18F-fluorodeoxyglucose positron emission tomography for the assessment of endo-bronchial involvement in granulomatosis with polyangiitis.

Bronchial stenosis is an uncommon but potentially life-threatening complication of granulomatosis with polyangiitis (GPA). The development of lower respiratory tract stenoses in patients with GPA is thought to be the result of persistent inflammation of the cartilaginous tissue. New assessment methods for this severe GPA complication are highly needed. Herein, we show the value of 18F-fluorodeoxyglycose positron emission tomography/computed tomography (18F-FDG-PET/CT) in the diagnosis, prediction of progression to bronchial stenosis and response to treatment of endobronchial involvement in a patient with GPA.

A real-world assessment of mycophenolate mofetil for remission induction in eosinophilic granulomatosis with polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a form of ANCA-associated vasculitis (AAV). Clinical trials demonstrating the efficacy of mycophenolate mofetil (MMF) for remission induction in AAV excluded patients with EGPA. Despite this, MMF is commonly used in these patients. The objective of this study was to evaluate, for the first time, the effectiveness and tolerance of MMF in EGPA remission induction. A retrospective, two-center, real-world study was conducted in patients with EGPA who received MMF in addition to prednisolone for newly diagnosed or relapsing disease between 2009 and 2019. Baseline, 3-, 6- and 12-month outcome data were extracted from electronic health records. The primary outcome was disease remission, defined as a Birmingham Vasculitis Activity Score of 0 at 6 months. Secondary outcomes included disease relapse, median prednisolone dose at 12 months and drug tolerance. In total, 15 patients (73% male, median age 57) with EGPA (11 newly diagnosed/4 relapsing) were identified. At 6 months, 67% had achieved disease remission. At 12 months, this was maintained (66.7%) and 4 patients had relapsed. All but one patient remained on MMF at study completion and all patients tolerated MMF. Our real-world data suggest that MMF is an effective and well-tolerated agent for achieving disease remission in EGPA. A future randomized controlled trial of MMF in this neglected orphan disease is now warranted.

Burden of illness associated with eosinophilic granulomatosis with polyangiitis: a systematic literature review and meta-analysis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare disease associated with vascular inflammation and multisystem organ damage. The literature reporting EGPA incidence or prevalence is limited. We performed a systematic literature review and meta-analysis to describe the incidence, prevalence, and disease burden associated with EGPA. Real-world, observational, English-language studies in MEDLINE, MEDLINE In-Process, and Embase up to 6 June, 2019, were included. A single investigator screened all identified titles/abstracts and extracted data; an additional, independent investigator repeated the screening and validated the extracted data. A random-effects meta-analysis was conducted to generate pooled estimates for EGPA incidence and prevalence. Data from 100 eligible publications were extracted (32 with incidence/prevalence data, 65 with morbidity/healthcare resource data; 3 with both types of data). Significant evidence of between-study heterogeneity for reported incidence (p = 0.0013-0.0016) and prevalence (p = 0.0001-0.0006) estimates was observed. Global and European pooled estimates (95% confidence interval) of EGPA incidence were 1.22 (0.93, 1.60) and 1.07 (0.94, 1.35) cases per million person-years, respectively; global and European pooled estimates (95% confidence interval) for EGPA prevalence were 15.27 (11.89, 19.61) and 12.13 (6.98, 21.06) cases per million individuals, respectively. The proportions of patients experiencing relapses, or who had nasal polyps or severe asthma, varied considerably across studies. EGPA healthcare resource use was high, with inpatient admissions and emergency department visits reported for 17-42% and 25-42% of patients, respectively. Our results indicate that although global and European EGPA incidence and prevalence is low, the associated disease burden is substantial. Key points • We performed a systematic literature review and meta-analysis of real-world, observational studies describing the incidence, prevalence, and disease burden associated with eosinophilic granulomatosis with polyangiitis (EGPA). • Based on meta-analysis data from 35 eligible studies reporting incidence and prevalence, the incidence and prevalence of EGPA were low (globally 1.22 cases per million person-years and 15.27 cases per million individuals, respectively). • Among the 49 studies with morbidity and/or healthcare resource data, most reported a large proportion of patients with EGPA relapses and comorbidities of nasal polyps and severe asthma. • Healthcare resource use was also high among patients with EGPA in these studies, with inpatient admissions and emergency department visits reported for 17-42% and 25-42% of patients, respectively. Taken together, these data indicate the substantial disease burden associated with EGPA.

Echocardiographic Assessment in Patients with Granulomatosis with Polyangiitis.

Granulomatosis with polyangiitis (GPA) is one of the most common forms of systemic vasculitis, which usually involves the upper and lower respiratory tract, but it may affect also multiple organs. The aim of the study was an echocardiographic evaluation of cardiac involvement in GPA patients during remission. Eighty eight patients with GPA were evaluated in the study. The control group consisted of 40 age and sex-matched patients without a previous history of cardiovascular disease. We found that there were no differences between GPA and control groups regarding left atrial enlargement and interventricular septal hypertrophy. In one GPA patient, all heart chambers were enlarged. Left ventricle systolic function was decreased (LVEF ≤ 50%) in eight patients with GPA, and left ventricle wall motion abnormalities were observed in 12 patients. Left ventricle relaxation dysfunction, mitral valve and tricuspid valve regurgitation were observed with the same frequency in both GPA and control groups. Aortic regurgitation was the single abnormality that occurred significantly more often in the GPA group than in controls (28% vs. 7.5%; p = 0.03). Pericardial effusion was observed in three GPA patients and in none from the control group. We conclude that the most common echocardiographic manifestation in GPA patients in remission was aortic valve regurgitation. However, cardiac involvement in such patients is rather rare and in the majority of cases clinically insignificant.

Intra- and inter-rater reliability of the modified ENT assessment score (ENTAS 2) in granulomatosis with polyangiitis: a prospective randomised trial.

OBJECTIVES: Ears nose and throat (ENT) involvement is found on a substantial proportion of patients with granulomatosis with polyangiitis (GPA). Structured, reliable ENT assessment is essential in the management of GPA patients. It is the aim of this study to determine the repeatability (intra-rater reliability) and reproducibility (inter-rater reliability) of the ENT Assessment Score (ENTAS 2). METHODS: The ENTAS 2 built the fundament of the prospective randomized trial. Anamnestic, video endoscopic and diagnostic data of 47 patients were used. A single assessor reference was created. GPA/ENT activity and damage were evaluated by three physicians at two time points (T1/T2). GPA/ENT activity was evaluated in dichotomy (yes/no) and grading (none/mild/moderate/high) and GPA/ ENT damage in dichotomy. RESULTS: ENTAS 2 activity evaluations intra-rater reliability was 80.7% (κ=0.56) in dichotomy and 72.8% (κ=0.41) in grading. ENTAS 2 damage evaluations showed 87.8% (κ=0.74) intra-rater reliability. ENTAS 2 activity inter-rater reliability at T1 was 62.2% (κ=0.43) in dichotomy and 51.1% (κ=0.29) in grading, at T2 it was 68.2% (κ=0.48) in dichotomy and 55.32% (κ=0.33) in grading. Inter-rater reliability of ENTAS 2 damage evaluation was 84.4% (κ=0.79) at T1 and 72.5% (κ=0.64) at T2. CONCLUSIONS: ENTAS 2 intra-rater reliability was high in dichotomous and graded GPA/ENT activity and damage evaluations. Inter-rater reliability was high in dichotomous activity and damage evaluations, but low in graded activity evaluations. The data demonstrate that the ENTAS 2 is a reliable score-system considering GPA/ENT activity and damage evaluations.

Structured clinical assessment of the ear, nose and throat in patients with granulomatosis with polyangiitis (Wegener's).

The objective of this prospective cross-sectional study is to describe the clinical otorhinolaryngological manifestations of granulomatosis with polyangiitis (Wegener's) (GPA) in a prospective cohort. All patients suffering from GPA seen in a tertiary centre between March 2007 and November 2008 had a detailed clinical assessment by an ENT surgeon of their ear, nose and head and neck complaints. An evaluation of whether there was disease activity and/or infection in each ENT area was made using the European Vasculitis Study Group guidelines. The number of patients assessed was 144. The proportion of female patients was 47 % (n = 69) and the median age was 57.7 years (IQ range 42.5-68.5). The prevalence of ENT involvement was 87 % (125/144). Hearing loss and abnormal tympanic membrane appearance were more common in patients with active disease and no infection (7/8 and 6/8, respectively, in active disease cf. 59/131 and 52/131, respectively, in remission). Nasal crusting was the most common nasal complaint recorded (52/144, 36 %) and bloody rhinorrhoea was the most common symptom in patients with disease activity. Rhinoscopy was highly sensitive in diagnosing disease activity (100 %). Subglottic stenosis was the most common head and neck manifestation (27/121, 22 %) and 74 % were symptomatic. In conclusion, the pattern and frequency of clinical ENT manifestations in GPA have been described in a large patient cohort. The use of tools readily available in the ENT clinic was essential to assess these patients accurately. This dataset will form the basis of an objective scoring system to measure disease activity in the ENT system.

Assessment of health-related quality of life as an outcome measure in granulomatosis with polyangiitis (Wegener's).

OBJECTIVE: To assess a generic measure of health-related quality of life (HRQOL) as an outcome measure in granulomatosis with polyangiitis (Wegener's) (GPA). METHODS: Subjects were participants in the Wegener's Granulomatosis Etanercept Trial (WGET) or the Vasculitis Clinical Research Consortium Longitudinal Study (VCRC-LS). HRQOL was assessed with the Short Form 36 (SF-36) health survey that includes physical and mental component summary scores (PCS and MCS, respectively). Disease activity was assessed with the Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG). RESULTS: The data from 180 subjects in the WGET (median followup 2.3 years, mean number of visits 10) and 237 subjects in the VCRC-LS (median followup 2.0 years, mean number of visits 8) were analyzed. A 1 unit increase in the BVAS/WG corresponded to a 1.15 unit (95% confidence interval [95% CI] 1.02, 1.29) decrease for the PCS and a 0.93 (95% CI 0.78, 1.07) decrease for the MCS in the WGET, and to a 1.16 unit decrease for the PCS (95% CI 0.94, 1.39) and a 0.79 unit decrease for the MCS (95% CI 0.51, 1.39) in the VCRC-LS. In both arms of the WGET study, SF-36 measures improved rapidly during the first 6 weeks of treatment followed by gradual improvement among patients achieving sustained remission (0.5 improvement in PCS per 3 months), but worsened slightly (0.03 decrease in PCS every 3 months) among patients not achieving sustained remission (P = 0.005). CONCLUSION: HRQOL, as measured by the SF-36, is reduced among patients with GPA. SF-36 measures are modestly associated with other disease outcomes and discriminate between disease states of importance in GPA.

Rituximab reversed cardiac involvement of Wegener's granulomatosis: magnetic resonance imaging assessment.

INTRODUCTION: Cardiac involvement is a rare manifestation of Wegener granulomatosis (WG). Because its prognosis can be poor, it must be diagnosed early to be treated adequately. We report the disease course of a patient who received rituximab to treat cardiac involvement documented by contrast-enhanced cardiac magnetic resonance imaging (ceCMR). CASE: This WG patient developed myocarditis with atrioventricular block. CeCMR proved useful in the diagnosis and follow-up of cardiac involvement. Several unsuccessful regimens preceded the prescription of rituximab. Two months later, regression of the myocarditis shown by ceCMR images was correlated with electrophysiological improvement. DISCUSSION: CeCMR assessment of a heart conduction defect in a patient with WG showed that this tool was useful for the diagnosis and follow-up of cardiac involvement in this vasculitis. Rituximab was an effective treatment in this patient.

Cost-effectiveness of prophylaxis against Pneumocystis carinii pneumonia in patients with Wegner's granulomatosis undergoing immunosuppressive therapy.

OBJECTIVE: To assess the incremental cost-effectiveness of 3 Pneumocystis carinii pneumonia (PCP) prophylaxis strategies in patients with Wegener's granulomatosis (WG) receiving immunosuppressive therapies: 1) no prophylaxis; 2) trimethoprim/sulfamethoxazole (TMP/SMX) 160 mg/800 mg 3 times a week, which is discontinued if patients experience an adverse drug reaction (ADR); and 3) TMP/SMX 160 mg/800 mg 3 times a week, which is replaced by monthly aerosolized pentamidine (300 mg) if patients experience an ADR. METHODS: A Markov state-transition model was developed to follow a hypothetical cohort of WG patients over their lifetimes starting from the time of initial exposure to the immunosuppressive therapy. The effect of PCP prophylaxis on life expectancy, quality-adjusted life expectancy, average discounted lifetime cost (ADLC), and incremental cost-effectiveness was estimated based on data obtained from a literature review. Direct medical costs were examined from a societal perspective, and costs and benefits were discounted at 3% annually. RESULTS: No prophylaxis resulted in a life expectancy of 13.36 quality-adjusted life years (QALY) at an ADLC of $4,538. In comparison, prophylaxis with TMP/ SMX alone increased the QALY to 13.54 and was cost saving, with an ADLC of $3,304. The addition of pentamidine in patients who had an ADR to TMP/SMX resulted in 13.61 QALY, with an ADLC of $7,428. Compared with TMP/SMX alone, TMP/SMX followed by pentamidine increased the QALY by 0.07 at an incremental cost of $58,037 per QALY. Both TMP/SMX alone and TMP/SMX followed by pentamidine prophylaxis strategies dominated the no prophylaxis strategy until the incidence of PCP fell below 0.2% and 2.25%, respectively. Institution of pentamidine therapy for patients with a TMP/SMX ADR increased quality-adjusted life expectancy compared with that with TMP/ SMX alone until the incidence of PCP rose above 7.5%. CONCLUSION: Prophylaxis using TMP/SMX alone increased life expectancy and reduced cost for patients with WG receiving immunosuppressive therapy. Replacing TMP/SMX with monthly aerosolized pentamidine in cases of ADR further increased life expectancy, although at an increased cost.