Subject(s)
Anaphylaxis/diagnosis , Hypersensitivity/diagnosis , Laxatives/administration & dosage , Polyethylene Glycols/administration & dosage , Preoperative Care/adverse effects , Aged , Anaphylaxis/drug therapy , Anaphylaxis/etiology , Basophil Degranulation Test , Chlorpheniramine/therapeutic use , Colonoscopy , Edema , Female , Humans , Hypersensitivity/complications , Hypersensitivity/drug therapy , Hypersensitivity, Immediate , Hypotension , Methylprednisolone/therapeutic use , ParesthesiaABSTRACT
BACKGROUND: Information on F12 mutation hereditary angioedema (HAE) is still limited, but Spain is now recognized as having one of the highest concentrations of cases in Western Europe. OBJECTIVE: To describe unique features of HAE in Spanish carriers of the F12 mutation and investigate a potential role for angiotensin-converting enzyme (ACE) and aminopeptidase-P polymorphisms in disease expression. METHODS: This was a prospective observational cohort study of 35 individuals (80% females) from 9 unrelated families carrying the p.Thr309Lys mutation. We analyzed detailed medical records and complement activity (C4, C1q, C1 inhibitor) and screened for mutations in exon 9 of the F12 gene and 2 polymorphisms: XPNPEP2 c-2399A and the ACE insertion/deletion polymorphism. RESULTS: The p.Thr309Lys mutation was found in all individuals. Three of the 9 index patients had a clinically negative family history, and 72% of males and 29% of females were asymptomatic. Sixteen females (44% estrogen dependent, 56% estrogen sensitive) were clearly symptomatic. The most common locations of attacks were the abdomen (63%), face (25%), and peripheral structures (6%). Triggers other than hyperestrogenic states included stress and minor trauma or pressure. Short-term treatment with C1-inhibitor concentrate and icatibant and long-term prophylaxis with tranexamic acid were useful. The combination of the I allele and A allele was detected in 17% of patients. CONCLUSION: The polymorphisms analyzed were not a major determinant of disease expression in our population. We recommend searching for F12 mutations in women with edema attacks without associated wheals and with normal C1-inhibitor levels, particularly when they develop symptoms during hyperestrogenic states or are of Western European or African origin.