Autoimmune and Inflammatory Disorders Research (28)
Inflammasome and immune disorders (15)
Adolescent and Pediatric Healthcare (10)
Rheumatoid Arthritis Research and Therapies (8)
Vasculitis and related conditions (8)
Güngörer V, Ünal D, Çakan M, Ayduran S, Gül Ü , et al.
Clinical rheumatology •
Syndrome of undifferentiated recurrent fever (SURF) is an autoinflammatory disorder that is recognised in an increasing number of patients. In this study, we aimed to assess the data of SURF patients from the main reference centres in our country. Data for this retrospective multicentre observational cohort study were obtained from the records of SURF patients aged 0-18 years who were followed up in 10 pediatric rheumatology clinics in Türkiye between 2010 and June 2023. Patients with recurrent fever that could not be explained by periodic fever, aphthous stomatitis, pharyngitis and adenopathy (PFAPA) and hereditary recurrent fevers and had no other cause were included in the study. Of the 134 patients included in the study, 74 (55.2%) were male. The median age at diagnosis was 67 months. The most common symptom was abdominal pain in 98 (73.1%), arthralgia in 82 (61.2%), malaise in 77 (57.5%). The age at symptom onset was ≤ 5 years in 109 patients (81.3%). Pharyngitis was more common symptom in children aged ≤ 5 years (p = 0.008), headache, arthralgia, chest pain were more common findings in children > 5 years (p = 0.008, p = 0.032, p = 0.045). There were 113 patients receiving colchicine alone or in combination therapy and 74.3% of them achieved complete or partial remission. The presence of abdominal pain (p = 0.021, OR = 0.254) increased the remission rate with colchicine. SURF patients present with a wide range of clinical manifestations. Distinguishing between SURF and PFAPA is not concrete. Further omics studies will enlighten whether there is a true group of SURF. Key Points • SURF is an autoinflammatory disease that is becoming increasingly recognised. • The clinical manifestations of SURF are quite heterogeneous. • Colchicine and anti-IL-1 treatment is effective in most SURF patients. • It is controversial whether it should be called SURF or PFAPA-like syndrome, especially in children aged ≤ 5 years.
Mutlu F, Kasap M, Yaprak Bayrak B, Sarıhan M, Şahin N , et al.
Pediatric research •
Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome is a recurrent fever syndrome. The exact etiopathogenesis of PFAPA syndrome remains unknown. Biological fluids or tissues may provide disease-specific biomarkers that may help clinicians to find new pathogenic pathways. Tonsil tissues of seven patients with PFAPA were collected during the tonsillectomy. Seven patients who underwent tonsillectomy for reasons other than chronic tonsillitis were enrolled as a control group. The nHPLC LC-MS/MS system was used for protein identification and label-free quantification. Bioinformatics analysis was carried out using the UniProt accession numbers of the identified proteins. Proteomics analysis revealed to identity of proteins of which at least 23 were up and 57 were downregulated. Bioinformatics analysis of differentially regulated proteins by STRING indicated that protein folding and clearance machinery were interrupted in PFAPA patients compared to the controls. The affected pathways underlined the importance of the mitochondrial electron transport chain and ATP biosynthesis process. Although it is not clear that changes in tonsil protein expression whether directly related to pathogenesis or simply result of chronic inflammation, the identification of tonsil biomarkers for PFAPA may provide clinicians an opportunity to understand disease pathogenesis or develop new molecular targets for treatments. Proteomics analyses of tonsils revealed the identity of 80 proteins of which at least 23 were up and 57 were downregulated. Bioinformatics analysis underlined the importance of mitochondrial ETC and regulation of ATP biosynthetic process. This is the first study evaluating the proteomics of the tonsils of PFAPA patients. The identification of tonsil biomarkers for PFAPA may provide clinicians an opportunity to understand disease pathogenesis or develop new molecular targets for treatments.
Özaslan Z, Şen A, Uçar SA, Çakan M, Sanisoğlu B , et al.
European journal of pediatrics •
Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome (PFAPA) are the most common autoinflammatory syndromes in children. This study aimed to evaluate the clinical and laboratory parameters that may predict colchicine responsiveness.This retrospective, multicenter, cross-sectional study involved nine pediatric rheumatology centers from our country., The patients diagnosed with PFAPA were compared on the basis of their responses to colchicine. In the 806 (42.3% female 57.7% male) patients, the most common clinical findings were fever (100%), exudative tonsillitis (86.5%), pharyngitis (80.9%), and aphthous stomatitis (50.5%). The mean attack frequency was 13.5 ± 6.8 attacks per year lasting for a mean of 3.9 ± 1.1 days. Colchicine treatment was attempted in 519 (64.4%) patients, with 419 (80.7%) showing a favorable response. In patients who underwent MEFV gene analysis (70.8%), the most common variant was M694V heterozygous (16.8%). The presence of pharyngitis (p = 0.03, 95% CI 0.885 to 0.994), the presence of arthralgia (p = 0.04, 95% CI 0.169 to 0.958), and having more frequent attacks (p = 0.001, 95% CI 0.028 to 0.748) were found to be associated with colchicine unresponsiveness, whereas the carriage of the M694V variant (p = 0.001, 95% CI 0.065 to 0.242) was associated with colchicine responsiveness. This study identified the presence of pharyngitis, arthralgia, and increased attack frequency in patients with PFAPA as factors predicting colchicine unresponsiveness, whereas the carriage of the M694V variant emerged as a predictor of colchicine responsiveness. Predicting colchicine response at disease onset may facilitate a more effective management of PFAPA. • Colchicine treatment can be used in the prophylaxis of PFAPA disease. • Having the MEFV variant is the most commonly known factor in predicting response to colchicine. • The presence of pharyngitis or arthralgia, and more frequent attacks in PFAPA disease were found to be independently associated with colchicine unresponsiveness. • Carrying the M694V variant was identified as the sole factor predicting colchicine responsiveness.