CanVasc consensus recommendations for the use of avacopan in antineutrophil cytoplasm antibody-associated vasculitis: 2022 addendum.

OBJECTIVE: In 2020, the Canadian Vasculitis Research Network (CanVasc) published their updated recommendations for the management of ANCA-associated vasculitides (AAV). The current addendum provides further recommendations regarding the use of avacopan in AAV based on a review of newly available evidence. METHODS: An updated systematic literature review on avacopan (formerly, CCX168) using Medline, Embase, and the Cochrane Library was performed for publications up to September 2022. New recommendations were developed and categorized according to the EULAR grading levels, as done for previous CanVasc recommendations. A modified Delphi procedure and videoconferences were used to reach ≥80% consensus on the inclusion, wording and grading of each recommendation. RESULTS: Three new recommendations were developed. They focus on avacopan therapy indication and duration, as well as timely glucocorticoid tapering. CONCLUSION: These 2022 addended recommendations provide rheumatologists, nephrologists and other specialists caring for patients with AAV with guidance for the use of avacopan, based on current evidence and consensus from Canadian experts.

VEXAS syndrome: A review of bone marrow aspirate and biopsies reporting myeloid and erythroid precursor vacuolation.

Myeloid and erythroid precursor vacuolation is a common dysplastic finding associated with myeloid malignancies, toxins, drug, and nutritional deficiencies. It has been described as a core morphologic feature in VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. We sought to determine the number of cases attributable to VEXAS syndrome in bone marrow biopsies and aspirates (BAMB) reporting myeloid precursor vacuolation. We reviewed 1318 individual BAMB reports from January 2020 to July 2021 where "vacuole(s)," "vacuolation," or "vacuolated" was reported. Bone marrow biopsies with vacuolation confined to blasts or those completed as routine workup prior to stem cell transplant or post induction chemotherapy for AML (acute myeloid leukemia) were excluded. Myeloid and erythroid precursor vacuolation was noted in 219 reports representing 210 patients. The most common etiology was myelodysplastic syndrome (MDS) (38.6%), AML (16.7%), lymphoproliferative disorders and multiple myeloma (7.6%), drug or toxin exposure (5.2%) myeloproliferative neoplasm (MPN) or MPN/MDS overlap syndrome (4.3%). VEXAS syndrome was determined to be the etiology in 2.9% of patients. Two additional cases of VEXAS syndrome with bone marrow biopsies reported in the specified time frame did not explicitly report myeloid or erythroid precursor vacuolation but were identified based on clinical suspicion and repeat BAMB review. Myeloid and erythroid precursor vacuolation is a dysplastic feature attributable to VEXAS syndrome in at least 2.9% of cases. Standardized reporting of vacuolization, triaging of molecular sequencing and optimal treatment of this disorder are critical issues facing those seeing patients with suspected VEXAS syndrome.

Causes of hypereosinophilia in 100 consecutive patients.

BACKGROUND: Hypereosinophilia (HE, persistent peripheral blood eosinophilia > 1.5 × 109 /L) and hypereosinophilic syndrome (HES, HE with end-organ damage) are classified as primary (due to a myeloid clone), secondary (due to a wide variety of reactive causes), or idiopathic. Diagnostic evaluation of eosinophilia is challenging, in part because secondary causes of HE/HES such as lymphocyte-variant HES (L-HES) and vasculitis are difficult to diagnose, and emerging causes such as immunoglobulin G4-related disease (IgG4-RD) have rarely been examined. OBJECTIVE AND METHODS: We reviewed 100 consecutive patients with HE/HES who underwent extensive evaluation for primary and secondary eosinophilia at a single tertiary care center to determine causes of HE/HES in a modern context. RESULTS: Six patients had primary HE/HES, 80 had a discrete secondary cause identified, and 14 had idiopathic HE/HES. The most common causes of secondary eosinophilia were L-HES/HES of unknown significance (L-HESus) (20), IgG4-RD (9), and eosinophilic granulomatosis with polyangiitis (EGPA) (8). CONCLUSIONS: In contrast to other large published series of HE/HES, most patients in this study were found to have a discrete secondary cause of eosinophilia and only 14 were deemed idiopathic. These findings highlight the importance of extensive evaluation for secondary causes of eosinophilia such as L-HES, IgG4-RD, and EGPA.

Mortality in ANCA-associated vasculitis: ameta-analysis of observational studies.

OBJECTIVE: To determine the magnitude of all-cause mortality risk in patients with antineutrophil cytoplasmic antibodies-associated vasculitis (AAV) compared with the general population through a meta-analysis of observational studies. METHODS: We searched Medline and Embase databases from their inception to April 2015. Observational studies that met the following criteria were assessed by two researchers: (1) clearly defined AAV identified by either the American College of Rheumatology 1990 classification criteria or the 2012 Chapel Hill Consensus Conference disease definitions, and (2) reported standardised mortality ratios (SMR) and 95% CI. We calculated weighted-pooled summary estimates of SMRs (meta-SMRs) for all-cause mortality using random-effects model, tested for publication bias and heterogeneity. RESULTS: Ten studies met the inclusion criteria, comprising 3338 patients with AAV enrolled from 1966 to 2009, and a total of 1091 observed deaths. Overall, we found a 2.7-fold increased risk of death in patients with AAV when compared with the general population (meta-SMR: 2.71 (95% CI 2.26 to 3.24)). Analysis on studies that included only granulomatosis with polyangiitis cases also indicated a similar mortality risk (meta-SMR: 2.63 (95% CI 2.02 to 3.43)). There was no significant publication bias or small-study effect. Subgroup analyses showed that mortality risks were higher in older cohorts, with a trend towards improvement over time (ie, those with their midpoint of enrolment periods that were between 1980-1993 and 1994-1999, vs 2000-2005). CONCLUSION: Published data indicate there is a 2.7-fold increase in mortality among patients with AAV compared with the general population.

Single organ hepatic artery vasculitis as an unusual cause of epigastric pain: A case report.

BACKGROUND: Single-organ vasculitis (SOV) is characterized by inflammation of a blood vessel, affecting one organ, such as the skin, genitourinary system, or the aorta without systemic features. Gastrointestinal SOV is rare, with hepatic artery involvement reported only in two prior published cases. Herein, we presented a case of isolated hepatic artery vasculitis presenting after Pfizer-BioNTech mRNA corona virus disease 2019 (COVID-19) vaccination. CASE SUMMARY: A 50-year-old woman with hypertension presented to our Emergency Department with recurrent diffuse abdominal pain that localized to the epigastrium and emesis without diarrhea that began eight days after the second dose of the Pfizer-BioNTech COVID-19 vaccine. Blood work revealed an elevated C-reactive protein (CRP) of 19 mg/L (normal < 4.8 mg/L), alkaline phosphatase 150 U/L (normal 25-105 U/L), gamma-glutamyl transferase (GGT) 45 U/L (normal < 43 U/L) and elevated immunoglobulins (Ig) G 18.4 g/L (normal 7-16 g/L) and IgA 4.4 g/L (normal 0.7-4 g/L). An abdominal computed tomography revealed findings in keeping with hepatic artery vasculitis. A detailed review of her history and examination did not reveal infectious or systemic autoimmune causes of her presentation. An extensive autoimmune panel was unremarkable. COVID-19 polymerase chain reaction nasopharyngeal swab, human immunodeficiency virus, viral hepatitis and Heliobacter pylori serology were negative. At six months, the patient's symptoms, and blood work spontaneously normalized. CONCLUSION: High clinical suspicion of SOV is required for diagnosis in patients with acute abdominal pain and dyspepsia.

Increased risk of venous thromboembolism in patients with granulomatosis with polyangiitis: A population-based study.

We assessed the risk and time trends of venous thromboembolism (VTE) including pulmonary embolism (PE) and deep venous thrombosis (DVT) in new granulomatosis with polyangiitis (GPA) cases compared to the general population. Using a population-level database from the entire province of British Columbia, Canada, we conducted a matched cohort study of all patients with incident GPA with up to ten age-, sex-, and entry time-matched individuals randomly selected from the general population. We compared incidence rates of VTE, PE, and DVT between the two groups, and calculated hazard ratios (HR), adjusting for relevant confounders. Among 549 individuals with incident GPA (57.6% female, mean age 55.4 years), the incidence rates for VTE, PE, and DVT were 7.22, 2.73, and 6.32 per 1,000 person-years, respectively; the corresponding rates were 1.36, 0.74, and 0.81 per 1,000 person-years among the 5,490 non-GPA individuals. Compared with the non-GPA cohort, the fully adjusted HRs among GPA patients were 2.90 (95% CI, 1.10-7.64), 4.70 (95% CI, 1.74-12.69), and 1.66 (95% CI, 0.52-5.27) for VTE, PE, and DVT, respectively. The risks of VTE, PE, and DVT were highest during the first year after GPA diagnosis with HR (95% CI) of 11.04 (1.37-88.72), 26.94 (4.56-159.24), and 2.68 (0.23-31.21), respectively. GPA patients are at significantly increased risk of PE, but not DVT. Monitoring for these complications is particularly warranted in this patient population, especially early after diagnosis.

Variations in Takayasu arteritis characteristics in a cohort of patients with different racial backgrounds.

OBJECTIVES: We aimed to describe differences in disease characteristics and outcomes in Takayasu arteritis (TA) patients with different racial backgrounds. METHODS: This was a retrospective cohort study consisting of TA patients seen at specialty vasculitis clinics from five academic hospitals across Canada. Disease features, treatments and outcomes were compared between White and non-White patients. RESULTS: The cohort included 113 patients, of which 51 were White. Over 50% of the non-White patients were Asian. Compared to non-White patients, White patients had higher CRP and ESR at diagnosis (33.6 mg/l versus 9.4 mg/l, p = 0.033; and 51 mm/h versus 24 mm/h, p = 0.047; respectively), and were less likely to have baseline cardiovascular comorbidities including dyslipidemia (11.8% versus 29%, p = 0.037). There were no significant differences between racial groups for other disease characteristics or outcomes. CONCLUSION: Patient race did not appear to play a significant role in determining disease characteristics and outcomes when comparing TA patients from various racial backgrounds living in the same country.

Rheumatology health care providers' views and practices on obesity and smoking cessation management in rheumatoid arthritis.

OBJECTIVE: To assess rheumatology health care providers' (HCPs) knowledge, beliefs, self-efficacy, practices, and perceived barriers pertaining to weight management and smoking cessation counselling in patients with rheumatoid arthritis (RA). METHOD: We administered an online survey to collect self-reported data on rheumatology HCPs' knowledge, beliefs, self-efficacy, perceived barriers, and practices related to weight management and smoking cessation counselling. Participants were recruited through invitation emails (with anonymous survey links) sent by three Canadian rheumatology organizations. RESULTS: Fifty-nine rheumatology HCPs (15 nurses, 44 physicians) completed the survey (response rate: 11%). Over 85% correctly identified associations between obesity, or smoking, and more severe or active RA, as well as poorer response to treatment. All but one participant agreed that it was part of their responsibility to discuss these issues with patients, but 78% (46/59) felt not or slightly confident in their ability to help patients quit smoking or achieve clinically significant weight loss. The majority did not routinely assist patients in accessing appropriate resources or providers (only 42% did for obesity, 36% for smoking), send referrals (2-44%, depending on referral), or offer relevant educational materials (15% for obesity, 20% for smoking). Common barriers included competing demands and lack of time, training, access to expertise, and knowledge of available programs. CONCLUSION: Most rheumatology HCPs understood the implications of cigarette smoking and obesity in RA and accepted responsibility in addressing these issues. However, they lacked the time, training, confidence, and knowledge of local resources to do so effectively. There is a need to bridge this gap. Key Points • Training through medical and nursing school as well as residency on weight management and smoking cessation counselling was nearly unanimously described as poor or fair. • Most rheumatology health care providers understood the implications of cigarette smoking and obesity in rheumatoid arthritis and accepted responsibility in addressing these issues; however, they lacked the time, training, confidence, and knowledge of local resources to do so effectively. • There is a need to bridge the gap between health care providers' intentions and actions, and this may include the development of guides outlining local weight management and smoking cessation expertise, programs, referral processes, and educational materials.

Indications and diagnostic outcome of antineutrophil cytoplasmic antibody testing in hospital medicine: a pattern of over-screening.

INTRODUCTION/OBJECTIVE: Antineutrophil cytoplasmic antibodies (ANCA) serology can aid in the diagnosis and classification of ANCA-associated vasculitides (AAV). However, it is often ordered in patients without clinical manifestations of vasculitis. In this retrospective chart review, we aim to better understand the clinical practices on ANCA testing. METHODS: We retrospectively reviewed patients' charts for the indications and diagnostic outcomes of ANCA tests. All ANCA tests ordered at two Canadian hospitals (a community hospital and an academic tertiary hospital) between January and December 2016 were included in the study. Descriptive statistics are used. RESULTS: A total of 302 ANCA tests were included. The majority (n = 198, 65.6%) were ordered without an indication for testing. For those patients with at least 1 clinical manifestation of AAV (n = 104), 25% were ANCA positive and 18.3% resulted in a diagnosis of AAV. In comparison, among those without a clinical manifestation of AAV (n = 198), only 1.5% were ANCA positive and none was diagnosed with AAV. All patients diagnosed with AAV had at least 1 indication for ANCA testing. The three most common clinical presentations in patients with a final diagnosis of AAV were glomerulonephritis (81.8%), pulmonary hemorrhage (45.5%), and multiple lung nodules (31.8%). CONCLUSION: To our knowledge, this is the first study that evaluates patients with both positive and negative ANCA test results in an inpatient setting. We demonstrated a low rate of ANCA positivity and AAV diagnosis in patients without clinical manifestations of AAV. Overall, there is a high rate of ANCA testing without an indication at our academic institution. This over-testing may be curbed by strategies such as a gating policy, culture changes, and clinician education. Key Points • AAV is a clinical-pathological diagnosis, and despite the usefulness of ANCA testing, it does not confirm nor rule out AAV. • ANCA testing for the diagnosis of AAV is generally only indicated when there is a clear manifestation of AAV. • Although patients with AAV may occasionally present without classic signs and symptoms, the diagnostic utility of ANCA serology in this setting is low, and testing is more likely to result in a false-positive or false-negative test. • If clinical suspicion remains high despite negative ANCA testing, clinicians should seek consultation with a rheumatologist.

CanVasc Consensus Recommendations for the Management of Antineutrophil Cytoplasm Antibody-associated Vasculitis: 2020 Update.

OBJECTIVE: In 2015, the Canadian Vasculitis Research Network (CanVasc) created recommendations for the management of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV) in Canada. The current update aims to revise existing recommendations and create additional recommendations, as needed, based on a review of new available evidence. METHODS: A needs assessment survey of CanVasc members informed questions for an updated systematic literature review (publications spanning May 2014 to September 2019) using Medline, Embase, and Cochrane. New and revised recommendations were developed and categorized according to the level of evidence and strength of each recommendation. The CanVasc working group used a 2-step modified Delphi procedure to reach > 80% consensus on the inclusion, wording, and grading of each new and revised recommendation. RESULTS: Eleven new and 16 revised recommendations were created and 12 original (2015) recommendations were retained. New and revised recommendations are discussed in detail within this document. Five original recommendations were removed, of which 4 were incorporated into the explanatory text. The supplementary material for practical use was revised to reflect the updated recommendations. CONCLUSION: The 2020 updated recommendations provide rheumatologists, nephrologists, and other specialists caring for patients with AAV in Canada with new management guidance, based on current evidence and consensus from Canadian experts.

Polyarteritis nodosa isolated to the testis and urinary bladder in the setting of cryptorchidism: a case report and literature review.

BACKGROUND: Polyarteritis nodosa is a small vessel to medium vessel vasculitis that frequently presents with multi-organ involvement, but can sometimes be limited to single organs such as the testes. Patients often require treatment with glucocorticoids, plus or minus additional immunosuppressive therapy depending on the severity of the disease. We describe a rare case of polyarteritis nodosa involving the right testis and urinary bladder without other systemic features of vasculitis. CASE PRESENTATION: A previously healthy 54-year-old First Nations Canadian man presented with intermittent gross hematuria. He underwent surgical excision of his right testis for cryptorchidism and a transurethral resection of a bladder mass. Histology showed an active medium vessel vasculitis in both organs. On extensive clinical, laboratory, and radiographic review, he had no systemic features of vasculitis. On 2-year follow-up, he has not required any systemic therapy and has not developed further symptoms. CONCLUSION: Single organ polyarteritis nodosa can sometimes be managed with surgical excision of the involved organ alone. Although our patient had two organs involved, we extrapolated the results of our literature search to guide his care. This case highlights the potential for surgical excision to cure polyarteritis nodosa despite the involvement of two organs in the absence of symptoms and signs of systemic vasculitis.

Concurrent inflammatory myopathy and myasthenia gravis with or without thymic pathology: A case series and literature review.

OBJECTIVES: The association of myasthenia gravis (MG) and inflammatory myositis (IM) is rare and typically only one of the diseases is present. The management of the 2 diseases differs, therefore it is important to recognize the concomitant presentation. Here, we report a case series of 7 patients with co-existing MG and IM with review of the literature. METHOD: We identified 7 patients with concurrent MG and IM who were followed at the Neuromuscular Disease Program at a tertiary referral center in Vancouver, British Columbia from 2004 to 2017. RESULT: All 7 patients had ocular or bulbar involvement as manifestation of MG. Three patients had simultaneous onset of MG and IM, 2 of whom presented with myasthenia crisis and fulminant myositis. In the other 4 patients, MG was the initial presentation and IM occurred 3-11 years after MG. Among these 7 patients, 4 had underlying thymic pathology, including 2 with benign thymoma and 2 with stage IV thymoma; all 4 patients had antibodies to acetylcholine receptor (AChR). Of the 3 patients with no thymic pathology by imaging or histology, 2 had positive AChR antibody titer. For treatment, the thymoma was resected and chemotherapy was administered if appropriate. Additional immunosuppressive therapies including high-dose glucocorticoid, intravenous immunoglobulin (IVIG), methotrexate, mycophenolate, or cyclosporine were necessary to achieve remission. Two patients with no thymoma had refractory MG and IM, and both responded to rituximab. We also conducted a literature review on the clinical characteristics and management of this condition, and compared the previously reported cases to the patients in our series. CONCLUSION: This is one of the largest case series of MG-IM overlap with or without thymic pathology. In this cohort, the 2 disease entities can occur simultaneously, or one presents before the other. Most of the patients responded well to steroid, acetylcholinesterase inhibitor, and immunosuppressive agents. In very refractory cases, rituximab appeared to be effective, which has not been reported for the treatment of this condition before.