Utility of anaerobic bottles for the diagnosis of bloodstream infections.

BACKGROUND: Obligate anaerobes usually account for less than 10% of bacteria recovered from blood cultures (BC). The relevance of routine use of the anaerobic bottle is under debate. The aim of this study was to evaluate the utility of anaerobic bottles for the diagnosis of bloodstream infections (BSI). METHODS: We conducted a 6-month, retrospective, monocentric study in a tertiary hospital. All positive BC were grouped into a single episode of bacteremia when drawn within 7 consecutive days. Bacteremia were classified into contaminants and BSI. Charts of patients with BSI due to obligate anaerobes were studied. RESULTS: A total of 19,739 blood cultures were collected, 2341 of which (11.9%) were positive. Anaerobic bottles were positive in 1528 (65.3%) of all positive BC but were positive alone (aerobic bottles negative) in 369 (15.8%). Overall 1081 episodes of bacteremia were identified, of which 209 (19.3%) had positive anaerobic bottles alone. The majority 126/209 (60.3%) were contaminants and 83 (39.7%) were BSI. BSI due to facultative anaerobes, obligate aerobes and obligate anaerobes were identified in 67 (80.7%), 3 (3.6%) and 13 (15.7%) of these 83 episodes, respectively. BSI due to obligate anaerobic bacteria were reported in 9 patients with gastro-intestinal disease, in 3 with febrile neutropenia and in 1 burned patient. CONCLUSIONS: Anaerobic bottles contributed to the diagnosis of a significant number of episodes of bacteremia. Isolated bacteria were mostly contaminants and non-obligate anaerobic pathogens. Rare BSI due to obligate anaerobes were reported mainly in patients with gastro-intestinal disorders and during febrile neutropenia.

Cutaneous presentation of adult T-cell leukemia/lymphoma (ATLL). Single-center study on 37 patients in metropolitan France between 1996 and 2016.

INTRODUCTION: Adult T-cell leukemia/lymphoma (ATLL) is a hematological malignancy associated with chronic HTLV-1 infection. AIM: To describe skin lesions in ATLL. METHODS: A descriptive, retrospective study between 1996 and 2016, including all patients diagnosed with ATLL at Saint-Louis Hospital (Paris, France). RESULTS: Thirty-seven ATLL patients were included. Fifteen patients (41%) had a cutaneous localization of the disease, which was present from the beginning of the disease for two thirds of them. ATLL types in patients with cutaneous localization of the disease were as follows: lymphoma, n=5, chronic, n=4, smoldering, n=4, acute, n=2. Half the patients had 2 or more cutaneous manifestations. The cutaneous localizations observed were as follows: nodulotumoral (n=8), plaques (n=7), multipapular (n=6), macular (n=4), purpuric (n=2). Among the 15 patients with cutaneous localization, median overall survival was significantly shorter in the acute and lymphoma types compared to the smoldering and chronic types (8.7 months vs. 79 months, P=0.003). DISCUSSION: ATLL is a hematologic malignancy with variable expression that is diagnosed only very rarely in metropolitan France, but that should be sought in patients from countries with high HTLV-1 prevalence in the event of a chronic eruption with patches, papules, plaques and/or tumors. The chronic and smoldering types are relatively indolent, whereas the acute and lymphoma forms have a poor prognosis.

HIV Tat induces a prolonged MYC relocalization next to IGH in circulating B-cells.

With combined antiretroviral therapy (cART), the risk for HIV-infected individuals to develop a non-Hodgkin lymphoma is diminished. However, the incidence of Burkitt lymphoma (BL) remains strikingly elevated. Most BL present a t(8;14) chromosomal translocation which must take place at a time of spatial proximity between the translocation partners. The two partner genes, MYC and IGH, were found colocalized only very rarely in the nuclei of normal peripheral blood B-cells examined using 3D-FISH while circulating B-cells from HIV-infected individuals whose exhibited consistently elevated levels of MYC-IGH colocalization. In vitro, incubating normal B-cells from healthy donors with a transcriptionally active form of the HIV-encoded Tat protein rapidly activated transcription of the nuclease-encoding RAG1 gene. This created DNA damage, including in the MYC gene locus which then moved towards the center of the nucleus where it sustainably colocalized with IGH up to 10-fold more frequently than in controls. In vivo, this could be sufficient to account for the elevated risk of BL-specific chromosomal translocations which would occur following DNA double strand breaks triggered by AID in secondary lymph nodes at the final stage of immunoglobulin gene maturation. New therapeutic attitudes can be envisioned to prevent BL in this high risk group.

Prevalence, risk factors, and impact on clinical outcome of extended-spectrum beta-lactamase-producing Escherichia coli bacteraemia: a five-year study.

BACKGROUND: The impact of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (ESBL-EC) bacteraemia on outcome remains controversial. METHODS: A retrospective analysis of the prevalence, risk factors, clinical features, and outcomes of all ESBL-EC bacteraemia in one French hospital over a 5-year period was performed. A case-control study was undertaken: cases had at least one ESBL-EC bacteraemia and controls a positive non-ESBL-EC bacteraemia. RESULTS: The prevalence of ESBL-EC bacteraemia increased from 5.2% of all positive E. coli blood cultures in 2005 to 13.5% in 2009 (p<0.003). CTX-M represented 70% of ESBL-EC bacteraemia strains, and strains were not clonally related. On adjusted analysis, the only significant risk factor for ESBL-EC bacteraemia was a previous ESBL-EC colonization (odds ratio 11.3, 95% confidence interval 1.2-107; p=0.003). Initial antimicrobial therapy was less frequently adequate in the ESBL-EC group (48% vs. 85%; p=0.003). The presence of ESBL-EC bacteraemia was not associated with a longer hospital stay (p=0.088). Day 30 mortality was high, but not significantly different in the two groups (30% vs. 27%; p=0. 82). CONCLUSION: The prevalence of ESBL-EC bacteraemia has been increasing dramatically. Previous colonization with ESBL-EC was a strong risk factor for ESBL-EC bacteraemia. More inadequate initial antimicrobial therapy was noted in the ESBL-EC group, but mortality and length of hospital stay were not significantly different from those of patients with non-ESBL-EC bacteraemia.

[Lung disease in adult common variable immunodeficiency]. / Atteintes respiratoires au cours du déficit immunitaire commun variable de l'adulte.

INTRODUCTION: Common variable immunodeficiency (CVID) is characterized by a defect in antibody production and may be complicated by infectious or non-infectious respiratory disease. BACKGROUND: In addition to recurrent infectious complications, mainly due to encapsulated bacteria, CVID may be complicated by diffuse infiltrative, non-infectious lung disease. The latter may be related to granulomatosis, lymphoid interstitial pneumonia, follicular bronchiolitis, follicular nodular hyperplasia, organizing pneumonia or lymphoma. Different lymphoid histological lesions can co-exist and form a new entity called GLILD (granulomatous lymphocytic interstitial lung disease), which is associated with a poor prognosis. Replacement of immunoglobulins significantly decreases the frequency and severity of infections but has no impact on the non-infectious complications. OUTLOOK: Studies are needed to determine the modalities of follow-up and better understand the long-term progress of GLILD. These studies should improve the management of GLILD in the context of immunosuppressive treatments, which increase the risk of infection in CVID. CONCLUSION: The identification of GLILD, which reflects a variable histological spectrum, rather than a well-defined entity, necessitates revising the approach to diffuse infiltrative lung diseases in CVID.

Efficiency of immunoglobulin G replacement therapy in common variable immunodeficiency: correlations with clinical phenotype and polymorphism of the neonatal Fc receptor.

Treatment of common variable immunodeficiency disorders (CVID) is based on replacement therapy using intravenous (i.v.) or subcutaneous (s.c.) immunoglobulin (Ig)G. Interindividual variation of IgG dose is common. A total of 380 CVID patients on stable IgG replacement from two prospective cohorts were analysed. An 'efficiency' index was defined as the ratio of serum IgG trough level minus IgG residual to the average weekly dose of IgG infusion. A reduced efficiency of IgG was associated independently with the i.v. route (P < 0·001) and with the presence of at least one CVID disease-related phenotype (lymphoproliferation, autoimmune cytopenia or enteropathy) (P < 0·001). High IgG efficiency was noted in patients homozygotes for the variable number tandem repeat (VNTR) 3/3 polymorphism of the neonatal Fc receptor gene [IgG Fc fragment receptor transporter alpha chain (FCGRT)] promoter, and this was particularly significant in patients treated with IVIG (P < 0.01). In a multivariate analysis, FCGRT VNTR 3/3 genotype (P = 0·008) and high serum albumin (P < 0·001) were associated independently with increased efficiency of i.v. Ig.

Human herpesvirus 8-related Castleman disease in the absence of HIV infection.

BACKGROUND: Castleman disease (CD) in the context of human immunodeficiency virus (HIV) infection is well described. It is almost always multicentric (MCD) and linked to human herpesvirus 8 (HHV-8). There are limited published data surrounding HHV-8-related CD among HIV-negative patients. METHODS: From January 1995 through June 2012, we identified in a single center 18 HIV-seronegative patients with HHV-8-related CD. We report on their clinical, pathological, and laboratory features. RESULTS: All cases were multicentric. Patients were aged 42-83 years and were referred with a relapsing remitting syndrome of fever (94%), constitutional symptoms (100%), peripheral lymphadenopathy (100%), splenomegaly (72%), hepatomegaly (50%), and edema (28%). Kaposi sarcoma was observed in 9 cases. Anemia and serum markers of inflammation were present in all cases. Polymerase chain reaction for HHV-8 DNA was positive on blood samples in all cases, whereas only 12 of 16 patients tested had positive HHV-8 serology at diagnosis. All cases showed the classic histological features of MCD, and LANA-1 immunostaining identified HHV-8-infected plasmablasts in 16 of 16 tested cases. Reactive hemophagocytic syndrome (44%), autoimmune hemolytic anemia (33%), and lymphoma (22%) were the commonest associated complications. Remission was obtained with etoposide in 13 of 15 cases. Rituximab allowed prolonged remission off therapy in 10 cases. Death occurred in 3 patients not treated with rituximab. These features were similar to those described in HIV-positive HHV-8-related MCD. Comparison between these 18 cases and 12 HIV-negative HHV-8-unrelated MCD cases showed marked discrepancies. CONCLUSIONS: HHV-8-associated MCD may be considered as a single clinicopathological entity regardless of HIV status.

[Pulmonary non-infectious diseases in common variable immunodeficiency]. / Manifestations pulmonaires non infectieuses du déficit immunitaire commun variable.

Few studies have described pulmonary non-infectious diseases (PNID) in patients with common variable immunodeficiency (CVID). Indeed the most frequent complications in these patients are infectious. The aim of our study is to analyze the characteristics of PNID in a retrospective study of patients with CVID of two pneumology departments in Paris (France), from 1990 to 2008. PNID was observed in 11 patients. Mean immunoglobulin serum level was 3.46g/L. The PNID observed were: arteriovenous pulmonary fistula: three; interstitial lung disease: three; asthma: two; mediastinal lymphadenopathy: four; emphysema: one; mesothelioma: one. Our study outlines the broad spectrum of pulmonary manifestations related to CVID. Clinicians should be aware of the diagnosis of PNID even in patients without classic infectious manifestations.

[Accessory spleens after splenectomy in a patient with common variable immunodeficiency]. / Rates accessoires après splénectomie pour thrombopénie immunologique chez un patient ayant un déficit immunitaire commun variable.

INTRODUCTION: Blood cells are mainly destroyed in the spleen during autoimmune cytopenia. Amongst the various therapeutic strategies, splenectomy is sometimes necessary during the disease course. However, splenosis or accessory spleens can account for autoimmune cytopenia relapse after initial splenectomy in these patients. CASE REPORT: We report an 18-year-old male with common variable immunodeficiency who presented with immunological thrombocytopenia. Splenectomy allowed remission of cytopenia, but a relapse was attributed to splenosis, because Jolly bodies were absent on blood smear. Laparoscopic splenectomy of accessory spleens induced long term remission. A literature review is performed. CONCLUSION: Fifteen to 20% of relapses of autoimmune cytopenia treated by splenectomy are related to accessory spleens. Ablation of accessory spleens can cure again the patients, including patients with accompanying common variable immunodeficiency.

Cerebral immunoglobulin light chain amyloid angiopathy-related hemorrhages.

INTRODUCTION: Cerebral amyloid angiopathy (CAA) is a common cause of intracerebral hemorrhage (ICH) particularly in elderly patients. In CAA-related hemorrhages, amyloid deposits in the brain vessel walls mainly contain amyloid beta-protein (A-beta). Rarely other forms of amyloid substances have been reported in sporadic CAA-related hemorrhages. METHODS: We report the case of a 44-year-old patient with recurrent ICH who had surgical evacuation of a large frontal hematoma. Following surgery, samples from the hematoma and adjacent cerebral cortex were obtained for histopathological examination. RESULTS: Within the recent hemorrhage, a few arteriolar walls were thickened with an amyloid deposit that was immunostained for immunoglobulin (Ig) M and light chain lambda. In the wall of some vessels, around the amyloid deposits, as well as in the adjacent cerebral cortex, there was an infiltration by monotypic lymphocytes and plasma cells expressing IgM and light chain lambda. No amyloid deposition was found outside the hemorrhage. There was no evidence of multiple myeloma, B-cell malignancy, or systemic amyloidosis. CONCLUSIONS: Recurrent ICH may be due to amyloid deposition of IgM lambda produced by monotypic proliferation of lymphocytes and plasma cells purely localized to the brain.

[Granulomatous disease in common variable immunodeficiency]. / Maladie granulomateuse au cours du déficit immunitaire commun variable.

PURPOSE: Common variable immunodeficiency (CVID), defined by defective production of immunoglobulins, is the most common primary immunodeficiency in adulthood requiring a medical follow-up. Repeated bacterial infections and/or autoimmune manifestations and/or benign lymphoproliferation (including follicular hyperplasia and/or granulomatous disease) are the hallmark of the disease. This review aims at describing recent advances in the understanding and treatment of granulomatous disease in CVID. CURRENT KNOWLEDGE AND KEY POINTS: Clinical features of granulomatous disease in CVID can mimic sarcoidosis, remarkable by the low levels of circulating immunoglobulins. Granulomas may be found in several organs in a single patient, and the main features are pulmonary, lymphoid, cutaneous, hepatic or splenic. The features of CVID is remarkable by the high frequency of autoimmune diseases complicating the immunodeficiency. Some immunological abnormalities have been described in such patients, including lymphopenia, decreased T-cells proliferations to mitogens and antigens. Rare polymorphisms in the gene encoding TNFalpha (Tumor Necrosis Factor) have been identified in CVID patients with granulomatous disease. FUTURE PROSPECTS AND PROJECTS: The evolution of the disease is severe, particularly when the lung is involved. Treatment consists in immunoglobulins substitution, immunosuppressive agents (corticosteroids, cyclophosphamide) and anti-TNFalpha antibodies. These treatments are difficult to manage in such immunocompromised patients.