Consensus protocols for the diagnosis and management of the hereditary autoinflammatory syndromes CAPS, TRAPS and MKD/HIDS: a German PRO-KIND initiative (original) (raw)
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Annals of the Rheumatic Diseases
BackgroundThe interleukin-1 (IL-1) mediated systemic autoinflammatory diseases, including the cryopyrin-associated periodic syndromes (CAPS), tumour necrosis factor receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency (MKD) and deficiency of the IL-1 receptor antagonist (DIRA), belong to a group of rare immunodysregulatory diseases that primarily present in early childhood with variable multiorgan involvement. When untreated, patients with severe clinical phenotypes have a poor prognosis, and diagnosis and management of these patients can be challenging. However, approved treatments targeting the proinflammatory cytokine IL-1 have been life changing and have significantly improved patient outcomes.ObjectiveTo establish evidence-based recommendations for diagnosis, treatment and monitoring of patients with IL-1 mediated autoinflammatory diseases to standardise their management.MethodsA multinational, multidisciplinary task force consisting of physician experts,...
Annals of the Rheumatic Diseases, 2020
Ultra-rare genetically defined IL-1 mediated autoinflammatory diseases (AIDs) include mevalonate kinase deficiency (MKD), tumor necrosis factor receptor associated periodic syndrome (TRAPS), cryopyrinopathies (CAPS) and deficiency of the IL-1 receptor antagonist (DIRA). These disorders start perinatally, the clinical disease manifestations include systemic inflammation; and late diagnosis and inappropriate treatment cause irreversible organ damage. The varying skills of treating rheumatologists and paediatricians illustrate the need for management guidance, however criteria for validated methodology is geared towards common diseases with more heterogeneous pathogenesis.The focus of this systematic review includes the evaluation of the existing literature and the evaluation of existing EULAR methodology for use in the ultra-rare diseases with defined pathomechanisms, CAPS, TRAPS, MKD and DIRAEULAR standardized operating procedures were followed during the review, including a meeting ...
Recommendations for the management of autoinflammatory diseases
Annals of the rheumatic diseases, 2015
Autoinflammatory diseases are characterised by fever and systemic inflammation, with potentially serious complications. Owing to the rarity of these diseases, evidence-based guidelines are lacking. In 2012, the European project Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) was launched to optimise and disseminate regimens for the management of children and young adults with rheumatic diseases, facilitating the clinical practice of paediatricians and (paediatric) rheumatologists. One of the aims of SHARE was to provide evidence-based recommendations for the management of the autoinflammatory diseases cryopyrin-associated periodic syndromes (CAPS), tumour necrosis factor (TNF) receptorassociated periodic syndrome (TRAPS) and mevalonate kinase deficiency (MKD). These recommendations were developed using the European League Against Rheumatism standard operating procedure. An expert committee of paediatric and adult rheumatologists was convened. Recommendations derived from the systematic literature review were evaluated by an online survey and subsequently discussed at a consensus meeting using Nominal Group Technique. Recommendations were accepted if more than 80% agreement was reached. In total, four overarching principles, 20 recommendations on therapy and 14 recommendations on monitoring were accepted with ≥80% agreement among the experts. Topics included (but were not limited to) validated disease activity scores, therapy and items to assess in monitoring of a patient. By developing these recommendations, we aim to optimise the management of patients with CAPS, TRAPS and MKD.
Hereditary Autoinflammatory Syndromes: A Brazilian Multicenter Study
Journal of Clinical Immunology, 2012
Objective To evaluate the prevalence of genetic defects in clinically suspected autoinflammatory syndromes (AIS) in a Brazilian multicenter study. Methods The study included 102 patients with a clinical diagnosis of Cryopyrin Associated Periodic Syndromes (CAPS), TNF Receptor Associated Periodic Syndrome (TRAPS), Familial Mediterranean Fever (FMF), Mevalonate Kinase Deficiency (MKD) and Pediatric Granulomatous Arthritis (PGA). One of the five AIS-related genes (NLRP3, TNFRSF1A, MEFV, MVK and NOD2) was evaluated in each patient by direct DNA sequencing, based on the most probable clinical suspect. Results Clinical diagnoses of the 102 patients were: CAPS (n028), TRAPS (n031), FMF (n017), MKD (n017) and PGA (n 09). Of them, 27/102 (26 %) had a confirmed genetic diagnosis: 6/28 (21 %) CAPS patients, 7/31 (23 %) TRAPS, 3/17 (18 %) FMF, 3/17 (18 %) MKD and 8/9 (89 %) PGA. Conclusion We have found that approximately one third of the Brazilian patients with a clinical suspicion of AIS have a confirmed genetic diagnosis.
Diagnosis and Management of Autoinflammatory Diseases in Childhood
Journal of Clinical Immunology, 2008
Introduction Autoinflammatory diseases are a group monogenic inflammatory conditions characterized by an early onset during childhood. Discussion Under the term "periodic fevers" are gathered some monogenic diseases (familial Mediterranean fever, mevalonate kinase deficiency, and tumor necrosis factor receptor-associated syndrome) characterized by periodic or recurrent episodes of systemic inflammation causing fever often associated with rash, serositis (peritonitis, pleuritis), lymphadenopathy, arthritis, and other clinical manifestations. Systemic reactive (AA) amyloidosis may be a severe long-term complication. Cryopyrinopathies are a group of conditions associated to mutations of the gene Cryopyrin that are responsible for a spectrum of diseases (familial cold autoinflammatory syndrome, Muckle-Wells syndrome, and chronic infantile neurological cutaneous and articular syndrome) characterized by a chronic or recurrent systemic inflammation variably associated with a number of clinical features, such as urticarial-like rash, arthritis, sensorineural deafness, and central nervous system and bone involvement. Other disorders are dominated by the presence of sterile pyogen abscesses prevalently affecting the skin, joints, and bones (pyogenic disorders). These include pyogenic sterile arthritis, pyoderma gangrenosum, and acne syndrome, and Majeed syndrome. Finally, some diseases, such as Blau's syndrome, are characterized by the appearance of typical noncaseating granulomatous inflammation affecting the joints, skin, and uveal tract (granulomatous disorders). In the present review, we will focus on the clinical presentation of these disorders in childhood and report on the available therapeutic strategies. Keywords Familial Mediterranean fever. mevalonate kinase deficiency. tumor necrosis factor (TNF) receptor-associated syndrome. cryopyrinopathies
Erratum to: Hereditary Autoinflammatory Syndromes: A Brazilian Multicenter Study
Journal of Clinical Immunology, 2012
Objective To evaluate the prevalence of genetic defects in clinically suspected autoinflammatory syndromes (AIS) in a Brazilian multicenter study. Methods The study included 102 patients with a clinical diagnosis of Cryopyrin Associated Periodic Syndromes (CAPS), TNF Receptor Associated Periodic Syndrome (TRAPS), Familial Mediterranean Fever (FMF), Mevalonate Kinase Deficiency (MKD) and Pediatric Granulomatous Arthritis (PGA). One of the five AIS-related genes (NLRP3, TNFRSF1A, MEFV, MVK and NOD2) was evaluated in each patient by direct DNA sequencing, based on the most probable clinical suspect. Results Clinical diagnoses of the 102 patients were: CAPS (n028), TRAPS (n031), FMF (n017), MKD (n017) and PGA (n 09). Of them, 27/102 (26 %) had a confirmed genetic diagnosis: 6/28 (21 %) CAPS patients, 7/31 (23 %) TRAPS, 3/17 (18 %) FMF, 3/17 (18 %) MKD and 8/9 (89 %) PGA. Conclusion We have found that approximately one third of the Brazilian patients with a clinical suspicion of AIS have a confirmed genetic diagnosis.
RMD Open, 2020
ObjectivesSeveral therapies are used for the treatment of rareautoinflammatory conditions like cryopyrin-associated periodic fever syndromes (CAPS), hyperimmunoglobulin Dsyndrome (HIDS)/mevalonate kinase deficiency (MKD) and tumour necrosis factor receptor-associated periodic syndrome (TRAPS). However, reviews reporting on treatment outcomes of these therapies are lacking.MethodsA systematic literature review was conducted using Embase, MEDLINE, MEDLINE-In Process and Cochrane databases to identify the randomised/non-randomised controlled trials (RCTs/non-RCTs) and real-world observational studies of CAPS, HIDS/MKD and TRAPS published as full-texts (January 2000–September 2017) or conference abstracts (January 2014–September 2017). Studies with data for ≥1 biologic were included. Studies with <5 patients were excluded.ResultsOf the 3 342 retrieved publications, 72 studies were included (CAPS, n=43; HIDS/MKD, n=9; TRAPS, n=7; studies with ≥2 cohorts, n=13). Most studies were full-...
2008
Objective. To identify a set of clinical parameters that can predict the probability of carrying mutations in one of the genes associated with hereditary autoinflammatory syndromes. Methods. A total of 228 consecutive patients with a clinical history of periodic fever were screened for mutations in the MVK, TNFRSF1A, and MEFV genes, and detailed clinical information was collected. A diagnostic score was formulated based on univariate and multivariate analyses in genetically positive and negative patients (training set). The diagnostic score was validated in an independent set of 77 patients (validation set). Results. Young age at onset (odds ratio [OR] 0.94, P ؍ 0.003), positive family history of periodic fever (OR 4.1, P ؍ 0.039), thoracic pain (OR 4.6, P ؍ 0.05), abdominal pain (OR 33.1, P < 0.001), diarrhea (OR 3.3, P ؍ 0.028), and oral aphthosis (OR 0.2, P ؍ 0.007) were found to be independently correlated with a positive genetic test result. These variables were combined in a linear score whose ability to predict a positive result on genetic testing was validated in an independent data set. In this latter set, the diagnostic score revealed high sensitivity (82%) and specificity (72%) for discriminating patients who were genetically positive from those who were negative. In patients with a high probability of having a positive result on genetic testing, a regression tree analysis provided the most reasonable order in which the genes should be screened. Conclusion. The proposed approach in patients with periodic fever will increase the probability of obtaining positive results on genetic testing, with good specificity and sensitivity. Our results further help to optimize the molecular analysis by suggesting the order in which the genes should be screened. Familial Mediterranean fever (FMF; MIM no. #249100), tumor necrosis factor receptor-associated periodic fever syndrome (TRAPS; MIM no. #142680), and mevalonate kinase deficiency (MKD; MIM no. #260920) are hereditary diseases caused by mutations of genes involved in the regulation or activation of the inflammatory response (1). These conditions are characterized by recurrent episodes of fever associated with a number of manifestations: rash, serositis, lymphadenopathy, and arthralgias/arthritis. Disease onset is commonly observed during the pediatric years, and a delay in the molecular diagnosis frequently occurs. Systemic reactive AA amyloidosis may be a severe long-term complication of these conditions.