French Vasculitis Study Group Research Articles

EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS WITH CARDIAC INVOLVEMENT

SESSION TITLE: Case Report Semifinalists 12 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Eosinophilic granulomatosis with polyangiitis (EGPA), a vasculitis of small- and medium-sized vessels, can be difficult to diagnose due to its diversity of manifestations. We present the case of a patient with respiratory failure and a prolonged course of symptoms prior to being diagnosed with EGPA and successfully treated. CASE PRESENTATION: A 51-year-old male with a history of asthma presented to the ED with cough, hemoptysis, fevers, and weight loss. Chest imaging demonstrated tree-in-bud opacities and mediastinal lymphadenopathy, found to be reactive lymph nodes on biopsy. Bronchoalveolar lavage showed eosinophilia and CBC revealed peripheral eosinophilia. Prednisone was started for presumed chronic eosinophilic pneumonia. He was later admitted to the MICU for worsening dyspnea and hemoptysis, was intubated for respiratory distress and noted to have multilobar infiltrates. Echocardiogram revealed a reduced ejection fraction (EF) of 21-25%, and angiogram ruled out ischemic cardiomyopathy. Despite steroids, his eosinophilia persisted and he was found to have a positive p-ANCA titer of 1:160. Purpuric lesions were noted on his lower extremities and skin biopsy demonstrated eosinophilic and lymphocytic infiltration. Given the suspicion for EGPA, cardiac MRI was performed and revealed a dilated left ventricle, severe global dysfunction, and delayed enhancement, consistent with eosinophilic myocarditis. The patient was transferred for endomyocardial biopsy, which revealed an eosinophil-rich interstitial infiltrate with associated myocardial necrosis, confirming his diagnosis of EGPA with cardiac involvement. He was treated with steroids and cyclophosphamide, with improvement in his pulmonary lesions on CT chest, increase in his EF to 36% on repeat cardiac MRI, and resolution of his peripheral eosinophilia. DISCUSSION: Our case illustrates a wide variety of manifestations of EGPA and the importance of keeping it in the differential diagnosis when such symptoms present. With treatment, 5-year overall survival of EGPA is greater than ninety percent. Exact triggers for EGPA are unknown, though it almost always presents in asthmatics with high allergen burden, both of which were features of our patient. Our patient had elevated ANCA titers; interestingly, it has been shown that ANCA positive patients are more likely to present with cardiac involvement(1). Furthermore, it has been demonstrated that extensive organ system involvement, especially cardiac, in EGPA is a poor prognostic factor(2); this necessitated the prompt diagnosis and initiation of treatment for our patient. CONCLUSIONS: This case highlights the importance of maintaining a high index of suspicion for EGPA in an asthmatic patient with new pulmonary, cardiac, skin, and neurologic symptoms; though EGPA is a rare disease, its prompt treatment can be of the utmost importance. Reference #1: Greco, A., Rizzo, MI., De Virgilio, A., et al. Churg-Strauss syndrome. Autoimmunity Reviews. (2015) 14(4): 341-348. Reference #2: Guillevin L., Pagnoux C., Seror, R. The Five-Factor Score revisited: assessment of prognoses of systemic necrotizing vasculititdes based on the French Vasculitis Study Group (FSVG) cohort. Medicine (Baltimore). (2011) 90(1): 19-27. DISCLOSURES: No relevant relationships by Carolyn Bendor-Grynbaum, source=Web Response No relevant relationships by Amy Espinal, source=Web Response No relevant relationships by Sushilkumar Gupta, source=Web Response No relevant relationships by Yizhak Kupfer, source=Web Response No relevant relationships by Radhames Ramos De Oleo, source=Web Response No relevant relationships by Chanaka Seneviratne, source=Web Response No relevant relationships by Shyam Shankar, source=Web Response No relevant relationships by Parita Soni, source=Web Response No relevant relationships by Shyam Sundaresh, source=Web Response

In ANCA-associated vasculitis in remission, tailored vs fixed-schedule rituximab did not differ for relapse at 28 months.

Source Citation Charles P, Terrier B, Perrodeau E, et al; French Vasculitis Study Group. Comparison of individually tailored versus fixed-schedule rituximab regimen to maintain ANCA-associated vasc...

Childhood- versus Adult-Onset Polyarteritis Nodosa Results from the French Vasculitis Study Group Registry

To investigate differences between childhood (cPAN)- and adult-onset polyarteritis nodosa (aPAN) patients. cPAN patients' clinical findings at onset and outcomes were compared to those of aPAN patients from the French Vasculitis Study Group registry matched for year of enrollment and initial systemic versus cutaneous disease. Their information on medications, disease activity and damage were collected. Kaplan-Meier relapse-free survival curves and the log-rank test were used to analyze cPAN versus aPAN differences for predefined outcomes. Twenty-one children with systemic and 13 with cutaneous PAN were compared with 84 systemic- and 27 cutaneous-matched aPAN patients. Median follow-up exceeded 5 years for both groups. At study entry, mononeuritis multiplex was less frequent in systemic cPAN than systemic aPAN (P = 0.04), and purpura and myalgias were less frequent in cutaneous cPAN than cutaneous aPAN (P < 0.03). During follow-up, systemic cPAN relapsed more often than matched systemic aPAN (P < 0.0001), while relapse rates were similar for cutaneous disease (P > 0.05). Mostly minor relapses, predominantly involving the skin, occurred in all 4 groups. At last visit, damage accrual was comparable for cPAN and aPAN patients, but fewer systemic cPAN patients were treatment-free (15% versus 42%; P = 0.03). Two (6%) cPAN and 8 (7%) aPAN patients died. Systemic PAN is equally severe in children and adults and carries a higher risk of relapse. The main cutaneous PAN features seem not to be influenced by age at disease onset.

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.

Childhood- versus adult-onset ANCA-associated vasculitides: A nested, matched case-control study from the French Vasculitis Study Group Registry.

To investigate differences between childhood-onset ANCA-associated vasculitides (cAAVs) and matched adult-onset controls (aAAVs). cAAV clinical pictures at onset and outcomes were compared to a randomly selected sample of aAAV patients from the French Vasculitis Study Group Registry. Cases and controls were matched for AAV (granulomatosis with polyangiitis [GPA], microscopic polyangiitis [MPA] or eosinophilic granulomatosis with polyangiitis [EGPA]), sex and year of enrollment. Medications, disease activity and damage were prospectively recorded. Kaplan-Meier curves and the log-rank test were used to analyze case-vs.-control differences for predefined outcomes. Comparing 35 cAAVs (25 GPA, 4 MPA, 6 EGPA) to 151 aAAVs (106 GPA, 17 MPA, 28 EGPA), their respective median follow-up durations were 71 and 64months (P=0.49), and, at baseline, children had less frequent myalgias (P=0.005) and peripheral neuropathy (P<0.001) but were more frequently febrile (P<0.05). Rates of renal involvement were comparable (13 [37%] cAAVs vs. 73 [48%] aAAVs; P=0.31). Initial GPA-associated ischemic abdominal pain and nasal cartilage damage were more common in cAAVs than aAAVs (P<0.05). During follow-up, the cAAV relapse rate was higher (24.5 vs. 18.7 flares per 100 patient-years; P<0.05) and, at last visit, cases had accumulated more damage, mostly ear, nose & throat sequelae (P=0.001), associated with longer maintenance therapy (P=0.03), than aAAV controls. Four (11.4%) cAAV and 13 (8.6%) aAAV patients died (P=0.53). cAAVs are severe diseases, characterized by a higher relapse rate, more accrued damage and longer maintenance therapy than for aAAVs.

A Rare Presentation of Eosinophilic Granulomatosis with Polyangiitis with Diffuse Lymphadenopathy

A Rare Presentation of Eosinophilic Granulomatosis with Polyangiitis with Diffuse Lymphadenopathy

Perspectives de traitement par biomédicaments dans la granulomatose éosinophilique avec polyangéite (Churg-Strauss)

After the inflammatory rheumatic diseases, eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss) perfectly illustrates the breakthrough of the advent of biologics in the management of ANCA-associated vasculitides. To improve the management of patients, biologics will have to demonstrate that they allow sustained remission, steroid sparing, and reduction of side effects and accrual damage, improvement of the quality of life of patients with an acceptable medico-economic ratio. Anti-CD20 rituximab treatment of EGPA remains at present not validated but large randomized trials are ongoing in France, both as induction and maintenance therapy. They are made possible thanks to the emergence of consensual definition of assessment criteria for this vasculitis and the structuring of investigators’ networks such as the French Vasculitis Study Group (FVSG). Interleukine-5 is another promising therapeutic target in EGPA, the blocking of which is the objective of an international pivotal mepolizumab trial, after its marketing authorization in eosinophilic asthma. Preliminary results are encouraging as maintenance therapy. Further trials will evaluate other targets in this rare disease, such as interleukin-4 and -13. Let us hope that this new era of biological response modifiers for EGPA allow the emergence of new therapies, which will improve patients’ quality of life.

Granulomatosis with polyangiitis according to geographic origin and ethnicity: clinical-biological presentation and outcome in a French population.

Granulomatosis with polyangiitis (GPA) mainly affects white Europeans, but rarely GPA may also affect non-Europeans. This study aimed to describe GPA clinical-biological presentation and outcome in black sub-Saharan Africans and Afro-Caribbeans and in North Africans. Among 914 GPA patients included in the French Vasculitis Study Group database, geographic origin and ethnicity were known for 760. Clinical-biological presentations and outcomes of white Europeans vs black sub-Saharans and Afro-Caribbeans and vs North Africans were analysed. Among the 760 patients, 689 (91%) were white Europeans, 33 (4.3%) were North Africans and 22 (2.9%) were sub-Saharans (n = 8) or Afro-Caribbeans (French West Indies, n = 14). Black sub-Saharans and Afro-Caribbeans, compared with white Europeans, were significantly younger at GPA diagnosis (P = 0.003), had more frequent central nervous system involvement (P = 0.02), subglottic stenosis (P = 0.002) and pachymeningitis (P = 0.009), and tended to have more frequent chondritis and retroorbital tumour. Median serum creatinine levels and Birmingham Vasculitis Activity Score were significantly lower in sub-Saharans and Afro-Caribbeans (P = 0.002 and P = 0.003, respectively). In contrast, in comparison with white Europeans, North Africans had only less frequent arthralgias (P = 0.004). Time to relapse was shorter for black sub-Saharans and Afro-Caribbeans compared with white Europeans [adjusted HR = 1.96 (95% CI: 1.09, 3.51) (P = 0.02)], and did not differ for North Africans. In contrast, overall survival was not significantly different according to ethnicity. Our findings indicated different GPA clinical presentations in white Europeans and sub-Saharans and Afro-Caribbeans, with black patients having more frequent severe granulomatous manifestations. In addition, time to relapse was significantly shorter for black sub-Saharans and Afro-Caribbeans compared with white Europeans.

Neutrophilic Dermatoses in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A French Multicenter Study of 17 Cases and Literature Review.

A few reports suggest combination of ANCA-associated vasculitis (AAV) and neutrophilic dermatoses (ND). We aimed to describe the main characteristics of patients presenting with both AAV and ND in a French cohort and through a systematic literature review, and to discuss the possible common pathogenic process involved.We conducted a retrospective study of patients with both conditions. Patients were selected via the French Internal Medicine Society (SNFMI) and the French Vasculitis Study Group (FVSG). A literature review focusing on a combination of both conditions, concentrated only on publications with well-established diagnoses and individual detailed data.Seventeen patients diagnosed with AAV and ND were identified in this cohort. Twelve patients had granulomatosis with polyangiitis (GPA), 4 had microscopic polyangiitis (MPA) and one had eosinophilic GPA (EGPA). Eight patients, all with GPA, displayed pyoderma gangrenosum (PG). Sweet's syndrome was observed in 6 patients (4 with MPA, one with GPA and one with EGPA) and erythema elevatum diutinum in the other three (2 with GPA and 1 with MPA). The literature review identified 33 additional patients with both conditions, including 26 with GPA. Altogether, of the 50 patients (17 from our study and 33 from the literature review), 33 (66%) patients presented with PG associated with GPA in 29 cases (89%). Corticosteroids were the first-line treatment in conjunction with an immunosuppressive agent in most cases. Outcomes were good and a total of 15 patients experienced a relapse. Patients who relapsed were more likely to have ear, nose and throat manifestation than patients who did not [12/15 (80%) relapsing patients vs. 15/35 (43%) non-relapsing patients; p = 0.03)].In our stud, the most frequent association concerned GPA and PG. ND should be considered and specifically researched within the spectrum of cutaneous manifestations observed in AAV.

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.

Pituitary involvement in granulomatosis with polyangiitis: report of 9 patients and review of the literature.

Pituitary dysfunction is a rare manifestation of granulomatosis with polyangiitis (GPA) (Wegener). The main aim of this multicenter retrospective study was to describe the characteristics and outcomes of pituitary manifestations in patients with GPA included in the French Vasculitis Study Group database.Among the 819 GPA patients included in the database, 9 (1.1%) had pituitary involvement. The median age at diagnosis of GPA and pituitary involvement was 46 and 50.8 years, respectively. Pituitary involvement was present at onset of GPA in 1 case and occurred later in 8 patients after a median follow up of 58.5 months. When pituitary dysfunction occurred, 8 patients had active disease at other sites including ENT (n = 6), eye (n = 4), or central nervous system (n = 3) involvement. The most common hormonal dysfunctions were diabetes insipidus (n = 7) and hypogonadism (n = 7). Magnetic resonance imaging was abnormal in 7 patients. The most common lesions were an enlargement of the pituitary gland, thickening of the pituitary stalk, and loss of posterior hypersignal on T1-weighed images. All patients were treated with corticosteroid therapy and 8 patients received immunosuppressive agents for the pituitary involvement, including cyclophosphamide (n = 3), rituximab (n = 2), and methotrexate (n = 3). After a median follow-up of 9.2 years, GPA was in complete remission in 7 patients, but 8 patients were still under hormone replacement therapy. Among the 5 patients who had a subsequent MRI, 2 had complete resolution of pituitary lesions.By combining our study and the literature review, the frequency of hypogonadism and diabetes insipidus, among the patients with pituitary dysfunction, can be estimated at 78% and 71% respectively. Despite a high rate of systemic disease remission on maintenance therapy, 86% of the patients had persistent pituitary dysfunction. The patients who recovered from pituitary dysfunction had all been treated by cyclophosphamide.Pituitary disease in GPA occurs mostly several months or years after diagnosis. There is no correlation between hormonal, radiologic, and systemic outcome. Although immunosuppressive drugs improve the systemic disease, hormonal deficiencies usually persist. It is therefore important to shorten diagnostic delays and treat these patients early in the course of disease before irreversible damage occur.

FRI0449 Retro-Orbital Granuloma in Granulomatosis with Polyangiitis

BackgroundRetro-orbital granuloma is a rare and devastating component of granulomatosis with poliangiitis (GPA). Current medical treatment protocols are falling short and outcomes are poor [1-2].ObjectivesTo investigate the frequency, clinical features...

Editorial introductions

Editorial introductions

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.

Treatment of primary systemic necrotizing vasculitides: the role of biotherapies

Treatments of systemic necrotizing vasculitides have progressed markedly over the past few decades. The first attempts to obtain better-adapted therapeutic strategies evaluated the indications of conventional drugs, and their abilities to prolong survival and prevent relapses, while decreasing the severity and number of side effects. The French Vasculitis Study Group, the European Vasculitis Study Group or the Vasculitis Clinical Research Consortium organized most of the prospective clinical trials that have contributed to optimizing targeted treatment strategies. Recent therapeutic strategies include: immunomodulating methods (e.g. plasma exchanges), products (e.g. intravenous immunoglobulins) or, more recently, new agents called biotherapies. Some of the latter, mainly anti-CD20 monoclonal antibodies, have achieved promising effects and are now being evaluated in prospective trials.

Editorial introductions

Current Opinion in Rheumatology was launched in 1989. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of Rheumatology is divided into 15 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS Alfred Mahr Prof. Mahr, MD, MPH, PhD, was appointed Chief of Internal Medicine at Hospital Saint-Louis at the University Paris 7-Diderot in Paris, France, in 2010. His major interest is in providing clinical care for patients with systemic vasculitides (e.g., ANCA-associated vasculitis, giant cell arteritis, Behçet's disease, Henoch-Schönlein purpura), connective tissue diseases and other multi-systemic rheumatic disorders. He received an MPH degree and a PhD degree in public health-epidemiology. Prof. Mahr's research focuses on the elucidation of the epidemiology and etiology and on diagnostic and therapeutic aspects of systemic vasculitides. He was actively involved in many studies of the French Vasculitis Study Group (FVSG), the European Vasculitis Study Group (EUVAS) as well as the North American Vasculitis Clinical Research Consortium (VCRC). He has authored and co-authored about 100 peer-reviewed articles and book chapters. Prof. Mahr has served as an Associate Editor for Rheumatology (Oxford) since 2011. Terrence GibsonTerrence GibsonDr Gibson was appointed to his current post in 1976 after training in London, UK, and Philadelphia, USA. Subsequently he spent extended periods working in New Zealand and Pakistan. An interest in metabolic medicine and gout prompted a series of studies to explore the relationship of hyperuricemia with obesity, hyperlipidemia, diet, hypertension and renal function. He was the first to identify the link between beer consumption and gout and the impairment of urate clearance that predisposes the Maori people of New Zealand to hyperuricemia. While maintaining an interest in gout, Dr Gibson has broad interests and has published more than 120 peer reviewed papers covering a wide spectrum including the epidemiology and characteristics of rheumatic and other diseases in Pakistan. He has edited a general medicine textbook (2009), a student book on rheumatology and was previously Editor of the British Journal of Rheumatology (now Rheumatology). He works as a rheumatologist and an acute physician. Cees KallenbergCees KallenbergCees G.M. Kallenberg, MD, graduated from the Medical School of the University of Leiden, the Netherlands. He was registered as an internist in 1980 and successfully completed his PhD studies on “Raynaud's Phenomenon and Systemic Autoimmune Disease” in 1982 at the University Medical Center, Groningen, the Netherlands. He was appointed as Associate Professor in Internal Medicine - Clinical Immunology in 1985 and as full Professor in 1993. He chaired the Department of Rheumatology and Clinical Immunology at the Groningen University, the Netherlands, until May 1, 2011. His main research is on systemic autoimmune diseases, in particular ANCA-associated vasculitides, systemic lupus erythematosus, and Sjögren's syndrome. He has written more than 500 articles on these subjects in international peer-reviewed journals. He is an invited speaker on his research topics at all major international meetings, and is an editorial board member of several journals in clinical immunology, nephrology and rheumatology.

Systemic Vasculitis During the Course of Systemic Sclerosis

Although the presence of antineutrophil cytoplasmic antibodies (ANCA) has been reported in patients with systemic sclerosis (SSc), the association of SSc and systemic vasculitis has rarely been described. We obtained information on cases of systemic vasculitis associated with SSc in France from the French Vasculitis Study Group and all members of the French Research Group on Systemic Sclerosis.We identified 12 patients with systemic vasculitis associated with SSc: 9 with ANCA-associated systemic vasculitis (AASV) and 3 with mixed cryoglobulinemia vasculitis (MCV). In all AASV patients, SSc was of the limited type. The main complication of SSc was pulmonary fibrosis. Only 2 patients underwent a D-penicillamine regimen before the occurrence of AASV. The characteristics of AASV were microscopic polyangiitis (n = 7) and renal limited vasculitis (n = 2). Anti-myeloperoxidase antibodies were found in 8 of the 9 patients. The Five Factor Score was above 1 in 3 of the 9 patients. Of the 3 patients with MCV, Sjögren syndrome was confirmed in 2. We compared our findings with the results of a literature review (42 previously reported cases of AASV with SSc).Although rare, vasculitis is a complication of SSc. AASV is the most frequent type, and its diagnosis can be challenging when the kidney is injured. Better awareness of this rare association could facilitate earlier diagnosis and appropriate management to reduce damage.

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

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. 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. 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. 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.

Subglottic Stenosis Is a Form of Limited Wegener’s Granulomatosis

To the Editor: In a recent report in The Journal , Pagnoux, et al 1 performed a retrospective analysis of patients with localized granulomatosis with polyangiitis (Wegener’s, GPA) from the French Vasculitis Study Group database, which accounts for almost 500 patients collected from 1982 to 2003. The aim of the study was to estimate the frequency and describe the characteristics of patients with strictly localized disease that did not progress to a generalized form. In their analysis, Pagnoux, et al searched for patients with disease limited to only one organ and with followup of more than a year, to ensure that there was no progression to a systemic form of disease. Compared to previous reports, they found a relatively lower prevalence of the limited form of GPA: 3.2% vs 15%–30%2,3. Interestingly, … Address correspondence to Dr. Espinoza. E-mail: lespin1{at}Isuhsc.edu

Incidence and predictors of urotoxic adverse events in cyclophosphamide‐treated patients with systemic necrotizing vasculitides

To assess hemorrhagic cystitis and urinary tract cancer incidence and predictors in cyclophosphamide (CYC)-treated patients with systemic necrotizing vasculitis (SNV). The French Vasculitis Study Group database, which contains longitudinal data on SNV patients, was searched for urinary tract cancer and/or hemorrhagic cystitis occurrences in patients diagnosed as having Wegener's granulomatosis (WG), microscopic polyangiitis, Churg-Strauss syndrome, or polyarteritis nodosa. The observed incidence of urinary tract cancer was compared to the expected incidence in the general population by calculating standardized incidence ratios (SIRs). Relationships between urinary tract cancer and/or hemorrhagic cystitis and 10 variables, including CYC dosage and administration route, were investigated by survival analyses for a nested subgroup of patients for whom detailed information on CYC exposure was available. Among the 805 patients observed over 4,230 patient-years (mean followup 5.3 years), 22 cases of hemorrhagic cystitis and 7 of urinary tract cancer were identified in 27 patients. The SIRs for urinary tract cancer were 5.00 for all patients with SNV (P = 0.001) and 5.96 for patients with WG (P = 0.03). Based on 467 patients with detailed CYC information, cumulative CYC dose (hazard ratio [HR] for 10-gm increments 1.09; P = 0.03), ever-oral CYC administration (HR 5.50; P = 0.001), and WG (HR 2.96; P = 0.01) independently predicted urinary tract cancer and/or hemorrhagic cystitis. According to univariate analyses, smoking (ever) (HR 8.20; P = 0.02) and a prior hemorrhagic cystitis episode (HR 5.20; P = 0.046) significantly predicted urinary tract cancer. Our findings indicate that CYC treatment of SNV is associated with a 5-fold higher risk of developing urinary tract cancer. Urotoxicity risk in SNV is associated with the cumulative CYC dose and its oral administration, and might be higher in WG.