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OBJECTIVE: Data on the long-term outcome of patients with childhood-onset Systemic Lupus Erythematosus (cSLE) are scarce. Aims of this study were to describe the long-term outcomes of cSLE and to identify factors associated with the development of damage and persistent disease activity. METHODS: We conducted a retrospective multicentre study using data from the PEDIALUP registry of the Juvenile Inflammatory Rheumatism (JIR) cohort database. Demographic characteristics, clinical manifestations, laboratory, radiological, histological and treatment data were collected from medical records during follow-up. RESULTS: A total of 138 patients with cSLE, diagnosed between 1971 and 2015, were included. With a median follow-up of 15.4 [9.6-22.4] years, 51% of patients had a SLICC-Damage Index score ≥ 1 at last follow-up with the musculoskeletal, cutaneous, renal, neurological, and cardiovascular damage being the most common manifestations. The proportion of patients with a SLICC-DI score ≥ 1 increased significantly with the duration of the follow-up (p< 0.001). On multivariate analysis, duration of follow-up was associated with increased risk of cumulative damage (OR 1.08, 95% CI 1.01, 1.15, p= 0.035). At the last visit, 34% of patients still had active disease with a SLEDAI score of ≥ 6. On multivariate analysis, Sub-Saharan African ethnicity was associated with 7-fold increased odds of having active disease at the last visit compared with Caucasians (OR 7.44, 95% CI 2.24, 24.74, p= 0.0002). CONCLUSION: The prevalence of damage remains high in patients with cSLE even when the diagnosis of c-SLE has been made in the recent decades.
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Mastocytosis is a heterogeneous disease characterized by an abnormal accumulation of mast cells (MCs) in 1 or several organs. Although a somatic KIT D816V mutation is detected in â¼85% of patients, attempts to demonstrate its oncogenic effect alone have repeatedly failed, suggesting that additional pathways are involved in MC transformation. From 3 children presenting with both Greig cephalopolysyndactyly syndrome (GCPS, Mendelian Inheritance in Man [175700]) and congenital mastocytosis, we demonstrated the involvement of the hedgehog (Hh) pathway in mastocytosis. GCPS is an extremely rare syndrome resulting from haploinsufficiency of GLI3, the major repressor of Hh family members. From these familial cases of mastocytosis, we demonstrate that the Hh pathway is barely active in normal primary MCs and is overactive in neoplastic MCs. GLI3 and KIT mutations had a synergistic, tumorigenic effect on the onset of mastocytosis in a GCPS mouse model. Finally, Hh inhibitors suppressed neoplastic MC proliferation in vitro and extend the survival time of mice with aggressive systemic mastocytosis (ASM). This work revealed, for the first time, the involvement of Hh signaling in the pathophysiology of mastocytosis and demonstrated the cooperative effects of the KIT and Hh oncogenic pathways in mice with ASM, leading to the identification of new promising therapeutic targets.
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Acrocefalosindactilia/complicaciones , Proteínas Hedgehog/metabolismo , Mastocitosis/complicaciones , Transducción de Señal , Acrocefalosindactilia/metabolismo , Animales , Células Cultivadas , Niño , Humanos , Mastocitosis/metabolismo , Ratones Endogámicos C57BL , Ratones SCID , Células Tumorales CultivadasRESUMEN
OBJECTIVE: To evaluate genetic, demographic and clinical features in patients with cryopyrin-associated periodic syndrome (CAPS) from the Eurofever Registry, with a focus on genotype-phenotype correlations and predictive disease severity markers. METHODS: A web-based registry retrospectively collected data on patients with CAPS. Experts in the disease independently validated all cases. Patients carrying NLRP3 variants and germline-mutation-negative patients were included. RESULTS: 136 patients were analysed. The median age at disease onset was 9â months, and the median duration of follow-up was 15â years. Skin rash, musculoskeletal involvement and fever were the most prevalent features. Neurological involvement (including severe complications) was noted in 40% and 12% of the patients, respectively, with ophthalmological involvement in 71%, and neurosensory hearing loss in 42%. 133 patients carried a heterozygous, germline mutation, and 3 patients were mutation-negative (despite complete NLRP3 gene screening). Thirty-one different NLRP3 mutations were recorded; 7 accounted for 78% of the patients, whereas 24 rare variants were found in 27 cases. The latter were significantly associated with early disease onset, neurological complications (including severe complications) and severe musculoskeletal involvement. The T348M variant was associated with early disease onset, chronic course and hearing loss. Neurological involvement was less strongly associated with V198M, E311â K and A439â V alleles. Early onset was predictive of severe neurological complications and hearing loss. CONCLUSIONS: Patients carrying rare NLRP3 variants are at risk of severe CAPS; onset before the age of 6â months is associated with more severe neurological involvement and hearing loss. These findings may have an impact on treatment decisions.
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Proteínas Portadoras/genética , Síndromes Periódicos Asociados a Criopirina/genética , Sistema de Registros , Adolescente , Adulto , Alelos , Artralgia/etiología , Artralgia/genética , Artritis/etiología , Artritis/genética , Niño , Preescolar , Estudios de Cohortes , Conjuntivitis/etiología , Conjuntivitis/genética , Síndromes Periódicos Asociados a Criopirina/complicaciones , Síndromes Periódicos Asociados a Criopirina/fisiopatología , Europa (Continente) , Exantema/etiología , Exantema/genética , Femenino , Genotipo , Mutación de Línea Germinal , Cefalea/etiología , Cefalea/genética , Pérdida Auditiva Sensorineural/etiología , Pérdida Auditiva Sensorineural/genética , Heterocigoto , Humanos , Lactante , Masculino , Meningitis/etiología , Meningitis/genética , Mutación , Mialgia/etiología , Mialgia/genética , Proteína con Dominio Pirina 3 de la Familia NLR , Papiledema/etiología , Papiledema/genética , Fenotipo , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Uveítis/etiología , Uveítis/genética , Adulto JovenRESUMEN
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.
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Enfermedades Autoinflamatorias Hereditarias/genética , Receptores Tipo I de Factores de Necrosis Tumoral/genética , Adolescente , Adulto , Anciano , Niño , Preescolar , Estudios de Cohortes , Progresión de la Enfermedad , Exantema/etiología , Femenino , Fiebre/etiología , Genotipo , Enfermedades Autoinflamatorias Hereditarias/complicaciones , Enfermedades Autoinflamatorias Hereditarias/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Dolor/etiología , Fenotipo , Sistema de Registros , Estudios Retrospectivos , Factores de Tiempo , Adulto JovenRESUMEN
Antiphospholipid syndrome (APS) is a chronic autoimmune disease involving vascular thrombosis and/or obstetric morbidity and persistent antibodies to phospholipids or certain phospholipid-associated proteins. It is a rare condition in adults and even rarer in children. The diagnosis of APS can be facilitated by the use of classification criteria based on a combination of clinical and biological features. APS may be rapidly progressive with multiple, often synchronous thromboses, resulting in life-threatening multiple organ failure. This form is known as "catastrophic antiphospholipid syndrome" (CAPS). It may be primary or associated with systemic lupus erythematosus (associated APS) and in very rare cases with other systemic autoimmune diseases. General practitioners and paediatricians may encounter APS in patients with one or more vascular thromboses. Because APS is so rare and difficult to diagnosis (risk of overdiagnosis) any suspected case should be confirmed rapidly and sometimes urgently by an APS specialist. First-line treatment of thrombotic events in APS includes heparin followed by long-term anticoagulation with a VKA, usually warfarin. Except in the specific case of stroke, anticoagulants should be started as early as possible. Any temporary discontinuation of anticoagulants is associated with a high risk of thrombosis in APS. A reference/competence centre specialised in autoimmune diseases must be urgently consulted for the therapeutic management of CAPS.
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Síndrome Antifosfolípido , Enfermedades Autoinmunes , Lupus Eritematoso Sistémico , Trombosis , Embarazo , Femenino , Humanos , Adulto , Niño , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/terapia , Anticuerpos Antifosfolípidos , Anticoagulantes/uso terapéutico , Lupus Eritematoso Sistémico/complicaciones , Trombosis/diagnóstico , Trombosis/epidemiología , Trombosis/etiología , Enfermedades Autoinmunes/complicacionesRESUMEN
Multisystem inflammatory syndrome in children (MIS-C) is a novel post-infectious disease occurring in the context of SARS-CoV2 infection. COVID-19 vaccines have been authorized since December 2020, and adverse events including myocarditis have been reported following vaccination. We describe the cases of two pediatric patients presenting with clinical and laboratory features suggestive of MIS-C a few days after receiving their first dose of the Pfizer BNT162b2 vaccine. The outcome was favorable for both patients (after corticosteroid and immunoglobulin administration for one patient). These cases suggest an association between the COVID-19 vaccine and the occurrence of MIS-C.
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Vacunas contra la COVID-19 , COVID-19 , Niño , Humanos , Vacuna BNT162 , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , ARN Viral , SARS-CoV-2 , Síndrome , VacunaciónAsunto(s)
Cromosomas Humanos Par 8/genética , Duplicación de Gen , Factor 6 de Diferenciación de Crecimiento/genética , Deformidades Congénitas de la Mano/genética , Artropatías/congénito , Osificación Heterotópica/genética , Esclerodermia Sistémica/genética , Sindecano-2/genética , Femenino , Humanos , MasculinoRESUMEN
OBJECTIVE: Longer-term effects of prolonged selective interleukin-1ß blockade with canakinumab were evaluated in the largest cohort of cryopyrin-associated periodic syndrome (CAPS) patients studied to date. METHODS: Adult and paediatric CAPS patients (n=166, including canakinumab-naive and pretreated patients from previous studies) received canakinumab subcutaneously 150 mg or 2 mg/kg (≤40 kg) every 8 weeks for up to 2 years. Response and relapse was assessed using scores for disease activity, skin rash and C-reactive protein (CRP) and/or serum amyloid A (SAA) levels. RESULTS: Complete response was achieved in 85 of 109 canakinumab-naive patients (78%; 79/85 patients within 8 days, and five patients between days 10 and 21). Of 141 patients with an available relapse assessment, 90% did not relapse, their CRP/SAA levels normalised (<10 mg/l) by day 8, and remained in the normal range thereafter. Median treatment duration was 414 days (29-687 days). Upward adjustments of dose or frequency were needed in 24.1% patients; mostly children and those with severe CAPS. Predominant adverse events (AE) were infections (65.7%) of mostly mild-to-moderate severity. Serious AE reported in 18 patients (10.8%) were mainly infections and were responsive to standard treatment. The majority of patients (92%) reported having no injection-site reactions and only 8% patients reported mild-to-moderate reactions. Patients receiving vaccination (15%) showed normal immune response. CONCLUSIONS: Subcutaneous canakinumab 150 mg every 8 weeks was well tolerated and provided substantial disease control in children and adults across all CAPS phenotypes. Higher canakinumab doses in younger patients and more severe CAPS disease were efficacious in achieving complete responses without evidence of increased AE. TRIAL REGISTRATION NUMBER: NCT00685373 (clinicaltrials.gov).
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Anticuerpos Monoclonales/administración & dosificación , Síndromes Periódicos Asociados a Criopirina/tratamiento farmacológico , Interleucina-1beta/antagonistas & inhibidores , Adolescente , Adulto , Anciano , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Peso Corporal , Proteína C-Reactiva/metabolismo , Niño , Preescolar , Síndromes Periódicos Asociados a Criopirina/inmunología , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Humanos , Inyecciones Subcutáneas , Persona de Mediana Edad , Fenotipo , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto JovenRESUMEN
A guideline group consisting of a pediatric rheumatologist, internists, rheumatologists, immunologists, a physiotherapist and a patient expert elaborated guidelines related to the management of juvenile dermatomyositis on behalf of the rare autoimmune and autoinflammatory diseases network FAI2R. A systematic search of the literature published between 2000 and 2015 and indexed in PubMed was undertaken. Here, we present the expert opinion for diagnosis and treatment in juvenile dermatomyositis.
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Dermatomiositis/diagnóstico , Dermatomiositis/terapia , Niño , Terapia Combinada , Dermatomiositis/complicaciones , Diagnóstico Diferencial , Testimonio de Experto , Francia , HumanosRESUMEN
Hereditary spherocytosis (HS) is the commonest inherited disorder of the erythrocyte membrane in Northern Europe and North America. It is marked by a regenerative anemia which varies widely from asymptomatic patients to severe hemolysis. In 75% of HS patients, inheritance is autosomal dominant. The diagnosis of HS is easily made when there are a family history, hemolytic anemia, reticulocytosis, spherocytes and increased hyperdense cells. Specialized testing to clarify the nature of membrane disorder is required when the film appearance is atypical without a positive family history, in the absence of a family history, in the newborn and before the splenectomy, to rule out the stomatocytosis which is contraindicated. The indication for splenectomy is dependent on the degree of anemia and its clinical manifestation.
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Esferocitosis Hereditaria/diagnóstico , Esferocitosis Hereditaria/terapia , Niño , Colecistectomía , Membrana Eritrocítica/fisiología , Transfusión de Eritrocitos , Eritropoyetina , Humanos , Proteínas Recombinantes , Esferocitosis Hereditaria/genética , EsplenectomíaRESUMEN
Retroperitoneal fibrosis (RF) is a rare disease in children. We report the case of a 15-year-old boy who presented with a 2-month history of dorsal pain and a 2-week history of fever. The erythrocyte sedimentation rate and serum C-reactive protein value were high. Magnetic resonance imaging revealed a large heterogeneous retroperitoneal mass, suggestive of RF. Percutaneous biopsy of inguinal lymph node provided the diagnosis of anaplastic large cell lymphoma. This is the first report of RF revealing malignancy in childhood. It emphasizes that malignancy must be carefully searched for in children with unexplained RF.
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Linfoma Anaplásico de Células Grandes , Fibrosis Retroperitoneal , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biopsia , Humanos , Ganglios Linfáticos/patología , Linfoma Anaplásico de Células Grandes/tratamiento farmacológico , Linfoma Anaplásico de Células Grandes/patología , Imagen por Resonancia Magnética , Masculino , Fibrosis Retroperitoneal/diagnóstico , Fibrosis Retroperitoneal/etiología , Resultado del TratamientoRESUMEN
Monogenic auto-inflammatory diseases are characterized by genetic abnormalities coding for proteins involved in innate immunity. They were initially described in mirror with auto-immune diseases because of the absence of circulating autoantibodies. Their main feature is the presence of peripheral blood inflammation in crisis without infection. The best-known auto-inflammatory diseases are mediated by interleukines that consisted in the 4 following diseases familial Mediterranean fever, cryopyrinopathies, TNFRSF1A-related intermittent fever, and mevalonate kinase deficiency. Since 10 years, many other diseases have been discovered, especially thanks to the progress in genetics. In this review, we propose the actual panorama of the main known auto-inflammatory diseases. Some of them are recurrent fevers with crisis and remission; some others evaluate more chronically; some are associated with immunodeficiency. From a physiopathological point of view, we can separate diseases mediated by interleukine-1 and diseases mediated by interferon. Then some polygenic inflammatory diseases will be shortly described: Still disease, Schnitzler syndrome, aseptic abscesses syndrome. The diagnosis of auto-inflammatory disease is largely based on anamnesis, the presence of peripheral inflammation during attacks and genetic analysis, which are more and more performant.
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Enfermedades Autoinflamatorias Hereditarias/diagnóstico , Diagnóstico Diferencial , Predisposición Genética a la Enfermedad , Enfermedades Autoinflamatorias Hereditarias/genética , Enfermedades Autoinflamatorias Hereditarias/fisiopatología , Humanos , Inmunidad Innata/genética , Inmunidad Innata/inmunología , Inflamación/inmunología , MutaciónRESUMEN
Interleukin (IL)-1 inhibitors have been increasingly used for treating autoinflammatory diseases during the last 10 years, but the spectrum of their possible side effects is not yet fully known. Here, we bring physicians' attention to a new severe complication of IL-1 inhibitors, manifesting as a probable drug reaction with eosinophilia and systemic symptoms (DRESS) in two patients.
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Síndrome de Hipersensibilidad a Medicamentos/metabolismo , Síndrome de Hipersensibilidad a Medicamentos/patología , Enfermedades Autoinflamatorias Hereditarias/metabolismo , Enfermedades Autoinflamatorias Hereditarias/patología , Interleucina-1/metabolismo , Receptores de Interleucina-1/metabolismo , Animales , Femenino , Prueba de Histocompatibilidad , Humanos , Receptores de Interleucina-1/antagonistas & inhibidoresRESUMEN
Defective apoptosis caused by mutations of the Fas gene can lead to an autoimmune lymphoproliferative syndrome (ALPS). The main autoimmune manifestations are haematological: hemolytic anemia, thrombocytopenia and neutropenia. We described 3 patients with ALPS presenting as a lymphoproliferative syndrome associated with a Coomb's negative autoimmune hemolytic anemia and dyserythropoiesis predominating on the more mature erythroblasts. Fas apoptosis deficiency was evidenced in the 3 patients by the demonstration of an increased number of CD4(-)CD8(-)TCRalphabeta(+) T cells, a decreased apoptotic response of activated T lymphocytes to anti-Apo 1-3 monoclonal antibody and the presence of a heterozygous mutation of the Fas receptor gene.
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Anemia Diseritropoyética Congénita/genética , Anemia Hemolítica Autoinmune/genética , Apoptosis/genética , Receptor fas/genética , Preescolar , Hepatomegalia/genética , Humanos , Lactante , Masculino , Mutación , Esplenomegalia/genéticaRESUMEN
PURPOSE: To develop French recommendations about the management of vaccinations, the screening of cervical cancer and the prevention of pneumocystis pneumonia in systemic lupus erythematosus (SLE). METHODS: Thirty-seven experts qualified in internal medicine, rheumatology, dermatology, nephrology and pediatrics have selected recommendations from a list of proposition based on available data from the literature. For each recommendation, the level of evidence and the level of agreement among the experts were specified. RESULTS: Inactivated vaccines do not cause significant harm in SLE patients. Experts recommend that lupus patient should receive vaccinations accordingly to the recommendations and the schedules for the general public. Pneumococcal vaccination is recommended for all SLE patients. Influenza vaccination is recommended for immunosuppressed SLE patients. Live attenuated vaccines should be avoided in immunosuppressed patients. Yet, recent works suggest that they can be considered in mildly immunosuppressed patients. Experts have recommended a cervical cytology every year for immunosuppressed patients. No consensus was obtained for the prevention of pneumocystis pneumonia. CONCLUSION: These recommendations can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of SLE patients.
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Testimonio de Experto , Control de Infecciones/normas , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/terapia , Guías de Práctica Clínica como Asunto , Adolescente , Adulto , Francia , Humanos , Huésped Inmunocomprometido , Control de Infecciones/métodos , Infecciones/diagnóstico , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/inmunología , Literatura de Revisión como Asunto , Vacunación/normas , Adulto JovenRESUMEN
UNLABELLED: Thrombotic events are often diagnosed with a delay that may be responsible for definite post-thrombotic syndrome. CASE REPORTS: We report two cases, which emphasize the difficulty of the diagnosis of venous thrombosis in two boys, at age 11 and 12 respectively. The occurrence of a leg pain led to a misdiagnosis of arthritis of hip in both cases. CONCLUSION: Venous thrombosis must be searched for in children with unexplained persistent pain in leg. Precocious anticoagulation is essential for preventing post-thrombotic syndrome.
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Errores Diagnósticos , Trombosis de la Vena/diagnóstico , Artritis/diagnóstico , Niño , Diagnóstico Diferencial , Humanos , Pierna/patología , Masculino , Dolor/etiología , Trombosis de la Vena/patologíaRESUMEN
UNLABELLED: Evans' Syndrome (ES) is defined as the combination of immune thrombocytopenia (ITP) and autoimmune haemolytic anemia (AIHA), in the absence of any known underlying etiology. Pathophysiology, epidemiology and outcome remain unclear. POPULATION: Thirty-six children (20 male, 16 female), who were diagnosed in the SHIP french centres (Société d'hématologie et d'immunologie pédiatrique) between 1990 and 2002 with ES, were included in this retrospective study. RESULTS: Median age at diagnosis was 4 years. In 21 children, ES occurred in the setting of consanguinity, family history of autoimmune/inflammatory disease, associated autoimmune disorder or immunoregulatory abnormalities (serum imunoglobulins, peripheral blood lymphocytes subsets, low level of the C3-C4 complement components, nuclear antibodies). Several successive treatments were used in this serie (median: 3, range: 0-10) including corticosteroid therapy (35/36), intravenous immunoglobulins (32/36), immunosuppressive agents (14/36), splenectomy (9/36) and anti CD 20 monoclonal antibodies (6/36). Patients with a low level of serum immunoglobulins were more often non-responders to corticosteroidtherapy/intravenous immunoglobulins and required more frequently further therapy (P=0.03). Three patients died (intracranial bleeding, N=2, Guillain-Barre syndrome; N=1). CONCLUSION: ES was a severe, life-threatening disease, requiring aggressive immunosuppressive therapy in as many as half the patients. Our forthcoming study aims to (i) describe homogeneously-studied and prospectively-analysed cohort of childhood ES, (ii) separate ES from specific immune deficiency (especially fas gene mutations), generalised autoimmune/inflammatory disorders and genetic diseases, (iii) identify well-defined ES subsets, (iv) establish prognostic factors and optimal treatment within these subsets.
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Anemia Hemolítica Autoinmune/patología , Púrpura Trombocitopénica Idiopática/patología , Adolescente , Corticoesteroides/uso terapéutico , Edad de Inicio , Anemia Hemolítica Autoinmune/tratamiento farmacológico , Anemia Hemolítica Autoinmune/genética , Anemia Hemolítica Autoinmune/inmunología , Niño , Preescolar , Estudios de Cohortes , Consanguinidad , Femenino , Francia , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Lactante , Masculino , Pronóstico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Púrpura Trombocitopénica Idiopática/genética , Púrpura Trombocitopénica Idiopática/inmunología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , SíndromeRESUMEN
OBJECTIVES: To analyse the effect of biological agents (BAs) in terms of achieving inactive disease (ID) or clinical remission (CR) in patients with systemic juvenile idiopathic arthritis (SJIA), to describe effects of switching or discontinuing a BA and to assess the proportion of patients able to maintain ID or CR off steroids and after withdrawing BA therapy. METHODS: Retrospective study in a French paediatric rheumatology reference centre using the CEMARA (CEntre des MAladies RAres) register. RESULTS: Seventy-seven patients were included with a cumulative follow-up of 245.5 patient-years (median 1.1, range 0.5-8.0). On a first BA, ID was achieved in 37 patients, including 1 patient out of 12 patients on etanercept, 26 patients out of 51 on anakinra and 7 out of 10 on canakinumab. One patient on abatacept and two patients on tocilizumab also achieved ID. Switching of BA was common. The switch to a second (n=34), third (n=18) or fourth (n=4) BA resulted in ID in a further 13 patients, either on canakinumab (n=6) or tocilizumab (n=7). At last follow-up, 40 patients were in CR (27 patients off steroids, 5 patients having never received steroid treatment), either on (n=29) or off (n=11) BA. CONCLUSIONS: In this series of patients with SJIA, interleukin-1 inhibitors were associated with a higher proportion of ID than tumour necrosis factor inhibitors when used as first BA. Switching allowed some patients to achieve ID when treated with canakinumab or tocilizumab. CR was eventually achieved in more than half of the patients.
RESUMEN
OBJECTIVE: To document more fully the characteristics of chronic recurrent multifocal osteomyelitis (CRMO) in pediatric patients, to collect data on the outcomes and management of the disease, and to define prognostic factors. METHODS: One hundred seventy-eight patients were included (123 female patients and 55 male patients), with a mean ± SD age at diagnosis of 10.9 ± 2.9 years. Inclusion criteria were a diagnosis of CRMO, evidence of at least one lesion of osteitis confirmed by imaging, and development of the syndrome before age 18 years. RESULTS: Longitudinal clinical and imaging studies revealed that only 12 of 178 CRMO patients (7%) had unifocal lesions at the last medical visit. We were able to apply the clinical chronic nonbacterial osteomyelitis score to 110 of 178 patients (62%), which indicated that bone biopsy could have been avoided in 27 cases (25%). At the last medical visit, disease was in remission in only 73 of 171 patients (43%) (41% receiving therapy) after a mean ± SD of 47.9 ± 38.9 months; 44 of 171 patients (26%) experienced sequelae. Using cluster analysis, the CRMO cohort was separated into 3 homogeneous phenotypes (severe, mild, and intermediate). Patients with the severe phenotype had the worst prognosis. This group was entirely composed of male patients, most of whom had the multifocal form of CRMO and inflammatory syndrome. Patients with the mild phenotype had the best prognosis. This group was primarily composed of female patients with a unifocal form of CRMO and infrequent clavicle involvement and inflammatory syndrome. Patients with the intermediate phenotype had a good prognosis but greater reliance on treatment. This group primarily included female patients with multifocal lesions and inflammatory syndrome. CONCLUSION: This is the largest CRMO cohort described in the literature to date. Clinical evolution and imaging investigations confirmed the multifocal pattern of the disease. Three distinct subgroups of CRMO patients were distinguished, with very different prognoses.