Complete Response to Thalidomide and Dexamethasone in a Patient with Necrobiotic Xanthogranuloma (NXG) Associated with Monoclonal Gammopathy of Uncertain Significance (MGUS)

Necrobiotic xanthogranuloma (NXG) is a slowly progressive, destructive and infiltrating xanthomatous cutaneous lesions with plaques and is associated with monoclonal paraproteinemia, predominantly IgG. Here, we describe the first case of NXG associated with MGUS, treated with Thalidomide plus Dexamethasone, achieving complete resolution of the skin lesions and sustaining response over 3 years post cessation of treatment.

Case: The patient is a 79 y/o male who first presented in January 2003 with multiple ulcerated, erythematous, painful skin lesions associated with telangiectasia on the back, buttock, and both upper and lower extremities. He had no facial or peri-orbital lesions, previously described in this disorder. A biopsy of the back lesion showed involvement of the reticular dermis and subcutaneous fatty tissue areas of granuloma formation with ulcerative background with changes consisting of multinucleated giant cells of several different histologies confirming the diagnosis of NXG. Plasma cells were noted in small amounts throughout the biopsy and within the nerves seen in the specimen. Laboratory work up showed hematocrit 33%, normal kidney function, and IgG kappa monoclonal protein with M spike of 0.83g/dl, serum IgG level 1980mg/dl and normal IgA, and IgM. Absence of Bence Jones protein in urine. Myeloma survey was negative for any lytic lesions. Bone marrow biopsy was notable for 10% clonal plasmacytosis, with normal trilinear hematopoeisis.

Treatment: With the diagnosis of NXG with underlying MGUS and ulcerated fungating skin lesions, in May 2003 he was started on thalidomide 100mg daily with subsequent increase to 200mg daily along with dexamethasone at 20 mg daily for 4 days q 2 wks. Patient had marked improvement in the lesions with decline in M spike and at 8 months achieved immunofixation negative CR with complete resolution of all skin lesions. Dexamethasone was decreased to 20 mg days 1–4 q month 6 months after starting it, then completely stopped 3 mos later due to intolerance. Thalidomide was continued until October 2005 when it was discontinued due to symptomatic bradycardia. He has been off therapy since then and his lesions have remained in remission over 3 years since cessation of treatment. He has maintained stable IgG since cessation of treatment.

Conclusion: Necrobiotic xanthogranuloma remains a rare condition. Management has included surgery, radiation, plasmapheresis, Intralesional corticosteroids, and systemic cytotoxic agents such as alkylating agents, interferon alpha-2b, methotrexate, hydroxychloroquine, and azathioprine. Responses with all these therapy have been incomplete or transient. Our patient was treated with thalidomide and dexamethasone for 2 years. Our case is the first to use a combination of thalidomide and pulsed dexamethasone, and achieving a sustained complete resolution of lesions providing a newer therapeutic alternative for this rare and difficult to treat disease. In the future, thalidomide analogue lenalidomide may be an attractive option in this disease.