Background
We compared serum levels of S100A12, a proinflammatory protein predominantly secreted by neutrophils, in children with newly diagnosed childhood-onset systemic lupus erythematosus (cSLE), ...systemic juvenile arthritis (sJIA), and systemic undefined recurrent fevers (SURFS) to examine its role as a diagnostic and discriminative marker of inflammation and to indirectly point out the importance of neutrophils and innate immunity in the pathogenesis of these diseases.
Materials and methods
In a cross-sectional study, the serum levels of S100A12 protein of 68 children (19 with cSLE, 18 with sJIA, 7 with SURFS, and 24 controls) were determined by enzyme-linked immunosorbent assay and compared between groups and with clinical and laboratory findings.
Results
The median serum S100A12 levels were 469 ng/mL in the cSLE group, 6103 ng/mL in the sJIA group, 480 ng/mL in the SURFS group, and 44 ng/mL in the control group. Children with cSLE, sJIA, and SURFS had significantly higher serum S100A12 levels compared to the control group (
p
< 0.0001). sJIA patients had the highest levels of S100A12 in comparison to other patients (
p
< 0.0001), while there was no significant difference between children with cSLE and SURFS.
Conclusion
Elevated serum SA100A12 levels in children with cSLE, sJIA, and SURFS may indicate intense neutrophil activation, which may play an important role in innate immunity in chronic inflammation in these diseases. Serum S100A12 levels could be used as a diagnostic marker of inflammation and be suitable for distinguishing sJIA and other disorders.
The purpose of this study was to evaluate the prevalence and severity of skin involvement in children with IgA vasculitis (IgAV) and its relationship with clinical and biochemical parameters and the ...risk of developing IgA vasculitis nephritis (IgAVN), the only cause of long-term morbidity and the main prognostic factor in IgAV patients.
This national multicenter retrospective study included 611 patients under the age of 18 years with IgAV referred to five Croatian tertiary hospitals between 2009 and 2019. Patient data were collected from a database with systematic analysis of IgAV patients in the Croatian population.
Among the 611 children, 205 (33.55%) had purpura on the lower extremities, in 207 (33.88%) the rash extended on the trunk, in 149 (24.39%) it extended to the upper extremities, in 32 (5.24%) the rash was generalized, while 15 (2.47%) had the most severe skin symptoms: bullae, ulcerations, and necroses. IgAVN developed in 130 (21.28%) and persistent IgAVN (present for >3 months) in 48 (7.86%) children. Multivariate logistic regression found that presence of ulcerations and necroses (OR 3.20 95% CI 1.03-9.91), persistent purpura (OR 2.89 95% CI 1.71-4.88), and higher age (OR 1.16 95% CI 1.09-1.23) were significant predictors of IgAVN, whereas persistent purpura (OR 20.11 95% CI 1.09-372.52), male sex (OR 3.32 95% CI 1.13-9.80), and higher age (OR 1.15 95% CI 1.00-1.30) were predictors of persistent IgAVN. Among the laboratory parameters, higher serum urea (OR 1.43 95% CI 1.03-2.00) and reduction in activated partial thromboplastin time (OR 0.83 95% CI 0.74-0.93) were shown to have a significant impact on increasing the risk of persistent IgAVN.
With increasing severity and duration of cutaneous manifestations in IgAV, the risk of developing IgAVN increases, making the prognosis worse, with a greater likelihood to need more aggressive treatment.
Biological agents are widely used in the treatment of autoimmune rheumatic disorders. We report on serious adverse events during treatment with anti-tumor necrosis factor antibody in two of our ...patients with juvenile idiopathic arthritis. One patient was treated with a biological agent due to juvenile idiopathic arthritis complicated by uveitis, developing miliary tuberculosis during treatment. After treatment with antituberculotics, she recovered completely. Her underlying disease is currently in remission. Another patient was treated for juvenile spondyloarthritis and developed an inflammatory process of the central nervous system with serious neurological deficits. He was treated with high-dose corticosteroids, followed by slowly tapering doses of corticosteroids. His neurological deficits improved, but are still present. Similar cases have been described previously, but there are no recommendations how to treat arthritis afterwards in such patients. We would like to emphasize the need of developing guidelines for further treatment of arthritis after the occurrence of serious adverse effects during treatment with biological agents. Key words: Rheumatology; Arthritis, juvenile; Tumor necrosis factor-alpha--adverse effects; Neurologic manifestations; Tuberculosis, miliary
To describe the clinical characteristics, treatment response and genetic findings in a large cohort of patients with undefined systemic autoinflammatory diseases (SAIDs).
Clinical and genetic data ...from patients with undefined SAIDs were extracted from the Eurofever registry, an international web-based registry that retrospectively collects clinical information on patients with autoinflammatory diseases.
This study included 187 patients. Seven patients had a chronic disease course, 180 patients had a recurrent disease course. The median age at disease onset was 4.3 years. Patients had a median of 12 episodes per year, with a median duration of 4 days. Most commonly reported symptoms were arthralgia (n=113), myalgia (n=86), abdominal pain (n=89), fatigue (n=111), malaise (n=104) and mucocutaneous manifestations (n=128). In 24 patients, relatives were affected as well. In 15 patients, genetic variants were found in autoinflammatory genes. Patients with genetic variants more often had affected relatives compared with patients without genetic variants (p=0.005). Most patients responded well to non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, colchicine and anakinra. Complete remission was rarely achieved with NSAIDs alone. Notable patterns were found in patients with distinctive symptoms. Patients with pericarditis (n=11) were older at disease onset (33.8 years) and had fewer episodes per year (3.0/year) compared with other patients. Patients with an intellectual impairment (n=8) were younger at disease onset (2.2 years) and often had relatives affected (28.6%).
This study describes the clinical characteristics of a large cohort of patients with undefined SAIDs. Among these, patients with pericarditis and intellectual impairment appear to comprise distinct subsets.
Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disease. It is thought that many common variant gene loci of weak effect act additively to predispose to common autoimmune ...diseases, while the contribution of rare variants remains unclear. Here we describe that rare coding variants in lupus-risk genes are present in most SLE patients and healthy controls. We demonstrate the functional consequences of rare and low frequency missense variants in the interacting proteins BLK and BANK1, which are present alone, or in combination, in a substantial proportion of lupus patients. The rare variants found in patients, but not those found exclusively in controls, impair suppression of IRF5 and type-I IFN in human B cell lines and increase pathogenic lymphocytes in lupus-prone mice. Thus, rare gene variants are common in SLE and likely contribute to genetic risk.
Abstract Objective To define the clinical, radiologic and molecular characteristics of a patient with early progressive osteoarthritis and mild spondyloepiphyseal dysplasia. Methods We describe an ...18-year-old girl with early progressive osteoarthritis and mild spondyloepiphyseal dysplasia. The index case underwent a physical examination, anthropometric measurements and radiologic and laboratory studies. DNA of the patient and her only living parent (mother) was sequenced for the type II collagen gene (COL2A1). Results Mild scoliosis was noticed in the proband at the age of 13 years. At the same age, she began to have arthralgia in almost all the joints and osteoarthritis progressed fast, necessitating a hip, knee and ankle prosthesis at the age of 18 years. She was eumorphic with no ocular or hearing abnormalities. Molecular testing of the COL2A1 gene revealed a p.Gly204Val mutation. The mutation was absent in the healthy mother. Conclusion This patient provides further proof that an early osteoarthritic phenotype can be caused by a mutation in the COL2A1 gene.
Objective
COVID‐19–associated pediatric vasculitis, other than Kawasaki disease (KD)–like vasculitis in multisystem inflammatory syndrome in children (MIS‐C), is very rare. This study sought to ...analyze the characteristics, treatment, and outcomes in patients with COVID‐19–associated pediatric vasculitis (excluding KD‐like vasculitis in MIS‐C).
Methods
The inclusion criteria were as follows: 1) age <18 years at vasculitis onset; 2) evidence of vasculitis; 3) evidence of SARS–CoV‐2 exposure; and 4) ≤3 months between SARS–CoV‐2 exposure and vasculitis onset. Patients with MIS‐C were excluded. The features of the subset of patients in our cohort who had COVID‐19–associated pediatric IgA vasculitis/Henoch Schönlein purpura (IgAV/HSP) were compared against a pre‐pandemic cohort of pediatric IgAV/HSP patients.
Results
Forty‐one patients (median age 8.3 years; male to female ratio 1.3) were included from 14 centers and 6 countries. The most frequent vasculitis subtype was IgAV/HSP (n = 30). The median duration between SARS–CoV‐2 exposure and vasculitis onset was 13 days. Involvement of the skin (92.7%) and of the gastrointestinal system (61%) were the most common manifestations of vasculitis. Most patients (68.3%) received glucocorticoids, and 14.6% also received additional immunosuppressive drugs. Remission was achieved in all patients. All of the patients with IgAV/HSP in our cohort had skin manifestations, while 18 (60%) had gastrointestinal involvement and 13 (43.3%) had renal involvement. When we compared the features of this subset of 30 patients to those of a pre‐pandemic pediatric IgAV/HSP cohort (n = 159), the clinical characteristics of fever and renal involvement were more common in our COVID‐19–associated pediatric IgAV/HSP cohort (fever, 30% versus 5%, respectively P < 0.001; renal involvement, 43.3% versus 17.6%, respectively P = 0.002). Recovery without treatment and complete recovery were each less frequent among our COVID‐19‐associated pediatric IgAV/HSP patients compared to the pre‐pandemic pediatric IgAV/HSP cohort (recovery without treatment, 10% versus 39%, respectively P = 0.002; complete recovery, 86.7% versus 99.4%, respectively P = 0.002).
Conclusion
This is the largest cohort of children with COVID‐19–associated vasculitis (excluding MIS‐C) studied to date. Our findings suggest that children with COVID‐19–associated IgAV/HSP experience a more severe disease course compared to pediatric IgAV/HSP patients before the pandemic.
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