Effects of low dose ultraviolet A-1 phototherapy on morphea.

AIM: 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. METHODS: Three patients with severe plaque type morphea in different stages were studied: one patient with late-stage lesions having stable sclerotic plaques; another patient with active inflammatory lesions; and a third patient with late-stage lesions associated with overlying lichen sclerosus et atrophicus (LSA). The treatment given was low dose UVA-1 phototherapy with single doses of 20 J/cm2 administered four times a week for 6 weeks, and once a week for another 6 weeks. RESULTS: Following UVA-1 phototherapy, the sclerotic plaques resolved, leaving smooth and soft tanned skin with normal structure, consistency and folding capability. In morphea with overlying LSA the elastic fibers did not completely return to the superficial papillary dermis despite the clinical clearance of both morphea and LSA. These data suggest that low dose UVA-1 phototherapy may improve, but not completely reverse, the histopathological changes of LSA. No side effects were observed during or after treatment. CONCLUSION: Our observations show in three patients that low-dose UVA-1 phototherapy is highly effective for treatment of all stages of morphea, including early inflammatory and late sclerotic lesions, and morphea with overlying lichen sclerosus et atrophicus. Because of its safety and efficacy, low dose UVA-1 phototherapy appears to be the treatment modality of choice.

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 degrees 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.

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.

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.

[Severe course of a mutilating pansclerotic circumscribed scleroderma in childhood. Clinical aspects and therapy]. / Schwerer Verlauf einer mutilierenden pansklerotischen zirkumskripten Sklerodermie im Kindesalter. Klinik und Therapie.

Disabling 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.

Deficiency of a novel retinoblastoma binding protein 2-homolog is a consistent feature of sporadic human melanoma skin cancer.

Using RNA arbitrarily primed PCR, the authors selected for transcripts with cell cycle-related differential expression in cultured human melanocytes. Among the partial cDNAs cloned, a novel cDNA was identified, which showed 54% identity to the recently cloned cDNA of the retinoblastoma binding protein-2 (RBP2). The 6.5-kB full-length cDNA of this RBP2-related gene, termed RBP2 homolog 1 (RBP2-H1), was obtained from a human teratocarcinoma cDNA library. Two independent libraries from human malignant melanomas were negative. A computerized sequence analysis revealed highly conserved motifs with possible functional meaning: two domains that, in the RBP2 homolog, mediate the binding and interaction with the proteins encoded by the retinoblastoma susceptibility gene, the TATA-binding protein, and the oncoprotein rhombotin 2; in addition, two DNA-binding zinc finger/leukemia-associated protein motifs were detected. Because a functional role in cell-cycle control and transcriptional activation can be envisioned, we investigated the expression of this novel transcript in normal fetal and adult tissues, as well as tissues of benign and malignant melanocytic tumors. By conducting multiple Northern blot, RT-PCR, and in situ hybridization analyses, the authors showed that the corresponding mRNA is expressed in virtually all normal tissues. Accordingly, they found RBP2-H1 expression in microdissected tissue samples from benign melanocytic nevi (n = 10). In contrast, the transcript is significantly down-regulated or even lost in tissue samples from human malignant melanomas (n = 13), melanoma metastases (n = 10), and melanoma cell lines (n = 7). The authors concluded that the loss or down-regulation of RBP2-H1 expression could be a useful molecular marker for a transformed phenotype in the human melanocytic system.

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 degrees C to 42 degrees C (71.6-107.6 degrees 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 degrees C (98.6 degrees F) and above. Photosensitization was significantly decreased at lower temperatures. These data indicate that a bath temperature of 37 degrees C (98.6 degrees 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.

Kinetics of photosensitivity in bath-PUVA photochemotherapy.

BACKGROUND: Bath-PUVA is used to treat a variety of dermatoses. However, the kinetics of 8-methoxypsoralen during treatment are not completely clarified. OBJECTIVE: The purpose of this study was to investigate the intensity of the phototoxic response and the persistence of phototoxicity after bath-PUVA. METHODS: Twelve volunteers were exposed to UVA doses ranging from 0.5 to 40 J/cm2 from 10 to 240 minutes after bath-PUVA treatment. The resulting phototoxic response of the skin was determined. RESULTS: Irradiation 10 minutes after the psoralen bath led to the lowest assessed minimal phototoxic dose (MPD) of 1.42 J/cm2 (mean, SD +/- 0.29). Thereafter, the MPD increased significantly and sharply every hour. At 4 hours after the psoralen bath, UVA doses up to 40 J/cm2 failed to induce any phototoxic erythema (MPD). CONCLUSION: For optimal effects, UVA irradiation has to be administered immediately after the psoralen bath; no restrictive behavior is necessary after bath-PUVA treatment.

Low-dose UVA 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.

[Balneophotochemotherapy of lichen ruber. Personal results and comparison with photochemotherapy modalities employed up to now]. / Balneophotochemotherapie des Lichen ruber. Eigene Ergebnisse und Vergleich mit bisher angewandten Photochemotherapiemodalitäten.

Twelve patients with extensive lichen planus, resistant to different regimes of prior external and internal therapy, were treated with PUVA-bath photochemotherapy (psoralen bath followed by UVA irradiation) using bath water containing 0.5 mg/L of 8-methoxypsoralen (8-MOP). In 11 of the 12 patients, the skin lesions showed a significant improvement or even complete remission within six weeks of treatment. In one patient, only limited clinical improvement could be achieved. A mean of 19.1 (SD +/- 3.6) PUVA-bath treatments were carried out. The mean cumulative UVA-dose given until clearance of the lichen planus was 16.7 (SD +/- 4.8) J/cm2. No side effects were seen except an increased phototoxic reaction in two patients manifested as slight erythema. The results of this trial show, that PUVA-bath photochemotherapy with 8-MOP is an effective therapeutic alternative to all other known therapies in the treatment of extensive, exanthematic and also hypertrophic-hyperkeratotic lichen planus. In comparison to oral PUVA therapy and PUVA-bath therapy using 4,s',8-trimethoxypsoralen, balneophotochemotherapy with 8-MOP shows an excellent efficiency-side effect correlation. The clearance of the refractive skin lesions by balneophotochemotherapy with 8-MOP demonstrates the superiority of this therapy over all other common therapeutic modalities used for lichen planus.

[The successful monotherapy of hypereosinophilic dermatitis with PUVA-bath photochemotherapy]. / Erfolgreiche Monotherapie der hypereosinophile Dermatitis mit PUVA-Bad-Photochemotherapie.

A 70-year-old woman with long-standing hypereosinophilic dermatitis improved strikingly with PUVA-bath photochemotherapy. The single UVA doses ranged from 0.3 to 3.3 J/cm2. After 19 treatment sessions pruritus disappeared, and after 32 treatments the erythematous maculae completely cleared. Under continuous treatment three times a week, no relapse has occurred to date. PUVA-bath photochemotherapy seems to be a promising new treatment modality without systemic side effects for patients with hypereosinophilic dermatitis.

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 l of an 8-MOP water solution (0.5 mg/l, 37 degrees 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.