Povezanost kožnih manifestacija i kliničkih značajki IgA vaskulitisa

Introduction: IgA vasculitis (IgAV ) is the most common systemic vasculitis in childhood. Purpuric rash is a mandatory criterion for diagnosing IgAV , it is mostly localized on the lower extremities and gluteal region, although it can also appear atypically affecting the face, trunk and upper extremities. In the most severe cases, ulcerations, necrosis and bullae can be present. Objectives: To evaluate the characteristics of cutaneous manifestations in patients with IgAV and to examine its association with clinical features. Subjects and methods: Retrospective analysis of data from patients with IgAV diagnosed and treated at the Referral Centre for Paediatric and Adolescent Rheumatology of the Ministry of Health of the Republic of Croatia, in the period from January 2009 to December 2021. Results: IgAV was diagnosed in 234 patients, 124 boys and 110 girls with the median (range) age at the time of diagnosis of 6.5 (4.5–8.2) years. All patients had a purpuric rash, and in 127 of them (54.3%) IgAV began with a rash. Cutaneous manifestations were most often presented in the form of palpable purpura and/or petechiae (87.2%) and in all patients were localized on the lower extremities. In 103 patients (44%) purpuric rash spread further to the upper extremities, trunk and/or face. At least one skin relapse occurred in 47 patients (20.1%). The most severe cutaneous manifestations which included ulcerations and necrosis developed in 11 patients (4.7%). Patients with cutaneous manifestations spread above the waist had a more statistically significant gastrointestinal involvement compared to patients with cutaneous manifestations affecting the lower extremities and gluteal region (50.5% vs. 36.6%, p=0.033), higher incidence of IgA vasculitis nephritis (IgAVN ) (31.1% vs. 19.8%, p=0.048) and were more frequently treated with systemic glucocorticoids (68% vs. 52.7%, p=0.018) and angiotensin-converting enzyme inhibitors (14.5% vs. 5.3%, p=0.016). Almost all patients with ulcerations and necrosis required treatment with systemic glucocorticoids compared to the rest (90.9% vs. 57.8%,p=0.031). Conclusion: We observed that patients with purpuric rash spread above the waist have more frequently affected gastrointestinal system and a higher incidence of IgAVN . The prevalence of ulcerations and necrosis in IgAV is less common than the standard purpuric rash and this group of patients required systemic glucocorticoid therapy.Uvod: IgA vaskulitis (IgAV ) najčešći je sistemski vaskulitis dječje dobi. Purpurični osip ključan je kriterij za dijagnozu IgAV -a, a najčešće je rasprostranjen po donjim udovima i gluteusima, iako može biti proširen i na atipičnim mjestima poput lica, trupa i gornjih udova. U najtežim slučajevima mogu biti prisutne ulceracije, nekroze i bule. Cilj: Utvrditi osobitosti kožnih promjena u bolesnika s IgAV -om te ispitati njihovu povezanost s kliničkim značajkama. Ispitanici i metode: Retrospektivna analiza podataka bolesnika s IgAV -om dijagnosticiranih i liječenih u Referentnom centru za pedijatrijsku i adolescentnu reumatologiju Ministarstva zdravstva RH, u razdoblju od siječnja 2009. do prosinca 2021. godine. Rezultati: IgAV je dijagnosticiran u 234 bolesnika, 124 dječaka i 110 djevojčica s medijanom (rasponom) dobi u trenutku dijagnoze 6,5 (4,5 – 8,2) godina. Svi su bolesnici imali kožni osip, a u njih 127 (54,3%) IgAV je i započeo osipom. Kožne promjene najčešće su bile zastupljene u obliku palpabilne purpure i/ili petehija (87,2%) i u svih bolesnika bile su lokalizirane po donjim udovima. U 103 bolesnika (44%) kožni osip se dalje proširio na ruke, trup i/ili lice. U 47 bolesnika (20,1%) došlo je do barem jednog recidiva kožnih promjena. Najteže kožne promjene u vidu ulceracija i nekroza razvilo je 11 bolesnika (4,7%). Bolesnici s kožnim promjenama proširenim iznad donjih udova imali su statistički značajno češće zahvaćen gastrointestinalni sustav u odnosu na bolesnike s kožnim osipom ograničenim na donje udove i glutealno (50,5% u odnosu na 36,6%, p=0,033), veću pojavnost nefritisa (IgAVN) (31,1% u odnosu na 19,8%, p=0,048) te su češće liječeni sistemskim glukokortikoidima (68% u odnosu na 52,7%, p=0,018) i inhibitorima angiotenzin konvertaze (14,5% u odnosu na 5,3%, p=0,016). Gotovi svi bolesnici s ulceracijama i nekrozama zahtjevali su liječenje sistemskim glukokortikoidima u odnosu na sve preostale bolesnike (90,9% u odnosu na 57,8%, p=0,031). Zaključak: Uočili smo da bolesnici s kožnim osipom proširenim iznad donjih udova imaju češće zahvaćen gastrointestinalni sustav i češću pojavu IgAVN -a. Učestalost ulceracija i nekroza u IgAV -u rjeđa je od klasične slike kožnog osipa i takvi bolesnici zahtijevali su liječenje sistemskim glukokortikoidima

An Update on Glomerulopathies

An Update on Glomerulopathies - Clinical and Treatment Aspects is a systemic overview of recent advances in clinical aspects and therapeutic options in major syndromes of glomerular pathology. The book contains twenty four chapters divided conveniently into five sections. The first section deals with primary glomerulopathies, and the second section is devoted to glomerulopathies complicating infectious conditions. The third section deals with systemic autoimmune disorders and vasculitides which constitute major causes of glomerular disease and often renal failure. The fourth section includes chapters discussing the glomerular involvement in some major metabolic and systemic conditions. The final section has chapters which relate to some general aspects of glomerular diseases. This book will form an excellent reference tool for practicing and academic nephrology community

Genetics of immunoglobulin-A vasculitis (Henoch-Schönlein purpura): An updated review

Immunoglobulin-A vasculitis (IgAV) is classically a childhood small-sized blood vessel vasculitis with predominant involvement of the skin. Gastrointestinal and joint manifestations are common in patients diagnosed with this condition. Nephritis, which is more severe in adults, constitutes the most feared complication of this vasculitis. The molecular bases underlying the origin of IgAV have not been completely elucidated. Nevertheless, several pieces of evidence support the claim that genes play a crucial role in the pathogenesis of this disease. The human leukocyte antigen (HLA) region is, until now, the main genetic factor associated with IgAV pathogenesis. Besides a strong association with HLA class II alleles, specifically HLA-DRB1 alleles, HLA class I alleles also seem to influence on the predisposition of this disease. Other gene polymorphisms located outside the HLA region, including those coding cytokines, chemokines, adhesion molecules as well as those related to T-cells, aberrant glycosylation of IgA1, nitric oxide production, neoangiogenesis, renin-angiotensin system and lipid, Pyrin and homocysteine metabolism, may be implicated not only in the predisposition to IgAV but also in its severity. An update of the current knowledge of the genetic component associated with the pathogenesis of IgAV is detailed in this review.Acknowledgements: RL-Mis supported by the Miguel Servet I programme of the Spanish Ministry of Economy and Competitiveness through the grant CP16/ 00033. FG is recipient of a Sara Borrell postdoctoral fellowship from the “Instituto Carlos III de Salud” at the Spanish Ministry of Health (Spain) (CD15/00095). SR-M is supported by funds from the RETICS Program (RIER) (RD16/0012/0009). FDC is supported by the Ramón y Cajal programme of the Spanish Ministry of Economy and Competitiveness through the grant RYC-2014-16458

Studies of the pathogenesis of IgA nephropathy and Henoch-Schönlein purpura, with special reference to Streptococcus pyogenes infections and complement

IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis and Henoch-Schönlein purpura (HSP) the most common form of vasculitis in childhood. HSP may affect kidneys, a complication termed Henoch-Schönlein nephropathy (HSN). Renal pathology in HSN resembles that seen in IgAN. The pathogenesis of IgAN and HSP is so far unclear. Both are characterized by tissue deposits of underglycosylated polymeric IgA1 and the debut or exacerbations are regularly preceded by infections usually affecting the respiratory tract and often caused by group A streptococci (GAS). GAS express the surface bound M protein, which varies in sequence between strains and in certain serotypes includes an IgA-binding region (IgA-BR). The complement system, an important part of the innate immune system, is activated during IgAN and HSN reflected by the common finding of mesangial depositions of C3. Paper I-III investigated whether IgA-binding M proteins are involved in the pathogenesis of IgAN and HSP. In the first study we examined tissue samples from pediatric patients with IgAN and HSP and detected IgA-BR co-localizing in the mesangial region with IgA in most of the kidney samples from patients with IgAN and HSN and skin samples from patients with HSP. In the second study we showed that pediatric patients with IgAN had higher antibody levels to IgA-BR than age-matched controls. The third study showed that the IgA-binding M protein from GAS serotype 4 (M4) had a significantly higher binding affinity for underglycosylated polymeric IgA1 than for other forms of IgA1. Mesangial cells stimulated with M4 exhibited increased synthesis and secretion of IL-6. Co-stimulation with both M4 and IgA1 induced excessive IL-6 secretion. IgA1 also induced C3 secretion from mesangial cells, which was enhanced when the cells were co-stimulated with M4. Paper IV identified a novel mutation heterozygous mutation in exon 2 of the factor H gene (CFH) in a child with IgAN complicated by thrombotic microangiopathy (TMA) most probably triggered by malignant hypertension. In addition, three heterozygous CFH polymorphisms were identified, known to increase the risk for TMA. This genotype may thus have contributed to the combined phenotype of IgAN and TMA. This thesis provides evidence for the involvement of GAS expressing IgA-binding M proteins in the etiology and pathogenesis of IgAN and HSP. An N terminal mutation in CFH may have influenced the course and pathological findings in IgAN and particularly conferred susceptibility for TMA

Aspectos clínicos y factores asociados a compromiso renal en pacientes pediátricos con púrpura de Schönlein Henoch

INTRODUCCIÓN: La púrpura de Schönlein Henoch (PSH) es la vasculitis más frecuente de la infancia. Es generalmente autolimitada, con morbilidad renal a largo plazo. OBJETIVO: Determinar la frecuencia de las manifestaciones clínicas de la PSH y las variables asociadas al compromiso renal en pacientes con PSH del Servicio de Reumatología pediátrica de la Clínica Universitaria Reina Fabiola durante el periodo 2015-2020. MATERIALES Y METODOS: Estudio observacional, retrospectivo, transversal, analítico. Se incluyeron pacientes menores de 15 años con diagnóstico de PSH. Variables: edad, sexo, mes de diagnóstico, compromiso dermatológico, renal, gastrointestinal, articular y recurrencia y/o persistencia y otras manifestaciones. Análisis estadístico: test T de Student, test chi cuadrado y regresión logística multivariada. RESULTADOS: Se analizaron 107 pacientes, 61 (57%) de sexo femenino, con una media (desviación estándar, DE) de edad de 6,49 (3,48) años. El 100% presentó compromiso dérmico, 19 (18%) púrpura persistente o recurrente, 21 (19%) síntomas gastrointestinales, 38 (36%) compromiso articular y 21 (20%) manifestaciones renales. Se asoció con compromiso renal a pacientes con edad mayor a 7 años (p=0.0064), púrpura persistente o recurrente (p=0.0001), compromiso articular (p=0,0135) y dolor abdominal (p=0,0136). En el análisis multivariado, la púrpura persistente o recurrente se asoció con compromiso renal (OR=7,16; IC95%: 1,81-28,25); p=0.005). CONCLUSIONES: La púrpura persistente o recurrente fue considerada factor de riesgo para presentar compromiso renal y además se evidenció una asociación entre pacientes mayores a 7 años, compromiso articular y dolor abdominal con compromiso renal

Correlation between serum cystatin C, thrombomodulin and T lymphocyte subsets in children with Henoch-Schonlein purpura

19-24Henoch-Schönlein Purpura (HSP) is a systemic small vessel, leucocytoclastic vasculitis disease affecting children, and the abdominal pain and joint pain are its classic triad. Here, we studied the correlation between serum cystatin C (CysC), thrombomodulin (TM), and T lymphocyte subsets in HSP cases, and the diagnostic values of these indices. A total of 120 HSP children treated at The 940th Hospital of Joint Logistics Support Force of the Chinese People's Liberation Army from January 2019 to May 2020 participated in this study. Another 64 healthy children receiving routine physical examination in the same time range were enrolled as a control group. In the early morning of the next day after admission, the cubital venous blood was collected. The serum levels of CysC were measured by immunoturbidimetry, the TM was detected using ELISA, while the T lymphocyte subsets were detected by flow cytometry. Univariate and multivariate logistic regression analyses were performed to determine the susceptibility factors. The receiver operating characteristic (ROC) curves were plotted to evaluate the predictive values of CysC, TM and T lymphocyte subset alone and their combination for HSP. The serum levels of CysC, TM, and cluster of differentiation 8 (CD8+) of HSP children significantly increased and their CD3+, CD4+ levels and CD4+/CD8+ ratio significantly decreased compared with those of control group (P+, CD4+ levels and CD4+/CD8+, whereas positively with CD8+ level (P<0.05). Diet, infection, drugs, exercise-induced tiredness, air pollution, family environment, family inheritance, age, winter and spring were the susceptibility factors for children with HSP. The diagnosis using CysC, TM and T lymphocyte subsets had an AUC of 0.901, sensitivity of 93.1%, and specificity of 90.2%. In conclusion, the combined monitoring of serum CysC, TM, and T lymphocyte subsets in children with HSP can raise the accurate diagnosis rate

Correlation between serum cystatin C, thrombomodulin and T lymphocyte subsets in children with Henoch-Schonlein purpura

Henoch-Schönlein Purpura (HSP) is a systemic small vessel, leucocytoclastic vasculitis disease affecting children, and the abdominal pain and joint pain are its classic triad. Here, we studied the correlation between serum cystatin C (CysC), thrombomodulin (TM), and T lymphocyte subsets in HSP cases, and the diagnostic values of these indices. A total of 120 HSP children treated at The 940th Hospital of Joint Logistics Support Force of the Chinese People's Liberation Army from January 2019 to May 2020 participated in this study. Another 64 healthy children receiving routine physical examination in the same time range were enrolled as a control group. In the early morning of the next day after admission, the cubital venous blood was collected. The serum levels of CysC were measured by immunoturbidimetry, the TM was detected using ELISA, while the T lymphocyte subsets were detected by flow cytometry. Univariate and multivariate logistic regression analyses were performed to determine the susceptibility factors. The receiver operating characteristic (ROC) curves were plotted to evaluate the predictive values of CysC, TM and T lymphocyte subset alone and their combination for HSP. The serum levels of CysC, TM, and cluster of differentiation 8 (CD8+) of HSP children significantly increased and their CD3+, CD4+ levels and CD4+/CD8+ ratio significantly decreased compared with those of control group (P&lt;0.05). The serum levels of CysC and TM were significantly correlated negatively with CD3+, CD4+ levels and CD4+/CD8+, whereas positively with CD8+ level (P&lt;0.05). Diet, infection, drugs, exercise-induced tiredness, air pollution, family environment, family inheritance, age, winter and spring were the susceptibility factors for children with HSP. The diagnosis using CysC, TM and T lymphocyte subsets had an AUC of 0.901, sensitivity of 93.1%, and specificity of 90.2%. In conclusion, the combined monitoring of serum CysC, TM, and T lymphocyte subsets in children with HSP can raise the accurate diagnosis rate

Salivary Immunoglobulin A (IgA) in children with IgA vasculitis

Abstract Introduction: The local salivary immunoglobulin A (IgA) is the predominant immunoglobulin in the saliva and plays an important role in the local immune defence system. It is believed that an abnormal production of IgA can cause systemic inflammatory diseases such as IgA vasculitis and IgA nephropathy. First and foremost, IgA vasculitis is the most common form of childhood vasculitis which is characterized by a skin rash and a classical triad of symptoms involving the gastrointestinal system, musculoskeletal and renal system which is not always present. The incidence of IgA related disease is increasing across the world and it is a leading cause of chronic kidney disease. It should be noted that previous literature has demonstrated that poor oral hygiene may trigger IgA production and some studies have shown that children affected by IgA vasculitis are highly likely to suffer from dental caries pulp infection / inflammation, periapical infections and periodontal disease. Aim: The aim of the project is to determine whether children with IgAV have an increased production of salivary IgA by exploring the existing literature, piloting saliva collection methods, and validating the analytic performance of an assay to quantify salivary IgA as a potential biomarker for IgA induced vasculitis. Methods: This study was cross-sectional pilot study. Children were recruited from Alder Hey Children's NHS Foundation Trust Hospital. The target populations were three groups of children, the first group of children were those with a diagnosis of immunoglobulin A vasculitis (IgAV) who attended Alder Hey Children's NHS Foundation Trust Hospital for renal monitoring. The second group of children were termed a dental control group which was children who were attending the clinic at the paediatric dental department, Alder Hey Children’s Hospital. The third group of children were classed as a healthy control cohort. Patients were recruited as part of the IgA vasculitis (IgAV) study during their routine clinical follow up visitsfor regular kidney check-ups. A data collection sheet were used to collect data regarding the disease activity and oral health status using specific dental scoring tools. The Child Oral Health Impact Profile (COHIP) Questionnaire were completed and used in this study. The saliva samples were collected by either salivabio passive drool method or forced method. Saliva samples were centrifuged for 10 minutes at 800 g to remove any cells or debris and then the sample was isolated, stored and frozen at -80 degrees Celsius in 200 microL aliquots. Finally, IgA immunoglobulin was extracted and 7 quantified using Enzyme Linked Immunosorbent Assay (ELISA) assays. Initially healthy adult control samples were used to optimize the experiments. The study had full ethical approval. Results: A total of 15 children were recruited in this study. Of these, 5 patients had a diagnosis of IgAV, 5 children had a diagnosis of dental and oral issues, and the remaining 5 children were recruited as healthy controls. From this cohort, 10 (66.67%) of them were males and 5 (33.33%) were females. The median age of the first group which is the healthy cohort was 7 years, for the second group which is the IgAV the median was 8 years and for the third cohort which was patient with oral and dental caries the median age was 11 years. In the first group, the healthy control, the youngest participant was five years old and the eldest was eleven. In the IgAV cohort, the youngest child was six years old and the eldest was twelve. In the third group, which consisted of patients with oral and dental issues, the youngest participant was 8 years old and the eldest was 12 years old. The age range of the 15 children was 7 years. The concentration values of 108.1075, 55.2175, and 75.49 were recorded for the dental group, healthy group, and IgAV group, respectively. There was no significant differences were observed between the three groups. Furthermore, there was no statistically significant difference in the levels of IgA between the forced and passive samples which was taken from adult control to optimise the different methods to collect saliva. Regarding the Child Oral Health Impact Profile Questionnaire (COHIP) given to adult controls, three participants found it very good (37.5%), while one thought it was fair (12.5%). In terms of overall rating, three participants rated it very good, while one rated it poor. To make it easier for children, we provided a Modified Oral Health Questionnaire for the dental group. Out of five participants, two rated their dental health as 7, one as 9, one as 8, and one as 5. Overall, the questionnaire received an average rating of 7.2 out of 10, which is generally considered good based on the collected responses. Conclusion: This pilot study was not able to demonstrate any difference in the IgA concentrations in children with IgAV compared to children who had oral and dental concerns or healthy controls. Several factors could contribute to this outcome, that include the study limitations such as the small sample sizes. Further studies are required to explore the role of salivary IgA in this inflammatory disease