Recurrent fever, aphthous stomatitis, pharyngitis, cervical lymphadenitis (PFAPA)
For the first time in the international literature, 12 cases of the disease were described by the American doctor Gary Marshall and co-authors in 1987. Currently, it is considered the most common disease of the group of periodic fevers. Many studies have been conducted to identify the genetic basis but have not yet identified a single clear mutation (such as in case of Familial Mediterranean fever) but have confirmed some genetic similarities with Behçet’s disease and recurrent aphthous ulcers. Another specific feature is that, both in Armenia and in other countries, a significant number of patients with PFAPA have one or two of the mutations that cause FMF (in case of two mutations it could be the presence of two diseases at the same time). As with other recurrent fevers, the pathogenesis is associated with disturbances in the activity of interleukins and inflammasomes.
The disease’s prevalence is slightly higher among boys. In the majority of cases, clinical manifestations are expressed before the age of 5 years, but cases are also described at a later age, including in adults.
Clinical manifestations are known recurrent attacks of fever lasting 3 – 7 days, with an average frequency of 2 – 8 weeks, pharyngotonsillitis (more often exudative), aphthous. Lymphadenitis which mainly involves the anterior cervical nodes. There are usually no complaints between exacerbations. It is known that during the course of the disease there can be “disease-free periods” that can last for months, relatively more often in the summer. Many cases of the disease pass spontaneously.
Clinical diagnosis is based on the aforementioned 4 signs: recurrent fever, pharyngotonsillitis, lymphadenitis, periodicity. The presence of similar phenomena among close relatives is in favor of the diagnosis. Diarrhea, chest pains, rash, arthritis are among the signs against the diagnosis.
Differential diagnosis should be made with FMF, recurrent streptococcal tonsillitis, Behçet’s disease, other rheumatological diseases, as well as with the recently described Syndrome of Undifferentiated Recurrent fever.
The specific nature of the disease has made blinded randomized trials of treatment modalities extremely difficult, and currently recommended treatment approaches are based on experience and international expert consensus.
Four driving options/steps are offered. It is recommended to start with antipyretics, to which some children can respond positively. However, dexamethasone or prednisone may be the mainstay of treatment and diagnosis. When prescribing, it should be taken into account that in 25-50% of cases, the frequent usage of dexamethasone can lead to an increase in the frequency of exacerbations. Colchicine is prescribed as a preventive measure, which can be useful in some cases. Studies have shown that low levels of vitamin D contribute to the frequency of exacerbations. When deciding on surgical intervention, tonsillectomy, it is necessary to take into account the validity of the diagnosis, the frequency of exacerbations, the effectiveness of drug treatment, and the impact of the disease on the quality of life. If the exacerbations do not stop after the intervention, it is necessary to consider the possibility of other recurrent fevers.
Hope this helps!
Sergey Sargsyan, MD, Ph.D.
Advisor to the Minister of Health on Pediatrics
Head of the ICAH of Arabkir MC
Chair of Pediatrics N2 of YSMU
