Nine year follow-up of a rare case of angioedema due to acquired C1-inhibitor deficiency with late onset and good response to attenuated androgen

BACKGROUND: Angioedema due to acquired deficiency of C1-inhibitor (C1-INH-AAE) is a rare disease sharing some clinical and laboratory similarities with hereditary angioedema, but with late onset and no positive family history. The underlining cause may be malignant or due to autoimmune diseases, but some cases remain idiopathic. CASE PRESENTATION: We report a case of a 75 year old woman suffering from recurrent episodes of angioedema since the age of 66, considered first induced by treatment with angiotensin-converting-enzyme inhibitors (ACEI). She continued to have angioedema attacks during 6 years after discontinuation of ACEI, until evaluation in our clinic in 2014, when C1 inhibitor esterase (C1-INH) deficiency was confirmed. The extended medical evaluation for inflammatory, allergic, autoimmune and neoplasic diseases was negative. C1-INH and complement fraction C4 plasma levels were significantly decreased at all measurements, but no diagnostic criteria for diseases known to induce C1-INH deficiency could be found. We first initiated daily prophylactic treatment with tranexamic acid, with no amelioration after 3 months. During the last and most severe attack, with the first facial and laryngeal edema, we have switched to attenuated androgen danazol. The evolution was very good, with prompt remission of angioedema and significant increase of C1-INH and C4 plasma levels after 2 weeks of daily danazol use. She completed 3 years of continuous treatment with low daily maintenance dose of danazol (ongoing), with no angioedema attack. We closely monitored C1-INH and C4 plasma levels, possible danazol side effects and any signs suggesting late onset of C1-INH deficiency causal disease. CONCLUSION: We reported a particular case of rare angioedema due to acquired deficiency of C1-inhibitor, which has no clear cause after long follow-up, but good response to attenuated androgen. We concluded that the awareness of angioedema due to C1-INH deficiency should be increased within medical community and therapeutic options should be more clearly indicated and available for all diagnosed cases.