Maya Debbaneh

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.

Diet and psoriasis, part I: Impact of weight loss interventions

One of the most frequently asked questions by patients with psoriasis is whether dietary changes can improve their condition. Included in this discussion is whether dietary weight loss can benefit their skin disease. Obesity has been associated with a proinflammatory state and several studies have demonstrated a relationship between body mass index and psoriasis severity. However, the question of whether weight loss interventions can impact psoriasis outcome is less clear. Here, we review the literature to examine the efficacy of weight loss interventions, both dietary and surgical, on psoriasis disease course.

Diet and psoriasis, part II: Celiac disease and role of a gluten-free diet

Patients with psoriasis have been shown to have a higher prevalence of other autoimmune diseases including celiac disease, a condition marked by sensitivity to dietary gluten. A number of studies suggest that psoriasis and celiac disease share common genetic and inflammatory pathways. Here we review the epidemiologic association between psoriasis and celiac disease and perform a meta-analysis to determine whether patients with psoriasis more frequently harbor serologic markers of celiac disease. We also examine whether a gluten-free diet can improve psoriatic skin disease.

Tonsillectomy as a treatment for psoriasis: a review.

Abstract Psoriasis is a chronic skin disorder that affects 1% to 3% of the general population worldwide. Streptococcal infection, especially streptococcal pharyngitis, has been shown to be a significant trigger of psoriasis in some patients, possibly by sensitizing T cells to keratin epitopes in the skin. Due to the role of the palatine tonsils as an immunological organ that may generate autoreactive T cells, tonsillectomy has been investigated as a treatment for psoriasis. Tonsillectomy originally gained acceptance in Japan as a treatment for palmoplantar pustulosis, a condition that shares features with pustular psoriasis. Subsequently, tonsillectomy has been used for the treatment of plaque psoriasis and guttate psoriasis. Recently, the first randomized, controlled clinical trial of tonsillectomy was performed. Here, we review the available evidence for the benefit of tonsillectomy as a treatment for palmoplantar pustulosis and psoriasis. We also discuss molecular studies aimed at understanding the role of tonsils in skin disease.

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.

Antiviral gene expression in psoriasis.

Psoriasis patients have relatively infrequent cutaneous viral infections compared to atopic dermatitis patients. Increased expression of four antiviral proteins (MX1, BST2, ISG15 and OAS2) has been reported in psoriatic skin and genetic studies of psoriasis have identified susceptibility genes in antiviral pathways.

Diminished humoral responses against and reduced gene expression levels of human endogenous retrovirus-K (HERV-K) in psoriasis

BackgroundPsoriasis is a multifactorial, chronic disease of skin affecting 2-3% of the world’s population. Genetic studies of psoriasis have identified a number of susceptibility genes that are involved in anti-viral immunity. Furthermore, physiological studies have also found an increase in anti-viral proteins in psoriatic skin. These findings suggest the presence of an anti-viral state in psoriatic skin. However, the triggers for this anti-viral cascade and its consequences for host immunity are not known. Endogenous retroviruses have previously been described in many autoimmune diseases including psoriasis.MethodsIn the present study we examined the humoral immune response against human endogenous retrovirus-K (HERV-K) proteins and the cutaneous expression levels of multiple HERV-K genes in psoriasis patients and healthy controls.ResultsIn psoriatic sera we observed a significant decrease in IgM response against three HERV-K proteins: Env surface unit (SU), Env transmembrane protein (TM), and Gag capsid (CA) in comparison to sera obtained from blood bank healthy controls. A decrease in IgG response was also observed against CA. Furthermore, using quantitative RT-PCR we observed a decrease in the expression of HERV-K Env, Gag, Pol and Rec as well as ERV-9 genes in lesional psoriatic skin as compared to healthy skin.ConclusionsTogether, our results suggest that the pro-inflammatory, anti-viral state in psoriasis is associated with diminished expression of HERV-K gene transcripts and a concomitant decrease in humoral responses to HERV-K. Our results indicate that a simple model where continuous, minimally changing HERV-K expression serves as an antigenic trigger in psoriasis might not be correct and further studies are needed to decipher the possible relationship between psoriasis and HERVs.

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.