P. Blanche

Detection of myocardial involvement in patients with sarcoidosis applying T2-weighted, contrast-enhanced, and cine magnetic resonance imaging: initial results of a prospective study.

Purpose To assess myocardial magnetic resonance imaging (MRI) findings in sarcoidosis. Methods Cardiac assessment was prospectively performed in patients with sarcoidosis and included physical examination, electrocardiogram, echocardiography, thallium-201 myocardial scintigraphy, and coronary angiography if coronary disease was suspected. T2-weighted black-blood single-shot and inversion recovery fast spin echo, functional gradient echo, and T1-weighted gadolinium-DTPA-enhanced cardiac MRI examinations were performed in 40 patients while other cardiac disease was excluded. Results Results of the MRI images were normal in cardiac-asymptomatic stage I or Lofgren syndrome patients (n = 4). Among the patients with cardiac-asymptomatic multiple organ sarcoidosis, 17 of 31 patients (54%) had MRI myocardial abnormalities similar to those observed in five patients with cardiac symptoms: nodular peripheral increased intramyocardial signal intensity on both T2-weighted and contrast-enhanced images (n = 5), focal or patchy increased signal on contrast-enhanced images with or without myocardial thickening (n = 10), and focal increased signal only on T2-weighted images with or without myocardial thinning (n = 2). Focal contractility abnormalities were noticed in nine patients. Conclusions These preliminary results emphasize the occurrence of subclinical myocardial MRI abnormalities in patients with ongoing systemic sarcoidosis.

Response to antiviral treatment in hepatitis C virus-associated marginal zone lymphomas.

A link between chronic hepatitis C virus (HCV) infection and low-grade B-cell lymphomas has been suggested by epidemiological studies. Marginal zone lymphomas (MZLs) including splenic lymphomas with villous lymphocytes are among the most frequently reported subgroups in the setting of chronic HCV infection. In this study, we examined the effect of antiviral treatment in eight patients with HCV-associated MZL. We found that five out of eight patients have responded to interferon alpha and ribavirin. In some cases, hematologic responses were correlated to virologic responses. In addition, we report a case of large granular lymphocyte leukemia occurring in association with MZL and HCV, and responding to interferon and ribavirin. We suggest that there is an etiologic link between HCV and antigen-driven lymphoproliferative disorders.

HIV Combination Therapy: Immune Restitution Causing Cryptococcal Lymphadenitis Dramatically Improved by Anti-inflammatory Therapy

Two patients with AIDS developed microscopically verified focal cryptococcal lymphadenitis while treated with highly active anti-retroviral therapy for 8 and 15 months. Both were treated with fluconazole as a secondary prophylaxis for prior cryptococcal meningitis. Cryptococcus neoformans did not grow. Amphotericin was ineffective. Anti-inflammatory drugs had a dramatic effect.

Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with clonal lymphoproliferative disorders after orthotopic liver transplantation: a report of three cases

BACKGROUND/AIMS Post-transplant lymphoproliferative disorders (PT-LPD) are a well-known complication of organ transplantation. Their incidence after liver transplantation in adults ranges from 1.8 to 4%. Reduction of immunosuppression led to remission in a few cases. Other treatments include chemotherapy, interferon alpha therapy and/or intravenous-immunoglobulins, or antiviral drugs. However, monoclonal antibodies directed against B-cell specific antigens have rarely been used in those patients. Our aim was to study the feasibility and efficacy of Rituximab, a new, promising human chimeric antibody that recognizes the CD20 antigen, for the treatment of patients with clonal lymphoproliferative disorders after orthotopic liver transplantation. METHODS Rituximab (IDEC-C2HB8; Roche Laboratories, Neuilly-sur-Seine, France) was administered at a 375 mg/m2 dose on days 1, 8, 15, and 22, in an outpatient setting, in three patients with PT-LPD. The tumor was classified as polymorphic PT-LPD in two cases and PT-LPD with features of large cell lymphoma in one case. All the tumors expressed the CD20 antigen and were EBV-related, and the clonality was confirmed in all three cases. The 4 injections of the anti-CD20 monoclonal antibody were associated with reduced immunosuppression in the three patient. RESULTS The treatment with Rituximab was well tolerated without any side effects. The two patients with polymorphic PT-LPDs underwent rapid complete remission, whereas the treatment modalities were ineffective in the patient with the large-cell non-Hodgkin-lymphoma. CONCLUSION These results must be confirmed in a larger cohort of liver transplant recipients suffering from lymphoproliferation. However, they indicate rapid efficiency of Rituximab in association with reduced immunosuppression in these disorders.

Tuberculosis Due to Mycobacterium bovis after Alemtuzumab Administration

We describe a patient with relapsing B chronic lymphocytic leukemia who developed systemic bacille Calmette-Guérin infection (BCGitis) after administration of alemtuzumab (Campath-1H).

Characteristics of Vogt-Koyanagi-Harada Disease in a French Cohort: Ethnicity, Systemic Manifestations, and HLA Genotype Data

Purpose: To assess in patients followed in a French referral center the clinical spectrum of Vogt-Koyanagi-Harada (VKH) disease and the HLA-DRB1*04 genotype. Methods: Patients previously diagnosed as having VKH disease were re-evaluated in a cross-sectional study using the VKH Committees revised criteria. High-resolution HLA-DRB1 genotyping was performed. Results: Eleven white patients satisfied ophthalmologic diagnostic criteria. All originated from Mediterranean countries. Nine and 3 patients had neurologic and/or cutaneous abnormalities, respectively. Among DRB1*04-positive patients, the HLA-DRB1*0405 subtype was 71%. Conclusion: These VKH patients predominantly had an incomplete form. The HLA-DRB1*0405 subtype allele was enriched in a group of Mediterranean stock.

Lack of evidence of an association between HHV-8 and multiple myeloma.

HHV-8 has been proposed to play a role in the pathogenesis of multiple myeloma (MM) and other dysglobulinaemias. PCR and in situ hybridization studies detected this virus in dendritic cells (DCs) from long-term cultured bone marrow stroma (LTBMSCs).1 PCR positivity for HHV-8 in bone marrow biopsy samples was also reported.2,3 However, sera of MM patients are negative for anti-HHV-8 antibodies. We decided to study the presence of HHV-8 in various haematologic compartments of patients with MM or other dysglobulinaemias. Thirteen patients were enrolled: nine with MM, one with primary AL amyloidosis, one with polyneuropathy-organomegaly-endocrinopathy-monoclonal-skin (POEMS) syndrome, and two with Waldenstrom’s macroglobulinaemia (WM) (Table 1). Serology was performed by using an immunofluorescence assay done on the BCP-1 cell line.8 Sera from five patients with classic Kaposi’s sarcoma (KS) and from five patients with AIDS-associated KS were used as controls. All DNA samples were subjected to KS330233, KS330233 nestedPCR and v-IL-6 PCR amplification under conditions described elsewhere.9 PCR products were hybridized with specific digdUTP labelled probes as previously reported.10 Amplification of the human b-globin gene was performed in all samples. DNA from the BCP-1 cells served as positive control. The search for the HHV-8 genome was performed from DNA extracted from: (1) Peripheral blood mononuclear cells (PBMCs). (2) Dendritic cells (DCs) generated from PBMCs (PBMCs were cultured in a cocktail of cytokines composed of 3 ng/ml GM-CSF + 25 ng/ml stem cell factor + 50 ng/ml Flt3Ligand + 10 ng/ml TNF a. 10 ng/ml of interleukin-4 were added after 5 days of culture. At day 12, FACS analysis was performed with antibodies to CD1a (CD1a-PE, Coulter, France), HLA-Dr (DR-PE, Coulter) and CD14 (CD14-FITC, Coulter), to determine the percentage of DCs). (3) Total bone marrow mononuclear cells (BMMCs). (4) Long-term bone marrow stromal cells (LTBMSCs) cultured for 10, 15 or 20 days as previously described.11 (5) Fresh bone marrow (BM) biopsies in some patients. None of our 13 patients with MM or other dysglobulinaemias had HHV-8 antibodies (Table 1), whereas all 10 control patients did. HHV-8 DNA sequences could not be detected in PBMCs samples. At day 12 of culture, 20–60% CD1a+, HLADR+, CD14− dendritic cells were generated from the PBMCs of patients with MM. PCR amplification for HHV-8 was negative in all samples tested (Table 1). The KS330233 and v-IL-6 sequences of HHV-8 could not be detected in any of the bone marrow samples, either in total BMMCs, in fresh BM biopsies, or in LTBMSCs whatever the duration of culture (10, 15 and 20 days) (Table 1). In addition, patient 10 with a POEMS syndrome and patient 11 with a primary AL amyloidosis were also negative for HHV8 in per-

Relevance of diagnostic investigations in patients with uveitis: Retrospective cohort study on 300 patients

OBJECTIVE The diagnostic workup of uveitis is a challenge due to the wide range of diagnoses and the lack of a well-codified diagnostic procedure. We aimed to evaluate the relevance of diagnostic investigations for the etiological diagnosis of uveitis. METHODS Retrospective cohort study of patients referred for etiological diagnosis of uveitis. Uveitis related to ophthalmological diseases or occurring during the course of previously diagnosed diseases were not included. RESULTS Three hundred patients were included. Chest CT-scan was suggestive of sarcoidosis in 83 (29%). Features associated with abnormal CT-scan were: snowballs and/or peripheral multifocal choroiditis (PMC) upon ocular examination (P=0.004), blood lymphopenia (P<0.0001), angiotensin converting enzyme (ACE) level>1.5 ULN (P=0.0003). Bronchoscopy showed granuloma in 18 (11%) while alveolar lymphocytosis suggestive of sarcoidosis was reported in 45 (27%). Presence of granuloma on bronchial biopsies was always associated with chest CT-scan abnormalities, whereas 31% of patients with alveolar lymphocytosis had normal CT-scans. Features associated with contributive bronchoscopy were: snowballs and/or PMC (P=0.003), ACE>1.5 ULN (P=0.007), abnormal chest-CT scan (P<0.0001). Salivary gland biopsy revealed granuloma in 12 patients (5%). Cerebral MRI was abnormal in 15 patients (9%) who mostly presented with snowballs and/or retinal vasculitis. Finally, the main causes of uveitis were latent tuberculosis (25%) and sarcoidosis (22%), but 34% remained of undetermined origin. Uveitis relapses were observed in 31% and did not differ between patients with an identified diagnosis and those with idiopathic uveitis. CONCLUSION Identification of factors associated with abnormal investigations might improve the optimal diagnostic workup adapted to each patient.

Rituximab as first-line therapy for acquired haemophilia A: a single-centre 10-year experience.

B. ROSSI,* P. BLANCHE,* V. ROUSSEL-ROBERT,† A. BEREZN E,* S. COMBE,† P. COPPO,‡ L. GUILLEVIN,* C. LE JEUNNE,* L. MOUTHON,* N. OUNNOUGHENE,† N. STIELTJES† and M. GROH* *Department of Internal Medicine, National Referral Center for Rare Autoimmune and Systemic Diseases, Hôpital Cochin, Assistance Publique Hôpitaux de Paris, Universit e Paris Descartes; †Centre des h emophiles, Hôpital Cochin, Assistance Publique Hôpitaux de Paris Universit e Paris Descartes; and ‡Department of Hematology, Hôpital Saint-Antoine, Assistance Publique Hôpitaux de Paris, Universit e Pierre et Marie Curie, Paris, France

Efficacy and safety of rituximab for systemic lupus erythematosus‐associated immune cytopenias: A multicenter retrospective cohort study of 71 adults

The aim of the study was to assess the efficacy and safety of rituximab (RTX) for treating systemic lupus erythematosus (SLE)‐associated immune cytopenias. This multicenter retrospective cohort study of adults from French referral centers and networks for adult immune cytopenias and SLE involved patients ≥18 years old with a definite diagnosis of SLE treated with RTX specifically for SLE‐associated immune cytopenia from 2005 to 2015. Response assessment was based on standard definitions. In total, 71 patients, 61 women (85.9%), with median age 36 years [interquartile range 31‐48], were included. The median duration of SLE at the time of the first RTX administration was 6.1 years [2.6‐11.6] and the reason for using RTX was immune thrombocytopenia (ITP) for 44 patients (62.0%), autoimmune hemolytic anemia (AIHA) for 16 (22.5%), Evans syndrome for 10 (14.1%), and pure red cell aplasia for one patient. Before receiving RTX, patients had received a mean of 3.1 ± 1.3 treatments that included corticosteroids (100%), and hydroxychloroquine (88.5%). The overall initial response rate to RTX was 86% (91% with ITP, 87.5% with AIHA, and 60% with Evans syndrome), including 60.5% with complete response. Median follow‐up after the first injection of RTX was 26.4 months [14.3‐71.2]. Among 61 initial responders, relapse occurred in 24 (39.3%); for 18, RTX retreatment was successful in 16 (88.8%). Severe infections occurred after RTX in three patients, with no fatal outcome. No cases of RTX‐induced neutropenia were observed. In conclusion, RTX seems effective and relatively safe for treating SLE‐associated immune cytopenias.