D2.430 - Two cases of acquired angioedema: one with splenic lymphoma and the other with Waldenström’s macroglobulinemia

Background: Acquired angioedema with C1-inhibitor deficiency (AAE-C1-INH) is a rare condition resembling hereditary angioedema (HAE), but with low or dysfunctional C1-inhibitor (C1-INH) resulting from either due to autoantibody binding or lymphoproliferative diseases, mainly lymphatic malignancies. Being about 10-fold rarer than HAE it is believed that AAE-C1-INH prevalence is between 1:100,000and 1:150,000.  There is very limited knowledge about this disorder and no approved therapies for this condition.  

Case presentation: We present two cases of acquired angioedema, one patient diagnosed with splenic lymphoma and the other with Waldenstrom’s macroglobulinemia. Consent for publication has been obtained for the following two case presentations.

Case 1: An 83-year-old male a with history of abdominal pain and distention, facial and tongue swelling unresponsive to H1-antihistamines and oral steroids, absent C4, C1INH and CH 50. C1q was 38 (N:83-125) ug/L. He was found to have splenic lymphoma and was treated with radiation therapy. Lymphoma went into remission and angioedema subsided. Lymphoma and angioedema recurred, was treated with further radiation and the angioedema subsided again.

Case 2: A 52-year-old female presented with episodes of severe abdominal pain, vomiting, and swelling of hands, feet, lips and buttocks. C4 was <0.01 (N:0.1-0.4 g/L), C1-INH 0.08 (N: 0.21-0.39 g/L), IgM 8.3 (N 0.4-2.3 g/L), IgG 4.3 (N:7-16 g/L), IgM-ACL >150 (N: <12 units), CRP 81 (N: <10). She received eight 21-day cycles of combination chemotherapy for her lymphoplasmacytic lymphoma with rituximab (375mg/m²), cyclophosphamide (750 mg/m²) and prednisone (60 mg/m²).  She completed the treatment and received maintenance therapy with rituximab (375 mg/m²) every 3 months for 2 years. Her C4, C1-INH, serum IgM, IgG, IgM-ACL and CRP all returned to normal levels. Clinically, her angioedema and other symptoms have all subsided.

Conclusion: Acquired angioedema is a very rare occurrence with lymphoproliferative disorder. Treating the underlying disorder with radiation therapy and rituximab may lead to complete resolution of acquired angioedema.