Diagnostic errors and delay of keratitis fugax hereditaria

Abstract

Aims/Purpose: To chart misdiagnoses associated with keratitis fugax hereditaria (KFH), an autosomal dominant periodic corneal autoinflammatory disease, and the frequency of misdiagnosed KFH in patients diagnosed with unspecified anterior uveitis, herpes keratitis, or unspecified keratitis.Methods: Charts of patients with genetically confirmed KFH (n = 94) were reviewed. Two Finnish biobanks provided 2037 DNA samples meeting the inclusion criterion of a diagnosis KFH can be misdiagnosed with and the exclusion criterion of having a common underlying cause of anterior uveitis, such as rheumatoid arthritis. The NLRP3 c.61G>C variant was detected using restriction fragment length polymorphism analysis, and Sanger sequencing for confirmation. Age, sex, ocular and other diagnoses, and laboratory results were collected from patients carrying the variant.Results: The time between first symptoms and the diagnosis of KFH ranged from 0 to 62 years (median, 21; interquartile range [IQR], 8–45). Analysis of patient charts revealed that the most common misdiagnoses were acute anterior uveitis (51% of all misdiagnoses/26% of all patients), conjunctivitis (26%/13%), or recurrent erosion (21%/11%). A mild anterior chamber inflammation was observed in 30% of patients, 0.5+ or 1+ by Standardization of Uveitis Nomenclature (SUN) criteria. Of the biobank samples, 12/2037 (0.59%; 95% confidence interval [CI] 0.56%–0.61%) carried the c.61G>C variant: 11 diagnosed with anterior uveitis, and one with unspecified keratitis. Three had previously been diagnosed with KFH. The age range of the 12 variant carriers varied from 38 to 79 (median, 63; IQR, 48–76) with nine females and three males.Conclusions: KFH is most frequently misdiagnosed as anterior uveitis. In Finland, it might be beneficial to add testing for the NLRP3 c.61G>C variant in existing laboratory test packages for anterior uveitis.