Basement membrane changes in psoriatic patients on long-term topical corticosteroid therapy

It has been observed that the beneficial anti-inflammatory effects of topical steroids in psoriasis are counteracted by increasing instability of the disease, with rebound phenomena associated with the cessation of these drugs. We report the occurrence of multi-layered fragmentation and disorganization of the basal laminae in active, untreated psoriatic lesions, resolving and uninvolved, inadvertently steroid-treated psoriatic skin, as well as in a variety of non-psoriatic dermatoses treated with fluorinated topical steroids for prolonged periods. These changes, which were associated with a moderate to severe loss of dermal collagen, were not found in untreated and treated psoriatic controls, with or without concomitant alpha 1-antitrypsin deficiency, who had not received steroids, suggesting that they were probably the consequence of prolonged fluorinated steroid use. This conclusion is supported by the observation that the largest number of layers (10-15) of fragmented basal laminae was noted in the patients who had received fluorinated steroids for 6 years or more, while those on 4 years or less of fluorinated steroid therapy exhibited only three to seven layers of fragmented basal laminae. In psoriatic lesions, the fragmentation of the basal lamina was associated with the presence of basal keratinocyte herniations (BKH), the frequency of which has been shown to parallel clinical psoriatic activity. The persistence of these electron-microscopic markers of psoriatic activity (i.e. BKH) in psoriatic plaques treated with prolonged fluorinated steroids suggests that loss of integrity of the basement membrane, as indicated by the presence of multi-layered fragmentation of the basal lamina, may account for the instability of the psoriatic lesions treated with prolonged topical fluorinated steroids.