Prolonged Latency Period of Danazol-Induced Liver Injury in a Patient With Hereditary Angioedema

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Danazol is an androgenic compound used to treat a variety of conditions including immune thrombocytopenic purpura (ITP), endometriosis, and hereditary angioedema. In the case of hereditary angioedema there are few drugs that have shown long term benefit to reduce the frequency of acute attacks. Danazol is one of the uncommon and few drugs that have shown such a benefit, but it has been implicated as having several deleterious effects [1]. Here we describe a case of a young man who was previously diagnosed with Hereditary Angioedema Type III (hereditary angioedema with normal C1 inhibitor) who developed drug induced liver injury after prolonged use of danazol for angioedema prophylaxis. A 34-year-old male with a prior diagnosis of hereditary angioedema presented to our hospital with orofacial swelling. He has three to four angioedema flares per year and has been intubated on at least seven occasions for concerns over impending airway compromise. Three years prior to his presentation he was started on Danazol for prophylaxis, which reduced the frequency of the flares. On this presentation to our hospital, the patient was incidentally noted to have significant elevations in several aminotransferases in a hepatocellular pattern without evidence of liver failure. An extensive workup was done to evaluate for possible causes of this elevation including viremia, sepsis, toxins, autoimmune, and other drug reactions. That workup was negative and his only medication was danazol, which was discontinued. After discontinuation of the medication his aminotransferases normalized.This case emphasizes the importance of including drug induced liver injury on the differential even several years after initiation of a drug. Danazol is a relatively uncommonly used medication and while the literature has described several etiological causes of liver injury, there is little data describing its incidence and latency period. Typically liver injury occurs between 5 days and 3 months of starting a medication although certain drugs are known to have much longer latency periods, such as amiodarone [3]. At this time more data needs to be collected in order to evaluate the features of liver injury with danazol.

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