Erythema action spectrum of topical 8-methoxypsoralen-sensitized skin re-evaluated: implications for routine clinical practice.

BACKGROUND: Published methodology used to determine psoralen plus ultraviolet A (PUVA) erythemal action spectrum does not reflect current clinical practice for psoralen sensitization. We re-evaluated the PUVA action spectrum using aqueous 8-methoxypsoralen (8-MOP) 2·6 mg L(-1) as used routinely in current clinical practice. OBJECTIVES: To determine the UVA erythema action spectrum of topical 8-MOP-sensitized normal skin. METHODS: Twenty healthy volunteers with skin phototypes I-V were recruited. Forearms were psoralen-sensitized at 37 °C for 10 min. Six UVA irradiations at 10-nm intervals between 325 and 375 nm were randomly allocated to forearm sites and were applied using a 10-nm bandwidth irradiation monochromator. The visual minimal phototoxic dose (MPD) was recorded on each site at 96 h. RESULTS: Volunteer Boston phototypes were: I, n = 2; II, n = 6; III, n = 6; IV, n = 5 and V, n = 1. The mean MPD (J cm(-2) ) for all subjects at each wavelength was as follows: 325 nm, 0·64 (SD 0·37); 335 nm, 0·80 (SD 0·58); 345 nm, 0·96 (SD 0·55); 355 nm, 1·50 (SD 0·85); 365 nm, 2·19 (SD 0·90); and 375 nm, 2·89 (SD 1·06). Therefore, the relative sensitization at each wavelength (erythemal action spectrum) was: 1, 0·83, 0·67, 0·43, 0·29 and 0·22. There were significant differences between the PUVA erythemal effectiveness at different wavelengths but none between skin types. CONCLUSIONS: This study has established the erythemal action spectrum for bath/soak PUVA therapy as is currently performed. In all volunteers, the peak sensitivity was at 325 nm. All volunteers showed a similar trend across the wavelengths studied irrespective of skin type. The determination of the action spectrum for PUVA-induced erythema is important as it permits reliable estimates of erythemal efficacy of any UVA source where the emission spectrum of the lamp is known or can be measured.

Targeted ultraviolet B phototherapy: definition, clinical indications and limitations.

Targeted ultraviolet B (UVB) phototherapy is defined as UVB radiation applied only to clinically diseased skin, with sparing of adjacent normal skin, unlike conventional phototherapy, which involves irradiation of both diseased and normal skin. Targeted UVB radiation is a relatively new concept, which is now widely available because of advances in technology. Devices developed for targeted UVB phototherapy of the skin include the monochromatic excimer laser and lamp, both of which are now used by dermatologists in developed and developing countries. The aim of this review is to collate data from research studies on targeted phototherapy and to provide a concise description of currently available devices, their clinical indications and therapeutic efficacy. Additionally, potential adverse effects are summarized, and the limitations of these novel devices are highlighted.

Minimal phototoxic dose (MPD) measurements for topical photochemotherapy using a semiautomated MPD tester.

BACKGROUND: The traditional method of assessing minimal phototoxic dose (MPD) prior to photochemotherapy with psoralen-ultraviolet A (PUVA) is inconvenient and cannot directly determine PUVA start doses. A handheld minimal erythema dose UVB tester can be modified by fitting a TL-10 UVA compact fluorescence lamp (CFL). OBJECTIVES: To determine whether MPD testing is possible with a CFL and to calculate a fixed factor to convert observed MPD to PUVA-equivalent MPD. METHODS: Patients had two sets of MPD tests performed on symmetrical, contralateral sites on the lower back. MPD test results from a panel of PUVA lamps were compared with MPD from the modified handheld tester. Additionally, a questionnaire survey was completed by 43 U.K. phototherapy units to assess routine practice concerning MPD testing prior to PUVA therapy. RESULTS: Thirty-seven patients with psoriasis were recruited. Boston phototypes in the 31 with conclusive MPD reactions were: I, four; II, 11; III, 12; and IV, four. The handheld MPD results were linearly related to the PUVA panel MPD results as follows: PUVA MPD = 0·48 × handheld MPD + 0·17 J cm(-2). The measured PUVA MPD was 0·48 of the handheld MPD, not 0·15 as predicted by the published PUVA action spectrum. CONCLUSIONS: The modified MPD tester is a convenient and safe method for PUVA MPD testing, overcoming many problems of the 'traditional method'. The difference between the PUVA and TL-10 lamps was lower than predicted from published studies. This suggests that formal re-evaluation of the erythema action spectrum for PUVA is now needed.

A management algorithm for congenital erythropoietic porphyria derived from a study of 29 cases.

BACKGROUND: Congenital erythropoietic porphyria (CEP) is an autosomal recessive photomutilating porphyria with onset usually in childhood, where haematological complications determine prognosis. Due to its extreme rarity and clinical heterogeneity, management decisions in CEP are often difficult. OBJECTIVES: To develop a management algorithm for patients with CEP based on data from carefully characterized historical cases. METHODS: A single investigator collated data related to treatments and their outcomes in 29 patients with CEP from the U.K., France, Germany and Switzerland. RESULTS: Six children were treated with bone marrow transplantation (BMT); five have remained symptomatically cured up to 11.5 years post-transplantation. Treatments such as oral charcoal, splenectomy and chronic hypertransfusion were either of no benefit or were associated with complications and negative impact on health-related quality of life. Lack of consistent genotype-phenotype correlation meant that this could not be used to predict disease prognosis. The main poor prognostic factors were early age of disease onset and severity of haematological manifestations. CONCLUSIONS: A management algorithm is proposed where every patient, irrespective of disease severity at presentation, should receive a comprehensive, multidisciplinary clinical assessment and should then be reviewed at intervals based on their predicted prognosis, and the rate of onset of complications. A BMT should be considered in those with progressive, symptomatic haemolytic anaemia and/or thrombocytopenia. Uroporphyrinogen III synthase genotypes associated with poor prognosis would additionally justify consideration for a BMT. Rigorous photoprotection of the skin and eyes from visible light is essential in all patients.

Review of the 90th annual meeting of the british association of dermatologists, 6-8 july 2010, manchester, UK.

This is a synopsis of the main research and clinical findings presented at the British Association of Dermatologists meeting held during 6-8 July 2010 in Manchester, U.K. The conference highlighted the biological, epidemiological and therapeutic advances that have been made recently in the field of dermatology. This synopsis is a selection of the major findings from the meeting; it is not intended to be a substitute for reading the conference proceedings and related references quoted in this article.

Differing obstetric outcomes of rosacea fulminans in pregnancy: report of three cases with review of pathogenesis and management.

Rosacea fulminans (RF) is a rare facial dermatosis characterized by the sudden onset of severe facial inflammation consisting of numerous pustules, cystic swellings and coalescing sinuses. The standard treatment is the retinoid drug isotretinoin in combination with systemic corticosteroids or with high-dose oral tetracycline antibiotics. We report three recent cases of RF in pregnancy with differing obstetric outcomes: an intrauterine death, a termination of pregnancy, and a normal vaginal delivery. The pathogenesis of RF is considered and therapeutic options in pregnancy are reviewed.

Serum 25-hydroxyvitamin D in erythropoietic protoporphyria.

BACKGROUND: Vitamin D, produced by the action of sunlight on skin, is an important hormone for calcium homeostasis and has been implicated as tumour-protective agent. Some previous studies of photosensitive patients who actively avoid sunlight have failed to show convincing evidence of vitamin D insufficiency. OBJECTIVES: The aim of this study was to characterize the vitamin D status of a large cohort of patients with erythropoietic protoporphyria (EPP). METHODS: U.K. patients with EPP were recruited prospectively and seen locally by a single study investigator. A blood sample was taken for vitamin D assay. All blood analyses were performed in the same laboratory. RESULTS: A cohort of 201 patients with known EPP was seen over a 7-month period between January and July. Thirty-four patients (17%) were deficient in vitamin D and 126 (63%) had insufficient vitamin D. Both insufficiency and deficiency were significantly associated with the total erythrocyte protoporphyrin concentration and inversely with the time in minutes to the onset of symptoms following sunlight exposure. CONCLUSIONS: This is the first report of significant levels of vitamin D deficiency and insufficiency in a large cohort of patients with a photodermatosis. Such individuals are at risk of associated adverse events. In future, clinicians should consider monitoring 25-hydroxyvitamin D levels and instigating oral supplementation or dietary advice if appropriate.

Rate of acute adverse events for narrow-band UVB and Psoralen-UVA phototherapy.

BACKGROUND: Ultraviolet (UV) radiation therapies are commonly used to treat a wide range of dermatological conditions. However, no published data exist regarding the rate of acute adverse events occurring within the different UV therapy modalities. AIM: The aim of this study was to determine the rate of acute adverse events experienced by patients receiving narrow-band UVB or photochemotherapy in 3 neighboring dermatology units. METHOD: Standardized adverse event forms from all 3 units were retrospectively analysed over a 12-month period between October 2003 and September 2004. The treatments included were narrow-band UVB and systemic, bath and hand/foot PUVA. RESULTS: A total of 8784 treatments were given over the study period. The total number of acute adverse events recorded for all phototherapy treatments was 70 (0.8%). The rates of acute adverse events for each treatment modality were 0.6% for narrow-band UVB, 1.3% for systemic PUVA, 1.3% for bath PUVA and 0.8% for hand/foot PUVA. Adverse events were due to patient non-compliance with standard operating procedures in 15 cases (21%) and operator error in 2 (3%). Only 4 of the acute adverse events were considered to be severe, accounting for 0.05% of all treatments. CONCLUSIONS: The rates of acute adverse events with phototherapy in this analysis were low, in particular the rate of severe adverse events. The highest rate was seen with both systemic and bath PUVA. The number of adverse events resulting from operator error was low. These published rates for adverse events associated with narrow-band UVB and PUVA may help other units when analyzing their own rate of adverse events.

Validation of a semiautomated method of minimal erythema dose testing for narrowband ultraviolet B phototherapy.

BACKGROUND: The most widely used method for establishing the minimal erythema dose (MED) before narrowband ultraviolet (UV) B phototherapy is time-consuming, inconvenient and may yield inconsistent results. OBJECTIVES: To assess the equivalence of MED assessment using a filtered xenon arc lamp UV source, a semiautomated MED tester, and a UV-opaque template method of MED determination with a panel of TL-01 311-nm UVB fluorescent tubes. Secondly, to gauge the current usage of MED testing, and the method used, in a large sample of U.K. phototherapy units. Thirdly, to assess variation in UV output of the semiautomated skin tester immediately after switching on to identify optimum warm-up time. Finally, to assess reproducibility of MED testing by assessing within-patient variability and interobserver variability of MED test results. METHODS: Sixty-five patients about to undergo UVB phototherapy had their MED determined using three different methods. Within each patient we compared the values of MED determined by a semiautomated Durham MED tester, a panel of narrowband UVB lamps with a UV-opaque template constructed by a phototherapist, and a 310-nm filtered xenon arc lamp with a liquid light guide. MED test results were assessed by clinical evaluation using a 6500 K colour temperature examination lamp. The output of the semiautomated MED tester was measured by spectroradiometer over a period of 20 min in order to identify the time to steady output. Reproducibility of MED testing with the semiautomated MED tester was carried out in 25 normal volunteers. All MEDs were assessed by at least two independent observers. A postal questionnaire was sent to 78 U.K. phototherapy units to assess routine practice concerning MED testing prior to narrowband UVB phototherapy. RESULTS: The semiautomated MED tester showed consistency with the panel method (r = 0.92, panel MED = -0.57 + 1.14 x Durham MED). The semiautomated MED tester produced a slightly lower MED result than the panel MED. Reproducibility tests showed high interobserver agreement (kappa value = 0.79), and high consistency for successive day testing (kappa value = 0.79). Questionnaires were returned from 67 of 78 phototherapy units (85%) and revealed that 19 units (28%) were routinely using MED testing prior to UVB therapy. CONCLUSIONS: This study has shown the Durham MED tester to be a convenient, valid and reproducible method for determining patient MED values prior to narrowband UVB phototherapy when used under carefully controlled lighting, by experienced observers.

Modulation of ultraviolet (UV) transmission by emollients: relevance to narrowband UVB phototherapy and psoralen plus UVA photochemotherapy.

BACKGROUND: Patients with psoriasis undergoing or about to undergo ultraviolet (UV) phototherapy and photochemotherapy often have thick scale on their plaques which can prevent the penetration of UV radiation. Emollients are used to moisturize the skin and to prevent or reduce some of the milder side-effects ('dryness', itching) sometimes experienced during UV therapy. However, emollients can alter the UV transmission of skin and thus may alter the clinical effects of phototherapy and photochemotherapy. OBJECTIVES: We tested 30 of the topical emollients in the British National Formulary (BNF) using a standard in vitro technique used to test sunscreens. We also surveyed U.K. phototherapy units to establish routine practice for emollient use in phototherapy and photochemotherapy. METHODS: We used a standard in vitro technique to measure the monochromatic protection factors (MPFs) of 30 non-bath emollients from the BNF. An application rate of 2 mg cm-2 was used. For the assessment of effects during narrowband UVB (TL-01) phototherapy, the mean of the protection factors at 310 and 315 nm was calculated; for psoralen plus UVA photochemotherapy the mean UVA protection factor was used. A questionnaire survey was used to assess routine practice concerning emollient use prior to phototherapies in phototherapy units throughout the U.K. RESULTS: In the UVA range, 17 of the 30 emollients gave protection factors of 1.2 or above. In the UVB range, 23 of 30 had an MPF of 1.2 or above. Yellow soft paraffin had the highest protection factor in the UVB range. Of 78 centres surveyed, 57 returned completed questionnaires (73%). Seventeen of 57 (30%) centres routinely used emollients immediately prior to administering phototherapy treatments. The remaining 40 of 57 (70%) did not. Forty-five (79%) responding centres recommended the use of emollients after phototherapy. CONCLUSIONS: This study has revealed considerable variability in the practice of emollient use before phototherapy treatments. Although the majority of centres included in this study did not routinely use emollients, almost one third did. Our in vitro measurement of 30 emollients revealed marked variation in UV transmission, with many emollients blocking sufficient UV to affect the response to therapy.

Guidelines for prescribing azathioprine in dermatology.

Azathioprine has been available as an immunosuppressive agent for over 40 years, and current routine usage in dermatology is not restricted to licensed indications. Advances in understanding the metabolic fate of azathioprine have led to significant changes in prescribing practice and toxicity monitoring by U.K. dermatologists. The current state of knowledge concerning the use of azathioprine in dermatology is summarized, with identification of strength of evidence. Clinical indications and contraindications for azathioprine usage in dermatology are identified. Evidence-based recommendations are made for routine safety monitoring of patients treated with azathioprine, including pretreatment assessment of red blood cell thiopurine methyltransferase activity.

Rosacea fulminans in pregnancy.

Rosacea fulminans is a rare condition with a female preponderance and unknown aetiology, characterized by the abrupt onset of papules, pustules and erythema affecting the face. Corticosteroids and isotretinoin are regarded as the two main therapeutic agents. We report a case associated with pregnancy, and discuss the therapeutic implications. This is the first published report of rosacea fulminans in pregnancy complicated by stillbirth.