ASPEN, COLO. – Daily colchicine may have a role as early therapy in children with PFAPA syndrome, Dr. Eli Somekh reported at a conference on pediatric infectious diseases sponsored by the Children's Hospital, Denver, and the University of Colorado.
Eight of 10 children with severe PFAPA (periodic fever, aphthous stomatitis, pharyngitis, adenitis) syndrome demonstrated a marked decrease in frequency of episodes in response to colchicine at 0.5-1.0 mg/day. Indeed, the average interval between episodes expanded from roughly 1.5 weeks before colchicine to 7.5 weeks afterwards. In one case, the attack frequency stretched to one episode every 18 weeks after placement on the drug, said Dr. Somekh, chairman of the department of pediatrics at the Edith Wolfson Medical Center, Holon, Israel.
The pediatrician also noted that prednisone appears to be effective in aborting episodes at much lower doses than typically employed.
PFAPA is the most common cause of periodic fever in children. Because the disorder hasn't been fully described, Dr. Somekh and his coworkers reviewed in detail the records of 54 consecutive children who had well-documented PFAPA and were seen at the center beginning in 1999.
The following clinical diagnostic criteria were employed:
▸ Fevers recurring with clockwork regularity and early age of onset.
▸ One or more of the following: pharyngitis, aphthous stomatitis, and/or cervical lymphadenitis.
▸ Normal growth and development.
▸ Complete lack of symptoms between episodes.
▸ Exclusion of cyclic neutropenia.
Of the 54 PFAPA patients, 33 were boys. The mean age of onset was 1.9 years. Episodes lasted an average of 5.3 days with a peak temperature of 40.1degrees C. Episodes occurred on average once every 3.7 weeks with no seasonality.
In all, 52 children presented with pharyngitis, 35 with abdominal pain, 33 with cervical lymphadenopathy, and 21 with aphthous stomatitis. Of note, only 15 children displayed the classic cluster of symptoms comprising pharyngitis, stomatitis, and lymphadenitis.
“We saw more abdominal pain and less aphthous stomatitis than reported in the original published series of PFAPA,” Dr. Somekh observed.
The investigators identified four patterns of disease over time. In 23 patients, the frequency of episodes gradually decreased over the years. In two patients, the frequency gradually increased. In 15 patients, there was no change in frequency. And 14 patients displayed a previously undescribed pattern of alternating remissions and relapses; that is, after regularly experiencing episodes every few weeks, they stopped having them altogether for months or even years before the episodes returned.
Forty-eight patients were treated with corticosteroids, typically a single dose of prednisone at 0.6 mg/kg, resulting in termination of attacks in a mean of 10 hours. This dose is lower than what others have reported using, and because low-dose therapy results in fewer side effects, it is the best way to go, the pediatrician said.
Half of patients experienced no change in frequency of episodes after steroid therapy. In 9 children the frequency increased, whereas in 15 it decreased.
Forty-one patients were placed on antibiotics, deemed to be without any benefit in all but one.
Other investigators have reported cimetidine to be beneficial in patients with PFAPA, but Dr. Somekh said his own experience has been that the drug has only a slight effect.
The pathogenesis of PFAPA remains unclear. “Patients are usually healthier than their siblings–less flu, less asthma and bronchitis,” he noted. “So probably their immune system is just fine, even perhaps working too hard. And as far as we know, their prognosis is excellent. We don't see an increase in neoplastic or neurologic disorders.”
Dr. Gerard Rabalais commented that he and his colleagues at the University of Louisville (Ky.) see many PFAPA patients, probably in part because Dr. Gary Marshall, professor of pediatrics there, is credited with the first description of the syndrome back in 1987.
Of late, they have been treating episodes with 2-3 days of prednisone, a practice to reconsider in light of the impressive Israeli experience with single low-dose therapy, said Dr. Rabalais, professor and chairman of the department of pediatrics at the university.
He added that Dr. Marshall recommends tonsillectomy for the most severely affected patients. It is curative in roughly two-thirds of cases.
Dr. Somekh noted that others have also reported tonsillectomy to be of great benefit in 60%-80% of treated PFAPA patients. In his series of 54 patients, all six children who underwent tonsillectomy were cured.
'We saw more abdominal pain and less apthous stomatitis than reported in the original published series of PFAPA.' DR. SOMEKH