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.
Signs and symptoms
Cause
Possible causes include primarily factors or it may be due to an initial infection.
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), interleukin-1-related genes (interleukin-1β, interleukin 1 RN, CASP1, interleukin 18 RAP) and interferon induced (AIM2, IP-10/CXCL10) genes. T cell associated (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 (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.
Diagnosis
PFAPA is usually diagnosed based on clinical criteria, since no specific laboratory test confirms the condition. It most often begins in early childhood, typically before five years of age, though adolescent and adult cases have also been reported.[1]
Children present with recurrent febrile episodes lasting two to eight days, recurring every few weeks. During episodes, at least one of the three hallmark signs is present: aphthous stomatitis, pharyngitis, or cervical adenitis. Many patients experience more than one of these symptoms at the same time.[2]
Several sets of diagnostic criteria have been proposed. The modified Marshall criteria require regularly recurring fevers with onset before five years of age, associated aphthous ulcers, pharyngitis, or cervical adenitis, exclusion of upper respiratory infection, and normal growth and development.[3]
During attacks, inflammatory markers such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and white blood cell count are typically elevated, while results return to normal between episodes.[4]
PFAPA is a diagnosis of exclusion. Important differential diagnoses include recurrent infectious pharyngitis, cyclic neutropenia, primary immunodeficiencies, and monogenic periodic fever syndromes such as familial Mediterranean fever, mevalonate kinase deficiency, and TNF receptor–associated periodic syndrome.[5]
A rapid response to a single dose of corticosteroids at the onset of fever often with symptom resolution within 24 hours is considered supportive of PFAPA and helps distinguish it from infectious causes. Antibiotics do not alter the course of the episodes. [6]
Treatment
One treatment often used is a dose of a corticosteroid at the beginning of each fever episode. A single dose usually ends the fever within several hours. However, in some children, they can cause the fever episodes to occur more frequently. Interleukin-1 inhibition appears to be effective in treating this condition.
There has been some evidence for the use of medications to reduce the frequency of flare-ups, including colchicine and cimetidine.
Surgical removal of the tonsils appears to be beneficial compared to no surgery in symptom resolution and number of future episodes. However, the evidence to support surgery is of moderate quality.
Children with PFAPA have an impaired quality of life, which may be treated via individual Psychotherapy.
Prognosis
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