Ümraniye Eğitim ve Araştırma Hastanesi

Corticosteroid use in PFAPA syndrome: clinical practice data from the JIR-CliPS Survey Study and a comprehensive literature review.

CS are used to abort disease flares in periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome. We aimed to obtain a global overview of physicians' CS usage strategies and analyse the data in the literature regarding CS use in PFAPA syndrome. The Juvenile Inflammatory Rheumatism Clinical Practice Strategies (JIR-CliPS) PFAPA questionnaire included nine questions on CS use in addition to the demographic data questions. The survey was distributed via e-mail to potential respondents. The MEDLINE/PubMed and Scopus databases were searched systematically to extract the data regarding CS use in PFAPA syndrome. From 47 countries, 144 physicians (female/male = 2.6; 67.4% paediatric rheumatologists) answered the survey. Most respondents (n = 133; 92.4%) prescribe CS in PFAPA flares. The most frequently prescribed CS was prednisolone (63.2%). The definition of response to CS was indicated as 'response within 12 h' by the highest number of respondents (n = 61; 42.4%). When CS cause an increase in attack frequency, most (57.9%) consider another treatment if this causes a decrease in quality of life. Forty-four (30.6%) respondents were 'routinely' prescribing CS to PFAPA patients, and this practice was more frequent among more experienced physicians (P < 0.001). We identified 46 articles in the literature describing 4564 PFAPA patients treated with CS. Prednisone was the most frequently preferred CS (48.2%). Response to CS was around 95%, although an increase in attack frequency was noted in almost 35% of the patients. Physicians frequently use CS for PFAPA in their routine clinical practice. Regarding treatment modification, the quality of life was a prominent consideration for physicians.

Exploring factors for predicting colchicine responsiveness in children with PFAPA.

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.

Evaluation of common NLRP3 Q703K variant in pediatric patients with autoinflammatory disease: CAPS and PFAPA.

Gain-of-function mutations of the NLR family pyrin domain containing 3 (NLRP3) gene have been implicated in autoinflammatory diseases. The NLRP3 Q703K variant is a common variant associated with Cryopyrin-associated periodic syndromes (CAPS) and periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome. However, the genotype-phenotype correlation between NLRP3 Q703K variant, CAPS and PFAPA is unclear. In this study, we aimed to investigate the frequency of the NLRP3 Q703K variant in patients with and without autoinflammatory disease and characterize the phenotype in only Q703K variant positive patients. A retrospective analysis of 639 patients with autoinflammatory symptoms was conducted. Patients underwent next-generation sequencing (NGS) panel analysis of 16 genes, including NLRP3. For the 68 patients carrying the only Q703K variant, their clinical and demographic information was evaluated. Genetic data from 1461 patients without autoinflammatory symptoms were used as the control group. Of our 639 autoinflammatory symptomatic patients, the Q703K mutation was detected in 68 (5.3% allele frequency). Heterozygous mutations were detected in 141 patients without autoinflammatory symptoms (4.8% allele frequency, p=0.4887). Of the patients with variant in Q703K, 10 patients were diagnosed with CAPS , 7 patients were diagnosed with PFAPA and the remaining 39 were diagnosed with undefined systemic autoinflammatory disease (uSAID) Conclusions. The Q703K variant, which is seen with similar frequency in the control and autoinflammatory groups, is also of higher prevalence in patients with mild CAPS symptoms and PFAPA syndrome. This variant, together with other undetected genetic variants or epigenetic modifications, may be responsible for the corresponding phenotype. As such, it is essential for clinicians to evaluate their patients using both genetic and clinical evaluations.

Editorial: Hereditary Periodic Fevers and Autoinflammatory Diseases.

Long-term follow-up of tonsillectomy efficacy in children with PFAPA syndrome.

The role of tonsillectomy in the periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome, is controversial. Although some studies reported high success rates with tonsillectomy, further investigations are needed with larger numbers of patients. To seek the long-term outcomes of tonsillectomy in periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome. Case series; multi-center study. The study comprised 23 patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome who underwent surgery (tonsillectomy with or without adenoidectomy) between January 2009 and November 2014. 21 (91%) of 23 patients had complete resolution immediately after surgery. One patient had an attack 24h after surgery, but has had no further attacks. One patient had three attacks with various intervals, and complete remission was observed after 3 months. Tonsillectomy is a good option for the treatment of periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome.