Periodic fever, aphthous stomatitis, pharyngitis and adenitis
|Periodic fever, aphthous stomatitis, pharyngitis and adenitis|
|Classification and external resources|
Periodic fever, aphthous stomatitis, pharyngitis and adenitis or periodic fever aphthous pharyngitis and cervical adenopathy (PFAPA) syndrome is a medical condition, typically starting in young children, in which high fever occurs periodically at intervals of about 3–5 weeks, frequently accompanied by aphthous-like ulcers, pharyngitis and/or cervical adenitis (cervical lymphadenopathy). The syndrome was described in 1987 and named two years later.
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 ulcers, pharyngitis and/or 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.
According to recent information that has been gathered, there has been some genetic links that are possible.
The condition appears to be the result of a disturbance of innate immunity. The changes in the immune system are complex and include increased expression of complement related genes (C1QB, C2, SERPING1), interleulkin-1-related genes (interleukin-1B, 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.
A possible treatment for PFAPA is a single dose of prednisone (1–2 mg per kg body mass) at the beginning of each fever episode. A single dose usually terminates the fever within several hours. However, in some children, prednisone causes the fever episodes to occur more frequently (and more regularly). In several studies, adenotonsillectomy was found to completely resolve symptoms. Yet other studies had differing results, most being positive. Parents of children with PFAPA regularly report improvements after the children have had surgical treatment. Some children stop having episodes, others have a break in the cycle for a few months and then it comes back but the episodes are less intense.
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.   However, PFAPA has been found in adults and may not spontaneously resolve.[non-primary source needed]
- Thomas, Kenneth Tyson; Feder, Lawton, Edwards (1999). "Periodic fever syndrome in children". Journal of Pediatrics (Mosby, Inc.) 135: 1–5. doi:10.1016/S0022-3476(99)70316-1. Retrieved 2008-03-07.
- Padeh, Shai; (eight others) (1999). "Periodic fever, aphthous stomatitis, pharyngitis, and adenopathy syndrome: Clinical characteristics and outcome". Journal of Pediatrics (Mosby, Inc.) 135 (1): 98–101. doi:10.1016/S0022-3476(99)70335-5. PMID 10393612. Retrieved 2008-03-07.
- Long, Sarah S. (1999). "Syndrome of Periodic Fever, Aphthous stomatitis, Pharyngitis, and Adenitis (PFAPA) - What it isn't. What is it?". Journal of Pediatrics (Mosby, Inc.) 135: 1–5. doi:10.1016/S0022-3476(99)70316-1. Retrieved 2008-03-07.
- 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 (2011) Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) is a disorder of innate immunity and Th1 activation responsive to IL-1 blockade. Proc Natl Acad Sci U S A
- Licameli, Greg, MD, MHCM; Jeffrey, Jessica, MA; Luz, Jennifer, BS; Jones, Dwight, MD; Kenna, Margaret, MD, MPH, Archives of Otolaryngology - Head and Neck Surgery, 2008;134(2):136-140.
- Greg Licameli, MD, MHCM; Maranda Lawton, MS, PA-C; Margaret Kenna, MD, MPH; Fatma Dedeoglu, MD:Long-term Surgical Outcomes of Adenotonsillectomy for PFAPA Syndrome. In: Arch Otolaryngol Head Neck Surg. 2012;138(10):902-906
- Padeh, S; Stoffman, N; Berkun, Y (May 2008). "Periodic fever accompanied by aphthous stomatitis, pharyngitis and cervical adenitis syndrome (PFAPA syndrome) in adults.". The Israel Medical Association journal : IMAJ 10 (5): 358–60. PMID 18605359.