Background Muckle-Wells Syndrome(MWS) is a rare autosomal dominant disorderincluded inthe groupofhereditaryperiodic feversyndromes1. It is characterized byrecurrentand self-limitedepisodesof fever, rash, joint painand conjunctivitissince childhood. Sensorineural deafnessand amyloidosisappear lateranddetermine the disease prognosis2. It has been demonstratedthatthere is an associationwithmutationsNLRP3 gene, which encodescryopyrin, a proteinresponsible for the regulationoftheproductionofproinflammatory cytokines, such as interleukin-1 beta3.
Objectives To describe a case series of MWS of a tertiary hospital.
Methods All patients followed at the Rheumatology Department of Virgen Macarena Hospital were included. Medical records of these patients were reviewed. They were all diagnosed by periodic fevers genetic tests.
Results A total of 9 patients with genetically proved MWS are included in this study. The first case is a 46 year old male, diagnosed of rheumatoid arthritis at the age of 27. During follow up he had recurrent flares of fever, urticaria, anemia, sensoneural hearing loss and elevated acute phase reactants, with poor control despite treatment with several DMARDs and anti-TNF. Genetic study demonstrated the mutation p.Thr-348-Met in exon 3 heterozygous NLRP3 gene. He started Canakinumab 150 mg subcutaneously every 8 weeks and entered on clinical and laboratory remission. Second, we present a family with six affected individuals (Figure 1), two of whom died of terminal renal failure secondary to amyloidosis, and 4 patients alive, a boy, his sister and her two children. In all of them, it had been shown the presence of the mutation in the gene NLRP3 D303N. They present crisis fever, urticaria and conjunctivitis, sensorineural hearing loss. Organic amyloidosis has been proved in one of the sons. Three of them hace started Canakinumab, with favorable response. The next case is a 29 years old male who, since he was 17, presents esporadic outbreaks of fever and conjunctivitis lasting two weeks. Genetic analysis showed a deletion of bp (A) in exon 3 NLRP3 gene, heterozygous, a mutation not described before. Nowadays he is asymptomatic and requires no treatment. Finally, we present the case of a patient with recurrent fever and urticarial rash, with bilateral sensorineural hearing loss. His brother has MWS and is followed up in another hospital. Genetic analysis showed pR260W mutation in the NLRP3 gene.
Conclusions MWS is a rare disease with a potentially fatal prognosis, which can be diagnosed with certainty by genetic testing when suspicion is high and when they are ruled out other processes. Once the diagnosis has been established there is an effective treatment with IL-1beta inhibition drugs4. Here 9 patients with different mutations are presented, including a not previously reported mutation.
Muckle TJ, et al. Urticaria, deafness, and amyloidosis: a new heredo-familial syndrome. QJM 1962;31:235-48
Calvo I, López Montesinos B, Marco Puche, A. Syndrome of Muckle-Wells and autoinflammatory familiar syndrome induced by cold. Med Clin (Barc) 2011;136(Supl 1):16-21
Houten, SM, Frenkel, J, Waterham, HR. Isoprenoid biosynthesis in hereditary periodic fever syndromes and inflammation. Cell Mol Life Sci 2003;60:1118-34
Lachmann HJ, et al. Use of canakinumab in the cryopyrin-associated periodic syndrome. N Engl J Med2009 Jun 4;360(23):2416-25
Disclosure of Interest None Declared
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.