Iva Brito

Tumor Necrosis Factor-α −308 Genotypes Influence Inflammatory Activity and TNF-α Serum Concentrations in Children with Juvenile Idiopathic Arthritis

Objective. Considering the relevance of tumor necrosis factor-α (TNF-α) in the pathophysiology of juvenile idiopathic arthritis (JIA), it is likely that polymorphisms in its promoter area may be relevant in disease susceptibility and activity. We investigated if clinical measures of JIA activity and TNF-α serum concentrations were associated with TNF-α −308 genotypes. Methods. Portuguese patients with JIA in 5 pediatric rheumatology centers were recruited consecutively, along with a control group of healthy subjects. Demographic and clinical data and blood samples were collected from each patient. DNA was extracted for analysis of TNF-α gene promoter polymorphisms at position −308 by restriction fragment-length polymorphism. Results. One hundred fourteen patients and 117 controls were evaluated; 57% of patients presented the oligoarticular subtype, 25% the polyarticular subtype, 8% the systemic subtype, and 9% had enthesitis-related arthritis and 5% psoriatic arthritis. Twenty-four percent of the patients presented the −308 GA/AA genotypes and 76% the −308 GG genotype, similar to findings in controls. Patients with the −308 GA/AA genotype had higher degree of functional impairment, erythrocyte sedimentation rate, 100-mm visual analog scale score for disease activity, and TNF-α levels compared to those with the −308 GG genotype. Conclusion. TNF-α −308 GA/AA genotypes were found to be related to higher inflammatory activity and worse measures of disease activity in Portuguese patients with JIA. They were not associated with susceptibility to JIA.

Using the Juvenile Arthritis Disease Activity Score Based on Erythrocyte Sedimentation Rate or C-Reactive Protein Level: Results From the Portuguese Register

Our aims were to evaluate the correlation between Juvenile Arthritis Disease Activity Score 27‐joint reduced count (JADAS27) with erythrocyte sedimentation rate (ESR) and JADAS27 with C‐reactive protein (CRP) scores and to test the agreement of both scores on classifying each disease activity state. We also aimed at verifying the correlation of the 2 scores across juvenile idiopathic arthritis (JIA) categories and to check the correlation between JADAS27‐ESR and clinical JADAS27 (JADAS27 without ESR).

Effectiveness and long-term retention of anti-tumour necrosis factor treatment in juvenile and adult patients with juvenile idiopathic arthritis: data from Reuma.pt

OBJECTIVES Assess the effectiveness and safety of biologic therapy as well as predictors of response at 1 year of therapy, retention rate in biologic treatment and predictors of drug discontinuation in JIA patients in the Portuguese register of rheumatic diseases. METHODS We prospectively collected patient and disease characteristics from patients with JIA who started biological therapy. Adverse events were collected during the follow-up period. Predictors of response at 1 year and drug retention rates were assessed at 4 years of treatment for the first biologic agent. RESULTS A total of 812 JIA patients [65% females, mean age at JIA onset 6.9 years (s.d. 4.7)], 227 received biologic therapy; 205 patients (90.3%) were treated with an anti-TNF as the first biologic. All the parameters used to evaluate disease activity, namely number of active joints, ESR and Childhood HAQ/HAQ, decreased significantly at 6 months and 1 year of treatment. The mean reduction in Juvenile Disease Activity Score 10 (JADAS10) after 1 year of treatment was 10.4 (s.d. 7.4). According to the definition of improvement using the JADAS10 score, 83.3% respond to biologic therapy after 1 year. Fourteen patients discontinued biologic therapies due to adverse events. Retention rates were 92.9% at 1 year, 85.5% at 2 years, 78.4% at 3 years and 68.1% at 4 years of treatment. Among all JIA subtypes, only concomitant therapy with corticosteroids was found to be univariately associated with withdrawal of biologic treatment (P = 0.016). CONCLUSION Biologic therapies seem effective and safe in patients with JIA. In addition, the retention rates for the first biologic agent are high throughout 4 years.

Clinical phenotype and outcome in lupus according to age: a comparison between juvenile and adult onset

OBJECTIVE To study differences in demographic, clinical and immunologic characteristics, activity and cumulative organ damage according to age of onset in systemic lupus erythematosus (SLE). METHODS Cross-sectional study was performed including 204 SLE patients. Characteristics were compared between juvenile and adult-onset SLE patients using parametric and nonparametric tests (SPSS 23.0). RESULTS Juvenile-SLE patients had malar rash more often (78.9% vs 53%; p=0.001), oral ulcers (45.5% vs 17.5%; p=0.001), neurological involvement (13.1% vs 3.6%; p=0.02) nephritis (50% vs 33.9%), p=0.04) and haematological manifestations such as hemolytic anaemia (23.6% vs 5.4%; p=0.002) and leukopenia (46.1% vs 4.2%; p<0.001). Arthritis was more prevalent in adult-onset patients (70.9% vs 90%; p<0.04). Overall, 20% of juvenile patients had chronic damage (Systemic Lupus International Collaborating Clinics/Damage Index [SLICC/DI]≥1), However, the percentage of patients with irreversible damage was higher in the adult SLE patient group (24%, p=0.04). No statistically significant differences were found in other characteristics studied. CONCLUSION In summary, our study confirms the existence of differences in clinical manifestations, according to age at diagnosis of SLE. Juvenile-SLE patients showed a more aggressive clinical presentation.

Juvenile idiopathic arthritis in adulthood: fulfilment of classification criteria for adult rheumatic diseases, long-term outcomes and predictors of inactive disease, functional status and damage

Objectives To determine how adult juvenile idiopathic arthritis (JIA) patients fulfil classification criteria for adult rheumatic diseases, evaluate their outcomes and determine clinical predictors of inactive disease, functional status and damage. Methods Patients with JIA registered on the Rheumatic Diseases Portuguese Register (Reuma.pt) older than 18 years and with more than 5 years of disease duration were included. Data regarding sociodemographic features, fulfilment of adult classification criteria, Health Assessment Questionnaire, Juvenile Arthritis Damage Index—articular (JADI-A) and Juvenile Arthritis Damage Index—extra-articular (JADI-E) damage index and disease activity were analysed. Results 426 patients were included. Most of patients with systemic JIA fulfilled criteria for Adult Stills disease. 95.6% of the patients with rheumatoid factor (RF)-positive polyarthritis and 57.1% of the patients with RF-negative polyarthritis matched criteria for rheumatoid arthritis (RA). 38.9% of the patients with extended oligoarthritis were classified as RA while 34.8% of the patients with persistent oligoarthritis were classified as spondyloarthritis. Patients with enthesitis-related arthritis fulfilled criteria for spondyloarthritis in 94.7%. Patients with psoriatic arthritis maintained this classification. Patients with inactive disease had lower disease duration, lower diagnosis delay and corticosteroids exposure. Longer disease duration was associated with higher HAQ, JADI-A and JADI-E. Higher JADI-A was also associated with biological treatment and retirement due to JIA disability and higher JADI-E with corticosteroids exposure. Younger age at disease onset was predictive of higher HAQ, JADI-A and JADI-E and decreased the chance of inactive disease. Conclusions Most of the included patients fulfilled classification criteria for adult rheumatic diseases, maintain active disease and have functional impairment. Younger age at disease onset was predictive of higher disability and decreased the chance of inactive disease.

Genetic Predictors of Poor Prognosis in Portuguese Patients with Juvenile Idiopathic Arthritis: Data from Reuma.pt

Introduction. This study aimed to assess the genetic determinants of poor outcome in Portuguese patients with juvenile idiopathic arthritis (JIA). Methods. Our study was conducted in Reuma.pt, the Rheumatic Diseases Portuguese Register, which includes patients with JIA. We collected prospectively patient and disease characteristics and a blood sample for DNA analysis. Poor prognosis was defined as CHAQ/HAQ >0.75 at the last visit and/or the treatment with biological therapy. A selected panel of single nucleotide polymorphisms (SNPs) associated with susceptibility was studied to verify if there was association with poor prognosis. Results. Of the 812 patients with JIA registered in Reuma.pt, 267 had a blood sample and registered information used to define “poor prognosis.” In univariate analysis, we found significant associations with poor prognosis for allele A of TNFA1P3/20 rs6920220, allele G of TRAF1/C5 rs3761847, and allele G of PTPN2 rs7234029. In multivariate models, the associations with TRAF1/C5 (1.96 [1.17–3.3]) remained significant at the 5% level, while TNFA1P3/20 and PTPN2 were no longer significant. Nevertheless, none of associations found was significant after the Bonferroni correction was applied. Conclusion. Our study does not confirm the association between a panel of selected SNP and poor prognosis in Portuguese patients with JIA.

Childhood polyarteritis nodosa presenting as stroke and arterial hypertension

A 6-year-old boy with frequent episodes of fever, myalgia and arthralgia, presented with arterial hypertension (HTN). When he was 2 years old he was extensively investigated due to a small thalamic stroke, but no diagnosis was made. While being evaluated for HTN, he presented with a medullar ischaemic stroke. Antinuclear and antineutrophil cytoplasmic antibodies were negative; there was no kidney failure, urinalysis changes or skin lesions. In the presence of recurrent fevers, ischaemic strokes and HTN, we suspected the …

Intracardiac thrombosis in Behçet's disease: a life threatening event

a b s t r a c t An adolescent with a recent diagnostic of Behcets Disease was admitted with fever and intracardiac lesions detected on a routine transthoracic echocardiography, suggestive of endocarditis. Due to the absence of improvement after several rounds of antibiotics the patient was submitted to contrast-enhanced cardiac magnetic resonance imaging that showed signs of intracardiac thrombosis, superior vena cava syndrome and pulmonary thromboembolism. The patient underwent surgery to excise the lesions and has been treated with cyclophosphamide and high dose prednisolone achieving complete remission. Intracardiac thrombosis is a rare manifestation of Behcets Disease, and is associated with a poor prognosis. These patients usually require a combination of anticoagulation and immunosuppression to achieve remission.

Trombose intracardíaca na doença de Behçet: evento com risco de vida

An adolescent with a recent diagnostic of Behçets Disease (BD) was admitted with fever and intracardiac lesions detected on a routine transthoracic echocardiography, suggestive of endocarditis. Due to the absence of improvement after several rounds of antibiotics the patient was submitted to contrast-enhanced cardiac MRI that showed signs of intracardiac thrombosis, superior vena cava syndrome and pulmonary thromboembolism. The patient underwent surgery to excise the lesions and has been treated with cyclophosphamide and high dose prednisolone achieving complete remission. Intracardiac thrombosis is a rare manifestation of BD, and is associated with a poor prognosis. These patients usually require a combination of anticoagulation and immunosuppression to achieve remission.

Acute calcific periarthritis in proximal interphalangeal joint: An unusual cause of acute finger pain

A 27-year-old right-hand-dominant female presented to the emergency department due to severe pain in the right third finger with associated swelling, that had developed five days previously. She denied any history of trauma, fever, systemic complaints or arthralgias at other joints. On examination, she showed redness, swelling, local heat and tenderness of the radial side of the proximal interphalangeal (PIP) joint of the right third finger. She had limited passive and active mobilization of the finger because of pain. No other abnormalities were noted. The initial radiographs showed a well-circumscribed ovoid calcification adjacent to the radial and volar aspects of the PIP joint of the right third finger (Fig. 1). Laboratory investigation revealed normal leukocyte count, normal serum uric acid, calcium, phosphorus, alkaline phosphatase and parathyroid hormone levels, and a mildly elevated C-reactive protein at 10.3 mg/L (normal <3.0 mg/L). An ultrasound performed 3 day later demonstrated an ovoid heterogeneous calcific mass (Fig. 2). The patient was managed conservatively with nonsteroidal antiinflammatory drugs, ice compression and immobilization. Three weeks later, the patient experienced complete resolution of swelling and pain and exhibited full range of motion. Follow-up radiographs after two months showed complete disappearance of the calcification (Fig. 3).