Refractory classic juvenile pityriasis rubra pilaris successfully treated with a combination of etanercept and methotrexate

Dear Editor Pityriasis rubra pilaris (PRP) is a rare dermatosis that remains difficult to treat. We described a case that showed no response to initial therapy, which included acitretin and oral corticosteroid. The patient was successfully treated with a combination of intravenous weekly dose of methotrexate (MTX) at 7.5 mg weekly and subcutaneously injections with etanercept at 12.5 mg two times a week. A 7-year-old girl with widespread erythematous follicular papules and palmoplantar hyperkeratosis that started 3 years ago was diagnosed with PRP in other hospital on the basis of the classical manifestations and pathological changes (Figure ). Initially, the patient was given 20 mg acitretin daily for 1 month. The acitretin dosage was then reduced to 10 mg daily for 20 days. However, the patient did not show remission under this treatment. Afterward, the patient was given 40 mg prednisone daily and 5 mg oral MTX weekly for 4 weeks, which exacerbated the symptoms. The patient showed resistance to traditional therapies for PRP and was later transferred to our inpatient department. The patient's birth, medical, family, and surgical histories were unremarkable. Physical examination revealed well-demarcated and generalized erythema on the face, trunk, and extremities. Rough hyperkeratotic follicular papules and characteristic small islands of normal skin were present. Palmoplantar hyperkeratosis was also observed (Figure ). No palpable lymphadenopathy was detected. Routine blood tests, such as full blood count and blood chemistry, showed values within normal limits. Screening tests for hepatitis B, hepatitis C, HIV, rapid plasma regain, treponema pallidum particle agglutination assay, PPD, and T-spot were all negative. Anticardiolipin antibodies, ANAs, and ANCAs showed no abnormality before therapy. The disease was refractory, and the patient was resistant to traditional systemic therapies. Thus, we decided to initiate therapies combining weekly doses of intravenous MTX (7.5 mg) with subcutaneous injections of etanercept (12.5 mg) two times a week. After 3 weeks, the erythematous lesions completely subsided, leaving hypopigmented macules. Palmoplantar hyperkeratosis was also alleviated, and the skin smoothened (Figure ). No recurrent lesions were observed during the follow-up period of 0.5 year. The pathogenesis of PRP remains unclear, and no standard treatment has been established. The current therapy of PRP is based on experience from small case series and case reports. A meta-analysis suggested that isotretinoin, MTX, and biological therapy were the firstline, second-line, and third-line treatments for PRP, respectively. However, biologics such as infliximab, etanercept, adalimumab, ustekinumab, and secukinumab, have also been successfully used for PRP treatment. Biologics could be a promising tool for PRP treatment. A treatment combining MTX and biologics could reduce antibody production, although the production of antibodies against etanercept hardly ever