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

Dozens of University of Michigan, Ann Arbor, medical students walked out of their white coat ceremony July 24 as a keynote speaker began to talk.

A Twitter video of the walkout has gone viral. By press time, the video had garnered more than 9.5 million views.

The walkout comes days after more than 340 medical students at the school signed a petition opposing the selection of Michigan assistant professor Kristin Collier, MD, for the ceremony because of her anti-abortion views, according to The Michigan Daily.

In response to the incident, a medical school spokeswoman told this news organization that Dr. Collier was chosen to be speaker “based on nominations and voting by members of the UM Medical School Gold Humanism Honor Society, which is comprised of medical students, house officers, and faculty.”

The press statement continued, “The White Coat Ceremony is not a platform for discussion of controversial issues. Its focus will always be on welcoming students into the profession of medicine. Dr. Collier never planned to address a divisive topic as part of her remarks. However, the University of Michigan does not revoke an invitation to a speaker based on their personal beliefs.”

The university further stated that it remains committed to providing reproductive care for patients, including abortion care, which remains legal in Michigan following the recent U.S. Supreme Court ruling overturning abortion rights, according to the statement by Mary Masson, director of Michigan Medicine public relations.

The state has an abortion ban, but a recent court order temporarily blocked enforcement of it, according to the statement.

In her speech, Dr. Collier recognized the divisiveness of the issue. “I want to acknowledge the deep wounds our community has suffered over the past several weeks. We have a great deal of work to do for healing to occur. And I hope for today, for this time, we can focus on what matters the most, coming together with a goal to support our newly accepted students and their families.”

Following applause from the remaining audience, she continued to offer advice for the incoming students about how to thrive in their chosen profession.

Dr. Collier, a graduate of the med school and director of its Health, Spirituality, and Religion program, has 15.2K Twitter followers. She has been known to post anti-abortion sentiments, including those cited in the students’ petition.

“While we support the rights of freedom of speech and religion, an anti-choice speaker as a representative of the University of Michigan undermines the University’s position on abortion and supports the non-universal, theology-rooted platform to restrict abortion access, an essential part of medical care,” the petition reads, in part.

The petition states that the disagreement is not over personal opinions. “We demand that UM stands in solidarity with us and selects a speaker whose values align with institutional policies, students, and the broader medical community. This speaker should inspire the next generation of health care providers to be courageous advocates for patient autonomy and our communities.”

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

Dozens of University of Michigan, Ann Arbor, medical students walked out of their white coat ceremony July 24 as a keynote speaker began to talk.

A Twitter video of the walkout has gone viral. By press time, the video had garnered more than 9.5 million views.

The walkout comes days after more than 340 medical students at the school signed a petition opposing the selection of Michigan assistant professor Kristin Collier, MD, for the ceremony because of her anti-abortion views, according to The Michigan Daily.

In response to the incident, a medical school spokeswoman told this news organization that Dr. Collier was chosen to be speaker “based on nominations and voting by members of the UM Medical School Gold Humanism Honor Society, which is comprised of medical students, house officers, and faculty.”

The press statement continued, “The White Coat Ceremony is not a platform for discussion of controversial issues. Its focus will always be on welcoming students into the profession of medicine. Dr. Collier never planned to address a divisive topic as part of her remarks. However, the University of Michigan does not revoke an invitation to a speaker based on their personal beliefs.”

The university further stated that it remains committed to providing reproductive care for patients, including abortion care, which remains legal in Michigan following the recent U.S. Supreme Court ruling overturning abortion rights, according to the statement by Mary Masson, director of Michigan Medicine public relations.

The state has an abortion ban, but a recent court order temporarily blocked enforcement of it, according to the statement.

In her speech, Dr. Collier recognized the divisiveness of the issue. “I want to acknowledge the deep wounds our community has suffered over the past several weeks. We have a great deal of work to do for healing to occur. And I hope for today, for this time, we can focus on what matters the most, coming together with a goal to support our newly accepted students and their families.”

Following applause from the remaining audience, she continued to offer advice for the incoming students about how to thrive in their chosen profession.

Dr. Collier, a graduate of the med school and director of its Health, Spirituality, and Religion program, has 15.2K Twitter followers. She has been known to post anti-abortion sentiments, including those cited in the students’ petition.

“While we support the rights of freedom of speech and religion, an anti-choice speaker as a representative of the University of Michigan undermines the University’s position on abortion and supports the non-universal, theology-rooted platform to restrict abortion access, an essential part of medical care,” the petition reads, in part.

The petition states that the disagreement is not over personal opinions. “We demand that UM stands in solidarity with us and selects a speaker whose values align with institutional policies, students, and the broader medical community. This speaker should inspire the next generation of health care providers to be courageous advocates for patient autonomy and our communities.”

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

Dozens of University of Michigan, Ann Arbor, medical students walked out of their white coat ceremony July 24 as a keynote speaker began to talk.

A Twitter video of the walkout has gone viral. By press time, the video had garnered more than 9.5 million views.

The walkout comes days after more than 340 medical students at the school signed a petition opposing the selection of Michigan assistant professor Kristin Collier, MD, for the ceremony because of her anti-abortion views, according to The Michigan Daily.

In response to the incident, a medical school spokeswoman told this news organization that Dr. Collier was chosen to be speaker “based on nominations and voting by members of the UM Medical School Gold Humanism Honor Society, which is comprised of medical students, house officers, and faculty.”

The press statement continued, “The White Coat Ceremony is not a platform for discussion of controversial issues. Its focus will always be on welcoming students into the profession of medicine. Dr. Collier never planned to address a divisive topic as part of her remarks. However, the University of Michigan does not revoke an invitation to a speaker based on their personal beliefs.”

The university further stated that it remains committed to providing reproductive care for patients, including abortion care, which remains legal in Michigan following the recent U.S. Supreme Court ruling overturning abortion rights, according to the statement by Mary Masson, director of Michigan Medicine public relations.

The state has an abortion ban, but a recent court order temporarily blocked enforcement of it, according to the statement.

In her speech, Dr. Collier recognized the divisiveness of the issue. “I want to acknowledge the deep wounds our community has suffered over the past several weeks. We have a great deal of work to do for healing to occur. And I hope for today, for this time, we can focus on what matters the most, coming together with a goal to support our newly accepted students and their families.”

Following applause from the remaining audience, she continued to offer advice for the incoming students about how to thrive in their chosen profession.

Dr. Collier, a graduate of the med school and director of its Health, Spirituality, and Religion program, has 15.2K Twitter followers. She has been known to post anti-abortion sentiments, including those cited in the students’ petition.

“While we support the rights of freedom of speech and religion, an anti-choice speaker as a representative of the University of Michigan undermines the University’s position on abortion and supports the non-universal, theology-rooted platform to restrict abortion access, an essential part of medical care,” the petition reads, in part.

The petition states that the disagreement is not over personal opinions. “We demand that UM stands in solidarity with us and selects a speaker whose values align with institutional policies, students, and the broader medical community. This speaker should inspire the next generation of health care providers to be courageous advocates for patient autonomy and our communities.”

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.

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.

As scientists work on wearable technology that promises to revolutionize health care, researchers from the University of Texas at Austin and Texas A&M University, College Station, are reporting a big win in the pursuit of one highly popular target: a noninvasive solution for continuous blood pressure monitoring at home.

Not only that, but this development comes in the surprising form of a temporary tattoo. That’s right: Just like the kind that children like to wear.

The thin, sticker-like wearable electronic tattoos can provide continuous, accurate blood pressure monitoring, the researchers report in their new study.

“With this new technology, we are going to have an opportunity to understand how our blood pressure fluctuates during the day. We will be able to quantify how stress is impacting us,” says Roozbeh Jafari, PhD, a professor of biomedical engineering, electrical engineering, and computer science at Texas A&M, College Station, and a coauthor of the study.
 

Revealing the whole picture, not just dots

At-home blood pressure monitors have been around for many years now. They work just like the blood pressure machines doctors use at their office: You place your arm inside a cuff, press a button, feel a squeeze on your arm, and get a reading.

While results from this method are accurate, they are also just a moment in time. Our blood pressure can vary greatly throughout the day – especially among people who have labile hypertension, where blood pressure changes from one extreme to the other. So, looking at point-in-time readings is a bit like focusing on a few dots inside of a pointillism painting – one might miss the bigger picture.

Doctors may also find continuous monitoring useful for getting rid of false readings from “white coat syndrome.” Basically, this means a person’s blood pressure rises due to the anxiety of being in a doctor’s office but is not true hypertension.

Bottom line: The ability to monitor a person’s blood pressure continuously for hours or even days can provide clearer, and more accurate, insights into a person’s health.
 

How do health monitoring tattoos work?

Electronic tattoos for health monitoring are not completely new. John A. Rogers, PhD, of Northwestern University, Chicago, first put forth the idea of monitoring through temporary tattoos 12 years ago. Some concepts, such as UV monitoring tattoos, had already been adopted by scientists and put on the market. But the existing models weren’t suitable for monitoring blood pressure, according to Deji Akinwande, PhD, a professor of electrical and computer engineering at the University of Texas at Austin and another coauthor of the study.

“[UV monitoring tattoos] are very thick,” he says. “They create too much movement when used to measure blood pressure because they slide around.”

So, the Texas-based research team worked to develop an option that was slimmer and more stable.

“The key ingredient within e-tattoos is graphene,” says Dr. Akinwande.

Graphene is carbon that’s similar to what’s inside your graphite pencil. The material is conductive, meaning it can conduct small electrical currents through the skin. For blood pressure monitoring, graphene promotes bioelectrical impedance analysis (BIA), which is like the technology used in smart scales that measure body fat.

With e-tattoos, the thin layers of graphene stick to the skin and do not slide around, getting rid of “artifacts,” or bad data. The graphene e-tattoos can be worn on the skin for about a week – or roughly as long as the temporary tattoos kids love.

Once the graphene captures the raw data, a machine learning algorithm interprets the information and provides results in units used for measuring blood pressure: millimeters of mercury (mmHg), commonly referred to as blood pressure “points.”

How accurate are the results? The tests measured blood pressure within 0.2 ± 5.8 mmHg (systolic), 0.2 ± 4.5 mmHg (diastolic), and 0.1 ± 5.3 mmHg (mean arterial pressure). In other words: If this were a basketball player shooting baskets, the great majority of shots taken would be swishes and occasionally a few would hit the rim. That means good accuracy.
 

When will e-tattoos be available?

The teams of Dr. Jafari and Dr. Akinwande are working on a second generation of their e-tattoo that they expect to be available in the next 5 years.

The upgrade they envision will be smaller and compatible with smartwatches and phones that use Bluetooth technology and near-field communication (NFC) to transfer data and give it power. With these updates, e-tattoos for continuous blood pressure monitoring will be ready for clinical trials and mainstream use soon after.

“Everyone can benefit from knowing their blood pressure recordings,” Dr. Akinwande says. “It is not just for people at risk for hypertension but for others to proactively monitor their health, for stress and other factors.”

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

As scientists work on wearable technology that promises to revolutionize health care, researchers from the University of Texas at Austin and Texas A&M University, College Station, are reporting a big win in the pursuit of one highly popular target: a noninvasive solution for continuous blood pressure monitoring at home.

Not only that, but this development comes in the surprising form of a temporary tattoo. That’s right: Just like the kind that children like to wear.

The thin, sticker-like wearable electronic tattoos can provide continuous, accurate blood pressure monitoring, the researchers report in their new study.

“With this new technology, we are going to have an opportunity to understand how our blood pressure fluctuates during the day. We will be able to quantify how stress is impacting us,” says Roozbeh Jafari, PhD, a professor of biomedical engineering, electrical engineering, and computer science at Texas A&M, College Station, and a coauthor of the study.
 

Revealing the whole picture, not just dots

At-home blood pressure monitors have been around for many years now. They work just like the blood pressure machines doctors use at their office: You place your arm inside a cuff, press a button, feel a squeeze on your arm, and get a reading.

While results from this method are accurate, they are also just a moment in time. Our blood pressure can vary greatly throughout the day – especially among people who have labile hypertension, where blood pressure changes from one extreme to the other. So, looking at point-in-time readings is a bit like focusing on a few dots inside of a pointillism painting – one might miss the bigger picture.

Doctors may also find continuous monitoring useful for getting rid of false readings from “white coat syndrome.” Basically, this means a person’s blood pressure rises due to the anxiety of being in a doctor’s office but is not true hypertension.

Bottom line: The ability to monitor a person’s blood pressure continuously for hours or even days can provide clearer, and more accurate, insights into a person’s health.
 

How do health monitoring tattoos work?

Electronic tattoos for health monitoring are not completely new. John A. Rogers, PhD, of Northwestern University, Chicago, first put forth the idea of monitoring through temporary tattoos 12 years ago. Some concepts, such as UV monitoring tattoos, had already been adopted by scientists and put on the market. But the existing models weren’t suitable for monitoring blood pressure, according to Deji Akinwande, PhD, a professor of electrical and computer engineering at the University of Texas at Austin and another coauthor of the study.

“[UV monitoring tattoos] are very thick,” he says. “They create too much movement when used to measure blood pressure because they slide around.”

So, the Texas-based research team worked to develop an option that was slimmer and more stable.

“The key ingredient within e-tattoos is graphene,” says Dr. Akinwande.

Graphene is carbon that’s similar to what’s inside your graphite pencil. The material is conductive, meaning it can conduct small electrical currents through the skin. For blood pressure monitoring, graphene promotes bioelectrical impedance analysis (BIA), which is like the technology used in smart scales that measure body fat.

With e-tattoos, the thin layers of graphene stick to the skin and do not slide around, getting rid of “artifacts,” or bad data. The graphene e-tattoos can be worn on the skin for about a week – or roughly as long as the temporary tattoos kids love.

Once the graphene captures the raw data, a machine learning algorithm interprets the information and provides results in units used for measuring blood pressure: millimeters of mercury (mmHg), commonly referred to as blood pressure “points.”

How accurate are the results? The tests measured blood pressure within 0.2 ± 5.8 mmHg (systolic), 0.2 ± 4.5 mmHg (diastolic), and 0.1 ± 5.3 mmHg (mean arterial pressure). In other words: If this were a basketball player shooting baskets, the great majority of shots taken would be swishes and occasionally a few would hit the rim. That means good accuracy.
 

When will e-tattoos be available?

The teams of Dr. Jafari and Dr. Akinwande are working on a second generation of their e-tattoo that they expect to be available in the next 5 years.

The upgrade they envision will be smaller and compatible with smartwatches and phones that use Bluetooth technology and near-field communication (NFC) to transfer data and give it power. With these updates, e-tattoos for continuous blood pressure monitoring will be ready for clinical trials and mainstream use soon after.

“Everyone can benefit from knowing their blood pressure recordings,” Dr. Akinwande says. “It is not just for people at risk for hypertension but for others to proactively monitor their health, for stress and other factors.”

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

As scientists work on wearable technology that promises to revolutionize health care, researchers from the University of Texas at Austin and Texas A&M University, College Station, are reporting a big win in the pursuit of one highly popular target: a noninvasive solution for continuous blood pressure monitoring at home.

Not only that, but this development comes in the surprising form of a temporary tattoo. That’s right: Just like the kind that children like to wear.

The thin, sticker-like wearable electronic tattoos can provide continuous, accurate blood pressure monitoring, the researchers report in their new study.

“With this new technology, we are going to have an opportunity to understand how our blood pressure fluctuates during the day. We will be able to quantify how stress is impacting us,” says Roozbeh Jafari, PhD, a professor of biomedical engineering, electrical engineering, and computer science at Texas A&M, College Station, and a coauthor of the study.
 

Revealing the whole picture, not just dots

At-home blood pressure monitors have been around for many years now. They work just like the blood pressure machines doctors use at their office: You place your arm inside a cuff, press a button, feel a squeeze on your arm, and get a reading.

While results from this method are accurate, they are also just a moment in time. Our blood pressure can vary greatly throughout the day – especially among people who have labile hypertension, where blood pressure changes from one extreme to the other. So, looking at point-in-time readings is a bit like focusing on a few dots inside of a pointillism painting – one might miss the bigger picture.

Doctors may also find continuous monitoring useful for getting rid of false readings from “white coat syndrome.” Basically, this means a person’s blood pressure rises due to the anxiety of being in a doctor’s office but is not true hypertension.

Bottom line: The ability to monitor a person’s blood pressure continuously for hours or even days can provide clearer, and more accurate, insights into a person’s health.
 

How do health monitoring tattoos work?

Electronic tattoos for health monitoring are not completely new. John A. Rogers, PhD, of Northwestern University, Chicago, first put forth the idea of monitoring through temporary tattoos 12 years ago. Some concepts, such as UV monitoring tattoos, had already been adopted by scientists and put on the market. But the existing models weren’t suitable for monitoring blood pressure, according to Deji Akinwande, PhD, a professor of electrical and computer engineering at the University of Texas at Austin and another coauthor of the study.

“[UV monitoring tattoos] are very thick,” he says. “They create too much movement when used to measure blood pressure because they slide around.”

So, the Texas-based research team worked to develop an option that was slimmer and more stable.

“The key ingredient within e-tattoos is graphene,” says Dr. Akinwande.

Graphene is carbon that’s similar to what’s inside your graphite pencil. The material is conductive, meaning it can conduct small electrical currents through the skin. For blood pressure monitoring, graphene promotes bioelectrical impedance analysis (BIA), which is like the technology used in smart scales that measure body fat.

With e-tattoos, the thin layers of graphene stick to the skin and do not slide around, getting rid of “artifacts,” or bad data. The graphene e-tattoos can be worn on the skin for about a week – or roughly as long as the temporary tattoos kids love.

Once the graphene captures the raw data, a machine learning algorithm interprets the information and provides results in units used for measuring blood pressure: millimeters of mercury (mmHg), commonly referred to as blood pressure “points.”

How accurate are the results? The tests measured blood pressure within 0.2 ± 5.8 mmHg (systolic), 0.2 ± 4.5 mmHg (diastolic), and 0.1 ± 5.3 mmHg (mean arterial pressure). In other words: If this were a basketball player shooting baskets, the great majority of shots taken would be swishes and occasionally a few would hit the rim. That means good accuracy.
 

When will e-tattoos be available?

The teams of Dr. Jafari and Dr. Akinwande are working on a second generation of their e-tattoo that they expect to be available in the next 5 years.

The upgrade they envision will be smaller and compatible with smartwatches and phones that use Bluetooth technology and near-field communication (NFC) to transfer data and give it power. With these updates, e-tattoos for continuous blood pressure monitoring will be ready for clinical trials and mainstream use soon after.

“Everyone can benefit from knowing their blood pressure recordings,” Dr. Akinwande says. “It is not just for people at risk for hypertension but for others to proactively monitor their health, for stress and other factors.”

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

A novel liquid biopsy test, which uses two circulating proteins, appears to be effective for diagnosing two major liver conditions, according to a new study published in Gut.

The test could allow clinicians to determine the staging of both liver fibrosis and nonalcoholic steatohepatitis, wrote the researchers led by Giulia Angelini, PhD, a postdoctoral fellow focused on nonalcoholic fatty liver disease pathophysiology at the Catholic University of the Sacred Heart in Rome.

ftwitty/E+

“The diagnosis of nonalcoholic steatohepatitis (NASH) currently relies on invasive liver biopsy,” they wrote. “There is, therefore, an urgent need to find noninvasive biomarkers for NASH diagnosis, disease progression, and intervention response monitoring.”

The research team sought to identify a biomarker and algorithm able to predict the presence and severity of nonalcoholic steatohepatitis (NASH) or liver fibrosis. The study evaluated two proteins found in circulating monocytes, which are a type of white blood cell: PLIN2 as a predictor of histological NASH and RAB14 levels as a predictor of liver fibrosis.

The multicenter study included 250 patients, with 100 subjects in the discovery cohort from the Bariatric Surgery Versus Nonalcoholic Steatohepatitis trial, or BRAVES, and 150 subjects in the validation cohort from the Liquid Biopsy for NASH and Liver Fibrosis trial, or LIBRA. The patients had histologically proven nonalcoholic fatty liver disease or NASH with or without fibrosis.

After careful molecular analysis, the research team used neural network classifiers to predict the presence of NASH and NASH stages. The analysis for the prediction of the presence of NASH produced an accuracy of 93% in the discovery cohort and 92% in the validation cohort. Sensitivity and specificity were 95% and 90% in the discovery group and 88% and 100% in the validation group, respectively. The research team also used a neural network analysis to predict the stages of NASH, which showed an accuracy of 85% in the discovery group and 85.2% in the validation cohort.

RAB14 was used to predict liver fibrosis with a logistic model that included waist circumference, age, plasma glucose, high-density lipoprotein, and alanine aminotransferase. In the discovery group, accuracy was 99.2%, sensitivity was 100%, and specificity was 95.8%. In the validation group, accuracy was 97.6%, sensitivity was 99%, and specificity was 89.6%.

When RAB14 was used as the only variable in the model, the accuracy, sensitivity, and specificity in the discovery cohort were 86.4%, 96%, and 45.8%, respectively. In the validation cohort, they were 92.4%, 96.9%, and 34.5%, respectively. In both cohorts, half of the subjects without fibrosis were erroneously predicted as having fibrosis, but the diagnosis of fibrosis was correctly predicted in nearly all subjects.

A limitation of the study is that only White subjects were enrolled, which limits the generalizability to other racial/ethnic groups, the investigators wrote, although they don’t expect differences would be seen in other groups.

“PLIN2 and RAB14 may permit diagnosis of NASH and/or liver fibrosis with a simple blood test,” they wrote. “Our biomarkers can be used in community and population studies permitting to investigate the real prevalence of NASH and liver fibrosis. Moreover, since it requires only blood sampling, they are potentially valuable tools for population-based and prevention studies in children.”
 

A step forward

“Obesity is a silent pandemic with an expected prevalence rate that will exceed 50% globally by 2030, of which 25% of the adults have fatty liver and approximately 6.5% with NASH, a progressive form of fatty liver,” said Kalyan Ram Bhamidimarri, MD, chief of hepatology and associate professor of clinical medicine at the University of Miami, who was not involved in the research. “Liver biopsy is the current clinical standard to diagnose NASH, but relying on an invasive procedure like liver biopsy that is fraught with several risks in a consistently growing volume of individuals with obesity is unsustainable.

Courtesy University of Miami

“So, there is an unmet need to diagnose NASH without invasive procedures such as liver biopsy,” he said. He pointed out that many of the alternatives to liver biopsy, such as liver stiffness measurements and scoring systems, pose their own difficulties.

On the other hand, he noted that “blood-based tests that correlate well with liver biopsy, the so-called wet biomarkers or liquid liver biopsy, are easier to perform, accessed widely, and could be tested frequently to assess efficacy of therapies.”

The study was funded by Elucidating Pathways of Steatohepatitis (EPOS Horizon 2020), Stratification of Obese Phenotypes to Optimize Future Obesity Therapy (SOPHIA IMI), Metadeq Inc., and support from the Transcampus Initiative. The study authors declared various competing interests, including some who serve as an advisor or stock option holder for Metadeq Limited. Dr. Bhamidimarri reported no relevant conflicts of interest.

A novel liquid biopsy test, which uses two circulating proteins, appears to be effective for diagnosing two major liver conditions, according to a new study published in Gut.

The test could allow clinicians to determine the staging of both liver fibrosis and nonalcoholic steatohepatitis, wrote the researchers led by Giulia Angelini, PhD, a postdoctoral fellow focused on nonalcoholic fatty liver disease pathophysiology at the Catholic University of the Sacred Heart in Rome.

ftwitty/E+

“The diagnosis of nonalcoholic steatohepatitis (NASH) currently relies on invasive liver biopsy,” they wrote. “There is, therefore, an urgent need to find noninvasive biomarkers for NASH diagnosis, disease progression, and intervention response monitoring.”

The research team sought to identify a biomarker and algorithm able to predict the presence and severity of nonalcoholic steatohepatitis (NASH) or liver fibrosis. The study evaluated two proteins found in circulating monocytes, which are a type of white blood cell: PLIN2 as a predictor of histological NASH and RAB14 levels as a predictor of liver fibrosis.

The multicenter study included 250 patients, with 100 subjects in the discovery cohort from the Bariatric Surgery Versus Nonalcoholic Steatohepatitis trial, or BRAVES, and 150 subjects in the validation cohort from the Liquid Biopsy for NASH and Liver Fibrosis trial, or LIBRA. The patients had histologically proven nonalcoholic fatty liver disease or NASH with or without fibrosis.

After careful molecular analysis, the research team used neural network classifiers to predict the presence of NASH and NASH stages. The analysis for the prediction of the presence of NASH produced an accuracy of 93% in the discovery cohort and 92% in the validation cohort. Sensitivity and specificity were 95% and 90% in the discovery group and 88% and 100% in the validation group, respectively. The research team also used a neural network analysis to predict the stages of NASH, which showed an accuracy of 85% in the discovery group and 85.2% in the validation cohort.

RAB14 was used to predict liver fibrosis with a logistic model that included waist circumference, age, plasma glucose, high-density lipoprotein, and alanine aminotransferase. In the discovery group, accuracy was 99.2%, sensitivity was 100%, and specificity was 95.8%. In the validation group, accuracy was 97.6%, sensitivity was 99%, and specificity was 89.6%.

When RAB14 was used as the only variable in the model, the accuracy, sensitivity, and specificity in the discovery cohort were 86.4%, 96%, and 45.8%, respectively. In the validation cohort, they were 92.4%, 96.9%, and 34.5%, respectively. In both cohorts, half of the subjects without fibrosis were erroneously predicted as having fibrosis, but the diagnosis of fibrosis was correctly predicted in nearly all subjects.

A limitation of the study is that only White subjects were enrolled, which limits the generalizability to other racial/ethnic groups, the investigators wrote, although they don’t expect differences would be seen in other groups.

“PLIN2 and RAB14 may permit diagnosis of NASH and/or liver fibrosis with a simple blood test,” they wrote. “Our biomarkers can be used in community and population studies permitting to investigate the real prevalence of NASH and liver fibrosis. Moreover, since it requires only blood sampling, they are potentially valuable tools for population-based and prevention studies in children.”
 

A step forward

“Obesity is a silent pandemic with an expected prevalence rate that will exceed 50% globally by 2030, of which 25% of the adults have fatty liver and approximately 6.5% with NASH, a progressive form of fatty liver,” said Kalyan Ram Bhamidimarri, MD, chief of hepatology and associate professor of clinical medicine at the University of Miami, who was not involved in the research. “Liver biopsy is the current clinical standard to diagnose NASH, but relying on an invasive procedure like liver biopsy that is fraught with several risks in a consistently growing volume of individuals with obesity is unsustainable.

Courtesy University of Miami

“So, there is an unmet need to diagnose NASH without invasive procedures such as liver biopsy,” he said. He pointed out that many of the alternatives to liver biopsy, such as liver stiffness measurements and scoring systems, pose their own difficulties.

On the other hand, he noted that “blood-based tests that correlate well with liver biopsy, the so-called wet biomarkers or liquid liver biopsy, are easier to perform, accessed widely, and could be tested frequently to assess efficacy of therapies.”

The study was funded by Elucidating Pathways of Steatohepatitis (EPOS Horizon 2020), Stratification of Obese Phenotypes to Optimize Future Obesity Therapy (SOPHIA IMI), Metadeq Inc., and support from the Transcampus Initiative. The study authors declared various competing interests, including some who serve as an advisor or stock option holder for Metadeq Limited. Dr. Bhamidimarri reported no relevant conflicts of interest.

A novel liquid biopsy test, which uses two circulating proteins, appears to be effective for diagnosing two major liver conditions, according to a new study published in Gut.

The test could allow clinicians to determine the staging of both liver fibrosis and nonalcoholic steatohepatitis, wrote the researchers led by Giulia Angelini, PhD, a postdoctoral fellow focused on nonalcoholic fatty liver disease pathophysiology at the Catholic University of the Sacred Heart in Rome.

ftwitty/E+

“The diagnosis of nonalcoholic steatohepatitis (NASH) currently relies on invasive liver biopsy,” they wrote. “There is, therefore, an urgent need to find noninvasive biomarkers for NASH diagnosis, disease progression, and intervention response monitoring.”

The research team sought to identify a biomarker and algorithm able to predict the presence and severity of nonalcoholic steatohepatitis (NASH) or liver fibrosis. The study evaluated two proteins found in circulating monocytes, which are a type of white blood cell: PLIN2 as a predictor of histological NASH and RAB14 levels as a predictor of liver fibrosis.

The multicenter study included 250 patients, with 100 subjects in the discovery cohort from the Bariatric Surgery Versus Nonalcoholic Steatohepatitis trial, or BRAVES, and 150 subjects in the validation cohort from the Liquid Biopsy for NASH and Liver Fibrosis trial, or LIBRA. The patients had histologically proven nonalcoholic fatty liver disease or NASH with or without fibrosis.

After careful molecular analysis, the research team used neural network classifiers to predict the presence of NASH and NASH stages. The analysis for the prediction of the presence of NASH produced an accuracy of 93% in the discovery cohort and 92% in the validation cohort. Sensitivity and specificity were 95% and 90% in the discovery group and 88% and 100% in the validation group, respectively. The research team also used a neural network analysis to predict the stages of NASH, which showed an accuracy of 85% in the discovery group and 85.2% in the validation cohort.

RAB14 was used to predict liver fibrosis with a logistic model that included waist circumference, age, plasma glucose, high-density lipoprotein, and alanine aminotransferase. In the discovery group, accuracy was 99.2%, sensitivity was 100%, and specificity was 95.8%. In the validation group, accuracy was 97.6%, sensitivity was 99%, and specificity was 89.6%.

When RAB14 was used as the only variable in the model, the accuracy, sensitivity, and specificity in the discovery cohort were 86.4%, 96%, and 45.8%, respectively. In the validation cohort, they were 92.4%, 96.9%, and 34.5%, respectively. In both cohorts, half of the subjects without fibrosis were erroneously predicted as having fibrosis, but the diagnosis of fibrosis was correctly predicted in nearly all subjects.

A limitation of the study is that only White subjects were enrolled, which limits the generalizability to other racial/ethnic groups, the investigators wrote, although they don’t expect differences would be seen in other groups.

“PLIN2 and RAB14 may permit diagnosis of NASH and/or liver fibrosis with a simple blood test,” they wrote. “Our biomarkers can be used in community and population studies permitting to investigate the real prevalence of NASH and liver fibrosis. Moreover, since it requires only blood sampling, they are potentially valuable tools for population-based and prevention studies in children.”
 

A step forward

“Obesity is a silent pandemic with an expected prevalence rate that will exceed 50% globally by 2030, of which 25% of the adults have fatty liver and approximately 6.5% with NASH, a progressive form of fatty liver,” said Kalyan Ram Bhamidimarri, MD, chief of hepatology and associate professor of clinical medicine at the University of Miami, who was not involved in the research. “Liver biopsy is the current clinical standard to diagnose NASH, but relying on an invasive procedure like liver biopsy that is fraught with several risks in a consistently growing volume of individuals with obesity is unsustainable.

Courtesy University of Miami

“So, there is an unmet need to diagnose NASH without invasive procedures such as liver biopsy,” he said. He pointed out that many of the alternatives to liver biopsy, such as liver stiffness measurements and scoring systems, pose their own difficulties.

On the other hand, he noted that “blood-based tests that correlate well with liver biopsy, the so-called wet biomarkers or liquid liver biopsy, are easier to perform, accessed widely, and could be tested frequently to assess efficacy of therapies.”

The study was funded by Elucidating Pathways of Steatohepatitis (EPOS Horizon 2020), Stratification of Obese Phenotypes to Optimize Future Obesity Therapy (SOPHIA IMI), Metadeq Inc., and support from the Transcampus Initiative. The study authors declared various competing interests, including some who serve as an advisor or stock option holder for Metadeq Limited. Dr. Bhamidimarri reported no relevant conflicts of interest.

Researchers from France have identified two distinct phenotypes of fulminant COVID-19–related myocarditis in adults, with different clinical presentations, immunologic profiles, and outcomes.

Differentiation between the two bioclinical entities is important to understand for patient management and further pathophysiological studies, they said.

The first phenotype occurs early (within a few days) in acute SARS-CoV-2 infection, with active viral replication (polymerase chain reaction positive) in adults who meet criteria for multisystem inflammatory syndrome (MIS-A+).

Floaria Bicher/iStock/Getty Images Plus

In this early phenotype, there is “limited systemic inflammation without skin and mucosal involvement, but myocardial dysfunction is fulminant and frequently associated with large pericardial effusions. These cases more often require extracorporeal membrane oxygenation [ECMO],” Guy Gorochov, MD, PhD, Sorbonne University, Paris, said in an interview.

The second is a delayed, postinfectious, immune-driven phenotype that occurs in adults who fail to meet the criteria for MIS-A (MIS-A–).

This phenotype occurs weeks after SARS-CoV-2 infection, usually beyond detectable active viral replication (PCR–) in the context of specific immune response and severe systemic inflammation with skin and mucosal involvement. Myocardial dysfunction is more progressive and rarely associated with large pericardial effusions, Dr. Gorochov explained.

The study was published in the Journal of the American College of Cardiology.
 

Evolving understanding

The findings are based on a retrospective analysis of 38 patients without a history of COVID-19 vaccination who were admitted to the intensive care unit from March 2020 to June 2021 for suspected fulminant COVID-19 myocarditis.

Patients were confirmed to have SARS-CoV-2 infection by PCR and/or by serologic testing. As noted in other studies, the patients were predominantly young men (66%; median age, 27.5 years). Twenty-five (66%) patients were MIS-A+ and 13 (34%) were MIS-A–.

In general, the MIS-A– patients were sicker and had worse outcomes.

Specifically, compared with the MIS-A+ patients, MIS-A– patients had a shorter time between the onset of COVID-19 symptoms and the development of myocarditis, a shorter time to ICU admission, and more severe presentations assessed using lower left ventricular ejection fraction and sequential organ failure assessment scores.

MIS-A– patients also had higher lactate levels, were more likely to need venoarterial ECMO (92% vs 16%), had higher ICU mortality (31% vs. 4%), and a had lower probability of survival at 3 months (68% vs. 96%), compared with their MIS-A+ peers.

Immunologic differences

The immunologic profiles of these two distinct clinical phenotypes also differed.

In MIS-A– early-type COVID-19 myocarditis, RNA polymerase III autoantibodies are frequently positive and serum levels of antiviral interferon-alpha and granulocyte-attracting interleukin-8 are elevated.

In contrast, in MIS-A+ delayed-type COVID-19 myocarditis, RNA polymerase III autoantibodies are negative and serum levels of IL-17 and IL-22 are highly elevated.

“We suggest that IL-17 and IL-22 are novel criteria that should help to assess in adults the recently recognized MIS-A,” Dr. Gorochov told this news organization. “It should be tested whether IL-17 and IL-22 are also elevated in children with MIS-C.”

The researchers also observed “extremely” high serum IL-10 levels in both patient groups. This has been previously associated with severe myocardial injury and an increase in the risk for death in severe COVID-19 patients.

The researchers said the phenotypic clustering of patients with fulminant COVID-19–related myocarditis “seems relevant” for their management.

MIS-A– cases, owing to the high risk for evolution toward refractory cardiogenic shock, should be “urgently” referred to a center with venoarterial ECMO and closely monitored to prevent a “too-late” cannulation, especially under cardiopulmonary resuscitation, known to be associated with poor outcomes, they advised.

They noted that the five patients who died in their series had late venoarterial ECMO implantation, while undergoing multiple organ failures or resuscitation.

Conversely, the risk for evolution to refractory cardiogenic shock is lower in MIS-A+ cases. However, identifying MIS-A+ cases is “all the more important given that numerous data support the efficacy of corticosteroids and/or intravenous immunoglobulins in MIS-C,” Dr. Gorochov and colleagues wrote.

The authors of a linked editorial said the French team should be “commended on their work in furthering our understanding of fulminant myocarditis related to COVID-19 infection.”

Ajith Nair, MD, Baylor College of Medicine, and Anita Deswal, MD, MPH, University of Texas M.D. Anderson Cancer Center, both in Houston, noted that fulminant myocarditis is rare and can result from either of two mechanisms: viral tropism or an immune-mediated mechanism.

“It remains to be seen whether using antiviral therapy versus immunomodulatory therapy on the basis of clinical and cytokine profiles will yield benefits,” they wrote.

“Fulminant myocarditis invariably requires hemodynamic support and carries a high mortality risk if it is recognized late. However, the long-term prognosis in patients who survive the critical period is favorable, with recovery of myocardial function,” they added.

“This study highlights the ever-shifting understanding of the pathophysiology and therapeutic approaches to fulminant myocarditis,” Dr. Nair and Dr. Deswal concluded.

This research was supported in part by the Foundation of France, French National Research Agency, Sorbonne University, and Clinical Research Hospital. The researchers have filed a patent application based on these results. Dr. Nair and Dr. Deswal have no relevant disclosures.

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

Researchers from France have identified two distinct phenotypes of fulminant COVID-19–related myocarditis in adults, with different clinical presentations, immunologic profiles, and outcomes.

Differentiation between the two bioclinical entities is important to understand for patient management and further pathophysiological studies, they said.

The first phenotype occurs early (within a few days) in acute SARS-CoV-2 infection, with active viral replication (polymerase chain reaction positive) in adults who meet criteria for multisystem inflammatory syndrome (MIS-A+).

Floaria Bicher/iStock/Getty Images Plus

In this early phenotype, there is “limited systemic inflammation without skin and mucosal involvement, but myocardial dysfunction is fulminant and frequently associated with large pericardial effusions. These cases more often require extracorporeal membrane oxygenation [ECMO],” Guy Gorochov, MD, PhD, Sorbonne University, Paris, said in an interview.

The second is a delayed, postinfectious, immune-driven phenotype that occurs in adults who fail to meet the criteria for MIS-A (MIS-A–).

This phenotype occurs weeks after SARS-CoV-2 infection, usually beyond detectable active viral replication (PCR–) in the context of specific immune response and severe systemic inflammation with skin and mucosal involvement. Myocardial dysfunction is more progressive and rarely associated with large pericardial effusions, Dr. Gorochov explained.

The study was published in the Journal of the American College of Cardiology.
 

Evolving understanding

The findings are based on a retrospective analysis of 38 patients without a history of COVID-19 vaccination who were admitted to the intensive care unit from March 2020 to June 2021 for suspected fulminant COVID-19 myocarditis.

Patients were confirmed to have SARS-CoV-2 infection by PCR and/or by serologic testing. As noted in other studies, the patients were predominantly young men (66%; median age, 27.5 years). Twenty-five (66%) patients were MIS-A+ and 13 (34%) were MIS-A–.

In general, the MIS-A– patients were sicker and had worse outcomes.

Specifically, compared with the MIS-A+ patients, MIS-A– patients had a shorter time between the onset of COVID-19 symptoms and the development of myocarditis, a shorter time to ICU admission, and more severe presentations assessed using lower left ventricular ejection fraction and sequential organ failure assessment scores.

MIS-A– patients also had higher lactate levels, were more likely to need venoarterial ECMO (92% vs 16%), had higher ICU mortality (31% vs. 4%), and a had lower probability of survival at 3 months (68% vs. 96%), compared with their MIS-A+ peers.

Immunologic differences

The immunologic profiles of these two distinct clinical phenotypes also differed.

In MIS-A– early-type COVID-19 myocarditis, RNA polymerase III autoantibodies are frequently positive and serum levels of antiviral interferon-alpha and granulocyte-attracting interleukin-8 are elevated.

In contrast, in MIS-A+ delayed-type COVID-19 myocarditis, RNA polymerase III autoantibodies are negative and serum levels of IL-17 and IL-22 are highly elevated.

“We suggest that IL-17 and IL-22 are novel criteria that should help to assess in adults the recently recognized MIS-A,” Dr. Gorochov told this news organization. “It should be tested whether IL-17 and IL-22 are also elevated in children with MIS-C.”

The researchers also observed “extremely” high serum IL-10 levels in both patient groups. This has been previously associated with severe myocardial injury and an increase in the risk for death in severe COVID-19 patients.

The researchers said the phenotypic clustering of patients with fulminant COVID-19–related myocarditis “seems relevant” for their management.

MIS-A– cases, owing to the high risk for evolution toward refractory cardiogenic shock, should be “urgently” referred to a center with venoarterial ECMO and closely monitored to prevent a “too-late” cannulation, especially under cardiopulmonary resuscitation, known to be associated with poor outcomes, they advised.

They noted that the five patients who died in their series had late venoarterial ECMO implantation, while undergoing multiple organ failures or resuscitation.

Conversely, the risk for evolution to refractory cardiogenic shock is lower in MIS-A+ cases. However, identifying MIS-A+ cases is “all the more important given that numerous data support the efficacy of corticosteroids and/or intravenous immunoglobulins in MIS-C,” Dr. Gorochov and colleagues wrote.

The authors of a linked editorial said the French team should be “commended on their work in furthering our understanding of fulminant myocarditis related to COVID-19 infection.”

Ajith Nair, MD, Baylor College of Medicine, and Anita Deswal, MD, MPH, University of Texas M.D. Anderson Cancer Center, both in Houston, noted that fulminant myocarditis is rare and can result from either of two mechanisms: viral tropism or an immune-mediated mechanism.

“It remains to be seen whether using antiviral therapy versus immunomodulatory therapy on the basis of clinical and cytokine profiles will yield benefits,” they wrote.

“Fulminant myocarditis invariably requires hemodynamic support and carries a high mortality risk if it is recognized late. However, the long-term prognosis in patients who survive the critical period is favorable, with recovery of myocardial function,” they added.

“This study highlights the ever-shifting understanding of the pathophysiology and therapeutic approaches to fulminant myocarditis,” Dr. Nair and Dr. Deswal concluded.

This research was supported in part by the Foundation of France, French National Research Agency, Sorbonne University, and Clinical Research Hospital. The researchers have filed a patent application based on these results. Dr. Nair and Dr. Deswal have no relevant disclosures.

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

Researchers from France have identified two distinct phenotypes of fulminant COVID-19–related myocarditis in adults, with different clinical presentations, immunologic profiles, and outcomes.

Differentiation between the two bioclinical entities is important to understand for patient management and further pathophysiological studies, they said.

The first phenotype occurs early (within a few days) in acute SARS-CoV-2 infection, with active viral replication (polymerase chain reaction positive) in adults who meet criteria for multisystem inflammatory syndrome (MIS-A+).

Floaria Bicher/iStock/Getty Images Plus

In this early phenotype, there is “limited systemic inflammation without skin and mucosal involvement, but myocardial dysfunction is fulminant and frequently associated with large pericardial effusions. These cases more often require extracorporeal membrane oxygenation [ECMO],” Guy Gorochov, MD, PhD, Sorbonne University, Paris, said in an interview.

The second is a delayed, postinfectious, immune-driven phenotype that occurs in adults who fail to meet the criteria for MIS-A (MIS-A–).

This phenotype occurs weeks after SARS-CoV-2 infection, usually beyond detectable active viral replication (PCR–) in the context of specific immune response and severe systemic inflammation with skin and mucosal involvement. Myocardial dysfunction is more progressive and rarely associated with large pericardial effusions, Dr. Gorochov explained.

The study was published in the Journal of the American College of Cardiology.
 

Evolving understanding

The findings are based on a retrospective analysis of 38 patients without a history of COVID-19 vaccination who were admitted to the intensive care unit from March 2020 to June 2021 for suspected fulminant COVID-19 myocarditis.

Patients were confirmed to have SARS-CoV-2 infection by PCR and/or by serologic testing. As noted in other studies, the patients were predominantly young men (66%; median age, 27.5 years). Twenty-five (66%) patients were MIS-A+ and 13 (34%) were MIS-A–.

In general, the MIS-A– patients were sicker and had worse outcomes.

Specifically, compared with the MIS-A+ patients, MIS-A– patients had a shorter time between the onset of COVID-19 symptoms and the development of myocarditis, a shorter time to ICU admission, and more severe presentations assessed using lower left ventricular ejection fraction and sequential organ failure assessment scores.

MIS-A– patients also had higher lactate levels, were more likely to need venoarterial ECMO (92% vs 16%), had higher ICU mortality (31% vs. 4%), and a had lower probability of survival at 3 months (68% vs. 96%), compared with their MIS-A+ peers.

Immunologic differences

The immunologic profiles of these two distinct clinical phenotypes also differed.

In MIS-A– early-type COVID-19 myocarditis, RNA polymerase III autoantibodies are frequently positive and serum levels of antiviral interferon-alpha and granulocyte-attracting interleukin-8 are elevated.

In contrast, in MIS-A+ delayed-type COVID-19 myocarditis, RNA polymerase III autoantibodies are negative and serum levels of IL-17 and IL-22 are highly elevated.

“We suggest that IL-17 and IL-22 are novel criteria that should help to assess in adults the recently recognized MIS-A,” Dr. Gorochov told this news organization. “It should be tested whether IL-17 and IL-22 are also elevated in children with MIS-C.”

The researchers also observed “extremely” high serum IL-10 levels in both patient groups. This has been previously associated with severe myocardial injury and an increase in the risk for death in severe COVID-19 patients.

The researchers said the phenotypic clustering of patients with fulminant COVID-19–related myocarditis “seems relevant” for their management.

MIS-A– cases, owing to the high risk for evolution toward refractory cardiogenic shock, should be “urgently” referred to a center with venoarterial ECMO and closely monitored to prevent a “too-late” cannulation, especially under cardiopulmonary resuscitation, known to be associated with poor outcomes, they advised.

They noted that the five patients who died in their series had late venoarterial ECMO implantation, while undergoing multiple organ failures or resuscitation.

Conversely, the risk for evolution to refractory cardiogenic shock is lower in MIS-A+ cases. However, identifying MIS-A+ cases is “all the more important given that numerous data support the efficacy of corticosteroids and/or intravenous immunoglobulins in MIS-C,” Dr. Gorochov and colleagues wrote.

The authors of a linked editorial said the French team should be “commended on their work in furthering our understanding of fulminant myocarditis related to COVID-19 infection.”

Ajith Nair, MD, Baylor College of Medicine, and Anita Deswal, MD, MPH, University of Texas M.D. Anderson Cancer Center, both in Houston, noted that fulminant myocarditis is rare and can result from either of two mechanisms: viral tropism or an immune-mediated mechanism.

“It remains to be seen whether using antiviral therapy versus immunomodulatory therapy on the basis of clinical and cytokine profiles will yield benefits,” they wrote.

“Fulminant myocarditis invariably requires hemodynamic support and carries a high mortality risk if it is recognized late. However, the long-term prognosis in patients who survive the critical period is favorable, with recovery of myocardial function,” they added.

“This study highlights the ever-shifting understanding of the pathophysiology and therapeutic approaches to fulminant myocarditis,” Dr. Nair and Dr. Deswal concluded.

This research was supported in part by the Foundation of France, French National Research Agency, Sorbonne University, and Clinical Research Hospital. The researchers have filed a patent application based on these results. Dr. Nair and Dr. Deswal have no relevant disclosures.

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.