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-like ulcers, pharyngitis and cervical adenitis (cervical lymphadenopathy). The syndrome was described in 1987 and named two years later.[1][2][3]
| Periodic fever, aphthous stomatitis, pharyngitis and adenitis | |
|---|---|
| Other names | Periodic fever aphthous pharyngitis and cervical adenopathy (PFAPA) |
| Specialty | Pediatric, Rheumatology, Immunology |
| Symptoms | Fever recurring on a ~2–6 week cycle |
| Treatment | Tonsillectomy |
| Medication | Corticosteroids, Colchicine, Cimetidine |
Signs and symptoms
editThe key symptoms of PFAPA are those in its name: periodic high fever at intervals of about 3–5 weeks, as well as aphthous ulcers, 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 EBV, CMV, FMF) be excluded.[3]
Cause
editThe cause of PFAPA is unknown.[4] It is frequently discussed together with other periodic fever syndromes.[3]
Possible causes include primarily genetic factors or it may be due to an initial infection.
The condition appears to be the result of a disturbance of innate immunity.[5] The changes in the immune system are complex and include increased expression of complement related genes (C1QB, C2, SERPING1), interleukin-1-related genes (interleukin-1β, interleukin 1 RN, CASP1, interleukin 18 RAP) and interferon induced (AIM2, IP-10/CXCL10) genes. T cell associated genes (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 cytokines (interleukin 6, interleukin 18). Flares also manifest with a relative lymphopenia. Activated CD4+/CD25+ T-lymphocyte counts correlated negatively with serum concentrations of IP-10/CXCL10, whereas CD4+/HLA-DR+ T lymphocyte counts correlated positively with serum concentrations of the counterregulatory IL-1 receptor antagonist.[citation needed]
Diagnosis
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Treatment
editPFAPA syndrome typically resolves spontaneously. Treatment options are used to lessen the severity of episodes.[6] These treatments are either medical or surgical:
One treatment often used is a dose of a corticosteroid at the beginning of each fever episode.[4] A single dose usually ends the fever within several hours.[4] However, in some children, they can cause the fever episodes to occur more frequently.[4] Interleukin-1 inhibition appears to be effective in treating this condition.[5]
There has been some evidence for the use of medications to reduce the frequency of flare-ups, including colchicine and cimetidine.[7]
Surgical removal of the tonsils appears to be beneficial compared to no surgery in symptom resolution and number of future episodes.[6] The evidence to support surgery is; however, of moderate quality.[6]
Children with PFAPA have an impaired quality of life, which may be treated via individual counseling.[8]
Prognosis
editAccording to present research, PFAPA does not lead to other diseases and spontaneously resolves as the child gets older, with no long term physical effects.[2] [9] [10] However, PFAPA has been found in adults and may not spontaneously resolve.[11][non-primary source needed] Children with PFAPA experience lower physical, emotional, and psychosocial functioning.[8] Their performance in school is also substantially impacted.[8]
References
edit- ^ Thomas KT, Feder HM, Lawton AR, Edwards KM (July 1999). "Periodic fever syndrome in children". The Journal of Pediatrics. 135 (1): 15–21. doi:10.1016/S0022-3476(99)70321-5. PMID 10393598.
- ^ a b Padeh S, Brezniak N, Zemer D, Pras E, Livneh A, Langevitz P, et al. (July 1999). "Periodic fever, aphthous stomatitis, pharyngitis, and adenopathy syndrome: clinical characteristics and outcome". The Journal of Pediatrics. 135 (1). Mosby: 98–101. doi:10.1016/S0022-3476(99)70335-5. PMID 10393612. Archived from the original on 2013-02-22.
- ^ a b c Long SS (July 1999). "Syndrome of Periodic Fever, Aphthous stomatitis, Pharyngitis, and Adenitis (PFAPA)--what it isn't. What is it?". The Journal of Pediatrics. 135 (1). Mosby: 1–5. doi:10.1016/S0022-3476(99)70316-1. PMID 10393593.
- ^ a b c d Vigo G, Zulian F (November 2012). "Periodic fevers with aphthous stomatitis, pharyngitis, and adenitis (PFAPA)". Autoimmunity Reviews. 12 (1): 52–55. doi:10.1016/j.autrev.2012.07.021. PMID 22878272.
- ^ a b Stojanov S, Lapidus S, Chitkara P, Feder H, Salazar JC, Fleisher TA, et al. (April 2011). "Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) is a disorder of innate immunity and Th1 activation responsive to IL-1 blockade". Proceedings of the National Academy of Sciences of the United States of America. 108 (17): 7148–7153. Bibcode:2011PNAS..108.7148S. doi:10.1073/pnas.1103681108. PMC 3084055. PMID 21478439.
- ^ a b c Burton MJ, Pollard AJ, Ramsden JD, Chong LY, Venekamp RP (December 2019). "Tonsillectomy for periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome (PFAPA)". The Cochrane Database of Systematic Reviews. 2019 (12): CD008669. doi:10.1002/14651858.CD008669.pub3. PMC 6953364. PMID 31886897.
- ^ Vanoni F, Theodoropoulou K, Hofer M (June 2016). "PFAPA syndrome: a review on treatment and outcome". Pediatric Rheumatology Online Journal. 14 (1): 38. doi:10.1186/s12969-016-0101-9. PMC 4924332. PMID 27349388.
- ^ a b c Grimwood C, Kone-Paut I, Piram M, Rossi-Semerano L, Hentgen V (August 2018). "Health-related quality of life in children with PFAPA syndrome". Orphanet Journal of Rare Diseases. 13 (1): 132. doi:10.1186/s13023-018-0878-3. PMC 6085641. PMID 30092788.
- ^ Kontzias A (September 2022). "PFAPA Syndrome - Pediatrics". The Merck Manual.
- ^ "Periodic Fever Syndrome". Cleveland Clinic. 18 January 2019.
- ^ Padeh S, Stoffman N, Berkun Y (May 2008). "Periodic fever accompanied by aphthous stomatitis, pharyngitis and cervical adenitis syndrome (PFAPA syndrome) in adults" (PDF). The Israel Medical Association Journal. 10 (5): 358–360. PMID 18605359.