Autoimmune and Inflammatory Disorders Research (43)
Systemic Lupus Erythematosus Research (31)
Inflammasome and immune disorders (30)
Vasculitis and related conditions (26)
Ocular Diseases and Behçet’s Syndrome (16)
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.
Batu ED, Vezir E, Öğüş E, Özbaş Demirel Ö, Akpınar G , et al.
Rheumatology international •
Differentiating PFAPA (periodic fever, aphthosis, pharyngitis, and adenitis) syndrome from familial Mediterranean fever (FMF) could be challenging in some cases. Galectin-3 is a lectin with regulatory functions in apoptosis and inflammation. We aimed to test whether galectin-3 could be a biomarker for differentiating PFAPA syndrome from FMF. Patients with PFAPA syndrome, FMF, cryopyrin-associated periodic syndrome (CAPS), and streptococcal pharyngitis, and healthy controls were included in this study. Serum galectin-3 levels were measured using enzyme-linked immunosorbent assay. Eighty-seven patients (36 with PFAPA, 39 with FMF, 8 with CAPS, 4 with streptococcal pharyngitis), and 17 healthy controls were included. Blood samples were drawn during attacks from 20 PFAPA and 7 FMF patients and attack-free periods from 22 PFAPA, 35 FMF, and 8 CAPS patients. The median serum galectin-3 level in the PFAPA-attack group (1.025 ng/ml) was significantly lower than the levels in healthy control (2.367 ng/ml), streptococcal pharyngitis (3.021 ng/ml), FMF attack (2.402 ng/ml), and FMF-attack-free groups (2.797 ng/ml) (p = 0.006, 0.03, 0.01, and < 0.001, respectively). PFAPA-attack-free group had lower galectin-3 levels than the FMF-attack-free group (1.794 vs. 2.797 ng/ml, respectively; p = 0.01). Galectin-3 levels did not differ significantly between CAPS and attack-free PFAPA patients (1.439 ng/ml vs. 1.794 ng/ml, respectively; p = 0.63). In our study, for the first time, we defined galectin-3 as a promising biomarker that differs between PFAPA and FMF patients during both disease flares and attack-free periods. Further studies with high number of patients could validate its role as a biomarker.
Manthiram K, Preite S, Dedeoglu F, Demir S, Ozen S , et al.
Proceedings of the National Academy of Sciences of the United States of America •
Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most common periodic fever syndrome in children. The disease appears to cluster in families, but the pathogenesis is unknown. We queried two European-American cohorts and one Turkish cohort (total = 231) of individuals with PFAPA for common variants previously associated with two other oropharyngeal ulcerative disorders, Behçet's disease and recurrent aphthous stomatitis. In a metaanalysis, we found that a variant upstream of (rs17753641) is strongly associated with PFAPA (OR 2.13, = 6 × 10). We demonstrated that monocytes from individuals who are heterozygous or homozygous for this risk allele produce significantly higher levels of IL-12p70 upon IFN-γ and LPS stimulation than those from individuals without the risk allele. We also found that variants near , , and were significant susceptibility loci for PFAPA, suggesting that the pathogenesis of PFAPA involves abnormal antigen-presenting cell function and T cell activity and polarization, thereby implicating both innate and adaptive immune responses at the oropharyngeal mucosa. Our results illustrate genetic similarities among recurrent aphthous stomatitis, PFAPA, and Behçet's disease, placing these disorders on a common spectrum, with recurrent aphthous stomatitis on the mild end, Behçet's disease on the severe end, and PFAPA intermediate. We propose naming these disorders Behçet's spectrum disorders to highlight their relationship. alleles may be factors that influence phenotypes along this spectrum as we found new class I and II associations for PFAPA distinct from Behçet's disease and recurrent aphthous stomatitis.
Sag E, Demirel D, Demir S, Atalay E, Akca U , et al.
Seminars in arthritis and rheumatism •
Recently a new set of criteria proposed for the classification of auto inflammatory recurrent fevers including familial Mediterranean Fever (FMF). We aimed to compare the sensitivity and specificity of the new Eurofever/PRINTO classification criteria with those of the Tel Hashomer and Yalcinkaya-Ozen criteria. 151 consecutive FMF patients between February and May 2019 who were followed at Hacettepe University Department of Pediatric Rheumatology were included in this study. A group of 82 patients with periodic fever 66 periodic fever, aphthosis, pharyngitis and adenitis syndrome (PFAPA), nine cryopyrin-associated periodic syndrome (CAPS) and seven mevalonate kinase deficiency/hyperimmunoglobulin D syndrome (MKD/HIDS) patients) served as controls. GraphPad 6.0 was used for statistical analysis. Three different classification criteria were analyzed in 151 FMF patients with a median age at diagnosis of 5 years and in 82 controls with a median age at diagnosis of 3 years. The sensitivity of the new Eurofever/PRINTO criteria (96%) was highest (Tel Hashomer criteria-88.4% and Yalcinkaya-Ozen criteria-93.4%). However, the specificity of these criteria (73.1%) was lowest (Tel Hashomer criteria-92.6% and Yalcinkaya-Ozen criteria-84.1%). The new Eurofever/PRINTO criteria achieved the highest sensitivity (100%) in biallelic exon 10 mutation patients (Tel Hashomer criteria-87.4% and Yalcinkaya-Ozen criteria-94.2%). However, the new set had the lowest sensitivity (88.2%) in heterozygote exon 10 mutation patients (Tel Hashomer criteria 94.1% and Yalcinkaya-Ozen criteria 94.1%). In this Turkish cohort, the new Eurofever/PRINTO criteria have a better sensitivity but lower specificity with higher misclassifications than other two well-known criteria. The combination of clinical manifestations with genotype increased the sensitivity. The lower specificity may be due to the high carrier rate in our population. Although the ethnicity information lowers the specificity, 'clinical-only' criteria set may still guide the clinician to perform appropriate genetic testing in patients with recurrent fever.