RESUMO
Sarcoidosis occurs much more commonly in cohorts of connective tissue disease (1%) compared to the general population (0.01-0.04%). We present a case of concomitant connective tissue disease and cutaneous sarcoidal granulomas and discuss whether the observed granulomas represent a reactive phenomenon or true sarcoidosis. Click here for the corresponding questions to this CME article.
Assuntos
Doenças do Tecido Conjuntivo , Sarcoidose , Dermatopatias , Humanos , Dermatopatias/etiologia , Sarcoidose/complicações , Sarcoidose/diagnóstico , Granuloma/etiologia , Doenças do Tecido Conjuntivo/complicaçõesRESUMO
BACKGROUND: Blau syndrome (BS) is a rare dominantly-inherited autoinflammatory disorder characterized by the triad of arthritis, uveitis and dermatitis that is consequence of gain-of-function NOD2 mutations. We describe the clinical features and genetic basis of a family with two affected members in consecutive generations affected with childhood onset arthritis and uveitis. MATERIALS AND METHODS: Clinical features were retrospectively collected from clinical records. Genetic studies were performed using the Sanger method of DNA sequencing. RESULTS: The proband is a 44 years-old female, who was diagnosed with juvenile onset arthritis at the age of 9 years. She subsequently developed uveitis at age 12 and since then she was managed between the uveitis and rheumatology services. The proband's daughter developed episcleritis at the age of 7 years, and arthritis with bilateral intermediate uveitis two years later. NOD2 analyses revealed in both patients the heterozygous c.1494A>C transversion, predicted to lead the novel, missense p.E498D variant in the NOD2 protein. Additional studies including databases searches and in silico bioinformatic predictions strongly support the "likely pathogenic" classification for this novel variant. CONCLUSIONS: We report a novel pathogenic NOD2 variant in a multiplex family with clinical features compatible with the BS diagnosis. This condition is inherited as a dominant trait in its familial form and should be considered in patients with granulomatous uveitis in association with arthritis and/or dermatitis. Further insight into NOD2 variants and their downstream effects may have implications in the treatment of BS and other inflammatory granulomatous diseases.
Assuntos
Artrite/genética , Mutação de Sentido Incorreto/genética , Proteína Adaptadora de Sinalização NOD2/genética , Polimorfismo de Nucleotídeo Único , Sarcoidose/genética , Sinovite/genética , Uveíte/genética , Adulto , Artrite/diagnóstico , Criança , Feminino , Angiofluoresceinografia , Humanos , Relações Mãe-Filho , Mães , Núcleo Familiar , Linhagem , Estudos Retrospectivos , Sarcoidose/diagnóstico , Análise de Sequência de DNA , Sinovite/diagnóstico , Tomografia de Coerência Óptica , Uveíte/diagnósticoAssuntos
Dor Abdominal/etiologia , Doenças do Tecido Conjuntivo/tratamento farmacológico , Herpes Zoster/complicações , Herpes Zoster/diagnóstico , Hospedeiro Imunocomprometido , Imunossupressores/uso terapêutico , Aciclovir/uso terapêutico , Adulto , Antivirais/uso terapêutico , Azatioprina/efeitos adversos , Azatioprina/uso terapêutico , Feminino , Herpes Zoster/tratamento farmacológico , Humanos , Imunossupressores/efeitos adversos , Prednisolona/efeitos adversos , Prednisolona/uso terapêutico , Resultado do TratamentoRESUMO
Mice mounting an acute phase response, induced by sterile inflammation after a single s.c. injection of casein 24 h beforehand, were remarkably protected against lethal infection with Gram-positive or Gram-negative bacteria. This was associated with enhanced early clearance of bacteremia, greater phagocytosis and oxidative burst responses by neutrophils, and enhanced recruitment of neutrophils into tissues compared with control, nonacute phase mice. Casein-induced inflammation was also associated with increased concentrations of G-CSF in serum, and administration of neutralizing Ab to this cytokine completely abrogated protection against Escherichia coli infection after casein pretreatment. Injection of recombinant murine G-CSF between 3 and 24 h before infection conferred the same protection as casein injection. In contrast, the casein-induced acute phase response affected neither serum values of TNF-alpha, IL-1 beta, or IL-6 after E. coli infection nor susceptibility to LPS toxicity. Furthermore, protection against infection was unaffected in IL-1R knockout mice, which have deficient acute phase plasma protein responses, or after nonspecific inhibition of acute phase protein synthesis by D-galactosamine or specific depletion of complement C3 by cobra venom factor. Increased production of G-CSF in the acute phase response is thus a key physiological component of host defense, and pretreatment with G-CSF to prevent bacterial infection in at-risk patients now merits further study, especially in view of increasing bacterial resistance to antibiotics.