Greg Licameli, MD, with his daughter, Claire
A child spikes a fever, as high as 104 or 105 degrees, sometimes causing seizures. She's rushed to the ED, the hospital runs test after test and specialists are brought in, but no explanation is found. Many families-though no one knows how many-go through this cyclical nightmare. The fevers come like clockwork, aren't accompanied by any obvious symptoms and don't respond to antibiotics or fever reducers. Instead, they vanish on their own after four to five days, only to return four to six weeks later.
Yet this mysterious ailment seems to have a rather simple cure. A report in the February Archives of Otolaryngology and
Head and Neck Surgery finds tonsillectomy (with or without
adenoidectomy) is almost always curative. The reason, like the
illness, remains a mystery, as extensive pathology studies of the tonsils and adenoids have found no evidence of infection or
abnormality. But desperate families are opting for the surgery as
a last-ditch measure, and are finding it to be life-changing.
The paper, describing 27 children treated at Children's Hospital Boston from 2004 through 2006, offers the largest reported surgical experience to date with this poorly understood syndrome, known as PFAPA (periodic fever, aphthous ulcers, pharyngitis and adenitis). The children were enrolled prospectively; they ranged from 19 months to 12 years old, and many had suffered cyclical fevers for years. Twenty-six of 27 had complete fever resolution after surgery.
Greg Licameli, MD, FACS, of Children's Department of Otolaryngology, the paper's first author, has first-hand experience with PFAPA: his daughter, Claire, is described as a case report in the paper. As a toddler, she was getting fevers every 22 days that didn't respond to fever reducers. Between episodes, she seemed perfectly healthy. "She was seen by several experts at Children's," Dr. Licameli says. "The workup was always negative."
Searching the literature, he found two small reports of European children with unexplained cyclical fevers, some of whom got better after adenotonsillectomy. He decided to try it, and after Otolaryngology colleague Dwight Jones, MD, performed the operation, Claire's mysterious fevers disappeared. Other doctors began referring patients to Dr. Licameli, and some five years later, he's treated 60 children with PFAPA. The findings continue to hold up. "I tell parents, 'I don't know why tonsillectomy works, but it has a good chance of ridding your child of fevers,'" he says.
PFAPA was first described in the literature in 1987. Its hallmark is high fevers of a strict cyclical nature: Parents can often predict, to the day, when the fevers will arrive. Typically, fevers are the only symptom; while some children have pharyngitis, cervical lymph node enlargement and small punctate mouth ulcers, these
symptoms are nonspecific and often very subtle.
The incidence of PFAPA is unknown, but Dr. Licameli believes the condition isn't all that uncommon. And its cause remains obscure. The periodicity of the fevers, their persistence over years, the lack of response to antibiotics, the aphthous ulcers and cytokine elevations during and between episodes all seem to indicate an immune dysregulation, whereas the diverse ethnic backgrounds of the patients and cure after tonsillectomy point to an infectious cause. Dr. Licameli suspects that the tonsils harbor a chronic indolent infection to which the immune system is
hypersensitive. He and colleagues in Children's Division of Immunology plan to investigate further.
Before considering surgery, patients should first be evaluated for rheumatologic or infectious etiologies that can also cause cyclical fever, including juvenile rheumatoid arthritis, cyclic neutropenia, familial Mediterranean fever, Behçet disease, hyperimmunoglobulinemia D syndrome and tick-borne relapsing fever. These diseases can be distinguished by careful attention to accompanying symptoms or can be ruled out with genetic markers or blood or throat cultures.
Short of surgery, early corticosteroid treatment can quickly stop fevers, but seems to make them come more frequently.
One study reported success with cimetidine hydrochloride,
a histamine-receptor 2 blocker, but this finding has not
Dr. Licameli hopes his case series will increase physicians' awareness of PFAPA and allow children struggling with this condition to be offered surgery sooner. In virtually all cases,
surgery has improved patients' quality of life dramatically. Parents no longer have to worry about their child suffering seizures, missing school or having to be kept away from other children because of a fever. "We have a bunch of very grateful families," Dr. Licameli says.
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