Do we alter ultraviolet sensitivity in vivo with stratum corneum rehydration? A pilot study and review of the literature.

BACKGROUND: Numerous therapeutic schemes recommend topical administration of emollients immediately prior to ultraviolet (UV) B therapy. The rationale behind the clinical improvement is a presumed enhancement of UV transmission through the epidermis. Originating from this clinical observation, there has been some concern as to whether a well-hydrated skin in general might be more susceptible to actinic damage. OBJECTIVES: To investigate whether rehydration of healthy skin causes an altered UVB sensitivity in vivo. METHODS: We determined minimal erythema doses (MEDs) and erythema sum scores (ESSs) after differential rehydration of the skin in 10 healthy volunteers. In each subject six UVB phototests were performed after pretreatment with five different emulsifying ointments (unguentum emulsificans and dilutions with 30, 50, 70 and 90% aqua purificans) plus a negative control. In vivo evaluation of stratum corneum hydration was performed by measurement of electrical capacitance. RESULTS: The results of this randomized, double-blind in vivo study indicated that rehydration of normal stratum corneum with the emulsifying ointments tested did not result in a significantly altered sensitivity to the erythematous effects of UVB irradiation (no significant differences in MED and ESS). Furthermore, there was no correlation between measured stratum corneum hydration and the erythema response of healthy skin. CONCLUSIONS: Although many schemes recommend the administration of emollients prior to UV therapy, there have also been calls for caution, as an uncritical application may interfere with such treatment. We showed that the emulsifying ointments tested exhibited no photoprotective potential and thus are suitable for the pretreatment of psoriasis prior to phototherapy. It has long been discussed whether the effects of emollient pretreatment on response to UV occur only in psoriatic skin or also in healthy skin. Our results indicated that stratum corneum rehydration did not result in a significantly increased erythema response of healthy skin to UVB exposure. With regard to the use of rehydrating cosmetics in everyday life, the outcome of our pilot study is reassuring, as we could not confirm with our experimental design that well-hydrated healthy skin is more prone to actinic damage.

Does the minimal phototoxic dose after 8-methoxypsoralen baths correlate with the individual's skin phototype?

BACKGROUND/AIMS: Up to now no data have been available concerning whether there is a significant correlation between skin phototypes and the minimum phototoxic dose (MPD) after bath water delivery of 8-MOP. METHODS: The skin phototype of each of 46 patients was determined based on the individual past history of solar-induced burning and tanning. In addition, the MPD of each patient was assesed after photosensitization with a warm water bath (37 degrees C, 98.6 degrees F) containing 1.0 mg/l 8-methoxypsoralen (8-MOP). Statistical analysis was performed using a Mann-Whitney U-test and Spearman rank order correlation. RESULTS: The median MPD in patients with skin phototype II was 2.0 J/cm2 (range < or =0.5 to > or =3.5) versus 1.5 J/cm2 (range 1.0 to > or =3.5) in patients with skin phototype III. There was a considerable overlap between both groups. No significant difference was detected comparing both groups (P=0.7326) and Spearman rank order correlation revealed no correlation between skin phototype and MPD. CONCLUSION: Erythemal sensitivity in PUVA bath therapy, measured as MPD, is not correlated with sun-reactive skin phototype in skin types II and III. Thus skin phototype is not a suitable indicator for the initial UVA dose in PUVA bath photochemotherapy.

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.

The PUVA-turban as a new option of applying a dilute psoralen solution selectively to the scalp of patients with alopecia areata.

BACKGROUND: Alopecia areata is a burden for many patients and often resistant, even to extensive therapy. Orally administered PUVA therapy has been shown among numerous systemic and topical treatment modalities to be a therapeutic alternative. However, the clinical use of oral PUVA is often limited by systemic side effects. Bath-PUVA therapy offers an alternative solution because of the negligible systemic absorption of psoralen with this technique. Through use of a "PUVA-turban" it is now possible to administer a dilute bathwater solution containing 8-methoxypsoralen (8-MOP) to the scalp. OBJECTIVE: The purpose of this study was to determine whether PUVA turban therapy is effective in treating alopecia areata in different clinical stages. METHODS: We treated 9 patients with severe, rapidly progressing, treatment-resistant alopecia areata with PUVA-turban treatment as a modification of bath-PUVA therapy. At each treatment session a cotton towel was soaked with a 0.0001% 8-MOP solution (1 mg/L) at 37 degrees C, wrung gently to remove excess water, and wrapped around the patient's head in a turban fashion for 20 minutes. This was directly followed by UVA radiation. Treatment sessions were initially performed 3 to 4 times per week. RESULTS: The cumulative UVA doses given over treatment periods of up to 24 weeks were 60.9 to 178.2 J/cm(2), with single doses ranging from 0.3 to 8.0 J/cm(2). After up to 10 weeks of treatment, hair regrowth could be noticed in 6 of 9 patients. Two patients did not respond to the treatment, and one patient showed only vellus hair regrowth. CONCLUSION: PUVA-turban therapy can be considered a useful method of administering a dilute psoralen solution selectively to the scalp of patients. It has been shown to be a well-tolerated and, in some patients, efficient therapeutic alternative in the treatment of alopecia areata.

Epidermal H(2)O(2) accumulation alters tetrahydrobiopterin (6BH4) recycling in vitiligo: identification of a general mechanism in regulation of all 6BH4-dependent processes?

It has been shown in vivo that patients with the depigmentation disorder vitiligo accumulate hydrogen peroxide (H(2)O(2)) accompanied by low catalase levels and high concentrations of 6- and 7-biopterin in their epidermis. Earlier it was demonstrated that epidermal 4a-OH-tetrahydrobiopterin dehydratase, an important enzyme in the recycling process of 6(R)-L-erythro 5,6,7,8 tetrahydrobiopterin (6BH(4)), has extremely low activities in these patients concomitant with a build-up of the abiogenic 7-isomer (7BH(4)), leading to competitive inhibition of epidermal phenylalanine hydroxylase. A topical substitution for the impaired epidermal catalase with a pseudocatalase effectively removes epidermal H(2)O(2), yielding a recovery of epidermal 4a-OH-tetrahydrobiopterin dehydratase activities and physiologic 7BH(4) levels in association with successful repigmentation demonstrating recovery of the 6BH(4) recycling process. Examination of recombinant enzyme activities, together with 4a-OH-tetrahydrobiopterin dehydratase expression in the epidermis of untreated patients, identifies H(2)O(2)-induced inactivation of this enzyme. These results are in agreement with analysis of genomic DNA from these patients yielding only wild-type sequences for 4a-OH-tetrahydrobiopterin dehydratase and therefore ruling out the previously suspected involvement of this gene. Furthermore, our data show for the first time direct H(2)O(2) inactivation of the important 6BH(4) recycling process. Based on this observation, we suggest that H(2)O(2) derived from various sources could be a general mechanism in the regulation of all 6BH(4)-dependent processes.

Calcipotriol vs. tazarotene as combination therapy with narrowband ultraviolet B (311 nm): efficacy in patients with severe psoriasis.

BACKGROUND: Phototherapy has been shown to be one of the most effective treatment modalities for patients with psoriasis. Nevertheless, photocombination therapies capable both of reducing cumulative ultraviolet (UV) doses and of accelerating clearance of skin lesions are important and of high interest. There have been no published studies comparing the effect of narrowband UVB irradiation in combination with topical application of tazarotene vs. calcipotriol. OBJECTIVES: To determine, in a half-side manner, whether a combination of UVB (311 nm) and tazarotene is superior to UVB (311 nm) plus calcipotriol or vice versa. METHODS: Ten patients suffering from widespread symmetrical psoriasis were treated for at least 4 weeks with topical calcipotriol and tazarotene in a half-side distribution. Additionally, the whole body was irradiated with narrowband UVB (311 nm) four times a week. Before treatment and once weekly during therapy a modified Psoriasis Area and Severity Index was estimated for each body half. The total treatment time, number of treatment sessions and cumulative UVB dose necessary for clearance of skin lesions were determined in an observer-blind fashion for each patient. Furthermore, all patients completed a quality of life questionnaire. RESULTS: Clearance of psoriasis was observed after a median of 19 treatment sessions (range 14-28) and a median cumulative UVB dose of 22.98 J cm-2 (range 9.24-58.22) simultaneously for both body halves. On the side treated with topical tazarotene gel, four patients complained of itching and dryness of the skin, and skin irritation was observed in three of them. Six patients preferred the application of tazarotene gel, while four preferred calcipotriol. CONCLUSIONS: Our clinical comparison of narrowband UVB with either topical calcipotriol or topical tazarotene revealed no significant therapeutic difference between both regimens. Although these results need to be confirmed in larger patient groups, we feel that both photocombination therapies can broaden the therapeutic options for moderate to severe psoriasis vulgaris and may reduce the cumulative UVB dose during therapy.

In vivo delayed-type hypersensitivity in 109 patients with vitiligo.

BACKGROUND: Although the etiology of the depigmentation disorder vitiligo is still not completely understood, many investigators believe that an autoimmune reaction may play a major role. In this regard, T-lymphocyte-mediated immunity has been implicated frequently in the pathogenesis of the disease. Most studies have applied in vitro testing of cell-mediated immunity, however, rather than in vivo measurements. Therefore, our study was undertaken to define the cutaneous delayed-type hypersensitivity (DTH) in vivo reaction in association with the absence/presence of serum thyroid autoantibodies, which are a good representative marker for autoimmunity in patients with vitiligo. METHODS: DTH was evaluated in the normal pigmented skin of 109 vitiligo patients (29 men and 80 women) and in the depigmented skin of 27 of this group (5 men and 22 women) using the dermal application of seven common recall antigens together with a negative control. Individuals were considered to be hypoergic if the DTH sum score was 0.05). Further evaluation of these data showed no significant correlation between the presence of thyroid autoantibodies as well as selected clinical parameters and an aberration in cutaneous DTH. CONCLUSIONS: In contrast to earlier reports, our in vivo studies of cutaneous DTH reactions revealed no clinically significant aberrant cellular immunity in this patient group. These results indicate that the immune reaction in vitiligo may be only a secondary event in the pathogenesis of the disease.

Eosinophilic fasciitis treated with psoralen-ultraviolet A bath photochemotherapy.

Eosinophilic fasciitis is a rare disorder which can markedly affect the quality of life in individual patients. So far, no generally accepted and effective treatment modality has been available. Although the precise nature of eosinophilic fasciitis is still unknown, it is often regarded as a variant of localized scleroderma (morphoea). Phototherapy and photochemotherapy have been shown to be effective in the treatment of sclerodermatous skin lesions. We report a patient with eosinophilic fasciitis which was successfully treated with psoralen plus ultraviolet A bath photochemotherapy within 6 months.

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.