Genotoxic effect of simultaneous therapeutic exposure to polycyclic aromatic hydrocarbons and UV radiation.

Polycyclic aromatic hydrocarbons (PAHs) and ultraviolet radiation (UV) represent genotoxic factors that commonly occur in the living and working environment. The dermal form of exposure represents a significant part of the total load of dangerous chemical and physical environmental factors to which an organism is subjected. However, simultaneous dermal exposures to PAHs (pharmaceutical crude coal tar [CCT]) and UV (UVA and UVB) also have therapeutic uses. A typical example is Goeckerman therapy (GT) for psoriasis. The question of the therapeutic efficacy of GT and the related level of genotoxic danger is still under discussion. The aim of the present study was to compare four GT variants (G1-G4) in terms of efficacy and acceptable genotoxic hazard. Efficacy was expressed by the psoriasis area of severity index (PASI) score, genotoxic hazard by chromosomal aberration in peripheral lymphocytes. The lowest risk of genotoxic hazard and the lowest efficiency was observed in G1 variant (3% of the CCT and UVA + UVB). The efficacy of G2 (4% CCT and UVA + UVB), G3 (4% CCT and UVB), and G4 variants (5% CCT and UVA + UVB) was comparable. The highest risk of genotoxic hazard was found in the G3 variant. In the terms of sufficient efficacy and acceptable genotoxic hazard, a combination of 4% or 5% of CCT and UVA and UVB seems to be acceptable (variants G2 and G4).

Quality of life of patients with psoriasis.

OBJECTIVE: The two main aims of our study were to assess the quality of life (QOL) of patients with moderate or severe psoriasis treated by Goeckerman therapy and to compare QOL of our patients on the date of admission and 1 month after their discharge. METHODS: We performed a prospective study on 51 patients treated for chronic plaque psoriasis by Goeckerman regimen (GR). The psoriasis area involvement and severity was measured using the Psoriasis Area and Severity Index (PASI). Patients' health-related QOL was evaluated using Psoriasis Disability Index (PDI). RESULTS: In our study we demonstrated that the QOL of this sample of 51 patients with severe forms of psoriasis was relatively good; an average PDI value on the day of admission was 9.02, which represents a small effect on patient's QOL. We did not find any significant differences in QOL between younger and older respondents or between men and women. Despite good treatment efficiency, we did not find improvement in QOL 1 month after discharge. CONCLUSIONS: The QOL of our patients was relatively good. This could be explained by the fact that our patients have been suffering from psoriasis for many years and have probably adapted to their disease. QOL of our patients was not directly dependent on the extent and intensity of skin changes. Further studies on the connection between psoriasis therapy and patients' QOL are still highly needed.

Variation of selected genotoxic and epigenetic markers due to therapeutic exposure to PAHs and ultraviolet radiation.

BACKGROUND: Goeckerman therapy (GT) of psoriasis involves dermal application of crude coal tar containing polycyclic aromatic hydrocarbons (PAHs) and exposure to ultraviolet radiation (UVR). Little is known about GT influence on DNA epigenetics. OBJECTIVE: The study aim was to discover epigenetic mechanisms altered by the exposure related to the GT of psoriasis. METHODS: Observed group of patients with plaque psoriasis (n = 23) was treated by GT with 3 % CCT. Before and after GT, we analyzed the levels of benzo[a]pyrene-7,8-diol-9,10-epoxide-DNA adducts (BPDE-DNA), p53 protein in serum, 5-methylcytosine (5-mC, global DNA methylation), and methylation in selected CpG sites of p53 gene. RESULTS: We found a significant increase in the levels of BPDE-DNA (p < 0.01) and serum levels of p53 protein (p < 0.01) after GT, and an insignificant decrease in the percentage of 5-mC in peripheral blood DNA. Methylation of p53 CpG sites was affected neither by psoriasis nor by GT. The study confirmed good effectiveness of GT (significantly reduced psoriasis area and severity index; p < 0.001). CONCLUSION: Our findings indicate that there is a significantly increased genotoxic hazard related to the exposure of PAHs and UV radiation after GT of psoriasis. However, global DNA methylation and p53 gene methylation evade the effect of GT, as they remained unchanged (Tab. 4, Fig. 3, Ref. 50).

Goeckerman Therapy of Psoriasis: Genotoxicity, Dietary Micronutrients, Homocysteine, and MTHFR Gene Polymorphisms.

Goeckerman therapy (GT) of psoriasis vulgaris is based on the application of crude coal tar and ultraviolet radiation. We investigated DNA damage by the number of micronucleated binucleated cells (MNBC) in lymphocytes, serum homocysteine, vitamin B12, folic acid, and two polymorphisms (C677T and A1298C) in the MTHFR gene in 35 patients with exacerbated psoriasis vulgaris classified according to the psoriasis area and severity index (PASI) score and treated by GT. The median of PASI score decreased from nineteen to five, and MNBC increased from 10 to 18‰ after GT (p < 0.001 in both cases). Correlations of MNBC with homocysteine (Spearman's rho = 0.420, p = 0.012) and vitamin B12 (rho = -0.389, p = 0.021) before the therapy were observed. Hyperhomocysteinemia was an independent predictor of genotoxicity (OR 9.91; 95% CI, 2.09-55.67; p = 0.003). Homocysteine was higher in females than in males (13 vs. 12 µmol/L, p = 0.045). In contrast, vitamin B12 levels in the females were lower than in the males (160 vs. 192 pmol/L, p = 0.047). Vitamin B12 in the females were negatively influenced by smoking status (160 pmol/L in smokers vs. 192 pmol/L in non-smokers, p = 0.025). A significantly higher MNBC was found in CC homozygous patients (A1298C polymorphism) than in AC heterozygotes (32 vs. 16‰, p = 0.005) and AA homozygotes (32 vs. 18‰, p = 0.036). Our data showed that homocysteine participates in the pathogenesis of psoriasis. Its serum levels correlated with MNBC and allowed the prediction of DNA damage to appear within GT. Both micronutrients status and homocysteine metabolic pathway contribute to the genotoxicity of GT.

Serum Level of Antibodies (IgG, IgM) Against Benzo[a]pyrene-7,8-diol-9,10-epoxide-DNA Adducts in Children Dermatologically Exposed to Coal Tar.

Crude coal tar (CCT) contains polycyclic aromatic hydrocarbons (PAHs). Benzo[a]pyrene (BaP) is metabolized into a highly reactive metabolite benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) that is able to bind to DNA and creates BPDE-DNA adducts. Adducted DNA becomes immunogenic and induces immune response by production of antibodies against BPDE-DNA adducts (Ab-BPDE-DNA). Circulating Ab-BPDE-DNA was proposed as potential biomarker of genotoxic exposure to BaP (PAHs). Goeckerman therapy (GT) of psoriasis uses dermal application of CCT ointment (PAHs). In presented study (children with psoriasis treated by GT; n = 19) the therapy significantly increased the level of Ab-BPDE-DNA (EI = 0.29/0.19-0.34 vs. 0.31/0.25-0.40; median/lower-upper quartile; p < 0.01). The results support the idea of Ab-BPDE-DNA level as a possible tentative indicator of exposure, effects and susceptibility of the organism to the exposure of BaP (PAHs).

Droplet Digital PCR Analysis of GSTM1 Deletion Polymorphism in Psoriatic Subjects Treated with Goeckerman Therapy.

Goeckerman therapy (GT) represents an effective treatment of psoriasis including a combination of pharmaceutical grade crude coal tar (CCT) and ultraviolet irradiation (UV-R). Coal tar contains a mixture of polycyclic aromatic hydrocarbons. The best known carcinogenic polyaromate - benzo[a]pyrene is metabolized into a highly reactive benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE). Glutathione S-transferase M1 (GSTM1) catalyses the conjugation of drugs, toxins and products of oxidative stress with glutathione. The aim of the study is to found possible associations between GSTM1 genotypes and the level of BPDE-DNA adducts in 46 psoriatic patients treated with GT. For genotyping, droplet digital PCR was applied. The GSTM1 copy number was normalized to ß-globin reference gene. In five GSTM1*1/*1 subjects, the GSTM1 to ß-globin ratio moved from 0.99 to 1.03 with a median of 1.01. GSTM1*0/*1 heterozygotes (n = 20) contained only one GSTM1 function allele which conditioned the ratio 0.47-0.53 (median 0.50). GSTM1*0/*0 individuals (n = 21) showed no amplification of the null variants because of the large deletion in GSTM1. BPDE-DNA concentrations ranged from 1.8 to 66.3 ng/µg with a median of 12.3 ng/µg. GSTM1*0/*0 and GSTM1*0/*1 genotypes showed non-significantly higher concentrations of BPDE-DNA adducts than the GSTM1*1/*1 one (12.3 and 12.4 vs 7.8 ng/µg). The non-significant relationship between BPDE-DNA adducts and GSTM1 genotypes in psoriatic patients could be associated with relatively low doses of CCT and short-term UV-R exposures used in GT.

Psoriasis Vulgaris Successfully Treated with Goeckerman Treatment at Home: A Patient and Physician's Experience.

Goeckerman therapy is a highly effective treatment regimen for moderate-to-severe psoriasis. It involves regular exposure to ultraviolet B radiation and the application of crude coal tar. To our knowledge, only three centers in the USA currently offer a formal Goeckerman therapy treatment program; thus, access to this therapy is geographically limited. In this article, a motivated patient discusses his experience with generalized plaque psoriasis. This patient, while living in a Goeckerman-inaccessible area, deferred treatment with biologics and outpatient phototherapy to develop a modified Goeckerman regimen for at-home use. This home regimen, which did not involve the use of prescription-strength medications, resulted in full clearance of his psoriasis. We also discuss the patient's case from the perspective of a dermatology treatment team that has reviewed his experience.

The Patient's Guide to Psoriasis Treatment. Part 4: Goeckerman Therapy.

BACKGROUND: The Goeckerman regimen remains one of the oldest, most reliable treatment options for patients with moderate to severe psoriasis. Goeckerman therapy currently consists of exposure to ultraviolet B light and application of crude coal tar. The details of the procedure can be confusing and challenging to understand for the first-time patient or provider. OBJECTIVE: To present a freely available online guide and video on Goeckerman treatment that explains the regimen in a patient-oriented manner. METHODS: The Goeckerman protocol used at the University of California-San Francisco Psoriasis and Skin Treatment Center as well as available information from the literature were reviewed to design a comprehensive guide for patients receiving Goeckerman treatment. RESULTS: We created a printable guide and video resource that covers the supplies needed for Goeckerman regimen, the treatment procedure, expected results, how to monitor for adverse events, and discharge planning. CONCLUSION: This new resource is beneficial for prospective patients planning to undergo Goeckerman treatment, healthcare providers, and trainees who want to learn more about this procedure. Online media and video delivers material in a way that is flexible and often familiar to patients.