Clinical characteristics and genetic analyses of 187 patients with undefined autoinflammatory diseases

Abstract

ObjectivesTo describe the clinical characteristics, treatment response and genetic findings in a large cohort of patients with undefined systemic autoinflammatory diseases (SAIDs).MethodsClinical and genetic data from patients with undefined SAIDs were extracted from the Eurofever registry, an international web-based registry that retrospectively collects clinical information on patients with autoinflammatory diseases.ResultsThis study included 187 patients. Seven patients had a chronic disease course, 180 patients had a recurrent disease course. The median age at disease onset was 4.3 years. Patients had a median of 12 episodes per year, with a median duration of 4 days. Most commonly reported symptoms were arthralgia (n=113), myalgia (n=86), abdominal pain (n=89), fatigue (n=111), malaise (n=104) and mucocutaneous manifestations (n=128). In 24 patients, relatives were affected as well. In 15 patients, genetic variants were found in autoinflammatory genes. Patients with genetic variants more often had affected relatives compared with patients without genetic variants (p=0.005). Most patients responded well to non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, colchicine and anakinra. Complete remission was rarely achieved with NSAIDs alone. Notable patterns were found in patients with distinctive symptoms. Patients with pericarditis (n=11) were older at disease onset (33.8 years) and had fewer episodes per year (3.0/year) compared with other patients. Patients with an intellectual impairment (n=8) were younger at disease onset (2.2 years) and often had relatives affected (28.6%).ConclusionThis study describes the clinical characteristics of a large cohort of patients with undefined SAIDs. Among these, patients with pericarditis and intellectual impairment appear to comprise distinct subsets.

Clinical Features at Onset and Genetic Characterization of Pediatric and Adult Patients with TNF-α Receptor—Associated Periodic Syndrome (TRAPS): A Series of 80 Cases from the AIDA Network

“…In this subgroup, the mean age at onset was 29 years, and mild musculoskeletal symptoms (arthralgia and myalgia) were reported more frequently than other complaints. These findings are consistent with data recently published from the Eurofever registry by ter Haar et al on patients with undefined AIDs [22]: arthralgia, myalgia, and abdominal pain were often reported together with pericarditis, suggesting that the presence of this combination could be a clue for suspecting specific AIDs in patients with otherwise idiopathic pericarditis. Indeed, the extension of genetic analysis allowed the identification of the R92Q mutation in two out of eight cases.…”

Response to: ‘Novel NLRP12 variant presenting with familial cold autoimmunity syndrome phenotype’ by Gupta et al

“…Her case is not directly similar to any of the 187 cases we described in our paper on undefined autoinflammatory diseases 2…”

Response to: ‘Do we need the PFAPA syndrome in adults with non-monogenic periodic fevers?’ by Fayand et al

“…In two recent studies, the term of SURF (systemic undefined recurrent fevers) was proposed, with the actual aim to identify a more homogeneous group of patients with recurrent fevers characterised by a minor pharyngeal and lymph node involvement, an higher prevalence of arthritis and skin rash, and a good response to colchicine and anti-IL-1 blockers 7 8. At least in children, this subgroup of patients should be clearly distinguished from the more common PFAPA patients.…”