dermatology1.1 Flashcards
Functions of the skin
barrier to light and pathogens, vitamin D synthesis, water homeostasis, thermoregulation, insulation/ calorie reservoir, touch/sensation.
Components of skin
epidermis (stratified squamous epithelial layer), dermis (an underlying connective tissue layer, which includes the papillary layer of loose connective tissue that lies immediately under the epidermis and a deeper reticular layer composed of dense connective tissue), adnexal structures (including apocrine glands, eccrine glands, hair, nails, and sebaceous glands), and subcutaneous fat (composed of adipocytes). There are also regional variations of the skin, such as think hairless skin found on the palms and soles.
Vitamin D Synthesis
there are several ways to accomplish this, including: 7-dehydrocholesterol can be converted to cholecalciferol (Vitamin D3) in the skin by UVB. Cholecalciferol (Vitamin D3) and Ergocalciferol (Vitamin D2) can both be ingested and absorbed through the intestines. Vitamin D2 and Vitamin D3 are then converted to calcidiol (25-hydroxy Vitamin D) by the liver. 1,25-dihydroxy-Vitamin D (calcitriol) is the active form and is synthesized by the kidneys
Cells of the epidermis
includes keratinocytes, melanocytes, and Langerhans cells.
Keratinocytes
found in epidermis. Form barrier layer. Synthesize keratin, the major intracellular fibrous protein of the skin. Involved in a defined cycle of proliferation, differentiation, and programmed cell death (apoptosis).
Melanocytes
Pigment producing cells arising from the neural crest. Located primarily in the basal layer of the epidermis, in hair follicles. Melanocytes reside in the basal layer of the epidermis in a 1:10 ratio (melanocyte:keratinocyte). Each melanocyte (via its dendrites) supplies melanin to approximately 30 nearby keratinocytes. Synthesize melanin.
Melanin
synthesized in melanocytes and is a pigment derived from tyrosine. Melanin is packaged in granules called melanosomes. These granules are transferred from melanocytes to keratinocytes via dendritic processes Melanin in the basal keratinocytes protects DNA from UV damage
Langerhans cells
Found in small numbers in all of the epidermal layers. Dendritic cells in the epidermis derived from a bone marrow stem cell. Participate in cell-mediated immune reactions by processing and presenting antigens (circulate back and forth between skin and lymph nodes.
Skin color variation
it is not due to the number of melanocytes in the skin. It is due to he type of melanin produced (eumelanin or pheomelanin) and due to the distribution melanosomes. In light skin, melanosomes distributed in clusters above the nucleus and in dark skin, melanosomes distributed individually throughout the cytoplasm
eumelanin
melanin of black to brown pigment
pheomelanin
melanin of yellow to red-brown pigment.
Life cycle of keratinocytes
Epidermis is continually renewed by mitosis of keratinocytes in the basal layer and by the shedding of dead keratinocytes from the surface. This process typically takes 28 days. The layered nature of the epidermis (5 layers) is an expression of this developmental sequence compsed of stratum bsalis, stratum spinosum, stratum granulosum, stratum lucidum, and stratum corneum.
stratum basalis (germinativum)
The basal cell layer. Consists of a single layer of columnar or cuboidal cells (keratinocytes). Basal keratinocytes are the stem cells of the epidermis (the source of new keratinocytes and thus a site of intense proliferation). Cell attachments include hemidesmosomes (attach basal cells are firmly to the basal lamina of the dermal epidermal junction), desmosomes (attach keratinocytes to each other), and tonofilaments (protein structures of keratin filaments that insert into the dense plaques of desmosomes on the cytoplasmic side of the plasma membrane)
stratum spinosum
Has a “prickly” or spiny appearance due to desmosome attachments between cells. intercellular adhesion depends upon the tonofilament- desmosome interaction in the distribution of stress. synthesis of involucrin and membrane coating granules begins in this layer
stratum granulosum
the cells of this layer contain different types of granules. Keratohyalin granules contain Profilaggrin (filaggrin precursor). Filaggrin cross-links keratin tonofilaments and is important in the barrier function of the skin. Filaggrin is mutated in dry skin conditions including ichthyosis and atopic dermatitis.
stratum lucidum
under the light microscope, it appears as a thin, light staining band seen only in thick skin. Cells of this layer no longer have nuclei or organelles
stratum corneum
the outermost layers of epidermis. keratinocytes have lost their nuclei and organelles and the entire cell is filled with keratin. desmosomes still connect tightly packed adjacent cells
Papillary Layer
site of attachment to epidermis in the derms and is necessary for the epidermis development and differentiation. contains capillary network that is blood supply for epidermis. pathway for defense cells. contains Meissner’s corpuscles which sense touch
Reticular Layer
contains extensive collagen and elastic fibers that provide strength and flexibility in the dermis. houses (along with hypodermis) epidermal derivatives such as glands and hairs and plays a major role in their development and functioning. pathway for major blood vessels arranged specifically to facilitate thermoregulation. site of nerve tracts and major sensory receptors. Pacinian corpuscles sense vibration, pressure and touch
Encapsulated tough receptors
include meissner’s corpuscles and parcinian corpuscle
Meissner’s corpuscles
detect delicate touch, are most commonly found in the dermal papillae of thick skin, consist of Schwann cells and sensory nerve terminals wrapped by fibroblasts and collagen.
Pacinian corpuscles
are rapidly adapting receptors that detect changes in deep pressure (vibrations). are found in the dermis of both thin and thick skin. large structures resembling an onion. the concentric layers are composed of flattened connective tissue-like cells interspersed with intercellular fluid and collagen. a single sensory nerve fibers terminates within this structure
Adnexal structures of the skin
skin appendages. Includes apocrine sweat glands, eccrine sweat glands, hair, nails, and sebaceous glands.
Apocrine sweat glands
Specialized sweat glands located in the axillary, pubic and perianal regions. produce a milky, viscid, carbohydrate-rich secretion that is initially odorless; subsequent bacterial action leads to a characteristic axillary body odor. begin to function in puberty. have ducts which empty into hair follicles just above sebaceous glands
Eccrine sweat glands
Traditional sweat glands distributed over most of the body. Not found in the lips, under the nails or on the glans penis, glans clitoris, or labia minora. Watery, enzyme-rich secretion, initially isotonic, becomes hypotonic as Na+ is reabsorbed by the ducts. Important for thermoregulation
Hair
Develop in utero with down growth of the epidermis forming a pilosebaceous unit. The hair itself consists of a central medulla of soft keratin, and a cortex and cuticle of hard keratin. Hair growth is intermittent; a growth period of 2 to 3 years is followed by a rest period of several months. Pigment comes from melanocytes at the base of the hair. With contraction of the arrector pili muscle (smooth muscle), hairs stand on end (“goose bumps”)
Sebaceous glands
Oil glands which secrete sebum, a complex mixture of lipids. develop along with hair follicles and empty their secretion into the upper one-third of hair follicles. development accelerated at puberty
Dermis
a tough but elastic support structure that lies beneath the epidermis and above the subcutaneous tissue. The dermis contains blood vessels, nerves, and cutaneous appendages (hairs, sweat glands/ducts, etc.) that are important to the structure and function of the skin as an organ. The dermis ranges in thickness from about 1-4 mm, depending upon the body location. Clearly, this is much thicker than the epidermis, which is on average, only as thick as this piece of paper. The epidermis contains no blood vessels, it depends upon the dermis for all its nutritional support. The dermis also provides the strength, resiliency and plasticity of the skin. The dermis may be further subdivided into two zones: a) the papillary dermis (located immediately beneath the epidermis), and b) the reticular dermis located deeper in the tissue. Dermal matrix is a term often used to describe the admixture of collagen fibers, elastic fibers and ground substance all of which are synthesized by dermal fibroblasts.
skin appendages
also known as adnexal structures, is a term used by dermatopathologists to refer to the hair follicles, sebaceous glands (oil glands), and sweat glands found in the skin that are vital to protection and homeostasis.
The basic structure of the skin
The epidermis may be located on top and functions chiefly in protection. The dermis is located immediately beneath but above the fat. There are interlocking dermoepidermal junction.
Epidermal rete
The downward projections of epidermis, interdigitate with upward projections of the dermal papillae. This interlocking pattern affords both strength of adherence, and also increases the surface area between the epidermis and dermis, which is important as the dermis is the sole source of nutrients for the epidermis. On the hands and feet, this interlocking pattern becomes so pronounced that it contributed to the epidermal ridges, known better as “fingerprints.” The dermal papillae makes up the papillary dermis, while the deeper layer of the dermis is referred to as the reticular dermis.
Structural components of the dermis
The dermis is composed predominantly of collagen fibers, elastic fibers and ground substance. All these materials are synthesized by a highly productive, but sparsely populated, spindle-shaped cells in the dermis known as fibroblasts.
Collagen
Collagen is one of the basic building-blocks of the dermis. It provides essentially all the tensile strength of the skin. The body synthesizes many different forms of collagen which are numbered with Roman numerals.
Collagen I
This form comprises >85 wt. % of the adult dermis. It is also a major component of bone.
Collagen III
This type of collagen comprises a large part of the fetal dermis but is not a major portion of the adult dermis. It is thought that this difference in expression explains why adult skin forms scars and fetal skin is much more resistant to scar formation.
Collagen IV
This form is found in high concentration in the “basement membrane zone” which is present in the dermoepidermal junction. It is also more prominent around vessels and this explains the vascular fragility in some forms of Ehlers-Danlos syndrome.
Collagen VII
This form is found in the anchoring fibrils which are used by the body to attach the epidermis to the dermis.
The structure and synthesis of collagen
Procollagen is synthesized intracellularly within fibroblasts (likened to little tiny factories of the dermis). It consists of three separate chains of proteins arranged in an α-helical structure. Under the electron microscope this yields a characteristic pattern of striations with 68 nm intervals. The chains generally consist of repeated strings of glycine and two other proteins, forming a Gly-X-Y structure. The X and Y are usually proline and hydroxyproline. The synthesized collagen proteins are secreted and then are assembled into collagen fibrils extracelluraly. A number of cofactors are required to facilitate this extracellular assembly of collagen fibrils, the most famous of which is vitamin C (ascorbic acid).
Collagen without vitamin C
Without vitamin C, the collagen fibers will not attain their final desired strength. As a result, minor wounds will fail to heal, hair will grow abnormally, and the blood vessels will be quite fragile due to inadequate support from the surrounding collagen. Teeth will fall out for much the same reason, a lack of surrounding collagen support. The condition used to be common in sailors who went without fresh fruits or vegetables on long ocean journeys, and was known as scurvy. Scurvy is a classic example of an acquired abnormality in collagen production. Scurvy is no longer a common occurrence, but other congenital abnormalities in collagen formation may lead to well-recognized disorders. For example, Ehlers-Danlos syndrome (EDS)
Ehlers-Danlos syndrome (EDS)
is a group of related disorders of collagen synthesis. There are at least ten subtypes of EDS; however, all of the subtypes share varying degrees of the 4 major clinical features including: skin hyperextensibility, joint hypermobility, tissue fragility and poor wound healing. It is tempting to want to believe that the hyperextensible skin in EDS is due to a disorder in elastic fibers, but this is not the case; the disorder is due to abnormally formed collagen. EDS is a classic example of disordered collagen production due to genetic defects.
Elastic Fibers
Collagen fibers provide the skin with tensile strength, but elastic fibers provide the skin with resiliency. Roughly put, resiliency is the ability of the skin to be distorted but then return to its original shape. Elastic fibers are much smaller than collagen fibers. While collagen fibers form large eosinophilic (pink) bundles, easily recognized under the light microscope, elastic fibers are difficult to identify with standard staining techniques. Fortunately, elastic fibers are argyrophilic (silver-loving) and silver stains and other stains (such as the Verhoff-Van Gieson stain) may be performed to accentuate the presence of elastic fibers but will not stain collagen fibers. Just as there were acquired and hereditary disorders of collagen production, there exist analogous etiological disorders of elastic fibers. The most common acquired disorder of elastic is solar elastosis.
Solar elastosis
Over a lifetime, a person accumulates significant sunlight exposure, and this exposure leads to degeneration of the elastic fibers. These collagen bundles become dystrophic tend to “clump” and aggregate. These abnormal, sun-damaged elastic fibers become easy to appreciate on routine microscopy, as basophilic (blue) staining material within the superficial portions of the dermis. This solar elastosis is an important clue under the microscope as informs you instantaneously that the tissue is from a middle- aged or older person and was taken from a sun- exposed skin site. Such ancillary information will serve you well, as you study sun-induced neoplasms in the sections to come.
pseudoxanthoma elasticum (PXE)
Inherited forms of elastic disorders exist, but they are rather rare. The classic example is pseudoxanthoma elasticum (PXE), which is caused by a mutation in a gene encoding for part of the “multidrug resistance complex”, an entity you will also discuss in your pharmacology course. The complex is responsible for pumping compounds out of cells, and when it is mutated in a cancerous cell it may result in resistance to certain forms of chemotherapy. It is not well-understood exactly how this MDR defect leads to disease, but the ramifications in the skin and other organs are well-recognized. In PXE, the elastic fibers of the dermis become enlarged, tangled, and calcified, resulting in a characteristic purple-blue color upon routine histological examination. Clinically, the skin of the flexural areas of the body maintains a “plucked chicken” appearance that serves as a clue to the diagnosis. Elastic fibers of the blood vessels are also damaged leading to hypertension and bleeding disorders, particularly in the eye.
Ground Substance
Ground substance is a general term for a gelatinous material intercalated between and amongst the collagen bundles, elastic fibers, and appendageal structures of the dermis. It consists principally of two glycosaminoglycans: hyaluronic acid and dermatan sulphate. Glycosaminoglycans are complex molecules made up of proteins and sugars, and are capable of absorbing >10,000x their weight in water. It may be helpful to conceptualize this ground substance as “pie filling” made of long chains of sugar molecules. With the help of other compounds, called fibronectins (“glue”) this gel-like mass functions like a sponge. Crudely put, under pressure it can expel bound water and then take it up again. This process helps to facilitate nourishment of the overlying epidermis by easily allowing a water-based environment for diffusion. In contrast to collagen fibers, which are renewed mostly when necessary (injury), the ground substance is constantly being destroyed, by enzymes like hyaluronidase, and then renewed via production from fibroblasts.
Restylane
An excellent example of ground substance is the current cosmetic filler product called Restylane. This is simply pure hyaluronic acid produced via recombinant (yeast with plasmid) technology. Cosmetic dermatologists place this material under the skin to augment the tissue and remove lines and wrinkles. It is well-suited for this purpose for two reasons: a) it is a natural substance that is already present in the skin and it does not engender an immune response (unlike some bovine collagen fillers) and b) it absorbs a tremendous amount of water and amplifies the augmentation. Just like endogenously produced hyaluronic acid, Restylane is broken down by tissue hyaluronidases and it is not a permanent augmentation.
Cutaneous vascular system
The epidermis contains no blood supply, and it derives its nourishment via diffusion of materials through the ground substance of the dermis. The easiest way to conceptualize the blood vessels of the dermis is to divide it into superficial and deep vascular plexi. The cutaneous vascular system is also considered to be important for a number of other functions as well including wound healing, control homeostasis, and modulation of inflammation/leukocyte trafficking.
Cutaneous vascular and wound healing
the endothelium, a single-cell lining on the innermost surface of vessels, elaborates important cytokines including endothelial growth factor.
Cutaneous vascular control of homeostasis
via a structure called the Sucquet-Hoyer canal, a smooth muscle derived valve-like structure, blood may be directed toward the skin during overheating, or away from the skin in hypothermia.
Cutaneous vascular modulation of inflammation/leukocyte trafficking
via the expression of intracellular adhesion molecules (ICAMs) white blood cells begin the process of first adherence and rolling, and second diapedesis, so that they may exit the vasculature to fight infection in the skin and soft tissue.
suprapapillary plat
where actual capillary structures of the skin are contained, in the uppermost portion of the papillary dermis.
Auspitz sign
when the thickened scales of psoriasis are forcefully removed, pinpoint bleeding is noted at the area of removal. The sudden removal of epidermal scale leads to trauma in the capillaries of the uppermost papillary dermis, leading to the pin-point bleeding observed. The scale of psoriasis is entirely within the epidermis, and Auspitz sign does not violate the rule that there are no blood vessels in the epidermis.
Verruca
warts. Verrucas are benign, virally induced neoplasms (growth) that require an increased blood supply simply to support the virally-proliferating cells. These proliferating vessels may be identified as brownish, thrombosed capillary structures in the center of the verruca. Indeed, the presence of central thombosed capillary loops is a reassuring sign that the lesion is in fact a wart.
leukocytoclastic vasculitis
A common disease involving the post-capillary venules. In this condition, some type of insult leads to the formation of immune complexes. The most common cause is Strep infection, but allergies to medicines, cryoglobulin production from hepatitis C, or a myriad of other conditions may precipitate it. Indeed in a great many cases, the cause is never identified (cryptogenic or idiopathic). This is due to the precipitation of immune complexes in the walls of vessels. Therefore, this represents an excellent example of a Type III – Gell & Coombs reaction pattern. The deposition of immune complexes leads to inflammation. Neutrophils attach to the vessel wall and degranulate yielding damage and the extravasation of red blood cells into the dermis. This process of fibrinoid deposition in the vessel walls, with infiltrating neutrophils and neutrophil debris is called leukocytoclasia. Clinically, the vasculitis manifests as “palpable purpura”. It is palpable because of the inflammation, and it is purpuric due to the extravasation of RBCs. Such erythema is non- blanchable, because the RBCs have been extravasated into the dermis. Pressure applied to the skin with a finger does not make the redness go away as it would if the vessels were dilated but intact.
Necrosis of the epidermis
the epidermis is completely dependent upon the dermis for nutrition and support, any process which corrupts the dermal vascular plexi, whether a vasculitis (inflammation), vasculopathy (mechanical occlusion) or otherwise, if prolonged and/or severe, may lead to necrosis and sloughing of the epidermis.
Nervous tissue of the dermis
function in a similar function as does nervous tissue in other areas of the body, specifically to inform and protect. Free nerve endings pass through the upper dermis to terminate at the dermoepidermal junction and these structures are thought to be involved in the sensation both of pain and also of itch, which in dermatology is called pruritus. Pruritus originates in free nerve endings near the dermoepidermal junction and is conducted centripetally by afferent nerves entering the spinal cord via the dorsal roots. These afferent nerves for pruritus are small, unmyelinated C fibers with a slow conduction rate. After entering into the spinal cord, the primary neurons synapse with secondary neurons whose axons cross to the opposite side of the body and then travel cephalad. Finally, these sensations arrive at the cerebral cortex. Here the body is capable of identifying the location, nature, intensity and other qualities of the itch sensation. Investigation by positron emission tomography demonstrated the secondary activation of the pre-motor areas of the brain and probably there exist synaptic connections to the motor area of the cortex, which prepare for scratching.
Itch sensory
For a long time it was thought that itch represents a weak pain, and there was a debate whether the same nerves conduct itch and pain. Now it has been recognized that itch and pain are different and independent sensory modalities, even if local anesthesia or cutting of the sensitive nerves may abolish both. The following observations have led investigators to believe that receptors and transmission apparatus for itch and pain differ: itch elicits scratching, while pain yields a withdrawal response, morphine relieves pain but can actually produce pruritus, heating of the skin to 41°C relieves itch but not pain, and removal of the epidermis and upper dermis abolishes pruritus, but not pain. are structures which resemble an onion in cross-section. They are involved in pressure and vibratory sensation. It is not surprising, therefore, that they are most concentrated in the genital area.
Pacinian corpuscles
are structures which resemble an onion in cross-section. They are involved in pressure and vibratory sensation. It is not surprising, therefore, that they are most concentrated in the genital area.
Meissner’s corpuscles
resemble a pine-cone and are thought to be involved in fine touch and tactile discrimination. Such receptors are in highest concentration on the distal aspects of the digits, particularly the pulps of the fingers.
Congenital insensitivity to pain
Rarely a person is born with a congenital insensitivity to pain, most often with co-existing anhidrosis (an inability to sweat). The condition is caused by mutations in the neurotrophic tyrosine receptor kinase 1 (NTRK1) gene which encodes for the nerve growth factor receptor (NGFR). These children suffer from an enormous number of injuries to the skin and integument, including corneal erosions in >70%. They cannot feel the common danger signs which normally lead to protective responses. Such children have to be examined several times a day for cuts, scrapes, sand stuck in the eye, materials in the skin and other perils common to small children.
Hair Follicles
Nearly the entire body surface is covered by hair. Areas that specifically are NOT covered with hair include the palms, soles, glans penis, and labia minora. Before many in the audience start objecting, and adding other areas that are “hairless,” understand that we are talking about two different types of hair:
Terminal Hairs
These hairs are large, thick, coarse, pigmented. Terminal hairs, such as those on the scalp, a man’s beard area and possibly chest/back, and the pubic area, begin deep in the dermis at/near the dermal-subcutaneous junction.
Vellus Hairs
These hairs are small, fine, and apigmented. Such hairs are located diffusely on the body, and represented the types of hairs often on the ear, the lateral face of women, and the body in general.
The arrector pili muscle
a small, smooth-muscle which, when activated by the autonomic nervous system, brings the hair into a more erect position (“goose bumps”).
The sebaceous gland
secretes an oily substance called sebum onto the hair and indirectly onto the skin surface. The sebaceous glands are more prominent in the “oily” areas of the body, such as the face, neck, and chest and upper back.
Anatomy of a hair follicle
It is also common to divide the hair follicle into thirds with the infundibulum representing the upper third, the isthmus being the middle third (from the sebaceous duct to the insertion of the arrector pili), and the matrical area representing the lower third.
primitive ectodermal germ (PEG)
suffice to say the follicular unit is derived from the primitive ectodermal germ (PEG). Development of the PEG is an excellent example of embryologic induction (development of eye is the classic example in embryology). Induction means that the underlying mesenchyme, which will become the dermal papillae of the hair, induces formation of the PEG in the overlying fetal skin. Several bulges of the PEG are recognized as being significant: Lower bulge – attachment for arrector pili. Middle bulge – sebaceous gland. Upper bulge – apocrine gland (axillae, groin, or other areas with apocrine glands)
Androgenic alopecia (AKA androgenetic alopecia)
a common “illness” which illustrates some of the important properties of hair growth. The scalp of an adult contains >100,000 hairs, ~85% of which are in anagen (the growth phase), 10-15% in telogen (the resting phase), with the remainder (1-5%) in catagen (transition phase between anagen and telogen). Scalp hairs are terminal hairs. They are thick, usually pigmented, and lie deep in the dermis and subcutis. In androgenic alopecia (“pattern baldness”) the hairs become miniaturized, finer and lie higher in the dermis. Ultimately they come to resemble vellus hairs. In men, this yields the classic fronto-temporal or postero- occipital balding. In women, this leads to thinning of the hair on the crown area. Nearly 50% of both sexes are affected to some degree, although it is not as widely discussed in women. The process is not understood completely, but it is known that conversion of testosterone to 5-dihydrotestosterone is important in promoting this change. For this reason, finasteride, a 5-α-reductase inhibitor, which block this conversion, are used in the treatment of male pattern baldness. Both men and women are also treated with minoxidil, a drug known to promote the anagen phase of hair growth. Neither treatment is entirely satisfactory; research is ongoing.
Sebaceous glands
oil-secreting glands located predominantly in the “oily” areas of the body including the scalp, face, neck, upper chest, and upper back. Sebaceous glands are the classic example of a holocrine gland in that the method of secretion involved entire sebocytes (sebaceous gland cells) being secreted and in the process breaking-down to extrude the contents. Persons vary widely with regard to the basal level of sebum (oil) production. Sex hormones are requisite to sebum secretion. For this reason, disorders associated with the sebaceous glands, such as acne, are not prevalent until after adrenarche (puberty). While it does NOT appear that the glands are innervated by the autonomic nervous system, the exact mechanism that governs sebum production is poorly understood. One of the only medications to significantly decrease sebum production is isotretinoin (Accutane). This rather toxic medicine decreases sebum production by up to 90%, often permanently, yet the mechanism by which it does this is largely unknown.
Acne
a ubiquitious disorder of the pilosebaceous unit (the combined hair follicle and oil glands). It does not have single cause but is instead multifactorial. In brief, and with simplification appropriate to this course, plugging of the ostia of the pilosebaceous unit by hyperkeratotic debris leads to accumulation of oil within. Propionibacterium acnes, a normal bacterial commensal, then begins to multiply and converts sebum to pro-inflammatory fatty acids. When the pilosebaceous unit ruptures, the result is the characteristic inflammatory “zit”. Blocked pores themselves constitute comedones, that are further classified to be: open - “black heads” or closed - “white heads”.
Eccrine glands
what are often referred to as “general sweat glands”. The primary function of the eccrine unit is thermoregulation, which is accomplished through the cooling effects of evaporation of this sweat on the skin surface. Because they are so important in temperature regulation, they are located throughout the body, but are most numerous on the forehead, upper cutaneous lip, and palms/soles. Eccrine glands are a classic example of a merocrine secretion. Merocrine glands secrete WITHOUT either the apocrine blebbing, or holocrine shedding. Eccrine glands develop from an eccrine germ, which is DISTINCTLY different from the primitive ectodermal germ of the follicular unit.
three main components to the eccrine gland
The coiled secretory portion deep in the dermis, The intradermal duct (coiled and straight duct),The intraepidermal portion (called the acrosyringium
Eccrine sweat
composed of water, sodium, potassium lactate, urea, ammonia, serine, ornithine, citrulline, aspartic acid, heavy metals, organic compounds, and proteolytic enzymes. It is critical to recognize that even though sweating is mediated by the sympathetic portion of the autonomic nervous system it is triggered via acetylcholine secretion. Acetylcholine is a chemical otherwise associated with the parasympathetic nervous system.
Control of sweat
The fact that eccrine glands are controlled by the sympathetic nervous system explains why most people sweat more under stress (like public speaking). However, the fact that it is mediated via acetylcholine, a neurotransmitter often associated with parasympathetic responses, explains why certain drugs that increase acetylcholine levels, such as neostigmine, physostigmine and organophosphate-based pesticides, result in increased sweating despite a parasympathetic response systemically. Furthermore, this is why atropine poisoning (a drug which has anticholinergic activity) results in a warm, flushed, but anhidrotic (non-sweating) patient.
Apocrine Glands
Apocrine glands are outgrowths of the upper bulge of the primitive ectodermal germ, a fetal structure which yields the follicular unit. The apocrine glands are located only in the axillary and anogenital area. Although present at birth, they remain small and nonfunctional until after puberty. Specialized variants of apocrine glands include Moll’s glands on the eyelids, the cerumen (ear wax) glands of the external auditory canal, and the lactation glands of the breasts. At puberty, hormonal stimulation causes apocrine glands to become functional, and the glands respond mainly to sympathetic adrenergic stimuli initiated by emotional stress.
Anatomy of apocrine glands
Apocrine glands consist of a coiled portion deep in the dermis, and a straight duct which traverses the dermis and empties into the hair follicle. The coiled gland consists of one layer of secretory cells around a lumen that is approximately ten times the diameter of its eccrine counterpart. Contractile myoepithelial cells surround the coiled gland. The straight duct runs from the coiled gland to the hair follicle.
Apocrine secretion
The predominant mode of apocrine secretion is decapitation, a process where the apical portion of the secretory cell cytoplasm pinches-off and enters the lumen. Apocrine sweat consists mainly of sialomucin. Although odorless initially, as apocrine sweat comes in contact with normal bacterial flora on the surface of the skin, an odor develops. Apocrine sweat is more viscous and produced in smaller amounts than eccrine sweat. The exact function of apocrine glands is unclear, although they likely represent scent glands.
chromohidrosis
One disorder of apocrine glands is chromohidrosis (which literally translates into “colored sweat”). Chromhidrosis is exclusively apocrine in origin. Although apocrine glands are found in the genital area, chromhidrosis has been reported mostly only upon the face, axillae, and breast areola. Lipofuscin pigment is responsible for the colored sweat. This pigment is produced in the apocrine gland, and its various oxidative states account for the characteristic yellow, green, blue, or black secretions observed in apocrine chromhidrosis. Approximately 10% of people without true chromohidrosis have colored sweat which is regarded as minor, acceptable, and within the normal range. Apocrine chromhidrosis has no fully satisfactory cure or treatment.
Apoeccrine Glands
Apoeccrine glands are hybrid sweat glands that are found chiefly in the axilla. Apoeccrine glands may play a role in axillary hyperhidrosis. These hybrid glands have both a small diameter portion, similar to an eccrine gland, and a larger diameter portion that resembles an apocrine gland. Similar to eccrine glands, they respond mainly to cholinergic stimuli, and their ducts are long and open directly onto the skin surface. In some patients they constitute up to 45% of the sweat glands found in the axillary region. The truly impressive thing about apoeccrine glands is that they secrete nearly ten times as much sweat as eccrine glands, making them by far the most productive gland in the dermis.
Hyperhidrosis Involving Eccrine and/or Apoeccrine Glands
Localized hyperhidrosis is focal excessive sweating. It may be eccrine, particularly when it involves “clammy hands” or “sweaty feet, or it may be due to apoeccrine glands in the axilla. A positive family history is reported in 30%–50% of patients. Patients with focal hyperhidrosis generally do not sweat during sleep and therefore, most authorities consider it to be a disease of autonomic dysfunction. Although there is no standard definition of hyperhidrosis, less than 1 mL/m2 of sweat production per minute by eccrine glands at rest and at room temperature is considered normal. For practical purposes, any degree of sweating that interferes with the activities of daily living should be viewed as cause for investigation. One way to qualitatively document perspiration, for purposes of tracking treatment, is to apply an iodine solution (1%–5%) to a dry surface. After a few seconds starch is then sprinkled over this same area. The starch and iodine interact in the presence of sweat, producing a purple-black sediment. This purple area identifies the duct of the sweat gland.
Treatment of hyperhidrosis
There is a wide range of medical and surgical treatments available for patients with focal hyperhidrosis. Initial treatments focus on antiperspirant solutions or anticholinergic medications which decrease eccrine and apoeccrine output. Many patients want to pursue a thoracotomy with transaction of the sympathetic nerve trunk. Often physicians are a bit reluctant as this procedure has a high incidence of mild to severe compensatory hyperhidrosis (a new area of increased sweating), usually involving the trunk and lower limbs. Compensatory hyperhidrosis occurs in up to 86% of patients after thoracotomy. A new and exciting method of treating hyperhidrosis is the use of botulinum toxin A (Botox). When injected into the dermis and subcutis, the toxin blocks the release of acetylcholine from the nerves and thereby blocks the stimulus for sweat production. While it is quite effective, the result is both expensive (generally not covered by insurance) and transient, and for this reason its use is somewhat limited.
Atopic dermatitis
common skin disease, which may begin at any age, however, a majority begin before age 5. Prevalence is 7-17.2% in children. Often associated with xerosis (dry skin) and a history of atopy (asthma and allergic rhinitis). There are three stages including infantile, childhood and adult.
Diagnostic criteria of atopic dermatitis
must have itchy skin plus three or more of the following: history of involvement of skin creases (or face if patient is under 10 years), personal history of asthma or hay fever (or FH of atopic disease if patient is less than 4 years), history of dry skin within the last year, visible flexural eczema (or face if patient is less than four years old), or onset is under 2 years of age.
Pathogenesisof atopic dermatitis
barrier disrupted skin, filaggrin mutation, Staphlyococcus aureus acts as a superantigen, elevated IgE, eosinophilia, Th2 type cytokine (IL-4, IL-5, IL-10) immune response produced.
Irritant contact dermatitis
non-immunologically mediated reaction resulting from a direct cytotoxic effect. Either from a singe or repeated exposure to the irritant. There is no specific “test” for irritant dermatitis, irritant contact dermatitis is the most common type of contact dermatitis.
Types of irritants
strong irritants damage skin directly even is small amounts contacting the skin for a short time (strong acids and bases). Strong irritants generally carry warning labels and often suggest skin protection such as gloves should be used. Weak irritants are harmless by themselves, but frequent, repeated contact may damage skin (Soap and water, Skin products (even “baby” and “hypoallergenic”), Perfumes, Wool, Raw Foods (meat, fruits, or vegetables held while preparing foods), Body Secretions (feces, urine, saliva, sweat), and Friction).
Clinical appearance of spongiotic dermatitis
similar to atopic or allergic contact dermatitis. Clinical history and distribution/ pattern may give clues to diagnosis of irritant contact dermatitis. May burn more than itch.
Allergic Contact Dermatitis
Requires contact exposure of an allergen, immune response and development of “memory” T cells. Type IV, delayed-type hypersensitivity reaction usually starts 24-48 hours after exposure to the allergen, but it can be delayed longer. Patch testing is the gold standard diagnostic test of allergic contact dermatitis
Nickel sulfate
number one most frequent. Risk factors for sensitization are younger age, female sex and ear piercings. Rate of sensitization in the US is on the rise. Rates of sensitization in Europe are on the decline due to regulation of Nickel in common objects in contact with skin (jewelry, watches, zippers). The dimethlyglyoxime test is used to test metal objects for release of nickel.
Neomycin sulfate
the most commonly used topical antibiotic with gram positive and gram negative antibacterial activity. Cross-sensitivity can occur with gentamicin, kanamycin, streptomycin, spectinomycin, tobramycin, paromycin and buitirosin. Sensitivity is more common in patients with atopic dermatitis, stasis dermatitis and otitis externa.
Bacitracin
wide spread use has led to increase sensitization. Sensitivity is on the rise (prevalence 1989-90 only 1.5%). Used topically because of nephrotoxicity with systemic administration. Active against gram positive bacteria and spirochetes. Allergy occurs more commonly in patients with chronic skin conditions such as stasis ulcers.
Clinical Presentation of Seborrheic Dermatitis
Sharply demarcated patches (thin plaques) with pink or slightly orange-yellow erythema. Characterized by flaky, “greasy” scales. Occurs in infancy and post-puberty when sebaceous glands are active. Occurs in areas rich in sebaceous glands (scalp, face, ears, chest and intertriginous areas).
Adults of Seborrheic Dermatitis
Commonly involves the scalp, but is more diffuse lesions with finer scale than psoriasis. Facial involvement is usually symmetric over the medial eyebrows, nasolabial folds and ears. Course is chronic relapsing. More extensive and severe disease is seen in HIV pts. Seborrheic dermatitis is also common in Parkinson’s disease
Infants Seborrheic Dermatitis
“Cradle cap”. Begins 1 week after birth and may persist for several months. Often starts on the scalp and can become confluent with a thick scale covering most of the scalp. Often seen in the inguinal folds or axillae. Other areas may be involved including the face, posterior ears, neck, trunk and proximal extremities
Pathogenesis Seborrheic Dermatitis
Malassezia furfur. A yeast considered normal flora, but yeast number not directly related to seborrheic dermatitis. May be linked to imbalance of normal flora. P. acnes presence is greatly reduced in areas of seb derm. Seb Derm occurs in areas of active sebaceous glands, but not directly related to sebum production. Immune response to M. furfur may be due to production of toxic metabolites by M. furfur
Treatment of Infants with Seborrheic Dermatitis
Generally self-limited and mild. Bathing, mild shampoos and emollients. Ketoconazole cream. Hydrocortisone cream
Treatment of Adults with Seborrheic Dermatitis
Over the counter dandruff shampoos (zinc, salicyclic acid, tar). Ketoconazole shampoo. Ketoconazole cream. Interval low potency topical steroids. Calcineurin inhibitors (pimecrolimus, tacrolimus)
Stasis Dermatitis Pathogenesis
Chronic venous insufficiency of the lower extremities associated with lower extremity edema.
Complicating Factors of Stasis Dermatitis
Dryness. Itching. Allergic contact dermatitis due to use of topical preparations (i.e. topical antibiotics). ACD is found in 58-86% of patients with leg ulcers. Irritant Dermatitis due to wound exudates
Treatment of Stasis Dermatitis
Compression. Elevation. Exercise calf muscles. Vascular surgery. Topical steroids. Avoid allergens
Lichen Simplex Chronicus
Thick, scaly plaques with “lichenification” that result from chronic rubbing and scratching. Topical steroids are first line therapy. Antihistamines can be used for itching. Patients need to be counseled to break the itch-scratch cycle
Venous Stasis Ulcers.
Common in patients with a history of leg swelling, varicose veins or a history of blood clots. Primarily found on the medial lower leg just above the ankle. Red in color with yellow fibrinous base. Borders irregularly shaped. They may be purulent if infected.
Nummular Eczema
Also called Discoid Eczema. Most often occurs on legs, but can appear on arms and trunk. More common in men age 50+. Round patches may be red, scaly and become crusty. Tends to be stubborn. Moisturization, minimize soap and topical corticosteroids are first line therapy
Psoriasis
Affects up to 2% of the population. Positive FH in 36% of psoriasis pts. Psoriasis impacts quality of life
Clinical Subtypes of Psoriasis
Chronic Plaque Disease, Guttate, Erythroderma, Pustular Psoriasis, Psoriatic Arthritis Occurs in 5-20% of psoriasis patients
Comorbidities of Psoriasis
Epidemiologic studies have shown that in psoriasis patients associated disorders occur more frequently than expected. Arthritis, Crohn’s disease, Persistent low grade inflammation favors the development of insulin resistance, obesity and metabolic syndrome, Metabolic syndrome patients have accelerated atherosclerosis due to inflammation, Cardiovascular Disease (Patients in their 40s with severe psoriasis were more than 2x RR for heart attack than people without skin disease. Mild psoriasis raised the risk of heart attack by 20% for people in their 40s).
Treatment of psoriasis of Localized Disease
Calcipotriol (Vit D3 analog), Corticosteroids, Topical Retinoids, Phototherapy, UVB/NBUVB, PUVA
Treatment of psoriasis of Widespread disease +/- Psoriatic Arthritis
Methotrexate, Cyclosporin, Systemic Retinoids, Biologics, Anti-T lymphocyte, Anti-TNF alpha
Exanthematous Eruptions
10-20% in children are drug induced. 50-70% in adults are drug-induced. Responsible drugs: Aminopenicillins, Sulfonamides, Cephalosporins, Anticonvulsants, and Allopurinol
Drug Eruptions (maculopapular eruptions, morbilliform eruptions, drug rashes)
Differential diagnosis = Viral exanthema. (EBV, Enterovirus, Adenovirus, Early HIV, Parvovirus B19, CMV). Viral infections enhance the risk of drug eruption. Almost 100% of pts with infectious mononucleosis will get an exanthematous eruption if given ampicillin. HIV pts are more susceptible to drug eruptions
Treatment of Drug Eruptions
Discontinue the offending medication. Eruption will generally resolve spontaneously after 1-2 weeks. Supportive therapy for pruritus with topical steroids and anti-histamines. However, it can take up to 3 months to completely resolve
Urticaria
Histology: Shows dermal edema with eosinophils +/- neutrophils. Treatment = Antihistamines. Acute (< 6 weeks). Acute urticaria represents an immediate type I hypersensitivity reaction mediated by IgE antibodies. First exposure generates IgE antibodies. Upon re-exposure, antibody binds to IgE on mast cells and basophils causing degranulation with release of mediators such as histamine. Chronic (> 6 weeks)
Subtypes of basal cell carcinoma (BCC)
Nodular (75%) (micronodular and pigmented (6%)), Superficial (15%), Infiltrative (5%), Sclerosing (morpheaform) (3%)
Clinical appearance of basal cell carcinoma (BCC)
Skin cancers often don’t cause symptoms until they become quite large. Then they can bleed or even hurt. Basal cell carcinomas often appear as flat, firm, pale areas or as small, raised, pink or red, translucent, shiny, waxy areas that may bleed after minor injury. You might see one or more abnormal blood vessels, a depressed area in the center, or blue, brown, or black areas. Large BCCs may have oozing or crusted spots.
Pathophysiology of basal cell carcinoma (BCC)
Basal cell cancer begins in the lowest layer of the epidermis, called the basal cell layer. Basal cell carcinomas arise from pluripotential cells due to mutations in the hedgehog pathway. Most commonly mutations inactivate the patched 1 gene, a tumor suppressor gene. Other mutations may activate smoothened or hedgehog.
Clinical Course of basal cell carcinoma (BCC)
About 3 out of 4 skin cancers are basal cell carcinomas. They usually begin on areas exposed to the sun such as the head and neck. Basal cell carcinoma was once found mostly in middle-aged or older people. Now it is also being seen in younger people, perhaps because people are spending more time in the sun without protecting their skin. Basal cell carcinoma tends to grow slowly. It is very rare for a basal cell cancer to metastasize. But if it is not treated, it can grow into nearby areas and invade the bone or other tissues beneath the skin. Vismodegib, a small-molecule inhibitor of smoothened, was approved in January 2012 for the treatment of locally advanced and metastatic basal- cell carcinomas. After treatment, basal cell carcinoma can recur in the same place on the skin. Also, new basal cell cancers can start other places on the skin. Within 5 years of being diagnosed with basal cell cancer, 35% to 50% of people develop a new skin cancer.
Subtypes of Actinic Keratosis
Hypertrophic, Atrophic, Acantholytic, Lichenoid, Cutaneous Horn, and Actinic Cheilitis
Clinical presentation of Actinic Keratosis
Actinic keratoses (Intraepidermal neoplasia I) are the most common pre-malignant skin lesion. The actinic keratosis (AK) is the earliest identifiable lesion that can eventually develop into an invasive squamous cell carcinoma (SCC). AKs are diagnosed in 14% of all visits to dermatologists, following only acne and dermatitis in frequency. The nomenclature for AKs is controversial; some consider them “pre-cancerous” and others consider them to be a SCC confined to the lower portion of the epidermis. Actinic keratoses typically occur in fair-skinned individuals. In various northern hemisphere populations, 11-25% of adults have at least one, compared to 40-60% of adult Australians who live closer to the equator. One prospective study estimates that one AK/1000/year transforms into SCC, while retrospective studies predict that from 5-20% of all untreated AKs will progress to SCC. AK’s are typically produced by ultraviolet radiation, but ionizing radiation, arsenic, or polycyclic hydrocarbon exposure may also cause them. At least two prospective studies have demonstrated that sunscreen reduces the likelihood of developing more AKs. Actinic keratoses are distributed in areas of increased sun exposure and are characterized by hyperkeratosis and erythematous papules, which are often easier to palpate than to visualize.
Treatment options of of Actinic Keratosis
includes cryotherapy, 5-fluorouracil (topical), imiquimod (topical), diclofeac (topical), photodynamic therapy (PDT), and ingenol mebutate (topical)).
Cryotherapy
liquid nitrogen technique (196 C). indicated for discrete limited number of lesions.
5-fluorouracil (topical)
anti-neoplastic effect via thymidine synthase and subsequently DNA synthesis. Indicated for numerous lesion that are ill-defined. It is a skin irritant.
imiquimod (topical)
Immunomodulating, Toll-like receptor 7 agonist. Indicated for numerous lesion that are ill-defined. It is a skin irritant.
