IgA vasculitis (IgAV) is the most common childhood vasculitis. The main cause of morbidity and mortality in children with IgAV is nephritis (IgAVN), but the risk of its development, severity, and ...chronicity remain unclear. Erythrocyte glutathione S-transferase (e-GST) activity has been previously detected as a sensitive marker of kidney function impairment in several diseases. We spectrophotometrically assessed and correlated e-GST activity between 55 IgAV patients without nephritis (IgAVwN), 42 IgAVN patients, and 52 healthy controls. At disease onset, e-GST activity was significantly higher in IgAVN patients (median (interquartile range)) (5.7 U/gHb (4.4-7.5)) than in IgAVwN patients (3.1 U/gHb (2.2-4.2);
< 0.001), and controls (3.1 U/gHb (1.9-4.2);
< 0.001). Therewithal, there were no differences between the IgAVwN patients and controls (
= 0.837). e-GST activity was also significantly higher in the IgAVN patients than in the IgAVwN patients after 3 months (5.0 U/gHb (4.2-6.2) vs. 3.3 U/gHb (2.3-4.1);
< 0.001) and 6 months (4.2 U/gHb (3.2-5.8) vs. 3.3 U/gHb (2.1-4.1);
< 0.001) since the disease onset. Consistent correlations between e-GST activity and serum creatinine, estimated glomerular filtration rate (eGFR), and proteinuria levels were not detected. In conclusion, increased e-GST activity can serve as a subtle indicator of kidney function impairment in children with IgAV.
Endothelial cell injury is a hallmark of IgA vasculitis (IgAV), possibly associated with various factors, including oxidative stress. Certain single nucleotide polymorphisms (SNPs) of glutathione ...S-transferases (GST) genes have been shown to increase susceptibility to oxidative stress. The objective of our study was to evaluate the gene polymorphisms of GSTM1, GSTT1, GSTP1, and GSTA1 in patients with IgAV. DNA was extracted from the blood of 124 children with IgAV and 168 age-matched healthy controls. A higher frequency of the GSTM1 null genotype was observed in patients with gastrointestinal (GI) system involvement compared to those without GI system involvement (51.5% vs. 28.6%, p = 0.011). Additionally, the GSTM1 null genotype was less prevalent (30.8% vs. 69.2%, p = 0.032), while the GSTP1 Val/Val genotype was significantly more prevalent in patients who developed urogenital complications (scrotal swelling) during the course of the disease (60% vs. 40%, p = 0.039). This study is the first to suggest an association between GSTM1 and GSTP1 polymorphisms and various phenotypes observed during the clinical course of IgAV in the pediatric population. However, it was performed on a national and likely single ethnic cohort, too small for definitive conclusions, so larger studies are needed to confirm this association.
We investigated the polarisation of CD68+ macrophages and perforin and granulysin distributions in kidney lymphocyte subsets of children with IgA vasculitis nephritis (IgAVN). Pro-inflammatory ...macrophage (M)1 (CD68/iNOS) or regulatory M2 (CD68/arginase-1) polarisation; spatial arrangement of macrophages and lymphocytes; and perforin and granulysin distribution in CD3+ and CD56+ cells were visulaised using double-labelled immunofluorescence. In contrast to the tubules, iNOS+ cells were more abundant than the arginase-1+ cells in the glomeruli. CD68+ macrophage numbers fluctuated in the glomeruli and were mostly labelled with iNOS. CD68+/arginase-1+ cells are abundant in the tubules. CD56+ cells, enclosed by CD68+ cells, were more abundant in the glomeruli than in the tubuli, and co-expressed NKp44. The glomerular and interstitial/intratubular CD56+ cells express perforin and granulysin, respectively. The CD3+ cells did not express perforin, while a minority expressed granulysin. Innate immunity, represented by M1 macrophages and CD56+ cells rich in perforin and granulysin, plays a pivotal role in the acute phase of IgAVN.
Studies concerning the genetic background of IgA vasculitis (IgAV), a small-vessel vasculitis occurring predominantly in childhood, have confirmed that the HLA-DRB1 gene showed a strong association ...with disease susceptibility. The objective was to investigate human leukocyte antigen (HLA) polymorphisms among Croatian patients with IgAV and their influence on disease susceptibility and clinical heterogeneity. Thus, 130 children with IgAV and 202 unrelated healthy individuals were enrolled in the study. Genomic DNA was extracted from whole peripheral blood, and HLA-A, -B, -DRB1 and -DQB1 gene polymorphism analysis was performed. HLA-A*03 (21.4% vs. 12.38%,
= 0.0092), HLA-B*37 (2.9% vs. 0.2%,
= 0.0054) and HLA-DRB1*12 (3.1% vs. 0.7%,
= 0.0216) alleles were significantly more frequent in IgAV patients than in controls. High-resolution typing revealed significantly higher frequency of HLA-DRB1*10:01 and -DRB1*11:03 among IgAV patients with gastrointestinal manifestations of the disease in comparison to controls (
= 0.0021 and
= 0.0301, respectively), while HLA-DRB1*14:01P occurred significantly more often in the group of patients who developed nephritis during the course of the disease (17.5% vs. 4.5%,
= 0.0006). Our results demonstrated that there is an association of HLA-A*03, HLA-B*37 and HLA-DRB1*12 alleles with susceptibility to IgAV in the examined Croatian pediatric population. Studies which aim to determine the HLA profile may contribute to the elucidation of the genetic background of autoimmune diseases, including IgAV.
Inflammatory rheumatic diseases (IRD) and autoimmune liver diseases (AILD) share many similarities regarding epidemiology, genetics, immunology and therapeutic regimens, so it is not surprising that ...approximately 20% of patients with AILD are diagnosed with an IRD as well. Clinical features and biochemical hallmarks of IRD and AILD often intertwine and cross diagnostic criteria. Therefore, the real distinction of underlying disorders in a patient with these comorbidities may be challenging. The present report is the first report of simultaneously developed juvenile dermatomyositis (JDM) and autoimmune sclerosing cholangitis (ASC) with both entities fulfilling the latest guidelines for a definite diagnosis. Both of these diagnoses are difficult to definitely establish since ASC has a similar serologic profile as autoimmune hepatitis and liver histological analysis is frequently non-specific, whereas clinically amyopathic JDM diagnosis depends mostly on classical dermatological symptoms, while the rest of the diagnostic criteria, including the necessity for skin or muscle biopsy and the presence of myositis specific antibodies, are still not uniformed. In spite of these challenges, our patient clearly met European League Against Rheumatism/American College of Rheumatology classification criteria for CAJDM and The European Society for Pediatric Gastroenterology, Hepatology and Nutrition diagnostic criteria for ASC. Since elevated serum transaminases, the presence of serum antinuclear antibodies and hypergammaglobulinemia could be explained as a part of both JDM and ASC, the underlying pathophysiology remains debatable. Intriguingly, JDM and ASC share genetic predisposition including human leukocyte antigen allele DRB1*0301 and tumor necrosis factor α 308A allele. Furthermore, both humoral and cellular components of the adaptive immune system contribute to the pathogenesis of JDM and ASC. Moreover, recent findings indicate that the loss of the CD28 expression on T-cells plays a significant role in their pathogenesis along with the Th17 immune pathway. Despite these common features that suggest shared autoimmunity, AILD and autoimmune myositis are traditionally studied and managed independently. The lack of therapies that target the underlying cause results in a high rate of adverse events due to unspecific immunosuppressive therapy. Shared autoimmunity is an ideal area to develop new, targeted immunotherapy that would hopefully be beneficial for more than one disease.
Transfusion-related acute lung injury is a rare but potentially fatal complication, which may appear during or post-transfusion of blood products. Patients with macrophage activation syndrome, a ...serious life-threatening complication associated with systemic juvenile idiopathic arthritis, often require transfusion or administration of blood products for correction of cytopenia, coagulopathy and hypofibrinogenemia.
A 6-year-old girl with a past medical history of systemic juvenile idiopathic arthritis had the first relapse of the disease during which she developed macrophage activation syndrome. During this life-threatening complication, she received a second dose of whole blood derived filtered and irradiated platelets from a single male donor due to profound thrombocytopenia. Approximately one hour post-infusion, the patient developed progressive dyspnea, hypoxemia and bilateral pulmonary edema. She was promptly intubated and placed on mechanical ventilation for 40 h. Clinical, laboratory and radiological findings, as well as the success of supportive ventilation therapy were highly suggestive of transfusion-related acute lung injury, a life-threatening complication that occurs within six hours of blood component transfusion. Blood immunology showed no presence of anti-human neutrophil antigen and anti-leukocyte antigen class I and class II antibodies in the donor's or patient's plasma.
To the best of our knowledge, we report the first case of a child with systemic juvenile idiopathic arthritis complicated with macrophage activation syndrome who developed type II transfusion-related acute lung injury following platelet transfusion. It is important to consider transfusion-related acute lung injury in transfusion settings in these children and apply critical and restrictive approach for platelet transfusion.
Background:
We analysed clinical and biochemical parameters in predicting severe gastrointestinal (GI) manifestations in childhood IgA vasculitis (IgAV) and the risk of developing renal ...complications.
Methods:
A national multicentric retrospective study included children with IgAV reviewed in five Croatian University Centres for paediatric rheumatology in the period 2009–2019.
Results:
Out of 611 children, 281 (45.99%) had at least one GI manifestation, while 42 of 281 (14.95%) had the most severe GI manifestations. Using logistic regression several clinical risk factors for the severe GI manifestations were identified: generalized rash odds ratio (OR) 2.09 (95% confidence interval (CI) 1.09–4.01), rash extended on upper extremities (OR 2.77 (95% CI 1.43–5.34) or face OR 3.69 (95% CI 1.42–9.43) and nephritis (IgAVN) OR 4.35 (95% CI 2.23–8.50), as well as lower values of prothrombin time (OR 0.05 (95% CI 0.01–0.62), fibrinogen OR 0.45 (95% CI 0.29–0.70) and IgM OR 0.10 (95% I 0.03–0.35) among the laboratory parameters. Patients with severe GI involvement more frequently had relapse of the disease OR 2.14 (CI 1.04–4.39) and recurrent rash OR 2.61 (CI 1.27–5.38). Multivariate logistic regression found that the combination of age, GI symptoms at the beginning of IgAV and severity of GI symptoms were statistically significant predictors of IgAVN. Patients in whom IgAV has started with GI symptoms OR 6.60 (95% CI 1.67–26.06), older children OR 1.22 (95% CI 1.02–1.46) with severe GI form of IgAV (OR 5.90 (95% CI 1.12–31.15) were particularly high-risk for developing IgAVN.
Conclusion:
We detected a group of older children with the onset of GI symptoms before other IgAV symptoms and severe GI form of the IgAV, with significantly higher risk for acute and chronic complications of IgAV.
Introduction/objectives
Magnetic resonance imaging (MRI) is recommended for evaluation of changes in juvenile spondyloarthropathies (JSpA). To our knowledge, there is no previous prospective study ...analysing early changes on axial MRI. The objective is to investigate incidence of reparable changes on axial MRI in patients with established JSpA, lasting for less than 6 months.
Materials and methods
The pilot study included 27 patients with confirmed diagnosis of JSpA examined within 2 years. Prior to imaging, basic demographic and laboratory data and HLA-B27 were collected. Patients filled out a visual analogue scale for pain and a childhood health assessment questionnaire. A paediatric rheumatologist and a paediatric physiatrist examined patients and measured indices of flexion, extension and sagittal flexibility. Contrast-enhanced axial MRI examination and cervical x-ray were performed. Three experienced paediatric radiologists independently reviewed x-ray and MRI images of all patients.
Results
There was no significant correlation between early changes detected on MRI and other parameters. The study revealed early changes of the cervical spine to be the most common finding. More patients had positive cervical MRI than positive sacroiliac joint (SIJ) MRI. Cervical x-ray and MRI were equally useful for diagnosis regardless of other parameters.
Conclusion
Study showed new information on axial involvement, striking cervical spine as the most involved part. The biggest study limitation is the small number of patients. Establishing early JSpA diagnosis is of utmost importance, especially in the light of novel therapy introduced in every day practice. It seems that cervical spine involvement is more represented than previously described in literature, especially in comparison with SIJ.
Key Points
• Contrast-enhanced MRI is considered the gold standard for detection early changes in JSpA.
• Standardization of diagnostic criteria and better classification of changes using the unique scoring system for children are necessary.
• It seems that cervical spine involvement is more represented than previously described in the literature, especially in comparison with SIJ involvement.
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