[High anti-topoisomerase-1 autoantibodies levels are associated with the extension of skin fibrosis and vascular progression in patients with systemic sclerosis]. / Des taux élevés d'auto-anticorps anti-topo-isomérase-1 sont associés à l'extension de la fibrose cutanée et à la progression vasculaire chez les patients atteints de sclérodermie systémique.

BACKGROUND: Anti-centromere antibodies, anti-topoisomerase-1 antibodies (ATA), and anti-RNA-polymerase III antibodies are three Systemic Sclerosis (SSc)-specific autoantibodies. Their detection is helpful in determining the prognosis. We aimed to evaluate whether ATA levels were associated with disease severity at diagnosis or disease progression during follow-up in ATA positive patients. METHODS: We conducted a single-centre French retrospective observational study, between 2014 and 2021. ATA positive patients fulfilling the ACR/EULAR 2013 classification criteria for SSc with a minimal follow-up of 1 year and 2 ATA dosages were included. SSc patients with high IgG ATA levels at baseline (>240IU/mL) were compared with SSc patients with low levels (≤240IU/mL), at inclusion and at 1 and 3 years. A variation of at least 30 % of ATA levels was considered significant. RESULTS: Fifty-nine SSc patients were included and analysed. There was a predominance of women and of patients with diffuse interstitial lung disease. Patients with high ATA levels exhibited a higher skin sclerosis assessed by the modified Rodnan skin score (P=0.0480). They had a lower carbon monoxide transfer coefficient (P=0.0457), a lower forced vital capacity (FVC) (P=0.0427) and more frequently had a FVC under 80 %, when compared to patients with low ATA levels (P=0.0423). Initial high ATA levels were associated with vascular progression at one year (21.95 % vs. 0 %; P=0.0495). CONCLUSION: ATA levels are associated with skin sclerosis and vascular progression in SSc. Beyond the detection of ATA, quantifying this autoantibody might be of interest in predicting disease severity and prognosis in SSc.

First report of cryptococcosis due to Cryptococcus gattii sensu stricto VGI in an Ivorian HIV negative patient.

INTRODUCTION: Cryptococcus gattii species complex is endemic to tropical and subtropical regions and is described as a causative agent of cryptococcosis in immunocompetent individuals. CASE PRESENTATION: We describe the first case of cryptococcosis in a HIV-negative patient from Ivory Coast infected by Cryptococcus gattii sensu stricto VGI. Isolates were recovered from cerebrospinal fluid (CSF) prior to systemic antifungal treatment up to 42 days after detection of the presence of yeasts in the CSF. Eighteen isolates were recovered, genetic diversity and antifungal susceptibility analyses were performed. All the isolates belonged to the Cryptococcus gattii sensu stricto (B;VGI) and were identified as a new sequence type (ST) 553 by Multilocus Sequence Typing (MLST) analyses. Susceptibility testing showed that all the strains had a wild-type phenotype for fluconazole, amphotericin B and flucytosine. Treatment with fluconazole (1200mg/day) was initiated with success. CONCLUSION: This is the first case report of the presence of C. gattii sensu stricto VGI in a HIV-negative ivorian patient and the second report of the presence of species from the C. gattii complex species in this country.

Cost-Effectiveness of Three Alternative Boosted Protease Inhibitor-Based Second-Line Regimens in HIV-Infected Patients in West and Central Africa.

BACKGROUND: While dolutegravir has been added by WHO as a preferred second-line option for the treatment of HIV infection, boosted protease inhibitor (bPI)-based regimens are still needed as alternative second-line options. Identifying optimal bPI-based second-line combinations is essential, given associated high costs and funding constraints in low- and middle-income countries. We assessed the cost-effectiveness of three alternative bPI-based second-line regimens in Burkina Faso, Cameroon and Senegal. METHODS: We used data collected over 2010-2015 in the 2LADY trial/post-trial cohort. Patients with first-line antiretroviral therapy (ART) failure were randomly assigned to tenofovir/emtricitabine + lopinavir/ritonavir (TDF/FTC LPV/r; arm A), abacavir + didanosine + lopinavir/ritonavir (arm B), or tenofovir/emtricitabine + darunavir/ritonavir (arm C). Costs (US dollars, 2016), quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios were computed for each country over 24 months of follow-up and extrapolated to 5 years using a simulated patient-level Markov model. We assessed uncertainty using cost-effectiveness acceptability curves, scenarios and prices threshold analysis. RESULTS: In each country, over 24 months, arm A was significantly less costly than arms B and C (incremental costs ranging from US$410-$US721 and US$468-US$546 for B and C vs A, respectively) and offered similar health benefits (incremental QALY: - 0.138 to 0.023 and - 0.179 to 0.028, respectively). Over 5 years, arm A remained the least costly, health benefits not being significantly different between arms. Compared with arms B and C, in each study country, Arm A had a ≥ 95% probability of being cost-effective for a large range of cost-effectiveness thresholds, irrespective of the scenario considered. CONCLUSIONS: Using TDF/FTC LPV/r as a bPI-based second-line regimen provided the best economic value in the three study countries. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00928187.

Rituximab is an effective treatment in patients with pemphigus vulgaris and demonstrates a steroid-sparing effect.

BACKGROUND: Corticosteroids (CS) with or without adjuvant immunosuppressant agents are standard treatment for pemphigus vulgaris (PV). The efficacy of adjuvant therapies in minimizing steroid-related adverse events (AEs) is unproven. OBJECTIVES: To utilize data collected in a French investigator-initiated, phase III, open-label, randomized controlled trial to demonstrate the efficacy and safety of rituximab and seek approval for its use in PV. METHODS: This was an independently conducted post hoc analysis of the moderate-to-severe PV subset enrolled in the Ritux 3 study. Patients were randomized to rituximab plus 0·5 or 1·0 mg kg-1 per day prednisone tapered over 3 or 6 months, or 1·0 or 1·5 mg kg-1 per day prednisone alone tapered over 12 or 18 months, respectively (according to disease severity). The primary end point was complete remission at month 24 without CS (CRoff) for ≥ 2 months, and 24-month efficacy and safety results were also reported. RESULTS: At month 24, 34 of 38 patients (90%) on rituximab plus prednisone achieved CRoff ≥ 2 months vs. 10 of 36 patients (28%) on prednisone alone. Median total cumulative prednisone dose was 5800 mg in the rituximab plus prednisone arm vs. 20 520 mg for prednisone alone. Eight of 36 patients (22%) who received prednisone alone withdrew from treatment owing to AEs; one rituximab-plus-prednisone patient withdrew due to pregnancy. Overall, 24 of 36 patients (67%) on prednisone alone experienced a grade 3/4 CS-related AE vs. 13 of 38 patients (34%) on rituximab plus prednisone. CONCLUSIONS: In patients with moderate-to-severe PV, rituximab plus short-term prednisone was more effective than prednisone alone. Patients treated with rituximab had less CS exposure and were less likely to experience severe or life-threatening CS-related AEs. What's already known about this topic? Pemphigus vulgaris (PV) is the most common type of pemphigus. Corticosteroids, a standard first-line treatment for PV, have significant side-effects. Although their effects are unproven, adjuvant corticosteroid-sparing agents are routinely used to minimize steroid exposure and corticosteroid-related side-effects. There is evidence that the anti-CD20 antibody rituximab is effective in the treatment of patients with severe recalcitrant pemphigus and in patients with newly diagnosed pemphigus. What does this study add? This study provides a more detailed analysis of patients with PV enrolled in an investigator-initiated trial. Rituximab plus prednisone had a steroid-sparing effect and more patients achieved complete remission off prednisone. Fewer patients experienced grade 3 or grade 4 steroid-related adverse events than those on prednisone alone. This collaboration between academia and industry, utilizing independent post hoc analyses, led to regulatory authority approvals of rituximab in moderate-to-severe PV.

African ST173 Cryptococcus deuterogattii strains are commonly less susceptible to fluconazole: An unclear mechanism of resistance.

OBJECTIVES: Fluconazole (FCZ), either alone or in combination, is often administered for treatment of cryptococcal meningitis, especially in sub-Saharan Africa. Its extensive use has led to the emergence of FCZ-resistant strains. The mechanisms underlying FCZ resistance are poorly documented for yeasts belonging to the Cryptococcus gattii species complex. The literature suggests that resistance could be due to mutations in and/or overexpression of the ERG11 gene (encoding the 14-α-demethylase) and efflux pumps such as MDR and AFR (two subclasses of ABC transporters). Here we highlight the presence of genotype VGII strains (Cryptococcus deuterogattii) from the Ivory Coast with a rare sequence type (ST173) associated with high FCZ minimum inhibitory concentrations (MICs) compared with strains originating from the Pacific Northwest (USA). METHODS: Mechanisms of FCZ resistance were investigated in 28 Ivorian clinical C. deuterogattii isolates recovered from three patients during their antifungal treatment and follow-up. RESULTS: The results demonstrated that: (i) these strains exhibited no mutations in the ERG11 gene; (ii) some strains had increased ERG11 and MDR1 mRNA expression, whilst AFR1 and AFR2 were not overexpressed in strains with high FCZ MICs compared with the expression levels for strains with low FCZ MICs; and (iii) exposure to FCZ in strains with high MICs induced AFR1 mRNA overexpression. CONCLUSION: This study demonstrated that the FCZ resistance mechanism commonly described in Cryptococcus neoformans was not responsible for resistance to FCZ in rare subtype strains.

New technologies for controlling emerging infectious diseases in Guinea and the Democratic Republic of the Congo: their role in response to the Ebola epidemic.

Emerging infectious diseases appear recurrently and represent a threat to global health security. Africa is particularly exposed to the risks of infectious epidemics, due to both the number of circulating infectious agents, especially in wildlife, and the social and environmental factors that promote their epidemic spread. Ebola outbreaks in West Africa in 2014 and those in the DRC that began in 2018 were an opportunity to develop and deploy new diagnostic techniques in laboratories in Guinea and the Democratic Republic of the Congo (DRC). These tools made it possible to identify the infectious agent rapidly, to trace contamination chains in real time to enable effective interventions, and to develop a reliable serological tool for differential diagnoses. Today, equipped and functional facilities exist in both countries, led by Guinean and Congolese researchers trained to high levels of competence and benefiting from unique experience and field knowledge.

[Nodulocystic eruption induced by sorafenib]. / Éruption nodulo-kystique induite par le sorafénib.

INTRODUCTION: Sorafenib is a multikinase inhibitor used in the treatment of hepatocellular carcinoma, advanced renal cell carcinoma, and differentiated thyroid carcinoma. Cutaneous adverse events are numerous and occur frequently. PATIENTS AND METHODS: We present two cases of nodulocystic lesions associated with comedones in patients treated with sorafenib for hepatocellular carcinoma. In the first patient, a 64-year-old man, lesions appeared on the trunk one year after beginning sorafenib. Histopathological examination revealed a non-granulomatous, perivascular and perisudoral polymorphic cellular infiltrate associated with comedones and microcysts. These lesions progressed via inflammatory episodes interrupted by long periods of spontaneous remission without any specific treatment. In the second patient, a 53-year-old woman, a rash appeared on the buttocks three months after starting sorafenib and then spread to the lumbar region and thighs. Histopathological examination was consistent with granulomatous acne lesions. The initial treatment (oral tetracycline and zinc) given for 3 months proved ineffective. Patient follow-up over 3 years showed gradual regression without the appearance of any further lesions. DISCUSSION: In the literature, several reports discuss acneiform rashes in patients treated with targeted therapy. In most cases, these lesions were papulopustular without retentional lesions. There are few reports of nodulocystic eruptions associated with comedones following sorafenib therapy. The mechanisms of emergence of these lesions seem to involve inhibition of the RAF pathway, C-KIT, and the PDGF signaling pathway.

Septic shock secondary to an acute necrotizing community-acquired pneumonia with bacteremia due to Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an uncommon cause of necrotizing acute community-acquired pneumonia (CAP). Only thirteen cases have been previously reported in the literature. In this article, we describe a case of previously healthy 80-year-old male patient, who presented in septic shock caused by necrotizing CAP. Despite inadequate empiric antimicrobial treatment, the patient survived and was able to return to his home after three weeks of hospitalization. To the best of our knowledge, this is the second case of septic shock secondary to P. aeruginosa necrotizing CAP and bacteremia, with optimal clinical outcome. We highlight the evolution of this pathology remains unpredictable, despite the factors related to the host and the bacterium.

A single typical trichoscopic feature is predictive of tinea capitis: a prospective multicentre study.

BACKGROUND: Specific trichoscopic signs of tinea capitis (TC) were first described in 2008. The accuracy of this diagnostic tool has not been evaluated. OBJECTIVES: To assess the diagnostic accuracy of trichoscopy. METHODS: A prospective, multicentre study was done between March 2015 and March 2017 at the dermatology departments of four French university medical centres. Patients with a presumed diagnosis of TC were included. Trichoscopy was considered to be positive if at least one specific trichoscopic sign was observed. Trichoscopy results were compared with the gold standard for diagnosis of TC (mycological culture). RESULTS: One hundred patients were included. Culture was positive for 53 patients and negative for 47. The sensitivity of trichoscopy was 94% [95% confidence interval (CI) 88-100], specificity was 83% (95% CI 72-94), positive predictive value was 92% and negative predictive value was 86%. Comma hairs, corkscrew hairs, zigzag hairs, Morse-code-like hairs and whitish sheath were significantly more frequent in patients with a positive mycological culture (P < 0·001). Comma hairs were more frequent in patients with Trichophyton TC (P = 0·026), and zigzag hairs were more frequent in patients with Microsporum TC (P < 0·001). Morse-code-like hair was not observed in any patients with Trichophyton TC and therefore appears to be highly specific for Microsporum TC. CONCLUSIONS: The presence of a single trichoscopic finding is predictive of TC. Trichoscopy is a useful, rapid, painless, highly sensitive tool for the diagnosis of TC - even for dermoscopists with little experience of trichoscopy. It enhances physicians' ability to make treatment decisions. What's already known about this topic? Tinea capitis (TC) must be confirmed by a mycological culture that may take up to 6 weeks, delaying treatment. Specific trichoscopic signs of TC were first described in 2008, but the accuracy of trichoscopy for diagnosing TC has not previously been evaluated. What does this study add? The present series is the largest yet on the use of trichoscopy in the diagnosis of TC. Our results demonstrated that the presence of a single feature (comma hair, corkscrew hair, zigzag hair, Morse-code-like hair or whitish sheath) is predictive of TC. Trichoscopy is painless and highly sensitive. Morse-code-like hair appears to be highly specific for Microsporum TC.

Heterogeneity of virological suppression in the national antiretroviral programme of Cameroon (ANRS 12288 EVOLCAM).

OBJECTIVES: In terms of HIV infection, western and central Africa is the second most affected region world-wide, and the gap between the regional figures for the testing and treatment cascade and the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets is particularly worrying. We assessed the prevalence of virological suppression in patients routinely treated in 19 hospitals in Cameroon. METHODS: A cross-sectional survey was performed in adult patients receiving antiretroviral therapy (ART) in the Centre and Littoral regions. The prevalences of virological suppression (<1000 HIV-1 RNA copies/mL) were compared among all 19 hospitals using the χ2 test. Potential individual and health care-related determinants of virological suppression were assessed using multivariate logistic regression models. RESULTS: A total of 1700 patients (74% women; median age 41 years; median time on ART 3.7 years) were included in the study. The prevalence of virological suppression was 82.4% overall (95% confidence interval 80.5-84.2%). It ranged from 57.1 to 97.4% according to the individual hospital (P < 0.001). After adjustment, virological suppression was associated with age, CD4 cell count at ART initiation, disclosure of HIV status to family members, interruption of ART for more than two consecutive days, and location of patient's residence and hospital (rural/urban). These factors did not explain the heterogeneity of virological suppression between the study hospitals (P < 0.001). CONCLUSIONS: The overall prevalence of virological suppression was reassuring. Nevertheless, the heterogeneity of virological suppression among hospitals highlights that, in addition to programme-level data, health facility-level data are crucial in order to tailor the national AIDS programme's interventions with a view to achieving the third UNAIDS 90 target.