Diagnosis Of PFAPA Research Articles

Antibiotic prescriptions to children with periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis.

To investigate the rate of dispensed antibiotic prescriptions to children and adolescents with PFAPA and compare this with the rate for children in the general population. Furthermore, to compare dispensed antibiotic prescription rates before and after a diagnosis of PFAPA was established. Patients aged 0-17 years and diagnosed with PFAPA between 1 January 2006 to 31 October 2017 were included retrospectively. Data on dispensed drug prescriptions were obtained from the Swedish National Prescribed Drug Register. The PFAPA cohort received more antibiotic prescriptions than the general population in all but one of the age groups and time periods that were analysed. The largest difference was seen in 2014-2017 in the youngest age group (0-4 years) when children with PFAPA received 1218 antibiotic prescriptions per 1000 person years compared to 345 in the general population (IRR 3.5; 95% CI 2.8-4.4). The yearly number of antibiotic prescriptions to PFAPA patients was reduced from 2.1 before diagnosis to 0.8 after diagnosis, a reduction of 62%. This study shows higher rates of dispensed antibiotic prescriptions for children with PFAPA than in the general population. The reduction of prescriptions after an established PFAPA diagnosis indicates that antibiotics were previously incorrectly prescribed for PFAPA episodes.

Altered serum antibody levels in children with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis.

This study aimed to extend the literature by analyzing immunoglobulin (Ig) A, IgE, IgG, IgG2, IgG3, and IgM antibody levels in periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) patients. This study retrospectively analyzed the antibody test results of 20 pediatric patients (10 males, 10 females; mean age: 2.5±1.5 years; range, 0.5 to 5.4 years) with and without flare who were initially evaluated for a number of underlying diseases due to periodic fever/infectious symptoms but then diagnosed with PFAPA between January 2015 and December 2020. Antibody levels were determined by chemiluminescence microparticle immunoassay. The results were retrospectively compared with a group of healthy children after the PFAPA diagnosis was confirmed. The chemiluminescence microparticle immunoassay revealed 35%, 65%, 20%, 86.6%, and 55% of PFAPA cases with low serum levels of IgA, IgG, IgG2, IgG3, and IgM respectively, while 56.2% had high IgE levels. Moreover, low serum levels of at least two antibody classes or subclasses were reported in 80% of the PFAPA children. While cases with low IgG serum levels were with the highest incidence rates among the low IgG3 PFAPA patient population, both high IgE and low IgM cases were common in the rest of the patients. Our results suggest an association between PFAPA and low serum antibody levels, particularly of IgG3. Future studies are needed to confirm our conclusion.

Challenges in the diagnosis of periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome in developing countries-A decade of experience from North India.

BackgroundReports of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome from developing countries are sparse. Recognizing PFAPA is often challenging in these regions due to a higher incidence of infectious illnesses and significant resource constraints. Herein, we present our experience from North India regarding the diagnosis and management of PFAPA syndrome.MethodsWe reviewed cases of non-monogenic periodic fever syndrome diagnosed at our center from January 2011 to December 2021. A total of 17 children who fulfilled the Marshall criteria for PFAPA syndrome were included. Data regarding basic clinical features, treatment/outcome, and performance of the recently proposed Eurofever/PRINTO and Takeuchi criteria were analyzed.ResultsBesides recurrent fever, the triad of oral aphthae, pharyngitis, and adenitis was noted in only 18% of patients. Episodes of exudative pharyngitis/tonsillitis were documented in 24%. These figures were lower than the values reported from developed countries. The Takeuchi and Eurofever/PRINTO criteria were fulfilled in 76% and 71% cases, respectively. In addition to antipyretics and supportive care, intermittent steroid therapy was the main treatment modality used. Additional treatment with colchicine (n = 3) and thalidomide (n = 1) was used successfully in a few patients. Before the diagnosis of PFAPA, all patients had received multiple courses of antimicrobials (without microbiological confirmation). These included multiple courses of antibacterials for fever, pharyngotonsillitis, and/or cervical adenitis in all patients and antivirals for fever and aphthous stomatitis in a patient. Empiric antitubercular therapy had also been administered in two patients.ConclusionsA significant proportion of patients with PFAPA seem to remain undiagnosed in the Indian subcontinent. Increased awareness and improvement in basic healthcare facilities are crucial in enhancing the recognition of PFAPA, which would eliminate the unprecedented scale of undesirable antimicrobial use in such children.

477. Increased Referrals for New PFAPA (Aphthous Stomatitis, Pharyngitis, Adenitis) Diagnosis During the COVID-19 Pandemic

BackgroundCOVID-19 pandemic caused by SARS-CoV-2 resulted in a global health crisis in 2020. Quarantining, wearing masks and physical distancing- key infection prevention strategies implemented to stop the spread of COVID-19, also led to dramatic decreases in rates of common respiratory viral infection seen in young children. Due to lack of school and daycare exposure, we evaluated a larger than usual number of patients with periodic fevers without any known infectious contacts. Based on this observation, we conducted an analysis of all suspected cases of periodic fevers seen at our institution during the COVID-19 lockdown compared to prior seasons.MethodsThe clinical charts were queried for all patients presenting to any Lurie Children’s Hospital outpatient specialty clinic or laboratory with ICD diagnosis code of MO4.1 and MO4.8 (all recurrent and periodic fever syndromes) from June 1, 2020 through September 30, 2020, and compared to similar months the previous 2 years (2018 and 2019). Each patient chart was reviewed by the lead investigator to verify all new diagnoses of PFAPA. The number of new patients with PFAPA diagnosis were tallied and analyzed. Statistical comparisons were made using Kruskal-Wallis tests for monthly distributions in different years. ResultsWe noted a significant increase in patients with new PFAPA diagnosis between June through August 2020 compared to similar months in 2018 and 2019 (Figure1). Experienced pediatric infectious disease physicians and rheumatologists diagnosed majority of the cases. During these months, a monthly median (IQR) of 13 (11.5, 14.5) patients were diagnosed among different Lurie specialty clinics, which is more than 2.5 folds increase in new PFAPA patients from the previous two years which were about 5 (3.5, 6) (Figure 2).Number of Patients with New PFAPA Diagnosis There was a significant increase in number of new patients diagnosed with PFAPA between June through August 2020 compared to similar months in 2018 and 2019.Monthly Distribution Summary for New PFAPA Diagnosis Statistical comparisons were made using Kruskal- Wallis tests for monthly distributions in different yearsConclusionWe observed a significant increase in PFAPA patients referred to our institution soon after introduction of public health measures to slow spread of COVID-19. Given that most children were not in daycare, schools, or camps, we suspect that parents and pediatricians were able to recognize patterns of periodic fevers in children much quicker than preceding years, when fevers would typically be attributed to an infectious process. Disclosures Ravi Jhaveri, MD, AstraZeneca (Consultant)Dynavax (Consultant)Elsevier (Other Financial or Material Support, Editorial Stipend as Co-editor in Chief, Clinical Therapeutics)Seqirus (Consultant)

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.

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.

Performance of recently proposed periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome criteria in a region endemic for familial Mediterranean fever.

The periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is an auto-inflammatory condition characterized by recurrent episodes of fever accompanied by aphthosis, cervical adenitis, and pharyngitis. Diagnosis of PFAPA could be challenging due to clinic overlap with familial Mediterranean fever (FMF). An international consensus has been established recently, to define a new set of classification criteria for PFAPA syndrome. We aimed to evaluate the performance of recently proposed PFAPA criteria, to assess their utility in FMF regions. Patients diagnosed with PFAPA syndrome, FMF, and juvenile idiopathic arthritis (JIA) were included. Two investigators blindly evaluated all of patients for the newly proposed PFAPA criteria. A total of 542 patients (322 with PFAPA syndrome, 118 FMF and 102 JIA) were evaluated. Mean age of patients was 6.6 ± 2.81, 12.75 ± 3.9, and 12.42 ± 4.8years for PFAPA, FMF, and JIA, respectively. We found quite high sensitivity (89.7%) but insufficient specificity of newly proposed PFAPA criteria (69.5%). When applied to control patients separately, specificity was found to be 61% and 79.4% for FMF and JIA patients, respectively. Positive predictive value was 81%, while negative predictive value was 82%. Recently proposed PFAPA criteria have satisfactory sensitivity, but its specificity is still under expectation. There is a need for a distinctive criterion between PFAPA syndrome and FMF, in FMF endemic regions, e.g., cryptic tonsillitis rapidly responsive to single dose of glucocorticoids. Further studies with higher patients' number in different regions are needed.

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome: main features and an algorithm for clinical practice.

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is a recurrent fever syndrome of early childhood with increasing number of adult-onset cases. Although it is a self-limited disease, it may negatively affect the quality of life. The aim of this review is to present a detailed analysis of PFAPA syndrome and an algorithm for diagnosis, therapeutic options, and evaluation of outcome. A comprehensive literature search was conducted through the Cochrane Library, Scopus, and MEDLINE/PubMed databases. The main topics covered are the epidemiology, clinical manifestations, diagnosis, differential diagnosis, etiopathogenesis, genetics, management, disease course and prognosis, disease in adults, unsolved issues, and unmet needs in PFAPA. The diagnosis of PFAPA is mainly based on clinical classification criteria. The most relevant hypothesis for pathogenesis is that dysregulated immune system in a genetically predisposed individual responds to a yet unidentified trigger in an exaggerated way. The pedigree analyses suggest a genetic background for the disease with an autosomal dominant pattern of inheritance. For management, single-dose corticosteroids during attacks and tonsillectomy remain the most effective therapies, while colchicine is a promising option to decrease attack frequency. There remain unsolved issues in PFAPA such as the exact etiopathogenesis and genetic background, the reason why the inflammation is restricted to the oropharyngeal lymphoid tissue, reasons for clock-work regularity of attacks, and self-limited disease course. There is need for a valid diagnostic criteria set with a high performance for both children and adults and consensus on management of PFAPA.

RECURRENT AND CYCLIC FEVERS IN A PEDIATRIC PATIENT

Introduction Fevers are a common complaint among the pediatric population, and are frequently related to a viral or bacterial infection that resolves with conservative treatment or antibiotics. However, fevers of significance (greater than 38.4 degrees Celsius) occurring in a cyclic pattern with unusual associated symptoms are concerning for an underlying cause. Periodic fever syndromes are inherited disorders with recurrent fever and inflammation in the absence of infection or malignancy. Case Description A 6-year old previously healthy female presented for an evaluation for periodic fevers. Starting 2 years prior, she had fevers up to 39.5 degrees Celsius every 4 weeks associated with halitosis, joint pain, headaches, and vomiting. There were no reported aphthous ulcers or diagnosed pharyngitis. Prior immune and infectious workups were negative with multiple normal CBC differentials, pan-cultures, and immunoglobulins. However, inflammatory markers were elevated during the febrile periods and decreased when afebrile. The periodic fever gene sequencing panel was negative. Her fevers responded to corticosteroid doses at the onset of the episodes, but she required monthly doses for continuing cyclic fevers. However, when colchicine therapy was initiated the fevers resolved. Discussion This patient does not fit the classic description of periodic fever aphthous stomatitis pharyngitis adenitis syndrome (PFAPA) but she has abnormal symptoms associated with cyclic fevers. Although she had a negative periodic fever genetic panel, exome sequencing is pending and she continues to follow in clinic. This case is important as it deviates from the classic PFAPA diagnosis, but the patient responds appropriately to treatment with corticosteroids and colchicine.

Towards a new set of classification criteria for PFAPA syndrome

BackgroundDiagnosis of Periodic Fever, Aphthous stomatitis, Pharyngitis and Cervical Adenitis (PFAPA) syndrome is currently based on the modified Marshall’s criteria, but no validated evidence based classification criteria for PFAPA has been established so far.MethodsA multistep process, based on the Delphi and Nominal Group Technique was conducted. After 2 rounds of e-mail Delphi survey involving 21 experts in autoinflammation we obtained a list of variables that were discussed in an International Consensus Conference. Variables reaching the 80% of consensus between participants were included in the new classification criteria.In the second phase the new classification criteria and the modified Marshall’s criteria were applied on a cohort of 80 pediatric PFAPA patients to compare their performance.ResultsThe Delphi Survey was sent to 22 participants, 21 accepted to participate. Thirty variables were obtained from the survey and have been discussed at the Consensus Conference. Through the Nominal Group Technique we obtained a new set of classification criteria. These criteria were more restrictive in respect to the modified Marshall’s criteria when applied on our cohort of patients.ConclusionOur work led us to identify a new set of classification criteria for PFAPA syndrome, but they resulted to be too restrictive to be applied in daily clinical practice for the diagnosis of PFAPA.

An international delphi survey for the definition of the variables for the development of new classification criteria for periodic fever aphtous stomatitis pharingitis cervical adenitis (PFAPA)

BackgroundDiagnosis of Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) is currently based on a set of criteria proposed in 1999 modified from Marshall’s criteria. Nevertheless no validated evidence based set of classification criteria for PFAPA has been established so far. The aim of this study was to identify candidate classification criteria PFAPA syndrome using international consensus formation through a Delphi questionnaire survey.MethodsA first open-ended questionnaire was sent to adult and pediatric clinicians/researchers, asking to identify the variables thought most likely to be helpful and relevant for the diagnosis of PFAPA. In a second survey, respondents were asked to select, from the list of variables coming from the first survey, the 10 features that they felt were most important, and to rank them in descending order from most important to least important.ResultsThe response rate to the first and second Delphi was respectively 109/124 (88%) and 141/162 (87%). The number of participants that completed the first and second Delphi was 69/124 (56%) and 110/162 (68%). From the first Delphi we obtained a list of 92 variables, of which 62 were selected in the second Delphi. Variables reaching the top five position of the rank were regular periodicity, aphthous stomatitis, response to corticosteroids, cervical adenitis, and well-being between flares.ConclusionOur process led to identification of features that were felt to be the most important as candidate classification criteria for PFAPA by a large sample of international rheumatologists. The performance of these items will be tested further in the next phase of the study, through analysis of real patient data.

Diagnostic Criteria for Adult-Onset Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA) Syndrome.

To identify a set of variables that could discriminate patients with adult-onset periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome from subjects with fever of unknown origin (FUO). We enrolled 74 adults diagnosed with PFAPA syndrome according to the currently used pediatric diagnostic criteria and 62 additional patients with FUO. After having collected clinical and laboratory data from both groups, univariate and multivariate analyses were performed to identify the variables associated with PFAPA diagnosis. Odds ratio (OR) values, their statistical significance, and corresponding 95% confidence interval (CI) were evaluated for each diagnostic factor both at the univariate and multivariate analyses. Diagnostic accuracy was evaluated by the area under receiver operating characteristic (ROC) curve, while the leave-one-out cross-validation procedure was used to ensure that the model maintains the same diagnostic power when applied to new data. According to the multivariate analysis, the clinical variables that discriminated PFAPA patients were: fever episodes associated with cervical lymphadenitis (OR = 92; p < 0.0001), fever attacks associated with erythematous pharyngitis (OR = 231; p < 0.0001), increased inflammatory markers during fever attacks (OR = 588; p = 0.001), and the lack of clinical and laboratory signs of inflammation between flares (OR = 1202; p < 0.0001). These variables were considered for a diagnostic model which accounted for their OR values. The diagnostic accuracy of the proposed set of criteria corresponded to an area under ROC curve of 0.978 (95% CI 0.958-0.998), with a model sensitivity and specificity equal to 93.4% (95% CI 87.5-96.5%) and 91.7% (95% CI 82.8-96.7%), respectively. we have provided herein a set of clinical diagnostic criteria for adult-onset PFAPA syndrome. Our criteria represent an easy-to-use diagnostic tool aimed at identifying PFAPA patients among subjects with FUO with a high-predictive potential, as shown by its very high sensitivity and specificity.

Is colchicine an effective treatment in periodic fever, aphtous stomatitis, pharyngitis, cervical adenitis (PFAPA) syndrome?

IntroductionPFAPA syndrome is the most frequent periodic fever syndrome in non-Mediterranean patients. The pathogenesis is unclear and the treatment is purely symptomatic and not standardized. The aim of this study was to assess colchicine's efficacy as prophylactic treatment in PFAPA syndrome and to identify factors able to predict response to treatment. MethodsWe performed a retrospective, multicentric, cohort study of PFAPA patients under colchicine prophylaxis. PFAPA diagnosis was established according to Feder's criteria. Medical records were reviewed and analyzed for demographic, clinical and laboratory data. We distinguished one responder's group, defined as patients who had no more or twice fewer crises under colchicine and another one of non-responders. Subgroup analyses were performed using non-parametric Mann-Whitney test for quantitative data and calculating odds ratio and confidence interval for qualitative data. Difference between the two groups was considered significant for P-value<0.05 or a confidence interval different from 1. Results-conclusionTwenty children, 65% of whom were boys, were analyzed. Their mean age at disease onset was 2.3±1.5 years. Among the nine responder patients, five were MEFV (71%) heterozygotes: M694V mutation in four and V726A once. Heterozygous MEFV gene mutation tended to be more frequent in the responders group (71% versus 43%; OR=0.3 [0.03–2.7]). Non-responder patients had more chronic fatigue (82% versus 33%; OR=9 [1,14–71]) and had more oral aphtosis (82% versus 11%; OR=36 [1,7–141]) than the responders ones. Although not significant, colchicine treatment appeared more effective in patients with less complete PFAPA phenotype and MEFV heterozygosity.

Looking back at the diagnosis of PFAPA: a retrospecitve analysis of a prospective cohort study

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) is the most common periodic fever syndrome of childhood. The original diagnostic criteria were introduced in 1989. However, published studies show large heterogeneity in PFAPA patients, promting attempts at refining the criteria.

International periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis syndrome cohort: description of distinct phenotypes in 301 patients

The aims of this study were to describe the clinical features of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) and identify distinct phenotypes in a large cohort of patients from different countries. We established a web-based multicentre cohort through an international collaboration within the periodic fevers working party of the Pediatric Rheumatology European Society (PReS). The inclusion criterion was a diagnosis of PFAPA given by an experienced paediatric rheumatologist participating in an international working group on periodic fever syndromes. Of the 301 patients included from the 15 centres, 271 had pharyngitis, 236 cervical adenitis, 171 oral aphthosis and 132 with all three clinical features. A total of 228 patients presented with additional symptoms (131 gastrointestinal symptoms, 86 arthralgias and/or myalgias, 36 skin rashes, 8 neurological symptoms). Thirty-one patients had disease onset after 5 years and they reported more additional symptoms. A positive family history for recurrent fever or recurrent tonsillitis was found in 81 patients (26.9%). Genetic testing for monogenic periodic fever syndromes was performed on 111 patients, who reported fewer occurrences of oral aphthosis or additional symptoms. Twenty-four patients reported symptoms (oral aphthosis and malaise) outside the flares. The CRP was >50 mg/l in the majority (131/190) of the patients tested during the fever. We describe the largest cohort of PFAPA patients presented so far. We confirm that PFAPA may present with varied clinical manifestations and we show the limitations of the commonly used diagnostic criteria. Based on detailed analysis of this cohort, a consensus definition of PFAPA with better-defined criteria should be proposed.

Marshall syndrome (PFAPA). Experience of pediatric clinic from Sibiu

PFAPA is a chronic condition including recurrent fever episodes, aphthous stomatitis, pharyngitis and adenitis. The authors emphasize peculiarities regarding diagnosis, evolution and cytokinic profile for PFAPA patients. 22 patients with PFAPA were included in study. Patients that fulfilled diagnosis criteria were analyzed regarding symptoms onset age, period of time between episodes and between disease onset and diagnosis and also data about inflammatory status. Authors compared 2 groups: “PFAPA group” including 6 patients (between febrile episodes) and “Non-PFAPA group” including 4 healthy children. Both groups were analyzed regarding serum levels of inflammatory markers and cytokines in order to identify a biological sensitive marker for PFAPA evolution pattern. Data was statistically analyzed using “independent sample t test”. Results. Authors noticed a low suspicion index for PFAPA diagnosis (underdiagnosed disorder) and significant statistical differences between the 2 groups regarding C reactive protein (CRP) serum value. Conclusions. PFAPA diagnosis is established lately, so it’s useful to disseminate information about disease. CRP remains a sensitive marker for disease activity in PFAPA patients, even out of fever attacks.

489 Interleukin Phenotype in Patients with Pfapa

BackgroundPFAPA is a chronic condition including recurrent fever episodes, aphthous stomatitis, pharyngitis, adenitis. According to a previous study, even between febrile attacks, there is increasing of pro-inflammatory mediators.AimsTo evaluate serum...

PFAPA Syndrome in a Young Adult with a History of Tonsillectomy

Since its clinical definition in 1987, the syndrome called, "periodic fever, aphtous stomatitis, pharyngitis and cervical adenitis" syndrome (PFAPA) has been considered peculiar to pediatric age. In the recent literature there are a few case reports of PFAPA in adults. We describe a case of a 21-year-old female affected by PFAPA who presented a history of tonsillectomy at the age of four. To our knowledge this is the fourth case described with a diagnosis of PFAPA in an adult with a history of tonsillectomy during childhood. Although the role of tonsillectomy in the treatment of PFAPA is still controversial, due to the lack of definitive data in literature, this case suggests that fever episodes may relapse several years after surgery.

Tonsillectomy for management of PFAPA

Since the first report by Abramson in 1989 of unexpected complete resolution of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome (PFAPA) after tonsillectomy in 4 children (Ped Infect Dis J 1989;8:119-20), many case series reported the effectiveness in halting PFAPA in 64% to 100% of patients. In the only previously published randomized controlled trial from Finland, of management of PFAPA, tonsillectomy was curative within 6 months in all 14 patients in whom it was performed versus spontaneous resolution in 6 of 12 control patients (J Pediatr 2007;151:289-92). In the prospective study reported in this issue of The Journal by Garavello et al from Italy, 19 children with PFAPA were randomized to adenotonsillectomy (A&T) and 20 children were managed medically, with 18 months of follow-up in both groups. In the surgical group, 60% of children had immediate resolution compared with 5% in the non-surgical group. Although 40% of children in the surgical group did not have immediate resolution of PFAPA, over the ensuing 18 months, those who had surgery compared with those who had medical management had significantly fewer episodes (12 vs 179), shorter episodes (1.7 vs 3.5 days) (P values < .001), and all were “cured” of febrile episodes 12 months after surgery. The two major stumbling blocks in testing treatments for PFAPA are the small numbers of patients available for study and inability to confirm the diagnosis of PFAPA, or to know whether PFAPA indeed is a single disease. The ages of patients in the current study and delineation of other clinical characteristics convinces the reader that they are a good “fit” for a PFAPA diagnosis. The immediate “cure” in about one-half of the patients and waning of symptoms over time in the other half of the patients who underwent A&T may be a reasonable expectation for other patients with PFAPA. Shorter follow-up may explain the lower “cure” rates reported in some studies, and “contamination” with children with recurring tonsillitis (in whom tonsillectomy would yield rapid benefit) could explain higher “cure” rates in still other studies. Although adenoidectomy was performed in addition to tonsillectomy in this study, this study does not address the need for adenoidectomy. Finally, although the observation of rapid defervescence of an episode with administration of a corticosteroid was used as a diagnostic criterion for PFAPA in the study by Garavello et al, caution is warranted as the specificity of such a response has not been tested. Corticosteroid can cause rapid defervescence in febrile infections as well as periodic fevers due to other autoinflammatory diseases (such as tumor necrosis factor receptor-associated periodic syndrome or hyperimmunoglobulinemia D syndrome). Article page 250▸