Psoriasis: Ibbotson SH

Ibbotson SH, Bilsland D, Cox NH, Dawe RS, Diffey B, Edwards C, Farr PM, Ferguson J, Hart G, Hawk J, Lloyd J, Martin C, Moseley H, McKenna K, Rhodes LE, Taylor DK, Anonymous00115. · Pathobiology Unit, Ninewells Hospital and Medical School, Dundee, UK. · Br J Dermatol. · Pubmed #15327535 No free full text.

Abstract: Summary These guidelines for use of narrowband (TL-01) ultraviolet B have been prepared for dermatologists by the British Photodermatology Group on behalf of the British Association of Dermatologists. They present evidence-based guidance for treatment of patients with a variety of dermatoses and photodermatoses, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of background photobiology.

Ibbotson SH. · Photobiology Unit, University Department of Dermatology, Tayside University Hospitals NHS Trust, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK. · Br J Dermatol. · Pubmed #11903225 No free full text.

Abstract: Topical 5-aminolaevulinic acid (ALA) photodynamic therapy (PDT) is used increasingly for superficial non-melanoma skin cancer (NMSC) and dysplasia. However, the relative accumulation of the photosensitizer protoporphyrin IX (PpIX) in diseased tissue is not specific for neoplastic disease, and has been shown after the application of ALA to benign proliferative skin conditions such as viral warts and psoriasis. This review appraises the quality of evidence available for the use of topical ALA-PDT in the treatment of skin conditions other than NMSC. The diseases that have been studied in most detail are recalcitrant viral warts, acne, psoriasis and cutaneous T-cell lymphoma. Publications relating to the treatment of other diseases by topical PDT are restricted to small case series or case reports. The relevant literature will be discussed and the potential for topical PDT in the treatment of several skin diseases is highlighted, although more detailed studies are required to clarify the role of PDT beyond the treatment of NMSC.

Dawe RS, Yule S, Cameron H, Moseley H, Ibbotson SH, Ferguson J. · Photobiology Unit, Department of Dermatology, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK. · Br J Dermatol. · Pubmed #16120152 No free full text.

Abstract: BACKGROUND: Dead Sea (DS) salt solution soaks are used in combination with narrowband ultraviolet B (NB-UVB) to treat psoriasis in many centres, particularly in continental Europe. No previously published controlled study has assessed DS salt + NB-UVB balneophototherapy. OBJECTIVES: To compare DS salt balneophototherapy with NB-UVB monotherapy for chronic plaque psoriasis. METHODS: Sixty patients with chronic plaque psoriasis participated in this paired, controlled study, with pretreatment DS salt soaks randomly allocated to each participant's right or left study limb. Psoriasis severity was assessed with a Scaling, Erythema and Induration score by a blinded observer. Assessments were weekly during the therapy course, and thereafter 8-weekly until relapse or for up to 1 year after clearance. RESULTS: The mean area under the psoriasis severity-time curves during treatment was not detectably lower with DS salt balneophototherapy than with NB-UVB monotherapy (P = 0.099). The psoriasis severity score fell slightly more from beginning to end of courses with DS salt balneophototherapy than with NB-UVB monotherapy (P = 0.019). There was no detectable difference in times to relapse. CONCLUSIONS: In this population the addition of pretreatment DS salt soaks to NB-UVB did not result in a clinically important improvement in clearance of psoriasis.

Dawe RS, Cameron H, Yule S, Man I, Wainwright NJ, Ibbotson SH, Ferguson J. · Department of Dermatology, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK. · Br J Dermatol. · Pubmed #12828749 No free full text.

Abstract: BACKGROUND: In 1991, consensus guidelines recommended psoralen plus ultraviolet A photochemotherapy (PUVA) for those requiring second-line therapy for psoriasis. Narrowband (TL-01) UVB has since become more widely available, replacing the less effective broadband sources. Objectives To compare the efficacy of TL-01 UVB phototherapy and trimethoxypsoralen (TMP) bath-PUVA for chronic plaque psoriasis. PARTICIPANTS AND METHODS: A randomized, observer-masked, intraindividually controlled, paired (half-body) study was done in the Photo(chemo)therapy Unit in Ninewells Hospital and Medical School, Dundee. The study comprised 28 patients (skin phototypes I-III) with chronic plaque psoriasis. Each patient's body halves (sagittal plane) were treated independently, one-half with TL-01 UVB, the other with bath-PUVA. Both treatments were administered according to standard, optimized regimens. Treatment was continued until clearance or minimal residual activity (MRA), or a maximum of 30 treatments. The main outcome measures were treatments and time to clearance/MRA, the proportion reaching clearance/MRA, change in psoriasis severity score (scaling, erythema and induration) and remission durations. RESULTS: Of 18 who completed the study, all reached clearance/MRA with TL-01, but three were still not clear after 30 PUVA exposures. TL-01 achieved clearance/MRA a median of 11 (6.5-25; P = 0.001) days more quickly than PUVA, but required a median of 24.5 compared with 19 exposures [95% confidence interval (CI) for difference 1.5-5.5; P = 0.01]. Ten patients were withdrawn (four because of inadequate response of PUVA-treated halves). Analysed on an intention-to-treat basis, 21 of 28 (75%) of all participants reached clearance/MRA with TL-01 compared with 15 of 28 (54%) with PUVA (95% CI for difference 4-37%; P = 0.03). Remission durations did not differ. CONCLUSIONS: When administered according to these regimens in a skin phototype I-III population, TL-01 UVB is more efficacious than TMP bath-PUVA in the treatment of chronic plaque psoriasis.

Smith G, Wolf CR, Deeni YY, Dawe RS, Evans AT, Comrie MM, Ferguson J, Ibbotson SH. · Biomedical Research Centre, Ninewells Hospital and Medical School, DD1 9SY, Dundee, UK. · Lancet. · Pubmed #12711469 No free full text.

Abstract: BACKGROUND: Treatment of common skin diseases such as psoriasis is complicated by differences between individuals in response to topical drug treatment and photochemotherapy. Individuality in hepatic expression of drug-metabolising enzymes is an important determinant of systemic drug handling; we investigated whether similar variation in cutaneous gene expression contributes to individuality in response to topical therapies. METHODS: We used quantitative real-time RT-PCR to demonstrate the expression in skin of a recently identified cytochrome P450, CYP2S1, in healthy volunteers (n=27) and patients with psoriasis (n=29). We also investigated regulation of CYP2S1 by ultraviolet radiation, psoralen-ultraviolet A (PUVA), and topical drugs used to treat psoriasis. FINDINGS: We found that CYP2S1 is expressed in skin and showed pronounced individuality in constitutive expression of the enzyme and its induction after ultraviolet irradiation or topical drug treatment. Cutaneous expression of CYP2S1 was induced by ultraviolet radiation, PUVA, coal tar, and all-trans retinoic acid; expression was significantly higher in lesional psoriatic skin than in adjacent non-lesional skin (geometric mean 3.38 [95% CI 2.64-4.34] times higher; p<0.0001), which implies that topical drugs are differentially metabolised in psoriatic plaque and non-lesional skin. We showed that all-trans retinoic acid is metabolised by CYP2S1, which has higher cutaneous expression than CYP26, previously described as the specific cutaneous P450 retinoic-acid-metabolising enzyme. INTERPRETATION: These findings increase our understanding of the interaction between therapeutic agents and the skin and suggest a functional role for CYP2S1 in the metabolism of topical drugs and in mediating the response to photochemotherapy in psoriasis.

Cameron H, Dawe RS, Yule S, Murphy J, Ibbotson SH, Ferguson J. · Photobiology Unit, Department of Dermatology, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, U.K. · Br J Dermatol. · Pubmed #12410709 No free full text.

Abstract: BACKGROUND: The optimum treatment frequency for narrowband (TL-01) ultraviolet B (NB-UVB) in psoriasis is not yet known. We have previously found three times weekly to be preferable to five times weekly treatment in our population. OBJECTIVES: To compare twice weekly with three times weekly NB-UVB phototherapy in chronic plaque psoriasis. METHODS: In an observer-blinded, randomized comparison, patients with chronic plaque psoriasis referred from dermatology out-patient clinics in Tayside for NB-UVB phototherapy received either twice weekly (Monday and Friday) or three times weekly (Monday, Wednesday and Friday) whole-body NB-UVB phototherapy following our standard departmental treatment protocol. Treatment was continued to clearance or until the fourth treatment after minimal residual activity (MRA) was first documented. Number of days in treatment, number of treatments, total dose and time to relapse were recorded. RESULTS: In total, 113 patients were recruited, skin phototypes I-III: 58 in the twice weekly and 55 in the three times weekly group. Forty patients in the twice weekly group reached clearance/MRA, as did 44 in the three times weekly group. It took 1.5 (95% confidence interval 1.3-1.7) times longer to reach clearance/MRA with twice weekly therapy, a geometric mean of 88 vs. 58 days (P < 0.0001). Small differences in numbers of treatments and total dose to reach clearance tended to favour three times weekly therapy, but these were not significant. CONCLUSIONS: Three times weekly NB-UVB clears psoriasis significantly faster than twice weekly treatment, and therefore is preferable for most patients.

Dawe RS, Cameron H, Yule S, Man I, Ibbotson SH, Ferguson J. · Photobiology Unit, Department of Dermatology, University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland. · Arch Dermatol. · Pubmed #12164745 links to  free full text

Abstract: OBJECTIVE: To determine if UV-B phototherapy clears psoriasis through systemic effects. DESIGN: Randomized, within-subject comparison of change in psoriasis in 3 plaques in patients attending for whole-body UV-B therapy. Change in patients' psoriasis plaques covered during UV-B treatment was compared with plaques in an untreated control group. SETTING: University hospital phototherapy unit. PATIENTS: The study population comprised 17 patients with chronic plaque psoriasis treated with UV-B and 24 psoriasis control patients awaiting UV-B phototherapy. INTERVENTIONS: Treatment with a standard 3-times weekly narrowband TL-01 UV-B regimen. Three similar plaques were randomly allocated to be covered every treatment, covered for 2 of 3 weekly treatments, and exposed to local UV-B every treatment. Similar plaques were selected in control patients (awaiting but not yet started UV-B therapy). Severity of psoriasis plaques was assessed using a scaling, erythema, and induration (SEI) scoring system. MAIN OUTCOME MEASURES: Change in SEI score of the selected plaques over the complete treatment course for UV-B-treated patients and change over 3 weeks in SEI score of plaques covered during UV-B treatment compared with that of plaques in controls. RESULTS: There was a significant (P<.001) difference in how much the SEI score changed in the 3 plaques in UV-B-treated patients. It fell by a mean of 7.6 for uncovered plaques compared with 3.2 for plaques covered during each UV-B exposure (95% confidence interval for difference, 3.0 to 5.8). In patients awaiting UV-B, SEI score of plaques fell by a mean of 0.4 over 3 weeks, compared with a mean fall of 1.4 for covered plaques in UV-B-treated patients (95% confidence interval for difference in means, 0.1 to 2.0). CONCLUSIONS: If UV-B therapy has any systemic effect capable of improving psoriasis, this effect is small and unlikely to be of clinical importance. It is insufficient to alter interpretation of findings of within-subject comparative phototherapy studies. UV-B phototherapy works for chronic plaque psoriasis through local effects.

Smith G, Wilkie MJ, Deeni YY, Farr PM, Ferguson J, Wolf CR, Ibbotson SH. · Biomedical Research Centre, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK. · Br J Dermatol. · Pubmed #17916200 No free full text.

Abstract: BACKGROUND: The melanocortin 1 receptor (MC1R) is a highly polymorphic G protein-coupled receptor. Inheritance of various MC1R alleles has been associated with a red hair/fair skin phenotype, increased incidence of skin cancer and altered sensitivity to ultraviolet (UV) radiation. OBJECTIVES: To investigate whether MC1R genotype influences erythemal sensitivity to psoralen-UVA photochemotherapy (PUVA) in patients with psoriasis and other common skin diseases. METHODS: Patients (n = 111) about to start PUVA were recruited to the study. Erythemal responses were assessed visually at 72 h and 96 h following PUVA by assessment of the minimal phototoxic dose (MPD). MC1R genotype was determined by direct sequencing. RESULTS: Inheritance of the MC1R Arg(151)Cys allele was associated with a red hair phenotype (odds ratio 25.19, P = 0.0004). In contrast, inheritance of the Val(60)Leu and Arg(163)Gln SNPs was associated with increased PUVA erythemal sensitivity (reduced MPD) 72 h following treatment in all patients (n = 111; Val(60)Leu chi(2) = 5.764, P = 0.016; Arg(163)Gln chi(2) = 5.469, P = 0.019) and in a subset of patients with psoriasis (n = 55; Val(60)Leu chi(2) = 4.534, P = 0.033; Arg(163)Gln chi(2) = 7.298, P = 0.007). Inheritance of two or more MC1R SNPs was also associated with increased PUVA erythemal sensitivity (reduced MPD) in both patient groups (n = 111; chi(2) = 8.166, P = 0.017; n = 55; chi(2) = 10.303, P = 0.016). CONCLUSIONS: Our data demonstrate that MC1R genotype influences PUVA erythemal sensitivity in patients with psoriasis and other common skin diseases.

Smith G, Ibbotson SH, Comrie MM, Dawe RS, Bryden A, Ferguson J, Wolf CR. · Biomedical Research Centre and Photobiology Unit, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK. · Br J Dermatol. · Pubmed #16882163 No free full text.

Abstract: BACKGROUND: Individuality in the expression and regulation of hepatic drug-metabolizing enzymes (DMEs) and cytoprotective (CP) genes is an important determinant of treatment response. There is increasing evidence that many DMEs and CP genes are also expressed in human skin. Responses to topical drugs used to treat common skin diseases, such as psoriasis, are unpredictable and may potentially be rationalized, at least in part, by interindividual differences in cutaneous DME and CP gene expression. OBJECTIVES: We investigated whether three topical drugs [coal tar, all-trans retinoic acid (atRA) and clobetasol 17-propionate] used in routine clinical practice modulated the expression of a variety of DME and CP genes [cytochrome P450s, glutathione S-transferases (GSTs) and drug transporters] in healthy human skin in vivo. METHODS: Healthy adult volunteers (n = 30) were invited to participate in the study. Each subject was randomly allocated to receive two of the three study chemicals and one control site application. Crude coal tar (n = 13), atRA (n = 14) or clobetasol 17-propionate (n = 10) was applied under occlusion to photoprotected buttock skin for 96 h. A vehicle control (white soft paraffin) was also applied under the same conditions at an adjacent site in all subjects. Full-thickness punch biopsies (4-mm diameter) were then taken from treated and control sites. Total RNA was extracted and reverse transcribed into cDNA, which was used as a template in subsequent real-time polymerase chain reaction analysis, where fluorescent output was directly proportional to input cDNA concentration. Triplicate measurements of skin mRNA expression were made from each sample, and the arithmetic mean values taken. After logarithmic transformation, the paired t-test was used to compare values between treated and control skin. RESULTS: Cytochrome P450s CYP1A1, CYP1A2, CYP1B1, CYP2C18, quinone reductase (NQO-1), GSTP1, gamma-glutamyl cysteine synthetase (gamma-GCS), glutathione peroxidase-1 (GPx-1), cyclooxygenase-2 (COX-2) and haem oxygenase-1 (HO-1) were induced by coal tar; CYP26, NADPH P450 reductase (CPR), GSTP1 and HO-1 by atRA; and CYP3A5 by clobetasol 17-propionate. In contrast, CYP1A1 and CYP1A2 expression was suppressed by atRA, and gamma-GCS and MRP1 by clobetasol 17-propionate. Marked interindividual variation in gene regulation by topical drugs was seen for the majority of genes examined. CONCLUSIONS: These data demonstrate that topical drugs can modulate DME gene expression in human skin in vivo and indicate that variation in the expression and regulation of these genes may be a determinant of individuality in response to topical therapies for common skin diseases.

Beattie PE, Dawe RS, Ferguson J, Ibbotson SH. · No affiliation provided · Clin Exp Dermatol. · Pubmed #15347356 No free full text.

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Smith G, Dawe RS, Clark C, Evans AT, Comrie MM, Wolf CR, Ferguson J, Ibbotson SH. · Biomedical Research Center, Photobiology Unit, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK. · J Invest Dermatol. · Pubmed #12880432 links to  free full text

Abstract: There are unpredictable inter-individual differences in response to ultraviolet radiation, used in the treatment of psoriasis and other common skin diseases. It is therefore essential that we attempt to identify phenotypic markers that correlate with individual treatment outcomes. Exposure of human skin to ultraviolet radiation results in the generation of reactive intermediates and oxidative stress. Hepatic drug metabolizing and cytoprotective genes are induced as an adaptive response to xenobiotics and reactive intermediates; as several of these genes are present in skin, we hypothesized that their cutaneous expression and regulation may be implicated in responses to ultraviolet radiation. We used quantitative real-time reverse transcription-polymerase chain reaction to investigate interindividual differences in the cutaneous expression of a variety of drug metabolizing and cytoprotective genes, including cytochrome P450s, glutathione S-transferases and drug transporters, and investigated the regulation of gene expression by ultraviolet radiation and in lesional psoriatic skin. We confirmed significant induction of cyclooxygenase 2 (mean 3.63-fold, range 0.14-22.6, p<0.0001) by ultraviolet radiation and showed more modest (approximately 2-fold) inductions of glutathione peroxidase, and novel inductions of glutathione S-transferase P1 and the drug transporter multidrug resistance associated protein-1. Glutathione S-transferase P1 (3.74-fold, 1.3-33.1, p<0.0001) and multidrug resistance associated protein-1 (4.06-fold, 1.3-24.8, p<0.0001) were also significantly increased in psoriatic plaque, as were P450 CYP2E1 (3.64-fold, 1-28.9 p<0.0001) and heme oxygenase-1 (10.19-fold, 2.9-49.7, p<0.0001), implying a differential adaptive response to oxidant exposure in lesional psoriatic skin. We found considerable interindividual variation in constitutive gene expression and inducibility, indicating that these genes may be associated with individuality in response to ultraviolet radiation.

Ibbotson SH, Dawe RS, Farr PM. · Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne, UK. · J Invest Dermatol. · Pubmed #11348476 links to  free full text

Abstract: There is considerable interindividual variation in bioavailability of Methoxsalen (8-methoxypsoralen) after ingestion of the standard dose used in photochemotherapy (psoralen plus ultraviolet A). A dose change may be used to alter the degree of photosensitivity, although there is limited information on the effect of 8-methoxypsoralen dose alterations on phototoxicity within individuals. We studied the effect of changes of 8-methoxypsoralen dose over a narrow range in 15 subjects with psoriasis. Two hours after ingestion, serum 8-methoxypsoralen concentration was determined and phototesting was performed at 350 +/- 30 nm (0.45-14 J per cm2). The minimal phototoxic dose at 72 h was recorded, erythema was measured using a reflectance instrument, and dose-response curves were constructed. Each subject was tested on three occasions using doses of 25 mg per m2 (conventional dose) or conventional dose +/- 10 mg. Median serum 8-methoxypsoralen concentration increased from 96 to 143 to 229 ng per ml with dose increases from conventional dose - 10 mg to conventional dose and conventional dose + 10 mg, respectively (p < 0.001). The median minimal phototoxic dose and D0.025 (the objective equivalent of the minimal phototoxic dose derived from the dose-response curve) were significantly reduced with increasing 8-methoxypsoralen dose from conventional dose minus 10 mg (minimal phototoxic dose 1.7 J per cm2; D(0.025) 2.8 J per cm2) to conventional dose (1.2; 1.4 J per cm2) and conventional dose plus 10 mg (0.9; 1.0 J per cm2) (p < 0.001). Change in 8-methoxypsoralen dose had no detectable effect on the maximum slope of the psoralen plus ultraviolet A erythema dose-response curve. Thus, 8-methoxypsoralen dose changes within individuals, over a narrow but clinically relevant range, significantly altered the threshold response to psoralen plus ultraviolet A erythema but not the rate of increase in erythema with increasing ultraviolet A dose.