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ObjectivesSevere infections contribute to morbidity and mortality in antineutrophil cytoplasm antibody-associated vasculitis (AAV). This study aimed to identify risk factors associated with severe infections in participants of the Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis (RAVE) trial.MethodsData on 197 patients recruited into the RAVE trial were analysed. Participants received either rituximab (RTX) or cyclophosphamide (CYC), followed by azathioprine (AZA). Clinical and laboratory data of patients with and without severe infections (≥grade 3, according to the Common Terminology Criteria for Adverse Events version 3.0) were compared. Risk factors for severe infections were investigated using Cox-regression models.ResultsEighteen of 22 (82%) severe infections occurred within 6 months after trial entry, most commonly respiratory tract infections (15/22, 68%). At baseline, lower absolute numbers of CD19+ cells were observed in patients with severe infections either receiving RTX or CYC/AZA at baseline, while CD5+B and CD3+T cells did not differ between groups. In Cox-regression analysis, higher baseline serum immunoglobulin M levels were associated with the risk of severe infections, whereby a higher baseline total CD19+B cell number and prophylaxis againstPneumocystis jiroveciiwith trimethoprim-sulfamethoxazole (TMP/SMX) with decreased risk of severe infections. Use of TMP/SMX was associated with lower risk of severe infections in both groups, receiving either RTX or CYC/AZA.ConclusionsThe use of low-dose TMP/SMX is associated with reduced risk of severe infections in patients with AAV treated with either RTX or CYC/AZA. Reduced B cell subpopulations at start of treatment might be a useful correlate of reduced immunocompetence.

Avoiding end-stage kidney disease in patients with anti-neutrophil cytoplasmic antibody–associated vasculitis (AAV) has a high therapeutic priority. Although renal response is a crucial measure to capture clinically relevant changes, clinal trials have used various definitions and no well-studied key surrogate markers to predict renal outcome in AAV exist. Differences in clinical features and histopathologic and therapeutic approaches will influence the course of kidney function. Its assessment through traditional surrogates (i.e. serum creatinine, glomerular filtration rate, proteinuria, hematuria and disease activity scores) has limitations. Refinement of these markers and the incorporation of novel approaches such as the assessment of histopathological changes using cutting-edge molecular and machine learning mechanisms or new biomarkers could significantly improve prognostication. The timing is favourable since large datasets of trials conducted in AAV are available and provide a valuable resource to establish renal surrogate markers and, likely, aim to investigate optimized and tailored treatment approaches according to a renal response score. In this review we discuss important points missed in the assessment of kidney function in patients with AAV and point towards the importance of defining renal response and clinically important short- and long-term predictors of renal outcome.

OBJECTIVE To evaluate disease flare and postvaccination reactions (reactogenicity) in patients with rheumatic and musculoskeletal diseases (RMDs) following 2-dose SARS-CoV-2 messenger RNA (mRNA) vaccination. METHODS RMD patients (n = 1,377) who received 2-dose SARS-CoV-2 mRNA vaccination between December 16, 2020 and April 15, 2021 completed questionnaires detailing local and systemic reactions experienced within 7 days of each vaccine dose (dose 1 and dose 2), and 1 month after dose 2, detailing any flares of RMD. Associations between demographic/clinical characteristics and flares requiring treatment were evaluated using modified Poisson regression. RESULTS Among the patients, 11% reported flares requiring treatment; there were no reports of severe flares. Flares were associated with prior SARS-CoV-2 infection (incidence rate ratio [IRR] 2.09, P = 0.02), flares in the 6 months preceding vaccination (IRR 2.36, P

As the severe acute respiratory syndrome coronavirus 2 pandemic evolved and became a global health threat, the safety of immunosuppression in antineutrophil cytoplasmic antibody-associated vasculitis (AAV) became of utmost important for clinicians and patients. Although timely initiation of immunosuppressive therapy is critical to quell the acute inflammation and prevent AAV-associated mortality and morbidity, concerns for increased susceptibility to Coronavirus Disease 2019 (COVID-19), delayed viral clearance, and decreased humoral response to infection led to speculation about modification in induction therapy practices may be deployed by physicians caring for patients with AAV. This international retrospective cohort study investigated the influence of the COVID-19 pandemic on AAV induction therapy and patient outcomes in different parts of the world by studying differences in treatment regimens in the United States, United Kingdom, and Europe.

BACKGROUND: The incidence of venous thromboembolism (VTE) is increased in ANCA-associated vasculitis (AAV). We assessed the frequency of VTE observed among patients with AAV evaluated at our center and identified risk factors. METHODS: Patients from the Johns Hopkins Vasculitis Center cohort who were evaluated between 1998 and 2018 and had a diagnosis of granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) were eligible for analysis. Baseline demographics and clinical and serologic data were extracted. Univariate and multivariate analyses were performed to identify factors associated with VTE in AAV. RESULTS: A total of 162 patients with AAV were identified, 105 (65%) with GPA; 22 (14%) of these patients had a recorded VTE with a median time to VTE of 1 month. The mean (SD) age in the VTE versus non-VTE groups was 54±20 versus 55±17 years (P=0.99), 64% versus 60% female (P=0.93), 82% versus 49% PR3-ANCA positive (P=0.01), with a total mean BMI of 33.3±5.7 versus 28.3±6.1 kg/m(2), (P

Anti-glomerular basement membrane (GBM) disease is a rare, aggressive vasculitis with no validated prediction tools to assist its management. We investigated a retrospective multicenter international cohort with the aim to transfer the Renal Risk Score (RRS) and to identify patients that benefit from rescue immunosuppressive therapy. Of a total 191 patients, 174 patients were included in the final analysis (57% female, median age 59 years). Using Cox and Kaplan-Meier methods, the RRS was found to be a strong and effective predictor for end stage kidney disease (ESKD) with a model concordance of C=0.760. The 36-month renal survival was 100%, 62.4%, and 20.7% in the low-, moderate-, and high-risk groups, respectively (P0.001). The need for renal replacement therapy (RRT) at diagnosis and the percentage of normal glomeruli in the biopsy were independent predictors of ESKD (P0.001, P0.001). Considering the 129 patients initially requiring RRT, the best predictor for renal recovery was the percentage of normal glomeruli (C=0.622; P0.001), a split either side of 10% providing good stratification. A model with the predictors RRT and normal glomeruli (N) achieved superior discrimination (C=0.840, P0.001). Dividing patients into four risk groups led to a 36-month renal survival of 96.4% (no RRT, N≥10%), 74.0% (no RRT, N10%), 42.3% (RRT, N≥10%) and 14.1% (RRT, N10%), respectively. In summary, we demonstrate that the RRS concept is transferrable to anti-GBM disease. Stratifying patients according to the need for RRT at diagnosis and renal histology improves prediction, highlighting the importance of normal glomeruli. Here, we propose a stratification to assist in the management of anti-GBM disease.

The ANCA-associated vasculitides are characterized by systemic necrotizing vasculitis involving small vessels and accompanied by the presence of circulating ANCAs. Left untreated, they are fatal, and therapeutic advances in the last 2 decades have transformed them to a disease of relapsing and

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of disorders characterized by inflammation and destruction of small- and medium-sized blood vessels and the presence of circulating ANCA. Clinical disease phenotypes include granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis, and renal-limited vasculitis. Serologic classification of AAV into proteinase 3-ANCA disease and myeloperoxidase-ANCA disease correlates with a number of disease characteristics. AAV has a predilection for the kidney, with >75% of patients having renal involvement characterized by rapidly progressive glomerulonephritis. The cause and pathogenesis of AAV are multifactorial and influenced by genetics, environmental factors, and responses of the innate and adaptive immune system. Randomized controlled trials in the past 2 decades have refined the therapy of AAV and transformed AAV from a fatal disease to a chronic illness with relapsing course and associated morbidity. This article in AJKD's Core Curriculum in Nephrology series provides a detailed review of the epidemiology, pathogenesis, diagnosis, and advances in the management of AAV.

Background: The benefits of treating anti-neutrophil cytoplasmic autoantibody-associated vasculitis (AAV) in advancing age remains unclear with most published studies defining elderly as ≥65 years. This study aims to determine outcomes of induction immunosuppression in patients aged ≥75 years. Methods: A cohort of patients aged ≥75 years with a diagnosis of AAV between 2006 and 2018 was constructed from 2 centres. Follow-up was to 2 years or death. Analysis included multivariable Cox regression to compare mortality and end-stage renal disease (ESRD) based on receipt of induction immunosuppression therapy with either cyclophosphamide or rituximab. A systematic review of outcome studies was subsequently undertaken amongst this patient group through Pubmed, Cochrane and Embase databases from inception until October 16, 2019. Results: Sixty-seven patients were identified. Mean age was 79 ± 2.9 years and 82% (n = 55) received induction immunosuppression. Following systematic review, 4 studies were eligible for inclusion, yielding a combined total of 290 patients inclusive of our cohort. The aggregated 1-year mortality irrespective of treatment was 31% (95% CI 25–36%). Within our cohort, induction immunosuppression therapy was associated with a significantly lower 2-year mortality risk (hazard ratio [HR] 0.29 [95% CI 0.09–0.93]). The pooled HR by meta-analysis confirmed this with a significant risk reduction for death (HR 0.31 [95% CI 0.16–0.57], I2 = 0%). Treated patients had a lower pooled rate of ESRD, but was not statistically significant (HR 0.71 [95% CI 0.15–3.35]). Conclusion: This meta-analysis suggests that patients ≥75 years with AAV do benefit from induction immunosuppression with a significant survival benefit. Age alone should not be a limiting factor when considering treatment.

Objective To assess the frequency of venous thromboembolism (VTE) events in the Rituximab in Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis (RAVE) trial and identify novel potential risk factors. Methods VTE events in 197 patients enrolled in the RAVE trial were analyzed. Baseline demographic and clinical characteristics were recorded, and univariate and multivariate analyses were performed to identify factors associated with VTE in ANCA-associated vasculitis (AAV). Results VTE occurred in 16 patients (8.1%) with an overall average time to event of 1.5 months (range 1.0-2.75). In univariate analyses with calculation of hazard ratios (HRs) and 95% confidence intervals (95% CIs), heart involvement (HR 17.408 [95% CI 2.247-134.842]; P = 0.006), positive proteinase 3 (PR3)-ANCA (HR 7.731 [95% CI 1.021-58.545]; P = 0.048), pulmonary hemorrhage (HR 3.889 [95% CI 1.448-10.448]; P = 0.008), and the presence of red blood cell casts (HR 15.617 [95% CI 3.491-69.854]; P

SARS-CoV-2 vaccination elicited high levels of immunogenicity in immunocompetent people in the original vaccine trials1 2 though recent studies have shown blunted immunogenicity in patients with rheumatic diseases treated with lymphocyte depleting agents.3 4 B-lymphocytes have been implicated in the pathogenesis of anti-neutrophil cytoplasmic antibidy (ANCA)-associated vasculitis (AAV) and B-cell-targeted therapy with rituximab is recognised as an established induction and maintenance strategy in management.5 6 SARS-CoV-2 infection in patients with AAV has been associated with severe outcomes,7 while rituximab has been associated with worse outcomes among patients infected with SARS-CoV-2.8 9 A recent study by Bonelli et al found evidence of an ameliorated humoral response but possible inducible cellular response in five patients treated with rituximab.10 We studied the tolerability and humoral response to the SARS-CoV-2 vaccine series in 48 patients with a diagnosis of AAV. Patients underwent SARS-CoV-2 antispike antibody testing to assess humoral response. Antibody testing was performed using antispike IgG enzyme immunoassay (Roche Elecsys via Quest, DiaSorin Liaison assay via LabCorp or Euroimmun via Hopkins lab). Demographics, clinical information including immunosuppressive therapy were extracted from medical records. Time from last rituximab administration to receipt of the first dose of the vaccine was recorded. We recorded serum creatinine, white blood cell count, serum immunoglobulins, Cluster of CD19 and …

Scleroderma Renal Crisis (SRC) is the most common cause of Acute Kidney Injury (AKI) in scleroderma and occurs early during the disease course while ANCA Associated Vasculitis (AAV) is a rare cause of acute kidney injury occurring late in the disease course. We report a case of AKI with positive PR3 ANCA serology late in the disease course with a renal biopsy revealing findings of SRC.

Purpose of Review There is ongoing debate concerning the classification of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. That is, whether classification should be based on the serotype (proteinase 3 (PR3)- or myeloperoxidase (MPO)-ANCA) or on the clinical phenotype (granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA)). To add clarity, this review focused on integration of the most recent literature. Recent Findings Large clinical trials have provided evidence that a serology-based risk assessment for relapses is more predictive than distinction based on the phenotype. Research conducted in the past decade indicated that a serology-based approach more closely resembles the genetic associations, the clinical presentation (i.e., lung involvement), biomarker biology, treatment response, and is also predicting comorbidities (such as cardiovascular death). Summary Our review highlights that a serology-based approach could replace a phenotype-based approach to classify ANCA-associated vasculitides. In future, clinical trials and observational studies will presumably focus on this distinction and, as such, translate into a “personalized medicine.”

There continues to be rapid advancement in our understanding of the pathogenesis of immune-mediated kidney disease. This progress has culminated in the development of multiple therapeutic agents that have consistently improved renal and patient outcomes. The focus of this review is to discuss these recent advancements in immune-mediated kidney disease via the lens of direct and indirect immune-mediated mechanisms. In the direct immune-mediated disease, recently described antigens in anti-glomerular basement membrane (GBM) disease and membranous nephropathy are discussed, along with new therapeutic regimens in membranous nephropathy and focal segmental glomerulosclerosis. From an indirect immune-mediated disease standpoint, recent pivotal trials in antineutrophil cytoplasmic antibody vasculitis, lupus nephritis, and IgA nephropathy are examined from a real-world practice perspective. New molecular pathways in various disorders of alternate complement pathway are described, which in turn have led to development of various experimental therapies. In addition, pivotal and ongoing therapeutic trials in the aforementioned diseases are presented.

Introduction The coronavirus 2019 (COVID-19) pandemic has brought on challenges not only to acute care, but also chronic care of patients. Individuals maintained on immunosuppression appear to be especially susceptible to COVID-19 infection. Patients with ANCA-associated vasculitis (AAV) frequently require immunosuppression and may be at increased risk for developing COVID-19. The incidence and impact of COVID-19 on patients with AAV is currently not known. We aimed to investigate this impact via a telephone questionnaire-based patient survey and chart review. Methods A cross-sectional study of AAV patients followed at two centers was conducted. Data regarding demographics, disease characteristics and therapy were confirmed by chart review. A telephone survey was conducted to ascertain symptoms and contact exposure related to COVID-19, as well as changes in health care delivery during the pandemic period between January and July, 2020. Results Of the 206 patients surveyed, the median age was 64 years, 51% were female and mean (SD) disease duration was 7 (5) years. The majority had kidney (n = 160) and lung (n = 108) involvement. Seventy-five percent (n = 155) were receiving immunosuppression, with 77 patients (50%) receiving rituximab during the pandemic period. Of the 10 patients tested for severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) by PCR, three were positive. Patients had a significant disruption in care; none had an in-person visit and 69% had a telemedicine consultation. Rituximab maintenance was postponed in 21 patients. Twelve patients experienced disease relapse. Conclusion The incidence of COVID-19 in patients with AAV appears to be similar to that of the general population. For a patient population that requires active clinical surveillance, there is significant disruption in care as a result of the pandemic. Reduction of immunosuppression may not be indicated, and the risk of relapse likely far outweighs the risk of COVID-19. Electronic supplementary material The online version of this article (10.1007/s40620-020-00881-3) contains supplementary material, which is available to authorized users.

Objective To investigate the occurrence of venous thromboembolic events (VTE) in a large cohort of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) across the European Union, Turkey, Russia, UK and North America. Methods Patients with a definite diagnosis of AAV who were followed for at least 3 months and had sufficient documentation were included. Data on VTE, including either deep vein thrombosis or pulmonary embolism, were collected retrospectively from tertiary vasculitis centres. Univariate and multivariate regression models were used to estimate odds ratios (ORs) and 95% CIs. Results Over a median follow-up of 63 (interquartile range: 29, 101) months, VTE occurred in 278 (9.7%) of 2869 AAV patients with a similar frequency across different countries (from 6.3% to 13.7%), and AAV subtype [granulomatosis with polyangiitis: 9.8% (95% CI: 8.3, 11.6%); microscopic polyangiitis: 9.6% (95% CI: 7.9, 11.4%); and eosinophilic granulomatosis with polyangiitis: 9.8% (95% CI: 7.0, 13.3%)]. Most VTE (65.6%) were reported in the first-year post-diagnosis. Multiple factor logistic regression analysis adjusted for sex and age showed that skin (OR 1.71, 95% CI: 1.01, 2.92), pulmonary (OR 1.78, 95% CI: 1.04, 3.14) and kidney [eGFR 15–60 ml/min/1.73 m2, OR 2.86 (95% CI: 1.27, 6.47); eGFR Conclusion Two-thirds of VTE occurred during the initial phase of active disease. We confirmed previous findings from smaller studies that a decrease in kidney function, skin involvement and pulmonary disease are independently associated with VTE.

Since the first description of infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China in December 2019, it has evolved into a pandemic and emerged as an unprecedented worldwide crisis overwhelming healthcare systems globally. Analysis of the available literature to date suggests that, in addition to older age, patients with underlying co-morbidities including hypertension, diabetes, heart disease are at higher risk for severe disease with increased mortality. Practitioners around the world also have become increasingly concerned that immunosuppressed patients including those with autoimmune diseases may be at increased risk for developing Coronavirus Disease 2019 (COVID-19) with serious complications. Very little is known about how anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis modifies the susceptibility, clinical presentation and disease course of COVID-19. In this review, we discuss the mechanism of action and challenges of the current therapeutic armamentarium of ANCA-associated vasculitis and outline approaches to management of ANCA-associated vasculitis during the COVID-19 pandemic.

Objective Hydralazine has been implicated as an etiologic agent for lupus-like syndrome and vasculitis. Hydralazine-induced vasculitis frequently affects the kidney, but the long-term renal outcomes in these patients have not yet been studied. Methods Patients who had a diagnosis of ANCA-associated vasculitis (AAV) and were on hydralazine at the time of AAV diagnosis were included in this retrospective cohort study. Clinical and laboratory data were obtained from the review of medical records. Results Seven patients met the criteria for hydralazine-induced AAV. Five patients (71%) were African-American and four (57%) were female. The median age was 69 years at the time of diagnosis. All patients had renal involvement with two of them showing lung involvement as well. All patients had positive MPO antibody and one patient had positive PR3 antibody. ANA was positive in all patients, and three of seven patients had positive anti-histone antibody. All of them were treated with immunosuppression and withdrawal of hydralazine. Three patients reached end-stage renal disease. The median follow-up time was 13 months. Conclusion Renal involvement in hydralazine-induced AAV was universal and can be associated with a poor renal outcome despite immunosuppressive therapy.

The Coronavirus Disease 2019 (COVID-19) pandemic influenced the management of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. A paucity of data exists on outcome of patients with vasculitis following COVID-19, but mortality is higher than in the general population and comparable to patients undergoing haemodialysis or kidney transplant recipients (reported mortality rates of 20–25%). Delays in diagnosis have been reported, which are associated with sequelae such as dialysis-dependency. Management of ANCA-associated vasculitis has not changed with the aim to suppress disease activity and reduce burden of disease. The use of rituximab, an important and widely used agent, is associated with a more severe hospital course of COVID-19 and absence of antibodies following severe acute respiratory syndrome (SARS)-CoV-2 infections, which prone patients to re-infection. Reports on vaccine antibody response are scarce at the moment, but preliminary findings point towards an impaired immune response, especially when patients receive rituximab as part of their treatment. Seropositivity was reported in less than 20% of patients when rituximab was administered within the prior six months, and the antibody response correlated with CD19+ B-cell repopulation. A delay in maintenance doses, if disease activity allows, has been suggested using a CD19+ B-cell guided strategy. Other immunosuppressive measures, which are used in ANCA-associated vasculitis, also impair humoral and cellular vaccine responses. Regular measurements of vaccine response or a healthcare-policy time-based strategy are indicated to provide additional doses (“booster”) of COVID-19 vaccines. This review summarizes a recent educational forum and a recent virtual meeting of the European Vasculitis Society (EUVAS) focusing on COVID-19.

Background: The prognostic value of the anti-neutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis (GN) classification has been demonstrated in several cohorts with sclerotic class having the worst renal outcome. Relevant published data on factors predicting outcomes in sclerotic ANCA GN is limited. Methods: Sclerotic ANCA GN patients were recruited from 5 centers worldwide for this retrospective cohort study. We describe the clinical characteristics of this cohort and evaluate predictors of 1-year glomerular filtration rate (GFR) and end-stage renal disease (ESRD). Kidney function at 12 months as measured by Modification of Diet in Renal Disease estimated GFR (eGFR) was modeled by simple and multiple linear regression analyses. We used Cox proportional hazards regression modeling to evaluate ESRD-free survival. Results: Of the 50 patients, 92% were Caucasian and 60% male with a mean age of 61 years. While 72% had renal limited disease, 82% were MPO ANCA positive. Kidney biopsies contained a median of 20 (interquartile range [IQR] 15–34) glomeruli with 96% showing moderate to severe interstitial fibrosis. Overall, 96% of patients received immunosuppressive drug therapy and 16% received plasmapheresis. Treatment response was achieved in all but 1 patient. The median (IQR) eGFR at entry was 14.5 (9–19) mL/min/1.73 m2. Over a median (IQR) follow-up of 33.5 (17–82) months, 26 patients reached ESRD. Ten patients died with 6 of the deaths occurring within the first year of diagnosis. The hazard of progression to ESRD was significantly higher in those with lower GFR at study entry (p = 0.003) and with higher degree of tubular atrophy (p = 0.043). Conclusions: Renal recovery is rare among sclerotic ANCA GN patients requiring dialysis at entry and 12% of patients died in the first year. Entry GFR and tubular atrophy were significant predictors of GFR at 12 months and renal survival in patients with sclerotic class ANCA GN.

Objectives Intravenous immunoglobulin G (IVIG) is used to treat antineutrophil cytoplasmic antibody (ANCA) patients with recurrent infections as a result of hypogammaglobulinemia (HG) induced by treatment regimens. We sought to characterize clinical features, treatment, and outcomes for patients treated with the novel subcutaneous IgG (SCIG) for the aforementioned purpose. Methods We conducted a retrospective study of 136 patients in our ANCA database to identify patients with recurrent infections and HG subsequently treated with SCIG. Patient demographics, serologies, treatment, and immunological parameters were assessed. Results Of 136 patients, four were treated with SCIG. All were Caucasian, proteinase-3 (PR3)-positive, and the majority (n = 3) were females. All patients had pulmonary involvement, and regimens of cyclophosphamide (CYC) and/or rituximab (RTX) were employed for induction and remission. Three patients each experienced recurrent bouts of respiratory tract infections and shingles. Ig levels (G, M, and A) were reduced in all patients, except for one patient who had normal IgA levels. CD19/20 cells were depleted and CD3/4/8/NK cells were preserved in all patients. Three patients had no discernible antibody response to the pneumococcal vaccine (specific pneumococcal serotypes measured pre- and post-vaccine). The mean duration elapsed between the first rituximab administration and commencement of SCIG was 7.2 years. The IgG level normalized and none of the patients had a recurrence of infection since the initiation of SCIG. Conclusion This data, albeit preliminary, is the first series that demonstrates SCIG can be a reliable alternative to IVIG in ANCA patients with recurrent infections secondary to HG. Early identification of this subset of patients is likely to mitigate infectious risks, associated morbidity, and hospitalization.

Introduction The use of hydralazine has been associated with the development of lupus erythematosus and lupus-like syndromes. We performed this retrospective study to identify clinical characteristics of individuals who developed hydralazine-induced lupus. Material and methods We performed a single-center retrospective review of seven individuals who had a diagnosis of hydralazine-induced lupus by International Classification of Diseases, Ninth Revision (ICD9) code and were on hydralazine prior to their diagnosis. Clinical and laboratory data were obtained from a review of the medical record up to 12-month follow-up. Results Of the seven individuals with hydralazine-induced lupus, five were Caucasian (71%) and two were African-American. The mean age at the time of diagnosis was 62 years. Four (57%) were male. The majority of individuals were exposed to hydralazine for more than 12 months (83%). Four individuals had biopsy-proven lupus nephritis and four individuals had cardiopulmonary and skin involvement. Six patients were positive for antinuclear antibody (ANA) with a homogenous pattern, and five of those were positive for anti-histone antibody. Additionally, positive anti-double-stranded DNA (anti-dsDNA) antibody, anti-cardiolipin antibodies, low complements, positive lupus anticoagulant, and leukopenia were seen in 42% of our cohort. Of the five individuals in whom anti-myeloperoxidase (MPO) antibody was strongly positive, all had renal involvement defined by an elevated creatinine with three having biopsy-proven lupus nephritis. Three other individuals with MPO positivity had concurrent cardiopulmonary and skin involvement. Four individuals were positive for anti-proteinase 3 (PR3) antibody, three of whom were strongly positive with renal involvement defined by an elevated creatinine with two having biopsy-proven lupus nephritis. The level of anti-dsDNA antibody and anti-PR3 antibody normalized at three months while anti-MPO antibody took 12 months to normalize following cessation of hydralazine. When checked, low complement component 3 (C3) and anti-histone antibody persisted past 12 months. In addition to the withdrawal of hydralazine, six individuals were treated with hydroxychloroquine and five with mycophenolate mofetil. Three of four individuals with renal involvement received plasmapheresis and two received cyclophosphamide and hemodialysis. Conclusion Hydralazine can aggravate and unmask incipient lupus. Since the presentation can be varied, early recognition of symptoms is critical. Precautions should be taken before initiating this medication in individuals with certain risk factors. Once diagnosed, potential serological findings such as a positive anti-MPO/anti-PR3 antibody could predict more severe manifestations such as pulmonary-renal complications.

Overt renal disease in primary Sjögren's syndrome (pSS) manifests as interstitial nephritis and glomerulonephritis. This single centre study aims to describe the natural history and treatment outcome of renal disease in pSS.pSS patients with renal disease were identified, and clinical features, renal biopsy findings, treatment details and renal outcome were recorded.Of the 20 pSS patients with renal disease, 14 had interstitial nephritis (IN), 3 had glomerulonephritis (GN) and 3 had both entities. In the IN group, 3 patients presented with chronic kidney disease (CKD), 4 with renal tubular acidosis (RTA), 2 with symptomatic hypokalaemia, 4 with renal colic and 1 with haematuria/proteinuria. Eight of 14 patients with IN received systemic immunosuppression (IS) during renal disease course and in 6 patients no beneficial effect was observed on renal function, hypokalaemia and RTA. Six of 14 IN patients developed CKD while 5 of them preserved normal renal function during follow-up. In the GN group, 2 patients presented with CKD, 3 with proteinuria/haematuria and 1 with nephrotic proteinuria. GN renal biopsy findings revealed membranoproliferative (MPGN) (n=3), focal segmental glomerulosclerosis (n=1) and fibrillary glomerulopathy (n=1). All 3 MPGN patients had cryoglobulinaemia and in 1 patient cryoglobulinaemic MPGN was clinically diagnosed. All GN patients were treated with immunosuppressive therapy, with stabilisation or improvement of renal function in the 4 cryoglobulinaemia-associated GN patients only.Interstitial nephritis follows a slow course and does not improve with systemic immunosuppression while GN has a favourable treatment response in those with MPGN pathology.