Risk factors for severe Muckle‐Wells syndrome

Abstract

Objective. Muckle-Wells syndrome (MWS) is an inherited autoinflammatory disease resulting in exces-Methods. A multicenter cohort study of consecutive MWS patients was performed. Parameters assessed included clinical features, MWS Disease Activity Score (MWS-DAS), inflammation markers, and cytokine levels. E311K mutation-positive patients were compared with E311K mutation-negative patients. Putative risk factors for severe MWS (defined as an MWS-DAS score of >10) were assessed in univariate analyses, and significant predictors were entered into a multivariate model.Results. Thirty-two patients (15 male and 17 female) were studied. The most frequent organ manifestations were musculoskeletal symptoms and eye and skin disorders. Renal disease and hearing loss were seen in >50% of the patients. Genetically defined subcohorts had distinct phenotypes. Severe disease activity was documented in 19 patients (59%). Predictors of severe MWS identified at the time of diagnosis were female sex, hearing loss, musculoskeletal disease, increased erythrocyte sedimentation rate, and low hemoglobin level. Female sex and hearing loss remained significant after adjustment for age in a multivariate model (relative risk 1.8 and 2.6, respectively).Conclusion. MWS patients at high risk for severe disease can be identified at the time of diagnosis. Female patients presenting with hearing loss have the highest likelihood of manifesting severe MWS and should be considered a high-risk group.

Cryopyrin-associated Periodic Syndromes and the Eye

“…10 Most mutations are inherited in an autosomal dominant fashion, but sporadic occurrences are also seen. 8 The same mutation may cause a different phenotype, as evidenced by patient 1 and her mother, and as previously described. 7,8,11 This variable expressivity is not well understood but likely involves mutations with reduced penetrance and contributions from other genetic factors producing varied phenotypes.…”

“…[2][3][4][5] There have recently been a handful of reported cases of patients in the MWS spectrum presenting with aseptic meningitis and papilledema. 6,7 There have also been isolated reports of MWS patients presenting with uveitis (4 cases) 8 and episcleritis (3 cases). 7 To the best of our knowledge, no cases of MWS associated with aseptic meningitis, elevated intracranial pressure, papilledema, anterior uveitis, or panuveitis have been reported in the ophthalmic literature.…”

Nephrotic Syndrome and AA Amyloidosis Revealing Adult-Onset Cryopyrin-Associated Periodic Syndrome

“…2,4,5 These are gain-offunction mutations and involve constitutive cryopyrin activation, which causes a sustained and uncontrolled inflammatory response. A single mutation can cause different clinical phenotypes, probably due to the action of modifier genes and environmental factors.…”

Challenges in Diagnosing Muckle‐Wells Syndrome: Identifying Two Distinct Phenotypes

“…The data collection tool was subdivided into 3 domains: 1) demographic data, family history, socioeconomic status, and education; 2) patients' clinical phenotypes, including symptoms and functional impact; and 3) preclinical evaluation and diagnostic process. The data collection tool was modified from 2 previously reported tools (17,18).…”

“…Since 1962 the spectrum is constantly expanding; symptoms including fever, fatigue, conjunctivitis, arthralgia, arthritis, myalgia, irritability, headache, abdominal pain, oral ulcers, pericarditis, and male hypofertility have been reported (15)(16)(17)(18)(19). The clinical diversity results in a wide variety of specialties involved in the diagnostic evaluation of children and adults with MWS.…”