Scientists identify new treatment to combat PFAPA syndrome in children

Published on April 11, 2011 at 2:11 AM · 7 Comments

A preliminary study conducted by a team at the National Institutes of Health has identified a promising new treatment in children for the most common form of a rare disorder. The syndrome is called periodic fever associated with aphthous stomatitis, pharyngitis and cervical adenitis - or PFAPA - and is characterized by monthly flare-ups of fever, accompanied by sore throat, swollen glands and mouth lesions.

The proposed treatment, which will be validated in a larger study before it is recommended in treating PFAPA syndrome, wards off an inappropriate immune system attack without increasing the frequency of flare-ups, a problem caused by the current standard treatment with corticosteroids. The team of researchers from the National Human Genome Research Institute (NHGRI) and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) reported their findings in the April 8, 2011, early online edition of the Proceedings of the National Academy of Sciences.

"Until now, the basis of PFAPA has been a mystery," said senior author and NHGRI Scientific Director Daniel Kastner, M.D., Ph.D. "Advances in genomic analysis have allowed us to define a major role for the innate immune system, the body's first line of defense against infection. Targeting a specific product of white blood cells at the first sign of fever appears to abort the attacks."

Children with PFAPA syndrome experience attacks of fever, each lasting three to six days, usually three to eight weeks apart. Their predictability is so regular that parents have been known to make pediatric appointments a week ahead of when they expect their child to experience a PFAPA episode. Affected children experience their first attack before the age of 5, with fever episodes usually abating in adolescence or young adulthood. The only remedy for PFAPA, besides corticosteroids, is removal of an affected child's tonsils, which has a good rate of success in eliminating PFAPA syndrome, but is an invasive alternative.

The new experimental treatment resulted from the researchers using a systems biology approach, which entailed gene and protein expression and cell biology analysis in carefully selected patient and healthy control subjects, to determine the underlying disturbance of the immune system. They analyzed patient blood samples to detect which gene and protein networks are involved in the cell signaling and metabolic pathways activated in the disease.

The research group studied 21 patients with PFAPA syndrome along with an equal number of healthy children and 12 children with a distinctly different set of hereditary fever syndromes. They analyzed gene expression during episodes of fever and intervening periods when the children were well. The analysis revealed gene expression profiles that uniquely identified PFAPA immune response.

"Gene profiles during PFAPA flares are remarkably distinct from when children are asymptomatic," said Dr. Kastner, noting that the analysis also distinguished PFAPA syndrome from other periodic fevers. But when PFAPA patients are asymptomatic, their gene expression is similar to healthy children.

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  1. Rita Renault Rita Renault Brazil says:

    I hope you get to do the clinical trial. The kids and the their families would be very gratefull .
    Thank you very much for your help,
    Rita and family

  2. Noelle Martin Noelle Martin United States says:

    I am a medical student and I am doing a research project on any disease, and I chose PFAPA. I would love any more info or pictures you could email me. Thank you

  3. Rebeccah M Rebeccah M United States says:

    Really hope better treatment can be found and doctors can be better educated in diagnosing and treating PFAPA.  I have four little boys who have suffered with this since each was just a few months old.  Finally my oldest outgrew it.  I don't think I could handle any more with this.  My little guys fight fevers of 105-108, two have suffered multiple seizures, and all have had to miss out on so much in life . For my children it has sometimes been a fight for their lives, so THANK YOU to you doctors and scientists who study to find answers to our children's suffering.

    • Adriana Cardenas Adriana Cardenas United States says:

      Wow! God bless you with your four little ones.  It is difficult enough to deal with one child going through this.  Have you tried the removal of their tonsils.  I am still not sure what to do with my little one.

  4. ALICIA PEREZ ALICIA PEREZ United States says:

    My son suffered from this syndrome starting at age 3, with a fever of 105-106 and febrile seizure. He continued having the monthly high fever, exudative pharyngitis, cervical adenitis, sever chills, lasting usually 3-4 days, associated with abdominal discomfort and lack of appetite until age 6.
    Afterwards they occured less frequently then as a teenager he had similar episodes with stress or travel. As older child he had less adenitis and max fever 102-103, and had mouth sores. As an adult he has oral sores with stress, trauma and some foods. Problem was that he was born in 1980 and never had a diagnosis, I was blamed He missed a lot of school, and there was a lot of family disruption and sibling issues on account of his chronic illness. He was treated with phenobarbitol for one year to avoid the recurrence of seizures.
    His daughter started the same pattern, beginning at 12 months and has been referred to NIH at 19 months. I think there is still little awareness of PFAPA and it has been difficult to get her diagnosed despite my profession and experience.

  5. Kim H. Kim H. United States says:

    After missing 54 days of kindergarten and being sick every 3 weeks for months and months, our daughter was diagnosed with PFAPA when she was 6.  Under the guidance of doctors at Children's Memorial in Chicago, we spent a year treating the syndrome with Prednisone. We were unhappy with the unpredicatability of her 'episodes' as well as possiblity of giving her the Prednisone when the fever was not due to the PFAPA (ie:  fever due to an ear infection- pain arrived the day after the fever).  We decided to take out her tonsils and adnoids.  She did not have any other 'episodes' after that--HOORAY!    

    But..... now she is 18, and she is she has been getting sick frequently with high fever and swollen glands/lymphnodes.   Has anyone heard of this coming back after 11 years free of PFAPA illness/episodes?

    • Barbara Castellano Barbara Castellano United States says:

      My daughter had severe sore throats when younger, sometimes strep sometimes not. Began having more frequent episodes of high fevers, terrible sore throats about 1and ahalf yrs ago. She choose to get her tonsils removed August 2013. Has had at least four or five episodes of high fevers and severe sore throats lasting about 4-6 days since. Very frustrating. Her ENT is on board with the dx of PFAPA and I am also goin to take her to see an infectious disease dr.  Frustrating and discouraging. Not much you can do for your child when they are sick like this!

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