The irritancy of anthralin is inhibited by repeat applications of a subirritant concentration

Anthralin is a safe, effective treatment for psoriasis, but its efficacy is hampered by the side-effects of irritation and staining of the uninvolved skin, To avoid burning, it is customary to start at low concentrations and increase every 48-72h until the therapeutically effective concentration is reached, which takes time and appears to prolong treatment. Mie felt that i f the minimal erythema concentration (MEC) of anthralin could be determined initially in an individual, this ought to be near or at the final achievab le therapeutic concentration. Hence, by analogy with ultraviolet therapy, t reatment could start just below this concentration and thus avoid delay, A series of concentrations of anthralin in Lassar's paste was applied to the bad; for 3 h, and erythemal responses assessed at 24 and 48 h, MECs (0.015- 0.03%) were far below those usually reached during normal therapy, To test the possibility that the skin was adapting to anthralin, we pretreated area s of skin with a subirritant concentration of anthralin (0.007%) for 3 h on 2 consecutive days prior to application of the full dose series. On the pr etreated areas, the MEC increased fourfold from 0.015% to 0.06% (P < 0.01); the concentration of anthralin required to produce the mid-point on the do se-response curve increased from 0.06% to 0.25% (P = 0.01), demonstrating a clear adaptive response. One pretreatment produced a 52% reduction in eryt hema compared with control challenge, and maximal 61% inhibition was seen a fter three applications. Pretreatment with a subirritant concentration of a control irritant. croton oil, had no effect on the response to anthralin a nd vice versa, Pretreatment of skin with danthron, the non-irritant oxidati on product of anthralin, had no effect, suggesting that the attenuation eff ect is specific to native anthralin, To see whether the attenuation might b e due to modulation of xenobiotic metabolizing enzymes, skin was pretreated with inducers and inhibitors of the cytochrome P450 and NADPH-dependent qu inone reductase (NDQR) enzyme systems, However, no effect was seen. Tn conc lusion, we have shown that the irritant response to anthralin is attenuated by repeated applications of a subirritant concentration of anthralin; this is not a non-specific response to all irritants, but a specific property o f native anthralin, and the enzymes P450 and NDQR are apparently not respon sible for this effect.