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.

Impact of Ultraviolet Light on Vitiligo.

Vitiligo is a disorder of the melanocytes that results in a dynamic spectrum of skin depigmentation. Its etiology is complex and multifactorial, with data supporting several different hypotheses. Given its prominent phenotype, vitiligo has a significant negative impact on quality of life. Coupled with the chronic and incurable nature of the disease, this presents a formidable treatment challenge. Several treatment modalities have been instituted over the years, with varying efficacy. This chapter focuses on the use of ultraviolet light in vitiligo as an established therapeutic option.

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.

Increased rates of advanced thyroid cancer in California.

BACKGROUND: We have noted an unusually high rate of advanced thyroid cancers presenting from across California. We examined the rates of thyroid cancer presentation throughout California for potential geographic clustering. MATERIALS AND METHODS: A total of 26,983 patients with a new diagnosis of thyroid cancer (1999-2008) were abstracted from the California Cancer Registry and the Office of Statewide Health Planning and Development registry. Percentages of advanced thyroid cancer rates were calculated within each county (defined as those with distant metastatic stage; regional and/or distant metastatic stage [RM]) as well as those with well-differentiated thyroid cancer diagnosed before age 30. National averages were taken from Surveillance, Epidemiology, and End Results (SEER) data. RESULTS: There was no obvious clustering of advanced cases within certain regions in California; however, on average, the entire state of California had significantly higher rates of distant metastatic thyroid cancer (6.73%) and RM (34.92%) than the national SEER averages (4%, 29%, respectively, P < 0.001). Of the 47 California counties, 20 had significantly higher percentages of distant metastatic thyroid cancer than the national SEER average (range, 6%-13% versus 4%, P < 0.05), and 20 had a higher percentage of RM than the national SEER average (range, 35%-48% versus 29%, P < 0.05). Two California counties had higher rates of young patients with well-differentiated thyroid cancer (range, 14.29%-17.9%) than the national SEER average (12%). CONCLUSIONS: California exhibits more advanced thyroid cancers than the national SEER population average. Further studies are warranted to better understand etiologies for these disparities, which may include environmental impacts and/or delays in diagnosis.

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.

A Quick Review of the Cutaneous Findings of the Zika Virus.

The current outbreak of Zika virus is a growing public health concern, especially for pregnant women. Zika virus infection may manifest as a maculopapular skin eruption that progresses rostrocaudally, with or without hemorrhagic manifestations such as petechiae and gingival bleeding. Recognizing the cutaneous findings associated with Zika virus may aid in early diagnosis, particularly in individuals at increased risk for the disease.

Multiomic Analysis of the Gut Microbiome in Psoriasis Reveals Distinct Host‒Microbe Associations.

Psoriasis is a chronic, inflammatory skin disease that affects 2‒3% of the global population. Besides skin manifestations, patients with psoriasis have increased susceptibility to a number of comorbidities, including psoriatic arthritis, cardiovascular disease, and inflammatory bowel disease. To understand the systemic component of psoriasis pathogenesis, we performed a pilot study to examine the fecal metagenome, host colonic transcriptome, and host peripheral blood immune profiles of patients with psoriasis and healthy controls. Our study showed increased functional diversity in the gut microbiome of patients with psoriasis. In addition, we identified microbial species that preferentially associate with patients with psoriasis and which have been previously found to associate with other autoimmune diseases. Intriguingly, our data revealed three psoriasis subgroups that have distinct microbial and host features. Integrating these features revealed host‒microbe associations that are specific to psoriasis or particular psoriasis subgroups. Our findings provide insight into the factors that may affect the development of comorbidities in patients with psoriasis and may hold diagnostic potential for early identification of patients with psoriasis at risk for these comorbidities.

Outcomes and Risk Factors in Patients with Multiple Primary Melanomas.

The incidence and patient survival rates of melanoma have increased over the last several decades, with a growing population of patients who develop multiple primary melanomas (MPMs). To determine risk factors for developing MPMs and compare the survival of patients with MPMs to those with single primary melanomas, a prospective, multidisciplinary database of patients with melanoma at a single tertiary care institution was retrospectively reviewed. From 1985 to 2013, 6,963 patients with single primary melanomas and 305 patients with MPMs were identified. Mean follow-up was 8.3 ± 6.3 years for patients with single primary melanomas and 8.8 ± 5.9 years for patients with MPMs. Risk of developing multiple melanomas increased with age at diagnosis of first melanoma (hazard ratio [HR] = 1.20 for a 10-year increase in age, 95% confidence interval [CI] = 1.11-1.29, P < 0.001), male sex (HR = 1.44, 95% CI = 1.12-1.84, P = 0.005), and white race (HR = 3.07, 95% CI = 1.45-6.51). Patients with invasive MPMs had increased risk of melanoma-specific death both before (HR = 1.47, 95% CI = 1.0-2.2) and after adjusting for age, sex, site, race, family history of melanoma, personal history of other cancer, and Surveillance, Epidemiology, and End Results Program (SEER) stage (HR = 1.44, 95% CI = 0.95-2.2); however, this result did not reach statistical significance.

Alteration of the cutaneous microbiome in psoriasis and potential role in Th17 polarization.

BACKGROUND: Psoriasis impacts 1-3% of the world's population and is characterized by hyper-proliferation of keratinocytes and increased inflammation. At the molecular level, psoriasis is commonly driven by a Th17 response, which serves as a major therapeutic target. Microbiome perturbations have been associated with several immune-mediated diseases such as atopic dermatitis, asthma, and multiple sclerosis. Although a few studies have investigated the association between the skin microbiome and psoriasis, conflicting results have been reported plausibly due to the lack of standardized sampling and profiling protocols, or to inherent microbial variability across human subjects and underpowered studies. To better understand the link between the cutaneous microbiota and psoriasis, we conducted an analysis of skin bacterial communities of 28 psoriasis patients and 26 healthy subjects, sampled at six body sites using a standardized protocol and higher sequencing depth compared to previous studies. Mouse studies were employed to examine dermal microbial-immune interactions of bacterial species identified from our study. RESULTS: Skin microbiome profiling based on sequencing the 16S rRNA V1-V3 variable region revealed significant differences between the psoriasis-associated and healthy skin microbiota. Comparing the overall community structures, psoriasis-associated microbiota displayed higher diversity and more heterogeneity compared to healthy skin bacterial communities. Specific microbial signatures were associated with psoriatic lesional, psoriatic non-lesional, and healthy skin. Specifically, relative enrichment of Staphylococcus aureus was strongly associated with both lesional and non-lesional psoriatic skin. In contrast, Staphylococcus epidermidis and Propionibacterium acnes were underrepresented in psoriatic lesions compared to healthy skin, especially on the arm, gluteal fold, and trunk. Employing a mouse model to further study the impact of cutaneous Staphylcoccus species on the skin T cell differentiation, we found that newborn mice colonized with Staphylococcus aureus demonstrated strong Th17 polarization, whereas mice colonized with Staphylococcus epidermidis or un-colonized controls showed no such response. CONCLUSION: Our results suggest that microbial communities on psoriatic skin is substantially different from those on healthy skin. The psoriatic skin microbiome has increased diversity and reduced stability compared to the healthy skin microbiome. The loss of community stability and decrease in immunoregulatory bacteria such as Staphylococcus epidermidis and Propionibacterium acnes may lead to higher colonization with pathogens such as Staphylococcus aureus, which could exacerbate cutaneous inflammation along the Th17 axis.

RNA-seq and flow-cytometry of conventional, scalp, and palmoplantar psoriasis reveal shared and distinct molecular pathways.

It has long been recognized that anatomic location is an important feature for defining distinct subtypes of plaque psoriasis. However, little is known about the molecular differences between scalp, palmoplantar, and conventional plaque psoriasis. To investigate the molecular heterogeneity of these psoriasis subtypes, we performed RNA-seq and flow cytometry on skin samples from individuals with scalp, palmoplantar, and conventional plaque psoriasis, along with samples from healthy control patients. We performed differential expression analysis and network analysis using weighted gene coexpression network analysis (WGCNA). Our analysis revealed a core set of 763 differentially expressed genes common to all sub-types of psoriasis. In contrast, we identified 605, 632, and 262 genes uniquely differentially expressed in conventional, scalp, and palmoplantar psoriasis, respectively. WGCNA and pathway analysis revealed biological processes for the core genes as well as subtype-specific genes. Flow cytometry analysis revealed a shared increase in the percentage of CD4+ T regulatory cells in all psoriasis subtypes relative to controls, whereas distinct psoriasis subtypes displayed differences in IL-17A, IFN-gamma, and IL-22 production. This work reveals the molecular heterogeneity of plaque psoriasis and identifies subtype-specific signaling pathways that will aid in the development of therapy that is appropriate for each subtype of plaque psoriasis.

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.

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.

Outcomes of Melanoma In Situ Treated With Mohs Micrographic Surgery Compared With Wide Local Excision.

Importance: Melanoma in situ (MIS) is increasing in incidence, and expert consensus opinion recommends surgical excision for therapeutic management. Currently, wide local excision (WLE) is the standard of care. However, Mohs micrographic surgery (MMS) is now used to treat a growing subset of individuals with MIS. During MMS, unlike WLE, the entire cutaneous surgical margin is evaluated intraoperatively for tumor cells. Objective: To assess the outcomes of patients with MIS treated with MMS compared with those treated with WLE. Design, Setting, and Participants: Retrospective review of a prospective database. The study cohort consisted of 662 patients with MIS treated with MMS or WLE per standard of care in dermatology and surgery (general surgery, otolaryngology, plastics, oculoplastics, surgical oncology) at an academic tertiary care referral center from January 1, 1978, to December 31, 2013, with follow-up through 2015. Exposure: Mohs micrographic surgery or WLE. Main Outcomes and Measures: Recurrence, overall survival, and melanoma-specific survival. Results: There were 277 patients treated with MMS (mean [SD] age, 64.0 [13.1] years; 62.1% male) and 385 treated with WLE (mean [SD] age, 58.5 [15.6] years; P < .001 for age; 54.8% male). Median follow-up was 8.6 (range, 0.2-37) years. Compared with WLE, MMS was used more frequently on the face (222 [80.2%] vs 141 [36.7%]) and scalp and neck (23 [8.3%] vs 26 [6.8%]; P < .001). The median (range) year of diagnosis was 2008 (1986-2013) for the MMS group vs 2003 (1978-2013) for the WLE group (P < .001). Overall recurrence rates were 5 (1.8%) in the MMS group and 22 (5.7%) in the WLE group (P = .07). Mean (SD) time to recurrence after MMS was 3.91 (4.4) years, and after WLE, 4.45 (2.7) years (P = .73). The 5-year recurrence rate was 1.1% in the MMS group and 4.1% in the WLE group (P = .07). For WLE-treated tumors, the surgical margin taken was greater for tumors that recurred compared with tumors that did not recur (P = .003). Five-year overall survival for MMS was 92% and for WLE was 94% (P = .28). Melanoma-specific mortality for the MMS group was 2 vs 13 patients for the WLE group, with mean (SD) survival of 6.5 (4.8) and 6.1 (0.8) years, respectively (P = .77). Conclusions and Relevance: No significant differences were found in the recurrence rate, overall survival, or melanoma-specific survival of patients with MIS treated with MMS compared with WLE.

The Role of the Nervous System in the Pathophysiology of Psoriasis: A Review of Cases of Psoriasis Remission or Improvement Following Denervation Injury.

As most efforts in the last decade have focused on the immunologic basis of inflammatory skin disease, there has been less emphasis on the role of the nervous system in the disease process of psoriasis. Evidence in support of the neurocutaneous pathway has come from observations of patients experiencing unilateral improvement and even complete remission following nerve damage in the affected dermatomal region. The aim of this review was to investigate the role of neuropeptides in the intricate pathophysiology of psoriasis. The PubMed database was searched for individual case reports or case series that reported clearance or significant improvement in psoriatic disease in patients following documented nerve injury. A total of 11 cases were found that reported improvement of psoriatic lesions in areas afflicted by central or peripheral nerve injury. The most common causes of denervation were inadvertent surgical interruption, cerebrovascular accident, and poliomyelitis. In four cases the patients eventually regained neurologic function, which was associated with a recurrence of skin lesions. In cases of permanent nerve damage, there was remission of psoriasis. The cases reported in the literature to date provide clinical evidence that absence of neural input leads to psoriasis improvement, suggesting a crucial role of the nervous system in the pathophysiology of psoriatic disease. In fact, neuropeptides such as nerve growth factor, substance P, calcitonin gene-related peptide, and vasoactive intestinal peptide may be important contributors of psoriatic disease and potential targets for future therapies.

The Patient's Guide to Psoriasis Treatment. Part 1: UVB Phototherapy.

BACKGROUND: Psoriasis is a chronic immune-mediated disease that affects 2-3% of the world population. Ultraviolet B (UVB) phototherapy is an effective treatment for psoriasis compared to other systemic treatments. Currently there is a lack of easily accessible online patient educational material regarding this form of treatment. OBJECTIVE: To present a freely available online guide and video on UVB treatment that is informative to patients and increases the success and compliance of patients starting this therapy. METHODS: The UVB treatment protocol used at the University of California-San Francisco Psoriasis and Skin Treatment Center as well as available information from the literature was reviewed to design a comprehensive guide for patients receiving UVB treatment. RESULTS: We created a printable guide and video resource that reviews the fundamentals of UV light, UVB safety considerations, flow of treatment, side effects, and post-phototherapy skin care. CONCLUSION: This guide serves as a valuable resource for patients preparing for UVB phototherapy, the clinicians who treat them, and trainees wishing to learn more about this form of therapy.

The Patient's Guide to Psoriasis Treatment. Part 2: PUVA Phototherapy.

BACKGROUND: PUVA treatment is photochemotherapy for psoriasis that combines psoralen with UVA radiation. Although PUVA is a very effective treatment option for psoriasis, there is an absence of patient resources explaining and demonstrating the process of PUVA. Studies have shown that patients who viewed videos explaining the treatment procedures for various medical conditions had a greater understanding of their treatment and were more active participants in their health. OBJECTIVE: To present a freely available online guide and video on PUVA treatment designed for patient education on PUVA. METHODS: The PUVA treatment protocol used at the University of California-San Francisco Psoriasis and Skin Treatment Center as well as available information from the literature was reviewed to design a comprehensive guide for patients receiving PUVA treatment. RESULTS: We created a printable guide and video resource that reviews the benefits and risks of PUVA, discusses the three types of PUVA (hand-foot soak, full body soak, and systemic), demonstrates the PUVA process, and provides practical tips for safe use. CONCLUSION: Online media and video delivers material in a way that is flexible and often familiar to patients. This new format is beneficial for prospective patients planning to undergo PUVA treatment, health-care providers, and trainees who want to learn more about this treatment.