Treatment of multicentric reticulohistiocytosis with etanercept.

An otherwise healthy 46-year-old man presented with a 1-year history of an ill-defined acral eruption that had evolved over several weeks into reddish-brown papules and nodules, together with a progressive inflammatory polyarthritis. Skin lesions ranging from several millimeters to several centimeters in diameter were present on the dorsal and palmar aspects of the hands (Figure 1) and on the forearms, extensor elbows, chest, paranasal face, neck, pinnae, and scalp. A skin biopsy revealed an intradermal infiltrate composed predominantly of histiocytes and multinucleated giant cells. Many of the cells had abundant “ground glass” cytoplasm with fine periodic acid-Schiff–positive granules (Figure 2). There was severe stiffness, pain, and swelling associated with bilateral synovitis of the metacarpophalangeal joints, distal and proximal interphalangeal joints, wrists, elbows, shoulders, knees, ankles, and forefeet. Laboratoryvalues, includingcompletebloodcellcount, general chemistry panel, erythrocyte sedimentation rate, rheumatoid factor, and antinuclear antibodies were within normal limits except for an elevated total cholesterol level of262mg/dL(6.80mmol/L).The test result forperinuclear antineutrophil cytoplasmic antibodies was positive but no titer was reported and antibodies to myeloperoxidase were not obtained. A chest radiograph was unremarkable. The patient was diagnosed with multicentric reticulohistiocytosis (MRH) and initially managed with 20 mg of methotrexate weekly and 20 to 40 mg of prednisone daily for 2 months. Hydroxychloroquine was added to this regimen for 7 months with little benefit. Subsequent treatment with chlorambucil and prednisone for 3 months was accompanied by a worsening of the skin and joint disease. Radiographs taken 2 years after disease onset revealed erosive articular damage in the hands (Figure 3) and right hip. Combination therapy with cyclophosphamide (up to 200 mg daily), methotrexate (up to 25 mg weekly), and prednisone (20 mg daily) resulted in gradual improvement of only the skin eruption over 8 months, but cyclophosphamide was discontinued after the onset of gross hematuria. THERAPEUTIC CHALLENGE