Oral PUVA and topical steroids for treatment of oral manifestations of chronic graft-vs.-host disease.

BACKGROUND: Oral manifestations of chronic graft-vs.-host disease (cGVHD) can significantly affect the quality of life and severity often does not correlate with systemic manifestations. We evaluated the use of topical corticosteroids and the intraoral application of psoralen-UVA (PUVA) for treatment of oral manifestations of cGVHD. METHODS: Overall, 18 patients with oral manifestations of cGVHD were treated with either intraoral PUVA (n=7) or with topical corticosteroids (n=16). Four patients received intraoral PUVA after failure of topical steroids and one patient was treated with topical corticosteroids after failing treatment with intraoral PUVA. A glass fiber extension of an UVA source was used for manual intraoral application. Treatment with topical corticosteroids consisted of 0.1 mg/ml dexamethasone mouth wash four times a day in combination with antifungal prophylaxis. RESULTS: Four patients showed complete local response (CR) due to intraoral PUVA, two improved and one did not respond. Topical corticosteroids resulted in nine patients in CR, two improved and five did not respond. CONCLUSION: Intraoral PUVA as well as topical corticosteroids are effective in treatment of oral manifestations of oral GVHD with few side-effects and improve quality of life in patients with cGVHD.

Effect of photoreactivating light on UV radiation-induced alterations in human skin.

BACKGROUND/AIMS: Photoreactivating light (PRL) after ultraviolet radiation (UVR) exposure causes photoreversal of cyclobutane pyrimidine dimers through the activation of photolyase. Although photoreversal has been demonstrated in the "three kingdoms of life," its existence in man remains controversial. We sought evidence for photoreversal in man. METHODS AND RESULTS: Seven subjects were spot-irradiated at two sites with 4 minimal erythema doses (MED) of solar-simulating UVR. Of the two sites, one was then immediately exposed to a PRL source. Epidermal biopsies were taken immediately after exposure. No significant difference in the quantity of pyrimidine dimers was detected comparing the "UVR only" site to the "UVR, PRL-exposed" site. Biopsies were repeated 24 h later and no significant difference in p53 protein expression or dendritic cell number was detected. However, the "UVR, PRL-exposed" site showed a greater reduction in pyrimidine dimer quantity. CONCLUSIONS: We found no evidence for a direct effect of PRL causing photoreversal of UVR-induced pyrimidine dimers in man. Our results do, however, suggest that some indirect effect of PRL may enhance pyrimidine dimer repair in the 24-h period following UVR exposure.

Tanning salon exposure and molecular alterations.

BACKGROUND: Human studies of the short-term cellular effects of tanning salon exposures are lacking. Findings of such studies may prove extremely helpful in educating consumers considering or currently attending tanning salons. OBJECTIVE: Our purpose was to determine whether tanning salon exposure causes DNA alterations and p53 protein expression in epidermal keratinocytes and/or circulating peripheral lymphocytes. METHODS: Eleven subjects received 10 full-body tanning salon exposures over a 2-week period. UV-induced DNA cyclobutane pyrimidine dimers and p53 protein expression were examined, comparing pretreatment peripheral blood lymphocytes and epidermal biopsy specimens with analogous specimens obtained after the 10 tanning salon exposures. RESULTS: Cyclobutane pyrimidine dimers in DNA and p53 protein expression were detected in epidermal keratinocytes, but were absent in lymphocytes. CONCLUSION: Similar to outdoor sun exposure, short-term recreational tanning salon exposure causes molecular alterations believed essential in the development of skin cancer.

Two considerations for patients with psoriasis and their clinicians: what defines mild, moderate, and severe psoriasis? What constitutes a clinically significant improvement when treating psoriasis?

The definitions of psoriasis severity and clinically significant improvement in psoriasis are used to classify treatments, obtain Food and Drug Administration approval, and determine product labeling and reimbursement. The Medical Advisory Board of the National Psoriasis Foundation has addressed these issues because of their importance in the clinical trials that are conducted to gain FDA approval of indications. Narrow indications, which are without a sound rational basis, will-in this era of constant oversight by third party payers-affect physicians' ability to manage patients with psoriasis. Body surface area (BSA) is usually used to define severity for clinical trials. It is not optimal for defining psoriasis severity because there are some patients with low BSA involvement who have very severe psoriasis and some patients with high BSA involvement who have mild psoriasis. We conclude that a quality of life (QOL) standard is better than BSA measurement for identifying patients with severe psoriasis. The second issue is what defines clinically significant improvement for patients with psoriasis. Setting an arbitrarily high criterion of clinical efficacy for new psoriasis treatments will likely limit the development and approval of useful treatments. To maximize the availability of useful psoriasis treatments, it is our thesis that psoriasis treatments should be approved when they have been shown to produce a statistically significant level of improvement in well-designed clinical trials.

The effect of suntan parlor exposure on delayed and contact hypersensitivity.

Cutaneous and systemic immune function are believed to play an important role in cutaneous carcinogenesis. We therefore sought to determine whether the suntan parlor radiation sources commonly used in the United States cause measurable qualitative suppression of immune function and quantitative alterations in circulating T cell subpopulations. Subjects (n = 22) were recruited and randomly assigned to receive suntan parlor exposures (10 full-body UV exposures over a 2 week period, shielding only the right flexural arm) or no exposure. Baseline circulating T lymphocyte subpopulations (T helper lymphocyte, CD4; T suppressor/cytotoxic lymphocyte, CD8) were measured. Two weeks later (upon completion of UV exposures for those in this group), circulating T cell subpopulations were measured and dinitrochlorobenzene (DNCB) sensitization (in the UV group, on the UV-exposed buttock) was performed. Subsequent DNCB elicitation was performed in a bilateral fashion (in the UV group, on the right UV-shielded and the left UV-exposed upper arm). We found that subjects in the UV group demonstrated localized suppression of contact hypersensitivity sensitization and elicitation and also an increase in circulating CD8 cells when compared to the control group (P < or = 0.05). We conclude that suntan parlor exposures, as typically received in this country, suppress contact hypersensitivity and increase the circulating T suppressor/cytotoxic cell number quantity.

Phototherapy and photochemotherapy: an update.

Three types of phototherapy and 2 forms of photochemotherapy are now available for treatment of more than 40 diseases of the skin. Broadband ultraviolet B (UVB) phototherapy and oral psoralen photochemotherapy (PUVA) therapy are most widely available while there has been increased interest in topical PUVA therapy. Narrow-band UVB phototherapy and UVA-1 phototherapy offer potential for the future.

Consensus workshop on the toxic effects of long-term PUVA therapy.

The possibility that there is an increased risk of melanoma in patients with psoriasis treated with psoralen-UV-A (PUVA) therapy has raised concern on the part of physicians and patients about the long-term safety of this treatment. In response to this concern, the National Psoriasis Foundation sponsored a workshop at which invited participants with expertise in PUVA therapy, psoriasis treatment, melanoma and nonmelanoma skin cancer, and epidemiological and clinical trials were asked to develop a consensus on the following 3 issues: the risk of long-term adverse effects of PUVA therapy with emphasis on nonmelanoma and melanoma skin cancer; the guidelines for physicians and patients for selection and use of PUVA therapy with consideration of the risk-benefit ratio of this treatment compared with the risk-benefit ratios of alternative treatments; and the directions for further evaluation of the long-term effects Of PUVA therapy.

Sunlight: an environmental toxin for humans. A primer to advise patients.

Sunlight causes acute toxic effects such as sunburn, local and systemic immune suppression, and long-term adverse effects including photoaging and skin cancer. The degree of damage depends on the overall exposure-dose and individual susceptibility. Various strategies should be employed to minimize sun-exposure damage, including proper use of sunscreens and exposure avoidance. Public education might best be focused on protecting children and promoting awareness of photoaging changes in adults.

PUVA-induced phototoxicity: incidence and causes.

BACKGROUND: Phototoxicity is the most significant short-term adverse effect of PUVA therapy. OBJECTIVE: We attempted to determine the incidence and possible causes of phototoxicity of sufficient degree to cause interruption of treatment. METHODS: A retrospective study was conducted of 16,506 PUVA treatments given to 414 patients in two treatment centers. RESULTS: Phototoxicity occurred in 10.9% of patients and was an adverse effect in 0.3% of treatments. Problems with the treatment protocol were the main cause. CONCLUSION: Phototoxicity is a common adverse effect, and patients should be warned of this potential occurrence. Awareness of the causes may help to reduce the incidence of this problem.

PUVA therapy is preferable to UVB phototherapy in the management of HIV-associated dermatoses.

Both methoxsalen plus UVA (PUVA) therapy and UVB phototherapy are commonly used in the management of human immunodeficiency virus-associated dermatoses but UVB phototherapy appears to be the preferred treatment. There are several considerations, in particular therapeutic efficacy and therapeutic profile, which suggest that PUVA therapy might be more effective. This needs to be established in clinical trials.

Treatment of chronic graft-versus-host disease with ultraviolet irradiation and psoralen (PUVA).

Chronic graft-versus-host disease (GVHD) remains a difficult clinical problem to treat and manage. We have reviewed our treatment of 40 patients treated at a single institution with PUVA (ultraviolet irradiation and psoralen) over a 14 year period. Thirty-five patients were treated for refractory chronic GVHD and five patients were treated at presentation of high-risk chronic GVHD. Overall, 31 of 40 patients improved on PUVA treatment. Sixteen patients achieved a complete response to PUVA added to their GVHD regimen. Four of the 15 partial responders had complete resolution of cutaneous GVHD but persistence of other systemic manifestations. The remaining partial responders had at least a 50% improvement in GVHD. We have also used PUVA with a glass fiber extension to treat intra-oral GVHD. PUVA is well tolerated with a high rate of response in the skin and mild side effects except for three patients who had therapy discontinued after phototoxicity (burn).