Customize your JAMA Network experience by selecting one or more topics from the list below.
In 1969, Rosai and Dorfman1 first described a series of patients with sinus histiocytosis with massive lymphadenopathy, characterized by histiocytic infiltration of lymph nodes and tissue. To our knowledge, as of 2006, there were a total of 86 reported cases of cutaneous Rosai-Dorfman disease (CRDD) in the literature,2,3 with several additional cases reported since then.
Report of a Case
An African American woman in her 50s reported a sudden eruption of dozens of facial papules and nodules 3 months previously and a 7-month history of a groin plaque. She had been treated with cefadroxil, topical clobetasol, oral prednisone, and a short course of oral isotretinoin without significant benefit.
Physical examination revealed approximately 75 pink-domed papules on the cheeks, upper lip, and chin (Figure 1) and dozens of red-brown papules becoming confluent on the right inguinal and suprapubic skin. Laboratory examination revealed a mildly elevated erythrocyte sedimentation rate (32 mm/h) and total triglyceride levels (145 mg/dL). Findings of complete and differential blood cell counts, a comprehensive metabolic panel, serum protein electrophoresis, and a light chains assay were within normal limits. Complete computed tomography of the chest, abdomen, and pelvis revealed no significant retroperitoneal, mesenteric, or pelvic lymphadenopathy. Biopsies from the groin revealed a dense infiltrate of lymphocytes and large histiocytes with abundant pale cytoplasm (Figure 2). The histiocytes showed emperipolesis of lymphocytes and occasionally red blood cells. The histiocytes seen in CRDD stain positively for macrophage marker CD68. The histopathologic differential diagnosis also includes Langerhans cell histiocytosis. While S-100 may stain positively in both CRDD and Langerhans cell histiocytosis, findings of CD1a staining are characteristically negative in CRDD. In our case, cells did not stain with melanocyte markers Melan-A or HMB45 or with cytokeratin AE1/AE or CD34 as in epithelioid sarcoma. Findings of acid-fast bacilli and Grocott methenamine silver stainings were negative.
Patient observed at 1 month (A), 8 months (B), and 14 months (C) after initiation of treatment with methotrexate.
A dense infiltrate of lymphocytes, neutrophils, and large histocytes with abundant cytoplasm; histiocytes show emperipolesis of lymphocytes (hematoxylin-eosin, original magnification ×40).
The patient’s prednisone dose was tapered, and she began treatment with oral methotrexate, 15 mg once weekly, and significant improvement was noted over the next 11 months. Subsequently, the methotrexate dose was tapered to 5 mg weekly for the next 4 months, and patient showed a complete clinical response. During this time, she also received several intralesional Kenalog injections to the larger nodules of the face and groin.
There have been a variety of treatment techniques used for CRDD, including cryotherapy, surgical excision, irradiation, oral corticosteroids, dapsone, thalidomide, and isotretinoin. To our knowledge, the use of methotrexate alone or in combination with other agents has been reported in 9 cases of systemic Rosai-Dorfman, and a complete to partial response was reported in most cases.4 By contrast, methotrexate therapy has been reported in only 3 cases of CRDD, and partial or no improvement was reported.3,5,6 However, in all of these cases, the eruption had already been present for well over a year. In our patient, a lack of response to prednisone, preexisting diabetes, and significant disease burden prompted the choice of low-dose methotrexate, to which a complete clinical response was seen over 11 months.
Though the exact cause of CRDD remains unknown, the presence of Epstein-Barr virus, human herpesvirus 6 by polymerase chain reaction, and reported eruption after vaccination7 with spontaneous remission over months to years suggests that CRDD is a benign reactive process involving a particular pattern of immune dysregulation. Early diagnosis remains a challenge in CRDD owing to its nonspecific clinical manifestations, including variable numbers of papules, nodules, plaques, or tumors. Timely diagnosis and initiation of methotrexate therapy may be key to effecting a rapid clinical remission while this disease remains in its active phase.
Corresponding Author: Natalie Z. Sun, MD, Department of Dermatology, University Hospitals Case Medical Center, 11100 Euclid Ave Lakeside 3500, Cleveland, OH 44106 (email@example.com).
Published Online: April 30, 2014. doi:10.1001/jamadermatol.2013.8679.
Conflict of Interest Disclosures: None reported.
Sun NZ, Galvin J, Cooper KD. Cutaneous Rosai-Dorfman Disease Successfully Treated With Low-Dose Methotrexate. JAMA Dermatol. 2014;150(7):787–788. doi:10.1001/jamadermatol.2013.8679
Coronavirus Resource Center