Background: The spectrum of primary cutaneous CD30+ lymphoproliferative disease consists of lymphomatoid papulosis (LyP) at one extreme and CD30+ peripheral T-cell lymphoma (Ki-1+ lymphoma) presenting in the skin at the other extreme. Methotrexate has been reported to be effective in LyP, but the experience has been limited to single case reports or small series. Objective: The objective was to determine the effectiveness of methotrexate in the treatment of primary cutaneous CD30+ lymphoproliferative disease. Methods: We reviewed our 20-year experience with the use of methotrexate in 45 patients with relatively severe LyP, Ki-1+ lymphoma, and interface presentations. Results: During induction of methotrexate therapy patients received maximum doses ranging from 10 to 60 mg/week (median, 20 mg/week). Clinical improvement usually occurred quickly, typically at doses of 15 to 20 mg weekly, and satisfactory long-term control was achieved in 39 patients (87%) with maintenance doses given at 10- to 14-day intervals (range, 7 to 28 days). After methotrexate was discontinued, 10 patients remained free of CD30+ lesions from more than 24 months to more than 227 months (median, more than 127 months). The median total duration of methotrexate therapy for all patients exceeded 39 months (range, 2 to 205 months). Adverse effects were generally mild and transient and included fatigue (47%), nausea (22%), weight loss (13%), diarrhea or gastrointestinal cramping (10%), increased serum hepatic transaminase levels (27%), anemia (11%), or leukopenia (9%). Early hepatic fibrosis was found in 5 of 10 patients, all of whom had been treated for more than 3 years (range, 38 to 111 months). Conclusion: Low-dose methotrexate (25 mg or less given at 1- to 4-week intervals) is an effective and well-tolerated treatment of selected patients with primary cutaneous CD30+ lymphoproliferative disease.
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