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 (d...
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Format: | Article |
Language: | English |
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Hindawi Limited
2020-01-01
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Series: | Mediators of Inflammation |
Online Access: | http://dx.doi.org/10.1155/2020/8562485 |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Carla Gaggiano Antonio Vitale Laura Obici Giampaolo Merlini Alessandra Soriano Ombretta Viapiana Marco Cattalini Maria Cristina Maggio Giuseppe Lopalco Davide Montin Masen Abdel Jaber Lorenzo Dagna Raffaele Manna Antonella Insalaco Matteo Piga Francesco La Torre Virginia Berlengiero Viviana Gelardi Luisa Ciarcia Giacomo Emmi Piero Ruscitti Francesco Caso Rolando Cimaz José Hernández-Rodríguez Paola Parronchi Ludovico Luca Sicignano Elena Verrecchia Florenzo Iannone Jurgen Sota Salvatore Grosso Carlo Salvarani Bruno Frediani Roberto Giacomelli Maria Antonietta Mencarelli Alessandra Renieri Donato Rigante Luca Cantarini |
spellingShingle |
Carla Gaggiano Antonio Vitale Laura Obici Giampaolo Merlini Alessandra Soriano Ombretta Viapiana Marco Cattalini Maria Cristina Maggio Giuseppe Lopalco Davide Montin Masen Abdel Jaber Lorenzo Dagna Raffaele Manna Antonella Insalaco Matteo Piga Francesco La Torre Virginia Berlengiero Viviana Gelardi Luisa Ciarcia Giacomo Emmi Piero Ruscitti Francesco Caso Rolando Cimaz José Hernández-Rodríguez Paola Parronchi Ludovico Luca Sicignano Elena Verrecchia Florenzo Iannone Jurgen Sota Salvatore Grosso Carlo Salvarani Bruno Frediani Roberto Giacomelli Maria Antonietta Mencarelli Alessandra Renieri Donato Rigante Luca Cantarini 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 Mediators of Inflammation |
author_facet |
Carla Gaggiano Antonio Vitale Laura Obici Giampaolo Merlini Alessandra Soriano Ombretta Viapiana Marco Cattalini Maria Cristina Maggio Giuseppe Lopalco Davide Montin Masen Abdel Jaber Lorenzo Dagna Raffaele Manna Antonella Insalaco Matteo Piga Francesco La Torre Virginia Berlengiero Viviana Gelardi Luisa Ciarcia Giacomo Emmi Piero Ruscitti Francesco Caso Rolando Cimaz José Hernández-Rodríguez Paola Parronchi Ludovico Luca Sicignano Elena Verrecchia Florenzo Iannone Jurgen Sota Salvatore Grosso Carlo Salvarani Bruno Frediani Roberto Giacomelli Maria Antonietta Mencarelli Alessandra Renieri Donato Rigante Luca Cantarini |
author_sort |
Carla Gaggiano |
title |
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 |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
publisher |
Hindawi Limited |
series |
Mediators of Inflammation |
issn |
0962-9351 1466-1861 |
publishDate |
2020-01-01 |
description |
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. |
url |
http://dx.doi.org/10.1155/2020/8562485 |
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doaj-da552a75d67c4b77af5e5c513b5102312020-11-25T03:50:06ZengHindawi LimitedMediators of Inflammation0962-93511466-18612020-01-01202010.1155/2020/85624858562485Clinical 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 NetworkCarla Gaggiano0Antonio Vitale1Laura Obici2Giampaolo Merlini3Alessandra Soriano4Ombretta Viapiana5Marco Cattalini6Maria Cristina Maggio7Giuseppe Lopalco8Davide Montin9Masen Abdel Jaber10Lorenzo Dagna11Raffaele Manna12Antonella Insalaco13Matteo Piga14Francesco La Torre15Virginia Berlengiero16Viviana Gelardi17Luisa Ciarcia18Giacomo Emmi19Piero Ruscitti20Francesco Caso21Rolando Cimaz22José Hernández-Rodríguez23Paola Parronchi24Ludovico Luca Sicignano25Elena Verrecchia26Florenzo Iannone27Jurgen Sota28Salvatore Grosso29Carlo Salvarani30Bruno Frediani31Roberto Giacomelli32Maria Antonietta Mencarelli33Alessandra Renieri34Donato Rigante35Luca Cantarini36Clinical Pediatrics, Department of Molecular Medicine and Development, University of Siena, Siena, ItalyResearch Center of Systemic Autoinflammatory Diseases and Behçet’s Disease Clinic, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, ItalyAmyloidosis Research and Treatment Center, Fondazione IRCCS Policlinico San Matteo, Pavia, ItalyAmyloidosis Research and Treatment Center, Fondazione IRCCS Policlinico San Matteo, Pavia, ItalyDepartment of Internal Medicine, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, ItalyRheumatology Section, Department of Medicine, University of Verona, Verona, ItalyPaediatric Clinic, University of Brescia and Spedali Civili di Brescia, Brescia, ItalyUniversitary Department “Pro.S.A.M.I.”, University of Palermo, Palermo, ItalyRheumatology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, ItalyDivision of Immunology and Rheumatology, Department of Paediatric Infectious Diseases, University of Turin, Regina Margherita Children's Hospital, Turin, ItalyRheumatology Unit, Santa Chiara Hospital, Trento, ItalyUnit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Scientific Institute, Milan, ItalyPeriodic Fever Research Center, Institute of Internal Medicine, Catholic University of the Sacred Heart, Fondazione Policlinico A. Gemelli, Rome, ItalyDivision of Rheumatology, Department of Pediatric Medicine, Bambino Gesù Children’s Hospital, IRCCS, Rome, ItalyRheumatology Unit, Department of Medical Sciences, University and AOU of Cagliari, Cagliari, ItalyClinical Pediatrics, University of Bari, Bari, ItalyResearch Center of Systemic Autoinflammatory Diseases and Behçet’s Disease Clinic, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, ItalyResearch Center of Systemic Autoinflammatory Diseases and Behçet’s Disease Clinic, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, ItalyResearch Center of Systemic Autoinflammatory Diseases and Behçet’s Disease Clinic, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, ItalyDepartment of Experimental and Clinical Medicine, University of Firenze, Florence, ItalyRheumatology Unit, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, ItalyRheumatology Unit, Department of Clinical Medicine and Surgery, School of Medicine and Surgery, University Federico II, Naples, ItalyDepartment of Clinical Sciences and Community Health, University of Milan, Milan, ItalyVasculitis Research Unit and Autoinflammatory Diseases Clinical Unit, Department of Autoimmune Diseases, Hospital Clinic of Barcelona, IDIBAPS, University of Barcelona, Barcelona, SpainDepartment of Experimental and Clinical Medicine, University of Firenze, Florence, ItalyPeriodic Fever Research Center, Institute of Internal Medicine, Catholic University of the Sacred Heart, Fondazione Policlinico A. Gemelli, Rome, ItalyPeriodic Fever Research Center, Institute of Internal Medicine, Catholic University of the Sacred Heart, Fondazione Policlinico A. Gemelli, Rome, ItalyRheumatology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, ItalyResearch Center of Systemic Autoinflammatory Diseases and Behçet’s Disease Clinic, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, ItalyClinical Pediatrics, Department of Molecular Medicine and Development, University of Siena, Siena, ItalyDepartment of Internal Medicine, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, ItalyResearch Center of Systemic Autoinflammatory Diseases and Behçet’s Disease Clinic, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, ItalyRheumatology Unit, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, ItalyGenetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, ItalyGenetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, ItalyInstitute of Pediatrics, Periodic Fever Research Center, Università Cattolica Sacro Cuore, Fondazione Policlinico A. Gemelli, IRCCS, Rome, ItalyResearch Center of Systemic Autoinflammatory Diseases and Behçet’s Disease Clinic, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, ItalyThis 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.http://dx.doi.org/10.1155/2020/8562485 |