Itching for an answer: A review of potential mechanisms of scalp itch in psoriasis.

Scalp psoriatic itch is a common complaint and often poses a therapeutic challenge. The pathophysiology of this phenomenon is unclear. The unique anatomy of the scalp contains richly innervated hair follicles, abundant vasculature and perifollicular inflammatory cytokines which may all contribute to this common sensory complaint. The mast cell, in particular, is portrayed as one of the main itch conductors for its ability to trigger neurogenic inflammation, activate the peripheral hypothalamic-pituitary-adrenal-axis, process and integrate itch signalling through its interactions with the scalp hair follicles. Herein, we explain and speculate upon potential mechanisms underlying itchy scalp psoriasis, involving interconnections between the neuroimmune, neurovascular and neuroendocrine systems. Many factors may play roles in itchy scalp psoriasis including the scalp hair structure, immune system, endocrine system, nervous system and vascular system. These may warrant further exploration as therapeutic targets that go beyond the application of mere anti-inflammatory agents.

Case Report of Multiple Keratoacanthomas and Squamous Cell Carcinomas in a Patient Receiving Pembrolizumab.

PD-1 is expressed on antigen-stimulated T cells and induces a downstream signaling pathway that works by negative feedback to inhibit T cell proliferation, cytokine release, and cytotoxicity. PD-1 antibodies increase tumor cell killing peripherally and have a role in advanced melanoma treatment. We describe a case of an 84 year old female with stage 4 metastatic melanoma in a trial of the PD-1 inhibitor pembrolizumab who developed multiple keratoacanthomas after several months of treatment. While keratoacanthomas have been reported in patients taking BRAF inhibitors, no such reports exist for those on pembrolizumab, making this the first case report to point out this association for further investigative studies.

J Drugs Dermatol. 2017;16(5):513-515.

Tumor necrosis factor-α inhibitor-induced psoriasis: Systematic review of clinical features, histopathological findings, and management experience.

BACKGROUND: Tumor necrosis factor-α (TNF-α) inhibitors have been reported to induce new-onset psoriasis. OBJECTIVE: To better define the demographic, clinical features, and treatment approach of TNF-α inhibitor-induced psoriasis. METHODS: Systematic review of published cases of TNF-α inhibitor-induced psoriasis. RESULTS: We identified 88 articles with 216 cases of new-onset TNF-α inhibitor-induced psoriasis. The mean age at psoriasis onset was 38.5 years. The most common underlying diseases were Crohn disease (40.7%) and rheumatoid arthritis (37.0%). Patients underwent TNF-α therapy for an average of 14.0 months before psoriasis onset with 69.9% of patients experiencing onset within the first year. The majority of patients received skin-directed therapy, though patients who discontinued TNF therapy had the greatest resolution of symptoms (47.7%) compared with those who switched to a different TNF agent (36.7%) or continued therapy (32.9%). LIMITATIONS: Retrospective review that relies on case reports and series. CONCLUSION: While TNF-α inhibitor cessation may result in resolution of induced psoriasis, lesions may persist. Decisions regarding treatment should be weighed against the treatability of TNF-α inhibitor-induced psoriasis, the severity of the background rheumatologic or gastrointestinal disease, and possible loss of efficacy with cessation followed by retreatment. Skin-directed therapy is a reasonable initial strategy except in severe cases.

The dermatologic intimacy scale: quantitatively measuring the impact of skin disease on intimacy.

INTRODUCTION: Patient-reported outcome measures are increasingly utilized in dermatology to assess the impact of skin disease on quality of life. Despite recognition of the influence of skin disease on intimate relationships, an instrument to assess intimacy has not been developed. The objective of this study was to create the dermatologic intimacy scale (DIS) and administer the prototype to a patient population. METHODS: A group of healthcare providers at the University of California San Francisco created the DIS prototype. A total of 1676 psoriasis patients of an online community were invited to complete a cross-sectional survey including demographic information, DIS, body surface area (BSA) and anatomical involvement. RESULTS: A total of 1109 patients completed the survey in its entirety. Patients with moderate-to-severe psoriasis (BSA ≥3%) had a higher DIS score overall and for each individual question than patients with mild disease (BSA < 3%; p < .001). Patients with genitalia, nails, face, neck and scalp involvement had higher scores compared to patients without involvement (p < .001). CONCLUSIONS: Patients with more extensive disease and specific anatomical involvement experience a greater impact on intimacy. Interpretation is limited by patient response rate, as patients with or without intimacy issues may be more or less likely to respond. Further analysis is necessary for validation and interpretation.

The psychosocial impact of acne, vitiligo, and psoriasis: a review.

INTRODUCTION: Chronic skin conditions have been well reported to affect a patient's quality of life on multiple dimensions, including the psychosocial domain. Psychosocial is defined as the interrelation of social factors with an individual's thoughts and behavior. The assessment of the psychosocial impact of skin disease on a patient can help direct the dermatologists' treatment goals. To evaluate the psychosocial impact of skin disease, we conducted a review of the literature on three skin conditions with onsets at various stages of life: acne, vitiligo, and psoriasis. METHODS: A PubMed search was conducted in March 2015 using the terms "psychosocial" AND "acne", "psychosocial" AND "vitiligo", and "psychosocial" AND "psoriasis". The results were limited to articles published in English in the past 5 years studying patients of all ages. Results and their references were evaluated for relevance according to their discussion of psychosocial qualities in their patients and the validity of psychosocial assessments. The search for acne yielded 51 results, and eleven were found to be relevant; vitiligo yielded 30 results with ten found to be relevant; and psoriasis yielded 70 results with seven found to be relevant. RESULTS: According to the articles evaluated, 19.2% of adolescent patients with acne were affected in their personal and social lives. Social phobia was present in 45% of patients with acne compared to 18% of control subjects. Race and sex played a role in self-consciousness and social perceptions of the disease. Vitiligo negatively affected marriage potential and caused relationship problems in >50% of patients. Psoriasis negatively affected multiple domains of life, including work, relationships, and social activities. Anxiety and depression affected not only psoriasis patients but also their cohabitants; up to 88% of cohabitants had an impaired quality of life. CONCLUSION: Though all three skin conditions resulted in an increase in anxiety and depression among their patient populations, the psychosocial focus varied slightly for each disease. Overall, acne, vitiligo, and psoriasis can have negative psychosocial impact in different stages of life development.

A prospective, interventional assessment of the impact of ustekinumab treatment on psoriasis-related work productivity and activity impairment.

BACKGROUND: The negative impact of psoriasis on quality of life is well documented. Psoriasis is also associated with impairments in work productivity and daily activities. OBJECTIVES: This study was conducted to prospectively measure the impact of ustekinumab treatment on work productivity and daily activity impairments due to psoriasis, using the Work Productivity and Activity Index: Psoriasis instrument. METHODS: Thirty-two patients with moderate-to-severe plaque psoriasis received 36 weeks of ustekinumab and were followed every 4 weeks. During each visit, patients were evaluated using the Psoriasis Area Severity Index and Work Productivity and Activity Index: Psoriasis instrument. RESULTS: Thirty-two patients completed the study. There was no change in unemployment rate after treatment. Twenty-two patients who were employed at both baseline and week 36 experienced a significant decrease in total work productivity impairment, presenteeism and a non-significant decrease in absenteeism. All patients demonstrated significant reduction in total activity impairment. LIMITATIONS: This study was limited by the lack of a placebo group and a small sample size. CONCLUSIONS: This study demonstrates the benefits of ustekinumab treatment in terms of reducing psoriasis-related work productivity and activity impairments among patients with moderate-to-severe psoriasis.

Improvement of Nail and Scalp Psoriasis Using Apremilast in Patients With Chronic Psoriasis: Phase 2b and 3, 52-Week Randomized, Placebo-Controlled Trial Results.

INTRODUCTION: A significant portion of patients with psoriasis have scalp and nail involvement. It has been reported that 40% to 45% of patients with psoriasis have nail psoriasis, and up to 80% have scalp involvement. Nail and scalp psoriasis have often been found to be difficult to treat, due to the poor penetration and poor compliance of topical medication. Oral and biologic therapies have shown significant efficacy but often with undesirable side effects. Herein, we analyze the efficacy of apremilast, an oral phosphodiesterase-4 (PDE-4) inhibitor, in the treatment of nail and scalp psoriasis at 16-, 32-, and 52 weeks. METHODS: We reviewed the results of the phase IIb and phase III clinical trials for apremilast in treating nail and scalp psoriasis. RESULTS: In ESTEEM 1, patients on apremilast showed a 22.5%, 43.6%, and 60.2% improvement in NAPSI at weeks 16, 32, and 52. 33.3%, 45.2%, and 63% of patients achieved NAPSI-50, respectively. In ESTEEM 2, patients on apremilast showed a 29%, 60%, and 59.7% improvement in NAPSI at weeks 16, 32, and 52, with 44.6%, 55.4%, and 68.6% of patients achieving NAPSI-50. In PSOR-005 at week 16, patients on a dose of 30 mg twice weekly had a 42.9% improvement in NAPSI with 45.5% reaching NAPSI-50. For scalp psoriasis, 46.5%, 37.4%, and 73% of patients achieved an Sc-PGA of 0 or 1 at weeks 16, 32, and 52 in ESTEEM 1. In ESTEEM 2, 40.9%, 32.4%, and 62.5% of patients achieved an Sc-PGA of 0 or 1 at weeks 16, 32, and 52. CONCLUSION: With its limited safety profile of only diarrhea and headache and no additional lab requirements, apremilast may be a safer and more convenient alternative for patients with severe nail and scalp psoriasis.

An open label pilot study of supraerythemogenic excimer laser in combination with clobetasol spray and calcitriol ointment for the treatment of generalized plaque psoriasis.

A common therapeutic modality for psoriasis includes the combination of phototherapy with topical treatments. The recent development of targeted phototherapy with the excimer laser and spray formulations for topical treatments has increased the efficacy and convenience of these combinational therapies. Herein, we aim to assess the efficacy of a novel combination of therapies using the 308 nm excimer laser, clobetasol propionate spray and calcitriol ointment for the treatment of moderate to severe generalized psoriasis. In this 12-week study, patients with moderate to severe psoriasis received twice weekly treatments with a 308-nm excimer laser combined with clobetasol proprionate twice daily for a month followed by calcitriol ointment twice daily for the next month. Of the 30 patients enrolled, 83% of patients (25/30) achieved PASI-75 [65-94%, 95% confidence interval (CI)] at week 12. For PGA, there was an estimated decrease of 3.6 points (3.1-4.1, 95% CI, p < 0.0005) by week 12. In conclusion, the combination of excimer laser with alternating clobetasol and calcitriol application has shown to be a promising combination of therapies for the treatment of moderate to severe generalized psoriasis. Further evaluation may be conducted with a larger study inclusive of control groups and head-to-head comparisons against topical steroid and UVB therapy as monotherapies.

Supraerythemogenic excimer laser in combination with clobetasol spray and calcitriol ointment for the treatment of generalized plaque psoriasis: Interim results of an open label pilot study.

BACKGROUND: The combination of phototherapy and topical therapy is one of the most widely used treatment modalities for moderate to severe psoriasis. The development of targeted phototherapy with excimer laser and new topical spray formulations has made these therapies both more convenient and more effective. In this open label pilot study, we aim to assess the efficacy of combination therapy using 308-nm excimer laser, clobetasol propionate spray and calcitriol ointment for the treatment of moderate to severe generalized psoriasis. METHODS: In this 12-week study, patients with moderate to severe psoriasis received twice weekly treatment with XTRAC® Velocity 308-nm excimer laser combined with clobetasol propionate twice daily followed by calitriol ointment twice daily. RESULTS: To date, 21 patients have completed the protocol. By week 12, 76% of the patients had a reduction in Psoriasis Area and Severity Index by at least 75% (PASI-75) and 52% had a Physicians Global Assessment of "clear" or "almost clear". CONCLUSIONS: Excimer laser therapy combined with an optimized topical regimen that includes clobetasol spray followed by calictriol ointment appears to be an effective treatment for moderate to severe generalized psoriasis that avoids the risk of serious internal side effects associated with many systemic agents.

Plaque-based sub-blistering dosimetry: Reaching PASI-75 after two treatments with 308-nm excimer laser in a generalized psoriasis patient.

BACKGROUND: Generalized UVB phototherapy has been established as an effective and safe treatment for chronic plaque-type psoriasis for decades and in recent years, targeted 308-nm excimer laser has emerged as an equally safe and more effective treatment option. While traditional dosimetry for laser has been determined either through minimal erythema dose (MED) or a combination of the patient's Fitzpatrick skin type and the level of plaque induration, we have developed "Plaque-based Sub-blistering Dosimtery" based on observations that administering anywhere from 8 to 16 multiples of MED to psoriatic plaques has resulted in clearance after one treatment with longer remission rates than the traditional dosing protocol. CASE REPORT: The authors describe a case in which a patient achieved PASI 75 following only two treatments with 308 nm excimer laser using this new protocol. Biopsies taken before and after treatment reveal a dramatic decrease in CD4+T cells as well as TNF-alpha- and IL-2-producing T cells. CONCLUSION: This case demonstrates using a more aggressive dosing protocol determined by plaque testing is well-tolerated and can lead to excellent clearance with minimal side effects and comorbidity.

How to optimally manage unhappy, anxious, and difficult patients.

Patient satisfaction has been and is of growing importance in healthcare. Recent healthcare initiatives aim to provide physicians with performance feedback reports based partially on patient completed surveys; thus, patient satisfaction will be an even more important determinant of high quality care. In the field of dermatology, patient satisfaction is particularly relevant and at times difficult to achieve, since many patients are plagued with chronic skin diseases often requiring intensive topical regimens or undesirable systemic immunosuppressants. The discussion of patient satisfaction is usually restricted to encounters with the general clinic population leaving encounters with difficult patients largely underreported; therefore, we provide examples of more common difficult patient encounters a dermatologist may face with specific recommendations on how to best optimize patient satisfaction.

Memory regulatory T cells reside in human skin.

Regulatory T cells (Tregs), which are characterized by expression of the transcription factor Foxp3, are a dynamic and heterogeneous population of cells that control immune responses and prevent autoimmunity. We recently identified a subset of Tregs in murine skin with properties typical of memory cells and defined this population as memory Tregs (mTregs). Due to the importance of these cells in regulating tissue inflammation in mice, we analyzed this cell population in humans and found that almost all Tregs in normal skin had an activated memory phenotype. Compared with mTregs in peripheral blood, cutaneous mTregs had unique cell surface marker expression and cytokine production. In normal human skin, mTregs preferentially localized to hair follicles and were more abundant in skin with high hair density. Sequence comparison of TCRs from conventional memory T helper cells and mTregs isolated from skin revealed little homology between the two cell populations, suggesting that they recognize different antigens. Under steady-state conditions, mTregs were nonmigratory and relatively unresponsive; however, in inflamed skin from psoriasis patients, mTregs expanded, were highly proliferative, and produced low levels of IL-17. Taken together, these results identify a subset of Tregs that stably resides in human skin and suggest that these cells are qualitatively defective in inflammatory skin disease.

Successful use of the excimer laser for generalized psoriasis in an ustekinumab non-responder.

Effective treatments for moderate to severe psoriasis are phototherapy and biologics. These treatments are similar in that they both decrease cutaneous immune system hyperactivity yet do so via different mechanisms. Our patient, a 63 year old Asian male had a rapid response to treatment with the high dose excimer laser, having previously failed treatment with 28 weeks of ustekinumab therapy. A pre-treatment biopsy of a psoriatic plaque was found to contain relatively low levels of IFN-γ (Th1) and IL-17 (Th17) secreting T cells. Following treatment with the excimer laser, the patient had a quick improvement in PASI that was reflected by a 3-fold reduction in the number of live T cells found in the post-treatment biopsy. Although ustekinumab and the excimer laser both result in decreased levels of these cytokines, the excimer laser directly causes apoptosis of T cells and induces DNA damage in antigen presenting cells. Thus, the broader effects of phototherapy on immune cells compared to the targeted inhibition of IL-12 and IL-23 by ustekinumab likely account for the superior response observed.

The role of 39 psoriasis risk variants on age of psoriasis onset.

Recent genome-wide association studies (GWAS) have identified multiple genetic risk factors for psoriasis, but data on their association with age of onset have been marginally explored. The goal of this study was to evaluate known risk alleles of psoriasis for association with age of psoriasis onset in three well-defined case-only cohorts totaling 1,498 psoriasis patients. We selected 39 genetic variants from psoriasis GWAS and tested these variants for association with age of psoriasis onset in a meta-analysis. We found that rs10484554 and rs12191877 near HLA-C and rs17716942 near IFIH1 were associated with age of psoriasis onset with false discovery rate < 0.05. The association between rs17716942 and age of onset was not replicated in a fourth independent cohort of 489 patients (P = 0.94). The imputed HLA-C∗06:02 allele demonstrated a much stronger association with age of psoriasis onset than rs10484554 and rs12191877. We conclude that despite the discovery of numerous psoriasis risk alleles, HLA-C∗06:02 still plays the most important role in determining the age of onset of psoriasis. Larger studies are needed to evaluate the contribution of other risk alleles, including IFIH1, to age of psoriasis onset.

Psychodermatology: an overview.

Psychodermatology is an interface between dermatology and psychiatry. The different disorders within psychodermatology can be categorized in 2 ways: by the type of psychodermatologic disorder or by the underlying psychiatric disorder. The types of psychodermatologic disorders include psychophysiological, primary psychiatric, secondary psychiatric, and cutaneous sensory disorder. The psychiatric disorders include anxiety, depression, obsessive-compulsive disorder, and psychosis. This manuscript gives an overview of the different psychodermatologic disorders, underlying psychiatric disorders, and how to manage psychodermatology cases.

Quality-of-life effects of common dermatological diseases.

Chronic skin conditions can impact a patient's quality of life beyond the skin. This manuscript gives an overview of the negative impact of common chronic skin conditions, such as psoriasis, vitiligo, acne, and eczema measured by the validated quality of life instruments. Literature has shown that patients with vitiligo and acne are mostly affected by their psychosocial wellbeing, whereas psoriasis and atopic dermatitis patients are affected by both physical and psychosocial well-being. Effective treatments of the above skin conditions correlate with positive quality of life outcomes. Further studies are recommended to better understand factors affecting quality of life.

The Goeckerman regimen for the treatment of moderate to severe psoriasis.

Psoriasis is a chronic, immune-mediated inflammatory skin disease affecting approximately 2-3% of the population. The Goeckerman regimen consists of exposure to ultraviolet B (UVB) light and application of crude coal tar (CCT). Goeckerman therapy is extremely effective and relatively safe for the treatment of psoriasis and for improving a patient's quality of life. In the following article, we present our protocol for the Goeckerman therapy that is utilized specifically at the University of California, San Francisco. This protocol details the preparation of supplies, administration of phototherapy and application of topical tar. This protocol also describes how to assess the patient daily, monitor for adverse effects (including pruritus and burning), and adjust the treatment based on the patient's response. Though it is one of the oldest therapies available for psoriasis, there is an absence of any published videos demonstrating the process in detail. The video is beneficial for healthcare providers who want to administer the therapy, for trainees who want to learn more about the process, and for prospective patients who want to undergo treatment for their cutaneous disease.