Periodic Fever, Aphthous Stomatitis, Pharyngitis And Adenitis Syndrome Research Articles

Probiotic use in the prophylaxis of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome: a retrospective cohort study.

Periodic fever, aphthousstomatitis, pharyngitis, and adenitis (PFAPA) syndrome is an autoinflammatory recurrent fever syndrome that mainly affects children. Probiotics are currently used to prevent upper respiratory tract infections and flares of diseases associated with immune dysregulation. We aimed to evaluate the response to probiotic treatment in PFAPA patients. Patients with PFAPA syndrome who received probiotics and were followed between July 2019 and July 2021 were included in this retrospective study. Demographic and clinical features and response to probiotics were assessed. Twenty out of 111 children with PFAPA syndrome (F/M:1) were included. The median (min-max) ages at symptoms onset and diagnosis were 24 (3-72) and 51.5 (11-120) months, respectively. All 20 patients received probiotics during the disease course. The probiotic preparation they received included a combination of two lactobacilli as Lactobacillus plantarum HEAL9 (Lp HEAL9) and Lactobacillus paracasei 8700:2 (Lpa 8700:2). The median age at probiotic onset was 60 (33-192) months, while the duration of probiotic use was 4.5 (3-19) months. All patients except one experienced a decrease in attack frequency with probiotic use. After probiotic treatment, the median number of episodes during 3 monthsdecreased from 3 to 1 (p < 0.001). Eight (40%) patients had no attacks during the 3months after probiotic initiation. And, 5 (45%) of 11 patients who had ≥ 1 attacks on probiotics mentioned that the attack severity decreased significantly after probiotic initiation. Our results suggest that probiotic strains Lactobacillus plantarum HEAL9 and Lactobacillus paracasei 8700:2 could be beneficial in PFAPA patients by decreasing the attack frequency.

Assessment of sleep in children with periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome.

Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome is the most common cause of periodic fever in childhood. This study aimed to investigate sleep patterns and possible factors that are associated with sleep disturbances among children with PFAPA syndrome. Sixty-two patients with PFAPA and 68 age and sex matched healthy controls were enrolled in the study. Patients who had an attack during the former 2 weeks were not included. Demographic and anthropometric data, duration of fever episodes, laboratory results, and clinical manifestations of patients were recorded. The Children`s Sleep Habits Questionnaire was administered. The total sleep scores of patients with PFAPA were significantly higher than the control group (49.6 ± 10.7 vs. 38.3 ± 7.5, p = 0.002 ). Children with PFAPA had significantly higher scores regarding sleep-onset delay, sleep anxiety and night wakening (p=0.003, p=0.007, and p=0.014, respectively). Total sleep durations were similar between children with PFAPA and the control group. There was a significant positive correlation between the total sleep score and disease duration (r=0.425, p=0.002). Also there was a significant positive correlation between disease duration and sleep onset delay (r=0.561, p < 0.001) and night wakening (r=0.327, p=0.003). This study showed for the first time that patients with PFAPA have significantly disturbed sleep when compared to otherwise normal children. This study emphasized the need to assess sleep problems in children with PFAPA.

Immune Dysregulation in the Tonsillar Microenvironment of Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA) Syndrome.

Periodic Fever, Aphthous stomatitis, Pharyngitis and Adenitis (PFAPA) syndrome is an inflammatory disorder of childhood classically characterized by recurrent fevers, pharyngitis, stomatitis, cervical adenitis, and leukocytosis. While the mechanism is unclear, previous studies have shown that tonsillectomy can be a therapeutic option with improvement in quality of life in many patients with PFAPA, but the mechanisms behind surgical success remain unknown. In addition, long-term clinical follow-up is lacking. In our tertiary care center cohort, 62 patients with PFAPA syndrome had complete resolution of symptoms after surgery (95.3%). Flow cytometric evaluation demonstrates an inflammatory cell population, distinct from patients with infectious pharyngitis, with increased numbers of CD8+ T cells (5.9% vs. 3.8%, p < 0.01), CD19+ B cells (51% vs. 35%, p < 0.05), and CD19+CD20+CD27+CD38-memory B cells (14% vs. 7.7%, p < 0.01). Cells are primed at baseline with increased percentage of IL-1β positive cells compared to control tonsil-derived cells, which require exogenous LPS stimulation. Gene expression analysis demonstrates a fivefold upregulation in IL1RN and TNF expression in whole tonsil compared to control tonsils, with persistent activation of the NF-κB signaling pathway, and differential microbial signatures, even in the afebrile period. Our data indicates that PFAPA patient tonsils have localized, persistent inflammation, in the absence of clinical symptoms, which may explain the success of tonsillectomy as an effective surgical treatment option. The differential expression of several genes and microbial signatures suggests the potential for a diagnostic biomarker for PFAPA syndrome.

Síndrome PFAPA e as febres periódicas da infância: relato de caso

A síndrome da febre periódica, estomatite aftosa, faringite e adenite (periodic fever, aphthous stomatitis, pharyngitis and adenitis – PFAPA) é caracterizada por episódios recorrentes de febre alta, estomatite aftosa, faringite e adenite cervical em crianças de faixa etária entre um e cinco anos. As crises da doença ocorrem em um intervalo de cerca de 30 dias, e nesse período há dias em que as crianças apresentam-se saudáveis. Os sintomas tendem a se atenuar espontaneamente com o avanço da idade. A prednisona pode ser utilizada para controlar os sinais e sintomas nas crises. Em alguns casos, a tonsilectomia é a melhor opção terapêutica. Este artigo relata um caso de síndrome PFAPA e realiza uma revisão de sua literatura – clínica, diagnóstico e tratamento.

Long-Term Outcome of Classic and Incomplete PFAPA (Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis) Syndrome after Tonsillectomy

To compare the effectiveness of tonsillectomy and the long-term outcome of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome in patients fulfilling the classic diagnostic criteria and in those with regularly recurring fever as the only symptom or with onset of symptoms after age 5 years or both. We reviewed the medical records of 3852 children who underwent tonsillectomy between 1990 and 2007 and identified 108 children who did so because of regularly recurring fevers. The patients were invited to an outpatient visit and were classified into 2 groups: those who met (N = 58) and those who did not meet (N = 50) Thomas diagnostic criteria. We then compared the clinical profile and outcome of PFAPA symptoms after tonsillectomy between the 2 groups. In the group that met Thomas criteria, 97% (56/58) had complete resolution of fever episodes after tonsillectomy; in the group that did not meet Thomas criteria (50/50) had complete resolution of fever episodes after tonsillectomy (P = .25). The clinical profile of the periodic fevers and the occurrence of other illnesses during follow-up were similar in both groups. Thomas criteria identified 56 of 106 patients responding to tonsillectomy. Tonsillectomy was an effective treatment for patients with regularly recurring fever episodes who failed to meet the classic Thomas criteria. We suggest that PFAPA syndrome should be suspected and tonsillectomy considered in children with a late onset of symptoms (>5 years of age) or when fever is the only symptom during the episodes.

Tonsillar microbiota in children with PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and adenitis) syndrome.

Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) is a childhood febrile syndrome of unknown origin that is often cured with tonsillectomy. We aimed to compare the bacterial microbiota of the tonsils removed from PFAPA patients with those of controls. We used next-generation sequencing technology to investigate the bacterial microbiota of the tonsils of 30 PFAPA patients and 24 controls. We found significant differences in the presence and relative abundance of many bacteria between PFAPA cases and controls. For example, cyanobacteria, potential producers of microcystins and other toxins, were more common in the case samples (14/30, 47%) than in the controls (4/24, 17%, p = 0.02), and the mean relative abundance of cyanobacteria was higher in the case samples (0.2%) than in the controls (0.01%, p = 0.01). Streptococci were present in all samples in both groups, but their mean relative abundance was lower in the case samples (3.7%) than in the controls (9.6%, p = 0.01). Typical nasopharyngeal microbes such as fusobacteria, Prevotella, Tannerella, Porphyromonas, and Parvimonas dominated the microbiota of the tonsils in both groups. The microbiota of the tonsils removed from PFAPA patients differed significantly from those of the controls. Tonsillar microbiota may play a role in triggeringthe inflammatory processes that lead to symptoms of PFAPA.

The clinical characteristics of PFAPA syndrome

The periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome is considered as a non-inherited autoinflammatory disease of unknown etiology. The most common clinical manifestations are high fever episodes with clockwork periodicity every 3 to 8 weeks and lasts for about 3 to 6 days, associated to pharyngitis, aphthous stomatitis, and cervical adenitis.

FRI0558 Presentations and Clinical Outcomes of Patients Diagnosed with Pfapa

BackgroundThe periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome is considered as a non-inherited autoinflammatory disease of unknown etiology. The most common clinical manifestations are high fever episodes with...

Clinical and Genetic Characterization of Japanese Sporadic Cases of Periodic Fever, Aphthous Stomatitis, Pharyngitis and Adenitis Syndrome from a Single Medical Center in Japan

To investigate clinical presentation, genetic background and cytokine profile of Japanese sporadic cases of periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome. Nine PFAPA syndrome patients were recruited. DNA sequence analysis of auto inflammatory disorder susceptibility genes, MEFV, MVK, NLRP3, and TNFRSF1A, were performed. Serum cytokine levels and monocyte IL-1β levels were measured by ELISA. The study population consisted of six males and three females (mean age of onset 26.8months). Febrile episodes lasted 3-6days with symptom-free intervals ranging from 2 to 12weeks. Fever was accompanied by pharyngitis (n = 8), aphthous stomatitis (n = 4), and cervical adenitis (n = 5). White blood cells and C-reactive protein were increased during the attack phase. Mean IgD serum levels were 7.32 ± 9.51mg/dl during the attack phase, and were mildly elevated in two patients. Heterozygous MEFV, NLRP3 and TNFRSF1A variants were detected in four, one and three cases, respectively. Serum TNF-α and IL-18 levels were elevated during the attack-free and attack periods compared with controls. Other cytokines, IL-1β, IL-1ra, IL-6, and sTNFR1, were only increased during the attack phase. Oral prednisolone was administered to eight patients and immediately reduced fever. Tonsillectomy performed in five patients induced cessation of fever in four patients. One case with repeated fever attacks after tonsillectomy showed increased monocyte IL-1β production, similar to the other active case with genetic variants of auto inflammatory disorder-associated genes. Japanese PFAPA syndrome patients may have cytokine regulation dysfunction as a result of genetic variants of auto inflammatory disorder-associated genes.

Successful Treatment of PFAPA (Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis) Syndrome with Shinbuto*

Periodic fever with aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome is an autoimmune disorder and the most common disorder characterized by periodic fever in children. A male patient has been followed up from 11 months to 10 years of age because of repeated high fever. We prescribed antifebriles and antibiotics for each febrile episode without a beneficial effect to him each time. He required several days of rest at home to recover from each episode. During his most recent febrile episode at 10 years of age, we prescribed 5.0 g of shinbuto (TJ-30; Tsumura Co., Tokyo, Japan). His fever resolved the next day and he was able to attend school. His growth and development are normal. Shinbuto had a therapeutic effect in this patient with PFAPA syndrome and may be useful in this condition.

PW03-009 – Genetics of PFAPA syndrome

Periodic Fever, Aphthous stomatitis, Pharyngitis and Adenitis (PFAPA) syndrome is an autoinflammatory disorder of childhood and little is known about the underlying etiology. While mutations involving the IL-1 pathway have been identified in other recurrent fever disorders, including TNF-receptor associated periodic syndrome (TRAPS) and cryopyrin-associated periodic syndrome (CAPS), PFAPA syndrome is not traditionally considered to be a hereditary fever disorder.

Periodic Fever, Aphthous Stomatitis, Pharyngitis and Adenitis Syndrome

Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome is a non-hereditary autoinflammatory disease, characterized by relatively regular recurrence of febrile episodes of 3-6 days duration, accompanied by aphthous stomatitis, pharyngitis/tonsillitis, and/or cervical adenititis. It is considered to be the most common periodic fever syndrome in Japan. Although no responsible gene is identified, some genetic factors may confer the predisposition toward this disorder. Important differential diagnosis includes hereditary periodic syndromes and cyclic neutropenia. Although its etiology is still to be elucidated, a recent study suggested an environmentally triggered activation of complement and IL-1β/IL-18 during PFAPA syndrome flares, with induction of Th1-chemokines and subsequent retention of activated T cells in peripheral tissues. This study also demonstrated the possibility that IP-10/CXCL10 might serve as a potential biomarker to differentiate PFAPA syndrome from other periodic fever syndromes. Therapeutic strategy for PFAPA syndrome has not been well established. Recent advances in the understating of etiology and pathophysiology might lead to re-evaluation of recent therapeutic options and/or development of new treatment.

Profile of blood cells and inflammatory mediators in periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome

BackgroundThis study aimed to profile levels of blood cells and serum cytokines during afebrile and febrile phases of periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome to advance pathophysiological understanding of this pediatric disease.MethodsA cohort of patients with a median age of 4.9 years experiencing 'typical PFAPA' episodes participated in this study. Blood cells and serum cytokines were analyzed by CBC analysis and multiplex ELISA.ResultsOscillations in the concentration of blood cells during the afebrile and febrile phases of typical PFAPA syndrome were observed; novel findings include increased monocytes and decreased eosinophils during a febrile episode and increased thrombocytes in the afebrile interval. Relatively modest levels of pro-inflammatory cytokines were present in sera. IFNγ-induced cytokine IP10/CXCL10 was increased after the onset of fever while T cell-associated cytokines IL7 and IL17 were suppressed during afebrile and febrile periods.ConclusionsIdentification of dysregulated blood cells and serum cytokines is an initial step towards the identification of biomarkers of PFAPA disease and/or players in disease pathogenesis. Future investigations are required to conclusively discern which mediators are associated specifically with PFAPA syndrome.

PFAPA syndrome: new clinical aspects disclosed

Background: The recently described PFAPA (Periodic Fever, Aphthous stomatitis, Pharyngitis and Adenitis) syndrome is characterised by periodic fever, aphthous stomatitis, pharyngitis and adenitis. However, there are currently relatively few data...