Argentina Leon

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.

Etanercept for the treatment of refractory pyoderma gangrenosum: a brief series

Background  Pyoderma gangrenosum (PG) is a rare ulcerative inflammatory condition of unknown etiology. Therapy for PG involves local wound care along with topical and systemic anti‐inflammatory and other immunodulatory agents. Etanercept is one such immunomodulator with activity against the inflammatory cytokine, tumor necrosis factor.

An attempt to formulate an evidence-based strategy in the management of moderate-to-severe psoriasis: a review of the efficacy and safety of biologics and prebiologic options.

Psoriasis is a chronic skin disorder affecting up to 2.5% of the world’s population. Despite the myriad treatment options available, there is no uniformly accepted therapeutic approach for moderate-to-severe psoriasis. The objective of this review is to evaluate the relative efficacy and safety of available therapeutic options and to formulate general recommendations for the treatment of moderate-to-severe psoriasis. MEDLINE and Evidence Based Medicine (Cochrane) were used to perform a comprehensive search of the literature from 1986 to 2006. The most scientifically rigorous clinical trial published in the literature was selected for Psoriasis Area and Severity Index (PASI 75) comparison. Only information from clinical trials, human subjects and English language journals are reported in this study. The percentage of PASI 75 reduction at ∼ 12 weeks obtained by the following treatment options were: Goeckerman and RePUVA, 100%; calcipotriene plus PUVA, 87%; ciclosporin, 78.2 – 80.3%; infliximab, 80%; adalimumab 40 mg every other week, 53% and 40 mg/week, 80%; PUVA, 63%; methotrexate, 60%; NB-UVB, 55%; acitretin 52%; etanercept 50 mg twice weekly, 49% and 25 mg twice weekly, 34%; efalizumab, 31.4%; and alefacept 21%. Psoriatic treatments with safer profiles compared with other agents include bath PUVA, Goeckerman and RePUVA. Based on the literature review of efficacy and safety of biologics and prebiologic treatment options for moderate-to-severe psoriasis, the risk:benefit ratio seems most favorable for Goeckerman and RePUVA, followed by either etanercept or adalimumab.

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

Background: Tumor necrosis factor‐&agr; (TNF‐&agr;) inhibitors have been reported to induce new‐onset psoriasis. Objective: To better define the demographic, clinical features, and treatment approach of TNF‐&agr; inhibitor‐induced psoriasis. Methods: Systematic review of published cases of TNF‐&agr; inhibitor‐induced psoriasis. Results: We identified 88 articles with 216 cases of new‐onset TNF‐&agr; 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‐&agr; 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‐&agr; inhibitor cessation may result in resolution of induced psoriasis, lesions may persist. Decisions regarding treatment should be weighed against the treatability of TNF‐&agr; 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.

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

Abstract 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.

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 patients 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 patients 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 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.

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.

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.

Abstract 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.

The Spectrum of Ideation in Patients with Symptoms of Infestation: From Overvalued Ideas to the Terminal Delusional State

Delusional infestation (DI) is a type of monosymptomatic hypochondriacal psychosis characterized by the steadfast belief that one is infested with living organisms or inanimate material in the absence of objective proof. Although DI is generally regarded as a single psychotic phenotype characterized by either the presence or absence of a delusion, our experience has been that patients with DI present with varying levels of severity represented by various phenotypes along a continuum. Distinguishing where a particular patient presents on this spectrum has allowed us to modify our approach with greater sophistication and thereby optimize management. Our aim is to describe for the first time in dermatology the concept of the DI continuum with support from the psychiatric literature, and to provide practical therapeutic recommendations for each phenotype in the spectrum.