Adrian Tanew

Photochemotherapy for severe psoriasis without or in combination with acitretin: A randomized, double-blind comparison study

In a randomized, double-blind comparative study 60 patients with severe, widespread psoriasis were treated either with photochemotherapy (PUVA) alone or in combination with acitretin. Forty-eight patients completed the study; of these, 25 received placebo combined with PUVA and 23 received acitretin with PUVA. Marked or complete clearing of psoriasis occurred in 80% of the patients (20 of 25) without acitretin and in 96% of the patients (22 of 23) with adjunctive acitretin administration. The mean cumulative UVA dose given to patients in the acitretin-PUVA group was 42% less than that required for patients in the placebo-PUVA group. We conclude that acitretin substantially augments the efficacy of photochemotherapy in the treatment of severe psoriasis.

Half‐side comparison study on the efficacy of 8‐methoxypsoralen bath‐PUVA versus narrow‐band ultraviolet B phototherapy in patients with severe chronic atopic dermatitis

In patients with severe chronic atopic dermatitis (AD), both photochemotherapy [psoralen ultraviolet A (PUVA)] and narrow‐band (TL‐01) UV B phototherapy have been reported to be very effective. As no data exist on the relative therapeutic efficacy of these two regimens, we performed a randomized investigator‐blinded half‐side comparison study on 12 patients with severe chronic AD. Half‐side irradiation with threshold erythemogenic doses of 8‐methoxypsoralen bath‐PUVA and narrow‐band UVB was performed three times weekly over a period of 6 weeks. The severity of the disease was assessed separately for the paired halves of the patients’ bodies by a modified SCORAD score at baseline and after 2, 4 and 6 weeks of treatment. Ten of the 12 patients completed the trial. All but one showed marked improvement or complete remission with both treatments. The mean baseline SCORAD score decreased by 65·7% by the bath‐PUVA treatment and by 64·1% by the narrow‐band UVB treatment (P = 0·48). No serious adverse reactions to either of the two regimens were observed. Our data confirm the high efficacy of bath‐PUVA and narrow‐band UVB phototherapy in the treatment of patients with chronic severe AD. Both regimens appear to be equally effective when administered in equi‐erythemogenic doses.

Polymorphous light eruption: Action spectrum and photoprotection

Polymorphous light eruption is a common seasonal photodermatosis with a typical history and clinical picture. In the interval, when no lesions are present, the diagnosis relies on artificial reproduction of polymorphous light eruption by phototesting. Photochemotherapy (psoralens with ultraviolet A [PUVA]) is currently an effective preventive treatment. One hundred sixty-seven patients with either a history of polymorphous light eruption or manifest disease entered our study. Of 142 patients tested, 49% developed typical lesions of polymorphous light eruption at the test sites. In 56% the action spectrum was found to be in the ultraviolet A range, in 17% in the ultraviolet B range, and in 26% in both ranges. A total of 122 patients received preventive treatment with PUVA. Of these, fifty-one returned for follow-up. Of the patients who were followed up, 64% reported total protection during outdoor activities in the summer, 26% reported partial protection, and 10% were not protected. Failure to improve was unrelated to the action spectrum. The action spectrum and the incidence of positive results on phototests in our patient population differed from those reported by others. It is possible that differences in the test protocols and in the light sources used may account for this discrepancy. There is clearly a need for a standardized test procedure. However, the majority of patients benefit from PUVA pretreatment regardless of their action spectrum.

Treatment of vitiligo with khellin and ultraviolet A

Twenty-eight patients with vitiligo were treated with a new photochemotherapeutic regimen using khellin, a furanochromone, as photosensitizer, together with ultraviolet A (UVA) irradiation. Twenty-five patients received khellin orally and three patients were treated with topical khellin. Treatments were given three times weekly. As opposed to psoralens, khellin did not induce skin phototoxicity with UVA but it induced repigmentation similar to psoralens. The treatment success strongly depended on the number of treatments. More than 70% repigmentation was achieved in 41% of the patients who had received 100 to 200 treatments. This success rate is comparable to the rate obtained with psoralens. Seven patients experienced a mild elevation of liver transaminases within the early treatment phase and their treatments were discontinued. No long-term internal organ or skin toxicity was observed. The major advantage of khellin is that it does not lead to phototoxic skin erythema and thus can be considered safe for home treatment. Because of its photochemistry it may be considered less hazardous than psoralens regarding mutagenicity and carcinogenicity.

5-Methoxypsoralen (Bergapten) for photochemotherapy: Bioavailability, phototoxicity, and clinical efficacy in psoriasis of a new drug preparation

In a previous study we evaluated a microcrystalline preparation of 5-methoxypsoralen (5-MOP; Bergapten) for its photochemotherapeutic properties. Preliminary data indicated that the clinical efficacy of 5-MOP is comparable to that of 8-methoxypsoralen. 5-MOP appeared as a promising alternative photosensitizer for the management of psoriasis because of the almost complete lack of phototoxic and drug intolerance reactions that are frequently encountered in patients undergoing 8-MOP photochemotherapy. With a new liquid preparation of 5-MOP we have now extended our earlier investigation on a larger clinical scale and have correlated the clinical response with the bioavailability of the drug. Serum level determinations showed an absorption rate of only approximately 25% that of 8-MOP. When administered in the same dosage as 8-MOP, 5-MOP turned out to be significantly less effective; however, by doubling the oral dosage, comparable results in terms of clearing of psoriasis were obtained. Also with this high-dose 5-MOP regimen, no drug intolerance was noted and other side effects, such as severe erythema, pruritus, and nausea, occurred only rarely. We propose 5-MOP as a valuable alternative for photochemotherapy (PUVA) of PUVA-responsive diseases.

Skin Tumors in Photochemotherapy for Psoriasis: A Single-Center Follow-Up of 496 Patients

BACKGROUND The significance of oral psoralen photochemotherapy (PUVA) for the development of nonmelanoma skin cancers (NMSC) is still controversial. OBJECTIVE We evaluated 496 psoriatics, who received PUVA treatment according to the European PUVA protocol in order to reassess the influence of the cumulative UVA dose on the development of NMSC and to answer the question if there is a UVA threshold dose above which the carcinogenic risk is increased. METHODS The study was conducted as a retrospective investigation. All patients were seen personally. Age, sex, skin type, cumulative UVA dose and carcinogenic risk factors (arsenic, X-rays, tar, UVB, methotrexate) were recorded and investigated by marginal (MA) and partial effects analyses (PA) according to the Cox regression model. RESULTS In 14 patients (2.8%), one or multiple histologically confirmed NMSC were diagnosed. Nine patients (1.8%) had squamous cell carcinoma (SCC), 5 patients (1.0%) had basal cell carcinoma (BCC). No patient had both types of NMSC. None of the SCC had metastasized. By taking the appearance of BCC and SCC as the endpoint, arsenic [MA: relative risk (RR) = 7.62; PA:RR = 5.36], tar (MA:RR = 4.51; PA:RR = 3.83) and methotrexate (MTX; MA:RR = 4.97; PA:RR = 4.07) appear to produce strong and significant effects (p < 0.05), both in MA and PA. Using the endpoint SCC only, the effect of the natural logarithm of UVA (ln UVA; RR = 2.47), arsenic (RR = 11.2), tar (RR = 9.92) and MTX (RR = 7.1) is significant (p < 0.05) in MA. In PA, only the effect of arsenic (RR = 5.19) is strong and significant (p < 0.05) while the effects of tar (RR = 7.85), MTX (RR = 3.22) and ln UVA (RR = 2.77) are strong but of borderline significance (p = 0.05-0.11). Nonlinear effects of ln UVA on the risk of SCC were far from significant (p > 0.2). CONCLUSION PUVA with the European treatment protocol appears to be only a weak carcinogen by itself for SCC with a linear increase in tumor risk but not for BCC development.

Nonmelanoma skin tumors in long-term photochemotherapy treatment of psoriasis: An 8-year follow-up study

Two hundred ninety-seven long-term photochemotherapy (PUVA)-treated patients from an original cohort of 418 subjects reported in 1980 were reevaluated in a second follow-up in order to determine the risk of tumor development under long-term PUVA. Within an observation period of up to 8 years (mean, 63.1 months) six patients with squamous cell carcinomas and three with basal cell carcinomas were observed. Eight of the nine tumor patients had been exposed to potential carcinogens such as arsenic and/or ionizing radiation prior to PUVA treatment. Five with squamous cell carcinomas were skin type I or II; in four of the six patients with squamous cell carcinomas the tumors were located on unexposed skin areas. The mean cumulative ultraviolet A (UVA) dose in three of the six squamous cell carcinoma patients was three times as high as that in the group of nontumor patients. The other three squamous cell carcinoma patients had lower mean doses than nontumor patients, as did the three patients with basal cell carcinomas. Although the cumulative UVA dose may eventually turn out to be relevant for PUVA carcinogenesis, our present data do not sufficiently substantiate a correlation between cumulative UVA dose and squamous cell carcinoma formation in PUVA-treated patients. This report confirms that previous exposure to carcinogens appears to be the most important factor for nonmelanoma skin tumor formation in long-term PUVA patients.

Lethal photosensitization by endogenous porphyrins of PAM cells — modification by desferrioxamine

The effects of exogenous delta-aminolevulinic acid (ALA) on cultured PAM 212 cells were investigated. PAM cells exposed to ALA produce an excess of products of the heme biosynthesis pathway within hours. The endogenous porphyrins render the cells photosensitive in a time-, ALA dose- and irradiation-dependent manner. Independently of the ALA-induced photosensitized processes, ALA itself reduces the proliferation rate of PAM cells during the exponential growth phase. Iron deprivation by addition of the chelating agent desferrioxamine (df) accelerates the photosensitizing process, and thus makes it more efficient at lower ALA concentrations. The effects of df were compared with the effects of manganese-df and iron-df. The results indicate that iron trapping is the most important factor for the potentiation of ALA-stimulated photodynamic sensitization as well as for the dark toxicity. Iron complexing agents may thus be used to optimize ALA effects in the photodynamic treatment of cutaneous neoplasms with endogenous porphyrins.

Narrow-band ultraviolet B (TL-01) phototherapy is an effective and safe treatment option for patients with severe seborrhoeic dermatitis

Background Seborrhoeic dermatitis is a common papulosquamous dermatosis affecting 2–10% of the adult population. Current treatment options are limited and not always satisfactory.

Cyclosporin A in combination with photochemotherapy (PUVA) in the treatment of psoriasis

Forty patients with relapsing plaque psoriasis involving more than 20% body surface were treated either with cyclosporin A (CyA) plus PUVA or the retinoid etretinate plus PUVA (RePUVA). They initially received either CyA (2 weeks) or etretinate (I week) alone and then PUVA was given concomitantly until complete remission. The patients were monitored over a period of 6 months and any relapse recorded. With each combined treatment regimen, CyA plus PUVA and RePUVA, the patients cleared within comparable periods of time (mean treatment period og 5.3 vs. 4.7 weeks after initiation of therapy and 3.3 vs. 3.7 weeks after initiation of PUVA). However, the cumulative UVA dose required for clearance (110.9 J/cm2 vs. 62.1 J/cm2 (P < 0.05)) and the incidence of severe and early relapses were significantly higher in the CyA cohort. Within 6 months severe relapses had occurred in 58% of CyA plus PUVA but only in 15% of RePUVA‐treated patients (P < 0.001). This suggests that the CyA plus PUVA regimen as performed in this study is less effective than RePUVA.