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Pediatric Rheumatology Online Journal Oct 2023Anakinra is a recombinant interleukin-1 (IL-1) receptor antagonist used in systemic juvenile idiopathic arthritis (sJIA), refractory Kawasaki disease (KD) and...
BACKGROUND
Anakinra is a recombinant interleukin-1 (IL-1) receptor antagonist used in systemic juvenile idiopathic arthritis (sJIA), refractory Kawasaki disease (KD) and cryopyrin-associated autoinflammatory syndrome (CAPS). Anakinra associated hepatotoxicity, while rare, has been described in several cases in daily practice. In this case series the authors describe three pediatric patients with this side effect in the setting of severe macrophage activation syndrome (MAS) in KD and sJIA.
CASE PRESENTATION
The first patient was a 12-year-old boy who presented with fever, maculo-papular exanthema and polyarthralgia. Tonsillitis, distal limb induration and tender cervical lymph nodes were observed. Erythrocyte-sedimentation rate (ESR), C-reactive protein (CRP), ferritin (11,975 ng/mL), D-dimers (5,98 mg/L FEU) and soluble CD25 (3645 pg/mL) levels were elevated. Exclusion of sepsis / toxic shock syndrome warranted introduction of IV methylprednisolone and immunoglobulin (IG IV), with partial response. A MAS secondary to KD was assumed, and anakinra 2 mg/kg/day was introduced. Twenty days later he developed new-onset nausea and severe cyto-cholestasis, normalizing after 2 months of drug discontinuation. Posterior onset of polyarthritis and evanescent lead to a final diagnosis of sJIA. The second patient was a 2-year-old boy with a 10-day history of fevers, generalized rash, hepatosplenomegaly and strawberry tongue. Leucocytosis with neutrophilia and elevated CRP were observed. Initial treatment with IVIG in the setting of incomplete KD was ineffective. Mild anaemia, leukopenia and very high serum ferritin (maximum 26,128 ng/mL) ensued. Presumptive sJIA associated MAS was treated with IV methylprednisolone and anakinra 2 mg/kg/day, with prompt response. Four weeks later transaminitis was detected, and temporary anakinra suspension led to normalisation of laboratorial values. The third case related to a 4-year-old boy presenting with fever, maculopapular rash and cervical lymphadenopathy. CRP and ESR were elevated, and KD was diagnosed. IVIG and methylprednisolone were initiated with clinical worsening, warranting for anakinra introduction at 2 mg/kg/day. After three weeks, liver enzymes progressively elevated, resolving on 2 weeks of anakinra discontinuation.
CONCLUSIONS
To the best of our knowledge, this is the first case series describing anakinra associated hepatotoxicity in pediatric patients with rheumatic diseases other than sJIA, bringing additional insight to therapeutic monitoring in patients undergoing this treatment.
Topics: Male; Humans; Child; Child, Preschool; Interleukin 1 Receptor Antagonist Protein; Immunoglobulins, Intravenous; Rheumatology; Fever; Drug-Related Side Effects and Adverse Reactions; Arthritis, Juvenile; Exanthema; Methylprednisolone; Macrophage Activation Syndrome; Ferritins; Chemical and Drug Induced Liver Injury
PubMed: 37803456
DOI: 10.1186/s12969-023-00891-y -
Pediatric Rheumatology Online Journal Oct 2023Physiotherapy appears as a promising therapy option for patients with Juvenile Idiopathic Arthritis (JIA) [1, 2], but the effects of physiotherapy and jaw exercises on...
BACKGROUND
Physiotherapy appears as a promising therapy option for patients with Juvenile Idiopathic Arthritis (JIA) [1, 2], but the effects of physiotherapy and jaw exercises on JIA-related orofacial symptoms remain unknown [3]. The aim of this proof-of-concept study was to assess the impact of orofacial physiotherapy and home-exercise programs in patients with JIA and temporomandibular joint (TMJ) involvement.
METHODS
Twelve patients with JIA and TMJ involvement received a treatment of physiotherapy, complemented by prescribed home exercises spanning over eight weeks. Orofacial symptoms and dysfunction were monitored pre-treatment, during treatment, after treatment, and at a three-months follow-up.
RESULTS
Orofacial pain frequency and intensity significantly decreased during the course of the treatment (p = 0.009 and p = 0.006), with further reductions observed at the three-month follow-up (p = 0.007 and p = 0.002). During treatment, the mandibular function improved significantly in terms of maximal mouth opening capacity, laterotrusion, and protrusion.
CONCLUSIONS
This proof-of-concept study shows favourable effects of physiotherapy and home excercises in the management of JIA-related orofacial symptoms and dysfunctions.
Topics: Humans; Arthritis, Juvenile; Temporomandibular Joint Disorders; Temporomandibular Joint; Facial Pain; Physical Therapy Modalities
PubMed: 37828517
DOI: 10.1186/s12969-023-00900-0 -
Pediatric Rheumatology Online Journal Sep 2023Although the advent of new therapeutics for juvenile idiopathic arthritis (JIA) patients has considerably lessened the impact of the disease and reduced its sequelae,...
BACKGROUND
Although the advent of new therapeutics for juvenile idiopathic arthritis (JIA) patients has considerably lessened the impact of the disease and reduced its sequelae, the outcomes of JIA remain important in their lives. Disease repercussions and side effects of treatments may affect sexual health and cause psychological distress. This aim of the study was to determine the expectations of adolescent JIA patients and the perceptions of their parents regarding knowledge and communication with healthcare providers (HCPs) in the field of sexual health (SH).
METHODS
In France, from September 2021 to April 2022, a survey was conducted, using anonymous self-administered questionnaires, among JIA patients (adults (aged 18-45 years) to provide insights from their recollection of their adolescence) and their parents in nine rheumatology centers and three patient associations.
RESULTS
The responses to the 76 patient questionnaires and 43 parent questionnaires that were collected were analyzed. Half of the patients thought JIA impacted their romantic relationships, but the results were less clear-cut for their sexual activity; and 58.7% of the patients said they would be comfortable discussing the subject with HCPs, but only 26.3% had done so, mainly regarding biomedical issues. The patients and their parents thought that ideally, the topic should be addressed in an individual patient education session at the hospital (51.3% and 34.9%, respectively), in a regular consultation (47.4% and 53.5%), or in a dedicated consultation requested by the adolescent without the adolescent's parents being informed (38.2% and 20.9%). Most of the respondents thought HCPs should be proactive in SH (77.6% of the patients and 69.8% of their parents). More patients than parents said the following digital information tools must be used: videos (29.0% vs. 9.3%, p = 0.0127) and smartphone applications (25.0% vs. 9.3%, p = 0.0372).
CONCLUSION
HCPs should consider addressing the unmet need for SH discussions during their patient encounters. To meet this need, we propose concrete actions in line with the wishes of patients and parents.
CLINICAL TRIAL REGISTRATION NUMBER
NCT04791189.
Topics: Adult; Humans; Adolescent; Arthritis, Juvenile; Sexual Health; Communication; Parents; Surveys and Questionnaires
PubMed: 37670340
DOI: 10.1186/s12969-023-00884-x -
Diagnostics (Basel, Switzerland) Aug 2023Today, with rapid advances in technology, computer-based studies and Artificial Intelligence (AI) approaches are finding their place in every field, especially in the... (Review)
Review
Today, with rapid advances in technology, computer-based studies and Artificial Intelligence (AI) approaches are finding their place in every field, especially in the medical sector, where they attract great attention. The Temporomandibular Joint (TMJ) stands as the most intricate joint within the human body, and diseases related to this joint are quite common. In this paper, we reviewed studies that utilize AI-based algorithms and computer-aided programs for investigating TMJ and TMJ-related diseases. We conducted a literature search on Google Scholar, Web of Science, and PubMed without any time constraints and exclusively selected English articles. Moreover, we examined the references to papers directly related to the topic matter. As a consequence of the survey, a total of 66 articles within the defined scope were assessed. These selected papers were distributed across various areas, with 11 focusing on segmentation, 3 on Juvenile Idiopathic Arthritis (JIA), 10 on TMJ Osteoarthritis (OA), 21 on Temporomandibular Joint Disorders (TMD), 6 on decision support systems, 10 reviews, and 5 on sound studies. The observed trend indicates a growing interest in artificial intelligence algorithms, suggesting that the number of studies in this field will likely continue to expand in the future.
PubMed: 37627959
DOI: 10.3390/diagnostics13162700 -
Pediatric Rheumatology Online Journal Mar 2024Systemic juvenile idiopathic arthritis (sJIA) is a severe form of juvenile arthritis that is characterized by chronic joint inflammation and systemic symptoms such as...
BACKGROUND
Systemic juvenile idiopathic arthritis (sJIA) is a severe form of juvenile arthritis that is characterized by chronic joint inflammation and systemic symptoms such as fever, rash, and organ involvement. Anti-IL-6 receptor monoclonal antibody tocilizumab is an effective treatment. However, some patients still experience persisting or recurrent symptoms and the real-world effectiveness of canakinumab in Chinese patients with sJIA has never been reported. Therefore, this study aimed to assess the efficacy and safety of canakinumab in Chinese patients with sJIA using real-world data.
METHODS
We conducted a retrospective study on children with active sJIA. Clinical features, laboratory data, corticosteroid dosage, and adverse events (AEs) were collected at baseline and at 4, 8, 12, and 24 weeks after initiating canakinumab treatment.
RESULTS
Seven female and four male patients were included in the study. All patients had previously been treated with tocilizumab and were administered canakinumab for 12.4 ± 3.4 months. Notably, significant improvements were observed in both clinical signs and symptoms as well as laboratory indicators. Four children under corticosteroid treatment were able to successfully discontinue their corticosteroid therapy: one at week 4, two at week 12, and one at week 24. Notably, there was a significant reduction in the number of tender and swollen joints (P = 0.0059) as well as the systemic juvenile arthritis disease activity score (P < 0.0001). The most common AE was infection, but no patients experienced serious AEs. No cases of macrophage activation syndrome or death were reported during the follow-up period.
CONCLUSIONS
Canakinumab was found to be potentially efficacious and safe in Chinese patients with sJIA. No new AEs were observed with canakinumab treatment.
Topics: Child; Humans; Male; Female; Arthritis, Juvenile; Antibodies, Monoclonal; Retrospective Studies; Adrenal Cortex Hormones; Antibodies, Monoclonal, Humanized
PubMed: 38504360
DOI: 10.1186/s12969-024-00974-4 -
RMD Open Dec 2023Still's disease is more frequently observed in the paediatric context, but a delayed onset is not exceptional both in the adulthood and in the elderly. However, whether...
OBJECTIVE
Still's disease is more frequently observed in the paediatric context, but a delayed onset is not exceptional both in the adulthood and in the elderly. However, whether paediatric-onset, adult-onset and elderly-onset Still's disease represent expressions of the same disease continuum or different clinical entities is still a matter of controversy. The aim of this study is to search for any differences in demographic, clinical features and response to treatment between pediatric-onset, adult-onset and elderly-onset Still's disease.
METHODS
Subjects included in this study were drawn from the International AutoInflammatory Disease Alliance Network registry for patients with Still's disease.
RESULTS
A total of 411 patients suffering from Still's disease were enrolled; the disease occurred in the childhood in 65 (15.8%) patients, in the adult 314 (76.4%) patients and in the elderly in 32 (7.8%) patients. No statistically significant differences at post-hoc analysis were observed in demographic features of the disease between pediatric-onset, adult-onset and elderly-onset Still's disease. The salmon-coloured skin rash (p=0.004), arthritis (p=0.009) and abdominal pain (p=0.007) resulted significantly more frequent among paediatric patients than in adult cases, while pleuritis (p=0.015) and arthralgia (p<0.0001) were significantly more frequent among elderly-onset patients compared with paediatric-onset subjects. Regarding laboratory data, thrombocytosis was significantly more frequent among paediatric patients onset compared with adult-onset subjects (p<0.0001), while thrombocytopenia was more frequent among elderly-onset patients although statistical significance was only bordered. No substantial differences were observed in the response to treatments.
CONCLUSIONS
Despite some minor difference between groups, overall, demographic, clinical, laboratory and treatments aspects of Still's disease were similarly observed in patients at all ages. This supports that pediatric-onset, adult-onset and elderly-onset Still's disease is the same clinical condition arising in different ages.
Topics: Adult; Humans; Child; Aged; Still's Disease, Adult-Onset; Arthritis, Juvenile; Arthralgia
PubMed: 38053457
DOI: 10.1136/rmdopen-2023-003578 -
Clinical and Experimental Medicine Apr 2024Observational studies showed possible associations between systemic lupus erythematosus and multiple myeloma. However, whether there is a casual relationship between...
Observational studies showed possible associations between systemic lupus erythematosus and multiple myeloma. However, whether there is a casual relationship between different types of autoimmune diseases (type 1 diabetes mellitus, rheumatoid arthritis, systemic lupus erythematosus, psoriasis, multiple sclerosis, primary sclerosing cholangitis, primary biliary cirrhosis, and juvenile idiopathic arthritis) and multiple myeloma (MM) is not well known. We performed a two-sample Mendelian randomization (MR) study to estimate the casual relationship. Summary-level data of autoimmune diseases were gained from published genome-wide association studies while data of MM was obtained from UKBiobank. The Inverse-Variance Weighted (IVW) method was used as the primary analysis method to interpret the study results, with MR-Egger and weighted median as complementary methods of analysis. There is causal relationship between primary sclerosing cholangitis [OR = 1.00015, 95% CI 1.000048-1.000254, P = 0.004] and MM. Nevertheless, no similar causal relationship was found between the remaining seven autoimmune diseases and MM. Considering the important role of age at recruitment and body mass index (BMI) in MM, we excluded these relevant instrument variables, and similar results were obtained. The accuracy and robustness of these findings were confirmed by sensitivity tests. Overall, MR analysis suggests that genetic liability to primary sclerosing cholangitis could be causally related to the increasing risk of MM. This finding may serve as a guide for clinical attention to patients with autoimmune diseases and their early screening for MM.
Topics: Humans; Multiple Myeloma; Cholangitis, Sclerosing; Genome-Wide Association Study; Mendelian Randomization Analysis; Autoimmune Diseases; Lupus Erythematosus, Systemic
PubMed: 38564026
DOI: 10.1007/s10238-024-01327-x -
BMC Medicine Mar 2024Previous randomized controlled trials (RCTs) suggested that gut microbiota-based therapies may be effective in treating autoimmune diseases, but a systematic summary is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Previous randomized controlled trials (RCTs) suggested that gut microbiota-based therapies may be effective in treating autoimmune diseases, but a systematic summary is lacking.
METHODS
Pubmed, EMbase, Sinomed, and other databases were searched for RCTs related to the treatment of autoimmune diseases with probiotics from inception to June 2022. RevMan 5.4 software was used for meta-analysis after 2 investigators independently screened literature, extracted data, and assessed the risk of bias of included studies.
RESULTS
A total of 80 RCTs and 14 types of autoimmune disease [celiac sprue, SLE, and lupus nephritis (LN), RA, juvenile idiopathic arthritis (JIA), spondyloarthritis, psoriasis, fibromyalgia syndrome, MS, systemic sclerosis, type 1 diabetes mellitus (T1DM), oral lichen planus (OLP), Crohn's disease, ulcerative colitis] were included. The results showed that gut microbiota-based therapies may improve the symptoms and/or inflammatory factor of celiac sprue, SLE and LN, JIA, psoriasis, PSS, MS, systemic sclerosis, Crohn's disease, and ulcerative colitis. However, gut microbiota-based therapies may not improve the symptoms and/or inflammatory factor of spondyloarthritis and RA. Gut microbiota-based therapies may relieve the pain of fibromyalgia syndrome, but the effect on fibromyalgia impact questionnaire score is not significant. Gut microbiota-based therapies may improve HbA1c in T1DM, but its effect on total insulin requirement does not seem to be significant. These RCTs showed that probiotics did not increase the incidence of adverse events.
CONCLUSIONS
Gut microbiota-based therapies may improve several autoimmune diseases (celiac sprue, SLE and LN, JIA, psoriasis, fibromyalgia syndrome, PSS, MS, T1DM, Crohn's disease, and ulcerative colitis).
Topics: Humans; Colitis, Ulcerative; Crohn Disease; Celiac Disease; Diabetes Mellitus, Type 1; Fibromyalgia; Gastrointestinal Microbiome; Randomized Controlled Trials as Topic; Autoimmune Diseases; Psoriasis; Scleroderma, Systemic; Spondylarthritis; Lupus Erythematosus, Systemic
PubMed: 38475833
DOI: 10.1186/s12916-024-03303-4 -
Pediatric Rheumatology Online Journal Nov 2023Juvenile idiopathic arthritis (JIA) is a broad term used to describe arthritis of unknown origin. JIA commonly persists into adulthood, often causing substantial...
OBJECTIVE
Juvenile idiopathic arthritis (JIA) is a broad term used to describe arthritis of unknown origin. JIA commonly persists into adulthood, often causing substantial morbidity such as restricted joint function, which can lead to challenges in employment and independence. This study aims to identify diagnostic biomarkers and investigate the role of immune cells in the pathogenesis of rheumatoid factor-negative polyarticular juvenile idiopathic arthritis (RF-negative pJIA) and oligoarticular juvenile idiopathic arthritis (oJIA).
METHODS
We retrieved a JIA dataset from the GEO database and conducted an analysis of differentially expressed genes (DEGs). Subsequently, functional enrichment analysis was performed on the DEGs. Weighted gene co-expression network analysis (WGCNA) was utilized to identify key modules. Additionally, we constructed a protein‒protein interaction network to identify hub genes that serve as signature genes. Furthermore, we employed CIBERSORT to classify immune cell infiltration.
RESULTS
From the GSE20307 dataset, we identified a total of 1438 DEGs in RF-negative pJIA and 688 DEGs in oJIA. WGCNA clustered the data into 6 modules in pJIA and 4 modules in oJIA. Notably, the ME5 and ME2 modules exhibited significant associations with pJIA and oJIA, respectively. In both pJIA and oJIA, we identified six hub genes, four of which demonstrated high diagnostic sensitivity and specificity in pJIA, while five showed high diagnostic sensitivity and specificity in oJIA. CIBERSORT analysis suggested the potential involvement of these signature genes in immune cell infiltration.
CONCLUSION
In this study, we identified JUN, CXCL8, SOCS3, and KRAS as biomarkers for RF-negative pJIA and JUN, CXCL8, SOCS3, PTGS2, and NFKBIA as biomarkers for oJIA. Furthermore, our findings suggest that Tfh cells may play a role in the early onset of both RF-negative pJIA and oJIA.
Topics: Humans; Arthritis, Juvenile; Biomarkers; Gene Expression Profiling; Sensitivity and Specificity
PubMed: 38001449
DOI: 10.1186/s12969-023-00926-4 -
Pediatric Rheumatology Online Journal Sep 2023Childhood-onset rheumatoid arthritis (CORA), known as rheumatoid factor (RF)-positive juvenile idiopathic arthritis is a type of juvenile idiopathic arthritis that...
BACKGROUND
Childhood-onset rheumatoid arthritis (CORA), known as rheumatoid factor (RF)-positive juvenile idiopathic arthritis is a type of juvenile idiopathic arthritis that shares the same genetic factors and clinical features as adult-onset rheumatoid arthritis. In Africa, CORA hasn't been the subject of a specific study.
OBJECTIVES
The aim of this study is to describe the clinical features, disease activity, functional disability, and treatment of CORA at diagnosis in Senegal and compare the findings to other CORA populations.
METHODS
We conducted a mixed cohort study by reviewing the medical records of patients diagnosed with CORA with an age of symptom onset < 18 years according to the 2019 PRINTO provisional criteria for RF-positive JIA from January 2020 to December 2022 at rheumatology department of Aristide Le Dantec Hospital in Dakar, Senegal. We collected demographic, clinical, paraclinical and therapeutic data. Disease activity score was assessed by DAS28-ESR and DAS28-CRP. Functional disability was assessed using Health Assessment Questionnaire (HAQ) or Childhood HAQ.
RESULTS
A total of 21 patients were included. Eighteen (85.7%) were Females. The mean age at symptom onset was 13.0 ± 3.0 years, and at diagnosis was 16.4 ± 4.2 years. Morning stiffness, joint swelling, and joint deformities were found in 20, 18 and 13 patients respectively. Four patients had a family history of rheumatoid arthritis. Five patients had extra-articular involvement such as rheumatoid nodules. Two patients had interstitial lung disease. The biological inflammatory syndrome was found in 90% of cases. 16 of 21 (76.2%) patients had positive RF, and 18 of 20 (90%) patients had positive Anti-CCP. Seven of 12 (58.3%) patients had positive anti-nuclear antibodies. The mean DAS28-ESR was 5.7 ± 1.0. Fifteen (71.4%) patients had high disease activity (DAS28-ESR > 5.1). The mean DAS28-CRP was 5.4 ± 1.1. The median HAQ was 2.12 with a mean HAQ of 1.9. Nineteen (90.5%) patients were treated with methotrexate, while 17 (81%) had a combination of methotrexate and hydroxychloroquine. Oral prednisone was used in 17 (81%) cases. Non-steroidal anti-inflammatory drugs were used in 4 cases (19%). After 6 months of treatment, mean DAS28-CRP was 2.9.
CONCLUSION
In our study, CORA mainly affects 13-year-old girls, characterised by high disease activity with joint deformity and significant functional impairment. Treatment is mainly based on methotrexate, prednisone and hydroxychloroquine. Further studies are needed to determine the exact clinical phenotype of this disease.
Topics: Child; Adult; Female; Humans; Adolescent; Male; Senegal; Tertiary Care Centers; Arthritis, Juvenile; Methotrexate; Hydroxychloroquine; Prednisone; Cohort Studies; Africa, Western; Arthritis, Rheumatoid; Rheumatoid Factor
PubMed: 37700346
DOI: 10.1186/s12969-023-00889-6