Malignancy and immune disorders in patients with hereditary angioedema

Hereditary angioedema (HAE) is an inherited condition manifesting as recurrent angioedema episodes which is caused by deficiency or dysfunction of C1 inhibitor. Although complement dysregulation has historically been shown to be associated with various malignancy and immune disorders, it is currently not known if HAE patients are at an increased risk of developing malignancy or autoimmune conditions.

We reviewed the charts of 49 HAE patients and identified 6 patients who had a co-existing malignancy diagnosis (two with breast cancer, one with melanoma, one with pancreatic cancer, one with renal cancer and one with cervical dysplasia) and 6 patients who had a diagnosis of a co-existing immune disorder (two with rheumatoid arthritis, two with ulcerative colitis, one with chronic urticaria with hypothyroidism and one with Sjogren's syndrome). Nearly all malignancy cases occurred in older HAE patients (> 50 years) and malignancy was diagnosed before HAE in 3 of the patients.

Our case series identified multiple hereditary angioedema (HAE) patients with co-existing malignancy and immune disorders. Based on these findings, we would advocate that physicians managing HAE patients should maintain a high index of suspicion for these conditions and that in patients with angioedema, C1 inhibitor deficiency and malignancy, a diagnosis of HAE should still be considered in addition to acquired angioedema (AAE).