William A. Burke

Disseminated extramedullary plasmacytomas

A 53-year-old man developed multiple, widespread infiltrative tumors of his lips, eyelids, ears, distal fingers and toes, tongue, buccal mucosa, scrotum, and larynx. Biopsy results of three involved sites were similar, with dermal infiltration by well-differentiated plasma cells. Bone marrow aspirate and biopsy were essentially normal. The patient responded well to therapy with cyclophosphamide, doxorubicin, vincristine, and prednisone. Extramedullary plasmacytoma is a rare disease that most often arises in the upper respiratory tract. The relationship of this entity to other forms of myelomatosis is discussed.

Autoantibodies to Procollagen Type VII in EBA and Bullous Eruption of SLE Are HLA-DR2 Associated

Epidermolysis bullosa acquisita (EBA) is a chronic, acquired blistering disease characterized by circulating and tissue-bound IgG autoantibodies to the basement membrane zone of stratified squamous epithelium. In a preliminary study we found EBA to be associated with HLA-DR2 (1). Recently, EBA antibodies were found to react with epitopes present on a collagenase resistant domain of Type VII procollagen, a basement membrane zone (BMZ) matrix protein unique to stratified squamous epithelium (2). This feature distinguishes EBA antibodies from IgG anti-BMZ autoantibodies in all other diseases except the rare disorder, bullous eruption of systemic lupus erythematosus (BE-SLE). To determine whether HLA phenotype is a risk factor for the development of anti-Type VII procollagen, we typed 29 EBA patients (18 black, 11 white) from throughout the United States for 14 HLA-DR,DQ antigens. Twenty-five of the 29 patients were also typed for 39 HLA-A,B,C antigens. Six BE-SLE patients (all black), with anti-Type VII procollagen antibodies, also were typed for HLA antigens. The frequency of HLA antigens was compared with race matched U.S. population controls using the Fishers’ Exact test (3). The frequency of HLADR2 was increased significantly in both white EBA patients (P = 0.0006, RR = 13.05) and black EBA patients (P = 0.0013, RR = 4.81). HLA-DR2 also was present in five of six black BE-SLE patients (P = 0.0095, RR = 100.7). Our results indicate that individuals with anti-Type VII procollagen antibodies and a diagnosis of EBA or BE-SLE have an increased frequency of HLA-DR2. Published studies indicate that systemic lupus erythematosus is associated with HLA-DR2 and B8,DR3 in whites but not in blacks. Good-pasture’s disease, characterized by antibodies to Type IV collagen, is reported to be HLA-DR2 associated in whites. We conclude that HLA-DR2 or a closely linked gene constitutes an important risk factor for the development of anti-Type VIIprocollagen, EBA and BE-SLE.