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Inibidores de Janus Quinases , Piperidinas , Pirimidinas , Humanos , Pirimidinas/uso terapêutico , Pirimidinas/efeitos adversos , Piperidinas/uso terapêutico , Resultado do Tratamento , Inibidores de Janus Quinases/uso terapêutico , Feminino , Masculino , Criança , Adolescente , Fatores de Tempo , Pirróis/uso terapêutico , Estudos Retrospectivos , Esclerodermia Localizada/tratamento farmacológico , Esclerodermia Localizada/diagnóstico , Escleroderma SistêmicoRESUMO
OBJECTIVES: TNF inhibitors (TNFi) have dramatically changed the prognosis of juvenile idiopathic arthritis (JIA), but it is not clear how and when stop therapy. We aim to describe a multicentric cohort of JIA treated with adalimumab or etanercept who discontinued the treatment for persistent inactivity and to identify factors associated with relapse. METHODS: In a multicentric Italian retrospective cohort study, medical records of patients with oligoarticular and polyarticular JIA were evaluated if they stopped therapy for persistent inactivity after the first TNFi. RESULTS: 136 patients were enrolled (102 female, median age at onset 3 years (range 1-15), of whom 55.9% had oligoJIA, 40.4% uveitis and 72.8% ANA positivity. Adalimumab (59.3%) and etanercept (40.7%) were started at a median age of 6 years (range 1-16), TNFi were discontinued after a median time of 30 months (range 6-90), increasing the interval (76.5%), reducing the dose (18.4%) and abrupt discontinuation (16.9%). 79.4% of patients relapsed after a median time of 5 months (range 0.5-66). Patients with uveitis relapsed earlier (log rank χ² 16.4 p<0.0001), while patients who lengthened the interval of administration showed a later relapse (log rank χ² 6.95 p=0.008). Uveitis (HR 2.11 CI 1.34-3.31), age at onset (HR 0.909 CI 0.836-0.987), duration of tapering (HR 0.938 CI 0.893-0.985) and to have a persistent OligoJIA (HR 0.597 CI 0.368-0.968) are significant predictors of disease relapse (Mantel-Cox χ² 34.23 p<0.001). CONCLUSIONS: Younger age at onset, uveitis, duration of tapering, and not-persistent OligoJIA seem to be independent risk factors for earlier relapse after the first TNFi withdrawal.
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Objectives: Inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are poorly informative about interferon (IFN)-related disorders. In these conditions, the measure of the interferon score (IS), obtained by measuring the expression of IFN-stimulated genes, has been proposed. Flow cytometry-based assays measuring sialic-acid-binding Ig-like lectin 1 (Siglec-1) expression could be a more practical tool for evaluating IFN-inflammation. The study compared Siglec-1 measures with IS and other inflammatory indexes. We compared Siglec-1 measures with IS and other inflammatory indexes in real-world paediatric rheumatology experience. Methods: We recruited patients with immuno-rheumatological conditions, acute infectious illness and patients undergoing orthopaedic surgery as controls. Siglec-1 expression was measured in all samples, and IS, ESR and CRP were also recorded if available. Results: Overall, 98 subjects were enrolled in the study, with a total of 104 measures of Siglec-1. Compared with IS, Siglec-1 expression showed good accuracy (86.0%), specificity (72.7%) and sensitivity (85.7%). The measure of the percentage of Siglec-1-positive cells performed best at low levels of IFN-inflammation, while the measure of mean fluorescence intensity performed best at higher levels. Ex vivo studies on IFN-stimulated monocytes confirmed this behaviour. There was no link between Siglec-1 expression and either ESR or CRP, and positive Siglec-1 results were found even when ESR and CRP were normal. A high Siglec-1 expression was also recorded in subjects with acute infections. Conclusion: Siglec-1 measurement by flow cytometry is an easy tool to detect IFN-related inflammation, even in subjects with normal results of common inflammation indexes.
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Azetidinas , Purinas , Pirazóis , Sulfonamidas , Humanos , Pirazóis/uso terapêutico , Azetidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Purinas/uso terapêutico , Masculino , Feminino , Criança , Pré-Escolar , MutaçãoRESUMO
INTRODUCTION: Vascular events account for a considerable burden of morbidity and mortality in Behçet syndrome (BS). Thrombosis occurs in 1.8-21 % pediatric BS patients, even if the real prevalence is still largely unknown. OBJECTIVES: To report clinical features and outcomes of pediatric BS patients with thrombosis and to compare the demographic and clinical characteristics of BS patients with and without thrombosis. METHODS: Retrospective data collection of BS patients with thrombosis (T+) included in the EUROFEVER registry. BS patients without thrombosis (T-), belonging to the same rheumatology units, were matched in a 2:1 ratio. RESULTS: 37 T+ were compared to 74 T- patients. At onset, ICBD criteria fulfillment was higher in the T- group (p = 0.015). Caucasian patients were more often T-, Turkish patients were more frequent in T+ group (p = 0.002). At onset, pustulosis was most frequently observed in the T- (p < 0.001) as well as gastrointestinal symptoms (p < 0.001) and ocular involvement (p = 0.022). Neurological symptoms were more often described in T+ (p = 0.034). As for T+, thrombosis was reported at BS presentation in 8/37 (21.6 %). For the T + e patients who developed thrombosis later, oral aphthosis (p = 0.003), genital aphthosis (p = 0.014) were more frequently observed at BS onset, while pustulosis (p = 0.005) and fever (p = 0.043) coexisted with thrombosis. Thrombosis was mainly venous (26/37,70.3 %), involving the cerebral sinuses (21/37, 56.8 %). After thrombosis, 35/37 (94.6 %) T+ patients received an immunomodulatory treatment compared with 16/29 (55.2 %) pre-thrombosis. A recurrence was reported in 6/31(19.4 %). CONCLUSION: Thrombosis was reported at BS presentation in one fifth of cases. Pustolosis and fever were more frequently concomitant to thrombosis. Sinus veins were the most frequent site.
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Síndrome de Behçet , Sistema de Registros , Trombose , Humanos , Síndrome de Behçet/complicações , Síndrome de Behçet/epidemiologia , Masculino , Feminino , Criança , Adolescente , Estudos Retrospectivos , Trombose/etiologia , Trombose/epidemiologia , Europa (Continente)/epidemiologia , PrevalênciaRESUMO
BACKGROUND: H Syndrome is a rare genetic condition caused by biallelic pathogenic variants in the SLC29A3 gene. It is characterized by a wide range of clinical manifestations, many of which are related to the immune-rheumatological field. These include scleroderma-like skin changes, deforming arthritis, and enlarged lymph nodes. The condition also features cardiac and endocrine defects, as well as hearing loss, for which the immune pathogenesis appears less clear. Immunomodulatory medications have been shown to improve many symptoms in recent experiences. CASE PRESENTATION: A 21-year-old girl was referred to our institute after being diagnosed with H syndrome. Her medical history was characterized by the development of finger and toe deformities, which developed since the first years of life and progressively worsened with clinodactyly. At 6 years of age, she was diagnosed with diabetes mellitus without typical autoantibodies and with bilateral sensorineural hearing loss. She also complained of frequent episodes of lymphadenopathy, sometimes with colliquation and growth retardation due to pancreatic insufficiency. It wasn't until the genetic diagnosis of H syndrome that the continual increase in acute phase reactants was noticed, suggesting that an immunological pathogenesis may be the source of her problems. During her visit to our institute, she reported serious pain in both feet and hands and difficulty walking due to knee arthritis and muscle contractures. Conventional therapy with steroid injection in affected joints and methotrexate only led to partial improvement. After a thorough assessment of her inflammatory profile showing a high interferon score, the girl received treatment with baricitinib. Furthermore, based on recent data showing that SLC29A3 deficiency results in interferon production because of Toll-like Receptor 7 activation in lysosomes, hydroxychloroquine was also added. The combination of the two drugs resulted for the first time in a rapid and persistent normalization of inflammatory markers, paralleled by a dramatic improvement in symptoms. CONCLUSIONS: We describe the results of inhibiting IFN inflammation in H syndrome and discuss how JAK inhibitors and antimalarials might represent a mechanistically based treatment for this orphan drug disorder.
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Artrite , Contratura , Perda Auditiva Neurossensorial , Histiocitose , Doenças Reumáticas , Feminino , Humanos , Adulto Jovem , Adulto , Interferons , Proteínas de Transporte de NucleosídeosRESUMO
OBJECTIVES: Limited information is available on the clinical features, treatment modalities and outcomes of the juvenile idiopathic arthritis (JIA) categories of enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA). This study was aimed to describe the characteristics of Italian children with ERA and JPsA and to compare them with those of patients with the other categories of JIA. METHODS: Patients were part of a multinational sample included in a study aimed to investigate the prevalence of disease categories, treatment approaches, and disease status in patients from across different geographical areas (EPOCA Study). All patients underwent a retrospective assessment, based on the review of clinical chart, and a cross-sectional evaluation, which included assessment of physician- and parent-reported outcomes and laboratory tests, and recording of ongoing therapies. RESULTS: Of the 9081 children with JIA enrolled in the EPOCA Study, 1300 were recruited at 18 paediatric rheumatology centres in Italy. 45 (3.5%) had ERA and 49 (3.8%) had JPsA. Several remarkable differences in demographic features and frequency of articular and extra-articular manifestations, disease damage, impairment in physical function and health-related quality of life, school-related problems, comorbidities, and ongoing treatments were observed between ERA and JPsA and the other JIA categories. CONCLUSIONS: We described the characteristics of Italian children with ERA and JPsA and highlighted their peculiarities and their differences from the other JIA subsets. These data provide useful insights for future revisions of JIA classification and a benchmarking against which the features from other cohorts may be compared.
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Artrite Juvenil , Criança , Humanos , Artrite Juvenil/diagnóstico , Artrite Juvenil/tratamento farmacológico , Artrite Juvenil/epidemiologia , Estudos Retrospectivos , Estudos Transversais , Qualidade de Vida , Resultado do TratamentoRESUMO
BACKGROUND: Limping is a common clinical symptom in childhood; different clinical conditions may lead to limping and the diagnosis of the underlying cause may often be a challenge for the pediatrician. CASE PRESENTATION: We describe the clinical manifestations, radiological pictures and disease course of other causes of limping in childhood, through a case series of seven cases and a brief discussion of each disease. CONCLUSIONS: although trauma is the most common cause of acute limping, when there is no history of traumatic events and the limping has a chronic course, Juvenile Idiopathic Arthritis is usually the most likely clinical diagnosis. However, other some rare conditions should be taken into account if JIA is not confirmed or if it presents with atypical clinical picture.
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Artrite Juvenil , Sinovite , Humanos , Artrite Juvenil/complicações , Artrite Juvenil/diagnóstico , Sinovite/diagnóstico , Diagnóstico DiferencialRESUMO
BACKGROUND: Erythropoietic protoporphyria is a rare disorder which represents an important health problem in children, causing painful photosensitivity. Little is known on the correlation between genetic profile and clinical manifestations. The standard of care for Erythropoietic protoporphyria is based on avoiding sun and using sun protections, but recent literature has suggested that cimetidine may have a role in improving sun sensitivity. Herein we report our case series describing the successful use of cimetidine and analyzing potential phenotype-genotype correlations. CASE PRESENTATION: This case series describes five patients presented to our Rheumatology Service complaining sun sensitivity. Blood exams and genetic analysis were consistent with the diagnosis of erythropoietic protoporphyria. Four of 5 patients received cimetidine in addition to standard therapies and the effect of treatment was evaluated by Erythropoietic Protoporphyria - Quality of Life questionnaire. CONCLUSIONS: Erythropoietic protoporphyria usually manifests in early childhood after a short sun exposure. Skin manifestations are the main reason for investigations, although sometimes they can be more subtle, leading to a significant diagnostic delay. Skin diseases in children can have profound effects on their family and social relationships. A treatment with cimetidine appears to be an excellent therapeutic option in children with Erythropoietic protoporphyria.
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Transtornos de Fotossensibilidade , Protoporfiria Eritropoética , Criança , Humanos , Pré-Escolar , Protoporfiria Eritropoética/diagnóstico , Protoporfiria Eritropoética/terapia , Protoporfiria Eritropoética/complicações , Ferroquelatase/genética , Cimetidina , Qualidade de Vida , Diagnóstico Tardio , Transtornos de Fotossensibilidade/etiologiaRESUMO
BACKGROUND: Tocilizumab is a humanized monoclonal antibody that acts as an IL-6 receptor antagonist. Intravenous tocilizumab is considered an option for children with anti-TNF refractory juvenile idiopathic arthritis-associated uveitis. In contrast, the potential of subcutaneous drug use with this indication is more controversial. Due to the decreased availability of intravenous tocilizumab during the COVID-19 pandemic, we started using the subcutaneous formulation of the drug in children with anti-TNF refractory uveitis. The study analyzes the serum concentration of tocilizumab and its clinical response in patients with anti-TNF refractory uveitis who started or switched to subcutaneous administration from intravenous use. METHODS: Five patients with non-infectious uveitis were treated with subcutaneous tocilizumab. Ocular inflammation was evaluated on slit lamp examination during clinical control. Serum tocilizumab concentrations were determined by ELISA. RESULTS: The mean blood concentration of tocilizumab was 61.4 µg/mL (range 2.7-137.0.), with higher values than levels recorded in adult patients with rheumatoid arthritis treated with intravenous tocilizumab. Three patients entered clinical remission. One patient developed a mild relapse and was treated with topical steroids. Only one patient did not respond to therapy. The medication was well tolerated without severe infection or other adverse events. CONCLUSION: Our results support a possible role of subcutaneous tocilizumab in anti-TNF refractory uveitis.
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COVID-19 , Uveíte , Adulto , Humanos , Criança , Pandemias , Inibidores do Fator de Necrose Tumoral , Tratamento Farmacológico da COVID-19 , Uveíte/tratamento farmacológico , Uveíte/etiologiaRESUMO
Background: Percutaneous tibial nerve stimulation (PTNS) is widely used in the treatment of neurogenic detrusor overactivity (NDO) in multiple sclerosis (MS); however, controlled studies are still lacking.Objective:: To assess effectiveness of PTNS in MS patients with NDO unresponsive to pharmacological and behavioural therapies. Methods: MS patients with NDO were enrolled. Inclusion criteria were NDO not responding to pharmacological and behavioural therapies. Exclusion criteria were the presence of relevant comorbidities and urinary tract infections. Patients were evaluated using 3-day bladder diaries and validated questionnaires at baseline, after 4 weeks of educational therapy and after 12 PTNS sessions. The primary outcome measure was the percentage of patients considered responders after the behavioural therapy and after the PTNS in a historical controlled fashion (definition of 'responder' was reduction ⩾50% of urgency episodes). Results: A total of 33 patients (26 women, 7 men) were enrolled. Two patients dropped out for reasons not related to the protocol. Two out of 31 patients (6.5%) and 21/29 (72.4%) were considered responders at visits 1 and 2, respectively. In PTNS responders, a statistically significant improvement in both bladder diary results and standardized questionnaire scores was recorded, compared with that obtained with behavioural therapy alone. No serious adverse events were reported. Conclusion: This historically controlled study suggests that PTNS may be effective in improving NDO in MS patients.
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OBJECTIVES: The interferon score (IS) quantifies the expression of interferon-stimulated genes in peripheral blood, providing an indirect estimate of interferon-mediated inflammation in rheumatological disorders. This study explores the clinical significance of IS among a cohort of patients affected by juvenile idiopathic arthritis (JIA) and its relevance to disease stratification and prognosis. METHODS: All patients referred to the Rheumatology Service of the Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy, with a diagnosis of JIA (2001 ILAR criteria) were consecutively recruited. Systemic JIA was excluded. Demographic, clinical and laboratory data were collected for each patient in a structured database. Categorical variables were expressed as numbers (%) and compared by the χ2 test or Fisher's exact test. Principal Component Analysis (PCA) was performed with clinical and laboratory data. RESULTS: Forty-four patients were recruited (35 F, 9 M): 19 polyarticular, 13 oligoarticular, 6 oligoarticular-extended, 5 psoriatic and 1 enthesitis-related arthritis. Sixteen had a positive IS (≥3). Increased IS correlated with a higher number of involved joints ≥5 (p=0.013), increased erythrocyte sedimentation rate (ESR) (p=0.026) and hypergammaglobulinaemia (p=0.003). PCA highlighted a subgroup of patients who shared high levels of IS, ESR, C-reactive protein, hypergammaglobulinaemia, JADAS-27, polyarticular involvement and family history of autoimmunity. CONCLUSIONS: Although based on a small case series, our results may support the role of IS in better defining a subgroup of JIA subjects with stronger autoimmune features. The possible relevance of these results for therapeutic stratification remains to be explored.
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Artrite Juvenil , Interferon Tipo I , Criança , Humanos , Artrite Juvenil/diagnóstico , Hipergamaglobulinemia , Inflamação , PrognósticoRESUMO
OBJECTIVE: To develop and externally validate a prediction model for new-onset chronic uveitis in children with juvenile idiopathic arthritis (JIA) for clinical application. METHODS: Data from the international Pharmachild registry were used to develop a multivariable Cox proportional hazards model. Predictors were selected by backward selection, and missing values were handled by multiple imputation. The model was subsequently validated and recalibrated in 2 inception cohorts: the UK Childhood Arthritis Prospective Study (CAPS) study and the German Inception Cohort of Newly diagnosed patients with juvenile idiopathic arthritis (ICON) study. Model performance was evaluated by calibration plots and C statistics for the 2-, 4-, and 7-year risk of uveitis. A diagram and digital risk calculator were created for use in clinical practice. RESULTS: A total of 5,393 patients were included for model development, and predictor variables were age at JIA onset (hazard ratio [HR] 0.83 [95% confidence interval (95% CI) 0.77-0.89]), ANA positivity (HR 1.59 [95% CI 1.06-2.38]), and International League of Associations for Rheumatology category of JIA (HR for oligoarthritis, psoriatic arthritis, and undifferentiated arthritis versus rheumatoid factor-negative polyarthritis 1.40 [95% CI 0.91-2.16]). Performance of the recalibrated prediction model in the validation cohorts was acceptable; calibration plots indicated good calibration and C statistics for the 7-year risk of uveitis (0.75 [95% CI 0.72-0.79] for the ICON cohort and 0.70 [95% CI 0.64-0.76] for the CAPS cohort). CONCLUSION: We present for the first time a validated prognostic tool for easily predicting chronic uveitis risk for individual JIA patients using common clinical parameters. This model could be used by clinicians to inform patients/parents and provide guidance in choice of uveitis screening frequency and arthritis drug therapy.
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Artrite Juvenil , Artrite Psoriásica , Uveíte , Criança , Humanos , Artrite Juvenil/complicações , Artrite Juvenil/epidemiologia , Artrite Juvenil/diagnóstico , Estudos Prospectivos , Uveíte/epidemiologia , Uveíte/etiologia , Uveíte/diagnóstico , PrognósticoRESUMO
BACKGROUND: COPA syndrome is a rare hereditary inflammatory disease caused by mutations in the gene encoding the coatomer protein subunit alpha, causing excessive production of type I interferon. This case is a reminder for the general paediatrician, highlighting the relevance of the association between arthritis and lung involvement in toddlers. CASE PRESENTATION: We report the case of a 2-year-old girl with intermittent limping and joint pain. Her family history was relevant for a Still disease with lung involvement in the mother. Physical examination showed moderate wrist swelling. Laboratory findings on admission showed an increase in inflammatory markers, positive rheumatoid factor, antibodies antinuclear antibody (ANA) and cyclic citrullinated peptide (anti-CCP). Wrists' ultrasound documented synovial thickening, and chest X-rays showed an unexpected severe interstitial pneumopathy. Genetic testing confirmed the diagnosis of a heterozygous mutation of the COPA gene in c.841C > T (p.R281W). Janus kinase treatment was started (baricitinib, 4 mg daily per os) with a remarkable improvement in limping and joint pain after two weeks. CONCLUSIONS: In cases of recurrent arthritis with family history and multiple involvement organs, a genetic disorder should be suspected and genetic testing should be performed. Furthermore, this case suggests that therapy with jak inhibitors may be effective and safe in interferonopathies.
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Artrite Juvenil , Doenças Pulmonares Intersticiais , Feminino , Humanos , Pré-Escolar , Fator Reumatoide , Artrite Juvenil/complicações , Artrite Juvenil/diagnóstico , Artrite Juvenil/tratamento farmacológico , Artralgia , PulmãoRESUMO
[This corrects the article DOI: 10.3389/fsurg.2022.962824.].
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BACKGROUND: Primary Synovial Chondromatosis (PSC) is a rare benign tumor of the synovial membrane in which cartilage metaplasia produces calcific loose bodies within the articular space. Only a few cases are reported in the pediatric population and its etiology remains unknown. This condition typically affects large weight-bearing joints with pain, swelling and decrease range of motion. Due to its slow progressions, delayed diagnosis is frequent and differential diagnosis should consider other chronic arthritis and malignancies. While arthroscopic removal of loose bodies is the current treatment up to now, the association of partial or complete synovectomy is debated. CASE PRESENTATION: We report about a 14-year-old girl with a long-lasting right shoulder pain, especially during movements or exercise, localized tenderness and hypotonia of the glenohumeral joint. No previous trauma was mentioned. Blood exams, Mantoux test and plain radiography of the right shoulder were unremarkable. Ultrasound imaging revealed echogenic and calcified bodies stretching the glenohumeral joint and dislocating the long head of biceps tendon. Magnetic resonance showed a "rice-grain" pattern of the right shoulder. From an arthroscopic surgery, multiple loose white bodies were removed within the synovial membrane, and synovial chondromatosis was confirmed by histological analysis. At one month follow up visit, the patient completely recovered without pain. CONCLUSION: Synovial chondromatosis is a very uncommon cause of mono articular pain in children, especially when it affects shoulder. Pediatricians should keep in mind this condition to avoid delayed diagnosis and treatment, even in consideration of the low risk of malignant transformation. Through this case, we would highlight common diagnostic pitfalls and treatment of synovial chondromatosis.