Newer Therapies in Psoriasis.

Psoriasis is a systemic inflammatory condition that negatively affects the quality of life and medical health of 125 million individuals globally. Although psoriasis has historically been viewed as a skin-limited disease and managed with topical agents (eg, coal tar, corticosteroids, and vitamin D analogues), the recontextualization of psoriasis as a systemic condition involving multiple organ systems has prompted the development of numerous immunomodulating, systemic agents with more targeted mechanisms of action. This article briefly discusses the indications and nuances of new and developing therapeutic agents for psoriasis management.

People smoke for nicotine, but lose sexual and reproductive health for tar: a narrative review on the effect of cigarette smoking on male sexuality and reproduction.

PURPOSE: To systematically review the impact of smoking habits on cardiovascular (CV) as well as on male sexual and reproductive function and to provide updated evidence on the role of electronic cigarettes (e-Cig) on the same topics. METHODS: A comprehensive Medline, Embase, and Cochrane search was performed including the following words: smoking, CV system, CV risk, erectile dysfunction (ED), and male fertility. Publications from January 1, 1969 up to February 29, 2020 were included. RESULTS: Smoking has a tremendous negative impact on CV mortality and morbidity. Current smoking behavior is also negatively associated with erectile dysfunction (ED) and impaired sperm parameters. E-Cig can release significantly lower concentrations of harmful substances when compared to regular combustible cigarettes. Whether or not the latter can result in positive CV, sexual, and fertility outcomes is still under study. Preliminary studies showed that exposure to e-Cig leads to lower vascular damage when compared to the traditional cigarette use. However, data on the long-term effects of e-Cig are lacking. Similarly, preliminary data, obtained in animal models, have suggested a milder effect of e-Cig on erectile function and sperm parameters. CONCLUSION: Available evidence showed that e-Cig are much less dangerous when compared to the traditional tobacco use. However, it should be recognized that the risk related to e-Cig is still higher when compared to that observed in non-smoking patients. Hence, e-Cig should be considered as a potential tool, in the logic of harm reduction, to reduce the CV, sexual and fertility risk in patients refractory to the fundamental, healthy choice to definitively quit smoking.

Holistic development of coal tar lotion by embedding design of experiments (DoE) technique: preclinical investigations.

Background: The research work endeavors to develop a liquid dosage form of an efficacious antipsoriatic drug, i.e., coal tar, but having problems like variability and patient noncompliance.Methods: The emulsion was prepared by the wet gum method from standardized coal tar. The optimized lotion obtained after sequential experimental designs was characterized for various dosage form and/or coal tar-related properties including efficacy.Results: The formulation deposited more coal tar in the unit area of rat skin than marketed lotions. The efficacy of lotion in psoriasis animal models was more or equivalent to marketed lotions. The formulation showed one compartment body model dermatokinetics, nonirritancy after repeated applications, and stability at room conditions for a year.Conclusion: The formulation with desired attributes was successfully developed.

Atopic dermatitis: skin care and topical therapies.

Atopic dermatitis (AD) pathogenesis is strongly influenced by Type 2 innate lymphoid cell and T-helper cell type 2 lymphocyte-driven inflammation and skin barrier dysfunction. AD therapies attempt to correct this pathology, and guidelines suggest suggest basics of AD therapy, which include repair of the skin barrier through bathing practices and moisturizers, infection control, and further lifestyle modifications to avoid and reduce AD triggers.While some patients' AD may be controlled using these measures, inflammatory eczema including acute flares and maintenance therapy in more severe patients are treated with topical pharmacologic agents such as topical corticosteroids, topical calcineurin inhibitors, and, more recently, topical PDE-4 inhibitors. This model of basic skin therapy and, as needed, topical pharmacologic agents may be used to treat the vast majority of patients with AD and remains the staple of AD therapy.

Methotrexate iontophoresis versus coal tar ointment in palmoplantar psoriasis: A pilot study.

BACKGROUND: Palmoplantar psoriasis is often disabling and refractory to conventional therapy. Systemic drugs are indicated in its severe form, but side effects are a concern with their use. Methotrexate is one such systemic drug which is effective and cheap. To reduce systemic toxicity, methotrexate has been tried topically but results have been inconsistent due to poor drug penetration into the skin by passive diffusion. Iontophoresis may enhance its absorption and efficacy. AIM: To evaluate the efficacy and safety of topical methotrexate iontophoresis in comparison with coal tar ointment in the treatment of palmoplantar psoriasis. METHODS: Thirty-one patients with palmar and/or plantar psoriasis were selected for the study and 28 patients completed it. The side having more severe involvement was treated while the other palm/sole served as a control. Iontophoresis using methotrexate solution was carried out on the study palm/sole with the injectable preparation of methotrexate (50 mg/2 ml) once a week for the first 4 weeks and subsequently every two weeks, for a total of six sittings. The control palm/sole was treated with coal tar ointment on other days. Erythema, scaling, induration and fissuring scores were noted in both groups before and after treatment. RESULTS: Both study and control groups showed decreases in scores but the reduction was more in the study group, the difference being statistically significant. LIMITATIONS: Drawbacks of our study include the small sample size and the lack of follow-up. The study and control arms were not exactly matched and the study was not blinded. CONCLUSION: Methotrexate iontophoresis was safe and more effective than coal tar ointmentin palmoplantarpsoriasis.

Mechanism of action and effect of immune-modulating agents in the treatment of psoriasis.

OBJECTIVES: The aim of this work is to study the possible mechanisms through which different immune-modulating agents can produce their beneficial effects on treatment of psoriasis and to determine whether the supplementation of these agents for psoriasis patients induces regression of psoriasis. SUBJECTS AND METHODS: One hundred fifty participants were included in this study. The participants were divided into five groups: 1. Normal control group, 2. Psoriasis patients not taking any treatment, 3. Psoriasis patients treated with anti-psoriatic treatment (including coal tar, vitamin D3 analogues and corticosteroids). 4. Psoriasis patients treated with anti-psoriatic treatment and oral metformin (850mg twice daily) and 5. Psoriasis patients treated with anti-psoriatic treatment and oral pioglitazone (15mg once a day). Demographic characteristics, diabetic index, lipid profile and liver function tests were monitored. The CD4+ Tcells, CD8+ Tcells, CD4+/CD8+ ratio, interleukin-2 (IL-2), C-reactive protein (CRP) and ceruloplasmin (CP) were assayed. RESULTS: After treatment of psoriasis patients with a traditional anti-psoriatic drug in combination with metformin and peroxisome proliferator-activated receptor gamma (PPARɤ) agonist (pioglitazone), the CD4+ T cells, IL-2, CRP, CP, ALT and AST levels were statistically significantly decreased compared to psoriasis patients without treatment. Positive and significant correlations between CD4+ % and IL-2, CRP, CP, ALT and AST in psoriasis patients were recorded. CONCLUSIONS: The activation of PPAR-γ receptors by pioglitazone results in reduced formation of the proinflammatory cytokines and infiltration by inflammatory cells. Additionally, metformin acts as a modulator of the immune system in psoriasis patients and has a remarkable effect on the early stages of psoriasis. Therefore, either pioglitazone or metformin in combination with traditional anti-psoriatic drugs provides better results in the treatment of psoriasis than does each alone.

Dr Michaels® (Soratinex®) product for the topical treatment of psoriasis: a Hungarian/Czech and Slovak study.

Psoriasis is a chronic inflammatory T cell-mediated skin disease, affecting about 2% of Hungarian population. Genetic predisposition as well as environmental triggering factors, and innate immune processes play a role in its etiology. Treatment of psoriasis during the initial stages and first years of disease tend to be conservative and frequently based on topical agents. The aim of this study was to investigate and to describe the efficacy and safety of Dr Michaels® (Soratinex®) skin-care products for the topical treatment of stable chronic plaque psoriasis in a Hungarian population. Two-hundred-and-eight-six (120 female/166 male) patients, aged 10-80 years old (mean age 43 years) with mild to moderate plaque psoriasis had participated in the study. The products, including cleansing gel containing a coal tar solution, herbal oils and emulsifiers, were used twice daily and in the same manner for all the skin lesions. The study period was eight weeks. Assessment, using the Psoriasis Activity Severity Index (PASI) scores and photographic analysis, was done 2 weeks before treatment, at time 0, and after 2, 4, 6 and 8 weeks. Patient’s improvement was determined by the percentage reduction of the PASI scores. Side effects and tolerability were also evaluated. After 8 weeks treatment course, 46 patients had a moderate improvement, with the regression of 25-50% of skin lesions; 77 patients showed a good improvement, with the resolution of 51-75% of lesions. Another 115 patients had an outstanding improvement, with the regression of 76-98.9% of lesions. Only 13 patients did not achieve an improvement of psoriasis. Fifteen patients experienced folliculitis, which resolved after cessation of treatment. Seven patients worsened and discontinued treatment. Thirteen patients dropped out because of non-compliance. Our investigation demonstrates that Dr Michaels® (Soratinex®) products, an Australian treatment, can be used successfully in the treatment of stable chronic plaque psoriasis.

Genetic polymorphisms in biotransformation enzymes for benzo[a]pyrene and related levels of benzo[a]pyrene-7,8-diol-9,10-epoxide-DNA adducts in Goeckerman therapy.

Goeckerman therapy (GT) for psoriasis combines the therapeutic effect of crude coal tar (CCT) and ultraviolet radiation (UVR). CCT contains polycyclic aromatic hydrocarbons, some of which can form DNA adducts that may induce mutations and contribute to carcinogenesis. The aim of our work was to evaluate the relationship between concentrations of benzo[a]pyrene-7,8-diol-9,10-epoxide-DNA adducts (BPDE-DNA adducts) and rs4646903 (CYP1A1 gene), rs1048943 (CYP1A1), rs1056836 (CYP1B1), rs1051740 (EPHX1), rs2234922 (EPHX1) and rs8175347 (UGT1A1) polymorphic sites, and GSTM1 null polymorphism in 46 patients with chronic stable plaque psoriasis who underwent GT. The level of BPDE-DNA adducts was determined using the OxiSelect BPDE-DNA Adduct ELISA Kit. Polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis (rs4646903, rs1048943, rs1051740, and rs2234922), fragment analysis (rs8175347), real-time PCR (rs1056836), and digital droplet PCR polymorphism (GSTM1) were used. CYP1B1*1/*1 wild-type subjects and CYP1B1*3/*1 heterozygotes for rs1056836 formed significantly higher amounts of BPDE-DNA adducts than CYP1B1*3/*3 homozygotes (p=0.031 and p=0.005, respectively). Regarding rs1051740, individuals with EPHX1*3/*1 heterozygosity revealed fewer adducts than EPHX1*1/*1 wild-type subjects (p=0.026). Our data suggest that CYP1B1/EPHX1 genotyping could help to predict the risk of DNA damage and to optimize doses of coal tar and UVR exposure in psoriatic patients in whom GT was applied.

Influence of dermal exposure to ultraviolet radiation and coal tar (polycyclic aromatic hydrocarbons) on the skin aging process.

BACKGROUND: Ultraviolet radiation (UVR) and crude coal tar (CCT) containing PAHs can accelerate the skin-aging process (SAP). However, UVR induces the formation of an important protective factor in SAP (vitamin D). OBJECTIVE: To determine the relation of SAP to selected risks and benefits of combined dermal exposure to UVR and coal tar (PAHs). METHODS: The study group consisted of patients with chronic stable plaque psoriasis and treated by Goeckerman therapy (GT; daily dermal application of UVR and 5% CCT ointment). The levels of urinary 1-hydroxypyrene (1-OHP), oxidative stress (DNA and RNA damage), genotoxic damage (chromosomal aberration in peripheral lymphocytes; ABC), 25-hydroxy-vitamin D [25(OH)D] and the PASI score were evaluated before and after GT. RESULTS: Intensive dermal absorption of PAHs was confirmed by increased levels of 1-OHP (p<0.01). After the therapy, we found an increased level of oxidative stress (p<0.05), an increased level of genotoxic damage (ABC; p<0.001), a high efficiency of the treatment (p<0.001) and an elevated production of 25(OH)D (p<0.01). We also found a relationship between the duration of UVR and the genotoxic damage (p<0.01), vitD (p<0.05) and the PASI score (p<0.05). Furthermore, we found a relationship between oxidative stress and 25(OH)D (p<0.05) and between genotoxic damage and the PASI score (p<0.05). CONCLUSION: Dermal exposure to UVR and coal tar (PAHs) enhances the level of oxidative stress and genotoxic damage and thus contributes to SAP. However, the exposure is very effective as a treatment and elevates the production of 25(OH)D, the protective factor in SAP. According to our results, UVR is probably a more hazardous factor in SAP.

Phenol Toxicity Following Cutaneous Exposure to Creolin®: A Case Report.

INTRODUCTION: Phenol is a caustic that may cause cutaneous or gastrointestinal burns depending on the route of exposure. Significant absorption may result in systemic toxicity. We present a case of topical phenol exposure resulting in cutaneous burns and systemic phenol toxicity. CASE REPORT: A 9-year-old girl was exposed to Creolin(®), a general-purpose disinfectant containing phenol, when her mother applied this product to her head and upper torso. The patient required endotracheal intubation due to depressed mental status; she had cutaneous erythema in the distribution of contact with the cleanser. An initial EKG revealed sinus tachycardia with brief runs of monomorphic ventricular tachycardia. On hospital day (HD) 1, the area of erythema extended to both upper extremities and hyperpigmentation developed over the affected areas, which continued to darken during the hospital course. The patient was extubated late on HD 1. On HD 2, the patient's urine was noted to be a dark green color that resolved later that day. On HD 3, areas of desquamation and decreased sensation developed in skin areas of maximal contact with the cleanser. The patient developed a mild transaminitis with peak AST and ALT levels of 84 units/l and 99 units/l, respectively. The patient was discharged to home on HD 4. DISCUSSION: Our patient presented with signs of cutaneous and systemic phenol toxicity characterized by dermal burns, depressed mental status, cardiac dysrhythmias, and elevated hepatic transaminases. Phenol exposure may cause systemic toxicity following limited dermal exposure.

Dermatological exposure to coal tar and bladder cancer risk: a case-control study.

OBJECTIVE: Coal tar ointments are used as treatment of various skin diseases, especially psoriasis and eczema. These ointments contain several carcinogenic polycyclic aromatic hydrocarbons. Metabolites of these polycyclic aromatic hydrocarbons are excreted in the urine and therefore, dermatological use of coal tar may be associated with an increased risk of bladder cancer. The objective of this study was to evaluate the association between dermatological use of coal tar ointments and bladder cancer. MATERIAL AND METHODS: A population-based case-control study was conducted including 1,387 cases diagnosed with bladder cancer and 5,182 population controls. Information on the use of coal tar, history of skin disease, and known risk factors for bladder cancer was obtained through postal questionnaires. Logistic regression analyses were performed to estimate the risk of bladder cancer after coal tar treatment, adjusted for age, gender, smoking status, duration of smoking, and intensity of smoking. RESULTS: The use of coal tar ointments was approximately equal among cases and controls (3.8% vs. 3.0%, respectively). Dermatological application of coal tar was not significantly associated with bladder cancer (adjusted odds ratio = 1.37, 95% CI: 0.93-2.01). An inverse association between bladder cancer and a history of skin disease was observed (adjusted odds ratio = 0.74, 95% CI: 0.61-0.90). CONCLUSION: This is the first study with a specific aim to study the association between the use of coal tar preparations and bladder cancer. The results suggest that there is no reason for safety concerns with respect to the risk of bladder cancer after the use of coal tar preparations in dermatological practice.

Comparative evaluation of topical calcipotriol versus coal tar and salicylic acid ointment in chronic plaque psoriasis.

BACKGROUND: Calcipotriol is a newer topical treatment option available for plaque psoriasis and coal tar being one of the oldest treatment and still in use. AIMS: To evaluate and compare the differences in terms of efficacy, safety and relapse with Calcipotriol 0.005% (50 mcg/gm) and 6% coal tar and 3% salicylic ointment in patients with Plaque psoriasis. SETTING and DESIGNS: Study conducted on 60 patients of plaque psoriasis, who attended the skin OPD in our hospital. METHODS: The patients with mild to moderate plaque psoriasis were selected. 60 patients were enrolled for the study after obtaining informed consent. Subjects were asked to apply Calcipotriol 0.005% (50 mcg/gm) (Heximar Win care) twice a day on the right side plaques and on left side plaques, Petroleum jelly (Vaseline) in the morning and 6% coal tar and 3% salicylic ointment (Protar® Percos) at nighttime. PASI score was used to assess the reponse to therapy at 2nd, 4th, 6th and 8th week. After treatment subjects were observed for 6 weeks for any relapse. STATISTICAL ANALYSIS: It was done by paired t-test and independent sample t-test. CONCLUSIONS: The results showed that statistically significant difference was seen in the mean percentage reduction of PASI score between both the groups, at all the assessment visits, 2, 4, 6, and 8 weeks, the mean percentage reduction at 2 weeks for calcipotriol being 21±12.06 and for coal tar being 13.44±11.19 (P=0.000), at 4 weeks for calcipotriol was 40±16.71 and for coal tar 25±99 (P=0.000), at 6 weeks for calcipotriol was 53.99+-22.43 and for coal tar 41±21.23 (P=0.002), at 8 weeks for calcipotriol was 62.73±24.04 and for coal tar was 51.53±23.27 (P=0.11). Relapse was seen in 5/60 (8.3%) of patients on calcipotriol treated side and 9/60 (15%) of patients with coal tar treated side. Thus it can be concluded that calcipotriol cream is more efficacious when compared with coal tar and does have a quick response. It is well tolerated and acceptable cosmetically.

Topical therapies for the treatment of plaque psoriasis: systematic review and network meta-analyses.

The majority of people with psoriasis have localized disease, where topical therapy forms the cornerstone of treatment. We set out to summarize evidence on the relative efficacy, safety and tolerability of different topical treatments used in plaque psoriasis. We undertook a systematic review and meta-analyses of randomized trial data of U.K.-licensed topical therapies. The primary outcome was clear or nearly clear status stratified for (i) trunk and limbs; and (ii) scalp. Network meta-analyses allowed ranking of treatment efficacy. In total, 48 studies were available for trunk and limb psoriasis, and 17 for scalp psoriasis (22,028 patients in total); the majority included people with at least moderate severity psoriasis. Strategies containing potent corticosteroids (alone or in combination with a vitamin D analogue) or very potent corticosteroids dominated the treatment hierarchy at both sites (trunk and limbs, scalp); coal tar and retinoids were no better than placebo. No significant differences in achievement of clear or nearly clear status were observed between twice- and once-daily application of the same intervention or between any of the following: combined vitamin D analogue and potent corticosteroid (applied separately or in a single product), very potent corticosteroids, or potent corticosteroids (applied twice daily). Investigator and patient assessment of response differed significantly for some interventions (response rates to very potent corticosteroids: 78% and 39%, respectively). No significant differences were noted for tolerability or steroid atrophy, but data were limited. In conclusion, corticosteroids are highly effective in psoriasis when used continuously for up to 8 weeks and intermittently for up to 52 weeks. Coal tar and retinoids are of limited benefit. There is a lack of long-term efficacy and safety data available on topical interventions used for psoriasis.

Old King coal - molecular mechanisms underlying an ancient treatment for atopic eczema.

Traditional remedies for common disorders have been known for centuries, but insight into their mechanism of action is often limited. In this issue of the JCI, Joost Schalkwijk's research group at the Radboud University Nijmegen Medical Centre in The Netherlands advances our understanding of why topical coal tar is an effective treatment for atopic dermatitis (AD), both rationalizing the use of this traditional medicine, and providing the scientific basis for new therapeutic approaches.

Coal tar induces AHR-dependent skin barrier repair in atopic dermatitis.

Topical application of coal tar is one of the oldest therapies for atopic dermatitis (AD), a T helper 2 (Th2) lymphocyte-mediated skin disease associated with loss-of-function mutations in the skin barrier gene, filaggrin (FLG). Despite its longstanding clinical use and efficacy, the molecular mechanism of coal tar therapy is unknown. Using organotypic skin models with primary keratinocytes from AD patients and controls, we found that coal tar activated the aryl hydrocarbon receptor (AHR), resulting in induction of epidermal differentiation. AHR knockdown by siRNA completely abrogated this effect. Coal tar restored filaggrin expression in FLG-haploinsufficient keratinocytes to wild-type levels, and counteracted Th2 cytokine-mediated downregulation of skin barrier proteins. In AD patients, coal tar completely restored expression of major skin barrier proteins, including filaggrin. Using organotypic skin models stimulated with Th2 cytokines IL-4 and IL-13, we found coal tar to diminish spongiosis, apoptosis, and CCL26 expression, all AD hallmarks. Coal tar interfered with Th2 cytokine signaling via dephosphorylation of STAT6, most likely due to AHR-regulated activation of the NRF2 antioxidative stress pathway. The therapeutic effect of AHR activation herein described opens a new avenue to reconsider AHR as a pharmacological target and could lead to the development of mechanism-based drugs for AD.

Goeckerman therapy: a very effective, yet often forgotten treatment for severe generalized psoriasis.

As early as 1925, patients suffering from psoriasis have been effectively treated with combination crude coal tar and ultraviolet B radiation, commonly known as Goeckerman therapy. Even though the efficacy of Goeckerman therapy is as good as, if not better than, other more recently available treatment options, its use virtually disappeared after extended inpatient therapies became no longer feasible in the USA. Our clinic at the University of California San Francisco is one of the few outpatient dermatologic clinics that still offer Goeckerman therapy. We present a case report of a patient with severe generalized plaque-type psoriasis, who demonstrated dramatic improvement within 28 days of Goeckerman therapy. It is our hope that this case report serves to remind physicians that Goeckerman therapy is viable treatment option for patients with severe psoriasis, especially those with treatment-resistant psoriasis.

Expression of soluble sCD163 in serum of psoriatic patients is modulated by Goeckerman therapy.

BACKGROUND: CD163 is the monocyte/macrophage receptor for haptoglobin-haemoglobin complexes. The aim of this study was to assess the kinetics in the expression of CD163 on monocytes and the concentration of soluble sCD163 in serum of psoriatic patients in order to examine the effect of Goeckerman therapy. METHODS: sCD163 was measured in 71 patients before and after therapy, and in 57 healthy donors. A subgroup of 40 patients and 25 controls was used to assess the expression of membrane CD163. sCD163 was evaluated by ELISA. Flow cytometry method was used to determine the expression of membrane CD163 on monocytes, expressed as mean fluorescence index (MFI). RESULTS: Before therapy, the serum level of sCD163 was significantly higher in our patients than in controls (P=0.0154). However, we observed a profound decrease in sCD163 in our patients after therapy (P=0.0037). Similar to sCD163, pre-treatment expression of CD163 on monocytes was significantly more enhanced in patients than that in controls (P=0.0078). There was a trend towards down-regulation of the expression after therapy, nonetheless, the change was not statistically significant compared to the values before therapy (P=0.8666). This was also confirmed by comparison with controls which displayed lower expression of CD163 than patients after therapy (P=0.0019). The disease activity, expressed as PASI score, was significantly decreased in our patients by GT (P=0.0001). CONCLUSIONS: While sCD163 level in psoriatic patients was diminished after GT therapy, CD163 expression on monocytes was altered only to a minor extent.