Acquired Angioedema due to C1 Inhibitor Deficiency Preceding Splenic Marginal Zone Lymphoma: Further Insights from Clinical Practice

Abstract

<b><i>Background:</i></b> Acquired angioedema due to C1 inhibitor deficiency (AAE-C1-INH) is a very rare disease. In clinical practice, it may be difficult to differentiate AAE-C1-INH from hereditary angioedema due to C1-INH deficiency (HAE-C1-INH). In both conditions, patients are at an increased risk of death from asphyxiation due to upper airway obstruction. The association of AAE-C1-INH with lymphoproliferative and autoimmune diseases, and with presence of anti-C1-INH antibodies has been well documented, and treatment of the underlying condition may result in complete remission of angioedema. <b><i>Objectives:</i></b> To discuss the clinical evaluation, diagnosis, and treatment outcomes of AAE-C1-INH in the context of the care of 2 patients with recurrent isolated angioedema. <b><i>Methods:</i></b> Two patients were followed up prospectively at our clinic. Measurements of C3, C4, C1-INH, and C1q levels were carried out by nephelometry, and the functional activity of C1-INH was determined by a chromogenic assay. Hematological investigation included morphological and immunophenotyping analysis of peripheral blood, bone marrow, and spleen histopathology. Sequencing of the 8 exons and adjacent intronic regions of the <i>SERPING1</i> gene was performed using the Sanger method. <b><i>Results:</i></b> Two patients were diagnosed with AAE-C1-INH associated with splenic marginal zone lymphoma during follow-up. <b><i>Conclusions:</i></b> Close follow-up, including detailed clinical history, physical examination, and laboratory tests, of our patients with AAE-C1-INH was essential for the early diagnosis and successful treatment of the lymphoproliferative disease, leading to the resolution of the angioedema attacks.

Acquired Angioedema due to C1-Inhibitor Deficiency: A Challenging Condition

“…non-Hodgkin lymphomas, in one-third of the patients [6,7,13,14]. Splenic marginal zone lymphoma has been identified as a common condition in patients with AAE-C1-INH, representing 54-62% of the non-Hodgkin lymphomas identified [13,14]. AAE-C1-INH has also been associated with autoimmune diseases and/or anti-C1-INH autoantibodies [13].…”

“…In conjunction with C1-INH antigen levels, C1-INH functional activity, levels of C1q, and association with hematological and/or autoimmune conditions, it could be useful to establish the diagnosis of AAE-C1-INH. non-Hodgkin lymphomas, in one-third of the patients [6,7,13,14]. Splenic marginal zone lymphoma has been identified as a common condition in patients with AAE-C1-INH, representing 54-62% of the non-Hodgkin lymphomas identified [13,14].…”

“…Icatibant, a bradykinin B2 receptor antagonist, has been shown to be effective even for severe attacks, including those resistant to C1-INH concentrate [11]. The use of rituximab may reduce the frequency of angioedema attacks, particularly in the presence of anti-C1-INH autoantibodies and in the context of the treatment of lymphomas [14,16,17].…”

Acquired angioedema: an unusual presentation of haematological malignancy

“…Treatment of AAE in the setting of a lymphoproliferative disorder has been explored in a number of case reports and series 7–10. Current recommendations based on the existing literature state that acute treatment of attacks should be in the same manner as hereditary C1-INH deficiency, while an overall cure of the condition requires definitive treatment of the underlying malignancy, in this case SMZL 11…”