International Retrospective Chart Review of Treatment Patterns in Severe Familial Mediterranean Fever, Tumor Necrosis Factor Receptor–Associated Periodic Syndrome, and Mevalonate Kinase Deficiency/Hyperimmunoglobulinemia D Syndrome (original) (raw)
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Clinical and experimental rheumatology
Tumour necrosis factor-receptor associated periodic syndrome (TRAPS) is a rare autosomal dominant autoinflammatory disorder characterised by recurrent episodes of long-lasting fever and inflammation in different regions of the body, as musculo-skeletal system, skin, gastrointestinal tube, serosal membranes and eye. Inflammatory attacks usually start in the pediatric age with initial corticosteroid-responsiveness. Most reported cases of TRAPS involve patients of European ancestry and diagnosis can be formulated by the combination of genetic analysis and a compatible phenotype. Its prognosis is strictly dependent on the appearance of amyloidosis, secondary to uncontrolled relapsing inflammation. Thanks to a better understanding of its pathogenesis, the disease is now managed with anti-interleukin (IL)-1 antagonists, rather than corticosteroids or tumour necrosis factor (TNF) inhibitors. The aim of this review is to describe the current understanding and advances of TRAPS genetic basis...
Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS) or Familial Hibernian Fever
JCR: Journal of Clinical Rheumatology, 2008
Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is one of a number of well described hereditary periodic febrile syndromes. We report a case in an infant, with a strong family history of this disorder, who presented on day-of-life 4 with high fever, irritability, diarrhea, lethargy, and raised acute phase reactants. An extensive work-up, including a full sepsis evaluation, proved negative. Symptoms resolved spontaneously. Representation with similar symptoms at 7 months of age prompted successful diagnosis after full evaluation. Subsequent genetic mutation analysis has proven positive for the T50M mutation in exon 2 of the TNFRSF1A gene. To our knowledge, this is the youngest reported age of presentation of this rare autoinflammatory disorder which should be considered even at such a young age.
Annals of the rheumatic diseases
Objective To evaluate the genetic findings, demographic features and clinical presentation of tumour necrosis factor receptor-associated autoinflammatory syndrome (TRAPS) in patients from the Eurofever/ EUROTRAPS international registry. Methods A web-based registry collected retrospective data on patients with TNFRSF1A sequence variants and inflammatory symptoms. Participating hospitals included paediatric rheumatology centres and adult centres with a specific interest in autoinflammatory diseases. Cases were independently validated by experts in the disease. Results Complete information on 158 validated patients was available. The most common TNFRSF1A variant was R92Q (34% of cases), followed by T50M (10%). Cysteine residues were disrupted in 27% of cases, accounting for 39% of sequence variants. A family history was present in 19% of patients with R92Q and 64% of those with other variants. The median age at which symptoms began was 4.3 years but 9.1% of patients presented after 30 years of age. Attacks were recurrent in 88% and the commonest features associated with the pathogenic variants were fever (88%), limb pain (85%), abdominal pain (74%), rash (63%) and eye manifestations (45%). Disease associated with R92Q presented slightly later at a median of 5.7 years with significantly less rash or eye signs and more headaches. Children were more likely than adults to present with lymphadenopathy, periorbital oedema and abdominal pains. AA amyloidosis has developed in 16 (10%) patients at a median age of 43 years. Conclusions In this, the largest reported case series to date, the genetic heterogeneity of TRAPS is accompanied by a variable phenotype at presentation. Patients had a median 70 symptomatic days a year, with fever, limb and abdominal pain and rash the commonest symptoms. Overall, there is little evidence of a significant effect of age or genotype on disease features at presentation.
Mediators of Inflammation
This study explores demographic, clinical, and therapeutic features of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) in a cohort of 80 patients recruited from 19 Italian referral Centers. Patients’ data were collected retrospectively and then analyzed according to age groups (disease onset before or after 16 years) and genotype (high penetrance (HP) and low penetrance (LP) TNFRSF1A gene variants). Pediatric- and adult-onset were reported, respectively, in 44 and 36 patients; HP and LP variants were found, respectively, in 32 and 44 cases. A positive family history for recurrent fever was reported more frequently in the pediatric group than in the adult group (p<0.05). With reference to clinical features during attacks, pericarditis and myalgia were reported more frequently in the context of adult-onset disease than in the pediatric age (with p<0.01 and p<0.05, respectively), while abdominal pain was present in 84% of children and in 25% of adults (p<...
Modern Rheumatology Case Reports, 2018
Tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) is one of the representative autoinflammatory diseases characterised by prolonged periodic fever caused by a genetic mutation of the type 1 TNF receptor (TNFR1). Although its molecular pathophysiology mechanism has not been completely elucidated, therapeutic strategies have been developed based on the recent pathological findings, such as the intracellular stress due to deposition of misfolded mutant TNFR1. The effectiveness of the IL-1b inhibitor for TRAPS has been reported, and canakinumab was approved on December 2016 in Japan. We report a case of TRAPS who became secondarily resistant to predonisolone and etanercept, an anti-TNF agent, after eleven years of treatment. Subsequently, canakinumab, a IL-1b inhibitor, was introduced, resulting in prompt improvement of inflammatory symptoms. This is the first case report of Japanese TRAPS patient successfully treated by canakinumab.
The tumour necrosis factor receptor-associated periodic syndrome: current concepts
Expert reviews in molecular …, 2005
The tumour necrosis factor receptor (TNFR)-associated periodic syndrome (TRAPS) is an autosomal dominant, multisystemic, autoinflammatory disorder caused by mutations in the TNFR1 gene (TNFRSF1A). TRAPS seems to be the most common hereditary periodic fever (HPF) syndrome in some Western populations, and the second most prevalent HPF worldwide, behind familial Mediterranean fever (FMF). The proteins involved in susceptibility to TRAPS (TNFRSF1A) and FMF (pyrin) are both members of the death-domain-fold superfamily. Mutations affecting these proteins might cause dysregulation of innate immune responses, with a propensity to autoinflammation. Most TRAPS patients have reduced blood levels of soluble TNFRSF1A between attacks, with an inappropriately small increase during bouts of fever. The pathogenesis of the 'hyperinflammatory state' in TRAPS has been variously ascribed to a shedding defect of TNFRSF1A from the cell surface resulting in increased TNF inflammatory signalling, or impaired TNF apoptotic signalling. Some lowpenetrance TNFRSF1A variants also contribute to the clinical phenotype in individuals carrying other HPF-associated mutations, and have been reported in several disorders such as Behçet's disease and systemic lupus erythematosus. Synthetic anti-TNF agents provide a rational form of therapy for TRAPS, and have been shown to delay or indeed prevent development of systemic amyloidosis (AA type), a life-threatening complication in this condition.