MDedge Dermatology

For the seventh consecutive year, the Mayo Clinic in Rochester, Minn., took the top spot in the annual honor roll of best hospitals, published July 26 by U.S. News & World Report.

The 2022 rankings, which marks the 33rd edition, showcase several methodology changes, including new ratings for ovarian, prostate, and uterine cancer surgeries that “provide patients ... with previously unavailable information to assist them in making a critical health care decision,” a news release from the publication explains.

Additional expanded health equity measures assess “which hospitals provide more care to low-income patients and which have racial disparities in certain surgical outcomes,” said the release. Finally, a new metric called “home time” determines how successfully each hospital helps patients return home.
 

Mayo Clinic remains No. 1

For the 2022-2023 rankings and ratings, U.S. News compared more than 4,500 medical centers across the country in 15 specialties and 20 procedures and conditions. Of these, 493 were recognized as Best Regional Hospitals as a result of their overall strong performance.

The list was then narrowed to the top 20 hospitals, outlined in the honor roll below, that deliver “exceptional treatment across multiple areas of care.”

Following Mayo Clinic in the annual ranking’s top spot, Cedars-Sinai Medical Center in Los Angeles rises from No. 6 to No. 2, and New York University Langone Hospitals finish third, up from eighth in 2021.

Cleveland Clinic in Ohio holds the No. 4 spot, down two from 2021, while Johns Hopkins Hospital in Baltimore and UCLA Medical Center in Los Angeles tie for fifth place. Rounding out the top 10, in order, are: New York–Presbyterian Hospital–Columbia and Cornell, New York; Massachusetts General Hospital, Boston; Northwestern Memorial Hospital, Chicago; Stanford (Calif.) Health Care–Stanford Hospital.

The following hospitals complete the top 20 in the United States:

• 11. Barnes-Jewish Hospital, St. Louis
• 12. UCSF Medical Center, San Francisco
• 13. Hospitals of the University of Pennsylvania–Penn Presbyterian, Philadelphia
• 14. Brigham and Women’s Hospital, Boston
• 15. Houston Methodist Hospital
• 16. Mount Sinai Hospital, New York
• 17. University of Michigan Health–Michigan Medicine, Ann Arbor
• 18. Mayo Clinic–Phoenix
• 19. Vanderbilt University Medical Center, Nashville, Tenn.
• 20. Rush University Medical Center, Chicago

For the specialty rankings, the University of Texas MD Anderson Cancer Center, Houston, remains No. 1 in cancer care, the Cleveland Clinic is No. 1 in cardiology and heart surgery, and the Hospital for Special Surgery in New York is No. 1 in orthopedics.
 

Top five for cancer

• 1. University of Texas MD Anderson Cancer Center, Houston
• 2. Memorial Sloan Kettering Cancer Center, New York
• 3. Mayo Clinic, Rochester, Minn.
• 4. Dana-Farber/Brigham and Women’s Cancer Center, Boston
• 5. UCLA Medical Center, Los Angeles

Top five for cardiology and heart surgery

• 1. Cleveland Clinic
• 2. Mayo Clinic, Rochester, Minn.
• 3. Cedars-Sinai Medical Center, Los Angeles
• 4. New York–Presbyterian Hospital–Columbia and Cornell, New York
• 5. New York University Langone Hospitals

Top five for orthopedics

• 1. Hospital for Special Surgery, New York
• 2. Mayo Clinic, Rochester, Minn.
• 3. Cedars-Sinai Medical Center, Los Angeles
• 4. New York University Langone Hospitals
• 5. (tie) Rush University Medical Center, Chicago
• 5. (tie) UCLA Medical Center, Los Angeles

According to the news release, the procedures and conditions ratings are based entirely on objective patient care measures like survival rates, patient experience, home time, and level of nursing care. The Best Hospitals rankings consider a variety of data provided by the Centers for Medicare & Medicaid Services, American Hospital Association, professional organizations, and medical specialists.

The full report is available online.

A version of this article first appeared on Medscape.com.

For the seventh consecutive year, the Mayo Clinic in Rochester, Minn., took the top spot in the annual honor roll of best hospitals, published July 26 by U.S. News & World Report.

The 2022 rankings, which marks the 33rd edition, showcase several methodology changes, including new ratings for ovarian, prostate, and uterine cancer surgeries that “provide patients ... with previously unavailable information to assist them in making a critical health care decision,” a news release from the publication explains.

Additional expanded health equity measures assess “which hospitals provide more care to low-income patients and which have racial disparities in certain surgical outcomes,” said the release. Finally, a new metric called “home time” determines how successfully each hospital helps patients return home.
 

Mayo Clinic remains No. 1

For the 2022-2023 rankings and ratings, U.S. News compared more than 4,500 medical centers across the country in 15 specialties and 20 procedures and conditions. Of these, 493 were recognized as Best Regional Hospitals as a result of their overall strong performance.

The list was then narrowed to the top 20 hospitals, outlined in the honor roll below, that deliver “exceptional treatment across multiple areas of care.”

Following Mayo Clinic in the annual ranking’s top spot, Cedars-Sinai Medical Center in Los Angeles rises from No. 6 to No. 2, and New York University Langone Hospitals finish third, up from eighth in 2021.

Cleveland Clinic in Ohio holds the No. 4 spot, down two from 2021, while Johns Hopkins Hospital in Baltimore and UCLA Medical Center in Los Angeles tie for fifth place. Rounding out the top 10, in order, are: New York–Presbyterian Hospital–Columbia and Cornell, New York; Massachusetts General Hospital, Boston; Northwestern Memorial Hospital, Chicago; Stanford (Calif.) Health Care–Stanford Hospital.

The following hospitals complete the top 20 in the United States:

• 11. Barnes-Jewish Hospital, St. Louis
• 12. UCSF Medical Center, San Francisco
• 13. Hospitals of the University of Pennsylvania–Penn Presbyterian, Philadelphia
• 14. Brigham and Women’s Hospital, Boston
• 15. Houston Methodist Hospital
• 16. Mount Sinai Hospital, New York
• 17. University of Michigan Health–Michigan Medicine, Ann Arbor
• 18. Mayo Clinic–Phoenix
• 19. Vanderbilt University Medical Center, Nashville, Tenn.
• 20. Rush University Medical Center, Chicago

For the specialty rankings, the University of Texas MD Anderson Cancer Center, Houston, remains No. 1 in cancer care, the Cleveland Clinic is No. 1 in cardiology and heart surgery, and the Hospital for Special Surgery in New York is No. 1 in orthopedics.
 

Top five for cancer

• 1. University of Texas MD Anderson Cancer Center, Houston
• 2. Memorial Sloan Kettering Cancer Center, New York
• 3. Mayo Clinic, Rochester, Minn.
• 4. Dana-Farber/Brigham and Women’s Cancer Center, Boston
• 5. UCLA Medical Center, Los Angeles

Top five for cardiology and heart surgery

• 1. Cleveland Clinic
• 2. Mayo Clinic, Rochester, Minn.
• 3. Cedars-Sinai Medical Center, Los Angeles
• 4. New York–Presbyterian Hospital–Columbia and Cornell, New York
• 5. New York University Langone Hospitals

Top five for orthopedics

• 1. Hospital for Special Surgery, New York
• 2. Mayo Clinic, Rochester, Minn.
• 3. Cedars-Sinai Medical Center, Los Angeles
• 4. New York University Langone Hospitals
• 5. (tie) Rush University Medical Center, Chicago
• 5. (tie) UCLA Medical Center, Los Angeles

According to the news release, the procedures and conditions ratings are based entirely on objective patient care measures like survival rates, patient experience, home time, and level of nursing care. The Best Hospitals rankings consider a variety of data provided by the Centers for Medicare & Medicaid Services, American Hospital Association, professional organizations, and medical specialists.

The full report is available online.

A version of this article first appeared on Medscape.com.

For the seventh consecutive year, the Mayo Clinic in Rochester, Minn., took the top spot in the annual honor roll of best hospitals, published July 26 by U.S. News & World Report.

The 2022 rankings, which marks the 33rd edition, showcase several methodology changes, including new ratings for ovarian, prostate, and uterine cancer surgeries that “provide patients ... with previously unavailable information to assist them in making a critical health care decision,” a news release from the publication explains.

Additional expanded health equity measures assess “which hospitals provide more care to low-income patients and which have racial disparities in certain surgical outcomes,” said the release. Finally, a new metric called “home time” determines how successfully each hospital helps patients return home.
 

Mayo Clinic remains No. 1

For the 2022-2023 rankings and ratings, U.S. News compared more than 4,500 medical centers across the country in 15 specialties and 20 procedures and conditions. Of these, 493 were recognized as Best Regional Hospitals as a result of their overall strong performance.

The list was then narrowed to the top 20 hospitals, outlined in the honor roll below, that deliver “exceptional treatment across multiple areas of care.”

Following Mayo Clinic in the annual ranking’s top spot, Cedars-Sinai Medical Center in Los Angeles rises from No. 6 to No. 2, and New York University Langone Hospitals finish third, up from eighth in 2021.

Cleveland Clinic in Ohio holds the No. 4 spot, down two from 2021, while Johns Hopkins Hospital in Baltimore and UCLA Medical Center in Los Angeles tie for fifth place. Rounding out the top 10, in order, are: New York–Presbyterian Hospital–Columbia and Cornell, New York; Massachusetts General Hospital, Boston; Northwestern Memorial Hospital, Chicago; Stanford (Calif.) Health Care–Stanford Hospital.

The following hospitals complete the top 20 in the United States:

• 11. Barnes-Jewish Hospital, St. Louis
• 12. UCSF Medical Center, San Francisco
• 13. Hospitals of the University of Pennsylvania–Penn Presbyterian, Philadelphia
• 14. Brigham and Women’s Hospital, Boston
• 15. Houston Methodist Hospital
• 16. Mount Sinai Hospital, New York
• 17. University of Michigan Health–Michigan Medicine, Ann Arbor
• 18. Mayo Clinic–Phoenix
• 19. Vanderbilt University Medical Center, Nashville, Tenn.
• 20. Rush University Medical Center, Chicago

For the specialty rankings, the University of Texas MD Anderson Cancer Center, Houston, remains No. 1 in cancer care, the Cleveland Clinic is No. 1 in cardiology and heart surgery, and the Hospital for Special Surgery in New York is No. 1 in orthopedics.
 

Top five for cancer

• 1. University of Texas MD Anderson Cancer Center, Houston
• 2. Memorial Sloan Kettering Cancer Center, New York
• 3. Mayo Clinic, Rochester, Minn.
• 4. Dana-Farber/Brigham and Women’s Cancer Center, Boston
• 5. UCLA Medical Center, Los Angeles

Top five for cardiology and heart surgery

• 1. Cleveland Clinic
• 2. Mayo Clinic, Rochester, Minn.
• 3. Cedars-Sinai Medical Center, Los Angeles
• 4. New York–Presbyterian Hospital–Columbia and Cornell, New York
• 5. New York University Langone Hospitals

Top five for orthopedics

• 1. Hospital for Special Surgery, New York
• 2. Mayo Clinic, Rochester, Minn.
• 3. Cedars-Sinai Medical Center, Los Angeles
• 4. New York University Langone Hospitals
• 5. (tie) Rush University Medical Center, Chicago
• 5. (tie) UCLA Medical Center, Los Angeles

According to the news release, the procedures and conditions ratings are based entirely on objective patient care measures like survival rates, patient experience, home time, and level of nursing care. The Best Hospitals rankings consider a variety of data provided by the Centers for Medicare & Medicaid Services, American Hospital Association, professional organizations, and medical specialists.

The full report is available online.

A version of this article first appeared on Medscape.com.

The Diagnosis: Elephantiasis Nostras Verrucosa

Histopathology revealed a benign fibroepithelial polyp demonstrating areas of hyperkeratosis, acanthosis, and focal papillomatosis (Figure, A). Increased superficial vessels with dilated lymphatics, stellate fibroblasts, edematous stroma, and plasmolymphocytosis also were noted (Figure, B). Clinical and histopathological findings led to a diagnosis of lymphedema papules in the setting of elephantiasis nostra verrucosa (ENV).

Elephantiasis nostras verrucosa is a complication of long-standing nonfilarial obstruction of lymphatic drainage leading to grotesque enlargement of the affected areas. Common cutaneous manifestations of ENV include nonpitting edema, dermal fibrosis, and extensive hyperkeratosis with verrucous and papillomatous lesions.¹ In the beginning stages of ENV, the skin has a cobblestonelike appearance. As the disease progresses, the verrucous lesions continue to enlarge, giving the affected area a mossy appearance. Although less common, groupings of large papillomas similar to our patient’s presentation also can form.² Ulcer formation is more likely to occur in advanced disease states, increasing the risk for bacterial and fungal colonization. Elephantiasis nostras verrucosa classically affects the legs; however, this condition can develop in any area with chronic lymphedema. Cases of ENV involving the arms, abdomen, scrotum, and ear have been documented.^3-5

The pathogenesis of ENV involves the proliferation of fibroblasts and fibrosis secondary to lymphostasis and inflammation.⁶ When interstitial fluid builds up in the affected region, the protein-rich fluid is believed to trigger fibrogenesis and increase macrophage, keratinocyte, and adipocyte activity.⁷ Because of this inflammatory process, dilation and fibrosis of the lymphatic channels develop. Lymphatic obstruction can have several etiologies, most notably infection and malignancy. Staphylococcal lymphangitis and erysipelas create fibrosis of the lymphatic system and are the main infectious causes of ENV.⁶ Large tumors or lymphomas are insidious causes of lymphatic obstruction and should be ruled out when investigating for ENV. Other risk factors include obesity, chronic venous insufficiency, surgery, trauma, radiation, and uncontrolled congestive heart failure.^1,6,8

An ENV diagnosis is clinicopathologic, involving a comprehensive metabolic panel and complete blood cell count with differential. A biopsy is needed for pathologic confirmation and to rule out malignancy. Histologically, ENV is characterized by pseudoepitheliomatous hyperplasia, dermal fibrosis, hyperkeratosis of the epidermis, and dilated lymphatic vessels.^6,8 Additional studies for diagnosis include wound and lymph node culture, Wood lamp examination, and lymphoscintigraphy.

Given the chronic and progressive nature of the disease, ENV is difficult to treat. There currently is no standard of treatment, but the mainstay of management involves reducing peripheral edema. Lifestyle changes including weight loss, extremity elevation, and increased ambulation are helpful first-line therapies.³ Compression of the affected extremity using stockings or intermittent pneumatic compression devices has proven to be beneficial with long-term use.⁷ Patients should be followed for wound care to prevent the infection of ulcers.² Pharmacologic treatments include systemic retinoids, which have been shown to reduce the appearance of hyperkeratosis, verrucous lesions, and papillomatous nodules.⁶ Prophylactic antibiotics are reserved for advanced stages of disease or in patients with recurrent infections.^2,7 In severe cases of ENV that are unresponsive to medical management, surgical intervention such as lymphatic anastomosis and debulking may be considered.^9,10

Other diagnoses to consider for ENV include pretibial myxedema, lymphatic filariasis, Stewart-Treves syndrome, and papillomatosis cutis carcinoides. Pretibial myxedema is an uncommon dermatologic manifestation of Graves disease. It is a local autoimmune reaction in the cutaneous tissue characterized by hyperpigmentation, nonpitting edema, and nodules on the anterior leg. Histopathology shows increased hyaluronic acid and chondroitin as well as compression of dermal lymphatics.¹¹

Filariasis is a parasitic infection caused by Wuchereria bancrofti, Brugia malayi or Brugia timori, and Onchocerca volvulus.⁶ This condition presents with elephantiasis of the affected extremities but should be considered in areas endemic for filarial parasites such as tropical and subtropical countries.¹² Eosinophilia and identification of microfilaria in a peripheral blood smear would indicate parasitic infection. Stewart-Treves syndrome is a rare angiosarcoma that arises in areas of chronic lymphedema. This condition classically is seen on the upper extremities following a mastectomy with lymphadenectomy, lymph node irradiation, or both.

Stewart-Treves syndrome presents with coalescing purpuric macules and nodules that eventually coalesce into cutaneous masses. Histopathology reveals proliferating vascular channels that split apart dermal collagen with hyperchromatism and pleomorphism in the tumor endothelial cells that line these channels.¹³

Papillomatosis cutis carcinoides is a low-grade squamous cell carcinoma that occurs secondary to human papillomavirus commonly affecting the mouth, anogenital area, and the plantar surfaces of the feet. It presents with exophytic growths and ulcerated tumors that are unilateral and asymmetrical. The presence of blunt-shaped tumor projections extending deep into the dermis to form sinuses and keratin-filled cysts is characteristic of papillomatosis cutis carcinoides.¹⁴

The Diagnosis: Elephantiasis Nostras Verrucosa

Histopathology revealed a benign fibroepithelial polyp demonstrating areas of hyperkeratosis, acanthosis, and focal papillomatosis (Figure, A). Increased superficial vessels with dilated lymphatics, stellate fibroblasts, edematous stroma, and plasmolymphocytosis also were noted (Figure, B). Clinical and histopathological findings led to a diagnosis of lymphedema papules in the setting of elephantiasis nostra verrucosa (ENV).

Elephantiasis nostras verrucosa is a complication of long-standing nonfilarial obstruction of lymphatic drainage leading to grotesque enlargement of the affected areas. Common cutaneous manifestations of ENV include nonpitting edema, dermal fibrosis, and extensive hyperkeratosis with verrucous and papillomatous lesions.¹ In the beginning stages of ENV, the skin has a cobblestonelike appearance. As the disease progresses, the verrucous lesions continue to enlarge, giving the affected area a mossy appearance. Although less common, groupings of large papillomas similar to our patient’s presentation also can form.² Ulcer formation is more likely to occur in advanced disease states, increasing the risk for bacterial and fungal colonization. Elephantiasis nostras verrucosa classically affects the legs; however, this condition can develop in any area with chronic lymphedema. Cases of ENV involving the arms, abdomen, scrotum, and ear have been documented.^3-5

The pathogenesis of ENV involves the proliferation of fibroblasts and fibrosis secondary to lymphostasis and inflammation.⁶ When interstitial fluid builds up in the affected region, the protein-rich fluid is believed to trigger fibrogenesis and increase macrophage, keratinocyte, and adipocyte activity.⁷ Because of this inflammatory process, dilation and fibrosis of the lymphatic channels develop. Lymphatic obstruction can have several etiologies, most notably infection and malignancy. Staphylococcal lymphangitis and erysipelas create fibrosis of the lymphatic system and are the main infectious causes of ENV.⁶ Large tumors or lymphomas are insidious causes of lymphatic obstruction and should be ruled out when investigating for ENV. Other risk factors include obesity, chronic venous insufficiency, surgery, trauma, radiation, and uncontrolled congestive heart failure.^1,6,8

An ENV diagnosis is clinicopathologic, involving a comprehensive metabolic panel and complete blood cell count with differential. A biopsy is needed for pathologic confirmation and to rule out malignancy. Histologically, ENV is characterized by pseudoepitheliomatous hyperplasia, dermal fibrosis, hyperkeratosis of the epidermis, and dilated lymphatic vessels.^6,8 Additional studies for diagnosis include wound and lymph node culture, Wood lamp examination, and lymphoscintigraphy.

Given the chronic and progressive nature of the disease, ENV is difficult to treat. There currently is no standard of treatment, but the mainstay of management involves reducing peripheral edema. Lifestyle changes including weight loss, extremity elevation, and increased ambulation are helpful first-line therapies.³ Compression of the affected extremity using stockings or intermittent pneumatic compression devices has proven to be beneficial with long-term use.⁷ Patients should be followed for wound care to prevent the infection of ulcers.² Pharmacologic treatments include systemic retinoids, which have been shown to reduce the appearance of hyperkeratosis, verrucous lesions, and papillomatous nodules.⁶ Prophylactic antibiotics are reserved for advanced stages of disease or in patients with recurrent infections.^2,7 In severe cases of ENV that are unresponsive to medical management, surgical intervention such as lymphatic anastomosis and debulking may be considered.^9,10

Other diagnoses to consider for ENV include pretibial myxedema, lymphatic filariasis, Stewart-Treves syndrome, and papillomatosis cutis carcinoides. Pretibial myxedema is an uncommon dermatologic manifestation of Graves disease. It is a local autoimmune reaction in the cutaneous tissue characterized by hyperpigmentation, nonpitting edema, and nodules on the anterior leg. Histopathology shows increased hyaluronic acid and chondroitin as well as compression of dermal lymphatics.¹¹

Filariasis is a parasitic infection caused by Wuchereria bancrofti, Brugia malayi or Brugia timori, and Onchocerca volvulus.⁶ This condition presents with elephantiasis of the affected extremities but should be considered in areas endemic for filarial parasites such as tropical and subtropical countries.¹² Eosinophilia and identification of microfilaria in a peripheral blood smear would indicate parasitic infection. Stewart-Treves syndrome is a rare angiosarcoma that arises in areas of chronic lymphedema. This condition classically is seen on the upper extremities following a mastectomy with lymphadenectomy, lymph node irradiation, or both.

Stewart-Treves syndrome presents with coalescing purpuric macules and nodules that eventually coalesce into cutaneous masses. Histopathology reveals proliferating vascular channels that split apart dermal collagen with hyperchromatism and pleomorphism in the tumor endothelial cells that line these channels.¹³

Papillomatosis cutis carcinoides is a low-grade squamous cell carcinoma that occurs secondary to human papillomavirus commonly affecting the mouth, anogenital area, and the plantar surfaces of the feet. It presents with exophytic growths and ulcerated tumors that are unilateral and asymmetrical. The presence of blunt-shaped tumor projections extending deep into the dermis to form sinuses and keratin-filled cysts is characteristic of papillomatosis cutis carcinoides.¹⁴

The Diagnosis: Elephantiasis Nostras Verrucosa

Histopathology revealed a benign fibroepithelial polyp demonstrating areas of hyperkeratosis, acanthosis, and focal papillomatosis (Figure, A). Increased superficial vessels with dilated lymphatics, stellate fibroblasts, edematous stroma, and plasmolymphocytosis also were noted (Figure, B). Clinical and histopathological findings led to a diagnosis of lymphedema papules in the setting of elephantiasis nostra verrucosa (ENV).

Elephantiasis nostras verrucosa is a complication of long-standing nonfilarial obstruction of lymphatic drainage leading to grotesque enlargement of the affected areas. Common cutaneous manifestations of ENV include nonpitting edema, dermal fibrosis, and extensive hyperkeratosis with verrucous and papillomatous lesions.¹ In the beginning stages of ENV, the skin has a cobblestonelike appearance. As the disease progresses, the verrucous lesions continue to enlarge, giving the affected area a mossy appearance. Although less common, groupings of large papillomas similar to our patient’s presentation also can form.² Ulcer formation is more likely to occur in advanced disease states, increasing the risk for bacterial and fungal colonization. Elephantiasis nostras verrucosa classically affects the legs; however, this condition can develop in any area with chronic lymphedema. Cases of ENV involving the arms, abdomen, scrotum, and ear have been documented.^3-5

The pathogenesis of ENV involves the proliferation of fibroblasts and fibrosis secondary to lymphostasis and inflammation.⁶ When interstitial fluid builds up in the affected region, the protein-rich fluid is believed to trigger fibrogenesis and increase macrophage, keratinocyte, and adipocyte activity.⁷ Because of this inflammatory process, dilation and fibrosis of the lymphatic channels develop. Lymphatic obstruction can have several etiologies, most notably infection and malignancy. Staphylococcal lymphangitis and erysipelas create fibrosis of the lymphatic system and are the main infectious causes of ENV.⁶ Large tumors or lymphomas are insidious causes of lymphatic obstruction and should be ruled out when investigating for ENV. Other risk factors include obesity, chronic venous insufficiency, surgery, trauma, radiation, and uncontrolled congestive heart failure.^1,6,8

An ENV diagnosis is clinicopathologic, involving a comprehensive metabolic panel and complete blood cell count with differential. A biopsy is needed for pathologic confirmation and to rule out malignancy. Histologically, ENV is characterized by pseudoepitheliomatous hyperplasia, dermal fibrosis, hyperkeratosis of the epidermis, and dilated lymphatic vessels.^6,8 Additional studies for diagnosis include wound and lymph node culture, Wood lamp examination, and lymphoscintigraphy.

Given the chronic and progressive nature of the disease, ENV is difficult to treat. There currently is no standard of treatment, but the mainstay of management involves reducing peripheral edema. Lifestyle changes including weight loss, extremity elevation, and increased ambulation are helpful first-line therapies.³ Compression of the affected extremity using stockings or intermittent pneumatic compression devices has proven to be beneficial with long-term use.⁷ Patients should be followed for wound care to prevent the infection of ulcers.² Pharmacologic treatments include systemic retinoids, which have been shown to reduce the appearance of hyperkeratosis, verrucous lesions, and papillomatous nodules.⁶ Prophylactic antibiotics are reserved for advanced stages of disease or in patients with recurrent infections.^2,7 In severe cases of ENV that are unresponsive to medical management, surgical intervention such as lymphatic anastomosis and debulking may be considered.^9,10

Other diagnoses to consider for ENV include pretibial myxedema, lymphatic filariasis, Stewart-Treves syndrome, and papillomatosis cutis carcinoides. Pretibial myxedema is an uncommon dermatologic manifestation of Graves disease. It is a local autoimmune reaction in the cutaneous tissue characterized by hyperpigmentation, nonpitting edema, and nodules on the anterior leg. Histopathology shows increased hyaluronic acid and chondroitin as well as compression of dermal lymphatics.¹¹

Filariasis is a parasitic infection caused by Wuchereria bancrofti, Brugia malayi or Brugia timori, and Onchocerca volvulus.⁶ This condition presents with elephantiasis of the affected extremities but should be considered in areas endemic for filarial parasites such as tropical and subtropical countries.¹² Eosinophilia and identification of microfilaria in a peripheral blood smear would indicate parasitic infection. Stewart-Treves syndrome is a rare angiosarcoma that arises in areas of chronic lymphedema. This condition classically is seen on the upper extremities following a mastectomy with lymphadenectomy, lymph node irradiation, or both.

Stewart-Treves syndrome presents with coalescing purpuric macules and nodules that eventually coalesce into cutaneous masses. Histopathology reveals proliferating vascular channels that split apart dermal collagen with hyperchromatism and pleomorphism in the tumor endothelial cells that line these channels.¹³

Papillomatosis cutis carcinoides is a low-grade squamous cell carcinoma that occurs secondary to human papillomavirus commonly affecting the mouth, anogenital area, and the plantar surfaces of the feet. It presents with exophytic growths and ulcerated tumors that are unilateral and asymmetrical. The presence of blunt-shaped tumor projections extending deep into the dermis to form sinuses and keratin-filled cysts is characteristic of papillomatosis cutis carcinoides.¹⁴

More than half of studies testing anticancer drugs against each other have rules with regard to dose modification and growth support that favor the experimental drug arm, a new analysis suggests.

“We found it sobering that this practice is so common,” Timothée Olivier, MD, with Geneva University Hospital and the University of California, San Francisco, said in an interview.

Trials may be “rigged” in a way where the new therapy appears more effective than if the trial would have been designed with fairer rules, he explained.

This leaves open the question of whether new drugs are truly superior to older ones or if instead different outcomes are caused by more aggressive dosing or growth factor support, the investigators said.

Dr. Olivier, with UCSF coinvestigators Alyson Haslam, PhD, and Vinay Prasad, MD, reported their findings online in the European Journal of Cancer.

‘Highly concerning’

Different drug modification rules or growth factor support guidance may affect the results of randomized controlled trials (RCTs) of testing new cancer agents.

For their study, Dr. Olivier and colleagues did a cross-sectional analysis of all 62 head-to-head registration RCTs that led to Food and Drug Administration approval between 2009 and 2021.

All of the trials examined anticancer drugs in the advanced or metastatic setting where a comparison was made between arms regarding either dose modification rules or myeloid growth factors recommendations.

The researchers assessed imbalance in drug modification rules, myeloid growth factor recommendations, or both, according to prespecified rules.

They discovered that 40 of the 62 trials (65%) had unequal rules for dose medication, granulocyte colony-stimulating factor (G-CSF) use, or both.

Six trials (10%) had rules favoring the control arm, while 34 (55%) had rules favoring the experimental arm. Among these, 50% had unequal drug modification rules, 41% had unequal G-CSF rules, and 9% had both.

Dr. Olivier said in an interview the results are “highly concerning because when you are investigating the effect of a new drug, you don’t want to have a false sense of a drug’s effect because of other factors not directly related to the drug’s efficacy.”

“If you introduce unfair rules about dose modification or supporting medication that favors the new drug, then you don’t know if a positive trial is due to the effect of the new drug or to the effect of differential dosing or supporting medication,” he added.
 

Blame industry?

Dr. Olivier said the fact that most registration trials are industry-sponsored is likely the primary explanation of the findings.

“Industry-sponsored trials may be designed so that the new drug has the best chance to get the largest ‘win,’ because this means more market share and more profit for the company that manufactures the drug. This is not a criticism of the industry, which runs on a business model that naturally aims to gain more market share and more profit,” Dr. Olivier said.

“However, it is the role and duty of regulators to reconcile industry incentives with the patients’ best interests, and there is accumulating data showing the regulators are failing to do so,” he added.

Addressing this problem will likely take buy-in from multiple stakeholders.

Awareness of the problem is a first step and understanding the influence of commercial incentives in drug development is also key, Dr. Olivier said.

Institutional review boards and drug regulators could also systematically evaluate drug dosing modification and supportive medication rules before a trial gets underway.

Regulators could also incentivize companies to implement balanced rules between arms by not granting drug approval based on trials suffering from such flaws.

“However, financial conflict of interest is present at many levels of drug development, including in drug regulation,” Dr. Olivier noted.

He pointed to a recent study that found when hematology-oncology medical reviewers working at the FDA leave the agency, more than half end up working or consulting for the pharmaceutical industry.

Dr. Olivier wondered: “How can one fairly and independently appraise a medical intervention if one’s current or future revenue depends on its source?”

The study was funded by Arnold Ventures, through a grant paid to UCSF. Dr. Olivier and Dr. Haslam had no relevant disclosures. Dr. Prasad reported receiving royalties from Arnold Ventures.

A version of this article first appeared on Medscape.com.

More than half of studies testing anticancer drugs against each other have rules with regard to dose modification and growth support that favor the experimental drug arm, a new analysis suggests.

“We found it sobering that this practice is so common,” Timothée Olivier, MD, with Geneva University Hospital and the University of California, San Francisco, said in an interview.

Trials may be “rigged” in a way where the new therapy appears more effective than if the trial would have been designed with fairer rules, he explained.

This leaves open the question of whether new drugs are truly superior to older ones or if instead different outcomes are caused by more aggressive dosing or growth factor support, the investigators said.

Dr. Olivier, with UCSF coinvestigators Alyson Haslam, PhD, and Vinay Prasad, MD, reported their findings online in the European Journal of Cancer.

‘Highly concerning’

Different drug modification rules or growth factor support guidance may affect the results of randomized controlled trials (RCTs) of testing new cancer agents.

For their study, Dr. Olivier and colleagues did a cross-sectional analysis of all 62 head-to-head registration RCTs that led to Food and Drug Administration approval between 2009 and 2021.

All of the trials examined anticancer drugs in the advanced or metastatic setting where a comparison was made between arms regarding either dose modification rules or myeloid growth factors recommendations.

The researchers assessed imbalance in drug modification rules, myeloid growth factor recommendations, or both, according to prespecified rules.

They discovered that 40 of the 62 trials (65%) had unequal rules for dose medication, granulocyte colony-stimulating factor (G-CSF) use, or both.

Six trials (10%) had rules favoring the control arm, while 34 (55%) had rules favoring the experimental arm. Among these, 50% had unequal drug modification rules, 41% had unequal G-CSF rules, and 9% had both.

Dr. Olivier said in an interview the results are “highly concerning because when you are investigating the effect of a new drug, you don’t want to have a false sense of a drug’s effect because of other factors not directly related to the drug’s efficacy.”

“If you introduce unfair rules about dose modification or supporting medication that favors the new drug, then you don’t know if a positive trial is due to the effect of the new drug or to the effect of differential dosing or supporting medication,” he added.
 

Blame industry?

Dr. Olivier said the fact that most registration trials are industry-sponsored is likely the primary explanation of the findings.

“Industry-sponsored trials may be designed so that the new drug has the best chance to get the largest ‘win,’ because this means more market share and more profit for the company that manufactures the drug. This is not a criticism of the industry, which runs on a business model that naturally aims to gain more market share and more profit,” Dr. Olivier said.

“However, it is the role and duty of regulators to reconcile industry incentives with the patients’ best interests, and there is accumulating data showing the regulators are failing to do so,” he added.

Addressing this problem will likely take buy-in from multiple stakeholders.

Awareness of the problem is a first step and understanding the influence of commercial incentives in drug development is also key, Dr. Olivier said.

Institutional review boards and drug regulators could also systematically evaluate drug dosing modification and supportive medication rules before a trial gets underway.

Regulators could also incentivize companies to implement balanced rules between arms by not granting drug approval based on trials suffering from such flaws.

“However, financial conflict of interest is present at many levels of drug development, including in drug regulation,” Dr. Olivier noted.

He pointed to a recent study that found when hematology-oncology medical reviewers working at the FDA leave the agency, more than half end up working or consulting for the pharmaceutical industry.

Dr. Olivier wondered: “How can one fairly and independently appraise a medical intervention if one’s current or future revenue depends on its source?”

The study was funded by Arnold Ventures, through a grant paid to UCSF. Dr. Olivier and Dr. Haslam had no relevant disclosures. Dr. Prasad reported receiving royalties from Arnold Ventures.

A version of this article first appeared on Medscape.com.

More than half of studies testing anticancer drugs against each other have rules with regard to dose modification and growth support that favor the experimental drug arm, a new analysis suggests.

“We found it sobering that this practice is so common,” Timothée Olivier, MD, with Geneva University Hospital and the University of California, San Francisco, said in an interview.

Trials may be “rigged” in a way where the new therapy appears more effective than if the trial would have been designed with fairer rules, he explained.

This leaves open the question of whether new drugs are truly superior to older ones or if instead different outcomes are caused by more aggressive dosing or growth factor support, the investigators said.

Dr. Olivier, with UCSF coinvestigators Alyson Haslam, PhD, and Vinay Prasad, MD, reported their findings online in the European Journal of Cancer.

‘Highly concerning’

Different drug modification rules or growth factor support guidance may affect the results of randomized controlled trials (RCTs) of testing new cancer agents.

For their study, Dr. Olivier and colleagues did a cross-sectional analysis of all 62 head-to-head registration RCTs that led to Food and Drug Administration approval between 2009 and 2021.

All of the trials examined anticancer drugs in the advanced or metastatic setting where a comparison was made between arms regarding either dose modification rules or myeloid growth factors recommendations.

The researchers assessed imbalance in drug modification rules, myeloid growth factor recommendations, or both, according to prespecified rules.

They discovered that 40 of the 62 trials (65%) had unequal rules for dose medication, granulocyte colony-stimulating factor (G-CSF) use, or both.

Six trials (10%) had rules favoring the control arm, while 34 (55%) had rules favoring the experimental arm. Among these, 50% had unequal drug modification rules, 41% had unequal G-CSF rules, and 9% had both.

Dr. Olivier said in an interview the results are “highly concerning because when you are investigating the effect of a new drug, you don’t want to have a false sense of a drug’s effect because of other factors not directly related to the drug’s efficacy.”

“If you introduce unfair rules about dose modification or supporting medication that favors the new drug, then you don’t know if a positive trial is due to the effect of the new drug or to the effect of differential dosing or supporting medication,” he added.
 

Blame industry?

Dr. Olivier said the fact that most registration trials are industry-sponsored is likely the primary explanation of the findings.

“Industry-sponsored trials may be designed so that the new drug has the best chance to get the largest ‘win,’ because this means more market share and more profit for the company that manufactures the drug. This is not a criticism of the industry, which runs on a business model that naturally aims to gain more market share and more profit,” Dr. Olivier said.

“However, it is the role and duty of regulators to reconcile industry incentives with the patients’ best interests, and there is accumulating data showing the regulators are failing to do so,” he added.

Addressing this problem will likely take buy-in from multiple stakeholders.

Awareness of the problem is a first step and understanding the influence of commercial incentives in drug development is also key, Dr. Olivier said.

Institutional review boards and drug regulators could also systematically evaluate drug dosing modification and supportive medication rules before a trial gets underway.

Regulators could also incentivize companies to implement balanced rules between arms by not granting drug approval based on trials suffering from such flaws.

“However, financial conflict of interest is present at many levels of drug development, including in drug regulation,” Dr. Olivier noted.

He pointed to a recent study that found when hematology-oncology medical reviewers working at the FDA leave the agency, more than half end up working or consulting for the pharmaceutical industry.

Dr. Olivier wondered: “How can one fairly and independently appraise a medical intervention if one’s current or future revenue depends on its source?”

The study was funded by Arnold Ventures, through a grant paid to UCSF. Dr. Olivier and Dr. Haslam had no relevant disclosures. Dr. Prasad reported receiving royalties from Arnold Ventures.

A version of this article first appeared on Medscape.com.

NEW YORK – A questionnaire-based screening tool appears to accelerate the time to diagnosis of axial involvement in patients presenting with psoriasis but no clinical signs of joint pain, according to a study called ATTRACT that was presented at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

The risk of a delayed diagnosis of an axial component in patients with psoriasis, meaning a delay in the underlying diagnosis of psoriatic arthritis (PsA), is substantial, according to Devis Benfaremo, MD, of the department of clinical and molecular science at Marche Polytechnic University, Ancona, Italy.

Ted Bosworth/MDedge News

There is “no consensus for the best strategy to achieve early detection of joint disease” in patients presenting with psoriasis, but Dr. Benfaremo pointed out that missing axial involvement is a particular problem because it is far more likely than swollen joints to be missed on clinical examination.

While about one in three patients with psoriasis have or will develop psoriatic arthritis, according to the National Psoriasis Foundation, delays in diagnosis are common, according to Dr. Benfaremo. In patients with undiagnosed PsA characterized by axial involvement alone, subtle symptoms can be overlooked or attributed to other causes.

There are several screening questionnaires to detect joint symptoms in patients presenting with psoriasis, such as the five-question Psoriasis Epidemiology Screening Tool, but the questionnaire tested in the ATTRACT trial is focused on detecting axial involvement specifically. It was characterized as the first to do so.

In the ongoing ATTRACT study, 253 patients with psoriasis but no history of PsA or axial disease have been enrolled so far. In the study, patients are screened for PsA based on a patient-completed yes-or-no questionnaire, which takes only a few minutes to complete.

“It is a validated questionnaire for axial [spondyloarthritis], but we have adopted it for detection of psoriasis patients with PsA,” Dr. Benfaremo explained.

The questionnaire for axial spondyloarthritis (axSpA) was initially evaluated and validated by Fabian Proft, MD, head of the clinical trials unit at Charité Hospital, Berlin. In addition to a patient self-completed questionnaire, Dr. Proft and coinvestigators have also created a related questionnaire to be administered by physicians.

In the ATTRACT study, patients completed the questionnaire on an electronic device in the waiting room. Positive answers to specific questions about symptoms, which addressed back pain and joint function as well as joint symptoms, divided patients into three groups:

• Group A patients did not respond positively to any of the symptom questions that would prompt suspicion of axial disease. These represented about one-third of those screened so far.
• Group B patients were those who answered positively to at least two questions that related to a high suspicion of axial involvement. These represented 45% of patients.
• The remaining patients were placed in Group C, a category of intermediate risk based on positive responses to some, but not all, questions relating to axial symptoms.

Those in group B are being referred to rheumatology. Patients in group C are given “conditional” eligibility based on the presence of additional risk factors.
 

AxSpA screening tool ‘makes sense’ for potential use in PsA

The primary outcome of the ATTRACT trial is early identification of axial PsA. Correctly identifying patients with or without peripheral joint involvement is one of several secondary outcomes. The identification of patients who fulfill Assessment Spondyloarthritis International Society (ASAS) criteria for axSpA is another secondary outcome.

Of the 114 patients placed in group B and analyzed so far, 87 have completed an assessment by a rheumatologist with laboratory analyses and imaging, as well as a clinical examination.

Of those 87 assessed by a rheumatologist, 17 did not have either axial or peripheral inflammation. Another 19 were diagnosed with axial disease, including 14 who met ASAS criteria. A total of 10 were classified as having PsA with peripheral inflammation, according to Classification for Psoriatic Arthritis criteria, and 41 are still being considered for a diagnosis of axial or peripheral PsA on the basis of further workup.

“Among the patients with axial PsA, only 10% had elevated C-reactive protein levels,” according to Dr. Benfaremo, echoing previous evidence that inflammatory biomarkers by themselves have limited value for identifying psoriasis patients at high risk of joint involvement.

The findings are preliminary, but Dr. Benfaremo reported that the questionnaire is showing promise for the routine stratification of patients who should be considered for a rheumatology consultation.

If further analyses validate the clinical utility of these stratifications, there is the potential for a substantial acceleration to the diagnosis of PsA.

When contacted to comment about this work, Dr. Proft said that there is an important need for new strategies reduce delay in the diagnosis of PsA among patients presenting with psoriasis. He thinks the screening tool he developed for axSpA “makes sense” as a potential tool in PsA.

“If validated, this could be a very useful for earlier identification of PsA,” Dr. Proft said. He reiterated the importance of focusing on axial involvement.

“Previous screening tools have focused on symptoms of PsA more generally, but inflammation in the peripheral joints is something that you can easily see in most patients,” he said.

In addition to the patient-completed questionnaire and the physician-administered questionnaire, Dr. Proft has also evaluated an online self-referral tool for patients.

“If we can diagnose PsA earlier in the course of disease, we can start treatment earlier, prevent or delay joint damage, and potentially improve outcomes for patients,” Dr. Proft said. He considers this an important direction of research.

Dr. Benfaremo and Dr. Proft reported no potential conflicts of interest.

NEW YORK – A questionnaire-based screening tool appears to accelerate the time to diagnosis of axial involvement in patients presenting with psoriasis but no clinical signs of joint pain, according to a study called ATTRACT that was presented at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

The risk of a delayed diagnosis of an axial component in patients with psoriasis, meaning a delay in the underlying diagnosis of psoriatic arthritis (PsA), is substantial, according to Devis Benfaremo, MD, of the department of clinical and molecular science at Marche Polytechnic University, Ancona, Italy.

Ted Bosworth/MDedge News

There is “no consensus for the best strategy to achieve early detection of joint disease” in patients presenting with psoriasis, but Dr. Benfaremo pointed out that missing axial involvement is a particular problem because it is far more likely than swollen joints to be missed on clinical examination.

While about one in three patients with psoriasis have or will develop psoriatic arthritis, according to the National Psoriasis Foundation, delays in diagnosis are common, according to Dr. Benfaremo. In patients with undiagnosed PsA characterized by axial involvement alone, subtle symptoms can be overlooked or attributed to other causes.

There are several screening questionnaires to detect joint symptoms in patients presenting with psoriasis, such as the five-question Psoriasis Epidemiology Screening Tool, but the questionnaire tested in the ATTRACT trial is focused on detecting axial involvement specifically. It was characterized as the first to do so.

In the ongoing ATTRACT study, 253 patients with psoriasis but no history of PsA or axial disease have been enrolled so far. In the study, patients are screened for PsA based on a patient-completed yes-or-no questionnaire, which takes only a few minutes to complete.

“It is a validated questionnaire for axial [spondyloarthritis], but we have adopted it for detection of psoriasis patients with PsA,” Dr. Benfaremo explained.

The questionnaire for axial spondyloarthritis (axSpA) was initially evaluated and validated by Fabian Proft, MD, head of the clinical trials unit at Charité Hospital, Berlin. In addition to a patient self-completed questionnaire, Dr. Proft and coinvestigators have also created a related questionnaire to be administered by physicians.

In the ATTRACT study, patients completed the questionnaire on an electronic device in the waiting room. Positive answers to specific questions about symptoms, which addressed back pain and joint function as well as joint symptoms, divided patients into three groups:

• Group A patients did not respond positively to any of the symptom questions that would prompt suspicion of axial disease. These represented about one-third of those screened so far.
• Group B patients were those who answered positively to at least two questions that related to a high suspicion of axial involvement. These represented 45% of patients.
• The remaining patients were placed in Group C, a category of intermediate risk based on positive responses to some, but not all, questions relating to axial symptoms.

Those in group B are being referred to rheumatology. Patients in group C are given “conditional” eligibility based on the presence of additional risk factors.
 

AxSpA screening tool ‘makes sense’ for potential use in PsA

The primary outcome of the ATTRACT trial is early identification of axial PsA. Correctly identifying patients with or without peripheral joint involvement is one of several secondary outcomes. The identification of patients who fulfill Assessment Spondyloarthritis International Society (ASAS) criteria for axSpA is another secondary outcome.

Of the 114 patients placed in group B and analyzed so far, 87 have completed an assessment by a rheumatologist with laboratory analyses and imaging, as well as a clinical examination.

Of those 87 assessed by a rheumatologist, 17 did not have either axial or peripheral inflammation. Another 19 were diagnosed with axial disease, including 14 who met ASAS criteria. A total of 10 were classified as having PsA with peripheral inflammation, according to Classification for Psoriatic Arthritis criteria, and 41 are still being considered for a diagnosis of axial or peripheral PsA on the basis of further workup.

“Among the patients with axial PsA, only 10% had elevated C-reactive protein levels,” according to Dr. Benfaremo, echoing previous evidence that inflammatory biomarkers by themselves have limited value for identifying psoriasis patients at high risk of joint involvement.

The findings are preliminary, but Dr. Benfaremo reported that the questionnaire is showing promise for the routine stratification of patients who should be considered for a rheumatology consultation.

If further analyses validate the clinical utility of these stratifications, there is the potential for a substantial acceleration to the diagnosis of PsA.

When contacted to comment about this work, Dr. Proft said that there is an important need for new strategies reduce delay in the diagnosis of PsA among patients presenting with psoriasis. He thinks the screening tool he developed for axSpA “makes sense” as a potential tool in PsA.

“If validated, this could be a very useful for earlier identification of PsA,” Dr. Proft said. He reiterated the importance of focusing on axial involvement.

“Previous screening tools have focused on symptoms of PsA more generally, but inflammation in the peripheral joints is something that you can easily see in most patients,” he said.

In addition to the patient-completed questionnaire and the physician-administered questionnaire, Dr. Proft has also evaluated an online self-referral tool for patients.

“If we can diagnose PsA earlier in the course of disease, we can start treatment earlier, prevent or delay joint damage, and potentially improve outcomes for patients,” Dr. Proft said. He considers this an important direction of research.

Dr. Benfaremo and Dr. Proft reported no potential conflicts of interest.

NEW YORK – A questionnaire-based screening tool appears to accelerate the time to diagnosis of axial involvement in patients presenting with psoriasis but no clinical signs of joint pain, according to a study called ATTRACT that was presented at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

The risk of a delayed diagnosis of an axial component in patients with psoriasis, meaning a delay in the underlying diagnosis of psoriatic arthritis (PsA), is substantial, according to Devis Benfaremo, MD, of the department of clinical and molecular science at Marche Polytechnic University, Ancona, Italy.

Ted Bosworth/MDedge News

There is “no consensus for the best strategy to achieve early detection of joint disease” in patients presenting with psoriasis, but Dr. Benfaremo pointed out that missing axial involvement is a particular problem because it is far more likely than swollen joints to be missed on clinical examination.

While about one in three patients with psoriasis have or will develop psoriatic arthritis, according to the National Psoriasis Foundation, delays in diagnosis are common, according to Dr. Benfaremo. In patients with undiagnosed PsA characterized by axial involvement alone, subtle symptoms can be overlooked or attributed to other causes.

There are several screening questionnaires to detect joint symptoms in patients presenting with psoriasis, such as the five-question Psoriasis Epidemiology Screening Tool, but the questionnaire tested in the ATTRACT trial is focused on detecting axial involvement specifically. It was characterized as the first to do so.

In the ongoing ATTRACT study, 253 patients with psoriasis but no history of PsA or axial disease have been enrolled so far. In the study, patients are screened for PsA based on a patient-completed yes-or-no questionnaire, which takes only a few minutes to complete.

“It is a validated questionnaire for axial [spondyloarthritis], but we have adopted it for detection of psoriasis patients with PsA,” Dr. Benfaremo explained.

The questionnaire for axial spondyloarthritis (axSpA) was initially evaluated and validated by Fabian Proft, MD, head of the clinical trials unit at Charité Hospital, Berlin. In addition to a patient self-completed questionnaire, Dr. Proft and coinvestigators have also created a related questionnaire to be administered by physicians.

In the ATTRACT study, patients completed the questionnaire on an electronic device in the waiting room. Positive answers to specific questions about symptoms, which addressed back pain and joint function as well as joint symptoms, divided patients into three groups:

• Group A patients did not respond positively to any of the symptom questions that would prompt suspicion of axial disease. These represented about one-third of those screened so far.
• Group B patients were those who answered positively to at least two questions that related to a high suspicion of axial involvement. These represented 45% of patients.
• The remaining patients were placed in Group C, a category of intermediate risk based on positive responses to some, but not all, questions relating to axial symptoms.

Those in group B are being referred to rheumatology. Patients in group C are given “conditional” eligibility based on the presence of additional risk factors.
 

AxSpA screening tool ‘makes sense’ for potential use in PsA

The primary outcome of the ATTRACT trial is early identification of axial PsA. Correctly identifying patients with or without peripheral joint involvement is one of several secondary outcomes. The identification of patients who fulfill Assessment Spondyloarthritis International Society (ASAS) criteria for axSpA is another secondary outcome.

Of the 114 patients placed in group B and analyzed so far, 87 have completed an assessment by a rheumatologist with laboratory analyses and imaging, as well as a clinical examination.

Of those 87 assessed by a rheumatologist, 17 did not have either axial or peripheral inflammation. Another 19 were diagnosed with axial disease, including 14 who met ASAS criteria. A total of 10 were classified as having PsA with peripheral inflammation, according to Classification for Psoriatic Arthritis criteria, and 41 are still being considered for a diagnosis of axial or peripheral PsA on the basis of further workup.

“Among the patients with axial PsA, only 10% had elevated C-reactive protein levels,” according to Dr. Benfaremo, echoing previous evidence that inflammatory biomarkers by themselves have limited value for identifying psoriasis patients at high risk of joint involvement.

The findings are preliminary, but Dr. Benfaremo reported that the questionnaire is showing promise for the routine stratification of patients who should be considered for a rheumatology consultation.

If further analyses validate the clinical utility of these stratifications, there is the potential for a substantial acceleration to the diagnosis of PsA.

When contacted to comment about this work, Dr. Proft said that there is an important need for new strategies reduce delay in the diagnosis of PsA among patients presenting with psoriasis. He thinks the screening tool he developed for axSpA “makes sense” as a potential tool in PsA.

“If validated, this could be a very useful for earlier identification of PsA,” Dr. Proft said. He reiterated the importance of focusing on axial involvement.

“Previous screening tools have focused on symptoms of PsA more generally, but inflammation in the peripheral joints is something that you can easily see in most patients,” he said.

In addition to the patient-completed questionnaire and the physician-administered questionnaire, Dr. Proft has also evaluated an online self-referral tool for patients.

“If we can diagnose PsA earlier in the course of disease, we can start treatment earlier, prevent or delay joint damage, and potentially improve outcomes for patients,” Dr. Proft said. He considers this an important direction of research.

Dr. Benfaremo and Dr. Proft reported no potential conflicts of interest.

Single ulcers, anal lesions, and mouth sores are all unique symptoms of the current monkeypox outbreak, according to the largest international monkeypox case series to date. These findings underscore the need to broaden case definitions for the disease, researchers say.

“While we expected various skin problems and rashes, we also found that 1 in 10 people had only a single skin lesion in the genital area, and 15% had anal and/or rectal pain,” John Thornhill, MD, PhD, the lead author of the research, said in a press release. Dr. Thornhill is a consultant physician in sexual health and HIV and a clinical senior lecturer at Barts NHS Health Trust and Queen Mary University of London. “These different presentations highlight that monkeypox infections could be missed or easily confused with common sexually transmitted infections such as syphilis or herpes,” he said.

Since April 2022, more than 15,000 cases of monkeypox have been reported in 66 countries where the virus was previously not known to be present. The virus, a less severe cousin of smallpox, is endemic to areas of central and west Africa. In the current outbreak, infections have overwhelmingly been found in men who have sex with men.

In a study published in the New England Journal of Medicine, researchers reported clinical details and outcomes of 528 monkeypox infections across 16 countries. All the cases were diagnosed between April 27 and June 24, 2022. Ninety-five percent of the cases were suspected to have been transmitted through sexual activity, 98% of patients identified as gay or bisexual men, and 75% of the patients were White. The median age of patients in this case series was 38 years, and 90% of infections occurred in Europe. Forty-one percent of patients were HIV-positive, and 96% of these individuals were receiving antiretroviral therapy. Among patients whose HIV status was negative or unknown, 57% reported using preexposure prophylaxis against HIV. About 3 in 10 (29%) individuals tested positive for concurrent sexually transmitted infections.

Nearly three out of four patients (73%) had anogenital lesions, and 41% had mucosal lesions. Fifty-four patients had one genital lesion, and 64% had fewer than 10 lesions in total. Fever (62%), swollen lymph nodes (56%), lethargy (41%), and myalgia (31%) were commonly reported symptoms prior to the development of the rash. Seventy patients (13%) required hospitalization, most commonly for severe anorectal pain and soft-tissue superinfection. Just 5% of patients received monkeypox-specific treatment: intravenous or topical cidofovir (2%), tecovirimat (2%), and vaccinia immune globulin (<1%).

The study “importantly reinforces our current understanding that the overwhelming majority of cases have been sexually associated, predominantly in men who have sex with men,” Jeffrey Klausner, MD, PhD, an infectious disease specialist at the University of Southern California, Los Angeles, said in an interview with this news organization. He was not involved with the research. “Anyone can get monkeypox, but it is most effectively spread through what we call dense networks – where there is a frequent, close personal contact,” he said. “It just happens that gay men and other men who have sex with men have some of those networks.”

The fact that most lesions are present in the genital and anal region – which is unique to this outbreak – points to transmission of the infection during intimate contact, he noted. Still, there is not enough evidence to suggest that monkeypox is spread through sexual transmission. While most semen samples in the study tested positive for monkeypox viral DNA, it is not known whether there is enough virus present to cause transmission, Dr. Thornhill said. He noted that more research is needed.

Dr. Klausner also emphasized the importance of developing new tests to diagnose monkeypox earlier to prevent spread. The lab test for monkeypox requires a swab from a lesion, but this study showed that most patients had notable symptoms prior to developing the standard rash or lesions, he said. Reliable tests using saliva or throat swabs could help detect infections faster, he noted. Patients are thought to be most contagious when they develop lesions, Dr. Klausner said, so diagnosing patients before this stage would allow them to be isolated sooner.

The California-based lab company Flow Health announced a saliva-based PCR test for monkeypox on July 9, although the Food and Drug Administration cautioned that test results from other sample types beside lesion swabs may be inaccurate. “The FDA is not aware of clinical data supporting the use of other sample types, such as blood or saliva, for monkeypox virus testing,” the agency said in a statement on July 15. “Testing samples not taken from a lesion may lead to false test results.”

Dr. Klausner reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Single ulcers, anal lesions, and mouth sores are all unique symptoms of the current monkeypox outbreak, according to the largest international monkeypox case series to date. These findings underscore the need to broaden case definitions for the disease, researchers say.

“While we expected various skin problems and rashes, we also found that 1 in 10 people had only a single skin lesion in the genital area, and 15% had anal and/or rectal pain,” John Thornhill, MD, PhD, the lead author of the research, said in a press release. Dr. Thornhill is a consultant physician in sexual health and HIV and a clinical senior lecturer at Barts NHS Health Trust and Queen Mary University of London. “These different presentations highlight that monkeypox infections could be missed or easily confused with common sexually transmitted infections such as syphilis or herpes,” he said.

Since April 2022, more than 15,000 cases of monkeypox have been reported in 66 countries where the virus was previously not known to be present. The virus, a less severe cousin of smallpox, is endemic to areas of central and west Africa. In the current outbreak, infections have overwhelmingly been found in men who have sex with men.

In a study published in the New England Journal of Medicine, researchers reported clinical details and outcomes of 528 monkeypox infections across 16 countries. All the cases were diagnosed between April 27 and June 24, 2022. Ninety-five percent of the cases were suspected to have been transmitted through sexual activity, 98% of patients identified as gay or bisexual men, and 75% of the patients were White. The median age of patients in this case series was 38 years, and 90% of infections occurred in Europe. Forty-one percent of patients were HIV-positive, and 96% of these individuals were receiving antiretroviral therapy. Among patients whose HIV status was negative or unknown, 57% reported using preexposure prophylaxis against HIV. About 3 in 10 (29%) individuals tested positive for concurrent sexually transmitted infections.

Nearly three out of four patients (73%) had anogenital lesions, and 41% had mucosal lesions. Fifty-four patients had one genital lesion, and 64% had fewer than 10 lesions in total. Fever (62%), swollen lymph nodes (56%), lethargy (41%), and myalgia (31%) were commonly reported symptoms prior to the development of the rash. Seventy patients (13%) required hospitalization, most commonly for severe anorectal pain and soft-tissue superinfection. Just 5% of patients received monkeypox-specific treatment: intravenous or topical cidofovir (2%), tecovirimat (2%), and vaccinia immune globulin (<1%).

The study “importantly reinforces our current understanding that the overwhelming majority of cases have been sexually associated, predominantly in men who have sex with men,” Jeffrey Klausner, MD, PhD, an infectious disease specialist at the University of Southern California, Los Angeles, said in an interview with this news organization. He was not involved with the research. “Anyone can get monkeypox, but it is most effectively spread through what we call dense networks – where there is a frequent, close personal contact,” he said. “It just happens that gay men and other men who have sex with men have some of those networks.”

The fact that most lesions are present in the genital and anal region – which is unique to this outbreak – points to transmission of the infection during intimate contact, he noted. Still, there is not enough evidence to suggest that monkeypox is spread through sexual transmission. While most semen samples in the study tested positive for monkeypox viral DNA, it is not known whether there is enough virus present to cause transmission, Dr. Thornhill said. He noted that more research is needed.

Dr. Klausner also emphasized the importance of developing new tests to diagnose monkeypox earlier to prevent spread. The lab test for monkeypox requires a swab from a lesion, but this study showed that most patients had notable symptoms prior to developing the standard rash or lesions, he said. Reliable tests using saliva or throat swabs could help detect infections faster, he noted. Patients are thought to be most contagious when they develop lesions, Dr. Klausner said, so diagnosing patients before this stage would allow them to be isolated sooner.

The California-based lab company Flow Health announced a saliva-based PCR test for monkeypox on July 9, although the Food and Drug Administration cautioned that test results from other sample types beside lesion swabs may be inaccurate. “The FDA is not aware of clinical data supporting the use of other sample types, such as blood or saliva, for monkeypox virus testing,” the agency said in a statement on July 15. “Testing samples not taken from a lesion may lead to false test results.”

Dr. Klausner reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Single ulcers, anal lesions, and mouth sores are all unique symptoms of the current monkeypox outbreak, according to the largest international monkeypox case series to date. These findings underscore the need to broaden case definitions for the disease, researchers say.

“While we expected various skin problems and rashes, we also found that 1 in 10 people had only a single skin lesion in the genital area, and 15% had anal and/or rectal pain,” John Thornhill, MD, PhD, the lead author of the research, said in a press release. Dr. Thornhill is a consultant physician in sexual health and HIV and a clinical senior lecturer at Barts NHS Health Trust and Queen Mary University of London. “These different presentations highlight that monkeypox infections could be missed or easily confused with common sexually transmitted infections such as syphilis or herpes,” he said.

Since April 2022, more than 15,000 cases of monkeypox have been reported in 66 countries where the virus was previously not known to be present. The virus, a less severe cousin of smallpox, is endemic to areas of central and west Africa. In the current outbreak, infections have overwhelmingly been found in men who have sex with men.

In a study published in the New England Journal of Medicine, researchers reported clinical details and outcomes of 528 monkeypox infections across 16 countries. All the cases were diagnosed between April 27 and June 24, 2022. Ninety-five percent of the cases were suspected to have been transmitted through sexual activity, 98% of patients identified as gay or bisexual men, and 75% of the patients were White. The median age of patients in this case series was 38 years, and 90% of infections occurred in Europe. Forty-one percent of patients were HIV-positive, and 96% of these individuals were receiving antiretroviral therapy. Among patients whose HIV status was negative or unknown, 57% reported using preexposure prophylaxis against HIV. About 3 in 10 (29%) individuals tested positive for concurrent sexually transmitted infections.

Nearly three out of four patients (73%) had anogenital lesions, and 41% had mucosal lesions. Fifty-four patients had one genital lesion, and 64% had fewer than 10 lesions in total. Fever (62%), swollen lymph nodes (56%), lethargy (41%), and myalgia (31%) were commonly reported symptoms prior to the development of the rash. Seventy patients (13%) required hospitalization, most commonly for severe anorectal pain and soft-tissue superinfection. Just 5% of patients received monkeypox-specific treatment: intravenous or topical cidofovir (2%), tecovirimat (2%), and vaccinia immune globulin (<1%).

The study “importantly reinforces our current understanding that the overwhelming majority of cases have been sexually associated, predominantly in men who have sex with men,” Jeffrey Klausner, MD, PhD, an infectious disease specialist at the University of Southern California, Los Angeles, said in an interview with this news organization. He was not involved with the research. “Anyone can get monkeypox, but it is most effectively spread through what we call dense networks – where there is a frequent, close personal contact,” he said. “It just happens that gay men and other men who have sex with men have some of those networks.”

The fact that most lesions are present in the genital and anal region – which is unique to this outbreak – points to transmission of the infection during intimate contact, he noted. Still, there is not enough evidence to suggest that monkeypox is spread through sexual transmission. While most semen samples in the study tested positive for monkeypox viral DNA, it is not known whether there is enough virus present to cause transmission, Dr. Thornhill said. He noted that more research is needed.

Dr. Klausner also emphasized the importance of developing new tests to diagnose monkeypox earlier to prevent spread. The lab test for monkeypox requires a swab from a lesion, but this study showed that most patients had notable symptoms prior to developing the standard rash or lesions, he said. Reliable tests using saliva or throat swabs could help detect infections faster, he noted. Patients are thought to be most contagious when they develop lesions, Dr. Klausner said, so diagnosing patients before this stage would allow them to be isolated sooner.

The California-based lab company Flow Health announced a saliva-based PCR test for monkeypox on July 9, although the Food and Drug Administration cautioned that test results from other sample types beside lesion swabs may be inaccurate. “The FDA is not aware of clinical data supporting the use of other sample types, such as blood or saliva, for monkeypox virus testing,” the agency said in a statement on July 15. “Testing samples not taken from a lesion may lead to false test results.”

Dr. Klausner reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

INDIANAPOLIS – An investigational topical treatment for dystrophic epidermolysis bullosa (DEB) known as beremagene geperpavec (B-VEC) showed durable and statistically significant improvement in complete wound healing at 3 and 6 months compared with placebo, according to results from a small phase 3 study.

DEB is a serious, ultra-rare genetic blistering disease caused by mutations in the COL7A1 gene, encoding for type VII collagen and leading to skin fragility and wounds. No approved therapies are currently available. In the study, treatment was generally well tolerated.

Doug Brunk/MDedge News

“B-VEC is the first treatment that has not only been shown to be effective, but the first to directly target the defect through topical application,” the study’s principal investigator, Shireen V. Guide, MD, said in an interview during a poster session at the annual meeting of the Society for Pediatric Dermatology. “It delivers type VII collagen gene therapy to these patients, which allows healing in areas that they may have had open since birth. It’s been life-changing for them.”

B-VEC is a herpes simplex virus (HSV-1)-based topical, redosable gene therapy being developed by Krystal Biotech that is designed to restore functional COL7 protein by delivering the COL7A1 gene. For the phase 3, multicenter, double-blind, placebo-controlled study known GEM-3, Dr. Guide, who practices dermatology in Rancho Santa Margarita, Calif., and her colleagues, including Peter Marinkovich, MD, from Stanford (Calif.) University, and Mercedes Gonzalez, MD, from the University of Miami, enrolled 31 patients aged 6 months and older with genetically confirmed DEB. Each patient had one wound treated randomized 1:1 to treatment with B-VEC once a week or placebo for 6 months. The mean age of the 31 study participants was 17 years, 65% were male, 65% were White, and 19% were Asian.

The primary endpoint was complete wound healing (defined as 100% wound closure from exact wound area at baseline, specified as skin re-epithelialization without drainage) at 6 months. Additional endpoints included complete wound healing at 3 months and change in pain associated with wound dressing changes.

At 3 months, 70% of wounds treated with B-VEC met the endpoint of complete wound healing, compared with 20% of wounds treated with placebo (P < .005). At 6 months, 67% of wounds treated with B-VEC met the endpoint of complete wound healing compared with 22% of those treated with placebo (P < .005).

Of the total wounds that closed at 3 months, 67% of wounds treated with B-VEC were also closed at 6 months, compared with 33% of those treated with placebo (P = .02). In other findings, a trend toward decreased pain was observed in wounds treated with B-VEC vs. those treated with placebo.

B-VEC was well tolerated with no treatment-related serious adverse events or discontinuations. Three patients experienced a total of five serious adverse events during the study: anemia (two events), and cellulitis, diarrhea, and positive blood culture (one event each). None were considered related to the study drug.

Dr. Guide, who is on staff at Children’s Health of Orange County, Orange, Calif., characterized B-VEC as “very novel because it’s very practical.”

To date, all treatments for DEB “have been extremely labor intensive, including skin grafting and hospitalizations. It’s a topical application that can be done in the office and potentially applied at home in the future. It’s also durable. Not only are the [treated] areas closing, but they are staying closed.”

Kalyani S. Marathe, MD, MPH, director of the dermatology division at Cincinnati Children’s Hospital, who was asked to comment on the study, said that topical application of B-VEC “allows the side effect profile to be very favorable. The results are remarkable in the amount of wound healing and reduction in pain.”

The tolerability of this medication “is crucial,” she added. “EB patients have a lot of pain from their wounds and so any treatment needs to be as painless as possible for it to be usable. I’m very excited about the next phase of studies for this medication and hopeful that it heralds new treatments for our EB patients.”

In June 2022, the manufacturer announced that it had submitted a biologics license application to the Food and Drug Administration for approval of B-VEC for the treatment of DEB, and that it anticipates submitting an application for marketing authorization with the European Medical Agency (EMA) in the second half of 2022.

Dr. Guide disclosed that she has served as an investigator for Krystal Biotech, Innovaderm Research, Arcutis, Premier Research, Paidion, and Castle Biosciences. Dr. Marathe disclosed that she has served as an adviser for Verrica, and that Cincinnati Children’s Hospital is a site for the next phase studies for B-VEC.

*This story was updated on July 25. 

INDIANAPOLIS – An investigational topical treatment for dystrophic epidermolysis bullosa (DEB) known as beremagene geperpavec (B-VEC) showed durable and statistically significant improvement in complete wound healing at 3 and 6 months compared with placebo, according to results from a small phase 3 study.

DEB is a serious, ultra-rare genetic blistering disease caused by mutations in the COL7A1 gene, encoding for type VII collagen and leading to skin fragility and wounds. No approved therapies are currently available. In the study, treatment was generally well tolerated.

Doug Brunk/MDedge News

“B-VEC is the first treatment that has not only been shown to be effective, but the first to directly target the defect through topical application,” the study’s principal investigator, Shireen V. Guide, MD, said in an interview during a poster session at the annual meeting of the Society for Pediatric Dermatology. “It delivers type VII collagen gene therapy to these patients, which allows healing in areas that they may have had open since birth. It’s been life-changing for them.”

B-VEC is a herpes simplex virus (HSV-1)-based topical, redosable gene therapy being developed by Krystal Biotech that is designed to restore functional COL7 protein by delivering the COL7A1 gene. For the phase 3, multicenter, double-blind, placebo-controlled study known GEM-3, Dr. Guide, who practices dermatology in Rancho Santa Margarita, Calif., and her colleagues, including Peter Marinkovich, MD, from Stanford (Calif.) University, and Mercedes Gonzalez, MD, from the University of Miami, enrolled 31 patients aged 6 months and older with genetically confirmed DEB. Each patient had one wound treated randomized 1:1 to treatment with B-VEC once a week or placebo for 6 months. The mean age of the 31 study participants was 17 years, 65% were male, 65% were White, and 19% were Asian.

The primary endpoint was complete wound healing (defined as 100% wound closure from exact wound area at baseline, specified as skin re-epithelialization without drainage) at 6 months. Additional endpoints included complete wound healing at 3 months and change in pain associated with wound dressing changes.

At 3 months, 70% of wounds treated with B-VEC met the endpoint of complete wound healing, compared with 20% of wounds treated with placebo (P < .005). At 6 months, 67% of wounds treated with B-VEC met the endpoint of complete wound healing compared with 22% of those treated with placebo (P < .005).

Of the total wounds that closed at 3 months, 67% of wounds treated with B-VEC were also closed at 6 months, compared with 33% of those treated with placebo (P = .02). In other findings, a trend toward decreased pain was observed in wounds treated with B-VEC vs. those treated with placebo.

B-VEC was well tolerated with no treatment-related serious adverse events or discontinuations. Three patients experienced a total of five serious adverse events during the study: anemia (two events), and cellulitis, diarrhea, and positive blood culture (one event each). None were considered related to the study drug.

Dr. Guide, who is on staff at Children’s Health of Orange County, Orange, Calif., characterized B-VEC as “very novel because it’s very practical.”

To date, all treatments for DEB “have been extremely labor intensive, including skin grafting and hospitalizations. It’s a topical application that can be done in the office and potentially applied at home in the future. It’s also durable. Not only are the [treated] areas closing, but they are staying closed.”

Kalyani S. Marathe, MD, MPH, director of the dermatology division at Cincinnati Children’s Hospital, who was asked to comment on the study, said that topical application of B-VEC “allows the side effect profile to be very favorable. The results are remarkable in the amount of wound healing and reduction in pain.”

The tolerability of this medication “is crucial,” she added. “EB patients have a lot of pain from their wounds and so any treatment needs to be as painless as possible for it to be usable. I’m very excited about the next phase of studies for this medication and hopeful that it heralds new treatments for our EB patients.”

In June 2022, the manufacturer announced that it had submitted a biologics license application to the Food and Drug Administration for approval of B-VEC for the treatment of DEB, and that it anticipates submitting an application for marketing authorization with the European Medical Agency (EMA) in the second half of 2022.

Dr. Guide disclosed that she has served as an investigator for Krystal Biotech, Innovaderm Research, Arcutis, Premier Research, Paidion, and Castle Biosciences. Dr. Marathe disclosed that she has served as an adviser for Verrica, and that Cincinnati Children’s Hospital is a site for the next phase studies for B-VEC.

*This story was updated on July 25. 

INDIANAPOLIS – An investigational topical treatment for dystrophic epidermolysis bullosa (DEB) known as beremagene geperpavec (B-VEC) showed durable and statistically significant improvement in complete wound healing at 3 and 6 months compared with placebo, according to results from a small phase 3 study.

DEB is a serious, ultra-rare genetic blistering disease caused by mutations in the COL7A1 gene, encoding for type VII collagen and leading to skin fragility and wounds. No approved therapies are currently available. In the study, treatment was generally well tolerated.

Doug Brunk/MDedge News

“B-VEC is the first treatment that has not only been shown to be effective, but the first to directly target the defect through topical application,” the study’s principal investigator, Shireen V. Guide, MD, said in an interview during a poster session at the annual meeting of the Society for Pediatric Dermatology. “It delivers type VII collagen gene therapy to these patients, which allows healing in areas that they may have had open since birth. It’s been life-changing for them.”

B-VEC is a herpes simplex virus (HSV-1)-based topical, redosable gene therapy being developed by Krystal Biotech that is designed to restore functional COL7 protein by delivering the COL7A1 gene. For the phase 3, multicenter, double-blind, placebo-controlled study known GEM-3, Dr. Guide, who practices dermatology in Rancho Santa Margarita, Calif., and her colleagues, including Peter Marinkovich, MD, from Stanford (Calif.) University, and Mercedes Gonzalez, MD, from the University of Miami, enrolled 31 patients aged 6 months and older with genetically confirmed DEB. Each patient had one wound treated randomized 1:1 to treatment with B-VEC once a week or placebo for 6 months. The mean age of the 31 study participants was 17 years, 65% were male, 65% were White, and 19% were Asian.

The primary endpoint was complete wound healing (defined as 100% wound closure from exact wound area at baseline, specified as skin re-epithelialization without drainage) at 6 months. Additional endpoints included complete wound healing at 3 months and change in pain associated with wound dressing changes.

At 3 months, 70% of wounds treated with B-VEC met the endpoint of complete wound healing, compared with 20% of wounds treated with placebo (P < .005). At 6 months, 67% of wounds treated with B-VEC met the endpoint of complete wound healing compared with 22% of those treated with placebo (P < .005).

Of the total wounds that closed at 3 months, 67% of wounds treated with B-VEC were also closed at 6 months, compared with 33% of those treated with placebo (P = .02). In other findings, a trend toward decreased pain was observed in wounds treated with B-VEC vs. those treated with placebo.

B-VEC was well tolerated with no treatment-related serious adverse events or discontinuations. Three patients experienced a total of five serious adverse events during the study: anemia (two events), and cellulitis, diarrhea, and positive blood culture (one event each). None were considered related to the study drug.

Dr. Guide, who is on staff at Children’s Health of Orange County, Orange, Calif., characterized B-VEC as “very novel because it’s very practical.”

To date, all treatments for DEB “have been extremely labor intensive, including skin grafting and hospitalizations. It’s a topical application that can be done in the office and potentially applied at home in the future. It’s also durable. Not only are the [treated] areas closing, but they are staying closed.”

Kalyani S. Marathe, MD, MPH, director of the dermatology division at Cincinnati Children’s Hospital, who was asked to comment on the study, said that topical application of B-VEC “allows the side effect profile to be very favorable. The results are remarkable in the amount of wound healing and reduction in pain.”

The tolerability of this medication “is crucial,” she added. “EB patients have a lot of pain from their wounds and so any treatment needs to be as painless as possible for it to be usable. I’m very excited about the next phase of studies for this medication and hopeful that it heralds new treatments for our EB patients.”

In June 2022, the manufacturer announced that it had submitted a biologics license application to the Food and Drug Administration for approval of B-VEC for the treatment of DEB, and that it anticipates submitting an application for marketing authorization with the European Medical Agency (EMA) in the second half of 2022.

Dr. Guide disclosed that she has served as an investigator for Krystal Biotech, Innovaderm Research, Arcutis, Premier Research, Paidion, and Castle Biosciences. Dr. Marathe disclosed that she has served as an adviser for Verrica, and that Cincinnati Children’s Hospital is a site for the next phase studies for B-VEC.

*This story was updated on July 25. 

A U.S. study describes the immune response to COVID-19 infection that damages the brain’s blood vessels and may lead to short- and long-term neurologic symptoms.

It seems that the virus does not infect the brain directly. The scientists found evidence that antibodies – proteins produced by the immune system in response to viruses and other invaders – are involved in an attack on the cells lining the brain’s blood vessels, leading to inflammation and damage. The study was published in the journal Brain.
 

Brain tissue autopsy

“Patients often develop neurological complications with COVID-19, but the underlying pathophysiological process is not well understood,” Avindra Nath, MD, stated in a National Institutes of Health news release. Dr. Nath, who specializes in neuroimmunology, is the clinical director at the National Institute of Neurological Disorders and Stroke (NINDS) and the senior author of the study. “We had previously shown blood vessel damage and inflammation in patients’ brains at autopsy, but we didn’t understand the cause of the damage. I think in this paper we’ve gained important insight into the cascade of events.”

In this study, Dr. Nath and his team examined brain tissue from a subset of patients from their previous study. The nine individuals, ages 24-73 years, died shortly after contracting COVID-19. They were chosen because structural brain scans showed signs of blood vessel damage in the brain. The samples were compared with those from 10 controls. The team looked at neuroinflammation and immune responses using immunohistochemistry.

As in their earlier study, researchers found signs of leaky blood vessels based on the presence of blood proteins that normally do not cross the blood-brain barrier. This suggests that the tight junctions between the endothelial cells in the blood-brain barrier have been damaged.
 

Neurologic symptoms’ molecular basis

Dr. Nath and his colleagues discovered deposits of immune complexes on the surface of the cells. This finding is evidence that damage to endothelial cells was likely due to an immune response.

These observations suggest an antibody-mediated attack that activates endothelial cells. When endothelial cells are activated, they express proteins called adhesion molecules that cause platelets to stick together.

“Activation of the endothelial cells brings platelets that stick to the blood vessel walls, causing clots to form and leakage to occur. At the same time, the tight junctions between the endothelial cells get disrupted, causing them to leak,” Dr. Nath explained. “Once leakage occurs, immune cells such as macrophages may come to repair the damage, setting up inflammation. This, in turn, causes damage to neurons.”

Researchers found that in areas with damage to the endothelial cells, more than 300 genes showed decreased expression, whereas six genes were increased. These genes were associated with oxidative stress, DNA damage, and metabolic dysregulation. As the NIH news release notes, this may provide clues to the molecular basis of neurologic symptoms related to COVID-19 and offer potential therapeutic targets.

Together, these findings give insight into the immune response damaging the brain after COVID-19 infection. But it remains unclear what antigen the immune response is targeting, because the virus itself was not detected in the brain. It is possible that antibodies against the SARS-CoV-2 spike protein could bind to the angiotensin-converting enzyme 2 receptor used by the virus to enter cells. More research is needed to explore this hypothesis.
 

‘Brain fog’ explained?

The study may also have implications for understanding and treating long-term neurologic symptoms after COVID-19, which include headache, fatigue, loss of taste and smell, sleep problems, and “brain fog.” Had the patients in the study survived, the researchers believe they would likely have developed long COVID.

“It is quite possible that this same immune response persists in long COVID patients, resulting in neuronal injury,” said Dr. Nath. “There could be a small, indolent immune response that is continuing, which means that immune-modulating therapies might help these patients. So, these findings have very important therapeutic implications.”

The results suggest that treatments designed to prevent the development of the immune complexes observed in the study could be potential therapies for post-COVID neurologic symptoms.

This study was supported by the NINDS Division of Intramural Research (NS003130) and K23NS109284, the Roy J. Carver Foundation, and the Iowa Neuroscience Institute.

A version of this article first appeared on Medscape.com. This article was translated from Medscape French edition.

A U.S. study describes the immune response to COVID-19 infection that damages the brain’s blood vessels and may lead to short- and long-term neurologic symptoms.

It seems that the virus does not infect the brain directly. The scientists found evidence that antibodies – proteins produced by the immune system in response to viruses and other invaders – are involved in an attack on the cells lining the brain’s blood vessels, leading to inflammation and damage. The study was published in the journal Brain.
 

Brain tissue autopsy

“Patients often develop neurological complications with COVID-19, but the underlying pathophysiological process is not well understood,” Avindra Nath, MD, stated in a National Institutes of Health news release. Dr. Nath, who specializes in neuroimmunology, is the clinical director at the National Institute of Neurological Disorders and Stroke (NINDS) and the senior author of the study. “We had previously shown blood vessel damage and inflammation in patients’ brains at autopsy, but we didn’t understand the cause of the damage. I think in this paper we’ve gained important insight into the cascade of events.”

In this study, Dr. Nath and his team examined brain tissue from a subset of patients from their previous study. The nine individuals, ages 24-73 years, died shortly after contracting COVID-19. They were chosen because structural brain scans showed signs of blood vessel damage in the brain. The samples were compared with those from 10 controls. The team looked at neuroinflammation and immune responses using immunohistochemistry.

As in their earlier study, researchers found signs of leaky blood vessels based on the presence of blood proteins that normally do not cross the blood-brain barrier. This suggests that the tight junctions between the endothelial cells in the blood-brain barrier have been damaged.
 

Neurologic symptoms’ molecular basis

Dr. Nath and his colleagues discovered deposits of immune complexes on the surface of the cells. This finding is evidence that damage to endothelial cells was likely due to an immune response.

These observations suggest an antibody-mediated attack that activates endothelial cells. When endothelial cells are activated, they express proteins called adhesion molecules that cause platelets to stick together.

“Activation of the endothelial cells brings platelets that stick to the blood vessel walls, causing clots to form and leakage to occur. At the same time, the tight junctions between the endothelial cells get disrupted, causing them to leak,” Dr. Nath explained. “Once leakage occurs, immune cells such as macrophages may come to repair the damage, setting up inflammation. This, in turn, causes damage to neurons.”

Researchers found that in areas with damage to the endothelial cells, more than 300 genes showed decreased expression, whereas six genes were increased. These genes were associated with oxidative stress, DNA damage, and metabolic dysregulation. As the NIH news release notes, this may provide clues to the molecular basis of neurologic symptoms related to COVID-19 and offer potential therapeutic targets.

Together, these findings give insight into the immune response damaging the brain after COVID-19 infection. But it remains unclear what antigen the immune response is targeting, because the virus itself was not detected in the brain. It is possible that antibodies against the SARS-CoV-2 spike protein could bind to the angiotensin-converting enzyme 2 receptor used by the virus to enter cells. More research is needed to explore this hypothesis.
 

‘Brain fog’ explained?

The study may also have implications for understanding and treating long-term neurologic symptoms after COVID-19, which include headache, fatigue, loss of taste and smell, sleep problems, and “brain fog.” Had the patients in the study survived, the researchers believe they would likely have developed long COVID.

“It is quite possible that this same immune response persists in long COVID patients, resulting in neuronal injury,” said Dr. Nath. “There could be a small, indolent immune response that is continuing, which means that immune-modulating therapies might help these patients. So, these findings have very important therapeutic implications.”

The results suggest that treatments designed to prevent the development of the immune complexes observed in the study could be potential therapies for post-COVID neurologic symptoms.

This study was supported by the NINDS Division of Intramural Research (NS003130) and K23NS109284, the Roy J. Carver Foundation, and the Iowa Neuroscience Institute.

A version of this article first appeared on Medscape.com. This article was translated from Medscape French edition.

A U.S. study describes the immune response to COVID-19 infection that damages the brain’s blood vessels and may lead to short- and long-term neurologic symptoms.

It seems that the virus does not infect the brain directly. The scientists found evidence that antibodies – proteins produced by the immune system in response to viruses and other invaders – are involved in an attack on the cells lining the brain’s blood vessels, leading to inflammation and damage. The study was published in the journal Brain.
 

Brain tissue autopsy

“Patients often develop neurological complications with COVID-19, but the underlying pathophysiological process is not well understood,” Avindra Nath, MD, stated in a National Institutes of Health news release. Dr. Nath, who specializes in neuroimmunology, is the clinical director at the National Institute of Neurological Disorders and Stroke (NINDS) and the senior author of the study. “We had previously shown blood vessel damage and inflammation in patients’ brains at autopsy, but we didn’t understand the cause of the damage. I think in this paper we’ve gained important insight into the cascade of events.”

In this study, Dr. Nath and his team examined brain tissue from a subset of patients from their previous study. The nine individuals, ages 24-73 years, died shortly after contracting COVID-19. They were chosen because structural brain scans showed signs of blood vessel damage in the brain. The samples were compared with those from 10 controls. The team looked at neuroinflammation and immune responses using immunohistochemistry.

As in their earlier study, researchers found signs of leaky blood vessels based on the presence of blood proteins that normally do not cross the blood-brain barrier. This suggests that the tight junctions between the endothelial cells in the blood-brain barrier have been damaged.
 

Neurologic symptoms’ molecular basis

Dr. Nath and his colleagues discovered deposits of immune complexes on the surface of the cells. This finding is evidence that damage to endothelial cells was likely due to an immune response.

These observations suggest an antibody-mediated attack that activates endothelial cells. When endothelial cells are activated, they express proteins called adhesion molecules that cause platelets to stick together.

“Activation of the endothelial cells brings platelets that stick to the blood vessel walls, causing clots to form and leakage to occur. At the same time, the tight junctions between the endothelial cells get disrupted, causing them to leak,” Dr. Nath explained. “Once leakage occurs, immune cells such as macrophages may come to repair the damage, setting up inflammation. This, in turn, causes damage to neurons.”

Researchers found that in areas with damage to the endothelial cells, more than 300 genes showed decreased expression, whereas six genes were increased. These genes were associated with oxidative stress, DNA damage, and metabolic dysregulation. As the NIH news release notes, this may provide clues to the molecular basis of neurologic symptoms related to COVID-19 and offer potential therapeutic targets.

Together, these findings give insight into the immune response damaging the brain after COVID-19 infection. But it remains unclear what antigen the immune response is targeting, because the virus itself was not detected in the brain. It is possible that antibodies against the SARS-CoV-2 spike protein could bind to the angiotensin-converting enzyme 2 receptor used by the virus to enter cells. More research is needed to explore this hypothesis.
 

‘Brain fog’ explained?

The study may also have implications for understanding and treating long-term neurologic symptoms after COVID-19, which include headache, fatigue, loss of taste and smell, sleep problems, and “brain fog.” Had the patients in the study survived, the researchers believe they would likely have developed long COVID.

“It is quite possible that this same immune response persists in long COVID patients, resulting in neuronal injury,” said Dr. Nath. “There could be a small, indolent immune response that is continuing, which means that immune-modulating therapies might help these patients. So, these findings have very important therapeutic implications.”

The results suggest that treatments designed to prevent the development of the immune complexes observed in the study could be potential therapies for post-COVID neurologic symptoms.

This study was supported by the NINDS Division of Intramural Research (NS003130) and K23NS109284, the Roy J. Carver Foundation, and the Iowa Neuroscience Institute.

A version of this article first appeared on Medscape.com. This article was translated from Medscape French edition.

As the number of monkeypox cases keeps growing, a discussion has opened on whether it should be considered a sexually transmitted disease like herpes, gonorrhea, or HIV.

Monkeypox is almost always spread through skin-to-skin contact and, in the West, many of the cases have occurred among men who have sex with men.

But health experts say that doesn’t make it an STD – at least not in “the classic sense.”

“Monkeypox is not a sexually transmitted disease in the classic sense (by which it’s spread in the semen or vaginal fluids), but it is spread by close physical contact with lesions,” infectious diseases expert Robert L. Murphy, MD, of Northwestern Medicine, Chicago, said in a news release.

He said the current monkeypox outbreak was more like a meningitis outbreak among gay men a few years ago.

Rowland Kao, PhD, a professor of veterinary epidemiology and data science at the University of Edinburgh, said that an “STD is one where intimate, sexual contact is critical to the transmission – where sexual acts are central to the transmission,” Newsweek reported.

“Some infections are transmitted by any type of close contact, of which sexual activity is one. Monkeypox is one of those – it’s the close contact that matters, not the sexual activity itself.”

But calling monkeypox an STD could deter measures to limit its spread, another expert told Newsweek.

“My uneasiness about labeling it as an STD is that for most STDs, wearing a condom or avoiding penetration or direct oral-anal/oral-genital contact is a good way of preventing transmission,” said Paul Hunter, MD, a professor of health protection at the University of East Anglia, Norwich, England.

“But for monkeypox, even just naked cuddling is a big risk. So labeling it an STD could actually work against control if people felt they just had to wear a condom.”

Denise Dewald, MD, a pediatric specialist at University Hospitals Cleveland Medical Center, said monkeypox is not an STD – but it could become an entrenched virus.

“Monkeypox will become established in the pediatric and general population and will transmit through daycares and schools,” she tweeted. “It is not an STD. It is like MRSA. This isn’t rocket science.”

One thing is certain: More and more people are getting monkeypox. It’s been endemic in Western and Central Africa for years, and cases in Europe and North America were identified in May.

Globally, more than 14,000 cases have been identified, World Health Organization Director-General Tedros Adhanom Ghebreyesus said on July 20, according to the Center for Infectious Disease Research and Policy. Five people in Africa have died. In the United Kingdom, more than 2,100 cases have been identified.

In the United States, more than 2,500 confirmed monkeypox cases have been detected, with cases reported from every state except Alaska, Maine, Montana, Mississippi, Vermont, and Wyoming, the CDC said on July 21.

A version of this article first appeared on WebMD.com.

As the number of monkeypox cases keeps growing, a discussion has opened on whether it should be considered a sexually transmitted disease like herpes, gonorrhea, or HIV.

Monkeypox is almost always spread through skin-to-skin contact and, in the West, many of the cases have occurred among men who have sex with men.

But health experts say that doesn’t make it an STD – at least not in “the classic sense.”

“Monkeypox is not a sexually transmitted disease in the classic sense (by which it’s spread in the semen or vaginal fluids), but it is spread by close physical contact with lesions,” infectious diseases expert Robert L. Murphy, MD, of Northwestern Medicine, Chicago, said in a news release.

He said the current monkeypox outbreak was more like a meningitis outbreak among gay men a few years ago.

Rowland Kao, PhD, a professor of veterinary epidemiology and data science at the University of Edinburgh, said that an “STD is one where intimate, sexual contact is critical to the transmission – where sexual acts are central to the transmission,” Newsweek reported.

“Some infections are transmitted by any type of close contact, of which sexual activity is one. Monkeypox is one of those – it’s the close contact that matters, not the sexual activity itself.”

But calling monkeypox an STD could deter measures to limit its spread, another expert told Newsweek.

“My uneasiness about labeling it as an STD is that for most STDs, wearing a condom or avoiding penetration or direct oral-anal/oral-genital contact is a good way of preventing transmission,” said Paul Hunter, MD, a professor of health protection at the University of East Anglia, Norwich, England.

“But for monkeypox, even just naked cuddling is a big risk. So labeling it an STD could actually work against control if people felt they just had to wear a condom.”

Denise Dewald, MD, a pediatric specialist at University Hospitals Cleveland Medical Center, said monkeypox is not an STD – but it could become an entrenched virus.

“Monkeypox will become established in the pediatric and general population and will transmit through daycares and schools,” she tweeted. “It is not an STD. It is like MRSA. This isn’t rocket science.”

One thing is certain: More and more people are getting monkeypox. It’s been endemic in Western and Central Africa for years, and cases in Europe and North America were identified in May.

Globally, more than 14,000 cases have been identified, World Health Organization Director-General Tedros Adhanom Ghebreyesus said on July 20, according to the Center for Infectious Disease Research and Policy. Five people in Africa have died. In the United Kingdom, more than 2,100 cases have been identified.

In the United States, more than 2,500 confirmed monkeypox cases have been detected, with cases reported from every state except Alaska, Maine, Montana, Mississippi, Vermont, and Wyoming, the CDC said on July 21.

A version of this article first appeared on WebMD.com.

As the number of monkeypox cases keeps growing, a discussion has opened on whether it should be considered a sexually transmitted disease like herpes, gonorrhea, or HIV.

Monkeypox is almost always spread through skin-to-skin contact and, in the West, many of the cases have occurred among men who have sex with men.

But health experts say that doesn’t make it an STD – at least not in “the classic sense.”

“Monkeypox is not a sexually transmitted disease in the classic sense (by which it’s spread in the semen or vaginal fluids), but it is spread by close physical contact with lesions,” infectious diseases expert Robert L. Murphy, MD, of Northwestern Medicine, Chicago, said in a news release.

He said the current monkeypox outbreak was more like a meningitis outbreak among gay men a few years ago.

Rowland Kao, PhD, a professor of veterinary epidemiology and data science at the University of Edinburgh, said that an “STD is one where intimate, sexual contact is critical to the transmission – where sexual acts are central to the transmission,” Newsweek reported.

“Some infections are transmitted by any type of close contact, of which sexual activity is one. Monkeypox is one of those – it’s the close contact that matters, not the sexual activity itself.”

But calling monkeypox an STD could deter measures to limit its spread, another expert told Newsweek.

“My uneasiness about labeling it as an STD is that for most STDs, wearing a condom or avoiding penetration or direct oral-anal/oral-genital contact is a good way of preventing transmission,” said Paul Hunter, MD, a professor of health protection at the University of East Anglia, Norwich, England.

“But for monkeypox, even just naked cuddling is a big risk. So labeling it an STD could actually work against control if people felt they just had to wear a condom.”

Denise Dewald, MD, a pediatric specialist at University Hospitals Cleveland Medical Center, said monkeypox is not an STD – but it could become an entrenched virus.

“Monkeypox will become established in the pediatric and general population and will transmit through daycares and schools,” she tweeted. “It is not an STD. It is like MRSA. This isn’t rocket science.”

One thing is certain: More and more people are getting monkeypox. It’s been endemic in Western and Central Africa for years, and cases in Europe and North America were identified in May.

Globally, more than 14,000 cases have been identified, World Health Organization Director-General Tedros Adhanom Ghebreyesus said on July 20, according to the Center for Infectious Disease Research and Policy. Five people in Africa have died. In the United Kingdom, more than 2,100 cases have been identified.

In the United States, more than 2,500 confirmed monkeypox cases have been detected, with cases reported from every state except Alaska, Maine, Montana, Mississippi, Vermont, and Wyoming, the CDC said on July 21.

A version of this article first appeared on WebMD.com.

Few people like to pay taxes, and physicians are no exception.

For the Medscape Physicians and Taxes Report 2022, physicians shared information about their tax debt as well as how they feel about the U.S. tax code, audits, and the prospects for the future.

Even though it may not always seem that way to physicians, their family tax bills – around $75,406 on average – are in line with the other top 10% of U.S. taxpayers, according to an examination of IRS data by the Tax Foundation. However, when it comes to local taxes, the Tax Foundation found that physicians pay more than average. (Forty-three states collect tax on individual incomes.)

The average physician’s family pays a 35% marginal tax rate, compared with the top marginal tax rate in the United States of 37%. (The marginal tax rate is the highest amount of tax charged on each additional dollar after the IRS bracket rates are applied to your income.)

According to Alexis Gallati, founder of Cerebral Tax Advisors, a Knoxville, Tenn.–based firm that caters to medical professionals, doctors also should pay attention to their effective tax rate, or the percentage of income they pay in taxes. It takes into account differing tax rates on ordinary income, capital gains, and other income sources, she says. “It gives a better 30,000-foot view of your tax situation.”

Some high-income families are required to pay the Alternative Minimum Tax (AMT), though in 2019 that applied to only one-tenth of U.S. households. The AMT is designed to make sure that high earners with many options for exemptions and deductions still contribute a minimum amount of tax. Only 13% of physicians surveyed said they paid the AMT, though 29% were unsure.
 

Filing taxes as painful as paying them

According to a 2021 Gallup poll, 50% of Americans think they pay too much tax. (About 44% think their tax bill is about right, and a kindhearted 4% think they pay too little.) Doctors are outliers on this one, with 75% saying they pay too much in taxes.

When asked what they would do to fix the tax system, the physicians in the Medscape survey had a wide array of proposed solutions, from “drop the corporate tax rate to nearly nothing to stimulate the economy” to “everyone should pay equitably. There are too many loopholes for the very wealthy.”

Some of the complaints were less about tax rates than the process of filing. One respondent said: “I would love for this system to not be our personal responsibility. Why should it be my duty to pay someone every year to do my taxes?”

About 48% of physicians prepare their own taxes (about the same percentage as the rest of the population), with most of those filing electronically, primarily because it saves time and the software is easy to use. Intuit TurboTax was the most popular online software, with 22% of respondents saying they currently used this product.

Of those who did pay someone to prepare their taxes, the complexity of their taxes cost them; the average respondent paid about three times the average rate for the service. In the long run, the cost might have been recouped.

Navjeet Chahal, managing partner and CEO of Chahal and Associates, a San Francisco–area firm specializing in working with physicians, points out that tax advisors don’t just fill out the forms; they proactively advise physicians about how they can limit their taxes. And indeed, most respondents feel that they got their money’s worth, with 70% saying their tax preparers charged a fair fee.

Though the physicians surveyed tended to think they pay too much tax, and several mentioned particular gripes with the system, the complexity of the tax code didn’t seem to be a big issue. While 82% of Americans polled in 2021 by Pew Research said they were bothered “a lot” or “some” by the complexity of the tax system, 68% of physicians agreed or slightly agreed that the U.S. tax system “makes sense.”
 

Gimme a break

Physicians are the beneficiaries of several types of tax breaks. Contributing to a pretax 401(k) account was the most common exemption, with 60% of physicians surveyed using this plan. Other tax breaks cited by respondents were: contributing to charity (54%), home mortgage interest (46%), and writing off business expenses (39%).

About one in five physicians has experienced an audit, but that risk has declined significantly in recent years, thanks to tighter IRS budgets. Overall, only about 1 in 167 U.S. taxpayers were audited in 2020, according to the IRS. Even for taxpayers reporting $5 million or more in income, the audit rate is only about 0.25%, the Government Accountability Office says.

The odds of a physician being summoned to a meeting with an auditor probably won’t increase for a few years, Mr. Gallati said. But the good news for doctors is bad news for lower-income Americans. “The IRS is woefully understaffed and underfunded, with the result that the agency is going for lower-hanging fruit and auditing more people in lower income brackets,” she said in an interview.

While one respondent described his experience with the IRS as “the audit from hell,” others thought it not so bad, with 72% saying the auditors treated them fairly. One respondent described the audit as “boring, short, and successful for me. The IRS owed me money.”

When it comes to taxes, physician respondents, on the whole, did not seem to be optimistic about the future. About 61% expect an increase in their tax rate because of Biden administration policies. One respondent veered into hyperbole with the comment: “I believe taxes will increase for physicians until they have no more money!”

Mr. Chahal doesn’t see it that way. He pointed out that recent attempts to raise taxes completely failed. “I personally don’t see that happening unless there’s a significant shift in the House and the Senate.”

A version of this article first appeared on Medscape.com.

Few people like to pay taxes, and physicians are no exception.

For the Medscape Physicians and Taxes Report 2022, physicians shared information about their tax debt as well as how they feel about the U.S. tax code, audits, and the prospects for the future.

Even though it may not always seem that way to physicians, their family tax bills – around $75,406 on average – are in line with the other top 10% of U.S. taxpayers, according to an examination of IRS data by the Tax Foundation. However, when it comes to local taxes, the Tax Foundation found that physicians pay more than average. (Forty-three states collect tax on individual incomes.)

The average physician’s family pays a 35% marginal tax rate, compared with the top marginal tax rate in the United States of 37%. (The marginal tax rate is the highest amount of tax charged on each additional dollar after the IRS bracket rates are applied to your income.)

According to Alexis Gallati, founder of Cerebral Tax Advisors, a Knoxville, Tenn.–based firm that caters to medical professionals, doctors also should pay attention to their effective tax rate, or the percentage of income they pay in taxes. It takes into account differing tax rates on ordinary income, capital gains, and other income sources, she says. “It gives a better 30,000-foot view of your tax situation.”

Some high-income families are required to pay the Alternative Minimum Tax (AMT), though in 2019 that applied to only one-tenth of U.S. households. The AMT is designed to make sure that high earners with many options for exemptions and deductions still contribute a minimum amount of tax. Only 13% of physicians surveyed said they paid the AMT, though 29% were unsure.
 

Filing taxes as painful as paying them

According to a 2021 Gallup poll, 50% of Americans think they pay too much tax. (About 44% think their tax bill is about right, and a kindhearted 4% think they pay too little.) Doctors are outliers on this one, with 75% saying they pay too much in taxes.

When asked what they would do to fix the tax system, the physicians in the Medscape survey had a wide array of proposed solutions, from “drop the corporate tax rate to nearly nothing to stimulate the economy” to “everyone should pay equitably. There are too many loopholes for the very wealthy.”

Some of the complaints were less about tax rates than the process of filing. One respondent said: “I would love for this system to not be our personal responsibility. Why should it be my duty to pay someone every year to do my taxes?”

About 48% of physicians prepare their own taxes (about the same percentage as the rest of the population), with most of those filing electronically, primarily because it saves time and the software is easy to use. Intuit TurboTax was the most popular online software, with 22% of respondents saying they currently used this product.

Of those who did pay someone to prepare their taxes, the complexity of their taxes cost them; the average respondent paid about three times the average rate for the service. In the long run, the cost might have been recouped.

Navjeet Chahal, managing partner and CEO of Chahal and Associates, a San Francisco–area firm specializing in working with physicians, points out that tax advisors don’t just fill out the forms; they proactively advise physicians about how they can limit their taxes. And indeed, most respondents feel that they got their money’s worth, with 70% saying their tax preparers charged a fair fee.

Though the physicians surveyed tended to think they pay too much tax, and several mentioned particular gripes with the system, the complexity of the tax code didn’t seem to be a big issue. While 82% of Americans polled in 2021 by Pew Research said they were bothered “a lot” or “some” by the complexity of the tax system, 68% of physicians agreed or slightly agreed that the U.S. tax system “makes sense.”
 

Gimme a break

Physicians are the beneficiaries of several types of tax breaks. Contributing to a pretax 401(k) account was the most common exemption, with 60% of physicians surveyed using this plan. Other tax breaks cited by respondents were: contributing to charity (54%), home mortgage interest (46%), and writing off business expenses (39%).

About one in five physicians has experienced an audit, but that risk has declined significantly in recent years, thanks to tighter IRS budgets. Overall, only about 1 in 167 U.S. taxpayers were audited in 2020, according to the IRS. Even for taxpayers reporting $5 million or more in income, the audit rate is only about 0.25%, the Government Accountability Office says.

The odds of a physician being summoned to a meeting with an auditor probably won’t increase for a few years, Mr. Gallati said. But the good news for doctors is bad news for lower-income Americans. “The IRS is woefully understaffed and underfunded, with the result that the agency is going for lower-hanging fruit and auditing more people in lower income brackets,” she said in an interview.

While one respondent described his experience with the IRS as “the audit from hell,” others thought it not so bad, with 72% saying the auditors treated them fairly. One respondent described the audit as “boring, short, and successful for me. The IRS owed me money.”

When it comes to taxes, physician respondents, on the whole, did not seem to be optimistic about the future. About 61% expect an increase in their tax rate because of Biden administration policies. One respondent veered into hyperbole with the comment: “I believe taxes will increase for physicians until they have no more money!”

Mr. Chahal doesn’t see it that way. He pointed out that recent attempts to raise taxes completely failed. “I personally don’t see that happening unless there’s a significant shift in the House and the Senate.”

A version of this article first appeared on Medscape.com.

Few people like to pay taxes, and physicians are no exception.

For the Medscape Physicians and Taxes Report 2022, physicians shared information about their tax debt as well as how they feel about the U.S. tax code, audits, and the prospects for the future.

Even though it may not always seem that way to physicians, their family tax bills – around $75,406 on average – are in line with the other top 10% of U.S. taxpayers, according to an examination of IRS data by the Tax Foundation. However, when it comes to local taxes, the Tax Foundation found that physicians pay more than average. (Forty-three states collect tax on individual incomes.)

The average physician’s family pays a 35% marginal tax rate, compared with the top marginal tax rate in the United States of 37%. (The marginal tax rate is the highest amount of tax charged on each additional dollar after the IRS bracket rates are applied to your income.)

According to Alexis Gallati, founder of Cerebral Tax Advisors, a Knoxville, Tenn.–based firm that caters to medical professionals, doctors also should pay attention to their effective tax rate, or the percentage of income they pay in taxes. It takes into account differing tax rates on ordinary income, capital gains, and other income sources, she says. “It gives a better 30,000-foot view of your tax situation.”

Some high-income families are required to pay the Alternative Minimum Tax (AMT), though in 2019 that applied to only one-tenth of U.S. households. The AMT is designed to make sure that high earners with many options for exemptions and deductions still contribute a minimum amount of tax. Only 13% of physicians surveyed said they paid the AMT, though 29% were unsure.
 

Filing taxes as painful as paying them

According to a 2021 Gallup poll, 50% of Americans think they pay too much tax. (About 44% think their tax bill is about right, and a kindhearted 4% think they pay too little.) Doctors are outliers on this one, with 75% saying they pay too much in taxes.

When asked what they would do to fix the tax system, the physicians in the Medscape survey had a wide array of proposed solutions, from “drop the corporate tax rate to nearly nothing to stimulate the economy” to “everyone should pay equitably. There are too many loopholes for the very wealthy.”

Some of the complaints were less about tax rates than the process of filing. One respondent said: “I would love for this system to not be our personal responsibility. Why should it be my duty to pay someone every year to do my taxes?”

About 48% of physicians prepare their own taxes (about the same percentage as the rest of the population), with most of those filing electronically, primarily because it saves time and the software is easy to use. Intuit TurboTax was the most popular online software, with 22% of respondents saying they currently used this product.

Of those who did pay someone to prepare their taxes, the complexity of their taxes cost them; the average respondent paid about three times the average rate for the service. In the long run, the cost might have been recouped.

Navjeet Chahal, managing partner and CEO of Chahal and Associates, a San Francisco–area firm specializing in working with physicians, points out that tax advisors don’t just fill out the forms; they proactively advise physicians about how they can limit their taxes. And indeed, most respondents feel that they got their money’s worth, with 70% saying their tax preparers charged a fair fee.

Though the physicians surveyed tended to think they pay too much tax, and several mentioned particular gripes with the system, the complexity of the tax code didn’t seem to be a big issue. While 82% of Americans polled in 2021 by Pew Research said they were bothered “a lot” or “some” by the complexity of the tax system, 68% of physicians agreed or slightly agreed that the U.S. tax system “makes sense.”
 

Gimme a break

Physicians are the beneficiaries of several types of tax breaks. Contributing to a pretax 401(k) account was the most common exemption, with 60% of physicians surveyed using this plan. Other tax breaks cited by respondents were: contributing to charity (54%), home mortgage interest (46%), and writing off business expenses (39%).

About one in five physicians has experienced an audit, but that risk has declined significantly in recent years, thanks to tighter IRS budgets. Overall, only about 1 in 167 U.S. taxpayers were audited in 2020, according to the IRS. Even for taxpayers reporting $5 million or more in income, the audit rate is only about 0.25%, the Government Accountability Office says.

The odds of a physician being summoned to a meeting with an auditor probably won’t increase for a few years, Mr. Gallati said. But the good news for doctors is bad news for lower-income Americans. “The IRS is woefully understaffed and underfunded, with the result that the agency is going for lower-hanging fruit and auditing more people in lower income brackets,” she said in an interview.

While one respondent described his experience with the IRS as “the audit from hell,” others thought it not so bad, with 72% saying the auditors treated them fairly. One respondent described the audit as “boring, short, and successful for me. The IRS owed me money.”

When it comes to taxes, physician respondents, on the whole, did not seem to be optimistic about the future. About 61% expect an increase in their tax rate because of Biden administration policies. One respondent veered into hyperbole with the comment: “I believe taxes will increase for physicians until they have no more money!”

Mr. Chahal doesn’t see it that way. He pointed out that recent attempts to raise taxes completely failed. “I personally don’t see that happening unless there’s a significant shift in the House and the Senate.”

A version of this article first appeared on Medscape.com.

INDIANAPOLIS – Onset of recurrent reactive infectious mucocutaneous eruption (RIME) was most common among males between the ages of 11 and 12 years, which is younger than previously described, in a single-center retrospective study. In addition, 71% of patients with recurrent disease experienced 1-2 recurrences – episodes that were generally milder and occurred at variable intervals.

Those are among key findings from the study of 50 patients with RIME, presented by Catherina X. Pan at the annual meeting of the Society for Pediatric Dermatology.

Reactive infectious mucocutaneous eruption (RIME) is a novel term encompassing an array of rare, parainfectious mucositis diseases, noted Ms. Pan, a fourth-year medical student at Harvard Medical School, Boston. Previously known as Mycoplasma pneumoniae-induced rash and mucositis (MIRM), common clinical characteristics of RIME include less than 10% body surface area involvement of polymorphic skin lesions (vesiculobullous or targetoid macules/papules); erosive oral, genital, and/or ocular mucositis involving more than two sites, and evidence of prior infection including but not limited to upper respiratory infection, fever, and cough.

In addition to M. pneumoniae, other pathogens have been implicated, she said. “While the underlying etiology of the disease is not entirely clear, it’s become increasingly known that RIME tends to recur in a subset of patients.”

A cohort study of 13 patients with RIME found that Black race, male sex, and older age were predominant among the five patients who developed recurrent disease.

The estimated recurrence rate is between 8% and 38%, but the clinical characteristics of patients who develop recurrent RIME tend to be poorly understood, Ms. Pan said.

Along with her mentor, Sadaf Hussain, MD, of the department of dermatology at Boston Children’s Hospital, Ms. Pan conducted a retrospective chart review to characterize the clinical history and course of disease in patients diagnosed with recurrent RIME. They extracted data between January of 2000 and March of 2022 using ICD-10 codes used by board-certified dermatologists at Boston Children’s Hospital, as well as a text search for RIME or MIRM in the dermatology notes. Patients were included if they had a RIME/MIRM diagnosis by a board-certified dermatologist and/or infection on PCR/serology and mucositis involvement with limited skin involvement.

The study population included 50 patients: 24 with recurrent RIME and 26 with isolated RIME. The majority (66%) were male, and the mean age of RIME onset was between 11 and 12 years old, which is up to two years younger than previously reported in the case series of 13 patients. Most of the study participants (79%) were White, but there were no significant differences in patients who had recurrent RIME and those who had isolated RIME in terms of age, sex, or race.
 

Isolated vs. recurrent RIME

However, compared with patients who had isolated RIME, a greater proportion of those with recurrent RIME had a history of atopic disease (46% vs. 23%, respectively; P = .136), as well as a history of tonsillectomy and adenoidectomy (25% vs. 4%; P = .045). “This has not been previously observed, but it may generate a hypothesis that patients with a history of frequent infection as well as amplified immune responses may be associated with disease recurrence,” Ms. Pan said.

The average number of episodes among patients with recurrent RIME was 3.5 and the interval between episodes was variable, at a mean of 10.2 months. Ms. Pan reported that 71% of recurrent RIME patients experienced 1-2 episodes, although one patient experienced 9 episodes.

Clinically, episodes among all patients with RIME were characterized by infectious prodromal symptoms (69%), oral lesions (95%), ocular lesions (60%), genital lesions (41%) and cutaneous lesions (40%). However, RIME recurrences were less severe and more atypical, with 49% involving only one mucosal surface and 29% involving two mucosal surfaces. Also, except for oral lesions, rates of infectious prodromal symptoms and other lesions significantly decreased among recurrences compared with initial RIME.

“Notably, we found that M. pneumoniae was the most common known cause of RIME, particularly among the initial episodes,” Ms. Pan said. “However, 61% of recurrent RIME episodes did not have a known cause in terms of infectious etiology. And, concordant with prior studies, we also found decreased severity [of RIME recurrences] as indicated by decreased rates of emergency department presentation, hospitalization, and duration of hospitalization.”

In other findings, psychiatric complications such as anxiety and depression followed the onset of RIME in 33% of those with recurrent disease and 22% of those with isolated disease. In addition, the three most common treatments among all 50 patients were systemic steroids, topical steroids, and M. pneumoniae-specific antibiotics.

“While RIME is considered as typically milder than Stevens-Johnson syndrome and toxic epidermal necrolysis with low mortality rates, it can lead to severe complications including conjunctival shrinkage, corneal ulceration and scarring, blindness, and oral, ocular, urogenital synechiae,” Ms. Pan noted. “Increased use of corticosteroids and steroid-sparing agents such as IVIG have also been observed. Multidisciplinary care with ophthalmology, urology, and mental health services is critical.”

She acknowledged certain limitations of the study, including its retrospective, single-center design, and the possibility that milder cases may have been excluded due to a lack of accurate diagnosis or referral.

Carrie C. Coughlin, MD, who was asked to comment on the study results, pointed out that nearly half (24) of patients in the cohort experienced recurrent RIME. “This is a high proportion, suggesting counseling about the possibility of recurrence is more important than previously thought,” said Dr. Coughlin, director of the section of pediatric dermatology Washington University/St. Louis Children’s Hospital.

“Fortunately, recurrent cases tended to be less severe. However, many patients had more than one recurrence, making this challenging for affected patients.”

The researchers reported having no financial disclosures. Dr. Coughlin is on the board of the Pediatric Dermatology Research Alliance (PeDRA) and the International Immunosuppression and Transplant Skin Cancer Collaborative.

INDIANAPOLIS – Onset of recurrent reactive infectious mucocutaneous eruption (RIME) was most common among males between the ages of 11 and 12 years, which is younger than previously described, in a single-center retrospective study. In addition, 71% of patients with recurrent disease experienced 1-2 recurrences – episodes that were generally milder and occurred at variable intervals.

Those are among key findings from the study of 50 patients with RIME, presented by Catherina X. Pan at the annual meeting of the Society for Pediatric Dermatology.

Reactive infectious mucocutaneous eruption (RIME) is a novel term encompassing an array of rare, parainfectious mucositis diseases, noted Ms. Pan, a fourth-year medical student at Harvard Medical School, Boston. Previously known as Mycoplasma pneumoniae-induced rash and mucositis (MIRM), common clinical characteristics of RIME include less than 10% body surface area involvement of polymorphic skin lesions (vesiculobullous or targetoid macules/papules); erosive oral, genital, and/or ocular mucositis involving more than two sites, and evidence of prior infection including but not limited to upper respiratory infection, fever, and cough.

In addition to M. pneumoniae, other pathogens have been implicated, she said. “While the underlying etiology of the disease is not entirely clear, it’s become increasingly known that RIME tends to recur in a subset of patients.”

A cohort study of 13 patients with RIME found that Black race, male sex, and older age were predominant among the five patients who developed recurrent disease.

The estimated recurrence rate is between 8% and 38%, but the clinical characteristics of patients who develop recurrent RIME tend to be poorly understood, Ms. Pan said.

Along with her mentor, Sadaf Hussain, MD, of the department of dermatology at Boston Children’s Hospital, Ms. Pan conducted a retrospective chart review to characterize the clinical history and course of disease in patients diagnosed with recurrent RIME. They extracted data between January of 2000 and March of 2022 using ICD-10 codes used by board-certified dermatologists at Boston Children’s Hospital, as well as a text search for RIME or MIRM in the dermatology notes. Patients were included if they had a RIME/MIRM diagnosis by a board-certified dermatologist and/or infection on PCR/serology and mucositis involvement with limited skin involvement.

The study population included 50 patients: 24 with recurrent RIME and 26 with isolated RIME. The majority (66%) were male, and the mean age of RIME onset was between 11 and 12 years old, which is up to two years younger than previously reported in the case series of 13 patients. Most of the study participants (79%) were White, but there were no significant differences in patients who had recurrent RIME and those who had isolated RIME in terms of age, sex, or race.
 

Isolated vs. recurrent RIME

However, compared with patients who had isolated RIME, a greater proportion of those with recurrent RIME had a history of atopic disease (46% vs. 23%, respectively; P = .136), as well as a history of tonsillectomy and adenoidectomy (25% vs. 4%; P = .045). “This has not been previously observed, but it may generate a hypothesis that patients with a history of frequent infection as well as amplified immune responses may be associated with disease recurrence,” Ms. Pan said.

The average number of episodes among patients with recurrent RIME was 3.5 and the interval between episodes was variable, at a mean of 10.2 months. Ms. Pan reported that 71% of recurrent RIME patients experienced 1-2 episodes, although one patient experienced 9 episodes.

Clinically, episodes among all patients with RIME were characterized by infectious prodromal symptoms (69%), oral lesions (95%), ocular lesions (60%), genital lesions (41%) and cutaneous lesions (40%). However, RIME recurrences were less severe and more atypical, with 49% involving only one mucosal surface and 29% involving two mucosal surfaces. Also, except for oral lesions, rates of infectious prodromal symptoms and other lesions significantly decreased among recurrences compared with initial RIME.

“Notably, we found that M. pneumoniae was the most common known cause of RIME, particularly among the initial episodes,” Ms. Pan said. “However, 61% of recurrent RIME episodes did not have a known cause in terms of infectious etiology. And, concordant with prior studies, we also found decreased severity [of RIME recurrences] as indicated by decreased rates of emergency department presentation, hospitalization, and duration of hospitalization.”

In other findings, psychiatric complications such as anxiety and depression followed the onset of RIME in 33% of those with recurrent disease and 22% of those with isolated disease. In addition, the three most common treatments among all 50 patients were systemic steroids, topical steroids, and M. pneumoniae-specific antibiotics.

“While RIME is considered as typically milder than Stevens-Johnson syndrome and toxic epidermal necrolysis with low mortality rates, it can lead to severe complications including conjunctival shrinkage, corneal ulceration and scarring, blindness, and oral, ocular, urogenital synechiae,” Ms. Pan noted. “Increased use of corticosteroids and steroid-sparing agents such as IVIG have also been observed. Multidisciplinary care with ophthalmology, urology, and mental health services is critical.”

She acknowledged certain limitations of the study, including its retrospective, single-center design, and the possibility that milder cases may have been excluded due to a lack of accurate diagnosis or referral.

Carrie C. Coughlin, MD, who was asked to comment on the study results, pointed out that nearly half (24) of patients in the cohort experienced recurrent RIME. “This is a high proportion, suggesting counseling about the possibility of recurrence is more important than previously thought,” said Dr. Coughlin, director of the section of pediatric dermatology Washington University/St. Louis Children’s Hospital.

“Fortunately, recurrent cases tended to be less severe. However, many patients had more than one recurrence, making this challenging for affected patients.”

The researchers reported having no financial disclosures. Dr. Coughlin is on the board of the Pediatric Dermatology Research Alliance (PeDRA) and the International Immunosuppression and Transplant Skin Cancer Collaborative.

INDIANAPOLIS – Onset of recurrent reactive infectious mucocutaneous eruption (RIME) was most common among males between the ages of 11 and 12 years, which is younger than previously described, in a single-center retrospective study. In addition, 71% of patients with recurrent disease experienced 1-2 recurrences – episodes that were generally milder and occurred at variable intervals.

Those are among key findings from the study of 50 patients with RIME, presented by Catherina X. Pan at the annual meeting of the Society for Pediatric Dermatology.

Reactive infectious mucocutaneous eruption (RIME) is a novel term encompassing an array of rare, parainfectious mucositis diseases, noted Ms. Pan, a fourth-year medical student at Harvard Medical School, Boston. Previously known as Mycoplasma pneumoniae-induced rash and mucositis (MIRM), common clinical characteristics of RIME include less than 10% body surface area involvement of polymorphic skin lesions (vesiculobullous or targetoid macules/papules); erosive oral, genital, and/or ocular mucositis involving more than two sites, and evidence of prior infection including but not limited to upper respiratory infection, fever, and cough.

In addition to M. pneumoniae, other pathogens have been implicated, she said. “While the underlying etiology of the disease is not entirely clear, it’s become increasingly known that RIME tends to recur in a subset of patients.”

A cohort study of 13 patients with RIME found that Black race, male sex, and older age were predominant among the five patients who developed recurrent disease.

The estimated recurrence rate is between 8% and 38%, but the clinical characteristics of patients who develop recurrent RIME tend to be poorly understood, Ms. Pan said.

Along with her mentor, Sadaf Hussain, MD, of the department of dermatology at Boston Children’s Hospital, Ms. Pan conducted a retrospective chart review to characterize the clinical history and course of disease in patients diagnosed with recurrent RIME. They extracted data between January of 2000 and March of 2022 using ICD-10 codes used by board-certified dermatologists at Boston Children’s Hospital, as well as a text search for RIME or MIRM in the dermatology notes. Patients were included if they had a RIME/MIRM diagnosis by a board-certified dermatologist and/or infection on PCR/serology and mucositis involvement with limited skin involvement.

The study population included 50 patients: 24 with recurrent RIME and 26 with isolated RIME. The majority (66%) were male, and the mean age of RIME onset was between 11 and 12 years old, which is up to two years younger than previously reported in the case series of 13 patients. Most of the study participants (79%) were White, but there were no significant differences in patients who had recurrent RIME and those who had isolated RIME in terms of age, sex, or race.
 

Isolated vs. recurrent RIME

However, compared with patients who had isolated RIME, a greater proportion of those with recurrent RIME had a history of atopic disease (46% vs. 23%, respectively; P = .136), as well as a history of tonsillectomy and adenoidectomy (25% vs. 4%; P = .045). “This has not been previously observed, but it may generate a hypothesis that patients with a history of frequent infection as well as amplified immune responses may be associated with disease recurrence,” Ms. Pan said.

The average number of episodes among patients with recurrent RIME was 3.5 and the interval between episodes was variable, at a mean of 10.2 months. Ms. Pan reported that 71% of recurrent RIME patients experienced 1-2 episodes, although one patient experienced 9 episodes.

Clinically, episodes among all patients with RIME were characterized by infectious prodromal symptoms (69%), oral lesions (95%), ocular lesions (60%), genital lesions (41%) and cutaneous lesions (40%). However, RIME recurrences were less severe and more atypical, with 49% involving only one mucosal surface and 29% involving two mucosal surfaces. Also, except for oral lesions, rates of infectious prodromal symptoms and other lesions significantly decreased among recurrences compared with initial RIME.

“Notably, we found that M. pneumoniae was the most common known cause of RIME, particularly among the initial episodes,” Ms. Pan said. “However, 61% of recurrent RIME episodes did not have a known cause in terms of infectious etiology. And, concordant with prior studies, we also found decreased severity [of RIME recurrences] as indicated by decreased rates of emergency department presentation, hospitalization, and duration of hospitalization.”

In other findings, psychiatric complications such as anxiety and depression followed the onset of RIME in 33% of those with recurrent disease and 22% of those with isolated disease. In addition, the three most common treatments among all 50 patients were systemic steroids, topical steroids, and M. pneumoniae-specific antibiotics.

“While RIME is considered as typically milder than Stevens-Johnson syndrome and toxic epidermal necrolysis with low mortality rates, it can lead to severe complications including conjunctival shrinkage, corneal ulceration and scarring, blindness, and oral, ocular, urogenital synechiae,” Ms. Pan noted. “Increased use of corticosteroids and steroid-sparing agents such as IVIG have also been observed. Multidisciplinary care with ophthalmology, urology, and mental health services is critical.”

She acknowledged certain limitations of the study, including its retrospective, single-center design, and the possibility that milder cases may have been excluded due to a lack of accurate diagnosis or referral.

Carrie C. Coughlin, MD, who was asked to comment on the study results, pointed out that nearly half (24) of patients in the cohort experienced recurrent RIME. “This is a high proportion, suggesting counseling about the possibility of recurrence is more important than previously thought,” said Dr. Coughlin, director of the section of pediatric dermatology Washington University/St. Louis Children’s Hospital.

“Fortunately, recurrent cases tended to be less severe. However, many patients had more than one recurrence, making this challenging for affected patients.”

The researchers reported having no financial disclosures. Dr. Coughlin is on the board of the Pediatric Dermatology Research Alliance (PeDRA) and the International Immunosuppression and Transplant Skin Cancer Collaborative.