Periodic fever, aphthous stomatitis, pharyngitis and adenitis

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.[3]

The 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-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.

PFAPA 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]

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.[2] [9] [10] However, PFAPA has been found in adults and may not spontaneously resolve.[11] Children with PFAPA experience lower physical, emotional, and psychosocial functioning.[8] Their performance in school is also substantially impacted.[8]