PFAPA Research Articles

Differential cytokine profiles in pediatric patients with PFAPA syndrome and recurrent tonsillitis.

Objective : An attempt was made to identify characteristic cytokine profiles to distinguish periodic fever with aphthous stomatitis, pharyngitis and cervical adenitis syndrome (PFAPAS) from recurrent tonsillitis, of which clinical manifestations are similar to those of PFAPAS in children. Methods : Serum concentrations of IL-6, IL-4 and IFN-γ were measured during febrile episodes in pediatric patients. Results : The levels of IL-6 during febrile episodes were markedly increased above the upper limit of normal ranges in patients with both PFAPAS and recurrent tonsillitis, but there were no significant differences between groups. The levels of IL-4 during febrile episodes in PFAPAS patients were significantly lower than those in recurrent tonsillitis patients. The levels of IFN-γ during febrile episodes in PFAPAS patients were significantly higher than those in recurrent tonsillitis patients. Conclusion : In pediatric patients with PFAPAS, despite an increase of IL-6, IL-4 was suppressed with a marked increase of IFN-γ during febrile episodes. On the contrary, in febrile pediatric patients with recurrent tonsillitis, both IL-6 and IL-4, but not IFN-γ were increased. The characteristic cytokine profiles of IL-6, IL-4 and IFN-γ can be used for differential diagnosis of PFAPAS from recurrent tonsillitis in children in clinical ear, nose and throat (ENT) settings. J. Med. Invest. 68 : 38-41, February, 2021.

Diagnosis Process of PFAPA Syndrome in a Case Who Applied to the Pediatric Emergency Department with the Complaint of Fever and Later Found High CRP

Diagnosis Process of PFAPA Syndrome in a Case Who Applied to the Pediatric Emergency Department with the Complaint of Fever and Later Found High CRP

Clinical features and diagnosis of PFAPA syndrome: approach of the primary care physician

Clinical features and diagnosis of PFAPA syndrome: approach of the primary care physician

Children and Adults with PFAPA Syndrome: Similarities and Divergences in a Real-Life Clinical Setting.

Analogies or differences of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome in children and adults are barely known. The aim of our study was to compare the overall characteristics of a large cohort of patients, both children and adults, diagnosed with PFAPA syndrome. In the last decade, we identified 120 children and 63 adults with periodically recurring fevers, who fulfilled the criteria for PFAPA diagnosis. The two subcohorts were analyzed according to demographic features, clinical manifestations, laboratory data, and responses to therapies. The mean age of onset was 2.4 ± 1.5 and 19.7 ± 10.3years, respectively, in children and adults, while attacks occurred every 3.8 ± 0.8 and every 4.3 ± 2.3weeks, respectively, in children and adults. A higher prevalence of exudative pharyngitis was observed in children (58.8%), and the majority of children had only two cardinal signs during flares. In adults, there was a higher interpersonal variability of the intercritical periods. Inflammatory markers measured during non-febrile periods were normal in children but altered in the totality of adults during febrile periods. A strong efficacy of corticosteroids in controlling the pediatric syndrome was observed, but response rates to steroids were less brilliant in adults. Colchicine and interleukin-1 inhibitors were used in the management of the steroid-resistant adult syndrome. Conversely, tonsillectomy was performed in a very low number of children, but was effective in 60.7% of adults when treated after 16years. The mean age of disappearance of PFAPA symptoms has been 6.4 ± 2.4years in children, while only 27% of adults have shown a complete drug-free symptom regression. A linear conformity of the PFAPA syndrome has been observed between pediatric and adult patients. PFAPA symptoms tended to disappear with no sequelae in 94.1% of children, while the disease was still active in almost 3/4 of adults at the time of our assessment.

Closing in on PFAPA syndrome as “bad luck”

Closing in on PFAPA syndrome as “bad luck”

Recurrent Fever Diagnosis: A Case Disguised as PFAPA Syndrome

Recurrent Fever Diagnosis: A Case Disguised as PFAPA Syndrome

РFАРА-синдром: літературний огляд та власне клінічне спостереження

Аutoinflammatory diseases or syndromes (HAIDS) have attracted practical and scientific interest. This group of pathologies is united by similar clinical symptoms in the form of periodic fever, systemic inflammation and other clinical syndromes. PFAPA — syndrome or Marshall's syndrome is one of the most common representatives of this group of diseases. РFАРА syndrome (Marshall's syndrome) is considered an autoinflammatory disease of unknown etiology and not fully studied pathogenesis. Gene mutations, family inheritance and the modifying role of persistent intracellular infections are considered as the causes of development. Genetically determined immune responses and neutrophilic inflammation, the presence of immune dysregulation play a role in the pathogenesis of Marshall's syndrome. The incidence and prevalence of this condition in the pediatric population are unknown. The pathology is characteristic of early childhood, the syndrome is characterized periodic fever, aphthous stomatitis, pharyngitis or tonsillitis and cervical adenitis. Patients do not have disturbances in well-being between episodes, pathognomonic laboratory changes, have normal growth and development indicators. The syndrome occurs in children under 5 years, disappears in adolescence, has good+quality current, the treatment of which is the administration of corticosteroids. The pathology has no specific biological markers, so the diagnosis is made on the basis of clinical manifestations, a thorough analysis of the history and the exclusion of other possible causes of recurrence fever. Purpose: to highlight the complexity of the diagnosis of PFAPA–syndrome. Clinical case. The article describes own clinical case of a child with Marshall's syndrome. Recurrent attacks of fever with a specific frequency in combination with aphthous stomatitis, pharyngitis and cervical lymphadenitis, the absence of specific laboratory changes and the positive effect of the corticosteroids treatment it possible to diagnose the above diagnosis. Conclusion. Literature data and the above clinical case indicate the difficulty of diagnosing this syndrome, long-term irrational drug treatment without clinical effect. So physicians in many specialties need to remember the need for a detailed survey of patients and parents, pay attention to the time and frequency of symptoms described above, and their combinations, if Marshall's syndrome is suspected do not be afraid to prescribe glucocorticosteroids for therapeutic and prophylactic purposes. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of all participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Keywords: Marshall's syndrome, children, periodic fever, corticosteroids.

Çocuklarda Periyodik Ateş, Aftöz Stomatit, Farenjit ve Adenit (PFAPA) Sendromu: 82 Hastanın Retrospektif Olarak Değerlendirilmesi

Amaç: Periyodik ateş, aftöz stomatit, farenjit ve adenit (PFAPA) sendromu ani yükselen ateş, stomatit, farenjit ve adenit ile karakterize olup çocukluk çağında en yaygın görülen tekrarlayan ateş sendromudur. Bu çalışmada, bu hastalığa dair farkındalığı artırmak amacıyla PFAPA sendromu tanısı almış olan çocuklara dair klinik veriler değerlendirilmiştir. Gereç ve Yöntemler: Bu retrospektif çalışma 1 Ekim 2017—30 Haziran 2019 döneminde Diyarbakır Çocuk Hastalıkları Hastanesi Çocuk Enfeksiyon Polikliniği’nde PFAPA tanısıyla izlenmiş olan 82 hastayı kapsamıştır. Hastaların demografik özellikleri, klinik ve laboratuvar bulguları, gördüğü tedaviler ve tedaviye yanıtları ile ilgili veriler tıbbi kayıtlardan elde edilmiştir. Bulgular: Hastaların 52’si erkek, 30’u kızdı. Medyan şikayet başlangıç yaşı 18 (1–120) ay, medyan tanı yaşı 53 (12–172) aydı. Seksen iki hastanın hepsinde ateş ve farenjit, 56’sında lenfadenit, 48’inde kriptik tonsilit, 28’inde stomatit mevcuttu. Laboratuvar tetkiklerinde lökositoz (%46,38), nötrofili (%59,7) ve lenfopeni (%4,47) tespit edildi. C-reaktif protein hastaların %86,56’sında pozitif olup medyan değer 69,9 (6,19–279) mg/dl idi. Eritrosit sedimantasyon hızı medyan değeri 36 (7–101) ml/saat idi. Otuz dört (%41,46) hastada ateş nedeniyle en az bir kez hastaneye yatırılma hikayesi vardı. Elli sekiz (%71) hastanın birinci derece akrabalarında sık tonsilit atakları mevcuttu ve bunlardan 21’i (%25,6) tonsilektomi geçirmişti. Tüm hastalarda metilprednisolon tedavisine dramatik yanıt alınmıştı. Tartışma ve Sonuç: PFAPA sendromunda erken tanı gereksiz tetkik, tedavi ve hastaneye yatışları önlemek için önemlidir. Beş yaşından küçük olan ve yineleyen ateş ve tonsilit atakları ile getirilen, özellikle de ailesinde sık tonsilit geçirme veya tonsilektomi hikayesi olan çocuklarda ayırıcı tanıda PFAPA sendromu göz önünde bulundurulmalıdır.

Independent risk factors for resolution of periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome within 4 years after the disease onset.

Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome is a polygenic disease with unknown etiology. In this retrospective cohort study, we aimed to evaluate the risk factors for the resolution of PFAPA syndrome within 4 years after the onset. In total, 466 patients with PFAPA syndrome that are being followed up our department were included into the study. Between May 2020 and September 2020, medical charts of the patients were reviewed retrospectively. The median age of the patients at the time of the study and at disease onset were 8.6 (2.9-20.5; IQR 6.9-10.6) years and 18 (1-84; IQR 11-31) months. On univariate analysis age at disease onset (p = 0.003), positive family history of PFAPA syndrome (p = 0.04), absence of myalgia (p = 0.04), and absence of headache (p = 0.003) were all associated with the resolution of PFAPA syndrome within 4 years after the onset. Multivariate logistic regression analysis revealed that age at disease onset (OR 1.04, 95% CI 1.01-1.07, p = 0.002), positive family history of PFAPA syndrome (OR 2.69, 95% CI 1.12-6.48, p = 0.02), and absence of headache (OR 0.2, 95% CI 0.05-0.74, p = 0.01) were independent risk factors for the resolution of PFAPA syndrome within 4 years after the onset. We report later age of disease onset, positive family history of PFAPA syndrome, and absence of headache as independent risk factors for resolution of PFAPA syndrome within 4 years after the onset. • Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome is a multifactorial disease with unknown etiology. • Although, PFAPA syndrome usually resolves within 3-5 years after the disease onset, it can persist for years and even continue into adulthood. With our current knowledge, there is no clue to predict which patients will have a long disease course and which patients will not. • Later age of disease onset, positive family history of PFAPA syndrome and absence of headache as independent risk factors for resolution of PFAPA syndrome within 4 years after the onset.

The role of Mediterranean fever gene variants in patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome.

This study was conducted to investigate the relationship between clinic features and Mediterranean fever gene (MEFV) variants in patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome. In total, 167 patients with PFAPA syndrome were included in the study. Female:male ratio of the patients was 0.75 (72 females, 95 males). In total 59.9% of patients with PFAPA had at least one MEFV variant and the most common heterozygous variants were M694V in 29.3% of the patients (40/167), E148Q in 8.3% (14/167), and V726A in 7.1% (12/167). The median age at the disease onset was significantly higher and the median duration of the episodes was significantly lower in patient with variants in exon 10 comparing to the others (both p = 0.01). Similarly, the median age at the disease onset was significantly higher (p = 0.01) and the median duration of the episodes was significantly lower (p = 0.04) in patient with MEFV variants than in the remaining patients. There were no significant differences according to the genotypes of the patients in terms of both treatment response and the frequency of clinical findings.Conclusion: In PFAPA syndrome, MEFV variants may be a modifier for disease onset and attack duration. What is Known: • Due to periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome having clinical findings resembling familial Mediterranean fever (FMF), it can be difficult to distinguish PFAPA syndrome and FMF especially in endemic regions for FMF. • Underlying MEFV mutations could affect the periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome's clinical presentation and response to treatment. What is New: • Having one of the underlying MEFV variants is related to later disease onset and shorter episode duration in patients with PFAPA syndrome.

Performance of the new Eurofever/PRINTO classification criteria in Familial Mediterranean fever patients with a single exon 10 mutation in childhood

The diagnosis of Familial Mediterranean fever (FMF) based on clinical findings supported by genetic mutation. Recently, the new Eurofever/PRINTO classification criteria including genetic analysis were established. The aim of this study is to evaluate the performance of the new criteria in FMF patients with a single exon 10 mutation in childhood. The study group consisted of FMF patients who had a single exon 10 mutation in a referral center in Turkey. Patients with periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome were included as a control group. The medical charts of all patients were reviewed retrospectively. A total of 106 FMF patients (59 boys) were enrolled in the study group. The median age at first symptom was 5; the median age at diagnosis was 7years. The mean follow-up was 33 ± 35.4months. Majority of the patients (n = 58, 54.7%) had heterozygous M694V, 16 (15%) patients had M694V/E148Q and 13 (13.8%) patients had heterozygous M680I mutation. The sensitivity of the Yalcinkaya-Ozen criteria was 98.1% and it was 97.1% for the Eurofever/PRINTO classification criteria. The specificity of the new Eurofever/PRINTO classification criteria was 96.7% and it was 74.1% for the Yalcinkaya-Ozen criteria. The new Eurofever/PRINTO classification criteria have a good sensitivity as the Yalcinkaya-Ozen criteria in patients with a single exon 10 mutation. Additionaly, the new criteria have better specificity. It should be useful to apply the clinical only criteria where the carrier rate is high.

PIK3AP1 and SPON2 Genes Are Differentially Methylated in Patients With Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis (PFAPA) Syndrome.

Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome is the most common autoinflammatory disease in children and is often grouped together with hereditary periodic fever syndromes, although its cause and hereditary nature remain unexplained. We investigated whether differential DNA methylation was present in DNA from peripheral blood mononuclear cells (PBMC) in patients with PFAPA vs. healthy controls. A whole-epigenome analysis (MeDIP and MBD) was performed using pooled DNA libraries enriched for methylated genomic regions and identified candidate genes, two of which were further evaluated with methylation-specific restriction enzymes coupled with qPCR (MSRE-qPCR). The analysis showed that the PIK3AP1 and SPON2 gene regions are differentially methylated in patients with PFAPA. MSRE-qPCR proved to be a quick, reliable, and cost-effective method of confirming results from MeDIP and MBD. Our findings indicate that a B-cell adapter protein (PIK3AP1), as the PI3K binding inhibitor of inflammation, and spondin-2 (SPON2), as a pattern recognition molecule and integrin ligand, could play a role in the etiology of PFAPA. Their role and the impact of changed DNA methylation in PFAPA etiology and autoinflammation need further investigation.

Common genetic susceptibility loci link PFAPA syndrome, Behçet's disease, and recurrent aphthous stomatitis.

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 n = 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 IL12A (rs17753641) is strongly associated with PFAPA (OR 2.13, P = 6 × 10-9). 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 STAT4, IL10, and CCR1-CCR3 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. HLA alleles may be factors that influence phenotypes along this spectrum as we found new class I and II HLA associations for PFAPA distinct from Behçet's disease and recurrent aphthous stomatitis.

Current Therapeutic Options for the Main Monogenic Autoinflammatory Diseases and PFAPA Syndrome: Evidence-Based Approach and Proposal of a Practical Guide.

Monogenic autoinflammatory diseases are rare conditions caused by genetic abnormalities affecting the innate immunity. Previous therapeutic strategies had been mainly based on results from retrospective studies and physicians' experience. However, during the last years, the significant improvement in their genetic and pathogenic knowledge has been accompanied by a remarkable progress in their management. The relatively recent identification of the inflammasome as the crucial pathogenic mechanism causing an aberrant production of interleukin 1β (IL-1β) in the most frequent monogenic autoinflammatory diseases led to the introduction of anti–IL-1 agents and other biologic drugs as part of the previously limited therapeutic armamentarium available. Advances in the treatment of autoinflammatory diseases have been favored by the use of new biologic agents and the performance of a notable number of randomized clinical trials exploring the efficacy and safety of these agents. Clinical trials have contributed to increase the level of evidence and provided more robust therapeutic recommendations. This review analyzes the treatment of the most frequent monogenic autoinflammatory diseases, namely, familial Mediterranean fever, tumor necrosis factor receptor–associated periodic fever syndrome, hyperimmunoglobulin D syndrome/mevalonate kinase deficiency, and cryopyrin-associated periodic syndromes, together with periodic fever with aphthous stomatitis, pharyngitis, and cervical adenitis syndrome, which is the most common polygenic autoinflammatory disease in children, also occurring in adult patients. Finally, based on the available expert consensus recommendations and the highest level of evidence of the published studies, a practical evidence-based guideline for the treatment of these autoinflammatory diseases is proposed.

Value of colchicine as treatment for recurrent oral ulcers: A systematic review.

In oral medicine, colchicine is a therapeutic alternative for idiopathic recurrent aphthous stomatitis (RAS), Behçet disease (BD), periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome, and mouth and genitals ulcers with inflamed cartilage (MAGIC) syndrome. The present review aims to evaluate reliability of colchicine against recurrent oral ulcers. A systematic review was conducted, with the following PICO (Patient, Intervention, Control, Outcome) question: "In populations with idiopathic or secondary recurrent oral ulcers, is colchicine more effective in improving pain and accelerating healing, compared to other intervention or placebo?" Seven RCTs and 3 OCTs were considered eligible. Four RCTs focused on BD, two RCTs and three OCTs on RAS, and one RCT on PFAPA syndrome. Heterogeneity between RCTs prevented from meta-analysis. Regarding BD, no significant difference between colchicine and placebo was found in two of three placebo-controlled RCTs, whereas the third RCT showed benefit. A comparative RCT found ciclosporin more effective than colchicine for oral lesions of BD. One open-label RCT showed promising but partial results on colchicine in reducing PFAPA attacks, when compared to corticosteroids. Concerning RAS, colchicine appeared less effective than clofazimine, thalidomide and dapsone, and with outcomes similar to low-dosage corticosteroids but higher gastric discomfort than prednisolone. One OCT reported positive results compared with no treatment but a RCT found no difference with placebo. Role of colchicine as treatment for idiopathic or secondary recurrent oral ulcers is still controversial. Further standardized RCTs and crossover trials are needed.

Caracterización clínica del Síndrome de PFAPA en una Unidad de Pediatría de Atención Primaria: presentación de una serie de casos

The PFAPA syndrome (Periodic Fever, Adenopathy, Pharingitis, Afthae) is part of the differential diagnosis of periodic fever in children. Although there is a dysregulation of the immune system, its etiology is not completely clear. The diagnostic criteria are simple but non-specific, so we must consider a large group of autoinflammatory diseases in our differential diagnosis. A single dose of glucocorticoids given at the onset of an episode can dramatically abort fever attacks in a few hours. Nevertheless, there isn’t an effective treatment for the prevention of the episodes. We propose a review of this syndrome as a result of five cases in our health care center.

May cyproheptadine be a treatment choice for prophylaxis of PFAPA syndrome?

No abstract available.

Otoinflamatuar Periyodik Ateş Sendromları

Otoinflamatuar periyodik ateş sendromları, bulguları çoğunlukla çocukluk çağında başlayan, tekrarlayan ateş ve inflamasyon atakları ile karakterize doğal immün sistem bozukluğu sonucu ortaya çıkan hastalıklar grubudur. Ailevi Akdeniz ateşi (AAA) Türkiye gibi Akdeniz ülkelerinde en sık görülen periyodik ateş sendromudur. Diğer herediter otoinflamatuar periyodik ateş sendromları nadir hastalıklar olarak sınıflandırılmaktadır. Bu derlemede; AAA, tümör nekroz faktör (TNF) reseptörü ilişkili periyodik ateş sendromu (TRAPS), mevalonat kinaz (MVK) eksikliği, kriyopirin ilişkili periyodik ateş sendromu (CAPS) ve periyodik ateş, aftöz stomatit, farenjit ve adenit (PFAPA) sendromunun klinik özellikleri, önerilen sınıflandırma kriterleri ve tedavi seçenekleri değerlendirilmiştir.

Why and How Should We Treat Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA) Syndrome?

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is characterized by recurrent fever flares accompanied by symptoms and signs forming the disease acronym and alternating with asymptomatic periods. Despite the disease having a generally favorable outcome, with spontaneous remission after a few years, it does have a major impact on the quality of life of the child and his or her relatives. Beside symptomatic medications during fever flares, the most used treatment consists of a single dose of corticosteroids at flare onset to interrupt the attack; fever resolves usually within a few hours, but often with a shorter interval between the attacks. For these patients, colchicine has been shown to decrease the frequency of the flares. Other medications were also reported in case series of patients with PFAPA syndrome. These include the interleukin-1 blocker anakinra to treat flares, cimetidine (which showed no convincing effect), and other drugs with anecdotal use. The pediatrician faces a difficult question: should they wait for spontaneous disease resolution and only treat the flares medically, or should they propose tonsillectomy that may induce remission? Due to the lack of strong evidence, the answer will vary on an individual basis, depending on the impact on the patient's quality of life. The choice of the best therapeutic strategy will be based on the response to the flare-based therapy and on disease severity (quality of life, school performances); long-term data on the remission rate under the different therapeutic strategies are currently missing. More randomized controlled studies are needed to help the treating physician to choose the best therapy, as well as real-life long-term data to evaluate the long-term outcome of children with PFAPA syndrome.

Long-term management of patients with PFAPA syndrome.

To evaluate the long-term treatment results of patients with PFAPA syndrome and to determine their need for tonsillectomy. The clinical characteristics, treatments and long-term results of 16 patients admitted to the Pediatric and Otorhinolaryngology Clinic between 2015 and 2019 were retrospectively analyzed. Twelve male and four female patients were examined between 1.5 and 8years (mean age 4.8 ± 1.1) (75% male, 25% female). The mean duration of attacks was 4.4 ± 1.4weeks. Twelve patients recovered completely with single-dose steroid therapy. In the 4-year follow-up of 12 patients who were given a single dose of steroid therapy, there were no relapses.Surgical decisions were made for four patients whose attacks did not pass with steroid treatment.Two patients (75%) underwent adenotonsillectomy, and one patient underwent tonsillectomyWhile three of these patients did not have an attack again, one patient continued to have an attack every 8weeks. At the age of 9, his attacks were completely resolved spontaneously. All patients had fever. The most common concomitant symptoms were pharyngitis (94%), cervical adenitis (82%) and aphthous stomatitis (77%). Exudative tonsillitis was present in 25% of the patients. Medical treatment should be the first treatment option in patients with PFAPA syndrome. Although single-dose steroid treatment is effective in these patients, tonsillectomy is an important treatment option in refractory cases.