[Peripheral neuropathies during systemic diseases: Part II (vasculitis)]. / Neuropathies périphériques au cours des maladies de système : partie II (vascularites).

Primary systemic vasculitides, mainly of the small and medium-sized vessels, are frequently associated with peripheral neuropathies. When the disease is already known, the appearance of a neuropathy should suggest a specific injury, especially when associated with other systemic manifestations. Conversely, when neuropathy is inaugural, close collaboration between neurologists and internists is necessary to reach a diagnosis. A standardized electro-clinical investigation specifying the topography, the evolution and the mechanism of the nerve damage enables the positive diagnosis of the neuropathy. Several elements orient the etiological diagnosis and allow to eliminate the main differential diagnosis: non systemic vasculitic neuropathy. The existence of associated systemic manifestations (glomerular or vascular nephropathy, interstitial lung disease, intra-alveolar hemorrhage, ENT involvement…), biological markers (ANCA, cryoglobulinemia, rheumatoid factor), and invasive examinations allowing histological analysis (neuromuscular biopsy) are all useful tools for.

[Peripheral neuropathies during systemic diseases: Part I (connective tissue diseases and granulomatosis)]. / Neuropathies périphériques au cours des maladies de système : partie I (connectivites et granulomatoses).

Systemic diseases (connective disease, granulomatosis) may be associated with peripheral neuropathies. The diagnosis can be complex when the neuropathy is the presenting manifestation of the disease, requiring close collaboration between neurologists and internists. Conversely, when the systemic disease is already known, the main question remaining is its imputability in the neuropathy. Regardless of the situation, the positive diagnosis of neuropathy is based on a systematic and rigorous electro-clinical investigation, specifying the topography, the evolution and the mechanism of the nerve damage. Certain imaging examinations, such as nerve and/or plexus MRI, or other more invasive examinations (skin biopsy, neuromuscular biopsy) enable to specify the topography and the mechanism of the injury. The imputability of the neuropathy in the course of a known systemic disease is based mainly on its electro-clinical pattern, on which the alternatives diagnoses depend. In the case of an inaugural neuropathy, a set of arguments orients the diagnosis, including the underlying terrain (young subject), possible associated systemic manifestations (inflammatory arthralgias, polyadenopathy), results of first-line laboratory tests (lymphopenia, hyper-gammaglobulinemia, hypocomplementemia), autoantibodies (antinuclear, anti-native DNA, anti-SSA/B) and sometimes invasive examinations (neuromuscular biopsy).

Neuropathies périphériques associées aux syndromes lymphoprolifératifs : spectre clinique et démarche diagnostique.

Lymphoproliferative syndromes (multiple myeloma, Waldenström's disease, chronic lymphocytic leukemia, lymphomas) may be associated with peripheral neuropathies. The mechanism can be dysimmune, associated or not with monoclonal gammopathies; paraneoplastic; infiltrative; or more commonly, iatrogenic or due to vitamin deficiency. The diagnosis can be complex, especially when the neuropathy is the presenting manifestation, requiring a close cooperation between internists and neurologists. The positive diagnosis of the neuropathy is based on a systematic electro-clinical investigation, which specifies the topography and the mechanism of the nerve damage, sometimes reinforced by imaging examinations, in particular, nerve and/or plexus MRI. The imputability of the neuropathy to a lymphoproliferative syndrome is based on a set of arguments including the clinical context (B signs, tumour syndrome), first-line laboratory tests (hemogram, protein electrophoresis, viral serologies, complement), auto-antibodies discussed according to the neuropathy (anti-MAG, anti-gangliosides) and sometimes more invasive examinations (bone marrow or neuro-muscular biopsies).

Factors associated with tuberculosis-associated haemophagocytic syndrome: a multicentre case-control study.

SETTING: Tuberculosis (TB) is a potential trigger of haemophagocytic syndrome (HS) but little is known about the features of TB-associated HS.OBJECTIVE: To assess the risk factors associated with HS in patients with TB.DESIGN: We performed a multicentre case-control study assessing the medical records of adult patients diagnosed with proven TB with (TB/HS+) or without (TB/HS-) associated HS.RESULTS: Twenty-one patients with TB/HS+ (24% women, median age, 37 years [IQR 30-48]) were included in the study. Eleven patients (52%) were infected with human immunodeficiency virus and seven patients (33%) were immunocompromised due to other reasons. TB was disseminated in 17 patients (81%). Compared with 50 control TB patients (TB/HS-), patients with TB/HS+ were more likely to be immunocompromised (86% vs. 18%; P < 0.001) and to present with disseminated TB (80% vs. 12%; P < 0.001). The outcome was poorer in patients with TB/HS+, with a higher admission rate to intensive care (71% vs. 0%; P < 0.001) and a higher risk of death (38% vs. 7%; P = 0.005).CONCLUSION: TB/HS+ occurred more likely in immunocompromised patients and severely impaired the prognosis of TB. Further studies are needed to devise therapeutic strategies for patients with TB/HS+.

[Cervical spinal sarcoidosis mimicking compressive cervical myelopathy: Poor prognosis after surgery]. / Sarcoïdose médullaire mimant une myélopathie cervico-arthrosique : mauvais pronostic après chirurgie.

INTRODUCTION: Cervical spinal sarcoidosis can mimic compressive cervical myelopathy leading to potentially harmful surgical procedures before the diagnosis can be made. METHODS: Retrospective description of 3 patients and review of the literature. RESULTS: Twenty-seven patients (16 men/11 women), median age 58 years [range 29-74] were described. Neurosurgical procedures consisted of laminectomy (n=10), laminoplasty (n=15) and anterior discectomy (n=2). Immediately after surgery, 17 patients (63%) worsened or remained disabled. Among the 10 patients who improved, 9 worsened secondarily. The analysis of preoperative MRI showed T2 hypersignal lesions and contrast enhancement in all patients. Neurological symptoms were inaugural in 25/27 patients, and systemic involvement of the sarcoidosis was found after surgery in 15/27 patients. After surgery, all patients received corticosteroids, along with immunosuppressive therapy in 8 cases/27. After a follow-up of 24 [16-72] months; 13 patients were stabilized or worsened, 7 were partially improved. Three died of other cause. Only 5 recovered without sequelae. CONCLUSION: In patients with compressive cervical myelopathy, leptomeningeal contrast enhancement, a T2-weighted hypersignal exceeding the compression level on MRI, and the presence of extraneurological symptoms should point to inflammatory disease. These rare manifestations may be the first symptoms of sarcoidosis and should be recognized to avoid harmful surgical procedures and to provide appropriate medical treatment.

Hospitalization of HIV positive patients: Significant demand affecting all hospital sectors.

BACKGROUND: In a context of the evolution of severe morbidities in patients living with HIV (PLWH), the aim of this study was to describe reasons for hospitalization and the mode of care for the patients requiring hospitalization. METHODS: All admissions (≥24h) of PLWH to 10 hospitals in the south of Paris (COREVIH Ile-de-France Sud) between 1/1/2011 and 12/31/2011 were identified. The hospital database and the file of patients followed in the HIV referral department of each hospital were matched. Detailed clinical and biological data were collected, by returning to the individual medical records, for a random sample (65% of hospitalized patients). RESULTS: A total of 3013 hospitalizations (1489 patients) were recorded in 2011. The estimated rate of hospitalized patients was about 8% among the 10105 PLWH routinely managed in COREVIH Ile-de-France Sud in 2011. The majority (58.5%) of these hospitalizations occurred in a unit other than the HIV referral unit. Non-AIDS-defining infections were the main reason for admission (16.4%), followed by HIV-related diseases (15.6%), hepatic/gastrointestinal diseases (12.0%), and cardiovascular diseases (10.3%). The median length of stay was 5 days overall (IQR: 2-11), it was longer among patients admitted to a referral HIV care unit than to another ward. HIV infection had been diagnosed >10 years previously in 61.4% of these hospitalized patients. They often had associated comorbidities (coinfection HCV/HVB 40.5%, smoking 45.8%; hypertension 33.4%, dyslipidemia 28.8%, diabetes 14.8%). Subjects over 60 years old accounted for 15% of hospitalized patients, most of them were virologically controlled under HIV treatment, and cardiovascular diseases were their leading reason for admission. CONCLUSION: Needs for hospitalization among PLWH remain important, with a wide variety in causes of admission, involving all hospital departments. It is essential to prevent comorbidities to reduce these hospitalizations, and to maintain a link between the management of PLWH, that becomes rightly, increasing ambulatory, and recourse to specialized inpatient services.

Treatment of limbic encephalitis with anti-glioma-inactivated 1 (LGI1) antibodies.

We report a 72-year-old patient who developed acute limbic encephalitis initially considered of uncertain aetiology. Detailed information on clinical presentation, MRI appearance, antibody levels, cognitive impairment assessment, treatment and evolution of the patient is reported here. Since the early 2000s, many antibodies implied in central nervous system autoimmune disorders have been identified. Anti-glioma-inactivated 1 (LGI1) antibodies have been recently identified as associated with limbic encephalitis, as was the case in our patient.

Blood Epstein-Barr virus DNA load and risk of progression to AIDS-related systemic B lymphoma.

BACKGROUND: AIDS-related lymphoma (ARL) remains the main cause of AIDS-related deaths in the combined antiretroviral therapy (cART) era. Although most ARLs are associated with the Epstein-Barr virus (EBV), whether patients with high EBV burden are more at risk of developing ARL is unknown. This study investigated the relationship between high blood EBV DNA loads and subsequent progression to ARL. METHODS: We identified 43 cases of ARL diagnosed between 1988 and 2007 within two cohorts (ANRS SEROCO/HEMOCO and PRIMO) and for which stored serum and peripheral blood mononuclear cell (PBMC) samples were available within 3 years before ARL diagnosis. For each case, two controls matched for the cohort and CD4 cell count in the year of ARL diagnosis were selected. EBV DNA was measured in PBMCs and serum samples with a commercial kit. RESULTS: High levels of EBV DNA in PBMCs collected a median of 10 months before diagnosis were associated with an increased risk of developing systemic B lymphoma (adjusted odds ratio 2.47; 95% confidence interval 1.15; 5.32 for each 1 log copies/10(6) PBMC increase in EBV load) but not with primary brain lymphoma. CONCLUSION: In this study, HIV-infected patients with undetectable EBV DNA in PBMCs did not develop ARL in the following 3 years, while high levels of EBV DNA in PBMCs predicted subsequent progression to systemic B lymphoma. Clinicians should be aware of the increased risk of developing systemic B lymphoma in HIV-infected patients with a high blood EBV DNA load.

[Cat scratch disease with bone involvement: a case report and literature review]. / Maladie des griffes du chat avec localisations osseuses: une observation et revue de la littérature.

INTRODUCTION: Cat scratch disease is an infectious disease caused by Bartonella henselae. Most of the patients present with a lymphadenopathy associated with a local infection at the site of the cat scratch. Disseminated infection is uncommon. CASE REPORT: We report an immunocompetent 61-year-old woman who presented with a systemic cat scratch disease including a multifocal osteomyelitis. Diagnosis was confirmed by PCR on the adenopathy. A literature review identified 51 other cases of osteomyelitis associated with cat scratch disease, 14 of those confirmed by PCR. CONCLUSION: Bone involvement in cat scratch disease is rare, especially in adults. The diagnosis should be suspected on the basis of patient questioning. The antibiotherapy and the place of surgery are discussed.

Vaccination in adults with auto-immune disease and/or drug related immune deficiency: results of the GEVACCIM Delphi survey.

INTRODUCTION: There are insufficient data regarding the efficacy and safety of vaccination in patients with auto-immune disease (AID) and/or drug-related immune deficiency (DRID). The objective of this study was to obtain professional agreement on vaccine practices in these patients. METHODS: A Delphi survey was carried out with physicians recognised for their expertise in vaccinology and/or the caring for adult patients with AID and/or DRID. For each proposed vaccination practice, the experts' opinion and level of agreement were evaluated. RESULTS: The proposals relating to patients with AID specified: the absence of risk of AID relapse following vaccination; the possibility of administering live virus vaccines (LVV) to patients not receiving immunosuppressants; the pertinence of determining protective antibody titre before vaccination; the absence of need for specific monitoring following the vaccination. The proposals relating to patients with DRID specified that a 3-6 month delay is needed between the end of these treatments and the vaccination with LVV. There is no contraindication to administering LVV in patients receiving systemic corticosteroids prescribed for less than two weeks, regardless of their dose, or at a daily dose not exceeding 10mg of prednisone, if this involves prolonged treatment. Out of 14 proposals, the level of agreement between the experts was "very good" for eleven, and "good" for the remaining three. CONCLUSION: Proposals for vaccine practices in patients with AID and/or DRID should aid with decision-making in daily medical practice and provide better vaccine coverage for these patients.

[Autoimmune myelofibrosis with dermatomyositis]. / Myélofibrose auto-immune secondaire à une dermatomyosite.

We report a second observation of autoimmune myelofibrosis associated with an inflammatory myositis in a 30-year-old female. The links between myelofibrosis and autoimmunity are discussed.

Congenital dyserythropoietic anaemia, type I, in a Caucasian patient with retinal angioid streaks (homozygous Arg1042Trp mutation in codanin-1).

A congenital dyserythropoietic anaemia (CDA) was recognised in a French Caucasian male patient. Blood smears showed a pronounced aniso-poikilocytosis. Bone marrow light microscopy showed signs of dyserythropoesis, but no internuclear chromatin bridges. Electron microscopy disclosed erythroblast nuclei with the Swiss cheese aspect and the presence of cytoplasmic organelles, assessing the diagnosis of CDA I. The presence of internuclear chromatin bridges may thus be missing in CDA I. The patient proved to be homozygous for the Arg1042Trp mutation in codanin-1 (the 'Bedouin mutation'). By the age of 25, the patient's vision started to deteriorate as a result of retinal angioid streaks and macular abnormalities. Evolution was controlled and the patient, being nearly 50 yr old now, still has a partial use of his eyes. This second case of retinal angioid streaks reported in CDA I adds to the non-haematological features likely to be associated with this condition.

Hepatitis B virus-human immunodeficiency virus co-infection in France: a cross-sectional multicentre study.

This prospective, multicentre study was conducted between September and October 2003 in 38 French departments of internal medicine, infectious disease and hepatogastroenterology and included 406 consecutive HBV-infected patients (positive HBsAg), half of whom were HIV-infected (53%). The aim was to outline the main characteristics of hepatitis B virus (HBV)-human immunodeficiency virus (HIV) co-infected patients in French hospitals. HBV-HIV co-infected patients (85% were receiving HAART; mean CD4 count 447+/-245/microl, HIV RNA load<400 copies/ml, 67% of patients), compared to HIV-negative patients, were more often male, injecting drug users, HBeAg-positive and HCV-HIV co-infected (P<10(-4)). They underwent liver biopsy less often (31% vs. 51%, P<10(-4)), particularly those with severe immunodeficiency. They received anti-HBV treatment more often (75% vs. 45.7%, P<10(-4)), mainly lamivudine and tenofovir. Significant improvements in the management of such patients are awaited mainly in the appraisal of liver disease by either liver biopsy or non-invasive alternatives to liver biopsy.

[Risk factors for incident cervical intraepithelial neoplasia (CIN) among HIV-infected women: a prospective study]. / Facteurs de risque d'acquisition de lésions du col utérin dans une population de femmes infectées par le VIH: étude prospective.

OBJECTIVES: To study risk factors for incident cervical intraepithelial neoplasia (CIN) among HIV-infected women. PATIENTS AND METHODS: Prospective study of a population of 97 HIV-infected women with normal Pap smear at inclusion. RESULTS: Fourteen CIN (diagnosed by colposcopy and confirmed with biopsy) were observed within a median follow-up of 38 months (13 CIN 1, one CIN 2). The incidence of cervical lesions was estimated to be 2%, 7% and 10% respectively at one year, two and three years after inclusion, The time to occurrence was very variable (ranging from 7 months to 6 years) among our patients. No known risk factors, in particular neither the CD4 cell count nor antiretroviral treatment, were identified to be associated with occurrence of CIN in our study population. CONCLUSION: Regardless of their immune status and HIV treatments, extensive and prolonged gynaecological follow up of HIV-infected women remains necessary.

Beneficial effect of highly active antiretroviral therapy on the prognosis of AIDS-related systemic non-Hodgkin lymphomas.

The influence of HAART on the survival of patients with AIDS-related lymphoma (ARL) was evaluated. A retrospective analysis of 73 HIV-1-infected patients with proven ARL diagnosed between 1992 and 2000 was conducted. Patients received uniformly the same chemotherapy regimen according to CD4 cell counts at NHL diagnosis:, patients with CD4 cells below or above 100 cells x 10(6)/liter received CHOP or ACVBP regimens, respectively. Event-free survival (EFS) and survival were estimated by the Kaplan-Meir method and a Cox model was used to evaluate the effect of different variables on survival. At diagnosis of ARL, the median age was 37 years and 22 patients (30%) had prior AIDS-defining events. Median CD4 cell count was 99 x 10(6)/liter. The median follow-up was 60 months. Ann Arbor stage 3-4 was noted in 60 patients (82%) and bone marrow or meningeal involvement was present in 13 (17%) and 12 (16%) patients, respectively. Two groups were identified: group 1 (n = 38) included patients who had never received HAART and group 2 (n = 35) included those who received HAART either before the diagnosis or following ARL. There was no statistical significant differences in lymphoma extensive stage, presence of B symptoms, meningeal involvement, CD4 cell count at diagnosis, prior AIDS events, or chemotherapy regimens between the two groups. Median survival (MS) of the whole cohort of patients was 8 months. Estimated EFS was significantly higher (30 months) in group 2 compared to group 1 (6.1 months) (p = 0.03). In the multivariate Cox model HAART has an independent significant effect on EFS (p = 0.0085). No influence on outcome was found for other variables except for prior AIDS and bone marrow involvement. HAART has significantly improved the survival and EFS in patients with ARL, independently of chemotherapy regimen.

An explosive course of squamous cell penile cancer in an AIDS patient.

We report the case of a 37-year-old man in whom penile cancer was discovered while he was treated for AIDS 4 years after a human papillomavirus (HSV) infection. Despite initially localised disease with T1 N0 staging, he died of metastasis within 3 years. A brief review of the literature regarding HPV-related cancer in HIV-infected patients is presented and therapeutic options are discussed.

Detection of infectious HIV in circulating monocytes from patients on prolonged highly active antiretroviral therapy.

The existence of a reservoir of resting CD4+ T cells harboring latent replication-competent HIV has been demonstrated in patients on prolonged highly active antiretroviral therapy (HAART). Latently infected tissue macrophages may constitute a second HIV reservoir. The pool of these cells may be maintained by incoming infected monocytes from blood and/or by in situ viral replication. In this study, the presence of infectious HIV was investigated in highly purified monocytes from 5 patients receiving HAART with undetectable plasma viral load for up to 16 months. HIV was detected in freshly isolated monocytes and recovered following Staphylococcus aureus Cowan strain 1 (SAC) or lipopolysaccharide (LPS) activation. No new drug resistance-associated mutation was found in monocyte-associated HIV. These results demonstrate the long-term persistence of infectious virus in cells of the monocyte-macrophage lineage in patients receiving HAART. These cells are capable of releasing infectious virus under appropriate stimulations.

Weak anti-HIV CD8(+) T-cell effector activity in HIV primary infection.

HIV-specific CD8(+) T cells play a major role in the control of virus during HIV primary infection (PI) but do not completely prevent viral replication. We used IFN-gamma enzyme-linked immunospot assay and intracellular staining to characterize the ex vivo CD8(+) T-cell responses to a large variety of HIV epitopic peptides in 24 subjects with early HIV PI. We observed HIV-specific responses in 71% of subjects. Gag and Nef peptides were more frequently recognized than Env and Pol peptides. The number of peptides recognized was low (median 2, range 0-6). In contrast, a much broader response was observed in 30 asymptomatic subjects with chronic infection: all were responders with a median of 5 peptides recognized (range 1-13). The frequency of HIV-specific CD8(+) T cells among PBMC for a given peptide was of the same order of magnitude in both groups. The proportion of HIV-specific CD8(+)CD28(-) terminally differentiated T cells was much lower in PI than at the chronic stage of infection. The weakness of the immune response during HIV PI could partially account for the failure to control HIV. These findings have potential importance for defining immunotherapeutic strategies and establishing the goals for effective vaccination.