Síndrome de Muckle-Wells em quatro membros de uma família

Abstract

Muckle-Wells syndrome is a rare autosomal dominant disease that belongs to a group of hereditary febrile syndromes. It is characterized by recurrent and self-limited episodes of fever, urticaria, arthralgia, myalgia and conjunctivitis since childhood, which are related to exposure to cold temperatures. Lately, progressive sensorineural hearing loss occurs. Amyloidosis is the main complication and can be found in about 25% of the cases. It has been demonstrated that there is an association with mutations in the NLRP3 gene, which codifies cryopyrin, a protein responsible for regulating the production of proinflammatory cytokines, such as interleukin-1Beta. The authors report four cases of the disease within a family. Keywords: Arthralgia; Conjunctivitis; Fever; Genetic diseases, inborn; Interleukin-1Beta; Hearing loss, sensorineural; Urticaria Resumo: A síndrome de Muckle-Wells é doença autossômica dominante rara, incluída no grupo das sín-dromes febris hereditárias. Caracteriza-se por episódios recorrentes e autolimitados de febre, urticária, artralgia, mialgia e conjuntivite, desde a infância, relacionados com a exposição ao frio. Mais tardiamente, há perda auditiva neurossensorial progressiva. Amiloidose, a principal complicação, desenvolve-se em cerca de 25% dos casos. Associa-se a mutações no gene NLRP3 (antes CIAS1) que codifica a criopirina, proteína reguladora da produção de citocinas pró-inflamatórias, como a interleucina-1beta. Relata-se a ocorrência dessa doença incomum em quatro membros de uma única família.

Muckle-Wells Syndrome Across Four Generations in One Czech Family: Natural Course of the Disease

“…The study has identified 11 members of a single family with the clinical picture of MWS. The typical urticarial rash as a leading and the first symptom was present in all patients, similar to other reports (3, 12). Characteristics of CAPS patients reported to the Eurofever registry showed presence of rash in 97% of patients across the whole disease spectrum (3).…”

“…Disease symptoms had disappeared within hours to days from starting anakinra in all patients, which is in line with the published series (25). Improvement of hearing loss and amyloidosis was shown in individual patients when treatment was introduced early (12, 26). Rynne et al described reversibility of hearing loss in a 59 years-old woman with MWS but younger age might offer a window of opportunity for reversing hearing loss (26, 27).…”

“…Several extended families with multiple members affected with MWS, FCAS or their overlaps were reported (1, 8, 12, 14, 16, 21, 29). Nevertheless, none of them presented combination of clinical and laboratory characteristics of patients in different generations prior to the treatment nor the follow-up including standard patient-reported outcomes.…”

Evolving Concepts in the Pathogenesis of NASH: Beyond Steatosis and Inflammation

“…Mitochondria are a rich source of DAMPS [221,222] and their signalling molecules, such as ATP and formulated peptides (e.g., encoded by the NLRP3 gene), can induce inflammasome activation [221,223,224]. Mice with constitutively active NLRP3 have an overactive inflammasome pathway, which induces liver injury [225]. Additionally, increased ATP levels can propagate inflammation directly (via the P2X7 receptor in the inflammasome leading to increased IL-1β production) [226] and indirectly (via promotion of bacterial product entry into cells leading to activation of PAMPs) [227].…”

Skin symptoms as diagnostic clue for autoinflammatory diseases

“…The Muckle Well Syndrome manifests during childhood and adolescence by recurrent febrile episodes associated with vanishing non-pruritic urticarial rash, arthralgia, myalgia and conjunctivitis. 5 , 7 , 11 , 13 , 14 , 22 Fever may not be present. 2 Symptoms tend to last longer than in FCAS (12 to 36 hours).…”