Dermatology

A new systematic literature review suggests that there may be – at most – a weak link between COVID-19 and alopecia areata.

If there is a connection, it’s likely not a strong one, said study author Rachel E. Christensen, a graduate student at Rutgers Robert Wood Johnson Medical School, in an interview. “Based on the reported number of cases following COVID-19, alopecia areata appears to be low on the list of common skin manifestations of COVID-19,” she said. Of 402 articles screened from three databases in the review, only 11 were identified as related to alopecia areata (AA) and COVID-19, and only 9 of those met the study inclusion criteria. “This number alone highlights the very low number of published articles investigating this connection.”

The review was published in JAAD International.

While COVID-19 has been linked to a variety of skin conditions, a 2021 South Korean study of 7,958 cases and 218,779 controls found no connection between infection and AA even after covariates such as age, gender, and income level were taken into account. In a letter to the editor published in 2020, dermatologists in Turkey reported that the percentage of patients with AA at the dermatology outpatient clinic jumped from 0.97% in May 2019 to 1.48% in May 2020. The number of patients in each group wasn’t reported.

Systematic review

The investigators launched the systematic review to gain a wider perspective, although there are still limitations. On the one hand, Ms. Christensen said, “we do know that COVID-19, like other viruses, has been linked to various dermatological disorders.”

However, “it is difficult to tease apart whether any worsening of alopecia areata we see following COVID-19 is due to the virus itself or the increased psychological burden related to the infection or to the pandemic in general,” she said. Indeed, the authors of the report in Turkey attributed the rise in cases to stress.

For the review, the researchers analyzed studies from Italy (four), Turkey (two), Brazil (one), the United States (one), and Poland (one).

Six of the studies reported cases of new-onset AA following COVID-19 infection (seven cases; average age, 37 years; females, three). Another study was a retrospective review of 32 patients with preexisting AA who developed COVID-19; none experienced significant worsening of AA within 6 months.

The review also included a study based on a survey of 389 patients with AA. The investigators found that, at a median 2.14 months after infection, 44% of those who had COVID-19 vs. 12% of those who were COVID negative had a relapse. Finally, a case report noted a patient with preexisting AA whose condition worsened following COVID infection.

The findings suggest that AA “could be a dermatological manifestation of COVID-19, with cases most often appearing 1-2 months following infection,” the authors wrote. “However, the heterogeneity of study designs and high proportion of case reports make it challenging to draw any conclusion.”

In an interview, dermatologist Brett King, MD, PhD, of the department of dermatology, Yale University, New Haven, Conn., said the review findings suggest that “there is little concern of alopecia areata following COVID infection.

Does new-onset AA happen, and are there exacerbations of preexisting disease related to COVID infection? Probably yes, but rarely.”

However, he noted that another form of alopecia, telogen effluvium (TE), is more common after COVID-19 infection. According to Dr. King, who was not involved with the systematic review, TE is typically time-limited, compared with AA’s more common chronic waxing-and-waning course.

“Distinguishing TE and AA is usually straightforward because AA typically presents with well-circumscribed patches of hair loss,” such as circular patches, “while TE manifests as diffuse hair loss,” he explained. “Rarely, however, AA does manifest diffuse hair loss without patches, similar to TE. In those cases, it may be difficult to distinguish them. A biopsy may be helpful if there is a question of the diagnosis.”

No study funding is reported. The review authors and Dr. King report no relevant disclosures.

A new systematic literature review suggests that there may be – at most – a weak link between COVID-19 and alopecia areata.

If there is a connection, it’s likely not a strong one, said study author Rachel E. Christensen, a graduate student at Rutgers Robert Wood Johnson Medical School, in an interview. “Based on the reported number of cases following COVID-19, alopecia areata appears to be low on the list of common skin manifestations of COVID-19,” she said. Of 402 articles screened from three databases in the review, only 11 were identified as related to alopecia areata (AA) and COVID-19, and only 9 of those met the study inclusion criteria. “This number alone highlights the very low number of published articles investigating this connection.”

The review was published in JAAD International.

While COVID-19 has been linked to a variety of skin conditions, a 2021 South Korean study of 7,958 cases and 218,779 controls found no connection between infection and AA even after covariates such as age, gender, and income level were taken into account. In a letter to the editor published in 2020, dermatologists in Turkey reported that the percentage of patients with AA at the dermatology outpatient clinic jumped from 0.97% in May 2019 to 1.48% in May 2020. The number of patients in each group wasn’t reported.

Systematic review

The investigators launched the systematic review to gain a wider perspective, although there are still limitations. On the one hand, Ms. Christensen said, “we do know that COVID-19, like other viruses, has been linked to various dermatological disorders.”

However, “it is difficult to tease apart whether any worsening of alopecia areata we see following COVID-19 is due to the virus itself or the increased psychological burden related to the infection or to the pandemic in general,” she said. Indeed, the authors of the report in Turkey attributed the rise in cases to stress.

For the review, the researchers analyzed studies from Italy (four), Turkey (two), Brazil (one), the United States (one), and Poland (one).

Six of the studies reported cases of new-onset AA following COVID-19 infection (seven cases; average age, 37 years; females, three). Another study was a retrospective review of 32 patients with preexisting AA who developed COVID-19; none experienced significant worsening of AA within 6 months.

The review also included a study based on a survey of 389 patients with AA. The investigators found that, at a median 2.14 months after infection, 44% of those who had COVID-19 vs. 12% of those who were COVID negative had a relapse. Finally, a case report noted a patient with preexisting AA whose condition worsened following COVID infection.

The findings suggest that AA “could be a dermatological manifestation of COVID-19, with cases most often appearing 1-2 months following infection,” the authors wrote. “However, the heterogeneity of study designs and high proportion of case reports make it challenging to draw any conclusion.”

In an interview, dermatologist Brett King, MD, PhD, of the department of dermatology, Yale University, New Haven, Conn., said the review findings suggest that “there is little concern of alopecia areata following COVID infection.

Does new-onset AA happen, and are there exacerbations of preexisting disease related to COVID infection? Probably yes, but rarely.”

However, he noted that another form of alopecia, telogen effluvium (TE), is more common after COVID-19 infection. According to Dr. King, who was not involved with the systematic review, TE is typically time-limited, compared with AA’s more common chronic waxing-and-waning course.

“Distinguishing TE and AA is usually straightforward because AA typically presents with well-circumscribed patches of hair loss,” such as circular patches, “while TE manifests as diffuse hair loss,” he explained. “Rarely, however, AA does manifest diffuse hair loss without patches, similar to TE. In those cases, it may be difficult to distinguish them. A biopsy may be helpful if there is a question of the diagnosis.”

No study funding is reported. The review authors and Dr. King report no relevant disclosures.

A new systematic literature review suggests that there may be – at most – a weak link between COVID-19 and alopecia areata.

If there is a connection, it’s likely not a strong one, said study author Rachel E. Christensen, a graduate student at Rutgers Robert Wood Johnson Medical School, in an interview. “Based on the reported number of cases following COVID-19, alopecia areata appears to be low on the list of common skin manifestations of COVID-19,” she said. Of 402 articles screened from three databases in the review, only 11 were identified as related to alopecia areata (AA) and COVID-19, and only 9 of those met the study inclusion criteria. “This number alone highlights the very low number of published articles investigating this connection.”

The review was published in JAAD International.

While COVID-19 has been linked to a variety of skin conditions, a 2021 South Korean study of 7,958 cases and 218,779 controls found no connection between infection and AA even after covariates such as age, gender, and income level were taken into account. In a letter to the editor published in 2020, dermatologists in Turkey reported that the percentage of patients with AA at the dermatology outpatient clinic jumped from 0.97% in May 2019 to 1.48% in May 2020. The number of patients in each group wasn’t reported.

Systematic review

The investigators launched the systematic review to gain a wider perspective, although there are still limitations. On the one hand, Ms. Christensen said, “we do know that COVID-19, like other viruses, has been linked to various dermatological disorders.”

However, “it is difficult to tease apart whether any worsening of alopecia areata we see following COVID-19 is due to the virus itself or the increased psychological burden related to the infection or to the pandemic in general,” she said. Indeed, the authors of the report in Turkey attributed the rise in cases to stress.

For the review, the researchers analyzed studies from Italy (four), Turkey (two), Brazil (one), the United States (one), and Poland (one).

Six of the studies reported cases of new-onset AA following COVID-19 infection (seven cases; average age, 37 years; females, three). Another study was a retrospective review of 32 patients with preexisting AA who developed COVID-19; none experienced significant worsening of AA within 6 months.

The review also included a study based on a survey of 389 patients with AA. The investigators found that, at a median 2.14 months after infection, 44% of those who had COVID-19 vs. 12% of those who were COVID negative had a relapse. Finally, a case report noted a patient with preexisting AA whose condition worsened following COVID infection.

The findings suggest that AA “could be a dermatological manifestation of COVID-19, with cases most often appearing 1-2 months following infection,” the authors wrote. “However, the heterogeneity of study designs and high proportion of case reports make it challenging to draw any conclusion.”

In an interview, dermatologist Brett King, MD, PhD, of the department of dermatology, Yale University, New Haven, Conn., said the review findings suggest that “there is little concern of alopecia areata following COVID infection.

Does new-onset AA happen, and are there exacerbations of preexisting disease related to COVID infection? Probably yes, but rarely.”

However, he noted that another form of alopecia, telogen effluvium (TE), is more common after COVID-19 infection. According to Dr. King, who was not involved with the systematic review, TE is typically time-limited, compared with AA’s more common chronic waxing-and-waning course.

“Distinguishing TE and AA is usually straightforward because AA typically presents with well-circumscribed patches of hair loss,” such as circular patches, “while TE manifests as diffuse hair loss,” he explained. “Rarely, however, AA does manifest diffuse hair loss without patches, similar to TE. In those cases, it may be difficult to distinguish them. A biopsy may be helpful if there is a question of the diagnosis.”

No study funding is reported. The review authors and Dr. King report no relevant disclosures.

Lichen planus (LP) is a chronic, pruritic, inflammatory disease that can affect the skin, hair, nails, and mucosal surfaces. The exact cause is unknown, but possible causes include medications, dental amalgam fillings, or an autoimmune reaction. Drugs implicated in causing LP include beta-blockers, methyldopa, penicillamine, quinidine, and quinine. A meta-analysis of case-control studies show a statistically significant association between hepatitis C infection and LP patients; thus, all patients presenting with LP should be screened for hepatitis.¹ Individuals of all age groups and races can be affected by LP, but it is predominantly observed in middle-aged adults. Women are also twice as likely to get oral lichen planus.²

Atrophic lichen planus, the least common form of LP, presents as flat, violaceous papules with an atrophic, pale center. Although these papules can be found anywhere on the body, they most commonly affect the trunk and/or legs on areas of the skin previously affected by classical lichen planus.³ In most cases, LP is diagnosed by observing its clinical features. A biopsy is recommended to confirm the diagnosis for more atypical cases.

Courtesy Alaa Erras, University of California, San Diego, and Brooke Resh Sateesh, MD, San Diego Family Dermatology

Histopathology reveals thinning of the epidermis with flattening of the rete ridges, vacuolar degeneration of the basal layer, and a lichenoid mononuclear infiltrate in the papillary dermis.

Courtesy Alaa Erras, University of California, San Diego, and Brooke Resh Sateesh, MD, San Diego Family Dermatology

If the patient is diagnosed with LP but experiences no symptoms, treatment is not needed as LP may resolve spontaneously within 1-2 years. Recurrences are common, however. Lesions may heal with hyperpigmentation. Possible treatments that can help relieve symptoms of pruritus are high potency topical corticosteroids, calcineurin inhibitors, and antihistamines. In more severe and widespread cases, lesions may respond well to systemic corticosteroids or intralesional steroid injections.⁴ Phototherapy is reported to be effective as well. Acitretin, isotretinoin, methotrexate, hydroxychloroquine, and mycophenolate mofetil are all described in the literature. It is important to note that LP on mucous membranes may be more persistent and resistant to treatment.¹

In this patient, a punch biopsy was performed, confirming the diagnosis. The patient was treated with topical and intralesional steroids, as well as a course of prednisone, and her lesions improved with treatment. Hepatitis serologies were negative.

This case and photo were submitted by Ms. Erras of the University of California, San Diego, and Dr. Sateesh, of San Diego Family Dermatology, and edited by Donna Bilu Martin, MD.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.

References

1. Usatine R, Tinitigan M. Am Fam Physician. 2011 Jul 1;84(1):53-602.

2. Lichen planus, Johns Hopkins Medicine. [Cited 2022 Mar 13.]

3. Atrophic lichen planus, Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. [Cited 2022 Mar 13.]

4. ”Atrophic lichen planus,” Medscape, 2004 Feb 1. [Cited 2022 Mar 13.]

Lichen planus (LP) is a chronic, pruritic, inflammatory disease that can affect the skin, hair, nails, and mucosal surfaces. The exact cause is unknown, but possible causes include medications, dental amalgam fillings, or an autoimmune reaction. Drugs implicated in causing LP include beta-blockers, methyldopa, penicillamine, quinidine, and quinine. A meta-analysis of case-control studies show a statistically significant association between hepatitis C infection and LP patients; thus, all patients presenting with LP should be screened for hepatitis.¹ Individuals of all age groups and races can be affected by LP, but it is predominantly observed in middle-aged adults. Women are also twice as likely to get oral lichen planus.²

Atrophic lichen planus, the least common form of LP, presents as flat, violaceous papules with an atrophic, pale center. Although these papules can be found anywhere on the body, they most commonly affect the trunk and/or legs on areas of the skin previously affected by classical lichen planus.³ In most cases, LP is diagnosed by observing its clinical features. A biopsy is recommended to confirm the diagnosis for more atypical cases.

Courtesy Alaa Erras, University of California, San Diego, and Brooke Resh Sateesh, MD, San Diego Family Dermatology

Histopathology reveals thinning of the epidermis with flattening of the rete ridges, vacuolar degeneration of the basal layer, and a lichenoid mononuclear infiltrate in the papillary dermis.

Courtesy Alaa Erras, University of California, San Diego, and Brooke Resh Sateesh, MD, San Diego Family Dermatology

If the patient is diagnosed with LP but experiences no symptoms, treatment is not needed as LP may resolve spontaneously within 1-2 years. Recurrences are common, however. Lesions may heal with hyperpigmentation. Possible treatments that can help relieve symptoms of pruritus are high potency topical corticosteroids, calcineurin inhibitors, and antihistamines. In more severe and widespread cases, lesions may respond well to systemic corticosteroids or intralesional steroid injections.⁴ Phototherapy is reported to be effective as well. Acitretin, isotretinoin, methotrexate, hydroxychloroquine, and mycophenolate mofetil are all described in the literature. It is important to note that LP on mucous membranes may be more persistent and resistant to treatment.¹

In this patient, a punch biopsy was performed, confirming the diagnosis. The patient was treated with topical and intralesional steroids, as well as a course of prednisone, and her lesions improved with treatment. Hepatitis serologies were negative.

This case and photo were submitted by Ms. Erras of the University of California, San Diego, and Dr. Sateesh, of San Diego Family Dermatology, and edited by Donna Bilu Martin, MD.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.

References

1. Usatine R, Tinitigan M. Am Fam Physician. 2011 Jul 1;84(1):53-602.

2. Lichen planus, Johns Hopkins Medicine. [Cited 2022 Mar 13.]

3. Atrophic lichen planus, Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. [Cited 2022 Mar 13.]

4. ”Atrophic lichen planus,” Medscape, 2004 Feb 1. [Cited 2022 Mar 13.]

Lichen planus (LP) is a chronic, pruritic, inflammatory disease that can affect the skin, hair, nails, and mucosal surfaces. The exact cause is unknown, but possible causes include medications, dental amalgam fillings, or an autoimmune reaction. Drugs implicated in causing LP include beta-blockers, methyldopa, penicillamine, quinidine, and quinine. A meta-analysis of case-control studies show a statistically significant association between hepatitis C infection and LP patients; thus, all patients presenting with LP should be screened for hepatitis.¹ Individuals of all age groups and races can be affected by LP, but it is predominantly observed in middle-aged adults. Women are also twice as likely to get oral lichen planus.²

Atrophic lichen planus, the least common form of LP, presents as flat, violaceous papules with an atrophic, pale center. Although these papules can be found anywhere on the body, they most commonly affect the trunk and/or legs on areas of the skin previously affected by classical lichen planus.³ In most cases, LP is diagnosed by observing its clinical features. A biopsy is recommended to confirm the diagnosis for more atypical cases.

Courtesy Alaa Erras, University of California, San Diego, and Brooke Resh Sateesh, MD, San Diego Family Dermatology

Histopathology reveals thinning of the epidermis with flattening of the rete ridges, vacuolar degeneration of the basal layer, and a lichenoid mononuclear infiltrate in the papillary dermis.

Courtesy Alaa Erras, University of California, San Diego, and Brooke Resh Sateesh, MD, San Diego Family Dermatology

If the patient is diagnosed with LP but experiences no symptoms, treatment is not needed as LP may resolve spontaneously within 1-2 years. Recurrences are common, however. Lesions may heal with hyperpigmentation. Possible treatments that can help relieve symptoms of pruritus are high potency topical corticosteroids, calcineurin inhibitors, and antihistamines. In more severe and widespread cases, lesions may respond well to systemic corticosteroids or intralesional steroid injections.⁴ Phototherapy is reported to be effective as well. Acitretin, isotretinoin, methotrexate, hydroxychloroquine, and mycophenolate mofetil are all described in the literature. It is important to note that LP on mucous membranes may be more persistent and resistant to treatment.¹

In this patient, a punch biopsy was performed, confirming the diagnosis. The patient was treated with topical and intralesional steroids, as well as a course of prednisone, and her lesions improved with treatment. Hepatitis serologies were negative.

This case and photo were submitted by Ms. Erras of the University of California, San Diego, and Dr. Sateesh, of San Diego Family Dermatology, and edited by Donna Bilu Martin, MD.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.

References

1. Usatine R, Tinitigan M. Am Fam Physician. 2011 Jul 1;84(1):53-602.

2. Lichen planus, Johns Hopkins Medicine. [Cited 2022 Mar 13.]

3. Atrophic lichen planus, Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. [Cited 2022 Mar 13.]

4. ”Atrophic lichen planus,” Medscape, 2004 Feb 1. [Cited 2022 Mar 13.]

A biopsy was performed to exclude squamous cell carcinoma and an additional biopsy was sent for tissue culture for aerobic and acid-fast bacteria. The culture revealed a surprising diagnosis: cutaneous mycobacterium marinum.

Mycobacterium marinum is one of many nontuberculosis mycobacteria that may rarely cause infections in immunocompetent patients. M marinum is found worldwide in saltwater and freshwater. Infections may occur in individuals working in fisheries or fish markets, natural marine environments, or with aquariums. The infection may gain access through small, even unnoticed breaks in the skin. Papules, pustules, or abscesses caused by M marinum develop a few weeks after exposure and share many features with other common skin infections, including Staphylococcus aureus. Lymphatic involvement and sporotrichoid spread may occur. Immunocompromised patients can experience deeper involvement into tendons. Patients with significant soft tissue pain should undergo computed tomography, or preferably magnetic resonance imaging, to determine the extent of disease.

For immunocompetent patients and those with limited disease, as in this case, spontaneous resolution can occur after a year or more. However, because of the potential risk of more severe disease, treatment is recommended. M marinum is resistant to multiple antibiotics and there are no standardized treatment guidelines. Minocycline 100 mg bid for 3 weeks to 3 months is 1 accepted regimen for limited disease; treatment should be continued for 3 to 4 weeks following clinical resolution.¹ Patients with more widespread disease benefit from evaluation by Infectious Diseases. Patients exposed to atypical mycobacteria may have false positive QuantiFERON-TB Gold tests that are commonly performed prior to biologic therapies.²

This patient achieved complete resolution of his signs and symptoms after receiving minocycline 100 mg bid for 6 weeks. He continues to fish recreationally.

‌

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

A biopsy was performed to exclude squamous cell carcinoma and an additional biopsy was sent for tissue culture for aerobic and acid-fast bacteria. The culture revealed a surprising diagnosis: cutaneous mycobacterium marinum.

Mycobacterium marinum is one of many nontuberculosis mycobacteria that may rarely cause infections in immunocompetent patients. M marinum is found worldwide in saltwater and freshwater. Infections may occur in individuals working in fisheries or fish markets, natural marine environments, or with aquariums. The infection may gain access through small, even unnoticed breaks in the skin. Papules, pustules, or abscesses caused by M marinum develop a few weeks after exposure and share many features with other common skin infections, including Staphylococcus aureus. Lymphatic involvement and sporotrichoid spread may occur. Immunocompromised patients can experience deeper involvement into tendons. Patients with significant soft tissue pain should undergo computed tomography, or preferably magnetic resonance imaging, to determine the extent of disease.

For immunocompetent patients and those with limited disease, as in this case, spontaneous resolution can occur after a year or more. However, because of the potential risk of more severe disease, treatment is recommended. M marinum is resistant to multiple antibiotics and there are no standardized treatment guidelines. Minocycline 100 mg bid for 3 weeks to 3 months is 1 accepted regimen for limited disease; treatment should be continued for 3 to 4 weeks following clinical resolution.¹ Patients with more widespread disease benefit from evaluation by Infectious Diseases. Patients exposed to atypical mycobacteria may have false positive QuantiFERON-TB Gold tests that are commonly performed prior to biologic therapies.²

This patient achieved complete resolution of his signs and symptoms after receiving minocycline 100 mg bid for 6 weeks. He continues to fish recreationally.

‌

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

A biopsy was performed to exclude squamous cell carcinoma and an additional biopsy was sent for tissue culture for aerobic and acid-fast bacteria. The culture revealed a surprising diagnosis: cutaneous mycobacterium marinum.

Mycobacterium marinum is one of many nontuberculosis mycobacteria that may rarely cause infections in immunocompetent patients. M marinum is found worldwide in saltwater and freshwater. Infections may occur in individuals working in fisheries or fish markets, natural marine environments, or with aquariums. The infection may gain access through small, even unnoticed breaks in the skin. Papules, pustules, or abscesses caused by M marinum develop a few weeks after exposure and share many features with other common skin infections, including Staphylococcus aureus. Lymphatic involvement and sporotrichoid spread may occur. Immunocompromised patients can experience deeper involvement into tendons. Patients with significant soft tissue pain should undergo computed tomography, or preferably magnetic resonance imaging, to determine the extent of disease.

For immunocompetent patients and those with limited disease, as in this case, spontaneous resolution can occur after a year or more. However, because of the potential risk of more severe disease, treatment is recommended. M marinum is resistant to multiple antibiotics and there are no standardized treatment guidelines. Minocycline 100 mg bid for 3 weeks to 3 months is 1 accepted regimen for limited disease; treatment should be continued for 3 to 4 weeks following clinical resolution.¹ Patients with more widespread disease benefit from evaluation by Infectious Diseases. Patients exposed to atypical mycobacteria may have false positive QuantiFERON-TB Gold tests that are commonly performed prior to biologic therapies.²

This patient achieved complete resolution of his signs and symptoms after receiving minocycline 100 mg bid for 6 weeks. He continues to fish recreationally.

‌

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

Exposure to air pollution – even short term – may play a role in triggering psoriasis flares, according to new research from Italy, which found a significant association between exposure to higher levels of air pollution prior to patients presenting for psoriasis flares at medical visits, compared with visits unrelated to flares.

“We found that higher concentration of different air pollutants was associated with psoriasis flares in patients living in an industrialized city of the Po Valley” in Verona, Italy, report the authors of the study, published in JAMA Dermatology.

The findings underscore the need for clinicians to “consider environmental/external triggers in patients with chronic inflammatory diseases experiencing flares,” first author Francesco Bellinato, MD, of the Section of Dermatology and Venereology, University of Verona, Italy, told this news organization.

He and his coauthors conducted a case-crossover and cross-sectional longitudinal study that involved a retrospective analysis of data in 957 patients in Verona with chronic plaque psoriasis, who were evaluated every 3-4 months at an outpatient dermatology clinic for a median of 2.7 years.

Over the study period, disease flares, defined as an increase in the Psoriasis Area and Severity Index (PASI) of 5 or more points from the previous visit, occurred in 369 patients (38.6%), consistent with known flare rates in psoriasis. Participants in the study (mean age, 61) had median PASI scores of 12 during visits for psoriatic flares compared with PASI scores of 1 during control (no flare) visits (P < .001).

Evaluations of mean concentrations of several air pollutants within 10 miles of the patients over 4,398 visits showed that concentrations were significantly higher in the 60 days prior to the psoriasis flare, compared with control visits that were not related to flares (P < .05), after adjusting for factors including seasonality (by trimester, to adjust for weather conditions and UV/sunlight exposure) and the type of systemic psoriasis treatments patients were receiving (conventional or biological).

Increases in air pollutant levels prior to flares were observed among the 35.8% of patients who had a flare of at least a 50% increase in the PASI score, as well among the 47.2% of patients who had at least a 100% increase in PASI, compared with control visits not involving flares. In addition, mean and area-under-the-curve concentrations of air pollutants were higher in the 60 days before the visits among those with PASI 5 or greater, compared with those with PASI scores below 5, the authors add.

Dr. Bellinato noted that the associations were not limited to any particular subgroup. “The associations with air pollution and flares were observed in the entire population,” he said in an interview.

Vehicle, industry emissions

The pollutants that were measured were those mainly associated with fossil fuel combustion from vehicle and industry emissions, including carbon monoxide, nitrogen dioxide, other nitrogen oxides, benzene, coarse particulate matter (2.5-10.0 μm in diameter) and fine particulate matter (less than 2.5 μm in diameter).

They note that the risk of having a PASI score of 5 or greater was elevated even at thresholds of exposure that are largely considered safe. “Indeed, the risk for having a PASI score of 5 or greater was 40% to 50% higher at exposures as low as 20 μg/m³” of coarse particulate matter and 15 μg/m³ of fine particulate matter in the 60-day period prior to the visits, they write.

The authors referred to evidence linking air pollution with a worsening of a variety of inflammatory cutaneous diseases, including atopic dermatitis and acne, as well as photoaging. Psoriasis flares are known to be triggered by a variety of environmental factors, including infections or certain drugs; however, evidence of a role of air pollution has been lacking. Potential mechanisms linking the exposures to flares include the possibility that exhaust particles can activate skin resident T-cells, “resulting in abnormal production of proinflammatory cytokines including tumor necrosis factor α (TNF-α) and interleukins (ILs), including IL-1α, IL-1β, IL-6, and IL-8.8,” the authors write.

Their results, though inferring a causal relationship, fall short of showing a clear dose–response relationship between higher pollutant levels and an increased risk of psoriasis flares, possibly the result of a smaller sample size of subjects exposed to higher levels of pollution, they add.

Limitations of the study included the definition of flare, which used a clinical score that could be affected by other measurements, they point out, while strengths of the study included the large cohort of patients followed for over 7 years and the availability of daily measurements of air pollutants.

While the study suggests that environmental air pollutant fluctuations may affect psoriasis course,” the authors concluded, “further study is needed to examine whether these findings generalize to other populations and to better understand the mechanisms by which air pollution may affect psoriasis disease activity.”

Dr. Bellinato and four coauthors had no disclosures; the remaining authors had disclosures that included receiving personal fees from pharmaceutical companies that were outside of the submitted work.

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

Exposure to air pollution – even short term – may play a role in triggering psoriasis flares, according to new research from Italy, which found a significant association between exposure to higher levels of air pollution prior to patients presenting for psoriasis flares at medical visits, compared with visits unrelated to flares.

“We found that higher concentration of different air pollutants was associated with psoriasis flares in patients living in an industrialized city of the Po Valley” in Verona, Italy, report the authors of the study, published in JAMA Dermatology.

The findings underscore the need for clinicians to “consider environmental/external triggers in patients with chronic inflammatory diseases experiencing flares,” first author Francesco Bellinato, MD, of the Section of Dermatology and Venereology, University of Verona, Italy, told this news organization.

He and his coauthors conducted a case-crossover and cross-sectional longitudinal study that involved a retrospective analysis of data in 957 patients in Verona with chronic plaque psoriasis, who were evaluated every 3-4 months at an outpatient dermatology clinic for a median of 2.7 years.

Over the study period, disease flares, defined as an increase in the Psoriasis Area and Severity Index (PASI) of 5 or more points from the previous visit, occurred in 369 patients (38.6%), consistent with known flare rates in psoriasis. Participants in the study (mean age, 61) had median PASI scores of 12 during visits for psoriatic flares compared with PASI scores of 1 during control (no flare) visits (P < .001).

Evaluations of mean concentrations of several air pollutants within 10 miles of the patients over 4,398 visits showed that concentrations were significantly higher in the 60 days prior to the psoriasis flare, compared with control visits that were not related to flares (P < .05), after adjusting for factors including seasonality (by trimester, to adjust for weather conditions and UV/sunlight exposure) and the type of systemic psoriasis treatments patients were receiving (conventional or biological).

Increases in air pollutant levels prior to flares were observed among the 35.8% of patients who had a flare of at least a 50% increase in the PASI score, as well among the 47.2% of patients who had at least a 100% increase in PASI, compared with control visits not involving flares. In addition, mean and area-under-the-curve concentrations of air pollutants were higher in the 60 days before the visits among those with PASI 5 or greater, compared with those with PASI scores below 5, the authors add.

Dr. Bellinato noted that the associations were not limited to any particular subgroup. “The associations with air pollution and flares were observed in the entire population,” he said in an interview.

Vehicle, industry emissions

The pollutants that were measured were those mainly associated with fossil fuel combustion from vehicle and industry emissions, including carbon monoxide, nitrogen dioxide, other nitrogen oxides, benzene, coarse particulate matter (2.5-10.0 μm in diameter) and fine particulate matter (less than 2.5 μm in diameter).

They note that the risk of having a PASI score of 5 or greater was elevated even at thresholds of exposure that are largely considered safe. “Indeed, the risk for having a PASI score of 5 or greater was 40% to 50% higher at exposures as low as 20 μg/m³” of coarse particulate matter and 15 μg/m³ of fine particulate matter in the 60-day period prior to the visits, they write.

The authors referred to evidence linking air pollution with a worsening of a variety of inflammatory cutaneous diseases, including atopic dermatitis and acne, as well as photoaging. Psoriasis flares are known to be triggered by a variety of environmental factors, including infections or certain drugs; however, evidence of a role of air pollution has been lacking. Potential mechanisms linking the exposures to flares include the possibility that exhaust particles can activate skin resident T-cells, “resulting in abnormal production of proinflammatory cytokines including tumor necrosis factor α (TNF-α) and interleukins (ILs), including IL-1α, IL-1β, IL-6, and IL-8.8,” the authors write.

Their results, though inferring a causal relationship, fall short of showing a clear dose–response relationship between higher pollutant levels and an increased risk of psoriasis flares, possibly the result of a smaller sample size of subjects exposed to higher levels of pollution, they add.

Limitations of the study included the definition of flare, which used a clinical score that could be affected by other measurements, they point out, while strengths of the study included the large cohort of patients followed for over 7 years and the availability of daily measurements of air pollutants.

While the study suggests that environmental air pollutant fluctuations may affect psoriasis course,” the authors concluded, “further study is needed to examine whether these findings generalize to other populations and to better understand the mechanisms by which air pollution may affect psoriasis disease activity.”

Dr. Bellinato and four coauthors had no disclosures; the remaining authors had disclosures that included receiving personal fees from pharmaceutical companies that were outside of the submitted work.

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

Exposure to air pollution – even short term – may play a role in triggering psoriasis flares, according to new research from Italy, which found a significant association between exposure to higher levels of air pollution prior to patients presenting for psoriasis flares at medical visits, compared with visits unrelated to flares.

“We found that higher concentration of different air pollutants was associated with psoriasis flares in patients living in an industrialized city of the Po Valley” in Verona, Italy, report the authors of the study, published in JAMA Dermatology.

The findings underscore the need for clinicians to “consider environmental/external triggers in patients with chronic inflammatory diseases experiencing flares,” first author Francesco Bellinato, MD, of the Section of Dermatology and Venereology, University of Verona, Italy, told this news organization.

He and his coauthors conducted a case-crossover and cross-sectional longitudinal study that involved a retrospective analysis of data in 957 patients in Verona with chronic plaque psoriasis, who were evaluated every 3-4 months at an outpatient dermatology clinic for a median of 2.7 years.

Over the study period, disease flares, defined as an increase in the Psoriasis Area and Severity Index (PASI) of 5 or more points from the previous visit, occurred in 369 patients (38.6%), consistent with known flare rates in psoriasis. Participants in the study (mean age, 61) had median PASI scores of 12 during visits for psoriatic flares compared with PASI scores of 1 during control (no flare) visits (P < .001).

Evaluations of mean concentrations of several air pollutants within 10 miles of the patients over 4,398 visits showed that concentrations were significantly higher in the 60 days prior to the psoriasis flare, compared with control visits that were not related to flares (P < .05), after adjusting for factors including seasonality (by trimester, to adjust for weather conditions and UV/sunlight exposure) and the type of systemic psoriasis treatments patients were receiving (conventional or biological).

Increases in air pollutant levels prior to flares were observed among the 35.8% of patients who had a flare of at least a 50% increase in the PASI score, as well among the 47.2% of patients who had at least a 100% increase in PASI, compared with control visits not involving flares. In addition, mean and area-under-the-curve concentrations of air pollutants were higher in the 60 days before the visits among those with PASI 5 or greater, compared with those with PASI scores below 5, the authors add.

Dr. Bellinato noted that the associations were not limited to any particular subgroup. “The associations with air pollution and flares were observed in the entire population,” he said in an interview.

Vehicle, industry emissions

The pollutants that were measured were those mainly associated with fossil fuel combustion from vehicle and industry emissions, including carbon monoxide, nitrogen dioxide, other nitrogen oxides, benzene, coarse particulate matter (2.5-10.0 μm in diameter) and fine particulate matter (less than 2.5 μm in diameter).

They note that the risk of having a PASI score of 5 or greater was elevated even at thresholds of exposure that are largely considered safe. “Indeed, the risk for having a PASI score of 5 or greater was 40% to 50% higher at exposures as low as 20 μg/m³” of coarse particulate matter and 15 μg/m³ of fine particulate matter in the 60-day period prior to the visits, they write.

The authors referred to evidence linking air pollution with a worsening of a variety of inflammatory cutaneous diseases, including atopic dermatitis and acne, as well as photoaging. Psoriasis flares are known to be triggered by a variety of environmental factors, including infections or certain drugs; however, evidence of a role of air pollution has been lacking. Potential mechanisms linking the exposures to flares include the possibility that exhaust particles can activate skin resident T-cells, “resulting in abnormal production of proinflammatory cytokines including tumor necrosis factor α (TNF-α) and interleukins (ILs), including IL-1α, IL-1β, IL-6, and IL-8.8,” the authors write.

Their results, though inferring a causal relationship, fall short of showing a clear dose–response relationship between higher pollutant levels and an increased risk of psoriasis flares, possibly the result of a smaller sample size of subjects exposed to higher levels of pollution, they add.

Limitations of the study included the definition of flare, which used a clinical score that could be affected by other measurements, they point out, while strengths of the study included the large cohort of patients followed for over 7 years and the availability of daily measurements of air pollutants.

While the study suggests that environmental air pollutant fluctuations may affect psoriasis course,” the authors concluded, “further study is needed to examine whether these findings generalize to other populations and to better understand the mechanisms by which air pollution may affect psoriasis disease activity.”

Dr. Bellinato and four coauthors had no disclosures; the remaining authors had disclosures that included receiving personal fees from pharmaceutical companies that were outside of the submitted work.

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

Becker’s nevus

The history and physical exam are most consistent with Becker’s nevus, also known as Becker’s melanosis. This is a benign cutaneous hamartoma, usually found in males, characterized by a large, irregularly shaped brown patch, often with hypertrichosis.¹ Becker’s nevus can be congenital but is more commonly noticed in late childhood or early adolescence, with thickening, increased pigmentation, and hair growth. Becker’s nevus is considered an overgrowth of epidermal pigment cells and hair follicles and is thought to be attributable to postzygotic mutations (with ACTB mutations most reported).¹ It is often located unilaterally on the upper trunk but is occasionally present elsewhere on the body. Acne may occasionally develop within the nevus, which is believed to be triggered by puberty-associated androgens.¹ The lesion tends to persist indefinitely but has no propensity for malignant transformation.

Becker’s nevus is generally an isolated skin lesion without other anomalies. However, in rare instances, it may be associated with ipsilateral breast hypoplasia or hypoplastic defects of the muscle, skin, or skeleton, which is known as Becker’s nevus syndrome.² Treatment is not medically warranted for an isolated Becker’s nevus but may be pursued for cosmetic reasons. Although treatment is generally discouraged because of variable success, laser hair removal and laser therapy may be pursued to address the hypertrichosis and hyperpigmentation, respectively.
 

What is on the differential?

A café-au-lait macule (CALM) is a light- to dark-brown, oval lesion that commonly presents at birth or in early childhood. CALMs vary widely in size from less than 1.5 cm to more than 20 cm in diameter. They are asymptomatic and grow in proportion to the individual over time.³ Becker’s nevus can be distinguished from CALMs by the development of hypertrichosis, typical location and course, and other skin changes within the nevus.

Postinflammatory hyperpigmentation (PIH) is characterized by asymptomatic, darkened macules or patches that are brown to blue-gray in color. It is one of the most common causes of hyperpigmentation, particularly in skin of color, and can take months to years to resolve. PIH is caused by increased melanin production in response to a cutaneous inflammatory process, such as a drug reaction, allergy, mechanical or thermal injury, infection, phototoxicity, or an underlying skin condition.³ Our patient’s history with the lack of an inciting inflammatory process is more consistent with Becker’s nevus.

Erythema ab igne is a cutaneous reaction to heat that presents as a hyperpigmented patch with a reticular or mottled configuration and superficial venular telangiectasia. The lesion is initially erythematous and progresses to a pale pink to purplish dark-brown color.⁴ Causes include long-term use of a heating pad, laptop, electric blanket, or a hot water bottle. The absence of prolonged heat exposure in our patient’s history does not favor erythema ab igne.

Pigmentary mosaicism is characterized by a distinctive pattern of hyperpigmentation that follows the lines of ectodermal embryologic development, known as the lines of Blaschko.⁵ This condition is also known as linear and whorled nevoid hypermelanosis because of its streaky or swirl-like pattern. Pigmentary mosaicism can be present at birth or appear within the first few weeks of life. It is caused by genetic heterogeneity in neuroectodermal cells, which results in skin with areas of varying colors. Pigmentary mosaicism is unlikely in this case as our patient’s lesion does not follow the lines of Blaschko.
 

Ms. Laborada is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is the vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital. Ms. Laborada and Dr. Eichenfield have no relevant financial disclosures.

References

1. Atzmony L et al. J Cutan Pathol. 2020;47(8):681-5.

2. Danarti R et al. J Am Acad Dermatol. 2004;51(6):965-9.

3. Paller A and Mancini AJ. “Hurwitz Clinical Pediatric Dermatology: A textbook of skin disorders of childhood and adolescence” 4th ed. Philadelphia: Elsevier Saunders, 2011.

4. Patel DP. JAMA Dermatol. 2017;153(7):685.

5. Kromann AB et al. Orphanet J Rare Dis. 2018;13(1):39.

Becker’s nevus

The history and physical exam are most consistent with Becker’s nevus, also known as Becker’s melanosis. This is a benign cutaneous hamartoma, usually found in males, characterized by a large, irregularly shaped brown patch, often with hypertrichosis.¹ Becker’s nevus can be congenital but is more commonly noticed in late childhood or early adolescence, with thickening, increased pigmentation, and hair growth. Becker’s nevus is considered an overgrowth of epidermal pigment cells and hair follicles and is thought to be attributable to postzygotic mutations (with ACTB mutations most reported).¹ It is often located unilaterally on the upper trunk but is occasionally present elsewhere on the body. Acne may occasionally develop within the nevus, which is believed to be triggered by puberty-associated androgens.¹ The lesion tends to persist indefinitely but has no propensity for malignant transformation.

Becker’s nevus is generally an isolated skin lesion without other anomalies. However, in rare instances, it may be associated with ipsilateral breast hypoplasia or hypoplastic defects of the muscle, skin, or skeleton, which is known as Becker’s nevus syndrome.² Treatment is not medically warranted for an isolated Becker’s nevus but may be pursued for cosmetic reasons. Although treatment is generally discouraged because of variable success, laser hair removal and laser therapy may be pursued to address the hypertrichosis and hyperpigmentation, respectively.
 

What is on the differential?

A café-au-lait macule (CALM) is a light- to dark-brown, oval lesion that commonly presents at birth or in early childhood. CALMs vary widely in size from less than 1.5 cm to more than 20 cm in diameter. They are asymptomatic and grow in proportion to the individual over time.³ Becker’s nevus can be distinguished from CALMs by the development of hypertrichosis, typical location and course, and other skin changes within the nevus.

Postinflammatory hyperpigmentation (PIH) is characterized by asymptomatic, darkened macules or patches that are brown to blue-gray in color. It is one of the most common causes of hyperpigmentation, particularly in skin of color, and can take months to years to resolve. PIH is caused by increased melanin production in response to a cutaneous inflammatory process, such as a drug reaction, allergy, mechanical or thermal injury, infection, phototoxicity, or an underlying skin condition.³ Our patient’s history with the lack of an inciting inflammatory process is more consistent with Becker’s nevus.

Erythema ab igne is a cutaneous reaction to heat that presents as a hyperpigmented patch with a reticular or mottled configuration and superficial venular telangiectasia. The lesion is initially erythematous and progresses to a pale pink to purplish dark-brown color.⁴ Causes include long-term use of a heating pad, laptop, electric blanket, or a hot water bottle. The absence of prolonged heat exposure in our patient’s history does not favor erythema ab igne.

Pigmentary mosaicism is characterized by a distinctive pattern of hyperpigmentation that follows the lines of ectodermal embryologic development, known as the lines of Blaschko.⁵ This condition is also known as linear and whorled nevoid hypermelanosis because of its streaky or swirl-like pattern. Pigmentary mosaicism can be present at birth or appear within the first few weeks of life. It is caused by genetic heterogeneity in neuroectodermal cells, which results in skin with areas of varying colors. Pigmentary mosaicism is unlikely in this case as our patient’s lesion does not follow the lines of Blaschko.
 

Ms. Laborada is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is the vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital. Ms. Laborada and Dr. Eichenfield have no relevant financial disclosures.

References

1. Atzmony L et al. J Cutan Pathol. 2020;47(8):681-5.

2. Danarti R et al. J Am Acad Dermatol. 2004;51(6):965-9.

3. Paller A and Mancini AJ. “Hurwitz Clinical Pediatric Dermatology: A textbook of skin disorders of childhood and adolescence” 4th ed. Philadelphia: Elsevier Saunders, 2011.

4. Patel DP. JAMA Dermatol. 2017;153(7):685.

5. Kromann AB et al. Orphanet J Rare Dis. 2018;13(1):39.

Becker’s nevus

The history and physical exam are most consistent with Becker’s nevus, also known as Becker’s melanosis. This is a benign cutaneous hamartoma, usually found in males, characterized by a large, irregularly shaped brown patch, often with hypertrichosis.¹ Becker’s nevus can be congenital but is more commonly noticed in late childhood or early adolescence, with thickening, increased pigmentation, and hair growth. Becker’s nevus is considered an overgrowth of epidermal pigment cells and hair follicles and is thought to be attributable to postzygotic mutations (with ACTB mutations most reported).¹ It is often located unilaterally on the upper trunk but is occasionally present elsewhere on the body. Acne may occasionally develop within the nevus, which is believed to be triggered by puberty-associated androgens.¹ The lesion tends to persist indefinitely but has no propensity for malignant transformation.

Becker’s nevus is generally an isolated skin lesion without other anomalies. However, in rare instances, it may be associated with ipsilateral breast hypoplasia or hypoplastic defects of the muscle, skin, or skeleton, which is known as Becker’s nevus syndrome.² Treatment is not medically warranted for an isolated Becker’s nevus but may be pursued for cosmetic reasons. Although treatment is generally discouraged because of variable success, laser hair removal and laser therapy may be pursued to address the hypertrichosis and hyperpigmentation, respectively.
 

What is on the differential?

A café-au-lait macule (CALM) is a light- to dark-brown, oval lesion that commonly presents at birth or in early childhood. CALMs vary widely in size from less than 1.5 cm to more than 20 cm in diameter. They are asymptomatic and grow in proportion to the individual over time.³ Becker’s nevus can be distinguished from CALMs by the development of hypertrichosis, typical location and course, and other skin changes within the nevus.

Postinflammatory hyperpigmentation (PIH) is characterized by asymptomatic, darkened macules or patches that are brown to blue-gray in color. It is one of the most common causes of hyperpigmentation, particularly in skin of color, and can take months to years to resolve. PIH is caused by increased melanin production in response to a cutaneous inflammatory process, such as a drug reaction, allergy, mechanical or thermal injury, infection, phototoxicity, or an underlying skin condition.³ Our patient’s history with the lack of an inciting inflammatory process is more consistent with Becker’s nevus.

Erythema ab igne is a cutaneous reaction to heat that presents as a hyperpigmented patch with a reticular or mottled configuration and superficial venular telangiectasia. The lesion is initially erythematous and progresses to a pale pink to purplish dark-brown color.⁴ Causes include long-term use of a heating pad, laptop, electric blanket, or a hot water bottle. The absence of prolonged heat exposure in our patient’s history does not favor erythema ab igne.

Pigmentary mosaicism is characterized by a distinctive pattern of hyperpigmentation that follows the lines of ectodermal embryologic development, known as the lines of Blaschko.⁵ This condition is also known as linear and whorled nevoid hypermelanosis because of its streaky or swirl-like pattern. Pigmentary mosaicism can be present at birth or appear within the first few weeks of life. It is caused by genetic heterogeneity in neuroectodermal cells, which results in skin with areas of varying colors. Pigmentary mosaicism is unlikely in this case as our patient’s lesion does not follow the lines of Blaschko.
 

Ms. Laborada is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is the vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital. Ms. Laborada and Dr. Eichenfield have no relevant financial disclosures.

References

1. Atzmony L et al. J Cutan Pathol. 2020;47(8):681-5.

2. Danarti R et al. J Am Acad Dermatol. 2004;51(6):965-9.

3. Paller A and Mancini AJ. “Hurwitz Clinical Pediatric Dermatology: A textbook of skin disorders of childhood and adolescence” 4th ed. Philadelphia: Elsevier Saunders, 2011.

4. Patel DP. JAMA Dermatol. 2017;153(7):685.

5. Kromann AB et al. Orphanet J Rare Dis. 2018;13(1):39.

Survival rates of biologics and other novel immunomodulatory drugs vary substantially across chronic inflammatory diseases, and rates are highest for rituximab in rheumatoid arthritis (RA) and golimumab in axial spondyloarthritis (axSpA), but with similar rates seen for most drugs used in the treatment of psoriasis and psoriatic arthritis (PsA), according to findings from a study of two Danish registries.

Drug survival refers to “the probability that patients will remain on a given drug, and is a proxy for efficacy as well as safety in daily clinical practice,” wrote Alexander Egeberg, MD, PhD, of the department of dermatology at Copenhagen University Hospital–Bispebjerg, and colleagues. Although the use of biologics has expanded for inflammatory diseases, real-world data on drug survival in newer agents such as interleukin (IL)-17, IL-23, and Janus kinase inhibitors are lacking, they said.

In a study published in Seminars in Arthritis and Rheumatism, the researchers reviewed data from the DANBIO and DERMBIO registries of patients in Denmark with inflammatory diseases including rheumatoid arthritis (RA), axial spondyloarthritis (AxSpA), psoriatic arthritis (PsA), and psoriasis.

The study population included 12,089 adults: 5,104 with RA, 2,157 with AxSpA, 2,251 with PsA, and 2,577 with psoriasis. Patients’ mean age at the time of first treatment for these conditions was 57.8 years, 42.3 years, 49 years, and 45 years, respectively. Participants were treated with biologics or novel small molecule therapies for RA, AxSpA, PsA, or psoriasis between January 2015 and May 2021 (from the DANBIO database) and November 2009 to November 2019 (DERMBIO database).

In adjusted models, drug survival in RA was highest for rituximab followed by baricitinib, etanercept, and tocilizumab. Drug survival in AxSpA was highest for golimumab, compared with all other drugs, followed by secukinumab and etanercept. Survival was lowest for infliximab. In PsA, drug survival was roughly equal for most drugs, including golimumab, secukinumab, and ixekizumab, with the lowest survival observed for tofacitinib and infliximab, compared with all other drugs. Drug survival in psoriasis was highest with guselkumab, followed by ustekinumab and IL-17 inhibitors.

However, the number of treatment series “was low for some drugs, and not all differences were statistically significant, which could influence the overall interpretability of these findings,” the researchers noted in their discussion.

Notably, the high treatment persistence for rituximab in RA patients needs further confirmation, the researchers said. “In Denmark, rituximab is often the biologic drug of choice in RA patients with a history of cancer while there is a reluctancy to use TNF [tumor necrosis factor] inhibitors in such patients; this may have prolonged the drug survival for rituximab treated patients due to limited treatment alternatives,” they said.

The findings were limited by several factors, including the observational study design and changes in guidelines over the course of the study, the researchers noted. Other limitations included the inability to adjust for certain variables, such as antibody status, body weight, and smoking, because of missing data, and a lack of data on the underlying reasons for drug discontinuation, they said.

However, the results were strengthened by the large number of patients and completeness of the registries, the researchers emphasized. The range in responses to different drug types across diseases supports the need for individualized treatments with attention to underlying disease, patient profile, and treatment history, they concluded.

The study received no outside funding. Eight coauthors reported financial ties to a number of pharmaceutical companies.

Survival rates of biologics and other novel immunomodulatory drugs vary substantially across chronic inflammatory diseases, and rates are highest for rituximab in rheumatoid arthritis (RA) and golimumab in axial spondyloarthritis (axSpA), but with similar rates seen for most drugs used in the treatment of psoriasis and psoriatic arthritis (PsA), according to findings from a study of two Danish registries.

Drug survival refers to “the probability that patients will remain on a given drug, and is a proxy for efficacy as well as safety in daily clinical practice,” wrote Alexander Egeberg, MD, PhD, of the department of dermatology at Copenhagen University Hospital–Bispebjerg, and colleagues. Although the use of biologics has expanded for inflammatory diseases, real-world data on drug survival in newer agents such as interleukin (IL)-17, IL-23, and Janus kinase inhibitors are lacking, they said.

In a study published in Seminars in Arthritis and Rheumatism, the researchers reviewed data from the DANBIO and DERMBIO registries of patients in Denmark with inflammatory diseases including rheumatoid arthritis (RA), axial spondyloarthritis (AxSpA), psoriatic arthritis (PsA), and psoriasis.

The study population included 12,089 adults: 5,104 with RA, 2,157 with AxSpA, 2,251 with PsA, and 2,577 with psoriasis. Patients’ mean age at the time of first treatment for these conditions was 57.8 years, 42.3 years, 49 years, and 45 years, respectively. Participants were treated with biologics or novel small molecule therapies for RA, AxSpA, PsA, or psoriasis between January 2015 and May 2021 (from the DANBIO database) and November 2009 to November 2019 (DERMBIO database).

In adjusted models, drug survival in RA was highest for rituximab followed by baricitinib, etanercept, and tocilizumab. Drug survival in AxSpA was highest for golimumab, compared with all other drugs, followed by secukinumab and etanercept. Survival was lowest for infliximab. In PsA, drug survival was roughly equal for most drugs, including golimumab, secukinumab, and ixekizumab, with the lowest survival observed for tofacitinib and infliximab, compared with all other drugs. Drug survival in psoriasis was highest with guselkumab, followed by ustekinumab and IL-17 inhibitors.

However, the number of treatment series “was low for some drugs, and not all differences were statistically significant, which could influence the overall interpretability of these findings,” the researchers noted in their discussion.

Notably, the high treatment persistence for rituximab in RA patients needs further confirmation, the researchers said. “In Denmark, rituximab is often the biologic drug of choice in RA patients with a history of cancer while there is a reluctancy to use TNF [tumor necrosis factor] inhibitors in such patients; this may have prolonged the drug survival for rituximab treated patients due to limited treatment alternatives,” they said.

The findings were limited by several factors, including the observational study design and changes in guidelines over the course of the study, the researchers noted. Other limitations included the inability to adjust for certain variables, such as antibody status, body weight, and smoking, because of missing data, and a lack of data on the underlying reasons for drug discontinuation, they said.

However, the results were strengthened by the large number of patients and completeness of the registries, the researchers emphasized. The range in responses to different drug types across diseases supports the need for individualized treatments with attention to underlying disease, patient profile, and treatment history, they concluded.

The study received no outside funding. Eight coauthors reported financial ties to a number of pharmaceutical companies.

Survival rates of biologics and other novel immunomodulatory drugs vary substantially across chronic inflammatory diseases, and rates are highest for rituximab in rheumatoid arthritis (RA) and golimumab in axial spondyloarthritis (axSpA), but with similar rates seen for most drugs used in the treatment of psoriasis and psoriatic arthritis (PsA), according to findings from a study of two Danish registries.

Drug survival refers to “the probability that patients will remain on a given drug, and is a proxy for efficacy as well as safety in daily clinical practice,” wrote Alexander Egeberg, MD, PhD, of the department of dermatology at Copenhagen University Hospital–Bispebjerg, and colleagues. Although the use of biologics has expanded for inflammatory diseases, real-world data on drug survival in newer agents such as interleukin (IL)-17, IL-23, and Janus kinase inhibitors are lacking, they said.

In a study published in Seminars in Arthritis and Rheumatism, the researchers reviewed data from the DANBIO and DERMBIO registries of patients in Denmark with inflammatory diseases including rheumatoid arthritis (RA), axial spondyloarthritis (AxSpA), psoriatic arthritis (PsA), and psoriasis.

The study population included 12,089 adults: 5,104 with RA, 2,157 with AxSpA, 2,251 with PsA, and 2,577 with psoriasis. Patients’ mean age at the time of first treatment for these conditions was 57.8 years, 42.3 years, 49 years, and 45 years, respectively. Participants were treated with biologics or novel small molecule therapies for RA, AxSpA, PsA, or psoriasis between January 2015 and May 2021 (from the DANBIO database) and November 2009 to November 2019 (DERMBIO database).

In adjusted models, drug survival in RA was highest for rituximab followed by baricitinib, etanercept, and tocilizumab. Drug survival in AxSpA was highest for golimumab, compared with all other drugs, followed by secukinumab and etanercept. Survival was lowest for infliximab. In PsA, drug survival was roughly equal for most drugs, including golimumab, secukinumab, and ixekizumab, with the lowest survival observed for tofacitinib and infliximab, compared with all other drugs. Drug survival in psoriasis was highest with guselkumab, followed by ustekinumab and IL-17 inhibitors.

However, the number of treatment series “was low for some drugs, and not all differences were statistically significant, which could influence the overall interpretability of these findings,” the researchers noted in their discussion.

Notably, the high treatment persistence for rituximab in RA patients needs further confirmation, the researchers said. “In Denmark, rituximab is often the biologic drug of choice in RA patients with a history of cancer while there is a reluctancy to use TNF [tumor necrosis factor] inhibitors in such patients; this may have prolonged the drug survival for rituximab treated patients due to limited treatment alternatives,” they said.

The findings were limited by several factors, including the observational study design and changes in guidelines over the course of the study, the researchers noted. Other limitations included the inability to adjust for certain variables, such as antibody status, body weight, and smoking, because of missing data, and a lack of data on the underlying reasons for drug discontinuation, they said.

However, the results were strengthened by the large number of patients and completeness of the registries, the researchers emphasized. The range in responses to different drug types across diseases supports the need for individualized treatments with attention to underlying disease, patient profile, and treatment history, they concluded.

The study received no outside funding. Eight coauthors reported financial ties to a number of pharmaceutical companies.

White-to-pink friable plaques occurring acutely in the vulva is concerning for one form of secondary syphilis that affects mucous membranes: condyloma lata.

Known as the great imitator for its variety of clinical presentations, syphilis is a sexually transmitted infection (STI) caused by the spirochete Treponema pallidum. Three to 10 days following contact with the spirochete, a painless ulcer or chancre forms and subsequently resolves—sometimes without notice.

Secondary syphilis develops from hematogenous spread of bacteria taking many forms—most commonly a widespread rash over the whole body of many (although sometimes faint) macules or papules up to about 1 cm in size and haphazardly spread out about every 1 cm. Palms and soles may be affected, even if faintly. Another, less common form of secondary syphilis includes the friable plaques (often in the anogenital area, as pictured) that are highly concentrated with bacteria. These occur 3 to 12 weeks after the appearance of a primary chancre and are variably symptomatic.

The differential diagnosis includes genital warts, vulvar carcinoma, and pemphigus vegetans. The relatively rapid, multifocal presentation helps to separate this disorder from vulvar carcinoma. A biopsy can distinguish the 2. However, diagnosis is better made with serology using nontreponemal tests, such as the rapid plasma reagin (RPR) test. Treponemal tests (assaying immunoglobulin [Ig]M and IgG to Treponema pallidum) are also an option and are very specific. Following this, an RPR titer can help guide treatment. Darkfield microscopy, which can reveal spirochetes directly, isn’t readily available but could be used to diagnose condyloma lata.

Patients who have been given a diagnosis of syphilis should be offered screening for other STIs, including HIV. Anyone who has had sexual contact with the patient within the previous 90 days should be notified, tested, and treated. Patients with primary or secondary syphilis should be treated with 2.4 million units of intramuscular (IM) benzathine penicillin G in a single dose—regardless of whether they test positive for HIV. To exclude tertiary syphilis, a careful neurologic exam should take place at the time of diagnosis and again 6 and 12 months after treatment (sooner if follow-up may be uncertain). Consider treatment failure if RPR titers haven’t fallen fourfold in 12 months. In 2022, the Centers for Disease Control and Prevention released a notice that COVID-19-vaccinated patients may have false-positive RPR titers performed from Bio-Rad Laboratories (BioPlex 2200 Syphilis Total & RPR kit).¹

In this case, the patient tested positive for treponemal antibodies and had an RPR titer of 1:128. She was treated with IM benzathine penicillin with lasting clearance.

‌

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

White-to-pink friable plaques occurring acutely in the vulva is concerning for one form of secondary syphilis that affects mucous membranes: condyloma lata.

Known as the great imitator for its variety of clinical presentations, syphilis is a sexually transmitted infection (STI) caused by the spirochete Treponema pallidum. Three to 10 days following contact with the spirochete, a painless ulcer or chancre forms and subsequently resolves—sometimes without notice.

Secondary syphilis develops from hematogenous spread of bacteria taking many forms—most commonly a widespread rash over the whole body of many (although sometimes faint) macules or papules up to about 1 cm in size and haphazardly spread out about every 1 cm. Palms and soles may be affected, even if faintly. Another, less common form of secondary syphilis includes the friable plaques (often in the anogenital area, as pictured) that are highly concentrated with bacteria. These occur 3 to 12 weeks after the appearance of a primary chancre and are variably symptomatic.

The differential diagnosis includes genital warts, vulvar carcinoma, and pemphigus vegetans. The relatively rapid, multifocal presentation helps to separate this disorder from vulvar carcinoma. A biopsy can distinguish the 2. However, diagnosis is better made with serology using nontreponemal tests, such as the rapid plasma reagin (RPR) test. Treponemal tests (assaying immunoglobulin [Ig]M and IgG to Treponema pallidum) are also an option and are very specific. Following this, an RPR titer can help guide treatment. Darkfield microscopy, which can reveal spirochetes directly, isn’t readily available but could be used to diagnose condyloma lata.

Patients who have been given a diagnosis of syphilis should be offered screening for other STIs, including HIV. Anyone who has had sexual contact with the patient within the previous 90 days should be notified, tested, and treated. Patients with primary or secondary syphilis should be treated with 2.4 million units of intramuscular (IM) benzathine penicillin G in a single dose—regardless of whether they test positive for HIV. To exclude tertiary syphilis, a careful neurologic exam should take place at the time of diagnosis and again 6 and 12 months after treatment (sooner if follow-up may be uncertain). Consider treatment failure if RPR titers haven’t fallen fourfold in 12 months. In 2022, the Centers for Disease Control and Prevention released a notice that COVID-19-vaccinated patients may have false-positive RPR titers performed from Bio-Rad Laboratories (BioPlex 2200 Syphilis Total & RPR kit).¹

In this case, the patient tested positive for treponemal antibodies and had an RPR titer of 1:128. She was treated with IM benzathine penicillin with lasting clearance.

‌

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

White-to-pink friable plaques occurring acutely in the vulva is concerning for one form of secondary syphilis that affects mucous membranes: condyloma lata.

Known as the great imitator for its variety of clinical presentations, syphilis is a sexually transmitted infection (STI) caused by the spirochete Treponema pallidum. Three to 10 days following contact with the spirochete, a painless ulcer or chancre forms and subsequently resolves—sometimes without notice.

Secondary syphilis develops from hematogenous spread of bacteria taking many forms—most commonly a widespread rash over the whole body of many (although sometimes faint) macules or papules up to about 1 cm in size and haphazardly spread out about every 1 cm. Palms and soles may be affected, even if faintly. Another, less common form of secondary syphilis includes the friable plaques (often in the anogenital area, as pictured) that are highly concentrated with bacteria. These occur 3 to 12 weeks after the appearance of a primary chancre and are variably symptomatic.

The differential diagnosis includes genital warts, vulvar carcinoma, and pemphigus vegetans. The relatively rapid, multifocal presentation helps to separate this disorder from vulvar carcinoma. A biopsy can distinguish the 2. However, diagnosis is better made with serology using nontreponemal tests, such as the rapid plasma reagin (RPR) test. Treponemal tests (assaying immunoglobulin [Ig]M and IgG to Treponema pallidum) are also an option and are very specific. Following this, an RPR titer can help guide treatment. Darkfield microscopy, which can reveal spirochetes directly, isn’t readily available but could be used to diagnose condyloma lata.

Patients who have been given a diagnosis of syphilis should be offered screening for other STIs, including HIV. Anyone who has had sexual contact with the patient within the previous 90 days should be notified, tested, and treated. Patients with primary or secondary syphilis should be treated with 2.4 million units of intramuscular (IM) benzathine penicillin G in a single dose—regardless of whether they test positive for HIV. To exclude tertiary syphilis, a careful neurologic exam should take place at the time of diagnosis and again 6 and 12 months after treatment (sooner if follow-up may be uncertain). Consider treatment failure if RPR titers haven’t fallen fourfold in 12 months. In 2022, the Centers for Disease Control and Prevention released a notice that COVID-19-vaccinated patients may have false-positive RPR titers performed from Bio-Rad Laboratories (BioPlex 2200 Syphilis Total & RPR kit).¹

In this case, the patient tested positive for treponemal antibodies and had an RPR titer of 1:128. She was treated with IM benzathine penicillin with lasting clearance.

‌

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

THE COMPARISON

A Multicolored (pink, brown, and white) indurated plaques in a butterfly distribution on the face of a 30-year-old woman with a darker skin tone.

B Pink, elevated, indurated plaques with hypopigmentation in a butterfly distribution on the face of a 19-year-old woman with a lighter skin tone.

Cutaneous lupus erythematosus may occur with or without systemic lupus erythematosus. Discoid lupus erythematosus (DLE), a form of chronic cutaneous lupus, is most commonly found on the scalp, face, and ears.¹

Epidemiology

DLE is most common in adult women (age range, 20–40 years).² It occurs more frequently in women of African descent.^3,4

Key clinical features in people with darker skin tones

Clinical features of DLE lesions include erythema, induration, follicular plugging, dyspigmentation, and scarring alopecia.¹ In patients of African descent, lesions may be annular and hypopigmented to depigmented centrally with a border of hyperpigmentation. Active lesions may be painful and/or pruritic.²

DLE lesions occur in photodistributed areas, although not exclusively. Photoprotective clothing and sunscreen are an important part of the treatment plan.¹ Although sunscreen is recommended for patients with DLE, those with darker skin tones may find some sunscreens cosmetically unappealing due to a mismatch with their normal skin color.⁵ Tinted sunscreens may be beneficial additions.

Worth noting

Approximately 5% to 25% of patients with cutaneous lupus go on to develop systemic lupus erythematosus.⁶

Health disparity highlight

Discoid lesions may cause cutaneous scars that are quite disfiguring and may negatively impact quality of life. Some patients may have a few scattered lesions, whereas others have extensive disease covering most of the scalp. DLE lesions of the scalp have classic clinical features including hair loss, erythema, hypopigmentation, and hyperpigmentation. The clinician’s comfort with performing a scalp examination with cultural humility is an important acquired skill and is especially important when the examination is performed on patients with more tightly coiled hair.⁷ For example, physicians may adopt the “compliment, discuss, and suggest” method when counseling patients.⁸

THE COMPARISON

A Multicolored (pink, brown, and white) indurated plaques in a butterfly distribution on the face of a 30-year-old woman with a darker skin tone.

B Pink, elevated, indurated plaques with hypopigmentation in a butterfly distribution on the face of a 19-year-old woman with a lighter skin tone.

Cutaneous lupus erythematosus may occur with or without systemic lupus erythematosus. Discoid lupus erythematosus (DLE), a form of chronic cutaneous lupus, is most commonly found on the scalp, face, and ears.¹

Epidemiology

DLE is most common in adult women (age range, 20–40 years).² It occurs more frequently in women of African descent.^3,4

Key clinical features in people with darker skin tones

Clinical features of DLE lesions include erythema, induration, follicular plugging, dyspigmentation, and scarring alopecia.¹ In patients of African descent, lesions may be annular and hypopigmented to depigmented centrally with a border of hyperpigmentation. Active lesions may be painful and/or pruritic.²

DLE lesions occur in photodistributed areas, although not exclusively. Photoprotective clothing and sunscreen are an important part of the treatment plan.¹ Although sunscreen is recommended for patients with DLE, those with darker skin tones may find some sunscreens cosmetically unappealing due to a mismatch with their normal skin color.⁵ Tinted sunscreens may be beneficial additions.

Worth noting

Approximately 5% to 25% of patients with cutaneous lupus go on to develop systemic lupus erythematosus.⁶

Health disparity highlight

Discoid lesions may cause cutaneous scars that are quite disfiguring and may negatively impact quality of life. Some patients may have a few scattered lesions, whereas others have extensive disease covering most of the scalp. DLE lesions of the scalp have classic clinical features including hair loss, erythema, hypopigmentation, and hyperpigmentation. The clinician’s comfort with performing a scalp examination with cultural humility is an important acquired skill and is especially important when the examination is performed on patients with more tightly coiled hair.⁷ For example, physicians may adopt the “compliment, discuss, and suggest” method when counseling patients.⁸

THE COMPARISON

A Multicolored (pink, brown, and white) indurated plaques in a butterfly distribution on the face of a 30-year-old woman with a darker skin tone.

B Pink, elevated, indurated plaques with hypopigmentation in a butterfly distribution on the face of a 19-year-old woman with a lighter skin tone.

Cutaneous lupus erythematosus may occur with or without systemic lupus erythematosus. Discoid lupus erythematosus (DLE), a form of chronic cutaneous lupus, is most commonly found on the scalp, face, and ears.¹

Epidemiology

DLE is most common in adult women (age range, 20–40 years).² It occurs more frequently in women of African descent.^3,4

Key clinical features in people with darker skin tones

Clinical features of DLE lesions include erythema, induration, follicular plugging, dyspigmentation, and scarring alopecia.¹ In patients of African descent, lesions may be annular and hypopigmented to depigmented centrally with a border of hyperpigmentation. Active lesions may be painful and/or pruritic.²

DLE lesions occur in photodistributed areas, although not exclusively. Photoprotective clothing and sunscreen are an important part of the treatment plan.¹ Although sunscreen is recommended for patients with DLE, those with darker skin tones may find some sunscreens cosmetically unappealing due to a mismatch with their normal skin color.⁵ Tinted sunscreens may be beneficial additions.

Worth noting

Approximately 5% to 25% of patients with cutaneous lupus go on to develop systemic lupus erythematosus.⁶

Health disparity highlight

Discoid lesions may cause cutaneous scars that are quite disfiguring and may negatively impact quality of life. Some patients may have a few scattered lesions, whereas others have extensive disease covering most of the scalp. DLE lesions of the scalp have classic clinical features including hair loss, erythema, hypopigmentation, and hyperpigmentation. The clinician’s comfort with performing a scalp examination with cultural humility is an important acquired skill and is especially important when the examination is performed on patients with more tightly coiled hair.⁷ For example, physicians may adopt the “compliment, discuss, and suggest” method when counseling patients.⁸

A large-scale meta-analysis has verified that the gut microbiome does influence patients’s response to immune checkpoint inhibitor (ICI) therapy in advanced melanoma, but the relationship appears to be more complex than previously thought.

Overall, researchers identified a panel of species, including Roseburia spp. and Akkermansia muciniphila, associated with responses to ICI therapy. However, no single species was a “fully consistent biomarker” across the studies, the authors explain.

This “machine learning analysis confirmed the link between the microbiome and overall response rates (ORRs) and progression-free survival (PFS) with ICIs but also revealed limited reproducibility of microbiome-based signatures across cohorts,” Karla A. Lee, PhD, a clinical research fellow at King’s College London, and colleagues report. The results suggest that “the microbiome is predictive of response in some, but not all, cohorts.”

The findings were published online Feb. 28 in Nature Medicine.

Despite recent advances in targeted therapies for melanoma, less than half of the those who receive a single-agent ICI respond, and those who receive combination ICI therapy often suffer from severe drug toxicity problems. That is why finding patients more likely to respond to a single-agent ICI has become a priority.

Previous studies have identified the gut microbiome as “a potential biomarker of response, as well as a therapeutic target” in melanoma and other malignancies, but “little consensus exists on which microbiome characteristics are associated with treatment responses in the human setting,” the authors explain.

To further clarify the microbiome–immunotherapy relationship, the researchers performed metagenomic sequencing of stool samples collected from 165 ICI-naive patients with unresectable stage III or IV cutaneous melanoma from 5 observational cohorts in the Netherlands, United Kingdom, and Spain. These data were integrated with 147 samples from publicly available datasets.

First, the authors highlighted the variability in findings across these observational studies. For instance, they analyzed stool samples from one UK-based observational study of patients with melanoma (PRIMM-UK) and found a small but statistically significant difference in the microbiome composition of immunotherapy responders versus nonresponders (P = .05) but did not find such an association in a parallel study in the Netherlands (PRIMM-NL, P = .61).

The investigators also explored biomarkers of response across different cohorts and found several standouts. In trials using ORR as an endpoint, two uncultivated Roseburia species (CAG:182 and CAG:471) were associated with responses to ICIs. For patients with available PFS data, Phascolarctobacterium succinatutens and Lactobacillus vaginalis were “enriched in responders” across 7 datasets and significant in 3 of the 8 meta-analysis approaches. A muciniphila and Dorea formicigenerans were also associated with ORR and PFS at 12 months in several meta-analyses.

However, “no single bacterium was a fully consistent biomarker of response across all datasets,” the authors wrote.

Still, the findings could have important implications for the more than 50% of patients with advanced melanoma who don’t respond to single-agent ICI therapy.

“Our study shows that studying the microbiome is important to improve and personalize immunotherapy treatments for melanoma,” study coauthor Nicola Segata, PhD, principal investigator in the Laboratory of Computational Metagenomics, University of Trento, Italy, said in a press release. “However, it also suggests that because of the person-to-person variability of the gut microbiome, even larger studies must be carried out to understand the specific gut microbial features that are more likely to lead to a positive response to immunotherapy.”

Coauthor Tim Spector, PhD, head of the Department of Twin Research & Genetic Epidemiology at King’s College London, added that “the ultimate goal is to identify which specific features of the microbiome are directly influencing the clinical benefits of immunotherapy to exploit these features in new personalized approaches to support cancer immunotherapy.”

In the meantime, he said, “this study highlights the potential impact of good diet and gut health on chances of survival in patients undergoing immunotherapy.”

This study was coordinated by King’s College London, CIBIO Department of the University of Trento and European Institute of Oncology in Italy, and the University of Groningen in the Netherlands, and was funded by the Seerave Foundation. Dr. Lee, Dr. Segata, and Dr. Spector have disclosed no relevant financial relationships.

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

A large-scale meta-analysis has verified that the gut microbiome does influence patients’s response to immune checkpoint inhibitor (ICI) therapy in advanced melanoma, but the relationship appears to be more complex than previously thought.

Overall, researchers identified a panel of species, including Roseburia spp. and Akkermansia muciniphila, associated with responses to ICI therapy. However, no single species was a “fully consistent biomarker” across the studies, the authors explain.

This “machine learning analysis confirmed the link between the microbiome and overall response rates (ORRs) and progression-free survival (PFS) with ICIs but also revealed limited reproducibility of microbiome-based signatures across cohorts,” Karla A. Lee, PhD, a clinical research fellow at King’s College London, and colleagues report. The results suggest that “the microbiome is predictive of response in some, but not all, cohorts.”

The findings were published online Feb. 28 in Nature Medicine.

Despite recent advances in targeted therapies for melanoma, less than half of the those who receive a single-agent ICI respond, and those who receive combination ICI therapy often suffer from severe drug toxicity problems. That is why finding patients more likely to respond to a single-agent ICI has become a priority.

Previous studies have identified the gut microbiome as “a potential biomarker of response, as well as a therapeutic target” in melanoma and other malignancies, but “little consensus exists on which microbiome characteristics are associated with treatment responses in the human setting,” the authors explain.

To further clarify the microbiome–immunotherapy relationship, the researchers performed metagenomic sequencing of stool samples collected from 165 ICI-naive patients with unresectable stage III or IV cutaneous melanoma from 5 observational cohorts in the Netherlands, United Kingdom, and Spain. These data were integrated with 147 samples from publicly available datasets.

First, the authors highlighted the variability in findings across these observational studies. For instance, they analyzed stool samples from one UK-based observational study of patients with melanoma (PRIMM-UK) and found a small but statistically significant difference in the microbiome composition of immunotherapy responders versus nonresponders (P = .05) but did not find such an association in a parallel study in the Netherlands (PRIMM-NL, P = .61).

The investigators also explored biomarkers of response across different cohorts and found several standouts. In trials using ORR as an endpoint, two uncultivated Roseburia species (CAG:182 and CAG:471) were associated with responses to ICIs. For patients with available PFS data, Phascolarctobacterium succinatutens and Lactobacillus vaginalis were “enriched in responders” across 7 datasets and significant in 3 of the 8 meta-analysis approaches. A muciniphila and Dorea formicigenerans were also associated with ORR and PFS at 12 months in several meta-analyses.

However, “no single bacterium was a fully consistent biomarker of response across all datasets,” the authors wrote.

Still, the findings could have important implications for the more than 50% of patients with advanced melanoma who don’t respond to single-agent ICI therapy.

“Our study shows that studying the microbiome is important to improve and personalize immunotherapy treatments for melanoma,” study coauthor Nicola Segata, PhD, principal investigator in the Laboratory of Computational Metagenomics, University of Trento, Italy, said in a press release. “However, it also suggests that because of the person-to-person variability of the gut microbiome, even larger studies must be carried out to understand the specific gut microbial features that are more likely to lead to a positive response to immunotherapy.”

Coauthor Tim Spector, PhD, head of the Department of Twin Research & Genetic Epidemiology at King’s College London, added that “the ultimate goal is to identify which specific features of the microbiome are directly influencing the clinical benefits of immunotherapy to exploit these features in new personalized approaches to support cancer immunotherapy.”

In the meantime, he said, “this study highlights the potential impact of good diet and gut health on chances of survival in patients undergoing immunotherapy.”

This study was coordinated by King’s College London, CIBIO Department of the University of Trento and European Institute of Oncology in Italy, and the University of Groningen in the Netherlands, and was funded by the Seerave Foundation. Dr. Lee, Dr. Segata, and Dr. Spector have disclosed no relevant financial relationships.

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

A large-scale meta-analysis has verified that the gut microbiome does influence patients’s response to immune checkpoint inhibitor (ICI) therapy in advanced melanoma, but the relationship appears to be more complex than previously thought.

Overall, researchers identified a panel of species, including Roseburia spp. and Akkermansia muciniphila, associated with responses to ICI therapy. However, no single species was a “fully consistent biomarker” across the studies, the authors explain.

This “machine learning analysis confirmed the link between the microbiome and overall response rates (ORRs) and progression-free survival (PFS) with ICIs but also revealed limited reproducibility of microbiome-based signatures across cohorts,” Karla A. Lee, PhD, a clinical research fellow at King’s College London, and colleagues report. The results suggest that “the microbiome is predictive of response in some, but not all, cohorts.”

The findings were published online Feb. 28 in Nature Medicine.

Despite recent advances in targeted therapies for melanoma, less than half of the those who receive a single-agent ICI respond, and those who receive combination ICI therapy often suffer from severe drug toxicity problems. That is why finding patients more likely to respond to a single-agent ICI has become a priority.

Previous studies have identified the gut microbiome as “a potential biomarker of response, as well as a therapeutic target” in melanoma and other malignancies, but “little consensus exists on which microbiome characteristics are associated with treatment responses in the human setting,” the authors explain.

To further clarify the microbiome–immunotherapy relationship, the researchers performed metagenomic sequencing of stool samples collected from 165 ICI-naive patients with unresectable stage III or IV cutaneous melanoma from 5 observational cohorts in the Netherlands, United Kingdom, and Spain. These data were integrated with 147 samples from publicly available datasets.

First, the authors highlighted the variability in findings across these observational studies. For instance, they analyzed stool samples from one UK-based observational study of patients with melanoma (PRIMM-UK) and found a small but statistically significant difference in the microbiome composition of immunotherapy responders versus nonresponders (P = .05) but did not find such an association in a parallel study in the Netherlands (PRIMM-NL, P = .61).

The investigators also explored biomarkers of response across different cohorts and found several standouts. In trials using ORR as an endpoint, two uncultivated Roseburia species (CAG:182 and CAG:471) were associated with responses to ICIs. For patients with available PFS data, Phascolarctobacterium succinatutens and Lactobacillus vaginalis were “enriched in responders” across 7 datasets and significant in 3 of the 8 meta-analysis approaches. A muciniphila and Dorea formicigenerans were also associated with ORR and PFS at 12 months in several meta-analyses.

However, “no single bacterium was a fully consistent biomarker of response across all datasets,” the authors wrote.

Still, the findings could have important implications for the more than 50% of patients with advanced melanoma who don’t respond to single-agent ICI therapy.

“Our study shows that studying the microbiome is important to improve and personalize immunotherapy treatments for melanoma,” study coauthor Nicola Segata, PhD, principal investigator in the Laboratory of Computational Metagenomics, University of Trento, Italy, said in a press release. “However, it also suggests that because of the person-to-person variability of the gut microbiome, even larger studies must be carried out to understand the specific gut microbial features that are more likely to lead to a positive response to immunotherapy.”

Coauthor Tim Spector, PhD, head of the Department of Twin Research & Genetic Epidemiology at King’s College London, added that “the ultimate goal is to identify which specific features of the microbiome are directly influencing the clinical benefits of immunotherapy to exploit these features in new personalized approaches to support cancer immunotherapy.”

In the meantime, he said, “this study highlights the potential impact of good diet and gut health on chances of survival in patients undergoing immunotherapy.”

This study was coordinated by King’s College London, CIBIO Department of the University of Trento and European Institute of Oncology in Italy, and the University of Groningen in the Netherlands, and was funded by the Seerave Foundation. Dr. Lee, Dr. Segata, and Dr. Spector have disclosed no relevant financial relationships.

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

A new study has found that methotrexate plus leflunomide outperforms methotrexate alone as a treatment option for patients with psoriatic arthritis (PsA).

“We believe that prescribing this combination in routine practice is viable when combined with shared decision-making and strict monitoring of side effects,” write Michelle L.M. Mulder, MD, of the department of rheumatology at Sint Maartenskliniek in Nijmegen, the Netherlands, and her coauthors. Their findings were published in The Lancet Rheumatology.

The latest treatment guidelines from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the European Alliance of Associations for Rheumatology recommend conventional synthetic disease-modifying antirheumatic drugs for patients with active PsA, but Dr. Mulder and her colleagues note a distinct lack of information on their effectiveness, especially this particular combination.

To assess the efficacy and safety of methotrexate plus leflunomide, they launched a single-center, double-blind, randomized trial that included 78 Dutch patients with PsA. The majority of the participants in this trial – dubbed COMPLETE-PsA – were men (64%), and the median age of the patients was 55 years. All had active disease at baseline; the median swollen joint count (SJC) and tender joint count were 4.0 in both groups.

Participants were assigned to receive either methotrexate plus leflunomide (n = 39) or methotrexate plus placebo (n = 39). After 16 weeks, mean Psoriatic Arthritis Disease Activity Score (PASDAS) had improved for patients in the combination therapy group in comparison with the monotherapy group (3.1; standard deviation, 1.4 vs. 3.7; SD, 1.3; treatment difference, –0.6; 90% confidence interval, –1.0 to –0.1; P = .025). The combination therapy group also achieved PASDAS low disease activity at a higher rate (59%) than did the monotherapy group (34%; P = .019).

Other notable differences after 16 weeks included improvements in SJC for 66 joints (–3.0 in the combination therapy group vs. –2.0 in the monotherapy group) and significantly better skin and nail measures – such as active psoriasis and change in body surface area – in the methotrexate plus leflunomide group.

When asked who should be prescribed the combination therapy and who should be prescribed methotrexate going forward, Dr. Mulder told this news organization, “At the moment, we have insufficient knowledge on who will benefit most or who will develop clinically relevant side effects. It seems warranted to discuss with every patient which approach they would prefer. This could be a step-down or -up approach.

“We hope to be able to better predict treatment response and side effects in the future via post hoc analysis of our study and via extensive flow-cytometric phenotyping of immune blood cells taken at baseline,” she added.

Three patients in the combination therapy group experienced serious adverse events, two of which were deemed unrelated to leflunomide. The most frequently occurring adverse events were nausea or vomiting, tiredness, and elevated alanine aminotransferase. Mild adverse events were more common in the methotrexate plus leflunomide group. No participants died, and all patients with adverse events recovered completely.

“It appears good practice to do blood draws for laboratory tests on liver enzymes at least monthly for the first 4 months and every 4 months after that once stable dosing is achieved, as well as have a telephone consultation after 6-8 weeks to talk about possible side effects a patient might experience and change or add therapy if necessary,” Dr. Mulder added.

Study turns perception of combination therapy into reality

It had already been perceived by rheumatologists that methotrexate plus leflunomide was an effective combo for PsA, and this study reinforces those beliefs, Clementina López-Medina, MD, PhD, and colleagues from the University of Cordoba (Spain), write in an accompanying editorial.

They highlight this study’s notable strengths, one of which was defining “active disease” as two or more swollen joints, which opened the study up to a larger patient population. The editorialists also underline the confirmation that leflunomide plus methotrexate reduces both joint symptoms and skin involvement in this subset of patients, which had also been found in a previous study.

“Leflunomide is usually considered as a second-line option after methotrexate is unsuccessful,” they note, “despite the fact that methotrexate did not show superiority over placebo in previous trials.”

The editorialists were not surprised that the combination therapy was more toxic than the monotherapy. Rheumatologists could use these data to individualize treatment accordingly, they write, while keeping an eye on “gastrointestinal disturbances.”

Overall, Dr. López-Medina and colleagues say that the study results should “be considered not only in daily clinical practice but also in the development of future recommendations.”

Leflunomide: Forgotten no longer, at least for PsA

“I think we probably underutilize leflunomide,” Arthur Kavanaugh, MD, professor of medicine and director of the Center for Innovative Therapy at the University of California, San Diego, told this news organization. “Sometimes medicines get ‘old,’ for lack of a better term, and fall a little bit of out of favor, sometimes unnecessarily. Leflunomide falls into that category. Because it’s older, it doesn’t get as much buzz as what’s new and shiny.

“I was not surprised by the results on the joints,” he said, “because we know from previous studies that leflunomide works in that regard. What did surprise me is that the skin got better, especially with the combination.”

Regarding the side effects for the combination therapy, he commended the authors for limiting potential uncertainty by using such a high dose of methotrexate.

“By going with a dose of 25 mg [per week], no one can say, ‘They pulled their punches and methotrexate monotherapy would’ve been just as good if it was given at a higher dose,’ “ he said. “And they also used leflunomide at a high dose. It makes you wonder: Could you use lower doses, and do lower doses mean fewer lab test abnormalities? This positive study does lend itself to some other permutations in terms of study design.

“Even though this was a small study,” he added, “it brings us right back to: We should really consider leflunomide in the treatment of PsA.”

The authors acknowledge their study’s limitations, including the fact that it was conducted in a single country and the absence of a nontreatment placebo group. They also note the higher percentage of women in the methotrexate plus leflunomide group, “which might have lowered the treatment response and increased the adverse event rate, resulting in bias.”

The study was funded by a Regional Junior Researcher Grant from Sint Maartenskliniek. The authors reported numerous potential conflicts of interest, including receiving payment, research grants, and consulting and speaker fees from various pharmaceutical companies.

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

A new study has found that methotrexate plus leflunomide outperforms methotrexate alone as a treatment option for patients with psoriatic arthritis (PsA).

“We believe that prescribing this combination in routine practice is viable when combined with shared decision-making and strict monitoring of side effects,” write Michelle L.M. Mulder, MD, of the department of rheumatology at Sint Maartenskliniek in Nijmegen, the Netherlands, and her coauthors. Their findings were published in The Lancet Rheumatology.

The latest treatment guidelines from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the European Alliance of Associations for Rheumatology recommend conventional synthetic disease-modifying antirheumatic drugs for patients with active PsA, but Dr. Mulder and her colleagues note a distinct lack of information on their effectiveness, especially this particular combination.

To assess the efficacy and safety of methotrexate plus leflunomide, they launched a single-center, double-blind, randomized trial that included 78 Dutch patients with PsA. The majority of the participants in this trial – dubbed COMPLETE-PsA – were men (64%), and the median age of the patients was 55 years. All had active disease at baseline; the median swollen joint count (SJC) and tender joint count were 4.0 in both groups.

Participants were assigned to receive either methotrexate plus leflunomide (n = 39) or methotrexate plus placebo (n = 39). After 16 weeks, mean Psoriatic Arthritis Disease Activity Score (PASDAS) had improved for patients in the combination therapy group in comparison with the monotherapy group (3.1; standard deviation, 1.4 vs. 3.7; SD, 1.3; treatment difference, –0.6; 90% confidence interval, –1.0 to –0.1; P = .025). The combination therapy group also achieved PASDAS low disease activity at a higher rate (59%) than did the monotherapy group (34%; P = .019).

Other notable differences after 16 weeks included improvements in SJC for 66 joints (–3.0 in the combination therapy group vs. –2.0 in the monotherapy group) and significantly better skin and nail measures – such as active psoriasis and change in body surface area – in the methotrexate plus leflunomide group.

When asked who should be prescribed the combination therapy and who should be prescribed methotrexate going forward, Dr. Mulder told this news organization, “At the moment, we have insufficient knowledge on who will benefit most or who will develop clinically relevant side effects. It seems warranted to discuss with every patient which approach they would prefer. This could be a step-down or -up approach.

“We hope to be able to better predict treatment response and side effects in the future via post hoc analysis of our study and via extensive flow-cytometric phenotyping of immune blood cells taken at baseline,” she added.

Three patients in the combination therapy group experienced serious adverse events, two of which were deemed unrelated to leflunomide. The most frequently occurring adverse events were nausea or vomiting, tiredness, and elevated alanine aminotransferase. Mild adverse events were more common in the methotrexate plus leflunomide group. No participants died, and all patients with adverse events recovered completely.

“It appears good practice to do blood draws for laboratory tests on liver enzymes at least monthly for the first 4 months and every 4 months after that once stable dosing is achieved, as well as have a telephone consultation after 6-8 weeks to talk about possible side effects a patient might experience and change or add therapy if necessary,” Dr. Mulder added.

Study turns perception of combination therapy into reality

It had already been perceived by rheumatologists that methotrexate plus leflunomide was an effective combo for PsA, and this study reinforces those beliefs, Clementina López-Medina, MD, PhD, and colleagues from the University of Cordoba (Spain), write in an accompanying editorial.

They highlight this study’s notable strengths, one of which was defining “active disease” as two or more swollen joints, which opened the study up to a larger patient population. The editorialists also underline the confirmation that leflunomide plus methotrexate reduces both joint symptoms and skin involvement in this subset of patients, which had also been found in a previous study.

“Leflunomide is usually considered as a second-line option after methotrexate is unsuccessful,” they note, “despite the fact that methotrexate did not show superiority over placebo in previous trials.”

The editorialists were not surprised that the combination therapy was more toxic than the monotherapy. Rheumatologists could use these data to individualize treatment accordingly, they write, while keeping an eye on “gastrointestinal disturbances.”

Overall, Dr. López-Medina and colleagues say that the study results should “be considered not only in daily clinical practice but also in the development of future recommendations.”

Leflunomide: Forgotten no longer, at least for PsA

“I think we probably underutilize leflunomide,” Arthur Kavanaugh, MD, professor of medicine and director of the Center for Innovative Therapy at the University of California, San Diego, told this news organization. “Sometimes medicines get ‘old,’ for lack of a better term, and fall a little bit of out of favor, sometimes unnecessarily. Leflunomide falls into that category. Because it’s older, it doesn’t get as much buzz as what’s new and shiny.

“I was not surprised by the results on the joints,” he said, “because we know from previous studies that leflunomide works in that regard. What did surprise me is that the skin got better, especially with the combination.”

Regarding the side effects for the combination therapy, he commended the authors for limiting potential uncertainty by using such a high dose of methotrexate.

“By going with a dose of 25 mg [per week], no one can say, ‘They pulled their punches and methotrexate monotherapy would’ve been just as good if it was given at a higher dose,’ “ he said. “And they also used leflunomide at a high dose. It makes you wonder: Could you use lower doses, and do lower doses mean fewer lab test abnormalities? This positive study does lend itself to some other permutations in terms of study design.

“Even though this was a small study,” he added, “it brings us right back to: We should really consider leflunomide in the treatment of PsA.”

The authors acknowledge their study’s limitations, including the fact that it was conducted in a single country and the absence of a nontreatment placebo group. They also note the higher percentage of women in the methotrexate plus leflunomide group, “which might have lowered the treatment response and increased the adverse event rate, resulting in bias.”

The study was funded by a Regional Junior Researcher Grant from Sint Maartenskliniek. The authors reported numerous potential conflicts of interest, including receiving payment, research grants, and consulting and speaker fees from various pharmaceutical companies.

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

A new study has found that methotrexate plus leflunomide outperforms methotrexate alone as a treatment option for patients with psoriatic arthritis (PsA).

“We believe that prescribing this combination in routine practice is viable when combined with shared decision-making and strict monitoring of side effects,” write Michelle L.M. Mulder, MD, of the department of rheumatology at Sint Maartenskliniek in Nijmegen, the Netherlands, and her coauthors. Their findings were published in The Lancet Rheumatology.

The latest treatment guidelines from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the European Alliance of Associations for Rheumatology recommend conventional synthetic disease-modifying antirheumatic drugs for patients with active PsA, but Dr. Mulder and her colleagues note a distinct lack of information on their effectiveness, especially this particular combination.

To assess the efficacy and safety of methotrexate plus leflunomide, they launched a single-center, double-blind, randomized trial that included 78 Dutch patients with PsA. The majority of the participants in this trial – dubbed COMPLETE-PsA – were men (64%), and the median age of the patients was 55 years. All had active disease at baseline; the median swollen joint count (SJC) and tender joint count were 4.0 in both groups.

Participants were assigned to receive either methotrexate plus leflunomide (n = 39) or methotrexate plus placebo (n = 39). After 16 weeks, mean Psoriatic Arthritis Disease Activity Score (PASDAS) had improved for patients in the combination therapy group in comparison with the monotherapy group (3.1; standard deviation, 1.4 vs. 3.7; SD, 1.3; treatment difference, –0.6; 90% confidence interval, –1.0 to –0.1; P = .025). The combination therapy group also achieved PASDAS low disease activity at a higher rate (59%) than did the monotherapy group (34%; P = .019).

Other notable differences after 16 weeks included improvements in SJC for 66 joints (–3.0 in the combination therapy group vs. –2.0 in the monotherapy group) and significantly better skin and nail measures – such as active psoriasis and change in body surface area – in the methotrexate plus leflunomide group.

When asked who should be prescribed the combination therapy and who should be prescribed methotrexate going forward, Dr. Mulder told this news organization, “At the moment, we have insufficient knowledge on who will benefit most or who will develop clinically relevant side effects. It seems warranted to discuss with every patient which approach they would prefer. This could be a step-down or -up approach.

“We hope to be able to better predict treatment response and side effects in the future via post hoc analysis of our study and via extensive flow-cytometric phenotyping of immune blood cells taken at baseline,” she added.

Three patients in the combination therapy group experienced serious adverse events, two of which were deemed unrelated to leflunomide. The most frequently occurring adverse events were nausea or vomiting, tiredness, and elevated alanine aminotransferase. Mild adverse events were more common in the methotrexate plus leflunomide group. No participants died, and all patients with adverse events recovered completely.

“It appears good practice to do blood draws for laboratory tests on liver enzymes at least monthly for the first 4 months and every 4 months after that once stable dosing is achieved, as well as have a telephone consultation after 6-8 weeks to talk about possible side effects a patient might experience and change or add therapy if necessary,” Dr. Mulder added.

Study turns perception of combination therapy into reality

It had already been perceived by rheumatologists that methotrexate plus leflunomide was an effective combo for PsA, and this study reinforces those beliefs, Clementina López-Medina, MD, PhD, and colleagues from the University of Cordoba (Spain), write in an accompanying editorial.

They highlight this study’s notable strengths, one of which was defining “active disease” as two or more swollen joints, which opened the study up to a larger patient population. The editorialists also underline the confirmation that leflunomide plus methotrexate reduces both joint symptoms and skin involvement in this subset of patients, which had also been found in a previous study.

“Leflunomide is usually considered as a second-line option after methotrexate is unsuccessful,” they note, “despite the fact that methotrexate did not show superiority over placebo in previous trials.”

The editorialists were not surprised that the combination therapy was more toxic than the monotherapy. Rheumatologists could use these data to individualize treatment accordingly, they write, while keeping an eye on “gastrointestinal disturbances.”

Overall, Dr. López-Medina and colleagues say that the study results should “be considered not only in daily clinical practice but also in the development of future recommendations.”

Leflunomide: Forgotten no longer, at least for PsA

“I think we probably underutilize leflunomide,” Arthur Kavanaugh, MD, professor of medicine and director of the Center for Innovative Therapy at the University of California, San Diego, told this news organization. “Sometimes medicines get ‘old,’ for lack of a better term, and fall a little bit of out of favor, sometimes unnecessarily. Leflunomide falls into that category. Because it’s older, it doesn’t get as much buzz as what’s new and shiny.

“I was not surprised by the results on the joints,” he said, “because we know from previous studies that leflunomide works in that regard. What did surprise me is that the skin got better, especially with the combination.”

Regarding the side effects for the combination therapy, he commended the authors for limiting potential uncertainty by using such a high dose of methotrexate.

“By going with a dose of 25 mg [per week], no one can say, ‘They pulled their punches and methotrexate monotherapy would’ve been just as good if it was given at a higher dose,’ “ he said. “And they also used leflunomide at a high dose. It makes you wonder: Could you use lower doses, and do lower doses mean fewer lab test abnormalities? This positive study does lend itself to some other permutations in terms of study design.

“Even though this was a small study,” he added, “it brings us right back to: We should really consider leflunomide in the treatment of PsA.”

The authors acknowledge their study’s limitations, including the fact that it was conducted in a single country and the absence of a nontreatment placebo group. They also note the higher percentage of women in the methotrexate plus leflunomide group, “which might have lowered the treatment response and increased the adverse event rate, resulting in bias.”

The study was funded by a Regional Junior Researcher Grant from Sint Maartenskliniek. The authors reported numerous potential conflicts of interest, including receiving payment, research grants, and consulting and speaker fees from various pharmaceutical companies.

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