Anne Bourgarit

Tenofovir-Related Nephrotoxicity in Human Immunodeficiency Virus-Infected Patients: Three Cases of Renal Failure, Fanconi Syndrome, and Nephrogenic Diabetes Insipidus

We report 3 cases of renal toxicity associated with use of the antiviral agent tenofovir. Renal failure, proximal tubular dysfunction, and nephrogenic diabetes insipidus were observed, and, in 2 cases, renal biopsy revealed severe tubular necrosis with characteristic nuclear changes. Patients receiving tenofovir must be monitored closely for early signs of tubulopathy (glycosuria, acidosis, mild increase in the plasma creatinine level, and proteinuria).

Explosion of tuberculin-specific Th1-responses induces immune restoration syndrome in tuberculosis and HIV co-infected patients.

Objectives:To test the hypothesis that an acute exacerbation of mycobacteria-specific Th1 response after HIV infection control by HAART causes immune restoration syndrome (IRS) in HIV–tuberculosis (TB) coinfected patients. Design:Prospective, multicenter study of 19 consecutive untreated HIV–TB coinfected patients included when initiating antimycobacterial therapy and sequentially evaluated during HAART and at time of IRS. IRS was defined according to classical clinical diagnostic criteria. Patients were declared IRS− if no IRS occurred within 3 months after HAART initiation. Methods:Mycobacteria-specific [purified protein derivative (PPD), ESAT-6, 85B] Th1 cells producing interferon (IFN)-γ quantified by ELISpot, in vitro production of 25 cytokines/chemokines in antigen-stimulated peripheral blood mononuclear cell (PBMC) supernatants quantified by chemiluminescence. Results:Seven patients (37%) experienced IRS (IRS+). Mycobacteria-specific (PPD) Th1 IFN-γ-producing cells increased sharply during IRS (median, 2970 spot forming cells/106 PBMC), but not the cytomegalovirus-specific responses tested as control. Only three IRS+ patients had low ESAT-6− but no 85B-specific responses. IRS− patients did not develop acute PPD-specific responses except in one case. In addition, at time of IRS a peak of PPD-specific Th1 cytokines/chemokines [interleukin (IL)-2, IL-12, IFN-γ, IP10 and monokine-induced by IFN-γ] without Th2 cytokines, and a peak of non-specific inflammatory cytokines/chemokines (TNF-α, IL-6, IL-1β, IL-10, RANTES and MCP-1) occurred. These findings were independent from CD4 cell count, viral loads or time of HAART initiation. Conclusion:An acute exacerbation of Th1 responses against mycobacterial antigens appears to cause IRS in patients co-infected with HIV and TB. This key event provides new evidence valuable for the diagnosis and treatment of IRS.

Tuberculosis-Associated Immune Restoration Syndrome in HIV-1-Infected Patients Involves Tuberculin-Specific CD4 Th1 Cells and KIR-Negative γδ T Cells

Tuberculosis (TB)-associated immune restoration syndrome (IRS) is a frequent event (10 to 30%) in HIV-1-infected patients receiving antiretroviral treatment and is associated with an increased number of IFN-γ-producing tuberculin-specific cells. To further understand the immune mechanisms of TB-IRS and to identify predictive factors, we prospectively analyzed the Th1 and TCRγδ T cells known to be involved in mycobacterial defenses and dendritic cells at baseline and after antiretroviral and TB treatment in 24 HIV-1+ patients, 11 with and 13 without IRS. At baseline, these two groups differed by significantly lower proportions of TCRγδ and Vδ2+ T cells displaying the inhibitory receptors CD94/NKG2 and CD158ah,b in IRS patients. The two groups did not differ in the baseline characteristics of CD8 or CD4 T cells or TLR-2 expression on monocytes or myeloid/plasmacytoid dendritic cells. During IRS, the increase in tuberculin-specific IFN-γ-producing cells involved only highly activated effector memory multifunctional (IFN-γ+TNF-α+IL-2−) CD4 T cells, whereas activated HLA-DR+ CD4+ T cells also increased during IRS. In contrast, dendritic cells decreased significantly during IRS and there were no changes in TLR-2 expression. Finally, the Vδ2+ T cells, mostly killer Ig-related receptor (KIR) (CD94/NKG2− and CD158−), significantly peaked during IRS but not in non-IRS patients. In conclusion, IRS is associated with an increase in the number of activated tuberculin-specific effector memory CD4 T cells and of KIR−Vδ2+ TCRγδ+ T cells. Higher proportions of Vδ2+TCRγδ+ T cells lacking KIR expression are present as baseline and distinguish patients who will develop IRS from those who will not.

HIV Type 2 Demyelinating Encephalomyelitis

A human immunodeficiency virus (HIV) type 2 (HIV-2)-infected African patient developed inflammatory demyelinating lesions of the optic nerves, spinal cord, and brain, which coincided with a decreasing CD4 cell count and with active HIV-2 replication. This case provides evidence that HIV-2 is neurotropic, extends the range of known HIV-2-associated neurological complications, and confirms the overlap between the neurological complications of HIV type 1 and HIV-2 infection.

Adding Azathioprine to Remission-Induction Glucocorticoids for Eosinophilic Granulomatosis with Polyangiitis, Microscopic Polyangiitis or Polyarteritis Nodosa without Poor Prognosis Factors A Randomized–Controlled Trial

In most patients with nonsevere systemic necrotizing vasculitides (SNVs), remission is achieved with glucocorticoids alone, but one‐third experience a relapse within 2 years. This study was undertaken to determine whether the addition of azathioprine (AZA) to glucocorticoids could achieve a higher sustained remission rate of newly diagnosed nonsevere eosinophilic granulomatosis with polyangiitis (Churg‐Strauss) (EGPA), microscopic polyangiitis (MPA), or polyarteritis nodosa (PAN).

Paradoxical anti-TNF-associated TB worsening: Frequency and factors associated with IRIS

OBJECTIVES Paradoxical tuberculosis (TB) worsening, an example of the immune reconstitution inflammatory syndrome (IRIS), is an increasing phenomenon now described in several settings, including anti-tumor necrosis factor (TNF) discontinuation during biotherapy-induced TB. To better recognize it, we analyzed the frequency and factors associated with anti-TNF-induced TB-IRIS. METHODS Case-control study on anti-TNF-associated TB patients. IRIS cases, defined with the following consensus criteria, were matched to two controls (anti-TNF-associated TB without IRIS). IRIS frequency was based on the French RATIO registry. Conditional logistic-regression identified IRIS risk factors. RESULTS Fourteen patients developed anti-TNF-associated TB-IRIS within medians of 45 [IQR 22-131] days after starting anti-TB therapy and 110 [IQR 63-164] days after the last anti-TNF infusion. Each case was matched to two controls by year of TB diagnosis. IRIS-associated factors were (odds ratio [95% CI]): disseminated TB (11.4 [1.4-92.2], P=0.03), history of Mycobacterium tuberculosis exposure (12.7 [1.6-103.0], P=0.02) and steroid use at the time of TB diagnosis (4.6 [1.2-17.2], P=0.02). The RATIO registry IRIS frequency was 7%. CONCLUSION After stopping biotherapy, paradoxical anti-TNF-associated TB worsening occurred most often in patients with disseminated TB. Although diagnosis remains difficult, physicians must be aware of IRIS because prolonged anti-TB treatment is not needed but, paradoxically, immunosuppressant reintroduction may be.

Latent Tuberculosis Infection Screening and 2-Year Outcome in Antiretroviral-Naive HIV-Infected Patients in a Low-Prevalence Country

BACKGROUND Diagnosis and treatment of latent tuberculous infection decrease the incidence of tuberculosis (TB) in HIV-infected patients. OBJECTIVES To evaluate the diagnostic yield of two IFN-γ release assays and tuberculin skin testing for the screening of latent infection in HIV-infected patients. METHODS We performed a prospective study in 29 referral centers for HIV care in France. Asymptomatic, antiretroviral-naive patients infected with HIV-1 who consented to participate underwent two commercial tests (T-SPOT.TB and QuantiFERON-TB Gold In-Tube ELISA test [QFT]) and skin test at enrollment and were followed up for clinical events during 24 months. RESULTS Between March 2009 and 2011, 506 patients were included, of whom 415 performed the three tests. Median age was 38 years (interquartile range, 31-45 yr), with median CD4 cell count of 466/μL (337-615 μL), and HIV viral load of 4.5 log10 copies/ml (3.6-4.9 log10 copies/ml). At least one IFN-γ release assay was positive for 55 (13.5%) patients: QFT (n = 43), T-SPOT.TB (n = 34), both (n = 22). Skin test was positive (>5 mm) in 66 (15.9%) patients, with intertest agreement at 81 to 86%. On multivariate analysis, positive IFN-γ release assay was only correlated with country of birth (8.4% for France vs. 17.9% for high-prevalence countries, P = 0.004). Of the 55 patients with positive IFN-γ release assay, 8 (14.5%) developed active TB, all within 120 days. No other case of active TB was diagnosed. Once active TB was excluded, IFN-γ release assay-based latent infection prevalence was 11.8%. CONCLUSIONS Systematic screening for latent TB infection by IFN-γ release assay identifies a population at high risk of active TB over the next months. An extensive diagnostic work-up for active TB must follow positive IFN-γ release assay, before considering treatment of latent infection. Clinical trial registered with www.clinicaltrials.gov (NCT00805272).

Outcome of endoscopy-negative iron deficiency anemia in patients above 65: A longitudinal multicenter cohort.

AbstractAfter the age of 65 years, iron deficiency anemia (IDA) requires the elimination of digestive neoplasia and is explored with upper and lower gastrointestinal (GI) endoscopy. However, such explorations are negative in 14% to 37% of patients. To further evaluate this issue, we evaluated the outcomes of patients aged over 65 years with endoscopy-negative IDA.We retrospectively analyzed the outcomes of in-patients over the age of 65 years with IDA (hemoglobin <12 g/dL and ferritin <70 &mgr;g/L) who had negative complete upper and lower GI endoscopies in 7 tertiary medical hospitals. Death, the persistence of anemia, further investigations, and the final diagnosis for IDA were analyzed after at least 12 months by calling the patients’ general practitioners and using hospital records.Between 2004 and 2011, 69 patients (74% women) with a median age of 78 (interquartile range (IQR) 75–82) years and hemoglobin and ferritin levels of 8.4 (IQR 6.8–9.9) g/dL and 14 (IQR 8–27) &mgr;g/L, respectively, had endoscopy-negative IDA, and 73% of these patients received daily antithrombotics. After a follow-up of 41 ± 22 months, 23 (33%) of the patients were dead; 5 deaths were linked with the IDA, and 45 (65%) patients had persistent anemia, which was significantly associated with death (P = 0.007). Further investigations were performed in 45 patients; 64% of the second-look GI endoscopies led to significant changes in treatment compared with 25% for the capsule endoscopies. Conventional diagnoses of IDA were ultimately established for 19 (27%) patients and included 3 cancer patients. Among the 50 other patients, 40 (58%) had antithrombotics.In endoscopy-negative IDA over the age of 65 years, further investigations should be reserved for patients with persistent anemia, and second-look GI endoscopy should be favored. If the results of these investigations are negative, the role of antithrombotics should be considered.

Lyme : être ou ne pas être, telle est la question !

A l’oree de 2017, a l’heure de la toute-puissante medecine scientifique et factuelle, il nous a semble opportun, a travers ce dernier editorial de l’annee 2016 de Medecine Therapeutique, de mettre en lumiere le combat « fratricide », quoique a fleurets mouchetes, qui se mene autour de la maladie de Lyme [1], la « grande simulatrice » des xxe et xxie siecles au meme titre que la syphilis dans les siecles passes.La France de 2017, tout comme celle du siecle des Lumieres, [...]

Une fausse jaunisse noire

ObservationM. X est âge de 64 ans et d’origine marocaine. Il vit en France depuis 20 ans et est maintenant a la retraite apres avoir travaille dans le bâtiment. Il est ancien fumeur mais n’a pas d’autres antecedents medicaux. Il est revenu d’un voyage de 5 mois dans ses montagnes natales et consulte aux urgences le meme jour, pousse par sa famille. Il se plaint d’une « chaleur » qui va et vient, de sueurs nocturnes, d’une toux seche, d’arthralgies et de douleurs abdominales [...]