A unique case of delayed diagnosis of early onset acquired angioedema

Abstract

Acquired angioedema (AAE) is a very rare condition caused by an acquired deficiency in C1 esterase inhibitor (C1 INH). Pathogenesis of AAE can entail abnormal B cell lymphoproliferation ranging from benign monoclonal gammopathy of undetermined significance (MGUS) to malignant forms of lymphoma. Symptoms related to MGUS or malignancy are often salient and age is often used as a diagnostic tool in considering in making this diagnosis. These bradykinin-mediated angioedema episodes commonly involve face, gastrointestinal system, and pharynx with associated potential for fatality and lack associated urticaria. Hence early diagnosis is vital. This case is unique, in that it describes a very early age of presentation of AAE related to MGUS. Given young age and lack of symptoms associated with MGUS, diagnosis was delayed and significant patient morbidity and healthcare expenses occurred which could have been avoided. A 41 year-old male presented to the allergy/immunology clinic with facial, lip, and tongue swelling following tooth extraction. His history began 5 years prior, after suffering complications from a motor vehicle accident including anterograde amnesia, multiple broken ribs, and a splenic hemorrhage requiring splenectomy. Six months after the accident he developed acute onset bilateral facial swelling, lip swelling, and difficulty breathing. He had no family history of angioedema, was not taking any medications, and his serum tryptase level checked during the episode was normal. He was diagnosed with presumed food-induced allergic angioedema. The patient suffered four additional episodes of varying degree over the next five years and developed clinical depression. Immunological evaluation showed low C1-INH, low C1-INH functional percentage, C4, C2, and C1q, consistent with AAE. Further workup to determine the etiology of AAE included serum protein electrophoresis demonstrating an M-spike in the gamma region with immunofixation showing a monoclonal protein band and a serum IgM level of 1.3 g/dl. The patient was diagnosed with AAE related to MGUS.

Angioedema as the first presentation of B-cell non-Hodgkin lymphoma – an unusual case with normal C1 esterase inhibitor level: a case report

“…Thus serum C1, C1q, C2, C4 level and C1-INH protein levels will be lower than the normal (AAE Type I). This mechanism is well described and reported in many case reports [ 2 – 4 , 6 , 8 , 17 ]. Although not common, a monoclonal antibody that inactivates the C1-INH leading to non-functional C1-INH resulting in angioedema had also been reported [ 15 , 17 , 18 ].…”

“…Angioedema is a life-threatening condition which is being described as a transient, non-pruritic, non-pitting localized swelling of cutaneous and mucosal tissues, which often involves upper respiratory tract or gastrointestinal tract [ 1 , 2 ]. Neurological and cardiac involvement had also been described [ 4 , 12 ].…”

“…Angioedema is a life-threatening condition described as a transient, non-pruritic, non-pitting localized swelling of cutaneous and mucosal tissues. It often presents with facial, tongue, laryngeal or abdominal edema [ 1 , 2 ]. Several forms of angioedema are described; hereditary, acquired, allergen associated and idiopathic.…”

“…Several forms of angioedema are described; hereditary, acquired, allergen associated and idiopathic. Acquired angioedema is reported as a rare clinical manifestation [ 2 – 4 ]. However it is a well-recognized phenomenon associated with non-Hodgkin lymphoma (NHL) [ 5 – 7 ], commonly B cell type [ 1 , 8 ] as well as other lymphoproliferative disorders (lymphosarcoma, chronic lymphocytic leukemia, Waldenstrom’s macroglobulinemia and multiple myeloma [ 4 , 9 ]).…”

Acquired Angioedema Revealing a B cell Non Hodgkin Lymphoma in A Tunisian Man

“…It often presents with facial, tongue, laryngeal or abdominal edema and may be life threatening [2]. Acquired C1-inhibitor deficiency or acquired angioedema (AAE) clinical characteristic are similar to those of hereditary C1-inhibitor deficiency known as hereditary angioedema (HAE), however family history is absent in the first case.…”