Guillaume Le Guenno

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.

The spectrum of type I cryoglobulinemia vasculitis: new insights based on 64 cases.

AbstractType I cryoglobulinemia vasculitis (CryoVas) is considered a life-threatening condition; however, data on the characteristics and outcome are scarce. To analyze the presentation, prognosis, and efficacy and safety of treatments of type I CryoVas, we conducted a French nationwide survey that included 64 patients with type I CryoVas between January 1995 and July 2010: 28 patients with monoclonal gammopathy of unknown significance (MGUS) and 36 with hematologic malignancy.Type I monoclonal CryoVas was characterized by severe cutaneous involvement (necrosis and ulcers) in almost half the patients and high serum cryoglobulin levels, contrasting with a lower frequency of glomerulonephritis than expected. The 1-, 3-, 5-, and 10-year survival rates were 97%, 94%, 94%, and 87%, respectively. Compared to MGUS, type I CryoVas related to hematologic malignancy tended to be associated with a poorer prognosis. Therapeutic regimens based on alkylating agents, rituximab, thalidomide or lenalinomide, and bortezomib showed similar efficacy on vasculitis manifestations, with clinical response rates from 80% to 86%.Data from the CryoVas survey show that the prognosis of type I CryoVas does not seem to be as poor as previously suggested. Besides alkylating agents, the use of regimens based on rituximab, thalidomide or lenalinomide, and bortezomib are interesting alternative options, although the exact role of each strategy remains to be defined.

Safety and efficacy of rituximab in adult immune thrombocytopenia: results from a prospective registry including 248 patients

We conducted a prospective multicenter registry of 248 adult patients with immune thrombocytopenia (ITP) treated with rituximab to assess safety. We also assessed response and predictive factors of sustained response. In total, 173 patients received 4 infusions of 375 mg/m(2) and 72 received 2 fixed 1-g infusions 2 weeks apart. The choice of the rituximab regimen was based on the physicians preference and not patient characteristics. Overall, 38 patients showed minor intolerance to rituximab infusions; infusions had to be stopped for only 3 patients. Seven showed infection (n = 11 cases), with an incidence of 2.3 infections/100 patient-years. Three patients died of infection 12 to 14 months after rituximab infusions, but the role of rituximab was questionable. In total, 152 patients (61%) showed an overall initial response (platelet count ≥30 × 10(9)/L and ≥2 baseline value). At a median follow-up of 24 months, 96 patients (39%) showed a lasting response. On multivariate analysis, the probability of sustained response at 1 year was significantly associated with ITP duration <1 year (P = .02) and previous transient complete response to corticosteroids (P = .05). The pattern of response was similar with the 2 rituximab regimens. With its benefit/risk ratio, rituximab used off-label may remain a valid option for treating persistent or chronic ITP in adults. This trial was registered at www.clinicaltrials.gov as #NC1101295.

Kinetic profiles and management of hepatitis B virus reactivation in patients with immune-mediated inflammatory diseases.

Immunosuppressive therapy may trigger hepatitis B virus (HBV) reactivation for increased morbidity and mortality. We aimed to describe HBV reactivation in patients receiving treatment for immune‐mediated inflammatory diseases (IMIDs) and to evaluate a predefined algorithm for its prevention.

Anti-IgE Monoclonal Antibody (Omalizumab) in Refractory and Relapsing Eosinophilic Granulomatosis With Polyangiitis (Churg-Strauss): Data on Seventeen Patients

To describe the efficacy and safety of omalizumab, an anti‐IgE monoclonal antibody, in patients with refractory and/or relapsing eosinophilic granulomatosis with polyangiitis (Churg‐Strauss) (EGPA).

Pituitary Involvement in Granulomatosis With Polyangiitis: Report of 9 Patients and Review of the Literature

AbstractPituitary 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.

Anti‐IgE monoclonal antibody (omalizumab) in refractory and relapsing eosinophilic granulomatosis with polyangiitis (Churg‐Strauss): Data from 17 patients

To describe the efficacy and safety of omalizumab, an anti‐IgE monoclonal antibody, in patients with refractory and/or relapsing eosinophilic granulomatosis with polyangiitis (Churg‐Strauss) (EGPA).

Intravenous immunoglobulin as immunomodulating agent in ANCA‐associated vasculitides: a French nationwide study of 92 patients

Intravenous immunoglobulin (IVIG) represents a therapeutic alternative in antineutrophil cytoplasmic antibody–associated vasculitides (AAV), but its efficacy has been evaluated in only 2 small prospective trials. The aim of this study was to evaluate the efficacy and safety of IVIG in patients with AAV.

Successful treatment with azathioprine of relapsing Rosai-Dorfman disease of the central nervous system

Rosai-Dorfman disease (RDD) is a rare non-Langerhans histiocytosis that usually presents with lymphadenopathy. Although isolated involvement of the CNS was considered to be uncommon, numerous cases have been reported in recent years. For RDD of the CNS, the treatment consists, in general, of surgery. In cases of partial resection or relapse, chemotherapy regimens, corticosteroids, and/or radiotherapy have yielded negative results. The authors describe the case of a 57-year-old man with a history of chronic Q fever who presented with aphasia and partial seizure. Computed tomography of the brain revealed a left frontotemporal lesion that was suggestive of a meningioma. The lesion was partially resected and histopathological evaluation revealed the presence of RDD. Nineteen months later, a Jacksonian seizure prompted MRI evaluation, which disclosed a local recurrence of the tumor. Computed tomography and FDG-PET demonstrated that the RDD involved no other site, but the presence of ileitis, noted on ileoscopy, led to the diagnosis of Crohn disease. Treatment with the purine analog azathioprine was initiated, leading to an objective and sustained response in both the RDD tumor and ileitis over 35 months of follow-up. This case report highlights the potential use of a purine analog in cases of relapsing RDD of the CNS and a possible common defect of macrophage regulation in RDD, Crohn disease, and Q fever.

A Randomized and Double-Blind Controlled Trial Evaluating the Safety and Efficacy of Rituximab for Warm Auto-Immune Hemolytic Anemia in Adults (the RAIHA study)

This Phase 3 multicentre randomized double‐blind and placebo‐controlled trial aimed to compare the efficacy and safety of rituximab (RTX) to placebo for treating newly diagnosed warm autoimmune hemolytic anemia (wAIHA) in adults receiving prednisone. Adults with a confirmed diagnosis of wAIHA who previously received corticosteroids for less than 6 weeks could be included. At inclusion, all patients received prednisone at a daily dose of 1 mg/kg for 2 weeks, and then tapered according to a pre‐defined recommended reduction scheme. Besides prednisone, eligible patients received 2 infusions of RTX or placebo at a fixed dose of 1,000 mg 2‐week apart. The primary endpoint was overall response rate (complete response [CR] + partial response [PR]) in an intent‐to‐treat (ITT) analysis at 1 year. A total of 32 patients (17 females [53%], mean age at inclusion 71 ± 16 years) were enrolled and randomized. In all, 27 patients were followed for at least 1 year and their data were evaluable for response. With an ITT analysis, the overall response rate at 1 year was 75% [95%CI: 47.6‐92.7] with 11 CR and 1 PR with RTX versus 31% [11.0‐58.7] (5 CR) with placebo (P = 0.032). At 2 years, 10/16 patients with RTX versus 3/16 with placebo still showed CR (P = 0.011). Overall, eight severe infections occurred during follow‐up, six with placebo and two with RTX (P = 0.39). At 2 years, six patients with placebo had died, but none with RTX (P = 0.017). Compared to placebo, RTX combined with prednisone may be effective and safe for treating newly‐diagnosed wAIHA in adults. Am. J. Hematol. 92:23–27, 2017.