Background TNF receptor associated periodic syndrome (TRAPS) is an autoinflammatory syndrome. Diagnosis relies on genetic testing. More than 70 TNFRSF1A pathogenic sequence variants (PSV) have been reported but it is not known if there are phenotype genotype correlations and interpretation of the significance of R92Q, a common variant of unknown significance (VUS), is often problematic.
Objectives To analyse the presenting clinical features of patients with TNFRSF1A PSV and of those with inflammatory symptoms and the R92Q VUS.
Methods Anonymised data derived from patient recall and case records were entered by specialist physicians to a web-based registry (www.printo.it).
Results 46 TNFRSF1A PSV were identified in 86 patients; 11 (13%) carried the T50M PSV and in 40 (47%) a cysteine residue was affected; 61% patients reported a family history of similar symptoms; 52% were male; 94% were Caucasian and the mean age at symptom onset was 7.6 yrs (range: neonatal to 49 yrs). In 9% symptoms onset after aged 30 yrs. Median attack duration was 10 days and the median number of symptomatic days/yr was 51.5 (range: 8 – 365). Patients with the R92Q VUS were 98% Caucasian, 46% male and 17% reported a family history. Symptoms onset at a median of 10 yrs (range: neonatal to 52.6 yrs). Median attack duration was 6.5 days and the median number of symptomatic days/yr was 57. Clinical features seen in attacks are summarised in the table. Patients with the R92Q VUS were significantly less likely to have rash and more likely to have attacks features of headache, cervical adenopathy, headache and/or pharyngitis than patients with TNFRSF1A PSV. AA amyloidosis complicated 16 cases (19%) including 7 cysteine PSV (17.5%), 2 (18%) T50M and no patients with R92Q. Among patients with clear TNFRSF1A PSV no phenotype genotype correlations were identified.
Conclusions The phenotype of PSV confirmed TRAPS is very variable with no pathognomonic pattern and no increased severity with cysteine or the T50M PSVs; musculoskeletal pain, fever, gastrointestinal symptoms and constitutional upset are most frequent. Even though there may have been a bias to entering patients with severe R92Q associated disease into the registry there are significant differences compared to patients with PSVs with a later presentation and more upper respiratory tract type symptoms reminiscent of those seen in PFAPA.
Disclosure of Interest None Declared