Atopic Dermatitis, and the Role for a Ceramide-Dominant, Physiologic Lipid-Based Barrier Repair Emulsion
September 2013 | Volume 12 | Issue 9 | Original Article | 1024 | Copyright © September 2013
Leon Kircik MD,a,b Firas Hougeir MD,c and Joseph Bikowski MDd
aMount Sinai Medical Center, New York, NY
bPhysicians Skin Care, PLLC, Louisville, KY; cAtlanta, GA
dSkin Care Center, Sewickley, PA
Over the last half century, and especially over the last 15 years, understanding of the structure and function of the stratum corneum has evolved tremendously. Once conceptualized as an inactive film formed by lifeless, disintegrating keratinocytes, the stratum corneum is now recognized as a viable, functional structure that plays an important role in maintaining skin health and possibly mediating cutaneous diseases. Researchers and clinicians have also come to realize that the barrier functions not only to prevent the entry of exogenous factors, such as irritants or allergens, but that it also can mediate disease. We had already realized that dysfunction of the barrier may itself directly contribute to the pathogenesis of skin diseases, notably atopic dermatitis. More specifically, evidence shows that epidermal barrier dysfunction is likely to be a precursor of cutaneous inflammation.1,2
J Drugs Dermatol.
The Epidermal Barrier
The stratum corneum, which measures just 10 to 20μm in thickness,3,4 was once thought of as a passive film-like barrier comprised of dead and disintegrating corneocytes.5,6 Beginning in the 1960s researchers began to recognize
that the stratum corneum was not simply a lifeless barrier. However, the clinical significance of this recognition was slower to develop. There were two important publications that brought the stratum corneum to life. Kligmanâ€™s â€œBiology of the Stratum Corneumâ€ and a book chapter by Peter Elias titled â€œThe Epidermal Permaeability Barrier: From Saran Wrap to Biosenserâ€ were major contributions to our present day understanding of stratum corneum.7
The bricks and mortar model of the stratum corneum, though now recognized as incomplete and outdated, nonetheless remains
a reasonable basis for conceptualizing the components of the stratum corneum. Corneocytesâ€”the bricksâ€”are comprised
primarily of keratin macrofibrils protected externally by a cornified cell envelope. These are cohesively held together by corneodesmosomes.3 The cornified cell envelope is composed predominantly of proteins (eg, loricin, involucrin) and a covalently
bound outer lipid monolayer that is primarily made up of long chain ceramides.3,4,8,9 Corneodesmosomes anchor corneocytes within the stratum corneum; they are composed of specialized proteins: desmoglein-1, desmocollin-1, and corneodesmosin. Over time, proteloytic enzymes degrade the cohesive force between
corneocytes, resulting in physiologic desquamation.3,8-10
The intercellular lamellar lipid membraneâ€”the mortarâ€”is a bilayered
intercellular membrane. It is comprised of three major classes of lipid components present in a relative ratio of approximately
3:1:1: ceramides, cholesterol, and fatty acids. These major physiological stratum corneum lipids are produced enzymatically within the stratum corneum from specific precursor lipids.3,4,6,11-13
These precursor lipids are derived from lamellar bodies within the granular layer, namely glycosylceramides, sphingomyelin, and phospholipids and are extruded from lamellar bodies along with antimicrobial peptides.
It is now recognized that the physiological properties of these lipids, in this specific composition, permit the stratum corneum to perform its primary function of maintaining homeostasis by regulating water content, regulating water flux, and modifying transepidermal water loss.4,11,14
While it is not accurate to imagine the stratum corneum as an inactive, passive barrier, it is important to recognize that an optimally
functioning, dynamic stratum corneum does in fact serve a protective role. Among common exogenous factors against which the stratum corneum may protect the skin are irritants, allergens, and microbial organisms; climatic changes, especially those that cause low ambient humidity; and acute and chronic photodamage.
Additionally, ingested agents as well as topical or systemic medications can affect the stratum corneum.