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 48-72 h until the therapeutically effective concentration is reached, which takes time and appears to prolong treatment. We felt that if the minimal
erythema concentration (MEC) of
anthralin could be determined initially in an individual, this ought to be near or at the final achievable therapeutic concentration. Hence, by analogy with
ultraviolet therapy, treatment could start just below this concentration and thus avoid delay. A series of concentrations of
anthralin in
Lassar's paste was applied to the back 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 areas 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 pretreated 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 dose-response curve increased from 0. 06% to 0.25% (P = 0.01), demonstrating a clear adaptive response. One pretreatment produced a 52% reduction in
erythema compared with control challenge, and maximal 61% inhibition was seen after three applications. Pretreatment with a subirritant concentration of a control
irritant,
croton oil, had no effect on the response to
anthralin and vice versa. Pretreatment of skin with
danthron, the non-
irritant oxidation product of
anthralin, had no effect, suggesting that the attenuation effect is specific to native
anthralin. To see whether the attenuation might be due to modulation of
xenobiotic metabolizing
enzymes, skin was pretreated with inducers and inhibitors of the
cytochrome P450 and
NADPH-dependent
quinone reductase (NDQR)
enzyme systems. However, no effect was seen. In conclusion, 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 of native
anthralin, and the
enzymes P450 and NDQR are apparently not responsible for this effect.