View source for Periodic fever, aphthous stomatitis, pharyngitis and adenitis

{{Infobox medical condition (new)
| name          = Periodic fever, aphthous stomatitis, pharyngitis and adenitis
| synonyms      = '''Periodic fever aphthous pharyngitis and cervical adenopathy''' ('''PFAPA''')
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| specialty     = [[Pediatric]], [[Rheumatology]], [[Immunology]]
| symptoms      = [[Fever]] recurring on a ~2–6 week cycle
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| treatment     = [[Tonsillectomy]]
| medication    = [[Corticosteroids]], [[Colchicine]], [[Cimetidine]]
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'''Periodic fever, aphthous stomatitis, pharyngitis and adenitis''' syndrome is a medical condition, typically occurring in young children, in which high [[fever]] occurs periodically at intervals of about 3–5 weeks, frequently accompanied by [[Aphthous stomatitis#RAS type ulceration|aphthous-like ulcer]]s, [[pharyngitis]] and cervical adenitis ([[cervical lymphadenopathy]]). The syndrome was described in 1987 and named two years later.<ref name="ThomasPFAPA">{{cite journal | vauthors = Thomas KT, Feder HM, Lawton AR, Edwards KM | title = Periodic fever syndrome in children | journal = The Journal of Pediatrics | volume = 135 | issue = 1 | pages = 15–21 | date = July 1999 | pmid = 10393598 | doi = 10.1016/S0022-3476(99)70321-5 }}</ref><ref name="padeh_PFAPA" /><ref name="SarahLongPFAPA" />
==Signs and symptoms==
The key symptoms of PFAPA are those in its name: periodic high [[fever]] at intervals of about 3–5 weeks, as well as [[aphthous ulcer]]s, [[pharyngitis]] and [[adenitis]]. In between episodes, and even during the episodes, the children appear healthy. At least 6 months of episodes. Diagnosis requires recurrent negative throat cultures and that other causes (such as [[Epstein–Barr virus|EBV]], [[Cytomegalovirus|CMV]], [[Familial Mediterranean fever|FMF]]) be excluded.<ref name="SarahLongPFAPA">{{cite journal | vauthors = Long SS | title = Syndrome of Periodic Fever, Aphthous stomatitis, Pharyngitis, and Adenitis (PFAPA)--what it isn't. What is it? | journal = The Journal of Pediatrics | volume = 135 | issue = 1 | pages = 1–5 | date = July 1999 | pmid = 10393593 | doi = 10.1016/S0022-3476(99)70316-1 | publisher = Mosby | doi-access = free }}</ref>
==Cause==
The cause of PFAPA is unknown.<ref name=Vigo2012>{{cite journal | vauthors = Vigo G, Zulian F | title = Periodic fevers with aphthous stomatitis, pharyngitis, and adenitis (PFAPA) | journal = Autoimmunity Reviews | volume = 12 | issue = 1 | pages = 52–55 | date = November 2012 | pmid = 22878272 | doi = 10.1016/j.autrev.2012.07.021 }}</ref> It is frequently discussed together with other [[periodic fever syndrome]]s.<ref name="SarahLongPFAPA" />
Possible causes include primarily [[gene]]tic factors or it may be due to an initial [[infection]].
The condition appears to be the result of a disturbance of innate immunity.<ref name="Stojanov2011">{{cite journal | vauthors = Stojanov S, Lapidus S, Chitkara P, Feder H, Salazar JC, Fleisher TA, Brown MR, Edwards KM, Ward MM, Colbert RA, Sun HW, Wood GM, Barham BK, Jones A, Aksentijevich I, Goldbach-Mansky R, Athreya B, Barron KS, Kastner DL | display-authors = 6 | title = Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) is a disorder of innate immunity and Th1 activation responsive to IL-1 blockade | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = 17 | pages = 7148–7153 | date = April 2011 | pmid = 21478439 | pmc = 3084055 | doi = 10.1073/pnas.1103681108 | bibcode = 2011PNAS..108.7148S | doi-access = free }}</ref> The changes in the immune system are complex and include increased expression of complement related genes ([[C1QB]], [[Complement component 2|C2]], [[SERPING1]]), interleukin-1-related genes ([[interleukin-1β]], [[Interleukin-1 receptor antagonist|interleukin 1 RN]], [[CASP1]], [[IL18RAP|interleukin 18 RAP]]) and [[interferon]] induced ([[AIM2]], IP-10/[[CXCL10]]) genes. [[T cell]] associated [[gene]]s ([[CD3 (immunology)|CD3]], [[CD8B]]) are down regulated. Flares are accompanied by increased serum levels of activated T lymphocyte chemokines (IP-10/CXCL10, MIG/[[CXCL9]]), [[G-CSF]] and proinflammatory [[cytokine]]s ([[interleukin 6]], [[interleukin 18]]). Flares also manifest with a relative [[lymphopenia]]. Activated [[CD4]]<sup>+</sup>/[[CD25]]<sup>+</sup> T-lymphocyte counts correlated negatively with serum concentrations of IP-10/CXCL10, whereas CD4<sup>+</sup>/[[HLA-DR]]<sup>+</sup> T lymphocyte counts correlated positively with serum concentrations of the counterregulatory IL-1 receptor antagonist.{{citation needed|date=June 2020}}
==Diagnosis==
{{Empty section|date=July 2018}}
==Treatment==
PFAPA syndrome typically resolves spontaneously. Treatment options are used to lessen the severity of episodes.<ref name=":0">{{cite journal | vauthors = Burton MJ, Pollard AJ, Ramsden JD, Chong LY, Venekamp RP | title = Tonsillectomy for periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome (PFAPA) | journal = The Cochrane Database of Systematic Reviews | volume = 2019 | issue = 12 | pages = CD008669 | date = December 2019 | pmid = 31886897 | pmc = 6953364 | doi = 10.1002/14651858.CD008669.pub3 }}</ref> These treatments are either medical or surgical:
One treatment often used is a dose of a [[corticosteroid]] at the beginning of each fever episode.<ref name=Vigo2012/> A single dose usually ends the fever within several hours.<ref name=Vigo2012/> However, in some children, they can cause the fever episodes to occur more frequently.<ref name=Vigo2012/> [[Interleukin-1]] inhibition appears to be effective in treating this condition.<ref name="Stojanov2011" />
There has been some evidence for the use of medications to reduce the frequency of flare-ups, including [[colchicine]] and [[cimetidine]].<ref name="ped-rheum">{{cite journal | vauthors = Vanoni F, Theodoropoulou K, Hofer M | title = PFAPA syndrome: a review on treatment and outcome | journal = Pediatric Rheumatology Online Journal | volume = 14 | issue = 1 | pages = 38 | date = June 2016 | pmid = 27349388 | pmc = 4924332 | doi = 10.1186/s12969-016-0101-9 | doi-access = free }}</ref>
Surgical removal of the tonsils appears to be beneficial compared to no surgery in symptom resolution and number of future episodes.<ref name=":0" /> The evidence to support surgery is; however, of moderate quality.<ref name=":0" />
Children with PFAPA have an impaired quality of life, which may be treated via individual [[Psychotherapy|counseling]].<ref name=":1">{{cite journal | vauthors = Grimwood C, Kone-Paut I, Piram M, Rossi-Semerano L, Hentgen V | title = Health-related quality of life in children with PFAPA syndrome | journal = Orphanet Journal of Rare Diseases | volume = 13 | issue = 1 | pages = 132 | date = August 2018 | pmid = 30092788 | pmc = 6085641 | doi = 10.1186/s13023-018-0878-3 | doi-access = free }}</ref>
==Prognosis==
According to present research, PFAPA does not lead to other diseases and spontaneously resolves as the child gets older, with no long term physical effects.<ref name="padeh_PFAPA">{{cite journal | vauthors = Padeh S, Brezniak N, Zemer D, Pras E, Livneh A, Langevitz P, Migdal A, Pras M, Passwell JH | display-authors = 6 | title = Periodic fever, aphthous stomatitis, pharyngitis, and adenopathy syndrome: clinical characteristics and outcome | journal = The Journal of Pediatrics | volume = 135 | issue = 1 | pages = 98–101 | date = July 1999 | pmid = 10393612 | doi = 10.1016/S0022-3476(99)70335-5 | url = http://padeh.net/Jpedpfapa.htm | url-status = dead | publisher = Mosby | archive-url = https://archive.today/20130222074700/http://padeh.net/Jpedpfapa.htm | archive-date = 2013-02-22 }}</ref>
<ref>{{Cite web | vauthors = Kontzias A | date = September 2022 | work = The Merck Manual | url=http://www.merck.com/mmpe/sec19/ch297/ch297g.html |title = PFAPA Syndrome - Pediatrics}}</ref>
<ref>{{Cite web | url=http://my.clevelandclinic.org/disorders/periodic_fever_syndrome/rheumatology_overview.aspx | title=Periodic Fever Syndrome | work = Cleveland Clinic | date = 18 January 2019 }}</ref>
However, PFAPA has been found in adults and may not spontaneously resolve.<ref>{{cite journal | vauthors = Padeh S, Stoffman N, Berkun Y | title = Periodic fever accompanied by aphthous stomatitis, pharyngitis and cervical adenitis syndrome (PFAPA syndrome) in adults | journal = The Israel Medical Association Journal | volume = 10 | issue = 5 | pages = 358–360 | date = May 2008 | pmid = 18605359 | url = http://www.ima.org.il/FilesUpload/IMAJ/0/43/21995.pdf }}</ref>{{npsn|date=December 2013}} Children with PFAPA experience lower physical, emotional, and psychosocial functioning.<ref name=":1" /> Their performance in school is also substantially impacted.<ref name=":1" />
== References ==
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== External links ==
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{{General symptoms and signs}}
[[Category:Fever]]
[[Category:Pediatrics]]
[[Category:Autoinflammatory syndromes]]
[[Category:Otorhinolaryngology]]