BackgroundDifferent diagnostic and classification criteria are available for hereditary recurrent fevers (HRF)—familial Mediterranean fever (FMF), tumour necrosis factor receptor-associated periodic fever syndrome (TRAPS), mevalonate kinase deficiency (MKD) and cryopyrin-associated periodic syndromes (CAPS)—and for the non-hereditary, periodic fever, aphthosis, pharyngitis and adenitis (PFAPA). We aimed to develop and validate new evidence-based classification criteria for HRF/PFAPA.MethodsStep 1: selection of clinical, laboratory and genetic candidate variables; step 2: classification of 360 random patients from the Eurofever Registry by a panel of 25 clinicians and 8 geneticists blinded to patients’ diagnosis (consensus ≥80%); step 3: statistical analysis for the selection of the best candidate classification criteria; step 4: nominal group technique consensus conference with 33 panellists for the discussion and selection of the final classification criteria; step 5: cross-sectional validation of the novel criteria.ResultsThe panellists achieved consensus to classify 281 of 360 (78%) patients (32 CAPS, 36 FMF, 56 MKD, 37 PFAPA, 39 TRAPS, 81 undefined recurrent fever). Consensus was reached for two sets of criteria for each HRF, one including genetic and clinical variables, the other with clinical variables only, plus new criteria for PFAPA. The four HRF criteria demonstrated sensitivity of 0.94–1 and specificity of 0.95–1; for PFAPA, criteria sensitivity and specificity were 0.97 and 0.93, respectively. Validation of these criteria in an independent data set of 1018 patients shows a high accuracy (from 0.81 to 0.98).ConclusionEurofever proposes a novel set of validated classification criteria for HRF and PFAPA with high sensitivity and specificity.

No abstract

Neonatal lupus erythematosus is an uncommon syndrome, which is caused by transplacental passage of maternal autoantibodies to Sjögren's syndrome A or B autoantigens. The clinical presentation includes distinctive cutaneous lesions resembling those seen in systemic lupus erythematosus, hepatobiliary disease, and cytopenias, which disappear with the clearance of maternal autoantibodies. The most severe presentation is a total atrioventricular heart block, which begins during the second trimester of gestation and is irreversible. The risk of having a child with neonatal lupus erythematosus in mothers who test positive for autoantibodies to Sjögren's syndrome autoantigens is approximately 2% for first pregnancies or if previous babies were healthy. The risk increases by approximately tenfold if a previous child had neonatal lupus erythematosus syndrome. The diagnosis of neonatal lupus erythematosus is made when the mother has autoantibodies to Sjögren's syndrome autoantigens, and the fetus or newborn develops atrioventricular heart block, or the newborn develops the typical rash or hepatic or hematologic manifestations in the absence of other explanation. Fetal echocardiography from the 16th to the 26th week of gestation is advised in mothers with autoantibodies to Sjögren autoantigens. The detection of a slow fetal heart rate or the postnatal diagnosis of atrioventricular heart block warrants immediate maternal testing for these autoantibodies if not previously tested.

The syndrome of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA syndrome) is the most common cause of periodic fever in childhood. The current pharmacological treatment includes corticosteroids, which usually are efficacious in the management of fever episodes, colchicine, for the prophylaxis of febrile episodes, and other medication for which efficacy has not been proven so far. Tonsillectomy is an option for selected patients. Usually PFAPA syndrome resolves during adolescence, but there is increasing evidence that this condition may persist into adulthood.

PFAPA syndrome is the most common autoinflammatory syndrome in children from Western countries. In spite of its strong familial clustering, its genetic basis and inheritance pattern are still unknown. We performed a comprehensive genetic study on 68 individuals from 14 families. Linkage analysis suggested a susceptibility locus on chromosome 8, but direct molecular sequencing did not support this initial statistical finding. Exome sequencing revealed the absence of any gene that was mutated in all patients. Exhaustive screening of genes involved in other autoinflammatory syndromes or encoding components of the human inflammasome showed no DNA variants that could be linked to PFAPA molecular pathology. Among these, the previously-reported missense mutation V198M in the NLRP3 gene was clearly shown not to co-segregate with PFAPA. Our results on this relatively large cohort indicate that PFAPA syndrome is unlikely to be a monogenic condition. Moreover, none of the several genes known to be involved in inflammation or in autoinflammatory disorders seem to be relevant, alone, to its etiology, suggesting that PFAPA results from oligogenic or complex inheritance of variants in multiple disease genes and/or non-genetic factors.

In Henoch-Schönlein syndrome, signs of nervous system dysfunction are uncommon but clinically relevant. This review helps clinicians managing Henoch-Schönlein syndrome with nervous system dysfunction.

Objectives: During hospitalization in neonatal intensive care units, neonates are exposed to many painful procedures within a stressful environment. To date, many evidence-based guidelines are available. However, the quality of these guidelines and their clinical application remain unclear. This systematic review aimed to determinie the quality of existing guidelines on the management of procedural pain in neonates and to summarize the recommendations provided by these guidelines. Materials and Methods: A structured search was conducted in Embase, PubMed, CINAHL, JBI database, and gray literature resources in November 2018 to identify relevant guidelines published from 2007 onward. Published guidelines and guidelines from complementary searches were included in the treating assessment or management of procedural pain in neonates. The methodological quality was analyzed using the Appraisal of Guidelines for Research and Evaluation (AGREE) II Instrument. Results: A total of 1154 records were identified. After screening for eligibility, 17 guidelines were included in this review. Among these, 11 were identified to be high-quality guidelines. Besides the usual recommendations for pharmacological and nonpharmacological treatments, the inclusion of parents, improving interprofessional collaboration, and considering the setting were identified as important elements. Discussion: The results of this review show that there is a need to improve the methodological quality of guidelines for procedural pain in newborns. The set of recommendations for procedural pain prevention needs to involve not only pharmacological and nonpharmacological pain treatment but also parents and interprofessional collaboration. It is also essential to take into account facilitators, barriers, and the context to improve pain management.

Background Tubulointerstitial nephritis and uveitis (TINU) is defined as the occurrence of tubulointerstitial nephritis and uveitis in the absence of other systemic diseases. The most comprehensive review on this condition was published in 2001. Methods We conducted a systematic review of the literature on cases of TINU syndrome. Medline an EMBASE databases were screened. Full-length articles or letters reporting cases with both tubulointerstitial nephritis and uveitis were selected. We investigated differences between males/females and pediatric and adult cases. Multivariate analysis was performed to identify potential risk factors for chronic kidney disease development. Results 233 articles reporting 592 TINU cases were retained for analysis. The median age of the included subjects was 17 (interquartile range 13-46) years, with a female predominance (65%). Uveitis most frequently (52%) followed renal disease, and was mostly anterior (65%) and bilateral (88%). Children tended to have more ocular relapses while they were slightly less likely than adults to suffer from acute kidney injury and to develop chronic kidney disease. Adult age, as well as posterior or panuveitis, were associated with an increased risk of developing chronic kidney disease. Conclusions TINU affects both children and adults, with some differences between these two categories. Adult age and the presence of a posterior uveitis or panuveitis appear to be associated with the development of chronic kidney disease.