IgA Vasculitis Cases Research Articles

Genome-wide studies define new genetic mechanisms of IgA vasculitis.

IgA vasculitis (IgAV) is a pediatric disease with skin and systemic manifestations. Here, we conducted genome, transcriptome, and proteome-wide association studies in 2,170 IgAV cases and 5,928 controls, generated IgAV-specific maps of gene expression and splicing from blood of 255 pediatric cases, and reconstructed myeloid-specific regulatory networks to define disease master regulators modulated by the newly identified disease driver genes. We observed significant association at the HLA - DRB1 (OR=1.55, P=1.1×10 -25 ) and fine-mapped specific amino-acid risk substitutions in DRβ1. We discovered two novel non-HLA loci: FCAR (OR=1.51, P=1.0×10 -20 ) encoding a myeloid IgA receptor FcαR, and INPP5D (OR=1.34, P=2.2×10 -09 ) encoding a known inhibitor of FcαR signaling. The FCAR risk locus co-localized with a cis-eQTL increasing FCAR expression; the risk alleles disrupted a PRDM1 binding motif within a myeloid enhancer of FCAR . Another risk locus was associated with a higher genetically predicted levels of plasma IL6R. The IL6R risk haplotype carried a missense variant contributing to accelerated cleavage of IL6R into a soluble form. Using systems biology approaches, we prioritized IgAV master regulators co-modulated by FCAR , INPP5D and IL6R in myeloid cells. We additionally identified 21 shared loci in a cross-phenotype analysis of IgAV with IgA nephropathy, including novel loci PAID4, WLS , and ANKRD55 .

#823 Effect of dapsone on the treatment of refractory IgA vasculitis

Abstract Background and Aims IgA vasculitis (IgAV), previously known as Henoch-Schönlein purpura, is a systemic IgA-mediated vasculitis of the small vessels commonly seen in children. The natural history of IgAV is generally self-limiting. However, one-third of patients experience symptom recurrence and a refractory course. We performed this study to examine the use of dapsone (4,4'-sulfonyldianiline or diaminodiphenyl sulfone) in refractory IgAV cases. Method A literature search of PubMed databases retrieved 16 articles published until May 31, 2023. A total of 38 patients with IgAV were recruited. Results A palpable purpura persisted in nearly all the patients with refractory course, followed by joint pain (25 of 38 patients; 69.2%). Hematuria and proteinuria were noted in 11 (28.9%) and 7 (18.4%) of the patients, respectively. Treatment response within 1-2 days was obtained in 12 of 38 patients (31.6%), compared to within ≥3 days in 22 patients (57.9%). Relapse after treatment discontinuation was reported in 21 patients (55.3%) but not in 11 patients (28.9 %). Twelve of the 38 patients (31.6%) reported adverse effects of dapsone, including arthralgia (5.3%), rash (5.3%), dapsone hypersensitivity syndrome (2.6%), methemoglobinemia (21%), and hemolysis (15.8%). These findings indicate that dapsone may have a beneficial effect on refractory IgAV. Conclusion It is observed that in spite of several adverse effects, dapsone treatment exerts a beneficial effect in IgAV patients with prolonged cutaneous manifestation refractory to corticosteroid. Close renal monitoring may be needed to discover renal involvement of IgAV. Multicenter randomized placebo-controlled trials are necessary to determine the standard dosage of dapsone at initial or tapering of treatment in IgAV patients.

A case of vasculitis triggered by infective endocarditis in a patient undergoing maintenance hemodialysis: a case report

BackgroundImmunoglobulin A vasculitis (IgA vasculitis) is one of the most common forms of vasculitis in children. It rarely occurs in adults. It is a systemic vasculitis with IgA deposition and is characterized by the classical tetrad of purpura, arthritis/arthralgia, gastrointestinal and renal involvement. Certain types of infections, and pharmacological agents have been reported to be associated with IgA vasculitis. Here, we describe a case of IgA vasculitis triggered by infective endocarditis in a patient undergoing maintenance hemodialysis.Case presentationA 70-year-old man undergoing hemodialysis was admitted because of skin purpura, abdominal pain, diarrhea, and lower back pain. We suspected him as IgA vasculitis based on the clinical features and skin biopsy findings. Transesophageal echocardiography revealed infective endocarditis, which predisposed him to IgA vasculitis. He was treated with antibiotics and low-dose corticosteroids, which led to resolution of vasculitis.ConclusionsThis is the first case of IgA vasculitis triggered by infective endocarditis in a patient undergoing hemodialysis. Patients undergoing hemodialysis are at a high risk of infection because of immune dysfunction and frequent venipuncture. The incidence of infective endocarditis associated with IgA vasculitis is very low, but it has been repeatedly reported. Therefore, it is necessary to consider infective endocarditis in patients with clinical features that indicate IgA vasculitis.

Use of Rituximab as an Off-Label Medication in Glomerular Diseases: Clinical Perspective

Objectives: The aim of this study was to review the use rituximab (RTX) and outcomes in immune-mediated glomerular diseases (glomerulonephritis [GN]) and to compare it to the established literature. Methods: Adult GN patients who received RTX between January 2014 and January 2018 in three public hospitals were reviewed. Membranous nephropathy (MN) and minimal change disease (MCD) were considered diseases with the literature supporting RTX use. Lupus nephritis (LN), primary focal segmental glomerulosclerosis (1^o FSGS), IgA nephropathy, IgG4-related disease (IgG4-RD), and C3GN had insufficient literature support for RTX use. Clinical remission was assessed 6 months after receiving RTX. Results: A total of 61 cases were analyzed. RTX was an add-on therapy in 87%. The remission rate was 95% in the MCD and MN versus 56% in the off-label group (p = 0.002). LN patients had a mean initial estimated glomerular filtration rate (eGFR) of 69 mL/min. All class III LN achieved remission, and 11 of 21 class IV achieved remission. The mean initial eGFR for 1^o FSGS was 33 mL/min, and it did not improve, and only 2 of 5 had partial resolution of proteinuria. Proteinuria improved in 3 of 5 IgG4-RD cases with eGFR stabilization but failed to improve in C3GN cases with eGFR deterioration. Vasculitis cases (6 ANCA-associated vasculitis and 2 IgA vasculitis) were analyzed separately. Remission was achieved in only 2 ANCA-associated vasculitis cases, and none in IgA vasculitis cases. Conclusions: Our data support the use of RTX in resistant MCD and MN. RTX showed success in LN and IgG4-RD but not FSGS or C3GN. The small number of cases of vasculitis does not allow drawing a conclusion on RTX effectiveness.

Clinical characteristics and associating risk factors of gastrointestinal perforation in children with IgA vasculitis

Background IgA vasculitis (IgAV) is a common small vessel vasculitis in children. Gastrointestinal perforation (GP) rarely presents as a complication of IgAV and is not well characterized. This study is aimed to investigate the clinical features, diagnosis, and risk factors of GP in children with IgAV. Methods We retrospectively reviewed the clinical data of children with IgAV who attended our hospital between January 2014 and June 2018. The clinical risk factors and the corresponding treatments were analyzed for the children with IgAV complication with GP. Results In total, 10,791 children with IgAV were reviewed in this study. GP was observed in 11 children with IgAV, accounted for 0.10% of the total cases. Among those GP patients, 1 case was gastric perforation, 10 cases were intestinal perforation. Five GP cases were identified by abdominal CT. Ultrasonography was failed to detect the occurrence of GP in five cases. The average duration of abdominal pain in the GP cases was 9.3 days, and 9 cases (81.8%) presented with abdominal pain for over 7 days. Gastric/intestinal perforation repair were performed for 3 IgAV GP cases under open surgery. The other eight cases were treated through enterectomy. In comparison with the patients without GP, the GP patients had significant higher rates in the aspect of the abdominal or mixed type of IgAV, abdominal pain duration more than 7 days, hematochezia, renal damage, and methylprednisolone treatment with the daily dosage more than 2 mg/kg. Conclusion GP children accounted for 0.10% of the total IgAV cases. The risk of GP is elevated in IgAV patients who has gastrointestinal symptoms and/or other symptoms such as hematochezia, renal damage, a prolonged abdominal pain (>7 days), administration of methylprednisolone (>2 mg/kg). Abdominal CT is highly recommended for the early detection of GP in IgAV patients. Key messages Gastrointestinal perforation (GP) rarely presents as a complication of IgAV and is not well characterized. 11 out of 10,791 children with IgAV developed GP, accounting for 0.10% of the total number of cases. Abdominal CT is highly recommended for the early detection of GP in IgAV patients.

Drug-induced IgA vasculitis in children and adults: Revisiting drug causality using a dual pharmacovigilance-based approach.

IgA vasculitis (IgAV) is an immune complex small-vessel vasculitis. Drug-induced IgAV cases were rarely reported in the literature. Drug causality assessment is challenging as many other etiological factors can be involved. We performed a pharmacovigilance study to identify the main drugs reported to induce IgAV. We used the French pharmacovigilance database (FPVD) and the WHO global individual case safety reports database (VigiBase) to retrieve IgAV cases. Cases from the FPVD were reviewed by two investigators using predefined criteria. Disproportionality analyses (case - non-case approach) were conducted in VigiBase to identify drugs significantly associated with IgAV reporting. Of the 467 IgAV cases retrieved from the FPVD, 115 (47 children and 68 adults) have been assessed as definite or probable, reported with 178 suspected drugs. Overall IgAV cases were mainly male (58%), with a median age of 33.5 (8.0-63.3) years. No death was reported. Besides, we identified 1558 possible IgAV cases in VigiBase. Among them, 40 were associated with a disproportionality in IgAV reporting. Drugs were mainly vaccines, antibiotics and TNF-α blockers, these finding being consistent in both databases. IgAV reporting with TNF-α blockers was significantly associated with their use in inflammatory bowel diseases, psoriasis or ankylosing spondylitis compared to other indications. Our systematic study enables the identification of culprit drugs in drug-induced IgAV. These results strengthen the immune pathophysiology of IgAV and the role of underlying disease. The list of suspected drugs may be useful for physicians to manage patients with IgAV and consider appropriate drug discontinuation. What is already known about this subject? IgA vasculitis has multifactorial etiology. To date, possible culprit drugs have been reported only in case reports. What does this study add? Using a dual pharmacovigilance-based approach, we identified drugs associated with the occurrence of IgA vasculitis, such as all types of vaccines, major antibiotics and immunomodulatory agents, mainly TNF-α blockers. How might this impact on clinical practice or future developments? Physicians should be aware of drug-induced IgA vasculitis and we provide evidence on the most frequent implicated drugs.

Low-dose corticosteroid with mizoribine might be an effective therapy for elderly-onset ISKDC grade VI IgA vasculitis

Both the diagnosis of elderly-onset IgA vasculitis (IgAV) and its prognosis can be difficult because of its rarity and the likely presence of comorbidities. Furthermore, the treatment of elderly-onset IgAV remains controversial: the ideal dosages of corticosteroid and/or immunosuppressants have not been determined. In the elderly, corticosteroid adverse effects can lead to severe outcomes, and a consensus regarding its benefit and risk balance has not been reached. We report a case of IgAV in an 89-year-old patient who was admitted to our hospital to investigate a 30-day history of palpable purpura and pitting edema on her leg. A renal biopsy showed membranoproliferative glomerulonephritis with IgA deposits (The International Study of Kidney Disease in Children (ISKDC) grade VI), which is a predictor of a poor prognosis; these findings led to early intervention with low-dose corticosteroid (15mg/day) and mizoribine. As a result, a complete remission without obvious adverse effects was obtained. Early intervention with low-dose corticosteroid and mizoribine based on renal histopathology results might be an effective treatment for elderly-onset ISKDC grade VI IgAV.

Incidence of IgA vasculitis in children estimated by four-source capture-recapture analysis: a population-based study.

The aim was to describe the epidemiological characteristics of childhood IgA vasculitis (IgAV) defined by the EULAR/PRINTO/Paediatric Rheumatology European Society criteria in a population-based sample from France and ascertain its incidence over 3 years by a four-source capture-recapture analysis. Cases were prospectively collected in Val de Marne county, a suburb of Paris, with 263 874 residents <15 years old. Children with incident IgAV living in this area from 2012 to 2014 were identified by four sources of case notification (emergency departments, paediatrics departments, private-practice paediatricians and general practitioners). Annual incidence was calculated, and a capture-recapture analysis was used with log-linear modelling to estimate case-finding completeness. We identified 147 incident cases [78 boys; mean age 6.5 (s.d.:2.6) years]. The annual incidence (95% CI) was 18.6 (13.6, 24.5)/100 000 children. Although only 10% of children were exclusively identified by non-hospital sources, the completeness of case finding was 62%, with an undercount-corrected annual incidence (95% CI) of 29.9 (23.7, 37.3)/100 000 children. The annual distribution of diagnoses consistently showed a trough in summer months; 72% of children had infectious symptoms (mainly upper respiratory tract) a few days before IgAV onset; and 23% had a North African background. Our study supports secular and geospatial stability in childhood IgAV incidence and adds further indirect evidence for a possible role of a ubiquitous, non-emerging infectious trigger. Incidence studies from understudied areas are needed to disentangle the role of genetic factors better. Capture-recapture analysis suggests that a substantial portion of IgAV cases may remain unrecognized in epidemiological surveys.

IgA vasculitis in adults: the performance of the EULAR/PRINTO/PRES classification criteria in adults.

BackgroundIn 2010, EULAR/PRINTO/PRES proposed new classification criteria for paediatric IgA vasculitis (IgAV) that have a higher diagnostic sensitivity than the 1990 ACR criteria. These criteria have so far not been evaluated in adults, in whom IgAV is considered as a rare disease. Our main objective was to compare the diagnostic performance of EULAR/PRINTO/PRES and ACR classification criteria in adult IgAV.MethodsAdult IgAV cases fulfilling the 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides (ICHCCNV) definition of IgAV at a secondary/tertiary rheumatology referral centre were critically reviewed in a partially retrospective and partially prospective manner. First, we compared the diagnostic sensitivity of ACR and EULAR/PRINTO/PRES criteria in this group of patients. Second, the diagnostic specificity of ACR and EULAR/PRINTO/PRES was determined by applying these criteria to a control group of patients with other systemic vasculitides.ResultsBetween 1 January 2010 and 31 December 2014 350 new cases of systemic vasculitis were identified. IgAV was diagnosed in 129, and other systemic vasculitides in 221 (123 had large, six medium and 92 small vessel vasculitis) cases according to ICHCCNV. The diagnostic sensitivity and specificity of the IgAV EULAR/PRINTO/PRES criteria were 99.2 % (95 % CI 95.4–99.9 %) and 86.0 % (95 % CI 80.7–90.3 %), and of the ACR criteria 86.8 % (95 % CI 79.7–92.1 %) and 81.0 % (95 % CI 75.2–85.9 %), respectively with an inter-criteria agreement of 77.5 % (95 % CI: 70.8–84.1 %).ConclusionsIn the adult population the EULAR/PRINTO/PRES IgAV classification criteria had a higher sensitivity and specificity than the ACR criteria.

経過中に DIC を発症し，腎不全に至った IgA 血管炎の 1 例

経過中に DIC を発症し，腎不全に至った IgA 血管炎の 1 例

FRI0444 Comparison of ACR (1990) and Eular/Printo/Pres (2010) Classification Criteria in Adult IGA Vasculitis

BackgroundIn 2010 EULAR/PRINTO/PRES proposed new classification criteria for IgA vasculitis (IgAV).(1) In paediatric patient population these criteria have a higher diagnostic sensitivity than the older American College of Rheumatology (ACR)...