Effects of Probiotic Addition to Corticosteroid Treatment for PFAPA

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) was first described in 1987 in a study of 12 pediatric patients. PFAPA is predominately considered a pediatric illness with onset typically occurring under the age of 5. This syndrome is characterized by periodic febrile episodes (39°C - 42°C) lasting an average of 4 days with recurrence approximately every 21-30 days. Patients classically exhibit at least one of three major associated symptoms; aphthous stomatitis, pharyngitis, or cervical adenitis. Between periods of fever, patients are asymptomatic and do not experience long-term deleterious effects on growth or development. Currently, the etiology of this syndrome is unknown but does not appear to be heritable or target specific populations.

Due to a lack of applicable diagnostic tests, the identification of PFAPA is predominantly dependent on patient history and physical examination. This methodology relies heavily upon clinical presentation of the patient's illness to rule out other causes of periodic fever. As a result of the unknown cause of PFAPA, there are several proposed treatment approaches available. Corticosteroids are the current standard of care; typically a single dose of prednisolone (1 mg/kg), given upon first signs of fever with a subsequent dose during the febrile period if necessary. Several studies have shown that administration of prednisolone was sufficient to abort the febrile episode. However, this treatment method typically results in a decrease in the healthy interval between fever reoccurrence. The reduction in fever allows for children to attend school and participate in other activates, but the increased frequency provides additional complications for children and parents.

Oral cimetidine, a histamine H-2 receptor agonist that results in reduced production of stomach acid, has also been used as possible treatment. This treatment has shown to inhibit febrile episodes, it was only effective in <30% of patients.

If medication therapy fails to resolve recurrent febrile episodes, the option of tonsillectomy presents a possible alternative. PFAPA syndrome was shown to resolve in the majority of patients, however this not preferred as a first line treatment due to the risks associated with surgery and general anesthesia.

Recently published literature suggests a potential new treatment for PFAPA targeting chemokines and proinflammatory cytokines. A possible method for the inhibition of cyclic inflammatory responses in PFAPA would be the exposure of patients to a safe level of continuous low-grade inflammation, resulting from an immune response. In previous studies investigating allergy and eczema relief in pediatric populations, it was shown that administration of probiotics induced elevated levels of inflammatory markers. These low level inflammatory responses resulted in no adverse effects and provided an immunologic activation benefit. Use of probiotics provides a previously unstudied approach to the treatment of PFAPA. Dr. Nicholas Bennett has also observed anecdotal evidence that patients who self-administered probiotics experienced relief of their PFAPA symptoms.