Cholestasis-induced pruritus treated with ultraviolet B phototherapy: an observational case series study.

BACKGROUND & AIMS: Pruritus is a disabling complication of cholestatic liver disorders. Its management remains challenging. Ultraviolet B (UVB) phototherapy has been successfully used to treat pruritus in other indications. METHODS: This is an observational case series. The study population consists of 13 patients (10 females, mean age 52 years) with pruritus due to different cholestatic liver disorders: PBC (n=4), PSC (n=2), drug-induced (n=3) and persistent cholestasis after liver transplantation (LT) (n=4). Serum alkaline phosphatase levels were: 686 ± 363 µ/L and serum bile acids levels: 147 ± 15 µmol/L. In all patients, conventional medical treatment had failed to control pruritus. Perception of pruritus was recorded by the visual analogue scale (VAS). RESULTS: The mean follow-up was 3 years. Ten patients (77%) had more than 60% reduction in perceived pruritus of which 4 had more than an 80% reduction. Median [25-75% percentiles] VAS score before and after treatment decreased from 8.0 [8.0-10] to 2.0 [1.5-2.1] (p<0.001). The mean number of irradiations required to obtain this effect was 26 ± 17 (average duration of phototherapy: 8 weeks). No significant changes in cholestatic serum markers were observed. Four patients (30%) needed an additional phototherapy course because of recurrent pruritus and in all of them again a marked improvement of pruritus was observed. The therapy was well tolerated, except in two patients who developed, during retreatment, pronounced erythema in one case and paresthesia in the other case. CONCLUSIONS: UVB phototherapy appears to be a promising and well tolerated treatment also for cholestasis-associated pruritus.

Real-life practice study of the clinical outcome and cost-effectiveness of photodynamic therapy using methyl aminolevulinate (MAL-PDT) in the management of actinic keratosis and basal cell carcinoma.

Clinical trials have shown that photodynamic therapy using methyl aminolevulinate (MAL-PDT) is an effective treatment for actinic keratosis (AK), and nodular and superficial basal cell carcinoma (nBCC and sBCC) unsuitable for other available therapies. Economic evaluation models have shown that it is a cost effective intervention as well. The objectives of this prospective, observational, one arm study were (i) to verify in a real-life practice study the results obtained in previous clinical trials with MAL-PDT in the treatment of AK, nBCC and sBCC; (ii) to calculate the real-life cost of treatment and validate predictions from an economic evaluation model. Patients with AK and/or BCC were selected according to Belgian reimbursement criteria for treatment with MAL-PDT. Clinical response, cosmetic outcome and tolerability were assessed. MAL-PDT cost was calculated and compared to published model cost data. Data were collected from 247 patients (117 AK, 130 BCC). A complete clinical response was obtained for 83% of AK (85/102) and BCC (97/116) patients. A good or excellent cosmetic outcome was obtained for 95% of AK patients and 93% of BCC patients. Tolerability was good: only 2 patients withdrew for adverse events. Clinical results were similar to previous studies. Total cost of care per patient was euro 381 for AK, euro 318 for nBCC, and euro 298 for sBCC. Total cost per lesion was euro 58 for AK (identical to model prediction), euro 316 for nBCC and euro 178 for sBCC (both within 20% of model prediction). The clinical results of MAL-PDT in this real-life practice study confirm those demonstrated in previous clinical trials. Costs calculated from this study confirm predicted cost-effectiveness in the original model for MAL-PDT in the management of AK and BCC.

Topical methyl aminolaevulinate photodynamic therapy versus cryotherapy for superficial basal cell carcinoma: a 5 year randomized trial.

This multicentre, randomized study compared photodynamic therapy using topical methyl aminolaevulinate (MAL PDT), a non-invasive modality, with cryotherapy for treatment of superficial basal cell carcinoma. Sixty patients with 114 lesions were treated with MAL cream (160 mg/g) applied for 3 hours before illumination (570-670 nm, light dose 75 J/cm) (1 session), and 58 with 105 lesions received cryotherapy (2 freeze-thaw cycles). Patients with an incomplete response at 3 months received 2 further MAL PDT sessions (n = 20) or repeat cryotherapy (n = 16). 100 lesions treated with MAL PDT and 93 lesions treated with cryotherapy were in complete response at 3 months after the last treatment and evaluable for recurrence over 5 years. There was no difference in 5-year recurrence rates with either treatment (20% with cryotherapy vs. 22% with MAL PDT, p = 0.86). However, more patients had an excellent cosmetic outcome with MAL PDT (60% vs. 16% with cryotherapy, p = 0.00078). These results provide support for the use of MAL PDT as a non-invasive, selective treatment alternative for primary superficial basal cell carcinoma.

Allergic and photoallergic contact dermatitis from ketoprofen: results of (photo) patch testing and follow-up of 42 patients.

BACKGROUND: Photoallergic contact dermatitis from topical ketoprofen (KP), a nonsteroidal anti-inflammatory agent, is a well-known side effect. OBJECTIVES: To investigate photo-contact allergic reactions to KP and other nonsteroidal anti-inflammatory drugs (NSAIDs), sunscreens, and fragrance components as well as the presence of prolonged photosensitivity related to it. PATIENTS/METHODS: From June 1993 to June 2007, 42 patients were patch tested and photopatch tested with the ingredients of a KP preparation and other relevant substances. A questionnaire was performed in order to determine the importance of prolonged photosensitivity; 40/42 did respond. RESULTS: 38 patients showed photo-contact reaction, 1 photoaggravated reaction, and 3 contact allergic (CA) reaction to KP. Simultaneous photo-contact allergic reactions were frequently observed not only to structurally related but also to non-structurally related NSAIDs and sunscreens. Simultaneous CA to fragrance components was common. 1/3 of the patients reported prolonged photosensitivity, i.e. from 1 up to 14 years after having stopped KP application. CONCLUSIONS: The history is often not a good guidance to determine KP-related (photo) allergic contact dermatitis and the severe clinical symptoms sometimes require hospitalization, and/or systemic corticosteroids. As for the association between KP and sunscreen intolerance (being 1 of the possible causal factors for recurrent dermatitis), routine standard photopatch testing with KP might be indicated.

Guidelines on the use of photodynamic therapy for nonmelanoma skin cancer: an international consensus. International Society for Photodynamic Therapy in Dermatology, 2005.

Topical photodynamic therapy (PDT) is used to treat nonmelanoma skin cancers, such as actinic keratoses, Bowen's disease, and basal cell carcinoma (superficial and nodular). This article presents up-to-date, practical, evidence-based recommendations on the use of topical PDT using 5-aminolevulinic acid or methyl aminolevulinate for the treatment (and prevention) of nonmelanoma skin cancers. A systematic literature review was conducted (using MEDLINE), and recommendations were made on the basis of the quality of evidence for efficacy, safety/tolerability, cosmetic outcome, and patient satisfaction/preference. Topical PDT is highly effective in the treatment of actinic keratoses, Bowen's disease, superficial and thin nodular basal cell carcinomas, with cosmesis typically superior to that achieved with existing standard therapies. PDT may also be a means of preventing certain nonmelanoma skin cancers in immunosuppressed patients.

Effect of vehicles and esterification on the penetration and distribution of hypericin in the skin of hairless mice.

To study the in vivo penetration and skin distribution of hypericin, the compound (0.1%) was formulated in 10 different vehicles that are commonly used in pharmaceutical compounding, and applied on the skin of hairless mice for 4h. After application of hypericin in PEG ointment, white petrolatum or unguentum emulsificans, fluomicroscopic analysis of skin sections revealed penetration to be confined to the stratum corneum. On the contrary, Beeler base, unguentum sorbatis 100 and cremor non ionicus caused penetration of hypericin in the viable epidermis. To reduce the prominent depot formation in the stratum corneum, which was observed irrespectively of the formulation applied, hypericin was esterified into its hydrolyzable acetate derivative. The influence of esterification proved to be substantial when hypericin acetate (0.15%) was incorporated in unguentum sorbatis 100, as hypericin-related fluorescence could be detected deeply within the dermis. Moreover, accumulation in the sebaceous glands was found to be prominent. These results indicate the value of further studies regarding the application of hypericin and hypericin acetate as topical photosensitizers for photodynamic therapy.

Influence of application and formulation factors on the penetration of hypericin in normal mouse skin and UV induced skin tumors.

Hypericin, a naturally occurring photosensitizer, is currently being investigated for topical use in photodynamic therapy (PDT). In a previous study, it was found that hypericin can be delivered in the epidermis of hairless mouse skin after a 4-h application in Beeler base. With the intention to further optimize the penetration conditions, the present study examines the effect of the concentration of hypericin in the cream, the application time, the presence of penetration enhancers and occlusion on the penetration of hypericin in the skin of hairless mice. Experiments with different hypericin concentrations and application times indicated that application of 0.1% hypericin for 12-24 h maximizes the accumulation of hypericin-related fluorescence in the skin, as estimated by fluorescence microscopy with image analysis. Depending on the formulation, the use of an occlusive dressing did not alter, or even reduced the accumulation of hypericin in the viable layers. Also, the addition of propylene glycol (30%) and oleic acid (5%) did not change hypericin fluorescence levels in the epidermis. Conversely, incorporation of ethanol (40%, integrated in a gel, and added to Beeler base) increased dramatically the fluorescence levels in all skin layers. Consequently, the optimized conditions were used to investigate the penetration of hypericin into UV induced skin tumors. It was found that application under occlusion of hypericin, formulated in the gelcream containing ethanol, during 24 h enabled the penetration of hypericin in the entire skin lesions with a relatively homogenous distribution. In conclusion, our results suggest the possible use of 0.1% hypericin in a gelcream containing ethanol for PDT of skin lesions.

Protection from visible light by commonly used textiles is not predicted by ultraviolet protection.

Interest is increasing in the prevention of acute and chronic actinic damage provided by clothing. This interest has focused mainly on protection against ultraviolet irradiation, but it has now also turned to protection against visible light. This change is mainly due to the action spectrum in the visible light range of some photodermatoses and the increasing interest in photodynamic therapy. The ultraviolet protection provided by commercially available textiles can be graded by determining an ultraviolet protection factor. Several methods have already been used to determine the ultraviolet protection factor. The fact that protection from visible light by textiles cannot be predicted by their ultraviolet protection makes the situation more complicated. This study attempts to determine whether or not the ultraviolet protection factor value of a particular textile is a good parameter for gauging its protection in the visible light range and concludes that a protection factor of textile materials against visible light needs to be developed. This development should go beyond the protection factor definition used in this article, which has some limitations, and should take into account the exact action spectrum for which the protection is needed.

Topical treatment of disseminated superficial actinic porokeratosis with hypericin-photodynamic therapy: a case report.

Hypericin is a photo-active dye originating from the St. John's wort. Two patients with disseminated superficial actinic porokeratosis (DSAP) were treated with photodynamic therapy (PDT) using topical hypericin. Although a partial response was obtained in one patient topical hypericin-PDT does not emerge as a promising treatment for DSAP.

Porphyria cutanea tarda and liver disease. A retrospective analysis of 17 cases from a single centre and review of the literature.

BACKGROUND/AIMS: Sporadic Porphyria Cutanea Tarda (sPCT) is associated with liver disease, e.g. HCV infection, haemochromatosis and especially alcoholic liver disease. We conducted a retrospective analysis on the prevalence of liver disorders in association with Porphyria Cutanea Tarda (PCT), in a university referral centre. METHODS: The PCT cases were retrieved from computerized databases. Patient files lacking information on the presence of concomitant liver disease were excluded from further analysis. RESULTS: 29 PCT patients were retrieved from our databases, of which 17 patients with sPCT were retained for further analysis. Patients were middle aged (mean age: 43 +/- 3) and there was no gender difference (10 males vs. 7 females). Almost all patients had iron overload (14/17). 5 patients had chronic HCV, with type 1b in 3 of them, 7 abused alcohol, 4 patients had hereditary haemochromatosis (3 homozygous C282Y--1 heterozygous H63D/C282Y). In 3 patients sPCT was associated with medication intake and one patient had chronic hepatitis B (HBV). 13 patients were treated with phlebotomies, with success in 11/13. 4 patients were treated with chloroquine, 3 of which also underwent phlebotomies. Of the 5 patients with HCV, 3 were successfully treated with combined antiviral therapy; one of them is planned to be treated; one patient never received therapy and was lost from follow-up. One patient developed hepatocellular carcinoma (HCC) during a median follow-up of 24 years. CONCLUSIONS: We found a significant association between sPCT and liver disorders, such as chronic HCV infection, alcohol abuse, iron overload and hereditary haemochromatosis. Therefore, patients presenting with PCT should be screened for concomitant liver disease. Iron overload is present in a majority of patients, the majority of patients can be successfully treated with phlebotomies. The risk of developing HCC in our sPCT patients and in literature is low.

The history of phototherapy: something new under the sun?

Phototherapy has a very long, albeit mostly anecdotal history. Real interest in the use of ultraviolet irradiation in the treatment of various diseases started in the 19th century and reached a climax when Niels Finsen received the Nobel Prize in 1903 for his therapeutic results with lupus vulgaris. This marked the start of modern phototherapy. It was used in thermal stations for treatment of tuberculosis, in the treatment of leg ulcers in wartime, and in the treatment of skin diseases. This article reviews the history of a treatment modality that greatly changed modern dermatologic treatment, although it is as old as mankind.

Photo(chemo) therapy for vitiligo.

Vitiligo has always been difficult to treat. Several modes of treatment are available, but the therapeutic effect varies greatly, and rarely does one achieve complete repigmentation. One of the most efficient treatment methods is photo(chemo) therapy. Already in ancient Egypt, vitiligo lesions were treated with extracts of the Ammi maius plant followed by exposure to the sun. This principle is at the basis of the photochemotherapy or PUVA therapy, whereby UVA irradiations are given 2 h after administration of 8-methoxypsoralen, a photosensitizer. Another efficient treatment form is UVB phototherapy, particularly narrow-band UVB. This not only gives good therapeutic results but also has the advantage of eliminating the need for a photosensitizer. All these treatments must be applied for many months to be efficient. They can also be combined with various surgical skin-grafting techniques. A newer approach is targeted UVB phototherapy, whereby xenon-chloride lasers or monochromatic excimer light is used.

Diagnosis and treatment of solar urticaria.

Solar urticaria is one of the most annoying of the photodermatoses. It can be difficult to diagnosis because of phototesting problems, and it is not easy to treat. The different treatment modalities available all have their practical problems, so it is difficult to provide the patient with adequate protection. In many patients, however, treatment can reduce the symptoms and allow regular exposure of the skin to natural sunlight as the skin becomes more tolerant to the provoking wavelengths, the result being more complete protection.