Efficacy and Safety of Plasma Exchange as an Adjunctive Therapy for Rapidly Progressive IgA Nephropathy and Henoch-Schönlein Purpura Nephritis: A Systematic Review.

Patients with IgA nephropathy (IgAN), including Henoch-Schönlein purpura nephritis (HSP), who present with rapidly progressive glomerulonephritis (RPGN) have a poor prognosis despite aggressive immunosuppressive therapy. The utility of plasmapheresis/plasma exchange (PLEX) for IgAN/HSP is not well established. This systematic review aims to assess the efficacy of PLEX for IgAN and HSP patients with RPGN. A literature search was conducted using MEDLINE, EMBASE, and through Cochrane Database from inception through September 2022. Studies that reported outcomes of PLEX in IgAN or HSP patients with RPGN were enrolled. The protocol for this systematic review is registered with PROSPERO (no. CRD42022356411). The researchers systematically reviewed 38 articles (29 case reports and 9 case series articles) with a total of 102 RPGN patients (64 (62.8%) had IgAN and 38 (37.2%) had HSP). The mean age was 25 years and 69% were males. There was no specific PLEX regimen utilized in these studies, but most patients received at least 3 PLEX sessions that were titrated based on the patient's response/kidney recovery. The number of PLEX sessions ranged from 3 to 18, and patients additionally received steroids and immunosuppressive treatment (61.6% of patients received cyclophosphamide). Follow-up time ranged from 1 to 120 months, with the majority being followed for at least 2 months after PLEX. Among IgAN patients treated with PLEX, 42.1% (n = 27/64) achieved remission; 20.3% (n = 13/64) achieved complete remission (CR) and 18.7% (n = 12/64) partial remission (PR). 60.9% (n = 39/64) progressed to end-stage kidney disease (ESKD). Among HSP patients treated with PLEX, 76.3% (n = 29/38) achieved remission; of these, 68.4% (n = 26/38) achieved CR and 7.8% achieved (n = 3/38) PR. 23.6% (n = 9/38) progressed to ESKD. Among kidney transplant patients, 20% (n = 1/5) achieved remission and 80% (n = 4/5) progressed to ESKD. Adjunctive plasmapheresis/plasma exchange with immunosuppressive therapy showed benefits in some HSP patients with RPGN and possible benefits in IgAN patients with RPGN. Future prospective, multi-center, randomized clinical studies are needed to corroborate this systematic review's findings.

IgA vasculitis following COVID-19 vaccination.

Immunoglobulin A (IgA) vasculitis is generally triggered by infectious causes, but it has also been reported after immunisation with various vaccines. Herein, we report two cases of IgA vasculitis after receiving the first or second dose of the Pfizer-BioNTech BNT16B2b2 mRNA vaccine. Two men, aged 22 and 30 years, developed palpable purpura on the extremities and arthritis. One patient also complained of fever and gastrointestinal symptoms. Laboratory findings revealed mild leucocytosis and slightly elevated C-reactive protein levels, although the platelet count and coagulation profile were within normal levels in both cases. Proteinuria and microhaematuria were seen in one patient. Skin biopsies were performed in both patients and revealed leucocytoclastic vasculitis. The deposits of IgA and C3 were shown in immunofluorescence studies in one patient. Both patients were diagnosed with IgA vasculitis and treated with prednisolone, and their symptoms resolved within 1 week after initiation of treatment. The coronavirus disease 2019 mRNA vaccine could trigger IgA vasculitis; however, a coincidence cannot be ruled out.

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

BACKGROUND: Immunoglobulin 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 PRESENTATION: A 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. CONCLUSIONS: This 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.

Post-COVID-19 vaccination IgA vasculitis in an adult.

Leukocytoclastic vasculitis has been reported in the setting of COVID-19 infection and post-COVID-19 vaccination. We report a case of IgA vasculitis (IgAV) post-COVID-19 vaccination, with immunoglobulin A (IgA) immune deposits in the skin and renal involvement. SARS-CoV spike protein immunohistochemical staining was negative. IgAV with skin and renal involvement is a potential reaction to COVID-19 vaccination.

Pathogenesis of IgA Vasculitis: An Up-To-Date Review.

Immunoglobin A (IgA) vasculitis (IgAV), formerly called the Henoch-Schönlein purpura (HSP), is a small vessel vasculitis, characterized by IgA1-dominant immune deposition at diseased vessel walls. IgAV is the most common form of vasculitis in children; typical symptoms include palpable purpura, arthritis or arthralgia, abdominal pain, and hematuria or proteinuria. Galactose-deficient IgA1 is detected in the tissues of the kidney and skin in patients with IgAV; it forms immune complexes leading to subsequent immune reactions and injuries. This report provides the recent advances in the understanding of environmental factors, genetics, abnormal innate and acquired immunity, and the role of galactose-deficient IgA1 immunocomplexes in the pathogenesis of IgAV.

Role of the IL33 and IL1RL1 pathway in the pathogenesis of Immunoglobulin A vasculitis.

Cytokines signalling pathway genes are crucial factors of the genetic network underlying the pathogenesis of Immunoglobulin-A vasculitis (IgAV), an inflammatory vascular condition. An influence of the interleukin (IL)33- IL1 receptor like (IL1RL)1 signalling pathway on the increased risk of several immune-mediated diseases has been described. Accordingly, we assessed whether the IL33-IL1RL1 pathway represents a novel genetic risk factor for IgAV. Three tag polymorphisms within IL33 (rs3939286, rs7025417 and rs7044343) and three within IL1RL1 (rs2310173, rs13015714 and rs2058660), that also were previously associated with several inflammatory diseases, were genotyped in 380 Caucasian IgAV patients and 845 matched healthy controls. No genotypes or alleles differences were observed between IgAV patients and controls when IL33 and IL1RL1 variants were analysed independently. Likewise, no statistically significant differences were found in IL33 or IL1RL1 genotype and allele frequencies when IgAV patients were stratified according to the age at disease onset or to the presence/absence of gastrointestinal (GI) or renal manifestations. Similar results were disclosed when IL33 and IL1RL1 haplotypes were compared between IgAV patients and controls and between IgAV patients stratified according to the clinical characteristics mentioned above. Our results suggest that the IL33-IL1RL1 signalling pathway does not contribute to the genetic network underlying IgAV.

The coexistence of IgA vasculitis and tuberculosis: a case-based review.

Immunoglobulin (Ig) A vasculitis (IgAV), formerly known as Henoch-Schonlein purpura (HSP), is a relatively uncommon form of vasculitis primarily targeting the skin, gastrointestinal system, and the kidneys. Although the pathogenesis has not yet been well identified, several triggering factors, such as infections, drugs, have been implicated in the development of IgAV. Tuberculosis (TB), albeit rare, may precipitate IgAV. Herein, we have presented a case manifested by purpuric skin rash and proteinuria 6 weeks following diagnosis of pulmonary tuberculosis while receiving anti-TB drugs. The case was diagnosed as having active tuberculosis and TB-related IgA vasculitis with multi-organ involvement. In this case-based review, we recruited cases with TB-related Ig A vasculitis from the literature and discussed the features of tuberculosis that mimic vasculitides and vice versa. We also discussed the difficulties in diagnosis and the therapeutic approach in the light of the literature.

A child with Henoch-Schonlein purpura secondary to a COVID-19 infection.

Henoch-Schonlein purpura (HSP) is a common IgA-mediated small vessel vasculitis of childhood that affects several systems. It is characterised by a tetrad of dermatological, abdominal, joint and renal manifestations. HSP can occur secondary to upper respiratory tract infections, medications, vaccinations and malignancies. COVID-19 is caused by SARS-CoV-2, a single-stranded RNA virus from the Beta-Coronaviridae family, and often presents as a respiratory infection with symptoms ranging from a mild common cold-like illness to severe pneumonia. It has also been reported to exhibit extrapulmonary manifestations, including but not limited to cardiac, thrombotic, hepatocellular and dermatological complications. We report a case of a 4-year-old boy who presented with clinical features of HSP, with detailed history that revealed a recent recovery from a COVID-19 upper respiratory tract infection, indicating a possible correlation between the two.

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 (15 mg/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.

Therapeutic Potential of Carbon Monoxide (CO) and Hydrogen Sulfide (H2S) in Hemolytic and Hemorrhagic Vascular Disorders-Interaction between the Heme Oxygenase and H2S-Producing Systems.

Over the past decades, substantial work has established that hemoglobin oxidation and heme release play a pivotal role in hemolytic/hemorrhagic disorders. Recent reports have shown that oxidized hemoglobins, globin-derived peptides, and heme trigger diverse biological responses, such as toll-like receptor 4 activation with inflammatory response, reprogramming of cellular metabolism, differentiation, stress, and even death. Here, we discuss these cellular responses with particular focus on their mechanisms that are linked to the pathological consequences of hemorrhage and hemolysis. In recent years, endogenous gasotransmitters, such as carbon monoxide (CO) and hydrogen sulfide (H2S), have gained a lot of interest in connection with various human pathologies. Thus, many CO and H2S-releasing molecules have been developed and applied in various human disorders, including hemolytic and hemorrhagic diseases. Here, we discuss our current understanding of oxidized hemoglobin and heme-induced cell and tissue damage with particular focus on inflammation, cellular metabolism and differentiation, and endoplasmic reticulum stress in hemolytic/hemorrhagic human diseases, and the potential beneficial role of CO and H2S in these pathologies. More detailed mechanistic insights into the complex pathology of hemolytic/hemorrhagic diseases through heme oxygenase-1/CO as well as H2S pathways would reveal new therapeutic approaches that can be exploited for clinical benefit.

Henoch-Schönlein purpura in a patient with oesophageal cancer: A case report.

RATIONALE: Understanding the association between Henoch-Schönlein purpura (HSP) and malignancy is essential for early diagnosis and treatment of the potential lethal disease. To the best of our knowledge, there has been only one published case of HSP coexisting with oesophageal cancer. Here, we report another patient diagnosed with HSP and oesophageal squamous carcinoma simultaneously. PATIENT CONCERNS: A 60-year-old Chinese male was referred to our hospital because of intermittent abdominal pain, abdominal distension, melena, lower extremities purpura. Positive laboratory values included pancytopenia, microscopic hematuria, nephrotic proteinuria, hematochezia, hypoalbuminemia, hyperlipidaemia, hypocomplementemia, and increased levels of hepatobiliary enzymes and immunoglobulin (Ig) A. Gastrocolonoscopy showed multiple erosion lesion on descending duodenum, terminal ileum, and ileal flap. Biopsy of these lesions suggested non-specific inflammation. DIAGNOSES: HSP (IIIb type) was diagnosed based on renal pathology examination in accordance with the International Study of Kidney Disease in Children (ISKDC) classification. Liver biopsy confirmed the diagnosis of nodular cirrhosis (Ishak 5). Gastroscopy unintentionally revealed three oesophagus lesions. Pathology study suggested intermediate differentiated squamous cell carcinoma (cTNM IB). INTERVENTIONS: Before admission, he was administered intravenous Ig 10 g once daily(qd) for 10 days, methylprednisolone 40 mg qd for a week, followed by prednisolone 50 mg qd for almost 8 weeks. Endoscopic submucosal dissection (ESD) was performed to remove all lesions with negative margin after prednisolone was tapered (5 mg per week until 10 mg qd). OUTCOMES: Despite prednisone being tapered to 2.5 mg qd within 2 months, complete remission of HSP and esophageal malignancy was achieved after the resection of the esophagus lesions during 12 months follow-up. LESSONS: We report a rare case of oesophageal squamous cell carcinoma initially presented as HSP. This case suggests the importance of evaluating adult patients with HSP for an underlying malignancy.

Pulmonary tuberculosis presenting as henoch-schönlein purpura: Case report and literature review.

INTRODUCTION: Henoch-Schönlein purpura (HSP) is an extremely rare condition in patients with pulmonary tuberculosis, with only a few reported cases. Compared to patients with typical clinical symptoms, it is difficult to make a definitive diagnosis when HSP presents as an initial manifestation in pulmonary tuberculosis patients. Herein, a case of pulmonary tuberculosis that showed HSP at first was reported, and the related literatures were reviewed. PATIENT CONCERNS: A 24-year-old man presented with palpable purpura on the extremities, accompanied by abdominal pain, bloody stools, and knee pain. DIAGNOSES: The patient was diagnosed with pulmonary tuberculosis based on the results of interferon gamma release assays, purified protein derivative test, and computed tomography. INTERVENTIONS: The patient was treated with vitamin C and chlorpheniramine for 2 weeks, and the above-mentioned symptoms were relieved. However, 3 weeks later, the purpura recurred with high-grade fever and chest pain during the inspiratory phase. The patient was then treated with anti-tuberculosis drugs, and the purpura as well as the high fever disappeared. OUTCOMES: The patient recovered well and remained free of symptoms during the follow-up examination. CONCLUSION: Pulmonary tuberculosis presenting with HSP as an initial manifestation is not common. Therefore, it is difficult to clinically diagnose and treat this disease. When an adult patient shows HSP, it is important to consider the possibility of tuberculosis to avoid misdiagnosis and delayed treatment.

Severe Attack of Henoch-Schönlein Purpura With Neurological Involvement During Adalimumab Treatment for Crohn's Disease.

Tumour necrosis factor-α [TNF-α] inhibitors have revolutionised the management of chronic inflammatory conditions. A number of cutaneous adverse events have been reported with TNF inhibition, including vasculitis. Most reactions are mild and rarely warrant treatment withdrawal. Here we describe a patient with Crohn's disease treated with adalimumab in whom severe multivisceral Henoch-Schönlein purpura developed, including neurological involvement, requiring definitive TNF blocker withdrawal.

Association of the infectious triggers with childhood Henoch-Schonlein purpura in Anhui province, China.

BACKGROUND: Although the specific etiology of Henoch-Schonlein purpura (HSP) is still unknown, several kinds of infectious triggers have been proved to participate in its pathogenesis. The objectives of present study were to analyze the association of the infectious triggers with childhood HSP in Anhui province, China. METHODS: 1200 HSP children were recruited from January 2015 to December 2017. Serum antistreptolysin O titer, TORCH, Epstein-Barr virus, helicobacter pylori (HP), Mycoplasma antibodies (MP-Ab), tubercle bacillus antibody (TB-Ab), respiratory pathogens (legionella pneumophila, chlamydia pneumoniae, adenovirus, respiratory syncytial virus, influenza A virus, influenza B virus, rickettsia, parainfluenza virus) were determined. Patients' histories were obtained by interviews and questionnaires. RESULTS: The annual incidence of HSP was 8.13-9.17 per 100,000. HSP occurred more commonly in spring and winter than in summer with an obvious west-to-east gradient. On admission, several potential infections were identified in 611 cases (50.92%). The infectious agents including streptococcus, HP, MP, parainfluenza, respiratory syncytial virus, TB and toxoplasma gondii were identified in 205 cases (17.08%), 71 cases (5.92%), 58 cases (4.83%), 6 cases (0.5%), 1 case (0.08%), 1 case (0.08%) and 1 case (0.08%) respectively. 123 cases (10.25%) relapsed or recurred more than one time; the mean number was 2.92, and the mean interval was 11.4 weeks. The infection was the most frequent trigger regardless of clinical phenotypes and relapse/recurrence. Symptomatic treatment plus adjunctive anti-infectious agents could significantly improve the remission rate of purpura in the infectious cases (x2=24.60, p<0.01). CONCLUSIONS: Streptococcus is the most frequent infectious agent in HSP children regardless of clinical phenotype or relapse/recurrence. The complete elimination of infectious triggers may help relieve cutaneous purpura.

IgA vasculitis (Henoch - Schönlein Purpura) as the first manifestation of juvenile Systemic Lupus Erythematosus: Case-control study and systematic review.

BACKGROUND: We have recognized 15 children with jSLE and the antecedent of IgA vasculitis (HSP). This association is not broadly present in the literature. AIM: To know the age and gender distribution of children with IgA vasculitis (HSP), compare it to our IgA vasculitis (HSP) + jSLE cases, and identify prognostic factors to develop jSLE within our case series, IgA vasculitis (HSP) vs. IgA vasculitis (HSP) + jSLE. METHODS: A systematic review was carried out to know the age and gender distribution of children with IgA vasculitis (HSP). The information obtained plus data from 110 children with IgA vasculitis (HSP) from the Instituto Nacional de Pediatría were used to compare groups and identify prognostic factors. We performed a case-control study in patients < 18 years, consisting of 15 cases retrospectively identified with IgA vasculitis (HSP) + jSLE, and 110 IgA vasculitis (HSP) control subjects. RESULTS: The information of 12,819 IgA vasculitis (HSP) subjects from the systematic review and 110 IgA vasculitis (HSP) controls was obtained and compared to our 15 IgA vasculitis (HSP) + jSLE cases. The mean age of IgA vasculitis (HSP) was 7.1-years vs. 10.4-years of IgA vasculitis (HSP) + jSLE at the HSP diagnosis. Female to male ratio of IgA vasculitis (HSP) was 1:1.33 vs. 1:0.25 of IgA vasculitis (HSP) + jSLE. Patients with IgA vasculitis (HSP) + jSLE had lower levels of Hemoglobin (Hb) compared to patients with IgA vasculitis (HSP) 109 g/L vs. 141 g/L. For the development of jSLE, we found older age and lower levels of Hb as prognostic factors with OR [95% CI]: 1.37 [1.06, 1.89] and 5.39 [2.69, 15.25], respectively. CONCLUSION: IgA vasculitis (HSP) + jSLE patients are older and have lower levels of Hb than patients with IgA vasculitis (HSP). It is necessary to confirm these findings through a prospective study.

Primary IgA Vasculitis with Nephritis in a Patient with Rheumatoid Arthritis Diagnosed by Anti-galactose-deficient IgA1 Immunostaining.

Renal disease is a common complication of rheumatoid arthritis (RA) and can occur secondary to RA or be induced by therapeutic agents. Recently, glomerular deposition of galactose-deficient IgA1 (Gd-IgA1) was identified as a feature of primary IgA vasculitis with nephritis (IgA-VN). We herein report a case of IgA-VN in an RA patient whose disease activity was controlled by treatment with etanercept. To distinguish between primary IgA-VN and secondary IgA-VN caused by RA or etanercept, we performed immunostaining of renal biopsy sections with the Gd-IgA1-specific antibody KM55. Positive KM55 staining confirmed the diagnosis of primary IgA-VN in a patient with RA.