Ultrastructural changes in PAM cells after photodynamic treatment with delta-aminolevulinic acid-induced porphyrins or photosan.

Photodynamic therapy (PDT) is the combination of a photosensitizing drug (Ps) with light in the presence of oxygen leading to the generation of reactive molecular species and destruction of cancer cells. In this study we compared PDT with two Ps, the hematoporphyrin derivative Photosan (Ph) and delta-aminolevulinic acid (ALA)-induced endogenous protoporphyrin IX, with respect to mitochondrial function and ultrastructural alterations. The effects of PDT were investigated in PAM 212 cells after different Ps incubation times, light doses, and post-treatment periods. Both Ps induced a light dose-dependent impairment of the mitochondrial function with the dose-response curve being steep for ALA and flat for Ph. The prolongation of the incubation time from 4 to 20 h resulted in an increased reduction of mitochondrial activity after ALA PDT but not after Ph PDT. Treatment with an irradiation dose that decreased mitochondrial activity by 50% (IC50) led to early and profound changes of mitochondrial morphology in ALA photosensitized cells, whereas photosensitization with Ph resulted in more pronounced alterations of lysosomes. We conclude that at bioequivalent sublethal PDT exposures of PAM 212 cells, ALA-induced damage is primarily restricted to mitochondria, whereas Ph-induced cytotoxicity is mediated by damage of the lysosomal system.

Narrowband UV-B phototherapy vs photochemotherapy in the treatment of chronic plaque-type psoriasis: a paired comparison study.

OBJECTIVE: To compare the therapeutic efficacy of narrowband (TL-01) UV-B phototherapy vs photochemotherapy (psoralen-UV-A [PUVA]) in patients with chronic plaque-type psoriasis. DESIGN: Open, nonrandomized, intraindividually controlled paired comparison study. SETTING: Phototherapeutic unit in a university hospital. PATIENTS: Twenty-five patients with chronic plaque-type psoriasis. INTERVENTIONS: Paired irradiations with threshold erythemogenic doses of narrowband UV-B and PUVA were given to the patients' dorsal aspect including the arms and legs. Treatment was performed 3 times weekly until complete or almost complete clearing with one or both regimens or over a maximum period of 18 exposures. MAIN OUTCOME MEASURES: Assessment of the Psoriasis Area and Severity Index (PASI) in each half of the patient's dorsal aspect before and after treatment with the 2 regimens. RESULTS: The median pretreatment PASI score of 16 (range, 6.2-23.4) was reduced by 84% to 2.5 (range, 0-12.6) by the narrowband UV-B treatment and by 89% to 1.8 (range, 0-8.2) by the PUVA treatment. Statistical analysis of these data showed a tendency for PUVA being superior to narrowband UV-B although the difference remained below the level of significance (P = .17). However, a clear effect of the pretreatment PASI score on the therapeutic outcome was found. Patients with higher baseline PASI scores responded significantly better to PUVA than to narrowband UV-B (P = .03). CONCLUSIONS: Our data demonstrate that in many patients with plaque-type psoriasis, narrowband UV-B is comparably as effective as PUVA and, given the lack of photosensitizer-related adverse reactions and the possibly lower long-term cancer risk, can be considered as first-line treatment. Treatment with PUVA, on the other hand, remains the mainstay for patients with high PASI scores who do not respond or whose psoriasis cannot be controlled adequately by narrowband UV-B.

Disappointing results and low tolerability of photodynamic therapy with topical 5-aminolaevulinic acid in psoriasis. A randomized, double-blind phase I/II study.

BACKGROUND: Based on good results in the treatment of superficial skin tumours, since the early 1990s topical photodynamic therapy with aminolaevulinic acid (ALA PDT) has been used for disseminated, inflammatory dermatoses including psoriasis. However, there is still a lack of well-documented trials. OBJECTIVE: A prospective randomized, double-blind phase I/II intrapatient comparison study was conducted in 12 patients to investigate whether topical ALA PDT is an effective treatment for chronic plaque-type psoriasis. METHODS: In each patient three psoriatic plaques were randomly treated with a light dose of 20 J/cm(2) and 0.1%, 1% and 5% ALA, respectively. Treatment was conducted twice a week until complete clearance or for a maximum of 12 irradiations. Therapeutic efficacy was assessed by weekly determination of the psoriasis severity index (PSI). RESULTS: The mean percentage improvement was 37.5%, 45.6% and 51.2% in the 0.1%, 1% and 5% ALA-treated groups, respectively. Irradiation had to be interrupted several times because of severe burning and pain sensation. CONCLUSION: Topical ALA PDT did not prove to be an appropriate treatment option for plaque-type psoriasis due to disappointing clinical efficacy, the time-consuming treatment procedure and its unfavourable adverse event profile.

Topical aminolaevulinic acid-based photodynamic therapy as a treatment option for psoriasis? Results of a randomized, observer-blinded study.

BACKGROUND: Topical aminolaevulinic acid-based photodynamic therapy (ALA-PDT) has recently been tried in small open studies for several inflammatory dermatoses including psoriasis. OBJECTIVES: The purpose of this randomized, within patient comparison study was to investigate whether topical ALA-based PDT using a range of light doses can induce a satisfactory response in localized psoriasis. PATIENTS AND METHODS: Twenty-nine patients with chronic plaque type psoriasis were enrolled in the study. After keratolytic pretreatment three psoriatic plaques in each patient were randomly allocated to PDT with 1% ALA and a light dose of 5 J cm(-2), 10 J cm(-2) or 20 J cm(-2), respectively. Treatment was performed twice weekly until complete clearance or for a maximum of 12 irradiations. As a measure of clinical response the psoriasis severity index (PSI) of the three target plaques was assessed separately by an observer blinded to the treatment at baseline, before each PDT treatment and 3-4 days after the last irradiation. RESULTS: Eight patients withdrew prematurely from the study. Keratolytic pretreatment alone reduced the baseline PSI in all three dose groups by about 25%. Subsequent PDT with 20 J cm(-2) resulted in a final reduction of PSI by 59%, PDT with the lower doses of 10 J cm(-2) and 5 J cm(-2) decreased the baseline PSI by 46% and 49%, respectively. The difference in clinical efficacy between 20 J cm(-2) and 10 J cm(-2) or 5 J cm(-2) was statistically significant (P = 0.003; P = 0.02), whereas no difference was found between 10 J cm(-2) and 5 J cm(-2) (P = 0.4). All patients reported some degree of PDT-induced stinging or burning during irradiation. CONCLUSIONS: The unsatisfactory clinical response and frequent occurrence of pain during and after irradiation renders topical ALA-based PDT an inadequate treatment option for psoriasis.

Correlation between 8-methoxypsoralen bath-water concentration and photosensitivity in bath-PUVA treatment.

BACKGROUND: Bath-PUVA treatment, originally established in Scandinavia, offers several advantages over oral PUVA and has become increasingly popular in recent years. Outside Scandinavia 8-methoxypsoralen (8-MOP) is the prevailing photosensitizer for this PUVA modality and is used arbitrarily in a wide range of concentrations. Up to the present, data are lacking on the impact of 8-MOP bath-water concentration on UVA dosimetry. OBJECTIVE: We investigated the influence of increasing 8-MOP bath-water concentrations on photosensitivity in bath-PUVA treatment. METHODS: Fifteen healthy volunteers without abnormal photosensitivity or recent exposure to ultraviolet radiation were included in an intraindividually controlled comparison study. In all volunteers the minimal phototoxic dose (MPD) was determined on the volar side of their forearms after immersion for 20 minutes in 4 different 8-MOP bath-water concentrations (0.5, 1, 2.5, and 5 mg/L). The correlation between 8-MOP concentration and photosensitivity (defined as the reciprocal value of the MPD) was analyzed by linear regression analysis. In addition, the time course of erythema formation and the UVA dose-erythema response curve was assessed for each psoralen concentration. RESULTS: The median MPD and the 25%-75% interquartile were 5.7 J/cm(2) (5.7-8), 4 J/cm(2) (4-5.7), 2.8 J/cm(2) (2.8-5.7), and 2 J/cm(2) (2-2.8) at an 8-MOP concentration of 0.5, 1, 2.5, and 5 mg/L, respectively. Linear regression analysis revealed a significant correlation between 8-MOP bath-water concentration and photosensitivity (r = 0.98; P =.019). Bath-PUVA-induced erythema peaked after a median time interval of 3 days, with a range of 2 to 4 days. The slope of the UVA dose-erythema response curve was similar for all psoralen concentrations. CONCLUSION: UVA dose requirements in bath-PUVA treatment decrease linearly with increasing 8-MOP concentrations. A single MPD assessment at 72 hours after the UVA exposure is inappropriate for accurate determination of the patients' photosensitivity. The hazard of wrong UVA dosimetry is comparable at all psoralen concentrations.

Oral dexamethasone pulse treatment for vitiligo.

BACKGROUND: Oral corticosteroid pulse therapy has provided inconsistent results in the treatment of Indian patients with vitiligo. OBJECTIVE: We wanted to evaluate the efficacy, safety, and tolerability of oral dexamethasone pulse therapy in a cohort of Austrian patients with vitiligo. METHODS: Twenty-nine patients with vitiligo were included in the study. Of these, 25 had progressive and 4 had stable disease. The patients were given weekly pulses of 10 mg dexamethasone each on 2 consecutive days followed by 5 days off treatment for a maximum period of 24 weeks. Clinical response and side effects were evaluated in monthly intervals. Plasma cortisol and corticotropin levels were monitored before and up to 6 days after the dexamethasone pulse in the first and fourth week of treatment in 14 patients. RESULTS: After a mean treatment period of 18.2 +/- 5.2 weeks, the disease activity was arrested in 22 of 25 patients (88%) who had active vitiligo before the study. Marked repigmentation occurred in 2 patients (6.9%) and moderate or slight repigmentation in 3 patients (10.3%) each. No response was noted in 21 patients (72.4%). Side effects were recorded in 20 patients (69%) and included weight gain, insomnia, acne, agitation, menstrual disturbance, and hypertrichosis. Plasma cortisol and corticotropin values were markedly decreased 24 hours after the second dexamethasone dose, yet returned to baseline values within the off treatment period before the next dexamethasone pulse. CONCLUSION: Our data show that oral dexamethasone pulse treatment is effective in arresting progression of vitiligo yet fails to induce satisfactory repigmentation in the great majority of our patient cohort. Mild to moderate side effects are common with this treatment modality; however, sustained suppression of endogenous cortisol production does not occur with the pulse regimen.

Photodynamic therapy using topical methyl 5-aminolevulinate compared with cryotherapy for actinic keratosis: A prospective, randomized study.

BACKGROUND: Actinic keratoses (AKs) are the most common premalignant tumors. Without treatment, a significant number of patients with AK will experience squamous cell carcinoma. Photodynamic therapy (PDT) using the new highly selective photosensitizer methyl 5-aminolevulinate is a promising new treatment modality for AK. OBJECTIVE: We investigated the complete response rates, cosmetic outcome, and patient satisfaction after photodynamic therapy (PDT) using methyl 5-aminolevulinate (Metvix) versus cryotherapy in the treatment of AKs. METHODS: Patients were randomized to receive either cryotherapy with liquid nitrogen spray or PDT using methyl 5-aminolevulinate cream 160 mg/g, 3 hours application time, and red light (75 J/cm(2)). RESULTS: Efficacy results from 193 patients with 699 lesions (92% face/scalp and 93% thin/moderately thick) were analyzed. Overall complete response rates after 3 months were 69% for PDT and 75% for cryotherapy. Both treatments gave higher response rates in thin lesions (PDT 75%, cryotherapy 80%). PDT gave better cosmetic results and higher patient satisfaction than cryotherapy. CONCLUSION: PDT using methyl 5-aminolevulinate is an attractive treatment option for patients with AK, with a response rate similar to that of cryotherapy, but with superior cosmetic results and high patient satisfaction.