RARE DISEASE
Tumor necrosis factor receptor 1 associated periodic syndrome
Tumor necrosis factor receptor 1 associated periodic syndrome
Tumor necrosis factor receptor 1 associated periodic syndrome
Synonyms: Familial Hibernian fever, TNF receptor 1-associated periodic syndrome, TRAPS syndrome
Synonyms: Familial Hibernian fever, TNF receptor 1-associated periodic syndrome, TRAPS syndrome
Synonyms: Familial Hibernian fever, TNF receptor 1-associated periodic syndrome, TRAPS syndrome
Drug discovery
2
drugs
With orphan designations
Overview
Tumor necrosis factor receptor 1-associated periodic syndrome (TRAPS) is a rare autosomal dominant autoinflammatory disorder caused by TNFRSF1A gene mutations, leading to dysregulated NF-κB signaling and systemic inflammation. It features recurrent fever episodes (1–3 weeks) with migratory myalgia, erythematous rash, serosal inflammation, and periorbital edema. Complications include AA amyloidosis (∼10% of cases) and increased cardiovascular risk [1][2][5][8].
Burden
Chronic inflammation increases amyloidosis risk (renal/hepatic involvement) [1][2][6]
Recurrent hospitalizations, reduced quality of life, and treatment-resistant pericarditis in severe cases [4][8][14]
Lifetime management required; mortality linked to amyloidosis complications and cardiovascular events [1][4][8]
Therapies
First-line: IL-1 inhibitors (anakinra, canakinumab) for long-term control [3][6][14]
Second-line: TNF inhibitors (etanercept) with variable response; avoid monoclonal anti-TNF agents (infliximab) due to paradoxical flares [3][7][14]
Adjunctive: Corticosteroids for acute flares, NSAIDs for symptom relief [1][14]
Categories: rare genetic diseases, rare immunological diseases, rare skin diseases, rare systemic and rheumatological diseases, rare systemic or rheumatologic diseases of childhood
Research Papers
141 drug discovery papers about Tumor necrosis factor receptor 1 associated periodic syndrome, with 1 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
141 drug discovery papers about Tumor necrosis factor receptor 1 associated periodic syndrome, with 1 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
antibodies
2026-08-01 | A Novel TNFRSF1A Gene Variant in a Patient with Recurrent Fevers and Amyloidosis: A Case Report
Background TNF Receptor Associated Periodic Syndrome (TRAPS) is a rare autosomal dominant autoinflammatory disorder. It is caused by pathogenic variants in the TNFRSF1A gene which encodes the TNF receptor 1. These mutations impair receptor shedding and disrupt TNFα signaling, leading to uncontrolled inflammation with recurrent fever, serositis, and myalgia.[1] Left untreated, chronic inflammation may result in AA amyloidosis and end-stage renal disease (ESRD). Early recognition and treatment with IL-1 inhibitors can mitigate deterioration and prevent irreversible complications such as amyloidosis. Here we present a case of TRAPS complicated by amyloidosis and associated with a novel variant in TNFRSF1A. Case Report A 48-year-old male was referred for early childhood onset, recurrent 3-5-day febrile episodes accompanied by severe abdominal pain, large joint arthralgias and myalgias. He was treated intermittently with corticosteroids and NSAIDs, with incomplete response. At 43 years old he developed chronic kidney disease with renal biopsy compatible with amyloidosis. This eventually progressed to ESRD requiring hemodialysis. Genetic testing was performed when he was 48 years old and revealed a heterozygous missense variant in TNFRSF1A (c.214_215delinsCT, p.Cys72Leu). The mutation resides in exon 3 within the extracellular cysteine-rich domain, and was predicted to disrupt disulfide bond formation, resulting in misfolded receptor protein and defective TNFα signaling. Substitutions at the same residue (Cys72Arg, Cys72Ser) had been previously demonstrated to be causative for TRAPS.[2] His asymptomatic parents did not carry the mutation. As such, this de novo Cys72Leu variant was classified as Likely Pathogenic, and the patient was diagnosed with TRAPS. Anakinra 100 mg SC daily was started which prevented further attacks. However, he remains on hemodialysis and is on the waitlist for renal transplant. Conclusion In summary, our case highlights the importance of early recognition of autoinflammatory diseases like TRAPS, in order to initiate targeted treatment and prevent life altering complications such as amyloidosis and ESRD. We report a novel variant in the TNFRSF1A gene, adding to the literature of mutations causing TRAPS. Further studies are needed to functionally characterize the biological impact of Cys72Leu, as well as to elucidate the complex mechanisms between TNF receptor dysfunction and IL-1 signaling. References [1.] Gaggiano C. Mediators Inflamm 2020;7:8562485. [2.] Lachmann HJ. Ann Rheum Dis 2014;73:2160-7.
2026-07-21 | A Case of Adult-Onset TNF Receptor-Associated Periodic Syndrome (TRAPS) with Somatic Mosaicism Treated with an IL-1 Inhibitor.
Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is a rare autoinflammatory disorder, and adult-onset cases caused by somatic mosaic TNFRSF1A variants are exceptionally rare. A man in his 60s developed recurrent febrile episodes with rash and polyarthralgia and was initially misdiagnosed with a biliary infection and adult-onset Still's disease. Hybrid capture-based next-generation sequencing identified a somatic mosaic TNFRSF1A variant with a variant allele frequency of 19%, thus establishing the diagnosis of TRAPS. Treatment with canakinumab resulted in complete clinical remission and successful glucocorticoid tapering.
2026-05-29 | Pediatric Rheumatic Disorders Revisited: Integrating Imaging and Pathophysiologic Insights across the Autoinflammatory-Autoimmune Continuum.
Recent advances in immunologic and molecular research on rheumatic diseases have significantly improved understanding of the diverse group of immune-mediated disorders. Rheumatic diseases were traditionally considered autoimmune diseases, caused by impaired adaptive immunity and often associated with pathogenic autoantibodies. However, in the late 20th century, certain genetic rheumatic diseases-such as tumor necrosis factor receptor-associated periodic syndrome (TRAPS) and familial Mediterranean fever (FMF)-were found to result from antigen-independent activation of innate immune cells and the subsequent cytokine-mediated inflammation. This discovery introduced the new concept of autoinflammatory diseases, characterized by dysregulation of innate immunity. Although autoimmune and autoinflammatory diseases were initially regarded as distinct categories, substantial overlap has become evident. For instance, autoantibodies can be detected in disorders primarily affecting innate immunity, while recent cytokine-targeting therapies have proven effective for classic autoimmune diseases, such as systemic lupus erythematosus (SLE) and dermatomyositis. These insights led to the concept of an autoinflammatory-autoimmune continuum, highlighting that dysregulation of the interaction between innate and adaptive immune systems contributes to the clinical symptoms of rheumatic diseases. The authors explore clinical, imaging, pathophysiologic, and therapeutic aspects of pediatric rheumatic diseases through the lens of this continuum, providing a comprehensive overview of current diagnostic and treatment strategies. © RSNA, 2026 Supplemental material is available for this article.
2026-04-04 | When to suspect monogenic autoinflammatory diseases in patients with digestive symptoms?
Autoinflammatory diseases are characterized by dysregulation of the innate immune system. This article provides an updated overview of autoinflammatory diseases with gastrointestinal manifestations and outlines the clinical situations in which gastroenterologists should consider these conditions. The most prevalent form worldwide is familial Mediterranean fever (FMF), which is associated with mutations in the MEFV (MEditerranean FeVer) gene and presents with recurrent episodes of serositis, primarily peritonitis, accompanied by systemic inflammation. From a biological standpoint, a peripheral inflammatory syndrome is typically observed during acute attacks; however, in some cases inflammation may persist chronically. At the molecular level, these diseases involve numerous genes encoding proteins that participate in the activation or regulation of inflammatory pathways within innate immune cells. Initially, four monogenic disorders were described FMF, TNF receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency (MKD), and cryopyrin-associated periodic syndromes (CAPS) collectively referred to as the four historical autoinflammatory diseases. Each year, new monogenic autoinflammatory diseases are identified thanks to rapid advances in genetic sequencing technologies. The recent identification of somatic forms of monogenic diseases, including certain cryopyrinopathies and, in 2020, VEXAS syndrome, has added a new level of complexity to the field.
2026-03-29 | Unclassified autoinflammatory syndrome with TRAPS-like symptoms and severe oropharyngeal disease treated successfully with canakinumab.
PURPOSE: To report an unclassified autoinflammatory syndrome with TRAPS-like and Behçet-like features presenting with severe inflammatory pharyngeal wall involvement threatening the airway, successfully controlled with canakinumab. CASE DESCRIPTION: A 40-year-old woman had a 20-year history of recurrent oral and genital ulcers, uveitis, photosensitive rash, episodic neurological symptoms and relapsing arthritis with prominent sternoclavicular involvement, negative autoimmune serology and nonspecific chronic inflammatory changes on biopsy. A heterozygous TNFRSF1A variant of uncertain significance supported a TRAPS spectrum diagnosis. Conventional disease-modifying agents and several biologics achieved only partial or transient responses; anakinra was discontinued because of severe injection-site reactions. She then developed a painful, progressively enlarging inflammatory thickening of the posterior and lateral pharyngeal walls with dysphagia and impending airway compromise on MRI. High-dose glucocorticoids and background immunosuppression were insufficient. Canakinumab 300 mg every 4 weeks induced rapid symptom relief and near-complete radiological resolution within 2 months, with sustained remission on 150 mg every 4 weeks plus conventional therapy. Close collaboration between rheumatology and otorhinolaryngology in similar cases is warranted.
proteins
2023-10-09 | A patient with tumor necrosis factor receptor-associated periodic syndrome misdiagnosed as Kawasaki disease: A case report and literature review.
This article reports a case of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) misdiagnosed as Kawasaki disease and summarizes the clinical features and therapeutic progress of TRAPS and the relationship between its clinical manifestations and gene mutations. We retrospectively analyzed a patient with tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) -mutated auto-inflammatory disease who was misdiagnosed with Kawasaki disease in another hospital. The clinical features and therapeutic progress of TRAPS were analyzed by combining clinical features and gene reports of this case and literature review. TRAPS onset occurred in a female pediatric patient at the age of 4 months. The child and in his father at the age of 6 years, both of whom manifested periodic fever, and recurrent rash, as well as elevated leukocytes, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) during episodes but normal between episodes. This child carried a heterozygous mutation in TNFRSF1A located in the region 6442923-6442931 on chromosome 12. The nucleic acid alteration was: c.298 (exon3) _c.306 (exon3) 291 delCTCAGCTGC, resulting in a 3 amino acid deletion p.L100_C 102del 292 (p.Leu100_Cys102del) (NM_001065). After etanercept treatment, the symptoms of fever and rash disappeared, and the levels of ESR, CRP, interleukin (IL)-1, IL-6, and TNF-α levels were normal. Subsequently, no liver, kidney, or cardiac amyloidosis and severe etanercept-related adverse events were observed at 1-year follow-up. TRAPS pathogenesis is associated with TNFRSF1A mutation, which is characterized by periodic episodes of fever, mostly accompanied by recurrent rashes, periorbital edema, abdominal pain, and serious complications of organ amyloidosis. Moreover, etanercept can effectively alleviate the clinical symptoms and high inflammation level of TRAPS.
2021-12-17 | Real-Life Indications of Interleukin-1 Blocking Agents in Hereditary Recurrent Fevers: Data From the JIRcohort and a Literature Review.
Interleukin (IL)-1 inhibitors represent the main treatment in patients with colchicine-resistant/intolerant familial Mediterranean fever (crFMF), mevalonate kinase deficiency (MKD), and tumor necrosis factor receptor-associated periodic syndrome (TRAPS). However, the reasons for the use of IL-1 inhibitors in these diseases are still not completely clarified. Identify real-life situations that led to initiating anakinra or canakinumab treatment in hereditary recurrent fevers (HRFs), combining data from an international registry and an up-to-date literature review. Data were extracted from the JIRcohort, in which clinical information (demographic data, treatment, disease activity, and quality of life) on patients with FMF, MKD, and TRAPS was retrospectively collected. A literature search was conducted using Medline, EMBASE, and Cochrane databases. Complete data of 93 patients with HRF (53.8% FMF, 31.2% MKD, and 15.1% TRAPS) were analyzed. Data from both the registry and the literature review confirmed that the main reasons for use of IL-1 blockers were the following: failure of previous treatment (n = 57, 61.3% and n = 964, 75.3%, respectively), persistence of disease activity with frequent attacks (n = 44, 47.3% and n = 1,023, 79.9%) and/or uncontrolled inflammatory syndrome (n = 46, 49.5% and n = 398, 31.1%), severe disease complication or associated comorbidities (n = 38, 40.9% and n = 390, 30.4%), and worsening of patients' quality of life (n = 36, 38.7% and n = 100, 7,8%). No reasons were specified for 12 (16.4%) JIRcohort patients and 154 (12%) patients in the literature. In the absence of standardized indications for IL-1 inhibitors in crFMF, MKD, and TRAPS, these results could serve as a basis for developing a treat-to-target strategy that would help clinicians codify the therapeutic escalation with IL-1 inhibitors.
2021-11-24 | [Periodic fever syndrome associated with mutations in the TNF type 1 receptor gene: A differential diagnosis of familial Mediterranean fever that should not be overlooked in patients of Mediterranean origin].
Tumor Necrosis Factor Type 1 Receptor Associated Periodic Syndrome (TRAPS) is a rare autosomal dominant autosomal autoinflammatory disease associated with mutations in the TNF type 1 receptor gene (TNFRSF1A). It is characterized by relatively long recurrent febrile seizures with an average duration of 7 days accompanied by arthralgia, myalgia, and usually a rash. In a patient of Mediterranean origin with recurrent fever, familial Mediterranean fever is the first diagnosis to be suspected by argument of frequency. A retrospective observational study was conducted on patients from Mediterranean origin followed for TRAPS and included in the "Juvenile Inflammatory Rheumatism" (JIR) observational cohort in the national French autoinflammatory center. The age of onset of symptoms, age of diagnosis, number of years of wandering and treatments received were collected for each index case. Nine patients from 6 families of Mediterranean origin were included. A molecular diagnosis confirmed TRAPS in all patients. The median age at diagnosis was 26 years, the mean number of years of wandering was 17 years. The diagnosis of FMF was made first in all patients. AA amyloidosis revealed TRAPS in 2 patients. Colchicine was started without any efficacy in all cases. Five patients were treated with interleukin-1 inhibitory biotherapy with 100% efficacy. In a patient of Mediterranean origin presenting with recurrent febrile abdominal pain of AA amyloidosis, the first diagnosis to be suspected is FMF. Long relapses, dominant transmission, a non-Mediterranean relative, and the ineffectiveness of colchicine should evoke TRAPS.
2020-04-15 | TNF receptor signalling in autoinflammatory diseases.
Autoinflammatory syndromes are a group of disorders characterized by recurring episodes of inflammation as a result of specific defects in the innate immune system. Patients with autoinflammatory disease present with recurrent outbreaks of chronic systemic inflammation that are mediated by innate immune cells, for the most part. A number of these diseases arise from defects in the tumour necrosis factor receptor (TNFR) signalling pathway leading to elevated levels of inflammatory cytokines. Elucidation of the molecular mechanisms of these recently defined autoinflammatory diseases has led to a greater understanding of the mechanisms of action of key molecules involved in TNFR signalling, particularly those involved in ubiquitination, as found in haploinsufficiency of A20 (HA20), otulipenia/OTULIN-related autoinflammatory syndrome (ORAS) and linear ubiquitin chain assembly complex (LUBAC) deficiency. In this review, we also address other TNFR signalling disorders such as TNFR-associated periodic syndrome (TRAPS), RELA haploinsufficiency, RIPK1-associated immunodeficiency and autoinflammation, X-linked ectodermal dysplasia and immunodeficiency (X-EDA-ID) and we review the most recent advances surrounding these diseases and therapeutic approaches currently used to target these diseases. Finally, we explore therapeutic advances in TNF-related immune-based therapies and explore new approaches to target disease-specific modulation of autoinflammatory diseases.
2019-03-17 | Treating TNF Receptor Associated Periodic Fever Syndrome in End-Stage Renal Failure
Tumor necrosis factor receptor associated periodic syndrome (TRAPS) is a rare monogenic autoinflammatory disease. Its most severe manifestation is secondary amyloidosis. A 44-year-old male presented with nephrotic syndrome. Kidney biopsy was conclusive for secondary amyloidosis. The patient and his children had a history of recurrent febrile periods since infancy. All subjects were positive for a heterozygous variant of the TNFRSF1A gene, confirming TRAPS diagnosis. The patient progressed to end-stage renal failure and developed recurrent pericarditis episodes. He was started on anakinra while on hemodialysis with marked reduction of his serum amyloid A protein (SAA) levels. Meanwhile he received a cadaveric renal transplant and maintains anakinra treatment. Despite renal failure being the most feared complication of AA amyloidosis caused by TRAPS, little data is available about safety of anti-IL-1 treatment in patients with severe kidney failure. The authors report this case of a patient on dialysis treated with anakinra in which no complications were registered. Though amyloidosis is established, the authors believe containing its progression and reducing inflammatory activity can improve patient prognosis and reduce recurrence of amyloidosis in kidney transplant, as has been demonstrated in transplanted patients due to familial Mediterranean fever amyloidosis.
small molecules
2026-06-18 | The use of JAK inhibitors and tocilizumab in the management of TRAPS: a sibling case study.
Tumour necrosis factor (TNF) receptor-1 associated periodic syndrome (TRAPS) is an autoinflammatory condition. Most treatment options require regular injections, posing challenges for individuals with needle phobia. We reviewed the medical records of two siblings, a now 14-year-old female, and her 10-year-old brother, both diagnosed with TRAPS in early infancy. Both children responded to on-demand oral corticosteroid therapy, but due to frequent flares, persistent biochemical inflammation and poor growth, steroid-sparing therapies were required. Non-standard first-line therapies were subsequently selected as the eldest child had developed a needle phobia, and she was commenced on an oral Janus kinase (JAK) inhibitor. The younger brother was treated with tocilizumab, reflecting parental preference to minimise frequent injections. Over the last two years, both children have demonstrated significant improvement, with almost no further TRAPS flares, normalisation of baseline inflammatory markers and improvements in their growth trajectories. No adverse effects were reported on either agent. JAK inhibitor therapy and tocilizumab were effective in our two cases of TRAPS. To our knowledge, this is the first report describing the use of a JAK inhibitor in TRAPS, while also adding to the limited published experience with tocilizumab in TRAPS.
2023-10-18 | Efficacy and safety of thalidomide in children with monogenic autoinflammatory diseases: a single-center, real-world-evidence study.
Monogenic autoinflammatory diseases (AIDs) are rare inflammatory diseases caused by genetic variants. The pathogenesis is complex and treatment options are limited. This study aimed to describe the safety and efficacy of thalidomide in the treatment of monogenic AIDs. This was a single-center, single-arm, real-world study. From September 2016 to August 2021, patients with monogenic AIDs who met the inclusion and exclusion criteria were given thalidomide for 12 months. There was a 3-month run-in period before dosing. The efficacy and adverse events were evaluated and recorded every 3 months. After 3 and 12 months of thalidomide treatment, clinical manifestations, disease activity score, inflammatory markers, and background medication adjustments were compared with baseline for efficacy analyses. A total of 16 patients entered this study, including 3 with Aicardi-Goutières syndrome (AGS), 4 Blau syndrome, 2 chronic infantile neurologic cutaneous articular syndrome (CINCA), 2 A20 haploinsufficiency (HA20), 1 adenosine deaminase 2 deficiency(DADA2), 1 familial Mediterranean fever (FMF),1 tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS), 1 PLCγ2-associated antibody deficiency and immune dysregulation (PLAID), and 1 stimulator of interferon genes-associated vasculopathy with onset in infancy(SAVI). The efficacy rate in the 16 patients after 3-month and 12-month thalidomide treatment in patients was 56.3%. Twelve patients completed the study, the fever improved in all of them, rash improved in 7 patients, and 5 patients stopped using glucocorticoids or other immunosuppressive agents. C-reactive protein was normal in 8 patients and erythrocyte sedimentation rate was normal in 11 patients. Anorexia and nausea occurred in 2 cases, with no other reported drug-related adverse reactions. The largest cohort of monogenic AIDs with the treatment of thalidomide demonstrated that thalidomide can help reduce disease activity and inflammation, reduce the dosage of glucocorticoids, and improve clinical outcomes. Thalidomide is relatively safe in monogenic AIDs.
2022-01-13 | Selective termination of the fetus in multiple pregnancies using ultrasound-guided radiofrequency ablation.
To evaluate the perinatal outcomes in women with selective termination using ultrasound-guided radiofrequency ablation (RFA). Complicated monochorionic (MC) twin pregnancies and multiple pregnancies with an indication for selective termination by ultrasound-guided coagulation of the umbilical cord with RFA under local anesthesia between July 2013 and Jan 2020 were reviewed. We analyzed the indications, gestational age at the time of the procedure, cycles of RFA, duration of the procedure, and perinatal outcome. Three hundred and thirteen patients were treated during this period. Seven of whom were lost of follow-up. The remaining 306 cases, including 266 pairs of monochorionic diamniotic (MCDA) twins (86.93%), two pairs of monoamniotic twins (0.65%), 30 dichorionic triamniotic (DCTA) triplets (1%), and three monochorionic triamniotic (MCTA) triplets (0.98%), were analyzed. Indications included twin-to-twin transfusion syndrome (TTTS) (n = 91), selective fetal growth restriction (sFGR) (n = 83), severe discordant structural malformation (n = 78), multifetal pregnancy reduction (MFPR) (n = 78), twin reverse arterial perfusion sequence (TRAPS) (n = 19), and twin anemia-polycythemia sequence (TAPS) (n = 3). Upon comparison of RFA performed before and after 20 weeks, the co-twin loss rate (20.9% vs. 21.5%), the incidence of preterm premature rupture of membranes (PPROM) within 24 h (1.5% vs. 1.2%), and the median gestational age at delivery [35.93 (28-38) weeks vs. 36 (28.54-38.14) weeks] were similar (p > 0.05). RFA is a reasonable option when indicated in multiple pregnancies and complicated monochorionic pregnancies. In our experience, the overall survival rate was 78.76% with RFA in selective feticide, and early treatment increases the likelihood of survival for the remaining fetus because the fetal loss rate is similar before and after 20 weeks.
2021-07-16 | 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.
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 < 0.01). Abdominal pain was significantly associated also to the presence of HP mutations (p < 0.01), while oral aphthosis was more frequently found in the LP variant group (p < 0.05). Systemic amyloidosis occurred in 25% of subjects carrying HP variants. As concerns laboratory features, HP mutations were significantly associated to higher ESR values (p < 0.01) and to the persistence of steadily elevated inflammatory markers during asymptomatic periods (p < 0.05). The presence of mutations involving a cysteine residue, abdominal pain, and lymphadenopathy during flares significantly correlated with the risk of developing amyloidosis and renal impairment. Conversely, the administration of colchicine negatively correlated to the development of pathologic proteinuria (p < 0.05). Both NSAIDs and colchicine were used as monotherapy more frequently in the LP group compared to the HP group (p < 0.01). Biologic agents were prescribed to 49 (61%) patients; R92Q subjects were more frequently on NSAIDs monotherapy than other patients (p < 0.01); nevertheless, they required biologic therapy in 53.1% of cases. At disease onset, the latest classification criteria for TRAPS were fulfilled by 64/80 (80%) patients (clinical plus genetic items) and 46/80 (57.5%) patients (clinical items only). No statistically significant differences were found in the sensitivity of the classification criteria according to age at onset and according to genotype (p < 0.05). This study describes one of the widest cohorts of TRAPS patients in the literature, suggesting that the clinical expression of this syndrome is more influenced by the penetrance of the mutation rather than by the age at onset itself. Given the high phenotypic heterogeneity of the disease, a definite diagnosis should rely on both accurate working clinical assessment and complementary genotype.
2021-07-09 | Role of Colchicine Treatment in Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS): Real-Life Data from the AIDA Network.
To analyze the potential role of colchicine monotherapy in patients with tumor necrosis factor receptor associated periodic syndrome (TRAPS) in terms of control of clinical and laboratory manifestations. Patients with TRAPS treated with colchicine monotherapy were retrospectively enrolled; demographic, clinical and therapeutic data were collected and statistically analysed after having clustered patients according to different times at disease onset, penetrance of mutations, dosage of colchicine, and different disease manifestations. 24 patients (14 males; 15 with pediatric disease onset) treated with colchicine monotherapy were enrolled. Colchicine resulted in a complete response in 3 (12.5%) cases, partial response in 14 (58.3%) patients, and lack of response in 7 (29.2%) patients. There were not significant differences in colchicine response between pediatric and adult disease onset (p = 0.42), between low- and high-penetrance mutations (p = 0.62), and according to different dosages (p = 0.66). No significant differences were identified in the frequency of specific disease manifestations between patients experiencing any response to colchicine and patients with lack of response. Colchicine monotherapy is useful in a low percentage of TRAPS patients; nevertheless, it could be attempted in patients with milder phenotypes and at a lower risk of developing reactive amyloidosis.
antibodies
2026-08-01 | A Novel TNFRSF1A Gene Variant in a Patient with Recurrent Fevers and Amyloidosis: A Case Report
Background TNF Receptor Associated Periodic Syndrome (TRAPS) is a rare autosomal dominant autoinflammatory disorder. It is caused by pathogenic variants in the TNFRSF1A gene which encodes the TNF receptor 1. These mutations impair receptor shedding and disrupt TNFα signaling, leading to uncontrolled inflammation with recurrent fever, serositis, and myalgia.[1] Left untreated, chronic inflammation may result in AA amyloidosis and end-stage renal disease (ESRD). Early recognition and treatment with IL-1 inhibitors can mitigate deterioration and prevent irreversible complications such as amyloidosis. Here we present a case of TRAPS complicated by amyloidosis and associated with a novel variant in TNFRSF1A. Case Report A 48-year-old male was referred for early childhood onset, recurrent 3-5-day febrile episodes accompanied by severe abdominal pain, large joint arthralgias and myalgias. He was treated intermittently with corticosteroids and NSAIDs, with incomplete response. At 43 years old he developed chronic kidney disease with renal biopsy compatible with amyloidosis. This eventually progressed to ESRD requiring hemodialysis. Genetic testing was performed when he was 48 years old and revealed a heterozygous missense variant in TNFRSF1A (c.214_215delinsCT, p.Cys72Leu). The mutation resides in exon 3 within the extracellular cysteine-rich domain, and was predicted to disrupt disulfide bond formation, resulting in misfolded receptor protein and defective TNFα signaling. Substitutions at the same residue (Cys72Arg, Cys72Ser) had been previously demonstrated to be causative for TRAPS.[2] His asymptomatic parents did not carry the mutation. As such, this de novo Cys72Leu variant was classified as Likely Pathogenic, and the patient was diagnosed with TRAPS. Anakinra 100 mg SC daily was started which prevented further attacks. However, he remains on hemodialysis and is on the waitlist for renal transplant. Conclusion In summary, our case highlights the importance of early recognition of autoinflammatory diseases like TRAPS, in order to initiate targeted treatment and prevent life altering complications such as amyloidosis and ESRD. We report a novel variant in the TNFRSF1A gene, adding to the literature of mutations causing TRAPS. Further studies are needed to functionally characterize the biological impact of Cys72Leu, as well as to elucidate the complex mechanisms between TNF receptor dysfunction and IL-1 signaling. References [1.] Gaggiano C. Mediators Inflamm 2020;7:8562485. [2.] Lachmann HJ. Ann Rheum Dis 2014;73:2160-7.
2026-07-21 | A Case of Adult-Onset TNF Receptor-Associated Periodic Syndrome (TRAPS) with Somatic Mosaicism Treated with an IL-1 Inhibitor.
Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is a rare autoinflammatory disorder, and adult-onset cases caused by somatic mosaic TNFRSF1A variants are exceptionally rare. A man in his 60s developed recurrent febrile episodes with rash and polyarthralgia and was initially misdiagnosed with a biliary infection and adult-onset Still's disease. Hybrid capture-based next-generation sequencing identified a somatic mosaic TNFRSF1A variant with a variant allele frequency of 19%, thus establishing the diagnosis of TRAPS. Treatment with canakinumab resulted in complete clinical remission and successful glucocorticoid tapering.
2026-05-29 | Pediatric Rheumatic Disorders Revisited: Integrating Imaging and Pathophysiologic Insights across the Autoinflammatory-Autoimmune Continuum.
Recent advances in immunologic and molecular research on rheumatic diseases have significantly improved understanding of the diverse group of immune-mediated disorders. Rheumatic diseases were traditionally considered autoimmune diseases, caused by impaired adaptive immunity and often associated with pathogenic autoantibodies. However, in the late 20th century, certain genetic rheumatic diseases-such as tumor necrosis factor receptor-associated periodic syndrome (TRAPS) and familial Mediterranean fever (FMF)-were found to result from antigen-independent activation of innate immune cells and the subsequent cytokine-mediated inflammation. This discovery introduced the new concept of autoinflammatory diseases, characterized by dysregulation of innate immunity. Although autoimmune and autoinflammatory diseases were initially regarded as distinct categories, substantial overlap has become evident. For instance, autoantibodies can be detected in disorders primarily affecting innate immunity, while recent cytokine-targeting therapies have proven effective for classic autoimmune diseases, such as systemic lupus erythematosus (SLE) and dermatomyositis. These insights led to the concept of an autoinflammatory-autoimmune continuum, highlighting that dysregulation of the interaction between innate and adaptive immune systems contributes to the clinical symptoms of rheumatic diseases. The authors explore clinical, imaging, pathophysiologic, and therapeutic aspects of pediatric rheumatic diseases through the lens of this continuum, providing a comprehensive overview of current diagnostic and treatment strategies. © RSNA, 2026 Supplemental material is available for this article.
2026-04-04 | When to suspect monogenic autoinflammatory diseases in patients with digestive symptoms?
Autoinflammatory diseases are characterized by dysregulation of the innate immune system. This article provides an updated overview of autoinflammatory diseases with gastrointestinal manifestations and outlines the clinical situations in which gastroenterologists should consider these conditions. The most prevalent form worldwide is familial Mediterranean fever (FMF), which is associated with mutations in the MEFV (MEditerranean FeVer) gene and presents with recurrent episodes of serositis, primarily peritonitis, accompanied by systemic inflammation. From a biological standpoint, a peripheral inflammatory syndrome is typically observed during acute attacks; however, in some cases inflammation may persist chronically. At the molecular level, these diseases involve numerous genes encoding proteins that participate in the activation or regulation of inflammatory pathways within innate immune cells. Initially, four monogenic disorders were described FMF, TNF receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency (MKD), and cryopyrin-associated periodic syndromes (CAPS) collectively referred to as the four historical autoinflammatory diseases. Each year, new monogenic autoinflammatory diseases are identified thanks to rapid advances in genetic sequencing technologies. The recent identification of somatic forms of monogenic diseases, including certain cryopyrinopathies and, in 2020, VEXAS syndrome, has added a new level of complexity to the field.
2026-03-29 | Unclassified autoinflammatory syndrome with TRAPS-like symptoms and severe oropharyngeal disease treated successfully with canakinumab.
PURPOSE: To report an unclassified autoinflammatory syndrome with TRAPS-like and Behçet-like features presenting with severe inflammatory pharyngeal wall involvement threatening the airway, successfully controlled with canakinumab. CASE DESCRIPTION: A 40-year-old woman had a 20-year history of recurrent oral and genital ulcers, uveitis, photosensitive rash, episodic neurological symptoms and relapsing arthritis with prominent sternoclavicular involvement, negative autoimmune serology and nonspecific chronic inflammatory changes on biopsy. A heterozygous TNFRSF1A variant of uncertain significance supported a TRAPS spectrum diagnosis. Conventional disease-modifying agents and several biologics achieved only partial or transient responses; anakinra was discontinued because of severe injection-site reactions. She then developed a painful, progressively enlarging inflammatory thickening of the posterior and lateral pharyngeal walls with dysphagia and impending airway compromise on MRI. High-dose glucocorticoids and background immunosuppression were insufficient. Canakinumab 300 mg every 4 weeks induced rapid symptom relief and near-complete radiological resolution within 2 months, with sustained remission on 150 mg every 4 weeks plus conventional therapy. Close collaboration between rheumatology and otorhinolaryngology in similar cases is warranted.
proteins
2023-10-09 | A patient with tumor necrosis factor receptor-associated periodic syndrome misdiagnosed as Kawasaki disease: A case report and literature review.
This article reports a case of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) misdiagnosed as Kawasaki disease and summarizes the clinical features and therapeutic progress of TRAPS and the relationship between its clinical manifestations and gene mutations. We retrospectively analyzed a patient with tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) -mutated auto-inflammatory disease who was misdiagnosed with Kawasaki disease in another hospital. The clinical features and therapeutic progress of TRAPS were analyzed by combining clinical features and gene reports of this case and literature review. TRAPS onset occurred in a female pediatric patient at the age of 4 months. The child and in his father at the age of 6 years, both of whom manifested periodic fever, and recurrent rash, as well as elevated leukocytes, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) during episodes but normal between episodes. This child carried a heterozygous mutation in TNFRSF1A located in the region 6442923-6442931 on chromosome 12. The nucleic acid alteration was: c.298 (exon3) _c.306 (exon3) 291 delCTCAGCTGC, resulting in a 3 amino acid deletion p.L100_C 102del 292 (p.Leu100_Cys102del) (NM_001065). After etanercept treatment, the symptoms of fever and rash disappeared, and the levels of ESR, CRP, interleukin (IL)-1, IL-6, and TNF-α levels were normal. Subsequently, no liver, kidney, or cardiac amyloidosis and severe etanercept-related adverse events were observed at 1-year follow-up. TRAPS pathogenesis is associated with TNFRSF1A mutation, which is characterized by periodic episodes of fever, mostly accompanied by recurrent rashes, periorbital edema, abdominal pain, and serious complications of organ amyloidosis. Moreover, etanercept can effectively alleviate the clinical symptoms and high inflammation level of TRAPS.
2021-12-17 | Real-Life Indications of Interleukin-1 Blocking Agents in Hereditary Recurrent Fevers: Data From the JIRcohort and a Literature Review.
Interleukin (IL)-1 inhibitors represent the main treatment in patients with colchicine-resistant/intolerant familial Mediterranean fever (crFMF), mevalonate kinase deficiency (MKD), and tumor necrosis factor receptor-associated periodic syndrome (TRAPS). However, the reasons for the use of IL-1 inhibitors in these diseases are still not completely clarified. Identify real-life situations that led to initiating anakinra or canakinumab treatment in hereditary recurrent fevers (HRFs), combining data from an international registry and an up-to-date literature review. Data were extracted from the JIRcohort, in which clinical information (demographic data, treatment, disease activity, and quality of life) on patients with FMF, MKD, and TRAPS was retrospectively collected. A literature search was conducted using Medline, EMBASE, and Cochrane databases. Complete data of 93 patients with HRF (53.8% FMF, 31.2% MKD, and 15.1% TRAPS) were analyzed. Data from both the registry and the literature review confirmed that the main reasons for use of IL-1 blockers were the following: failure of previous treatment (n = 57, 61.3% and n = 964, 75.3%, respectively), persistence of disease activity with frequent attacks (n = 44, 47.3% and n = 1,023, 79.9%) and/or uncontrolled inflammatory syndrome (n = 46, 49.5% and n = 398, 31.1%), severe disease complication or associated comorbidities (n = 38, 40.9% and n = 390, 30.4%), and worsening of patients' quality of life (n = 36, 38.7% and n = 100, 7,8%). No reasons were specified for 12 (16.4%) JIRcohort patients and 154 (12%) patients in the literature. In the absence of standardized indications for IL-1 inhibitors in crFMF, MKD, and TRAPS, these results could serve as a basis for developing a treat-to-target strategy that would help clinicians codify the therapeutic escalation with IL-1 inhibitors.
2021-11-24 | [Periodic fever syndrome associated with mutations in the TNF type 1 receptor gene: A differential diagnosis of familial Mediterranean fever that should not be overlooked in patients of Mediterranean origin].
Tumor Necrosis Factor Type 1 Receptor Associated Periodic Syndrome (TRAPS) is a rare autosomal dominant autosomal autoinflammatory disease associated with mutations in the TNF type 1 receptor gene (TNFRSF1A). It is characterized by relatively long recurrent febrile seizures with an average duration of 7 days accompanied by arthralgia, myalgia, and usually a rash. In a patient of Mediterranean origin with recurrent fever, familial Mediterranean fever is the first diagnosis to be suspected by argument of frequency. A retrospective observational study was conducted on patients from Mediterranean origin followed for TRAPS and included in the "Juvenile Inflammatory Rheumatism" (JIR) observational cohort in the national French autoinflammatory center. The age of onset of symptoms, age of diagnosis, number of years of wandering and treatments received were collected for each index case. Nine patients from 6 families of Mediterranean origin were included. A molecular diagnosis confirmed TRAPS in all patients. The median age at diagnosis was 26 years, the mean number of years of wandering was 17 years. The diagnosis of FMF was made first in all patients. AA amyloidosis revealed TRAPS in 2 patients. Colchicine was started without any efficacy in all cases. Five patients were treated with interleukin-1 inhibitory biotherapy with 100% efficacy. In a patient of Mediterranean origin presenting with recurrent febrile abdominal pain of AA amyloidosis, the first diagnosis to be suspected is FMF. Long relapses, dominant transmission, a non-Mediterranean relative, and the ineffectiveness of colchicine should evoke TRAPS.
2020-04-15 | TNF receptor signalling in autoinflammatory diseases.
Autoinflammatory syndromes are a group of disorders characterized by recurring episodes of inflammation as a result of specific defects in the innate immune system. Patients with autoinflammatory disease present with recurrent outbreaks of chronic systemic inflammation that are mediated by innate immune cells, for the most part. A number of these diseases arise from defects in the tumour necrosis factor receptor (TNFR) signalling pathway leading to elevated levels of inflammatory cytokines. Elucidation of the molecular mechanisms of these recently defined autoinflammatory diseases has led to a greater understanding of the mechanisms of action of key molecules involved in TNFR signalling, particularly those involved in ubiquitination, as found in haploinsufficiency of A20 (HA20), otulipenia/OTULIN-related autoinflammatory syndrome (ORAS) and linear ubiquitin chain assembly complex (LUBAC) deficiency. In this review, we also address other TNFR signalling disorders such as TNFR-associated periodic syndrome (TRAPS), RELA haploinsufficiency, RIPK1-associated immunodeficiency and autoinflammation, X-linked ectodermal dysplasia and immunodeficiency (X-EDA-ID) and we review the most recent advances surrounding these diseases and therapeutic approaches currently used to target these diseases. Finally, we explore therapeutic advances in TNF-related immune-based therapies and explore new approaches to target disease-specific modulation of autoinflammatory diseases.
2019-03-17 | Treating TNF Receptor Associated Periodic Fever Syndrome in End-Stage Renal Failure
Tumor necrosis factor receptor associated periodic syndrome (TRAPS) is a rare monogenic autoinflammatory disease. Its most severe manifestation is secondary amyloidosis. A 44-year-old male presented with nephrotic syndrome. Kidney biopsy was conclusive for secondary amyloidosis. The patient and his children had a history of recurrent febrile periods since infancy. All subjects were positive for a heterozygous variant of the TNFRSF1A gene, confirming TRAPS diagnosis. The patient progressed to end-stage renal failure and developed recurrent pericarditis episodes. He was started on anakinra while on hemodialysis with marked reduction of his serum amyloid A protein (SAA) levels. Meanwhile he received a cadaveric renal transplant and maintains anakinra treatment. Despite renal failure being the most feared complication of AA amyloidosis caused by TRAPS, little data is available about safety of anti-IL-1 treatment in patients with severe kidney failure. The authors report this case of a patient on dialysis treated with anakinra in which no complications were registered. Though amyloidosis is established, the authors believe containing its progression and reducing inflammatory activity can improve patient prognosis and reduce recurrence of amyloidosis in kidney transplant, as has been demonstrated in transplanted patients due to familial Mediterranean fever amyloidosis.
small molecules
2026-06-18 | The use of JAK inhibitors and tocilizumab in the management of TRAPS: a sibling case study.
Tumour necrosis factor (TNF) receptor-1 associated periodic syndrome (TRAPS) is an autoinflammatory condition. Most treatment options require regular injections, posing challenges for individuals with needle phobia. We reviewed the medical records of two siblings, a now 14-year-old female, and her 10-year-old brother, both diagnosed with TRAPS in early infancy. Both children responded to on-demand oral corticosteroid therapy, but due to frequent flares, persistent biochemical inflammation and poor growth, steroid-sparing therapies were required. Non-standard first-line therapies were subsequently selected as the eldest child had developed a needle phobia, and she was commenced on an oral Janus kinase (JAK) inhibitor. The younger brother was treated with tocilizumab, reflecting parental preference to minimise frequent injections. Over the last two years, both children have demonstrated significant improvement, with almost no further TRAPS flares, normalisation of baseline inflammatory markers and improvements in their growth trajectories. No adverse effects were reported on either agent. JAK inhibitor therapy and tocilizumab were effective in our two cases of TRAPS. To our knowledge, this is the first report describing the use of a JAK inhibitor in TRAPS, while also adding to the limited published experience with tocilizumab in TRAPS.
2023-10-18 | Efficacy and safety of thalidomide in children with monogenic autoinflammatory diseases: a single-center, real-world-evidence study.
Monogenic autoinflammatory diseases (AIDs) are rare inflammatory diseases caused by genetic variants. The pathogenesis is complex and treatment options are limited. This study aimed to describe the safety and efficacy of thalidomide in the treatment of monogenic AIDs. This was a single-center, single-arm, real-world study. From September 2016 to August 2021, patients with monogenic AIDs who met the inclusion and exclusion criteria were given thalidomide for 12 months. There was a 3-month run-in period before dosing. The efficacy and adverse events were evaluated and recorded every 3 months. After 3 and 12 months of thalidomide treatment, clinical manifestations, disease activity score, inflammatory markers, and background medication adjustments were compared with baseline for efficacy analyses. A total of 16 patients entered this study, including 3 with Aicardi-Goutières syndrome (AGS), 4 Blau syndrome, 2 chronic infantile neurologic cutaneous articular syndrome (CINCA), 2 A20 haploinsufficiency (HA20), 1 adenosine deaminase 2 deficiency(DADA2), 1 familial Mediterranean fever (FMF),1 tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS), 1 PLCγ2-associated antibody deficiency and immune dysregulation (PLAID), and 1 stimulator of interferon genes-associated vasculopathy with onset in infancy(SAVI). The efficacy rate in the 16 patients after 3-month and 12-month thalidomide treatment in patients was 56.3%. Twelve patients completed the study, the fever improved in all of them, rash improved in 7 patients, and 5 patients stopped using glucocorticoids or other immunosuppressive agents. C-reactive protein was normal in 8 patients and erythrocyte sedimentation rate was normal in 11 patients. Anorexia and nausea occurred in 2 cases, with no other reported drug-related adverse reactions. The largest cohort of monogenic AIDs with the treatment of thalidomide demonstrated that thalidomide can help reduce disease activity and inflammation, reduce the dosage of glucocorticoids, and improve clinical outcomes. Thalidomide is relatively safe in monogenic AIDs.
2022-01-13 | Selective termination of the fetus in multiple pregnancies using ultrasound-guided radiofrequency ablation.
To evaluate the perinatal outcomes in women with selective termination using ultrasound-guided radiofrequency ablation (RFA). Complicated monochorionic (MC) twin pregnancies and multiple pregnancies with an indication for selective termination by ultrasound-guided coagulation of the umbilical cord with RFA under local anesthesia between July 2013 and Jan 2020 were reviewed. We analyzed the indications, gestational age at the time of the procedure, cycles of RFA, duration of the procedure, and perinatal outcome. Three hundred and thirteen patients were treated during this period. Seven of whom were lost of follow-up. The remaining 306 cases, including 266 pairs of monochorionic diamniotic (MCDA) twins (86.93%), two pairs of monoamniotic twins (0.65%), 30 dichorionic triamniotic (DCTA) triplets (1%), and three monochorionic triamniotic (MCTA) triplets (0.98%), were analyzed. Indications included twin-to-twin transfusion syndrome (TTTS) (n = 91), selective fetal growth restriction (sFGR) (n = 83), severe discordant structural malformation (n = 78), multifetal pregnancy reduction (MFPR) (n = 78), twin reverse arterial perfusion sequence (TRAPS) (n = 19), and twin anemia-polycythemia sequence (TAPS) (n = 3). Upon comparison of RFA performed before and after 20 weeks, the co-twin loss rate (20.9% vs. 21.5%), the incidence of preterm premature rupture of membranes (PPROM) within 24 h (1.5% vs. 1.2%), and the median gestational age at delivery [35.93 (28-38) weeks vs. 36 (28.54-38.14) weeks] were similar (p > 0.05). RFA is a reasonable option when indicated in multiple pregnancies and complicated monochorionic pregnancies. In our experience, the overall survival rate was 78.76% with RFA in selective feticide, and early treatment increases the likelihood of survival for the remaining fetus because the fetal loss rate is similar before and after 20 weeks.
2021-07-16 | 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.
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 < 0.01). Abdominal pain was significantly associated also to the presence of HP mutations (p < 0.01), while oral aphthosis was more frequently found in the LP variant group (p < 0.05). Systemic amyloidosis occurred in 25% of subjects carrying HP variants. As concerns laboratory features, HP mutations were significantly associated to higher ESR values (p < 0.01) and to the persistence of steadily elevated inflammatory markers during asymptomatic periods (p < 0.05). The presence of mutations involving a cysteine residue, abdominal pain, and lymphadenopathy during flares significantly correlated with the risk of developing amyloidosis and renal impairment. Conversely, the administration of colchicine negatively correlated to the development of pathologic proteinuria (p < 0.05). Both NSAIDs and colchicine were used as monotherapy more frequently in the LP group compared to the HP group (p < 0.01). Biologic agents were prescribed to 49 (61%) patients; R92Q subjects were more frequently on NSAIDs monotherapy than other patients (p < 0.01); nevertheless, they required biologic therapy in 53.1% of cases. At disease onset, the latest classification criteria for TRAPS were fulfilled by 64/80 (80%) patients (clinical plus genetic items) and 46/80 (57.5%) patients (clinical items only). No statistically significant differences were found in the sensitivity of the classification criteria according to age at onset and according to genotype (p < 0.05). This study describes one of the widest cohorts of TRAPS patients in the literature, suggesting that the clinical expression of this syndrome is more influenced by the penetrance of the mutation rather than by the age at onset itself. Given the high phenotypic heterogeneity of the disease, a definite diagnosis should rely on both accurate working clinical assessment and complementary genotype.
2021-07-09 | Role of Colchicine Treatment in Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS): Real-Life Data from the AIDA Network.
To analyze the potential role of colchicine monotherapy in patients with tumor necrosis factor receptor associated periodic syndrome (TRAPS) in terms of control of clinical and laboratory manifestations. Patients with TRAPS treated with colchicine monotherapy were retrospectively enrolled; demographic, clinical and therapeutic data were collected and statistically analysed after having clustered patients according to different times at disease onset, penetrance of mutations, dosage of colchicine, and different disease manifestations. 24 patients (14 males; 15 with pediatric disease onset) treated with colchicine monotherapy were enrolled. Colchicine resulted in a complete response in 3 (12.5%) cases, partial response in 14 (58.3%) patients, and lack of response in 7 (29.2%) patients. There were not significant differences in colchicine response between pediatric and adult disease onset (p = 0.42), between low- and high-penetrance mutations (p = 0.62), and according to different dosages (p = 0.66). No significant differences were identified in the frequency of specific disease manifestations between patients experiencing any response to colchicine and patients with lack of response. Colchicine monotherapy is useful in a low percentage of TRAPS patients; nevertheless, it could be attempted in patients with milder phenotypes and at a lower risk of developing reactive amyloidosis.
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Drug Discovery Landscape
2 orphan drug designations for Tumor necrosis factor receptor 1 associated periodic syndrome, including 1 approved therapy.
2 orphan drug designations for Tumor necrosis factor receptor 1 associated periodic syndrome, including 1 approved therapy.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Canakinumab [Ilaris] | antibodies | EMA | 2012-11-08 | — | Novartis Europharm Limited |
canakinumab [Ilaris] | antibodies | FDA | 2012-09-04 | 2016-09-23 | Novartis Pharmaceuticals Corporation |
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