Methotrexate as a corticosteroid-sparing agent in leprosy reactions: A French multicenter retrospective study.

INTRODUCTION: Leprosy reactions (LRs) are inflammatory responses observed in 30%-50% of people with leprosy. First-line treatment is glucocorticoids (GCs), often administered at high doses with prolonged courses, resulting in high morbi-mortality. Methotrexate (MTX) is an immunomodulating agent used to treat inflammatory diseases and has an excellent safety profile and worldwide availability. In this study, we describe the efficacy, GCs-sparing effect and safety of MTX in LRs. METHODS: We conducted a retrospective multicentric study in France consisting of leprosy patients receiving MTX for a reversal reaction (RR) and/or erythema nodosum leprosum (ENL) since 2016. The primary endpoint was the rate of good response (GR) defined as the complete disappearance of inflammatory cutaneous or neurological symptoms without recurrence during MTX treatment. The secondary endpoint was the GCs-sparing effect, safety and clinical relapse after MTX discontinuation. RESULTS: Our study included 13 patients with LRs (8 men, 5 women): 6 had ENL and 7 had RR. All patients had had at least one previous course of GCs and 2 previous treatment lines before starting MTX. Overall, 8/13 (61.5%) patients had GR, allowing for GCs-sparing and even GCs withdrawal in 6/11 (54.5%). No severe adverse effects were observed. Relapse after MTX discontinuation was substantial (42%): the median relapse time was 5.5 months (range 3-14) after stopping treatment. CONCLUSION: MTX seems to be an effective alternative treatment in LRs, allowing for GCs-sparing with a good safety profile. Furthermore, early introduction during LRs may lead to a better therapeutic response. However, its efficacy seems to suggest prolonged therapy to prevent recurrence.

C-reactive protein: An easy marker for early differentiation between leptospirosis and dengue fever in endemic area.

In tropical regions, leptospirosis and dengue fever (DF) are infectious diseases of epidemiological importance and have overlapping symptomatic features. The objective of this study was to identify the factors associated to diagnosing leptospirosis that differentiate it to DF at the initial hospital evaluation. A multicenter retrospective study was conducted comparing confirmed leptospirosis to DF cases. Clinical/laboratory findings were compiled at hospital admission on Reunion Island between 2018 and 2019. Multivariable logistic regression was used to identify the predictors of leptospirosis. In total, 98 leptospirosis and 673 DF patients were included with a mean age of 47.8 (±17.1) and 48.9 (±23.3) years, respectively. In the multivariate analyses, the main parameters associated with leptospirosis were: i) increased neutrophil counts, ii) C-reactive protein values, iii) the absence of prolonged partial thromboplastin time, and iv) a decrease of platelets. The most discriminating parameter was C-reactive protein (CRP). With a threshold of 50mg/L, CRP taken alone had a sensitivity of 94% and a specificity of 93.5%. The positive and negative likelihood ratios were 14.5 and 0.06, respectively. In the setting of an early presumptive diagnosis, we found that an increased CRP value (>50 mg/L) could help diagnose leptospirosis and aid the decision process for hospital surveillance and/or a potential antibiotic treatment regimen.

Use of healthcare reimbursement data to monitor bacterial sexually transmitted infection testing in France, 2006 to 2020.

BackgroundDiagnoses of bacterial sexually transmitted infections (STIs) have increased in France since the 2000s. The main strategy to control STI transmission is recommending/facilitating access to condom use, testing, and antibiotic treatments.AimThis study analyses the evolution of STI testing in the private sector in France from 2006 to 2020.MethodsNational health insurance reimbursement data were used to determine numbers and rates of individuals aged ≥ 15 years tested for diagnoses of chlamydia, gonorrhoea and syphilis in the private sector in France and to describe their evolution from 2006 to 2020.ResultsUpward tendencies in testing were observed from 2006 to 2019 for all three STIs. The highest testing rates were identified in people aged 25‒29-years old. The observed testing-increase from 2017 to 2019 was twice as high in young people (< 25 years old) as in older people. In 2019, chlamydia, gonorrhoea and syphilis testing rates were respectively 45.4 (+ 21% since 2017), 41.3 (+ 60%), and 47.2 (+ 22%) per 1,000 inhabitants. For all STIs combined, the number of tested individuals decreased by 37% between March and April 2020 during the first COVID-19 epidemic wave and lockdown in France.ConclusionImprovements found in STI testing rates may have resulted from better awareness, especially among young people and health professionals, of the importance of testing, following prevention campaigns. Nevertheless, testing levels remain insufficient considering increasing diagnoses. In 2020, the COVID-19 pandemic had a considerable impact on STI testing. Partner notification and offering diverse testing opportunities including self-sampling are essential to control STI epidemics particularly in exposed populations.

Differentiating COVID-19 and dengue from other febrile illnesses in co-epidemics: Development and internal validation of COVIDENGUE scores.

OBJECTIVES: The purpose of this cohort study was to develop two scores able to differentiate coronavirus 2019 (COVID-19) from dengue and other febrile illnesses (OFIs). METHODS: All subjects suspected of COVID-19 who attended the SARS-CoV-2 testing center of Saint-Pierre hospital, Reunion, between March 23 and May 10, 2020, were assessed for identifying predictors of both infectious diseases from a multinomial logistic regression model. Two scores were developed after weighting the odd ratios then validated by bootstrapping. RESULTS: Over 49 days, 80 COVID-19, 60 non-severe dengue and 872 OFIs were diagnosed. The translation of the best fit model yielded two scores composed of 11 criteria: contact with a COVID-19 positive case (+3 points for COVID-19; 0 point for dengue), return from travel abroad within 15 days (+3/-1), previous individual episode of dengue (+1/+3), active smoking (-3/0), body ache (0/+5), cough (0/-2), upper respiratory tract infection symptoms (-1/-1), anosmia (+7/-1), headache (0/+5), retro-orbital pain (-1/+5), and delayed presentation (>3 days) to hospital (+1/0). The area under the receiver operating characteristic curve was 0.79 (95%CI 0.76-0.82) for COVID-19 score and 0.88 (95%CI 0.85-0.90) for dengue score. Calibration was satisfactory for COVID-19 score and excellent for dengue score. For predicting COVID-19, sensitivity was 97% at the 0-point cut-off and specificity 99% at the 10-point cut-off. For predicting dengue, sensitivity was 97% at the 3-point cut-off and specificity 98% at the 11-point cut-off. CONCLUSIONS: COVIDENGUE scores proved discriminant to differentiate COVID-19 and dengue from OFIs in the context of SARS-CoV-2 testing center during a co-epidemic.

Efficacité et tolérance du méthotrexate au cours des réactions lépreuses de type 1 et de type 2 : étude rétrospective multicentrique

Introduction La lèpre est une des premières causes de neuropathies dans le monde. Son évolution peut être marquée par des complications immunologiques appelées réactions lépreuses. La réaction de type 1 ou réaction de réversion (RR) est responsable d’une infiltration rapide et douloureuse des lésions cutanées et de névrites potentiellement sévères et irréversibles. La réaction de type 2 ou érythème noueux lépreux (ENL), est une réaction à complexes immuns caractérisée par des nodules inflammatoires douloureux associés à des signes généraux. La prise en charge thérapeutique des réactions lépreuses repose avant tout sur la corticothérapie générale prolongée, source de morbidité importante. La thalidomide, alternative thérapeutique efficace dans l’ENL, est d’utilisation limitée par sa toxicité et sa tolérance médiocre. Au cours de la RR, des immunosuppresseurs conventionnels comme la ciclosporine ou l’azathioprine ont été utilisés mais les données d’efficacité et de tolérance sont parcellaires dans cette indication, et leur disponibilité réduite dans les pays d’endémie. Dans la littérature, une vingtaine de cas d’efficacité du MTX ont été rapportés. L’objectif de l’étude vise à analyser l’efficacité et la tolérance du méthotrexate (MTX) au cours des réactions lépreuses ainsi que l’épargne cortisonique. Matériel et méthodes Il s’agit d’une étude rétrospective multicentrique incluant l’ensemble des patients suivis pour une lèpre et ayant reçu du MTX dans le cadre d’une réaction lépreuse de type 1 et 2 depuis 2016. Résultats Un total de 13 patients ont été inclus, 5 femmes et 8 hommes. Les réactions étaient : ENL (n=10) et RR (n=9). La dose médiane de MTX était de 20mg par semaine avec une durée médiane de traitement de 14 mois. Au cours du traitement, 9/13 patients n’ont pas eu de récidive réactionnelle sous MTX. Parmi les 4 patients ayant récidivé, on notait 3 RR et 2 ENL. La dose de prednisone était réduite de 86 % en moyenne lors de l’arrêt du MTX. Un sevrage en corticoïdes était obtenu chez 5 des 11 patients sous CTC. La tolérance du MTX était correcte. Un patient a présenté une cytolyse grade II. Parmi les 8 patients ayant arrêté le MTX (3 pour conception, 1 pour cytolyse, 1 pour nausées, 2 pour inefficacité, 1 pour COVID-19) 6 ont récidivé dans un délai médian de 8 mois après l’arrêt du MTX (3–13). Discussion Il s’agit de la plus grande cohorte rapportant l’intérêt du MTX pour limiter les récidives réactionnelles au cours de la lèpre et permettre une épargne cortisonique. Le MTX semble être une alternative de choix dans le traitement des réactions lépreuses corticodépendantes avec un profil de tolérance favorable. L’efficacité suspensive plaide en faveur d’une utilisation prolongée pour limiter la fréquence des rechutes à l’arrêt. La disponibilité et le coût réduit du MTX permettent d’envisager une utilisation dans les pays d’endémie.

Utilisation du méthotrexate dans le psoriasis modéré à sévère en France : résultats d’une enquête de pratiques

Introduction Évaluation des modalités de prescription du méthotrexate (MTX), traitement de 1re intention proposé par les recommandations françaises pour le psoriasis modéré à sévère, par les dermatologues en France. Matériel et méthodes Enquête de pratiques auprès des dermatologues membres de Reso entre octobre et décembre 2020. Résultats Deux cent cinquante quatre dermatologues ont répondu : 74 hospitaliers, 93 libéraux et 87 mixtes ;71 avaient une consultation dédiée au psoriasis. Deux cent trente sept prescrivaient du MTX dans le psoriasis modéré à sévère de l’adulte, 57 % en 1re ligne de traitement systémique. Quarante six réalisaient une dose test au début du traitement. Le MTX était prescrit par voie orale 54,7 % des cas, sous cutanée (SC) 44,8 % et intra-musculaire 0,4 %. La posologie initiale hebdomadaire du MTX était <15mg pour 30 % et ≥15mg pour 70 %. En cas de réponse thérapeutique insuffisante, 16,9 % passaient à une administration SC, 8,4 % changeaient de traitement et 74,7 % augmentaient la posologie du MTX. En cas d’effets secondaires digestifs, 72,6 % passaient à une administration SC, 12,2 % diminuaient la posologie du MTX,15,2 % changeaient de traitement. Au total, 98,7 % déclaraient prescrire de l’acide folique avec le MTX et 79,3 % des tests évaluant le risque de fibrose hépatique. Depuis le début de la pandémie de COVID-19, 54 % déclaraient que leurs prescriptions de MTX étaient restées stables, 30 % qu’elles avaient diminué, 1,3 % qu’elles avaient augmenté ;11.8 % déclaraient n’avoir pas mis en route de MTX depuis le début de la pandémie. Les modalités de prescription selon le type d’exercice sont précisées dans le tableau 1. Il n’y avait pas de différence selon l’ancienneté d’exercice. Discussion Les résultats de cette enquête soulignent l’hétérogénéité des pratiques dans la prescription du MTX dans le psoriasis modéré à sévère de l’adulte ;20 % des dermatologues interrogés déclarent réaliser une dose test, actuellement non obligatoire. L’administration orale est privilégiée alors que des données récentes ont mis en évidence une efficacité et une tolérance meilleures de la voie SC dans une cohorte de patients allemands. La pandémie de COVID-19 a eu un impact sur la prescription de MTX. Des données ont mis en évidence l’absence de surrisque de forme grave de COVID-19 sous traitement systémique du psoriasis que ce soit en phase d’initiation ou d’entretien. Nous avons mis en évidence des différences de pratiques entre dermatologues hospitaliers/mixtes et libéraux, mais pas selon l’ancienneté d’exercice. Limites caractère déclaratif des données et mode de recrutement des dermatologues interrogés, par un réseau dédié aux dermatoses inflammatoires chroniques. Les résultats montrent que le méthotrexate est utilisé par la majorité des dermatologues interrogés pour le psoriasis modéré à sévère de l’adulte. L’actualisation des modalités de prescriptions au vu des dernières recommandations et publications, pourrait contribuer à réduire l’hétérogénéité des pratiques.

Use of Methotrexate in the Treatment of Moderate to Severe Plaque Psoriasis in France: A Practice Survey.

PURPOSE: To evaluate the modalities of methotrexate prescription for moderate to severe psoriasis by dermatologists in France. PATIENTS AND METHODS: We performed a national online practice survey between October and December 2020. RESULTS: A total of 254 dermatologists responded, 237 reported prescribing methotrexate for moderate to severe psoriasis in adults, of which 57% as a first line systemic treatment. Nineteen percent reported performing a test dose at the initiation of treatment. Methotrexate was prescribed orally in 54.7% of cases, subcutaneously in 44.8% of cases and intramuscularly in 0.4% of cases. The initial weekly dose of methotrexate was <15 mg for 30% of the dermatologists and ≥15 mg for 70% of them. Two hundred and three dermatologists had already change the route of administration for methotrexate from the oral to injectable form due to poor tolerance (48.3%), lack of efficacy (35%) or lack of compliance (16.7%). Two hundred thirty-four dermatologists (98.7%) reported prescribing folic acid with methotrexate, and 79.3% reported prescribing tests evaluating the risk of hepatic fibrosis. Forty-three percent of dermatologists have not initiated or have reduced their prescriptions since the beginning of the pandemic of COVID-19. Prescribing patterns were different according to the type of practice (private practice versus hospital/mixed practice). CONCLUSION: Methotrexate is used by the majority of dermatologists interviewed for moderate to severe psoriasis in adults, with heterogeneity of practices.

Distinguishing non severe cases of dengue from COVID-19 in the context of co-epidemics: A cohort study in a SARS-CoV-2 testing center on Reunion island.

BACKGROUND: As coronavirus 2019 (COVID-19) is spreading globally, several countries are handling dengue epidemics. As both infections are deemed to share similarities at presentation, it would be useful to distinguish COVID-19 from dengue in the context of co-epidemics. Hence, we performed a retrospective cohort study to identify predictors of both infections. METHODOLOGY/PRINCIPAL FINDINGS: All the subjects suspected of COVID-19 between March 23 and May 10, 2020, were screened for COVID-19 within the testing center of the University hospital of Saint-Pierre, Reunion island. The screening consisted in a questionnaire surveyed in face-to-face, a nasopharyngeal swab specimen for the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) reverse transcription polymerase chain-reaction and a rapid diagnostic orientation test for dengue. Factors independently associated with COVID-19 or with dengue were sought using multinomial logistic regression models, taking other febrile illnesses (OFIs) as controls. Adjusted Odds ratios (OR) and 95% Confidence Intervals (95%CI) were assessed. Over a two-month study period, we diagnosed 80 COVID-19, 61 non-severe dengue and 872 OFIs cases eligible to multivariate analysis. Among these, we identified delayed presentation (>3 days) since symptom onset (Odds ratio 1.91, 95% confidence interval 1.07-3.39), contact with a COVID-19 positive case (OR 3.81, 95%CI 2.21-6.55) and anosmia (OR 7.80, 95%CI 4.20-14.49) as independent predictors of COVID-19, body ache (OR 6.17, 95%CI 2.69-14.14), headache (OR 5.03, 95%CI 1.88-13.44) and retro-orbital pain (OR 5.55, 95%CI 2.51-12.28) as independent predictors of dengue, while smoking was less likely observed with COVID-19 (OR 0.27, 95%CI 0.09-0.79) and upper respiratory tract infection symptoms were associated with OFIs. CONCLUSIONS/SIGNIFICANCE: Although prone to potential biases, these data suggest that non-severe dengue may be more symptomatic than COVID-19 in a co-epidemic setting with higher dengue attack rates. At clinical presentation, nine basic clinical and epidemiological indicators may help to distinguish COVID-19 or dengue from each other and other febrile illnesses.