Successful treatment of multicentric reticulohistiocytosis with alendronate: evidence for a direct effect of bisphosphonate on histiocytes.

We describe the case of a 44-year-old Japanese woman with severe nodular erythematous skin lesions and arthritis mutilans who was admitted for further treatment of multicentric reticulohistiocytosis. Skin and synovial biopsies showed heavy infiltration with tartrate-resistant acid phosphatase-positive histiocytes and multinucleated giant cells. Immunohistochemical analysis showed that some of the mononuclear cells in the skin were positive for RANKL. After 1 month of Alendronate, an aminobisphosphonate, given at a dosage of 10 mg once a week intravenously for the first 6 weeks and then once a month thereafter, the arthritis and skin nodules improved, and the remission has continued for more than 2 years. The findings in this patient suggest that osteoclast-like multinucleated giant cells differentiate locally in the skin from infiltrating histiocytes with the help of RANKL-positive stromal cells and that alendronate acts directly on cells of monocyte/macrophage lineage in humans. Thus, alendronate should be added to the list of drugs for the treatment of multicentric reticulohistiocytosis.