Search Results (39)

Mitochondria, which have critical roles in energy metabolism and oxidative regulation, also have a role in immune regulation including T cell activation, NET formation, inflammation, and apoptosis. More than 50% of those with systemic lupus erythematosus (SLE) have lupus nephritis due to kidney damage from immune complex deposition. Disease severity is reported to be greater in certain lineages. Mitochondrial DNA (mtDNA) haplogroups, which reflect maternal lineages, may modulate immune balance and disease outcomes in SLE. Methods: DNA was extracted from 25 consecutive, consenting pediatric patients that fulfilled the 1997 criteria for SLE and their maternal mitochondrial DNA (mtDNA) haplogroups were determined through next-generation sequencing (NGS). Results: This study evaluated the associations between mtDNA haplogroups, lupus nephritis, and organ damage in four mtDNA haplogroups: African (n = 5), Amerindian (n = 12), Asian (n = 4), and Caucasian (n = 4). Clinical data, SLE Disease Activity Index (SLEDAI-2K), SLICC Damage Index (SDI), and renal biopsy findings were analyzed. Median SLEDAI-2K scores were higher in Amerindian (10) and African (8) patients than in the Caucasian (5.5) and Asian (3) groups, with significant differences between Amerindian vs. Caucasian (p = 0.045) and Amerindian vs. Asian (p = 0.008). Irreversible organ damage (SDI > 1) was more frequent in Amerindian (54%) and African (40%) patients. Lupus nephritis occurred most often and most severely (Class III–IV, CKD) in the Amerindian (85%) and African (80%) groups, while Caucasian and Asian patients more often showed milder, membranous disease without CKD. Conclusion: Although limited by the small sample size, pediatric SLE severity and renal involvement were found to be greater in Amerindian and African mtDNA haplogroups, suggesting that mitochondrial lineage may contribute to ethnic disparities in SLE. Full article

Introduction: Rheumatic diseases, including spondyloarthritis, systemic lupus erythematosus, Takayasu’s nonspecific aortoarteritis, Behcet’s disease, and Kawasaki disease, are more prevalent among Asian populations. The indigenous Sakha people, who live in the harsh conditions of the North and the Arctic regions, exhibit a unique pattern of health issues. AIM: The objective of the study is to characterize the ethnic characteristics of juvenile idiopathic arthritis (JIA) among children from the indigenous population of the Republic of Sakha (Yakutia) and compare them with Caucasians (Russians) living in the same region. This comparison aims to inform the development of tailored diagnostic and treatment strategies. Methods: The comprehensive, single-center, retrospective cohort study included medical data of all Sakha (n = 168) and Russian ethnic patients (n = 48) with JIA who were examined and treated at the Pediatric Center’s Cardiorheumatology Department at the Republican Hospital No. 1–M.E. Nikolaev National Center of Medicine—between 2016 and 2023. The ethnicity was self-reported. The standard clinical procedures and laboratory assessments, as well as the current treatment regimen, were thoroughly reviewed. Results: It was found that children of Sakha descent had a later onset of juvenile idiopathic arthritis (JIA), which was associated with the enthesitis-related arthritis (ERA) categories (51.2% vs. 18.3%, p = 0.0002). They also exhibited higher prevalence of enthesitis (19% vs. 2.0%, p = 0.003), sacroiliitis (23.8% vs. 2.0%, p = 0.0003), and HLA-B27 antigen positivity (46.3% vs. 14.6%, p = 0.00005). The Sakha population exhibited a notably higher prevalence (41.7%) of ERA, compared to the Russian population (33.3%; p = 0.0003), and they initiated biologic therapy at a later stage. However, remission rates were lower among Sakha children (29.2%) than among Russian children (72.2%, p = 0.002), as was their likelihood of achieving remission (Log-Rank test, p = 0.005), regardless of the JIA categories (p = 0.008). Sakha children had a 64.4% reduced chance of achieving remission on the first bDMARD, compared to Russian children (HR = 0.36, 95% CI: 0.18–0.71, p = 0.004). Conclusions: Distinct variations in the progression and treatment outcomes of JIA were observed between Sakha children and Caucasians. A tailored approach to the care of JIA patients is essential, considering their ethnic background. Full article

Background/Objectives: Henoch–Schönlein purpura (HSP), or IgA vasculitis, is the most common small-vessel vasculitis in children, yet Indian cohort data remain limited. We aimed to describe the clinical profile, renal involvement, treatment patterns, relapse, and outcomes of pediatric HSP at a tertiary centre in South India. Methods: We conducted a retrospective review of children <18 years diagnosed with HSP (January 2013–October 2018) using EULAR/PRINTO/PRES criteria. Demographics, clinical features, laboratory parameters, treatments, and outcomes were abstracted from records and analyzed in SPSS (descriptive statistics; Chi-square/Fisher’s exact and t/non-parametric tests as appropriate). Subgroup comparisons included renal vs. non-renal disease and age <6 vs. ≥6 years. An exploratory analysis examined predictors of nephritis. Results: Of 43 children identified, 2 were excluded (misclassified as systemic lupus erythematosus); 41 were analyzed. Mean age was 8.5 years (range 3–17), male: female 1.4:1. A preceding febrile illness or upper respiratory tract infection was noted in 41.4% and 17%, respectively. Palpable purpura was universal; joint involvement 73.1%, abdominal pain 61.0%, vomiting 41.5%. Renal involvement 17% occurred only in children ≥6 years; exploratory testing supported a strong age-linked signal for nephritis. Laboratory abnormalities included anemia (48.7%), thrombocytosis (19.5%), and elevated ESR (51.2%). Skin biopsy (n = 29) showed IgA and complement deposition; renal biopsy (n = 2) showed ISKDC grades II–III. Treatments included NSAIDs 71.6%, corticosteroids 31.7%, and dapsone 24.4% (used for severe systemic/persistent cutaneous disease). Rash relapse 7.3% clustered with joint plus abdominal symptoms and was not observed among children with nephritis. At a mean 18.9-month follow-up, one child required long-term antihypertensives; no child progressed to end-stage renal disease. Conclusions: Pediatric HSP in this South-Indian cohort followed a largely self-limited course with favourable renal outcomes. Age ≥6 years flagged higher renal risk, supporting age-targeted urine and blood-pressure surveillance, while relapse appeared to follow a non-renal trajectory (joint/abdominal clustering). Steroid and dapsone use reflected clinical severity rather than relapse risk. Findings align with Indian series and suggest lower renal morbidity than some East-Asian reports, adding region-specific evidence to guide monitoring and counselling. Full article

Diagnosis of neuropsychiatric (NP) involvement in pediatric systemic lupus erythematosus (pNPSLE) remains challenging due to NP symptom heterogeneity, lack of specific clinical criteria and validated diagnostic biomarkers, and invasiveness of common diagnostic methods for CNS disease. Although some biomarkers have been identified in adults, their sensitivity, specificity, and clinical applicability in pNPSLE are uncertain. We performed a systematic review according to PRISMA guidelines to evaluate the current evidence on biomarkers associated with pNPSLE. We searched four databases using appropriate search terms for articles in English. After applying our selection criteria, we included 29 studies, from which we manually extracted relevant parameters, including study design, sample size, patient and disease characteristics, biomarker information, and effect sizes. The risk of bias, study quality, and quality of evidence were assessed with standard methods. Most studies had low quality, small samples, and were performed in single centers, which limited the quality of evidence of the biomarkers investigated. Biomarkers showing promising results, with high specificity and sensitivity or predictive value, included CSF neopterin, serum anti-ganglioside M1, a five-biomarker panel including neuronal proteins and anti-ribosomal P, and serum anti-neuronal. Our findings highlight the need for further replication and functional validation studies in pNPSLE. Full article

Chimeric antigen receptor (CAR) T cell immunotherapy has changed the landscape of B cell hematological malignancies’ management, while it has recently shown promising results in the treatment of refractory autoimmune rheumatic disorders (ARDs). Targeting B cell antigens such as CD19 and BCMA, CAR-T cell therapy can induce sustained remission by the elimination of autoreactive B cell populations resistant to the standard of care treatment options. Clinical data from case reports and small case series demonstrate profound clinical responses in ARDs, including systemic lupus erythematosus (SLE), systemic sclerosis (SSc), idiopathic inflammatory myopathies (IIMs), rheumatoid arthritis (RA), antiphospholipid syndrome (APS), and primary Sjögren’s syndrome (pSS). Treatment outcomes include reduced disease activity, normalization of serologic markers, improved organ function, and drug-free remission, even after B cell reconstitution. Additionally, toxicities, primarily limited to mild cytokine release syndrome (CRS), were generally manageable with supportive care. Encouraging preliminary results have led to the development of several ongoing clinical trials investigating CAR-T cell therapy across multiple ARDs and patient populations, including pediatric patients. This review summarizes the current clinical experience and provides a comprehensive overview of ongoing clinical trials exploring CAR-T cell immunotherapy for ARDs. Full article

Background: Youth with chronic rheumatologic diseases undergo medical experiences that can lead to post-traumatic stress disorder (PTSD). Understudied in pediatric rheumatology, medical PTSD can be significantly distressing and impairing. Objective: This study explored the prevalence of medical PTSD symptoms in youth with chronic inflammatory arthritis and associated factors, including pain, disease activity, mental health history, and anxiety sensitivity. Methods: A cross-sectional study of 50 youth (ages 8–18) with juvenile idiopathic arthritis (JIA) and childhood-onset systemic lupus erythematous (cSLE) was conducted at a pediatric rheumatology clinic. Participants completed self-report measures assessing post-traumatic stress symptoms (CPSS-V), pain, anxiety sensitivity (CASI), pain-related self-efficacy (CSES), adverse childhood experiences (ACEs), and fibromyalgia symptoms (PSAT). Clinical data included diagnoses, disease activity, treatment history, and demographics. Results: Forty percent had trauma symptoms in the moderate or more severe range. The 14% likely meeting criteria for probable medical PTSD were older (median 17 vs. 15 years, p = 0.005), had higher pain scores (median 4 vs. 3, p = 0.008), more ACEs (median 3 vs. 1, p = 0.005), higher anxiety sensitivity scores (median 39 vs. 29, p = 0.008), and higher JIA disease activity scores (median cJADAS-10 11.5 vs. 7.5, p = 0.032). They were also more likely to report a history of depression (71 vs. 23%, p = 0.020). No associations were found with hospitalization or injected/IV medication use. Conclusions: Medical trauma symptoms are prevalent in youth with chronic inflammatory arthritis. Probable PTSD was associated with pain and psychological distress. These findings support the need for trauma-informed care in pediatric rheumatology. Full article

Kikuchi–Fujimoto disease (KFD) is a rare condition characterized by necrotizing lymphadenitis and fever, often associated with immune dysregulation. Histologically, it features necrotic foci with abundant histiocytes and plasmacytoid dendritic cells but notably lacks neutrophils and eosinophils. Recent evidence reveals a notable prevalence among pediatric patients, who may exhibit distinct features compared to adults. We reported the case of an 11-year-old girl presenting with persistent fever, cervical adenopathy, and a malar rash, leading to a diagnosis of KFD following lymph node biopsy, which revealed non-suppurative necrosis and histiocytic infiltration. Empirical treatment with antivirals and antibiotics was ineffective, but corticosteroid therapy achieved symptom remission. A literature review identified 48 relevant studies involving 386 pediatric cases, with histopathological findings consistent with classical descriptions of KFD. Cutaneous involvement was reported in 11.14% of cases, ranging from maculopapular rashes to lupus-like eruptions. Notable complications included the development of systemic lupus erythematous, Sjögren syndrome, and rare instances of hemophagocytic syndrome or central nervous system involvement. Kikuchi–Fujimoto disease should be considered in the differential diagnosis of pediatric patients presenting with fever and lymphadenopathy, taking into account a higher frequency of cutaneous manifestations in pediatric cases. A skin biopsy may be helpful in diagnosing KFD and provide valuable information regarding the potential risk of developing systemic lupus erythematosus in the future. Full article

Background: Percutaneous ultrasound-guided renal biopsy (PRB) is a key element for diagnosis and management of several renal pathologies. We aimed to lay out the experience of our pediatric nephrology unit performing PRBs. The rationale and findings of these biopsies, safety issues and considerations of the extracted data are going to be analyzed. Methods: A retrospective study was conducted from 2008 to 2023 based on the review of the medical records of pediatric patients who underwent PRBs. In total, 216 kidney biopsies in 206 patients were performed: 115 (53.2%) during the 2008–2015 period and 101 (46.8%) during the 2016–2023 period. Results: The most frequent clinical indication for PRBs was nephritic syndrome followed by nephrotic syndrome, observed in 84 (40.8%) and 72 (34.9%) patients, respectively. The predominant diagnosis was minimal change disease (MCD) (23.3%), followed by focal segmental glomerulosclerosis (FSGS) (15%) equal to lupus nephritis (LN) (15%), and immunoglobulin A nepropathy (10.2%). Minor complications, such as subcapsular hematomas were observed in approximately 15% of patients while no therapeutic intervention was needed. Conclusions: This report is the first review of pathohistological data covering a pediatric population over a 15-year period in Greece and one of the largest in southeastern Europe, especially in the Balkan region. The main indication for a PRB was nephritic syndrome; however, MCD was the main histological diagnosis. This study emphasis the fact that PRBs constitute a safe and reliable method of diagnostic approach to kidney diseases in childhood and offers important information on therapeutic approaches as well as the prognosis of these patients. Full article

Background: Datasets on rare diseases, like pediatric acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), have small sample sizes that hinder machine learning (ML). The objective was to develop an interpretable ML framework to elucidate actionable insights from small tabular rare disease datasets. Methods: The comprehensive framework employed optimized data imputation and sampling, supervised and unsupervised learning, and literature-based discovery (LBD). The framework was deployed to assess treatment-related infection in pediatric AML and ALL. Results: An interpretable decision tree classified the risk of infection as either “high risk” or “low risk” in pediatric ALL (n = 580) and AML (n = 132) with accuracy of ∼79%. Interpretable regression models predicted the discrete number of developed infections with a mean absolute error (MAE) of 2.26 for bacterial infections and an MAE of 1.29 for viral infections. Features that best explained the development of infection were the chemotherapy regimen, cancer cells in the central nervous system at initial diagnosis, chemotherapy course, leukemia type, Down syndrome, race, and National Cancer Institute risk classification. Finally, SemNet 2.0, an open-source LBD software that links relationships from 33+ million PubMed articles, identified additional features for the prediction of infection, like glucose, iron, neutropenia-reducing growth factors, and systemic lupus erythematosus (SLE). Conclusions: The developed ML framework enabled state-of-the-art, interpretable predictions using rare disease tabular datasets. ML model performance baselines were successfully produced to predict infection in pediatric AML and ALL. Full article

A prolonged preoperatory aPTT in children is often the cause of a delay of scheduled surgeries and the repetition of multiple blood tests, with the consequent wasting of resources and significant discomfort for children and parents. The aim of this review is to analyze the situations in which an isolated prolongation of aPTT is found during preoperative evaluation in children, especially when it is due to the presence of antiphospholipid antibodies, providing the readers with the keys to interpret this situation and the possibility to correctly evaluate the hemorrhagic risk of a patient. Full article

Childhood rosacea is a lesser known, yet significant, skin condition presenting diagnostic and treatment challenges. Although often underdiagnosed due to unclear diagnostic criteria, it manifests similarly to adult rosacea, with features such as papulopustular, telangiectasia, granulomatous, idiopathic facial aseptic granuloma, and ocular rosacea. The complex pathophysiology involves genetic, immunological, and environmental factors. Distinguishing childhood rosacea from conditions like acne, steroid rosacea, sarcoidosis, and lupus vulgaris is crucial but complicated by the lack of established criteria. Treatment strategies, mainly extrapolated from adult management protocols, include topical therapies, systemic medications, and laser treatments, adapted for pediatric patients. Special attention is given to ocular rosacea, often preceding skin manifestations, necessitating multidisciplinary care. The review underscores the urgent need for clear diagnostic guidelines, increased awareness, and tailored pediatric treatment protocols to improve patient outcomes and mitigate the condition’s evolution into adulthood. Full article

We investigated the impact of synthetic nucleic acid antigens on the autoantibody profiles in patients with localized scleroderma, an autoimmune skin disease. Anti-DNA antibodies, including double-stranded DNA (dsDNA) and single-stranded DNA (ssDNA), are common among autoimmune diseases, such as systemic lupus erythematosus and localized scleroderma. Based on recent studies, we hypothesized that the sequence of nucleic acid antigens has an impact on the autoimmune reactions in localized scleroderma. To test our hypothesis, we synthesized a panel of DNA and RNA antigens and used them for autoantibody profiling of 70 children with localized scleroderma compared with the healthy controls and patients with pediatric systemic lupus erythematosus (as a disease control). Among the tested antigens, dsD4, which contains the sequence of the human oncogene BRAF, showed a particularly strong presence in localized scleroderma but not systemic lupus erythematosus. Disease activity in patients was significantly associated with dsD4 autoantibody levels. We confirmed this result in vivo by using a bleomycin-induced mouse model of localized scleroderma. When administered intraperitoneally, dsD4 promoted an active polyclonal response in the mouse model. Our study highlights sequence specificity for nucleic acid antigens in localized scleroderma that could potentially lead to developing novel early-stage diagnostic tools. Full article

Childhood-onset systemic lupus erythematosus is an inflammatory and autoimmune condition characterized by heterogeneous multisystem involvement and a chronic course with unpredictable flares. Kidney involvement, commonly called lupus nephritis, mainly presents with immune complex-mediated glomerulonephritis and is more frequent and severe in adults. Despite a considerable improvement in long-term renal prognosis, children and adolescents with lupus nephritis still experience significant morbidity and mortality. Moreover, current literature often lacks pediatric-specific data, leading clinicians to rely exclusively on adult therapeutic approaches. This review aims to describe pediatric lupus nephritis and provide an overview of the novel perspectives on the pathogenetic mechanisms, histopathological classification, therapeutic approach, novel biomarkers, and follow-up targets in children and adolescents with lupus nephritis. Full article

Numerous interrelationships are known in the literature that have the final effect of unmasking or influencing various pathologies. Among these, the present article aims to discuss the connection between systemic lupus erythematosus (SLE) and the human microbiome. The main purpose of this work is to popularize information about the impact of dysbiosis on the pathogenesis and evolutionary course of pediatric patients with SLE. Added to this is the interest in knowledge and awareness of adjunctive therapeutic means that has the ultimate goal of increasing the quality of life. The means by which this can be achieved can be briefly divided into prophylactic or curative, depending on the phase of the condition in which the patient is. We thus reiterate the importance of the clinician acquiring an overview of SLE and the human microbiome, doubled by in-depth knowledge of the physio-pathogenic interactions between the two (in part achieved through the much-studied gut-target organ axes—brain, heart, lung, skin), with the target objective being that of obtaining individualized, multimodal and efficient management for each individual patient. Full article

Background: Pediatric lupus nephritis (LN) is one of the most serious manifestations of systemic lupus erythematosus (SLE) in children, determining the outcomes of the disease. There are no standardized treatment protocols for pediatric LN, and the role of biologics has not yet been conclusively defined. Objectives: analyze the safety and efficacy of rituximab biosimilar BCD020 in pediatric patients with lupus nephritis. Methods: in a retrospective cohort study, the data from the case histories of 25 patients with LN (10 boys and 15 girls) with an onset age of 13 (9–16) years, who failed conventional non-biologic treatment or developed corticosteroid dependence/toxicity, were included. The diagnosis was made using Systemic Lupus International Collaborating Clinics (SLICC) classification criteria. Rituximab biosimilar BCD020 was prescribed in a dosage of 375 mg/m² every week (2–4 infusions) with repeated courses every 6–12 months (2–4 infusions) according to disease activity, B-cell depletion, and IgG levels. The dynamics of clinical and laboratory data, the activity of the disease by SLEDAI, and corticosteroid doses were assessed at the onset and during the rituximab trial. Results: The main patient’s characteristics were: Pre-rituximab non-biologic conventional treatment included: cyclophosphamide 15 (60%), MMF 8 (32%), azathioprine 3 (12%), hydroxychloroquine 12 (48%), and pulse therapy of methylprednisolone followed by oral methylprednisolone 25 (100%). The time before rituximab was 7.0 (3.0–24.0) months, and the whole observation period was 7.0 (0; 24) months. The initial pre-rituximab treatment slightly reduced SLEDAI levels and the proportion of patients with LN. A significant reduction of SLEDAI, the anti-dsDNA level, proteinuria, hematuria, C4 complement, ESR, and the median corticosteroid dose by 80% from the initial value, as well as the proportion of patients without corticosteroids, was observed after rituximab administration. Two deaths were observed due to catastrophic SLE with macrophage activation syndrome, accompanied by a severe infection (invasive aspergillosis, n = 2). Three patients developed serious adverse events: pneumonia (n = 2), transient agranulocytosis (n = 1) after the third rituximab infusion, and meningitis, caused by Listeria monocytosis, after the first rituximab infusion. Eight patients received antibacterial treatment for different respiratory infections without hospital admissions. Conclusions: Rituximab biosimilar BCD020 showed effectiveness in LN, whereas previous non-biologic treatment was insufficiently effective. Randomized controlled trials are required to evaluate the efficacy and safety of rituximab and evaluate the benefits when compared with conventional SLE treatment. Full article