Periodic Fever Syndrome

What are Periodic Fever Syndromes (PFS)?


These syndromes refer to rare autoinflammatory diseases that cause periodic (episodic) fevers that do not have an infectious (virus, bacteria) cause. It causes sterile recurrent systemic inflammatory flares without significant levels of either autoantibodies or autoreactive T cells.

Many of these syndromes are hereditary (passed down from parents) and result from a mutation (defect or mistake) in a gene (this is the code that determines the structure of our proteins).


The syndromes are defined by the gene defect as well as by the clinical features of the syndrome, the parts of the body affected in addition to fever, the age of the child when the syndrome starts, and the ethnicity (the area of the world where the child or parents originate from) of the child and parents. Many of these syndromes have a specific treatment, often based on understanding the problem caused by the genetic defect.


How is it diagnosed?

  • Physician exclusion of infection, autoimmune, primary immunodeficiency and neoplastic disease

  • Proved inflammation during flares (elevated CRP, ESR, ferritin and SAA)

  • Biopsy

  • Image exams (i.e. MRI, CT scan, X-Ray)


How do I differentiate them?

  • The results of any tests need to be followed up by an expert physician to make sure it really is what the doctor suspects. Often, there are only minor differences among all of the PFS or they can only be differentiated based on genetics.


Are PFS contagious?

These syndromes are not contagious.      


How do Periodic Fever Syndromes affect life?

Flares are unpredictable and therefore, they can seriously affect both social and education/working life. The symptoms are variable, and it is very difficult to get them properly diagnosed. Due to these diseases being RARE and because the majority of doctors are not familiar with these, many patients are misdiagnosed, undergo unnecessary surgeries, are prescribed unnecessary tests and medications, prolonging their pain and suffering. These conditions, especially delayed diagnosis, may cause depression, anxiety or isolation.


What are the most common triggers for these syndromes?


  • Illness

  • Stress

  • Accidents

  • Infections

  • Positive Emotions

  • Menstruation

  • Climate

  • Some Foods

  • Negative Emotions

  • Lack of Sleep

  • Physical Exertion

How to know if it’s more than just a virus?


As described in a recent report by Hal M. Hoffman, MD and Lori Broderick, MD, from the Children’s Hospital of San Diego, La Jolla, California (see reference below), there are five signs of possible autoinflammatory disease in children:


  1. More than three episodes of fever over 101°F (38.3°C) with no explained infectious etiology.

  2. Having predictable patterns of characteristic course of each episode.

  3. Having specific symptoms during episodes, including non-pruritic skin eruptions, joint or bone pain, severe abdominal pain, and conjunctivitis, with no upper respiratory infection symptoms.

  4. Episodes may be triggered by specific stimuli, such as cold exposure or vaccines.

  5. A family history of autoinflammatory disease or amyloidosis.


Two or more of these signs might suggest that an autoinflammatory disorder is possible and should be investigated.


- “Periodic Fever Syndromes” by Shai Padeh. Pediatric Clinics of North America, April 2005, Vol. 52, Issue 2, Pages 577-609.

-“Distinguish between autoinflammatory, autoimmune disorders in children” by Sharon Worcester Frontline Medical News. Publish date: August 13, 2016.

- “The role of the inflammasome in patients with autoinflammatory diseases” by Hal M. Hoffman. The Journal of Allergy and Clinical Immunology, July 2016, Volume 138, Issue 1, Pages 3–14.