Systemic Necrotizing Vasculitides Research Articles

Incidence of Tuberculosis in Systemic Necrotizing Vasculitides: A Population-Based Study From an Intermediate-Burden Country.

Objective: Tuberculosis (TB) has a significant impact on public health; however, its incidence in patients with systemic necrotizing vasculitides (SNV) remains unknown. Therefore, we evaluated the incidence of TB in patients with SNV using a nationwide claims database.Methods: The Health Insurance and Review Agency database was used to identify patients diagnosed with SNV between 2010 and 2018. The standardized incidence ratio (SIR) was calculated to compared the risk of TB between patients and the general population, based on the 2016 annual national TB report. The incidence of TB after SNV diagnosis was compared by estimating age- and sex- adjusted incidence rate ratio (IRR). A time-dependent Cox regression analysis was performed to estimate factors associated with TB.Results: Among the included 2,660 patients, 51 (1.9%) developed TB during the follow-up period. The risk of TB was significantly higher in patients with SNV [SIR 6.09, 95% confidence interval (CI) 4.53–8.00], both in men (SIR 5.95) and women (SIR 6.26), than in the general population; this increased risk was consistent in all disease subtypes, except eosinophilic granulomatosis with polyangiitis. Additionally, the incidence of TB was the highest in patients with SNV within the first 3 months after diagnosis (adjusted IRR: 8.90 compared to TB ≥ 12 months). In Cox regression analysis, the diagnosis of microscopic polyangiitis [hazard ratio (HR) 3.22, 95% CI 1.04–9.99], granulomatosis with polyangiitis (HR 4.63, 95% CI 1.53–14.02), and polyarteritis nodosa (HR 3.51, 95% CI 1.13–10.88) were independent factors associated with TB.Conclusion: Even when considering the high incidence of TB in the geographic region, the risk of TB increased in patients with SNV, with a difference based on disease subtypes. Moreover, taking into account of the high incidence of TB in SNV, vigilant monitoring for TB is required especially during the early disease period.

Handgrip strength is a comorbidity marker in systemic necrotizing vasculitides and predicts the risk of fracture and serious adverse events.

Sarcopenia has been associated with poor outcomes in various medical and surgical conditions. However, its impact in systemic necrotizing vasculitides (SNV) had never been characterized. We aimed to assess the prevalence, associated factors and prognostic impact of sarcopenia in SNV. Patients with SNV were successively included in a prospective longitudinal study assessing comorbidities. At inclusion, we evaluated sarcopenia by assessing skeletal muscle mass index using DXA and muscle strength using handgrip strength. Vasculitis and treatments-related events were recorded and analysed using Cox models. One hundred and twenty patients were included. At inclusion, low handgrip strength (<30 kg for men and 20 kg for women) was identified in 28 (23%) patients, while no patient exhibited low skeletal muscle mass index (<7.23 kg/m2 for men and 5.67 kg/m2 for women). Low handgrip strength was associated with age (P<0.0001), type of vasculitis (P=0.01), vasculitis damage index (P=0.01), history of falls (P=0.0002), osteoporosis (P=0.04), low serum albumin (P=0.003) and prealbumin (P=0.0007), high CRP (P=0.001), high FRAX® tool (P=0.002) and low bone mineral density at femoral neck (P=0.0002). After median follow-up of 42 months, low handgrip strength was associated with higher risk of bone fracture [HR 4.25 (1.37-13.2), P=0.01] and serious adverse events [HR 2.80 (1.35-5.81), P=0.006]. Handgrip strength is associated in SNV with nutritional status and comorbidities such as bone disease, and seems to predict, as in other medical conditions, the risk of fracture and serious adverse events during follow-up. In contrast, assessment of skeletal muscle mass index in this population remains uncertain.

Corrigendum to: Predictive factors of severe infections in patients with systemic necrotizing vasculitides: data from 733 patients enrolled in five randomized controlled trials of the French Vasculitis Study Group.

OBJECTIVES Infections remain a major cause of morbidity and mortality in systemic necrotizing vasculitides (SNV). We aimed to identify factors predicting severe infections (SI) in SNV. METHODS Data from five randomized controlled trials (RCTs) enrolling 733 patients were pooled. The primary end point was the occurrence of SI, defined by the need of a hospitalization and/or intravenous anti-infectious treatment and/or leading to death. RESULTS After a median follow-up of 5.2 (interquartile range 3-9.7) years, 148 (20.2%) patients experienced 189 SI, and 98 (66.2%) presented their first SI within the first 2 years. Median interval from inclusion to SI was 14.9 (4.3-51.7) months. Age ≥65 years (hazard ratio (HR) 1.49 [1.07-2.07]; P=0.019), pulmonary involvement (HR 1.82 [1.26-2.62]; P=0.001) and Five Factor Score ≥1 (HR 1.21 [1.03-1.43]; P=0.019) were independent predictive factors of SI. Regarding induction therapy, the occurrence of SI was associated with the combination of GCs and CYC (HR 1.51 [1.03-2.22]; P = 0.036), while patients receiving only GCs were less likely to present SI (HR 0.69 [0.44-1.07]; P = 0.096). Finally, occurrence of SI had a significant negative impact on survival (P<0.001). CONCLUSION SI in SNV are frequent and impact mortality. Age, pulmonary involvement and Five Factor Score are baseline independent predictors of SI. No therapeutic regimen was significantly associated with SI but patients receiving glucocorticoids and CYC as induction tended to have more SI.

Predictive factors of severe infections in patients with systemic necrotizing vasculitides: data from 733 patients enrolled in five randomized controlled trials of the French Vasculitis Study Group.

Infections remain a major cause of morbidity and mortality in systemic necrotizing vasculitides (SNV). We aimed to identify factors predicting severe infections (SI) in SNV. Data from five randomized controlled trials (RCTs) enrolling 733 patients were pooled. The primary end point was the occurrence of SI, defined by the need of a hospitalization and/or intravenous anti-infectious treatment and/or leading to death. After a median follow-up of 5.2 (interquartile range 3-9.7) years, 148 (20.2%) patients experienced 189 SI, and 98 (66.2%) presented their first SI within the first 2 years. Median interval from inclusion to SI was 14.9 (4.3-51.7) months. Age ≥65 years (hazard ratio (HR) 1.49 [1.07-2.07]; P=0.019), pulmonary involvement (HR 1.82 [1.26-2.62]; P=0.001) and Five Factor Score ≥1 (HR 1.21 [1.03-1.43]; P=0.019) were independent predictive factors of SI. Regarding induction therapy, the occurrence of SI was associated with the combination of GCs and CYC (HR 1.51 [1.03-2.22]; P = 0.036), while patients receiving only GCs were less likely to present SI (HR 0.69 [0.44-1.07]; P = 0.096). Finally, occurrence of SI had a significant negative impact on survival (P<0.001). SI in SNV are frequent and impact mortality. Age, pulmonary involvement and Five Factor Score are baseline independent predictors of SI. No therapeutic regimen was significantly associated with SI but patients receiving glucocorticoids and CYC as induction tended to have more SI.

Mortality in systemic necrotizing vasculitides: A retrospective analysis of the French Vasculitis Study Group registry.

The aim of the study was to describe the evolution of mortality and cause-specific mortality over time in patients with systemic necrotizing vasculitides (SNV), including polyarteritis nodosa (PAN), granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Patients with SNV from the French Vasculitis Study Group registry were divided into 5 groups according to the date of diagnosis: <1980, 1980-1989, 1990-1999, 2000-2010, and ≥ 2010. The causes of death were classified as vasculitis, infection, cardiovascular, malignancy, miscellaneous, or unknown. Among the 2217 patients included (PAN 16.1%, GPA 41.7%, EGPA 22.6%, MPA 19.6%), overall incidence of death was 2.26 per 100 person-years. The overall survival improved during each period considered. The 5-year survival rate increased from 72.2% (95% confidence interval [CI] 59.7-87.2) for patients diagnosed before 1980 to 94.5% (95% CI 90.4-98.8) after 2010 (p < 0.001). Periods of diagnosis, age, and male gender were independently associated with a poor survival with a non-significant difference between vasculitis. The incidence of mortality between the 1980s and after 2010 significantly decreased for vasculitis-related (p = 0.03) and cardiovascular-related deaths (p = 0.04). Incidence of death by infection remained stable between the 1980s and the 2000s but no death by infection occurred after 2010. The incidence of death by malignancy remained stable over time. Overall survival of SNV patients has improved since the 1980s with the decrease of vasculitis- and cardiovascular-related deaths, but cancer-related mortality remained stable. These results highlight malignancy as the current target to improve the overall prognosis.

Adding Azathioprine to Remission-Induction Glucocorticoids for Eosinophilic Granulomatosis With Polyangiitis (Churg-Strauss), Microscopic Polyangiitis, or Polyarteritis Nodosa Without Poor Prognosis Factors: A Randomized, Controlled Trial.

In most patients with nonsevere systemic necrotizing vasculitides (SNVs), remission is achieved with glucocorticoids alone, but one-third experience a relapse within 2 years. This study was undertaken to determine whether the addition of azathioprine (AZA) to glucocorticoids could achieve a higher sustained remission rate of newly diagnosed nonsevere eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA), microscopic polyangiitis (MPA), or polyarteritis nodosa (PAN). All patients included in this double-blind trial received glucocorticoids, gradually tapered over 12 months, and were randomized to receive AZA or placebo for 12 months, with stratification according to SNV (EGPA or MPA/PAN). The primary end point was the combined rate of remission induction failures and minor or major relapses at month 24. Ninety-five patients (51 with EGPA, 25 with MPA, and 19 with PAN) met the inclusion criteria, were randomized, and received at least 1 dose of AZA (n = 46) or placebo (n = 49). At month 24, 47.8% of the patients receiving AZA versus 49% of the patients receiving placebo had remission induction failures or relapses (P = 0.86). Secondary end points were comparable between the AZA and placebo arms. These included initial remission rate (95.7% versus 87.8%), total relapse rate (44.2% versus 40.5%), and glucocorticoid use. Two patients in the placebo arm died; 22 patients in the AZA arm (47.8%) and 23 patients in the placebo arm (46.9%) experienced ≥1 severe adverse event. For EGPA patients, the primary end point (48% in the AZA arm versus 46.2% in the placebo arm) and the percent of patients who experienced asthma/rhinosinusitis exacerbations (24% in the AZA arm versus 19.2% in the placebo arm) were comparable between treatment arms. Addition of AZA to glucocorticoids for the induction of remission of nonsevere SNVs does not improve remission rates, lower relapse risk, spare steroids, or diminish the EGPA asthma/rhinosinusitis exacerbation rate.

Plasma exchanges for the treatment of severe systemic necrotizing vasculitides in clinical daily practice: Data from the French Vasculitis Study Group

The use of plasma exchanges (PLEX) in systemic necrotizing vasculitides (SNV) still need to be codified. To describe indications, efficacy and safety of PLEX for the treatment of SNV, we conducted a multicenter retrospective study on patients with ANCA-associated vasculitis (AAV) or non-viral polyarteritis nodosa (PAN) treated with PLEX. One hundred and fifty-two patients were included: GPA (n = 87), MPA (n = 56), EGPA (n = 4) and PAN (n = 5). PLEX were used for rapidly progressive glomerulonephritis (RPGN) in 126 cases (86%), alveolar hemorrhage in 64 cases (42%), and severe mononeuritis multiplex in 23 cases (15%). In patients with RPGN, there was a significant improvement in renal function compared to baseline value (P < 0.0001), the plateau being reached at month 3 after PLEX initiation, and estimated glomerular filtration rate improved especially as the number of PLEX increased. In patients with alveolar hemorrhage, mechanical ventilation was discontinued in all patients after a median time of 15 days. Patients treated for mononeuritis multiplex showed improvement of severe motor weakness. After a median follow of 22 months, 18 deaths (12%) were recorded, mainly in patients with RPGN and within the first 6 months. Incidence of end-stage renal disease and/or death was similar between groups of different baseline renal function, but was increased in MPO-ANCA compared to PR3-ANCA. Adverse events attributable to PLEX were recorded in 63%. No death occurred during PLEX. This large series describes indications, efficacy and safety of PLEX in daily practice. Randomized controlled studies are ongoing to define optimal indications, PLEX regimen and concomitant medications.

Characteristics, prognosis, and outcomes of cutaneous ischemia and gangrene in systemic necrotizing vasculitides: A retrospective multicenter study

ObjectivesTo describe the prevalence, characteristics, and outcome of cutaneous ischemia, and whether it can occur in systemic necrotizing vasculitides (SNVs), i.e., polyarteritis nodosa, granulomatosis with polyangiitis, and eosinophilic granulomatosis with polyangiitis and microscopic polyangiitis. MethodsWe conducted a retrospective analysis of all patients with SNV who were included in the French Vasculitis Study Group cohort database between March 1963 and September 2007. We compared characteristics and outcomes for patients with and without cutaneous ischemia (digital necrosis and/or isolated necrotic cutaneous ulcers). ResultsAmong the 1304 patients with a diagnosis of SNVs, 40 (3.1%) had digital necrosis and 25 (1.9%) had isolated necrotic cutaneous ulcers, with an equal distribution among SNVs. Presence of cutaneous ischemia was associated with past and/or current smoking [odds ratio (OR), 1.73; 95% confidence interval (95% CI), 1.02–2.95] and history of coronary artery disease (2.40; 1.01–6.00), as well as with other cutaneous manifestations (6.54; 3.21–8.67), gastrointestinal tract perforations (4.29; 1.41–13.07), and arthralgias (1.84; 1.10–3.07) during diagnosis. Ten patients with digital necrosis underwent extremity amputation, but no patient with isolated necrotic cutaneous ulcers (p = 0.007) underwent it. Smoking was the main risk factor of amputation (OR, 9.1; 1.7–48.9). At a mean follow-up of 10 years, cutaneous ischemia was identified as an independent predictor of vasculitis relapse (hazard ratio, 1.47; 95% CI, 1.05–2.05) and all-cause death (1.66; 1.01–2.74). ConclusionsCutaneous ischemia is a rare manifestation of SNVs but is associated with an increased risk of relapse and mortality. Tobacco use is associated with amputation, which emphasizes the importance of managing conventional cardiovascular risk factors in SNV patients.

FRI0343 Factors associated with major cardiovascular events in patients with primary systemic necrotizing vasculitides: results of a longitudinal long-term follow-up study

BackgroundPrimary systemic necrotizing vasculitides (SNV) were shown to be associated with more frequent subclinical atherosclerosis, independently of cardiovascular (CV) risk factors and C-reactive protein (CRP) level, suggesting that SNV might...

Ophthalmologic Manifestations of Systemic Necrotizing Vasculitides at Diagnosis: A Retrospective Study of 1286 Patients and Review of the Literature

To determine the frequencies and types of ophthalmologic manifestations in patients with systemic necrotizing vasculitides (SNV), including polyarteritis nodosa (PAN) and ANCA-associated vasculitides (granulomatosis with polyangiitis (Wegener's, GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA); Churg-Strauss syndrome (CSS)) and review the literature on eye involvement in these diseases. This retrospective analysis was conducted on the ophthalmologic manifestations of SNV patients entered into the French Vasculitis Study Group database between July 1955 and August 2008. Among the 1286 identified patients, 214 (16.6%) had ophthalmologic manifestations at diagnosis, significantly more often in GPA (117/343, 34.1%) than in EGPA (30/270, 11.1%; P = 0.0001), PAN (42/393, 10.7%; P = 0.0001) or MPA (25/280, 8.9%; P = 0.0001). The 3 most common recorded ophthalmologic manifestations were conjunctivitis (89, (7%)), episcleritis (56, (4%)), and/or blurred vision (44, (3%)), mainly caused by retinal vasculitis in 5, oculomotor nerve palsy in 4, uveitis in 4 and/or optic neuropathy in 3. Orbital inflammatory tumor, another common feature was rather specific to GPA (23/349, 6.6% (P = 0.0001)) compared to other SNV. The literature on ophthalmologic manifestations of SNV is limited to case reports except for GPA, in which the eye involvement frequency ranged from 29% to 57%. Eye manifestations were more common in GPA than MPA, PAN and EGPA, but can be sight-threatening in any SNV. Given the heterogeneity of ophthalmologic involvement in SNV, close collaboration between the ophthalmologists and internists is critical.

Pregnancies in systemic necrotizing vasculitides: report on 12 women and their 20 pregnancies

To describe pregnancies of women with systemic necrotizing vasculitides (SNVs), i.e. PAN, WG, Churg-Strauss syndrome (CSS) or microscopic polyangiitis (MPA), followed over the past 15 years at four French centres. Retrospective analysis of women whose SNV appeared during pregnancy or who became pregnant after SNV diagnosis. Among the 12 women identified, one experienced rupture of pancreatic artery microaneurysms at 27 weeks revealing PAN, leading to surgical haemostasis and caesarean delivery. Eleven others started 19 pregnancies after SNV diagnosis (8 in four WG, 6 in three CSS, 1 each in three PAN and 2 in one MPA); 14 conceived during vasculitis remission. Two ended in first-trimester abortions, four miscarried; the remaining 13 pregnancies yielded 14 live newborns (1 twin pregnancy), with 7 pre-term births. Life-threatening complications occurred during 3 of these latter 13 pregnancies and required caesarean delivery. The twin pregnancy (in a CSS patient with initial vasculitis-related cardiac involvement, but in remission at conception) was complicated by transient maternal cardiac failure at 32 weeks. One WG patient with vasculitis-related renal damage developed thrombotic microangiopathy-associated renal impairment at 32 weeks, and another WG patient had severe pneumonia at 37 weeks. Other pregnancies were uneventful or with minor vasculitis manifestations. Pregnant SNV patients should be monitored closely, because miscarriages and pre-term births are not uncommon. Pregnancy does not seem to have a major impact on vasculitis activity. However, life-threatening manifestations can occur, especially in patients with vasculitis-related cardiac or renal damage.

Temporal artery biopsy: a diagnostic tool for systemic necrotizing vasculitis. French Vasculitis Study Group.

To describe the clinical, biologic, and histologic features of temporal artery biopsy (TAB)-localized systemic necrotizing vasculitides (SNV), and to assess their frequency among elderly patients undergoing TAB for suspected giant cell (temporal) arteritis (GCA). The frequency of a TAB localization of SNV was prospectively assessed in a multicenter study of elderly patients undergoing TAB for suspected GCA. All patients with SNV fulfilling the American College of Rheumatology criteria for a specific vasculitic syndrome and with evidence of vasculitis on TAB were included in a retrospective, descriptive study. SNV was diagnosed based on the TAB in 1.4% of the patients with suspected GCA and in 4.5% of the positive (inflamed) TAB specimens. We retrospectively selected 27 patients (18 female, 9 male; mean +/- SD age 62+/-15 years, range 22-79 years) with SNV and TAB-localized vasculitis. Only 2 of these patients were known to have SNV before TAB localization. Twenty-two patients (81%) had cephalic symptoms, including jaw claudication in 33%, clinically abnormal temporal arteries in 33%, and neuro-ophthalmologic symptoms in 11%. All patients had systemic symptoms suggestive of SNV and histologically proven NV in the TAB specimens (70%) or elsewhere in other biopsy sites (74%). Abnormal biologic results suggestive of SNV were present in 17 patients (63%). For 4 patients, the TAB-documented involvement led to initial misdiagnoses of GCA, and systemic manifestations that developed under steroid therapy revealed the correct diagnosis. The final diagnoses of the patients were polyarteritis nodosa (PAN) (n = 11), Churg-Strauss syndrome (n = 6), micropoly-angiitis (n = 3), Wegener's granulomatosis (n = 3), hepatitis B virus-related PAN (n = 2), hepatitis C virus-related cryoglobulinemic vasculitis (n = 1), and rheumatoid vasculitis (n = 1). TAB-localized SNV presents a major diagnostic dilemma because it can mimic GCA. Careful analysis of clinical, biologic, and histologic data should lead to the correct diagnosis and help guide the clinician's choice of appropriate therapy.