Acquired angioedema as the presenting feature of lymphoproliferative disorders of mature B-lymphocytes

Acquired complement component 1 (C1) inhibitor deficiency with consequent angioedema is a rare condition that may indicate an underlying neoplasm of B-lymphocytes or plasma cells.

Three patients with C1 inhibitor deficiency and late-onset angioedema were studied to establish the presence and to characterize the nature of any underlying lymphoproliferative disorder.

Each of the patients was found to have a low-grade B-lineage lymphoma. In one patient, the underlying disorder, best characterized as splenic lymphoma with villous lymphocytes, was occult initially. The other two patients had splenic lymphoma with villous lymphocytes and small lymphocytic lymphoma, respectively. Two of the patients had an immunoglobulin M (IgM) serum paraprotein with cold agglutinin activity; the third patient had no paraprotein, but his cells expressed monoclonal membrane IgM. Two of the patients initially did not require specific anti-lymphoma therapy and responded to therapy with an attenuated androgen; in the third patient, splenectomy and cytotoxic chemotherapy led to resolution of the acquired angioedema. In all three patient, there was considerable delay in diagnosis consequent to lack of awareness of this syndrome.

The presence of a neoplasm of B-lymphocytes was established eventually in all three patients, although in one patient it was occult initially. In each case, the lymphocytes were mature B-lymphocytes that either showed cytologic evidence of plasma cell differentiation or secreted a paraprotein. Underlying lymphoma is common in patients who are seen initially with late-onset angioedema. Angioedema is an important, potentially life-threatening complication of lymphoma. Optimal patient management requires that both angioedema and the underlying lymphoma are recognized.