Nasal polyposis and immunoglobulin-G subclass deficiency.

OBJECTIVE: Study of the association between immunoglobulin-G (IgG) subclass deficiency and nasal polyposis. MATERIAL AND METHODS: Longitudinal study (5 years) in a prospective cohort of 161 nasal polyposis patients. Analysis of the association between humoral immunodeficiency, rhinologic symptoms, endoscopy score and prescribed doses of local and systemic corticosteroids. RESULTS: The prevalence of IgG subclass deficiency was 13.7% (22/161). One patient was diagnosed with common variable immunodeficiency (CVID). No significant differences were observed between the groups with and without pre-treatment deficiency for symptom severity, endoscopic score or local or systemic corticosteroid regimens at baseline or during the 5 years, following initiation of medical and surgical treatment. Only the Lund-Mackay CT score was significantly higher in the pre-treatment deficiency group. CONCLUSION: There was no correlation between the presence of humoral deficiency and either symptom evolution after medical and surgical treatment or the dose of corticosteroids needed to control disease. Thus, a link between IgG subclass deficiency and nasal polyposis seems unlikely.

[Sinonasal polyposis associated with a deficiency subclass immunoglobulin G: Place of substitution immunoglobulins]. / Polypose nasosinusienne associée à un déficit en sous-classes d'Immunoglobuline G: place de la substitution en immunoglobulines polyvalentes.

PURPOSE: To study the effect of the introduction of a substitution by intravenous Immunoglobulins (Ig IV) at patients with immunoglobulins G (IgG) subclasses deficiency and nasal polyposis. MATERIAL AND METHODS: Prospective study concerning five patients with IgG subclasses deficiency and nasal polyposis treated by Ig IV. Rhinologic, otologic and pulmonary symptoms, exacerbations of nasal polyposis, chronic otitis and asthma as well as the number of antibiotics and corticoids treatments were counted during the Ig IV substitution. OBJECTIVES: To study the association between IgIV substitution and the number of exacerbations of nasal polyposis, chronic otitis, asthma and the number of antibiotics and corticoids treatments in patients with IgG subclasses deficiency and nasal polyposis. RESULTS: Five patients with a IgG subclass deficiency and nasal polyposis were substituted. The number of antibiotics and corticoids cures increased at one patient and remained stable at four others. The number of sinus, ear and lung infections as well as the global rhinologic score of symptoms and the endoscopic stage of the nasal polyposis remained stable. In the absence of efficiency of the treatment, this one was interrupted at the end of 6 months for patients n° 1 and n° 3, 24 months for patient n° 4 and 42 months for patient n° 5. CONCLUSION: The current study failed to highlight clinical improvement in patients wih IgG subclasses deficiency and nasal polyposis treated by Ig IV. A previous study had not allowed to find a link between IgG subclasses deficiency and severity of nasal polyposis, what seems to be confirmed by the absence of improvement brought during the substitution of this deficit in the current study.

Liver-related deaths in HIV-infected patients between 1995 and 2005 in the French GERMIVIC Joint Study Group Network (Mortavic 2005 study in collaboration with the Mortalité 2005 survey, ANRS EN19).

BACKGROUND: More than 10 years after the introduction of combination antiretroviral therapy (cART), we examined the trend in the proportion of deaths caused by end-stage liver disease (ESLD) in HIV-infected adults in France between 1995 and 2005. DESIGN AND METHODS: In 2005, 34 departments prospectively recorded all deaths in HIV-infected patients who were followed in those departments (around 24 000). RESULTS: were compared with those of four previous cross-sectional surveys conducted since 1995 using the same methodology. Results Among 287 reported deaths in 2005, 100 (35%) were related to AIDS, and 48 (17%) to ESLD. Three out of four patients who died from ESLD-related causes had chronic hepatitis C. Excessive alcohol consumption was reported in approximately half of the patients (48%). At death, 62% of patients had undetectable HIV viral load and the median CD4 count was 237 cells/microL. From 1995 to 2005, the proportion of deaths caused by ESLD increased from 2 to 17% (P<0.001). The proportion of deaths caused by hepatocellular carcinoma increased from 5% in 1995 to 25% in 2005 (P=0.0337). CONCLUSIONS: Over the 10 years from 1995 to 2005, the proportion of deaths caused by hepatitis C virus-related ESLD has increased in HIV-infected patients. ESLD is currently a leading cause of death in this population, with hepatocellular carcinoma representing a quarter of liver-related deaths. Recommendations for the detection of hepatocellular carcinoma should be strictly applied in these patients.

Drug resistance profiles for the HIV integrase gene in patients failing raltegravir salvage therapy.

OBJECTIVES: Recent data showed the selection of mutations in the integrase gene, mainly involving position 148 or 155, in patients displaying virological failure (VF) on raltegravir (RAL) therapy. Here, we describe the development of RAL resistance, in both plasmatic and cellular compartments, in three heavily pretreated HIV-infected patients failing RAL-containing regimens. METHODS: Three of 17 patients receiving RAL displayed VF. The entire integrase gene, isolated from plasma and peripheral blood mononuclear cells (PBMC), was sequenced. A clonal analysis was performed in one patient at the time of VF. RESULTS: At the time of VF, RAL-resistance mutations were selected: (i) Q148R in patients 1 and 3; (ii) T66A and E92Q in patient 2. A gradual accumulation of new mutations was observed in all patients, including G140S, Q148H and N155H in patient 1, L74I in patient 2, and G140S in patient 3. Clonal analysis showed the coexistence, in patient 1, of the two common resistance pathways (mutations Q148R/H and N155H) found in distinct quasi-species. In addition, RAL-resistance mutations were detected in HIV DNA in all patients. CONCLUSIONS: Having rapidly established, resistance to RAL evolves and diversifies, and is likely to impact the efficacy of subsequently used second-generation integrase inhibitors. Moreover, RAL-resistance mutations can be archived early in PBMC.

A case-control study of risk factors for hepatitis C infection in patients with unexplained routes of infection.

Twenty to 40% of hepatitis C virus (HCV)-infected patients do not have a recognized parenteral risk factor, suggesting that still-unidentified modes of transmission exist. In order to investigate potential routes of HCV transmission for patients with no recognized parenteral risk factor, we conducted a multicentre case-control study. A total of 450 HCV-seropositive patients with no history of transfusion or intravenous drug use and 757 controls were recruited from the general population and matched for sex, age, geographical residence and number of chronic diseases. All subjects answered an interviewer-administered questionnaire on potential risk factors for HCV. Eighty per cent of cases had chronic hepatitis or cirrhosis. Respective percentages of genotypes 1, 2, 3, 4 and 5 were 65, 14, 11, 5 and 4. Among the 66 items considered, multivariate analysis identified 15 independent risk factors for HCV infection: nosocomial [admission to medical (odds ratio, OR = 2.1) or surgical ward (OR = 1.7), digestive endoscopy (OR = 1.9), abortion (OR = 1.7)], outpatient treatments [cutaneous ulcer and wound care (OR = 10.1), diathermy (OR = 3.0), gamma globulin (OR = 1.7), intravenous (OR = 1.7) or intramuscular (OR = 1.4) injections, varicose vein sclerotherapy (OR = 1.6), acupuncture (OR = 1.5)] and lifestyle-associated [intranasal cocaine use (OR = 4.5), practice of contact sports (OR = 2.3), beauty treatments (OR = 2.0), professional pedicure/manicure (OR = 1.7)]. These factors could explain 73% of community-acquired hepatitis C. In conclusion, for patients with unexplained routes of HCV infection, our data incriminate previously unidentified risk factors (abortions, some dermatological procedures, outpatient injections, contact sports, beauty treatments, professional pedicure/manicure) and confirm those already recognized (hospitalization, digestive endoscopy, acupuncture and intranasal cocaine use).

Intramedullary abscess resulting from disseminated cryptococcosis despite immune restoration in a patient with AIDS.

We report on a case of cryptococcal intramedullary abscess, which occurred three years after a disseminated cryptococcosis and two years after a lymph node cryptococcal recurrence in a HIV-infected patient who exhibited a long-standing immune restoration. At the time of diagnosis, CD4(+) lymphocyte-count was 640x10(6)/l and HIV viral load was undetectable. Spinal involvement is rare during cryptococcosis of the central nervous system. As far as we are aware, there is only one case of proven intramedullary cryptococcal abscess reported in the literature and this case is then the second one. The significant and sustained increase in CD4 count following effective antiretroviral therapy was probably associated with only a partial immune restitution that did not allow to avoid the occurrence of the cryptococcal medullar abscess. Finally, this case raises the question of when to stop secondary prophylaxis of cryptococcal disease after increase in CD4 cell count under antiretroviral therapy.

[Efficacy of intravenous immunoglobulin in the treatment of Birdshot retinochoroiditis]. / Efficacité et tolérance des immunoglobulines intraveineuses dans le traitement de la rétinochoroïdopathie de type Birdshot.

AIM: To evaluate the efficacy of intravenous immunoglobulin (IVIg) in the treatment of Birdshot retinochoroiditis. PATIENTS AND METHODS: Eighteen patients were followed-up prospectively in a total number of 37 patients recorded. Inclusion criteria were birdshot retinochoroiditis (BRC) according to the criteria defined by Ryan et al., and a decrease in visual acuity (VA). Efficacy was assessed by measurements of visual acuity and a decrease in inflammation and macular edema on fluorescein angiograms. RESULTS: Sex ratio=1, mean age was 51 (range 29 to 72 years), HLA A29 was positive in 100% of the patients. VA at baseline was 0.6+/-2.4 (range 0.25 to 0.9). Angiography showed retinal vasculitis in 32 patients (86.48%) and cystoid macular edema in 16 patients (43.24%). IVIg was administered at a dosage of 0.4g/kg/d for 4 days then 0.6g/kg/d for 2 days every 4 weeks. Follow-up lasted a mean of 2.7+/-2.0 years (range, 4 months to 5.6 years). Visual acuity of 35 out of 66 eyes (53%) increased by 2.6+/-1.5 (range 1 to 5). In 19 eyes out of 66 (29%), VA remained stable and in 12 eyes out of 66 (18%), VA decreased by -1.8+/-0.8 (ranges-4 to -1). Inflammation on fluorescein angiography improved in 17 patients (81%) and cystoid macular edema decreased in 65% of the cases. Side effects were rare. Treatment was discontinued for side effects in only 3 patients. DISCUSSION: BRC is a chronique disease threatening vision. Treatments including systemic corticosteroids and cyclosporin A may result in severe long-term side effects. IVIg is well tolerated and may be therapeutic alternative for the treatment of BRC.

HIV-specific effector cytotoxic T lymphocytes and HIV-producing cells colocalize in white pulps and germinal centers from infected patients.

Human immunodeficiency virus (HIV) infection is characterized by the massive infiltration of secondary lymphoid organs with activated CD8(+) T lymphocytes. While converging data indicated that these cells were HIV-specific cytotoxic T lymphocytes (CTLs) responsible for HIV spread limitation, direct evidence was lacking. Here, the presence of HIV-specific effector CTLs was demonstrated directly ex vivo in 15 of 24 microdissected splenic white pulps from an untreated patient and in 1 of 24 tonsil germinal centers from a second patient with incomplete viral suppression following bitherapy. These patients had plasma HIV RNA loads of 5900 and 820 copies per milliliter. The frequencies of HIV-1 DNA(+) cells in their lymphoid organs were more than 1 in 50 and 1 in 175, respectively. Spliced viral messenger RNA (a marker for ongoing viral replication) was present in most immunocompetent structures tested. Conversely, CTL activity was not found in spleens from 2 patients under highly active antiretroviral therapy, with undetectable plasma viral load. These patients had much lower spleen DNA(+) cell frequencies (1 in 2700 and 1 in 3800) and no white pulps containing spliced RNA. CTL effector activity as well as spliced viral messenger RNA were both concentrated in the white pulps and germinal centers. This colocalization indicates that viral replication in immunocompetent structures of secondary lymphoid organs triggers anti-HIV effector CTLs to these particular locations, providing clues to target therapeutic intervention.

[Primary pulmonary hypertension in human immunodeficiency virus infection. Study of 9 cases amd review of the literature]. / Hypertension artérielle pulmonaire primitive au cours de l'infection par le virus de l'immunodéficience humaine. Etude de neuf observations et revue de la littérature.

PURPOSE: In medical literature, primary pulmonary hypertension occurs in 0.5% of human immunodeficiency virus (HIV)-infected patients, irrespective of the stage of the HIV disease, and is more frequent in drug users. Plexogenic arteriopathy is the most frequent histological lesion. METHODS: We retrospectively report on nine cases of primary pulmonary hypertension during HIV infection. RESULTS: The subjects were four women and five men, mean age 38 years old. Four of them had been sexually contaminated and five had contracted the disease through intravenous drug use. At the time primary pulmonary hypertension was diagnosed, mean CD4 cell count was 234 +/- 217/mm3 and the viral load was low or undetectable. Primary pulmonary hypertension has been diagnosed an average of 7 months after the first cardiovascular clinical signs had started. Despite anti-coagulant (7/9 cases), vasodilatator (4/9 cases) and/or diuretic (7/9 cases) therapy, the progression of the disease quickly turned out to be negative (seven deaths). CONCLUSION: Diagnosis of primary pulmonary hypertension should be considered when unexplained dyspnea occurs in an HIV-positive patient. At initial evaluation, alterations of hemodynamic parameters are usually less severe than during idiopathic primary pulmonary hypertension, but their progression is quicker and more severe, independent of the patient's immune status. Current data do not allow the determination of whether antiretroviral therapy is active in primary pulmonary hypertension evolution. Therapeutic evaluation with prostacyclin is currently being carried out. While the life expectancy of HIV-infected patients extends, primary pulmonary hypertension occurrence could increase and call for early diagnosis, thus allowing for specific care.

The cumulative occurrence of resistance mutations in the HIV-1 protease gene is associated with failure of salvage therapy with ritonavir and saquinavir in protease inhibitor-experienced patients.

Salvage therapy with ritonavir (RTV) and saquinavir (SQV) failed to achieve virological and immunological improvement in 24 HIV-infected patients who discontinued triple therapy with RTV or indinavir (IDV) because of failure or intolerance to treatment. Changes in the HIV-1 protease gene sequence were analyzed prospectively in 14 patients. No primary protease mutation was found prior to the use of protease inhibitors. After 7 months of treatment with IDV or RTV, primary resistance mutations at codons pol 46 and/or pol 82 were observed in 11 of 13 patients. After 16 weeks on RTV-SQV, novel primary mutations related to SQV emerged in 7 of 13 patients, together with an increase in the number of secondary resistance mutations. Our observations indicate that the cumulative occurrence of resistance mutations in the protease gene was associated with failure of antiretroviral therapy. The presence of mutations to a first protease inhibitor may represent a risk factor for the failure of a subsequent treatment with a second line protease inhibitor.

[Human immunodeficiency virus resistance to antiretroviral drugs]. / Résistance du virus de l'immunodéficience humaine aux antirétroviraux.

Antiretroviral compounds can select viral strains presenting mutations of the HIV genome. Certain genotypic modifications are expressed by phenotypic resistance. There is no cross resistance between different classes of compounds (nucleosides, non nucleosides, antiproteases), but cross resistance is common within a given therapeutic class. HIV resistance to antiretroviral compounds is one of the principal causes of failure of antiretroviral treatments but cannot explain all escapes. The number of resistance mutations is higher in patients with high viral loads and in patients on multiple drug regimens. Currently resistance testing is limited to clinical research protocols. The usefulness of resistance testing remains to be validated. However the most eminent indications are epidemiological surveillance of primary resistance in primary infections, therapeutic adaptation after accidental exposure to HIV, and management of seropositive pregnant women. Recent retrospective studies have shown that the genotype and the phenotype after a first line treatment failure predict response to certain therapeutic combinations. In the near future, resistance testing could be useful to adapt antiviral strategies after earlier treatment failure.

Thrombomodulin: an overview and potential implications in vascular disorders.

Thrombomodulin (TM), a high affinity thrombin receptor present on endothelial cell membrane, plays an important role as a natural anticoagulant. It acts as a cofactor of thrombin-catalyzed activation of protein C, and inhibits the procoagulant functions of thrombin. TM is also located in other cells (keratinocytes, osteoblasts, macrophages,...) where it might be involved in cell differentiation or in inflammation. In the presence of cytokines, activated neutrophils and macrophages, endothelial TM is cleaved enzymatically, releasing soluble fragments which circulate in the blood and are eliminated in urine. Plasma TM level (pTM) can be measured using a two-site enzyme-linked immunosorbent assay (ELISA). pTM level is regarded as a molecular marker reflecting injury of endothelial cells. It is often increased in case of diffuse endothelial damage as in disseminated intravascular coagulation, diabetic microangiopathy, Plasmodium falciparum and rickettsial infections. pTM is also a predictive marker of hypertensive complications in pregnancy. In several systemic inflammatory diseases, pTM levels are correlated to the activity of the disease.

[Episcleritis and brucellosis. Apropos of a case]. / Episclérite et brucellose. A propos d'un cas.

A 35-year-old man presented a case of recurrent episcleritis revealing brucellosis. No concurrent diagnosis other than brucellosis could account for the episcleritis. Moreover his status was dramatically improved by specific antibiotherapy. A review of the literature showed that uveitis and optic neuropathies are the most common ocular manifestations of brucellosis. To the best of our knowledge, this is the first case of episcleritis associated with brucellosis.

[Transmission modes of hepatitis C virus]. / Modes de transmission du virus de l'hépatite C.

SITUATION IN FRANCE: The prevalence of hepatitis C virus (HCV) infection in the French population is estimated at 1%, a level similar to that in other western countries. USUAL CONTAMINATION ROUTES: Epidemiological studies, together with gene typing, have made it possible to distinguish transmission modes. A history of intravenous drug abuse or transfusion is found in 60 to 80% of all subjects infected by the HCV. Other documented modes of contamination include hemodialysis, organ transplantation, accidental occupational-related puncture and mother-infant transmission. OTHER ROUTES: Sexual or intra-familial nonsexual transmission is uncommon and related to the length of exposure and the stage of HCV infection in the "source" subjects. Cases of HCV transmission have been reported during medical procedures. Currently the mode of of transmission is unknown in 20 to 40% of the cases.