In a randomized trial involving children with severe systemic juvenile idiopathic arthritis, the anti–interleukin-6 receptor antibody tocilizumab was effective (response rate, 85% with tocilizumab ...vs. 24% with placebo). Adverse events included serious infections and neutropenia.
Systemic juvenile idiopathic arthritis (JIA) is characterized by chronic arthritis, systemic manifestations (spiking fever, rash, hepatosplenomegaly, lymphadenopathy, and serositis), and substantially elevated inflammatory markers.
1
It is the most severe subtype of JIA; approximately half the patients have an unremitting course of chronic polyarthritis (with or without persistent systemic features). Substantial joint damage and disability often develop in these patients.
2
,
3
Treatment remains challenging because of the limited efficacy of methotrexate
4
and tumor necrosis factor inhibitors
5
,
6
and because of the major toxicity of high-dose glucocorticoids. Efficacy of the interleukin-1 inhibitor anakinra has been reported in a subset of patients.
7
– . . .
Our aim was to describe a monocentric cohort of young adult patients with juvenile idiopathic arthritis (JIA), assessing the risk of relapse after transition to adult care.
We conducted a ...retrospective study and collected clinical, serological, and demographic data of young adult patients (18-30 years old) referred to the Transition Clinic of a single Italian centre between January 2020 and March 2023. Patients with systemic-onset JIA were excluded. Primary outcome was disease relapse, defined by Wallace criteria. Risk factors were analysed by Cox proportional hazards regression.
Fifty patients with age 18-30 years old were enrolled in the study and followed for a median 30 months. The median disease duration at transition was 15 years. Twenty (40%) patients were on conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and 38 (76%) were on biological DMARDs through adulthood. Twenty-three patients relapsed after transitioning to adult care for a median 9-month follow-up (IQR 0-46.5). Most relapses involved the knees (69.6%). The univariate analysis identified monoarthritis (HR 4.67, CI 1.069-20.41, p value = 0.041) as the main risk factor for relapse within the first 36 months of follow-up. Early onset, ANA positivity, past and ongoing treatment with csDMARDs or bDMARDs, therapeutic withdrawal, and disease activity within 12 months before transition did not significantly influence the risk of relapse.
In JIA patients, the risk of relapse after transitioning to adult care remains high, irrespective of disease subtype and treatment. The main risk factor for the early occurrence of articular activity is monoarticular involvement.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Conventional pharmacological therapies for the treatment of juvenile idiopathic arthritis (JIA) consist of non-biological, disease-modifying antirheumatic drugs, among which methotrexate (MTX) is the ...most commonly prescribed. However, there is a lack of consensus-based clinical and therapeutic recommendations for the use of MTX in the management of patients with JIA. Therefore, the Methotrexate Advice and RecommendAtions on Juvenile Idiopathic Arthritis (MARAJIA) Expert Meeting was convened to develop evidence-based recommendations for the use of MTX in the treatment of JIA.
The preliminary executive committee identified a total of 9 key clinical issues according to the population, intervention, comparator, outcome (PICO) approach, and performed an evidence-based, systematic, literature review. During the subsequent Expert Meeting, the relevant evidence was assessed and graded, and 10 recommendations were made.
Recommendations relating to the efficacy, optimal dosing and route of administration and duration of treatment with MTX in JIA, and to the issue of folic acid supplementation to prevent MTX side effects, use of MTX in the treatment of chronic JIA-associated uveitis, combination treatment with biologic agents, and the use of vaccinations in patients with JIA were developed. The selected topics were considered to represent clinically important issues facing clinicians caring for patients with JIA. Evidence was insufficient to formulate recommendations for the use of biomarkers predictive of treatment response.
These consensus recommendations provide balanced and evidence-based recommendations designed to have broad value for physicians and healthcare clinicians involved in the clinical management of patients with JIA.
Localized scleroderma (LS) is a complex disease characterized by a mixture of inflammation and fibrosis of the skin that, especially in the pediatric population, also affects extracutaneous tissues ...ranging from muscle to the central nervous system. Although developmental origins have been hypothesized, evidence points to LS as a systemic autoimmune disorder, as there is a strong correlation to family history of autoimmune disease, the presence of shared HLA types with rheumatoid arthritis, high frequency of auto-antibodies, and elevated circulating chemokines and cytokines associated with T-helper cell, IFNγ, and other inflammatory pathways. This inflammatory phenotype of the peripheral blood is reflected in the skin via microarray, RNA Sequencing and tissue staining. Research is underway to identify the key players in the pathogenesis of LS, but close approximation of inflammatory lymphocytic and macrophage infiltrate with collagen and fibroblasts deposition supports the notion that LS is a disease of inflammatory driven fibrosis. The immune system is dynamic and undergoes changes during childhood, and we speculate on how the unique features of the immune system in childhood could potentially contribute to some of the differences in LS between children and adults. Interestingly, the immune phenotype in pediatric LS resembles to some extent the healthy adult cellular phenotype, possibly supporting accelerated maturation of the immune system in LS. We discuss future directions in better understanding the pathophysiology of and how to better treat pediatric LS.
Scleroderma in children Zulian, Francesco
Best practice & research. Clinical rheumatology,
August 2017, 2017-08-00, 20170801, Letnik:
31, Številka:
4
Journal Article
Recenzirano
Juvenile scleroderma with its two varieties, juvenile localized scleroderma and systemic sclerosis (SSc), represents the third most frequent rheumatic disease in childhood. In juvenile SSc, new ...developments have been recently reported in the fields of classification and monitoring. The introduction of new classification criteria for adult SSc has stimulated new ideas on how to improve the performance of the provisional 2007 PRES/ACR/EULAR pediatric criteria. The introduction of a multidimensional severity score, named “J4S,” which includes parameters on growth, skin, and internal organ involvement, has improved the approach to the patients in the daily practice to guide decision-making.
In localized scleroderma, the wider application of clinical and instrumental scoring systems has greatly improved both assessment and monitoring. Finally, a multicenter consensus statement and long-term follow-up studies have confirmed the important role of methotrexate for the treatment.
Juvenile scleroderma syndromes, including the systemic and the localized varieties, represent the third most frequent chronic rheumatic conditions in pediatric rheumatology practice. In children, ...systemic sclerosis shows a significantly less frequent involvement of all organs, a higher prevalence of arthritis and myositis, and a better outcome than in adults. Recently, new classification criteria were proposed, which help improve patient care by enabling earlier, more definite diagnoses and by standardizing the conduct of clinical trials. Localized scleroderma is the more frequent subtype of scleroderma in childhood. It comprises a group of distinct conditions that involve mainly the skin and subcutaneous tissues. They range from small plaques of fibrosis involving only the skin to diseases causing significant functional deformity with various extracutaneous features.
Aim of this study was to investigate the activation of the IFNγ pathway in the affected liver and in the blood of patients with secondary hemophagocytic lymphohistiocytosis (sHLH). To this purpose, ...the mRNA expression levels of IFNG and IFNγ-inducible genes as well as Tyrosine (701)-phosphorylated signal transducer and activator of transcription 1 (STAT1) protein levels were evaluated in the liver and in peripheral blood mononuclear cells (PBMCs) of three patients with sHLH with predominant liver involvement. The mRNA expression levels of IFNG and IFNγ-inducible genes were markedly higher in patient livers compared to control livers and to one disease control liver. Conversely, slight differences in the expression levels of Type I IFN-inducible genes and other classical inflammatory cytokine genes were found. Further supporting the activation of the IFNγ pathway, higher protein levels of phosphorylated and total STAT1 were detected in patient livers compared to control livers. When the expression of the same genes analysed in liver tissues was evaluated in PBMCs collected from 2 out of 3 patients before the liver biopsy, we found that mRNA levels of IFNγ-inducible genes were markedly increased. Accordingly, high circulating levels of IFNγ-inducible CXCL9 were observed in patients. Altogether, these data demonstrate the selective and marked up-regulation of the IFNγ pathway in the liver tissue and blood of patients with active sHLH. Finally, we show that measurement of circulating CXCL9 levels and evaluation of IFNγ-inducible gene expression levels in PBMCs may represent a new valid tool to better identify patients with suspected HLH with predominant liver involvement.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Juvenile osteoperiostites (JOP) are a group of inflammatory bone diseases whose differential diagnosis is often difficult. The main conditions are acute osteomyelitis (AOM), chronic non-bacterial ...osteomyelitis (CNO) and the Goldbloom syndrome (GS). The study was aimed to develop an algorithm to enable an early diagnosis of JOP. Clinical records of patients with AOM, CNO and GS, followed at our Center over the past 10 years, were reviewed. Twelve additional patients with GS were selected from PubMed/MEDLINE literature search. Data collected included demographics, clinical manifestations, laboratory and instrumental investigations at disease onset. The association between categorical variables was investigated, and the segmentation of patients with different diagnoses was analyzed through a classification tree model (CTREE package) in order to build up a diagnostic algorithm. Ninety-two patients (33 CNO, 44 AOM, 15 GS) entered the study. Among 30 variables considered at onset, nine (age at onset, fever, weight loss, symmetry, focality, functional limitation, anemia, elevated ESR, CRP) resulted statistically significant in differentiating the three clinical entities from each other and were chosen to build up a decisional tree. Three variables, symmetry of bone involvement, presence of fever and age at disease onset, resulted significant to discriminate each of the three diseases from the others. The performance of the diagnostic algorithm was validated by comparing the diagnoses provided by the model with the real diagnoses and showed 85.9% accuracy.
Conclusion
: We propose a diagnostic algorithm, based on simple clinical data, which can help guide a prompt and appropriate diagnosis of JOP.
What is Known:
• Juvenile osteoperiostitis (JOP) are a group of inflammatory bone diseases followed by various pediatric specialists.
• The distinction between these conditions is not easy as clinical and laboratory features often overlap.
What is New:
• We propose a diagnostic algorithm, based on clinical data of real patients, with high degree accuracy.
• This instrument can help guide the prompt and appropriate diagnosis of JOP.
Objectives
Juvenile localized scleroderma (JLS) is a rare chronic autoimmune disease which can also affect bones and muscles. Nevertheless, muscle loss was not previously investigated in patients ...with JLS. Thus, the aim of this study was to retrospectively evaluate deep involvement and assess and quantify sarcopenia in JLS patients using magnetic resonance imaging (MRI).
Methods
Fourteen children with JLS (nine females, mean age ± SD, 7.1 ± 3.6 years) referring to our tertiary center from January 2012 to January 2018 who underwent at least one MRI examination including axial T1-weighted and short tau inversion recovery images were included. Two readers assessed in consensus superficial and deep involvement. Muscle edema, muscle fatty infiltration, and sarcopenia were independently scored (absent, moderate, or severe) and the Cohen’s kappa coefficient computed. Skin perimeter, subcutaneous area, muscle area, and muscle volume were independently measured using the contralateral unaffected extremity as reference (paired Student’s
t
test,
p
< 0.05). The intraclass correlation coefficient (ICC) was used to investigate the reliability of the measurements.
Results
All patients showed superficial involvement with subcutaneous fat atrophy being the most common finding (13 patients). Bone marrow edema occurred in five patients. Muscle edema affected ten children (moderate in seven, severe in three;
k
= 0.89), muscle fatty replacement occurred in one case (severe;
k
= 1.00), and sarcopenia was detected in eight patients (severe in two;
k
= 0.78). All quantitative parameters were lower on the affected side than on the unaffected contralateral limb (
p
< 0.05, each) and all measurements showed a high reliability (ICC > 0.750, each).
Conclusion
Patients with JLS can be affected by sarcopenia and quantitative analyses allow a robust characterization of such finding.
Key Points
• Deep involvement in juvenile localized scleroderma is frequently characterized by sarcopenia.
• In juvenile localized scleroderma, muscle edema and sarcopenia are mostly moderate while fatty infiltration, even if rare, can be severe.
• Sarcopenia can be reliably quantified in children with juvenile localized scleroderma using MRI.
To evaluate the efficacy of levofolinic acid (LVF) administered 48 h before methotrexate (MTX) in reducing gastrointestinal side effects without interference with drug efficacy.
A prospective ...observational study was performed including patients with Juvenile Idiopathic Arthritis (JIA) reporting significant gastrointestinal discomfort after MTX despite taking a dose of LVF 48 h after MTX. Patients with anticipatory symptoms were excluded. A LVF supplemental dose was added 48 h before MTX and patients were followed every 3-4 months. At each visit data on gastrointestinal symptoms, disease activity (JADAS, ESR, CRP values) and treatment changes were collected. Friedman test for repeated measures analyzed differences between these variables over time.
Twenty-one patients were recruited and followed for at least 12 months. All patients received MTX subcutaneously (mean 9.54 mg/m2) and LVF 48 h before and after MTX (mean 6.5 mg/dose), 7 received a biological agent too. Complete remission of gastrointestinal side effects was reported in 61.9% of study patients at first visit (T1) and increased over time (85.7%, 95.2%, 85.7% and 100% at T2, T3, T4, T5, respectively). MTX efficacy was maintained as showed by significant reduction of JADAS and CRP (p = 0.006 and 0.008) from T1 to T4 and it was withdrawn for remission in 7/21.
LVF given 48 h before MTX significantly reduced gastrointestinal side effects and did not reduce drug's efficacy. Our results suggest that this strategy may improve compliance and quality of life in patients with JIA and other rheumatic diseases treated with MTX.
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