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1.
Actas dermo-sifiliogr. (Ed. impr.) ; 110(9): 710-727, nov. 2019. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-185563

RESUMO

La piel es el órgano más extenso y más expuesto del cuerpo humano. Ello implica un magnífico terreno para el diagnóstico precoz de las enfermedades sistémicas que cursan con afectación sistémica y para las cuales la piel se vuelve un marcador diagnóstico. Las bases conceptuales y los criterios diagnósticos de muchas de estas entidades se han visto modificados o ampliados en los últimos años, con lo que la aproximación a la biopsia cutánea y la evaluación de los signos dermatopatológicos útiles en el diagnóstico precoz han variado también. En esta revisión intentamos hacer un enfoque de algunos de los procesos sistémicos con repercusión cutánea que más han variado conceptualmente en las últimas décadas


The skin is the largest and most exposed organ in the human body and the ideal place to look for signs that aid in the early diagnosis of systemic diseases with cutaneous effects. As the concepts that underpin our understanding of many of these diseases have evolved or expanded in recent years, there have also been changes in the criteria we use for early diagnosis, including our approaches to skin biopsy and dermatopathologic evaluation. This review focuses on some of the systemic processes with skin manifestations for which our basic understanding has changed most in recent decades


Assuntos
Humanos , Doenças Hereditárias Autoinflamatórias/diagnóstico , Diagnóstico Precoce , Tela Subcutânea/patologia , Doença Relacionada a Imunoglobulina G4/patologia , Biópsia , Doenças Hereditárias Autoinflamatórias/patologia , Síndrome de Behçet/patologia , Pioderma Gangrenoso/patologia , Artrite Juvenil/complicações , Exantema , Diagnóstico Diferencial , Linfadenite Histiocítica Necrosante/complicações , Nefropatias/patologia
2.
Lakartidningen ; 1162019 Oct 29.
Artigo em Sueco | MEDLINE | ID: mdl-31661147

RESUMO

Periodic Fever, Aphthous Stomatitis, Pharyngitis and Cervical Adenitis (PFAPA) syndrome is the most common autoinflammatory disorder among children in many parts of the world and an important differential diagnosis in children presenting with recurrent fever episodes. Commonly, PFAPA has an onset under the age of 5 years. Fever episodes in PFAPA usually last 3-6 days and are associated with one or more of the cardinal symptoms aphthous stomatitis, pharyngitis and cervical adenitis. The fever episodes typically recur with an interval of 3-6 weeks, often with a striking regularity. During the episodes, the patient has elevated inflammatory variables such as CRP and serum amyloid A (SAA) and may sometimes have additional symptoms such as abdominal pain, nausea and leg pain. Between the fever episodes, the patient is typically free of symptoms with normalized inflammatory variables and grows normally. Awareness and recognition of PFAPA is key to providing the patient with adequate treatment and avoiding misdiagnosis.


Assuntos
Doenças Hereditárias Autoinflamatórias/diagnóstico , Biomarcadores/sangue , Pré-Escolar , Diagnóstico Diferencial , Feminino , Febre/diagnóstico , Febre/tratamento farmacológico , Febre/etiologia , Doenças Hereditárias Autoinflamatórias/classificação , Doenças Hereditárias Autoinflamatórias/complicações , Doenças Hereditárias Autoinflamatórias/tratamento farmacológico , Humanos , Inflamação/sangue , Linfadenite/diagnóstico , Linfadenite/tratamento farmacológico , Linfadenite/etiologia , Masculino , Faringite/diagnóstico , Faringite/tratamento farmacológico , Faringite/etiologia , Estomatite Aftosa/diagnóstico , Estomatite Aftosa/tratamento farmacológico , Estomatite Aftosa/etiologia , Síndrome
3.
Int J Rheum Dis ; 22(8): 1489-1497, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31131563

RESUMO

AIM: The syndrome of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) is a common inflammatory disease that presents with periodic fever. We aimed to establish more specific diagnostic criteria for PFAPA based on the clinical characteristics of PFAPA patients in our directory. METHOD: The clinical, laboratory, genetic, and family history details of 257 Japanese PFAPA patients treated at our and other affiliated hospitals between April 2000 and April 2018 were analyzed along with quantitative measurements of the number of CD64 molecules on neutrophils, and the levels of serum inflammatory cytokines. The sensitivity and specificity of the criteria were calculated for several diseases. RESULTS: Because recurrent fevers were crucial findings, they were defined as the required criterion. Tonsillitis/pharyngitis with white moss were important accompanying signs. Other symptoms associated with febrile episodes were cervical lymphadenitis with tenderness, aphthous stomatitis, sore throat, vomiting, and headache but not cough. A total of 159 (62%) patients had a family history of recurrent fevers, indicating autosomal dominant inheritance. C-reactive protein levels were extremely elevated during febrile attacks but normal in attack-free periods. Serum immunoglobulin D levels were high in 72 of the 199 tested patients. Oral glucocorticoid and cimetidine were extremely effective in all and 51.6% of the patients, respectively. We defined the above as supportive criteria. These criteria were sensitive and specific enough to distinguish PFAPA from other recurrent fever diseases. Raised serum interferon-γ levels and remarkable CD64 expression on neutrophils during flare-ups were recognized, indicating they contributed to diagnosis. CONCLUSION: Our new criteria are useful for diagnosing PFAPA.


Assuntos
Febre/diagnóstico , Doenças Hereditárias Autoinflamatórias/diagnóstico , Linfadenite/diagnóstico , Faringite/diagnóstico , Estomatite Aftosa/diagnóstico , Biomarcadores/sangue , Pré-Escolar , Citocinas/sangue , Feminino , Febre/sangue , Febre/imunologia , Febre/terapia , Glucocorticoides/uso terapêutico , Doenças Hereditárias Autoinflamatórias/sangue , Doenças Hereditárias Autoinflamatórias/imunologia , Doenças Hereditárias Autoinflamatórias/terapia , Hereditariedade , Antagonistas dos Receptores Histamínicos H2/uso terapêutico , Humanos , Lactente , Mediadores da Inflamação/sangue , Japão , Linfadenite/sangue , Linfadenite/imunologia , Linfadenite/terapia , Masculino , Proteína Cofatora de Membrana/sangue , Neutrófilos/imunologia , Linhagem , Faringite/sangue , Faringite/imunologia , Faringite/terapia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estomatite Aftosa/sangue , Estomatite Aftosa/imunologia , Estomatite Aftosa/terapia , Síndrome , Tonsilectomia , Resultado do Tratamento
4.
Acta otorrinolaringol. esp ; 70(2): 97-104, mar.-abr. 2019. tab, graf
Artigo em Inglês | IBECS | ID: ibc-178520

RESUMO

Introduction: Immune Mediated Inner Ear Disease (IMIED) is a rare form of sensorineural bilateral hearing loss, usually progressing in weeks to months and responsive to immunosuppressive treatment. Despite recent advances, there is no consensus on diagnosis and optimal treatment. Methods: A review of articles on IMIED from the last 10 years was conducted using PubMed(R) database. Results: IMIED is a rare disease, mostly affecting middle aged women. It may be a primary ear disease or secondary to autoimmune systemic disease. A dual immune response (both cellular and humoral) seems to be involved. Cochlin may be the inner ear protein targeted in this disease. Distinction from other (core common) forms of neurosensory hearing loss is a challenge. Physical examination is mandatory for exclusion of other causes of hearing loss; audiometry identifies characteristic hearing curves. Laboratory and imaging studies are controversial since no diagnostic marker is available. Conclusion: Despite recent research, IMIED diagnosis remains exclusive. Steroids are the mainstay treatment; other therapies need further investigation. For refractory cases, cochlear implantation is an option and with good relative outcome


Introducción: La enfermedad inmunomediada del oído interno (EIMOI) es una forma rara de pérdida auditiva bilateral sensorineural, que progresa generalmente en semanas a meses y responde al tratamiento inmunosupresor. A pesar de los recientes avances, no hay consenso sobre el diagnóstico y el tratamiento óptimo. Métodos: Se realizó una revisión de artículos sobre la EAOI de los últimos 10 años utilizando la base de datos PubMed(R). Resultados: La EIMOI es una enfermedad rara que afecta principalmente a las mujeres de 2 a 50 años de edad. Puede ser una enfermedad del oído primaria o secundaria a una enfermedad sistémica autoinmune. Parece estar involucrada una respuesta inmune dual (tanto celular como humoral). La coclina parece ser la proteína del oído interno diana en esta enfermedad. La distinción de otras formas de pérdida de audición neurosensorial es un desafío. El examen físico es obligatorio para la exclusión de otras causas de pérdida de la audición; la audiometría identifica curvas características de pérdida de audición. Los estudios de laboratorio y de imágenes son controvertidos, ya que no hay marcador diagnóstico disponible. Conclusión: A pesar de la investigación reciente, el diagnóstico de la EAOI sigue siendo de exclusión. Los esteroides siguen siendo el pilar del tratamiento; otras terapéuticas necesitan más investigación. Para los casos refractarios, la implantación coclear es una opción con buen resultado relativo


Assuntos
Humanos , Feminino , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Doenças do Labirinto/diagnóstico , Doenças do Labirinto/terapia , Perda Auditiva Bilateral/diagnóstico , Perda Auditiva Neurossensorial/complicações , Doença de Meniere/diagnóstico , Doença de Meniere/terapia , Perda Auditiva Bilateral/terapia , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/terapia , Doenças Hereditárias Autoinflamatórias/diagnóstico , Doenças Hereditárias Autoinflamatórias/terapia
5.
Dermatol Clin ; 37(2): 229-239, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30850045

RESUMO

The discoveries of new genes underlying genetic skin diseases have occurred at a rapid pace, supported by advances in DNA sequencing technologies. These discoveries have translated to an improved understanding of disease mechanisms at a molecular level and identified new therapeutic options based on molecular targets. This article highlights just a few of these recent discoveries for a diverse group of skin diseases, including tuberous sclerosis complex, ichthyoses, overgrowth syndromes, interferonopathies, and basal cell nevus syndrome, and how this has translated into novel targeted therapies and improved patient care.


Assuntos
Dermatopatias Genéticas/diagnóstico , Dermatopatias Genéticas/terapia , Doenças Autoimunes do Sistema Nervoso/diagnóstico , Doenças Autoimunes do Sistema Nervoso/genética , Doenças Autoimunes do Sistema Nervoso/terapia , Síndrome do Nevo Basocelular/diagnóstico , Síndrome do Nevo Basocelular/genética , Síndrome do Nevo Basocelular/terapia , Classe I de Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Dermabrasão , Fármacos Dermatológicos/uso terapêutico , Testes Genéticos , Doenças Hereditárias Autoinflamatórias/diagnóstico , Doenças Hereditárias Autoinflamatórias/genética , Doenças Hereditárias Autoinflamatórias/terapia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Eritrodermia Ictiosiforme Congênita/diagnóstico , Eritrodermia Ictiosiforme Congênita/genética , Eritrodermia Ictiosiforme Congênita/terapia , Inibidores de Janus Quinases/uso terapêutico , Terapia a Laser , Lipoma/diagnóstico , Lipoma/genética , Lipoma/terapia , Técnicas de Diagnóstico Molecular , Mosaicismo , Anormalidades Musculoesqueléticas/diagnóstico , Anormalidades Musculoesqueléticas/genética , Anormalidades Musculoesqueléticas/terapia , Malformações do Sistema Nervoso/diagnóstico , Malformações do Sistema Nervoso/genética , Malformações do Sistema Nervoso/terapia , Nevo/diagnóstico , Nevo/genética , Nevo/terapia , Pitiríase Rubra Pilar/diagnóstico , Pitiríase Rubra Pilar/genética , Pitiríase Rubra Pilar/terapia , Inibidores de Proteínas Quinases/uso terapêutico , Síndrome de Proteu/diagnóstico , Síndrome de Proteu/genética , Síndrome de Proteu/terapia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Análise de Sequência de DNA , Dermatopatias Genéticas/genética , Protetores Solares/uso terapêutico , Serina-Treonina Quinases TOR/antagonistas & inibidores , Esclerose Tuberosa/diagnóstico , Esclerose Tuberosa/genética , Esclerose Tuberosa/terapia , Ustekinumab/uso terapêutico
6.
BMJ Case Rep ; 12(3)2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30850566

RESUMO

We present a case of constrictive pericarditis with concomitant blood and bone marrow appearances of chronic myelomonocytic leukaemia (CMML). Despite surgical treatment with pericardiectomy, the patient deteriorated into multiorgan failure. Pericardial histology disclosed a typical inflammatory picture with no evidence of monocytic or malignant infiltrate. Following intensive collaboration between cardiologists, haematologists and rheumatologists via daily email exchanges, a diagnosis was reached of autoinflammatory constrictive pericarditis with a non-infiltrative coexisting CMML. The key to achieving a rapid and sustained response was a trial of high-dose steroids followed by intravenous immunoglobulins. This achieved restoration of cardiac function, resolution of symptoms and near normalisation of inflammatory markers. A diagnosis of concurrent CMML was confirmed at 3 months. The patient remains well, taking colchicine and steroids.


Assuntos
Doenças Hereditárias Autoinflamatórias/diagnóstico , Leucemia Mielomonocítica Crônica/complicações , Pericardiectomia/métodos , Pericardite Constritiva/patologia , Idoso , Bloqueio de Ramo/diagnóstico , Bloqueio de Ramo/fisiopatologia , Diagnóstico Diferencial , Doenças Hereditárias Autoinflamatórias/patologia , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Pericardite Constritiva/diagnóstico por imagem , Pericardite Constritiva/tratamento farmacológico , Pericardite Constritiva/cirurgia , Resultado do Tratamento
7.
Rheumatol Int ; 39(5): 911-919, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30783801

RESUMO

Systemic autoinflammatory diseases (sAIDs) are a heterogeneous group of disorders, having monogenic inherited forms with overlapping clinical manifestations. More than half of patients do not carry any pathogenic variant in formerly associated disease genes. Here, we report a cross-sectional study on targeted Next-Generation Sequencing (NGS) screening in patients with suspected sAIDs to determine the diagnostic utility of genetic screening. Fifteen autoinflammation/immune-related genes (ADA2-CARD14-IL10RA-LPIN2-MEFV-MVK-NLRC4-NLRP12-NLRP3-NOD2-PLCG2-PSTPIP1-SLC29A3-TMEM173-TNFRSF1A) were used to screen 196 subjects from adult/pediatric clinics, each with an initial clinical suspicion of one or more sAID diagnosis with the exclusion of typical familial Mediterranean fever (FMF) patients. Following the genetic screening, 140 patients (71.4%) were clinically followed-up and re-evaluated. Fifty rare variants in 41 patients (20.9%) were classified as pathogenic or likely pathogenic and 32 of those variants were located on the MEFV gene. We detected pathogenic or likely pathogenic variants compatible with the final diagnoses and inheritance patterns in 14/140 (10%) of patients for the following sAIDs: familial Mediterranean fever (n = 7), deficiency of adenosine deaminase 2 (n = 2), mevalonate kinase deficiency (n = 2), Muckle-Wells syndrome (n = 1), Majeed syndrome (n = 1), and STING-associated vasculopathy with onset in infancy (n = 1). Targeted NGS panels have impact on diagnosing rare monogenic sAIDs for a group of patients. We suggest that MEFV gene screening should be first-tier genetic testing especially in regions with high carrier rates. Clinical utility of multi-gene testing in sAIDs was as low as expected, but extensive genome-wide familial analyses in combination with exome screening would enlighten additional genetic factors causing disease.


Assuntos
Testes Genéticos , Doenças Hereditárias Autoinflamatórias/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala , Proteínas Adaptadoras de Transdução de Sinal/genética , Adenosina Desaminase/deficiência , Adenosina Desaminase/genética , Adolescente , Adulto , Agamaglobulinemia/diagnóstico , Agamaglobulinemia/genética , Anemia Diseritropoética Congênita/diagnóstico , Anemia Diseritropoética Congênita/genética , Proteínas Adaptadoras de Sinalização CARD/genética , Proteínas de Ligação ao Cálcio/genética , Criança , Pré-Escolar , Síndromes Periódicas Associadas à Criopirina/diagnóstico , Síndromes Periódicas Associadas à Criopirina/genética , Proteínas do Citoesqueleto/genética , Febre Familiar do Mediterrâneo/diagnóstico , Febre Familiar do Mediterrâneo/genética , Feminino , Doenças Hereditárias Autoinflamatórias/genética , Humanos , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Masculino , Deficiência de Mevalonato Quinase/diagnóstico , Deficiência de Mevalonato Quinase/genética , Pessoa de Meia-Idade , Proteínas de Transporte de Nucleosídeos/genética , Osteomielite/diagnóstico , Osteomielite/genética , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Pirina/genética , Análise de Sequência de DNA , Imunodeficiência Combinada Severa/diagnóstico , Imunodeficiência Combinada Severa/genética , Adulto Jovem
8.
Zhonghua Nei Ke Za Zhi ; 58(3): 237-240, 2019 Mar 01.
Artigo em Chinês | MEDLINE | ID: mdl-30803188

RESUMO

Fever and abdominal pain are common symptoms and could be main manifestations in patients with autoinflammatory diseases. A 48-year-old female patient was admitted with recurrent fever and abdominal pain for 9 years. Serum level of inflammatory markers synchronously fluctuated with fever, and returned to normal when fever subsided. The periodic episodes of fever occurred every 1 to 4 months and failed to respond to empirical antibiotics. Whole exome sequencing showed heterozygous mutation of NOD2 gene q902k, leading to the final diagnosis of autoinflammatory disease. Corticosteroid and tripterygiumglycosides were effective for the disease remission.


Assuntos
Dor Abdominal/etiologia , Febre/etiologia , Doenças Hereditárias Autoinflamatórias/diagnóstico , Proteína Adaptadora de Sinalização NOD2/genética , Úlcera/etiologia , Corticosteroides/uso terapêutico , Feminino , Glicosídeos/uso terapêutico , Doenças Hereditárias Autoinflamatórias/tratamento farmacológico , Doenças Hereditárias Autoinflamatórias/genética , Heterozigoto , Humanos , Pessoa de Meia-Idade , Mutação , Resultado do Tratamento
9.
Rheumatology (Oxford) ; 58(7): 1227-1238, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30715505

RESUMO

OBJECTIVES: Monogenic autoinflammatory disorders (AID) and primary immunodeficiencies can present early in life with features that may be mistaken for Behçet's disease (BD). We aimed to retrospectively describe the clinical and laboratory features of 11 paediatric cases referred for suspected BD who turned out to have an alternative, monogenic disease mimicking BD. METHODS: Retrospective, paediatric BD specialist multicentre case series. Next generation sequencing (NGS) or conventional candidate gene screening approaches were utilized, facilitated in some cases by functional assays. RESULTS: Eleven children referred with suspected BD underwent genetic screening because of atypical BD features, and/or presentation before age 5 years. Eight patients (73%) were Caucasian, two were Pakistani and one was Turkish; 55% were female. A positive family history of BD was reported in 54% cases. The median age of disease onset was 0.6 (range 0.2-2.3) years. All had systemic inflammation and oral ulceration; 5/11 had genital ulceration; 3/11 had ocular involvement; and 9/11 had cutaneous manifestations. Nine/11 had known disease-causing genetic mutations in: TNFAIP3 (n = 2), WDR1 (n = 2), NCF1, AP1S3, LYN, MEFV and GLA. The remaining two cases each had novel variants in STAT1 and TNFRSF1A. CONCLUSION: Rare monogenic diseases can mimic BD, particularly when presenting early in life. These observations are now informing a strategy to explore screening for genetic mimics of BD in a UK cohort of children and adults to better understand the proportion of UK BD patients who may in fact have an underlying monogenetic diagnosis.


Assuntos
Síndrome de Behçet/diagnóstico , Idade de Início , Síndrome de Behçet/genética , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Predisposição Genética para Doença , Testes Genéticos/métodos , Doenças Hereditárias Autoinflamatórias/diagnóstico , Doenças Hereditárias Autoinflamatórias/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Masculino , Mutação , Estudos Retrospectivos
10.
Presse Med ; 48(1 Pt 2): e77-e87, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30683466

RESUMO

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is a complex autoinflammatory disease with a clinical phenotype characterised by recurrent episodes of fever, systemic inflammation and symptoms and signs depicted in disease acronym. Although PFAPA is the most common autoinflammatory disease among children in many parts of the world, the condition is still an enigma, which include the regular episodes, the prompt responses to corticosteroids, the genetic bases for the familial clustering and therapeutic effects of tonsillectomy. This review explores PFAPA syndrome with the aim of describing the current clinical and scientific understanding of the condition.


Assuntos
Doenças Hereditárias Autoinflamatórias , Corticosteroides/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Terapia Combinada , Diagnóstico Diferencial , Febre/etiologia , Predisposição Genética para Doença , Doenças Hereditárias Autoinflamatórias/classificação , Doenças Hereditárias Autoinflamatórias/diagnóstico , Doenças Hereditárias Autoinflamatórias/genética , Doenças Hereditárias Autoinflamatórias/fisiopatologia , Humanos , Inflamação , Linfadenite/genética , Deficiência de Mevalonato Quinase/diagnóstico , Faringite/genética , Faringite/cirurgia , Prognóstico , Recidiva , Estomatite Aftosa/genética , Síndrome , Tonsilectomia
11.
Presse Med ; 48(1 Pt 2): e49-e59, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30665783

RESUMO

The systemic autoinflammatory disorders (SAIDs) are associated with dysregulation of the innate immune system, affecting pro-inflammatory cytokines and apoptosis pathways. The spectrum of SAIDs continues to grow with over 30 different disorders identified to date. The main indication for genetic referral is when a patient presents with clinical symptoms consistent with one or more of the SAIDs. Thus, in making a referral for DNA screening, clinical information that supports the choice for screening of one or more SAIDs genes is required. Many of the SAIDs can display overlapping, partial or atypical symptoms, which makes the differential diagnosis extremely difficult and thus heavily dependent on genetic testing. Various attempts have been aimed at improving the efficiency of SAIDs diagnosis by proposing a set of clinical criteria to guide the genetic analysis of the SAIDs. In the last decade, due to application of the next-generation sequencing (NGS) the genetic diagnosis in patients with SAIDs have greatly improved; novel diseases and disease-associated genes have been identified and remarkable progress has been made in the genetic characterization of the undiagnosed patients and the sporadic cases. To date more than 800 variants have been recorded on the Infevers database, an online repository for DNA changes in genes associated with SAIDs (http://fmf.igh.cnrs.fr/ISSAID/infevers/). Recently, it has been updated with the new guidelines for classification of genetic variants pathogenicity in the in four most recognised SAIDs genes: MEFV, TNFRSF1A, NLRP3 and MVK.


Assuntos
Testes Genéticos , Doenças Hereditárias Autoinflamatórias/diagnóstico , Bases de Dados Genéticas , Diagnóstico Diferencial , Previsões , Doenças Hereditárias Autoinflamatórias/classificação , Doenças Hereditárias Autoinflamatórias/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Técnicas de Diagnóstico Molecular
12.
J Pediatr ; 204: 270-274, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30361059

RESUMO

OBJECTIVES: To describe a cohort of pediatric patients diagnosed with periodic fever aphthous stomatitis, pharyngitis and adenitis (PFAPA) and familial Mediterranean fever (FMF) and compare them with children diagnosed solely with PFAPA (sPFAPA). STUDY DESIGN: Clinical, laboratory, and genetic data of all pediatric patients diagnosed with sPFAPA or PFAPA/FMF were retrospectively collected from 2 primary Israeli medical referral centers and compared. RESULTS: Of 270 patients with PFAPA, more than one-half were of Mediterranean ancestry. Among patients with PFAPA, 51 (18.9%) also were diagnosed with FMF (PFAPA/FMF). Genetic data on the 9 most common MEFV variants were available for 45 children (88%) in the PFAPA/FMF group. Two variants were found in 15 children (33.3 %), 1 variant was found 27 patients (60%), and 3 patients (6.6%) had no variants. Abdominal pain, myalgia, and arthralgia each were more commonly reported in the PFAPA/FMF group compared with the sPFAPA group (90% vs 49% [P < .0001]; 46% vs 23% [P = .02]; and 30% vs 17% [P = .049], respectively). Colchicine was more commonly prescribed for the PFAPA/FMF group compared with the sPFAPA group (82% vs 29%; P < .0001), but alleviation of PFAPA symptoms with colchicine was similar between groups (75% vs 63%; P = .23). CONCLUSION: We show a strong association between 2 common autoinflammatory syndromes, PFAPA and FMF, in patients from Mediterranean ancestry. Clinicians should be aware that presentation of 1 disease may clinically evolve into another. The association between PFAPA and FMF poses the question similar pathogenesis and genetic influence of the MEFV gene on PFAPA.


Assuntos
Doenças Hereditárias Autoinflamatórias/diagnóstico , Criança , Pré-Escolar , Colchicina/administração & dosagem , Feminino , Doenças Hereditárias Autoinflamatórias/tratamento farmacológico , Doenças Hereditárias Autoinflamatórias/genética , Humanos , Israel , Masculino , Mutação , Pirina/genética , Estudos Retrospectivos , Moduladores de Tubulina/administração & dosagem
13.
Immunol Allergy Clin North Am ; 39(1): 13-29, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30466770

RESUMO

The autoinflammatory diseases encompass approximately 30 monogenic disorders in which inborn errors in the innate immune system lead to episodic systemic inflammation. Largely mediated by dysregulation of myeloid cells, interleukin (IL)-1ß, type I interferon, and NF-κB, these disorders have rapidly expanded over the past several years, and increasing numbers of patients identified. Crossover disorders, bridging autoinflammation and immunodeficiency, have recently been described. This article focuses on the clinical presentation of IL-1 and interferon-driven autoinflammatory disorders, and discusses novel diseases with features of immunodeficiency. Approaches to the clinical diagnosis, genetic testing, and treatment of these disorders are addressed.


Assuntos
Doenças Hereditárias Autoinflamatórias/diagnóstico , Doenças Hereditárias Autoinflamatórias/terapia , Autoimunidade , Citocinas/metabolismo , Suscetibilidade a Doenças , Doenças Hereditárias Autoinflamatórias/etiologia , Doenças Hereditárias Autoinflamatórias/metabolismo , Humanos , Imunidade Inata , Inflamassomos/metabolismo
14.
Int Ophthalmol ; 39(1): 219-223, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29256170

RESUMO

PURPOSE: To report a childhood case of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) carrying the R92Q variant with a vision-threatening bilateral panuveitis. METHODS: Case report and review of the literature. RESULTS: A 7-year-old boy presented with an active bilateral panuveitis and a macular rash associated with fever. Fundus examination showed two choroidal lesions on the posterior pole of the right eye, and fluorescein angiography revealed early hypofluorescence and late hyperfluorescence of the lesions, which were hyper-autofluorescent. Extensive clinical laboratory analyses ruled out autoimmune diseases and systemic infection. The only remarkable finding was a positive IgG for herpes simplex 1. He underwent two successive diagnostic pars plana vitrectomies as well as cataract and glaucoma surgeries. Genetic analysis revealed a mutation in the TNFRSF1A gene, and the patient was diagnosed with TRAPS-associated bilateral panuveitis. He was treated with adalimumab and has been free of active inflammation since then. CONCLUSIONS: We present here the first case reported of panuveitis in a patient with TRAPS. This finding stresses the increasing importance of genetic analysis in search of autoinflammatory diseases to establish an adequate diagnosis and treatment in cases of uveitis of unknown etiology.


Assuntos
Febre/complicações , Doenças Hereditárias Autoinflamatórias/complicações , Pan-Uveíte/etiologia , Acuidade Visual , Vitrectomia/métodos , Criança , Febre/diagnóstico , Angiofluoresceinografia , Fundo de Olho , Testes Genéticos , Doenças Hereditárias Autoinflamatórias/diagnóstico , Humanos , Masculino , Oftalmoscopia , Pan-Uveíte/diagnóstico , Pan-Uveíte/cirurgia
15.
Clin Exp Rheumatol ; 36(6 Suppl 115): 86-89, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30418111

RESUMO

OBJECTIVES: Autoinflammatory diseases are characterised by abnormal hyperactivity of the innate immune system, causing systemic inflammation. The cryopyrin associated periodic syndrome (CAPS), the hyper IgD syndrome (HIDS) and the TNF receptor-associated periodic syndrome (TRAPS), are autoinflammatory conditions associated with mutations in the NLRP3, MVK and TNFRSF1A genes, respectively. We present the experience of our Department with these rare syndromes analysing genetic and clinical data of adult patients encountered between January 2011 and September 2017. METHODS: Eighty-eight adult patients with clinical suspicion of CAPS, HIDS and TRAPS were sequentially recruited and genetically tested for specific mutations in NLRP3, MVK and TNFRSF1A using Sanger sequencing. Clinical picture of mutation carriers was reviewed. Allele frequencies were compared to those described for the normal population by the 1000 Genomes project. RESULTS: Seventy-two of the 88 adult patients were found to be positive for mutations or polymorphisms. One patient carried two pathogenic MVK mutations (pV377I/c.1129G>A and c.850delG) and another one carried a pathogenic heterozygous pΑ439V/c.1316C>T NLRP3 mutation. Seventeen patients carried variants of uncertain significance. The pS434S/c.1302C>T NLRP3 mutation is slightly increased in our patients compared to the reference population and seems to correlate with severe symptom presentation. CONCLUSIONS: In rare cases, periodic fever and inflammatory symptoms in adults can be attributed to mutations in NLRP3, MVK and TNFRSF1A. Clinical assessment and genetic analysis are critical for proper diagnosis and treatment of autoinflammatory diseases.


Assuntos
Síndromes Periódicas Associadas à Criopirina/genética , Febre/genética , Doenças Hereditárias Autoinflamatórias/genética , Deficiência de Mevalonato Quinase/genética , Mutação , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Polimorfismo Genético , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Síndromes Periódicas Associadas à Criopirina/diagnóstico , Síndromes Periódicas Associadas à Criopirina/imunologia , Febre/diagnóstico , Febre/imunologia , Frequência do Gene , Predisposição Genética para Doença , Grécia , Doenças Hereditárias Autoinflamatórias/diagnóstico , Doenças Hereditárias Autoinflamatórias/imunologia , Humanos , Deficiência de Mevalonato Quinase/diagnóstico , Deficiência de Mevalonato Quinase/imunologia , Fenótipo , Estudos Retrospectivos , Fatores de Risco
16.
Pediatr Rheumatol Online J ; 16(1): 60, 2018 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-30241480

RESUMO

BACKGROUND: Diagnosis of Periodic Fever, Aphthous stomatitis, Pharyngitis and Cervical Adenitis (PFAPA) syndrome is currently based on the modified Marshall's criteria, but no validated evidence based classification criteria for PFAPA has been established so far. METHODS: A multistep process, based on the Delphi and Nominal Group Technique was conducted. After 2 rounds of e-mail Delphi survey involving 21 experts in autoinflammation we obtained a list of variables that were discussed in an International Consensus Conference. Variables reaching the 80% of consensus between participants were included in the new classification criteria. In the second phase the new classification criteria and the modified Marshall's criteria were applied on a cohort of 80 pediatric PFAPA patients to compare their performance. RESULTS: The Delphi Survey was sent to 22 participants, 21 accepted to participate. Thirty variables were obtained from the survey and have been discussed at the Consensus Conference. Through the Nominal Group Technique we obtained a new set of classification criteria. These criteria were more restrictive in respect to the modified Marshall's criteria when applied on our cohort of patients. CONCLUSION: Our work led us to identify a new set of classification criteria for PFAPA syndrome, but they resulted to be too restrictive to be applied in daily clinical practice for the diagnosis of PFAPA.


Assuntos
Doenças Hereditárias Autoinflamatórias/diagnóstico , Consenso , Técnica Delfos , Diagnóstico Diferencial , Febre/complicações , Doenças Hereditárias Autoinflamatórias/classificação , Humanos , Linfadenite/complicações , Faringite/complicações , Estomatite Aftosa/complicações , Síndrome
17.
Orphanet J Rare Dis ; 13(1): 156, 2018 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-30189864

RESUMO

BACKGROUND: Limited data are available on the experiences of patients with autoinflammatory diseases (AIDs) and their families along the path to diagnosis and treatment. We sought to describe these experiences in patients with AIDs including tumor necrosis factor receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency/hyperimmunoglobulin D syndrome (MKD/HIDS), and familial Mediterranean fever (FMF). METHODS: Ninety-minute, semi-structured qualitative interviews and 5-day written/video diaries were used to gather information on the experiences of patients with AIDs and their families. RESULTS: Twelve families of patients from the US (TRAPS [n = 4], MKD/HIDS [n = 5], FMF [n = 5]) participated in this study from August to November 2015. The study included two families with multiple afflicted siblings. Patients' ages ranged from 1 to 28 years. Most parents reported realizing that something was seriously wrong with their child after medical emergencies and/or hospitalizations, which initiated the difficult path to diagnosis. For most, the process included multiple specialist visits, extensive and repeated testing, and many misdiagnoses. Over time, 92% of parents reported losing confidence in the healthcare system's ability to find an answer to their child's symptoms, while they also struggled with unsupportive school personnel and dismissive friends and relatives. Patients and their parents reported holding on to memories of "what life was like" before the onset of symptoms and mourning their subsequent loss of "normalcy." Even after diagnosis, patients and parents continued to feel uncertain about what to expect in the future. CONCLUSIONS: All families emphasized the need for efficient early diagnosis of AIDs. Initiatives that improve the speed and accuracy of diagnosis, provide more comprehensive patient education, and support patients and families through the illness have the potential to significantly improve the quality of life of patients with AIDs and their families. Healthcare providers should be aware of the impact of the long diagnostic journey on families and work to create an environment of trust and collaboration in the face of a difficult and prolonged diagnostic process.


Assuntos
Febre/metabolismo , Doenças Hereditárias Autoinflamatórias/metabolismo , Deficiência de Mevalonato Quinase/metabolismo , Adolescente , Adulto , Criança , Pré-Escolar , Febre Familiar do Mediterrâneo/diagnóstico , Febre Familiar do Mediterrâneo/genética , Febre Familiar do Mediterrâneo/metabolismo , Feminino , Febre/diagnóstico , Febre/genética , Doenças Hereditárias Autoinflamatórias/diagnóstico , Doenças Hereditárias Autoinflamatórias/genética , Humanos , Lactente , Masculino , Deficiência de Mevalonato Quinase/diagnóstico , Deficiência de Mevalonato Quinase/genética , Qualidade de Vida , Adulto Jovem
18.
Ann Rheum Dis ; 77(11): 1599-1605, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30077992

RESUMO

INTRODUCTION: Autoinflammatory diseases can cause irreversible tissue damage due to systemic inflammation. Recently, the Autoinflammatory Disease Damage Index (ADDI) was developed. The ADDI is the first instrument to quantify damage in familial Mediterranean fever, cryopyrin-associated periodic syndromes, mevalonate kinase deficiency and tumour necrosis factor receptor-associated periodic syndrome. The aim of this study was to validate this tool for its intended use in a clinical/research setting. METHODS: The ADDI was scored on paper clinical cases by at least three physicians per case, independently of each other. Face and content validity were assessed by requesting comments on the ADDI. Reliability was tested by calculating the intraclass correlation coefficient (ICC) using an 'observer-nested-within-subject' design. Construct validity was determined by correlating the ADDI score to the Physician Global Assessment (PGA) of damage and disease activity. Redundancy of individual items was determined with Cronbach's alpha. RESULTS: The ADDI was validated on a total of 110 paper clinical cases by 37 experts in autoinflammatory diseases. This yielded an ICC of 0.84 (95% CI 0.78 to 0.89). The ADDI score correlated strongly with PGA-damage (r=0.92, 95% CI 0.88 to 0.95) and was not strongly influenced by disease activity (r=0.395, 95% CI 0.21 to 0.55). After comments from disease experts, some item definitions were refined. The interitem correlation in all different categories was lower than 0.7, indicating that there was no redundancy between individual damage items. CONCLUSION: The ADDI is a reliable and valid instrument to quantify damage in individual patients and can be used to compare disease outcomes in clinical studies.


Assuntos
Doenças Hereditárias Autoinflamatórias/diagnóstico , Índice de Gravidade de Doença , Adolescente , Adulto , Criança , Simulação por Computador , Síndromes Periódicas Associadas à Criopirina/complicações , Síndromes Periódicas Associadas à Criopirina/diagnóstico , Febre Familiar do Mediterrâneo/complicações , Febre Familiar do Mediterrâneo/diagnóstico , Doenças Hereditárias Autoinflamatórias/complicações , Humanos , Deficiência de Mevalonato Quinase/complicações , Deficiência de Mevalonato Quinase/diagnóstico , Variações Dependentes do Observador , Sistema de Registros , Reprodutibilidade dos Testes , Adulto Jovem
19.
Clin Rheumatol ; 37(12): 3449-3454, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30159790

RESUMO

Yao syndrome (YAOS), formerly named NOD2-associated autoinflammatory disease, is a periodic disease characterized by fever, dermatitis, polyarthritis, distal extremity swelling, and gastrointestinal and sicca-like symptoms associated with specific NOD2 sequence variants. All patients in the literature were Caucasians. Herein, we report the first case series of YAOS in China to further expand the clinical and genetic characteristics of this disorder. A retrospective review of patients who were diagnosed with YAOS at our tertiary medical center was conducted. Three Han Chinese women with YAOS were included. Recurrent fever occurred in all patients and each febrile episode lasted several days to several weeks, and asymptomatic intervals ranged from several weeks to several months. Two patients experienced intermittent arthritis/arthralgia and abdominal pain, and one had sicca-like symptoms. None had dermatitis. Three variants in NOD2 were identified, including Q902K, R541P, and Y514H. The patients' symptoms significantly improved after treatment with glucocorticoids and/or sulfasalazine. YAOS exists in the Chinese population, and it may be a global disorder. Our patients appear to exhibit somewhat distinct clinical phenotypes from those in the Caucasian population, and three novel NOD2 variants have been identified in the disease.


Assuntos
Genótipo , Doenças Hereditárias Autoinflamatórias/diagnóstico , Doenças Hereditárias Autoinflamatórias/terapia , Proteína Adaptadora de Sinalização NOD2/genética , Adulto , Grupo com Ancestrais do Continente Asiático , China/epidemiologia , Feminino , Febre/terapia , Pé/diagnóstico por imagem , Variação Genética , Glucocorticoides/uso terapêutico , Humanos , Inflamação/diagnóstico por imagem , Joelho/diagnóstico por imagem , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Mutação , Recidiva , Estudos Retrospectivos , Sulfassalazina/uso terapêutico
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