The stratum corneum: a moving subject
Authors: R. Marks
Journal: British Journal of Dermatology (2014)

When I was a young registrar the stratum corneum was not fashionable. 'Don't bother with that pink wispy stuff on the surface', was the advice offered by my mentors in dermatopathology, while pointing out the salient features in haematoxylin and eosin-stained, paraffin-embedded, microtome-cut sections of skin. This was more than 40 years ago and luckily things have moved on. The first meeting of which I'm aware that focused on the stratum corneum took place in Cardiff in 1981. Since then we have held several international symposia and initiated the International Society for Stratum Corneum Research (ISSCR) and witnessed the blossoming of the subject. Many of the revelations and the growing body of data on the stratum corneum were first brought into the public arena by the high priest of skin biology – Albert Kligman.1 It was his initial assertion that the stratum corneum was anything but dead that has changed attitudes. The development of better methods for investigating the structure of the horny layer greatly assisted in the development of a new interest in what had been regarded as irrelevant waste material (Figs 1-3). Being able to visualize the 'stacked coin arrangement' of the stratum corneum using fluorescein isothiocyanate (FITC) and fluorescence micrography or an alkali swelling method rapidly disabuses the observer from the view that the stratum corneum is the accumulation of haphazardly arranged dead detritus. The simple, but extremely useful and highly adaptable technique developed by Rod Dawber and myself in 1971,2 which we called skin surface biopsy also helped in expanding our understanding of the stratum corneum as a carefully crafted membrane playing a vital role in skin biology. These quite simple morphological techniques altered within a decade the way that we thought about the stratum corneum. Clearly the 'brick wall' concept with the horn cells thought of as bricks held together by a lipid cement was inadequate to explain either the complex barrier properties of the stratum corneum or the mysterious mechanisms of desquamation. Careful and sophisticated biochemistry moved the focus of research interest to proteolysis of the residual desmosomal structure – the corneodesmosome – linking individual corneocytes one to the other.3 The tryptases responsible turn out to be the results of complex sequences and activation systems – all this biochemical activity taking place in what used to be regarded as a lifeless degenerate cellular mess! One would not expect degenerate and lifeless stratum corneum to be responsive to local stimuli or alterations in nearby tissues, yet profound changes in corneocytes are always found after 'events' in the epidermis. All eczematous disorders are accompanied by reductions in size of the corneocytes – at least as judged by the mean surface area of corneocytes. This is presumably the result of a speeding up of epidermal cell production, which will influence the development of corneocytes. Changes in the barrier properties of the stratum corneum occur after quite modest changes in the environment. Alterations in the stratum corneum barrier to xenobiotics or the permeability to water can be detected some days after visual restoration of the normal skin surface following 'skin stripping' with sticky adhesive tape.4 Even more unexpected are measurable alterations in the permeability of the stratum corneum barrier after experiencing serious emotional trauma.5 The mechanisms responsible for these changes are by no means clear although it is likely that quite complex biochemical rearrangements take place. Several groups of researchers have contributed to the massive changes in the understanding of the lipid profile of the stratum corneum. In particular could be mentioned the work on the role of sterols by Peter Elias and on the ceramides or the researches of Ponec and colleagues in the Netherlands on the role of lipids on stratum corneum permeability. The rolling back of the clouds of ignorance surrounding the process of skin permeability is by no means yet complete, but it has 'moved' much further on from where we started. A hefty part of our increased knowledge about the horny layer has come from the devising, adapting and use of instruments and techniques to squeeze out information from the stratum corneum. Of special assistance in learning how stratum corneum function is affected by change in the ambient environment, by disease or by exposure to various xenobiotics, has been instruments that measure the flux of water vapour across the skin.6 The evaporimeter has been of special assistance. This device measures the flow of water vapour electronically across two electrodes and is quite simple to set up and use. Desquamation is the vital final endpoint of epidermal differentiation – yet we are for the most part bereft of a reliable way to measure the process. The techniques that we do possess estimate stratum corneum turnover and are of some limited clinical use. Assessments of skin surface contour or skin topography are products of the past two decades and have helped us follow changes following topical therapies and that occur in ageing and photodamage. Initial attempts used conceptually simple mechanical techniques that had been developed by the ceramics and metal industries. These employ the profilometric tracing of skin replicas. In the past decade more complex (but more sensitive and more accurate) techniques have been developed, which do not rely on skin surface replicas and use an optical method relying on a phase shift of projected parallel lines.7 So far I have pointed out the enormous strides made in our knowledge of the structure and function of the stratum corneum. But not only has there been an intellectual 'movement' when considering the stratum corneum, there is also a constant physical movement. Every aspect of our lives involves some kind of movement, whether it is the manipulation of the hand, arm and fingers such as occurs during writing or the leg and hip action during walking. Whatever the movement, the skin in the anatomical region concerned willingly complies with the instruction permitting movement of the part. Skin movement could be accomplished with redundant folds of skin and this seems to be the mechanism primarily responsible for movements around the elbows and wrists. However, movements of the fingers and toes, the face and the trunk need movement in the superficial parts of the overlying skin. A significant, but unknown proportion of this movement is due to the unfolding of the skin surface markings. If the pattern on the surface of the forearm is closely observed with a magnifying glass before and after some form of extending stress, the rhomboidal surface pattern can be observed to undergo concertina-like alterations. Some of the extensions must be the result of genuine extension in the stratum corneum itself.8 There have been several attempts at measuring the extensibility of the stratum corneum but as yet no method can be judged as completely satisfactory. Major problems remain, including the obtaining of the sample uncontaminated by underlying tissues and the performing of the tests in a constant ambient environment. Devices such as the gas bearing dynamometer, the twistometer and various needle indentometers designed to work in vivo all seem to show some intrinsic extensibility of the stratum corneum, but currently there is no ideal way of quantifying stratum corneum extensibility in vivo. It would be clinically useful to have such a measure when skin is severely inflamed as in acute eczema or psoriasis the stratum corneum becomes scaly and it loses its normal ability to extend. When attempts are made to extend skin affected in this way the sites that have lost the ability to stretch develop fissures and cracks. These are painful and not infrequently become infected and delay healing, thus becoming an unpleasant and annoying complication of conditions such as hand eczema and psoriasis. The stratum corneum is also an important component of the mechanical defensive shield system of skin preventing damage from sundry sharp articles encountered in the environment – most of the would-be unfriendly biting and/or stinging arthropods are rendered harmless by the tough, extensible resistant stratum corneum. The ability to extend when challenged is an important aspect of stratum corneum movement, but of course the stratum corneum moves continually in compliance with all body parts without thought or planning. The outline above should serve to convince – if this be necessary – of the great movement in our understanding of the biology of the stratum corneum including its little recognized important ability to physically move passively. Lest a sense of smug satisfaction flow over the reader, a realization of what we do not yet know should quickly follow. I will do no more than point out that we know precious little about percutaneous penetration or the control of desquamation. From a practical clinical point of view it would be useful to learn about metabolic activity or ambient drug levels from tiny stratum corneum samples. These and many other current unknowns are there to interest and tease our students.