imagem top



CHULC LOGOlogo HDElogo anuario


Filipa Ramos1, Marta Conde2, Fernando Martins3, José Gonçalo Marques4, Isabel Esteves4, Ana Berta Sousa5, João Farela Neves6, Cristina Henriques2, Gonçalo Cordeiro-Ferreira7, JA Pereira da Silva1, João Eurico Fonseca1, Helena Canhão1

1 - Serviço de Reumatologia Hospital de Santa Maria, CHLN, EPE;
2 - Unidade de Reumatologia , Hospital Dona Estefânia. CHLC - EPE;
3 -;
4 - Serviço de Pediatria Hospital de Santa Maria, CHLN, EPE; 5 Serviço de Genética Hospital de Santa Maria, CHLN, EPE; 6- Unidade de Imunodeficiências Primárias , Hospital Dona Estefânia. CHLC – EPE; 7 Director da area de Pediatria Médica , Hospital Dona Estefânia;

Congresso Português de Reumatologia 2014; Congresso Nacional; Poster
15º Congresso Nacional de Pediatria; Congresso Nacional, Comunicação Oral

Auto-inflammatory diseases (AIDs) are a newly understood group of conditions with expanding phenotypes and genetic markers. However, many AIDs are extremely rare and genotype-phenotype correlations, disease course, response to treatment and outcomes are difficult to characterize. Multicentre AIDs registries enable a better understanding of clinical features and outcomes of such diseases and are a valuable tool for clinical and translational research in this field. Objectives:  To assess clinical and genetic features of auto-inflammatory diseases registered at AIDs protocol.
Since September 2013 has a build-in protocol specifically developed for AIDs. Inclusion criteria in this protocol are monogenic AIDs or clinically confirmed AID with unknown genetic background. Monogenic AIDs includes familial mediterranean fever (FMF), mevalonate kinase deficiency (MKD), TNF receptor 1-associated periodic syndrome (TRAPS), cryopyrin-associated periodic syndrome (CAPS), chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE), Blau syndrome, pyogenic sterile arthritis, pyoderma gangrenosum and acne (PAPA), Majeed syndrome, deficiency of IL-1B receptor antagonist (DIRA), deficiency of IL-36 receptor antagonist (DITRA) and others like auto-inflammatory PLCG2-associated antibody deficiency and immune dysregulation (APLAID). Periodic fever, aphthous stomatitis, pharyngitis and adenopathy (PFAPA) syndrome and chronic recurrent multifocal osteomyelitis (CRMO) are included as AID with unknown genetic background. Undefined AID concerns clinically confirmed AID with more than three self-limited episodes of fever > 38,5ºC, increased inflammation markers and asymptomatic intervals between episodes in an otherwise healthy patient. Available data from this register were analyzed regarding genetic, epidemiological and clinical features. Results From the 74 patients currently included in AID protocol, 72 patients (44 males and 28 females) registered by two centres (35 from HSM and 37 from HDE), were analysed. Of these, 10 (13.9%) have been documented only prospectively and for 56 (77.8%) patients retrospective and prospective data have been made available. Mean age was 8.6±8.2 years (2.2 to 19.2 years), mean age at disease onset was 2.5±2.2 years, disease duration was 5.7±3.9 years andmean time between symptoms onset and clinical diagnosis was 2.9±1.5 years. The following diagnosis have been identified: FMF (n=2), MKD (n=2), TRAPS (n=1), PFAPA (n=47), CRMO (n=5), APLAID (n=1) and undefined AID (n=14). Confirmed mutations for monogenic AID were found in 5 patients: MEFV PG304R in1 patient with FMF; MVK pR277G, MVK p.Val377Ile and MVK p.Cys152Tyr in 2 patients with MKD, TNFRSF1A R92Q in 1 TRAPS patient and PLCG2 gene mutation in 1 APLAID patient.Regarding treatment, 2 FMF patients were treated with colchicine, corticosteroids on demand were used in all PFAPA patients and also for MKD, TRAPS, APLAID and 6 undefined AID patients. Biological therapy was used in patients with poorly controlled MKD (1 patient treated with anakinra), TRAPS (1 patient treated with etanercept) and undefined AID (canakinumab has been used in 1 patient). Of the 5 CRMO patients 4 were treated with prednisolone and pamidronate and 1 with prednisolone and methotrexate. Twenty seven blood samples from 3 patients have been collected at Biobanco-IMM. The collection of the remaining patients is ongoing.
Through this register AIDs can be systematically investigated paving the way to a better understanding of disease course, treatment responses and prognosis. This tool could be also valuable to enable genotype-phenotype correlations in order to identify new AIDs and new mutations.