Resident Rounds Part III: Multiple Myeloma Presenting as Fulminant Retiform Purpura
April 2014 | Volume 13 | Issue 4 | Feature | 498 | Copyright © 2014
Fridolin J. Hoesly MD and Jason C. Sluzevich MD
Department of Dermatology, Mayo Clinic, Jacksonville, FL
Retiform purpura secondary to underlying type 1 cryoglobulinemia can be a presenting sign of multiple myeloma. Severe pain may herald microvascular occlusion and impending ulceration. Recognizing the distinctive cutaneous and histopathologic features of this occlusive vasculopathy allows for timely diagnosis and treatment.
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A 51-year-old African American female presented with a 4-month history of progressive skin ulcers on the lower extremities, associated with severe and unrelenting paresthetic pain that preceded the skin lesions by several weeks. She was initially diagnosed with pyoderma gangrenosum in the setting of mild Crohn’s disease at an outside institution, but failed to improve with prednisone. Physical examination revealed retiform purpura and necrotic ulcerations over the lower legs, ankles, and plantar feet (Figure 1). Skin biopsy demonstrated PAS-positive hyaline material occluding small and medium-sized vessels, consistent with occlusive vasculopathy (Figure 2). Serum protein electrophoresis revealed an M-spike, identified as IgG lambda on immunofixation. Quantitative serum cryoglobulin testing demonstrated a significant IgG cryoprecipitate, yielding a diagnosis of type 1 cryoglobulinemia. Rheumatoid factor and hepatitis C testing was negative, C4 complement level was depressed, and urinalysis and serum creatinine were normal. Bone marrow biopsy revealed a dense plasma cell infiltrate containing IgG heavy chains, with monoclonal lambda light chains demonstrated by flow cytometry, diagnostic of multiple myeloma. Diffuse, notably asymptomatic, osseous lytic lesions were present on computed tomography of the chest, abdomen and pelvis (Figure 3). Within three weeks, the retiform purpura progressed to extensive ischemic ulcerations (Figure 4). The patient was placed on bortezomib and dexamethasone with good response, and within one month her ulcerations and pain improved dramatically (Figure 5).
Type I cryoglobulinemia is an important cause of retiform purpura, as it is usually secondary to an underlying lymphoproliferative disorder or plasma cell dyscrasia.1 Cutaneous lesions develop from thrombotic microvascular occlusion with monoclonal IgG or IgM, and may present with Raynaud phenomenon, livedo reticularis, or variably ulcerated purpuric macules and papules.2 In instances with complete vascular occlusion, as in our case, distinctive retiform (angular and/or branched) purpuric patches may ultimately progress to stellate and geographic ischemic ulcerations. Lower extremity involvement is prototypic with all types of cryoglobulinemia, as this dependent anatomic location facilitates immunoglobulin aggregation.
Type 1 cryoglobulinemia secondary to multiple myeloma is rare. In the largest case series to date, 2 of 7 patients exhibited purpura at presentation, while 3 others developed purpura and/or necrotic ulcerations later in the disease course.3 Paresthesias and/or livedo reticularis were also noted to rarely accompany the onset of purpura, whereas in our case, prominent paresthesias preceded clinically evident skin involvement by several weeks. Other systemic manifestations can include nephropathy, arthralgias/arthritis, hypertension, and liver disease, none of which were experienced by our patient despite fulminant skin involvement.1-3 Treatment of type I cryoglobulinemia is directed at the underlying etiology. In the setting of multiple myeloma, bortezomib, dexamethasone, melphalan, lenalidomide, and thalidomide alone and in combination have been reported to be effective.3, 4,5 Plasmapheresis can be employed as a temporizing measure to acutely remove cryoglobulins from the blood, especially for patients with rapidly progressive ulcerations or inadequate response to initial treatment.5 Plasmapheresis was considered in our patient, but prompt improvement on bortezomib and dexamethasone obviated the need.
Retiform purpura is an important clinical sign with an extensive differential diagnosis including small and medium vessel vasculitis, as well as a range of primary thrombotic and embolic vasculopathies. A comprehensive systemic workup guided by cutaneous histopathology is required to identify and appropriately treat the underlying condition.