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World Journal of Clinical Pediatrics Mar 2024Lung damage in systemic juvenile arthritis (sJIA) is one of the contemporary topics in pediatric rheumatology. Several previous studies showed the severe course and...
BACKGROUND
Lung damage in systemic juvenile arthritis (sJIA) is one of the contemporary topics in pediatric rheumatology. Several previous studies showed the severe course and fatal outcomes in some patients. The information about interstitial lung disease (ILD) in the sJIA is scarce and limited to a total of 100 cases.
AIM
To describe the features of sJIA patients with ILD in detail.
METHODS
In the present retrospective cohort study, information about 5 patients less than 18-years-old with sJIA and ILD were included. The diagnosis of sJIA was made according to the current 2004 and new provisional International League of Associations for Rheumatology criteria 2019. ILD was diagnosed with chest computed tomography with the exclusion of other possible reasons for concurrent lung involvement. Macrophage activation syndrome (MAS) was diagnosed with HLH-2004 and 2016 EULAR/ACR/PRINTO Classification Criteria and hScores were calculated during the lung involvement.
RESULTS
The onset age of sJIA ranged from 1 year to 10 years. The time interval before ILD ranged from 1 mo to 3 years. The disease course was characterized by the prevalence of the systemic features above articular involvement, intensive rash (100%), persistent and very active MAS (hScore range: 194-220) with transaminitis (100%), and respiratory symptoms (100%). Only 3 patients (60%) developed a clubbing phenomenon. All patients (100%) had pleural effusion and 4 patients (80%) had pericardial effusion at the disease onset. Two patients (40%) developed pulmonary arterial hypertension. Infusion-related reactions to tocilizumab were observed in 3 (60%) of the patients. One patient with trisomy 21 had a fatal disease course. Half of the remaining patients had sJIA remission and 2 patients had improvement. Lung disease improved in 3 patients (75%), but 1 of them had initial deterioration of lung involvement. One patient who has not achieved the sJIA remission had the progressed course of ILD. No cases of hyper-eosinophilia were noted. Four patients (80%) received canakinumab and one (20%) tocilizumab at the last follow-up visit.
CONCLUSION
ILD is a severe life-threatening complication of sJIA that may affect children of different ages with different time intervals since the disease onset. Extensive rash, serositis (especially pleuritis), full-blown MAS with transaminitis, lymphopenia, trisomy 21, eosinophilia, and biologic infusion reaction are the main predictors of ILD. The following studies are needed to find the predictors, pathogenesis, and treatment options, for preventing and treating the ILD in sJIA patients.
PubMed: 38596441
DOI: 10.5409/wjcp.v13.i1.88912 -
Genetics and Molecular Biology 2024Massive sequencing platforms allow the identification of complex clinical phenotypes involving more than one autosomal recessive disorder. In this study, we report on an...
Massive sequencing platforms allow the identification of complex clinical phenotypes involving more than one autosomal recessive disorder. In this study, we report on an adult patient, born to a related couple (third degree cousins), referred for genetic evaluation due to ectopia lentis, deafness and previous diagnosis of juvenile idiopathic arthritis. He was biochemically diagnosed as having Classic Homocystinuria (HCU); Sanger sequencing of the CBS gene showed the genotype NM_000071.2(CBS):c.[833T>C];[833T>C], compatible with the diagnosis of pyridoxine-responsive HCU. As he also had symptoms not usually associated with HCU, exome sequencing was performed. In addition to the variants found in the Sanger sequencing, the following variants were identified: NM_001256317.1(TMPRSS3):c.[413C>A];[413C>A]; and the NM_005807.6(PRG4):c.[3756dup]:[3756dup], confirming the diagnosis of autosomal recessive nonsyndromic deafness and Camptodactyly-Arthropathy-Coxa Vara-Pericarditis Syndrome (CACP), respectively. Genomic analysis allowed the refinement of the diagnosis of a complex case and improvement of the patient's treatment.
PubMed: 38593426
DOI: 10.1590/1678-4685-GMB-2022-0335 -
Arthritis Research & Therapy Apr 2024Our study aimed to provide real-world evidence on the treatment patterns, effectiveness and safety of canakinumab in France in Familial Mediterranean Fever (FMF),...
BACKGROUND
Our study aimed to provide real-world evidence on the treatment patterns, effectiveness and safety of canakinumab in France in Familial Mediterranean Fever (FMF), Mevalonate Kinase Deficiency (MKD), and Tumor necrosis factor Receptor Associated Periodic Syndrome (TRAPS).
METHODS
This study used the JIR cohort, a multicentre international registry created in 2013 to collect data on patients with juvenile inflammatory rheumatic diseases. French patients diagnosed with FMF, MKD or TRAPS and treated with canakinumab were included in this study.
RESULTS
31 FMF, 26 MKD and 7 TRAPS patients received canakinumab during the study period. Most of them initiated canakinumab at the recommended dose of 2 mg/kg or 150 mg, but less than half of FMF and MKD patients initiated it at the recommended frequency (every 4 weeks). Two years after initiation, the rate of patients still on treatment was 78.1% in FMF, 73.7% in MKD, and 85.7% in TRAPS patients. While the dose per injection remained globally the same over the course of the treatment, some adjustments of the dose intervals were observed. Six patients had a severe adverse event reported. Of those, three were possibly related to canakinumab.
CONCLUSION
This interim analysis showed a good maintenance of canakinumab treatment 2 years after initiation and confirmed its safety profile in real-life practice in France in patients diagnosed with FMF, MKD and TRAPS. The high variety of dose and interval combinations observed in canakinumab treated patients let suppose that physicians adapt the posology to individual situations rather than a fixed treatment plan.
Topics: Humans; Hereditary Autoinflammatory Diseases; Familial Mediterranean Fever; Antibodies, Monoclonal, Humanized; Mevalonate Kinase Deficiency; Syndrome
PubMed: 38589954
DOI: 10.1186/s13075-024-03316-7 -
Pediatric Rheumatology Online Journal Apr 2024Temporomandibular joint (TMJ) involvement is an often underrecognized complication of juvenile idiopathic arthritis (JIA) that can cause decreased mandibular growth,...
BACKGROUND
Temporomandibular joint (TMJ) involvement is an often underrecognized complication of juvenile idiopathic arthritis (JIA) that can cause decreased mandibular growth, altered facial morphology, and orofacial pain. It is estimated that the TMJ is affected in 30-45% of children with JIA. Standardized physical examination and imaging evaluations are important in accurately assessing active TMJ arthritis and sequalae. Little is known about the rate at which providers evaluate TMJ involvement in their clinical practice.
METHODS
Data were obtained from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. Data fields related to assessment for TMJ arthritis were added in 2019. Patients were included in the study if they had a diagnosis of JIA and had data recorded between January 2020 and August 2021. Standard descriptive statistics were used to describe demographic and clinical features.
RESULTS
A total of 17,761 visits were reviewed for a total of 7473 patients with JIA. A total of 52.7% of patients had maximal mouth opening (MMO) recorded as finger breadths or total incisal distance (TID). Only 8% had TID measured. A total of 5.0% had MRI with contrast performed. A total of 939 patients had a diagnosis of TMJ arthritis. Of these, 28.5% had an MRI documented, 83% had an MMO documented, and 40% had TID measured. Few patient-level characteristics were statistically related to having MMO assessed. MRI was more likely to be obtained in older and in female patients. MMO was recorded at a given visit > 80% of the time at 17 sites, and it was recorded < 1% of the time at 8 sites. MRIs were infrequently performed at all sites, with 27 sites having no MRIs obtained and only 7 sites having an MRI obtained at > 10% of visits.
CONCLUSIONS
MMO is not consistently measured in patients with JIA, and it is rarely measured quantitatively. Similarly, TMJ MRIs are rarely obtained in patients with JIA. Site of care is more associated with TMJ assessments than patient-level characteristics. These data suggest that provider education is needed to improve the assessment of the TMJ in patients with JIA to enable earlier recognition and prevent long-term complications.
Topics: Child; Humans; Female; Aged; Arthritis, Juvenile; Retrospective Studies; Rheumatology; Temporomandibular Joint; Temporomandibular Joint Disorders; Magnetic Resonance Imaging
PubMed: 38589909
DOI: 10.1186/s12969-024-00968-2 -
Cureus Mar 2024Purpose To determine the etiology and anatomic localization of uveitis, the frequency of intraocular pressure (IOP) elevation, and the type of secondary glaucoma and to...
The Frequency of Intraocular Pressure Elevation, Incidence of Secondary Glaucoma, and Surgical Treatment With Postoperative Complications in Pediatric and Adult Patients With Uveitis.
Purpose To determine the etiology and anatomic localization of uveitis, the frequency of intraocular pressure (IOP) elevation, and the type of secondary glaucoma and to assess the medical, surgical, and postoperative complications in adult and pediatric patients with acute or chronic uveitis. Methods A total of 307 eyes of 186 patients who were followed up in the Uvea-Behçet Unit of the Ophthalmology Department, Erciyes University, Turkey, were included in the study. Demographic, ocular, and systemic data were recorded; ophthalmological examinations were performed; and recurrences and complications of uveitis were identified. The eyes with IOP over 22 mmHg, types of secondary glaucoma, their etiologies, efficiency of medical and surgical treatments, and complications were recorded. Results The mean age was 33 ± 12 years (range: 6-65). Of the 186 patients, diagnoses were as follows: idiopathic uveitis in 84 (45.2%), Behçet disease in 65 (34.9%), ankylosing spondylitis in eight (4.3%), juvenile idiopathic arthritis in five (2.7%), herpetic keratouveitis in three (1.6%), Fuchs iridocyclitis in three (1.6%), Vogt-Koyanagi-Harada syndrome in three (1.6%), tuberculosis uveitis in three (1.6%), Crohn disease in three (1.6%), ocular toxoplasmosis in two (1.1%), multiple sclerosis in two (1.1%), Lyme disease in two (1.1%), rheumatoid arthritis in two (1.1%) and tubulointerstitial nephritis in one patient (0.5%). Secondary glaucoma was detected in 67 (21.9%) of 307 eyes, which developed in 13.7% and 26.8% of the eyes with acute and chronic uveitis, respectively. Of 67 eyes, it was open-angle glaucoma in 58 (86.5%), angle-closure glaucoma in six (9.0%), and neovascular glaucoma in three (4.5%). Control of IOP was achieved by medical therapy in 53 eyes (79.1%) and by surgery in 12 eyes (17.9%), whereas evisceration was required in two eyes (3.0%). Laser iridotomy was performed in four eyes (33.4%), trabeculectomy with mitomycin-C (MMC) in six eyes (50.0%), laser iridotomy plus trabeculectomy with MMC in one eye (8.3%), and express mini shunt implantation in one eye (8.3%). After surgery, IOP was controlled without anti-glaucomatous agents in six eyes (50%) and with anti-glaucomatous agents in the remaining six eyes (50.0%). Conclusion Secondary glaucoma is one of the most important complications of uveitis and may result in severe visual impairment. Early diagnosis and appropriate treatment can prevent these potential complications.
PubMed: 38586631
DOI: 10.7759/cureus.55734 -
The Journal of Pediatrics Apr 2024To understand the burden associated with pediatric chronic pain (CP) on the health care system compared with other costly chronic diseases prior to subspecialty care.
OBJECTIVES
To understand the burden associated with pediatric chronic pain (CP) on the health care system compared with other costly chronic diseases prior to subspecialty care.
STUDY DESIGN
In this retrospective cohort study, we assessed all-cause health care utilization and direct health care costs associated with pediatric CP (n = 91) compared with juvenile arthritis (n = 135), inflammatory bowel disease (n = 90), type 1 diabetes (n = 475) or type 2 diabetes (n = 289), anxiety (n = 7193), and controls (n = 273) 2 and 5 years prior to patients entering subspecialty care in Manitoba, Canada. Linked data from physician encounters, emergency department visits, hospitalizations, and prescriptions were extracted from administrative databases. Differences in health care utilization and direct health care costs associated with CP vs the other conditions were tested using negative binomial and zero-inflated negative binomial regression models, respectively.
RESULTS
After adjustment for age at diagnosis, sex, location of residence, and socioeconomic status, CP continued to be associated with the highest number of consulted physicians and subspecialists and the highest number of physician billings compared with all other conditions (P < .01, respectively). CP was significantly associated with higher physician costs than juvenile arthritis, inflammatory bowel disease, type 1 diabetes, type 2 diabetes, or controls (P < .01, respectively); anxiety was associated with the highest physician and prescription costs among all cohorts (P < .01, respectively).
CONCLUSION
Compared with chronic inflammatory and endocrinologic conditions, pediatric CP and anxiety were associated with substantial burden on the health care system prior to subspecialty care, suggesting a need to assess gaps and resources in the management of CP and mental health conditions in the primary care setting.
PubMed: 38582149
DOI: 10.1016/j.jpeds.2024.114046 -
Medicine Apr 2024The term "Rhupus" was employed to descriptively illustrate the overlap observed in some pediatric patients displaying features of both juvenile idiopathic arthritis...
INTRODUCTION
The term "Rhupus" was employed to descriptively illustrate the overlap observed in some pediatric patients displaying features of both juvenile idiopathic arthritis (JIA) and systemic lupus erythematosus (SLE). Although "Rhupus" is traditionally used in adults, we applied it broadly to emphasize this clinical overlap.
METHODS
We sought to identify studies that registered signs, symptoms, imaging characteristics, and treatments given to patients with JIA and SLE. We searched four databases using a Boolean search string, resulting in 231 articles after duplicate removal. Title and abstract screening yielded 57 articles for full-text assessment. Full reviewed 13 extracted data regarding sex, age of onset, serologic and imaging findings, and management strategies. The NIH quality assessment tool was applied to ensure the internal validity of the articles.
RESULTS
From the 13 articles evaluated that meet inclusion criteria, none had standardized diagnostic algorithms. The total number of patients in those articles is 26, without discussing treatment guidelines.
DISCUSSION
Clinical presentation, diagnostic parameters, and treatment of pediatric Rhupus were synthesized in this review. Fundamental keys help distinguish the joint presentation when Juvenile Idiopathic Arthritis or Lupus is present, compared with the signs and symptoms when developing the overlapping syndrome. We highlight the importance of physicians knowing about this rare condition and call all specialists to report new cases of the disease so a consensus can be reached to establish standardized guidelines for diagnosing and treating Rhupus syndrome.
Topics: Adult; Humans; Child; Arthritis, Juvenile; Arthritis, Rheumatoid; Lupus Erythematosus, Systemic; Syndrome
PubMed: 38579098
DOI: 10.1097/MD.0000000000036451 -
Translational Vision Science &... Apr 2024Nonanterior uveitis frequently involves the retinal vasculature; however, no molecular markers associated with the retinal vascular disease are currently known. In this...
PURPOSE
Nonanterior uveitis frequently involves the retinal vasculature; however, no molecular markers associated with the retinal vascular disease are currently known. In this study, we aimed to identify serum biomarker signatures associated with retinal vascular involvement in noninfectious pediatric uveitis.
METHODS
We performed a 384-plex targeted proteomic analysis of serum samples of 154 noninfectious pediatric uveitis patients diagnosed with nonanterior uveitis (n = 74), idiopathic chronic anterior uveitis (iCAU, n = 36), or juvenile idiopathic arthritis-associated uveitis (JIA-U, n = 44), as well as 22 noninflammatory pediatric controls. Data on retinal vascular involvement (i.e., papillitis, cystoid macular edema, retinal vasculitis, or retinal capillary leakage on optical coherence tomography and/or fluorescein angiography) were used to stratify cases in the nonanterior uveitis group.
RESULTS
In the analysis of nonanterior uveitis, we identified nine proteins significantly associated with retinal vascular involvement, including F13B, MYOM3, and PTPN9. These proteins were enriched through pathway enrichment analysis for the coagulation cascade. Comparing cases and controls, we identified 63 differentially expressed proteins, notably proteins involved in platelet biology and complement cascades, which could be primarily attributed to differences in serum proteomes between anterior uveitis and nonanterior uveitis groups.
CONCLUSIONS
Serum proteins related to the coagulation and complement cascade are associated with retinal vascular involvement in pediatric uveitis patients. Our results indicate involvement of mediators that could interact with the microcirculation in pediatric uveitis and might serve as potential biomarkers in personalized medicine in the future.
TRANSLATIONAL RELEVANCE
Our targeted proteomics analysis in serum of pediatric uveitis patients indicates involvement of mediators that could interact with the microcirculation in pediatric uveitis and might serve as potential biomarkers in personalized medicine in the future.
Topics: Humans; Child; Proteomics; Uveitis; Uveitis, Anterior; Retinal Diseases; Biomarkers
PubMed: 38573655
DOI: 10.1167/tvst.13.4.9 -
Journal of Children's Orthopaedics Apr 2024Literature regarding total hip arthroplasty for pediatric hip diseases is scarce. This review aims to portray the various orthopedic conditions of childhood that can... (Review)
Review
PURPOSE
Literature regarding total hip arthroplasty for pediatric hip diseases is scarce. This review aims to portray the various orthopedic conditions of childhood that can lead to significant impairment of the hip joint and, ultimately, to total hip arthroplasty in adolescence and adulthood.
METHODS
In total, 61 out of 3666 articles were selected according to (1) the diagnosis of one of the 12 pediatric hip pathologies (Legg-Perthes-Calvé disease, developmental dysplasia of the hip, slipped capital femoral epiphysis, neuromuscular hip dysplasia, post-traumatic avascular necrosis of the proximal femur, juvenile rheumatoid arthritis, achondroplasia, spondyloepiphyseal dysplasia, mucopolysaccharidosis, mucolipidosis, hip infections, and tumors) that required total hip arthroplasty; (2) minimum follow-up of 16 months; (3) assessed outcome with a clinical or radiologic score; (4) Methodological Items for Non-Randomized Studies quality score of 9 or higher. The following information for each pathology was retrieved: mean age at total hip arthroplasty, reason for total hip arthroplasty, type of total hip arthroplasty, surgical technique, mean follow-up, and outcomes.
RESULTS
Overall, the mean age at total hip arthroplasty for pediatric hip disease is in the sixth and seventh decade, except for tumors and skeletal dysplasias. The reason for performing total hip arthroplasty is often osteoarthrosis and abnormal anatomy. Prosthesis types change based on patient's conditions and technological advances; custom-made implants are used for tumors, juvenile rheumatoid arthritis, and skeletal dysplasias; for other diseases, the most frequent are modular cementless implants. Outcomes are generally good, and all studies portray functional and pain improvements.
CONCLUSION
Total hip arthroplasty is performed more frequently than in the past in patients with pediatric hip pathologies; it enhances patients' quality of life by reducing pain and improving function. However, revision rate in these patients is not negligible.
PubMed: 38567046
DOI: 10.1177/18632521241229608 -
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