Psoriasis: Farr PM

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.

Das S, Lloyd JJ, Walshaw D, Diffey BL, Farr PM. · Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP, U.K. · Br J Dermatol. · Pubmed #12410708 No free full text.

Abstract: BACKGROUND: Sunbeds fitted with conventional ultraviolet (UV) A lamps that have about 0.7% UVB emission are widely used by patients with psoriasis even though they are minimally effective. A new fluorescent sunbed lamp has been developed that emits a higher proportion of UVB (4.6%) than conventional lamps and also requires shorter exposure times to achieve equivalent erythema. OBJECTIVES: To perform a randomized, within-patient comparison of conventional sunbed lamps (Cleo Performance) with the new lamps (Cleo Natural) in the treatment of psoriasis. METHODS: A sunbed and canopy unit were modified to allow exposure to Cleo Performance lamps on one side of the body (front and back) and Cleo Natural lamps to the other side of the body. Two studies were done. In study 1, equal erythemal doses were given from the two lamp types. In study 2, equal exposure times were given. We treated 34 patients with psoriasis, giving 12 exposures over a period of 4 weeks. Assessment was made using a modified Psoriasis Area and Severity Index (PASI) score, individual plaque assessment and patient questionnaire. RESULTS: Fourteen patients completed each study. In study 1, there was no significant difference in median improvement in half-body PASI score for the two lamp types. In study 2, there was a significant difference in PASI score improvement between the two lamps (median Cleo Performance change minus median Cleo Natural change was - 2.20; 95% confidence interval - 3.75 to - 0.65; P = 0.006). CONCLUSIONS: That no difference in response was found when equal erythemal doses were given suggests that the spectral emission of the Cleo Natural lamp is of no greater advantage for clearance of psoriasis than conventional lamps. However, the Cleo Natural lamps are more erythemally powerful, and exposure times similar to those used in conventional sunbeds result in a significant improvement of psoriasis. The risk of non-melanoma skin cancer from different patterns of exposure to Cleo Natural lamps can be estimated using established numerical models.

Reynolds NJ, Franklin V, Gray JC, Diffey BL, Farr PM. · Department of Dermatology Medical School, Framlington Place, University of Newcastle upon Tyne, NE2 4HH, UK. · Lancet. · Pubmed #11438134 No free full text.

Abstract: BACKGROUND: Narrow-band ultraviolet B (UVB) is an effective treatment for psoriasis, and open studies suggest that this phototherapy might improve atopic eczema. We did a randomised controlled trial to compare narrow-band UVB, UVA, and visible light phototherapy as second-line, adjunctive treatments in adult patients with moderate to severe atopic eczema. METHODS: Phototherapy was administered twice a week for 12 weeks. 26 patients were randomly assigned narrow-band UVB, 24 were assigned UVA, and 23 visible fluorescent light. The primary endpoints were change in total disease activity (sum of scores at six body sites) and change in extent of disease after 24 treatments compared with baseline. Data were analysed by the method of summary measures. FINDINGS: 13 patients withdrew or were excluded from analysis. Mean reductions in total disease activity over 24 treatments in patients who received narrow-band UVB and UVA, respectively, were 9.4 points (95% CI 3.6 to 15.2) and 4.4 points (-1.0 to 9.8) more than in patients who received visible light. Mean reductions in extent of disease after 24 treatments with narrow-band UVB and UVA were 6.7% (1.5 to 11.9) and -1.0% (-5.3 to 3.3) compared with visible light. A small proportion of patients developed erythema after phototherapy or had a flare in their eczema sufficient to withdraw from treatment. INTERPRETATION: Narrow-band UVB is an effective adjunctive treatment for moderate to severe atopic eczema, and the treatment is well tolerated by most patients.

Turner RJ, Walshaw D, Diffey BL, Farr PM. · Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP, U.K. · Br J Dermatol. · Pubmed #11069502 No free full text.

Abstract: BACKGROUND: Ultraviolet (UV) A sunbeds are widely used by patients with psoriasis in an attempt to treat their skin disease. However, there is little evidence that UVA therapy improves psoriasis, and the long-term risks of sunbed exposure are not known. OBJECTIVES: To perform a randomized, placebo-controlled study of UVA sunbed therapy for psoriasis. METHODS: A sunbed and canopy unit was modified to allow UVA exposure on one side of the body (front and back), and 'placebo' visible light exposure on the other side of the body. We treated 38 patients with psoriasis, giving 12 exposures over a period of 4 weeks. Assessment was made using a modified Psoriasis Area and Severity Index (PASI) score, individual plaque assessment and patient questionnaire. RESULTS: In 17 patients (47%) the PASI score showed a greater reduction on the UVA side compared with placebo, in 11 patients (31%) no difference was recorded between the two sides, and in eight (22%) the improvement was greater on the placebo-treated side. Overall, the median pretreatment half-body modified PASI score was 4.4 units, reducing to 3.9 units on the UVA-treated side and 4.2 units on the placebo-treated side (P = 0. 044 for difference in response). Breakdown of the plaque score into the individual components of erythema, scale and thickness revealed significant improvement only with the score for erythema. Although the degree of improvement was small, 64% of patients felt that the response was sufficiently good that they would use a sunbed again to treat their psoriasis. CONCLUSIONS: Our results show that a short course of sunbed treatment does improve psoriasis in some patients, but that the degree of improvement is small.

Gordon PM, Diffey BL, Matthews JN, Farr PM. · Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom. · J Am Acad Dermatol. · Pubmed #10534635 No free full text.

Abstract: BACKGROUND: Although PUVA treatment of psoriasis is more effective than conventional or broad-band UVB phototherapy, two small studies have suggested that narrow-band or TL-01 phototherapy may have a therapeutic effect equal to PUVA. If confirmed, this would be of considerable importance as TL-01 therapy is likely to be considerably safer in the long term than PUVA. OBJECTIVE: The purpose of this study was to compare PUVA with narrow-band (TL-01) phototherapy in psoriasis. METHODS: We studied 100 patients with plaque-type psoriasis who were randomly allocated to twice-weekly treatment with PUVA or narrow-band UVB. RESULTS: Clearance of psoriasis was achieved in a significantly greater proportion of patients treated with PUVA (84%) than with TL-01 (63%) (P =.018), and with significantly fewer treatments (median number of treatments for clearance with PUVA, 16.7; with TL-01, 25.3; P =.001). Only 12% of those treated with TL-01 were clear of psoriasis 6 months after finishing treatment compared with 35% for PUVA (P =.002). CONCLUSION: When given twice weekly, PUVA is more effective for psoriasis than narrow-band UVB phototherapy.

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.

Diffey BL, Farr PM. · Department of Medical Physics, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE, UK. · Br J Dermatol. · Pubmed #17553037 No free full text.

Abstract: BACKGROUND: The use of narrowband ultraviolet (UV) B phototherapy to treat psoriasis and other disorders has increased markedly since the TL-01 lamps were introduced in the 1980s. While broadband UVB phototherapy has generally been considered to be a relatively safe treatment, some concern has been raised about the potential increased skin cancer risk with narrowband UVB. OBJECTIVES: The likelihood of a patient who is free of nonmelanoma skin cancer (NMSC) at the start of phototherapy developing a malignancy after a certain follow-up period will be dependent not only on the carcinogenic potential of the treatment but also on the age-conditional probability of natural occurrence. We were interested to explore the potential difficulty of designing studies to separate these two events. Methods Mathematical models were developed that combined age-conditional probabilities of developing NMSC due to natural causes with the risk of inducing these cancers from narrowband UVB phototherapy in order to estimate the excess number of cancers resulting from this therapeutic intervention in a cohort of patients. RESULTS: Within-department studies will be most unlikely to demonstrate that the number of NMSCs observed in follow-up studies is significantly different from that expected in an untreated population, even for a follow-up period of 20 years. CONCLUSIONS: Determination of the carcinogenic potential associated with narrowband UVB will require large multicentre studies typically involving several thousand new patients per year and followed up for 10 years or more.

Kirke SM, Lowder S, Lloyd JJ, Diffey BL, Matthews JN, Farr PM. · Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne, UK. · J Invest Dermatol. · Pubmed #17380117 links to  free full text

Abstract: UVB is widely used to treat psoriasis. Conventional broadband UVB lamps are less effective than narrowband UVB lamps, which have an emission peak at 311 nm. The long-term safety of narrowband UVB phototherapy is uncertain. "Selective" broadband UVB lamps, which have little emission <290 nm, are also available, but have not been adequately compared to narrowband UVB lamps. We performed a randomized comparison of narrowband UVB (TL-01 lamps) and selective broadband UVB (UV6 lamps) in 100 patients with psoriasis. The median number of exposures for clearance was 28.4 for TL-01 and 30.4 for UV6 (ratio of the medians 0.93; 95% confidence interval (CI) 0.80, 1.09; P=0.39). No significant difference was found in the proportion of patients achieving clearance: TL-01 56%, UV6 40% (odds ratio for clearance with TL-01 relative to UV6 was 2.00 (95% CI 0.87, 4.62), P=0.10). Side effects, including the development of erythema during phototherapy, were similar for the two lamp types. Risk estimates based on the human photocarcinogenesis action spectrum predict that narrowband UVB lamps will be 50% more carcinogenic for equal erythemal doses than selective broadband lamps (UV6). As these two lamp types appear to be of similar efficacy, phototherapy using a selective broadband source may be a safer option than use of narrowband UVB.

Das S, Lloyd JJ, Farr PM. · Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne, UK. · J Invest Dermatol. · Pubmed #11710951 links to  free full text

Abstract: Psoriasis may be treated with ultraviolet B from lamps that have a broad emission spectrum or, more effectively, with lamps that have a narrow emission spectrum at 311 +/- 2 nm. There are conflicting reports of either greater or lesser burning episodes with narrow-band compared to broad-band ultraviolet B, even when treatments are based on predetermined minimal erythema dose measurements. This suggests that either the characteristics of the dose-response curve for erythema or the time course for erythema may be different for the two lamps. We examined the erythemal response to narrow-band and broad-band ultraviolet B in 12 patients with psoriasis. A geometric series of 10 doses from each lamp type were used on nonlesional skin on the back. Dose-response curves were constructed from reflectance measurements of erythema at 24 h and 72 h after irradiation. No significant difference was found in steepness of the erythema dose-response curve for the two lamps at 24 or 72 h. Persistence of erythema was assessed as the percentage of erythema remaining at 72 h. The mean persistence was 63% for narrow-band and 64% for broad-band lamps (p = 0.94). Therefore, in terms of erythemal response, no evidence has been found for a difference in burning potential for the two lamps.

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.

Turner RJ, Sviland L, Charlton F, Farr PM. · Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom. · J Am Acad Dermatol. · Pubmed #10688720 No free full text.

Abstract: BACKGROUND: We have observed, in patients undergoing high-dose PUVA treatment, a type of keratosis not previously described. The lesions usually occur on the sides of the palms or soles and are clinically distinct. They are generally painless and often go unnoticed by patients. OBJECTIVE: We sought to further characterize these lesions both clinically and histologically. METHODS: Patients attending a PUVA clinic were screened for these keratoses. Other PUVA-related complications were recorded. Representative lesions were photographed, and biopsy specimens were taken. RESULTS: Biopsy specimens were taken from lesions in 10 patients. All had plaque psoriasis and had received high UVA doses (>1000 J/cm(2)) through PUVA therapy. All patients had PUVA-induced keratoses elsewhere, but the number varied greatly between patients. The hand and foot keratoses were well defined and circular and had a characteristic histologic appearance, with a sharp demarcation between normal and abnormal markedly pale-staining epidermis. CONCLUSION: These lesions are a further cutaneous manifestation of prolonged PUVA therapy.

Halpern SM, Anstey AV, Dawe RS, Diffey BL, Farr PM, Ferguson J, Hawk JL, Ibbotson S, McGregor JM, Murphy GM, Thomas SE, Rhodes LE. · Dermatology Unit, University Clinical Departments, University of Liverpool, Liverpool L69 3GA, UK. · Br J Dermatol. · Pubmed #10651690 No free full text.

Abstract: Psoralen photochemotherapy [psoralen ultraviolet A (PUVA)] plays an important part in dermatological therapeutics, being an effective and generally safe treatment for psoriasis and other dermatoses. In order to maintain optimal efficacy and safety, guidelines concerning best practice should be available to operators and supervisors. The British Photodermatology Group (BPG) have previously published recommendations on PUVA, including UVA dosimetry and calibration, patient pretreatment assessment, indications and contraindications, and the management of adverse reactions.1 While most current knowledge relates to oral PUVA, the use of topical PUVA regimens is also popular and presents a number of questions peculiar to this modality, including the choice of psoralen, formulation, method of application, optimal timing of treatment, UVA regimens and relative benefits or risks as compared with oral PUVA. Bath PUVA, i.e. generalized immersion, is the most frequently used modality of topical treatment, practised by about 100 centres in the U.K., while other topical preparations tend to be used for localized diseases such as those affecting the hands and feet. This paper is the product of a recent workshop of the BPG and includes guidelines for bath, local immersion and other topical PUVA. These recommendations are based, where possible, on the results of controlled studies, or otherwise on the consensus view on current practice.

Farr PM, Diffey BL. · No affiliation provided · Photodermatol Photoimmunol Photomed. · Pubmed #16436182 No free full text.

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