C. Gruss

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.

Chronic sclerodermic graft-versus-host disease refractory to immunosuppressive treatment responds to UVA1 phototherapy☆☆☆

Graft-versus-host disease is a frequent complication of allogenic bone marrow transplantation. Approximately 10% of patients suffering from chronic graft-versus-host disease develop sclerodermic graft-versus-host disease of the skin, which often does not respond to conventional immunosuppressive therapy. An alternative to immunosuppressive treatment is photochemotherapy. We describe a patient with chronic sclerodermic graft-versus-host disease who did not respond to a combination therapy of cyclosporine and prednisone and later mycophenolate mofetil plus prednisone. A combination therapy of mycophenolate mofetil (2 g/day) and low-dose UVA(1) therapy (single dose, 20 J/cm(2), 4 times per week over 6 weeks) resulted in striking clinical improvement of sclerodermic graft-versus-host disease.

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.

Assessment of minimal phototoxic dose following 8-methoxypsoralen bath: maximal reaction on average after 5 days

An essential procedure before starting bath psoralen ultraviolet (UV) A (PUVA) photochemotherapy is the evaluation of the minimal phototoxic dose (MPD), which is traditionally assessed 3 days after irradiation. However, there are no controlled studies supporting the 72 h peak of bath‐PUVA erythema. The aim of this study was therefore to determine the exact time course of the erythematous reaction in human skin following bath‐PUVA. For this purpose, the skin of 10 volunteers was exposed to 0·5–3·0 J/cm2 UVA directly after a 20‐min 8‐methoxypsoralen bath (0·5 mg/L, 37 °C). At 24, 48, 72, 96, 120 and 144 h (1–6 days) after irradiation, the MPD and the erythema sum score (ESS) were determined in each subject. The results showed a maximal erythematous reaction on average 5 days after irradiation. The mean MPD gradually decreased from day 2 (> 3·0 J/cm2) to day 5 (mean ± SD 1·15 ± 0·63 J/cm2) and started to increase at day 6 (mean ± SD 1·6 ± 0·52 J/cm2). The mean ± SD ESS correspondingly increased from day 2 (0 ± 0) to day 5 (10·5 ± 3·7) with a decrease at day 6 (7·5 ± 3·1) (difference between day 3 and beyond statistically significant at P < 0·05). As our study indicates a maximal erythematous reaction to the bath‐PUVA up to 5 days after irradiation, the traditional MPD assessment at 3 days generates a risk of phototoxic side‐effects within the phototherapy course by underestimating the phototoxic effect in some patients. These findings contribute towards a more defined understanding of the kinetics of the phototoxic reaction in bath‐PUVA therapy.

Transient and partial effect of high-dose intravenous immunoglobulin in polyarteritis nodosa.

A 57-year-old male patient suffered from polyarteritis nodosa. He presented with articular pain, polyneuropathy, subcutaneous nodules and nodes on the lower legs. After several immunosuppressive agents (methotrexate, mycophenolate mofetil and prednisolone) had proven to be ineffective, 2 g intravenous immunoglobulin (IVIG) per kilogram body weight were administered within 2 days in combination with 10 mg prednisolone per day. Subsequently, 6 cycles of IVIG were applied in increasing intervals from 4 to 6 weeks resulting in a minimum dosage of 0.33 g/kg/week IVIG. The polyarteritis improved within a few days after the first IVIG application. The intensity of polyneuropathy and arthralgia of polyarteritis decreased during the period of IVIG treatment. Finally, a dose reduction of less than 0.25 g/kg/week IVIG resulted in recurring polyarteritis nodosa, which could not be controlled by further administration of IVIG. Therefore, our data indicate that: (1) IVIG is partially effective in cases of polyarteritis nodosa, but the therapeutic effect is only transient; (2) the success of treatment may be correlated with the dose of IVIG per body weight and week; (3) the efficacy/cost ratio of IVIG in polyarteritis nodosa appears to be low.

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.