Refractory Abdominal Pain in a Patient with Chronic Lymphocytic Leukemia: Be Wary of Acquired Angioedema due to C1 Esterase Inhibitor Deficiency

Abstract

Acquired angioedema due to C1 inhibitor deficiency (C1INH-AAE) is a rare and potentially fatal syndrome of bradykinin-mediated angioedema characterized by episodes of angioedema without urticaria. It typically manifests with nonpitting edema of the skin and edema in the gastrointestinal (GI) tract mucosa or upper airway. Edema of the upper airway and tongue may lead to life-threatening asphyxiation. C1INH-AAE is typically under-diagnosed because of its rarity and its propensity to mimic more common abdominal conditions and allergic reactions. In this article, we present the case of a 62-year-old male with a history of recently diagnosed chronic lymphocytic leukemia (CLL) who presented to our hospital with recurrent abdominal pain, initially suspected to have Clostridium difficile colitis and diverticulitis. He received a final diagnosis of acquired angioedema due to C1 esterase inhibitor deficiency due to concomitant symptoms of lip swelling, cutaneous nonpitting edema of his lower extremities, and complement level deficiencies. He received acute treatment with C1 esterase replacement and icatibant and was maintained on C1 esterase infusions. He also underwent chemotherapy for his underlying CLL and did not experience further recurrence of his angioedema.

Long term follow-up of complement parameters to improve the management of acquired angioedema due to C1-inhibitor deficiency

“…Regarding the type of the underlying disease, we assessed similar incidence rates to the data found in the literature. 32% of our patients were diagnosed with a lymphoproliferative disorder, while the literature mentions 27–64% [ 1 , 8 , 9 , 15 , 26 ]. MGUS was found in 53% of our patients, while other studies reported 32–48% [ 4 , 10 , 15 , 26 ].…”

“…32% of our patients were diagnosed with a lymphoproliferative disorder, while the literature mentions 27–64% [ 1 , 8 , 9 , 15 , 26 ]. MGUS was found in 53% of our patients, while other studies reported 32–48% [ 4 , 10 , 15 , 26 ]. Besides following-up the C1–INH-AAE of our patients, they are regularly monitored for the underlying disease as well.…”

“…Angioedema can occur in all body regions and can lead to a life-threatening state; if the edema occurs in the larynx, it can lead to life-threatening laryngeal edema with suffocation [ 1 , 4 , 6 , 9 , 12 , 13 , 14 , 15 ].…”

How can the monitoring of complement parameters help to treat angioedema due to C1-inhibitor deficiency?

“…2,[6][7][8][9][10][11] Angioedema can occur in all body regions and can lead to a life-threatening state; if the edema occurs in the larynx, it can lead to suffocation. 1,4,6,9,[12][13][14][15] Several factors can have a role in the development of the symptoms; widely used angiotensin converting enzyme inhibitor (ACEIs) antihypertensives must be highlighted, 9,12,16 but estrogen containing oral contraceptives, 4,9,17 mechanical trauma, psychological stress, bacterial or viral infections may also contribute to the development of edematous attacks. 1,4,8 C1-INH-AAE often accompanies malignant diseases, usually lymphomas, monoclonal gammopathy of undetermined significance (MGUS) or autoimmune diseases that contribute to the development of the angioedema with the following: 2, 6, 8, 9, 13, 16, 18-20 1) the increased activation of the classic complement pathway causes an increased usage of the C1-INH protein, which causes a relative shortage.…”

Acquired Angioedema and Chronic Lymphocytic Leukemia: Unraveling the Complex Interplay and Addressing Refractory Cases

“…Chronic lymphocytic leukemia, a B-cell lymphoproliferative disorder, is characterized by the progressive accumulation of functionally incompetent lymphocytes, and its diagnosis may pose challenges due to variable and often benign clinical presentations [ 2 ]. The link between CLL and AAE highlights the importance of recognizing this association, as AAE may be associated with CLL, necessitating comprehensive evaluation and management strategies [ 3 ].…”