Abstract
Purpose: :
The cryopyrin-associated periodic syndromes (CAPS) are a group of rare autosomal dominant autoinflammatory disorders associated with mutations in the NLRP3 gene leading to excessive interleukin-1 release. CAPS encompasses three different entities: familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome and chronic infantile neurological cutaneous and articular syndrome (CINCA). Symptoms include rash, arthralgia, arthritis, fever, inflammation of the eyes and hearing loss. The aim of the study was to investigate the clinical, laboratory and genetic features of a 5-generation-family with CAPS considering particular uveitis.
Methods: :
A single center study of 37 family members was performed. NLRP3 gene mutations were determined. All patients had standardized clinical, laboratory and ophthalmologic assessments. The clinical and laboratory features of patients with confirmed NLRP3 mutations were compared with those of mutation-negative family-members.
Results: :
29 of the 37 family members presented an overlapping clinical phenotype of FCAS and MWS. 8 family members were asymptomatic. Fifteen (52%) of the 29 symptomatic family members carried the A439V mutation. Ten (67%) of the 15 mutation-positive patients and one (7%) of the 14 mutation-negative patients presented with bilateral anterior uveitis. The most common organ manifestations in the mutation-positive cohort were arthralgia (100%), arthritis (60%), rash (100%) including cold-induced rash (80%), conjunctivitis (73%), anterior uveitis (67%) and headaches (73%), and in the mutation-negative cohort arthralgia (71%), myalgia (50%), headaches (71%) and conjunctivitis (43%).
Conclusions: :
The NLRP3 mutation A439V may be associated with an overlapping clinical phenotype of FCAS and MWS. Uveitis seems to be associated with A439V and more common with this phenotype/genotype than reported in literature. Beside uveitis, there were no major clinical differences between mutation-positive and mutation-negative family members. For a significant number of patients, clinically diagnosed with FCAS/MWS overlap, a disease-associated mutation is not identifiable.
Keywords: uveitis-clinical/animal model