James Breeding

Coal tar phototherapy for psoriasis reevaluated: Erythemogenic versus suberythemogenic ultraviolet with a tar extract in oil and crude coal tar

Recent studies have questioned the therapeutic value of coal tar versus ultraviolet (UV) radiation and their relative necessity in phototherapy for psoriasis. In this investigation, different aspects of tar phototherapy have been studied in single-blind bilateral paired comparison studies. The effects of 1% crude coal tar were compared with those of petrolatum in conjunction with erythemogenic and suberythemogenic doses of ultraviolet light (UVB) using a FS72 sunlamp tubed cabinet. Crude coal tar was clinically superior to petrolatum with suberythemogenic ultraviolet. With the erythemogenic UVB, petrolatum was equal in efficacy to crude coal tar. Suberythemogenic UVB was also used adjunctively to compare the effects of a 5% concentration of a tar extract in an oil base to 5% crude coal tar in petrolatum or the oil base without tar. The tar extract in oil plus suberythemogenic UVB produced significantly more rapid improvement than the oil base plus UVB. The direct bilateral comparison of equal concentrations of tar extract in oil base versus crude coal tar in petrolatum in a suberythemogenic UV photo regimen revealed no statistical differences between treatments. In a study comparing tar extract in oil and the oil base without ultraviolet radiation, the tar extract in oil side responded more rapidly. This demonstrates a direct effect of tar alone in therapy. We have also studied the effects of erythemogenic and suberythemogenic UVB with and without tar extract in oil in the hairless mouse epidermal deoxyribonucleic acid (DNA) synthesis suppression assay. It was found that erythemogenic dosages of UVB produced near maximal inhibition of DNA synthesis with or without coal tars. Suberythemogenic dosages of UVB produced submaximal suppression of DNA synthesis that was enhanced by adjunctive coal tar but not by vehicle, findings which are consistent with the above clinical results. These studies suggest that coal tars combined with suberythemogenic UVB therapy is a practical alternative (to more aggressive UVB therapy without coal tar) which reduces the UVB exposure to the patient.

Cutaneous polyamines in psoriasis

The polyamines putrescine, spermidine and spermine are intimately associated with cellular growth and division. Previous studies ofthe polyamines and their rate limiting biosynthetic enzyme, ornithine decarboxylase, in psoriasis have shown significant changes compared with non‐psoriatic skin. We have further studied cutaneous polyamines in patients with psoriasis and in normal subjects. Epidermal shave biopsies were taken and assayed for ornithine decarboxylase activity and polyamine levels. Psoriasis lesions showed increased ornithine decarboxylase activity compared with vminvolved skin. The levels of ornithine decarboxylase activity in uninvolved psoriasis skin were also higher than in normals. There was increased putrescine in involved psoriasis compared with uninvolved and normal skin. Spermidine and spermine were increased in psoriasis skin and in vminvolved skin and compared with normals. The spermidine/spermine ratio was greatest in involved skin compared with uninvolved and normal.

Etretinate treatment for psoriasis inhibits epidermal ornithine decarboxylase

Previous studies of the polyamines and their biosynthetic enzyme ornithine decarboxylase (ODC) in psoriatic skin have revealed several abnormalities, including significantly elevated ODC activity. Retinoids have also been shown to modulate polyamine biosynthesis and inhibit ODC activity after different stimuli in various cell and tissue systems. The effect of etretinate has been studied on ODC activity in involved and uninvolved psoriasis skin. Increased ODC activity was found in pretreatment samples from both involved and uninvolved psoriatic skin compared with normal volunteers. Etretinate treatment significantly reduced ODC activity in both involved and uninvolved skin in psoriatics to a similar level of activity before any improvement in clinical appearance was noted. Inhibition of epidermal ODC activity in psoriasis may represent one mechanism of retinoid action on the abnormal skin psoriasis.

The pharmacological variability of crude coal tar

Although crude coal tar is a mixture of approximately 10,000 components, few attempts have been made to assess the pharmacological activity of individual components of purified tar products or of different coal tars themselves. The hairless mouse epidermal DNA synthesis suppression assay, which has been shown to be useful for predicting the antiproliferative activity of topical agents, has recently been used to assess the activity of crude coal tar, coal tar extracts and tar based shampoos. Using this assay, great variation in effectiveness (0–90%) was found among tar distillate fractions, suggesting that one source of potential variation of activity in commercial coal tar products is the non‐standard composition of crude coal tar itself.