A Look at Healthy, Distressed, and Diseased Skin PDF

A look at healthy, distressed and diseased skin Mignon Cristofoli Danka Tamburic Caroline Searing Terence Chung 1  Content 1) Biochemical processes that affect skin...

A look at healthy, distressed and diseased skin Mignon Cristofoli Danka Tamburic Caroline Searing Terence Chung 1  Content 1) Biochemical processes that affect skin appearance 2) What can cosmetics do? 3) Some skin conditions 4) Some common skin diseases 2  Skin – the window to our health Normal Jaundice- bilirubin build up, Palmar erythema - can be Acanthosis nigricans Rosacea: redness due to break down of red connected to issues with can be a sign of prediabetes or due to dilated blood blood cells thyroid, liver or rheumatoid diabetes vessels arthritis Skin is the visible indicator of the inner workings of the body Biochemical (including nutritional) imbalances of the body can be manifested on the skin 3 3 1) Biochemical processes that affect skin appearance Keratinisation Melanin production Sebum production Sweat production Blood supply to skin Wound healing Immune function https://img.webmd.com/dtmcms/live/webmd/consumer_assets/site_images/articles/image_article_collections/anatomy_pages/skin.jpg?resize=646px:*&output-quality=100 Inflammatory responses Can result in or impact: Oxidative stress Desquamation Stratum Corneum regeneration The integrity of dermis 4  Biochemical events that negatively affect skin health Extrinsic and intrinsic factors that affect biochemical activities Extrinsic Sun exposure and radiation (UV, Oxidation – ROS formation, affect on factors Visible, Infrared) cellular level, prevention Temperature (& Wind) Humidity (& Wind) Irregular desquamation – response to pH changes moisture, pH and bacteria Skin microflora composition Impaired SC regeneration Intrinsic Nutrition factors ―Proteins (amino acids) Loss of dermal integrity ―Carbohydrate (collagen, elastin and ―Fat hyaluronic acid) ―Vitamins ―Minerals Inflammation – (not covered today) Hydration UV damage – (not covered today) Gene and protein expression Hormone changes and stress 5  Oxidation: What is oxidative stress? Oxidative stress occurs when there is an imbalance between the production of free radicals and the body's ability to counteract their damaging effects through neutralisation with antioxidants. Oxidative damage is the harm sustained by cells and tissues due to an excess of free radicals. https://www.researchgate.net/publication/308983717/figure/fig3/AS:560713430646785@ 151069590 7439/Oxidative-stress-and-inflammation-imbalance-of-antioxidants-and-free-radicals.png 6  Some terminology Radical/ free radical = an atom or molecule with one or more electrons that are not paired together in an orbital. Can be neutral, positively or negatively charged. Eg chlorine as it appears in the periodic table is a neutral atom with 17 protons & 17 electrons. As it only has 7 electrons in its valence shell, one electron is unpaired, making it a radical. To stabilise it takes an electron and is written Cl-, will often appear as a dimer sharing electrons to achieve stability: Cl2 Examples of oxygen free radicals alkoxyl : R-O. (R could be methyl, ethyl etc) peroxyl (R-O-O.) (2 oxygens) hydroperoxyl (H-O-O.) 7  Terminology continued ROS (reactive oxygen species) - highly reactive molecules or ions (ie engage in chemical reactions with other molecules) containing at least one oxygen atom (Jakubczyk et al, 2020); comprise both free radicals (i.e. one or more unpaired electrons) and non-free radical oxygen intermediates Examples: hydrogen peroxide (H2O2), superoxide (O2 -), singlet oxygen (1O2), and the hydroxyl radical ( OH) ROS could also be N-based Examples: nitric oxide (NO.); nitrogen dioxide (NO2.) Pro-oxidant: any endobiotic or xenobiotic that induces oxidative stress either by generation of ROS or by inhibiting antioxidant systems. (Rahal et al, 2014) Free radicals can cause changes in proteins, lipids and DNA, i.e. oxidative damage 8  Cellular energy production Glucose is the preferred source of energy in human cells Fat is used second, and protein third preferred source Glycolysis is the first in the series of biochemical steps where glucose is broken down, releasing the energy it carries The ultimate aim is the generation of ATP molecules from ADP This is happening in cell organelles called mitochondria The process involved is called oxidative phosphorylation ATP is the universal energy currency used in the cells by almost all proteins that require energy to function 9 http://cronodon.com/images/mitochondrion_di1a2gram.jpg Cellular energy production scheme The electron transport chain is a series of proteins embedded in the inner mitochondrial membrane 10  Cellular damage and removal of ROS Free radical forms of the ROS molecules can cause uncontrolled irreversible covalent modification to proteins, lipids and DNA. The downstream chain reaction can result in wide-spread damage across the cell, contributing to the aging process ROS can be removed by endogenous antioxidants: eg the enzymes superoxide dismutase (SOD), glutathione peroxidase and catalase, that ultimately convert the high energy reactive molecules into water SOD deficiency can cause premature ageing 11 Example of oxidative damage: lipid peroxidation ROS attacks on lipids can cause lipid peroxidation, which can generate downstream products, e.g. lipid peroxyl radical They are less reactive than ROS However, they are considered more dangerous due to their ability to remain reactive far away from where they were originally generated They rapidly pass through the lipid bilayer and have the ability to cause long-range and widespread cellular damage 12  ROS theory of ageing The production of 90% of ATP relies on the functioning of the electron transport chain and the process of oxidative phosphorylation (10% comes from glycolysis outside the mitochondrion) The electron transport chain is a highly energetic process It can be ‘leaky’ and can generate ROS which in turn cause covalent damage to proteins, lipids and DNA, causing oxidative stress to cells The ROS theory of ageing proposes that ageing is the result of oxidative damage to cells and tissues arising from aerobic metabolism That means that ageing is inherent within our physiology 13 Oxidative damage pathway 14 Antioxidant & electron donation 15 Biorender.com Protection from ROS: small molecule, non-enzymatic antioxidants Antioxidants have the ability to inhibit or reverse the oxidation of other molecules by becoming oxidised themselves Can be lipophilic (e.g. vit E) and hydrophilic (e.g. vit C) Vitamin C – ascorbic acid Derivatives of vitamin E and vitamin C are often used in cosmetics due to their improved penetration and/or stability Stability and strength of antioxidants can vary It is better to use a mixture of antioxidants in a product, rather than just one 16  Oxidised forms of antioxidants Once they have donated electrons, antioxidants are no longer “active” Oxidised forms of antioxidants are stabilised due to resonance, i.e electrons are distributed across a number of atoms To become active again need to be regenerated Some antioxidants form stable end products after oxidation, but cannot be regenerated (eg. melatonin) Carr and Frei, 1999. 17 Antioxidant regeneration Antioxidants can be regenerated by other antioxidants Vit C and vit E act synergistically Vit C regenerates vit E Retinol can also regenerate vit E Glutathione can reduce vit C and vice versa Antioxidants can be regenerated by enzymes eg oxidised glutathione is reduced by glutathione reductase 18  remember reduction is the addition/ Antioxidant regeneration gain of an electron Qasem et al, 2016. Glutathione can be oxidised via glutathione peroxidase Glutathione (GSH)  Glutathione disulphide (GSSG) The reduction of oxidised glutathione: Glutathione reductase, NADPH + GSSG + H2O → 2 GSH + NADP+ + OH− The ratio of reduced to oxidised glutathione within cells is a measure of cellular oxidative stress. In healthy cells and tissue, more than 90% of the total glutathione pool is in the 19 reduced form (GSH).  Phytochemicals -antioxidants Plants are exposed to an extraordinary amount of UV High unsaturated fatty acids are also used in their lipid membranes to maintain fluidity Many antioxidants are needed to prevent lipid peroxidation Examples: Beta-carotene and carotenoids Ascorbic acid Tocopherols Polyphenols Melatonin (also produced in humans) They are often brightly coloured https://upload.wikimedia.org/wikipedia/commons/a/ac/Berries.jpg 20 Abnormal level of oxidative stress Basal oxidative stress: is the amount of oxidative stress (eg ROS) necessary for survival of a cell Severe oxidative stress can lead to cell damage and cell death Basal levels can be raised internally (INT) or externally (EXT) via: Physical exercise (INT) Increased calorie consumption (INT) Exposure to UV light (EXT) Smoking (EXT) Ozone (EXT) Air pollution (EXT) Rinnerthaler, Mark, et al. "Oxidative stress in aging human skin." Biomolecules 5.2 (2015): 545-589. 21  Extrinsic oxidative stress – air pollution Ozone exposure leads to depletion of SC tocopherol and vitamin C and an elevated level of lipid peroxidation Exposure to particulate matters (PMs) leads to increased level of metalloproteinases (MMPs), degradation of collagen, and increased inflammation. Topical application of Vit C, E and ferulic acid provides protection from air pollution induced oxidative stress Thiele, Jens J., et al. "Ozone-exposure depletes vitamin E and induces lipid peroxidation in murine stratum corneum." Journal of investigative dermatology 108.5 (1997): 753-757. Valacchi, Giuseppe, et al. "Vitamin C compound mixtures prevent ozone-induced oxidative damage in human keratinocytes as initial assessment of pollution protection." PloS one 10.8 (2015): e0131097. 22  ROS & other factors affects stem cells Impairment of DNA and protein repair mechanisms Impaired gene expression / protein expression caused by genetic mutation and toxic accumulation of DNA adducts and protein aggregates. Trigger programmed cell death, which avoids build up of dysfunctional cancerous cells. Reduced number of viable stem cells available for regeneration 23 stem cell niche: environment that supports stem cells Nature Medicine, 2014, 20, 870–880 (2014)  Desquamation: facts Outermost layer of stratum corneum is shed regularly On an average person, 0.7 kg of skin is shed per year Can be assisted via chemical and physical exfoliation Essential to regulation of stratum corneum structure and function The rate of desquamation is affected by: Hydration pH Skin microflora (Malassezia disrupt desquamation, also causes dandruff) Inflammation 24  Desquamation: mechanism Corneocytes are interconnected by corneodesmosomes Skin desquamation occurs by elimination of corneocytes at the skin surface It’s all about proteases ! Miyai, Masashi, et al. "Keratinocyte-specific mesotrypsin contributes to the desquamation process via kallikrein activation and LEKTIdegradation." Journal of Investigative Dermatology,134.6 (2014): 1665- 1674. 25  Desquamation: proteases involved Enzyme family kallikreins (KLK) has a major role, alongside other proteases They are secreted by granular kerotinocytes. KLKs cleave an amino terminal peptide from themselves in order to become activated Activated KLK cleaves corneodemosome and enables desquamation Enzyme family LEKTI* inhibits KLK activity LEKTI is necessary to keep proteolytic balance; many skin disorders occur if are out of balance KLK activity is elevated at low pH (more acidic), meaning that desquamation is What is a normal skin pH range? increased. 26 * Lympho-epithelial Kazal-type-related inhibitor  L- serine Kallikreins A family of serine proteases (contain amino acid serine) - Protease is a type of enzymes that cleaves other proteins (& itself sometimes!) Work as a cascade to amplify response Activity affected by skin hydration pH: Inhibited at high pH; optimal at neutral pH and increased at low pH Increased desquamation can occur in skin diseases such as psoriasis and atopic eczema. an increase can lead to premature desquamation and delayed barrier Nauroy, P. and Nyström, A., 2020. Kallikreins: Essential epidermal messengers for regulation of the skin 27 recovery microenvironment during homeostasis, repair and disease. Matrix Biology Plus, 6, p.100019.  Stratum corneum regeneration: facts Corneocyte cell turnover - every 28 days on average Stem cells are constantly dividing to supply the pool of cells that die/ are shed However, a cell is limited to 50-70 divisions Smaller number of active stem cells are available for cell regeneration in old age, which could lead to https://ars.els-cdn.com/content/image/3-s2.0-B9780128027349000093-f09-02-9780128027349.jpg SC degeneration 28 The integrity of dermis: facts What is the problem with this diagram? 29  Collagen All collagens are composed of 3 α-polypeptide chains folded into a collagen triple helix. Type 1 collagen accounts for 80% of the dry weight of dermis. Enzymes lysyl and prolyl hydroxylase are essential for the formation of 4-hydroxyproline, which enables the chain to fold into a stable triple helical structure. These enzymes require Fe(II), 2-oxoglutarate and ascorbate as co-factors, hence vit C is essential in trimerisation of Ehlers-Danlos syndrome collagen. 30  Collagen: role, synthesis and aging Collagen fibres provide structure, strength and firmness to dermis It is involved in skin healing Type 1 and type 3 collagen production are reduced in chronologically aged skin Collagens produced in aged skin are disorganised 31 Am J Pathol. 2006 Jun; 168(6): 1861–1868.  Collagen degradation: matrix-metalloproteinase (MMP) They are the responsible for removing any damaged proteins in extra-cellular matrix by truncating them into smaller peptides. It is over-expressed in photoaged, chronologically aged skin and damaged skin tissues. The over-expressed MMP in aged skin truncates and degrades existing collagen, hence reducing the elasticity of the skin. 32  Collagen: glycation and AGEs Collagen also acquires free-sugar molecules via glycation, a non- enzyme covalent attachment event that is stimulated by oxidative stress (ROS) and a high sugar level Over time, these sugar molecules lengthen and form advanced glycation end products (AGEs) that cross-link in between collagen molecules and cause a loss in skin elasticity AGEs formation is not reversible via enzymatic route. The best approach is prevention 33  Matrikines Matrikines are naturally occurring oligopeptides, some of which are formed as a result of collagen and elastin degradation. Can act as signal peptides for enhanced collagen production. Cosmetic active molecule: Palmitoyl tripeptide (pamitoyl-Gly-L-His-L-Lys) Advertised as ‘messenger peptide for collagen renewal’ Alkyl chain (C 16) improves the stability and penetration of the peptide (by preventing protease degradation and increasing partition coefficient). 34  Elastin and aging Elastin fibres provide elasticity and flexibility to dermis Contributing to 2-4% dry weight of dermis Elastin biosynthesis is relatively stable from 0 to 30-40 years old, rapidly Cutis laxa – genetic disorder, where skin is inelastic declining after that Elderly individuals have a diminished capacity to replace elastin lost through natural degenerative process 35  Hyaluronic acid https://cdn.shopify.com/s/files/1/108 9/4204/articles/hyaluronic- image_173aa697-01e2-4e07-a8ac- 6e9ddb5266f7_1400x.progressive.j pg?v=1563389514 Only 0.1- 0.3% of total dry weight of the dermis Polysaccharide comprising glucuronic acid and N-acetyl-glucosamine Highly hydrophilic; provides critical role in skin ‘plumpness’ Can bind up to 1000 times its volume in water Responsible for maintaining hydration of the dermis, where water makes up 60% of the total weight Cannot penetrate SC when applied externally; the molecule is too large 36 2) What can cosmetics do? Definition of cosmetics: A "cosmetic product" shall mean any substance or mixture intended to be placed in contact with the various external parts of the human body (epidermis, hair system, nails, lips and external genital organs) or with the teeth and the mucous membranes of the oral cavity with a view exclusively or mainly to cleaning them, perfuming them, changing their appearance and/or correcting body odours and/or protecting them or keeping them in good condition. 37 2) What can cosmetics do? An interpretation of the definition of cosmetics: They are used to ‘treat’ skin conditions, but not diseases. Skin conditions Xerosis Cellulite Sensitive skin, ageing skin (?) Skin diseases Infectious Non-infectious Disorders of pigmentation: too much and too little 38 3) Skin disorder: dry skin (xerosis) Common problem Can be congenital or acquired Can range from mild to severe Mild dry skin affects many people Thus is a topic of interest to cosmetic scientists – to understand the underlying causes and how current therapies treat the condition 39 The role of water in the SC Essential to hydrate the outer layers of the SC in order to maintain flexibility (and avoid it becoming brittle, which would impact barrier) To facilitate enzyme reactions involved in: SC maturation Desquamation Mechanisms for maintaining water content in SC Intercellular lamellar lipids The presence of fully matured corneocytes The presence of both intracellular and extracellular “natural moisturising factors” 40 What is dry skin? Characterised by decreased water content in the SC (normal approx. 10%) Dry skin results when TEWL increases due to a breakdown in barrier function allowing excessive water to be lost Many factors involved in barrier breakdown Condition is often worse on areas of the body with low sebum production: arms, legs (particularly shins) and trunk Problem increases with advancing age due to the decline in sebum production with age – nearly everyone over 60 years has dry skin Most people with dry skin do not have a disease 41 Critical steps in the formation of the SC 42 Natural moisturising factor (NMF) To help prevent water loss the epidermis contains a number of water retaining substances. NMF is the most important of these. Generated by hydrolysis of the protein filaggrin. Components: Free amino acids 40% Lactic acid Sodium PCA Urea, Urocanic acid Sugars Ions [Na, K, Ca, Mg] Choride, Citrate, Phosphate, Formate NMF make up 10% of the corneocytes mass and 20-30% of dry mass of SC. Levels of filaggrin are lower in aged skin. 43  Dry skin: SC Lipids lipid profiles decreased production Represent approx 20% of SC volume of filaggrin => reduced Appear as lamellar sheets in intercellular spaces desquamation => scales Major components: Ceramides 50% Cholesterol 25% Fatty acids 10-20% Skin must generate approx 100-150 mg of lipid/day to replace that lost through desquamation Patients with dry skin have increased fatty acid and decreased ceramide levels Sebum levels do not play a significant role in aetiology of xerosis, but do contribute 44 Structure of ceramides Although the correct ratio of lipids is required, the most important single component is the ceramides. Ceramides consist of a long-chain or sphingoid base (e.g. sphingosine) linked to a fatty acid via an amide bond. Several different classes of `free' ceramides, which differ mainly in the hydroxylation of the head group region, have been identified in the epidermis ‘two-tail lipids’ 45 Epidermal ceramides 46 Organisation of lamellar sheets 47 Arrangement of SC bilayers Dry skin cycle Proposes that the induction and propagation of dry skin conditions is best expressed as a cyclical model Implies that intervention is required at more than one point to break cycle 49  4) Skin diseases: self study Infectious Non-infectious Bacterial Psoriasis Viral Rosacea Fungal Eczema (atopic) Infestations Contact dermatitis Dermatitis All are contagious Not catching in themselves, but can become secondarily infected 50 Normal skin flora Normal flora of the skin includes many different types of bacteria Staphylococci Micrococci Corynebacteria Cutibacteria https://vimeo.com/38521902 Skin also has other micro- organisms present including yeasts and mites Microbiome 51 Distribution of normal flora 52 http://allergiesandyourgut.com/ Bacterial infections: staphylococcal and streptococcal Staphylococcal infections About 20% of people carry Staph. aureus in the nose, axilla or perineum Can infect the skin directly or secondarily if the skin barrier is broken Streptococcal infections Streptococcus pyogenes is the principal human skin pathogen Is sometimes carried in the nose and can contaminate and colonise damaged skin 53 Folliculitis Staphylococcal infection can affect hair follicles. Follicular pustules are seen in hair bearing areas, and are often associated with poor shaving or waxing technique, or poor salon hygiene May affect the beard area in men – sycosis barbae, in women it is more often seen on the lower legs Folliculitis is an acute pustular infection of multiple hair follicles A furuncle is an acute abscess formation in adjacent hair follicles A carbuncle is a deep abscess formed in a group of follicles Usually caused by Staph. aureus 54 Furuncle (boil) vs carbuncle 55  Impetigo Can be due to either staphylococcal or streptococcal infection Presents as superficial skin blisters often on the face Spread by direct contact from person to person 56 Other bacterial infections Lyme disease Caused by the spirochaete Borrelia burgdorferi Spread by deer tick bite At the site of the bite, which is usually on a limb, get a slowly expanding red ring (erythema chronicum migrans) Unfortunately, the classic ‘bull’s eye’ rash is not present in all cases Becoming an increasing problem in the UK High risk areas include Exmoor, New Forrest, Oxfordshire and Norfolk 57 Viral infections Like bacteria and fungi, viruses play an important role in the skin’s microbiome. They are however associated with a number of skin conditions: Warts Herpes simplex Herpes zoster Molluscum contagiosum 58 Viral warts Benign cutaneous tumours caused by infection with human papilloma virus Lots of subtypes of HPV : Type 2 is associated with common hand warts, Types 1 and 4 with plantar warts, Types 6, 11, 16 and 18 with genital warts Virus infects by direct inoculation Can be caught by touch, sexual contact or at the swimming baths 59 Herpes simplex cold sores Acute viral infection characterised by groups of watery blisters, commonly around the mouth and nose Last a few days Can recur as the virus remains in the body 60 Herpes zoster (shingles) Vesicles develop along the path of a nerve Thoracic dermatomes are most often involved, but can develop anywhere Usually only one side is affected Blisters dry to a crust Can be very painful Follows previous infection with chickenpox 61 Disorders caused by fungi Fungal infection in man is usually due to two groups of fungi Dermaphytes – multicellular filaments or hyphae Yeasts – unicellular, replicate by budding Usually confined to the stratum corneum but some may invade deeper tissues Exact features of dermaphytes infections depend on site affected Tinea capitis – on the scalp Tinea corporis – on the body Tinea pedis – on the feet (Athlete’s foot) Tinea cruris – in the groin Tinea unguium – in the nails 62 Candida albicans Yeast Normal inhabitant of the mouth and GI tract Can cause opportunistic infection: Genital (thrush) Intertrigo (in skin folds) Oral In nails Systemic 63 https://thehealthyjunkie.wordpress.com/ How many legs? Insects or mites? Lime disease tick 64 Non-infectious conditions Psoriasis Common, chronic scaly rash Hyperplastic disorder Non-infectious, immune mediated condition Affects 2% of the population in Europe and North America Less common in the tropics and in dark skinned people; tends to run in families Influenced by environmental factors Several different types Images from DermNet Hyperplasia is increased cell production in a normal tissue or organ. 65  Epidermal kinetics Autoimmune condition mediated by T lymphocytes They stimulate the proliferation of keratinocytes Epidermal cell proliferation rate increased x 20 or more (protease activity increased; the balance with protease inhibitor lost) The dysregulation in stimulation and desquamation results in the formation of thick plaques In addition, epidermal cells fail to secrete lipids, which leads to dry flaky skin 66 Epidermal kinetics the time taken by a cell to travel to the surface, once it has been formed, is probably 40-56 days in normal skin, and 6-8 days in psoriatic skin (Halprin, 1972) 67 Pathogenesis of psoriasis Precipitating factors Genetic influences Stress Infection Injury Hormones Medications UV light Alcohol and smoking Hot weather/sunlight 68 Gooderham, Papp & Lynde (2018) Eczema/Dermatitis Inflammatory response of the skin caused by both endogenous and exogenous agents Term dermatitis simply means “inflammation of…” Terms eczema and dermatitis often used interchangeably Classification is inconsistent (and can therefore be confusing) Type Variety Exogenous (contact) Allergic, irritant photoreaction Endogenous Atopic, seborrheic, discoid, venous Unclassified 69 Atopic eczema Precipitating factors House dust mite Grass pollens Animal dander Food allergy and intolerance Irritants: Wool Soap Perfumed or medicated products Plant bases for alternative products 70 Atopic eczema Chronic inflammation of the epidermis often associated with a personal or family history of asthma, allergic rhinitis or conjunctivitis Affects about 15% of population - inherited Primarily cased by a cellular immune deficiency and elevated levels of IgE. Result is a fundamental imbalance of immune function including defective T cell function (reduced capacity to produce certain cytokines) Big problem with itching and uncontrolled scratching 71 Irritant contact dermatitis Irritants cause more contact dermatitis than allergens Cannot tell them apart just by looking at them People with atopic eczema are more susceptible to the effects of irritants 80% of cases are Common irritants occupational Water Abrasives Chemicals Acid Alkalis (soap, detergents, ammonia preparations, oven cleaner) Solvents 72 Severity of dermatitis depends on: Amount and strength of the irritant Length and frequency of exposure Short heavy exposure or repeated/prolonged low exposure Skin susceptibility Thick, thin, oily, dry, very fair, previously damaged Environmental factors Temperature, humidity 73 Allergic contact dermatitis Common form of cell-mediated or delayed hypersensitivity hypersensitivity = term applied when an adaptive immune response is inappropriate or exaggerated to the degree that causes tissue damage 74 Clinical features Usually confined to area of contact Allergen can be transmitted from fingers to other areas Skin may be red, swollen, blistered or dry and bumpy Common allergens Nickel (jewellery, zips, fasteners) Fragrance (cosmetics, creams, soaps) Paraphenylenediamine (hair dye) Plants (primula, chrysanthemums, tea tree) Preservatives (cosmetics, creams and oils) Sunscreen additives Flavouring agents (toothpaste) 75  Disorders of pigmentation (hyper and hypo) Hyperpigmentation is mostly hypermelanosis Other causes of hyperpigmentation: Drugs Endocrine disorders (Addison’s disease) Genetic Metabolic – cirrhosis of liver Nutritional – carotene Post inflammatory – eczema Other – malignant melanoma, pigmented naevi, chronic renal failure 76 Lentigines and freckles Freckles are small flat brown marks on the face and other sun exposed areas They have normal numbers of melanocytes and darken on UV exposure Lentigines are dark brown marks that do not darken in the sun They contain an increased number of melanocytes 77 Melasma (Chloasma) Usually affects women Most common between 20-40 years Affects forehead, cheeks and upper lips More common in dark than fair skins Frequently occurs during pregnancy 78 Naevi Benign proliferation of one or more of normal constituents of the skin May be present at birth or develop later Most develop during childhood or adolescence May develop more due to sun exposure or pregnancy Known as “moles” Malignant melanoma Benign moles 79 Hypopigmentation Pigment loss may be generalised or patchy Generalised loss occurs with: Albinism Hypopituitarism Patchy loss is seen in: Vitiligo After inflammation Following exposure to some chemicals With certain infections (tinea versicolor) 80 Albinism Sufferers have little or no melanin pigment in their eyes, skin or hair Genetic mutation Individual unable to change amino acid tyrosine into melanin pigment 81 Vitiligo Common, acquired disorder that leads to patchy pale marks on the skin Associated with auto-immune disorders Onset usually between 10-30 years Male: female ratio 1:1 Affects 0.5% of the population Winnie Harlow 82  References Ananthapamanabhan K P, Mukherjee S, Chandar P (2013). Stratum corneum fatty acids: their critical role in preserving barrier integrity during cleansing. International Journal of Cosmetic Science 35: 337-345 Del Rosso J Q, Levin J (2011). The clinical relevance of maintaining the functional integrity of the stratum corneum in both health and disease- affected skin. The Journal of Clinical and Aesthetic Dermatology 4(9): 22- 42. Available online from www.ncbi.nlm.nih.gov/pmc/articles/PMC3175800/ Halprin, K.M., 1972. Epidermal “turnover time”—a re‐examination. British Journal of Dermatology, 86(1), pp.14-19. Johnson Jr, W., Bergfeld, W.F., Belsito, D.V., Hill, R.A., Klaassen, C.D., Liebler, D.C., Marks Jr, J.G., Shank, R.C., Slaga, T.J., Snyder, P.W. and Gill, L.J., 2018. Safety assessment of tripeptide-1, hexapeptide-12, their metal salts and fatty acyl derivatives, and palmitoyl tetrapeptide-7 as used in cosmetics. International journal of 83 toxicology, 37(3_suppl), pp.90S-102S.  References Qasem, A., Abdel-Aty, A., Abu-Suwa, H. and Naser, S.A., 2016. Oxidative stress due to Mycobacterium avium subspecies paratuberculosis (MAP) infection upregulates selenium- dependent GPx activity. Gut pathogens, 8, pp.1-9. Rawlings A V, Matts P J (2005) Stratum corneum moisturization at the molecular level: an update in relation to the skin cycle. Journal of Investigative Dermatology 124: 1099-1110 DermNet - the world’s leading free dermatology resource https://dermnetnz.org/ 84