Effects of the COVID-19 pandemic on head lice and scabies infestation dynamics: a population-based study in France.

BACKGROUND: Lockdowns and physical distancing have dramatically limited the circulation of SARS-CoV-2 and other common communicable infections. However, little is known about their impact on head lice and scabies. AIM: To assess the impact of the 2020 French National lockdowns (17 March-11 May 2020, and 30 October-15 December 2020) and physical distancing recommendations (from February 2020) on the dynamics of head lice and scabies infestations. METHODS: The weekly sales of topical head lice treatments, topical scabies treatments and oral ivermectin were extracted from the database of the healthcare science company IQVIA (60% of all French retail pharmacies) and analysed over a 5-year period (March 2016-December 2020). A periodic regression model was fitted to drug sales before the COVID-19 period (2016-2019) and extrapolated to compare the observed sales in 2020 to the expected sales. RESULTS: A decrease of the sales of tracer topical treatments for head lice and scabies was observed from March 2020, synchronously with the first French national lockdown. For the period March-December 2020, the mean reduction in observed vs. expected sales for head lice and scabies topical treatments was 44% and 14%, respectively. By contrast, although there was an observed decrease in oral ivermectin sales after March 2020, it was much lower (4%), probably because of studies reporting the potential positive effects of this drug on COVID-19 infection. CONCLUSION: COVID-19 lockdown and physical distancing reduce circulation of head lice and scabies in France. Further studies are needed to assess the long-term impact of these social behaviour changes.

Catastrophic adult-onset Still's disease as a distinct life-threatening clinical subset: case-control study with dimension reduction analysis.

OBJECTIVES: Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder. Diagnosing AOSD can be challenging, as disease presentation and clinical course are highly heterogeneous. For unclear reasons, a few patients develop life-threatening complications. Our objective was to determine whether these cases resulted from therapeutic delay or could represent a peculiar AOSD subset. METHODS: We conducted a multicentre retrospective study of 20 AOSD patients with organ failure requiring intensive care unit admission and 41 control AOSD patients without organ failure. Clinico-biological data at hospital admission were explored using supervised analyses and unsupervised dimension reduction analysis (factor analysis of mixed data, FAMD). RESULTS: Disease duration before admission was shorter in patients with life-threatening AOSD (median, 10 vs 20 days, p = 0.007). Disease duration before AOSD therapy initiation also tended to be shorter (median, 24 vs 32 days, p = 0.068). Despite this shorter disease duration, FAMD, hierarchical clustering and univariate analyses showed that these patients exhibited distinctive characteristics at first presentation, including younger age; higher frequency of splenomegaly, liver, cardiac and/or lung involvement; less frequent arthralgia; and higher ferritin level. In multivariate analysis, 3 parameters predicted life-threatening complications: lack of arthralgia, younger age and shorter time between fever onset and hospitalisation. CONCLUSION: This study suggests that life-threatening complications of AOSD occur very early, in a peculiar subset, which we propose to name catastrophic adult-onset Still's disease (CAOSD). Its exact burden may be underestimated and remains to be clarified through large multicentre cohorts. Further studies are needed to identify red flags and define the optimal therapeutic strategy.

Daily practices regarding safety monitoring of low-dose methotrexate and comparison to guidelines: A population-based cohort study.

PURPOSE: To describe daily practices regarding safety monitoring of methotrexate prescribed at low-(i.e.≤30mg/week). To identify determinants of these practices. To assess association between monitoring and early methotrexate discontinuation. METHODS: Population-based cohort study using the French claims database échantillongénéralistedebénéficiaires (EGB) over the period 2009-2015. Incident methotrexate users were included. The pre-treatment and post-treatment monitoring prescribed to these patients was analyzed. Determinants of monitoring were identified using a logistic regression model. Association between monitoring and early methotrexate discontinuation was assessed using Cox proportional-hazards model. RESULTS: During the study period, 615924 individuals had data in the EGB and 2472 (0.40%) were incident methotrexate users (63.3% women; mean age: 54.7±17.8 years; mean weekly dosage: 13.0±5.3mg). Among these incident users, only 50-70% had an albumin testing (67.0%); HIV (49.7%), hepatitis B (54.8%) or C (55.0%) serology; or chest X-ray (57.4%) within the year before initiating methotrexate. Only 65.7% had a least one CBC, transaminase and urea-creatinine testing combined within the three months before initiation. During the first three months of exposure, the median number of CBC, transaminase and urea-creatinine testing was 2 [1-4], 2 [1-4], and 2 [1-3], respectively. The monitoring modalities depend more on prescriber characteristics than on patient or treatment characteristics. There was a significant positive association between frequency of monitoring during exposure and early methotrexate discontinuation. CONCLUSION: Monitoring of patients prescribed low-dose methotrexate is much less frequent than recommended. Frequent monitoring is associated with early methotrexate discontinuation.

Long-term systemic glucocorticoid therapy and weight gain: a population-based cohort study.

OBJECTIVES: To describe the variation in weight gain in people chronically exposed to systemic glucocorticoids in primary care and to identify the risk factors for weight gain. METHODS: Data were analysed from the British database, The Health Improvement Network. Body weight variations of individuals prescribed systemic glucocorticoids for at least 3 months at a mean dose ≥10 mg/day were described. The risk factors associated with weight gain ≥10% of the usual weight were assessed. RESULTS: A total of 31 516 adults prescribed glucocorticoids and 26 967 controls were included in the study. During glucocorticoid exposure, only 12 475 (39.6%) individuals gained >2 kg compared with their usual weight. Younger women were more likely to gain weight (mean weight gain in 18-39-year-old glucocorticoid-exposed women: 3.6 kg (s.d. 8.6) compared with 2 kg (s.d. 7.3) in the control group; the absolute mean difference was 1.6 kg (95% CI 0.9, 2.2; P < 0.001). Weight gain ≥10% of the usual weight was observed in 10.2% (n = 3208) of those chronically exposed to glucocorticoids. Women, younger people, those living in areas of higher deprivation, smokers, those on higher doses of the drug and those previously exposed to glucocorticoids were at higher risk. The risk was lower in people prescribed glucocorticoids for an inflammatory condition when compared with asthma or chronic obstructive pulmonary disease. CONCLUSION: After taking into account usual weight rather than weight just before glucocorticoid initiation and the natural history of weight variation, the amount of weight gain induced by systemic glucocorticoids as prescribed in primary care is less than usually thought. CLINICAL TRIAL REGISTRATION: 18THIN081.

Risk Factors for Seborrhoeic Dermatitis Flares: Case-control and Case-crossover Study.

Patients with flares of seborrhoeic dermatitis were compared with control outpatients seen during the same time-period in a case-control study, and with themselves while in remission in a case-crossover study. All patients consulted the same office-based dermatologist. During the study period, 189 cases and 189 controls were included in the case-control study, and 81 cases in the case-crossover study. Multivariate analysis was performed. Case-control study results were the following: past history of tobacco consumption (odds ratio (OR) 2.2 (95% confidence interval (CI) 1.1-4.6)), conflict as a dispute during the past month (OR 10.6 (95% CI 1.0-114.3)), alcohol consumption on a regular basis (OR 10.2 (95% CI 2.0-52.6)), and higher level of stress during the past month (OR 8.2 (95% CI 3.4-19.9)). Case-crossover study results were the following: higher level of stress during the past month (OR 4.5 (1.7-12.2)), association borderline significant for higher level of alcohol consumption (OR 5.4 (0.8-34.9)). These risk factors for flares of seborrhoeic dermatitis should be taken into account carefully in the daily management of seborrhoeic dermatitis.

Cytopenia induced by low-dose methotrexate: An analysis of 433 cases from the French pharmacovigilance database.

INTRODUCTION: Up to 5% of individuals exposed to low-dose methotrexate (MTX) (i.e., ≤30 mg/week) may develop cytopenia. However, MTX-induced cytopenia have been poorly described. MATERIAL AND METHODS: All cases of cytopenia (i.e., anaemia, leukopenia, thrombocytopenia, bi- or pancytopenia) in patients receiving low-dose MTX reported to the French pharmacovigilance database during 2006-2016 were analysed. Three groups were defined: cytopenia due to MTX medication errors (e.g., daily rather than weekly administration), cytopenia in people receiving several medications including MTX, cytopenia in people receiving only MTX. RESULTS: 433 cases were analysed. Eighty-four cases (19.4%) were due to medication errors, 180 (41.6%) occurred in individuals exposed both to MTX and other drugs, and 169 (39.0%) occurred in individuals only exposed to MTX. By comparison to other patients, those with cytopenia due to medication errors were older (74 ±â€¯13 vs 69 ±â€¯15 years, p = 0.002), received more frequently MTX orally (92.9% vs 65.3%, p<0.001) and had more frequently pancytopenia (71.4% vs 54.4%, p = 0.005). By comparison to individuals exposed to multiple drugs (n = 180), those exposed only to MTX (n = 169) were older (71 ±â€¯15 vs 67 ±â€¯14, p = 0.02), and had more often pancytopenia (62.7% vs 46.7%, p = 0.001). Among those only exposed to MTX, most cases (n = 140, 82.8%) were considered as toxic rather than idiosyncratic reactions and a trigger (e.g. diarrhoea) was found in 59.3% of those cases. Overall 30 (6.9%) deaths occurred, including 8 in the "medication error" group and 8 in the "MTX only" group. CONCLUSION: These data may be useful for defining optimal biological monitoring of patients prescribed low-dose MTX.

Higher Frequency of Dipeptidyl Peptidase-4 Inhibitor Intake in Bullous Pemphigoid Patients than in the French General Population.

Dipeptidyl peptidase-4 inhibitors have been suspected to induce bullous pemphigoid (BP). The objective of this study was to compare the observed frequency of gliptin intake in a large sample of 1,787 BP patients diagnosed between 2012 and 2015 in France, with the expected frequency after indirect age standardization on 225,412 individuals extracted from the database of the National Healthcare Insurance Agency. The secondary objective was to assess the clinical characteristics and the course of gliptin-associated BP, depending on whether gliptin was continued or stopped. The observed frequencies of intake of the whole gliptin class and that of vildagliptin in the BP population were higher than those in the general population after age standardization (whole gliptin class: 6.0%; 95% confidence interval = 4.9-7.1% vs. 3.6%, observed-to-expected drug intake ratio = 1.7; 95% confidence interval = 1.4-2.0; P < 0.0001; vildagliptin = 3.3%; 95% confidence interval = 2.5-4.1% vs. 0.7%, ratio = 4.4; 95% confidence interval = 3.5-5.7; P < 0.0001). The association of any gliptin+metformin was also higher than in the general population, ratio = 1.8 (95% confidence interval = 1.3-2.4; P < 0.0001). Gliptin-associated BP had no specific clinical characteristics. Gliptin was stopped in 48 (45.3%) cases. Median duration to achieve disease control, rate, and delay of relapse were not different whether gliptin was stopped or continued. This study strongly supports the association between gliptin intake, particularly vildagliptin, and the onset of BP.

A comprehensive analysis of Lymphoma-associated haemophagocytic syndrome in a large French multicentre cohort detects some clues to improve prognosis.

Lymphoma-associated haemophagocytic syndrome (LAHS) accounts for most cases of secondary haemophagocytic syndrome (HS) and has been extensively described in Asian populations. However, little is known about the epidemiology of LAHS in Western countries. We herein report a case series of 71 LAHS patients in which the lymphomas were mainly of the aggressive type. Diagnoses included non-Hodgkin B cell lymphoma (46·5%) including human herpes virus 8-associated non-Hodgkin lymphoma (12·7%), T cell lymphoma (28·2%) and Hodgkin lymphoma (23·9%). An underlying immunodeficiency was described in 30 patients (42·3%). Early mortality within the 30 days following HS diagnosis was observed in 26·8% of cases. The overall survival was estimated at 45·7% [95% confidence interval, CI (35·4-59·0)] at 6 months, and 34·3% [95% CI (24·8-47·4)] at 2 years. Concurrent infection, age over 50 years, ethnicity and etoposide treatment were independently associated with mortality. While it appears that certain types of lymphomas were more prone to trigger HS, LAHS were not restricted to a few types of lymphoma. The overall prognosis was poor, with a particularly high rate of early mortality, highlighting the importance of both early recognition and choice of initial therapeutic management.

Diagnostic and management of life-threatening Adult-Onset Still Disease: a French nationwide multicenter study and systematic literature review.

BACKGROUND: Adult-onset Still disease (AOSD) is a rare systemic inflammatory disorder. A few patients develop organ complications that can be life-threatening. Our objectives were to describe the disease course and phenotype of life-threatening AOSD, including response to therapy and long-term outcome. METHODS: A multicenter case series of intensive care medicine (ICU) patients with life-threatening AOSD and a systematic literature review. RESULTS: Twenty patients were included. ICU admission mostly occurred at disease onset (90%). Disease manifestations included fever (100%), sore throat (65%), skin rash (65%), and arthromyalgia (55%). Serum ferritin was markedly high (median: 29,110 ng/mL). Acute respiratory failure, shock and multiple organ failure occurred in 15 (75%), 10 (50%), and 7 (35%) cases, respectively. Hemophagocytosis was demonstrated in eight cases. Two patients died. Treatment delay was significant. All patients received corticosteroids. Response rate was 50%. As second-line, intravenous immunoglobulins were ineffective. Anakinra was highly effective. After ICU discharge, most patients required additional treatment. Literature analysis included 79 cases of AOSD with organ manifestations, which mainly included reactive hemophagocytic syndrome (42%), acute respiratory failure (34%), and cardiac complications (23%). Response rate to corticosteroids was 68%. Response rates to IVIgs, cyclosporin, and anakinra were 50%, 80%, and 100%, respectively. CONCLUSIONS: AOSD should be recognized as a rare cause of sepsis mimic in patients with fever of unknown origin admitted to the ICU. The diagnosis relies on a few simple clinical clues. Early intensive treatment may be discussed. IVIgs should be abandoned. Long-term prognosis is favorable.

Epidermal necrolysis French national diagnosis and care protocol (PNDS; protocole national de diagnostic et de soins).

Epidermal necrolysis (EN) encompasses Stevens-Johnson syndrome (SJS, < 10% of the skin affected), Lyell syndrome (toxic epidermal necrolysis, TEN, with ≥30% of the skin affected) and an overlap syndrome (10 to 29% of the skin affected). These rare diseases are caused, in 85% of cases, by pharmacological treatments, with symptoms occurring 4 to 28 days after treatment initiation. Mortality is 20 to 25% during the acute phase, and almost all patients display disabling sequelae (mostly ocular impairment and psychological distress).The objective of this French national diagnosis and care protocol (protocole national de diagnostic et de soins; PNDS), based on a critical literature review and on a multidisciplinary expert consensus, is to provide health professionals with an explanation of the optimal management and care of patients with EN. This PNDS, written by the French National Reference Center for Toxic Bullous Dermatoses was updated in 2017 ( https://www.has-sante.fr/portail/jcms/c_1012735/fr/necrolyse-epidermique-syndromes-de-stevens-johnson-et-de-lyell ). The cornerstone of the management of these patients during the acute phase is an immediate withdrawal of the responsible drug, patient management in a dermatology department, intensive care or burn units used to dealing with this disease, supportive care and close monitoring, the prevention and treatment of infections, and a multidisciplinary approach to sequelae. Based on published data, it is not currently possible to recommend any specific immunomodulatory treatment. Only the culprit drug and chemically similar molecules must be lifelong contraindicated.