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.

Update on the immunological mechanism of action behind phototherapy.

Phototherapy is often used to treat inflammatory skin conditions such as psoriasis and eczema. Much progress has recently been made in understanding the mechanisms underlying the local, cutaneous immune effects induced by phototherapy. Unlike many immunosuppressive drugs used in the management of inflammatory skin disease, phototherapy not only targets effector immune cells but also appears to up-regulate regulatory T cells (Tregs). Additionally, phototherapy reverses epidermal barrier abnormalities common in these diseases, allowing for restoration of cutaneous homeostasis.

Emotional stress as a trigger for inflammatory skin disorders.

Dermatologic disorders comprise 15% to 20% of complaints seen in general practice. Skin disorders result in a negative impact to the patient not only physically but also psychologically, socially, and occupationally. The most common trigger for several inflammatory skin disorders, including psoriasis, is emotional stress. Understanding the significance of emotional triggers to common inflammatory dermatologic disorders is critical to the optimal management of these conditions. This article will provide an overview of the effects of emotional stress on skin disorders and psychotherapeutic options.

Body dysmorphic disorder.

Body dysmorphic disorder (BDD) is a DSM-IV disorder that is characterized by a distressing and excessive preoccupation with a slight or imagined defect of a physical feature. BDD causes significant impairment of psychosocial functioning and a decreased quality of life for patients. Though the disorder is commonly seen in the dermatology setting, the disease remains under recognized and under-treated. It is important for dermatologists to be aware of BDD as patients suffer greatly from the disease. In this review, we provide an update on the epidemiology, clinical features, and treatment options for BDD.

Trichotillomania.

Trichotillomania (TTM) is an impulse disorder in which patients chronically pull out hair resulting in noticeable hair loss. TTM is reported to affect as much as 4% of the population with the highest incidence in childhood and adolescence. The diagnostic criteria for TTM is likely to be revised in the planned fifth edition of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-V) to remove the requirement that the patient has "tension" followed by "relief" or "gratification" after hair pulling. First-line therapy is cognitive behavioral therapy, with strongest support for the subtype habit reversal training. Among pharmacologic therapy, clomipramine has been most effective in clinical trials. However, selective serotonin reuptake inhibitors are most commonly prescribed despite the lack of data supporting their efficacy. This article reviews the clinical features and treatment options for TTM to enhance knowledge and clinical management of TTM.

Adherence to adalimumab in patients with moderate to severe psoriasis.

Background The chronic and relapsing course of psoriasis is often associated with poor adherence to treatment. Adherence to topical treatment is abysmal. Adherence to systemic treatments also decreases over time, with an overall adherence rate of 67% for injectable biologic medications. Whereas overall trends in poor adherence have been documented, the fine details of adherence in individual patients is not well characterized. Purpose To assess adherence to adalimumab in patients with moderate to severe psoriasis. Methods Data on adherence were obtained from a 1-year open label trial including seven patients with moderate to severe psoriasis who agreed to participate in a randomized trial of standard physician education materials plus extended nurse education versus standard physician education materials alone. Adherence to treatment was recorded with electronic monitoring via Medication Event Monitoring System (MEMS) caps undisclosed to the patients. Patients were also instructed to note the time and date they used treatment in a journal. Results The subjects exhibited a broad range of adherence behaviors. Conclusions Adherence to adalimumab therapy for moderate-to-severe psoriasis is variable and can be very poor. The clinical impact of poor adherence to injectable biologic medications is not yet well characterized.

Patients' satisfaction with dermatology residents.

OBJECTIVES: Patients' perception of quality is a critical primary outcome of medical care. Important downstream effects of perceived quality include a more trusting attitude toward the physician, more adherence to treatment, and better treatment outcomes. Patients' satisfaction issues are important to address during dermatology residency training. The aim of the study was to determine patients' satisfaction with dermatology residents and identify potential areas that could be targeted to improve satisfaction. METHODS: Dermatology residents informed patients about a survey on an online doctor rating/patients' satisfaction Web site (www.DrScore.com), provided the patients with cards with the Web site address, and requested that they complete the survey. Respondents provided an overall rating, open comments, and detailed information in seven core areas. The numerical ratings were on a scale from 0 (not at all satisfied) to 10 (extremely satisfied). Patients had the option of indicating aspects of care that could be improved. Descriptive statistics are reported. RESULTS: A total of 148 surveys were collected with a mean rating for the six residents of 9.7 out of 10, with a range of 9.4 to 10. The average during the early period was 9.7 out of 10, whereas the average during the late period was 9.8 out of 10. Fifty-two surveys (35%) indicated areas for improvement, with the most common issues related to staff, parking availability, waiting time, waiting area, and ability to obtain information. CONCLUSIONS: Patients were generally satisfied with the care provided by dermatology residents. Areas for improvement were identified, but these were largely areas over which residents do not have direct control.

Oncogenic PKC-ι activates Vimentin during epithelial-mesenchymal transition in melanoma; a study based on PKC-ι and PKC-ζ specific inhibitors.

Melanoma is one of the fastest growing cancers in the United States and is accompanied with a poor prognosis owing to tumors being resistant to most therapies. Atypical protein kinase Cs (aPKC) are involved in malignancy in many cancers. We previously reported that aPKCs play a key role in melanoma's cell motility by regulating cell signaling pathways which induce epithelial-mesenchymal Transition (EMT). We tested three novel inhibitors; [4-(5-amino-4-carbamoylimidazol-1-yl)-2,3-dihydroxycyclopentyl] methyl dihydrogen phosphate (ICA-1T) along with its nucleoside analog 5-amino-1-((1R,2S,3S,4R)-2,3-dihydroxy-4-methylcyclopentyl)-1H-imidazole-4-carboxamide (ICA-1S) which are specific to protein kinase C-iota (PKC-ι) and 8-hydroxy-1,3,6-naphthalenetrisulfonic acid (ζ-Stat) which is specific to PKC-zeta (PKC-ζ) on cell proliferation, apoptosis, migration and invasion of two malignant melanoma cell lines compared to normal melanocytes. Molecular modeling was used to identify potential binding sites for the inhibitors and to predict selectivity. Kinase assay showed >50% inhibition for specified targets beyond 5 µM for all inhibitors. Both ICA-1 and ζ-Stat significantly reduced cell proliferation and induced apoptosis, while ICA-1 also significantly reduced migration and melanoma cell invasion. PKC-ι stimulated EMT via TGFß/Par6/RhoA pathway and activated Vimentin by phosphorylation at S39. Both ICA-1 and ζ-Stat downregulate TNF-α induced NF-κB translocation to the nucleus there by inducing apoptosis. Results suggest that PKC-ι is involved in melanoma malignancy than PKC-ζ. Inhibitors proved to be effective under in-vitro conditions and need to be tested in-vivo for the validity as effective therapeutics. Overall, results show that aPKCs are essential for melanoma progression and metastasis and that they could be used as effective therapeutic targets for malignant melanoma.

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.

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.

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.

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.