Adult Immunoglobulin A Vasculitis Research Articles

An Unusual Case of Abdominal Pain in a Geriatric Man

BackgroundImmunoglobulin A vasculitis, historically known as Henoch-Schönlein purpura, is a rare form of autoimmune-induced vasculitis most common in children. This disease is characterized by a purpuric rash, arthritis, digestive tract complication, and renal inflammation (Hopkins). Case ReportWe present the case of a 78-year-old man in the emergency department with findings of weakness, abdominal pain, and bloody diarrhea for 3 days and a new-onset bilateral lower extremity rash. Diagnostic imaging and labs diagnosed this patient with immunoglobulin A vasculitis (IgAV) with associated acute kidney injury and abdominal mesenteric edema.Why Should an Emergency Physician be Aware of This? Recognition of IgAV by emergency physicians and assessment of multiple organ involvement is critical to expedite treatment and minimize complications. Particularly, physicians should consider and recognize the increased severity and different presentation of IgAV in adults in comparison with the more widely known manifestation in children.

Impact of non-immune factors on renal prognosis in adult IgA Vasculitis with Nephritis：A Long-Term Retrospective Cohort Study.

Adult Immunoglobulin A vasculitis (IgAV) is documented to be associated with more renal involvement and poorer renal outcome compared to children, but adult IgAV nephritis (IgAV-N) data is rather limited. The present study aimed to describe the characteristics of adult IgAV-N and investigate the long-term prognostic factors. Clinical, morphological data from 106 adult biopsy-proven IgAV-N patients and follow-up data from 94 patients in a single Chinese center were analyzed in this retrospective study. Median follow-up time interval was 102 months. The median age of IgAV-N patients at biopsy was 38 (IQR 24-53) years, and 52.8% were male. The median blood pressure was 126/80 mmHg, and 25.5% of patients were hypertensive at baseline. The median initial proteinuria was 1.4 (IQR 0.7-2.2) g/24h, eGFR was 103 (IQR 84-121) mL/min/1.73 m2. The median time interval of onset to biopsy was eight (IQR 3- 40) weeks. In biopsy, the median percentage of global sclerosis was 5.9% (IQR 0.0-13.8), while 45.3% of patients had interstitial fibrosis and tubular atrophy. Furthermore, during follow-up, 7.4% patients died, 4.3% patients progressed to ESKD and 6.4% patients developed >30% eGFR reduction from baseline. Multivariate Cox proportional analyses revealed hypertension history and higher than 10% global sclerosis at presentation were independent prognostic factors for poor outcome. The present adult IgAV-N cohort revealed a relatively young onset age, fewer nephrotic syndrome and lower incidence of ESKD. Moreover, non-immune factors as history of hypertension and renal chronic histological lesions in biopsy played a crucial role in prognosis of IgAV-N.

Association of the Monocyte-to-High-Density Lipoprotein Cholesterol Ratio with Gastrointestinal Involvement of Immunoglobulin a Vasculitis.

To illustrate the association of monocyte to high-density lipoprotein cholesterol ratio (MHR) and other serum indicators with the pathogenesis and prognosis of immunoglobulin A vasculitis (IgAV) patients in different subgroups. A total of 158 adult patients and 113 healthy controls were enrolled, and the clinical presentation and laboratory indexes were comprehensively assessed. IgAV patients show significantly elevated levels of inflammatory parameters and lipid profiles compared to healthy controls (P < 0.05). Higher levels of the MHR and other normal inflammatory indicators were found in patients with Gastrointestinal (GI) involvement compared to other subgroups. And in group with GI involvement, significantly higher white blood cell (WBC), neutrophil, complement 4 (C4), NLR (neutrophil-to-lymphocyte ratio) and PLR (platelet-to-lymphocyte ratio) levels and lower levels of apolipoprotein-a (Apo-a) were observed. Their correlation analysis demonstrated positive results between MHR level and white blood cell (WBC) count (r = 0.416, P = 0.034), D-Dimer (r = 0.464, P = 0.026) and monocyte (r = 0.947, P < 0.001). And the time until first remission of skin purpura was shown positively correlated with their age (r = 0.456, P = 0.043), C-reactive protein (CRP) level (r = 0.641, P = 0.018), D-Dimer level (r = 0.502, P = 0.040) while negatively correlated with albumin (Alb) level (r=-0.626, P = 0.003) and low-density lipoprotein (LDL) level (r=-0.478, P = 0.033). Our study suggests that those biomarkers represented for inflammatory responses, lipid profile and immunological functions have significant differences in the subgroups of adult IgAV patients. In addition, we also found that MHR level may serve as a potential biomarker for the pathogenesis and prognosis of IgAV patients with GI involvement.

Biologics for immunoglobulin A vasculitis: targeting vasculitis or comorbid disease?

In this study, we aimed to evaluate the clinical features and treatments, including the use of biological disease-modifying anti-rheumatic drugs (bDMARDs) in a large cohort of pediatric and adult immunoglobulin A vasculitis (IgAV). Since data on the use of bDMARDs in IgAV are very limited, we collated the reasons for use of bDMARDs during the disease course. Patients who were enrolled in the Hacettepe University Vasculitis Research Centre (HUVAC) registry were included. In this prospective database dating from 2014, there were 436 IgAV patients classified as IgAV according to Ankara 2008 and/or American College of Rheumatology 1990 criteria. 88 adults and 330 pediatric IgAV patients were included as the main study group. Concomitant spondyloarthritis (SpA) was observed only in adult patients (10% vs 0% in children, p < 0.001). IgAV relapse was more common in adults than in children (p: 0.017). Adult patients were mostly treated with corticosteroid (p < 0.001) and conventional synthetic disease-modifying anti-rheumatic drug treatment (< 0.001), while more than half of the pediatric patients were followed up without immunosuppressive treatment. Ten (11%) adult patients used biologics. Among them, two patients used rituximab due to IgAV disease activity, three used infliximab due to SpA, three used etanercept due to SpA (one patient had a pediatric onset enthesitis-related arthritis), and two used anakinra due to recurrent familial Mediterranean fever attacks. This is the first study evaluating the use of all bDMARDs for any reason in the IgAV cohorts in the literature. None of the pediatric patients used biologics. Our data suggest biologics are mainly used for comorbid inflammatory diseases over refractory vasculitis in adult IgAV.

Prognostic Value of C4d Immunolabelling in Adult Patients With IgA Vasculitis.

Background and Objectives: Glomerular C4d deposits are associated the severity and outcomes of IgA nephropathy. Whether this holds true in immunoglobulin A vasculitis (IgAV) is not known. The main objective of the study was to analyze the prognostic value of glomerular C4d immunolabelling on kidney impairment in adults with IgAV.Design, Setting, Participants, Measurements: This retrospective cohort study included 120 adults with IgAV and a kidney biopsy performed between 1995 and 2018 in two French university hospital centers. All paraffin-embedded biopsies were reassessed according to Oxford classification. Immunofluorescence for C4d was performed in all cases. For analysis, patients were grouped according to positivity for C4d in the glomerular area. The main outcome was a composite endpoint of 50% increase in 24 h-proteinuria, or eGFR decrease by 50%, or kidney replacement therapy.Results: The median follow-up was 28.3 months. Twenty-three patients met the composite endpoint, 12 for kidney replacement therapy, 6 for an eGFR decrease >50% and 5 for a >50% increase in proteinuria. At time of biopsy, the median proteinuria was 1.9 g/24 h and the median eGFR 73.5 mL/min/1.73 m2. Among the 102 patients evaluable for C4d, 24 were positive on >30% glomeruli, mainly with a parieto-mesangial pattern. In this group, the initial proteinuria was more frequently nephrotic than in the C4d– group (60% vs. 33%, P = 0.039). Mesangial hypercellularity was more frequent in the C4d+ group (42% vs. 13%; P = 0.006) whereas macroscopic hematuria was more frequent in the C4d– group (18% vs. 0%; P = 0.03). After a median follow-up of 28 months, kidney survival did not differ according to C4d status.Conclusion: In a population of adult IgAV patients, glomerular positivity for C4d was associated with the severity of the kidney disease at presentation, but not with subsequent renal function deterioration.

Correlations of Serological Markers with Development of Systemic Involvement in Adult Immunoglobulin A Vasculitis: A Retrospective Study of 259 Patients in Central China.

Although relatively rare, adult immunoglobulin A vasculitis (IgAV) can lead to severe complications and longer hospitalization, and result in poor prognosis, when compared to childhood IgAV. Hence, early identification and prevention for patients prone to develop systemic involvement are essential. The purpose of this study was to explore the correlations of common serological markers with the development of systemic involvement in adult IgAV. A retrospective analysis was performed for adult IgAV patients, who were hospitalized in Wuhan Union Hospital between January 2016 and December 2019. A total of 259 patients were enrolled, and the pre-treatment serological markers were comprehensively assessed. In the present study, 49.0% and 33.2% of patients developed renal and gastrointestinal (GI) involvement, respectively. Furthermore, the elevated levels of white blood cells count, D-Dimer (D-D), C-reactive protein (CRP) and neutrophil granulocyte ratio (NE%) >60% were significantly associated with GI involvement in the univariate analysis, while the decrease in high density lipoprotein level, and the elevated D-D and CRP levels were significantly associated with renal involvement (P<0.05). Moreover, a prediction model that combined multiple markers was established by performing a logistic regression analysis, and this presented a more favorable value of prediction than the individual serological markers. The present study suggests that common serological markers have close correlations with systemic involvement in adult IgAV, and that the establishment of a prediction model for systemic involvement may be helpful in facilitating personalized therapeutic strategies and clinical management for IgAV patients.

Serum VEGF-A and VEGFR-1 levels in patients with adult immunoglobulin A vasculitis.

Immunoglobulin A vasculitis (IgAV) is classified as a leukocytoclastic vasculitis characterized by immune deposits in endothelial walls of small vessels causing vascular endothelial injury. The aim of the present study is to evaluate levels of vascular endothelial growth factor-A (VEGF-A) and VEGF receptor-1 (VEGFR-1) levels in adult IgAV patients. Thirty-seven adult IgAV patients admitted to the Rheumatology Clinic meeting the IgAV American College of Rheumatology (ACR) criteria and 32 control subjects were enrolled in the study. Disease activity was categorized as "remission" or "active" according to Birmingham Vasculitis Activity Score (BVAS). Serum VEGF-A, VEGFR-1 levels and VEGFR-1/VEGF-A ratio were evaluated in patient and control groups. Serum median VEGF-A, VEGFR-1 and VEGFR-1/VEGF-A ratios were significantly higher in the patient group when compared to controls (235.9 [155-308.4] pg/mL vs. 78.8 [29.7-210.3] pg/mL, 400 [277.2-724.3] pg/mL vs. 31.5 [12.5-214.4] pg/mL and 1.85 [0.57-2.97] vs. 0.46 [0.38-0.63] respectively, all P values <.001). VEGFR-1 had the strongest predictive value with a cut-off value of 0.6 with 75% sensitivity and 73% specificity (P<.001). This study is the first report indicating elevated serum VEGF-A, VEGFR-1, and more importantly VEGFR-1/VEGF-A ratio can be good representatives of the inflammatory processes together with vascular endothelial injury in adult IgAV patients. VEGFR-1 seems to be a more important indicator of the ongoing inflammation.

Immunoglobulin a Vasculitis in a Middle-Aged Male

Introduction: Immunoglobulin A vasculitis (IgAV), formerly Henoch—Schönlein purpura vasculitis, is a vasculitis commonly seen in children but seldomly seen in young adults, and rarely described in older patients. Classic presentation is a palpable cutaneous purpura on the lower extremities and buttocks with concomitant arthralgia. Studies have shown half of patients will present with gastrointestinal symptoms typically abdominal pain from ileus, intussusception and ischemia. Ileitis has only rarely been described as a presentation of IgAV in adults and the majority of such cases were seen in young adults. Case: 56-year-old Caucasian male with a history of hypertension and diabetes mellitus developed worsening abdominal pain for one month. Prior to his symptoms he was having daily bowel movements with no associated pain or gastrointestinal bleeding. He developed symptoms of constipation with abdominal pain and was started on polyethylene glycol and initially improved. Subsequently he developed a bilateral lower extremity purpuric rash which was diagnosed as a leukocytoclastic vasculitis and treated with oral sulfamethoxazole /trimethoprim. His rash improved, however due to worsening abdominal pain he presented to the hospital for evaluation. Upon initial examination his vital signs were unremarkable. His physical exam revealed a soft non-tender abdomen with bowel sounds present, and a resolving purpuric rash on the posterior bilateral lower extremities. Initial blood-work revealed leukocytosis of 14.5 K/cmm and acute kidney injury (AKI) with a creatinine of 2.15 mg/dL. Computed tomography with intravenous contrast showed findings suggestive of ileitis. Evaluation for multiple myeloma, cryoglobulinemia, and ANCA vasculitis was negative. Initially his kidney function improved with rehydration and his abdominal pain resolved with aggressive bowel regimen. Colonoscopy showed terminal ileitis with biopsies compatible with a vasculitic process. Given these findings and recurrent AKI renal biopsy was performed which showed IgA glomerulonephritis. He was started on high dose steroids and subsequently his kidney function improved with complete resolution of abdominal pain. Discussion: Although, classically associated with children and young adults, IgAV can present in older patients. Common symptoms of rash and arthralgia may be absent initially, however, this does not exclude IgAV. Findings of terminal ileitis, while rare, could be a sign of a vasculitis.

Insight into inflammatory cell and cytokine profiles in adult IgA vasculitis

Immunoglobulin A vasculitis (IgAV) is an immune complex, small vessel vasculitis with dominant IgA deposits in vessel walls, predominantly affecting the pediatric population. However, adults frequently have more severe gastrointestinal tract (GIT) and renal involvements as compared to children. Our aim was to study serological and cellular biomarkers to support clinicians in their diagnosis and the course of IgAV in adult patients. This cross-sectional study included 62 adult IgAV patients and 53 healthy blood donors (HBDs). Demographic and clinical data, as well as routine laboratory tests, were meticulously analyzed. Serum levels of IL-1β, IL-2, IL-6, IL-8, IL-9, IL-10, IL-17A, IL-23, TNF-α and serum amyloid A (SAA) were measured. Percentages of neutrophils, lymphocytes, and monocytes with neutrophil expression of L-selectin and integrin αM were determined by flow cytometry. SAA (12-fold), IL-6 (3-fold), IL-8 (2-fold), and TNF-α (2-fold) were significantly elevated in sera of adult IgAV patients compared to HBDs. There was a 16% elevation in neutrophils in IgAV patients, with IgAV neutrophils showing significantly higher CD62L surface expression. IgAV patients with GIT involvement exhibited elevated numbers of leukocytes, neutrophils, and neutrophil/lymphocyte (NLR), but lower neutrophil CD11b expression, as compared to IgAV patients without GIT. IgAV patients exhibit a low–medium grade inflammatory, neutrophil-driven response. Patients with GIT can be distinguished by their elevated NLR.

IgA Vasculitis in Adults

Immunoglobulin A vasculitis (IgAV) is a small vessel vasculitis with skin, joint, gastrointestinal and renal manifestations. Our understanding of the natural history of this disease is limited due to the overall low incidence of IgAV in adults and a lack of consensus regarding diagnostic criteria. In this review, we describe IgAV in the adult population, focusing on diagnostic and classification systems, and treatments strategies. Recent data from larger longitudinal adult cohorts demonstrate that IgAV is associated with significant morbidity and mortality. Treatment regimen remains controversial but emerging retrospective observational data support potential benefit of immunosuppression. As illustrated in trials of IgA nephropathy, immunosuppression carries significant risks of toxicity. Treatment regimen and selection of patients who will benefit from treatment remains challenging. Prospective treatment trials are needed to elucidate both the patient populations that will derive benefit and what treatment is most efficacious.

A Model Predicting Short Term Severity of IgA Vasculitis in Adults

Background: Predictors of short term severity of adult immunoglobulin A vasculitis (IgAV) are unknown. We aimed to determine clinical features predicting the severity of acute adult IgAV and thus to aid the management of adult IgAV in daily practice. Methods: Medical records of adult, histologically proven IgAV cases, diagnosed between 01.01.2010 and 30.06.2016 at our secondary/tertiary rheumatology centre were reviewed. The disease activity was assessed using Birmingham vasculitis activity score-3. Renal disease was defined severe when nephrotic syndrome or nephritic syndrome with acute renal failure developed. Gastrointestinal (GI) disease was severe in case of bloody diarrhoea, ileus or bowel perforation. Results: During the 78-month observation period, we identified 184 new IgAV cases (57.1% male; 43.5% ever smokers). Skin, GI, renal and joint involvement were present in 184 (generalized purpura above the waist in 47.8%), 63 (severe in 16), 88 (severe in 23), and 81 patients, respectively. Four patients died during acute disease due to vasculitis. Patients with generalized skin lesions had more commonly GI tract, severe GI tract, and kidney involvement. Current smoking was strongly associated with severity of kidney disease. In logistic regression and classification tree model the history of new onset abdominal pain or the presence of generalized purpura in ever smoker emerged as the best predictors of severe GI or renal disease. Conclusions: Based on clinical characteristics only, the presence of abdominal pain, purpura above the waist and smoking history, seem to be good predictors of short term severity of adult IgAV.