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:
- diffuse arm or leg pain
- abdominal pain
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.