Dermatology

A 4-mm punch biopsy performed on the central portion of a lesion revealed thickening of the epidermis and altered collagen in the dermis consistent with acquired reactive perforating collagenosis (ARPC).

ARPC is strongly associated with diabetes, renal disease, and malignancy. ARPC manifests as an eruption of intensely pruritic papules to small plaques (with a central plug or firm dry depression) on the trunk, or more commonly, on the extremities. The etiology is unclear but altered collagen from systemic disease, trauma, or cold exposure may trigger collagen elimination.¹ Secondary infection may occur due to the intensity of itching. ARPC develops in adulthood; epidemiologic data are lacking and prevalence has not been systematically assessed.²

Treatment approaches are based on small case reports and case series. Common antipruritic therapies, such as topical and intralesional steroids, oral antihistamines, and vitamin-D analogues, have had mixed success. UV therapy is effective for nephrogenic pruritus; case reports suggest it has also been helpful for ARPC. Similarly, keratolytics and topical and systemic retinoids have shown promise. Allopurinol, which reduces free radicals, has also demonstrated its utility.³

This patient was started on topical triamcinolone 0.1% cream bid and narrowband UV-B phototherapy 3 times weekly with marked improvement in her itching. Lesions decreased in number over 3 months of follow-up but did not completely resolve.

‌

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

A 4-mm punch biopsy performed on the central portion of a lesion revealed thickening of the epidermis and altered collagen in the dermis consistent with acquired reactive perforating collagenosis (ARPC).

ARPC is strongly associated with diabetes, renal disease, and malignancy. ARPC manifests as an eruption of intensely pruritic papules to small plaques (with a central plug or firm dry depression) on the trunk, or more commonly, on the extremities. The etiology is unclear but altered collagen from systemic disease, trauma, or cold exposure may trigger collagen elimination.¹ Secondary infection may occur due to the intensity of itching. ARPC develops in adulthood; epidemiologic data are lacking and prevalence has not been systematically assessed.²

Treatment approaches are based on small case reports and case series. Common antipruritic therapies, such as topical and intralesional steroids, oral antihistamines, and vitamin-D analogues, have had mixed success. UV therapy is effective for nephrogenic pruritus; case reports suggest it has also been helpful for ARPC. Similarly, keratolytics and topical and systemic retinoids have shown promise. Allopurinol, which reduces free radicals, has also demonstrated its utility.³

This patient was started on topical triamcinolone 0.1% cream bid and narrowband UV-B phototherapy 3 times weekly with marked improvement in her itching. Lesions decreased in number over 3 months of follow-up but did not completely resolve.

‌

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

A 4-mm punch biopsy performed on the central portion of a lesion revealed thickening of the epidermis and altered collagen in the dermis consistent with acquired reactive perforating collagenosis (ARPC).

ARPC is strongly associated with diabetes, renal disease, and malignancy. ARPC manifests as an eruption of intensely pruritic papules to small plaques (with a central plug or firm dry depression) on the trunk, or more commonly, on the extremities. The etiology is unclear but altered collagen from systemic disease, trauma, or cold exposure may trigger collagen elimination.¹ Secondary infection may occur due to the intensity of itching. ARPC develops in adulthood; epidemiologic data are lacking and prevalence has not been systematically assessed.²

Treatment approaches are based on small case reports and case series. Common antipruritic therapies, such as topical and intralesional steroids, oral antihistamines, and vitamin-D analogues, have had mixed success. UV therapy is effective for nephrogenic pruritus; case reports suggest it has also been helpful for ARPC. Similarly, keratolytics and topical and systemic retinoids have shown promise. Allopurinol, which reduces free radicals, has also demonstrated its utility.³

This patient was started on topical triamcinolone 0.1% cream bid and narrowband UV-B phototherapy 3 times weekly with marked improvement in her itching. Lesions decreased in number over 3 months of follow-up but did not completely resolve.

‌

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

A 55-YEAR-OLD MAN with hypertension and untreated hepatitis C virus (HCV) was referred to the Dermatology Clinic after reporting a 2-year history of photosensitivity and intermittent episodes of blistering and scars on the dorsal side of his hands and feet. No alcohol consumption or drug use was reported.

Physical examination revealed small and shallow erosions on the dorsal aspect of the hands and feet (but no visible blisters) and milium cysts (FIGURE 1A). Additionally, hypertrichosis and hyperpigmentation were observed in the zygomatic areas (FIGURE 1B). Complete blood count and kidney function test results were within normal ranges. Liver function tests showed slightly elevated levels of alanine aminotransferase (79 U/L; normal range, 0-41 U/L), aspartate aminotransferase (62 U/L; normal range, 0-40 U/L), and ferritin (121 ng/mL; normal range, 30-100 ng/mL). Serologies for syphilis, HIV, and hepatitis B virus were negative.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Diagnosis: Porphyria cutanea tarda

The clinical presentation, along with the elevated laboratory values, suggested that this might be a case of porphyria cutanea tarda (PCT). Therefore, a sample of the patient’s urine was examined under Wood lamp and compared to a sample from a healthy control. In the sample of urine from our patient, a vivid red-pink fluorescence could be visualized under the lamp (FIGURE 2), confirming the diagnosis.

The porphyrias are a group of metabolic diseases that affect the heme biosynthesis. They can be classified into 1 of 3 groups, according to clinical features:

• acute hepatic porphyrias, with neurovisceral symptoms (eg, acute intermittent porphyria),
• nonblistering cutaneous porphyrias, with severe photosensitivity but without bullae formation (eg, erythropoietic protoporphyria), or
• blistering cutaneous porphyrias (eg, PCT, hepatoerythropoietic porphyria, and variegate porphyria).

PCT is the most common type of porphyria, with a global prevalence of 1 per 10,000 people.^1,2 It affects adults after the third or fourth decade of life.

Porphyria cutanea tarda has a global prevalance of 1 per 10,000 people.

PCT involves dysfunction of the uroporphyrinogen decarboxylase enzyme (UROD), the fifth enzyme in heme biosynthesis, which catalyzes the conversion of uroporphyrinogen to coproporphyrinogen. This dysfunction causes the accumulation of porphyrinogens that are auto-oxidized to photosensitizing porphyrins.^1-4 PCT can be classified as “sporadic” or “familial” based on the absence or presence of UROD mutation. Approximately 80% of cases of PCT are sporadic.²

In sporadic PCT, triggers for UROD dysfunction include alcohol use, use of estrogens, hemochromatosis or iron overload, chronic HCV infection, and HIV infection.^1-4 HCV (which this patient had) is the most common infection associated with sporadic PCT, with a prevalence of about 50% among these patients.⁵

Continue to: Dermatologic manifestations of PCT

Dermatologic manifestations of PCT include photosensitivity, skin fragility, vesicles, bullae, erosions, and crusts observed in sun-exposed areas. A nonvirilizing type of hypertrichosis may appear prominently on the temples and the cheeks.^2-4 After blisters rupture, atrophy and scarring occur. Milia cysts can form on the dorsal side of the hands and fingers. Less common manifestations include pruritus, scarring alopecia, sclerodermatous changes, and periorbital purple-red suffusion.

Hepatic involvement is demonstrated with elevated serum transaminases and ­gamma-glutamyl transpeptidase. Hepatomegaly is common, and cirrhosis manifests in 30% to 40% of patients.^2-5 On liver biopsy, some degree of siderosis is found in 80% of patients with PCT, and most of them have increased levels of serum iron. The incidence of hepatocellular carcinoma in patients with PCT is greater than in patients with other liver diseases.²

A Wood lamp can be a useful diagnostic first step

Plasma or urine porphyrin lab tests are the gold standard for PCT diagnosis. These tests can be followed by more specific tests (eg, porphyrin fractionation) to exclude other forms of porphyria. However, if plasma or urine porphyrin testing is not readily available, a good first step is a Wood lamp exam, which can be performed on urine or stool. (Plasma or urine porphyrin testing may ultimately be necessary if there is doubt about the diagnosis following the Wood lamp screening.) Histopathologic examination does not confirm the diagnosis of PCT⁴; however, it can be helpful in differential diagnosis.

Wood lamp is a source of long-wave UV light (320 to 400 nm), visualized as a purple or violet light. When porphyrins are present in a urine sample, a red-pink fluorescence may be seen.^3,4,6 The Wood lamp examination should be performed in a completely dark room after the lamp has been warmed up for about 1 minute; time should be allowed for the clinician’s vision to adapt to the dark.⁶ There are no data regarding the sensitivity or specificity of the Wood lamp test in the diagnosis of PCT.

These conditions also cause skin fragility and photosensitivity

The differential diagnosis for PCT includes diseases that also cause skin fragility, blistering, or photosensitivity, such as pseudoporphyria, bullous systemic lupus erythematosus (SLE), and epidermolysis bullosa acquisita (EBA).³

Continue to: In pseudoporphyria

In pseudoporphyria, the clinical findings may be indistinguishable from PCT. Thus, the patient’s history will be especially important; suspect pseudoporphyria if the patient has a history of chronic renal failure or use of a photosensitizing drug.^1,3

Bullous SLE usually manifests with systemic involvement and widespread, tense bullae. Serologic investigation will demonstrate the presence of antinuclear antibodies in high titers (> 1:80), as well as other circulating autoantibodies.

Skin lesions of EBA usually manifest with skin fragility and noninflammatory tense bullae in traumatized skin, such as the extensor surfaces of the hands, feet, and fingers.

None of the above-mentioned diagnoses manifest with hypertrichosis or red-pink fluorescent urine on Wood lamp, and results of porphyrin studies would be normal.³

Address triggers, provide treatment

Once the diagnosis is confirmed, steps must be taken to avoid triggering factors, such as any alcohol consumption, use of estrogen, sun exposure (until plasma porphyrin levels are normal), and potential sources of excessive iron intake.

If plasma or urine porphyrin testing is not readily available, a good first step is a Wood lamp exam.

Two therapeutic options are available for treating PCT—whether it’s sporadic or familial. Phlebotomy sessions reduce iron overload and iron depletion and may prevent the formation of a porphomethene inhibitor of UROD. The other treatment option is antimalarial agents—usually hydroxychloroquine— and is indicated for patients with lower serum ferritin levels.^1-4 In patients with HCV-associated PCT, effective treatment of the infection has resulted in resolution of the PCT, in some cases.³

Treatment involving phlebotomy or an antimalarial agent can be stopped when plasma porphyrins reach normal levels.

Our patient was initially managed with 2 sessions of phlebotomy. He subsequently received treatment for the HCV infection at another hospital.

A 55-YEAR-OLD MAN with hypertension and untreated hepatitis C virus (HCV) was referred to the Dermatology Clinic after reporting a 2-year history of photosensitivity and intermittent episodes of blistering and scars on the dorsal side of his hands and feet. No alcohol consumption or drug use was reported.

Physical examination revealed small and shallow erosions on the dorsal aspect of the hands and feet (but no visible blisters) and milium cysts (FIGURE 1A). Additionally, hypertrichosis and hyperpigmentation were observed in the zygomatic areas (FIGURE 1B). Complete blood count and kidney function test results were within normal ranges. Liver function tests showed slightly elevated levels of alanine aminotransferase (79 U/L; normal range, 0-41 U/L), aspartate aminotransferase (62 U/L; normal range, 0-40 U/L), and ferritin (121 ng/mL; normal range, 30-100 ng/mL). Serologies for syphilis, HIV, and hepatitis B virus were negative.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Diagnosis: Porphyria cutanea tarda

The clinical presentation, along with the elevated laboratory values, suggested that this might be a case of porphyria cutanea tarda (PCT). Therefore, a sample of the patient’s urine was examined under Wood lamp and compared to a sample from a healthy control. In the sample of urine from our patient, a vivid red-pink fluorescence could be visualized under the lamp (FIGURE 2), confirming the diagnosis.

The porphyrias are a group of metabolic diseases that affect the heme biosynthesis. They can be classified into 1 of 3 groups, according to clinical features:

• acute hepatic porphyrias, with neurovisceral symptoms (eg, acute intermittent porphyria),
• nonblistering cutaneous porphyrias, with severe photosensitivity but without bullae formation (eg, erythropoietic protoporphyria), or
• blistering cutaneous porphyrias (eg, PCT, hepatoerythropoietic porphyria, and variegate porphyria).

PCT is the most common type of porphyria, with a global prevalence of 1 per 10,000 people.^1,2 It affects adults after the third or fourth decade of life.

Porphyria cutanea tarda has a global prevalance of 1 per 10,000 people.

PCT involves dysfunction of the uroporphyrinogen decarboxylase enzyme (UROD), the fifth enzyme in heme biosynthesis, which catalyzes the conversion of uroporphyrinogen to coproporphyrinogen. This dysfunction causes the accumulation of porphyrinogens that are auto-oxidized to photosensitizing porphyrins.^1-4 PCT can be classified as “sporadic” or “familial” based on the absence or presence of UROD mutation. Approximately 80% of cases of PCT are sporadic.²

In sporadic PCT, triggers for UROD dysfunction include alcohol use, use of estrogens, hemochromatosis or iron overload, chronic HCV infection, and HIV infection.^1-4 HCV (which this patient had) is the most common infection associated with sporadic PCT, with a prevalence of about 50% among these patients.⁵

Continue to: Dermatologic manifestations of PCT

Dermatologic manifestations of PCT include photosensitivity, skin fragility, vesicles, bullae, erosions, and crusts observed in sun-exposed areas. A nonvirilizing type of hypertrichosis may appear prominently on the temples and the cheeks.^2-4 After blisters rupture, atrophy and scarring occur. Milia cysts can form on the dorsal side of the hands and fingers. Less common manifestations include pruritus, scarring alopecia, sclerodermatous changes, and periorbital purple-red suffusion.

Hepatic involvement is demonstrated with elevated serum transaminases and ­gamma-glutamyl transpeptidase. Hepatomegaly is common, and cirrhosis manifests in 30% to 40% of patients.^2-5 On liver biopsy, some degree of siderosis is found in 80% of patients with PCT, and most of them have increased levels of serum iron. The incidence of hepatocellular carcinoma in patients with PCT is greater than in patients with other liver diseases.²

A Wood lamp can be a useful diagnostic first step

Plasma or urine porphyrin lab tests are the gold standard for PCT diagnosis. These tests can be followed by more specific tests (eg, porphyrin fractionation) to exclude other forms of porphyria. However, if plasma or urine porphyrin testing is not readily available, a good first step is a Wood lamp exam, which can be performed on urine or stool. (Plasma or urine porphyrin testing may ultimately be necessary if there is doubt about the diagnosis following the Wood lamp screening.) Histopathologic examination does not confirm the diagnosis of PCT⁴; however, it can be helpful in differential diagnosis.

Wood lamp is a source of long-wave UV light (320 to 400 nm), visualized as a purple or violet light. When porphyrins are present in a urine sample, a red-pink fluorescence may be seen.^3,4,6 The Wood lamp examination should be performed in a completely dark room after the lamp has been warmed up for about 1 minute; time should be allowed for the clinician’s vision to adapt to the dark.⁶ There are no data regarding the sensitivity or specificity of the Wood lamp test in the diagnosis of PCT.

These conditions also cause skin fragility and photosensitivity

The differential diagnosis for PCT includes diseases that also cause skin fragility, blistering, or photosensitivity, such as pseudoporphyria, bullous systemic lupus erythematosus (SLE), and epidermolysis bullosa acquisita (EBA).³

Continue to: In pseudoporphyria

In pseudoporphyria, the clinical findings may be indistinguishable from PCT. Thus, the patient’s history will be especially important; suspect pseudoporphyria if the patient has a history of chronic renal failure or use of a photosensitizing drug.^1,3

Bullous SLE usually manifests with systemic involvement and widespread, tense bullae. Serologic investigation will demonstrate the presence of antinuclear antibodies in high titers (> 1:80), as well as other circulating autoantibodies.

Skin lesions of EBA usually manifest with skin fragility and noninflammatory tense bullae in traumatized skin, such as the extensor surfaces of the hands, feet, and fingers.

None of the above-mentioned diagnoses manifest with hypertrichosis or red-pink fluorescent urine on Wood lamp, and results of porphyrin studies would be normal.³

Address triggers, provide treatment

Once the diagnosis is confirmed, steps must be taken to avoid triggering factors, such as any alcohol consumption, use of estrogen, sun exposure (until plasma porphyrin levels are normal), and potential sources of excessive iron intake.

If plasma or urine porphyrin testing is not readily available, a good first step is a Wood lamp exam.

Two therapeutic options are available for treating PCT—whether it’s sporadic or familial. Phlebotomy sessions reduce iron overload and iron depletion and may prevent the formation of a porphomethene inhibitor of UROD. The other treatment option is antimalarial agents—usually hydroxychloroquine— and is indicated for patients with lower serum ferritin levels.^1-4 In patients with HCV-associated PCT, effective treatment of the infection has resulted in resolution of the PCT, in some cases.³

Treatment involving phlebotomy or an antimalarial agent can be stopped when plasma porphyrins reach normal levels.

Our patient was initially managed with 2 sessions of phlebotomy. He subsequently received treatment for the HCV infection at another hospital.

A 55-YEAR-OLD MAN with hypertension and untreated hepatitis C virus (HCV) was referred to the Dermatology Clinic after reporting a 2-year history of photosensitivity and intermittent episodes of blistering and scars on the dorsal side of his hands and feet. No alcohol consumption or drug use was reported.

Physical examination revealed small and shallow erosions on the dorsal aspect of the hands and feet (but no visible blisters) and milium cysts (FIGURE 1A). Additionally, hypertrichosis and hyperpigmentation were observed in the zygomatic areas (FIGURE 1B). Complete blood count and kidney function test results were within normal ranges. Liver function tests showed slightly elevated levels of alanine aminotransferase (79 U/L; normal range, 0-41 U/L), aspartate aminotransferase (62 U/L; normal range, 0-40 U/L), and ferritin (121 ng/mL; normal range, 30-100 ng/mL). Serologies for syphilis, HIV, and hepatitis B virus were negative.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Diagnosis: Porphyria cutanea tarda

The clinical presentation, along with the elevated laboratory values, suggested that this might be a case of porphyria cutanea tarda (PCT). Therefore, a sample of the patient’s urine was examined under Wood lamp and compared to a sample from a healthy control. In the sample of urine from our patient, a vivid red-pink fluorescence could be visualized under the lamp (FIGURE 2), confirming the diagnosis.

The porphyrias are a group of metabolic diseases that affect the heme biosynthesis. They can be classified into 1 of 3 groups, according to clinical features:

• acute hepatic porphyrias, with neurovisceral symptoms (eg, acute intermittent porphyria),
• nonblistering cutaneous porphyrias, with severe photosensitivity but without bullae formation (eg, erythropoietic protoporphyria), or
• blistering cutaneous porphyrias (eg, PCT, hepatoerythropoietic porphyria, and variegate porphyria).

PCT is the most common type of porphyria, with a global prevalence of 1 per 10,000 people.^1,2 It affects adults after the third or fourth decade of life.

Porphyria cutanea tarda has a global prevalance of 1 per 10,000 people.

PCT involves dysfunction of the uroporphyrinogen decarboxylase enzyme (UROD), the fifth enzyme in heme biosynthesis, which catalyzes the conversion of uroporphyrinogen to coproporphyrinogen. This dysfunction causes the accumulation of porphyrinogens that are auto-oxidized to photosensitizing porphyrins.^1-4 PCT can be classified as “sporadic” or “familial” based on the absence or presence of UROD mutation. Approximately 80% of cases of PCT are sporadic.²

In sporadic PCT, triggers for UROD dysfunction include alcohol use, use of estrogens, hemochromatosis or iron overload, chronic HCV infection, and HIV infection.^1-4 HCV (which this patient had) is the most common infection associated with sporadic PCT, with a prevalence of about 50% among these patients.⁵

Continue to: Dermatologic manifestations of PCT

Dermatologic manifestations of PCT include photosensitivity, skin fragility, vesicles, bullae, erosions, and crusts observed in sun-exposed areas. A nonvirilizing type of hypertrichosis may appear prominently on the temples and the cheeks.^2-4 After blisters rupture, atrophy and scarring occur. Milia cysts can form on the dorsal side of the hands and fingers. Less common manifestations include pruritus, scarring alopecia, sclerodermatous changes, and periorbital purple-red suffusion.

Hepatic involvement is demonstrated with elevated serum transaminases and ­gamma-glutamyl transpeptidase. Hepatomegaly is common, and cirrhosis manifests in 30% to 40% of patients.^2-5 On liver biopsy, some degree of siderosis is found in 80% of patients with PCT, and most of them have increased levels of serum iron. The incidence of hepatocellular carcinoma in patients with PCT is greater than in patients with other liver diseases.²

A Wood lamp can be a useful diagnostic first step

Plasma or urine porphyrin lab tests are the gold standard for PCT diagnosis. These tests can be followed by more specific tests (eg, porphyrin fractionation) to exclude other forms of porphyria. However, if plasma or urine porphyrin testing is not readily available, a good first step is a Wood lamp exam, which can be performed on urine or stool. (Plasma or urine porphyrin testing may ultimately be necessary if there is doubt about the diagnosis following the Wood lamp screening.) Histopathologic examination does not confirm the diagnosis of PCT⁴; however, it can be helpful in differential diagnosis.

Wood lamp is a source of long-wave UV light (320 to 400 nm), visualized as a purple or violet light. When porphyrins are present in a urine sample, a red-pink fluorescence may be seen.^3,4,6 The Wood lamp examination should be performed in a completely dark room after the lamp has been warmed up for about 1 minute; time should be allowed for the clinician’s vision to adapt to the dark.⁶ There are no data regarding the sensitivity or specificity of the Wood lamp test in the diagnosis of PCT.

These conditions also cause skin fragility and photosensitivity

The differential diagnosis for PCT includes diseases that also cause skin fragility, blistering, or photosensitivity, such as pseudoporphyria, bullous systemic lupus erythematosus (SLE), and epidermolysis bullosa acquisita (EBA).³

Continue to: In pseudoporphyria

In pseudoporphyria, the clinical findings may be indistinguishable from PCT. Thus, the patient’s history will be especially important; suspect pseudoporphyria if the patient has a history of chronic renal failure or use of a photosensitizing drug.^1,3

Bullous SLE usually manifests with systemic involvement and widespread, tense bullae. Serologic investigation will demonstrate the presence of antinuclear antibodies in high titers (> 1:80), as well as other circulating autoantibodies.

Skin lesions of EBA usually manifest with skin fragility and noninflammatory tense bullae in traumatized skin, such as the extensor surfaces of the hands, feet, and fingers.

None of the above-mentioned diagnoses manifest with hypertrichosis or red-pink fluorescent urine on Wood lamp, and results of porphyrin studies would be normal.³

Address triggers, provide treatment

Once the diagnosis is confirmed, steps must be taken to avoid triggering factors, such as any alcohol consumption, use of estrogen, sun exposure (until plasma porphyrin levels are normal), and potential sources of excessive iron intake.

If plasma or urine porphyrin testing is not readily available, a good first step is a Wood lamp exam.

Two therapeutic options are available for treating PCT—whether it’s sporadic or familial. Phlebotomy sessions reduce iron overload and iron depletion and may prevent the formation of a porphomethene inhibitor of UROD. The other treatment option is antimalarial agents—usually hydroxychloroquine— and is indicated for patients with lower serum ferritin levels.^1-4 In patients with HCV-associated PCT, effective treatment of the infection has resulted in resolution of the PCT, in some cases.³

Treatment involving phlebotomy or an antimalarial agent can be stopped when plasma porphyrins reach normal levels.

Our patient was initially managed with 2 sessions of phlebotomy. He subsequently received treatment for the HCV infection at another hospital.

NEW YORK – Patients with chronic plaque psoriasis face a nearly twofold increased risk of nonalcoholic fatty liver disease (NAFLD), and the risk climbs higher in those with more severe skin involvement – and probably in those with psoriatic arthritis (PsA) as well, according to a systematic review and meta-analysis presented at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

“Our findings imply that psoriatic patients should be screened with an ultrasonographic exam in cases where there are metabolic features that are associated with NAFLD,” reported Francesco Bellinato, MD, a researcher in the section of dermatology and venereology, University of Verona (Italy).

In the pooled data, the risk of NAFLD among those with psoriasis relative to healthy controls fell just short of a twofold increase (odds ratio, 1.96; 95% CI, 1.70-2.26; P < .001). When stratified by studies that confirmed NAFLD by biopsy relative to ultrasonography, there was no significant heterogeneity.

Eight of the studies included an analysis of relative risk in the context of skin lesion severity defined by Psoriasis Area and Severity Index (PASI) score. Relative to those without NAFLD, psoriatic patients with NAFLD had a significant greater mean PASI score on a pooled weighted mean difference analysis (OR, 3.93; 95% CI, 2.01-5.84; P < .0001).

courtesy Dr. Francesco Belinato

For PsA relative to no PsA in the five studies that compared risk between these two groups, the risk of NAFLD was again nearly twofold higher. This fell short of conventional definition of statistical significance, but it was associated with a strong trend (OR, 1.83; 95% CI, 0.98-3.43; P = .06).

The risk of NAFLD among patients with psoriasis was not found to vary significantly when assessed by univariable meta-regressions across numerous characteristics, such as sex and body mass index.

In one of the largest of the observational studies included in the meta-analysis by Alexis Ogdie, MD, associate professor of medicine and epidemiology at the University of Pennsylvania, Philadelphia, and colleagues, data were analyzed in more than 1.5 million patients, which included 54,251 patients with rheumatoid arthritis. While the hazard ratio of NAFLD was increased for both psoriasis (HR, 2.23) and PsA (HR, 2.11), it was not elevated in those with RA (HR, 0.96).

Risk by severity, possible mechanisms

This study also included an analysis of NAFLD risk according to psoriasis severity. While risk was still significant among those with mild disease (HR, 1.18; 95% CI, 1.07-1.30), it was almost twofold greater in those with moderate to severe psoriasis (HR, 2.23; 95% CI, 1.73-2.87).

Dr. Bellinato conceded that the mechanisms underlying the association between psoriasis and NAFLD are unknown, but he said “metaflammation” is suspected.

“The secretion of proinflammatory, prothrombotic, and oxidative stress mediators in both psoriatic skin and adipose tissue might act systemically and promote insulin resistance and other metabolic derangements that promote the development and progression of NAFLD,” Dr. Bellinato explained.

He thinks that noninvasive screening methods, such as currently used methods to calculate fibrosis score, might be useful for evaluating patients with psoriasis for NAFLD and referring them to a hepatologist when appropriate.

Given the strong association with NAFLD, Dr. Bellinato suggested that “the findings of this meta-analysis pave the way for novel, large, prospective, and histologically based studies.”

Courtesy Dr. Joel M. Gelfand

The association between psoriasis and NAFLD is clinically relevant, agreed Joel M. Gelfand, MD, vice-chair of clinical research and medical director of the clinical studies unit, department of dermatology, University of Pennsylvania, Philadelphia.

“It is not clear if psoriasis causes fatty liver disease or vice versa, but clinicians should be aware of this association,” he said in an interview. Dr. Gelfand was a coauthor of the study by Dr. Ogdie and colleagues and led another more recent population-based study that implicated methotrexate as a factor in psoriasis-related hepatotoxicity.

If NAFLD is identified in a patient with psoriasis, treatments are limited, but Dr. Gelfand suggested that patients should be made aware of the risk. “Clinicians should encourage patients with psoriasis to take measures to protect their liver, such as avoiding drinking alcohol to excess and trying to maintain a healthy body weight,” he said.

Dr. Bellinato reported no conflicts of interest. Dr. Gelfand has financial relationships with more than 10 pharmaceutical companies, including those that make therapies for psoriasis.

NEW YORK – Patients with chronic plaque psoriasis face a nearly twofold increased risk of nonalcoholic fatty liver disease (NAFLD), and the risk climbs higher in those with more severe skin involvement – and probably in those with psoriatic arthritis (PsA) as well, according to a systematic review and meta-analysis presented at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

“Our findings imply that psoriatic patients should be screened with an ultrasonographic exam in cases where there are metabolic features that are associated with NAFLD,” reported Francesco Bellinato, MD, a researcher in the section of dermatology and venereology, University of Verona (Italy).

In the pooled data, the risk of NAFLD among those with psoriasis relative to healthy controls fell just short of a twofold increase (odds ratio, 1.96; 95% CI, 1.70-2.26; P < .001). When stratified by studies that confirmed NAFLD by biopsy relative to ultrasonography, there was no significant heterogeneity.

Eight of the studies included an analysis of relative risk in the context of skin lesion severity defined by Psoriasis Area and Severity Index (PASI) score. Relative to those without NAFLD, psoriatic patients with NAFLD had a significant greater mean PASI score on a pooled weighted mean difference analysis (OR, 3.93; 95% CI, 2.01-5.84; P < .0001).

courtesy Dr. Francesco Belinato

For PsA relative to no PsA in the five studies that compared risk between these two groups, the risk of NAFLD was again nearly twofold higher. This fell short of conventional definition of statistical significance, but it was associated with a strong trend (OR, 1.83; 95% CI, 0.98-3.43; P = .06).

The risk of NAFLD among patients with psoriasis was not found to vary significantly when assessed by univariable meta-regressions across numerous characteristics, such as sex and body mass index.

In one of the largest of the observational studies included in the meta-analysis by Alexis Ogdie, MD, associate professor of medicine and epidemiology at the University of Pennsylvania, Philadelphia, and colleagues, data were analyzed in more than 1.5 million patients, which included 54,251 patients with rheumatoid arthritis. While the hazard ratio of NAFLD was increased for both psoriasis (HR, 2.23) and PsA (HR, 2.11), it was not elevated in those with RA (HR, 0.96).

Risk by severity, possible mechanisms

This study also included an analysis of NAFLD risk according to psoriasis severity. While risk was still significant among those with mild disease (HR, 1.18; 95% CI, 1.07-1.30), it was almost twofold greater in those with moderate to severe psoriasis (HR, 2.23; 95% CI, 1.73-2.87).

Dr. Bellinato conceded that the mechanisms underlying the association between psoriasis and NAFLD are unknown, but he said “metaflammation” is suspected.

“The secretion of proinflammatory, prothrombotic, and oxidative stress mediators in both psoriatic skin and adipose tissue might act systemically and promote insulin resistance and other metabolic derangements that promote the development and progression of NAFLD,” Dr. Bellinato explained.

He thinks that noninvasive screening methods, such as currently used methods to calculate fibrosis score, might be useful for evaluating patients with psoriasis for NAFLD and referring them to a hepatologist when appropriate.

Given the strong association with NAFLD, Dr. Bellinato suggested that “the findings of this meta-analysis pave the way for novel, large, prospective, and histologically based studies.”

Courtesy Dr. Joel M. Gelfand

The association between psoriasis and NAFLD is clinically relevant, agreed Joel M. Gelfand, MD, vice-chair of clinical research and medical director of the clinical studies unit, department of dermatology, University of Pennsylvania, Philadelphia.

“It is not clear if psoriasis causes fatty liver disease or vice versa, but clinicians should be aware of this association,” he said in an interview. Dr. Gelfand was a coauthor of the study by Dr. Ogdie and colleagues and led another more recent population-based study that implicated methotrexate as a factor in psoriasis-related hepatotoxicity.

If NAFLD is identified in a patient with psoriasis, treatments are limited, but Dr. Gelfand suggested that patients should be made aware of the risk. “Clinicians should encourage patients with psoriasis to take measures to protect their liver, such as avoiding drinking alcohol to excess and trying to maintain a healthy body weight,” he said.

Dr. Bellinato reported no conflicts of interest. Dr. Gelfand has financial relationships with more than 10 pharmaceutical companies, including those that make therapies for psoriasis.

NEW YORK – Patients with chronic plaque psoriasis face a nearly twofold increased risk of nonalcoholic fatty liver disease (NAFLD), and the risk climbs higher in those with more severe skin involvement – and probably in those with psoriatic arthritis (PsA) as well, according to a systematic review and meta-analysis presented at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

“Our findings imply that psoriatic patients should be screened with an ultrasonographic exam in cases where there are metabolic features that are associated with NAFLD,” reported Francesco Bellinato, MD, a researcher in the section of dermatology and venereology, University of Verona (Italy).

In the pooled data, the risk of NAFLD among those with psoriasis relative to healthy controls fell just short of a twofold increase (odds ratio, 1.96; 95% CI, 1.70-2.26; P < .001). When stratified by studies that confirmed NAFLD by biopsy relative to ultrasonography, there was no significant heterogeneity.

Eight of the studies included an analysis of relative risk in the context of skin lesion severity defined by Psoriasis Area and Severity Index (PASI) score. Relative to those without NAFLD, psoriatic patients with NAFLD had a significant greater mean PASI score on a pooled weighted mean difference analysis (OR, 3.93; 95% CI, 2.01-5.84; P < .0001).

courtesy Dr. Francesco Belinato

For PsA relative to no PsA in the five studies that compared risk between these two groups, the risk of NAFLD was again nearly twofold higher. This fell short of conventional definition of statistical significance, but it was associated with a strong trend (OR, 1.83; 95% CI, 0.98-3.43; P = .06).

The risk of NAFLD among patients with psoriasis was not found to vary significantly when assessed by univariable meta-regressions across numerous characteristics, such as sex and body mass index.

In one of the largest of the observational studies included in the meta-analysis by Alexis Ogdie, MD, associate professor of medicine and epidemiology at the University of Pennsylvania, Philadelphia, and colleagues, data were analyzed in more than 1.5 million patients, which included 54,251 patients with rheumatoid arthritis. While the hazard ratio of NAFLD was increased for both psoriasis (HR, 2.23) and PsA (HR, 2.11), it was not elevated in those with RA (HR, 0.96).

Risk by severity, possible mechanisms

This study also included an analysis of NAFLD risk according to psoriasis severity. While risk was still significant among those with mild disease (HR, 1.18; 95% CI, 1.07-1.30), it was almost twofold greater in those with moderate to severe psoriasis (HR, 2.23; 95% CI, 1.73-2.87).

Dr. Bellinato conceded that the mechanisms underlying the association between psoriasis and NAFLD are unknown, but he said “metaflammation” is suspected.

“The secretion of proinflammatory, prothrombotic, and oxidative stress mediators in both psoriatic skin and adipose tissue might act systemically and promote insulin resistance and other metabolic derangements that promote the development and progression of NAFLD,” Dr. Bellinato explained.

He thinks that noninvasive screening methods, such as currently used methods to calculate fibrosis score, might be useful for evaluating patients with psoriasis for NAFLD and referring them to a hepatologist when appropriate.

Given the strong association with NAFLD, Dr. Bellinato suggested that “the findings of this meta-analysis pave the way for novel, large, prospective, and histologically based studies.”

Courtesy Dr. Joel M. Gelfand

The association between psoriasis and NAFLD is clinically relevant, agreed Joel M. Gelfand, MD, vice-chair of clinical research and medical director of the clinical studies unit, department of dermatology, University of Pennsylvania, Philadelphia.

“It is not clear if psoriasis causes fatty liver disease or vice versa, but clinicians should be aware of this association,” he said in an interview. Dr. Gelfand was a coauthor of the study by Dr. Ogdie and colleagues and led another more recent population-based study that implicated methotrexate as a factor in psoriasis-related hepatotoxicity.

If NAFLD is identified in a patient with psoriasis, treatments are limited, but Dr. Gelfand suggested that patients should be made aware of the risk. “Clinicians should encourage patients with psoriasis to take measures to protect their liver, such as avoiding drinking alcohol to excess and trying to maintain a healthy body weight,” he said.

Dr. Bellinato reported no conflicts of interest. Dr. Gelfand has financial relationships with more than 10 pharmaceutical companies, including those that make therapies for psoriasis.

The Food and Drug Administration has approved topical ruxolitinib (Opzelura) for the treatment of nonsegmental vitiligo in patients aged 12 years or older, the manufacturer, Incyte, announced on July 18. The treatment, which was approved for treating mild to moderate atopic dermatitis in September 2021, is a cream formulation of ruxolitinib, a Janus kinase 1 (JAK1)/JAK2 inhibitor.

Previously, no treatment was approved to repigment patients with vitiligo, says David Rosmarin, MD, vice chair for research and education in the department of dermatology at Tufts Medical Center, Boston. “It’s important to have options that we can give to patients that are both safe and effective to get them the desired results,” Dr. Rosmarin, the lead investigator of the phase 3 clinical trials of topical ruxolitinib, said in an interview. Vitiligo is “a disease that can really affect quality of life. Some people [with vitiligo] feel as if they’re being stared at or they’re being bullied; they don’t feel confident. It can affect relationships and intimacy.”

Approval was based on the results of two phase 3 trials (TruE-V1 and TruE-V2) in 674 patients with nonsegmental vitiligo aged 12 years or older. At 24 weeks, about 30% of the patients on treatment, applied twice a day, achieved at least a 75% improvement in the facial Vitiligo Area Scoring Index (F-VASI75), compared with about 8% and 13% among those in the vehicle groups in the two trials.

At 52 weeks, about 50% of the patients treated with topical ruxolitinib achieved F-VASI75.

Also, using self-reporting as measured by the Vitiligo Noticeability Scale, about 30%-40% of patients described their vitiligo as being “a lot less noticeable” or “no longer noticeable” at week 52. Dr. Rosmarin reported the 52-week results at the 2022 annual meeting of the American Academy of Dermatology.

The trial group used 1.5% ruxolitinib cream twice daily for the full year. The vehicle group began using ruxolitinib halfway through the trial. In this group, 26.8% and 29.6% achieved F-VASI 75 at 52 weeks in the two trials.

For treating vitiligo, patients are advised to apply a thin layer of topical ruxolitinib to affected areas twice a day, “up to 10% body surface area,” according to the prescribing information, which adds: “Satisfactory patient response may require treatment … for more than 24 weeks. If the patient does not find the repigmentation meaningful by 24 weeks, the patient should be reevaluated by the health care provider.”

The most common side effects during the vehicle-controlled part of the trials were development of acne and pruritus at the application site, headache, urinary tract infections, erythema at the application site, and pyrexia, according to the company.

The approved label for topical ruxolitinib includes a boxed warning about serious infections, mortality, cancer, major adverse cardiovascular events, and thrombosis – which, the warning notes, is based on reports in patients treated with oral JAK inhibitors for inflammatory conditions.

Dr. Rosmarin believes that using this drug with other therapies, like light treatment, might yield even better responses. The available data are in patients treated with ruxolitinib as monotherapy, without complementary therapies.

William Damsky, MD, PhD, professor of dermatology and dermatopathology at Yale University, New Haven, who was not involved in the trials, said what is most exciting about this drug is its novelty. Although some topical steroids are used off-label to treat vitiligo, their efficacy is far from what’s been observed in these trials of topical ruxolitinib, he told this news organization. “It’s huge for a number of reasons. … One very big reason is it just provides some hope” for the many patients with vitiligo who, over the years, have been told “that there’s nothing that could be done for their disease, and this really changes that.”

Dr. Rosmarin reports financial relationships with over 20 pharmaceutical companies. Dr. Damsky disclosed no relevant financial relationships.

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

The Food and Drug Administration has approved topical ruxolitinib (Opzelura) for the treatment of nonsegmental vitiligo in patients aged 12 years or older, the manufacturer, Incyte, announced on July 18. The treatment, which was approved for treating mild to moderate atopic dermatitis in September 2021, is a cream formulation of ruxolitinib, a Janus kinase 1 (JAK1)/JAK2 inhibitor.

Previously, no treatment was approved to repigment patients with vitiligo, says David Rosmarin, MD, vice chair for research and education in the department of dermatology at Tufts Medical Center, Boston. “It’s important to have options that we can give to patients that are both safe and effective to get them the desired results,” Dr. Rosmarin, the lead investigator of the phase 3 clinical trials of topical ruxolitinib, said in an interview. Vitiligo is “a disease that can really affect quality of life. Some people [with vitiligo] feel as if they’re being stared at or they’re being bullied; they don’t feel confident. It can affect relationships and intimacy.”

Approval was based on the results of two phase 3 trials (TruE-V1 and TruE-V2) in 674 patients with nonsegmental vitiligo aged 12 years or older. At 24 weeks, about 30% of the patients on treatment, applied twice a day, achieved at least a 75% improvement in the facial Vitiligo Area Scoring Index (F-VASI75), compared with about 8% and 13% among those in the vehicle groups in the two trials.

At 52 weeks, about 50% of the patients treated with topical ruxolitinib achieved F-VASI75.

Also, using self-reporting as measured by the Vitiligo Noticeability Scale, about 30%-40% of patients described their vitiligo as being “a lot less noticeable” or “no longer noticeable” at week 52. Dr. Rosmarin reported the 52-week results at the 2022 annual meeting of the American Academy of Dermatology.

The trial group used 1.5% ruxolitinib cream twice daily for the full year. The vehicle group began using ruxolitinib halfway through the trial. In this group, 26.8% and 29.6% achieved F-VASI 75 at 52 weeks in the two trials.

For treating vitiligo, patients are advised to apply a thin layer of topical ruxolitinib to affected areas twice a day, “up to 10% body surface area,” according to the prescribing information, which adds: “Satisfactory patient response may require treatment … for more than 24 weeks. If the patient does not find the repigmentation meaningful by 24 weeks, the patient should be reevaluated by the health care provider.”

The most common side effects during the vehicle-controlled part of the trials were development of acne and pruritus at the application site, headache, urinary tract infections, erythema at the application site, and pyrexia, according to the company.

The approved label for topical ruxolitinib includes a boxed warning about serious infections, mortality, cancer, major adverse cardiovascular events, and thrombosis – which, the warning notes, is based on reports in patients treated with oral JAK inhibitors for inflammatory conditions.

Dr. Rosmarin believes that using this drug with other therapies, like light treatment, might yield even better responses. The available data are in patients treated with ruxolitinib as monotherapy, without complementary therapies.

William Damsky, MD, PhD, professor of dermatology and dermatopathology at Yale University, New Haven, who was not involved in the trials, said what is most exciting about this drug is its novelty. Although some topical steroids are used off-label to treat vitiligo, their efficacy is far from what’s been observed in these trials of topical ruxolitinib, he told this news organization. “It’s huge for a number of reasons. … One very big reason is it just provides some hope” for the many patients with vitiligo who, over the years, have been told “that there’s nothing that could be done for their disease, and this really changes that.”

Dr. Rosmarin reports financial relationships with over 20 pharmaceutical companies. Dr. Damsky disclosed no relevant financial relationships.

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

The Food and Drug Administration has approved topical ruxolitinib (Opzelura) for the treatment of nonsegmental vitiligo in patients aged 12 years or older, the manufacturer, Incyte, announced on July 18. The treatment, which was approved for treating mild to moderate atopic dermatitis in September 2021, is a cream formulation of ruxolitinib, a Janus kinase 1 (JAK1)/JAK2 inhibitor.

Previously, no treatment was approved to repigment patients with vitiligo, says David Rosmarin, MD, vice chair for research and education in the department of dermatology at Tufts Medical Center, Boston. “It’s important to have options that we can give to patients that are both safe and effective to get them the desired results,” Dr. Rosmarin, the lead investigator of the phase 3 clinical trials of topical ruxolitinib, said in an interview. Vitiligo is “a disease that can really affect quality of life. Some people [with vitiligo] feel as if they’re being stared at or they’re being bullied; they don’t feel confident. It can affect relationships and intimacy.”

Approval was based on the results of two phase 3 trials (TruE-V1 and TruE-V2) in 674 patients with nonsegmental vitiligo aged 12 years or older. At 24 weeks, about 30% of the patients on treatment, applied twice a day, achieved at least a 75% improvement in the facial Vitiligo Area Scoring Index (F-VASI75), compared with about 8% and 13% among those in the vehicle groups in the two trials.

At 52 weeks, about 50% of the patients treated with topical ruxolitinib achieved F-VASI75.

Also, using self-reporting as measured by the Vitiligo Noticeability Scale, about 30%-40% of patients described their vitiligo as being “a lot less noticeable” or “no longer noticeable” at week 52. Dr. Rosmarin reported the 52-week results at the 2022 annual meeting of the American Academy of Dermatology.

The trial group used 1.5% ruxolitinib cream twice daily for the full year. The vehicle group began using ruxolitinib halfway through the trial. In this group, 26.8% and 29.6% achieved F-VASI 75 at 52 weeks in the two trials.

For treating vitiligo, patients are advised to apply a thin layer of topical ruxolitinib to affected areas twice a day, “up to 10% body surface area,” according to the prescribing information, which adds: “Satisfactory patient response may require treatment … for more than 24 weeks. If the patient does not find the repigmentation meaningful by 24 weeks, the patient should be reevaluated by the health care provider.”

The most common side effects during the vehicle-controlled part of the trials were development of acne and pruritus at the application site, headache, urinary tract infections, erythema at the application site, and pyrexia, according to the company.

The approved label for topical ruxolitinib includes a boxed warning about serious infections, mortality, cancer, major adverse cardiovascular events, and thrombosis – which, the warning notes, is based on reports in patients treated with oral JAK inhibitors for inflammatory conditions.

Dr. Rosmarin believes that using this drug with other therapies, like light treatment, might yield even better responses. The available data are in patients treated with ruxolitinib as monotherapy, without complementary therapies.

William Damsky, MD, PhD, professor of dermatology and dermatopathology at Yale University, New Haven, who was not involved in the trials, said what is most exciting about this drug is its novelty. Although some topical steroids are used off-label to treat vitiligo, their efficacy is far from what’s been observed in these trials of topical ruxolitinib, he told this news organization. “It’s huge for a number of reasons. … One very big reason is it just provides some hope” for the many patients with vitiligo who, over the years, have been told “that there’s nothing that could be done for their disease, and this really changes that.”

Dr. Rosmarin reports financial relationships with over 20 pharmaceutical companies. Dr. Damsky disclosed no relevant financial relationships.

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

Patients who take methotrexate for a variety of immune-mediated inflammatory diseases and pause taking the drug following receipt of a COVID-19 vaccine dose did not have a higher risk of disease flare and had higher antireceptor binding domain (anti-RBD) antibody titers and increased immunogenicity when compared with continuing the drug, three recent studies suggest.

In one study, British researchers examined the effects of a 2-week break in methotrexate therapy on anti-RBD titers following receipt of a third COVID-19 vaccine dose. In their paper published in The Lancet: Respiratory Medicine, they reported results from a randomized, open-label, superiority trial that suggested pausing the drug improved immunogenicity, compared with no break.

In two trials presented at the European Alliance of Associations for Rheumatology (EULAR) 2022 Congress, a team from India set out to determine whether holding methotrexate after receiving both doses of a COVID-19 vaccine, or holding it only after the second dose, was safe and effective. They found that pausing methotrexate only following the second dose contributed to a lower flare risk, and that patients had higher anti-RBD titers when holding methotrexate for 2 weeks following each dose.
 

Pausing methotrexate after booster

The 2-week methotrexate break and booster vaccine dose data in the Vaccine Response On Off Methotrexate (VROOM) trial showed that after a month, the geometric mean antispike 1 (S1)-RBD antibody titer was 10,798 U/mL (95% confidence interval [CI], 8,970-12,997) in the group that continued methotrexate and 22,750 U/mL (95% CI, 19,314-26,796) in the group that suspended methotrexate; the geometric mean ratio was 2.19 (P < .0001; mixed-effects model), reported Abhishek Abhishek, MD, PhD, professor of rheumatology at the University of Nottingham in Nottingham, England, and colleagues.

Prior research showed that stopping methotrexate therapy for 2 weeks following the seasonal influenza vaccine contributed to better vaccine immunity among patients with rheumatoid arthritis, but there was no impact of stopping the drug for up to 4 weeks before vaccination on vaccine-related immunity, the researchers noted.

It is crucial in maximizing long-lasting vaccine protection in people who are possibly susceptible through immune suppression at this point in the COVID-19 vaccination regimen, the study team noted.

“Evidence from this study will be useful for policymakers, national immunization advisory committees, and specialist societies formulating recommendations on the use of methotrexate around the time of COVID-19 vaccination. This evidence will help patients and clinicians make informed choices about the risks and benefits of interrupting methotrexate treatment around the time of COVID-19 vaccination, with implications for the potential to extend such approaches to other therapeutics,” they wrote.

In American College of Rheumatology (ACR) guidance for COVID-19 vaccination, the organization advised against using standard synthetic disease-modifying antirheumatic medicines such as methotrexate “for 1-2 weeks (as disease activity allows) after each COVID-19 vaccine dose,” given the at-risk population and public health concerns, Jeffrey A. Sparks, MD, MMSc, assistant professor of medicine and associate physician at Brigham and Women’s Hospital and Harvard Medical School, Boston, and Sara K. Tedeschi, MD, MPH, assistant professor of medicine at Harvard Medical School, noted in an accompanying editorial in The Lancet: Respiratory Medicine.

However, when the ACR developed this statement, there was only one trial involving patients with rheumatoid arthritis who paused methotrexate following seasonal influenza vaccination, the editorialists said.

Expert commentary

This current study is consistent with other studies over the last several months showing that methotrexate harms both humoral and cell-mediated COVID-19 responses, noted Kevin Winthrop, MD, MPH, professor of infectious disease and public health at Oregon Health & Science University, Portland, who was not involved in the study. “And so now the new wave of studies are like this one, where they are holding methotrexate experimentally and seeing if it makes a difference,” he said.

“The one shortcoming of this study – and so far, the studies to date – is that no one has looked at whether the experimental hold has resulted in a change in T-cell responses, which ... we are [now] recognizing [the importance of] more and more in long-term protection, particularly in severe disease. Theoretically, holding [methotrexate] might help enhance T-cell responses, but that hasn’t been shown experimentally.”

Dr. Winthrop pointed out that one might get the same benefit from holding methotrexate for 1 week instead of 2 and that there likely is a reduced risk of flare-up from underlying autoimmune disease.

It is still not certain that this benefit extends to other vaccines, Dr. Winthrop noted. “It is probably true for most vaccines that if you hold methotrexate for 1 or 2 weeks, you might see some short-term benefit in responsiveness, but you don’t know that there is any clinical meaningfulness of this. That’s going to take other long-term studies. You don’t know how long this benefit lasts.”
 

Pausing methotrexate during initial COVID vaccine doses

Patients with either rheumatoid arthritis or psoriatic arthritis had higher anti-RBD antibody titers when methotrexate was stopped after both doses of the AstraZeneca vaccine, or simply after the second dose, than when methotrexate was continued, according to results from two single-center, randomized controlled trials called MIVAC I and II, Anu Sreekanth, MD, of Sree Sudheendra Medical Mission in Kochi, Kerala, India, and colleagues reported at EULAR 2022.

Results from MIVAC I indicated that there was a higher flare rate when methotrexate was stopped after both vaccine doses, but there was no difference in flare rate in MIVAC II when methotrexate was stopped only after the second dose as opposed to stopping it after both doses.

In the MIVAC I trial, 158 unvaccinated patients were randomized 1:1 to a cohort in which methotrexate was held for 2 weeks after both doses and a cohort in which methotrexate was continued despite the vaccine. In MIVAC II, 157 patients continued methotrexate while receiving the first vaccine dose. These patients were subsequently randomized either to continue or to stop methotrexate for 2 weeks following the second dose.

The findings from MIVAC I demonstrated the flare rate was lower in the methotrexate-continue group than in the methotrexate-pause group (8% vs. 25%; P = .005) and that the median anti-RBD titer was significantly higher for the methotrexate-pause group than the methotrexate-continue group (2,484 vs. 1,147; P = .001).

The results from MIVAC II trial indicated that there was no difference in flare rates between the two study groups (7.9% vs. 11.8%; P = .15). Yet, the median anti-RBD titer was significantly higher in the methotrexate-pause cohort than in the methotrexate-continue cohort (2,553 vs. 990; P = .001).

The report suggests there is a flare risk when methotrexate is stopped, Dr. Sreekanth noted. “It appears more logical to hold only after the second dose, as comparable anti-RBD titers are generated” with either approach, Dr. Sreekanth said.

Expert commentary: MIVAC I and II

Inés Colmegna, MD, associate professor at McGill University in Montreal, noted that it was intriguing that the risk of flares in MIVAC II is half of that reported after each of the doses of MIVAC I. “It is also worth emphasizing that despite the reported frequency of flares, the actual disease activity [as measured by the Disease Activity Score in 28 joints] in patients who did or did not withhold methotrexate was similar.

“MIVAC I and II have practical implications as they help to adequately inform patients about the risk and benefit trade of withholding methotrexate post–COVID-19 vaccination,” Dr. Colmegna told this news organization.

“Additional information would help to [further] interpret the findings of these studies, including whether any of the participants were taking any other DMARDs; data on the severity of the flares and functional impact; analysis of factors that predict the risk of flares, such as higher doses of methotrexate; [and change in] disease activity scores pre- and postvaccination,” Dr. Colmegna concluded.

Dr. Abhishek disclosed relationships with Springer, UpTodate, Oxford, Immunotec, AstraZeneca, Inflazome, NGM Biopharmaceuticals, Menarini Pharmaceuticals, and Cadila Pharmaceuticals. Dr. Abhishek is cochair of the ACR/EULAR CPPD Classification Criteria Working Group and the OMERACT CPPD Working Group. Dr. Sparks disclosed relationships with Gilead, Boehringer Ingelheim, Amgen, Bristol-Myers Squibb, and AbbVie, unrelated to this study. Dr. Tedeschi disclosed relationships with ModernaTx and NGM Biopharmaceuticals. Dr. Winthrop disclosed a research grant and serving as a scientific consultant for Pfizer. Dr. Sreekanth  and Dr. Colmegna have disclosed no relevant financial relationships.

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

Patients who take methotrexate for a variety of immune-mediated inflammatory diseases and pause taking the drug following receipt of a COVID-19 vaccine dose did not have a higher risk of disease flare and had higher antireceptor binding domain (anti-RBD) antibody titers and increased immunogenicity when compared with continuing the drug, three recent studies suggest.

In one study, British researchers examined the effects of a 2-week break in methotrexate therapy on anti-RBD titers following receipt of a third COVID-19 vaccine dose. In their paper published in The Lancet: Respiratory Medicine, they reported results from a randomized, open-label, superiority trial that suggested pausing the drug improved immunogenicity, compared with no break.

In two trials presented at the European Alliance of Associations for Rheumatology (EULAR) 2022 Congress, a team from India set out to determine whether holding methotrexate after receiving both doses of a COVID-19 vaccine, or holding it only after the second dose, was safe and effective. They found that pausing methotrexate only following the second dose contributed to a lower flare risk, and that patients had higher anti-RBD titers when holding methotrexate for 2 weeks following each dose.
 

Pausing methotrexate after booster

The 2-week methotrexate break and booster vaccine dose data in the Vaccine Response On Off Methotrexate (VROOM) trial showed that after a month, the geometric mean antispike 1 (S1)-RBD antibody titer was 10,798 U/mL (95% confidence interval [CI], 8,970-12,997) in the group that continued methotrexate and 22,750 U/mL (95% CI, 19,314-26,796) in the group that suspended methotrexate; the geometric mean ratio was 2.19 (P < .0001; mixed-effects model), reported Abhishek Abhishek, MD, PhD, professor of rheumatology at the University of Nottingham in Nottingham, England, and colleagues.

Prior research showed that stopping methotrexate therapy for 2 weeks following the seasonal influenza vaccine contributed to better vaccine immunity among patients with rheumatoid arthritis, but there was no impact of stopping the drug for up to 4 weeks before vaccination on vaccine-related immunity, the researchers noted.

It is crucial in maximizing long-lasting vaccine protection in people who are possibly susceptible through immune suppression at this point in the COVID-19 vaccination regimen, the study team noted.

“Evidence from this study will be useful for policymakers, national immunization advisory committees, and specialist societies formulating recommendations on the use of methotrexate around the time of COVID-19 vaccination. This evidence will help patients and clinicians make informed choices about the risks and benefits of interrupting methotrexate treatment around the time of COVID-19 vaccination, with implications for the potential to extend such approaches to other therapeutics,” they wrote.

In American College of Rheumatology (ACR) guidance for COVID-19 vaccination, the organization advised against using standard synthetic disease-modifying antirheumatic medicines such as methotrexate “for 1-2 weeks (as disease activity allows) after each COVID-19 vaccine dose,” given the at-risk population and public health concerns, Jeffrey A. Sparks, MD, MMSc, assistant professor of medicine and associate physician at Brigham and Women’s Hospital and Harvard Medical School, Boston, and Sara K. Tedeschi, MD, MPH, assistant professor of medicine at Harvard Medical School, noted in an accompanying editorial in The Lancet: Respiratory Medicine.

However, when the ACR developed this statement, there was only one trial involving patients with rheumatoid arthritis who paused methotrexate following seasonal influenza vaccination, the editorialists said.

Expert commentary

This current study is consistent with other studies over the last several months showing that methotrexate harms both humoral and cell-mediated COVID-19 responses, noted Kevin Winthrop, MD, MPH, professor of infectious disease and public health at Oregon Health & Science University, Portland, who was not involved in the study. “And so now the new wave of studies are like this one, where they are holding methotrexate experimentally and seeing if it makes a difference,” he said.

“The one shortcoming of this study – and so far, the studies to date – is that no one has looked at whether the experimental hold has resulted in a change in T-cell responses, which ... we are [now] recognizing [the importance of] more and more in long-term protection, particularly in severe disease. Theoretically, holding [methotrexate] might help enhance T-cell responses, but that hasn’t been shown experimentally.”

Dr. Winthrop pointed out that one might get the same benefit from holding methotrexate for 1 week instead of 2 and that there likely is a reduced risk of flare-up from underlying autoimmune disease.

It is still not certain that this benefit extends to other vaccines, Dr. Winthrop noted. “It is probably true for most vaccines that if you hold methotrexate for 1 or 2 weeks, you might see some short-term benefit in responsiveness, but you don’t know that there is any clinical meaningfulness of this. That’s going to take other long-term studies. You don’t know how long this benefit lasts.”
 

Pausing methotrexate during initial COVID vaccine doses

Patients with either rheumatoid arthritis or psoriatic arthritis had higher anti-RBD antibody titers when methotrexate was stopped after both doses of the AstraZeneca vaccine, or simply after the second dose, than when methotrexate was continued, according to results from two single-center, randomized controlled trials called MIVAC I and II, Anu Sreekanth, MD, of Sree Sudheendra Medical Mission in Kochi, Kerala, India, and colleagues reported at EULAR 2022.

Results from MIVAC I indicated that there was a higher flare rate when methotrexate was stopped after both vaccine doses, but there was no difference in flare rate in MIVAC II when methotrexate was stopped only after the second dose as opposed to stopping it after both doses.

In the MIVAC I trial, 158 unvaccinated patients were randomized 1:1 to a cohort in which methotrexate was held for 2 weeks after both doses and a cohort in which methotrexate was continued despite the vaccine. In MIVAC II, 157 patients continued methotrexate while receiving the first vaccine dose. These patients were subsequently randomized either to continue or to stop methotrexate for 2 weeks following the second dose.

The findings from MIVAC I demonstrated the flare rate was lower in the methotrexate-continue group than in the methotrexate-pause group (8% vs. 25%; P = .005) and that the median anti-RBD titer was significantly higher for the methotrexate-pause group than the methotrexate-continue group (2,484 vs. 1,147; P = .001).

The results from MIVAC II trial indicated that there was no difference in flare rates between the two study groups (7.9% vs. 11.8%; P = .15). Yet, the median anti-RBD titer was significantly higher in the methotrexate-pause cohort than in the methotrexate-continue cohort (2,553 vs. 990; P = .001).

The report suggests there is a flare risk when methotrexate is stopped, Dr. Sreekanth noted. “It appears more logical to hold only after the second dose, as comparable anti-RBD titers are generated” with either approach, Dr. Sreekanth said.

Expert commentary: MIVAC I and II

Inés Colmegna, MD, associate professor at McGill University in Montreal, noted that it was intriguing that the risk of flares in MIVAC II is half of that reported after each of the doses of MIVAC I. “It is also worth emphasizing that despite the reported frequency of flares, the actual disease activity [as measured by the Disease Activity Score in 28 joints] in patients who did or did not withhold methotrexate was similar.

“MIVAC I and II have practical implications as they help to adequately inform patients about the risk and benefit trade of withholding methotrexate post–COVID-19 vaccination,” Dr. Colmegna told this news organization.

“Additional information would help to [further] interpret the findings of these studies, including whether any of the participants were taking any other DMARDs; data on the severity of the flares and functional impact; analysis of factors that predict the risk of flares, such as higher doses of methotrexate; [and change in] disease activity scores pre- and postvaccination,” Dr. Colmegna concluded.

Dr. Abhishek disclosed relationships with Springer, UpTodate, Oxford, Immunotec, AstraZeneca, Inflazome, NGM Biopharmaceuticals, Menarini Pharmaceuticals, and Cadila Pharmaceuticals. Dr. Abhishek is cochair of the ACR/EULAR CPPD Classification Criteria Working Group and the OMERACT CPPD Working Group. Dr. Sparks disclosed relationships with Gilead, Boehringer Ingelheim, Amgen, Bristol-Myers Squibb, and AbbVie, unrelated to this study. Dr. Tedeschi disclosed relationships with ModernaTx and NGM Biopharmaceuticals. Dr. Winthrop disclosed a research grant and serving as a scientific consultant for Pfizer. Dr. Sreekanth  and Dr. Colmegna have disclosed no relevant financial relationships.

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

Patients who take methotrexate for a variety of immune-mediated inflammatory diseases and pause taking the drug following receipt of a COVID-19 vaccine dose did not have a higher risk of disease flare and had higher antireceptor binding domain (anti-RBD) antibody titers and increased immunogenicity when compared with continuing the drug, three recent studies suggest.

In one study, British researchers examined the effects of a 2-week break in methotrexate therapy on anti-RBD titers following receipt of a third COVID-19 vaccine dose. In their paper published in The Lancet: Respiratory Medicine, they reported results from a randomized, open-label, superiority trial that suggested pausing the drug improved immunogenicity, compared with no break.

In two trials presented at the European Alliance of Associations for Rheumatology (EULAR) 2022 Congress, a team from India set out to determine whether holding methotrexate after receiving both doses of a COVID-19 vaccine, or holding it only after the second dose, was safe and effective. They found that pausing methotrexate only following the second dose contributed to a lower flare risk, and that patients had higher anti-RBD titers when holding methotrexate for 2 weeks following each dose.
 

Pausing methotrexate after booster

The 2-week methotrexate break and booster vaccine dose data in the Vaccine Response On Off Methotrexate (VROOM) trial showed that after a month, the geometric mean antispike 1 (S1)-RBD antibody titer was 10,798 U/mL (95% confidence interval [CI], 8,970-12,997) in the group that continued methotrexate and 22,750 U/mL (95% CI, 19,314-26,796) in the group that suspended methotrexate; the geometric mean ratio was 2.19 (P < .0001; mixed-effects model), reported Abhishek Abhishek, MD, PhD, professor of rheumatology at the University of Nottingham in Nottingham, England, and colleagues.

Prior research showed that stopping methotrexate therapy for 2 weeks following the seasonal influenza vaccine contributed to better vaccine immunity among patients with rheumatoid arthritis, but there was no impact of stopping the drug for up to 4 weeks before vaccination on vaccine-related immunity, the researchers noted.

It is crucial in maximizing long-lasting vaccine protection in people who are possibly susceptible through immune suppression at this point in the COVID-19 vaccination regimen, the study team noted.

“Evidence from this study will be useful for policymakers, national immunization advisory committees, and specialist societies formulating recommendations on the use of methotrexate around the time of COVID-19 vaccination. This evidence will help patients and clinicians make informed choices about the risks and benefits of interrupting methotrexate treatment around the time of COVID-19 vaccination, with implications for the potential to extend such approaches to other therapeutics,” they wrote.

In American College of Rheumatology (ACR) guidance for COVID-19 vaccination, the organization advised against using standard synthetic disease-modifying antirheumatic medicines such as methotrexate “for 1-2 weeks (as disease activity allows) after each COVID-19 vaccine dose,” given the at-risk population and public health concerns, Jeffrey A. Sparks, MD, MMSc, assistant professor of medicine and associate physician at Brigham and Women’s Hospital and Harvard Medical School, Boston, and Sara K. Tedeschi, MD, MPH, assistant professor of medicine at Harvard Medical School, noted in an accompanying editorial in The Lancet: Respiratory Medicine.

However, when the ACR developed this statement, there was only one trial involving patients with rheumatoid arthritis who paused methotrexate following seasonal influenza vaccination, the editorialists said.

Expert commentary

This current study is consistent with other studies over the last several months showing that methotrexate harms both humoral and cell-mediated COVID-19 responses, noted Kevin Winthrop, MD, MPH, professor of infectious disease and public health at Oregon Health & Science University, Portland, who was not involved in the study. “And so now the new wave of studies are like this one, where they are holding methotrexate experimentally and seeing if it makes a difference,” he said.

“The one shortcoming of this study – and so far, the studies to date – is that no one has looked at whether the experimental hold has resulted in a change in T-cell responses, which ... we are [now] recognizing [the importance of] more and more in long-term protection, particularly in severe disease. Theoretically, holding [methotrexate] might help enhance T-cell responses, but that hasn’t been shown experimentally.”

Dr. Winthrop pointed out that one might get the same benefit from holding methotrexate for 1 week instead of 2 and that there likely is a reduced risk of flare-up from underlying autoimmune disease.

It is still not certain that this benefit extends to other vaccines, Dr. Winthrop noted. “It is probably true for most vaccines that if you hold methotrexate for 1 or 2 weeks, you might see some short-term benefit in responsiveness, but you don’t know that there is any clinical meaningfulness of this. That’s going to take other long-term studies. You don’t know how long this benefit lasts.”
 

Pausing methotrexate during initial COVID vaccine doses

Patients with either rheumatoid arthritis or psoriatic arthritis had higher anti-RBD antibody titers when methotrexate was stopped after both doses of the AstraZeneca vaccine, or simply after the second dose, than when methotrexate was continued, according to results from two single-center, randomized controlled trials called MIVAC I and II, Anu Sreekanth, MD, of Sree Sudheendra Medical Mission in Kochi, Kerala, India, and colleagues reported at EULAR 2022.

Results from MIVAC I indicated that there was a higher flare rate when methotrexate was stopped after both vaccine doses, but there was no difference in flare rate in MIVAC II when methotrexate was stopped only after the second dose as opposed to stopping it after both doses.

In the MIVAC I trial, 158 unvaccinated patients were randomized 1:1 to a cohort in which methotrexate was held for 2 weeks after both doses and a cohort in which methotrexate was continued despite the vaccine. In MIVAC II, 157 patients continued methotrexate while receiving the first vaccine dose. These patients were subsequently randomized either to continue or to stop methotrexate for 2 weeks following the second dose.

The findings from MIVAC I demonstrated the flare rate was lower in the methotrexate-continue group than in the methotrexate-pause group (8% vs. 25%; P = .005) and that the median anti-RBD titer was significantly higher for the methotrexate-pause group than the methotrexate-continue group (2,484 vs. 1,147; P = .001).

The results from MIVAC II trial indicated that there was no difference in flare rates between the two study groups (7.9% vs. 11.8%; P = .15). Yet, the median anti-RBD titer was significantly higher in the methotrexate-pause cohort than in the methotrexate-continue cohort (2,553 vs. 990; P = .001).

The report suggests there is a flare risk when methotrexate is stopped, Dr. Sreekanth noted. “It appears more logical to hold only after the second dose, as comparable anti-RBD titers are generated” with either approach, Dr. Sreekanth said.

Expert commentary: MIVAC I and II

Inés Colmegna, MD, associate professor at McGill University in Montreal, noted that it was intriguing that the risk of flares in MIVAC II is half of that reported after each of the doses of MIVAC I. “It is also worth emphasizing that despite the reported frequency of flares, the actual disease activity [as measured by the Disease Activity Score in 28 joints] in patients who did or did not withhold methotrexate was similar.

“MIVAC I and II have practical implications as they help to adequately inform patients about the risk and benefit trade of withholding methotrexate post–COVID-19 vaccination,” Dr. Colmegna told this news organization.

“Additional information would help to [further] interpret the findings of these studies, including whether any of the participants were taking any other DMARDs; data on the severity of the flares and functional impact; analysis of factors that predict the risk of flares, such as higher doses of methotrexate; [and change in] disease activity scores pre- and postvaccination,” Dr. Colmegna concluded.

Dr. Abhishek disclosed relationships with Springer, UpTodate, Oxford, Immunotec, AstraZeneca, Inflazome, NGM Biopharmaceuticals, Menarini Pharmaceuticals, and Cadila Pharmaceuticals. Dr. Abhishek is cochair of the ACR/EULAR CPPD Classification Criteria Working Group and the OMERACT CPPD Working Group. Dr. Sparks disclosed relationships with Gilead, Boehringer Ingelheim, Amgen, Bristol-Myers Squibb, and AbbVie, unrelated to this study. Dr. Tedeschi disclosed relationships with ModernaTx and NGM Biopharmaceuticals. Dr. Winthrop disclosed a research grant and serving as a scientific consultant for Pfizer. Dr. Sreekanth  and Dr. Colmegna have disclosed no relevant financial relationships.

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

INDIANAPOLIS – In the opinion of Elena Pope, MD, MSc, it’s time to think of morphea in children as a systemic, chronic condition with associated extracutaneous manifestations and the potential for relapse.

“There is no correlation between the extent and activity of skin lesions and the presence, severity, and activity of extracutaneous manifestations,” Dr. Pope, professor of pediatrics at the University of Toronto and division head of pediatric dermatology at the Hospital for Sick Children in Toronto, said during the annual meeting of the Society for Pediatric Dermatology. “Treatment needs to be tailored to the extent of cutaneous manifestations, and I think we need to be aware of and address the impact on patients’ quality of life,” she added. There is also a need for more research “on targeted and better-tolerated therapies to put a stop to the progression of disease.”

Congenital morphea is a form of localized scleroderma that presents at birth but can be confused with port wine stain. Results from a multicenter retrospective review of 25 cases conducted by Dr. Pope and colleagues found that the median age at diagnosis was 2.9 years and 76% had linear-type lesions. In addition, 48% had extracutaneous involvement (all of these patients had linear morphea), most commonly of the central nervous system.

“It’s important to realize these lesions may become active over time,” Dr. Pope said. “In my experience, there are two different courses. Either you have innocuous lesions when the patients are born and they may become active around 3-4 years of age, or you have early intrauterine involvement, with lesions inactive at birth but with potential for significant damage in utero.”

She cautioned against treating a suspected port wine stain lesion with laser until congenital morphea is ruled out. “I’m aware of at least one lawsuit of a child where someone used a laser in a child who had progression with significant sclerosis,” she said. “The parents assumed it was the use of the laser that led to the progression, not the actual disease.”

Extracutaneous manifestations are common in morphea patients. A multicenter study of 750 patients with juvenile scleroderma found that 22% had extracutaneous manifestations. Almost half of patients (47%) had arthritis, but 17% had neurologic findings such as seizures and headaches, 9% had vascular manifestations, and 8% had uveitis. Subsequent studies found that neurological disease affects between 11% and 19% of cases, especially in those involving the head and neck.

“There is a wide range of manifestations from headache and neuropsychiatric changes to brain atrophy, seizures, and CNS cavernoma,” Dr. Pope said. “There also can be orthodental involvement such as malocclusion. It’s important to do a brain MRI, eye exam for uveitis, and don’t forget the orthodental assessment.”

She recalled a 10-year-old boy who presented to the Hospital for Sick Children with tissue loss on the forehead and eyebrow and eyelashes. He had no other congenital morphea symptoms and the MRI was normal, but the eye exam revealed uveitis. “It’s important to remember that uveitis is asymptomatic, so unless you look for it, you’re not going to find it,” she said.

According to unpublished data in 42 congenital morphea patients with lesions limited to the head and neck, who underwent MRI imaging at the Hospital for Sick Children, 57% had CNS changes that were ipsilateral in 68% of cases. “White matter changes were the most common, and to our surprise, there were patients who had progressive CNS disease, including CNS vasculitis, new lesions, and enhancement of prior stable lesions,” Dr. Pope said.

She recalled the case of an 8-year-old boy who presented to the hospital with intractable seizures. Upon completion of the MRI, one of the radiologists noted that the imaging showed subtle thinning of the forehead, and he was referred to Dr. Pope and colleagues for assessment. In the span of 4 years, despite aggressive treatment, the boy’s CNS disease progressed. “There was more enhancement, more tissue loss, his seizures are very hard to control, and he has many neurodevelopmental changes,” she recalled. “What I learned from this case is that skin activity does not correlate with imaging. Don’t assume that just because the skin is burnt out that the CNS will be the same. Also, the extent of skin disease does not predict involvement or progression of the CNS.”

Linear lesions on the lower extremities are a harbinger of orthopedic complications, which can occur in about half of patients. Joint contractures in this subset of patients are seen in about 81% of cases, while other sequelae can include arthritis, limb atrophy, leg-leg discrepancy, and angular deformity. “About 14% of patients require intervention,” Dr. Pope said. “In terms of working those patients up, you need to do an MRI and assess the extent of muscle and fascial involvement. Early physiotherapy and an orthopedic evaluation are also recommended.”

As for possible markers of morphea, antinuclear antibody is positive in 22%-68% of cases and correlates with disease severity, extracutaneous manifestations, and disease flare-up. Antihistone antibodies (AHA) are positive in about 47% of cases, “and that tends to correlate with the extent of skin and muscle involvement,” Dr. Pope said. “Anti–double-stranded DNA correlates with extent of disease, but the only known biomarker to date that correlates with disease activity is CXCL9/10. This has been documented in the skin as well as in the blood. So, this marker may help us determine if the patient needs to be treated or not.”



Treatments

For treatment of active localized disease, topical medications are helpful in some cases. Options include topical steroids, calcipotriol with or without betamethasone, imiquimod, and tacrolimus. “In my experience the combination of calcipotriol with betamethasone is best,” she said. “It really shuts down the activity fairly soon, and you can scale down to calcipotriol alone. I don’t find imiquimod very helpful for active lesions, although it has a role for inactive lesions.”

For patients with linear or generalized/mixed disease, “the combination of methotrexate and corticosteroids or methotrexate alone is probably the way to go,” Dr. Pope said. “The addition of steroids really depends on where the lesion is and how worried you are about other problems.”

According to the best available literature, 88% of patients should respond to treatment with methotrexate (MTX) and/or steroids within 3-6 months, and 74% within 3 months. “If they don’t, you have to wonder if the patient’s taking the medication, or you need to think about other alternative treatments,” she said. “Complete remission is possible in most of the patients, and the longer you treat the more you will see that. On average, most of us treat patients for about 3 years, but there are treatment failures as well. This can occur in up to 16% of patients.”

As for second-line treatment agents for congenital morphea, clinicians often turn to mycophenolate mofetil (MMF). Results from a retrospective longitudinal study of juvenile localized scleroderma patients found that after a mean of 9 years 91% of patients on MMF and 100% of patients on MTX had inactive disease. “There were no differences in relapse rates, although MMF seems to have a more sustained long-term effect and overall is better tolerated,” said Dr. Pope, who was not involved with the study. “However, it’s more immunosuppressive than MTX, which is important, especially in the era of COVID-19. You also need to think about the potential for more hematological suppression with MMF use.” If standard therapy fails, there is anecdotal data supporting the use of abatacept (which suppresses the T-cell activity in affected patients), tofacitinib (which inhibits transforming growth factor–beta), or dupilumab (which inhibits interleukin-4).

Dr. Pope emphasized the effect congenital morphea has on quality of life. Remarks from patients with facial morphea and their parents who participated in a focus group on the topic organized by the Hospital for Sick Children included, “You just want to stay inside because you are afraid of what people will say,” “They laugh at her. They make fun of her, and it’s terrible,” and “MTX makes me feel weird. I would throw up, feel dizzy.”

“You have to take that into consideration, because we cannot make the treatment worse than the disease,” Dr. Pope said. “There are many domains where patients could be affected, including skin symptoms, physical functioning, body image and social support, side effects of medication, and presence of extracutaneous manifestations. Predictors of poor quality of life include female sex and involvement of hands and feet.”

Dr. Pope disclosed that she has received grants/research support from AbbVie, Centocor, and Amgen. She has also received consulting fees from AbbVie, Sanofi, Novartis, Boehringer-Ingelheim, Phoenix, Amryt Pharma, and Timber Pharmaceuticals.

INDIANAPOLIS – In the opinion of Elena Pope, MD, MSc, it’s time to think of morphea in children as a systemic, chronic condition with associated extracutaneous manifestations and the potential for relapse.

“There is no correlation between the extent and activity of skin lesions and the presence, severity, and activity of extracutaneous manifestations,” Dr. Pope, professor of pediatrics at the University of Toronto and division head of pediatric dermatology at the Hospital for Sick Children in Toronto, said during the annual meeting of the Society for Pediatric Dermatology. “Treatment needs to be tailored to the extent of cutaneous manifestations, and I think we need to be aware of and address the impact on patients’ quality of life,” she added. There is also a need for more research “on targeted and better-tolerated therapies to put a stop to the progression of disease.”

Congenital morphea is a form of localized scleroderma that presents at birth but can be confused with port wine stain. Results from a multicenter retrospective review of 25 cases conducted by Dr. Pope and colleagues found that the median age at diagnosis was 2.9 years and 76% had linear-type lesions. In addition, 48% had extracutaneous involvement (all of these patients had linear morphea), most commonly of the central nervous system.

“It’s important to realize these lesions may become active over time,” Dr. Pope said. “In my experience, there are two different courses. Either you have innocuous lesions when the patients are born and they may become active around 3-4 years of age, or you have early intrauterine involvement, with lesions inactive at birth but with potential for significant damage in utero.”

She cautioned against treating a suspected port wine stain lesion with laser until congenital morphea is ruled out. “I’m aware of at least one lawsuit of a child where someone used a laser in a child who had progression with significant sclerosis,” she said. “The parents assumed it was the use of the laser that led to the progression, not the actual disease.”

Extracutaneous manifestations are common in morphea patients. A multicenter study of 750 patients with juvenile scleroderma found that 22% had extracutaneous manifestations. Almost half of patients (47%) had arthritis, but 17% had neurologic findings such as seizures and headaches, 9% had vascular manifestations, and 8% had uveitis. Subsequent studies found that neurological disease affects between 11% and 19% of cases, especially in those involving the head and neck.

“There is a wide range of manifestations from headache and neuropsychiatric changes to brain atrophy, seizures, and CNS cavernoma,” Dr. Pope said. “There also can be orthodental involvement such as malocclusion. It’s important to do a brain MRI, eye exam for uveitis, and don’t forget the orthodental assessment.”

She recalled a 10-year-old boy who presented to the Hospital for Sick Children with tissue loss on the forehead and eyebrow and eyelashes. He had no other congenital morphea symptoms and the MRI was normal, but the eye exam revealed uveitis. “It’s important to remember that uveitis is asymptomatic, so unless you look for it, you’re not going to find it,” she said.

According to unpublished data in 42 congenital morphea patients with lesions limited to the head and neck, who underwent MRI imaging at the Hospital for Sick Children, 57% had CNS changes that were ipsilateral in 68% of cases. “White matter changes were the most common, and to our surprise, there were patients who had progressive CNS disease, including CNS vasculitis, new lesions, and enhancement of prior stable lesions,” Dr. Pope said.

She recalled the case of an 8-year-old boy who presented to the hospital with intractable seizures. Upon completion of the MRI, one of the radiologists noted that the imaging showed subtle thinning of the forehead, and he was referred to Dr. Pope and colleagues for assessment. In the span of 4 years, despite aggressive treatment, the boy’s CNS disease progressed. “There was more enhancement, more tissue loss, his seizures are very hard to control, and he has many neurodevelopmental changes,” she recalled. “What I learned from this case is that skin activity does not correlate with imaging. Don’t assume that just because the skin is burnt out that the CNS will be the same. Also, the extent of skin disease does not predict involvement or progression of the CNS.”

Linear lesions on the lower extremities are a harbinger of orthopedic complications, which can occur in about half of patients. Joint contractures in this subset of patients are seen in about 81% of cases, while other sequelae can include arthritis, limb atrophy, leg-leg discrepancy, and angular deformity. “About 14% of patients require intervention,” Dr. Pope said. “In terms of working those patients up, you need to do an MRI and assess the extent of muscle and fascial involvement. Early physiotherapy and an orthopedic evaluation are also recommended.”

As for possible markers of morphea, antinuclear antibody is positive in 22%-68% of cases and correlates with disease severity, extracutaneous manifestations, and disease flare-up. Antihistone antibodies (AHA) are positive in about 47% of cases, “and that tends to correlate with the extent of skin and muscle involvement,” Dr. Pope said. “Anti–double-stranded DNA correlates with extent of disease, but the only known biomarker to date that correlates with disease activity is CXCL9/10. This has been documented in the skin as well as in the blood. So, this marker may help us determine if the patient needs to be treated or not.”



Treatments

For treatment of active localized disease, topical medications are helpful in some cases. Options include topical steroids, calcipotriol with or without betamethasone, imiquimod, and tacrolimus. “In my experience the combination of calcipotriol with betamethasone is best,” she said. “It really shuts down the activity fairly soon, and you can scale down to calcipotriol alone. I don’t find imiquimod very helpful for active lesions, although it has a role for inactive lesions.”

For patients with linear or generalized/mixed disease, “the combination of methotrexate and corticosteroids or methotrexate alone is probably the way to go,” Dr. Pope said. “The addition of steroids really depends on where the lesion is and how worried you are about other problems.”

According to the best available literature, 88% of patients should respond to treatment with methotrexate (MTX) and/or steroids within 3-6 months, and 74% within 3 months. “If they don’t, you have to wonder if the patient’s taking the medication, or you need to think about other alternative treatments,” she said. “Complete remission is possible in most of the patients, and the longer you treat the more you will see that. On average, most of us treat patients for about 3 years, but there are treatment failures as well. This can occur in up to 16% of patients.”

As for second-line treatment agents for congenital morphea, clinicians often turn to mycophenolate mofetil (MMF). Results from a retrospective longitudinal study of juvenile localized scleroderma patients found that after a mean of 9 years 91% of patients on MMF and 100% of patients on MTX had inactive disease. “There were no differences in relapse rates, although MMF seems to have a more sustained long-term effect and overall is better tolerated,” said Dr. Pope, who was not involved with the study. “However, it’s more immunosuppressive than MTX, which is important, especially in the era of COVID-19. You also need to think about the potential for more hematological suppression with MMF use.” If standard therapy fails, there is anecdotal data supporting the use of abatacept (which suppresses the T-cell activity in affected patients), tofacitinib (which inhibits transforming growth factor–beta), or dupilumab (which inhibits interleukin-4).

Dr. Pope emphasized the effect congenital morphea has on quality of life. Remarks from patients with facial morphea and their parents who participated in a focus group on the topic organized by the Hospital for Sick Children included, “You just want to stay inside because you are afraid of what people will say,” “They laugh at her. They make fun of her, and it’s terrible,” and “MTX makes me feel weird. I would throw up, feel dizzy.”

“You have to take that into consideration, because we cannot make the treatment worse than the disease,” Dr. Pope said. “There are many domains where patients could be affected, including skin symptoms, physical functioning, body image and social support, side effects of medication, and presence of extracutaneous manifestations. Predictors of poor quality of life include female sex and involvement of hands and feet.”

Dr. Pope disclosed that she has received grants/research support from AbbVie, Centocor, and Amgen. She has also received consulting fees from AbbVie, Sanofi, Novartis, Boehringer-Ingelheim, Phoenix, Amryt Pharma, and Timber Pharmaceuticals.

INDIANAPOLIS – In the opinion of Elena Pope, MD, MSc, it’s time to think of morphea in children as a systemic, chronic condition with associated extracutaneous manifestations and the potential for relapse.

“There is no correlation between the extent and activity of skin lesions and the presence, severity, and activity of extracutaneous manifestations,” Dr. Pope, professor of pediatrics at the University of Toronto and division head of pediatric dermatology at the Hospital for Sick Children in Toronto, said during the annual meeting of the Society for Pediatric Dermatology. “Treatment needs to be tailored to the extent of cutaneous manifestations, and I think we need to be aware of and address the impact on patients’ quality of life,” she added. There is also a need for more research “on targeted and better-tolerated therapies to put a stop to the progression of disease.”

Congenital morphea is a form of localized scleroderma that presents at birth but can be confused with port wine stain. Results from a multicenter retrospective review of 25 cases conducted by Dr. Pope and colleagues found that the median age at diagnosis was 2.9 years and 76% had linear-type lesions. In addition, 48% had extracutaneous involvement (all of these patients had linear morphea), most commonly of the central nervous system.

“It’s important to realize these lesions may become active over time,” Dr. Pope said. “In my experience, there are two different courses. Either you have innocuous lesions when the patients are born and they may become active around 3-4 years of age, or you have early intrauterine involvement, with lesions inactive at birth but with potential for significant damage in utero.”

She cautioned against treating a suspected port wine stain lesion with laser until congenital morphea is ruled out. “I’m aware of at least one lawsuit of a child where someone used a laser in a child who had progression with significant sclerosis,” she said. “The parents assumed it was the use of the laser that led to the progression, not the actual disease.”

Extracutaneous manifestations are common in morphea patients. A multicenter study of 750 patients with juvenile scleroderma found that 22% had extracutaneous manifestations. Almost half of patients (47%) had arthritis, but 17% had neurologic findings such as seizures and headaches, 9% had vascular manifestations, and 8% had uveitis. Subsequent studies found that neurological disease affects between 11% and 19% of cases, especially in those involving the head and neck.

“There is a wide range of manifestations from headache and neuropsychiatric changes to brain atrophy, seizures, and CNS cavernoma,” Dr. Pope said. “There also can be orthodental involvement such as malocclusion. It’s important to do a brain MRI, eye exam for uveitis, and don’t forget the orthodental assessment.”

She recalled a 10-year-old boy who presented to the Hospital for Sick Children with tissue loss on the forehead and eyebrow and eyelashes. He had no other congenital morphea symptoms and the MRI was normal, but the eye exam revealed uveitis. “It’s important to remember that uveitis is asymptomatic, so unless you look for it, you’re not going to find it,” she said.

According to unpublished data in 42 congenital morphea patients with lesions limited to the head and neck, who underwent MRI imaging at the Hospital for Sick Children, 57% had CNS changes that were ipsilateral in 68% of cases. “White matter changes were the most common, and to our surprise, there were patients who had progressive CNS disease, including CNS vasculitis, new lesions, and enhancement of prior stable lesions,” Dr. Pope said.

She recalled the case of an 8-year-old boy who presented to the hospital with intractable seizures. Upon completion of the MRI, one of the radiologists noted that the imaging showed subtle thinning of the forehead, and he was referred to Dr. Pope and colleagues for assessment. In the span of 4 years, despite aggressive treatment, the boy’s CNS disease progressed. “There was more enhancement, more tissue loss, his seizures are very hard to control, and he has many neurodevelopmental changes,” she recalled. “What I learned from this case is that skin activity does not correlate with imaging. Don’t assume that just because the skin is burnt out that the CNS will be the same. Also, the extent of skin disease does not predict involvement or progression of the CNS.”

Linear lesions on the lower extremities are a harbinger of orthopedic complications, which can occur in about half of patients. Joint contractures in this subset of patients are seen in about 81% of cases, while other sequelae can include arthritis, limb atrophy, leg-leg discrepancy, and angular deformity. “About 14% of patients require intervention,” Dr. Pope said. “In terms of working those patients up, you need to do an MRI and assess the extent of muscle and fascial involvement. Early physiotherapy and an orthopedic evaluation are also recommended.”

As for possible markers of morphea, antinuclear antibody is positive in 22%-68% of cases and correlates with disease severity, extracutaneous manifestations, and disease flare-up. Antihistone antibodies (AHA) are positive in about 47% of cases, “and that tends to correlate with the extent of skin and muscle involvement,” Dr. Pope said. “Anti–double-stranded DNA correlates with extent of disease, but the only known biomarker to date that correlates with disease activity is CXCL9/10. This has been documented in the skin as well as in the blood. So, this marker may help us determine if the patient needs to be treated or not.”



Treatments

For treatment of active localized disease, topical medications are helpful in some cases. Options include topical steroids, calcipotriol with or without betamethasone, imiquimod, and tacrolimus. “In my experience the combination of calcipotriol with betamethasone is best,” she said. “It really shuts down the activity fairly soon, and you can scale down to calcipotriol alone. I don’t find imiquimod very helpful for active lesions, although it has a role for inactive lesions.”

For patients with linear or generalized/mixed disease, “the combination of methotrexate and corticosteroids or methotrexate alone is probably the way to go,” Dr. Pope said. “The addition of steroids really depends on where the lesion is and how worried you are about other problems.”

According to the best available literature, 88% of patients should respond to treatment with methotrexate (MTX) and/or steroids within 3-6 months, and 74% within 3 months. “If they don’t, you have to wonder if the patient’s taking the medication, or you need to think about other alternative treatments,” she said. “Complete remission is possible in most of the patients, and the longer you treat the more you will see that. On average, most of us treat patients for about 3 years, but there are treatment failures as well. This can occur in up to 16% of patients.”

As for second-line treatment agents for congenital morphea, clinicians often turn to mycophenolate mofetil (MMF). Results from a retrospective longitudinal study of juvenile localized scleroderma patients found that after a mean of 9 years 91% of patients on MMF and 100% of patients on MTX had inactive disease. “There were no differences in relapse rates, although MMF seems to have a more sustained long-term effect and overall is better tolerated,” said Dr. Pope, who was not involved with the study. “However, it’s more immunosuppressive than MTX, which is important, especially in the era of COVID-19. You also need to think about the potential for more hematological suppression with MMF use.” If standard therapy fails, there is anecdotal data supporting the use of abatacept (which suppresses the T-cell activity in affected patients), tofacitinib (which inhibits transforming growth factor–beta), or dupilumab (which inhibits interleukin-4).

Dr. Pope emphasized the effect congenital morphea has on quality of life. Remarks from patients with facial morphea and their parents who participated in a focus group on the topic organized by the Hospital for Sick Children included, “You just want to stay inside because you are afraid of what people will say,” “They laugh at her. They make fun of her, and it’s terrible,” and “MTX makes me feel weird. I would throw up, feel dizzy.”

“You have to take that into consideration, because we cannot make the treatment worse than the disease,” Dr. Pope said. “There are many domains where patients could be affected, including skin symptoms, physical functioning, body image and social support, side effects of medication, and presence of extracutaneous manifestations. Predictors of poor quality of life include female sex and involvement of hands and feet.”

Dr. Pope disclosed that she has received grants/research support from AbbVie, Centocor, and Amgen. She has also received consulting fees from AbbVie, Sanofi, Novartis, Boehringer-Ingelheim, Phoenix, Amryt Pharma, and Timber Pharmaceuticals.

NEW YORK – On the basis of MRI images of the hand, a neural network has been trained to distinguish seronegative and seropositive rheumatoid arthritis (RA) from psoriatic arthritis (PsA) as well as from each other, according to a study that was presented at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

In the work so far, the neural network was correct about 70% of the time in the absence of any further clinical analyses, according to David Simon, MD, a rheumatologist in the department of internal medicine at Friedrich-Alexander University, Erlangen, Germany.

Ted Bosworth/MDedge News

Previous to this work, “there has been no study that has exclusively used hand MRI data and deep learning without requiring further expert input for the classification of arthritides,” Dr. Simon said.

In fact, when demographic and clinical data were added, there was no improvement in the performance of patient classification relative to the deep learning classification alone, according to the data presented by Dr. Simon.

The images were evaluated with residual neural networks (ResNet), which represents a sophisticated form of deep learning to facilitate the flow of information across the network layers as they form to improve accuracy in their ability to distinguish one form of disease from the other. The training was performed on images from the T1 coronal, T2 corona1, T1 coronal fat suppressed with contrast, T1 axial fat suppressed with contrast, and T2 fat suppressed axial sequences.

The study included hand MRI scans from 135 patients with seronegative RA, 190 with seropositive RA, 177 with PsA, and 147 with psoriasis. The performance was judged on the basis of area under the receiver operating characteristics curve (AUROC) with and without input of clinical characteristics. Patients who had psoriasis without clinical arthritis were included as a control population.

The AUROC for accuracy was 75% for seropositive RA relative to PsA, 74% for seronegative RA relative to PsA, and 67% for seropositive relative to seronegative RA. Of the patients who had psoriasis without arthritis, 98% were classified as PsA and 2% as RA.

Subsequent to the classification of the patients with psoriasis, 14 of the 147 (9.5%) have developed PsA so far over a relatively short follow-up. All of these were among those identified as PsA by neural network evaluation of the hand MRIs.

This suggests that “a PsA-like pattern may be present early in the course of psoriatic disease,” Dr. Simon said.

In the groups with joint disease, who had mean ages ranging from 56 to 65, the mean disease durations were 2.6 years for those with seropositive RA, 1.3 years for those with seronegative RA, and 0.8 years for those with PsA. The patients with psoriasis were younger (mean age, 40.5 years) but had a longer disease duration (mean 4.2 years).

All of the MRI sequences were relevant for classification, but contrast did not appear to help with accuracy.

“If the images with contrast enhancement were deleted, the loss of performance was only marginal,” Dr. Simon reported.

The accuracy of neural networks increases with data, making it likely that further refinements in methodology will lead to a greater degree of accuracy, according to Dr. Simon. While the methodology is not yet ready for routine use in the clinic, the study demonstrates that neural network analysis of hand MRI to distinguish forms of arthritis “is possible.” Further studies are planned toward the goal of creating a viable clinical tool.

“Of course, if we could create an accurate tool with ultrasound, this would be even more practical,” said Dr. Simon, recognizing the value of an office tool, but he cautioned that this would be far more challenging.

“The precision of MRI is an important factor for effective neural network training,” he said.

Utility: ‘In challenging cases if the accuracy improves’?

A viable method for objectively and rapidly distinguishing inflammatory joint diseases, particularly in patients with an ambiguous clinical presentation, is an unmet need, according to Philip J. Mease, MD, director of rheumatology research at Swedish Medical Center, Seattle.

Although the data presented are promising, Dr. Mease said in an interview that he believes there is a fair amount of work to be done before imaging analysis based on deep learning makes its way into routine clinical care. He is also hoping for methods to distinguish RA from PsA that are easier and less expensive, such as serum biomarkers. However, he agreed that a MRI-based tool could be useful when differentiating disease that is challenging.

“MRI is an expensive way for routine classification of disease, but this approach could be useful in challenging cases if the accuracy improves,” he said.

Meanwhile, other clinical researchers might want to test the principle. “You can try it,” said Dr. Simon, who reported that his team has made the methodology publicly available.

Dr. Simon reported no conflicts of interest. Dr. Mease reported financial relationships with more than 10 pharmaceutical companies, most of which make products used for the treatment of inflammatory joint diseases.

NEW YORK – On the basis of MRI images of the hand, a neural network has been trained to distinguish seronegative and seropositive rheumatoid arthritis (RA) from psoriatic arthritis (PsA) as well as from each other, according to a study that was presented at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

In the work so far, the neural network was correct about 70% of the time in the absence of any further clinical analyses, according to David Simon, MD, a rheumatologist in the department of internal medicine at Friedrich-Alexander University, Erlangen, Germany.

Ted Bosworth/MDedge News

Previous to this work, “there has been no study that has exclusively used hand MRI data and deep learning without requiring further expert input for the classification of arthritides,” Dr. Simon said.

In fact, when demographic and clinical data were added, there was no improvement in the performance of patient classification relative to the deep learning classification alone, according to the data presented by Dr. Simon.

The images were evaluated with residual neural networks (ResNet), which represents a sophisticated form of deep learning to facilitate the flow of information across the network layers as they form to improve accuracy in their ability to distinguish one form of disease from the other. The training was performed on images from the T1 coronal, T2 corona1, T1 coronal fat suppressed with contrast, T1 axial fat suppressed with contrast, and T2 fat suppressed axial sequences.

The study included hand MRI scans from 135 patients with seronegative RA, 190 with seropositive RA, 177 with PsA, and 147 with psoriasis. The performance was judged on the basis of area under the receiver operating characteristics curve (AUROC) with and without input of clinical characteristics. Patients who had psoriasis without clinical arthritis were included as a control population.

The AUROC for accuracy was 75% for seropositive RA relative to PsA, 74% for seronegative RA relative to PsA, and 67% for seropositive relative to seronegative RA. Of the patients who had psoriasis without arthritis, 98% were classified as PsA and 2% as RA.

Subsequent to the classification of the patients with psoriasis, 14 of the 147 (9.5%) have developed PsA so far over a relatively short follow-up. All of these were among those identified as PsA by neural network evaluation of the hand MRIs.

This suggests that “a PsA-like pattern may be present early in the course of psoriatic disease,” Dr. Simon said.

In the groups with joint disease, who had mean ages ranging from 56 to 65, the mean disease durations were 2.6 years for those with seropositive RA, 1.3 years for those with seronegative RA, and 0.8 years for those with PsA. The patients with psoriasis were younger (mean age, 40.5 years) but had a longer disease duration (mean 4.2 years).

All of the MRI sequences were relevant for classification, but contrast did not appear to help with accuracy.

“If the images with contrast enhancement were deleted, the loss of performance was only marginal,” Dr. Simon reported.

The accuracy of neural networks increases with data, making it likely that further refinements in methodology will lead to a greater degree of accuracy, according to Dr. Simon. While the methodology is not yet ready for routine use in the clinic, the study demonstrates that neural network analysis of hand MRI to distinguish forms of arthritis “is possible.” Further studies are planned toward the goal of creating a viable clinical tool.

“Of course, if we could create an accurate tool with ultrasound, this would be even more practical,” said Dr. Simon, recognizing the value of an office tool, but he cautioned that this would be far more challenging.

“The precision of MRI is an important factor for effective neural network training,” he said.

Utility: ‘In challenging cases if the accuracy improves’?

A viable method for objectively and rapidly distinguishing inflammatory joint diseases, particularly in patients with an ambiguous clinical presentation, is an unmet need, according to Philip J. Mease, MD, director of rheumatology research at Swedish Medical Center, Seattle.

Although the data presented are promising, Dr. Mease said in an interview that he believes there is a fair amount of work to be done before imaging analysis based on deep learning makes its way into routine clinical care. He is also hoping for methods to distinguish RA from PsA that are easier and less expensive, such as serum biomarkers. However, he agreed that a MRI-based tool could be useful when differentiating disease that is challenging.

“MRI is an expensive way for routine classification of disease, but this approach could be useful in challenging cases if the accuracy improves,” he said.

Meanwhile, other clinical researchers might want to test the principle. “You can try it,” said Dr. Simon, who reported that his team has made the methodology publicly available.

Dr. Simon reported no conflicts of interest. Dr. Mease reported financial relationships with more than 10 pharmaceutical companies, most of which make products used for the treatment of inflammatory joint diseases.

NEW YORK – On the basis of MRI images of the hand, a neural network has been trained to distinguish seronegative and seropositive rheumatoid arthritis (RA) from psoriatic arthritis (PsA) as well as from each other, according to a study that was presented at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

In the work so far, the neural network was correct about 70% of the time in the absence of any further clinical analyses, according to David Simon, MD, a rheumatologist in the department of internal medicine at Friedrich-Alexander University, Erlangen, Germany.

Ted Bosworth/MDedge News

Previous to this work, “there has been no study that has exclusively used hand MRI data and deep learning without requiring further expert input for the classification of arthritides,” Dr. Simon said.

In fact, when demographic and clinical data were added, there was no improvement in the performance of patient classification relative to the deep learning classification alone, according to the data presented by Dr. Simon.

The images were evaluated with residual neural networks (ResNet), which represents a sophisticated form of deep learning to facilitate the flow of information across the network layers as they form to improve accuracy in their ability to distinguish one form of disease from the other. The training was performed on images from the T1 coronal, T2 corona1, T1 coronal fat suppressed with contrast, T1 axial fat suppressed with contrast, and T2 fat suppressed axial sequences.

The study included hand MRI scans from 135 patients with seronegative RA, 190 with seropositive RA, 177 with PsA, and 147 with psoriasis. The performance was judged on the basis of area under the receiver operating characteristics curve (AUROC) with and without input of clinical characteristics. Patients who had psoriasis without clinical arthritis were included as a control population.

The AUROC for accuracy was 75% for seropositive RA relative to PsA, 74% for seronegative RA relative to PsA, and 67% for seropositive relative to seronegative RA. Of the patients who had psoriasis without arthritis, 98% were classified as PsA and 2% as RA.

Subsequent to the classification of the patients with psoriasis, 14 of the 147 (9.5%) have developed PsA so far over a relatively short follow-up. All of these were among those identified as PsA by neural network evaluation of the hand MRIs.

This suggests that “a PsA-like pattern may be present early in the course of psoriatic disease,” Dr. Simon said.

In the groups with joint disease, who had mean ages ranging from 56 to 65, the mean disease durations were 2.6 years for those with seropositive RA, 1.3 years for those with seronegative RA, and 0.8 years for those with PsA. The patients with psoriasis were younger (mean age, 40.5 years) but had a longer disease duration (mean 4.2 years).

All of the MRI sequences were relevant for classification, but contrast did not appear to help with accuracy.

“If the images with contrast enhancement were deleted, the loss of performance was only marginal,” Dr. Simon reported.

The accuracy of neural networks increases with data, making it likely that further refinements in methodology will lead to a greater degree of accuracy, according to Dr. Simon. While the methodology is not yet ready for routine use in the clinic, the study demonstrates that neural network analysis of hand MRI to distinguish forms of arthritis “is possible.” Further studies are planned toward the goal of creating a viable clinical tool.

“Of course, if we could create an accurate tool with ultrasound, this would be even more practical,” said Dr. Simon, recognizing the value of an office tool, but he cautioned that this would be far more challenging.

“The precision of MRI is an important factor for effective neural network training,” he said.

Utility: ‘In challenging cases if the accuracy improves’?

A viable method for objectively and rapidly distinguishing inflammatory joint diseases, particularly in patients with an ambiguous clinical presentation, is an unmet need, according to Philip J. Mease, MD, director of rheumatology research at Swedish Medical Center, Seattle.

Although the data presented are promising, Dr. Mease said in an interview that he believes there is a fair amount of work to be done before imaging analysis based on deep learning makes its way into routine clinical care. He is also hoping for methods to distinguish RA from PsA that are easier and less expensive, such as serum biomarkers. However, he agreed that a MRI-based tool could be useful when differentiating disease that is challenging.

“MRI is an expensive way for routine classification of disease, but this approach could be useful in challenging cases if the accuracy improves,” he said.

Meanwhile, other clinical researchers might want to test the principle. “You can try it,” said Dr. Simon, who reported that his team has made the methodology publicly available.

Dr. Simon reported no conflicts of interest. Dr. Mease reported financial relationships with more than 10 pharmaceutical companies, most of which make products used for the treatment of inflammatory joint diseases.

Vasculitis is a process in which blood vessels become inflamed and necrotic. Classic small vessel vasculitis reveals a leukocytoclastic vasculitis and most commonly presents as palpable purpura. Exercise-induced vasculitis (EIV) is a benign form of vasculitis involving the small vessels, brought on by exercise. It is also known as “golfer’s vasculitis.” A form of EIV has been described in the literature as “Disney dermatitis.” It is often seen in healthy adults after a long day of walking at the parks. Other forms of exercise, such as jogging, hiking, or swimming, may also cause the condition.

Clinically, EIV affects the lower legs and presents as purpuric macules. Edema may be present. Lesions may be asymptomatic or may present with pruritus or burning. Diagnosis is often made clinically. Skin biopsies for H&E and DIF (direct immunofluorescence) can help distinguish the type of vasculitis that is present. Laboratory tests may be needed to exclude other causes of vasculitis. Episodes may be recurrent.

Henoch-Schönlein purpura (HSP), also called anaphylactoid purpura, is a subtype of small-vessel vasculitis where IgA immunoglobulin is deposited in the vessel walls. It is the most common form of vasculitis is children (usually ages 4-8). In addition to skin, organs such as joints, kidneys, and intestines can be involved. Schamberg’s disease, or capillaritis, is also called pigmented purpura. In this benign condition, leakage from capillaries results in erythematous to brown patches on the lower extremities. A true vasculitis is not seen. The brown discoloration is due to hemosiderin deposition. Cryoglobulinemia is a rare condition in which abnormal immunoglobulin complexes deposit in tissues and vessels. Leukocytoclastic vasculitis is present in small vessels. Palpable purpura and livedo may be seen clinically, and systemic symptoms may be present.

Treatment of EIV is largely supportive as lesions will resolve on their own over 3-4 weeks. Postinflammatory hyperpigmentation may result. Temporary cessation of exercise and compression stockings can help speed up the resolution of lesions. Systemic medications used in the treatment of severe vasculitis, such as systemic steroids, dapsone, and colchicine, are not needed in EIV.
 

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.

Vasculitis is a process in which blood vessels become inflamed and necrotic. Classic small vessel vasculitis reveals a leukocytoclastic vasculitis and most commonly presents as palpable purpura. Exercise-induced vasculitis (EIV) is a benign form of vasculitis involving the small vessels, brought on by exercise. It is also known as “golfer’s vasculitis.” A form of EIV has been described in the literature as “Disney dermatitis.” It is often seen in healthy adults after a long day of walking at the parks. Other forms of exercise, such as jogging, hiking, or swimming, may also cause the condition.

Clinically, EIV affects the lower legs and presents as purpuric macules. Edema may be present. Lesions may be asymptomatic or may present with pruritus or burning. Diagnosis is often made clinically. Skin biopsies for H&E and DIF (direct immunofluorescence) can help distinguish the type of vasculitis that is present. Laboratory tests may be needed to exclude other causes of vasculitis. Episodes may be recurrent.

Henoch-Schönlein purpura (HSP), also called anaphylactoid purpura, is a subtype of small-vessel vasculitis where IgA immunoglobulin is deposited in the vessel walls. It is the most common form of vasculitis is children (usually ages 4-8). In addition to skin, organs such as joints, kidneys, and intestines can be involved. Schamberg’s disease, or capillaritis, is also called pigmented purpura. In this benign condition, leakage from capillaries results in erythematous to brown patches on the lower extremities. A true vasculitis is not seen. The brown discoloration is due to hemosiderin deposition. Cryoglobulinemia is a rare condition in which abnormal immunoglobulin complexes deposit in tissues and vessels. Leukocytoclastic vasculitis is present in small vessels. Palpable purpura and livedo may be seen clinically, and systemic symptoms may be present.

Treatment of EIV is largely supportive as lesions will resolve on their own over 3-4 weeks. Postinflammatory hyperpigmentation may result. Temporary cessation of exercise and compression stockings can help speed up the resolution of lesions. Systemic medications used in the treatment of severe vasculitis, such as systemic steroids, dapsone, and colchicine, are not needed in EIV.
 

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.

Vasculitis is a process in which blood vessels become inflamed and necrotic. Classic small vessel vasculitis reveals a leukocytoclastic vasculitis and most commonly presents as palpable purpura. Exercise-induced vasculitis (EIV) is a benign form of vasculitis involving the small vessels, brought on by exercise. It is also known as “golfer’s vasculitis.” A form of EIV has been described in the literature as “Disney dermatitis.” It is often seen in healthy adults after a long day of walking at the parks. Other forms of exercise, such as jogging, hiking, or swimming, may also cause the condition.

Clinically, EIV affects the lower legs and presents as purpuric macules. Edema may be present. Lesions may be asymptomatic or may present with pruritus or burning. Diagnosis is often made clinically. Skin biopsies for H&E and DIF (direct immunofluorescence) can help distinguish the type of vasculitis that is present. Laboratory tests may be needed to exclude other causes of vasculitis. Episodes may be recurrent.

Henoch-Schönlein purpura (HSP), also called anaphylactoid purpura, is a subtype of small-vessel vasculitis where IgA immunoglobulin is deposited in the vessel walls. It is the most common form of vasculitis is children (usually ages 4-8). In addition to skin, organs such as joints, kidneys, and intestines can be involved. Schamberg’s disease, or capillaritis, is also called pigmented purpura. In this benign condition, leakage from capillaries results in erythematous to brown patches on the lower extremities. A true vasculitis is not seen. The brown discoloration is due to hemosiderin deposition. Cryoglobulinemia is a rare condition in which abnormal immunoglobulin complexes deposit in tissues and vessels. Leukocytoclastic vasculitis is present in small vessels. Palpable purpura and livedo may be seen clinically, and systemic symptoms may be present.

Treatment of EIV is largely supportive as lesions will resolve on their own over 3-4 weeks. Postinflammatory hyperpigmentation may result. Temporary cessation of exercise and compression stockings can help speed up the resolution of lesions. Systemic medications used in the treatment of severe vasculitis, such as systemic steroids, dapsone, and colchicine, are not needed in EIV.
 

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.

A 24-YEAR-OLD WOMAN with a history of guttate psoriasis, for which she was taking adalimumab, presented with a 2-week history of diffuse papules and plaques on her neck, back, torso, and upper and lower extremities (FIGURE 1). She said that the lesions were pruritic and seemed similar to those that erupted during past outbreaks of psoriasis—although they were more numerous and progressive. So, the patient (a nurse) decided to take her biweekly dose (40 mg) of adalimumab 1 week early. After administration, the rash significantly worsened, spreading to the rest of her trunk and extremities.

Physical exam was notable for multiple erythematous papules and plaques with central clearing and light peripheral scaling on both arms and legs, as well as her chest and back. The patient also indicated she’d adopted a stray cat 2 weeks prior. Given the patient’s pet exposure and the annular nature of the lesions, a potassium hydroxide (KOH) preparation was done.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Diagnosis: Tinea corporis

The KOH preparation was positive for hyphae in 4 separate sites (trunk, left arm, left leg, and left neck), confirming the diagnosis of severe extensive tinea corporis (FIGURE 2).

Dermatophyte (tinea) infections are caused by fungi that invade and reproduce in the skin, hair, and nails. Dermatophytes, which include the genera Trichophyton, Microsporum, and Epidermophyton, are the most common cause of superficial mycotic infections. As of 2016, the worldwide prevalence of superficial mycotic infections was 20% to 25%.¹ Tinea corporis can result from contact with people, animals, or soil. Infections resulting from animal-to-human contact are often transmitted by domestic animals. In this case, the patient’s exposure was from her new cat.

Tinea corporis classically manifests as pruritic, erythematous patches or plaques with central clearing, giving it an annular appearance. The response to a tinea infection depends on the immune system of the host and can range in severity from superficial to severe.² There are 2 forms of severe dermatophytosis: invasive, which involves localized perifollicular sites or deep dermatophytosis, and extensive, which is confined to the stratum corneum but results in numerous lesions.³

The diagnosis of tinea corporis is commonly confirmed using direct microscopic examination with 10% to 20% KOH preparation, which will show branching and septate hyphal filaments.⁴

Several conditions with annular lesions comprise the differential

The findings of pruritic annular erythematous lesions on the patient’s neck, chest, trunk, and bilateral extremities led the patient to suspect this was a worsening case of her guttate psoriasis. Other possible diagnoses included pityriasis rosea, subacute cutaneous lupus erythematosus (SCLE), and secondary syphilis.

Continue to: Guttate psoriasis

Guttate psoriasis would not typically progress during treatment with adalimumab, although tumor necrosis factor (TNF) inhibitors have been associated with worsening psoriasis. Guttate psoriasis manifests with small, pink to red, scaly raindrop-shaped patches over the trunk and extremities.

Pityriasis rosea, a rash that resembles branches of a Christmas tree, was strongly considered given the appearance of the lesions on the patient’s back. It commonly manifests as round to oval lesions with a subtle advancing border and central fine scaling, similar in shape and color to the lesions seen in tinea corporis.

SCLE has been associated with use of TNF inhibitors, but our patient had no other lupus-like symptoms, such as fatigue, fever, headaches, or joint pain. SCLE lesions are often annular with raised pink to red borders similar in appearance to tinea corporis.

Secondary syphilis was ruled out in this patient because she had a negative rapid plasma reagin test. Secondary syphilis most commonly manifests with diffuse, nonpruritic pink to red-brown lesions on the palms and soles of patients. Patients often have prodromal symptoms that include fever, weight loss, myalgias, headache, and sore throat.

Terbinafine, Yes, but for how long?

Historically, terbinafine has been prescribed at 250 mg once daily for 2 weeks for extensive tinea corporis. However, recent studies in India suggest that terbinafine should be dosed at 250 mg twice daily, with longer durations of treatment, due to resistance.⁵ In the United States, it is reasonable to prescribe oral terbinafine 250 mg once daily for 4 weeks and then re-evaluate the patient in a case of extensive tinea corporis.

Other oral antifungals that can effectively treat extensive tinea corporis include itraconazole, fluconazole, and griseofulvin.¹ Itraconazole and terbinafine are equally effective and safe in the treatment of tinea corporis, although itraconazole is significantly more expensive.⁶ Furthermore, a recent study found that combination therapy with oral terbinafine and itraconazole is as safe as monotherapy and is an option when terbinafine resistance is suspected.⁷

Our patient was initially started on oral terbinafine 250 mg/d. After the first dose, the patient requested a change in medication because there was no improvement in the rash. The patient was then prescribed oral fluconazole 300 mg daily and the tinea cleared after 2 months of daily therapy. (We surmise the treatment course may have been prolonged due to the possible immunosuppressant effects of adalimumab.) At the completion of treatment for the tinea corporis, the patient was restarted on adalimumab 40 mg biweekly for her psoriasis. 

A 24-YEAR-OLD WOMAN with a history of guttate psoriasis, for which she was taking adalimumab, presented with a 2-week history of diffuse papules and plaques on her neck, back, torso, and upper and lower extremities (FIGURE 1). She said that the lesions were pruritic and seemed similar to those that erupted during past outbreaks of psoriasis—although they were more numerous and progressive. So, the patient (a nurse) decided to take her biweekly dose (40 mg) of adalimumab 1 week early. After administration, the rash significantly worsened, spreading to the rest of her trunk and extremities.

Physical exam was notable for multiple erythematous papules and plaques with central clearing and light peripheral scaling on both arms and legs, as well as her chest and back. The patient also indicated she’d adopted a stray cat 2 weeks prior. Given the patient’s pet exposure and the annular nature of the lesions, a potassium hydroxide (KOH) preparation was done.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Diagnosis: Tinea corporis

The KOH preparation was positive for hyphae in 4 separate sites (trunk, left arm, left leg, and left neck), confirming the diagnosis of severe extensive tinea corporis (FIGURE 2).

Dermatophyte (tinea) infections are caused by fungi that invade and reproduce in the skin, hair, and nails. Dermatophytes, which include the genera Trichophyton, Microsporum, and Epidermophyton, are the most common cause of superficial mycotic infections. As of 2016, the worldwide prevalence of superficial mycotic infections was 20% to 25%.¹ Tinea corporis can result from contact with people, animals, or soil. Infections resulting from animal-to-human contact are often transmitted by domestic animals. In this case, the patient’s exposure was from her new cat.

Tinea corporis classically manifests as pruritic, erythematous patches or plaques with central clearing, giving it an annular appearance. The response to a tinea infection depends on the immune system of the host and can range in severity from superficial to severe.² There are 2 forms of severe dermatophytosis: invasive, which involves localized perifollicular sites or deep dermatophytosis, and extensive, which is confined to the stratum corneum but results in numerous lesions.³

The diagnosis of tinea corporis is commonly confirmed using direct microscopic examination with 10% to 20% KOH preparation, which will show branching and septate hyphal filaments.⁴

Several conditions with annular lesions comprise the differential

The findings of pruritic annular erythematous lesions on the patient’s neck, chest, trunk, and bilateral extremities led the patient to suspect this was a worsening case of her guttate psoriasis. Other possible diagnoses included pityriasis rosea, subacute cutaneous lupus erythematosus (SCLE), and secondary syphilis.

Continue to: Guttate psoriasis

Guttate psoriasis would not typically progress during treatment with adalimumab, although tumor necrosis factor (TNF) inhibitors have been associated with worsening psoriasis. Guttate psoriasis manifests with small, pink to red, scaly raindrop-shaped patches over the trunk and extremities.

Pityriasis rosea, a rash that resembles branches of a Christmas tree, was strongly considered given the appearance of the lesions on the patient’s back. It commonly manifests as round to oval lesions with a subtle advancing border and central fine scaling, similar in shape and color to the lesions seen in tinea corporis.

SCLE has been associated with use of TNF inhibitors, but our patient had no other lupus-like symptoms, such as fatigue, fever, headaches, or joint pain. SCLE lesions are often annular with raised pink to red borders similar in appearance to tinea corporis.

Secondary syphilis was ruled out in this patient because she had a negative rapid plasma reagin test. Secondary syphilis most commonly manifests with diffuse, nonpruritic pink to red-brown lesions on the palms and soles of patients. Patients often have prodromal symptoms that include fever, weight loss, myalgias, headache, and sore throat.

Terbinafine, Yes, but for how long?

Historically, terbinafine has been prescribed at 250 mg once daily for 2 weeks for extensive tinea corporis. However, recent studies in India suggest that terbinafine should be dosed at 250 mg twice daily, with longer durations of treatment, due to resistance.⁵ In the United States, it is reasonable to prescribe oral terbinafine 250 mg once daily for 4 weeks and then re-evaluate the patient in a case of extensive tinea corporis.

Other oral antifungals that can effectively treat extensive tinea corporis include itraconazole, fluconazole, and griseofulvin.¹ Itraconazole and terbinafine are equally effective and safe in the treatment of tinea corporis, although itraconazole is significantly more expensive.⁶ Furthermore, a recent study found that combination therapy with oral terbinafine and itraconazole is as safe as monotherapy and is an option when terbinafine resistance is suspected.⁷

Our patient was initially started on oral terbinafine 250 mg/d. After the first dose, the patient requested a change in medication because there was no improvement in the rash. The patient was then prescribed oral fluconazole 300 mg daily and the tinea cleared after 2 months of daily therapy. (We surmise the treatment course may have been prolonged due to the possible immunosuppressant effects of adalimumab.) At the completion of treatment for the tinea corporis, the patient was restarted on adalimumab 40 mg biweekly for her psoriasis. 

A 24-YEAR-OLD WOMAN with a history of guttate psoriasis, for which she was taking adalimumab, presented with a 2-week history of diffuse papules and plaques on her neck, back, torso, and upper and lower extremities (FIGURE 1). She said that the lesions were pruritic and seemed similar to those that erupted during past outbreaks of psoriasis—although they were more numerous and progressive. So, the patient (a nurse) decided to take her biweekly dose (40 mg) of adalimumab 1 week early. After administration, the rash significantly worsened, spreading to the rest of her trunk and extremities.

Physical exam was notable for multiple erythematous papules and plaques with central clearing and light peripheral scaling on both arms and legs, as well as her chest and back. The patient also indicated she’d adopted a stray cat 2 weeks prior. Given the patient’s pet exposure and the annular nature of the lesions, a potassium hydroxide (KOH) preparation was done.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Diagnosis: Tinea corporis

The KOH preparation was positive for hyphae in 4 separate sites (trunk, left arm, left leg, and left neck), confirming the diagnosis of severe extensive tinea corporis (FIGURE 2).

Dermatophyte (tinea) infections are caused by fungi that invade and reproduce in the skin, hair, and nails. Dermatophytes, which include the genera Trichophyton, Microsporum, and Epidermophyton, are the most common cause of superficial mycotic infections. As of 2016, the worldwide prevalence of superficial mycotic infections was 20% to 25%.¹ Tinea corporis can result from contact with people, animals, or soil. Infections resulting from animal-to-human contact are often transmitted by domestic animals. In this case, the patient’s exposure was from her new cat.

Tinea corporis classically manifests as pruritic, erythematous patches or plaques with central clearing, giving it an annular appearance. The response to a tinea infection depends on the immune system of the host and can range in severity from superficial to severe.² There are 2 forms of severe dermatophytosis: invasive, which involves localized perifollicular sites or deep dermatophytosis, and extensive, which is confined to the stratum corneum but results in numerous lesions.³

The diagnosis of tinea corporis is commonly confirmed using direct microscopic examination with 10% to 20% KOH preparation, which will show branching and septate hyphal filaments.⁴

Several conditions with annular lesions comprise the differential

The findings of pruritic annular erythematous lesions on the patient’s neck, chest, trunk, and bilateral extremities led the patient to suspect this was a worsening case of her guttate psoriasis. Other possible diagnoses included pityriasis rosea, subacute cutaneous lupus erythematosus (SCLE), and secondary syphilis.

Continue to: Guttate psoriasis

Guttate psoriasis would not typically progress during treatment with adalimumab, although tumor necrosis factor (TNF) inhibitors have been associated with worsening psoriasis. Guttate psoriasis manifests with small, pink to red, scaly raindrop-shaped patches over the trunk and extremities.

Pityriasis rosea, a rash that resembles branches of a Christmas tree, was strongly considered given the appearance of the lesions on the patient’s back. It commonly manifests as round to oval lesions with a subtle advancing border and central fine scaling, similar in shape and color to the lesions seen in tinea corporis.

SCLE has been associated with use of TNF inhibitors, but our patient had no other lupus-like symptoms, such as fatigue, fever, headaches, or joint pain. SCLE lesions are often annular with raised pink to red borders similar in appearance to tinea corporis.

Secondary syphilis was ruled out in this patient because she had a negative rapid plasma reagin test. Secondary syphilis most commonly manifests with diffuse, nonpruritic pink to red-brown lesions on the palms and soles of patients. Patients often have prodromal symptoms that include fever, weight loss, myalgias, headache, and sore throat.

Terbinafine, Yes, but for how long?

Historically, terbinafine has been prescribed at 250 mg once daily for 2 weeks for extensive tinea corporis. However, recent studies in India suggest that terbinafine should be dosed at 250 mg twice daily, with longer durations of treatment, due to resistance.⁵ In the United States, it is reasonable to prescribe oral terbinafine 250 mg once daily for 4 weeks and then re-evaluate the patient in a case of extensive tinea corporis.

Other oral antifungals that can effectively treat extensive tinea corporis include itraconazole, fluconazole, and griseofulvin.¹ Itraconazole and terbinafine are equally effective and safe in the treatment of tinea corporis, although itraconazole is significantly more expensive.⁶ Furthermore, a recent study found that combination therapy with oral terbinafine and itraconazole is as safe as monotherapy and is an option when terbinafine resistance is suspected.⁷

Our patient was initially started on oral terbinafine 250 mg/d. After the first dose, the patient requested a change in medication because there was no improvement in the rash. The patient was then prescribed oral fluconazole 300 mg daily and the tinea cleared after 2 months of daily therapy. (We surmise the treatment course may have been prolonged due to the possible immunosuppressant effects of adalimumab.) At the completion of treatment for the tinea corporis, the patient was restarted on adalimumab 40 mg biweekly for her psoriasis. 

Treatment with berdazimer gel, a novel, topical nitric oxide–releasing agent, significantly improved clearance of molluscum contagiosum lesions, compared with placebo, in a study of 891 individuals at 55 clinics.

Molluscum contagiosum (MC) remains a common infection that, despite being self-limiting, may persist for months or years, and is associated with quality of life concerns and the need for ongoing therapy, wrote John C. Browning, MD, of Texas Dermatology and Laser Specialists, San Antonio, and colleagues, who conducted the phase 3 randomized study.

The infection is most common in children aged 1-14 years, and treatment may be needed in part to avoid infecting peers and family members, they said. No treatments for molluscum are currently approved by the Food and Drug Administration.

In the study, which was published in JAMA Dermatology, the researchers randomized 444 patients to berdazimer gel 10.3% and 447 to a placebo gel, applied once daily in a thin layer on all MC lesions for 12 weeks. The study was conducted at 55 clinics across the United States between Sept. 1, 2020, and July 21, 2021. The mean age of the patients was about 6.5 years (range was 0.9-49 years), and about 85% were White. Participants had 3-70 raised MC lesions; those with sexually transmitted MC or MC in the periocular area were excluded. The primary endpoint was complete clearance of MC lesions after 12 weeks of treatment. At 12 weeks, significantly more patients treated with berdazimer gel achieved complete clearance than those on vehicle (32.4% vs. 19.7%; P < .001). A total of 64 (14.4%) patients in the berdazimer group discontinued treatment because of MC clearance, compared with 40 patients (8.9%) in the vehicle group.

Most adverse events were mild or moderate, and rates of adverse events resulting in treatment discontinuation were low overall for both groups; the most common adverse events were application-site pain and erythema, which were mostly mild. Overall, 4.1% of berdazimer-treated patients and 0.7% of placebo patients discontinued the study because of adverse events.

The study findings were limited by several factors, including the small number of patients in subgroups for race, ethnicity, and age; and the lack of data on patients with sexually transmitted MC and on concomitant use with other topical MC therapies, the researchers noted.

However, the results represent the largest randomized clinical trial of berdazimer 10.3% to date, and support its potential as a first-line therapy for MC patients aged 6 months and older, according to the authors. “Berdazimer is under consideration as a first in-class therapeutic agent for MC and may provide a topical prescription alternative to other therapies used for this highly contagious and psychosocially challenging skin condition,” they said.

Having a reliable, steroid-free, safe, and efficacious medication to treat molluscum in the pediatric population, as early as age 6 months, that can be used at home would “change the whole therapeutic paradigm,” one of the study authors, Adelaide Hebert, MD, said in an interview at the Society for Pediatric Dermatology annual meeting in July, where she presented phase 2 data on berdazimer gel. “This is a common problem and the rate of infections among siblings if it goes untreated is 41%. Affected kids have a sense of isolation; they don’t get invited to swimming parties.”

The lack of a safe and effective topical therapy “has been challenging,” added Dr. Hebert, professor of dermatology and pediatrics, and chief of pediatric dermatology at the University of Texas, Houston. She noted that treatments that have been used but have not been successful include imiquimod. “I’m not impressed with tretinoin,” although it is prescribed for MC, and the most common treatment prescribed by pediatricians for molluscum – mupirocin – is “usually not effective,” she said.

Another MC treatment in trials

Another investigative treatment for molluscum contagiosum, VP-102, a drug-device combination of cantharidin 0.7% administered through a single-use precision applicator, has been evaluated in phase 3 studies of patients with MC aged 2 years and older. The results of two phase 3 studies were published in 2020.

In May 2022, Verrica Pharmaceuticals, which is developing VP-102, announced that Food and Drug Administration approval had been delayed because of deficiencies identified at a contract manufacturing organization, and that the company was working with the agency to bring VP-102 to the market as soon as possible.

A step in the right direction

Although MC is self-resolving, cases last an average of 13.5 months, and “many families look to fast-forward their child’s experience with the infection,” Vikash S. Oza, MD, a pediatric dermatologist at New York University, New York, wrote in an editorial that accompanied the berdazimer study.

“To truly create a paradigm shift in the decision to treat MC, a therapeutic treatment would need to be developed that would lead to resolution of the infection over a short time frame (ideally, weeks) with minimal discomfort,” Dr. Oza noted. “Both VP-102 and berdazimer gel, 10.3%, have the potential to be the first-ever MC therapies approved by the U.S. Food and Drug Administration,” and families seeking to reduce MC in visible areas would welcome this option for a home therapy, he said.

However, Dr. Oza emphasized that potential barriers to widespread use of these therapies include whether the efficacy can be maintained in patients who fail to comply with daily application, and the ongoing need for office-based therapy to manage sexually transmitted MC in adults and periocular and perianal MC in children. The study was funded by Novan. Lead author Dr. Browning disclosed grants from Novan during the conduct of the study; Dr. Hebert reported grants from the University of Texas Health Science Center McGovern Medical School-Houston during the conduct of the study. Disclosures of other authors included having reported equity in Novan during the conduct of the study and receiving a grant from Novan. Dr. Oza had no financial conflicts to disclose.

Treatment with berdazimer gel, a novel, topical nitric oxide–releasing agent, significantly improved clearance of molluscum contagiosum lesions, compared with placebo, in a study of 891 individuals at 55 clinics.

Molluscum contagiosum (MC) remains a common infection that, despite being self-limiting, may persist for months or years, and is associated with quality of life concerns and the need for ongoing therapy, wrote John C. Browning, MD, of Texas Dermatology and Laser Specialists, San Antonio, and colleagues, who conducted the phase 3 randomized study.

The infection is most common in children aged 1-14 years, and treatment may be needed in part to avoid infecting peers and family members, they said. No treatments for molluscum are currently approved by the Food and Drug Administration.

In the study, which was published in JAMA Dermatology, the researchers randomized 444 patients to berdazimer gel 10.3% and 447 to a placebo gel, applied once daily in a thin layer on all MC lesions for 12 weeks. The study was conducted at 55 clinics across the United States between Sept. 1, 2020, and July 21, 2021. The mean age of the patients was about 6.5 years (range was 0.9-49 years), and about 85% were White. Participants had 3-70 raised MC lesions; those with sexually transmitted MC or MC in the periocular area were excluded. The primary endpoint was complete clearance of MC lesions after 12 weeks of treatment. At 12 weeks, significantly more patients treated with berdazimer gel achieved complete clearance than those on vehicle (32.4% vs. 19.7%; P < .001). A total of 64 (14.4%) patients in the berdazimer group discontinued treatment because of MC clearance, compared with 40 patients (8.9%) in the vehicle group.

Most adverse events were mild or moderate, and rates of adverse events resulting in treatment discontinuation were low overall for both groups; the most common adverse events were application-site pain and erythema, which were mostly mild. Overall, 4.1% of berdazimer-treated patients and 0.7% of placebo patients discontinued the study because of adverse events.

The study findings were limited by several factors, including the small number of patients in subgroups for race, ethnicity, and age; and the lack of data on patients with sexually transmitted MC and on concomitant use with other topical MC therapies, the researchers noted.

However, the results represent the largest randomized clinical trial of berdazimer 10.3% to date, and support its potential as a first-line therapy for MC patients aged 6 months and older, according to the authors. “Berdazimer is under consideration as a first in-class therapeutic agent for MC and may provide a topical prescription alternative to other therapies used for this highly contagious and psychosocially challenging skin condition,” they said.

Having a reliable, steroid-free, safe, and efficacious medication to treat molluscum in the pediatric population, as early as age 6 months, that can be used at home would “change the whole therapeutic paradigm,” one of the study authors, Adelaide Hebert, MD, said in an interview at the Society for Pediatric Dermatology annual meeting in July, where she presented phase 2 data on berdazimer gel. “This is a common problem and the rate of infections among siblings if it goes untreated is 41%. Affected kids have a sense of isolation; they don’t get invited to swimming parties.”

The lack of a safe and effective topical therapy “has been challenging,” added Dr. Hebert, professor of dermatology and pediatrics, and chief of pediatric dermatology at the University of Texas, Houston. She noted that treatments that have been used but have not been successful include imiquimod. “I’m not impressed with tretinoin,” although it is prescribed for MC, and the most common treatment prescribed by pediatricians for molluscum – mupirocin – is “usually not effective,” she said.

Another MC treatment in trials

Another investigative treatment for molluscum contagiosum, VP-102, a drug-device combination of cantharidin 0.7% administered through a single-use precision applicator, has been evaluated in phase 3 studies of patients with MC aged 2 years and older. The results of two phase 3 studies were published in 2020.

In May 2022, Verrica Pharmaceuticals, which is developing VP-102, announced that Food and Drug Administration approval had been delayed because of deficiencies identified at a contract manufacturing organization, and that the company was working with the agency to bring VP-102 to the market as soon as possible.

A step in the right direction

Although MC is self-resolving, cases last an average of 13.5 months, and “many families look to fast-forward their child’s experience with the infection,” Vikash S. Oza, MD, a pediatric dermatologist at New York University, New York, wrote in an editorial that accompanied the berdazimer study.

“To truly create a paradigm shift in the decision to treat MC, a therapeutic treatment would need to be developed that would lead to resolution of the infection over a short time frame (ideally, weeks) with minimal discomfort,” Dr. Oza noted. “Both VP-102 and berdazimer gel, 10.3%, have the potential to be the first-ever MC therapies approved by the U.S. Food and Drug Administration,” and families seeking to reduce MC in visible areas would welcome this option for a home therapy, he said.

However, Dr. Oza emphasized that potential barriers to widespread use of these therapies include whether the efficacy can be maintained in patients who fail to comply with daily application, and the ongoing need for office-based therapy to manage sexually transmitted MC in adults and periocular and perianal MC in children. The study was funded by Novan. Lead author Dr. Browning disclosed grants from Novan during the conduct of the study; Dr. Hebert reported grants from the University of Texas Health Science Center McGovern Medical School-Houston during the conduct of the study. Disclosures of other authors included having reported equity in Novan during the conduct of the study and receiving a grant from Novan. Dr. Oza had no financial conflicts to disclose.

Treatment with berdazimer gel, a novel, topical nitric oxide–releasing agent, significantly improved clearance of molluscum contagiosum lesions, compared with placebo, in a study of 891 individuals at 55 clinics.

Molluscum contagiosum (MC) remains a common infection that, despite being self-limiting, may persist for months or years, and is associated with quality of life concerns and the need for ongoing therapy, wrote John C. Browning, MD, of Texas Dermatology and Laser Specialists, San Antonio, and colleagues, who conducted the phase 3 randomized study.

The infection is most common in children aged 1-14 years, and treatment may be needed in part to avoid infecting peers and family members, they said. No treatments for molluscum are currently approved by the Food and Drug Administration.

In the study, which was published in JAMA Dermatology, the researchers randomized 444 patients to berdazimer gel 10.3% and 447 to a placebo gel, applied once daily in a thin layer on all MC lesions for 12 weeks. The study was conducted at 55 clinics across the United States between Sept. 1, 2020, and July 21, 2021. The mean age of the patients was about 6.5 years (range was 0.9-49 years), and about 85% were White. Participants had 3-70 raised MC lesions; those with sexually transmitted MC or MC in the periocular area were excluded. The primary endpoint was complete clearance of MC lesions after 12 weeks of treatment. At 12 weeks, significantly more patients treated with berdazimer gel achieved complete clearance than those on vehicle (32.4% vs. 19.7%; P < .001). A total of 64 (14.4%) patients in the berdazimer group discontinued treatment because of MC clearance, compared with 40 patients (8.9%) in the vehicle group.

Most adverse events were mild or moderate, and rates of adverse events resulting in treatment discontinuation were low overall for both groups; the most common adverse events were application-site pain and erythema, which were mostly mild. Overall, 4.1% of berdazimer-treated patients and 0.7% of placebo patients discontinued the study because of adverse events.

The study findings were limited by several factors, including the small number of patients in subgroups for race, ethnicity, and age; and the lack of data on patients with sexually transmitted MC and on concomitant use with other topical MC therapies, the researchers noted.

However, the results represent the largest randomized clinical trial of berdazimer 10.3% to date, and support its potential as a first-line therapy for MC patients aged 6 months and older, according to the authors. “Berdazimer is under consideration as a first in-class therapeutic agent for MC and may provide a topical prescription alternative to other therapies used for this highly contagious and psychosocially challenging skin condition,” they said.

Having a reliable, steroid-free, safe, and efficacious medication to treat molluscum in the pediatric population, as early as age 6 months, that can be used at home would “change the whole therapeutic paradigm,” one of the study authors, Adelaide Hebert, MD, said in an interview at the Society for Pediatric Dermatology annual meeting in July, where she presented phase 2 data on berdazimer gel. “This is a common problem and the rate of infections among siblings if it goes untreated is 41%. Affected kids have a sense of isolation; they don’t get invited to swimming parties.”

The lack of a safe and effective topical therapy “has been challenging,” added Dr. Hebert, professor of dermatology and pediatrics, and chief of pediatric dermatology at the University of Texas, Houston. She noted that treatments that have been used but have not been successful include imiquimod. “I’m not impressed with tretinoin,” although it is prescribed for MC, and the most common treatment prescribed by pediatricians for molluscum – mupirocin – is “usually not effective,” she said.

Another MC treatment in trials

Another investigative treatment for molluscum contagiosum, VP-102, a drug-device combination of cantharidin 0.7% administered through a single-use precision applicator, has been evaluated in phase 3 studies of patients with MC aged 2 years and older. The results of two phase 3 studies were published in 2020.

In May 2022, Verrica Pharmaceuticals, which is developing VP-102, announced that Food and Drug Administration approval had been delayed because of deficiencies identified at a contract manufacturing organization, and that the company was working with the agency to bring VP-102 to the market as soon as possible.

A step in the right direction

Although MC is self-resolving, cases last an average of 13.5 months, and “many families look to fast-forward their child’s experience with the infection,” Vikash S. Oza, MD, a pediatric dermatologist at New York University, New York, wrote in an editorial that accompanied the berdazimer study.

“To truly create a paradigm shift in the decision to treat MC, a therapeutic treatment would need to be developed that would lead to resolution of the infection over a short time frame (ideally, weeks) with minimal discomfort,” Dr. Oza noted. “Both VP-102 and berdazimer gel, 10.3%, have the potential to be the first-ever MC therapies approved by the U.S. Food and Drug Administration,” and families seeking to reduce MC in visible areas would welcome this option for a home therapy, he said.

However, Dr. Oza emphasized that potential barriers to widespread use of these therapies include whether the efficacy can be maintained in patients who fail to comply with daily application, and the ongoing need for office-based therapy to manage sexually transmitted MC in adults and periocular and perianal MC in children. The study was funded by Novan. Lead author Dr. Browning disclosed grants from Novan during the conduct of the study; Dr. Hebert reported grants from the University of Texas Health Science Center McGovern Medical School-Houston during the conduct of the study. Disclosures of other authors included having reported equity in Novan during the conduct of the study and receiving a grant from Novan. Dr. Oza had no financial conflicts to disclose.