Risk factors for severe Muckle-Wells syndrome.
OBJECTIVE
Muckle-Wells syndrome (MWS) is an inherited autoinflammatory disease resulting in excessive interleukin-1 release. It is unknown whether demographic, clinical, or laboratory characteristics at the time of diagnosis may identify patients who are at high risk for severe disease activity. This study was undertaken to analyze clinical and laboratory features of MWS, compare genetically defined subcohorts, and identify risk factors for severe MWS.


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).


CONCLUSIONS
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.
Kümmerle-Deschner
Jasmin B
JB
University Hospital Tuebingen, Tuebingen, Germany.
Tyrrell
Pascal N
PN
Reess
Fabian
F
Kötter
Ina
I
Lohse
Peter
P
Girschick
Hermann
H
Huemer
Christian
C
Horneff
Gerd
G
Haas
Johannes-Peter
JP
Koitschev
Assen
A
Deuter
Christoph
C
Benseler
Susanne M
SM
D000293:Adolescent; D000328:Adult; D000368:Aged; D001799:Blood Sedimentation; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D015897:Comorbidity; D056587:Cryopyrin-Associated Periodic Syndromes / Q000097:blood / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D034381:Hearing Loss / Q000453:epidemiology; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009140:Musculoskeletal Diseases / Q000453:epidemiology; D009154:Mutation / Q000235:genetics*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010641:Phenotype; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D012737:Sex Factors; D055815:Young Adult
D002352:Carrier Proteins; D006454:Hemoglobins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human