Acquired Angioedema as the First Sign of Lymphoproliferative Disorder: Case Report and Review of Literature

Abstract

Acquired angioedema due to C1-inhibitor deficiency (AAE-C1INH) is a rare condition characterized by the localized swelling of the deeper skin layers and mucous membranes, especially the face, lips, tongue, throat, and gastrointestinal tract. AAE-C1INH is strongly associated with lymphoproliferative disorders, although it can also be linked to autoimmune conditions, solid tumors, infections, or even occur without an identifiable cause. We present the case of a 45-year-old female patient with complaints of recurrent abdominal pain, bloating, and joint swelling. Laboratory testing showed decreased C1q and C4 complement levels, and C1 esterase inhibitor levels, indicative of AAE-C1INH. Further work up confirmed a diagnosis of extranodal marginal zone lymphoma with involvement of the bone marrow and spleen. Treatment with rituximab led to resolution of angioedema symptoms and almost complete remission of underlying lymphoma. This case underscores the importance of evaluating an underlying lymphoproliferative disorder in AAE-C1INH. Therefore, the early participation of a multidisciplinary team including specialists in immunology, hematology, and oncology is necessary for appropriate management.

Keywords: acquired angioedema; autoimmune diseases; complement system proteins; lymphoproliferative disorders; marginal zone lymphoma; rituximab therapy.

Figure 1.

The bone marrow biopsy showed nodular proliferation of small lymphocytes (A, H&E ×20), which were positive for CD20 by immunostaining (B, ×20). Flow cytometry analysis or peripheral blood identified a monoclonal B-cell population, which was positive for CD19 and CD20 with kappa light restriction and negative for CD5 or CD10 (flow dot plots C-E).

Figure 2.

Complement markers levels after rituximab therapy.

Figure 3.

C1-INH functional levels after rituximab therapy.