Could hypereosinophilia at diagnosis estimate the current activity or predict relapse in systemic immunosuppressive drug-naïve patients with eosinophilic granulomatosis with polyangiitis?

In this study, we investigated whether hypereosinophilia (peripheral eosinophil ≥ 1500/mm3) at diagnosis could estimate the increased current activity and predict the poor prognosis during follow-up in patients with eosinophilic granulomatosis with polyangiitis (EGPA). We retrospectively reviewed the medical records of 42 patients with EGPA and finally included 30 systemic immunosuppressive drug-naïve patients. We obtained clinical and laboratory data including clinical manifestations, Birmingham vasculitis activity score (BVAS), five-factor score (FFS) (2009), and routine laboratory results. Hypereosinophilia was defined as peripheral eosinophil ≥ 1500/mm3. We divided EGPA patients based on hypereosinophilia and compared variables between the two groups. The cumulative relapse-free survival rates were compared by the Kaplan-Meier survival analysis. Patients with hypereosinophilia more commonly exhibited cutaneous manifestation than those without (50.0% vs. 14.3%, P = 0.038), but there were no significant differences in BVAS and FFS (2009) at diagnosis. Patients with hypereosinophilia showed the higher median WBC (14,200.0/mm3 vs. 7940.0/mm3) and CRP (17.6 mg/L vs. 2.0 mg/L) at diagnosis than those without. During follow-up, patients with hypereosinophilia at diagnosis exhibited the similar cumulative relapse-free survival rate to those without (P = 0.393). Whereas, patients with FFS (2009) at diagnosis ≥ 2, which was a well-known predictor of the poor prognosis of EGPA, exhibited the lower cumulative relapse-free survival rate than those with FFS (2009) < 2 (P = 0.030). Hypereosinophilia at diagnosis could neither estimate the current activity nor predict relapse in systemic immunosuppressive drug-naïve patients with EGPA unlike theoretical assumption.

The initial predictors of death in 153 patients with ANCA-associated vasculitis in a single Korean centre.

OBJECTIVES: We estimated the cumulative patient survival rates, the causes of death and the initial predictors of death in Korean patients with microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA) and eosinophilic GPA (EGPA). METHODS: We reviewed the medical records of 153 patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We collected clinical and laboratory data including ANCA, Birmingham vasculitis activity score (BVAS), five factor score (FFS) (2009), comorbidities, medications and prognosis (death and relapse). The hazard ratio (HR) of variables at diagnosis for death in the disease course was assessed by the Cox hazard model analysis. RESULTS: The mean age of 153 AAV patients (47 men and 106 women) was 55.2 years and the mean follow-up duration was 51.5 months. Fourteen of 153 patients (9.2%) died (7 MPA and 7 GPA patients) during the mean follow-up of 56.9 months. In all patients with AAV, 1 year-, 5 year- and 10 year-cumulative patient survival rates were 96.1%, 94.8% and 92.8%, respectively. The most common cause of death was infection of various causes. FFS (2009) ≥2 (HR 16.520, p=0.012) and diffuse alveolar haemorrhage (DAH) (HR 3.705, p=0.042) at diagnosis could predict death during the follow-up in AAV patients in multivariate COX regression analysis. CONCLUSIONS: The overall mortality rate was 9.2% and 10-year cumulative patient survival rate was 92.8%. At diagnosis, FFS (2009) ≥ 2 and DAH were independent predictors of death during the follow-up in Korean patients with MPA, GPA and EGPA.

Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss).

Eosinophilic granulomatosis with polyangiitis (EGPA), formerly called Churg-Strauss syndrome, is a systemic necrotizing vasculitis of small- and medium-size vessels, characterized by asthma and blood eosinophilia. EGPA typically occurs in patients with preexisting asthma, and involves the skin, lungs, and peripheral nerves. Poor-prognosis factors (i.e., involvement(s) of the gastrointestinal tract, heart, and/or kidney) have been assessed with the Five-Factor Score (FFS). One-third of the patients have anti-myeloperoxidase antineutrophil cytoplasm antibodies, and their presence seems to differentiate between two phenotypes, with different clinical characteristics and prognoses. Overall survival has improved markedly since the use of glucocorticoids and immunosuppressants, but relapse rates remain high. All patients require glucocorticoids, and for those with severe/refractory disease and FFS-defined poor prognoses, immunosuppressants should be used (cyclophosphamide for induction and azathioprine for maintenance therapy). Recent advances in EGPA management, including several novel immunomodulatory drugs and targeted biotherapies, were or are being evaluated to improve EGPA patients' prognoses.

Factors that predict in-hospital mortality in eosinophilic granulomatosis with polyangiitis.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic small-vessel vasculitis associated with asthma, eosinophilia, and necrotizing vasculitis. EGPA is potentially life-threatening and often involves peripheral neuropathies, peptic ulcers, cerebral vessel disease, and cardiovascular disease. However, there is limited understanding of the prognostics factors for patients with EGPA. We investigated the clinical features and factors affecting patients' in-hospital mortality, using a national inpatient database in Japan. METHODS: We retrospectively collected data of EGPA patients who required hospitalization between July 2010 and March 2013, using the Diagnosis Procedure Combination database. We evaluated EGPA patients' characteristics and performed multivariate logistic regression analyses to assess the factors associated with in-hospital mortality. RESULTS: A total of 2195 EGPA patients were identified. The mean age was 61.9 years, 42.1% (924/2195) were male, and 41.6% (914/2195) had emergent admission. In-hospital deaths occurred in 97/2195 patients (4.4%). Higher in-hospital mortality was associated with age older than 65 years, disturbance of consciousness on admission, unscheduled admission, respiratory disease, cardio-cerebrovascular disease, renal disease, sepsis, and malignant disease on admission. Lower mortality was associated with female gender and peripheral neuropathies. CONCLUSIONS: Our study revealed the clinical features of EGPA patients who required hospitalization and the factors associated with their mortality. These results may be useful for physicians when assessing disease severity or treatments for hospitalized EGPA patients.

Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): clinical characteristics and long-term followup of the 383 patients enrolled in the French Vasculitis Study Group cohort.

OBJECTIVE: Earlier studies of eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA), with limited patient numbers and followup durations, demonstrated that clinical presentation at diagnosis, but not outcome, differed according to antineutrophil cytoplasmic antibody (ANCA) status. This study was undertaken to describe the main characteristics of a larger patient cohort and their long-term outcomes. METHODS: A retrospective study of EGPA patients in the French Vasculitis Study Group cohort who satisfied the American College of Rheumatology criteria and/or Chapel Hill definitions was conducted. Patient characteristics and outcomes were compared according to ANCA status and year of diagnosis. RESULTS: We identified 383 patients diagnosed between 1957 and June 2009 (128 [33.4%] before 1997 or earlier) and followed up for a mean±SD of 66.8±62.5 months. At diagnosis, their mean±SD age was 50.3±15.7 years, and 91.1% had asthma (duration 9.3±10.8 years). Main manifestations included peripheral neuropathy (51.4%); ear, nose, and throat (ENT) signs (48.0%); skin lesions (39.7%); lung infiltrates (38.6%); and cardiomyopathy (16.4%). Among the 348 patients tested at diagnosis for ANCA, the 108 ANCA-positive patients (31.0%) had significantly more frequent ENT manifestations, peripheral neuropathy, and/or renal involvement, but less frequent cardiac manifestations, than the ANCA-negative patients. Vasculitis relapses occurred in 35.2% of the ANCA-positive versus 22.5% of the ANCA-negative patients (P=0.01), and 5.6% versus 12.5%, respectively, died (P<0.05). The 5-year relapse-free survival rate was 58.1% (95% confidence interval [95% CI] 45.6-68.6) for ANCA-positive and 67.8% (95% CI 59.8-74.5) for ANCA-negative patients (P=0.35). Multivariable analysis identified cardiomyopathy, older age, and diagnosis during or prior to 1996 as independent risk factors for death and lower eosinophil count at diagnosis as predictive of relapse. CONCLUSION: The characteristics and long-term outcomes of EGPA patients differ according to their ANCA status. Although EGPA relapses remain frequent, mortality has declined, at least since 1996.

A vasculitis centre based management strategy leads to improved outcome in eosinophilic granulomatosis and polyangiitis (Churg-Strauss, EGPA): monocentric experiences in 150 patients.

OBJECTIVE: To evaluate a vasculitis centre based management strategy for eosinophilic granulomatosis and polyangiitis (Churg-Strauss, EGPA). METHODS: A retrospective cohort study at a vasculitis referral centre was performed. All EGPA patients admitted from 1990 to 2009 were included. A structured interdisciplinary work-up for proof of diagnosis, Disease Extent Index and Birmingham Vasculitis Activity Score was performed. Immunosuppressive therapy was initiated and regularly adapted. Treatment targets were induction and maintenance of remission according to definitions given by the European League Against Rheumatism and the European Vasculitis Study Group. Outcomes were mortality, rate of remission, relapses, adverse events and prednisolone-dose. RESULTS: Out of 269 patients with suspected EGPA 150 fulfilled the inclusion criteria. Of those, 104 had more than one follow-up visit resulting in a mean follow up of 53±4.9 months. By using additional data sources the follow-up concerning survival was extended to 92±5 month. Severe organ manifestations occurred at heart (46%), kidney (18%) and lungs (10%). Cyclophosphamide was used in 107 patients (71%). The prednisolone-doses of all patients were within the targeted range (i.e. ≤7.5 mg) in 69% of the total follow-up time; the median dose at end of follow-up was 5mg/d. The 10-year survival rate was 89% resulting in mortality comparable to the general population (SMR 1.29). Only patients with cardiac failure associated with EGPA had an increased mortality (SMR 3.06). CONCLUSIONS: Regular re-evaluation and target-orientated adaption of therapy may lead to normalization of life expectancy and attenuation of disease progression. Continued centre based interdisciplinary treatment should be standard of care.

Long-term outcomes of 118 patients with eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) enrolled in two prospective trials.

The purpose of this study was to assess the outcomes of 118 patients with eosinophilic granulomatosis with polyangiitis (EGPA) enrolled in 2 prospective, randomized, open-label clinical trials (1994-2005), with or without Five-Factor Score (FFS)-defined poor-prognosis factors, focusing on survival, disease-free survival, relapses, clinical and laboratory findings, therapeutic responses, and factors predictive of relapse. Forty-four patients with FFS ≥ 1 were assigned to receive 6 or 12 cyclophosphamide pulses plus corticosteroids and the seventy-four with FFS = 0 received corticosteroids alone, with immunosuppressant adjunction when corticosteroids failed. Patients were followed (2005-2011) under routine clinical care in an extended study and data were recorded prospectively. Mean ± SD follow-up was 81.3 ± 39.6 months. Among the 118 patients studied, 29% achieved long-term remission and 10% died. Among the 115 patients achieving a first remission, 41% experienced ≥1 relapses, 26.1 ± 26.8 months after treatment onset, with 57% of relapses occurring when corticosteroid-tapering reached <10 mg/day. Treatment achieved new remissions in >90%, but relapses recurred in 38%. Overall survival was good, reaching 90% at 7 years, regardless of baseline severity. Age ≥65 years was the only factor associated with a higher risk of death during follow-up. The risk of relapse was higher for patients with anti-myeloperoxidase antibodies and lower for those with >3000 eosinophils/mm(3). Sequelae remained frequent, usually chronic asthma and peripheral neuropathy. In conclusion, EGPA patients' survival rate is very good when treatment is stratified according to the baseline FFS. Relapses are frequent, especially in patients with anti-myeloperoxidase antibodies and baseline eosinophilia <3000/mm(3).

[Development of morbidity and mortality in ANCA-associated vasculitis]. / Entwicklung von Morbidität und Mortalität bei ANCA-assoziierten Vaskulitiden.

The outcome of ANCA (antineutrophil cytoplasmic antibody)-associated vasculitis (AAV) has been significantly improved due to the combined use of cyclophosphamide (CYC) and glucocorticosteroids. Recent studies demonstrated a normalization of life expectancy for several subgroups of AAV patients. Mortality is highest in the first year after diagnosis and infections are the most frequent cause of death. Older age and renal failure are associated with worse outcome. The use of Pneumocystis jiroveci prophylaxis and subsequent activity-adapted GC dose reduction (target: below 10 mg per day) can substantially reduce the risk of severe infections. Late sequelae of CYC medication, such as cystitis and malignancy should be recognized and can be minimized by the usage of uroprotection with mesna and avoidance of high cumulative CYC doses.

Churg-Strauss syndrome: 2005-2008 update.

Churg-Strauss syndrome (CSS) is a rare necrotizing small-vessel vasculitis associated with eosinophil-rich granulomatous inflammation of tissues and vessels and is also associated with asthma and eosinophilia. Epidemiologic studies continue to show that CSS is the rarest of the necrotizing small-vessel vasculitides. However, it is not possible to know with any certainty if there has been an increase in incidence. There has been an attempt to divide the patients with CSS into an antineutrophil cytoplasmic antibody-positive and cytoplasmic antibody-negative group. The former group has an increased frequency of renal involvement, parenchymal pulmonary disease, constitutional symptoms, and peripheral and central nervous system involvement, whereas the latter group has more frequent cardiac disease. The role of eosinophils and antineutrophil cytoplasmic antibodies remains poorly defined but provocative. Leukotriene receptor antagonists do not appear to induce CSS but facilitate the tapering of glucocorticoids, which unmasks the condition. Glucocorticoids and cyclophosphamide remain the foundation of treatment for vasculitis, but there are other promising and less toxic alternatives on the horizon.

Outcome of thirty patients with ANCA-associated renal vasculitis admitted to the intensive care unit.

The natural course of as-yet-untreated ANCA-associated vasculitis (AAV) or complications of immunosuppressive treatment may result in rapid clinical deterioration with the need of admission to an intensive care unit (ICU). The aim of this retrospective study was to assess the outcome of patients with renal AAV admitted to the ICU in a single center. We reviewed the medical records of all 218 patients with AAV followed in our department between January 2001 and December 2006 and selected those admitted to the ICU. To assess the severity of critical illness, the Acute Physiology and Chronic Health Evaluation (APACHE II) and Sequential Organ Failure Assessment (SOFA) score on the first ICU day were calculated. Birmingham Vasculitis Activity Score (BVAS) was calculated to represent the total disease activity. Thirty patients with AAV (11 women, 19 men; mean age 61.5 +/- 13.2 years; 20 x cANCA, 10 x pANCA positive) were included. The most common reasons for ICU admission were as follows: active vasculitis (13 patients, 43.3 %), infections (7 patients, 23.3%), and other causes (10 patients, 33.3%). The in-ICU mortality was 33.3% (10 patients). The most common cause of death was septic shock (in 5 patients). The APACHE II (33.5 vs. 23.8) and SOFA scores (11.9 vs. 6.6), but not BVAS (11.5 vs. 16.1), were statistically significantly higher in non-survivors than in survivors (p < 0.01). In conclusion, the in-ICU mortality in AAV patients may be predicted by APACHE II and SOFA scores. While active vasculitis is the most frequent reason for ICU admission, the mortality rate is highest in patients with infectious complications.

Severe/uncontrolled asthma and overall survival in atopic patients with eosinophilic granulomatosis with polyangiitis.

BACKGROUND: Although asthma, rhinitis/rhinosinusitis and peripheral eosinophilia are present in virtually all patients with eosinophilic granulomatosis with polyangiitis (EGPA), the role of atopy in these patients is not well defined. OBJECTIVE: To clarify the role of atopy in patients affected with EGPA. METHODS: Clinical, laboratory and standard spirometry data have been abstracted from medical records. Only patients who underwent skin and/or specific IgE testing for common aeroallergens before the vasculitic phase were included. RESULTS: Overall, 33.5% (63) of our patients underwent skin and/or specific IgE testing to aeroallergens. Atopy related to aeroallergens was confirmed in 22.3% (two-third of those tested), and was associated with more severe/uncontrolled asthma (p < 0.001), including a greater use of oral glucocorticoids for respiratory manifestations the year before the diagnosis of EGPA (p = 0.013). Atopic patients with EGPA had higher total serum IgE levels and less renal disease at EGPA diagnosis compared to non-atopic patients (p < 0.05). Among atopic patients, the majority had multiple sensitizations (76%); dust mite and grass pollen were the most common respiratory allergens identified. The number of allergens did not correlate with peripheral eosinophilia, total serum IgE, ESR, or measures of airway obstruction (p > 0.05 in all cases). The presence of atopy increased the risk of severe/uncontrolled asthma, but not the risk of severe vasculitis (Five Factor Score≥1). Atopic patients had a better overall survival (p = 0.027). CONCLUSION: In EGPA, atopy is associated with better prognosis and more severe/uncontrolled asthma manifestations in the year before the development of vasculitis, but not with more severe vasculitis at presentation.

Outcome of patients with small-vessel vasculitis admitted to a medical ICU.

PURPOSES: This study aims to describe the clinical course and prognostic factors of patients with small-vessel vasculitis admitted to a medical ICU. METHODS: We reviewed the clinical records of 38 patients with small-vessel vasculitis admitted consecutively to the ICU between January 1997 and May 2004. The APACHE (acute physiology and chronic health evaluation) III prognostic system was used to determine the severity of illness on the first ICU day; the sequential organ failure assessment (SOFA) score was used to measure organ dysfunction, and the Birmingham vasculitis activity score for Wegener granulomatosis (BVAS/WG) was used to assess vasculitis activity. Outcome measures were the 28-day mortality and ICU length of stay. RESULTS: Nineteen patients (50%) had Wegener granulomatosis, 16 patients (42%) had microscopic polyangiitis, 2 patients had CNS vasculitis, and 1 patient had Churg-Strauss syndrome. Reasons for ICU admission included alveolar hemorrhage in 14 patients (37%), sepsis in 5 patients (13%), seizures in 3 patients (8%), and pneumonia in 2 patients (5%). The median ICU length of stay was 4.0 days (interquartile range, 2.0 to 6.0 days). The APACHE III score was lower in survivors than nonsurvivors (p = 0.010). The predicted hospital mortality was 54% for nonsurvivors and 21% for survivors (p = 0.0038). The mean SOFA score was 11.6 (SD, 2.6) in nonsurvivors, compared to 6.9 (SD, 2.4) in survivors (p = 0.0004). Mean BVAS/WG scores were 8.6 (SD, 3.6) in nonsurvivors and 4.7 (SD, 4.6) in survivors (p = 0.0889). Twenty-six percent of the patients received invasive mechanical ventilation, and 33% underwent dialysis. The 28-day and 1-year mortality rates were 11% and 29%, respectively. CONCLUSIONS: The mortality of patients with small-vessel vasculitis admitted to the ICU is lower than predicted, and alveolar hemorrhage is the most common reason for ICU admission.

[Churg-Strauss syndrome]. / Syndrome de Churg et Strauss.

Churg-Strauss syndrome is a systemic and pulmonary vasculitis, defined by its association with severe asthma and with hypereosinophilia of the blood and tissues. The systemic vasculitis is a small-vessel vasculitis frequently associated with purpura, mononeuritis multiplex, and, more rarely, with rapidly progressive glomerulonephritis or diffuse alveolar hemorrhage. Its prevalence of 7 to 13 per million population makes it one of the rarest of the systemic vasculitides. Anti-MPO (antimyeloperoxidase) pANCA (ANCA with a perinuclear fluorescence pattern) is present in 35-40% of cases and appears to determine a subgroup of patients with a higher frequency of renal damage, alveolar hemorrhage, and central nervous system damage. Cardiac involvement is an important cause of morbidity and the leading cause of mortality in Churg-Strauss syndrome. Treatment is based on corticosteroid therapy and immunosuppressive drugs (cyclophosphamide and azathioprine) and is determined according to validated prognostic criteria (Five-Factor Score). Complete remission occurs in almost 90% of cases, and the 10-year survival rate has reached 79.4%. Relapses are frequent (25% of cases) and even after recovery from vasculitis, most patients (90%) still have asthma requiring corticosteroid treatment.

Longterm Prognosis of 121 Patients with Eosinophilic Granulomatosis with Polyangiitis in Japan.

OBJECTIVE: We investigated the risk factors for relapse or prognosis of eosinophilic granulomatosis with polyangiitis (EGPA) in Japanese patients presenting to our hospital. METHODS: From June 1999 through March 2015, we retrospectively recruited 121 patients with EGPA according to the American College of Rheumatology criteria. Frequent relapse was defined as disease occurrence at least once every 2 years after a period of initial remission. The study endpoint was the last examination performed. We used multiple logistic regression to analyze risk factors for relapse or survival in EGPA. RESULTS: Gastrointestinal (GI) involvement with both abnormalities on endoscopy and biopsy (p < 0.01) and symptoms; myocardial involvement with both abnormalities on 1 or more cardiac investigations and symptoms (p < 0.01); and treatment at initial or maintenance with immunosuppressants (p < 0.01) or administration of intravenous immunoglobulin (IVIG; p < 0.01) were associated significantly more often with frequent relapse than with infrequent. Overall 5-, 10-, and 20-year survival rates were 91.1%, 83.7%, and 68.6%, respectively. Survival in EGPA was associated with age of onset < 65 years. Age at onset of EGPA was the only significant predictor of survival (p < 0.01). Myocardial or GI tract involvement did not affect mortality risk. CONCLUSION: Patients with myocardial or GI tract involvement had frequent relapses, but these conditions were not reflected in increased mortality. Treatment with immunosuppressants or IVIG in addition to corticosteroids might have improved the prognosis in Japanese patients with EGPA.

The Epidemiology of Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis in Olmsted County, Minnesota: A Twenty-Year US Population-Based Study.

OBJECTIVE: To estimate the annual incidence, prevalence, and mortality of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) and its subsets, granulomatosis with polyangiitis (Wegener's) (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA), in a US-based adult population. METHODS: All medical records of patients with a diagnosis of, or suspicion of having, AAV in Olmsted County, Minnesota from January 1, 1996 to December 31, 2015 were reviewed. AAV incidence rates were age- and sex-adjusted to the 2010 US white population. Age- and sex-adjusted prevalence of AAV was calculated on January 1, 2015. Survival rates observed in the study cohort were compared with expected rates in the Minnesota population. RESULTS: Of the 58 incident cases of AAV in Olmsted County during the study period, 23 (40%) were cases of GPA, 28 (48%) were cases of MPA, and 7 (12%) were cases of EGPA. Overall, 28 (48%) of the patients with AAV were women and 57 (98%) were white. The mean ± SD age at diagnosis was 61.1 ± 16.5 years. Thirty-four patients (61%) had myeloperoxidase (MPO)-ANCAs, and 17 (30%) were positive for proteinase 3 (PR3)-ANCAs; 5 (9%) were ANCA-negative. The annual incidence of AAV was 3.3 per 100,000 population (95% confidence interval [95% CI] 2.4-4.1). The incidence rates of GPA, MPA, and EGPA were 1.3 (95% CI 0.8-1.8), 1.6 (95% CI 1.0-2.2), and 0.4 (95% CI 0.1-0.6), respectively. The overall prevalence of AAV was 42.1 per 100,000 (95% CI 29.6-54.6). The mortality rate among AAV patients overall, and among patients with EGPA, those with MPA, and those with MPO-ANCAs, was increased in comparison to the Minnesota general population (each P < 0.05), whereas mortality rates among patients with GPA, those with PR3-ANCAs, and ANCA-negative patients did not differ from that in the general population. CONCLUSION: The annual incidence of AAV in Olmsted County, Minnesota over the 20 years of the study was 3.3 per 100,000, with a prevalence of 42.1 per 100,000, which is substantially higher than the rates reported in other areas worldwide. The incidence of GPA was similar to that of MPA. Patients with MPA and those with EGPA, but not patients with GPA, experienced higher rates of mortality than that in the Minnesota general population. MPO-ANCAs were a marker of poor survival in this population of patients with AAV.

Methotrexate versus cyclophosphamide for remission maintenance in ANCA-associated vasculitis: A randomised trial.

OBJECTIVES: The treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is based on remission-induction and remission-maintenance. Methotrexate is a widely used immunosuppressant but only a few studies explored its role for maintenance in AAV. This trial investigated the efficacy and safety of methotrexate as maintenance therapy for AAV. METHODS: In this single-centre, open-label, randomised trial we compared methotrexate and cyclophosphamide for maintenance in AAV. We enrolled patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA), the latter with poor-prognosis factors and/or peripheral neuropathy. Remission was induced with cyclophosphamide. At remission, the patients were randomised to receive methotrexate or to continue with cyclophosphamide for 12 months; after treatment, they were followed for another 12 months. The primary end-point was relapse; secondary end-points included renal outcomes and treatment-related toxicity. RESULTS: Of the 94 enrolled patients, 23 were excluded during remission-induction or did not achieve remission; the remaining 71 were randomised to cyclophosphamide (n = 33) or methotrexate (n = 38). Relapse frequencies at months 12 and 24 after randomisation were not different between the two groups (p = 1.00 and 1.00). Relapse-free survival was also comparable (log-rank test p = 0.99). No differences in relapses were detected between the two treatments when GPA+MPA and EGPA were analysed separately. There were no differences in eGFR at months 12 and 24; proteinuria declined significantly (from diagnosis to month 24) only in the cyclophosphamide group (p = 0.0007). No significant differences in adverse event frequencies were observed. CONCLUSIONS: MTX may be effective and safe for remission-maintenance in AAV. TRIAL REGISTRATION: clinicaltrials.gov NCT00751517.

Deaths occurring during the first year after treatment onset for polyarteritis nodosa, microscopic polyangiitis, and Churg-Strauss syndrome: a retrospective analysis of causes and factors predictive of mortality based on 595 patients.

Although combining corticosteroids and cyclophosphamide has greatly improved the prognoses of severe necrotizing vasculitides, some patients continue to have fulminating disease and die within the first year of diagnosis. To evaluate the characteristics of these patients, we retrospectively studied the files of 60 patients who died within the first year (20 patients with hepatitis B virus-associated polyarteritis nodosa [HBV-PAN], 18 with non-HBV PAN, 13 with microscopic polyangiitis [MPA], and 9 with Churg-Strauss syndrome [CSS]) and 535 first-year survivors (89 patients with HBV-PAN, 182 with non-HBV PAN, 140 with MPA, and 124 with CSS), 85 of whom died during a mean follow-up of 6.4 years. The 2 groups were compared for prognostic factors defined by the five-factor score (FFS) and Birmingham Vasculitis Activity Score at baseline, clinical signs, treatment, outcome, and causes of death. For first-year nonsurvivors, the clinical signs predictive of death were as follows: renal involvement (hazard ratio [HR], 1.6; 95% confidence intervals [CI], 1.09-2.3) or central nervous system involvement (HR, 2.3; 95% CI, 1.5-3.7), and a trend toward cardiomyopathy (HR, 1.4; 95% CI, 1.000-2.115). Older patients died earlier (HR, 1.04; 95% CI, 1.023-1.051). Gastrointestinal symptoms were most frequently associated with early death from HBV-PAN, while 83% of CSS patients died of cardiac involvement. Treatment had no significant impact on early death, except for patients with FFS > or = 2, for whom steroids alone were associated (p < 0.05). The major cause of early death was uncontrolled vasculitis (58%), followed by infection (26%). Cyclophosphamide-induced cytopenia and infection were responsible for 2 deaths. Despite these iatrogenic complications, early deaths were more frequently the consequence of insufficient or inappropriate therapy.

Primary systemic vasculitis: clinical features and mortality.

BACKGROUND: Wegener's granulomatosis (WG), Churg Strauss syndrome (CSS) and microscopic polyangiitis (MPA) are primary systemic vasculitides (PSV), the clinical features of which have been described from tertiary centres. AIM: To provide the first clinical description of MPA from a general hospital and compare clinical features with WG and CSS. DESIGN: Retrospective analysis of patient records. METHODS: Records of 99 PSV patients attending a single hospital, from 1988 to 2000, were reviewed for: clinical features, date/age at diagnosis, sex, duration of illness, anti-neutrophil cytoplasmic antibodies (ANCA), treatment, comorbidity and deaths. Cases were classified using ACR, CHCC and Lanham criteria/definitions. Birmingham vasculitis activity scores (BVAS) and damage index (VDI) were calculated. Survival was assessed using Cox proportional hazards model and standardized mortality ratios (SMRs). RESULTS: Compared to previous reports there was more ENT (29%) and respiratory (29%) but less renal (92%) involvement in MPA, and less ENT involvement in WG (81%). CSS showed high neurological (72%), cardiovascular (28%) and gastrointestinal (17%) involvement and the highest median (range) VDI (p = 0.01 vs. WG; p = 0.001 vs. MPA). BVAS1 was significantly lower in MPA than in WG [median (range) 15 (4-29) vs. 21 (6-39), (p = 0.001)] but not in CSS [20 (7-28), p = 0.08]. SMR (95%CI) for PSV was 4.8 (3.0-6.6); 5-year survival was 45.1% for MPA, 75.9% for WG and 68.1% for CSS. Age was a significant risk, but only to the same extent as in the reference population. When age was adjusted for, no other significant factor was found. DISCUSSION: The clinical characteristics seen here are similar to those in previous series. There are difficulties in using the MPA CHCC definitions in classification. There is a high proportion of neurological involvement in CSS, causing permanent damage. MPA may have a poorer prognosis than WG or CSS.

Clinical review: Vasculitis on the intensive care unit -- part 2: treatment and prognosis.

The second part of this review addresses the treatment and prognosis of the vasculitides Wegener's granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome and polyarteritis nodosa. Treatment regimens consist of an initial remission phase with aggressive immunosuppression, followed by a more prolonged maintenance phase using less toxic agents and doses. This review focuses on the initial treatment of fulminant vasculitis, the mainstay of which remains immunosuppression with steroids and cyclophosphamide. For Wegener's granulomatosis and microscopic polyangiitis plasma exchange can be considered for first-line therapy in patients with acute renal failure and/or pulmonary haemorrhage. Refractory disease is rare and is usually due to inadequate treatment. The vasculitides provide a particular challenge for the critical care team. Particular aspects of major organ support related to these conditions are discussed. Effective treatment has revolutionized the prognosis of these conditions. However, mortality is still approximately 50% for those requiring admission to intensive care unit. Furthermore, there is a high morbidity associated with both the diseases themselves and the treatment.

Lung Transplantation in patients with systemic diseases: an eleven-year experience at Papworth Hospital.

BACKGROUND: The presence of a systemic disease has traditionally been considered a contraindication to lung transplantation. METHODS: We present a retrospective review of 19 patients undergoing lung transplantation for end-stage pulmonary disease associated with a systemic illness since 1984. There were 11 male and 8 female patients, aged from 23 to 59 years (median 43 years) with end-stage pulmonary involvement by sarcoidosis (11 patients), Langerhan's cell histiocytosis (three patients), systemic vasculitis (four patients: three with systemic lupus erythrematosis, one with Churg-Strauss), and common variable immunodeficiency (one patient). Ten patients received a heart-lung transplant, and eight patients received a single lung transplant. One patient underwent single lung transplantation after an earlier heart-lung transplant. RESULTS: The 30-day mortality was 5.3%. Nine patients died overall. Two of these had systemic lupus erythrematosis with anticardiolipin antibodies and died from complications of their underlying vasculitis. The mean 1- and 2-year actuarial survivals for all patients were 71% (standard error +/- 10.8%) and 64% (standard error +/- 11.9%), respectively. All patients surviving longer than 3 months achieved an improvement in functional status to New York Heart Association class I or II, and a significant increase occurred in mean forced expiratory volume in 1 second and forced vital capacity. Disease recurrence without clinical significance occurred in two patients with sarcoidosis. Of the nine patients who died, seven had autopsies and none showed evidence of disease recurrence in the lungs. CONCLUSIONS: Patients with systemic diseases can be considered for lung transplantation and each case should be judged on its individual merits. However, patients with systemic lupus erythrematosis (particularly when associated with anticardiolipin antibodies) should probably not be offered lung transplantation because they are likely to develop further complications of their underlying vasculitis.