Muckle–Wells syndrome (MWS) is a rare genetic disorder characterised by recurrent urticaria, arthritis, sensorineural deafness, and general signs of inflammation and secondary amyloidosis. It affects the eyes in the form of conjunctivitis.1 We present a case of a female patient with MWS who presented to us with recurrent attacks of severe acute anterior uveitis which has not been reported previously in association with this syndrome.
A 56-year-old female patient presented to our A+E department with 2 days history of photophobia and blurred vision of left eye. The patient was a known case of MWS and had always suffered from episodes of conjunctivitis in the past in both eyes. On examination, her acuities were 6/6 in the right eye and 6/18 in the left eye. Anterior segment examination of the left eye showed keratic precipitates with inflammatory cells and a hypopyon in the anterior chamber (Figure 1). Fundus examination was unremarkable. The anterior uveitis resolved with standard treatment and the acuity recovered to 6/6. She presented again 2 months later with severe anterior uveitis, again responding quickly to conventional treatment. The patient is currently symptom free and is on the tapering dose of steroid drops.
MWS (first described in 1962)2 belongs to a group of hereditary periodic fever syndromes. These syndromes are characterised by intermittent attacks of fever. Four of these syndromes have been described. Familial Mediterranean fever and hyper IgD syndrome are transmitted as autosomal-recessive traits and MWS and tumour necrosis factor-receptor-associated periodic syndrome (TRAPS) are transmitted as autosomal-dominant trait.3
Patients with MWS suffer from acute febrile inflammatory episodes (denoted as ‘aguey bouts’ in Derbyshire, UK, where the first families with MWS were described). Each episode, which commonly manifests in childhood, include abdominal pain, arthritis, urticaria, and conjunctivitis. The disease may later be complicated by sensorineural deafness and secondary amyloidosis (type AA). The diagnosis is usually clinical and the CIAS1 gene (also called as NALP3 or PYPAF1) has been localised at chromosome 1q44 by linkage analysis.2 Two other syndromes, familial cold autoinflammatory syndrome (FCAS) and chronic infantile neurological cutaneous and articular syndrome, are associated with mutations in the CIAS1 gene.1
The CIAS1 (cold-induced autoinflammatory syndrome 1) gene is expressed in peripheral blood leukocytes and encodes a protein ‘cryopyrin’ with the same N-terminal domain as pyrin, a protein associated with familial Mediterranean fever. Cryopyrin appears to play a role in innate immune function by regulating the production of proinflammatory cytokines. Cryopyrin expression is also very similar in human and mouse. Significant expression of cryopryin occurs in mouse eye and skin tissue, which is consistent with symptoms observed in human cryopyrin-associated diseases.4 Several different mutations of CIAS1 gene, all located in exon 3 have been described.5 Our patient had an A439V mutation (genotyped in June 2004).
The clinical spectrum of diseases associated with CIAS1 mutations is very wide and includes other forms of familial urticaria which do not necessarily meet the clinical criteria of MWS and FCAS.5 This case has highlighted a new association with MWS.
http://www.orpha.net/data/patho/GB/uk-MWS.pdf. (accessed in September 2006).
Cuisset L, Drenth JPH, Berthelot JM, Meyrier A, Vaudour G, Watts RA et al. Genetic linkage of the Muckle–Wells syndrome to chromosome 1q44. Am J Hum Genet 1999; 65: 1054–1059.
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Anderson JP, Mueller JL, Rosengren S, Boyle DL, Schaner P, Cannon SB et al. Structural expression, and evolutionary analysis of mouse CIAS1. Gene 2004; 338 (1): 25–34.
Dode C, Le Du N, Cuisset L, Letourneur F, Berthelot JM, Vaudour G et al. New mutations of CIAS1. That are responsible for Muckle–Wells syndrome and familial cold urticaria: a novel mutation underlies both syndromes. Am J Hum Genet 2002; 70: 1498–1506.
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Shakeel, A., Gouws, P. Muckle–Wells syndrome: another cause of acute anterior uveitis. Eye 21, 849–850 (2007). https://doi.org/10.1038/sj.eye.6702704
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