Management of hereditary angioedema in resource-constrained settings: A consensus statement from Indian subcontinent

Abstract

Hereditary angioedema (HAE) is an uncommon disorder characterized clinically by recurrent episodes of nonitchy subcutaneous and/or submucosal swellings. The estimated prevalence of HAE is ~ 1: 10,000 to 1: 50,000. There are no prevalence data from India, however, estimates suggest that there are 27,000 to 135,000 patients with HAE in India at present. The majority of these, however, remain undiagnosed. Replacement of plasma-derived or recombinant C1-esterase inhibitor (C1-INH) protein, administered intravenously, is the treatment of choice during the management of acute episodes of angioedema (i.e., "on-demand treatment") and is also useful for short-term prophylaxis (STP) and long-term prophylaxis (LTP). This has been found to be effective and safe even in young children and during pregnancy. Until recently, none of the first-line treatment options were available for "on-demand treatment," STP or LTP in India. As a result, physicians had to use fresh frozen plasma for both "on-demand treatment" and STP. For LTP, attenuated androgens (danazol or stanozolol) and/or tranexamic acid were commonly used. These drugs have been reported to be useful for LTP but are associated with a significant risk of adverse effects. Intravenous pd-C1-INH, the first-line treatment option, is now available in India. However, because there is no universal health insurance, access to pd-C1-INH is a significant challenge. HAE Society of India has developed these consensus guidelines for India and other resource-constrained settings where plasma-derived C1-INH therapy is the only available first-line treatment option for the management of HAE and diagnostic facilities are limited. These guidelines have been developed because it may not be possible for all patients to access the recommended therapy and at the recommended doses as suggested by the international guidelines. Moreover, it may not be feasible to follow the evaluation algorithm suggested by the international guidelines.

Keywords: Androgens; hereditary angioedema; on-demand therapy; plasma derived C1-estrase inhibitor; prophylaxis; tranexamic acid.

Figure 1.

A simplified evaluation algorithm for patients with suspected HAE in resource-constrained settings. (Please note that C4 is approximately 80% sensitive and may be normal in up to 20% of patients with confirmed diagnosis of type 1 and 2 HAE. The sensitivity of C4 may increase when performed during an episode of angioedema. A normal C4 and low C1-INH should always raise suspicion of a sample handling error and repeat testing is advised.). *Needs functional C1-INH assay testing using enzyme-linked immunosorbent assay (ELISA) for confirmation of the diagnosis. Genetic testing for the index case is mandatory for establishing a diagnosis of normal C1-INH-HAE (either whole exome sequencing or targeted next-generation sequencing). ^#Seen in association with autoimmune diseases (such as Systemic lupus erythematosus) and lymphoproliferative disorders. When the onset of angioedema is after 4th decade of life and there is no family history, acquired angioedema caused by lymphoproliferative disorders must be considered. In patients with acquired angioedema caused by autoimmune diseases, clinical manifestations of autoimmune diseases are usually evident. C1q may be low in acquired angioedema and may help differentiate it from hereditary angioedema. ^&Commonly seen with the use of angiotensin convertase enzyme (ACE) inhibitor. C1-INH, C1-esterase inhibitor; HAE, hereditary angioedema.