Necrobiotic xanthogranuloma (NXG) is a chronic, progressive skin condition characterized by a granulomatous reaction with the potential to affect multiple organs that tends to be associated with paraproteinemia. Multiple treatments have been reported; herein, we present a case of extensive NXG successfully treated with topical nitrogen mustard (mechlorethamine).
A man in his 60s presented for treatment of striking violaceous and orange telangiectatic plaques and nodules circumferentially around the torso (Figure 1A). Thin, yellow plaques were also observed around his eyelids. The patient was noted to have thinner indurated plaques and patches on his back with 20% of his body surface area affected.
A, Clinical images of extensive annular violaceous plaques with yellow-orange centers arrayed across the torso at presentation. B, The torso is nearly clear after treatment with topical nitrogen mustard.
Histologically, biopsies of the lesions demonstrated an intense granulomatous inflammatory infiltrate involving the full thickness of the dermis (Figure 2A). There were foci of necrobiotic collagen surrounded by palisading large histiocytes and multinucleated giant cells with multiple nuclei and a wreath-like arrangement consistent with Touton cells (Figure 2B). Evaluation for a paraprotein revealed 2 peaks in the gamma region that were quantitated at 700 mg/dL and 1100 mg/dL identified as IgG-κ (to convert milligrams per deciliters to grams per liter, multiply by .01). The patient’s complete blood count test was within normal limits. A diagnosis of NXG was rendered and he was referred to hematology, who performed a bone marrow biopsy that excluded overt multiple myeloma. The patient was initially treated with hydroxychloroquine for 3 months for his NXG without response. Nightly use of topical nitrogen mustard (mechlorethamine 0.01% ointment) was prescribed.
A, Histopathological analysis shows an intense, pandermal mixed inflammatory infiltrate with granulomatous aggregates of histiocytes and lymphocytes and areas of altered collagen fibers. B, The granulomatous infiltrate displays numerous Touton-like giant cells with peripheral cytoplasmic foamy bubbles at higher magnification.
At a 12-week follow-up appointment, a dramatic improvement in the appearance of the cutaneous lesions was noted, with near complete resolution of the patches and plaques and small residual foci at the prior larger nodular areas. The patient continued topical nitrogen mustard with continued improvement over 12 additional weeks (Figure 1B). However, the patient subsequently developed ophthalmic symptoms, including vertical and abduction defects, blurred vision, and peripheral vision loss, attributed to ocular involvement of the NXG. The patient then began dexamethasone 20-mg doses twice a week and cyclophosphamide 300-mg/m2 doses on days 1, 8, and 15 of a 28-day cycle. He has shown clinical and laboratory improvement after 6 months.
Necrobiotic xanthogranuloma is a chronic granulomatous disorder with the potential to affect multiple organs and is strongly associated with paraproteinemias and lymphoproliferative disease. The typical cutaneous lesions are yellowish-to-orange and erythematous-to-violaceous papules, plaques, and nodules, often with overlying telangiectasias. Scarring and ulceration may also occur in a subset of patients. Ocular lesions are found in the vast majority of patients. For most patients, skin lesions initially start on the trunk or extremities and subsequently involve the periorbital area.1 Most cases are asymptomatic, although pain, and pruritus may occur.2 Extracutaneous sites may rarely be involved, including the lung, myocardium, larynx, pharynx, skeletal muscle, kidney, intestine, and ovary.3 Most importantly, approximately 90% of patients with NXG display a paraproteinemia, with IgG-κ monoclonal gammopathy being the most common.4
Histopathologically, NXG is characterized by a granulomatous inflammation in the dermis extending into the subcutaneous fat. There are zones of necrobiosis surrounded by granulomas with foreign body-type cells and Touton giant cells.5 Degenerated collagen is common, and cholesterol clefts within the necrobiosis are characteristic of NXG.5
Treatment approaches depend on whether the physician is treating the cutaneous NXG alone or alongside the paraproteinemia component. Successful treatments with corticosteroids (topical, intralesional, and/or systemic), alkylating agents (chlorambucil and cyclophosphamide), interferon alpha, thalidomide, lenalidomide, intravenous immunoglobulin, phototherapy, and plasmapheresis have been reported.3 Nitrogen mustard is an alkylating antineoplastic agent that has been used to treat cutaneous T-cell lymphoma for over 40 years with a good safety profile.6 Our patient demonstrated a significant improvement with topical nitrogen mustard, which may be a viable therapeutic option for some cases of NXG.
Corresponding Author: Misha Rosenbach, MD, Department of Dermatology, Hospital of the University of Pennsylvania, 3600 Spruce St, 2 Maloney Bldg, Philadelphia, PA 19104 (Misha.Rosenbach@uphs.upenn.edu).
Published Online: January 13, 2016. doi:10.1001/jamadermatol.2015.5151.
Conflict of Interest Disclosures: None reported.
Additional Contributions: We thank the patient for granting permission to publish this information.
Rodriguez O, Meyers C, Weiss BM, Elenitsas R, Rosenbach M. Necrobiotic Xanthogranuloma Treated With Topical Nitrogen Mustard (Mechlorethamine). JAMA Dermatol. 2016;152(5):589-590. doi:10.1001/jamadermatol.2015.5151