Chapter 12 401 decreased number of desmosomes, irregular corneocyte envelope structure, intercellular Malassezia yeasts, and massive quantities of unstructured intercellular lipids (refer to Figure 2). All of these features are consistent with a state in which the feedback between epidermal synthesis and maturation rate is lost and uncontrolled growth leads to corneocytes that are immature and not ready to be shed as individual cells reaching the surface. The intercellular lipid abnormalities are striking in amount as well as lack of order. As expected, there is a lack of true intercellular lipids (ceramides), with most of the lipids being sebaceous in origin.57 This is indicative of a lack of a temporally ordered series of events, resulting in low epidermal lipid secretion and a lack of proper organization into a functional stratum corneum. Simply topically applying such lipids is unlikely to be meaningful, as they cannot displace the sebaceous lipids, nor will they be able, in abstentia from the normal physiology, to initiate the formation of missing features such as a tight lamellar structure and the other characteristics required for proper function or orderly desquamation. The pathophysiological features observed at the symptom/sign and structure/function levels are also observed at the molecular level. Using new noninvasive biomarker sampling techniques, biomarkers associated with each pathophysiological step (i.e. inflammation, hyper-proliferation and barrier disruption) have been observed as significantly altered in D/SD populations vs. non-D/ SD control groups. Inflammatory bio-markers such as IL-1a14 and histamine58 are dramatically elevated in the D/SD condition, supporting the macro observations. Likewise, biomarkers of hyper- proliferation/differentiation (involucrin, specific keratins) and barrier disruption (human serum albumin and ceramides) are shown to be perturbed compared to a normal population. Treatment of dandruff and seborrheic dermatitis will be discussed below (for which discussion, please refer to Figure 8, as well), but it is appropriate to mention here that as certain treatments of the initiating cause, fungal interaction with the scalp, not only is the outward symptom of flakes improved, but the underlying