What do patients with TRAPS look like?

Trying to differentiate between the many (and ever-growing in number) autoinflammatory diseases is difficult.  They share many clinical features such as fever, abdominal pain, and elevation in inflammatory markers.  These diseases are so rare that  most physicians, even some rheumatologists, may never see them.  Genetic studies are only helpful to diagnose a fraction of these patients–we only know a handful of mutations that cause these syndromes.

This is why it was refreshing to read a new study that appeared in this month’s Annals of Rheumatic Diseases: The phenotype of TRAPS at presentation: a series of 158 cases from the Eurofever/EUROTRAPS international registry.  It provides us with clinical clues to help identify patients with TRAPS (tumor necrosis factor-receptor-associated autoinflammatory syndrome).

TRAPS is an autoinflammatory disease caused by mutations in TNFRSF1A, the gene that codes for the TNF receptor.  It is still unclear how the mutation actually brings about the features of the disease (some researchers believe that misfolding of the protein leads to cell stress and inflammation) .  TRAPS used to be called “Hibernian Fever” because it was first identified in an Irish family (Hibernia is the latin name for Ireland).  However, TRAPS has since been identified in patients of many ethnicities, not just in those of Irish descent.

The article summarizes the clinical and genetic features of 158 patients with TRAPS, the largest collection of TRAPS patients ever published.  It showed that patients with TRAPS have variable clinical features and can have a variety of mutations affecting the same gene.   Interestingly, although the disease is autosomal dominant, the majority of patients did not have a family history of the disease, as would be expected.

Most patients first presented with symptoms of TRAPS during early childhood, but 9% of patients did not have symptoms until at least age 30.  Most adult patients with TRAPS had had symptoms for over ten years before they were properly diagnosed!

Children and adults with TRAPS had recurrent attacks consisting of:

  • fever
  • diffuse arm or leg pain
  • abdominal pain
  • rash

Most patients had attacks lasting about 11 days, which affected them for a total of 70 days per year.   10% of patients with TRAPS developed amyloidosis, the most feared complication of this disease.  Amyloid is an abnormal protein that collects in various organs and causes them to malfunction; when it affects the kidney it usually leads to kidney failure requiring dialysis.

For me, the length of the febrile episodes (11 days), and the rash with limb pain, really set TRAPS apart from most of the other autoinflammatory diseases.  Nevertheless, our challenge remains to diagnose patients earlier in life, and provide them with more effective treatments.

9 thoughts on “What do patients with TRAPS look like?”

  1. It’s complicated indeed. I’m a 52 year old physician diagnosed by Mayo with TRAPS. NIH on the other hand thinks I have some new gene defect that they hope to find with whole exome sequencing. The divergence lies with varying opinions about the “R92Q” TNFSF1A ‘defect’. Is it a low-penetrance pathological mutation or a totally benign polymorphism? Or are there cofactors?

    Anyway, what THIS TRAPS patient looks like is confused. And I studied medicine…

    I must admit though that it is very interesting and very unpleasant. The IL-1 antagonist called “anakinra” has allowed me to stop all corticosteroids which is great, but the efficacy is still limited and life sure ain’t what it used to be.

    But I digress. I wrote to tell you how much I admire you writing.

    1. Hi Mark. Thanks for your kind words. The uncertainty about your diagnosis must be frustrating. You should know you’re not alone. One of my pediatric patients presented with symptoms that looked like PFAPA and responded to tonsillectomy. Many years later his fevers returned. Genetic testing showed he had R92Q. I can’t be sure he doesn’t have another gene contributing to his symptoms, but he definitely has something! And, like you, he tells me he doesn’t like feeling “TRAPy!”

      Hopefully we’ll get better answers to these diseases over the coming years….hang in there!

  2. I don’t feel too frustrated. I feel lucky. Had I presented even 20 years ago, we would have essentially no idea why I was sick or what, besides perhaps steroid therapy, to do for me.

    Kastner at NIH seems pretty confident that he’ll uncover something new because my case is so dramatically atypical in some ways. I presented suddenly about two years ago with sterile peritonitis, massive ascites, a rash and, of course, chronically elevated acute phase reactants but, it took a year to even arrive at the mere concept of an autoinflammatory illness. There were a lot of diagnostic dead-ends and significant negative results. But I am sure that you have heard all this many times from many patients.

    Finally, the information you presented on the relationship between inflammation and gut bugs is great. To answer the question you asked on that page, I appear to be almost pathologically intolerant of fiber and I would think that it is just IBS except that it raises my CRP (I’ve checked it). VERY interesting stuff.

    Anyway, thanks so much for your time.


    1. Mark. I am presenting similar to you (joint, vasculitis, rash, night sweats, headaches, systemic features etc.). Thus, TRAPS-ish… but doesn’t fit in the box… so likely uAID. My blood is with the NIH right now in the Vasculitis and Rheumatology Division with Dr. Grayson. They are doing whole genome and exome sequencing. My sister and mother present similarly… yet differently. My question to you is how long the sequencing portion took? When were they able to give you any definitive results? Just discovered this site today… love what this physician has put together as there is limited understanding of auto-inflammatory diseases. Would love some insight. All our hope is hinging on the NIH at the moment.


  3. I have been diagnosed with Traps for almost 20 years. Nothing helped to prevent attacks until I started a totally noninflamatory diet. No starch, sugar, dairy, alcohol or beans. No attacks for a year

Comments are closed.