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Sphingosine 1-phosphate (S1P) is a pleiotropic signaling molecule that interacts with five G-protein-coupled receptors (S1P1-5) to regulate cellular signaling pathways. S1P export is facilitated by Mfsd2b and spinster homologue 2 (Spns2). While mouse genetic studies suggest that Spns2 functions to maintain lymph S1P, Spns2 inhibitors are necessary to understand its biology and to learn whether Spns2 is a viable drug target. Herein, we report a structure-activity relationship study that identified the first Spns2 inhibitor 16d (SLF1081851). In vitro studies in HeLa cells demonstrated that 16d inhibited S1P release with an IC50 of 1.93 µM. Administration of 16d to mice and rats drove significant decreases in circulating lymphocyte counts and plasma S1P concentrations, recapitulating the phenotype observed in mice made deficient in Spns2. Thus, 16d has the potential for development and use as a probe to investigate Spns2 biology and to determine the potential of Spns2 as a drug target.

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Hidradenitis suppurativa (HS) is an inflammatory disorder that is characterized by chronic deep-seated nodules, abscesses, fistulae, sinus tracts, and scars in the axilla, inguinal area, submammary folds, and perianal area. This disfiguring condition is accompanied by pain, embarrassment, and a significantly decreased quality of life. Although the mechanism of HS has not been entirely elucidated, lesion formation is believed to center around follicular hyperkeratosis within the pilosebaceous-apocrine unit. Recent research has provided new insight into the role of cytokines in the pathogenesis of HS, helping close some existing knowledge gaps in the development of this condition. The first article in this continuing medical education series reviews HS epidemiology, clinical presentation, and classification. We also provide an update on the most recent understanding of HS pathogenesis, including the central role of inflammatory cytokines and other contributing factors, such as genetics, hormones, and pathogenic microorganisms.

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The treatment of hidradenitis suppurativa (HS) has remained challenging because of the many knowledge gaps regarding etiology. However, recent studies into the pathogenesis of HS have enabled the investigation of newer therapies. The second article in this continuing medical education series reviews the evidence for established therapies for HS, including anti-inflammatories, antibiotics, and surgery. New and emerging therapies that specifically target cytokines involved in HS pathogenesis will be covered. The potential therapeutic roles of anticytokine therapies, including both the expanded application of existing molecules as well as the specific development of novel therapies for HS are discussed. With increased attention on HS and with numerous clinical trials currently underway, we hope that the variety of treatment options for HS will be expanded.

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Prurigo nodularis (PN) is a disease in which chronic scratching and picking of the skin due to intense pruritis results in papulonodules, notably in areas that are accessible to the patient. The pathophysiology is hypothesized to be mediated by a Th2 helper cell response, similar to that seen in atopic dermatitis, therefore, treatment of PN with dupilumab would be expected to elicit a therapeutic response. We demonstrated that treatment of PN with dupilumab significantly decreased pruritis and the size and number of new lesions after 2 months of treatment. J Drugs Dermatol. 2019;18(9):940-942.

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Several new monoclonal antibodies that interfere with interleukin (IL) cascades have come to market in recent years. They follow a generation of drugs that block tumor necrosis factor (TNF). It has been well established that TNF is important in the containment of Mycobacterium tuberculosis (Mtb) and that blocking this cytokine increases the risk of tuberculosis (TB) infection. Thus, judicious screening for Mtb of patients taking TNF blocking drugs has been the standard of care. It remains unclear if the newer monoclonal, interleukin blocking drugs, which affect IL-12, IL-23, and IL-17 pathways are associated with risk of Mtb reactivation. Herein we discuss what is known about the immunologic response to Mtb and discuss the data that is currently available for the new interleukin monoclonal antibody blocking medications regarding the risk of latent TB reactivation or active TB infection.

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OBJECTIVE: To investigate the lost revenue associated with Medicaid patients in a university-based dermatology practice over a one-year period compared to non-Medicaid patients. Specifically, the goal was to investigate the change in revenue if Medicaid visits were associated with a range of copayments. RESULTS: The total billed across all encounters for the 2014 -2015 fiscal year was $31017159, of which $3715393 (13.61%) was for Medicaid. 'he total revenue for all encounters was $12267832, of which $420230 (3.55%) was for Medicaid. After adding potential copayments, the reduced financial impact that such fees would have had on our practice for the past fiscal year ranged from $745.85 at $0.05/visit to $149170 at $10/visit. CONCLUSION: Adding a small copaymentforMedicaid patients would decrease lost revenue. The degree of financial impact would vary based on the size of the copayment. Broad adoption of such a plan could significantly help hospitals reduce lost revenue.

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BACKGROUND: Results of molecular studies are redefining the diagnosis and management of a wide range of skin disorders. Dermatology training programs maintain a relative gap in relevant teaching. OBJECTIVE: To develop a curriculum in molecular diagnostics, genomics and personalized medicine for dermatology trainees at our institution. The aim is to provide trainees with a specialty-appropriate, working knowledge in clinical molecular dermatology. METHODS: The Departments of Dermatology and Pathology and Laboratory Medicine collaborated on the design and implementation of educational objectives and teaching modalities for the new curriculum. RESULTS: A multidisciplinary curriculum was developed. It comprises: (i) assigned reading from the medical literature and reference textbook; (ii) review of teaching sets; (iii) two 1 hour lectures; (iv) trainee presentations; (v) 1-week rotation in a clinical molecular pathology and cytogenetics laboratory; and (vi) assessments and feedback. Residents who participated in the curriculum to date have found the experience to be of value. CONCLUSIONS: Our curriculum provides a framework for other dermatology residency programs to develop their own specific approach to molecular diagnostics education. Such training will provide a foundation for lifelong learning as molecular testing evolves and becomes integral to the practice of dermatology.

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Visual impairment is a global epidemic. In developing countries, nutritional deficiency and cataracts continue to be the leading cause of blindness, whereas age-related macular degeneration (AMD) and cataracts are the leading causes in developed nations. The World Health Organization has instituted VISION 2020: "The Right to Sight" as a global mission to put an end to worldwide blindness. In industrialized societies, patients, physicians, researchers, nutritionists, and biochemists have been looking toward vitamins and nutrients to prevent AMD, cataracts, and dry eye syndrome (DES). Nutrients from the AREDS2 study (lutein, zeaxanthin, vitamin C, vitamin E, zinc, copper, eicosapentanoic acid [EPA], and docosahexanoic acid [DHA]) set forth by the National Institutes of Health remain the most proven nutritional therapy for reducing the rate of advanced AMD. Omega-3 fatty acids, especially DHA, have been found to improve DES in randomized clinical trials. Conflicting results have been seen with regard to multivitamin supplementation on the prevention of cataract.

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Lichenoid dermatoses, a group of inflammatory skin conditions with characteristic clinical and histopathologic findings, range from common to rare. Classic lichen planus typically presents as pruritic, polygonal, violaceous flat-topped papules and plaques; many variants in morphology and location also exist. Other lichenoid dermatoses share similar clinical presentations and histopathologic findings. These include lichenoid drug eruption, lichen planus-like keratosis, lichen striatus, lichen nitidus, and keratosis lichenoides chronica. Epidemiologic characteristics vary among each lichenoid disorder. While classic lichen planus is considered a disease of adults, other lichenoid dermatoses may be more common in younger populations. The literature contains an array of reports on the variations in presentation and successful management of lichen planus and lichenoid dermatoses among diverse populations. Familiarity with the characteristics of each lichenoid dermatosis, rare or common within each patient population, is key to accomplishing timely recognition and effective management.

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BACKGROUND: Newer psoriasis treatments tout higher efficacy but are generally more expensive. OBJECTIVE: We sought to estimate the cost efficacy of systemic psoriasis treatments that have been approved by the US Food and Drug Administration (FDA). METHODS: A literature review of systemic psoriasis treatments that have been approved by the FDA was performed for the primary end point of a 75% reduction in the Psoriasis Area and Severity Index score (PASI 75). Medication cost was referenced by wholesale acquisition cost (WAC), laboratory fees were obtained from the American Medical Association, and office visit fees are standard at our university. Total expenses were standardized by calculating cost per month of treatment considering the number needed to treat (NNT) to achieve PASI 75. RESULTS: Methotrexate ($794.05-1502.51) and cyclosporine ($1410.14-1843.55) had the lowest monthly costs per NNT to achieve PASI 75. The most costly therapies were infliximab ($8704.68-15,235.52) and ustekinumab 90 mg ($12,505.26-14,256.75). Monthly costs per NNT to achieve PASI 75 for other therapies were as follows: narrowband ultraviolet B light phototherapy ($2924.73), adalimumab ($3974.61-7678.78), acitretin ($4137.71-14,148.53), ustekinumab 45 mg ($7177.89-7263.99), psoralen plus ultraviolet A light phototherapy ($7499.46-8834.98), and etanercept ($8284.71-10,674.89). LIMITATIONS: Drug rebates and incentives, potential adverse effects, comorbidity risk reduction, ambassador programs, and combination therapies were excluded. CONCLUSION: Our study provides meaningful cost efficacy data that may influence psoriasis treatment selection.

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Lichen planus (LP) is an inflammatory skin condition with characteristic clinical and histopathological findings. Classic LP typically presents as pruritic, polygonal, violaceous flat-topped papules and plaques; many variants in morphology and location also exist, including oral, nail, linear, annular, atrophic, hypertrophic, inverse, eruptive, bullous, ulcerative, lichen planus pigmentosus, lichen planopilaris, vulvovaginal, actinic, lichen planus-lupus erythematosus overlap syndrome, and lichen planus pemphigoides. Clinical presentation of the rarer variant lesions may be largely dissimilar to classic LP and therefore difficult to diagnose based solely on clinical examination. However, histopathological examination of LP and LP-variant lesions reveal similar features, aiding in the proper diagnosis of the disease. Management of LP and LP variants aims to control symptoms and to decrease time from onset to resolution; it often involves topical corticosteroids, but varies depending on the severity and location of the lesion. The literature contains an array of reports on the variations in presentation and successful management of LP and its variants. A familiarity with LP and its variants is important in achieving timely recognition and management of the disease.

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IMPORTANCE: Hailey-Hailey disease, or familial benign chronic pemphigus, is a rare genodermatosis that can be challenging for both patients and dermatologists as the disease can significantly impact patients' quality of life and is often difficult to control. In recalcitrant cases, multiple treatment modalities are often needed to obtain benefit. Unfortunately, most of the available evidence pertaining to treatment is scattered across case reports and retrospective analyses. OBJECTIVE: To review successful treatments of Hailey-Hailey, synthesize the evidence, and provide recommendations for therapy. FINDINGS: The best evidence exists for treatment with topical steroids and topical antimicrobials. Refractory disease has shown the most benefit with addition of oral antibiotics, excisional procedures and botulinum toxin A. Other therapies are described but with much less supporting evidence. CONCLUSIONS: Herein we review the literature to identify successful treatments for Hailey-Hailey disease. We have outlined the treatments with the most evidence. The difficult nature of treating this disease requires that clinicians approach each patient differently. The literature shows that no one regiment works for all patients.

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