Hepatocellular focal nodular hyperplasia after danazol treatment for hereditary angio-oedema.

Hereditary angio-oedema (HAE) is a potentially life-threatening disease manifesting as recurrent attacks of laryngeal, intra-abdominal, facial or peripheral oedema. The disease is caused by mutations in the gene coding for C1-inhibitor, resulting in low antigenic or functional concentrations of this inhibitor of complement and kinin systems. Long-term prophylactic treatment is indicated in patients with frequent or severe attacks. Attenuated androgens, anti-fibrinolytic agents and C1-inhibitor concentrates may be used prophylactically. Attenuated androgens are usually effective, but are associated with adverse effects, such as weight gain, virilization in women , arterial hypertension and hepatotoxicity. Danazol is considered a significant risk factor for atherosclerosis, caused by unfavourable changes in the serum lipid profile (1). More recently, hepatocellular adenomas and carci-nomas have been reported in patients with HAE, taking danazol for long-term prophylaxis (2, 3). Focal nodular hyperplasia (FNH) is a common benign tumour of the liver, with unknown pathogenesis (4). There are a few reports linking FNH to use of anabolic androgens (5, 6) and high endogenous sex steroids (7), even to prolonged therapy with ketoconazole (8). We report here a patient with HAE on long-term prophylaxis with danazol, who developed FNH. CASE rEpOrT A 32-year-old woman was diagnosed with HAE at the age of 16 years. Since then she has been taking danazol (Danol ® , Sanofi-Synthelabo, New York) on a regular basis at a dosage of 400 mg daily. At lower dosages, she experienced abdominal cramps and swellings in the skin. She gained weight and stopped menstruating after introduction of danazol. At the age of 30 years she was diagnosed with polycystic ovarian syndrome, and clinical examination showed an atrophic uterus. She showed signs of virilization, with acne and hirsutism. Her serum lipid profile was abnormal with high total and low-density lipoprotein (LDL) cholesterol, and she was under treatment for arterial hypertension. The patientsíiver was monitored by transaminases and an annual ultrasonography. Transaminases were normal, but a tumour was found in the right liver lobe located centrally. Magnetic resonance tomography (Fig. 1) could not differentiate between a hepatocellu-lar adenoma and FNH, but an ultrasonography guided biopsy showed FNH. Danazol was then reduced to 100 mg daily, and the patient was instructed to administer infusions of C1-inhibitor concentrate (Berinert ® , ZLB-Behring. Marburg, Germany) intravenously. Disease control was obtained by 1000 IE Berinert ® every fourth day. Ultrasonographic follow-up showed no progression of the tumour after 1 year. DISCUSSION recent reports have …