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The use of ketotifen as long-term anti-inflammatory prophylaxis in children with PFAPA syndrome.

Introduction: Periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome (PFAPA) is the most frequent periodic fever syndrome in children. Its pathogenesis is still unknown, but some disease-modifying factors were observed. Several medications were tested for the long-term prophylaxis of inflammatory flares; however, none are standardly used. Methods: This prospective clinical trial enrolled 142 children (71 girls, 50%) meeting diagnostic criteria for PFAPA syndrome. We analysed selected clinical characteristics and compared laboratory parameters during the flare and attack-free period (at least two weeks after the attack). Moreover, we assessed the possible therapeutic effect of ketotifen on the duration of attack free-periods and clinical picture. Results: The mean age of patients was 6.81 ± 3.03 years and the mean age of onset of symptoms was 2.31 ± 2.02 years. No significant differences were observed between genders.We recorded a positive family history for PFAPA in 31.69% of patients. Attacks lasted for 2.8 ± 1.2 days, with intervals between attacks of 4 ± 1 weeks. We administered ketotifen in 111 (77.8%) patients, and a positive effect was observed in 86 (77.5%) of patients. We observed prolonged attack-free intervals in patients treated with ketotifen (14.7 ± 8.9 days in comparison with 4.4 ± 1.9 days before the treatment; p<0.001). The used dose of ketotifen was 0.08 ± 0.01 mg/kg/day. Mild side effects were observed in four patients (restlessness, irritability, agitation and constipation). Discussion: Our data supports the use of ketotifen for long-term prophylaxis in children with PFAPA syndrome with positive effects on the attenuation of disease activity and the prolongation of attack-free periods. Further well-designed studies should confirm the preliminary data.

Evaluation of the Levels of Blood Cells, Vitamin D, and Inflammatory Factors in Children with PFAPA Syndrome.

BACKGROUND: The syndrome of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA syndrome) is the most common type of recurrent fever in childhood. The aim of this study was evaluation of the levels of blood cells, vitamin D, and inflammatory factors in children with PFAPA syndrome. METHODS: This retrospective descriptive study was conducted on the recorded information of children with PFAPA syndrome referred to the children's specialty clinic of Imam Khomeini Hospital in Ilam city from March 2021 to February 2022. Complete demographic information, presence of underlying disease, changes in blood cells, vitamin D level and inflammatory factors were obtained from the patients' records. Diagnosis of PFAPA syndrome was performed according to Thomas' criteria. RESULTS: This study was conducted on 40 children with PFAPA syndrome. The majority of patients were male and in the age range of 3 - 4 years. The results show that the average percentage of neutrophil and lymphocyte cells in the blood of patients was 54.45% and 40.62%, respectively. Also, 6 (15%), 3 (7.5%), and 31 (77.5%) patients had normal neutrophil levels, neutropenia, and neutrophilia, respectively. Regarding lymphocyte cells, 26 (65%), 8 (20%), and 6 (15%) people had normal lymphocyte level, lymphocytosis and lymphopenia, respectively. ESR levels increased in all patients (average percentage: 16.72). CRP level was negative in 9 (22.5%) and +1 in 19 (47.5%) patients, respectively. The results showed that 33 (82.5%) patients were deficient in vitamin D level. CONCLUSIONS: The etiology and pathogenesis of PFAPA is still unknown; however, the rapid response to corticosteroid therapy is the indication of an immune deregulation. Treatment guidelines for PFAPA syndrome based on controlled studies are needed, as well as a better understanding of the disease itself.

Extreme Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA): a discrete group of patients.

OBJECTIVE: Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most common periodic fever syndrome in children; by definition, episodes occur every 2 to 8 weeks. However, in a subset of our patients, we noticed a higher frequency of attacks, of less than 2 weeks, which we refer to as extreme PFAPA (ePFAPA). This group consisted of patients who were extreme upon presentation of PFAPA, and those who became extreme after initiation of abortive corticosteroid treatment. We aimed to characterize demographic and clinical features of ePFAPA, including the two groups, and to compare them to patients with non-extreme PFAPA (nPFAPA). STUDY DESIGN: The medical records of 365 patients with PFAPA who attended Schneider Children's Medical Center of Israel from March 2014 to April 2021 were reviewed. Patients with concomitant familial Mediterranean fever were excluded. Characteristics of the ePFAPA (including subgroups) and nPFAPA groups were compared using Wilcoxon rank sum, Pearson's chi-squared, and Fisher's exact tests. RESULTS: Forty-seven patients (12.9%) were identified as having ePFAPA. Among patients with ePFAPA, compared to patients with nPFAPA, the median (interquartile range) age at disease onset was earlier: 1.5 years (0.7-2.5) vs. 2.5 years (1.5-4.0), P < 0.001; and diagnosis was younger: 2.6 years (2.0-3.6) vs. 4.5 years (3.0-6.2), P < 0.001. A higher proportion of patients with ePFAPA than nPFAPA were treated with colchicine prophylaxis (53% vs. 19%, P < 0.001), but symptoms and signs during flares did not differ significantly between these groups. Demographic and clinical characteristics were similar between patients with ePFAPA from presentation of PFAPA (22, 47% of those with ePFAPA) and ePFAPA from after corticosteroid treatment. CONCLUSION: About half the patients categorized with ePFAPA syndrome already had extreme features upon presentation. Patients with ePFAPA compared to nPFAPA presented and were diagnosed at an earlier age.

Gray zone in the spectrum of autoinflammatory diseases: familial Mediterranean fever accompanying periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome: single-center experience.

Despite the advanced knowledge concerning autoinflammatory diseases (AID), more data regarding the optimal treatment options and outcomes of the children who met the criteria of more than one AID are required. This study aimed to describe the demographic and clinical characteristics of children from familial Mediterranean fever (FMF)-endemic countries who meet both the FMF and the periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome criteria. Moreover, we aimed to measure the response rates to colchicine and tonsillectomy and evaluate the factors affecting the colchicine response in these patients. The study was conducted at pediatric rheumatology tertiary centre. A total of 131 patients (58 females; 73 males) who met both the modified Marshall and pediatric FMF criteria were included. The median age at onset was 18 months (1-77 months), and the mean age at diagnosis was 47 ± 21.88 months. The median interval between episodes was 21 (7-90) days. The median disease duration was 46 (6-128) months. Consanguineous marriage was detected in 17 (13%) of the patients. The most common clinical finding was fever (100%), followed by exudative pharyngitis (88.5%), abdominal pain (86.3%), arthralgia (61.8%), stomatitis (51.1%), adenitis (42%), myalgia (28.7%), chest pain (16%), maculopapular rash (12.2%), arthritis (8.4%), and erysipelas-like rash (4.6%). MEFV gene variants were identified in 106 (80.9%) patients. The most common variants were M694V heterozygous (29%). We found that patients with tonsillopharyngitis, aphthous stomatitis, and PFAPA family history were more likely to be colchicine-resistant and tonsillectomy responsive, while those with exon 10 MEFV gene mutations were more prone to have a favorable response to colchicine.     Conclusion: PFAPA syndrome patients with exon 10 MEFV gene mutation, showing typical FMF symptoms, should be treated with colchicine, even after tonsillectomy. In multivariate analysis, PFAPA family history and lack of exon 10 MEFV gene mutations were independent risk factors for colchicine resistance. Thus, tonsillectomy may be recommended as a possible treatment option for these patients. It has yet to be clarified when colchicine treatment will be discontinued in patients whose attacks ceased after tonsillectomy that was performed due to colchicine unresponsiveness. What is Known: • A certain number of patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome concomitantly fulfill the familial Mediterranean fever (FMF) criteria. • While colchicine is proposed as a first treatment choice in familial Mediterranean fever (FMF), corticosteroids are recommended as a first-line treatment in PFAPA syndrome patients. What is New: • In patients with concomitant PFAPA syndrome and FMF, PFAPA family history and lack of exon 10 MEFV gene mutation are predictive factors of colchicine resistance. • The presence of exon 10 MEFV gene mutations in patients with concomitant FMF and PFAPA syndrome has a favourable effect on response to colchicine treatment.

PFAPA syndrome in children.

ABSTRACT: Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome is, as the name implies, characterized by an extremely regular cycle of fevers that is accompanied by one or more other symptoms such as oral ulcers, pharyngitis, adenitis, tonsillitis, sore throat, cervical adenopathy, and headache. Originally known as Marshall syndrome, PFAPA is most commonly identified in children younger than age 5 years; however, adults may also present with the disease, though they may report additional symptoms. PFAPA is now understood to be a diagnosis of exclusion. Laboratory studies are typically unremarkable except for increases in acute phase reactants such as C-reactive protein. Treatment is primarily supportive and most frequently uses systemic steroids to suppress the inflammatory response. Acute flares are self-limited, and the syndrome typically resolves on its own as the child reaches age 7 or 8 years.

Adamantiades-Behçet disease: Between dermatology and ophthalmology.

Adamantiades-Behçet disease is an inflammatory, vascular disease of unknown etiology. The disease is named after two physicians, Benediktos Adamantiades and Hulȗsi Behçet, who both made significant contributions to the study of the disease. It was probably first described by Hippocrates in 500 BCE. Adamantiades-Behçet disease is most common in the region encompassing the ancient trade route known as the Silk Road. In Turkey, the disease is estimated to affect 80 to 370 people per 100,000 inhabitants, and it is also the country with the highest incidence rate. The frequency of the disease associated with the clinical picture differs from the origin of the onset. The disease is characterized by recurrent aphthous ulcers of the mouth, genitals, skin lesions, and eye lesions. The disease process can also involve other organs, including the joints, nervous system, large vessels, heart, and gastrointestinal tract. Aphthous oral ulcers appear as the first harbinger of the disease and affect almost all patients (97%-99%). The scientific interest in Adamantiades-Behçet disease has increased exponentially in the past decade.

TNFRSF1A-pR92Q variant identifies a subset of patients more similar to systemic undifferentiated recurrent fever than TNF receptor-associated periodic syndrome.

OBJECTIVES: To describe the clinical phenotype and response to treatment of autoinflammatory disease (AID) patients with the TNFRSF1A-pR92Q variant compared to patients with tumour necrosis factor receptor-associated periodic syndrome (TRAPS) due to pathogenic mutations in the same gene and patients diagnosed with other recurrent fever syndromes including periodic fever with aphthous stomatitis, pharyngitis, and adenitis (PFAPA) and syndrome of undefined recurrent fever (SURF). METHODS: Clinical data from pR92Q variant associated AID, classical TRAPS, PFAPA and SURF patients were obtained from the Eurofever registry, an international, multicentre registry enabling retrospective collection of data on AID patients. RESULTS: In this study, 361 patients were enrolled, including 77 pR92Q variant, 72 classical TRAPS, 152 PFAPA and 60 SURF patients. pR92Q carriers had an older age of disease onset than classical TRAPS and PFAPA patients. Compared to pR92Q variant patients, classical TRAPS patients had more relatives affected and were more likely to have migratory rash and AA-amyloidosis. Despite several differences in disease characteristics and symptoms between pR92Q variant and PFAPA patients, part of the pR92Q variant patients experienced PFAPA-like symptoms. pR92Q variant and SURF patients showed a comparable clinical phenotype. No major differences were observed in response to treatment between the four patient groups. Steroids were most often prescribed and effective in the majority of patients. CONCLUSIONS: Patients with AID carrying the TNFRSF1A-pR92Q variant behave more like SURF patients and differ from patients diagnosed with classical TRAPS and PFAPA in clinical phenotype. Hence, they should no longer be diagnosed as having TRAPS and management should differ accordingly.

Acute Immune-Mediated Lesions of the Oral Cavity.

Although acute immune-mediated lesions of the oral cavity (AIML) can have an onset over several months, they often demonstrate rapid onset and can be self-limited. Despite the self-limiting nature of some disorders, patients with AIML can have significant pain and multisystem involvement. It is vital for the oral health care provider to arrive at the proper diagnosis with distinction from overlapping conditions, as the oral manifestations may be harbingers of more serious systemic complications.

Adult-onset Periodic Fever, Aphthous Stomatitis, Pharyngitis and Cervical Adenitis Syndrome Responsive to Colchicine.

We herein report a rare case of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome that occurred in an 18-year-old man. He visited our hospital with recurrent episodes of a fever, pharyngitis and adenitis without suggestive findings of infection. These episodes resolved within 5 days and recurred quite regularly, with an interval of about 30 days. As the febrile episodes significantly impaired his quality of life, he was treated with colchicine (0.5 mg) as prophylaxis. This completely prevented the episodes during six months of follow-up. Colchicine may therefore be effective in cases of adult-onset PFAPA syndrome.

Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis Syndrome and Syndrome of Unexplained Recurrent Fevers in Children and Adults.

Children and adults with autoinflammatory disorders, who often experience recurrent fevers, rashes, cold-induced symptoms, conjunctivitis, lymphadenopathy, recurrent infections, aphthous stomatitis, and abnormal blood cell counts, may present to the allergist/immunologist because the symptoms mimic allergies and disorders of immunity. In recent years, there has been increased recognition of non-monogenic autoinflammatory disorders, including periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome and syndrome of undifferentiated recurrent fevers. For many clinical practitioners, the natural history, diagnostic criteria, differential diagnoses, and preferred therapies remain challenging because of the presumed rarity of patients and the evolving field of autoinflammation. Here, we aim to provide a practical framework for the clinical allergist/immunologist to evaluate and treat this patient population.

Evaluation of biochemical variables in patients with recurrent aphthous stomatitis.

PURPOSE: We investigated the effects of various biochemical agents on the etiopathogenesis of recurrent aphthous stomatitis (RAS). METHODS: We enrolled 70 RAS patients and 70 healthy volunteers. Peripheral venous blood samples were collected. We performed complete blood counts, then measured the levels of ferritin, vitamin B12, iron, magnesium, phosphorus, calcium, thyroid-stimulating hormone, T3, T4, and 25-hydroxy D3. RESULTS: The groups did not differ in terms of age (p = 0.912) or sex (p = 0.612). The levels of ferritin and 25-hydroxy vitamin D were significantly lower in RAS patients (both p Ë‚ 0.05). CONCLUSION: Vitamin D and/or ferritin deficiency may induce RAS. Measurements of vitamin D and ferritin may assist diagnosis and follow-up.

Long-term efficacy of tonsillectomy/adenotonsillectomy in patients with periodic fever aphthous stomatitis pharyngitis adenitis syndrome with special emphasis on co-existence of familial Mediterranean fever.

Periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA) syndrome is one of the most common autoinflammatory fever disorders in the childhood which may co-exists with familial Mediterranean fever (FMF) causing treatment complexity. As the role of surgery in PFAPA syndrome is still controversial, in this paper, our aim is to present our results of tonsillectomy/adenotonsillectomy in the treatment of PFAPA syndrome. Archives of a tertiary care hospital were investigated for patients who underwent tonsillectomy or adenotonsillectomy due to PFAPA Syndrome between 2010 and 2020. 344 patients were found but only 281 of them were accessible. Through phone call interview and chart review methods, preoperative and postoperative the number and severity of the attacks and general satisfaction after the operation were recorded and analyzed. Also, patients with concomitant FMF were analyzed separately. A total of 281 patients were included in the study. There was no improvement in 10 (3.55%) patients. Eight (2.84%) patients showed mild improvement, 29 (10.32%) patients had moderate improvement and 234 (83.27%) patients had full recovery after tonsillectomy. There were 266 PFAPA patients without FMF. No improvement, mild improvement, moderate improvement, and full recovery in this patient group were 5 (1.9%), 6 (2.3%), 25 (9.4%) and 230 (86.5%), respectively. FMF was present in 5.33% (15/281) of the patients. In PFAPA + FMF group 5 patients had no improvement (33.3%), 2 had mild improvement (13.3%), 4 had moderate improvement (26.7%) and 4 had full recovery (26.7%). Benefit of tonsillectomy was significantly lower in the patients with concomitant FMF when compared to the patients who did not have FMF (p < 0.001). Age of diagnosis, age of operation, severity of the disease, type of operation, and gender were found to have no significant relationship with the benefit from surgery (p < 0.05). According to the findings of this study, tonsillectomy is an effective long-term treatment for PFAPA syndrome with success rate of 83.27%. Also, preoperatively FMF should be considered in these patients, which dramatically reduces surgical efficacy.

Efficacy of canakinumab in a patient with adult-onset glucocorticoid-resistant periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome.

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome, a polygenic or multifactorial condition, is the most frequent autoinflammatory disease in children. There is increasing evidence that some patients may have a disease onset during adulthood. With regard to PFAPA syndrome treatment, single medium-to-high doses of glucocorticoids during flares constitute the therapy of choice in children and adults, colchicine may be useful in some patients, and tonsillectomy has been reported of utility mainly in paediatric patients. Interleukin-1 (IL-1) blockers have been sporadically used with good response in glucocorticoid-resistant cases. We report a patient with an adult onset of glucocorticoid-resistant PFAPA syndrome and inconsistent response to colchicine and anakinra, who later achieved a complete and sustained response to canakinumab. Although canakinumab seems to be a good therapeutic option in paediatric and adult patients with refractory PFAPA syndrome, the best anti-IL-1 agent and the sequence of administration have to be still determined in well-designed clinical trials.

[Marshall syndrome]. / Syndrome de Marshall.

MARSHALL SYNDROME. Marshall syndrome also known as PFAPA syndrome belongs to the group of autoinflammatory diseases. The acronym reflects the main clinical features of the disease: periodic fever, aphthous stomatitis, pharyngitis, and adenitis. It is the most common autoinflammatory disease, beginning between 1 and 5 years of age. There is little or no impact on growth, but the recurrence of febrile seizures can compromise the quality of life of patients. Clinical diagnosis meets positive and exclusion criteria. Putting it correctly allows a reassuring framework of care and avoids many unnecessary antibiotic treatments. Corticosteroid therapy is the reference treatment for the crisis. Tonsillectomy associated with adenoidectomy can be discussed but is not systematically recommended in this pathology, which is generally benign and most often heals spontaneously with age.

SYNDROME DE MARSHALL. Le syndrome de Marshall, aussi connu sous le nom de syndrome PFAPA, appartient au groupe des maladies auto-inflammatoires. L'acronyme reflète les principales caractéristiques cliniques de la maladie : fièvre périodique, aphtes, pharyngite, adénite. Il s'agit de la maladie auto-inflammatoire la plus fréquente, débutant entre 1 et 5 ans. Il n'y a pas ou peu de retentissement sur la croissance, mais la récurrence des accès fébriles peut obérer la qualité de vie des patients. Le diagnostic clinique répond à des critères positifs et d'exclusion. Bien poser celui-ci permet de poser un cadre de prise en charge rassurant pour l'entourage et d'éviter de nombreux traitements antibiotiques inutiles. La corticothérapie est le traitement de référence de la crise. L'amygdalectomie associée à l'adénoïdectomie peut être discutée mais n'est pas recommandée de façon systématique dans cette pathologie en général bénigne et guérissant le plus souvent spontanément avec l'âge.

[Experience of using bacteriophages in the complex treatment of children with aphthous stomatitis]. / Opyt ispol'zovaniya bakteriofagov v kompleksnom lechenii detei s aftoznym stomatitom.

Aphthous stomatitis (AS) is one of the most common diseases of the oral mucosa in children. A significant role in the pathogenesis of AS is assigned to the infectious-allergic factor. THE AIM: Of the work was to evaluate the clinical effectiveness of topical application of bacteriophages in the complex treatment of children with aphthous stomatitis. MATERIALS AND METHODS: The main group included 30 children with AS aged 4 to 15 years. The control group consisted of 20 healthy children without AS and without concomitant somatic pathology at the age of 4 to 15 years. The effectiveness of the therapy was evaluated based on the results of repeated bacteriological examination of the oral microflora, conducted 1 month after phage treatment, as well as the dynamics of clinical manifestations: reduction in size or complete epithelization of defects. RESULTS: The use of bacteriophage in the complex treatment of children with AS was accompanied by positive dynamics of clinical and laboratory parameters in all patients: a significant decrease in microbial contamination and the number of individual pathogenic microflora species against the background of normalization of local microbiocenosis in the oral cavity. CONCLUSION: The obtained clinical and laboratory data allowed improving the scheme of complex treatment of AS in children by the use of bacteriophages.

Oral manifestations serve as potential signs of ulcerative colitis: A review.

As an immune dysregulation-related disease, although ulcerative colitis (UC) primarily affects the intestinal tract, extraintestinal manifestations of the disease are evident, particularly in the oral cavity. Herein, we have reviewed the various oral presentations, potential pathogenesis, and treatment of oral lesions related to UC. The oral manifestations of UC include specific and nonspecific manifestations, with the former including pyostomatitis vegetans and the latter encompassing recurrent aphthous ulcers, atrophic glossitis, burning mouth syndrome, angular cheilitis, dry mouth, taste change, halitosis, and periodontitis. Although the aetiology of UC has not been fully determined, the factors leading to its development include immune system dysregulation, dysbiosis, and malnutrition. The principle of treating oral lesions in UC is to relieve pain, accelerate the healing of lesions, and prevent secondary infection, and the primary procedure is to control intestinal diseases. Systemic corticosteroids are the preferred treatment options, besides, topical and systemic administration combined with dietary guidance can also be applied. Oral manifestations of UC might accompany or precede the diagnosis of UC, albeit with the absence of intestinal symptoms; therefore, oral lesions, especially pyostomatitis vegetans, recurrent aphthous ulcer and periodontitis, could be used as good mucocutaneous signs to judge the occurrence and severity of UC, thus facilitating the early diagnosis and treatment of UC and avoiding severe consequences, such as colon cancer.

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome: Clinical characteristics and treatment outcomes - a single center study in Japan.

BACKGROUND: Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is an autoinflammatory disease occurring in children. Although PFAPA is the most common periodic fever syndrome found in children, there are only a few studies defining the clinical characteristics and the efficacy of treatment strategies among Japanese children. This study aimed to clarify the demographic characteristics and clinical features of patients with PFAPA syndrome and to evaluate treatment efficacy. METHODS: We retrospectively reviewed the clinical features of children with PFAPA who visited Saitama Children's Medical Center between January and December 2019. We also evaluated treatment strategies and their efficacy; abortive treatment with corticosteroids, prophylaxis with cimetidine or colchicine, and surgical management with tonsillectomy. RESULTS: A total of 100 Japanese children (61% male) with PFAPA were included. Median age of onset was 3 years, median duration of fever episodes was 5 days, and median interval between episodes was 4 weeks. The symptoms (frequencies) were pharyngitis (89%), exudate on tonsils (71%), cervical adenitis (50%), and aphthous stomatitis (49%). Approximately 37% of patients took prednisolone for aborting fever attacks, showing a 100% response; 93% were treated with cimetidine, showing an 79.6% response, and 18% were treated with colchicine, showing a 66.7% response. Only one patient underwent tonsillectomy. CONCLUSIONS: Among Japanese children with PFAPA, 28% of them were ≥5 years with a male predominance. Pharyngitis is the most frequent symptom associated with fever. Cimetidine is suitable for initial therapy because of its safety and efficacy.

Epidemiology and clinical features of PFAPA: a retrospective cohort study of 336 patients in western Sweden.

BACKGROUND: Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome is generally regarded as the most common autoinflammatory disease, but the epidemiology of the disease is largely unknown. The objectives of this study were to estimate the annual incidence and describe the clinical features of PFAPA in a large cohort from western Sweden. METHODS: The study retrospectively included children < 18 years of age diagnosed with PFAPA between 2006 and 2017 at three hospitals: NU Hospital Group, Skaraborg Hospital and Queen Silvia Children's Hospital. Patients were identified by searching for relevant diagnostic ICD-10 codes in the comprehensive electronic medical records and data were retrieved by reviewing case records. To estimate incidence, patients with symptom onset from January 1, 2006, to December 31, 2016, were included. Population data for the study area during this period were retrieved from Statistics Sweden. RESULTS: In this study, 336 patients with PFAPA were identified. Of these, 156 (46%) were girls and 180 (54%) were boys. Almost 90% of the children with PFAPA (291 patients) experienced their first symptoms before the age of 5 years and fewer than 3% presented at ages above 10 years. Pharyngitis was the most common symptom during febrile episodes, followed by cervical adenitis and aphthous stomatitis. Fourteen percent of the patients displayed atypical features, of which skin rash was the most common. To calculate incidence, 251 patients with symptom onset during the study period were identified. The mean annual incidence was estimated at 0.86/10,000 for children < 18 years of age and 2.6/10,000 for children < 5 years of age. CONCLUSIONS: This study adds to the understanding of the epidemiology of PFAPA syndrome by presenting incidence rates based on a large cohort and in different age groups in a population-based setting. It also shows the distribution of age of onset of PFAPA, with a peak in 1-year-olds and waning at older ages. Signs and symptoms of PFAPA syndrome were similar in children with symptom onset before vs. after 5 years of age.