Adult familial cryptogenic fibrosing alveolitis in the United Kingdom

Background-Familial cases of cryptogenic fibrosing alveolitis (CFA) have pr eviously been reported; however, the prevalence and genetic background of t his disorder are not known. The clinical and epidemiological findings of 25 families identified within the UK are reported. Methods-Adult pulmonary physicians in the UK were asked to identify all fam ilies under their care in which two or more individuals had been diagnosed with fibrosing alveolitis of unknown cause. A detailed structured questionn aire was sent to each proband to delineate possible environmental/occupatio nal exposures and to obtain complete pedigree data. Physicians were also as ked to provide clinical and diagnostic information. Results-Twenty five families were identified comprising 67 cases. Suitable data for analysis were available for 21 families (57 cases). The male:femal e ratio was 1.75:1 (p<0.05). A high resolution computed tomographic (HRCT) scan was performed in 93% and a diagnosis of CFA confirmed on biopsy specim ens in 32%. The mean age at diagnosis was 55.5 (2.5) years. Fifty percent o f cases were ever smokers acid 18% had been diagnosed as asthmatic. Exposur e to known fibrogenic agents was recorded by 36% of patients. Clinical sign s/symptoms and histological findings were indistinguishable from non-famili al cases. Conclusions-This study represents the largest cohort of familial CFA cases reported to date and confirms a prevalence of 1.34 cases per 10(6) in the U K population. Although rare, such cases represent an important subgroup in which a genetic susceptibility to pulmonary fibrosis is particularly eviden t. Familial patients are younger at diagnosis but otherwise indistinguishab le from nonfamilial cases. The mode of inheritance is as yet unclear but a number of genetic loci are Likely to be involved and are the subject of ong oing studies.