Bullous Pemphigoid Associated With Castleman Disease

Castleman disease (CD) is a rare, usually benign condition of unknown etiology resulting in extensive lymphoid proliferation. Castleman disease is associated with pemphigus vulgaris and paraneoplastic pemphigus.^{1 - 2} We report the first case of CD associated with bullous pemphigoid.

A 56-year-old white woman with non–insulin-dependent diabetes mellitus presented to her primary care physician with a pruritic eruption diagnosed as erythema multiforme. Hospitalization for treatment with intravenous steroids did not improve her condition. She was transferred to Vanderbilt University Medical Center, Nashville, Tenn, for evaluation.

Examination revealed extensive tense bullae with scattered lower-extremity targetoid and polycyclic plaques. There was no Nikolsky sign or oral lesions. A white blood cell count of 40.9 × 10³/µL with 50% eosinophils, a platelet count of 533 × 10³/µL, and a lactic dehydrogenase level of 1268 IU/L were noted. Findings of chemical analysis, liver function tests, sedimentation rate measurement, antinuclear antibody test, urinalysis, and anti-Ro and anti-La antibody tests were unremarkable. Results of a punch biopsy revealed profound tissue eosinophilia, dermoepidermal separation, and eosinophilic spongiosis consistent with bullous pemphigoid. Direct immunofluorescence findings revealed 1+ to 2+ linear dermoepidermal-junction C3 deposition. Autoantibodies against the epidermal side of salt–split skin basement membrane were detected (1:40) using specific anti-human IgG conjugate. Results of Western blot serum analysis revealed 230-kd and 180-kd antigens. Tetracycline and azathioprine treatment regimens were initiated without improvement.

Results of breast and pelvic examinations, mammography, chest radiography, stool hemoccult test, and Papanicolaou test were unremarkable. Findings from serum protein electrophoresis revealed monoclonal IgG-κ without associated hypogammaglobulinemia, suggesting a benign monoclonal gammopathy. Quantitative IgG, IgA, and IgM test results were unremarkable. Results of bone marrow biopsy analysis revealed hypercellularity with evidence of eosinophilia and mild plasmacytosis. Flow cytometry findings revealed mixed B and T cells without a monotypic population. The results of a computed tomographic scan revealed bilateral inguinal and axillary lymphadenopathy. Findings of a lymph node biopsy analysis revealed follicular hyperplasia with prominence of germinal centers and clinically significant interfollicular plasmacytosis plus eosinophilia, consistent with the plasma cell type of CD.

As the patient's condition improved, treatment with oral prednisone was initiated. At discharge, she was prescribed 80 mg of prednisone daily, 500 mg of tetracycline twice daily, 150 mg of azathioprine daily, 20 mg of famotidine twice daily, and insulin. She has been stable under treatment with 50 mg of azathioprine daily after the prednisone taper was completed and treatment with tetracycline was discontinued. Findings of a second computed tomographic scan revealed no residual lymphadenopathy.

Castleman disease is an atypical lymphoid proliferation. It is unclear whether it is reactive or neoplastic.^{1 - 2}

Castleman disease is classified into 2 histologic types: the hyaline-vascular type (90%) and the plasma-cell type (10%). It is also categorized into 2 clinical types: localized and multicentric. The plasma-cell type is most often abdominal and includes fever, fatigue, weight loss, hypergammaglobulinemia, anemia, leukocytosis, thrombocytosis, and hypoalbuminemia. Multicentric CD presents with diffuse lymphadenopathy and generally has an aggressive, fatal course. It is associated with malignancies such as lymphoma and Kaposi sarcoma^{2 - 5} and with human herpesvirus type 8.⁵

This case is unusual in that the patient had the rare multicentric plasma-cell type of CD without an aggressive, fatal course. Development of bullous pemphigoid in patients with CD may be related to underlying immune dysfunction. The pathogenesis is thought to be secondary to a reactive inflammatory process caused by autoimmune phenomenon, antigenic stimulation, or infections.²