Hereditary Angioedema Is Associated with Neuropathic Pain, Systemic Lupus Erythematosis and Systemic Mastocytosis in an Analysis of a Health Analytics Claims Database

Rationale: The plasma kallikrein kinin system (KKS) has been associated with a variety of diseases in addition to being a key mediator of hereditary angioedema (HAE). We asked whether HAE patients were predisposed to develop such KKS associated diseases:  abdominal aortic aneurysm, anaphylaxis, cardiac vasoplegia syndrome, Crohn’s disease, diabetic macular edema, idiopathic anaphylaxis, neuropathic pain, psoriasis, psoriatic arthritis, retinopathy, rheumatoid arthritis, systemic lupus erythematosus (SLE), system mastocytosis, systemic vasculitis, thrombotic cerebrovascular accident, and ulcerative colitis.

Methods: We utilized the Truven MarketScan Database containing individual-level claims data from medical payers and Medicare supplemental plans for 80 million lives in the U.S. from 1/2010 through 7/2014. Within this dataset, an HAE population (n=1063) and 2 control populations: an angioedema population (n=138,851) and the general population (n=79,971,098) exclusive of HAE patients were defined using a combination of ICD-9 and prescription drug codes. Claims for comorbid diseases were identified and compared across the populations with calculated odds ratios and 95% confidence intervals (CI).

Results: In the HAE population, SLE was observed 2.3 times more often (OR 2.30, 95%CI: 1.47-3.59) than the angioedema control population. Neuropathic pain was observed 1.45 times (OR 1.45, 95%CI: 1.01-2.09) and systemic mastocytosis 4.79 times (OR 4.79, 95%CI: 1.51-15.18) more often than the angioedema control population.

Conclusions: In an analysis of a large longitudinal claims database, comorbid diseases of SLE, neuropathic pain and systemic mastocytosis had a greater representation in HAE patients than other angioedema patients, suggesting that activity of the KKS may be contributing to the manifestations of these diseases.