Impact of gender on baseline presentation and outcome in adult IgA vasculitis.

OBJECTIVES: Adult IgA vasculitis (IgAV) is more common in males, but the potential impact of gender remains unclear. We aimed to describe the impact of gender on presentation and outcome in adult IgAV. METHODS: We retrospectively analysed data from a multicentre retrospective cohort of 260 patients (IGAVAS). Comparisons were made according to gender status. RESULTS: Data from 259 patients (95 females and 164 males) were analysed. Compared with females, baseline presentation in males was similar for cutaneous involvement (100% vs 100%, p= 1.0), joint involvement (60% vs 63%, p= 0.7), gastrointestinal involvement (57% vs 45%, p= 0.093) and glomerulonephritis (73% vs 64%, p= 0.16). Glomerulonephritis was more severe at baseline in males than in females, with a lower median estimated glomerular filtration rate (eGFR) (90 [IQR 59-105] vs 97 ml/min/1.73m2 [76-116], p= 0.015) and increased median proteinuria (0.84 vs 0.58 g/day, p= 0.01). There were no differences in histological findings in patients who had a kidney biopsy. Methylprednisolone was more frequently used in males (40% vs22%, p= 0.015), as were immunosuppressants, especially cyclophosphamide 24% vs 6%, p= 0.0025) and azathioprine (10% vs 2%, p= 0.038). Analysis of treatment response showed that males had more frequent refractory disease (30% vs 13%, p= 0.004). Long-term outcomes (mortality and progression to chronic kidney failure) did not differ. CONCLUSION: Kidney involvement in IgAV appears to more severe in males, which is supported by more intensive treatment contrasting with a lower response rate. This study raises the question of gender as a new prognostic factor in adult IgAV.

New insights into epidemiological data and impact of the COVID-19 pandemic on IgA vasculitis in children and adults: a French nationwide cohort.

IgA vasculitis (IgAV) is a small size vasculitis for which epidemiologic data are strikingly lacking, especially about the adult form. Additionally, the COVID-19 pandemic seems to have profoundly modified the incidence of this disease. Here, we aimed to establish some relevant epidemiological data in both pediatric and adult IgAV. We performed an observational study using a national database called "BNDMR" on IgAV, which gathers patients managed in the French network of experts on rare diseases. We primarily performed descriptive statistics over the 2010-2022 period. Then, we compared the North-South geographical areas, the seasonality, and the impact of COVID-19 with that of other patients reported in the same centers. We collected data from 1988 IgAV patients. The sex ratio was 1.57 for adults and 1.05 for children. The annual incidence in 2021 was 0.06 for 100,000 adults and 0.50 for 100,000 children. Compared with other diseases reported into the BNDMR, IgAV was more common in the South than in the North of France (OR 4.88 [4.17-5.74] in adults and OR 1.51 [1.35-1.68] in children). IgAV was also observed more frequently in winter and autumn. Strikingly, we observed a decrease in incidence during the COVID-19 pandemic period in children (OR 0.62 [0.47-0.81]). Our study provides both new insights and confirmations of IgAV epidemiological data: winter and autumn seasonality, more pronounced male predominance in adults, decreasing incidence of pediatric IgAV during the COVID-19 pandemic and increasing incidence in the South of France.

Characteristics of ANCA-associated vasculitis with aneurysms: Case series and review of the literature.

INTRODUCTION: ANCA-associated vasculitis (AAV) is an exceptional cause of small and large vascular aneurysms. Here, we present the phenotypic characteristics of patients with AAV associated with the presence of aneurysms. METHODS: We conducted a retrospective multicenter study and a systematic review of the literature. Only AAV patients with positive ANCA results and > 1 aneurysm(s) were enrolled. Patients were recruited through a call of observations among the French Vasculitis Study Group (FVSG) and the French Internal Medicine Network. Patients with aneurysm rupture were compared to those without. RESULTS: We enrolled 51 patients in the cohort, including 31 (67%) with granulomatosis with polyangiitis. The median Birmingham Vasculitis Activity Score was 18 [6-41]. A total of 92 aneurysms were noted, 74% of which involved medium-sized arteries, particularly the renal artery. During a follow-up of 24 [6-56] months, 22 (43%) patients experienced aneurysmal rupture, 91% of which involved medium-sized vessels. Patients with aneurysmal rupture showed significantly more pulmonary infiltrates and higher creatinine levels at baseline than patients without rupture. Initial treatments did not differ between the two groups. Ten (20%) patients died during the follow-up, including three from an aneurysmal rupture. CONCLUSION: Aneurysms were more frequently observed in GPA patients and predominantly affected medium-sized vessels, especially the renal arteries. The risk of rupture was high and occurred in >40% of patients. Because of their increased mortality, further studies are required to better manage this subset of patients.

[Adult IgA vasculitis]. / Vascularite à IgA de l'adulte.

ADULT IGA VASCULITIS. IgA vasculitis previously named rheumatoid purpura is a rare systemic vasculitis in adults involving small vessels and associated with the presence of immunoglobulin A deposits. IgA vasculitis is often triggerd by infections, taking medication and vaccination. It is characterised by the presence of vascular purpura associated with joint (arthralgia), gastrointestinal (abdominal pain) and sometimes renal involvement (glomerulonephritis). Gastrointestinal involvement can be lifethreatening (bowel perforation), while the longterm prognosis is shaped by the renal involvement (renal failure). In most cases, the disease has a good outcome and only symptomatic treatment is recommended. In more severe forms, corticosteroids, combined with another immunosuppressant or biotherapy, may be discussed on a casebycase basis.

VASCULARITE À IGA DE L'ADULTE. La vascularite à IgA, anciennement appelée purpura rhumatoïde, est une vascularite systémique liée à la présence de dépôts d'immunoglobulines A dans les vaisseaux de petit calibre. Elle fait souvent suite à un facteur déclenchant, comme une infection du tractus respiratoire, la prise d'un médicament ou une vaccination. Elle est caractérisée par la présence d'un purpura vasculaire associé à une atteinte articulaire (arthralgies typiquement des chevilles), gastrointestinale (douleurs abdominales) et parfois rénale (glomérulonéphrite). Le pronostic vital peut être engagé par l'atteinte gastrointestinale (risque de perforation digestive), alors que le pronostic à long terme est lié à l'atteinte rénale (risque d'insuffisance rénale chronique). La maladie évolue généralement favorablement, et seul un traitement symptomatique est conseillé. Dans les formes plus sévères, des corticostéroïdes, associés à un immunosuppresseur ou une biothérapie, peuvent être discutés au cas par cas.

IgA vasculitis with underlying monoclonal IgA gammopathy: innovative therapeutic approach targeting plasma cells. A case series.

OBJECTIVE: There is currently no evidence of the possible benefit of plasma cell-targeting therapies (PCTT) in immunoglobulin A (IgA) monoclonal gammopathy (MG) associated with IgA vasculitis (IgAV). We report the outcome of different PCTT regimens in a cohort of MG-IgAV. METHODS: We used a French network to retrospectively describe the outcome of MG-IgAV patients treated with PCTT. RESULTS: Five patients were included (mean age 65 years). All patients had severe baseline presentation including extensive necrotic purpura (n = 5), gastrointestinal involvement (n = 2), peripheral neuropathies (n = 2), and glomerulonephritis (n = 1). Two patients had IgA indolent multiple myeloma and three had IgA "MG of undetermined significance." Monotypic IgA deposition in the skin vessels wall was highlighted using an immunofluorescence assay. Cases of vasculitis in three patients (n = 3) were refractory to multiple line therapies, including cyclophosphamide (n = 3) or rituximab. Finally, PCTT including bortezomib plus cyclophosphamide and dexamethasone, bortezomib plus melphalan and prednisone, or bortezomib plus lenalidomide and dexamethasone were proposed, allowing complete remission in 4/5 patients without major adverse drug events. CONCLUSION: This study suggests that the MG-IgAV phenotype might be distinctive of usual IgAV (severe and refractory to conventional immunosuppressive regimens) and supports the benefit of PCTT. This study sheds new light on the overall biology of IgAV, strengthening the pathogenic role of the monoclonal IgA component in IgAV.

New insights on IgA vasculitis with underlying solid tumor: a nationwide French study of 30 patients.

OBJECTIVE: IgA vasculitis (IgAV) frequently occurs during or after a mucosal infection; it also rarely occurs in patients with cancer. We hypothesized that cancer could impact the baseline characteristics and/or outcome of vasculitis. We aimed to describe the presentation of IgAV in patients with cancer (IgAV ca+) compared to patients without cancer. METHODS: We conducted a nationwide retrospective study of adult patients in France who presented with both IgAV and cancer. Baseline characteristics were described and compared with those of the 260 patients included in a nationwide French IgAV study. RESULTS: Thirty patients were included. The mean age was 69 ± 12 years; 80% were men. Compared to patients without underlying cancer, IgAV ca+ patients were older (69 ± 12 vs. 50 ± 18 years; p < 0.0001) and they presented more frequently with necrotic purpura (53 vs. 26%; p < 0.002) and intra-alveolar hemorrhage (10 vs. 0.5%; p < 0.0001). IgAV ca+ patients frequently had elevated serum IgA levels (79 vs. 53%; p < 0.034); most (n = 22, 73%) had adenocarcinoma or urothelial carcinoma involving the large intestines (n = 6), bladder (n = 5), and lung (n = 5). Most IgAV ca+ patients had progressive cancer (n = 21); a minority had metastatic disease (n = 2) at IgAV diagnosis. After a median follow-up of 3 months, 8 deaths were observed but none was related to IgAV. CONCLUSION: Compared to their noncancer counterpart, patients with IgAV related to cancer were older and more frequently presented with necrotizing purpura, intra-alveolar hemorrhage, and elevated serum IgA levels. Adult patients with IgAV and these latter characteristics should be carefully screened for cancer. Key Points • Clinical and biological characteristics of patients presenting with IgAV are distinct depending on the underlying cause of vasculitis related to cancer. • Patients with IgAV related to cancer are older, and compared to their counterparts without IgAV, they present more frequently with necrotic purpura, alveolar hemorrhage, and elevated serum IgA levels. • All adult patients with IgAV should be screened for cancer, and there should be a focus on elderly male patients presenting with necrotic purpura and/or alveolar hemorrhage.

IgA Vasculitis With Underlying Liver Cirrhosis: A French Nationwide Case Series of 20 Patients.

OBJECTIVE: Immunoglobulin A vasculitis (IgAV) and nephropathy (IgAN) share common immunological mechanisms. Liver cirrhosis is well known to be associated with IgAN. Here, we aimed to describe the presentation and outcome of IgAV patients with underlying cirrhosis. METHODS: We conducted a French nationwide retrospective study of adult patients presenting with both IgAV and cirrhosis. Baseline characteristics were compared to those of the 260 patients included in the French nationwide IgAV registry (IGAVAS). RESULTS: Twenty patients were included, and 7 (35%) were female. The mean ± SD age was 62.7 ± 11 years. At baseline, compared with IGAVAS patients, patients with underlying cirrhosis were older (62.7 ± 11 vs 50.1 ± 18, P < 0.01) and displayed more constitutional symptoms (weight loss 25% vs 8%, P = 0.03). Patients with underlying cirrhosis were also more likely to exhibit elevated serum IgA levels (5.6 g/L vs 3.6 g/L, P = 0.02). Cirrhosis and IgAV were diagnosed simultaneously in 12 patients (60%). Cirrhosis was mainly related to alcohol intake (n = 15, 75%), followed by nonalcoholic steato-hepatitis (n = 2), chronic viral hepatitis (n = 1), hemochromatosis (n = 1), and autoimmune hepatitis (n = 1). During follow-up with a median of 17 months (IQR 12-84), 10/13 (77%) exhibited IgAV remission at Month 3. One patient presented a minor relapse. Six patients died, but no deaths were related to IgAV. CONCLUSION: We report the first case series of IgAV patients with underlining cirrhosis, to our knowledge, which was mainly alcohol related. The liver disease did not seem to affect baseline vasculitis characteristics. Physicians should investigate the existence of liver cirrhosis at IgAV diagnosis, especially in the context of alcohol abuse.