THE PH GRADIENT OVER THE STRATUM-CORNEUM DIFFERS IN X-LINKED RECESSIVE AND AUTOSOMAL-DOMINANT ICHTHYOSIS - A CLUE TO THE MOLECULAR-ORIGIN OF THE ACID SKIN MANTLE

In a search for pathogenetic mechanisms underlying retention hyperkera tosis, we examined the pH gradient over the stratum corneum in 13 male patients suffering from either x-linked recessive (XRI) or autosomal dominant ichthyosis vulgaris, For recording pH values, a flat glass el ectrode was repeatedly applied to the skin during tape stripping of mi ldly involved forearm skin. Before stripping, surface pH was higher in ichthyosis vulgaris (5.3 +/- 0.7; n = 7) than in XRI (4.6 +/- 0.4; n = 6: p < 0.05) and healthy control men (4.5 +/- 0.2; n = 7; p < 0.01). Removal of stratum corneum, which required 100-240 strippings in icht hyotic skin and 80-120 strippings in healthy control skin, disclosed m arkedly different pH variations in the two types of ichthyosis. The ma jor abnormality in ichthyosis vulgaris skin was that a neutral pH was attained already halfway through the horny layer, possibly reflecting a congenital lack of acidic breakdown products from keratohyaline. By contrast;, stripping of XRI skin revealed a shallow pH gradient that p lateaued at 6.2-6.6, instead of about 7 as in normal and ichthyosis vu lgaris skin, A likely explanation is the XRI-associated accumulation o f cholesterol sulfate in lower stratum corneum. Our results suggest th at the ''acid mantle'' of Is normal skin, which penetrates deep into t he stratum 6; corneum, is the combined result of cornification-associa ted; organic acids and back-diffusion of acid material from the surfac e. Becuase corneocyte desquamation involves many pH-dependent enzymes, abnormalities in the transcorneal pH gradient might play a role in th e pathogenesis of ichthyosis.