Physicians employ flexible diagnostic criteria for PFAPA in children

MEMPHIS, Tenn. — Surveyed rheumatologists and pediatric infectious disease physicians found wide diversity in how they diagnosed patients with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome, as well as patient treatment response, according to data presented at the St. Jude/PIDS Pediatric Infectious Diseases Research Conference.

“Children with [periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome (PFAPA)] present every month with high fevers, usually with tonsillitis, ulcers in their mouth and swollen lymph nodes,” Kalpana Manthiram, MD, from Vanderbilt University School of Medicine, told Infectious Diseases in Children. “The episodes are highly regular, almost to the point that parents can predict when the next one is going to happen and that is usually how they are presented to us.”

To determine whether diagnostic criteria and treatment strategies for PFAPA differed among physicians, Manthiram and colleagues conducted an online survey to pediatric rheumatologists (n = 120) from the Childhood Arthritis and Rheumatology Research Alliance and pediatric infectious disease physicians (n = 150) from the Pediatric Infectious Diseases Society.

Researchers defined the current diagnostic criteria for PFAPA as:

regularly recurring fevers with an early age of onset (aged younger than 5 years);
symptoms in the absence of upper respiratory tract infection with at least one of these clinical signs: aphthous stomatitis, cervical lymphadenitis, pharyngitis;
exclusion of cyclic neutropenia;
completely asymptomatic intervals between episodes; and
normal growth and development.

Although the majority of physicians applied most of the criteria features to diagnose PFAPA, the researchers learned that:

only 28% required an age of onset at younger than 5 years;
68% would diagnose PFAPA without aphthous stomatitis, pharyngitis or adenitis on exam;
33% did not require regular timing of episodes; and
56% considered episode resolution with steroids to be diagnostic of PFAPA.

“We also surveyed how frequently patients received genetic testing which is always an issue,” Manthiram said. “Most physicians said they tested 1% to 25% of their patients, but 21% reported that they never tested their patients who ultimately had PFAPA, and very few — only 4% — tested all of their patients. The focal features that physicians looked at were if they had features suggestive of a monogenetic fever syndrome, if there was an ethnic background suggestive of a monogenetic fever syndrome, a family history or if an episode did not resolve with a steroid.”

While steroids, tonsillectomy, antipyretics, and cimetidine were the most commonly used treatments by both types of physician, researchers observed that rheumatologists used additional drugs that infectious disease physicians did not, including colchicine, montelukast sodium, and anakinra. Among these, steroids were rated as “very effective” by 95% of respondents compared with tonsillectomy rated as “effective” by 67% of respondents.

“We found that physicians did not adhere to their original criteria, and that physicians almost used it as a field test: if it seems like PFAPA, then they diagnose it as PFAPA,” Manthiram said. “However, this suggests that we may need to re-examine the diagnostic criteria and whether these patients truly have PFAPA or an alternative diagnosis? Or, is PFAPA actually bigger and broader than what we expected?

“To address this, we are in the process of creating a registry for the United States for us to better track patient symptoms and progression over time.”

Reference:

Manthiram K, et al. Abstract R201516. Presented at: St. Jude/PIDS Pediatric Infectious Diseases Research Conference; Feb. 20-21, 2015; Memphis, Tennessee.

Disclosure: The researchers report no relevant financial disclosures.