Angioedema due to acquired deficiency of the C1-inhibitor is a bridging condition between autoimmunity and lymphoproliferation. We report 32 patients with acquired C1 inhibitor deficiency: 23 have anti C1-inhibitor autoantibodies; 13 have monoclonal gammopathies of unknown significance and 9 have non-Hodgkin's lymphoma. Our series suggest that different forms of B cell disorders coexist and/or evolve into each other in acquired angioedema. Haematologica 2007; 92:5: 716-718 Angioedema due to the acquired deficiency of the inhibitor of the first component of human complement (CI-INH) is a rare syndrome usually identified as acquired angioedema (AAE). One hundred and thirtysix cases are described literature.1-3 The clinical features of C1-INH deficiency, which can also be of genetic origin (hereditary angioedema, HAE), includes subcutaneous, non-pruritic swelling without accompanying urticaria, involvement of the upper respiratory tract, and partial obstruction of the gastrointestinal tract presenting as abdominal pain. Unlike HAE, AAE has no family history of angioedema, but is characterized by a This study aimed to clarify the relationship between the different forms of B cell proliferation present in AAE. Thirty-two patients were included, 23 of whom had been described elsewhere.3 Patients were followed for a median of 8 years (range: 1-24). C1-INH activity was measured with a chromogenic assay (Technochrome C1-INH, Technoclone GmbH, Vienna, Austria), antigenic measurements of C1-INH, C4 and C1q were performed by radial immunodiffusion (NOR-Partigen and [for C1q] LC-Partigen, Behring, Marburg, Germany), autoantibodies to C1-Inhibitor were detected by ELISA.4 Thirteen of 32 AAE patients (40%) fulfilled the diagnostic criteria for MGUS. According to a previous report 5 MGUS and autoantibodies to C1-INH shared the same heavy and light chain isotypes in 9 patients.Nine patients (28%) presented NHL. Based on WHO classification, 7 patients had indolent lymphoma (3 lymphoplasmacytoid lymphoma/Waldeström disease, 1 small lymphocytic lymphoma, 1 splenic marginal zone lymphoma, 1 nodal marginal zone B cells lymphoma) and 2 had high-grade malignant lymphoma (1 large B cell lymphoma and 1 mantle cell lymphoma with progression to large B cell lymphoma). All patients with indolent lymphoma had advanced stage with bone marrow infiltration. Follicular lymphoma, the most frequent istotype of indolent lymphoma, was only found in one patient. This agrees with other series of patients in which indolent lymphoma were described in the setting of autoimmune disorders. 6-7In 7 out of 9 patients, NHL was diagnosed at the onset of angioedema or developed thereafter after a minimum of 3 months to a maximum of 7 years. In 2 patients NHL was already present, but not treated, when angioedema appeared, after 6 years and 3 months respectively.Three patients received standard chemotherapy (CEOP: cyclophosphamide-vincristine and prednisone). One also received Rituximab and another received CEOP and subsequently fludarabine and cyclofosphamid...

Summary Thrombotic microangiopathies (TMAs) are rare but serious complications of bone marrow transplantation (BMT). Clinical manifestations are similar to those of thrombotic thrombocytopenic purpura (TTP), but prognosis is generally poorer despite plasma exchange. The enzymatic activity of the plasma metalloprotease ADAMTS13, which cleaves ultralarge thrombogenic multimers of von Willebrand factor (VWF) derived from activated endothelial cells, is very low or undetectable in patients with classic TTP, and protease deficiency is thought to play a mechanistic role in the formation of platelet thrombi in the microcirculation. This is the first prospective study to evaluate the incidence of TMA in 46 consecutively recruited patients undergoing autologous or allogeneic BMT and explore in parallel the behaviour of ADAMTS13, VWF antigen and VWF multimer size. The incidence of post‐BMT TMA was 6% (three of 46); all cases occurred after allogeneic BMT. Compared with baseline values plasma ADAMTS13 activity was significantly reduced in patients undergoing BMT, particularly after the conditioning regimen (mean values: 50 ± 22 vs. 77 ± 32%; P < 0·0001). In the three patients who developed TMA, ADAMTS13 decreased after conditioning, but was very low in one case only (8%). VWF antigen levels progressively increased after the conditioning regimen (228 ± 75 vs. 178 ± 76% at baseline, P = 0·002). The mean proportion of high‐molecular weight VWF multimers did not change in the various stages of BMT, even though ultralarge multimers were transiently found in same cases with and without TMA. Hence, the measurements evaluated in this study are not clinically useful to predict the occurrence of post‐BMT TMA.

C1-inhibitor (C1-INH) deficiency is the genetic defect underlying hereditary angioedema (HAE). Subjects with HAE suffer from recurrent angioedema that may result in death when it affects the larynx, severe abdominal pain when it affects the gastrointestinal mucosa and disfiguration when it affects the skin. The use of plasma-derived C1-INH concentrates to revert angioedema in HAE patients started in the 1970s. Since that time, three different preparations arrived onto the market, two of them are still present. Controlled studies and a large clinical experience indicate that C1-INH concentrate should be considered the treatment of choice for disabling angioedema attacks at any site. Efficacy has also been shown in preventing angioedema induced by invasive medical manoeuvres. Limited experience with repeated weekly infusions indicates that C1-INH can be used for long-term prophylaxis in selected patients. The safety profile is excellent and there are no reports of transmission of viral infections with the preparations available at present. C1-INH is licensed only in a limited number of countries. Clinical trials are ongoing at present to expand registration.