Previous Presentation: This article was presented at the American Society of Pediatric Otolaryngology 2012 Annual Meeting; April 22, 2012; San Diego, California. [jamanetwork.com]

Other than main diagnostic features were present in 43.5% of patients and this finding suggests the variability of presentation of this disorder. This finding is confirmed by other studies (Table 3). [dovepress.com]

OR4C45 1 100% Many novel variants, also present in controls MUC17 91 90% Mucin gene MUC16 26 90% Mucin gene TTN 18 90% Low coverage regions ZNF492/ZNF98 16 90% Many novel variants, also present in controls GOGAL6L1 14 90% Not well annotated gene PCMTD1 [ncbi.nlm.nih.gov]

It is also conceivable that a small percentage of adult patients with recurrent fevers could present the same clinical features of paediatric PFAPA deserving an appropriate treatment and follow-up. [ard.bmj.com]

• Cervical Lymphadenopathy

  However, as almost all adult patients with PFAPA syndrome present with high fever and at least two symbolic symptoms of this syndrome such as aphthous stomatitis, tonsillitis with white exudate, and/or cervical lymphadenopathy at a similar frequency as [onlinelibrary.wiley.com]

  Background Periodic Fever, Aphthous stomatitis, Pharyngitis and Cervical Adenitis (PFAPA) syndrome is characterized by regularly recurrent fever flares of early onset, accompanied by pharyngitis, cervical lymphadenopathy and oral aphthous ulcers [1]. [ped-rheum.biomedcentral.com]

  In our group of patients, pharyngitis (79%) and cervical lymphadenopathy (84%) were commonly found, while aphthous ulcers (44%) were not as frequently reported by the parents, patients, or primary care providers who monitored these patients when they [jamanetwork.com]

• Fever

  Other periodic fever syndromes PFAPA syndrome may resemble other periodic fever syndromes, but it can be distinguished by careful attention to symptoms as well as the fever cycle history. [jamanetwork.com]

  Abstract The syndrome of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA syndrome) is the most common cause of periodic fever in childhood. [ped-rheum.biomedcentral.com]

  Colchicine prophylaxis for frequent periodic fever, aphthous stomatitis, pharyngitis and adenitis episodes. Acta Paediatr 2008; 97: 1090-1092 36 Thomas KT, Feder HM, Lawton AR et al. Periodic fever syndrome in children. [thieme-connect.com]

  Periodic fever syndrome in children. Thomas KT1, Feder HM Jr, Lawton AR, Edwards KM. 4. J Pediatr. 1999 Jul;135(1):98-101. Periodic fever, aphthous stomatitis, pharyngitis, and adenopathy syndrome: clinical characteristics and outcome. [link.springer.com]

  In particular, the periodic pattern of fever is usually recognized tardily, leading to an avoidable diagnostic delay, highlighting the utility of a fever diary in patients with recurrent episodes of fever (15). [frontiersin.org]

• Pain

  Some children have other symptoms like joint pain, rash, abdominal pain, headache, vomiting or diarrhea. Children are completely well between episodes. [rheumatology.org]

  Children may complain of pain in the throat and they may find it hard to swallow because of this pain. They may also complain of pain in the mouth because of mouth ulcers. The glands in the neck may be enlarged. [aboutkidshealth.ca]

  “We hope that eventually children don’t have to experience such painful disruptions for years and that clinical trials and other follow-up tests can lead to a successful treatment plan.” [genome.gov]

  arthritis, and peritonitis HIDS Autosomal recessive MVK Effective Adenitis, arthritis, and abdominal pain TRAPS Autosomal recessive TNFRSFIA Effective Myalgia, conjunctivitis, and abdominal pain CAPS, cryopyrin‐associated periodic syndromes; HIDS, hyperimmunoglobulin [onlinelibrary.wiley.com]

  Common symptoms also include: Mouth sores (aphthous stomatitis) Sore throat with redness (pharyngitis) Enlarged lymph nodes of the neck (adenitis) White patches on the tonsils Less common symptoms include: Headache Joint pain Rash Belly (abdominal) pain [cedars-sinai.org]

• Lymphadenopathy

  Hyper-IgD syndrome presents with lymphadenopathy and high fever, but it is not as regularly periodic in nature as PFAPA syndrome. Symptoms include diarrhea, arthralgia, and maculopapular lesions that are distinct from aphthous stomatitis. [jamanetwork.com]

  Publication History 26 May 2011 13 October 2011 Publication Date: 28 February 2012 (online) Zusammenfassung Hintergrund und Fragestellung: Das PFAPA-Syndrom ist durch das gemeinsame Auftreten von periodischem Fieber, aphthöser Stomatitis und zervikaler Lymphadenopathie [thieme-connect.com]

  However, as almost all adult patients with PFAPA syndrome present with high fever and at least two symbolic symptoms of this syndrome such as aphthous stomatitis, tonsillitis with white exudate, and/or cervical lymphadenopathy at a similar frequency as [onlinelibrary.wiley.com]

  Background Periodic Fever, Aphthous stomatitis, Pharyngitis and Cervical Adenitis (PFAPA) syndrome is characterized by regularly recurrent fever flares of early onset, accompanied by pharyngitis, cervical lymphadenopathy and oral aphthous ulcers [1]. [ped-rheum.biomedcentral.com]

• Amyloidosis

  Familial Mediterranean fever involves periodic fever, but its symptoms of peritonitis, erysypeloid rash, and amyloidosis are not found in patients with PFAPA syndrome. [jamanetwork.com]

  Association of mutations in the NALP3/CIAS1/PYPAF1 gene with a broad phenotype including recurrent fever, cold sensitivity, sensorineural deafness, and AA amyloidosis. Arthritis Rheum. 46, 2445–2452 (2002). [ncbi.nlm.nih.gov]

• Chills

  Other described symptoms or signs are chills (80 %), headache (65 %) and digestive symptoms (nauseas, abdominalgia, diarrhoea) in a minor proportion and cutaneous exanthema5,6. [elsevier.es]

• Pharyngitis

  Das Vollbild ist gekennzeichnet durch periodische Fieberschübe, begleitet von einer aphthösen Stomatitis, Pharyngitis und zervikalen Lymphadenitis. [link.springer.com]

  Schlüsselwörter PFAPA-Syndrom - periodisches Fieber - aphthöse Stomatitis - Pharyngitis - zervikale Lymphadenitis - Erwachsene - Rezidiv - autoinflammatorische Syndrome Keywords PFAPA syndrome - periodic fever - aphthous stomatitis - pharyngitis - cervical [thieme-connect.com]

  Similar articles Tonsillectomy for periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome (PFAPA). Burton MJ, Pollard AJ, Ramsden JD. Burton MJ, et al. [pubmed.ncbi.nlm.nih.gov]

  Abstract The syndrome of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA syndrome) is the most common cause of periodic fever in childhood. [ped-rheum.biomedcentral.com]

  The fever cycle is associated with 1 or more of the following: aphthous stomatitis, pharyngitis, and cervical adenopathy. [jamanetwork.com]

• Sore Throat

  Less stringent recruitment criteria were applied and it was possible that patients with other types of recurrent sore throats might have been recruited and included in the trial. [cochrane.org]

  It causes repeated episodes of fever, mouth sores, sore throat, and swollen lymph nodes. PFAPA usually starts in early childhood between ages 2 and 5. In very rare cases, the syndrome may start in adulthood. [cedars-sinai.org]

  This syndrome includes recurrent episodes of fever with aphthous stomatitis (mouth sores) and pharyngitis (sore throat with redness). [rheumatology.org]

  Children with PFAPA can also have swollen neck glands, sore throat and/or sores in the mouth. Fever that occurs on a regular basis is called periodic fever. Swollen glands are called adenitis. Sore throat is called pharyngitis. [aboutkidshealth.ca]

• Abdominal Pain

  pain, arthritis, and peritonitis HIDS Autosomal recessive MVK Effective Adenitis, arthritis, and abdominal pain TRAPS Autosomal recessive TNFRSFIA Effective Myalgia, conjunctivitis, and abdominal pain CAPS, cryopyrin‐associated periodic syndromes; HIDS [onlinelibrary.wiley.com]

  Some children have other symptoms like joint pain, rash, abdominal pain, headache, vomiting or diarrhea. Children are completely well between episodes. [rheumatology.org]

  Rarely, patients experience rashes, headaches, abdominal pain, or arthralgia. [jamanetwork.com]

  Common symptoms also include: Mouth sores (aphthous stomatitis) Sore throat with redness (pharyngitis) Enlarged lymph nodes of the neck (adenitis) White patches on the tonsils Less common symptoms include: Headache Joint pain Rash Belly (abdominal) pain [cedars-sinai.org]

• Vomiting

  Some children have other symptoms like joint pain, rash, abdominal pain, headache, vomiting or diarrhea. Children are completely well between episodes. [rheumatology.org]

  […] also include: Mouth sores (aphthous stomatitis) Sore throat with redness (pharyngitis) Enlarged lymph nodes of the neck (adenitis) White patches on the tonsils Less common symptoms include: Headache Joint pain Rash Belly (abdominal) pain Nausea and vomiting [cedars-sinai.org]

  Associated symptoms were abdominal pain (23.1%), vomiting (10.2%), diarrhoea (7.7%), headache (5.1%) and arthralgia (5.1%) – (Figure 1). In 17.9% of patients, pharyngeal exudates were found. [dovepress.com]

• Aphthous Stomatitis

  Physicianse perspectives on the diagnosis and management of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome. [link.springer.com]

  Syndrome of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) in siblings. Clin Rheumatol 2009; 28: 1235-1237 [thieme-connect.com]

  Similar articles Tonsillectomy for periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome (PFAPA). Burton MJ, Pollard AJ, Ramsden JD. Burton MJ, et al. [pubmed.ncbi.nlm.nih.gov]

  Abstract The syndrome of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA syndrome) is the most common cause of periodic fever in childhood. [ped-rheum.biomedcentral.com]

  […] least one of three main signs: aphthous stomatitis, cervical adenitis and pharyngitis.1 The fever episodes have little or no response to common antipyretics. [dovepress.com]

• Aphthous Ulceration

  Skip to main content Language Options Periodic fever adenitis pharyngitis aphthous ulcer (PFAPA) syndrome P Periodic fever adenitis pharyngitis aphthous ulcer (PFAPA) syndrome Periodic fever adenitis pharyngitis aphthous ulcer (PFAPA) syndrome English [aboutkidshealth.ca]

  Patients with Behçet syndrome present with ulcers in the oral cavity, but these ulcers are large, painful, and numerous in contrast to the small, punctate ulcers that are frequently seen in PFAPA syndrome. [jamanetwork.com]

  Background Periodic Fever, Aphthous stomatitis, Pharyngitis and Cervical Adenitis (PFAPA) syndrome is characterized by regularly recurrent fever flares of early onset, accompanied by pharyngitis, cervical lymphadenopathy and oral aphthous ulcers [1]. [ped-rheum.biomedcentral.com]

• Erythema

  On physical examination, aphthous stomatitis, enlargement of the bilateral submandibular lymph nodes with tenderness, pharyngeal erythema, and enlarged palatine tonsils with white exudates were observed (Figure 1). [onlinelibrary.wiley.com]

• Arthritis

  Social/economic costs and health-related quality of life in patients with juvenile idiopathic arthritis in Europe. [frontiersin.org]

  […] and conjunctivitis FMF Autosomal recessive MEFV Ineffective Abdominal pain, arthritis, and peritonitis HIDS Autosomal recessive MVK Effective Adenitis, arthritis, and abdominal pain TRAPS Autosomal recessive TNFRSFIA Effective Myalgia, conjunctivitis [onlinelibrary.wiley.com]

  Semin Arthritis Rheum. 2016 Feb;45(4):471-4. doi: 10.1016/j.semarthrit.2015.07.005. Epub 2015 Jul 21. Colchicine as a therapeutic option in periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) syndrome. [link.springer.com]

  Arthritis Care Res. 2016;68:1859–1865. doi:10.1002/acr.22901 33. Costagliola G, Maiorino G, Consolini R. [dovepress.com]

  Systemic onset juvenile rheumatoid arthritis (Still disease) presents with high fevers and adenopathy as well as arthritis, rash, hepatosplenomegaly, pleuritis, and pericarditis. The fevers are not typically periodic, and patients are sicker. [jamanetwork.com]

• Headache

  Some children have other symptoms like joint pain, rash, abdominal pain, headache, vomiting or diarrhea. Children are completely well between episodes. [rheumatology.org]

  There are prodromal symptoms 24 hours before the beginning of fever in 75 % of patients and they are usually headache, irritability or unspecific mialgia. [elsevier.es]

  Compared to other studies, we have found myalgia, arthralgia and headache in a smaller proportion of patients, supported by the smaller median age of our patients. [dovepress.com]

  Common symptoms also include: Mouth sores (aphthous stomatitis) Sore throat with redness (pharyngitis) Enlarged lymph nodes of the neck (adenitis) White patches on the tonsils Less common symptoms include: Headache Joint pain Rash Belly (abdominal) pain [cedars-sinai.org]

Otherwise, the workup for each patient was negative for infectious processes, rheumatologic disorders, and genetic syndromes when performed as directed by the primary care physician or our rheumatology colleagues. [jamanetwork.com]

PFAPA syndrome: a review on treatment and outcome. [ped-rheum.biomedcentral.com]

Neither study masked participants and investigators to the type of treatment received. Participants in the control groups of both studies received standard medical treatment. [cochrane.org]

Additionally, the majority of the patients receive an inappropriate antibiotic treatment. [frontiersin.org]

Recent contributions to the literature have focused on the utility of surgical intervention as treatment. [jamanetwork.com]

A positive response to treatment (with steroids) also helps providers finalize the diagnosis. How is PFAPA syndrome treated? Healthcare providers are still working to figure out the best treatment for PFAPA. [cedars-sinai.org]

These diseases often require a more intensive therapeutic approach and have a more severe course and long-term prognosis. [ped-rheum.biomedcentral.com]

Discussion PFAPA is a common auto-inflammatory disease with an overall good prognosis. [ncbi.nlm.nih.gov]

Periodic fever with aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome belongs to the AIS group, although the etiology of this disease is still unknown. [ncbi.nlm.nih.gov]

Normally, a detailed anamnesis and physical exploration, together with certain analytical findings, are enough to direct the etiology of such episodes5,8-9 (table II). [elsevier.es]

Although the fever, stomatitis, and pharyngitis of cyclic neutropenia are very similar to PFAPA syndrome, the former disease process is distinguished by a cyclic decrease in neutrophils, abdominal pain, and diarrhea.4 Infectious vs immunologic etiology [jamanetwork.com]

However, none of these variants alone seem to be relevant for the disease etiology, suggesting an oligenic or polygenic background. [ped-rheum.biomedcentral.com]

PMID: 36116090 Epidemiology and clinical features of PFAPA: a retrospective cohort study of 336 patients in western Sweden. Rydenman K, Fjeld H, Hätting J, Berg S, Fasth A, Wekell P. Rydenman K, et al. [pubmed.ncbi.nlm.nih.gov]

Despite the current lack of a candidate gene for PFAPA syndrome, various studies point to the fact that this auto-inflammatory disease is not a sporadic disorder but based on a genetic predisposition.8 Major epidemiologic evidence for this assumption [nature.com]

The CoLaus study: a population-based study to investigate the epidemiology and genetic determinants of cardiovascular risk factors and metabolic syndrome. BMC Cardiovasc. Disord. 8, 6 (2008). [PMC free article] [PubMed] [Google Scholar] Brickell P. [ncbi.nlm.nih.gov]

[…] in ∼20% of patients with PFAPA.10 Such variants might increase the probability of dysregulated interleukin 1β production by monocytes during febrile episodes typical for PFAPA syndrome.10 Overall, the hitherto published functional studies point to a pathophysiologic [nature.com]

Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease (*). Annu. Rev. Immunol. 27, 621–668 (2009). [PMC free article] [PubMed] [Google Scholar] Marshall G. S., Edwards K. M., Butler J. & Lawton A. R. [ncbi.nlm.nih.gov]

The aim of treatment is to control symptoms during the episodes of fever, to shorten the duration of the episodes, and to prevent episodes from occurring. [rheumatology.org]

These may help prevent future episodes in a small number of children Surgery to remove the tonsils. This may prevent future episodes in some children. [cedars-sinai.org]

Disease Outcome The response to conventional treatment of the flares with corticosteroids and the need of preventive therapy with colchicine or adenotonsillectomy were reported. [frontiersin.org]

Glucocorticoids are highly effective in aborting the attacks, but there are limited data on the effectiveness of any preventive medication in PFAPA. [ped-rheum.biomedcentral.com]