Gregor von Kobyletzki

Low-dose UVA1 phototherapy for treatment of localized scleroderma

BACKGROUND For treatment of localized scleroderma numerous treatments, including ones with potentially hazardous side effects, are currently used with only limited success. OBJECTIVE We attempted to determine the efficacy of low-dose UVA1 irradiation in patients with severe localized scleroderma. METHODS Patients were irradiated with 20 J/cm2 UVA1 for 12 weeks (total number of treatments: 30; cumulative UVA1 dose: 600 J/cm2). RESULTS Low-dose UVA1 irradiation induced significant clinical improvement (clearance of > 80% of lesions) in 18 of 20 patients. Clearance was documented by clinical score as well as by 20 MHz ultrasound and histopathologic analysis. CONCLUSION Low-dose UVA1 phototherapy can be highly effective for sclerotic plaques, even in patients with advanced localized scleroderma and with lesions rapidly evolving despite conventional therapy.

Combined Treatment with Calcipotriol Ointment and Low-Dose Ultraviolet A1 Phototherapy in Childhood Morphea

Abstract: Various therapies for morphea have been used with limited success, including ones with potentially hazardous side effects. When morphea occurs in childhood it may lead to progressive and long‐lasting induration of the skin and subcutaneous tissue, growth retardation, and muscle atrophy. We report an open prospective study in which the efficacy of a combined treatment with calcipotriol ointment and low‐dose ultraviolet A1 (UVA1) phototherapy in childhood morphea was investigated. Nineteen children (mean age 8.5 years, range 3–13 years) with morphea were exposed to UVA1 (340–400 nm) phototherapy at a dose of 20 J/cm2 four times a week for 10 weeks. Forty phototherapy sessions resulted in a cumulative dose of 800 J/cm2 UVA1. In addition, calcipotriol ointment (0.005%) was applied twice a day. After 10 weeks, palpation and inspection showed a remarkable softening and repigmentation of formerly affected skin resulting in a highly significant (p < 0.001) decrease of the mean clinical score from 7.3 ± 0.9 at the beginning to 2.4 ± 0.9 (relative reduction 67.1%) at the end of combined therapy. Our results indicate that a combined therapy with calcipotriol ointment and low‐dose UVA1 phototherapy is highly effective in childhood morphea. Further controlled studies are necessary to investigate whether this combined therapy is superior to UVA1 phototherapy alone.

Effects of low dose ultraviolet A‐1 phototherapy on morphea

The effects of low dose ultraviolet A‐1 (UVA‐1) phototherapy on different clinical stages of morphea (localized scleroderma) were analyzed in this case study. Based on these data, the different types of phototherapy described in the literature and currently used for treatment of morphea are compared.

PUVA-bath photochemotherapy (PUVA-soak therapy) of recalcitrant dermatoses of the palms and soles

PUVA‐bath therapy has proven to avoid many side effects associated with oral 8‐methoxypsoralen (8‐MOP) treatment. In order to investigate the effectiveness of topical PUVA‐bath therapy (PUVA‐soak therapy) on chronic palmoplantar dermatoses, 30 patients with plaque‐type psoriasis, pustular psoriasis, endogenous eczema, dyshidrotic eczema and hyperkeratotic dermatitis of the palms and soles were treated over 8 weeks with PUVA‐soak using 8‐MOP. No additional treatment except skin moisturising cream such as unguentum emulsificans aquosum was used during the study period. The single UVA‐doses applied ranged from 0.3 to 3.0 J/cm2 (mean single dose of 1.8 J/cm2), with a mean cumulative dose of 48.6 J/cm2 per patient. Altogether 26 of 30 patients responded well within 8 weeks of treatment with 63% of all patients showing a complete remission and 23% showing considerable improvement, as shown by flattening of plaques, decreased scaling and erythema, as well as decreased vesicle and pustule formation. The condition responding best to our therapy was palmoplantar psoriasis followed by atopic eczema. Hyperkeratotic dermatitis displayed the poorest responding rates in this study. Unwanted side effects such as erythema, pain, blistering or patchy hyperpigmentation were not observed in any of the patients. We conclude that PUVA‐soak therapy can be highly efficient in the treatment of palmoplantar dermatoses, especially in the management of palmoplantar psoriasis.

Plasma levels of 8-methoxypsoralen following PUVA-bath photochemotherapy

Administration of 8‐methoxypsoralen (8‐MOP) in a dilute bath water solution is an effective therapeutic alternative to oral PUVA therapy, avoiding systemic side effects, offering better bioavailability of the psoralen and requiring much smaller amounts of UVA for induction of therapeutic effects. To obtain exact data about the percutaneous absorption of 8‐MOP during a psoralen bath, the plasma levels of the drug were determined in 26 patients with different skin diseases by a reverse high‐performance liquid chromatographic method. Fifteen patients receiving oral PUVA therapy (0.8 mg 8‐MOP/kg body weight) served as a positive control group. Bath solutions were prepared by diluting 15 ml of 0.5% stock solution of 8‐MOP in 150 l of bath water (0.5 mg/l, 37°C). Blood samples were drawn from patients 5, 30, 60, 120 and 180 min after the bath. In the oral PUVA group, blood samples were obtained 1½ h after administration of the drug. In 23 of 26 patients, 8‐MOP levels were undetectable in every blood sample. After 30 min, two patients showed detectable levels of 8‐MOP (5 ng/ml, 7 ng/ml), while 60 min after the PUVA bath 8‐MOP was detectable in only one volunteer (5 ng/ml). In patients receiving oral 8‐MOP therapy, serum levels varied between 45 and 360 ng/ml 1½ h after drug administration. Our data confirm extremely low 8‐MOP levels resulting from 8‐MOP bath water treatments and provide confirmation of the absence of systemic side effects in patients who are undergoing PUVA‐bath therapy.

UVA1 irradiation induces deoxyribonuclease dependent apoptosis in cutaneousT-cell lymphoma in vivo

Cutaneous T‐cell lymphoma (CTCL) is a malignancy of mature T‐cells, predominantly of the helper phenotype, that primarily invade the skin. Different photo‐ and chemotherapeutic treatments are known to be beneficial in early‐stage CTCL. This observation has initiated prospective investigations into the efficacy of phototherapeutic regimens. The purpose of our study was to investigate the ability of medium‐dose UVA1 phototherapy (60 J/cm2) to induce apoptosis (programmed cell death) in skin infiltrating T‐cells of CTCL in vivo. We describe the results of three different staining methods for formalin‐fixed, paraffin‐embedded tissue sections. The in situ end‐labeling (ISEL) procedure, nuclear staining using the DNA‐binding fluorochrome Hoechst 33342, and immunohistochemistry using polyclonal antibodies against recombinant mouse deoxyribonuclease I (DNase I) demonstrated that UVA1 irradiation was able to induce marked apoptosis in CTCL. Thereby, ISEL and Hoechst staining clearly revealed DNA‐condensation and nuclear fragmentation, accompanied by the formation of typical “apoptotic bodies”. The accumulation of DNase I immunoreactivity in the cytoplasm of lymphocytes in UVA1 irradiated skin indicated that DNase I or DNase I‐related endonucleases may have acted as apoptotic endonuclease(s) which were synthesized after UVA1 irradiation prior to their apoptotic elimination.

UV transmission and UV protection factor (UPF) measured on split skin following exposure to UVB radiation — correlation with the minimal erythema dose (MED)

In this study the ultraviolet (UV) transmission of split skin exposed to UVB radiation and of non‐exposed skin was compared in the 280–390 nm wavelength range and quantified. In addition, the correlation between the increase in the minimal erythema dose (MED) associated with a defined exposure to UVB and the ultraviolet protection factor (UPF) calculated from the transmission data was investigated. The study population consisted of 12 patients. Two pieces of split skin of the same thickness (0.3 mm) were taken from the right thigh of each patient. One specimen was removed from an area of non‐exposed healthy skin and the other from an area which had been exposed to UVB radiation for a period of 12 days in which the initial dose of 1/3 MED was raised by 1/3 MED every 4 days. The split skin specimens were stretched over a special frame; subsequently, the UV transmission was determined with a spectrophotometer. The mean values obtained for UV transmission were all significantly below the initial data for non‐exposed split skin. In the UV range of 280–390 nm, the transmission measured in the exposed specimens was 49.1% of the value measured in the non‐exposed split skin (P<0.05). The corresponding values for the UVA range (315–390 nm) and the UVB range (280315 nm) were 50.1% and 29.5%, respectively (P<0.05), based on the initial transmission data obtained from non‐exposed skin. The clinical determination of MED after 12 days of exposure to UVB yielded mean values that were 3.2 times the initial values. Moreover, the mean UPFs calculated from the transmission data measured at the end of the 12‐day exposure period were also about three times the initial values. The present study has thus established a significant correlation between the clinical MED values and the UPFs calculated from the transmission data measured following exposure to UVB.

Schwerer Verlauf einer mutilierenden pansklerotischen zirkumskripten Sklerodermie im Kindesalter Klinik und Therapie

ZusammenfassungDie pansklerotische Morphea der Kindheit ist die schwerste Variante der zirkumskripten Sklerodermie. Sie ist charakterisiert durch eine rasche Progression einer tiefen kutanen Fibrosierung. Die Prognose bezüglich einer normalen Lebensführung ist schlecht, das Krankheitsbild kann sogar zum Tode führen. Vorgestellt wird ein besonders schwerer Krankheitsverlauf mit kutanen Ulzerationen, ausgeprägten Beugekontrakturen und Mutilationen. Als mögliches Korrelat zu den Mutilationen fanden sich in der feingeweblichen Untersuchung schwerste Veränderungen der kleinen Gefäße mit einer intravasalen Kalzinose. Unter UVA1-Phototherapie kam es zu einer Besserung der Sklerose und der Hautdicke, so daß die Phototherapie auch bei einem derartig schweren Krankheitsbild ein möglicher Therapieansatz sein könnte.SummaryDisabling pansclerotic morphea of childhood is the most severe variant of localized scleroderma. It is characterized by rapid progression of deep cutaneous fibrosis expanding over large areas of body surface. The prognosis in terms of normal life activity is poor and the disease may even take a fatal course. Presented is a case with extremely severe and rapidly progressive lesions resulting in cutaneous ulcerations joint contractures, and multilaing deformities of the extremities. Histopathological analysis revealed extensive intravascular calcinosis of the small vessels, which may be an important factor in the pathogenesis of this poorly understood disease. UVA1-phototherapy was performed and induced a softening of sclerosis and a distinct decrease of skin thickness. Based on these observations UVA1-phototherapy may be promising in the treatment of extensive sclerotic disease of this kind, and possibly other diseases accompanied by excessive sclerosis.

Effects of water temperature on photosensitization in bath-PUVA therapy with 8-methoxypsoralen.

The pharmacokinetic aspects of bath‐PUVA are not completely clarified. Therefore, we determined the phototoxic response of human skin following psoralen baths at temperatures ranging from 32°C to 42°C (71.6–107.6°F) and UVA doses ranging from 0.5 to 5.5 J/cm2. The highest therapeutical photosensitization (i.e., lowest minimal phototoxic dose) was assessed at temperatures of 37°C (98.6°F) and above. Photosensitization was significantly decreased at lower temperatures. These data indicate that a bath temperature of 37°C (98.6°F) should be used to gain optimal therapeutic efficiency in a clinical setting. Furthermore, in order to minimize the risk of adverse phototoxic effects in bath‐PUVA, it is important to use a constant temperature during the psoralen bath.

Time course of 8-methoxypsoralen-induced skin photosensitization in PUVA-bath photochemotherapy

In recent years PUVA‐bath photochemotherapy has been shown to be an effective treatment modality for several dermatoses. A limitation of PUVA‐bath photochemotherapy has been the lack of guidelines for optimal performance, including the time course of photosensitization of the skin exposed to the 8‐methoxypsoralen (8‐MOP) bath water solution. In the present study 12 healthy volunteers were exposed to a 20 min bath in 150 1 of an 8‐MOP water solution (0.5 mg/1, 37°C). Immediately, as well as 1, 2, 3 and 5 h after the 8‐MOP bath, irradiation was performed with increasing doses of UVA (0.5, 1, 2, 3, 5 J/cm2) on 2 cm2 test areas. The minimal phototoxic dose (MPD) was determined 72 h after the UVA exposure. In all volunteers, photosensitization was highest immediately after the bath, with a MPD significantly below 5 J/cm2 (0.5‐2 J/cm2). One hour after the bath, erythema could be induced by 2 to 5 J/cm2 UVA. Two hours after the bath, erythema could be induced using irradiation of 5 J/cm2 only in two volunteers. Three and five hours after the 8‐MOP bath, no erythema could be induced in any volunteer by UVA doses up to 5 J/cm2. Our results indicate that optimal bath‐PUVA requires UVA irradiation immediately after the 8‐MOP bath. Further, these results imply that no restrictions on further sun exposure are mandatory 3 h after the 8‐MOP bath, thus allowing the patient to pursue normal life activities.