Background: Takayasu’s arteritis (TA) is a systemic vasculitis that primarily affects the aorta and major arteries. Despite aggressive treatment with glucocorticoids (GCs) and non-biological disease-modifying antirheumatic drugs (nbDMARDs), about 30% of patients experience resistance to therapy or relapse. This study aimed to identify risk factors associated with refractory and relapse TA in pediatric patients. Methods: A retrospective, open-label, case–control study was conducted with 56 pediatric patients with TA diagnosed between February 2011 and October 2022. Fourteen patients were excluded due to insufficient data in their medical records, leaving 42 for further analysis. The patients were divided into two groups: Group 1 (18 patients) with no evidence of relapse and Group 2 (24 patients) with relapse despite first-line treatment at the end of the follow-up period. Clinical, laboratory, and instrumental data were collected and analyzed using R v4.2 and Python v3.10. Results: The median time to relapse was 18 [IQR: 13; -] months according to the Kaplan–Meier curve. Patients with ITAS.A with a diagnosis of TA ≥ 12 had a higher probability of relapse, according to the log-rank criterion (p = 0.006). Symptoms of critical ischemia, such as limb claudication, were more common in Group 2 at diagnosis (p = 0.047), and a trend toward a longer diagnostic delay was observed (p = 0.067). Conclusions: Pediatric patients with an initial ITAS.A score above 12 have a higher risk of relapse when treated with a combination of GCs and nbDMARDs as first-line treatment. Further research is needed to identify high-risk patients more accurately and optimize therapeutic strategies.

The prognosis of Takayasu arteritis (TA) depends on timely and adequate therapy, but in about half of patients, the disease is refractory to standard therapy or recurs against the background of a decrease in the dose of glucocorticoids (GCs). The use of biological disease-modifying antirheumatic drugs (bDMARDs) in the treatment of TA looks promising, however, the experience of their use in TA in children is presented by isolated observations. Objective of the study: to evaluate the efficacy and safety of tocilizumab (TCZ) in the treatment of refractory and recurrent forms of TA in children. Materials and methods of research: the study retrospectively included 9 children who were prescribed TCZ when standard therapy was ineffective. Before starting TCZ therapy, all patients were diagnosed with an active form of the disease. The median duration of TCZ therapy was 24 months. Results: against the background of TCZ therapy, the median ESR decreased from 22 to 5 mm/h (p value <0,01), the level of C-reactive protein from 6 to 0 mg/l (p value <0,025). All patients achieved remission. No relapses were observed. The median GCs dose decreased from 0,377 to 0,15 mg/kg/day for prednisolone, 2 patients with GCs were completely canceled. The ITAS.A activity index decreased from 3–12 (median 7) to 0 in 7 and to 1 in 2 more patients. The drug was well tolerated. Adverse reactions included one case of pityriasis versicolor and one case of postoperative phlegmon of the neck and subclavian region on the right. Conclusion: TCZ has shown efficacy and safety for the induction and maintenance of remission in children with TA. The presented results of the study indicate the prospects for further study of the use of TCZ for TA in pediatric practice.

A retrospective study contains clinical and immunological characteristics of juvenile systemic scleroderma manifestations in 78 children according to data from a single rheumatology center. The average age of onset was 8.3 years, girls outnumbered boys, the form with diffuse skin involvement was more common, and among visceral involvement, the gastrointestinal tract and lungs were the most commonly affected; antinuclear factor was detected in 81% of children, anticentromere antibodies in 31%, and antitopoisomerase antibodies in 8.5%. The 5-year survival rate of patients in the main group was 100%, and the probability of survival at 74 months was 70%. Our data largely coincide with the studies of other authors. No obvious natural pathomorphosis of juvenile systemic scleroderma has been established in the 2000s compared to 1960–1980; therapeutic pathomorphosis of the disease is likely to occur. Key words: pathomorphosis, age of onset, visceral involvement, autoantibodies, survival

IgG4-related disease (IgG4-RD) is a rare fibro-inflammatory condition with scarce data on its clinical spectrum and management in the pediatric population.We present a single-center observational study of six children with clinically and morphologically confirmed IgG4-RD. We analyzed the age of onset, time to diagnosis, and comprehensive clinical, imaging, laboratory, and histopathological findings at presentation and during follow-up (range: 3 months to 7 years). The 2020 revised comprehensive diagnostic criteria for IgG4-RD were used. The diagnosis was based on a biopsy of orbital tissue with detection of signs of fibrosis, obliterating phlebitis, and subsequent immunohistochemical testing for the presence of IgG4. The disease manifested itself in 4 patients with orbital pseudotumor, in 1 patient with diabetes insipidus, in 1 patient with fever, signs of high inflammatory and immunological activity. The diagnostic delay ranged from 3 to 12 months. Treatment regimens included glucocorticoids combined with cytostatic agents (n=3), cytostatic monotherapy (n=2), and initial glucocorticoid monotherapy (n=1). Three patients achieved a good clinical and radiological response without disease progression. One patient experienced multiple relapses while on topical steroid therapy, which were successfully controlled after switching to systemic cytostatic therapy. Two children achieved incomplete remission. They were advised to continue rituximab therapy. This case series underscores the diagnostic challenge and phenotypic diversity of pediatric IgG4-RD. The most common clinical manifestation in our patients was orbital involvement. Prednisone and cytostatic agents were effective for inducing and maintaining remission. Our findings contribute to the evolving understanding of this rare condition in childhood.

The purposes of the study were as follows: to perform a comparative analysis of demographic and clinical data in children with Takayasu's arteritis (TA) who underwent surgical treatment of the underlying disease, to determine approaches to surgical interventions and to evaluate its outcomes. Materials and methods of the research: 51 children (boys:girls ratio 1:4.7) aged from 8 months till 17 years old (11 [9; 14] years as median) with a reliable TA diagnosis were observed from February, 2001 till January, 2022. The median age of the TA debut was 11 [9; 14] years. The single-center (I.M. Sechenov University Children's Clinical Hospital with the N.F. Filatov Clinical Institute of Children's Health of the I.M. Sechenov First Moscow State Medical University located in Moscow, Russia) case-control study included 40 patients: Group 1 (n=10) consisted of patients who underwent the surgical intervention, and Group 2 (n=30) consisted of children who have not been indicated for surgical treatment at the end of the follow-up. Patients did not differ statistically significantly in terms of gender (p=1.0), age (p=0.729), disease duration (p=0.542) and duration of follow-up at the hospital (p=0.708). The data that the authors have evaluated included gender, age, duration of the disease, including before the diagnosis was verified, the clinical picture at the onset and the type of TA, data from laboratory and instrumental studies before diagnosis and during follow-up, treatment options, assessment of the TA activity according to the ITAS-A score. Results: the median duration of TA before diagnosis was statistically significantly higher in the Group 1 (p=0.013) and amounted to 23.5 [13; 36] months (9.5 [2; 20] months in the Group 2). The median systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the onset on the TA diagnosis in patients from the Group 1 (165.0 and 110.0 mm Hg, respectively) were statistically significantly higher (p<0.001) than in the Group 2 (116.5 and 65.0 mm Hg, respectively). The arterial hypertension (p<0.001) and headaches (p=0.006) were statically significantly more often in patients from the Group 1, while in patients from the Group 2 the general inflammatory reactions were more typical, such as episodes of fever (80%, p=0.003) and weight loss (33.3%). The median amount of vessels involved in the pathological process at the onset of TA in the Group 1 patients (6.5; [4; 8]) was also statistically significantly higher (p=0.043) than in the Group 2 patients (4; [3 ; 6]). In patients of the 1st Group, the abdominal aorta (90%, p=0.006), descending thoracic aorta (70%, p=0.007) and renal arteries (70%, p<0.001) were affected statistically significantly more often. The Group 1 patients had 14 surgical interventions in total. The median SBP decreased after the 1st surgical intervention from 170 [160; 172] to 130 [105; 145] mm Hg, and the median DBP dropped from 110 [100; 114] to 70 [65; 85] mm Hg. The early postoperative period proceeded favorably after 13 out of total of 14 surgical interventions: in a single patient the neck phlegmon was developed on the same side a week after subclavian-carotid prosthesis on the right side. During the observation period in the hospital there were no deaths recorded in the Group 2. In a single female patient from Group 1 the aneurysm of the anastomosis of the infrarenal aorta ruptured on the 42nd month after the surgical intervention, which has led to her death. Conclusion: the duration of TA before the start of therapy, the extensive damage to the arterial bed, including involvement of the abdominal aorta and renal arteries, the absence or mild severity of the general inflammatory syndrome and arterial hypertension at the onset of the disease increase the likelihood of surgical treatment. The surgical intervention for TA should be carried out against the background of immunosuppressive therapy, according to the strict indications and considering the risk/benefit ratio for each patient.

Juvenile scleroderma (JS), comprising localized (JLSd) and systemic (JSSc) forms, is a rare autoimmune disorder. This study investigated associations of polymorphisms in extracellular matrix (MMP1, MMP9) and vascular homeostasis (NOS3) genes with JS risk and immunological phenotypes. A case–control study involved 215JS patients (194 JLSd, 21 JSSc) and 72 controls. SNPs (MMP1 rs1799750, MMP9 rs3918242, NOS3 rs1799983) were genotyped using real-time PCR followed by minisequencing and mass spectrometric analysis of reaction products. Associations with disease risk, subtypes, and immunological markers were analyzed statistically. The MMP9 (rs3918242) CT genotype was significantly associated with JLSd (OR = 2.23, 95% CI: 1.14–4.37, p = 0.022), showing a trend in linear facial forms. The NOS3 (rs1799983) GG genotype demonstrated a trend toward association with JSSc (OR = 2.61, 95% CI: 0.92–7.37, p = 0.065). No significant associations were found for rs1799750 MMP1 and risk of disease development. The MMP9 risk genotype did not correlate with scleroderma-specific autoantibodies, while the NOS3 GG genotype was associated with lower serum levels of anti-collagen IV antibodies (p = 0.039). Genetic associations differ for JS subtypes: MMP9 with JLSd and NOS3 with JSSc. Children with CT polymorphism MMP9 (rs3918242) and with NOS3 (rs1799983) GG genotype were found to be genetically predisposed for the development of JS.