Evidence-based provisional clinical classification criteria for autoinflammatory periodic fevers

Abstract

The objective of this work was to develop and validate a set of clinical criteria for the classification of patients affected by periodic fevers. Patients with inherited periodic fevers (familial Mediterranean fever (FMF); mevalonate kinase deficiency (MKD); tumour necrosis factor receptor-associated periodic fever syndrome (TRAPS); cryopyrin-associated periodic syndromes (CAPS)) enrolled in the Eurofever Registry up until March 2013 were evaluated. Patients with periodic fever, aphthosis, pharyngitis and adenitis (PFAPA) syndrome were used as negative controls. For each genetic disease, patients were considered to be 'gold standard' on the basis of the presence of a confirmatory genetic analysis. Clinical criteria were formulated on the basis of univariate and multivariate analysis in an initial group of patients (training set) and validated in an independent set of patients (validation set). A total of 1215 consecutive patients with periodic fevers were identified, and 518 gold standard patients (291 FMF, 74 MKD, 86 TRAPS, 67 CAPS) and 199 patients with PFAPA as disease controls were evaluated. The univariate and multivariate analyses identified a number of clinical variables that correlated independently with each disease, and four provisional classification scores were created. Cut-off values of the classification scores were chosen using receiver operating characteristic curve analysis as those giving the highest sensitivity and specificity. The classification scores were then tested in an independent set of patients (validation set) with an area under the curve of 0.98 for FMF, 0.95 for TRAPS, 0.96 for MKD, and 0.99 for CAPS. In conclusion, evidence-based provisional clinical criteria with high sensitivity and specificity for the clinical classification of patients with inherited periodic fevers have been developed.

Results of molecular genetic screening of mutations in the NLRP3, TNFRSF1A, and MVK genes in patients with autoinflammatory diseases and systemic juvenile arthritis

“…Осуще-ствлялись попытки выявления каких-либо мутаций у паци-ентов с СЮА, они представлены в отдельных зарубежных публикациях, а в России пока эксклюзивны [12][13][14]. Экс-пертами в области изучения АВЗ для их идентификации предложены алгоритмы диагностики, включающие клини-ческие классификационные критерии, рекомендации по лечению [15][16][17][18][19]. Разработаны также диагностический счет для определения степени риска наличия АВЗ и показания для проведения молекулярно-генетического анализа [20].…”

Current Knowledge on Procaspase-1 Variants with Reduced or Abrogated Enzymatic Activity in Autoinflammatory Disease

“…Periodic fever is frequently accompanied by other symptoms such as abdominal pain, arthralgia, and sometimes arthritis, myalgia, and signs specific for the respective disorder. However, there is great variation among individuals with the same mutations even within one family, and fever can be irregular, rare, or absent altogether even when there are other symptoms of severe inflammation [6][7][8]. Amyloidosis is a possible severe complication of most of these disorders.…”

Early Onset of Periodic Fever Syndrome in a Patient Carrying Both Tumor Necrosis Factor Receptor Superfamily 1A and Mediterranean Fever Mutations

“…The patient fulfilled the Eurofever clinical diagnostic/classification criteria for TRAPS. 4 Genetic testing revealed that the child carried heterozygous mutations in two autoinflammatory genes: C30Y in the TNFRSF1A gene and K695R in the MEFV gene. For a few years, febrile attacks accrued every eight to 10 weeks and were well-controlled with short, intermittent courses of oral steroids.…”