Amikishiyev S, Kalaycı T, Deniz R, Soltanova L, Sen B , et al.
Rheumatology (Oxford, England) •
Genetic screening for systemic autoinflammatory disorders (SAIDs) often does not yield a definite diagnosis based on pathogenic variants. Instead, many patients are found to carry combinations of variants of uncertain significance (VUS), either in isolation or alongside pathogenic or likely pathogenic variants. We herein aimed to investigate the relationship between clinical phenotypes and genotypes in patients identified as carriers of variants in ≥2 autoinflammatory genes. We conducted a retrospective analysis of patients who underwent genetic screening for SAIDs. Inclusion criteria were the presence of variants in ≥2 autoinflammatory genes, including both VUS and pathogenic/likely pathogenic variants. Clinical features were reviewed and compared across genetic profiles. Forty-four (29.5%) of 149 referred patients were identified as having ≥2 gene variants. Fifteen (36.3%) were classified as familial Mediterranean fever (FMF), and some had non-FMF findings in association with additional variants. An additional five patients were diagnosed with VEXAS syndrome (n = 1), deficiency of adenosine deaminase 2 (DADA2, n = 2), A20 haploinsufficiency (HA20, n = 1), DADA2 and HA20 overlap (n = 1). The remaining patients were grouped as having NLRP1-AID (n = 1), NLRC4-AID (n = 1), NLRP1 and NLRC4-AID (n = 1) overlap, PFAPA-like (n = 2), and Behçet disease-like (n = 7) disorder according to their dominant phenotype. Twelve (27.2%) patients could not be classified into any groups. The presence of multiple variants in autoinflammatory genes is a common finding in patients with SAID-like symptoms but does not always correlate with a known diagnosis. Follow-up of this group of patients with so-called 'mixed autoinflammatory disorder' (MAID) is necessary for the evaluation of their clinical course and long-term prognosis.
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.
Kalayci F, Yigit M, Kuruc AI, Cevirici T, Celikel Acar B
Journal of paediatrics and child health •
This study aims to present the clinical characteristics of patients with PFAPA syndrome, and to compare the effects of corticosteroid usage, colchicine prophylaxis, and tonsillectomy on the frequency of attacks in patients with PFAPA syndrome. Patients aged between 6 months and 18 years presenting to our Paediatric Rheumatology clinic between 2017 and 2021 who were diagnosed with PFAPA syndrome and followed up for a minimum of 12 months were included in this study. The demographic and clinical characteristics of the patients, laboratory findings, attack durations, and treatments were recorded. Our study, comprised of 195 patients, included four groups: untreated (n = 58), corticosteroid (n = 43), colchicine (n = 62), and tonsillectomy (n = 32). There was no significant difference between the treatment groups in terms of attack frequencies before treatment initiation (p > 0.05). When attack frequencies before and after treatment initiation were observed, a decrease in attack frequency compared to the pre-treatment period was observed in the tonsillectomy group (from 12 to 3 attacks) (p < 0.001) and the colchicine group (from 12 attacks to 1 attack) (p < 0.001). It was noted that using steroids during three or more attacks increased attack frequency compared to the pre-treatment period (p < 0.0001). Tonsillectomy resulted in a more significant reduction in attack frequency compared to the colchicine group (p < 0.001). Using corticosteroids during an attack has been shown to effectively control attacks. However, the repeated use of corticosteroids increases the frequency of attacks. Colchicine prophylaxis leads to a reduction in attack frequency in the majority of cases. Tonsillectomy can successfully control the disease in most cases.
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.
Öner N, Çelikel E, Tekin ZE, Güngörer V, Tekgöz N , et al.
Irish journal of medical science •
To evaluate the effect of vitamin D supplementation on the frequency and duration of attacks in patients of PFAPA syndrome with low vitamin D levels. This retrospective study comprised PFAPA patients with vitamin D deficiency/insufficiency between 2018 and 2023. The frequency and duration of PFAPA attacks before and after vitamin D supplementation were noted. Seventy-one patients were included. Of the 71 patients, 24 (33.8%) had vitamin D insufficiency, and 47 (66.2%) had vitamin D deficiency. In patients with vitamin D insufficiency, mean attack frequency and mean attack duration before vitamin D supplementation were 4.3 ± 1.9/year and 2.2 ± 1.6 days, respectively, while mean attack frequency and mean attack duration after vitamin D supplementation were 3.5 ± 2.7/year per year and 1.3 ± 0.9 days respectively (p = 0.2, p = 0.2, respectively). In patients with vitamin D deficiency, mean attack frequency and mean attack duration before vitamin D supplementation were 7.4 ± 2.1/year and 2.2 ± 1.6 days, respectively, while mean attack frequency and mean attack duration after vitamin D supplementation were 3.3 ± 2.4/year and 1.3 ± 0.9 days respectively (p < 0.01, p = 0.04, respectively). When the vitamin D level and the frequency of attacks were compared, the cut-off value of vitamin D was found to be 29.7 nmol/L. In PFAPA patients with low vitamin D levels, the frequency and duration of PFAPA attacks were reduced with vitamin D supplementation. Especially at vitamin D level cut-off > 29.7 nmol/L, the frequency of attacks reduced significantly.