Autoinflammatory Diseases: Clinical and Genetic Advances

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.

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“…1,2 Headaches, 3 abdominal pain, 3,4 and growth retardation can still be observed in the clinical condition. Later, there is progressive.…”

Section: Discussionmentioning

confidence: 99%

Síndrome de Muckle-Wells em quatro membros de uma família

Pereira

Vale

et al. 2010

An. Bras. Dermatol.

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“…Blood monocytes from patients with some of these disorders, especially cryopyrinopathies and HIDS, readily release more IL-1β than do monocytes from unaffected controls (7,8).…”

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confidence: 99%

Reactive oxygen species–independent activation of the IL-1β inflammasome in cells from patients with chronic granulomatous disease

Veerdonk

Smeekens

Joosten

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

228

166

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Humans with chronic granulomatous diseases (CGDs) due to mutations in p47-phox have defective NADPH activity and thus cannot generate NADPH-dependent reactive oxygen species (ROS). The role of ROS in inflammation is controversial; some in vitro studies suggest that ROS are crucial for secretion of IL-1β via inflammasome activation, whereas mice defective for ROS and patients with CGD have a proinflammatory phenotype. In this study, we evaluated activation of the IL-1β inflammasome in cells from CGD patients. In contrast to previous studies using the small molecule diphenylene iodonium (DPI) as a ROS inhibitor, we found no decrease in either caspase-1 activation or secretion of IL-1β and IL-18 in primary CGD monocytes. Moreover, activation of CGD monocytes by uric acid crystals induced a 4-fold higher level of IL-1β secretion compared with that seen in monocytes from unaffected subjects, and this increase was not due to increased synthesis of the IL-1β precursor. In addition, Western blot analysis of CGD cells revealed that caspase-1 activation was not decreased, but rather was increased compared with control cells. Examination of the effects exerted by the inhibition of ROS activity by DPI revealed that the decrease in IL-1β secretion by DPI was actually due to inhibition of IL-1β gene expression. Thus, inconsistent with the proinflammatory role of ROS, the present findings support the concept that ROS likely dampen inflammasome activation. The absence of ROS in CGD monocytes may explain the presence of an inflammatory phenotype characterized by granulomas and inflammatory bowel disease occurring in CGD patients.antioxidants | colitis | gout | inflammation | uric acid

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“…Although joint and skin involvement can be seen in various forms, fever is almost always present. These symptoms can also be accompanied by systemic indings such as abdominal pain, myalgia, ocular involvement, serositis, amyloidosis, and neurological signs [63,65].…”

Section: Autoinlammatory Syndromesmentioning

confidence: 99%

“…They are more commonly seen as erysipelas-like plaques in the lower extremities in FMF. Erythematous macules and urticarial lesions are seen in HIDS [51,65].…”

Section: Autoinlammatory Syndromesmentioning

confidence: 99%

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Urticarial Syndromes

Gökalp¹,

Bulur²

2017

A Comprehensive Review of Urticaria and Angioedema

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Urticaria is a common dermatological condition that can occur in acute and chronic forms. Common urticaria is generally easy to diagnose; however, urticarial syndromes should be considered in cases where lesions persist for greater than 24-36 h, the location of lesions has bilateral symmetry, urticarial lesions are accompanied by additional elementary lesions, and/or the patient presents with additional systemic symptoms. Additionally, urticarial syndromes should be considered for patients with typical urticarial lesions that do not respond to systemic antihistamine treatment. Hyperpigmentation or bruising can be observed following resolution of urticarial syndromes. Many cutaneous and systemic diseases can cause urticarial syndromes. Systemic causes of urticarial syndromes can afect multiple organ systems and may be accompanied by systemic symptoms such as fever, asthenia, and arthralgia. Clinicopathologic correlation is essential for the accurate diagnosis of urticarial syndromes. In this chapter, cutaneous and systemic etiologies of urticarial syndromes are reviewed.

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Autoinflammatory Diseases: Clinical and Genetic Advances

Cited by 124 publications

References 131 publications

Síndrome de Muckle-Wells em quatro membros de uma família

Síndrome de Muckle-Wells em quatro membros de uma família

Reactive oxygen species–independent activation of the IL-1β inflammasome in cells from patients with chronic granulomatous disease

Urticarial Syndromes

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