Pediatric Rheumatology最新文献

Introduction: Mycophenolate Mofetil (MMF) has become one of the cornerstone treatments of lupus nephritis (LN). It is converted into mycophenolic acid (MPA), an active metabolite, that displays high inter- and intra-individual pharmacokinetic variability. However, the routine monitoring of MPA trough level is still debatable.

Objectives: The present study aims to evaluate the relationship between MPA trough levels and both clinical outcomes and drug-related adverse effects during the maintenance phase of LN in Egyptian patients.

Methods: We included thirty-five adults and twenty-nine children with biopsy-proven class III and IV LN, who had been maintained on steroid and MMF as maintenance therapy for more than six months. Clinical and laboratory markers of lupus activity as well as MMF adverse events were reported. MPA trough levels were measured by High-Performance Liquid Chromatography (HPLC).

Results: There was a significant association between low MPA trough levels and both flares and SLEDAI scores in the adult group (P = 0.027 and 0.019, respectively). Moreover, high MPA trough levels were associated with higher risk of gastritis in the same age group (P = 0.007). There was no significant association with any of the parameters studied in the pediatric group. Gastritis was the most frequent side effect in both age groups.

Conclusion: MPA trough levels correlated with disease activity and gastritis in adult LN patients, and this may help to optimize MMF dosage in these patients. However, MPA concentration-effect relationships were not observed in pediatric patients.

Background: Cyclophosphamide (CYC) is an inactive alkylating agent that transforms the alkyl radicals into other molecules and is used in combination with systemic corticosteroids in the treatment of many childhood rheumatic diseases, such as systemic lupus erythematosus (SLE), and ANCA-associated vasculitis (AAV). In recent years, rituximab (RTX), a B-cell-targeting anti-CD20 monoclonal antibody, has emerged as a new alternative treatment modality over CYC for induction therapy of childhood-onset rheumatic diseases. Clinicians adopt different practices for using CYC particularly in relation to indications, posology, pre-treatment laboratory work-up, post-treatment follow-up, and screening pre- and post-treatment vaccination status. This study aimed to evaluate the principles and approaches of administering CYC therapy in pediatric rheumatology and pediatric nephrology practices and to compare the clinician preferences for CYC and RTX in induction therapy of childhood-onset rheumatic diseases.

Methods: This study includes a web-based questionnaire executed on 87 participants (56 pediatric rheumatologists (PRs) and 31 pediatric nephrologists (PNs)). Both pediatric subspecialties evaluated and compared the most common indications for CYC treatment, pre-treatment consent protocols, pre-and post-treatment laboratory tests, dosing strategies, and side effects.

Results: Childhood-onset SLE (95%) and AAV (69%) were the most common diseases for which CYC treatment is used. All clinicians, except 2 PNs prescribed CYC via intravenous route. 61% of the PRs and 71% of PNs reported using a monthly dose of 500 mg/m² CYC for 6 months in accordance with the National Institutes of Health (NIH) protocol. All clinicians conducted pre-CYC treatment assessments of complete blood count and kidney function tests. Hepatitis B (82%), chickenpox (76%), and mumps-measles-rubella (72%) were the most frequently assessed vaccines. Adverse effects associated with CYC include cytopenia (86%), nausea (52%), liver toxicity (20%), hair loss (31%), hemorrhagic cystitis (37%), allergic reactions (16%), dyspnea (5%), and infertility (2%). 9 clinicians stated that they performed gonad-sparing interventions before CYC, which clarifies why CYC was more commonly preferred in the induction therapy of SLE and AAV over RTX by both PRs and PNs.

Conclusions: Clinicians still tend to choose CYC over RTX in induction therapy of SLE and AAV and mostly prefer the high-dose CYC treatment regimen suggested by the NIH.

Background: Non-infectious paediatric granulomatous uveitis (PGU) is a rare disease that is idiopathic in more than half of affected children. The diagnosis of definite ocular sarcoidosis (OS) must be supported by the presence of non-caseating granulomas detected in biopsy, and is therefore a challenge in children with PGU. This study investigated the utility of minor salivary gland biopsy (MSGB) in the diagnosis of definite OS in PGU.

Methods: Twenty-six consecutive children with PGU diagnosed between 2018 and 2023 and with a systematically performed MSGB within 3 months of the diagnosis were enrolled.

Results: The median age at PGU diagnosis was 11.6 (4.2-16.5) years, and 54% of the children were boys. PGU consisted mainly of bilateral (92%) pan-uveitis (96%). MSGB detected non-caseating granulomas (MSGB+) in 12/26 (46%) children. In all, 13 of the 26 (50%) children were diagnosed with definite OS, and 8 (31%) had idiopathic uveitis. MSGB had a sensitivity of 92%, and a NPV of 93% in the diagnosis of definite OS in children with PGU. Compared to MSGB- children, those who were MSGB + were more frequently older than 10 years of age at diagnosis (p = 0.02), had a higher rate of general signs (p = 0.003), extra-ocular organ involvement (p = 0.005) and polyclonal hypergammaglobulinaemia (p = 0.03). The most frequent extra-ocular organ involvements at OS diagnosis were renal (46%) and thoracic (46%). First-line therapy was systemic corticosteroids in 88% of the children. During a median follow-up time of 3.1 (0.6-6.3) years after PGU diagnosis, 88% of the children needed methotrexate and/or anti-tumour necrosis factor-alpha therapy to achieve inactive uveitis.

Conclusions: MSGB is useful to improve the diagnosis of OS and to reduce the incidence of uveitis considered idiopathic in PGU. MSGB could be considered in PGU patients, particularly those > 10 years of age with general signs and/or hypergammaglobulinaemia.

Background: The clinical remission rate of articular juvenile idiopathic arthritis (JIA) differs according to the disease categories. At present, there is no consensus regarding drug withdrawal after remission is achieved.

Objectives: To clarify the clinical remission rate and drug withdrawal status of patients with juvenile idiopathic arthritis (JIA).

Methods: We conducted a retrospective observational study in patients who developed articular JIA by 2017 and were followed up (2013-2022). The Wallace criteria were used as remission criteria.

Results: Forty-nine patients were included, i.e., 16 (33%) with polyarticular JIA (PJIA) and 33 (67%) with oligoarticular JIA (OJIA). Rheumatoid factor-positive (RF +) PJIA had significantly higher biological disease-modifying antirheumatic drug (bDMARD) introduction rates (86%, p < 0.01). The rate of clinical remission off medication was significantly higher in OJIA (67%). Numerous cases of RF + PJIA (50%), RF-negative (RF -) PJIA (25%), and OJIA (30%) flared within 2 years after conventional synthetic disease-modifying antirheumatic drug withdrawal. Patients with RF - PJIA and OJIA (two cases each) discontinued bDMARDs. Both RF - PJIA cases (100%) and half of OJIA cases (50%) flared within 2 years after bDMARD withdrawal. In one case of OJIA, remission was maintained after withdrawal of all drugs.

Conclusions: OJIA had the highest rate of clinical remission off medication (67%) versus others. In OJIA, it was possible to discontinue all drugs in some patients with OJIA receiving bDMARDs. In PJIA requiring bDMARDs, withdrawal of bDMARDs was difficult all two cases.

Background: This study aimed to describe the characteristics and outcomes of children and adolescents with autoimmune inflammatory rheumatic diseases (AIIRD) who were admitted to the pediatric intensive care unit (PICU). The accuracy of the Pediatric Risk of Mortality (PRISM) III and Pediatric Index of Mortality (PIM) 3 scores to predict the mortality were investigated.

Methods: This was a retrospective cohort study. Children and adolescents with AIIRD aged ≤ 18 years who were admitted to the PICU at the largest university-based referral center in Thailand during July 2011 to June 2021 were included.

Results: There were 122 PICU admissions from 74 patients; mean age of 12.0 ± 4.3 years, 74.3% female. Majority of AIIRD were systemic lupus erythematosus (SLE) (83.8%), followed by systemic juvenile idiopathic arthritis (5.4%), juvenile dermatomyositis (JDM) (2.7%) and microscopic polyangiitis (2.7%). The main cause of admission was combined infection and disease flare (29.5%). Pneumonia was the main site of infection. Acinetobacter baumanii was the most common causative agent. Macrophage activation syndrome occurred in 8 (6.5%) admissions. The mortality rate of PICU admissions was 14.8% from 18 deaths; 17 with SLE and 1 with JDM. Mechanical ventilation (aOR 24.07, 95%CI:1.33-434.91, P= 0.031), pneumothorax (aOR 24.08, 95%CI:1.76-328.86, P = 0.017 and thrombocytopenia (aOR 8.34, 95%CI:1.31-53.73, P = 0.025) were associated with mortality. The risk of mortality rate as predicted by the PRISM III score increased with a score ≥ 9. For the PIM 3 score, the risk of mortality increased if the score ≥ 3. The area under the ROC curve for the PRISM III and PIM 3 scores was 0.741 (95%CI: 0.633-0.849), P = 0.001 and 0.804 (95%CI: 0.685-0.924), P < 0.001, respectively. The model calibration using the Hosmer-Lemeshow goodness of fit test demonstrated a chi-square of 4.335, P = 0.826 for PRISM III and 7.987, P = 0.435 for PIM 3.

Conclusion: SLE was the main AIIRD that required admission to the PICU. Mechanical ventilation, pneumothorax and thrombocytopenia were associated with mortality in pediatric patients with AIIRD. The PRISM III and PIM 3 scores demonstrated good calibration, while the PIM 3 score provided better discrimination ability in the prediction of mortality for pediatric AIIRD.

Background: Research and management of juvenile idiopathic arthritis (JIA) are challenging due to its heterogeneous nature, chronicity, and unpredictable, multidimensional long-term outcomes.

Main body: Long-term studies have consistently shown that a majority of children with JIA reach adulthood with ongoing disease activity, on medication, or with recurrent flares. The heterogeneity is evident both between and within the present JIA categories based on The International League of Associations for Rheumatology (ILAR) JIA classification system. Several baseline predicting factors are known, but prediction modelling is only in the initial phase, and more models need to be tested in independent cohorts and possibly also supplemented with new biomarkers. Many have criticized the ILAR classification system, but new or updated classification systems have not yet been validated and proved their superiority. The lack of prediction possibilities for long-term outcomes and the limited alignment between JIA classification categories and adult rheumatic conditions are challenges for research, may limit the accessibility to treatment, and hamper a smooth transition to adult care.

Conclusion: We need more prospective, long-term studies based on unselected JIA cohorts with disease onset in the biologic era that can aid decision-making for individualized early treatment, suggest intervention studies, and ensure our patients the best possible transition to adulthood and the best likelihood of optimal health and quality of life.

Background: In 2018, intravenous abatacept was approved for the treatment of refractory polyarticular-course juvenile idiopathic arthritis (JIA) in Japan. However, reports describing the effectiveness and safety of abatacept in clinical practice in Japanese patients with refractory polyarticular-course JIA are limited. Therefore, this postmarketing surveillance study aimed to evaluate the real-world safety and effectiveness of abatacept in Japanese pediatric patients with refractory polyarticular-course JIA.

Methods: This study evaluated patients included in an all-case postmarketing surveillance study between February 2018 and August 2020 who were treated with intravenous abatacept. Data on the safety and effectiveness of the registered patients were collected during the 52-week follow-up period. Disease activities were evaluated using Juvenile Arthritis Disease Activity Score 27 (JADAS-27). The effect of abatacept on a child's growth was assessed using the height and weight standard deviation scores (SDS).

Results: A total of 82 patients were registered in this study, of whom 14.6% and 85.4% were males and females, respectively. The proportion of patients with oligoarticular, rheumatoid factor (RF)-negative polyarticular, and RF-positive polyarticular JIA was 12.2, 28.0, and 54.9%, respectively. The incidence of adverse drug reactions (ADRs) and serious ADRs was 22.0% and 2.4%, respectively. During the study period, 64.7% of the patients achieved JADAS-27 low disease activity or less. A significant difference in JADAS-27 scores in patients with RF-positive polyarticular JIA was observed between baseline and 24 or 52 weeks after abatacept administration. The height and weight SDS tended to improve during abatacept treatment.

Conclusions: Abatacept is effective in polyarticular-course JIA, particularly in RF-positive patients, and in restoring a child's growth. Additionally, the incidence of ADRs is similar to that observed in the clinical trial. The results of the study suggest that abatacept is a useful therapeutic option for treating refractory polyarticular-course JIA in real-world settings in Japan.

Background: Fasciitis-panniculitis syndrome (FPS) typically presents with swelling and skin hardening. Its histopathological characteristics include inflammatory cell infiltration and fibrous thickening of the subcutaneous tissue and fascia. Panniculitides in children are rare and only a small number of juvenile FPS cases have been reported. We encountered a case of a 10-year-old boy in which autoantibodies reactive to adipocyte pericellular fibers were detected in relapsing FPS.

Case presentation: The patient developed a high fever and skin swelling with pain and erythema on the right side of his body following an abrasion injury on his right wrist at the age of 5 years, and was suspected of having streptococcal toxic shock-like syndrome, for which he received antimicrobials, immunoglobulin therapy, debridement, and plasma exchange. The same manifestations with similar magnetic resonance imaging (MRI) findings of high signal on short tau inversion recovery showing the spread of inflammation in the fat tissue and fascia was observed twice at the age of 6 years. Serological analyses for conventional autoantibodies, bone marrow aspiration, and whole-exome sequencing examination were non-remarkable. Prednisolone was effective in ameliorating the above putative autoinflammatory syndrome. The patient was admitted at the age of 10 years with similar clinical and MRI findings indicative of recurrence of the same disease. En bloc biopsy from the skin to the fascia showed thickening of collagen fibers, infiltration of inflammatory cells composed mainly of neutrophils and lymphocytes, and necrotizing vasculitis in the fat tissue and fascia. Immunohistochemical staining of the en bloc biopsy sections indicated infiltration of T lymphocytes and macrophages in the perivascular connective tissue and fibrinoid necrosis, supporting the diagnosis of FPS. Induction therapy with prednisolone resulted in a remission. IgG purified from the patient's serum reacted with pericellular basement membranes in the subcutaneous fat tissue by immunohistochemistry. The patient is currently taking famotidine to prevent relapses and is making good progress in his recovery.

Conclusions: Although pathogenic autoantibodies have not been described in FPS, our results suggest that fat-tissue-reactive autoantibodies may be involved in the pathogenesis of FPS.