PFAPA Syndrome – Periodic fever, aphthous stomatitis, pharyngitis, adenitis

PFAPA syndrome is the most common cause of periodic fever in children. It typically starts in early childhood (between ages 2 and 5) and tends to be more common among males. Febrile episodes, called flares, last 3 to 6 days and recur about every 28 days. The syndrome causes fevers (being the main symptom) as well as sore throat, mouth ulcers, swollen lymph nodes, fatigue, chills, abdominal pain and headache. Patients are healthy between episodes, and growth is normal. PFAPA is the only periodic fever syndrome where the child outgrows the disease. However, there is evidence that in some cases, it may persist into adulthood. It is recommended that patients are screened clinically or genetically for other known periodic syndromes before diagnosing the patient with PFAPA. PFAPA is not caused by an infection. It’s not contagious. Antibiotics do not work at all.

Characteristics of Periodic fever, aphthous stomatitis, pharyngitis, adenitis

Diagnosis

Diagnosis is based on clinical findings. This is the diagnostic criteria used for PFAPA:

Regularly recurring fevers with an early age of onset (<5 years of age)
Upper respiratory infection with at least 1 of the following clinical signs:
1. Mouth ulcers or aphthae (aphthous stomatitis)
2. Lymph nodes in the neck (cervical lymphadenitis)
3. Sore throat (pharyngitis)
Completely healthy (asymptomatic) between episodes
Normal growth and development

Treatment

There is no medication to prevent this disease. However, glucocorticoids are highly effective in aborting the attacks. A single dose of prednisone (1– 2 mg/kg) given at the onset of an episode can dramatically abort fever attacks within a few hours (it may take up to 4 hours). Mouth ulcers, however, can take longer to resolve. If one dose is not effective, a second dose may be given the following day.

The administration of corticosteroids does not prevent future fever attacks. One has to know that in some cases, the use of corticosteroids may cause the patient to flare more often. Some parents prefer to avoid the use of corticosteroids by trying to control the fevers, alternating paracetamol (i.e. Tylenol in the US) and ibuprofen (Advil or Motrin in the US).

A medication which is worth trying is Colchicine, even though it’s not always effective in PFAPA patients. It reduces inflammation and, therefore, also the frequency and the severity of flares. Colchicine may be an interesting option for patients with frequent episodes.

Adenotonsillectomy

Tonsillectomy in PFAPA syndrome has proven to be a very effective method for most PFAPA patients. In a study from 2012 (see reference no. 2 below), 99 out of 102 patients with PFAPA showed complete resolution of symptoms. In a more recent study from 2018, it included 555 children with PFAPA who underwent either Tonsillectomy (TE) or adenotonsillectomy (ATE). TE or ATE had a curative effect in 509 of the 555 children with PFAPA (92%). Nevertheless, post-surgical complications should be considered (haemorrhage).

Tonsillectomy should be reserved for selected patients who do not respond to medical treatment and children with long-lasting disease affecting their quality of life.

Vitamin D

Vitamin D plays an important role in all the autoinflammatory diseases, including PFAPA. It is being considered as a possible regulator of inflammation. This is why low vitamin D levels are associated with autoinflammatory diseases.

Vitamins to reduce flares

Many US parents report that giving their PFAPA child tart cherry and vitamin D3 has shortened the flares from 4–5 days to about 2.5 days, and the fevers have become less severe. Even though these are over-the-counter vitamins which can be easily be bought at any supermarket, please discuss it with the treating physician. We are not encouraging parents anything, and we are certainly not endorsing any of these products. We just felt that if these two products have helped many patients, it was important to mention it:

Enzymatic Therapy Tart Cherry Ultra Chewable Tablets
Zahler Junior D3 Chewable 1000IU, Kids Vitamin D

Mouth ulcers

In Germany, there is a great paste for mouth ulcers. It is for children ages 2 and up. In Switzerland, the name is: SOLCOSERYL akut PasteSolcoseryl Dental Adhaesivpaste 5g.

In the US, one of the creams used by parents is Orabase by Colgate. It provides fast relief for mouth ulcers.