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.

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.

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.

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.

Goeckerman therapy for the treatment of eczema: a practical guide and review of efficacy.

The Goeckerman regimen, consisting of the application of crude coal tar combined with exposure to ultraviolet radiation, was formulated in 1925 for the treatment of psoriasis. While some centers have adapted the Goeckerman regimen for the treatment of eczema, there are no published reports of its efficacy in this condition. Here, we explain how the Goeckerman regimen has been modified for use in an eczema population at the University of California San Francisco (UCSF). We reviewed the treatment records of eczema patients treated with the modified Goeckerman regimen over a 6-year period at UCSF. We found that the Goeckerman regimen was effective in treating patients with severe baseline disease, inducing a mean remission period of 7.2 months. The treatment was tolerated well with mild folliculitis and occasional ultraviolet B phototoxicity noted as the only adverse reactions. Since the use of Goeckerman as a treatment for severe eczema is both effective and safe, it should be considered an excellent alternative or adjunct to the systemic therapies currently being used.

The influence of psoriatic plaques pretreatment with crude coal tar vs. petrolatum on the efficacy of narrow-band ultraviolet B: a half-vs.-half intra-individual double-blinded comparative study.

BACKGROUND/PURPOSE: The value of psoriatic plaques pretreatment with specific topical preparations in the setting of NB-ultraviolet-B (UVB) therapy is debatable. It may be clarified through a comparative assessment between crude coal tar and petrolatum as pretreatment candidates. METHODS: A prospective study included 40 patients with plaque psoriasis undergoing NB-UVB therapy. We compared among three treatment regimens: NB-UVB alone (control group; n=20) as well as NB-UVB preceded by crude coal tar 3% on one side and petrolatum on the other side (cases group I and II; n=20). Tar and petrolatum were topically applied thrice/day the day before NB-UVB exposure. Applications were removed using olive oil directly before NB-UVB exposure. Regimens' frequency was thrice/week and the clinical outcome was assessed, through both psoriasis area and severity index (PASI) and physician global assessment (PGA) scores, at baseline and 3 months later. RESULTS: There were significant (P<0.01) decreases in both PASI and PGA scores in all the groups. In comparison with the controls, cases revealed significantly (P<0.05) higher improvement percentages in both PASI and PGA scores for both tar and petrolatum. This influence, through the PGA score, was significantly (P<0.05) in favor of petrolatum. CONCLUSION: The pretreatment of psoriatic plaques with either petrolatum or crude coal tar may enhance the therapeutic outcome of NB-UVB, which appeared to favor petrolatum.

Comparison of clobetasol propionate cream plus coal tar vs. topical psoralen and solar ultraviolet A therapy in palmoplantar psoriasis.

AIM: Palmoplantar psoriasis (PPP) produces significant morbidity and requires prompt treatment. Topical agents form the mainstay of therapy. We compared the efficacy and side-effect profile of a steroid/coal-tar combination with topical psoralen and solar ultraviolet A (PUVAsol) in PPP. METHODS: In total, 52 patients with PPP were randomized to receive either a combination of clobetasol propionate cream and coal tar daily (group 1) or topical PUVAsol on alternate days (group 2) for 16 weeks. Response was assessed as change in Psoriasis Activity and Severity Index (PASI) and Patient Global Assessment (PGA). RESULTS: Of the 52 patients, 43 completed the treatment phase. There was a reduction in PASI for the palms and soles in both treatment groups throughout the treatment period until week 16. There was a greater reduction in PASI in palmar psoriasis with topical PUVAsol, and a greater reduction in psoriasis of the soles with the steroid/coal-tar combination. In both groups, patients perceived 'good improvement'. Improvement or cure in palmar lesions was observed in 90% of cases in the topical steroid/coal-tar group and in 75% of cases in the topical PUVAsol group; for the soles, these figures were 76% and 79%, respectively. No adverse effects were experienced with the steroid/coal-tar combination, whereas for the topical PUVAsol, phototoxicity occurred in 22% of cases. CONCLUSION: Both treatments had comparable efficacy. In both groups, patients experienced 'good improvement' after 16 weeks of therapy.

Efficacy and tolerability of a cosmetically acceptable coal tar solution in the treatment of moderate plaque psoriasis: a controlled comparison with calcipotriene (calcipotriol) cream.

BACKGROUND: Topical coal tar is a well known and effective treatment for psoriasis, but the messiness, staining, odor, and inconvenience associated with its use make patient satisfaction and compliance a challenge. OBJECTIVE: To determine the efficacy, patient tolerability, and cosmetic acceptability of a new topical liquor carbonis distillate (LCD) 15% solution compared with calcipotriene (calcipotriol) cream in patients with moderate, chronic plaque psoriasis. STUDY DESIGN: A randomized, single-blind, active-controlled, parallel-group, clinical trial consisting of a 12-week treatment phase and a 6-week post-treatment follow-up phase. SETTING: Outpatient dermatology research unit in an academic hospital. PATIENTS: Sixty adults with moderate, chronic plaque psoriasis (3-15% body surface area affected) not receiving other psoriasis therapies. INTERVENTION: Patients were randomized to apply either an LCD 15% solution (Psorent) or a commercially available calcipotriene 0.005% cream (Dovonex) to their psoriasis areas (excluding the head) twice daily at home for 12 weeks. ASSESSMENTS: A blinded investigator evaluated the patients' psoriasis using a modified Psoriasis Area and Severity Index (PASI) that excluded the head, and a Physician's Global Assessment (PGA) scale at weeks 0 (baseline), 2, 4, 8, and 12 (end of treatment), and 18 (6 weeks after treatment was withdrawn). Patients assessed their psoriasis symptoms and quality of life and completed a cosmetic acceptability survey about their medication. OUTCOME MEASURES: The changes in the baseline PASI scores after 12 weeks of treatment were compared between LCD and calcipotriene groups. Additional comparisons were performed for success rates during treatment (PASI 75 and PASI 50), changes in PGA scores, patient-reported psoriasis symptom scores, patients' quality-of-life scores, and recurrence rates during post-treatment follow-up. RESULTS: Both treatment groups showed improvement in psoriasis severity and quality of life. However, the LCD group had greater mean reductions in PASI scores: 58% vs 37% in the calcipotriene group (p < 0.05) at week 12. Additionally, the LCD group had more patients (14/27) with absent or minimal psoriasis on the PGA scale than the calcipotriene group (6/28) by the end of treatment (p < 0.05). LCD-treated patients also maintained their improvement better than calcipotriene-treated patients through week 18 after treatment was withdrawn for 6 weeks. Both treatments were well tolerated and cosmetically acceptable to patients. CONCLUSION: The newly formulated LCD solution, applied twice daily at home for 12 weeks, was more effective and as well tolerated and cosmetically acceptable as the calcipotriene cream over 12 weeks of treatment and 6 weeks of follow-up. The LCD solution is a patient-accepted and effective corticosteroid-sparing treatment alternative for psoriasis patients.

Tolerability and cosmetic acceptability of liquor carbonis distillate (coal tar) solution 15% as topical therapy for plaque psoriasis.

Although generally recognized as an effective therapy for psoriasis, coal tar therapy lost appeal in modern clinical practice due to poor patient acceptability of its aesthetic properties. A new liquor carbonis distillate (LCD) solution 15% (equivalent to coal tar 2.3%) that uses an evaporative and transparent vehicle, fragrance, and a dab-on applicator was developed. Cosmetic acceptability of the LCD solution was compared to calcipotriene cream 0.005% during a randomized, active-controlled, investigator-blinded clinical trial. Participants with moderate plaque psoriasis applied LCD solution or calcipotriene cream twice daily to body lesions for 12 weeks and then were followed for 6 additional weeks without treatment. Participants completed a cosmetic acceptability survey about their medications after starting therapy. Mean ratings for aesthetic and product performance attributes were high in both groups; however, more participants treated with LCD solution versus calcipotriene cream rated their product as more convenient and beneficial compared to prior psoriasis therapies. Ratings of the scent, staining, drying time, and dab-on applicator for the LCD solution were favorable. Participant experience with LCD solution in this study suggests that it is a cosmetically acceptable psoriasis treatment that is comparable to calcipotriene cream.

Urinary mutagenicity and genotoxic risk in children with psoriasis after therapeutic exposure to polycyclic aromatic hydrocarbons and ultraviolet radiation.

The Goeckerman regimen (GR) for the treatment of psoriasis comprises dermal application of crude coal tar (polycyclic aromatic hydrocarbons, PAHs) and exposure to ultraviolet radiation (UVR). PAHs and UVR are mutagenic and carcinogenic agents. We evaluated dermal absorption of PAHs as well as the mutagenic and genotoxic effects of GR in 16 children with psoriasis, by determining levels of 1-hydroxypyrene (1-OHP), 1-,2-,3-,4-hydroxyphenanthrene, (1-OHPhe, 2-OHPhe, 3-OHPhe, and 4-OHPhe), urinary mutagenicity (Salmonella mutagenicity assay, Ames test) and numbers of chromosomal aberrations in peripheral lymphocytes (CA), in urine and/or blood, before and after GR. The Psoriasis Area and Severity Index (PASI) score was used to evaluate clinical efficacy of GR. Compared with pre-treatment levels, there were significant increases in urinary concentrations of 1-OHP (p<0.001), 1-OHPhe (p<0.001), 2-OHPhe (p<0.001), 3-OHPhe (p<0.001), and 4-OHPhe (p<0.01), indicating a high degree of dermal absorption of PAHs. There were also significantly increased numbers of revertants in the Ames test in two different strains (YG1041-S9, p<0.01; YG1041+S9, p<0.001; TA98+S9, p<0.01), which demonstrates urinary mutagenicity. We also found a significant increase in the number of CA (p<0.001) and significantly decreased number of CA (p<0.01) at 81 days post-treatment, suggesting that GR has a temporary genotoxic effect. The PASI scores were significantly decreased after GR (p<0.001), confirming the clinical benefit of GR. In conclusion, our results demonstrate mutagenic and temporary genotoxic effects of GR in the group of 16 treated child patients.