Literature review of perceptual learning modules in medical education: What can we conclude regarding dermatology?

INTRODUCTION: Visual pattern recognition is important in many different medical fields, particularly in dermatology. Perceptual learning modules (PLM) are software programs developed to enhance visual pattern recognition through the sequential presentation of images that trainee must quickly diagnose. The aim of this literature review was to determine the scope and effectiveness of PLM in medical education. METHODS: We carried out a search of MEDLINE, EMBASE, Web of Science and ERIC from its inception through to July 1, 2017. All articles describing an educational intervention based on perceptual learning in a medical field were included. Two investigators worked independently on study selection and data extraction. RESULTS: Of 191 references selected, 5 studies were included in the final analysis: 3 before-after studies and 2 randomized studies comparing 12 to 236 trainees taking PLM with 12 to 316 trainees not taking PLM. Four studies reported a statistically significant increase in diagnostic accuracy (lower error rate) and fluency (shorter response time) following PLM interventions (dermatology, pathology, echocardiography), with long-term persistence of the effect in three studies. CONCLUSION: PLM is a promising educational tool to teach pattern recognition that may be used in dermatology and other medical fields to improve diagnostic accuracy and rapidity in daily practice.

Cutaneous drug-induced lupus erythematosus: Clinical and immunological characteristics and update on new associated drugs.

Cutaneous drug-induced lupus erythematosus (CDILE) is a lupus-like syndrome related to drug exposure which typically resolves after drug discontinuation. It can present as a systemic or a sole cutaneous form and different drugs may be associated with each form. CDILE pharmacoepidemiology is constantly changing. Indeed, older drugs primarily associated with systemic CDILE are no longer prescribed and new drugs associated with either cutaneous or systemic CDILE have emerged. The present study discusses the clinical and laboratory aspects of CDILE and the postulated pathogenesis, and it provides an update on implicated drugs. We performed a literature review to single out the new drugs associated with CDILE in the past decade (January 2010-June 2020). Among 109 drugs reported to induce CDILE in 472 patients, we identified anti-TNFα, proton-pump inhibitors, antineoplastic drugs, and, in particular, checkpoint inhibitors, as emerging drugs in CDILE. Most of the published studies are cases reports or small case series, and further larger studies as well as the development of validated classification criteria are needed to better understand and characterize their implication in CDILE.

[What is neutrophilic urticaria?] / Qu'est-ce que l'urticaire neutrophilique ?

Some debate continues to surround the existence of neutrophilic urticaria (NU) as a nosological entity. Certain authors consider NU as a banal form of urticaria since an infiltrate predominantly made up of polynuclear neutrophils (PNN) is seen in certain cases of chronic and acute urticaria. Moreover, it has been stated that the histological appearance of chronic urticaria varies according to the time between appearance of the plaque and the performance of biopsy: the presence of PNN may occur later. According to the literature, there appear to be no specific clinical characteristics associated with the presence of PNN at histology. Most cases exhibit moderate laboratory inflammatory syndrome. Data concerning therapeutic response are contradictory: some studies have shown no significant difference in terms of therapeutic response in relation to banal urticaria, while only one study has demonstrated superior response to dapsone in the case of histologically demonstrated neutrophilic infiltrate. There does not appear to be any disease more frequently associated in the event of NU. In conclusion, the available data concerning NU are insufficient to confirm the existence of this condition. A prospective study comparing routine acute and chronic urticaria biopsies would be extremely useful to better characterise the relationships between cellular infiltrate and therapeutic response.

[Omalizumab for the treatment of chronic urticaria: Real-life findings]. / Traitement de l'urticaire chronique par omalizumab : données en vie réelle.

OBJECTIVE: Assessment of the efficacy and safety of omalizumab in chronic urticaria refractory to conventional treatment (H1-antihistamines at high dosage and montelukast) in real-life practice. PATIENTS AND METHODS: A retrospective, descriptive, single-centre study was performed of the data for all patients presenting refractory chronic spontaneous urticaria or inducible urticaria and receiving omalizumab (300mg every four weeks) from November 2012 to June 2016. RESULTS: In all, 23 patients were included. Omalizumab led to complete or significant remission in 19 patients (83%) with chronic urticaria, with remission in 9 patients (47%) occurring within 72hours of the first injection. One patient had a partial response and 3 (13%) showed no response. Only 2 patients (9%) in complete remission stopped their treatment at 1 and 3 years. 52% of patients presented non-serious adverse events, which in one case resulted in treatment withdrawal. CONCLUSION: Omalizumab exhibited good real-life efficacy in a small series of chronic urticaria patients in France.

New insights into the phenotypes of atopic dermatitis linked with allergies and asthma in children: An overview.

Atopic dermatitis (AD) is a complex disease with multiple causes and complex mechanistic pathways according to age of onset, severity of the illness, ethnic modifiers, response to therapy and triggers. A group of difficult-to-manage patients characterized by early-onset AD and severe lifelong disease associated with allergic asthma and/or food allergy (FA) has been identified. In this study, we focus on these severe phenotypes, analysing their links with other atopic comorbidities, and taking into account the results from recent cohort studies and meta-analyses. The main hypothesis that is currently proposed to explain the onset of allergic diseases is an epithelial barrier defect. Thus, the atopic march could correspond to an epithelial dysfunction, self-sustained by a secondary allergenic sensitization, explaining the transition from AD to allergic asthma. Furthermore, AD severity seems to be a risk factor for associated FA. Results from population-based, birth and patient cohorts show that early-onset and severe AD, male gender, parental history of asthma, and early and multiple sensitizations are risk factors leading to the atopic march and the development of asthma. The importance of environmental factors should be recognized in these high-risk children and prevention programs adapted accordingly. Effective targeted therapies to restore both barrier function and to control inflammation are necessary; early emollient therapy is an important approach to prevent AD in high-risk children. Clinicians should also keep in mind the specific risk of atopic comorbidities in case of filaggrin loss-of-function mutations and the rare phenotypes of orphan syndromes due to heritable mutations in skin barrier components.

Interleukin-32 promotes detachment and activation of human Langerhans cells in a human skin explant model.

BACKGROUND: Cross-talk between skin keratinocytes (KCs) and Langerhans cells (LCs) plays a fundamental role in the body's first line of immunological defences. However, the mechanism behind the interaction between these two major epidermal cells is unknown. Interleukin (IL)-32 is produced in inflammatory skin disorders. We questioned the role of IL-32 in the epidermis. OBJECTIVES: We aimed to determine the role of IL-32 produced by KCs on surrounding LCs. METHODS: We used an ex vivo human explant model from healthy donors and investigated the role of IL-32 on LC activation using imaging, flow cytometry, reverse transcriptase quantitative polymerase chain reaction and small interfering (si)RNA treatment. RESULTS: Modified vaccinia virus ankara (MVA) infection induced KC death alongside the early production of the proinflammatory cytokine IL-32. We demonstrated that IL-32 produced by MVA-infected KCs induced modest but significant morphological changes in LCs and downregulation of adhesion molecules, such as epithelial cell adhesion molecule and very late antigen-4, and CXCL10 production. The treatment of KCs with IL-32-specific siRNA, and anti-IL-32 blocking antibody significantly inhibited LC activation, demonstrating the role of IL-32 in LC activation. We also found that some Toll-like receptor ligands induced a very high level of IL-32 production by KCs, which initiated LC activation. CONCLUSIONS: We propose, for the first time, that IL-32 is a molecular link between KCs and LCs in healthy skin, provoking LC migration from the epidermis to the dermis prior to their migration to the draining lymph nodes.

Randomized clinical trial between polyacrylate-polyalcohol copolymer (PPC) and dextranomer-hyaluronic acid copolymer (Dx/HA) as bulking agents for endoscopic treatment of primary vesicoureteral reflux (VUR).

OBJECTIVE: To compare the radiological and clinical outcomes of endoscopic treatment of primary VUR using polyacrylate-polyalcohol copolymer (PPC-Vantris®) or dextranomer-hyaluronic acid copolymer (Dx/HA-Deflux®). MATERIALS AND METHODS: From October 2014 to April 2017, patients with primary VUR grade III to V that needed endoscopic treatment (ET) were eligible for this randomized clinical trial. We excluded toilet-trained patients with lower urinary tract symptoms. Patients were randomized and allocated into two groups: PPC group and Dx/HA group. After endoscopic treatment a voiding cystourethrography (VCUG) was performed at 6 months; if VUR was still present a second ET was performed. Radiological success was considered if postoperative VUR grade was 0 and clinical success rate was considered if no more fUTI appeared during follow-up. RESULTS: Forty-six patients were eligible but 2 did not accept the trial. Forty-four patients with 73 refluxing ureters were included. PPC: 34 refluxing ureters; and Dx/HA: 39 refluxing ureters. Both groups were statistically homogeneous and comparable. Mean follow-up was 27.6 months. Radiological success rate (82.2%) and clinical success rate (92.3%) were similar in both groups (p > 0.05). The volume of bulking agent used in those successfully treated was greater in Dx/HA group (p < 0.05). Distal ureter was excise in all cases of ureteral reimplantation after PPC treatment; however, distal ureter was preserved in all ureters reimplanted after Dx/HA injection. CONCLUSION: PPC and Dx/HA had similar outcomes, but we must warn that ureteral reimplantation after endoscopic treatment with PPC is difficult because of the periureteral fibrosis.

[Prevalence of hydroxychloroquine-induced side-effects in dermatology patients: A retrospective survey of 102 patients]. / Prévalence des effets indésirables de l'hydroxychloroquine (Plaquenil®) dans une population dermatologique : étude rétrospective sur 102 patients.

AIM: Our aim was to assess the prevalence of adverse effects (AEs) pertaining to the use and withdrawal of hydroxychloroquine (HCQ) in dermatological outpatients. PATIENTS AND METHODS: We conducted a retrospective study between January 2013 and June 2014 that included consecutive patients currently or previously receiving HCQ seen in our department. AEs were collated using a standardized questionnaire and validated by clinical and laboratory examination. Drug causality was evaluated using the updated French drug reaction causality assessment method. The main evaluation criterion was the prevalence of AEs in which HCQ had an intrinsic imputability score of I>2. RESULTS: We included 102 patients (93 of whom were women, with a median age of 44.5; range: 22-90years). HCQ was given for cutaneous lupus in most cases (n=70). At least one AE was reported for 55 patients. Among the 91 reported AEs, 59 (65%) had an HCQ intrinsic imputability score I>2. AEs were responsible for permanent HCQ discontinuation in 19 cases. Of these, 8 were unrelated to HCQ based on imputability score. The most common AEs associated with HCQ were gastrointestinal and cutaneous signs. Of the 8 patients diagnosed with retinopathy, only 3 were confirmed after reevaluation. CONCLUSION: AEs associated with HCQ were reported for over 50% of patients and were responsible for permanent HCQ discontinuation in one-third of cases. A more in-depth evaluation of imputability seems necessary, particularly regarding ophthalmological symptoms, since in two thirds of cases the reasons for discontinuation were not related to HCQ.

Infection rate of Aedes aegypti mosquitoes with dengue virus depends on the interaction between temperature and mosquito genotype.

Dengue fever is the most prevalent arthropod-transmitted viral disease worldwide, with endemic transmission restricted to tropical and subtropical regions of different temperature profiles. Temperature is epidemiologically relevant because it affects dengue infection rates in Aedes aegypti mosquitoes, the major vector of the dengue virus (DENV). Aedes aegypti populations are also known to vary in competence for different DENV genotypes. We assessed the effects of mosquito and virus genotype on DENV infection in the context of temperature by challenging Ae. aegypti from two locations in Vietnam, which differ in temperature regimes, with two isolates of DENV-2 collected from the same two localities, followed by incubation at 25, 27 or 32°C for 10 days. Genotyping of the mosquito populations and virus isolates confirmed that each group was genetically distinct. Extrinsic incubation temperature (EIT) and DENV-2 genotype had a direct effect on the infection rate, consistent with previous studies. However, our results show that the EIT impacts the infection rate differently in each mosquito population, indicating a genotype by environment interaction. These results suggest that the magnitude of DENV epidemics may not only depend on the virus and mosquito genotypes present, but also on how they interact with local temperature. This information should be considered when estimating vector competence of local and introduced mosquito populations during disease risk evaluation.

[Vascular anomalies in the neonatal period]. / Anomalías vasculares de presentación neonatal.

OBJECTIVE: Vascular anomalies in the neonatal period are a diagnostic challenge for the lack of evident signs, symptoms and follow-up, and the convenience of restricting aggressive diagnostic tests. The aim of this work is to review the characteristics of neonatal cases presented to our Vascular Anomalies Unit in the last 5 years. MATERIALS AND METHODS: All cases of suspected vascular anomaly presented to our unit before 1 month of age between 2010 and 2015 were reviewed, diagnostic tests and treatments carried out with chronology were analyzed. Presumptive diagnosis and final diagnosis (when available) were compared. RESULTS: Fifteen vascular tumors were found, 2 with visceral involvement: 6 infantile hemangiomas (IH), 3 NICH, 4 RICH, 1 tufted hemangioma, 1 unspecified liver vascular tumor, 3 venous malformations (2 equivocal MRI and a hyperkeratotic venous malformation), 4 lymphatic malformations, 3 of them macrocystic, and 2 vascular lesions that were diagnosed of fibrosarcoma and sclerema neonatorum and they were not vascular anomalies. Only 3 patients with macrocystic lymphatic malformations had prenatal diagnosis. CONCLUSION: Accurate diagnosis of vascular anomalies during the first month of life is difficult, even with MRI. Only in a few cases early treatment is needed, so it is worth taking time to follow-up. Different types of treatment (observation, propranolol, biopsy, laser, embolization, and resection) will depend on the condition to be treated. A continuous observation can avoid unnecessary procedures and risks.

OBJETIVOS: Las anomalías vasculares de presentación neonatal suponen un reto diagnóstico por la ausencia de semiología florida, de historia evolutiva y la conveniencia de restringir pruebas diagnósticas agresivas. El objetivo es revisar las características de los casos neonatales presentados a nuestra Unidad de Anomalías Vasculares en los últimos 5 años. MATERIAL Y METODOS: Se recogen todos los casos de sospecha de anomalía vascular presentados a nuestra Unidad antes de 1 mes de edad entre 2010 y 2015. Se revisa el momento del diagnóstico en relación con la anomalía, las pruebas diagnósticas y los tratamientos efectuados con su cronología. Se comparan el diagnóstico de presunción y el de certeza, cuando lo hay. RESULTADOS: Se incluyen 26 pacientes: 15 tumores vasculares, 2 de ellos con afectación visceral (6 hemangiomas infantiles (HI), 3 NICH, 4 RICH, 1 hemangioma en penacho, 1 tumor vascular hepático no especificado. 3 malformaciones venosas: 2 con RM equívoca y una malformación venosa hiperqueratótica. 4 malformaciones linfáticas: 3 macroquísticas y una microquística. 2 lesiones muy vasculares que se diagnosticaron posteriormente (fibrosarcoma y adiponecrosis) y no eran anomalías vasculares. Solo 3 pacientes tenían diagnóstico prenatal, las malformaciones linfáticas macroquísticas. CONCLUSION: El diagnóstico preciso de las anomalías vasculares durante el primer mes de vida es difícil, incluso con RM. En pocos casos se necesita un tratamiento precoz, por lo que conviene dar tiempo a la evolución, al menos durante unas semanas. Los diferentes tipos de tratamiento (observación, propranolol, biopsia, láser, embolización, exéresis) dependerán de la patología a tratar. Una observación continuada puede evitar procedimientos y riesgos innecesarios.

Immediate hypersensitivity to iodinated contrast media: diagnostic accuracy of skin tests and intravenous provocation test with low dose.

BACKGROUND: The diagnosis of HSR to iodinated contrast media (ICM) is challenging based on clinical history and skin tests. OBJECTIVE: This study evaluates the negative predictive value (NPV) of skin tests and intravenous provocation test (IPT) with low-dose ICM in patients with suspected immediate hypersensitivity reaction (HSR) to ICM. METHODS: Thirty-seven patients with suspected immediate hypersensitivity reaction to ICM were included retrospectively. Skin tests and a single-blind placebo-controlled intravenous provocation test (IPT) with low-dose iodinated contrast media (ICM) were performed. RESULTS: Skin tests with ICM were positive in five cases (one skin prick test and five intradermal test). Thirty-six patients were challenged successfully by IPT, and only one patient had a positive challenge result, with a grade I reaction by the Ring and Messmer classification. Ten of 23 patients followed up by telephone were re-exposed to a negative tested ICM during radiologic examination; two experienced a grade I immediate reaction. CONCLUSIONS & CLINICAL RELEVANCE: For immediate hypersensitivity reaction to ICM, the NPV for skin tests and IPT with low dose was 80% (95% CI 44-97%).

Decreased tryptophan and increased kynurenine levels in mastocytosis associated with digestive symptoms.

The main metabolism pathway of tryptophan is protein formation, but it can also be metabolized into serotonin and kynurenine. Indoleamine 2,3-dioxygenase (IDO) is the enzyme that catalyzes the degradation of tryptophan into kynurenine. Mastocytosis is a heterogeneous disease characterized by mast cell accumulation in various tissues with 57% of patients having gastrointestinal involvement. We studied tryptophan metabolism in mastocytosis patients displaying or not gastrointestinal features and healthy subjects (n = 26 in each group). Mastocytosis patients with digestive symptoms displayed significantly increased kynurenine level and IDO activity as compared to healthy controls and mastocytosis patients without digestive symptoms. This could be linked to mast cell-mediated digestive inflammation among patients with mastocytosis. This work is the first focusing on kynurenine pathway in a mast cell disease and could help to understand the pathogenesis of digestive features in mastocytosis as well as in other mast cell-mediated diseases.

Temporal genetic stability of Stegomyia aegypti (= Aedes aegypti) populations.

The mosquito Stegomyia aegypti (= Aedes aegypti) (Diptera: Culicidae) is the primary vector of viruses that cause yellow fever, dengue and Chikungunya fever. In the absence of effective vaccines, the reduction of these diseases relies on vector control strategies. The success of these strategies is tightly linked to the population dynamics of target populations. In the present study, 14 collections from St. aegypti populations separated by periods of 1-13 years were analysed to determine their temporal genetic stability. Although temporal structure is discernible in most populations, the degree of temporal differentiation is dependent on the population and does not obscure the geographic structure of the various populations. The results suggest that performing detailed studies in the years prior to and after population reduction- or modification-based control interventions at each target field site may be useful in assessing the probability of success.

Chronic urticaria and hormones: Is there a link?

BACKGROUND: While the role of oestrogens in bradykinin angioedema (AE) has been clearly demonstrated, scarce data are available about the role of sex hormones in chronic urticaria (CU). OBJECTIVES: To gather information from a population of women with various forms of CU [chronic spontaneous urticaria (CSU), including a subtype of isolated histaminic AE and a classic subtype of association of wheals and AE, and exclusive inducible urticaria (IU)] about the impact of sex hormones and reproductive factors on their symptoms. METHODS: This was a cross-sectional study comprising interviews of 200 women consulting for CU at nine centres throughout France between May and July 2013. The dermatologists filled in an online questionnaire on the impact of reproductive factors (puberty, contraception and pregnancy) and hormonal treatments on the course of CU, including CSU and IU, in the presence of the women. RESULTS: Most of the women did not experience CU before puberty and if so, puberty did not influence the course of CU. Only 16 women had experienced a pregnancy during CU which caused a worsening of symptoms in four. Hormonal contraception was associated with aggravation in a minority of women, mostly women with CSU (10%). Women with isolated histaminic AE did not exhibit any female sex hormone dependency. CONCLUSIONS: It would appear that sex hormones act as a trigger in only a small subset of women with CU. Nevertheless, this should be taken into account to improve patient management.