“The role of the tonsils in all of the fever syndromes is quite fascinating, and I also think it’s interesting the parents have similar pharyngeal or oropharyngeal symptoms when they were children,” she said, noting that some research has been investigating tonsil cells for a better understanding of these syndromes.
“I think the decision to do a tonsillectomy is very dependent upon families,” she said. “I certainly don’t recommend it first thing, but there are some patients who have had these episodes for 2 or 3 years, the family is falling apart, and [the parents] are unable to go to work. In those situations, I will say this looks like something we should do.”
Familial fever syndromes
Dr. Edwards covered several familial fever syndromes during the remainder of the presentation using case studies to introduce each one. The first, familial Mediterranean fever (FMF), also known as Armenian disease, results from a mutation in the MEFV gene and occurs among those of Sephardic and Ashkenazi Jewish, Middle Eastern Arab, Armenian, Italian, North African or Turkish ethnicities.
Episodes last 12-72 hours, and clinical features include an erysipeloid rash and inflammation of various membranes, causing abdominal, chest or joint pain (serositis of the peritoneum, pleura or synovia, respectively). Treatment with colchicine can prevent FMF’s most significant complication, amyloidosis, which can otherwise lead to renal failure. About 95% of patients experience improvement, and 75% have remission with colchicine, and anakinra is an additional treatment option.
The second familial syndrome, hyperimmunoglobulinemia D with periodic fever syndrome, or hyper IgD (HIDS), has an early age of onset, typically before 12 months and with more than half before 6 months. Resulting from mutations in the MVK gene (and hence also called mevalonate kinase deficiency), HIDS primarily afflicts those with European ancestry, and about half of patients are of Dutch ancestry. Despite the syndrome’s name, about 22% of patients have normal IgD levels, and high IgD levels may indicate other conditions, so high IgD labs are not diagnostic. Diagnosis is based on genetic testing and elevated mevalonic acid levels in urine.
Stress, vaccination, or an upper respiratory infection may trigger a HIDS episode that lasts 3-7 days with clinical features that include a widespread red rash – frequently on the lower legs – as well as oral or vaginal ulcers. More than 80% of patients report swollen lymph nodes, abdominal pain, and joint pain, particularly in the knees, ankles, wrists, and elbows. More than half of patients report diarrhea, vomiting, skin lesions, headache, cold chills, or arthritis.
The final fever syndrome Dr. Edwards covered was tumor necrosis factor receptor–associated periodic syndrome (TRAPS), also called Hibernian fever. Resulting from mutations in TNFRSF1A gene, this condition first appeared in Scottish and Irish populations but can occur among any ethnicity. Episodes can last from a few days to 1-2 weeks, and can include migratory nonspecific pain, a rash, abdominal pain, joint pain, chest pain, mouth sores, puffy eyes, and various inflammatory eye symptoms, such as uveitis, iritis, and conjunctivitis.
Although PFAPA is the most common pediatric periodic fever syndrome, a thorough fever history and family history can help clinicians identify whether a familial syndrome is involved.