• Pericardial effusion
• Hepatic, renal, and multiorgan dysfunction.

The FDA notes that differentiation syndrome may be mistaken for cardiogenic pulmonary edema, pneumonia, or sepsis.

Treatment

If healthcare providers suspect differentiation syndrome, they should promptly administer oral or intravenous corticosteroids, such as dexamethasone at 10 mg every 12 hours, according to the FDA.

Providers should also monitor hemodynamics until improvement and provide supportive care as necessary.

If patients continue to experience renal dysfunction or severe pulmonary symptoms requiring intubation or ventilator support for more than 48 hours after starting corticosteroids, enasidenib should be stopped until signs and symptoms of differentiation syndrome are no longer severe.

Corticosteroids should be tapered only after the symptoms resolve completely, as differentiation syndrome may recur if treatment is stopped too soon.

Cases of differentiation syndrome

The FDA notes that, in the phase 1/2 trial that supported the U.S. approval of enasidenib, at least 14% of patients experienced differentiation syndrome.

The manufacturer’s latest safety report includes 5 deaths (from May 1, 2018, to July 31, 2018) associated with differentiation syndrome in patients taking enasidenib.

Differentiation syndrome was listed as the only cause of death in two cases. In the remaining three cases, patients also had hemorrhagic stroke, pneumonia and sepsis, and sepsis alone.

One patient received systemic corticosteroids promptly but may have died of sepsis during hospitalization. In another patient, differentiation syndrome was not diagnosed or treated promptly. Treatment details are not available for the remaining three patients, according to the FDA.

The FDA has also performed a systematic analysis of differentiation syndrome in 293 patients treated with enasidenib (n=214) or ivosidenib (n=179).

With both drugs, the incidence of differentiation syndrome was 19%. The condition was fatal in 6% (n=2) of ivosidenib-treated patients and 5% (n=2) of enasidenib-treated patients.

Additional results from this analysis are scheduled to be presented at the 2018 ASH Annual Meeting (abstract 288).

With more than 3,000 scientific abstracts at the 2018 annual meeting of the American Society of Hematology, it can be tough to figure out what research is most relevant to practice. But the editorial advisory board of Hematology News is making it easier this year with their picks for what to watch and why.

Lymphomas

Brian T. Hill, MD, of the Cleveland Clinic, offered his top picks in lymphoma research. Results of the phase 3 international Alliance North American Intergroup Study A041202 will be presented during the ASH plenary session at 2 p.m. PT on Sunday, Dec. 2 in Hall AB of the San Diego Convention Center (Abstract 6). The study compared bendamustine plus rituximab with ibrutinib and the combination of ibrutinib plus rituximab to see if the ibrutinib-containing therapies would have superior progression-free survival (PFS) in chronic lymphocytic leukemia (CLL), compared with chemoimmunotherapy. Results indicate that ibrutinib had superior PFS in older patients with CLL and could be a standard of care in this population.

The study is worth watching because it is the first report of a head-to-head trial of chemotherapy versus ibrutinib for first-line treatment of CLL, Dr. Hill said.

Two more studies offer important reports of “real world” experiences with chimeric antigen receptor (CAR) T-cell therapy.

In one multicenter retrospective study, researchers evaluated the outcomes of axicabtagene ciloleucel (axi-cel) CAR T-cell therapy for relapsed/refractory aggressive B-cell lymphoma when it is used a standard care. The researchers will report that 30-day responses in the real-world setting were comparable to the best responses seen in the ZUMA-1 trial. The full results will be reported at 9:30 a.m. PT on Saturday, Dec. 1 in Pacific Ballroom 20 of the Marriott Marquis San Diego Marina (Abstract 91).

Another retrospective analysis looked at the use of axi-cell and revealed some critical differences from ZUMA-1, specifically the overall response rate (ORR) and complete response (CR) rate were lower than those reported in the pivotal clinical trial. The findings will be reported at 9:45 a.m. PT on Saturday, Dec. 1 in Pacific Ballroom 20 of the Marriott Marquis San Diego Marina (Abstract 92).

Researchers will also present the unblinded results from the ECHELON-2 study, which compared the efficacy and safety of brentuximab vedotin in combination with cyclophosphamide, doxorubicin, and prednisone (CHP) versus standard CHOP for the treatment of patients with peripheral T-cell lymphoma. The results will be presented at 6:15 p.m. PT on Monday, Dec. 3 in room 6F of the San Diego convention center (Abstract 997).

Previously reported blinded pooled data showed that the treatment was well tolerated with 3-year PFS of 53% and OS of 73%.

“This should be a new standard of care for T-cell lymphomas,” Dr. Hill said.
 

CAR T-cell therapy

There are a number of abstracts featuring the latest results on CAR T-cell therapy. Helen Heslop, MD, of Baylor College of Medicine, Houston, recommended an updated analysis from the ELIANA study, which looked at the efficacy and safety of tisagenlecleucel in for children and young adults with relapsed/refractory acute lymphoblastic leukemia (ALL).

“Longer-term follow-up of the ELIANA study shows encouraging remission-duration data in pediatric and young adults with ALL without additional therapy,” Dr. Heslop said.

The findings will be presented at 4:30 p.m. PT on Monday, Dec. 3 in room 6A at the San Diego Convention Center (Abstract 895).

Another notable presentation will feature results from a phase 1B/2 trial evaluating infusion of CAR T cells targeting the CD30 molecule and encoding the CD28 endodomain (CD30.CAR-Ts) after lymphodepleting chemotherapy in patients with relapsed or refractory CD30+ Hodgkin lymphoma and non-Hodgkin lymphoma.

The researchers will report that there was a significant PFS advances for who received the highest dose level of the CAR T treatment, combined with bendamustine and fludarabine.

The study will be presented at 11 a.m. PT on Monday, Dec. 3 in room 6F at the San Diego Convention Center (Abstract 681).

Dr. Heslop also recommends another study being presented in the same session, which also shows encouraging results with CD30.CAR-Ts. Dr. Heslop is one of the co-investigators on the phase 1 RELY-30 trial, which is evaluating the efficacy of CD30.CAR-Ts after lymphodepleting chemotherapy. Preliminary results suggest a substantial improvement in efficacy. The findings will be presented at 10:45 a.m. PT on Monday, Dec. 3 in room 6F of the San Diego Convention Center (Abstract 680).
 

MDS/MPN

Vikas Gupta, MD, of Princess Margaret Cancer Center in Toronto, highlighted three abstracts to watch in the areas of myelodysplastic syndrome (MDS) and myeloproliferative neoplasms (MPN).

The phase 3 Medalist trial is a randomized double-blind placebo controlled study of luspatercept to treatment anemia in patients with MDS with ring sideroblasts who require red blood cell transfusion. The researchers will report significantly reduced transfusion burdens for luspatercept, compared with placebo.

“This is a practice-changing, pivotal trial in the field of MDS for the treatment of anemia,” Dr. Gupta said.

The findings will be presented at 2 p.m. PT on Sunday, Dec. 2 during the plenary session in Hall AB in the San Diego Convention Center (Abstract 1).

Also during the Sunday plenary session is a presentation on MPN therapy (Abstract 4). Researchers will present data on secreted mutant calreticulins as rogue cytokines trigger thrombopoietin receptor (TpoR) activation, specifically in CALR-mutated cells.

“This study investigates in to the mechanistic oncogenetic aspects of mutant calreticulin, and has potential for therapeutic approaches in the future,” Dr. Gupta said.

The ASH meeting will also feature the final analysis of the MPN-RC 112 consortium trial of pegylated interferon alfa-2a versus hydroxyurea for the treatment of high-risk polycythemia vera (PV) and essential thrombocythemia (ET). The researchers will report that the CR rates at 12 and 24 months were similar in patients treated with pegylated interferon alfa-2a and hydroxyurea, but pegylated interferon alfa-2a was associated with a higher rate of serious toxicities.

“There is a continuous debate on optimal first-line cytoreductive therapy for high risk PV/ET, and this is one of the first randomized study to answer this question,” Dr. Gupta said.

The findings will be presented at 7 a.m. PT on Monday, Dec. 3 in Grand Hall D at the Manchester Grand Hyatt San Diego (Abstract 577).
 

AML

For attendees interested in the latest developments in acute myeloid leukemia, Thomas Fischer, MD, of Otto-von-Guericke-University Magdeburg (Germany), highlighted three don’t-miss sessions.

In an analysis of a large cohort of FLT3-ITD mutated AML patients in the RATIFY trial, researchers looked at the prognostic impact of ITD insertion site.

“Interestingly, in this large cohort of 452 FLT3-ITD mutated AML, the negative prognostic impact of beta1-sheet insertion site of FLT3-ITD could be confirmed,” Dr. Fischer said. “Further analysis of a potential predictive effect on outcome of midostaurin treatment is ongoing and will be very interesting.”

The findings will be presented at 5 p.m. PT on Sunday, Dec. 2 in Seaport Ballroom F at the Manchester Grand Hyatt San Diego (Abstract 435).

Another notable presentation features results from the phase 2 RADIUS trial, a randomized study comparing standard of care, with and without midostaurin, after allogeneic stem cell transplant in FLT3-ITD–mutated AML.

“Here, efficacy and toxicity of midostaurin was investigated in a [minimal residual disease] situation post-alloSCT,” Dr. Fischer said. “Interestingly, adding midostaurin to standard of care reduced the risk of relapse at 18 months post-alloSCT by 46%.”

The complete findings will be presented at 10:45 a.m. PT on Monday, Dec. 3 in Seaport Ballroom F at the Manchester Grand Hyatt San Diego (Abstract 662).

Dr. Fischer singled out another study looking at the efficacy and safety of single-agent quizartinib in patients with FLT3-ITD mutated AML. In this large, randomized trial the researchers noted a significant improvement in CR rates and survival benefit with the single agent FLT3 inhibitors, compared with salvage chemotherapy for patients with relapsed/refractory mutated AML.

The findings will be presented at 8 a.m. on Monday, Dec. 3 in Seaport Ballroom F at the Manchester Grand Hyatt San Diego (Abstract 563).
 

Notable posters

Courtesy Baylor College of Medicine

Iberia Romina Sosa, MD, PhD, of Baylor College of Medicine in Houston, suggested several posters worth visiting in the areas of thrombosis and bleeding.

Poster 1134 looks at the TNF-alpha driven inflammation and mitochondrial dysfunction in the platelet hyperreactivity of aging and MPN.

How do you know if your therapy for thrombotic thrombocytopenic purpura is working? Poster 3736 examines the measurement of cell-derived microparticles as a possible tool to monitor response to therapy.

You don’t have to be taking aspirin to have a bleeding profile characteristic with consumption of a cyclooxygenase inhibitor. Poster 1156 provides a first report of a platelet function disorder caused by autosomal recessive inheritance of PTGS1.

Poster 2477 takes a closer look at fitusiran, an antithrombin inhibitor, which improves thrombin generation in patients with hemophilia A or B. Protocol amendments for safety monitoring move fitusiran to phase 3 trials, Dr. Sosa said.

mschneider@mdedge.com

With more than 3,000 scientific abstracts at the 2018 annual meeting of the American Society of Hematology, it can be tough to figure out what research is most relevant to practice. But the editorial advisory board of Hematology News is making it easier this year with their picks for what to watch and why.

Lymphomas

Brian T. Hill, MD, of the Cleveland Clinic, offered his top picks in lymphoma research. Results of the phase 3 international Alliance North American Intergroup Study A041202 will be presented during the ASH plenary session at 2 p.m. PT on Sunday, Dec. 2 in Hall AB of the San Diego Convention Center (Abstract 6). The study compared bendamustine plus rituximab with ibrutinib and the combination of ibrutinib plus rituximab to see if the ibrutinib-containing therapies would have superior progression-free survival (PFS) in chronic lymphocytic leukemia (CLL), compared with chemoimmunotherapy. Results indicate that ibrutinib had superior PFS in older patients with CLL and could be a standard of care in this population.

The study is worth watching because it is the first report of a head-to-head trial of chemotherapy versus ibrutinib for first-line treatment of CLL, Dr. Hill said.

Two more studies offer important reports of “real world” experiences with chimeric antigen receptor (CAR) T-cell therapy.

In one multicenter retrospective study, researchers evaluated the outcomes of axicabtagene ciloleucel (axi-cel) CAR T-cell therapy for relapsed/refractory aggressive B-cell lymphoma when it is used a standard care. The researchers will report that 30-day responses in the real-world setting were comparable to the best responses seen in the ZUMA-1 trial. The full results will be reported at 9:30 a.m. PT on Saturday, Dec. 1 in Pacific Ballroom 20 of the Marriott Marquis San Diego Marina (Abstract 91).

Another retrospective analysis looked at the use of axi-cell and revealed some critical differences from ZUMA-1, specifically the overall response rate (ORR) and complete response (CR) rate were lower than those reported in the pivotal clinical trial. The findings will be reported at 9:45 a.m. PT on Saturday, Dec. 1 in Pacific Ballroom 20 of the Marriott Marquis San Diego Marina (Abstract 92).

Researchers will also present the unblinded results from the ECHELON-2 study, which compared the efficacy and safety of brentuximab vedotin in combination with cyclophosphamide, doxorubicin, and prednisone (CHP) versus standard CHOP for the treatment of patients with peripheral T-cell lymphoma. The results will be presented at 6:15 p.m. PT on Monday, Dec. 3 in room 6F of the San Diego convention center (Abstract 997).

Previously reported blinded pooled data showed that the treatment was well tolerated with 3-year PFS of 53% and OS of 73%.

“This should be a new standard of care for T-cell lymphomas,” Dr. Hill said.
 

CAR T-cell therapy

There are a number of abstracts featuring the latest results on CAR T-cell therapy. Helen Heslop, MD, of Baylor College of Medicine, Houston, recommended an updated analysis from the ELIANA study, which looked at the efficacy and safety of tisagenlecleucel in for children and young adults with relapsed/refractory acute lymphoblastic leukemia (ALL).

“Longer-term follow-up of the ELIANA study shows encouraging remission-duration data in pediatric and young adults with ALL without additional therapy,” Dr. Heslop said.

The findings will be presented at 4:30 p.m. PT on Monday, Dec. 3 in room 6A at the San Diego Convention Center (Abstract 895).

Another notable presentation will feature results from a phase 1B/2 trial evaluating infusion of CAR T cells targeting the CD30 molecule and encoding the CD28 endodomain (CD30.CAR-Ts) after lymphodepleting chemotherapy in patients with relapsed or refractory CD30+ Hodgkin lymphoma and non-Hodgkin lymphoma.

The researchers will report that there was a significant PFS advances for who received the highest dose level of the CAR T treatment, combined with bendamustine and fludarabine.

The study will be presented at 11 a.m. PT on Monday, Dec. 3 in room 6F at the San Diego Convention Center (Abstract 681).

Dr. Heslop also recommends another study being presented in the same session, which also shows encouraging results with CD30.CAR-Ts. Dr. Heslop is one of the co-investigators on the phase 1 RELY-30 trial, which is evaluating the efficacy of CD30.CAR-Ts after lymphodepleting chemotherapy. Preliminary results suggest a substantial improvement in efficacy. The findings will be presented at 10:45 a.m. PT on Monday, Dec. 3 in room 6F of the San Diego Convention Center (Abstract 680).
 

MDS/MPN

Vikas Gupta, MD, of Princess Margaret Cancer Center in Toronto, highlighted three abstracts to watch in the areas of myelodysplastic syndrome (MDS) and myeloproliferative neoplasms (MPN).

The phase 3 Medalist trial is a randomized double-blind placebo controlled study of luspatercept to treatment anemia in patients with MDS with ring sideroblasts who require red blood cell transfusion. The researchers will report significantly reduced transfusion burdens for luspatercept, compared with placebo.

“This is a practice-changing, pivotal trial in the field of MDS for the treatment of anemia,” Dr. Gupta said.

The findings will be presented at 2 p.m. PT on Sunday, Dec. 2 during the plenary session in Hall AB in the San Diego Convention Center (Abstract 1).

Also during the Sunday plenary session is a presentation on MPN therapy (Abstract 4). Researchers will present data on secreted mutant calreticulins as rogue cytokines trigger thrombopoietin receptor (TpoR) activation, specifically in CALR-mutated cells.

“This study investigates in to the mechanistic oncogenetic aspects of mutant calreticulin, and has potential for therapeutic approaches in the future,” Dr. Gupta said.

The ASH meeting will also feature the final analysis of the MPN-RC 112 consortium trial of pegylated interferon alfa-2a versus hydroxyurea for the treatment of high-risk polycythemia vera (PV) and essential thrombocythemia (ET). The researchers will report that the CR rates at 12 and 24 months were similar in patients treated with pegylated interferon alfa-2a and hydroxyurea, but pegylated interferon alfa-2a was associated with a higher rate of serious toxicities.

“There is a continuous debate on optimal first-line cytoreductive therapy for high risk PV/ET, and this is one of the first randomized study to answer this question,” Dr. Gupta said.

The findings will be presented at 7 a.m. PT on Monday, Dec. 3 in Grand Hall D at the Manchester Grand Hyatt San Diego (Abstract 577).
 

AML

For attendees interested in the latest developments in acute myeloid leukemia, Thomas Fischer, MD, of Otto-von-Guericke-University Magdeburg (Germany), highlighted three don’t-miss sessions.

In an analysis of a large cohort of FLT3-ITD mutated AML patients in the RATIFY trial, researchers looked at the prognostic impact of ITD insertion site.

“Interestingly, in this large cohort of 452 FLT3-ITD mutated AML, the negative prognostic impact of beta1-sheet insertion site of FLT3-ITD could be confirmed,” Dr. Fischer said. “Further analysis of a potential predictive effect on outcome of midostaurin treatment is ongoing and will be very interesting.”

The findings will be presented at 5 p.m. PT on Sunday, Dec. 2 in Seaport Ballroom F at the Manchester Grand Hyatt San Diego (Abstract 435).

Another notable presentation features results from the phase 2 RADIUS trial, a randomized study comparing standard of care, with and without midostaurin, after allogeneic stem cell transplant in FLT3-ITD–mutated AML.

“Here, efficacy and toxicity of midostaurin was investigated in a [minimal residual disease] situation post-alloSCT,” Dr. Fischer said. “Interestingly, adding midostaurin to standard of care reduced the risk of relapse at 18 months post-alloSCT by 46%.”

The complete findings will be presented at 10:45 a.m. PT on Monday, Dec. 3 in Seaport Ballroom F at the Manchester Grand Hyatt San Diego (Abstract 662).

Dr. Fischer singled out another study looking at the efficacy and safety of single-agent quizartinib in patients with FLT3-ITD mutated AML. In this large, randomized trial the researchers noted a significant improvement in CR rates and survival benefit with the single agent FLT3 inhibitors, compared with salvage chemotherapy for patients with relapsed/refractory mutated AML.

The findings will be presented at 8 a.m. on Monday, Dec. 3 in Seaport Ballroom F at the Manchester Grand Hyatt San Diego (Abstract 563).
 

Notable posters

Courtesy Baylor College of Medicine

Iberia Romina Sosa, MD, PhD, of Baylor College of Medicine in Houston, suggested several posters worth visiting in the areas of thrombosis and bleeding.

Poster 1134 looks at the TNF-alpha driven inflammation and mitochondrial dysfunction in the platelet hyperreactivity of aging and MPN.

How do you know if your therapy for thrombotic thrombocytopenic purpura is working? Poster 3736 examines the measurement of cell-derived microparticles as a possible tool to monitor response to therapy.

You don’t have to be taking aspirin to have a bleeding profile characteristic with consumption of a cyclooxygenase inhibitor. Poster 1156 provides a first report of a platelet function disorder caused by autosomal recessive inheritance of PTGS1.

Poster 2477 takes a closer look at fitusiran, an antithrombin inhibitor, which improves thrombin generation in patients with hemophilia A or B. Protocol amendments for safety monitoring move fitusiran to phase 3 trials, Dr. Sosa said.

mschneider@mdedge.com

With more than 3,000 scientific abstracts at the 2018 annual meeting of the American Society of Hematology, it can be tough to figure out what research is most relevant to practice. But the editorial advisory board of Hematology News is making it easier this year with their picks for what to watch and why.

Lymphomas

Brian T. Hill, MD, of the Cleveland Clinic, offered his top picks in lymphoma research. Results of the phase 3 international Alliance North American Intergroup Study A041202 will be presented during the ASH plenary session at 2 p.m. PT on Sunday, Dec. 2 in Hall AB of the San Diego Convention Center (Abstract 6). The study compared bendamustine plus rituximab with ibrutinib and the combination of ibrutinib plus rituximab to see if the ibrutinib-containing therapies would have superior progression-free survival (PFS) in chronic lymphocytic leukemia (CLL), compared with chemoimmunotherapy. Results indicate that ibrutinib had superior PFS in older patients with CLL and could be a standard of care in this population.

The study is worth watching because it is the first report of a head-to-head trial of chemotherapy versus ibrutinib for first-line treatment of CLL, Dr. Hill said.

Two more studies offer important reports of “real world” experiences with chimeric antigen receptor (CAR) T-cell therapy.

In one multicenter retrospective study, researchers evaluated the outcomes of axicabtagene ciloleucel (axi-cel) CAR T-cell therapy for relapsed/refractory aggressive B-cell lymphoma when it is used a standard care. The researchers will report that 30-day responses in the real-world setting were comparable to the best responses seen in the ZUMA-1 trial. The full results will be reported at 9:30 a.m. PT on Saturday, Dec. 1 in Pacific Ballroom 20 of the Marriott Marquis San Diego Marina (Abstract 91).

Another retrospective analysis looked at the use of axi-cell and revealed some critical differences from ZUMA-1, specifically the overall response rate (ORR) and complete response (CR) rate were lower than those reported in the pivotal clinical trial. The findings will be reported at 9:45 a.m. PT on Saturday, Dec. 1 in Pacific Ballroom 20 of the Marriott Marquis San Diego Marina (Abstract 92).

Researchers will also present the unblinded results from the ECHELON-2 study, which compared the efficacy and safety of brentuximab vedotin in combination with cyclophosphamide, doxorubicin, and prednisone (CHP) versus standard CHOP for the treatment of patients with peripheral T-cell lymphoma. The results will be presented at 6:15 p.m. PT on Monday, Dec. 3 in room 6F of the San Diego convention center (Abstract 997).

Previously reported blinded pooled data showed that the treatment was well tolerated with 3-year PFS of 53% and OS of 73%.

“This should be a new standard of care for T-cell lymphomas,” Dr. Hill said.
 

CAR T-cell therapy

There are a number of abstracts featuring the latest results on CAR T-cell therapy. Helen Heslop, MD, of Baylor College of Medicine, Houston, recommended an updated analysis from the ELIANA study, which looked at the efficacy and safety of tisagenlecleucel in for children and young adults with relapsed/refractory acute lymphoblastic leukemia (ALL).

“Longer-term follow-up of the ELIANA study shows encouraging remission-duration data in pediatric and young adults with ALL without additional therapy,” Dr. Heslop said.

The findings will be presented at 4:30 p.m. PT on Monday, Dec. 3 in room 6A at the San Diego Convention Center (Abstract 895).

Another notable presentation will feature results from a phase 1B/2 trial evaluating infusion of CAR T cells targeting the CD30 molecule and encoding the CD28 endodomain (CD30.CAR-Ts) after lymphodepleting chemotherapy in patients with relapsed or refractory CD30+ Hodgkin lymphoma and non-Hodgkin lymphoma.

The researchers will report that there was a significant PFS advances for who received the highest dose level of the CAR T treatment, combined with bendamustine and fludarabine.

The study will be presented at 11 a.m. PT on Monday, Dec. 3 in room 6F at the San Diego Convention Center (Abstract 681).

Dr. Heslop also recommends another study being presented in the same session, which also shows encouraging results with CD30.CAR-Ts. Dr. Heslop is one of the co-investigators on the phase 1 RELY-30 trial, which is evaluating the efficacy of CD30.CAR-Ts after lymphodepleting chemotherapy. Preliminary results suggest a substantial improvement in efficacy. The findings will be presented at 10:45 a.m. PT on Monday, Dec. 3 in room 6F of the San Diego Convention Center (Abstract 680).
 

MDS/MPN

Vikas Gupta, MD, of Princess Margaret Cancer Center in Toronto, highlighted three abstracts to watch in the areas of myelodysplastic syndrome (MDS) and myeloproliferative neoplasms (MPN).

The phase 3 Medalist trial is a randomized double-blind placebo controlled study of luspatercept to treatment anemia in patients with MDS with ring sideroblasts who require red blood cell transfusion. The researchers will report significantly reduced transfusion burdens for luspatercept, compared with placebo.

“This is a practice-changing, pivotal trial in the field of MDS for the treatment of anemia,” Dr. Gupta said.

The findings will be presented at 2 p.m. PT on Sunday, Dec. 2 during the plenary session in Hall AB in the San Diego Convention Center (Abstract 1).

Also during the Sunday plenary session is a presentation on MPN therapy (Abstract 4). Researchers will present data on secreted mutant calreticulins as rogue cytokines trigger thrombopoietin receptor (TpoR) activation, specifically in CALR-mutated cells.

“This study investigates in to the mechanistic oncogenetic aspects of mutant calreticulin, and has potential for therapeutic approaches in the future,” Dr. Gupta said.

The ASH meeting will also feature the final analysis of the MPN-RC 112 consortium trial of pegylated interferon alfa-2a versus hydroxyurea for the treatment of high-risk polycythemia vera (PV) and essential thrombocythemia (ET). The researchers will report that the CR rates at 12 and 24 months were similar in patients treated with pegylated interferon alfa-2a and hydroxyurea, but pegylated interferon alfa-2a was associated with a higher rate of serious toxicities.

“There is a continuous debate on optimal first-line cytoreductive therapy for high risk PV/ET, and this is one of the first randomized study to answer this question,” Dr. Gupta said.

The findings will be presented at 7 a.m. PT on Monday, Dec. 3 in Grand Hall D at the Manchester Grand Hyatt San Diego (Abstract 577).
 

AML

For attendees interested in the latest developments in acute myeloid leukemia, Thomas Fischer, MD, of Otto-von-Guericke-University Magdeburg (Germany), highlighted three don’t-miss sessions.

In an analysis of a large cohort of FLT3-ITD mutated AML patients in the RATIFY trial, researchers looked at the prognostic impact of ITD insertion site.

“Interestingly, in this large cohort of 452 FLT3-ITD mutated AML, the negative prognostic impact of beta1-sheet insertion site of FLT3-ITD could be confirmed,” Dr. Fischer said. “Further analysis of a potential predictive effect on outcome of midostaurin treatment is ongoing and will be very interesting.”

The findings will be presented at 5 p.m. PT on Sunday, Dec. 2 in Seaport Ballroom F at the Manchester Grand Hyatt San Diego (Abstract 435).

Another notable presentation features results from the phase 2 RADIUS trial, a randomized study comparing standard of care, with and without midostaurin, after allogeneic stem cell transplant in FLT3-ITD–mutated AML.

“Here, efficacy and toxicity of midostaurin was investigated in a [minimal residual disease] situation post-alloSCT,” Dr. Fischer said. “Interestingly, adding midostaurin to standard of care reduced the risk of relapse at 18 months post-alloSCT by 46%.”

The complete findings will be presented at 10:45 a.m. PT on Monday, Dec. 3 in Seaport Ballroom F at the Manchester Grand Hyatt San Diego (Abstract 662).

Dr. Fischer singled out another study looking at the efficacy and safety of single-agent quizartinib in patients with FLT3-ITD mutated AML. In this large, randomized trial the researchers noted a significant improvement in CR rates and survival benefit with the single agent FLT3 inhibitors, compared with salvage chemotherapy for patients with relapsed/refractory mutated AML.

The findings will be presented at 8 a.m. on Monday, Dec. 3 in Seaport Ballroom F at the Manchester Grand Hyatt San Diego (Abstract 563).
 

Notable posters

Courtesy Baylor College of Medicine

Iberia Romina Sosa, MD, PhD, of Baylor College of Medicine in Houston, suggested several posters worth visiting in the areas of thrombosis and bleeding.

Poster 1134 looks at the TNF-alpha driven inflammation and mitochondrial dysfunction in the platelet hyperreactivity of aging and MPN.

How do you know if your therapy for thrombotic thrombocytopenic purpura is working? Poster 3736 examines the measurement of cell-derived microparticles as a possible tool to monitor response to therapy.

You don’t have to be taking aspirin to have a bleeding profile characteristic with consumption of a cyclooxygenase inhibitor. Poster 1156 provides a first report of a platelet function disorder caused by autosomal recessive inheritance of PTGS1.

Poster 2477 takes a closer look at fitusiran, an antithrombin inhibitor, which improves thrombin generation in patients with hemophilia A or B. Protocol amendments for safety monitoring move fitusiran to phase 3 trials, Dr. Sosa said.

mschneider@mdedge.com

Instances of stroke and arterial dissection in the head and neck have been reported in some multiple sclerosis patients soon after an infusion of alemtuzumab (Lemtrada), according to a safety announcement issued by the Food and Drug Administration on Nov. 29.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Since the FDA approved alemtuzumab in 2014 for relapsing forms of MS, 13 cases of ischemic and hemorrhagic stroke or arterial dissection have been reported worldwide via the FDA Adverse Event Reporting System, but “additional cases we are unaware of may have occurred,” the FDA said in the announcement.

Most of the patients who developed stroke or arterial lining tears showed symptoms within a day of taking the medication, although one patient reported symptoms three days after treatment. The drug is given via intravenous infusion and is generally reserved for patients with relapsing MS who have not responded adequately to other approved MS medications, according to the FDA.

Symptoms include sudden onset of the following: severe headache or neck pain; numbness or weakness in the arms or legs, especially on only one side of the body; confusion or trouble speaking or understanding speech; vision problems in one or both eyes; and dizziness, loss of balance, or difficulty walking.

As a result of the reports, the FDA has updated the drug label prescribing information and the patient Medication Guide to reflect these risks, and added the risk of stroke to the medication’s existing boxed warning.

Health care providers should remind patients of the potential for stroke and arterial dissection at each treatment visit and advise them to seek immediate medical attention if they experience any of the symptoms reported in previous cases. “The diagnosis is often complicated because early symptoms such as headache and neck pain are not specific,” according to the agency, but patients complaining of such symptoms should be evaluated immediately.

Alemtuzumab was also approved in May 2001 for treating B-cell chronic lymphocytic leukemia (B-CLL) under the brand name Campath. The FDA will update the Campath label to reflect the new warnings and risks.

Instances of stroke and arterial dissection in the head and neck have been reported in some multiple sclerosis patients soon after an infusion of alemtuzumab (Lemtrada), according to a safety announcement issued by the Food and Drug Administration on Nov. 29.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Since the FDA approved alemtuzumab in 2014 for relapsing forms of MS, 13 cases of ischemic and hemorrhagic stroke or arterial dissection have been reported worldwide via the FDA Adverse Event Reporting System, but “additional cases we are unaware of may have occurred,” the FDA said in the announcement.

Most of the patients who developed stroke or arterial lining tears showed symptoms within a day of taking the medication, although one patient reported symptoms three days after treatment. The drug is given via intravenous infusion and is generally reserved for patients with relapsing MS who have not responded adequately to other approved MS medications, according to the FDA.

Symptoms include sudden onset of the following: severe headache or neck pain; numbness or weakness in the arms or legs, especially on only one side of the body; confusion or trouble speaking or understanding speech; vision problems in one or both eyes; and dizziness, loss of balance, or difficulty walking.

As a result of the reports, the FDA has updated the drug label prescribing information and the patient Medication Guide to reflect these risks, and added the risk of stroke to the medication’s existing boxed warning.

Health care providers should remind patients of the potential for stroke and arterial dissection at each treatment visit and advise them to seek immediate medical attention if they experience any of the symptoms reported in previous cases. “The diagnosis is often complicated because early symptoms such as headache and neck pain are not specific,” according to the agency, but patients complaining of such symptoms should be evaluated immediately.

Alemtuzumab was also approved in May 2001 for treating B-cell chronic lymphocytic leukemia (B-CLL) under the brand name Campath. The FDA will update the Campath label to reflect the new warnings and risks.

Instances of stroke and arterial dissection in the head and neck have been reported in some multiple sclerosis patients soon after an infusion of alemtuzumab (Lemtrada), according to a safety announcement issued by the Food and Drug Administration on Nov. 29.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Since the FDA approved alemtuzumab in 2014 for relapsing forms of MS, 13 cases of ischemic and hemorrhagic stroke or arterial dissection have been reported worldwide via the FDA Adverse Event Reporting System, but “additional cases we are unaware of may have occurred,” the FDA said in the announcement.

Most of the patients who developed stroke or arterial lining tears showed symptoms within a day of taking the medication, although one patient reported symptoms three days after treatment. The drug is given via intravenous infusion and is generally reserved for patients with relapsing MS who have not responded adequately to other approved MS medications, according to the FDA.

Symptoms include sudden onset of the following: severe headache or neck pain; numbness or weakness in the arms or legs, especially on only one side of the body; confusion or trouble speaking or understanding speech; vision problems in one or both eyes; and dizziness, loss of balance, or difficulty walking.

As a result of the reports, the FDA has updated the drug label prescribing information and the patient Medication Guide to reflect these risks, and added the risk of stroke to the medication’s existing boxed warning.

Health care providers should remind patients of the potential for stroke and arterial dissection at each treatment visit and advise them to seek immediate medical attention if they experience any of the symptoms reported in previous cases. “The diagnosis is often complicated because early symptoms such as headache and neck pain are not specific,” according to the agency, but patients complaining of such symptoms should be evaluated immediately.

Alemtuzumab was also approved in May 2001 for treating B-cell chronic lymphocytic leukemia (B-CLL) under the brand name Campath. The FDA will update the Campath label to reflect the new warnings and risks.