Influence of diet on the gut microbiome and implications for human health.

Recent studies have suggested that the intestinal microbiome plays an important role in modulating risk of several chronic diseases, including inflammatory bowel disease, obesity, type 2 diabetes, cardiovascular disease, and cancer. At the same time, it is now understood that diet plays a significant role in shaping the microbiome, with experiments showing that dietary alterations can induce large, temporary microbial shifts within 24 h. Given this association, there may be significant therapeutic utility in altering microbial composition through diet. This review systematically evaluates current data regarding the effects of several common dietary components on intestinal microbiota. We show that consumption of particular types of food produces predictable shifts in existing host bacterial genera. Furthermore, the identity of these bacteria affects host immune and metabolic parameters, with broad implications for human health. Familiarity with these associations will be of tremendous use to the practitioner as well as the patient.

Interventional treatments for Hailey-Hailey disease.

Hailey-Hailey disease or familial benign chronic pemphigus is a rare blistering dermatosis that is characterized by recurrent erythematous plaques with a predilection for the skin folds. For extensive Hailey-Hailey disease that is recalcitrant to conventional therapy, laser ablation, photodynamic therapy, electron beam radiotherapy, botulinum toxin type A, dermabrasion, glycopyrrolate, and afamelanotide have been reported as useful treatments, but comparative trials are lacking. This review discusses the various treatment modalities for Hailey-Hailey disease and a summary of the evidence for the most recommended treatments.

Update on the Systemic Risks of Superpotent Topical Steroids.

INTRODUCTION: The potential for systemic effects due to percutaneous absorption of superpotent topical steroids has been a longstanding concern. The Food and Drug Administration currently recommends limiting the use of superpotent topical steroids to 50g per week for 2 or 4 consecutive weeks depending on the formulation, which is mostly based on the exact duration with which phase 3 clinical trials were allowed to be conducted per the FDA. This article reviews all published clinical incidence of adrenal adverse effects in the medical literature, specifically Cushing's syndrome (CS) and pathologic adrenal suppression (PAAS), to try to ascertain a more realistic limit for the safe use of superpotent topical steroids as it pertains to its potential systemic effects.

METHODS: Literature search was conducted using PubMed. Only cases of CS and PAAS secondary to the use of Class I superpotent topical steroids were included. Pediatric cases and full articles unavailable in English were excluded.

RESULTS: There were a total of 14 cases of CS and 5 cases of subsequent PAAS found in the current literature.

DISCUSSION: From our review of these cases, if the amount used per week is within FDA guidelines, it appears that patients needed to use superpotent topical steroids for far greater than 2 or 4 weeks to develop CS or PAAS. CS did not necessarily predict occurrence of PAAS, but in all cases CS appeared to be a prerequisite for developing PAAS. All cases of CS and all but one case of PAAS were reversible. If excessive amount of greater than 50g per week is avoided, it appears that superpotent topical steroids may be safe to use consecutively for months, perhaps even years, without causing systemic effects.

J Drugs Dermatol. 2017;16(7):643-648.

Use of an oral phosphodiesterase-4 inhibitor (apremilast) for the treatment of chronic, severe atopic dermatitis: a case report.

Atopic dermatitis (AD) is a common inflammatory dermatosis characterized by pruritus, erythema, induration, and lichenification. Current treatment options for generalized atopic dermatitis are limited and have potentially serious adverse effects, especially in patients with severe, chronic AD who frequently require systemic anti-inflammatory agents. Apremilast, an oral phosphodiesterase-4 inhibitor, was FDA approved in September 2014 for the treatment of moderate-to-severe plaque psoriasis. However, its upstream anti-inflammatory effects, ease of use as an oral agent, and mild side-effect profile make it an interesting treatment option for AD as well. Herein, we present a patient with a life-long history of AD recalcitrant to topical steroids and cyclosporine who attained subjective and objective improvement in pruritus and erythema after 10-week treatment with apremilast.

Anti-IL-17 Agents for Psoriasis: A Review of Phase III Data.

BACKGROUND: Studies investigating the molecular basis of psoriasis have established the central roles of TNFa, interleukin (IL)-12, IL-22 and IL-23, and now there is increasing evidence that IL-17 plays a vital role in the complex pathophysiology of this disease. Preclinical and phase II studies of medications targeting IL-17 and its receptor have thus far proved to be promising. METHODS: We reviewed the results of the phase III clinical trials for the anti-IL-17 agents secukinumab, ixekizumab and brodalumab in order to assess the efficacy and safety profile of each agent. RESULTS: By week 12, the proportion of patients reaching a 75% improvement from baseline Psoriasis Area and Severity Index (PASI 75) was comparable between the different agents (secukinumab 83%, ixekizumab 89%, and brodalumab 85%). The safety profiles of the agents were similar with the most frequently reported adverse events of nasopharyngitis, upper respiratory infections, headache, and injection site reaction. CONCLUSION: The anti-IL-17 agents demonstrated a rapid and robust clinical improvement accompanied by a favorable short-term safety profile. The results of the phase III trials continue to reinforce the theory that the IL-17 pathway is an essential target in psoriasis treatment.

Impact of the Pregnancy and Lactation Labeling Rule (PLLR) on Practicing Dermatologists.

On June 30th 2015, the FDA instituted a new system for the categorization of drug safety during pregnancy and lactation, known as the Pregnancy and Lactation Labeling Rule (PLLR), which replaces the "A, B, C, D, X" pregnancy labeling categories. The new rule will apply to all newly approved prescription medications, with a staggered phase-in for prescription drugs approved prior to the effective date. In this article, we provide a brief description of the major changes introduced by the PLLR and discuss the major implication of this new categorization system for clinical dermatologists.

Psoriasis treatment in HIV-positive patients: a systematic review of systemic immunosuppressive therapies.

The management of psoriatic disease in the human immunodeficiency virus (HIV)-positive population is challenging. The clinical course often is progressive and refractory; therefore, first- and second-line therapies including topical agents, phototherapy, and oral retinoids often are inadequate. Most other currently available systemic therapies for psoriatic disease are immunosuppressive, which poses a distinct clinical challenge. A comprehensive systematic review of the literature via a PubMed search of articles indexed for MEDLINE using the terms psoriasis and HIV and psoriatic arthritis and HIV combined with several systemic immunosuppressive agents yielded a total of 25 reported cases of systemic immunosuppressive therapies used to treat psoriatic disease in HIV-positive patients including methotrexate, cyclosporine, etanercept, adalimumab, infliximab, and ustekinumab. The limited data suggest that biologic therapies may be effective for cases of psoriasis recalcitrant to other systemic agents and may have a positive effect on CD4 and viral counts when used in combination with highly active antiretroviral therapy (HAART); however, further studies are needed.

Survey of Patch Test Business Models in the United States by the American Contact Dermatitis Society.

BACKGROUND: Allergic contact dermatitis (ACD) remains a significant burden of disease in the United States. Patch testing is the criterion standard for diagnosing ACD, but its use may be limited by reimbursement challenges. OBJECTIVE: This study aimed to assess the current rate of patch test utilization among dermatologists in academic, group, or private practice settings to understand different patch testing business models that address these reimbursement challenges. METHODS: All members of the American Contact Dermatitis Society received an online survey regarding their experiences with patch testing and reimbursement. RESULTS: A "yes" response was received from 28% of survey participants to the question, "Are you or have you been less inclined to administer patch tests or see patients needing patch tests due to challenges with receiving compensation for patch testing?" The most commonly reported barriers include inadequate insurance reimbursement and lack of departmental support. CONCLUSIONS: Compensation challenges to patch testing limit patient access to appropriate diagnosis and management of ACD. This can be addressed through a variety of innovative business models, including raising patch testing caps, negotiating relative value unit compensation, using a fixed salary model with directorship support from the hospital, and raising the percentages of collection reimbursement for physicians.

Oral (Systemic) Botanical Agents for the Treatment of Psoriasis: A Review.

INTRODUCTION: Patients with psoriasis often use botanical therapies as part of their treatment. It is important for clinicians to be aware of the current evidence regarding these agents as they treat patients. METHODS: A systematic literature search was conducted using the PubMed, MEDLINE, and EMBASE database for randomized clinical trials assessing the use of botanical therapeutics for psoriasis. The search included the following keywords: "psoriasis" and "plant" or "herbal" or "botanical." Citations within articles were also reviewed to identify relevant sources. The results were then further refined by route of administration, and the oral (systemic) botanical agents are reviewed herein. RESULTS: A total of 12 controlled and uncontrolled clinical trials addressing the use of oral, systemic botanical agents for psoriasis were assessed in this review. While overall evidence is limited in quantity and quality, HESA-A, curcumin, neem extract, and, to a lesser degree, Traditional Chinese Medicine seem to be the most efficacious agents. CONCLUSION: The literature addresses a large amount of studies in regards to botanicals for the treatment of psoriasis. While most agents appear to be safe, further research is necessary for evidence-based recommendation of oral botanical agents to psoriasis patients.

Emerging targeted therapies for plaque psoriasis - impact of ixekizumab.

BACKGROUND: Recent studies into the pathogenesis of psoriasis have identified the importance of interleukin 17 (IL-17) in disease activity and have thus provided a new target for biologic therapy. Ixekizumab, the most recent US Food and Drug Administration (FDA)-approved anti-IL-17 biologic agent, appears to be a promising medication for patients suffering from moderate-to-severe plaque psoriasis. METHODS: We reviewed the results of phase III trials for ixekizumab in order to assess the efficacy, safety, and impact on quality of life of this agent in the treatment of plaque psoriasis. Additionally, we compared these results to phase II and phase III trials for other biologic psoriasis medications including the anti-IL-23 agents tildrakizumab and guselkumab, the combined anti-IL-12 and anti-IL-23 agent ustekinumab, and the anti-IL-17 agents brodalumab and secukinumab. RESULTS: Pooled results from individual studies demonstrate that among the most efficacious dosing regimens of these anti-interleukin therapies, ixekizumab achieves higher Psoriasis Area and Severity Index 75 rates and similar or higher static Physician Global Assessment 0-1 rates than the other anti-IL-17 and anti-IL-23 agents. The safety profile of ixekizumab is similar to these agents, with nasopharyngitis, upper respiratory infection, headache, arthralgia, and injection-site erythema as the most commonly reported adverse events. CONCLUSION: Ixekizumab is a highly efficacious, newly FDA-approved treatment for moderate-to-severe plaque psoriasis that demonstrates a robust clinical response, significant improvement in patient quality of life, and a favorable safety profile.

Topical Botanical Agents for the Treatment of Psoriasis: A Systematic Review.

BACKGROUND: Patients with psoriasis often enquire about the use of numerous botanical therapeutics. It is important for dermatologists to be aware of the current evidence regarding these agents. METHODS: We conducted a systematic literature search using the PubMed, MEDLINE, and EMBASE databases for controlled and uncontrolled clinical trials that assessed the use of topical botanical therapeutics for psoriasis. The search included the following keywords: 'psoriasis' and 'plant' or 'herbal' or 'botanical'. We also reviewed citations within articles to identify additional relevant sources. We then further refined the results by route of administration and the topical botanical agents are reviewed herein. RESULTS: A total of 27 controlled and uncontrolled clinical trials addressing the use of topical botanical agents for psoriasis were assessed in this review. We found that the most highly studied and most efficacious topical botanical therapeutics were Mahonia aquifolium, indigo naturalis, aloe vera, and, to a lesser degree, capsaicin. The most commonly reported adverse effects were local skin irritation, erythema, pruritus, burning, and pain. However, the overall evidence for these therapeutics remains limited in quantity and quality. CONCLUSION: The literature addresses a large number of studies in regard to botanicals for the treatment of psoriasis. While most agents appear to be safe, further research is necessary before topical botanical agents can be consistently recommended to patients.

Eczema as an adverse effect of anti-TNFα therapy in psoriasis and other Th1-mediated diseases: a review.

INTRODUCTION: There have been rare reports of eczema occurring as an adverse effect of anti-tumor necrosis factor-alpha (TNFα) therapy. METHODS: A literature search was conducted on PubMed for articles describing new onset or worsening of preexisting eczema during anti-TNFα therapy for the treatment of various inflammatory diseases. RESULTS: Eczema as an adverse effect of anti-TNFα therapy may occur in approximately 5-20% of patients with various Th1-mediated inflammatory diseases such as psoriasis, inflammatory arthritis and inflammatory bowel disease. Personal history of atopy appears to increase this risk. Out of the anti-TNFα agents indicated for the treatment of moderate-to-severe psoriasis, infliximab may be more strongly associated with development or exacerbation of preexisting eczema. DISCUSSION: Inhibitors of key mediators in the Th1 pathway such as TNFα are successful therapeutic targets for the treatment of various inflammatory conditions such as psoriasis, psoriatic arthritis, rheumatoid arthritis and inflammatory bowel disease. Blocking the Th1 pathway may create an imbalance favoring increased activity of the opposing Th2 pathway implicated in inflammatory conditions such as eczema. Further research is needed to better understand the role of the Th1/Th2 balance in various inflammatory diseases and how the immunologic environment is affected by immunotherapies.

Obsessive-compulsive skin disorders: a novel classification based on degree of insight.

Individuals with obsessive-compulsive features frequently visit dermatologists for complaints of the skin, hair or nails, and often progress towards a chronic relapsing course due to the challenge associated with accurate diagnosis and management of their psychiatric symptoms. The current DSM-5 formally recognizes body dysmorphic disorder, trichotillomania, neurotic excoriation and body focused repetitive behavior disorder as psychodermatological disorders belonging to the category of Obsessive-Compulsive and Related Disorders. However there is evidence that other relevant skin diseases such as delusions of parasitosis, dermatitis artefacta, contamination dermatitis, AIDS phobia, trichotemnomania and even lichen simplex chronicus possess prominent obsessive-compulsive characteristics that do not necessarily fit the full diagnostic criteria of the DSM-5. Therefore, to increase dermatologists' awareness of this unique group of skin disorders with OCD features, we propose a novel classification system called Obsessive-Compulsive Insight Continuum. Under this new classification system, obsessive-compulsive skin manifestations are categorized along a continuum based on degree of insight, from minimal insight with delusional obsessions to good insight with minimal obsessions. Understanding the level of insight is thus an important first step for clinicians who routinely interact with these patients.

Dietary Behaviors in Psoriasis: Patient-Reported Outcomes from a U.S. National Survey.

INTRODUCTION: Psoriasis patients demonstrate high interest in the role of diet on their skin condition. However, data are lacking to describe dietary interventions among psoriasis patients and associated outcomes. This study aims to identify common dietary habits, interventions and perceptions among patients with psoriasis, and to examine patient-reported skin outcomes in response to these interventions. METHODS: We administered a 61-question survey to the National Psoriasis Foundation membership asking psoriasis patients about dietary habits, modifications, skin responses, and perceptions. RESULTS: A total of 1206 psoriasis patients responded to the survey. Compared to age- and sex-matched controls, psoriasis patients consumed significantly less sugar, whole grain fiber, dairy, and calcium (p < 0.001), while consuming more fruits, vegetables, and legumes (p < 0.01). Eighty-six percent of respondents reported use of a dietary modification. The percentage of patients reporting skin improvement was greatest after reducing alcohol (53.8%), gluten (53.4%), nightshades (52.1%), and after adding fish oil/omega-3 (44.6%), vegetables (42.5%), and oral vitamin D (41%). Specific diets with the most patients reporting a favorable skin response were Pagano (72.2%), vegan (70%), and Paleolithic (68.9%). Additionally, 41.8% of psoriasis respondents reported that a motivation for attempting dietary changes was to improve overall health. CONCLUSION: This national survey is among the first to report the dietary behaviors of patients with psoriasis. The data provided from this large cohort may benefit patients and clinicians as they discuss the role of diet in managing both psoriasis and associated cardiometabolic comorbidities.