Short incubation with methyl aminolevulinate for photodynamic therapy of actinic keratoses.

BACKGROUND: Photodynamic therapy (PDT) using methyl aminolevulinate (MAL) is an effective first-line treatment for actinic keratoses. A reduced incubation period may have practical advantages. OBJECTIVE: This study aims to evaluate the effect of incubation time (1 vs. 3 h), MAL concentration (160 mg/g vs. 80 mg/g) and lesion preparation in the setting of MAL-PDT for treatment of actinic keratosis (AK). DESIGN: Open, randomized, parallel-group multicentre study. SETTING: Outpatient dermatology clinics. SUBJECTS: One hundred and twelve patients with 384 previously untreated AK. Most lesions (87%) were located on the face and scalp and were thin (55%) or moderately thick (34%). METHODS: Lesions were debrided, and MAL cream (160 mg/g or 80 mg/g) was applied before illumination with red light (570-670 nm; light dose, 75 J/cm2). Patients were followed up at 2 and 3 months. Sixty patients (54%) were re-treated and assessed at 6 months. MAIN OUTCOME: Complete lesion response rates 3 and 12 months after last treatment. RESULTS: For lesions on the face/scalp, lesion complete response rates were 78% for thin AK and 74% for moderately thick AK lesions after 1 h vs. 96% and 87% after 3 h incubation with MAL 160 mg/g. Lesion recurrence rates at 12 months after two treatments were similar [19% (3 of 16) with 1 h vs. 17% (3 of 18) with 3 h 160 mg/kg MAL-PDT] and lower than for 80 mg/g MAL-PDT (44-45%). CONCLUSION: MAL-PDT using a 1-h incubation may be sufficient for successful treatment of selected AK lesions.

[High-dose vitamin therapy as prophylaxis against porphyria cutanea uremica]. / Hochdosierte Vitamingabe zur Verhinderung einer Porphyria cutanea urämica?

50 Patients with chronic renal failure undergoing hemodialysis with or without porphyria cutanea tarda (PCT)-like skin changes were investigated. The total porphyrin amount in erythrocytes, plasma and dialysate and the distribution of porphyrin metabolites in plasma and dialysate were measured. In plasma, the group of patients with skin changes (referred as PCU = porphyria cutanea uremica) showed significantly increased uroporphyrin levels as compared to the non-symptomatic group. In addition, significant differences concerning the ratio uro-/coproporphyrin in plasma were shown: non-symptomatic patients with 0.87, as opposed to the PCU group with 3.7. Considerable differences between the level of vitamin ingestion were identified between the groups. Patients with PCU took distinctly less vitamins C, E and B than patients without symptoms.

Identification of mutations in the uroporphyrinogen III cosynthase gene in German patients with congenital erythropoietic porphyria.

The porphyrias are heterogeneous disorders arising from predominantly inherited catalytic deficiencies of specific enzymes along the heme biosynthetic pathway. Congenital erythropoietic porphyria is a very rare disease that is inherited as an autosomal recessive trait and results from a profound deficiency of uroporphyrinogen III cosynthase, the fourth enzyme in heme biosynthesis. The degree of severity of clinical symptoms mainly depends on the amount of residual uroporphyrinogen III cosynthase activity. In this study, we sought to characterize the molecular basis of congenital erythropoietic porphyria in Germany by studying four patients with congenital erythropoietic porphyria and their families. Using PCR-based techniques, we identified four different mutations: C73R, a well-known hotspot mutation, the promoter mutation -86A that was also described previously, and two novel missense mutations, designated G236V and L237P, the latter one encountered in the homozygous state in one of the patients. Our data from the German population further emphasize the molecular heterogeneity of congenital erythropoietic porphyria as well as the advantages of molecular genetic techniques as a diagnostic tool and for the detection of clinically asymptomatic heterozygous mutation carriers within families.

[Photodynamic therapy of cutaneous leishmaniasis. A promising new therapeutic modality]. / Photodynamische Therapie bei kutaner Leishmaniose. Eine viel versprechende neue Therapiemodalität.

We report about a 19-year-old Turkish patient who presented with cutaneous leishmaniasis after a holiday in Turkey. Cutaneous leishmaniasis often heals spontaneously leading to life-long immunity, but it can persist and lead to extensive scarring. In the literature, many therapeutic modalities have been reported; however, they can be accompanied by severe side effects. In our patient, photodynamic therapy resulted in healing of the lesion with only slight hypopigmentation.

[Cutaneous leishmaniasis]. / Kutane Leishmaniose.

Leishmaniasis is a vector-borne disease caused by an obligate intracellular protozoa, Leishmania, which resides in macrophages. The parasite is transmitted by an infected female sandfly. The incidence of cutaneous leishmaniasis approaches 2 million new cases per year with 90% of the cases occurring in the "Old World", while the "New World" accounts for the rest. Infection may be restricted to the skin with development of characteristic ulcers, or may affect the mucous membranes in its mucocutaneous form. The clinical diagnosis is verified by the presence of amastigotes in slit-skin smears. Therapeutic modalities include systemic treatments such as the pentavalent antimony compound sodium stibogluconate, liposomal formulations of amphotericin B, oral ketoconazole or itraconazole, as well as topical paromomycin sulphate, local heat, freezing with liquid nitrogen, or photodynamic therapy. An effective vaccine is not available.

[Onchocerciasis]. / Onchozerkose.

Onchocerciasis is an infestation caused by the nematode, Onchocerca volvulus, and characterized by eye manifestations, skin lesions and troublesome itching. Although partially controlled by international mass treatment programs, onchocerciasis remains a major health hazard in endemic areas in Africa, Arabia, and the Americas. Onchocerciasis is spread by bites from infested blackflies which transmit larvae that subsequently develop into adult filariae. Skin findings are commonly non-specific, and include severe pruritus, acute and chronic dermatitis, vitiligo-like hypopigmentation and atrophy. Onchocercal ocular disease has a large spectrum of manifestations and may even lead to blindness. Diagnosis is usually made by direct visualization of the larvae emerging from superficial skin biopsies, "skin snips". In some cases, the microfilariae can also be directly observed with a slit lamp when they migrate into the anterior chamber of the eye. Ivermectin is highly microfilaricidal, and is the current drug of choice for both skin and ocular manifestations.

Cytochrome p450A1 polymorphisms in a Caucasian population with porphyria cutanea tarda.

Porphyria cutanea tarda (PCT) is the most frequent porphyria in humans. The familial type is in contrast to the sporadic type due to an inherited defect of the uroporphyrinogen-II-decarboxylase (URO-D) and both types need additional porphyrinogens to lead to the clinical manifestation of the disease. Various factors such as xenobiotics (i.e. polycyclic aromatic hydrocarbons), alcohol, hormones and viral liver infections (hepatitis B and C) are known to induce porphyria. Cytochrome p450 enzymes play a crucial role in the metabolism of porphyrogens and therefore might have an important influence on the pathogenesis of hepatic porphyrias. Association of CYP1A2 polymorphisms with susceptibility to both types of PCT has already been described in Danish patients. We investigated 65 caucasian patients with PCT in comparison to a healthy control group concerning the tpe of PCT and the cytochrome p4501A1 polymorphisms (m1, m2 and m4) using polymerase chain reaction (PCR) and a restriction fragment length polymorphism. We found an increased incidence of the m4 polymorphism in the familial type of PCT (odds ratio 5.5, P-value 0.01), whereas the m1 and m2 mutations, might be provoked by a higher susceptibility to porphyrogens via the cytochrome p4501A1 m4 polymorphism.