Term
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Definition
[image]
layer thickness:
epidermis - 0.8 mm (palms) to 0.006 mm (eyelid)
dermis 3-5 mm
subcutaneous varies with fat content
the skin acts as a 2 way barrier to prevent absorption or loss of water and electrolytes
the barrier resides in the outermost layer of the epidermis, the stratum corneum, as evidenced by approximately equal rates of penetration of chemicals through isolated stratum corneum or whole skin
having lost their nuclei and cytoplasmic organelles, the corneocytes of the stratum corneum are nonviable
the intercellular spaces are filled with hydrophobic lamellar lipids derived from membrane coating granules
the combination of hydrophilic cornified cells in hydrophobic intercellular material provides a barrier to both hydrophilic and hydrophobic substances
in dermatological diseases, the thickened epidermis may further diminish the penetration of pharmacological agents into the dermis |
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Term
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Definition
[image]
stratum corneum
stratum lucidum
stratum granulosum
stratum spinosum
stratum basale (germinativum) |
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Term
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Definition
keratinized stratified squamous epithelium
4 principal cell types:
keratinocytes ~90%
melanocytes ~8%
Langerhans cells ~1%
Merkel cells ~1%
the epidermis is the outer layer of the skin, composed of terminally differentiated stratified squamous epithelium, acting as the body's major barrier against an inhospitable environment
the epidermis is avascular, nourished by diffusion from the dermis, and composed of 4 types of cells, i.e. keratinocytes, melanocytes, Langerhans cells, and the Merkel cells
KERATINOCYTES
the predominant cell type in the epidermis, the outermost layer of the human skin
the primary function of keratinocytes is the formation of a barrier against environmental damage such as pathogens (bacteria, fungi, parasites, viruses) heat, UV radiation, and water loss
a number of structural proteins (filaggrin, keratin), enzymes (proteases), lipids and antimicrobial peptides (defensins) contribute to maintain the important barrier function of the skin
the fully CORNIFIED keratinocytes (keratinization) that form the outermost layer are constantly shed off and replaced by new cells
the average renewal/turnover time for the epidermis is 21 days
MELANOCYTES
melanin producing cells located in the bottom layer (the stratum basale) of the skin's epidermis
melanin is a pigment that is responsible primarily for the color of skin
the increased production of melanin in human skin is called melanogenesis
production of melanin is stimulated by DNA damage induced by UVB radiation, and it leads to a delayed development of a tan
LANGERHANS CELLS
dendritic cells (i.e. antigen presenting cells) of the epidermis, containing large granules called Birbeck granules
they are also normally present in lymph nodes and other organs, including the stratum spinosum layer of the epidermis
MERKEL CELLS
oval receptor cells found in the skin of vertebrates that have synaptic contacts with somotosensory afferents
they are associated with the sense of light touch discrimination of shapes and textures
they can turn malignant and form a skin tumor known as Merkel cell carcinoma |
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Term
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Definition
normally consists of 25-30 layers of flattened DEAD keratinocytes that lack nuclei
keratinocytes continuously shed/replaced
between the cells are lipids
protects deeper skin structure: water loss, bacterial invasion |
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Term
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Definition
present only in the thick skin regions of the fingertips, palms, and soles
DEAD keratinocytes: large amounts of keratin (fibrous protein) |
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Term
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Definition
middle of the epidermis
keratinocytes undergoing apoptosis
processing of keratinization (cornification) of epidermal layer:
loss of nuclei and organelles, keratin monomers assemble into filaments, providing strength
lamellar granules produce lipid rich material, acts as barrier
CORNIFICATION is the process of forming an epidermal barrier in stratified squamous epithelial tissue (i.e. conversion of epithelium to the stratified squamous type)
cornification is characterized by:
1) production of keratin
2) production of small proline-rich (SPRR) proteins and transglutaminase which eventually form a cornified cell envelope beneath the plasma membrane
3) terminal differentiation
4) loss of nuclei and organelles, in the final stages of cornification metabolism ceases and the cells are almost completely filled by keratin
KERATIN
refers to a family of fibrous structural proteins
keratin is the key structural material making the outer layer of human skin
it is also the key structural component of hair and nails
keratin monomers assemble into bundles to form intermediate filaments, which are tough and insoluble and form strong unmineralized tissue
keratin filaments are abundant in keratinocytes in the cornified layer of the epidermis; these are cells which have undergone keratinization (cornification)
keratohyalin is a protein structure found in granules in the stratum granulosum of the epidermis, which produce keratin and are involved in keratinization |
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Term
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Definition
8 to 10 layers of keratinocytes
provides strength and flexibility to skin
outer layers start the keratinization process
2 particular cells found here:
Langerhans cells - immune response
Merkel cells - tactile response |
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Term
| stratum BASALE (GERMINATIVUM) |
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Definition
1 layer of keratinocytes - stem cells found here
3 other particular cells found here:
Langerhans cell - immune response
Merkel cell - tactile response
melanocytes - produce melanin
the basal cells of the stratum germinativum can be considered the stem cells of the epidermis
they are undifferentiated, and they proliferate
they create "daughter" cells that migrate superficially, differentiating as they do so
the keratinocytes of the stratum germinativum undergo mitosis continually throughout the individual's life |
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Term
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Definition
the DERMIS is a layer of skin between the epidermis (with which it makes up the cutis) and subcutaneous tissues, and is composed of 2 layers, the papillary and reticular dermis
structural components of the dermis are collagen, elastic fibers, and extrafibrillar matrix (previously called ground substance)
the dermis is the second, deeper part of the skin
primarily connective tissue
papillary region: microscopic fine, elastic fibers
reticular region: attached to the subcutaneous layer; fibroblasts, collagen bundles, and elastic fibers
combination of collagen and elastic fibers provides skin with strength, extensibility (stretch), and elasticity
stretch marks are often the result of the rapid stretching of the skin associated with rapid growth (common in puberty) or weight gain (e.g. pregnancy or muscle building) or in some cases, severe pulling force on skin that overcomes the dermis's elasticity
dermis composition:
collagen ~75%
elastin ~4%
reticulin ~0.4%
ground substance ~20%
COLLAGEN
a group of naturally occurring proteins
in nature, it is found exclusively in animals
it is the main protein of connective tissue
it is the most abundant protein in mammals, making up about 25-35% of the whole body protein content and 75% of dermis
ELASTIN
a protein in connective tissue that is elastic and allows many tissues in the body to resume their shape after stretching or contracting
elastin helps skin to return to its original position when it is poked or pinched
elastin is also an important load bearing tissue in the bodies of mammals and used in places where mechanical energy is required to be stored
RETICULIN
is a term used to describe a type of fiber in connective tissue composed of type III collagen
GROUND SUBSTANCE
is a term for the non-cellular components of extracellular matrix containing the fibers |
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Term
| reticular region of the dermis |
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Definition
[image]
structures: adipose cells, hair follicles, nerves, sebaceous glands (sebum), sudoriferous glands (sweat)
SEBACEOUS GLANDS are microscopic glands in the skin that secrete an oily/waxy matter, called SEBUM, to lubricate the skin and hair of mammals
PERCENT COMPOSITION OF SEBUM: 25% wax monoesters; 41% triglycerides; 16% free fatty acids; 12% squalene
SUDORIFEROUS GLANDS (I.E. SWEAT GLANDS) are small tubular structures of the skin that produce sweat. there are 2 KINDS OF SWEAT GLANDS:
eccrine sweat glands - are found only in primates and reach their greatest development in humnas. they are distributed all over the body (except for the lips, tip of penis, and clitoris) although their density varies from region to region. humans utilize eccrine sweat glands as primary form of cooling
apocrine sweat glands are larger, have different mechanisms of secretion, and are limited to axilla (armpits) and perianal areas in humans |
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Term
| cutaneous surface area: the rule of 9's |
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Definition
[image]
the "rule of nines" is used to determine the total percentage of area for each major section of the body
for children and infants, the Lund-Browder chart is used to assess the burned body surface area
different percentages are used because the ratio of the combined surface area of the head and neck to the surface area of the limbs it typically larger in children than that of an adult
the rule of nines assesses the percentage of burn and is used to help guide treatment decisions including fluid resuscitation and becomes part of the guidelines to determine transfer to a burn unit |
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Term
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Definition
largest organ of the body (weight and SA)
2 parts - epidermis and dermis
epidermis: keratin and lipids
dermis: collagen and elastic fibers; follicles, nerves, and glands
the rule of 9's |
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Term
| skin function: thermoregulation |
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Definition
sweat: evaporation
blood flow: dilation and constriction
THERMOREGULATION is the ability of an organism to keep its body temperature within certain boundaries, even when the surrounding temperature is very different
an endotherm is an animal that regulates its own body temperature, typically by keeping it a constant level
to regulate body temperature, an organism may need to prevent heat gains in arid environments
evaporation of water, either across respiratory surfaces or across the skin in those animals possessing sweat glands, helps in cooling body temperature to within the organism's tolerance range |
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Term
| skin function: blood reservoir |
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Definition
normal temperature
8-10% total volume in skin |
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Term
| skin function: protection |
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Definition
microbial
abrasion
heat
chemicals
dehydration |
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Term
| skin function: cutaneous sensation |
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Definition
tactile
pressure
temperature change
pain |
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Term
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Definition
insensible loss:
~400 mL/day (adult)
sweat > 200 mL/day
fever??
assists in temperature control
excrete water, salt, carbon dioxide, ammonia, and urea
insensible water loss: the amount of fluid lost on a daily basis from the lungs, skin, respiratory tract, and water excreted in the feces
the exact amount cannot be measured, but it is estimated to be between 40 and 600 mL in an adult under normal circumstances
during fever will lose a lot more water |
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Term
| skin function: absorption |
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Definition
negligible for water and water soluble materials
vitamins A, D, E, K can be absorbed
toxic absorption: acetone, CCl4, poison ivy/oak, salts of Pb, Hg, and As |
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Term
| skin function: calcitriol production (vitamin D) |
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Definition
requires UV radiation from the sun
VITAMIN D is a group of fat soluble prophormones, the 2 major forms of which are vitamin D2 (or ergocalciferol) and vitamin D3 (or cholecalciferol)
vitamin D obtained from sun exposure, food, and supplements is biologically inert and must undergo 2 hydroxylation reactions to be activated in the body
calcitriol (1,25-dihydroxycholecalciferol) is the active form of vitamin D found in the body
the term vitamin D also refers to these metabolites and other analogues of these substances |
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Term
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Definition
thermoregulation
blood reservoir
protection
sensation
excretion
absorptions
vitamin D metabolism
the skin has many essential functions, including protection, thermoregulation, immune responsiveness, biochemical synthesis, sensory detection, and social and sexual communication
therapy to correct dysfunction in any of these activities may employ chemical agents that can be dlivered systemically, intralesionally, or topically and physical agents to which the skin can be exposed, including ultraviolet and ionizing radiation |
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Term
| dermatological pharmacology |
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Definition
a unique aspect of dermatological pharmacology is the direct accessibility of the skin as a target organ for diagnosis and treatment
topical and dermatological agents are employed alone or in conjunction with phototherapy and/or systemic medications in the management of most dermatological conditions
therapeutic agents can reach epidermal keratinocytes and immunocompetient cells in the epidermis and the underlying dermis that are involved in the pathogenesis of numerous cutaneous diseases |
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Term
| pathophysiology of disease of the skin |
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Definition
the treatment of skin damage produced by trauma or disease is aimed at:
healing or eliminating the disease
replacing or amplifying normal skin function
skin treatment preparations therefore include:
preparations aimed at the specific disease state
preparations that increase protection from the environment and prevent loss of protein, electrolytes, water, and heat
although skin disease can be disfiguring and affect the quality of life, it is rarely life threatening (but can be...infection common cause)
the risk/benefit ratio of any treatment must be considered when deciding on therapy
there are a number of skin disorders for which there is no safe and effective treatment, but under such circumstances the importance of camouflage creams and wigs might be used |
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Term
| dermatological does not equal topical |
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Definition
DERMATOLOGICAL means skin or scalp
requires FOR EXTERNAL USE ONLY
TOPICAL means any external body surface, including the eye, ear, nasal mucosa, and the mucus membranes of the mouth, retum, vagina, or urethra |
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Term
| absorption of the drug depends on: |
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Definition
1. body site (e.g. drug absorption is low from the palms and soles, higher from the scalp and face, and very high from the scrotum ad vulva)
2. skin hydration (e.g. oil in water emulsions and occlusive dressings); skin hydration increases drug absorption
3. skin condition (e.g. damage due to inflammation or burns increases absorption) |
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Term
DRUGS USED TO TREAT SKIN DISEASE ARE IDEALLY NOT ABSORBED BEYOND THE SKIN
choice of vehicle depends on: |
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Definition
1. the solubility of the active drug (MONOMOLECULAR)
2. the ability of the vehicle to hydrate the stratum corneum and therefore enhance penetration
3. the stability of the drug in the vehicle
4. the ability of the vehicle to retard evaporation from the surface of the skin (e.g. ointments) |
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Term
| most common diseases of the skin |
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Definition
10-20% of all consultations in general practive
eczema (a.k.a. dermatitis) ~5%
acne ~1%
urticaria (a.k.a. hives) ~1%
psoriasis ~0.5%
viral warts > 1%
skin cancer ~0.1% |
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Term
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Definition
skin cracking, redness, oozing, bleeding, flaking, itching (pruritis)
inflammation (acute/chronic): IgE, TH2 cells
intracellular edema (spongiosis)
skin thickening (chronic)
alterations in primary cellular components of skin:
keratinocytes retain nuclei (parakeratosis)
keratinocytes less packed
epidermal hyperplasia (acanthosis)
exzema and dermatitis are interchangeable terms and describe a pattern of inflammation in the skin characterized by the presence of intercellular edema (spongiosis) in the epidermis rather than a single disease
these include dryness and recurring skin rashes which are characterized by one or more of these symptoms: redness, skin edema, itching, and dryness, crusting, flaking, blistering, cracking, oozing, or bleeding
eczema is sometimes referred to as "the itch that rashes" since the itch, when scratched, results in the appearance of a rash
areas of temporary skin discoloration may appear and are sometimes due to healed lesions, although scarring is rare
eczema diagnosis is generally based on the appearance of inflamed, tichy skin in eczema sensitive areas such as face, chest, and other skin crease areas
in some people eczema may "bubble up" and ooze
in others, the condition may appear more scaly, dry, and red
chronic scratching causes the skin to take on a leathery texture because the skin thickens (lichenification)
ACANTHOSIS is diffuse epidermal hyperplasia
SPONGIOSIS is mainly intercellular edema between the keratinocytes and the epidermis
PARAKERATOSIS is a mode of keratinization characterized by the retention of nuclei in the stratum corneum
the causes of eczema are many and varied, and depend on the particular type of eczema that a person has |
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Term
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Definition
thought to be a hereditary condition, being genetically linked
it is proposed that people with atopic eczema are sensitive to allergens in the environment which are harmless to others
in atopy there is an excessive reaction by the immune system producing inflamed, irritated, and sore skin
associated atopic conditions include asthma and hay fever
itchy rash is particularly noticeable on face and scalp, neck, inside elbows, behind knees, and buttocks
in general, atopic dermatitis will come and go, often based on external factors |
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Term
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Definition
2 types:
allergic - resulting from a delayed reaction to some allergen, such as poison ivy or nickel
irritant - resulting from direct reaction to a solvent, for example
allergic contact dermatitis is cell mediated, type IV hypersensitivity reaction involving T cells, arising after a characteristic sensitization step |
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Term
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Definition
dry skin that becomes so serious it turns into eczema
it worsens in dry winter weather, and limbs and trunk are most often affected
the itchy, tender skin resembles a dry, cracked, river bed
this disorder is very common among older population |
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Term
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Definition
a skin disorder affecting the scalp, face, and trunk causing scaly, flaky, itchy, red skin
it particularly affects the sebum gland rich areas of skin
scaly pimples and red patches sometimes appear in various adjacent places
in newborns it causes a thick, yellow crusty scalp rash called cradle cap which seems related to lack of biotin, and is often curable
worsening of seborrheic dermatitis is a common finding in Parkinson's disease and related neurological conditions
pronounced seborrhoeic dermatitis is one of the earliest and most common findings in HIV/AIDS, even in the era of highly active antiretroviral therapy (HAART) |
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Term
| eczema treatments: glucocorticosteroids |
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Definition
anti inflammatory
vasoconstriction
reduced keratinocyte proliferation - skin atrophy with prolonged use (fragile-skin)
to increase the effectiveness of a topical corticosteroid, a dermatologist may recommend:
soak and smear therapy
wet wrap therapy
behavior modification
occlusive film
glucocorticoids are remarkably efficacious in the treatment of a wide variety of inflammatory dermatoses
TOPICAL GLUCOCORTICOSTEROIDS ARE THE MAINSTAY OF TREATMENT OF ATOPIC ECZEMA
as a result, a large number of different preparations and concentrations of topical glucocorticoids of varying potencies are available
a typical regimen for an eczematous eruption is 1% hydrocortisone ointment applied locally twice daily
effectiveness is enhanced by application of the topical steroid under an occlusive film, such as a plastic wrap
unfortunately, the risk of systemic absorption also is increased by occlusive dressings, and this can be a significant problem when the more potent glucocorticoids are applied to inflamed skin
glucocorticoids are administered systemically for severe episodes of acute dermatologic disorders and for exacerbations of chronic disorders
CORTICOSTEROIDS MUST BE USED SPARINGLY TO AVOID POSSIBLE SIDE EFFECTS, THE MOST COMMON OF WHICH IS THAT THEIR PROLONGED USE CAN CAUSE THE SKIN TO THIN AND BECOME FRAGILE (ATROPHY)
BECAUSE OF THIS, IF USED ON THE FACE OR OTHER DELICATE SKIN, LOW STRENGTH STEROID IS USUALLY USED
ADDITIONALLY, HIGH STRENGTH STEROIDS USED OVER LARGE AREAS OR UNDER OCCLUSION, MAY BE SIGNIFICANTLY ABSORBED INTO THE BODY, CAUSING HYPOTHALAMIC PITUITARY ADRENAL AXIS SUPPRESSION (HPA AXIS SUPPRESSION)
FINALLY BY THEIR IMMUNOSUPPRESSIVE ACTION THEY CAN, IF USED WITHOUT ANTIBIOTICS OR ANTIFUNGAL DRUGS, LEAD TO SOME SKIN INFECTIONS (FUNGA OR BACTERIAL)
MOA:
they are anti-inflammatory and vasoconstricting, and reduce keratinocyte cell division
they are classified into four groups, according to their vasoconstricting potency, which correlates remarkably well with their clinical efficacy
THE FLUORINATED GLUCOCORTICOSTEROIDS ARE PARTICULARLY POTENT AND ARE ABSORBED SYSTEMICALLY
SYSTEMIC steroids are rarely necessary in the treatment of atopic eczema, even in adults
they show relative lack of efficiency, tachyphylaxis and rebound and can interfere with growth particularly during the adolescent growth spurt
ADDITIONALLY "ANTI-INFLAMMATORY" MECHANISMS OF GLUCOCORITCOID ACTION ARE NUMEROUS, INCLUDING APOPTOSIS OF LYMPHOCYTES, INHIBITORY EFFECTS ON THE ARACHIDONIC ACID CASCADE, DEPRESSION OF PRODUCTION OF MANY CYTOKINES, AND MYRIAD EFFECTS ON INFLAMMATORY CELLS
YOU HAVE COVERED AND RE-COVERED THE ARACHIDONIC CASCADE AND STEROID ACTION THEREIN, THUS THIS IS VIABLE TEST MATERIAL
[image] |
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Term
| eczema treatments: immunosuppressants |
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Definition
A. CYCLOSPORINE
atopic dermatitis
capsule or liquid form
B. PIMECROLIMUS
pimecrolimus cream
C. TACROLIMUS
tacrolimus ointment
skin cancer and non-Hodgkin's lymphoma
the efficacy of cyclosporine in atopic eczema was discovered by chance in patients undergoing organ transplantation who had coexisten eczema
clinical trails in both adults and children have shown efficacy which is often rapid in onset but the condition relapses within weeks of stopping therapy
it is currently recommended in adults for short term treatment of severe atopic eczema which has failed to respond to conventional therapy
cyclosporine acts mainly on T lymphocytes, AS PREVIOUSLY ADDRESSED IN "EYE LECTURES" (may also have a direct effect on DNA synthesis and proliferation in keratinocytes)
tacrolimus and pimecrolimus induce immunosuppression by inhibiting the first phase of T cell activation (similar to cyclosporine, but via different route)
the first phase of T cell activation causes transcriptional activation of immediate and early proteins (e.g. IL2, IL3, IL4, and granulocyte-macrophage colongy stimulating factor (GMCSF), and interferon gamma) that allow T cells to progress from the G- to G1 phase
TACROLIMUS BINDS TO AN IMMUNOPHILIN TERMED FK BINDING PROTEIN (FKBP), specifically FKBP12
immunophilins (cyclophilin and FK binding proteins) are immunosuppressant binding proteins that are distributed in all cellular compartments and play an important role in protein activation
the tacrolimus-FK binding protein complex binds to and inhibits the phosphatase activity of calcineurin
the calcineurin enzyme catalyzes critical dephosphorylation reactions necessary for early lymphokine gene transcription
calcineurin inhibition results in blockade of signal transduction by the cytosol component of the nuclear factor of activated T cells (NFAT), which results in a failure to activate NFAT regulated genes
NFAT activated genes include those required for B cell activation (IL4 and CD40 ligand) and those required for T cell activation (IL2, TNF alpha, and interferon gamma)
reduced circulating levels of T cell activators result in inhibition of T cell proliferative responses to antigens and mitogens including mixed lymphocyte reactivity and cytotoxic T cell generation
compared to cyclosporine, tacrolimus is about 100 times more potent in inhibiting T cell proliferation responses |
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Term
| eczema treatments: antihistamines |
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Definition
SKIN MAST CELLS (H1, H2, H4 RECEPTORS):
reduce severe itching
sedative affect
FIRST GENERATION H1 ANTIHISTAMINES:
diphenhydramine
hydroxyzine HCl
SECOND GENERATION H1-ANTIHISTAMINES:
cetirizine
loratidine
desloratidine
fexofenadine HCl
histamine is a potent vasodilator, bronchial smooth muscle constriction, AND STIMULANT OF NOCICEPTIVE TYPE ITCH NERVES
histamine is in mast cells, basophils, and platelets
human skin mast cells express H1, H2, and H4 receptors but not H3 receptors
H1 and H2 receptors are involved in wheal formation and erythema, whereas only H1 receptor agonists cause pruritus
complete blockade of H1 receptors does not totally relieve itching and combinations of H1 and H2 blockers may be superior to H1 blockers alone
H1 antagonists are widely used in the treatment of atopic eczema in an effort to alleviate the itch (i.e. pruritus)
although many clinical trails have suggested that the beneficial effect of antihistamines is due to their sedative effect (inhibiting scratching)
oral antihistamines, particularly H1 receptor antagonists, have some anticholinergic activity and are sedating, making them useful for the control of pruritus
first generation sedating H1 receptor antagonists include hydroxyzine HCl, which is given in a dose of 0.5 mg/kg every 6 hours |
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Term
| eczema treatments: moisturizers and emollients |
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Definition
hydrate and reduce water loss: help restore barrier function
used to treat:
atopic dermatitis
allergic contact dermatitis
irritant contact dermatitis
OTC
fragrances = irritants
bath emollients
soap substitutes (detergents)
this treatment option does more than traditional moisturizers, which sit on top of the skin and prevent water loss
barrier repair moisturizers, also known as physiologic moisturizers, not only reduce water loss; they help rebuild the skin
patients say these products also calm the burning and itching
creams and ointments that improve skin hydration are called emollients
ointments are generally greasy preparations which are insoluble in water and anhydrous, and are more occlusive than creams
some newer ointments have both a hydrophilic and lipophilic component while others are water soluble ointments
emollients reduce the excess transepidermal water loss, a feature of eczema, as evidenced by surface electrical capacitance, measurement of transepidermal water loss, and moulding of skin surface replicas
thus they help restore barrier function but do not have an anti-inflammatory effect
they can soothe itching by their cooling effect but this is a transient benefit
there is some evidence that they reduce the susceptibility of eczematous skin to irritants |
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Term
| eczema treatments: coal tar |
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Definition
atopic eczema
seborrheic eczema (coal tar shampoos)
dandruff
psoriasis
actions:
antipruitic
antiseptic/antifungal
astringent
prevents rapid growth of skin cells
coal tar is indicated for the symptomatic management of pruritus and irritation caused by dandruff, seborrheic dermatitis, atopic dermatitis, eczema, and psoriasis
treatment with coal tar and UV light or sunlight can be beneficial because of its photosensitizing action
offical USP coal tar preparations include crude coal tar, coal tar topical solution, and coal tar ointment
crude coal tar is produced as a byproduct secondary to the destructive distillation of coal, and it can be further refined into coal tar topical solution or ointment
coal tar has a soothing effect on inflamed skin and has been used for many years to treat the types of eczema listed above
today, coal tar comes in numerous preparations, and some of these are available over the counter
best results are typically seen when use is supervised by a dermatologist
while effective and free of serious side effects, patients often prefer other treatment options because coal tar has an unpleasant odor and stains just about everything it touches
most coal tar preparations used for dermatologic disorders contain 2-5% coal tar
coal tar is applied topically in various formulations such as creams, gels, ointments, bath preparations, shampoos, liquid preparations (lotions and emulsions), and cleansing bars and solutions
coal tar exhibits keratoplastic (thickening of keratin layers) and mild irritant activity
coal tar may decrease the quantity and size of epidermal cells produced and inhibit mitosis, possibly through removal of oxygen in the skin
shampoo and soap preparations may exert their action through absorption into the epidermis and enhancement of scale removal
it has been suggested that a reaction similar to that following exposure to sunlight can occur in the epidermis through interactions between the peroxides in coal tar and epidermal sulfydryl groups
subsequently, epidermal proliferation may be decreased
coal tar preparations are also believed to possess antipruritic, antiseptic, stringent, antifungal, vasoconstrictive, and photosensitizing properties
what it does:
helps control itching, flaking and redness
helps prevent the rapid growth of skin cells that causes seborrheic dermatitis
while coal tar shampoos can effectively reduce the rapid growth and shedding of skin cells caused by seborrheic dermatitis, these shampoos tend to discolor blond, gray, and bleached hair |
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Term
| how can eczema be prevented, beyond pharmacy? |
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Definition
eczema outbreaks can usually be avoided with some simple precautions
the following suggestions may help to reduce the severity and frequency of flare-ups:
moisturize frequently
avoid sudden changes in temperature or humidity
avoid sweating or overheating
reduce stress
avoid scratchy materials (e.g. wool or other irritants)
avoid harsh soaps, detergents, and solvents
avoid environmental factors that trigger allergies (e.g. pollens, molds, mites, and animal dander)
be aware of any foods that may cause an outbreak and avoid those foods |
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Term
| acne (i.e. acne vulgaris) |
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Definition
40-50 millions people in US
~80% of 12-25 years
locations: face, mouth, chin, back, and chest
females > males
significant social impact and severe emotional distress |
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Term
| acne misconceptions and variables |
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Definition
acne is caused by dirt:
acne is caused by a number of things, but dirt isn't one of them
blemishes form when dead skin cells mix with your body's natural oil, forming a plug in the tiny hair follicles commonly called pores
acne is just a cosmetic condition:
yes, acne does affect the way people look - it's not a serious threat to a person's physical health, but it can also affect the way an individual feels and cause low self esteem and even depression
acne is for teenagers only:
although acne is associated with onset of adolescence, the truth is acne can strike at any age, and continue throughout life
certain foods cause acne:
acne is generally thought not to be caused by eating "wrong" foods
instead it is caused by the actions of bacteria
while controversy remains, and some preliminary information evaluating low vs. high glycemic diets appears to indicate an acne-benefit with low glycemic diet there are no clear results
make up causes acne:
most make ups today are non-comedogenic, which means they won't clog your pores
when shopping for cosmetics, look for products that are non-comedogenic, oil-free (water based) and hypoallergenic (no added fragrance)
acne is caused by too much sex:
it's true that androgens are contributing factors (contributing to oil production)
while these and other hormones may initiate sex drive, your sexual habits have no effect on acne
sweating cleans out your pores:
while working out is an important part of a healthy lifestyle, it can cause flareups for some people
vigorous exercise stimulates oil production, which combines with heat, perspiration, and friction to aggravate acne on the forehead, chest, and back
sun exposure helps acne:
minimal amounts of sun exposure may initially improve the appearance of acne - as the skin darkens, blemishes may be less noticeable
but prolonged exposure promotes more rapid exfoliation of dead skin cells, so you're more likely to get clogged pores
in addition, acne's unsightly souvenirs, post inflammatory hyperpigmentation and macules, will actually get darker if you spend time in the sun
scrubbing and toning the skin stops acne:
since acne is not caused by dirt, excessive washing won't make it go away
harsh OTC exfoliants using apricot pits or walnut shells can actually irritate or tear the skin, increasing the chances of infection and more breakouts
likewise, alcohol based toners can strip the skin of necessary oils, leaving it dry and irritated - and more likely to start producing more oil
more acne medications the better when breaking out:
to much medicine can cause excessive drying and additional problems (based on type and form of medication)
smoking induces acne:
false |
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Term
| acne is a disease of the pilosebaceous unit |
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Definition
1. increased sebum (NOT ACTUALLY CASUAL)
2. sloughing of FOLLICULAR keratinocytes (plugging); hyperkeratinization
3. bacterial growth
4. inflammation
at least 4 factors are important in the development of acne: PLUGGING OF THE HAIR FOLLICLE with abnormally cohesive desquamated cells, SEBACEOUS GLAND HYPERACTIVITY, PROLIFERATION OF BACTERIA (especially Propionibacterium acnes) within sebum and INFLAMMATION
acne is characterized by keratin plugs int eh sebaceous duct opening, inflammatory papules, pustules, nodules, cysts, and scars
the rash occurs where there is a high density of pilosebaceous glands (e.g. on the face, back, and chest
androgenic stimulation of the sebaceous glands at puberty accounts for the high prevalence of acne at puberty, and the active pilosebaceous follicles are heavily colonized by Propionibacterium acnes
the mechanism for keratin plug formation is poorly understood, but is generally thought to be via hyperkeratinization
continued gland secretion then results in swelling of the glands and ducts, which nodule and cyst formation and the induction of an inflammatory response, which produces inflammatory papules and pustules
HYPERKERATINIZATION:
a disorder of the cells lining the inside of a hair follicle
it is the normal function of these cells to detach or slough off (desquamate) from the skin lining at normal intervals
the dead cells are then forced out of the follicle (primarily by the growing hair)
however, in hyperkeratinization, this process is interrupted and a number of these dead skin cells do not leave the follicle because of an excess of keratin, a natural protein found in the skin
this excess of keratin, which is influenced by genetics, results in an increased adherence/bonding of dead skin cells together
this cohesion of cells will block or "cap" the hair follicle (leading to keratosis pilaris) or clog the sebaceous/oil duct (leading to acne) |
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Term
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Definition
COMEDONES: (closed and open) - whiteheads and blackheads
PAPULES: small or larger skin colored acne bumps
PUSTULES: bumps filled with white or yellow pus
NODULES/CYSTS: large pus filled, firm, occurring in dermis or hypodermis
the follicle, which is lined with skin cells, contains sebaceous glands that produce oil (sebum)
normally the skin cells that line the follicle are shed and brought to the skin's surface by the sebum and washed away
however, when the cells stick together instead of shedding, they form a plug or blockage
a clogged pore is a commonly used term for a plugged follicle
beneath the plug, a sac is formed (known as a microcomedone) that contains dead skin cells and oil
bacteria (propionibacterium acnes) grow freely in this environment, feeding on the dead skin cells and oil for fuel
as the sac continues to grow either a WHITEHEAL (KNOWN AS A CLOSED COMEDONE), or a BLACKHEAD (OPEN COMEDONE) forms
in more serious cases, the sac will become larger spurred on by the cells that the body sends into the sac to fight the infection, inflammation will result; and a bump (papule or pustule), painful nodule or cyst will develop |
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Term
| Propionibacterium acnes (P. acnes) |
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Definition
anaerobic gram positive bacterium
P. acnes is a relatively slow growing, typically aerotolerant anaerobic bacterium that is linked to the skin condition acne
P. acnes can be killed by benzoyl peroxide, tetracycline group and other antibiotics, and many antibacterial preparations
however, tetracycline resistant P. acnes is now quite common
clindamycin is also frequently used
new facts show that P. acnes are sensitive to some macrolides such as azithromycin which has a wide spectrum of action |
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Term
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Definition
normalizing shedding into the pore to prevent blockage
killing bacteria
anti-inflammatory effects
hormonal therapy
combination
a combination of treatments can greatly reduce the amount and severity of acne in many cases
those treatments that are most effective tend to have greater potential for side effects and need a greater degree of monitoring, so a step wise approach is often taken |
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Term
| acne treatment: benzoyl peroxide |
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Definition
antimicrobial (OXYGEN FREE RADICALS)
keratolytic
comedolytic (i.e. reduced black and white heads)
anti-inflammatory
sebostatic?
gels, lotions, cleansers of various strengths
can be irritating, allergic reactions, and bleaching
benzoyl peroxide exhibits antimicrobial effects against Propionibacterium acnes, which is the predominant organism in sebaceous follicles and comedones
the antibacterial effects of benzoyl peroxide are due to the release of free radical oxygen species, which are capable of oxidizing bacterial proteins
resolution of acne usually occurs within 4-6 weeks of initiation of treatment
resolution coincides with a reduction in levels of P. acnes, lipids, and free fatty acids in the skin follicle
benzoyl peroxide also demonstrates keratolytic activity, which produces drying and desquamative actions that contribute to its efficacy in comedone treatment
it also have drying actions, sebostatic effects, and causes mild skin desquamation
benzoyl peroxide improves both inflammatory and non-inflammatory acen lesions
benzoyl peroxide is effective as monotherapy in mild cases of acne and is used as an adjuvant in moderate to severe cases of acne |
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Term
| acne treatment: retinoids |
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Definition
retinoic acid receptors (RAR):
nuclear receptors
cell differentiation and proliferation
apoptosis (programmed cell death)
effects in: multiple sclerosis, amyotropic lateral sclerosis, neurodegenerative/Alzheimer's, psychiatric, cancer (bexarotene), dermatological (acne, psoriasis)
retinoids are mediators of cell differentiation and proliferation, apoptosis (programmed cell death), and reproduction
cells regulate the formation of specific retinoid isomers depending upon the cellular action required
the numerous effects of retinoids reflect the complex biology of the nuclear receptors that mediate retinoid activity
3 principle isoforms of RAR:
alpha, beta, gamma
homodimers and heterodimers:
RAR/RXR
PPAR/RXR
retinoids exert their effects through binding to specific nuclear retinoid receptors, which are members of the steroid thyroid superfamily of nuclear receptors
retinoid receptors are divided into retinoid X receptors (RXRs) and retinoic acid receptors (RARs); both types can be further divided into 3 subtypes: alpha, beta, and gamma
these receptor subtypes are further divided into many isoforms
retinoid receptors are structurally similar but have different affinities for different types of retinoids and distribution varies throughout the body resulting in a wide range of actions
retinoids and acne effects:
inhibition of hyperkeratinization
promotion of normal keratinocytes
reduce inflammatory response
inhibition of sebum production
comedolytic
decrease P. acnes in follicles |
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Term
| 3 generations of retinoids |
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Definition
1. first generation retinoids:
RETINOL, retinal, TRETINOIN (Retin-A)
ISOTRETINOIN (dermal or systemic)
2. second generation retinoids:
ATRETINATE, ACITRETIN (psoriasis)
3. third generation retinoids (arotinoids):
ADAPALENE (RARgamma and RARbeta)
modulates cellular differentation (keratinization); potent anti-inflammation
the RETINOIDS are a class of chemical compounds that are related chemically to vitamin A
retinoids are used in medicine, primarily due to the way they regulate epithelial cell growth
the primary action of isotretinoin in the treatment of acne is a reversible inhibition of sebum production through a reduction in the size of sebaceous glands and possible inhibition of follicular keratinization
the latter mechanism may be responsible for its beneficial effects in treating keratinization disorders
sebum production can be reversibly reduced by 10% of pretreatment levels
given in high dosages, isotretinoin can indirectly reduce the concentration of P. acnes bacteria through decreased sebum production
isotretinoin may inhibit prostaglandin E2 and collagenase, which would account for its anti-inflammatory effect
adapalene binds to specific retinoic acid nuclear receptors but does not bind to the cytosolic receptor proteins
adapalene reportedly penetrates deeply into the hair follicle
as a result of its actions, adapalene modulates cell differentiation and keratinization
adapalene also possesses potent anti-inflammatory and comedolytic properties |
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Term
| isotretinoin (oral administration) |
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Definition
targets all pathophysiologic factors in acne
decreases size and secretion of the sebaceous glands
normalizes follicular keratinization thus preventing formation of new comedones indirectly inhibiting P acnes growth
exerts an anti-inflammatory effect
many side effect but most tolerable
reserved for nodulocystic acne, but now being used more frequently for non-responsive moderate acne
accutane, amnesteem, sotret, claravis
isotretinoin is a medication used for the treatment of severe acne
it is sometimes used in prevention of certain skin cancers
it is a retinoid, meaning it is derived from vitamin A and is found in small quantities naturally in the body
oral isotretinoin is marketed under various trad neames, most commonly ACCUTANE or ROACCUTANE while topical isotretinoin is most commonly marketed under the trade names ISOTREX or ISOTREXIN |
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Term
| cancer chemoprevention with retinoids |
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Definition
vitamin A deficiency with:
squamous metaplasia
increased cell proliferation
hyperkeratosis
carcinoma
isotretinoin - partial regression of multiple basal cell carcinomas
acitretin - reduce skin cancer in psoriasis pateints
tazarotene - has shown efficacy in some basal cell carcinomas
HIGH DOSE
BEXAROTENE (TARGRETIN) is a retinoid that selectively binds RXRs. betarotene has been used in patients with cutaneous T cell lymphoma
systemic and topical retinoids have been used successfully to treat premalignant skin conditions and may have a role in chemoprevention of skin malignancies
high dose isotretinoin has suppressed skin cancers in patients with increased risk of skin malignancy from congenital disorders such as xeroderma pigmentosa and nevoid basal cell carcinoma syndrome
to achieve an anticncer effect, toxic doses of retinoids generally are required
acitretin at a dose of 25 mg/day or more appears to reduce the risk of skin cancer by about 25% among patients with psoriasis who are at high risk for squamous cell carcinoma b/c of prior use of 8-methoxypsoralen and UV radiation or other carcinogenic modalities for psoriasis
tretinoin cream applied one or BID decreased the size and number of actinic keratoses by 50% in one multicenter study
high doses of isotretinoin produce partial regression of multiple basal cell carcinomas but are more effective in suppressing the formation of new tumors, as demonstrated in patients with xeroderma pigmentosum
isotretinoin also prevents second primary tumors in patients who have had a previous squamous cell carcinoma of the head and neck
isotretinoin also is effective for oral leukoplakia
topical tazarotene has shown efficacy in some basal cell carcinomas
BEXAROTENE is a retinoid that selectively binds RXRs
bexarotene has been used in patients with cutaneous T cell lymphoma
b/c it is metabolized by CYP3A4, inhibitors of CYP3A4 (imidazole, antifungals, and macrolide antibiotics) will increase and inducers of CYP3A4 system will decrease plasma levels of bexarotene
side effects include lipid abnormalities, hypothyroidism secondary to a reversible RXR mediated suppression of TSH gene expression, pancreatitis, leukopenia, and GI symptoms
blood lipid and thyroid function should be measured before initiating therapy and periodically thereafter |
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Term
| acne treatment: hormone therapy |
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Definition
decrease free testosterone levels, by increasing sex hormone binding globulin, leading to decreased sebum production
inhibit ovary production of androgen (suppression of ovulation)
norgestimate and ethinyl estradiol or norethindrone acetate with ethinyl estradiol
reasons to choose hormone therapy for women:
desires oral contraception
hormonal acne
androgenic alopecia (aka female pattern hair thinning)
adult onset acne
PCOS
adrenal hyperandrogenism |
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Term
| acne treatment: keratolytics (i.e. exfoliators) |
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Definition
softening and separation of the stratum corneum of the epidermis reducing obstruction
1. sulfur:
antiseptic, antiparasitic, antiseborrheic, and keratolytic
2. salicyclic acid:
a beta-hydroxy acid that is thought to function through solubilization of "intercellular cement", reducing corneocyte adhesion
3-6% for keratolytic action
3. resorcinol:
a phenol derivative that is mildly keratolytic as well as bactericidal and fungicidal
used with salicyclic acid
4. retinoids (isotretinoin)
keratolytes are used in acne to reduce pore occlusion which is characteristic of acne |
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Term
| acne treatment: azelaic acid |
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Definition
natural occurring dicarboxylic acid
antibacterial and anti-inflammatory
antikeratizing (decreasing filaggrin - keratin filament aggregating protein)
comedolytic action
mild to moderate acne
used with combined Rx - oral antibiotics, topical retinoids
the efficacy of azelaic acid in acne is due to an antimicrobial effect and an antikeratinizing effect on the follicular epidermis
the antimicrobial effects of azelaic acid involves inhibition of synthesis of microbial cellular proteins
the exact MOA is unknown
azelaic acid possesses bacteriostatic properties against a variety of aerobic microorganisms, especially S. epidermidis and P. acnes which are known to be elevated in acne bearing skin
at high concentrations, azelaic acid is bactericidal against S. epidermidis and P. acnes
by reducing the concentration of bacteria present on the skin, azelaic acid decreases the inflammation associated with acne lesions
azelaic acid may also possess a direct antiinflammatory effect by scavenging oxygen radicals
the anti-keratinizing effect of azelaic acid may be due to decreased synthesis of filaggrin (keratin filament aggregating protein)
by inhibiting filaggrin, azelaic acid may normalize the keratinitation of the follicle and produce a reduction in non-inflamed acne lesions
azelaic acid does not affect sebum excretion |
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Term
| acne treatment: macrolide antibiotics |
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Definition
considered to be bacteriostatic, but high doses may be bacteriocidal
used in combination with benzyl peroxide
against P. acnes
1. erythromycin
topical/systemic
2. azithromycin
systemic
3. clarithromycin
topical/systemic
macrolides bind irreversibly to 50s subunit of rRNA -> inhibit protein translocation steps of protein synthesis -> inhibits protein synthesis |
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Term
| acne treatment: tetracyclines |
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Definition
tetracycline, minocycline, doxycycline
systemic administration
entry of tetracyclines is mediated by transport proteins unique to the bacterial inner cytoplasmmic membrane
broad spectrum antibiotics:
are bacteriostatic but also are effective against some other organisms other than bacteria (mycoplasma, spirochetes, amoebae)
tetracyclines block tRNA access to mRNA ribosome complex -> inhibits protein synthesis |
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Term
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Definition
psoriasis is a chronic inflammatory skin disease, which increased growth of skin cells (scaling)
psoriasis has no known cause
the tendency toward developing psoriasis is inherited in genes
psoriasis is not contagious
psoriasis gets better and worse spontaneously and can have periodic remission (clear skin)
psoriasis is controllable with medication
psoriasis is currently not curable
there are many therapies including newer BIOLOGIC DRUGS
PSORIASIS is a chronic, non infectious disease that affects mainly the skin
it is currently suspected to be autoimmune in origin
it occurs when the immune system sends out faulty signals that speed up the growth cycle of skin cells
psoriasis is not contagious
it commonly causes red, scaly patches to appear on the skin, although some patients have no dermatological symptoms
the scaly patches caused by psoriasis, called psoriatic plaques, are areas of inflammation and excessive skin production
skin rapidly accumulates at these sites and takes on a silvery-white appearance
plaques frequently occur on the skin of the elbows and knees, but can affect any area including the scalp, palms of hands and soles of feet, and genitals
there are 5 types of psoriasis: plauqe, guttate, inverse, pustular, and erythrodermic
the most common for, plaque psoriasis, appears as raised, red patches or lesions covered with a silvery white buildup of dead skin cells, called scale
psoriasis can occur on any part of the body and is associated with other serious health conditions, such as diabetes, heart disease, and depression
for mild disease that involves only small areas of the body (like less than 10% of the total skin surface), topical (skin applied) creams, lotions, and sprays may be very effective and safe to use
occasionally, a small local injection of steroids directly into a tough or resistant isolated psoriasis plaque may be helpful
for moderate to severe disease that involves much larger areas of the body (like 20% or more of the total skin surface), topical products may not be effective or practical to apply
these cases may require systemic or total body treatments such as pills, light treatments, or injections
stronger medications usually have greater associated possible risks |
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Term
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Definition
minimize or eliminate signs (i.e. scales and plaques)
reduce flare ups and associated impact (itching, inflammation) |
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Term
| psoriasis therapy - nonpharm |
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Definition
reduce stress
moisturizers
oatmeal baths (colloidal oatmeal: phenols and saponins)
sunscreens (sunburns may trigger flare up)
gentle cleaning
phototherapy (nonionizing electromagnetic radiation (UVB)) |
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Term
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Definition
steroids (topical)
anti-inflammatory, anti-proliferative, immunosuppressive, vasoconstrictive
retinoids (tazarotene - topical or acitretin - systemic)
salicylic acid (topical)
calcineurin inhibitors
pimecrolimus (topical)
cyclosporine (systemic)
methotrexate (systemic) |
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Term
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Definition
TNFa is a pro-inflammatory cytokine that will cause the cardinal signs of inflammation to occur:
heat (local and fever via hypothalamus)
swelling
redness
pain
loss of function
TNFa acting at its receptors can induce:
apoptotic cell death
CELLULAR PROLIFERATION (macrophages, neutrophils)
differentiation
tumorigenesis (potential lymphoma risk with antagonism)
cellular adhesion
vascular permeability
inflammation
a local increase in concentration of TNF will cause the cardinal signs of inflammation to occur
it is a cytokine involved in systemic inflammation and is a member of a group of cytokines that all stimulate the acute phase reaction
TNF was thought to be produced primarily by macrophages, but it is produced also by a broad variety of cell types including lymphoid cells, mast cells, endothelial cells, cardiac myocytes, adipose tissue, fibroblasts, and neuronal tissue
large amounts of TNF are released in response to lipopolysaccharide, and other bacterial products, and IL1
it is a potent chemoattractant for neutrophils, and promotes the expression of adhesion molecules on endothelial cells, helping neutrophils migrate
on macrophages - stimulates phagocytosis, and production of IL1 oxidants and the inflammatory lipid prostaglandin E2 PGE2
on other tissues - increasing insulin resistance |
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Term
biologic agents for psoriasis: tumor necrosis factor alpha (TNFa) blockers
etanercept (Enbrel) |
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Definition
MOA:
a dimeric fusion protein
consists of the extracellular ligand binding portion of the p75 TNF receptor
binds to an inactivates TNFa
there are 2 TNF receptors
by binding and inactivating TNFa, TNFa cannot bind to its normal receptors to produce an inflammatory reaction
ADRs with etanercept are mild to moderate infection site reactions
etanercept is FDA approved for the treatmetn of psoriasis, psoriatic arthritis, rheumatoid arthritis, juvenile rhematoid arthritis, and ankylosing spondylitis |
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Term
biologic agents for psoriasis: tumor necrosis factor alpha (TNFa) blockers
others |
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Definition
infliximab (Remicade)
adalimumab (Humira)
golimumab (Simponi)
antibodies directed against TNFa; binds to and inhibits TNFa from interacting with its receptor
infliximab, adalimumab, and golimumab are antibodies against TNFa
these druge reduce the amount of active TNFa in the body by binding to it and preventing it from signaling the receptors for TNFa on the surface of cells |
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Term
biologic agents for psoriasis: T cell blockers
alefacept (Amevive) |
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Definition
fusion protein
leukocyte function - block activation
associated antigen 3 (LFA-3) binding CD2
apoptotic induction via binding cytotoxic cells (NK cells, CD8)
psoriasis is a prototypical inflammatory skin disorder in which specific T cell populations are stimulated by undefined antigen(s) presented by antigen presenting cells
T cells release proinflammatory cytokins (TNF and IFN) that induce keratinocyte and endothelial cell proliferation
several immunomodulator drugs are approved for the treatment of moderate to severe psoriasis
they include: alefacept (Amevive), etanercept (Enbrel) and infliximab (Remicade)
although there are limited long term data regarding the efficacy and safety of biological agents soley for the treatment of psoriasis, similar if not identical therapies have been used extensively in the treatment of rheumatoid arthritis and Crohn's disease
the major advantage of biological agents in the treatment of psoriasis appears to be that they specifically target the activity of T lymphocytes and cytokins that mediate inflammation with fewer side effects than traditional systemic immunosuppressive/cytotoxic agents
alefacept was the 1st immunobiological agent approved for the treatment of moderate to severe psoriasis in patients who are candidates for systemic therapy
alefacept consists of a recombiant fully human fusion protein composed of the binding site of the leukocyte function associated antigen 3 (LFA3) protein and a human IgG1 Fc domain
the LFA3 portion of the alefacept molecule binds to CD2 on the surface of T cells, thus blocking the necessary costimulation step in T cell activation
importantly, since CD2 is expressed preferentially on memory effector T cells, naive T cells largely are unaffected by alefacept
a second important action of alefacept is its ability to induce apoptosis of memory effector T cells through simultaneous binding of its IgG1 protion to immunoglobulin receptors on cytotoxic cells and its LFA3 portion to CD2 on T cells, thus inducing granzyme mediated apoptosis of memory effector T cells |
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Term
biologic agents for psoriasis: cytokine blockers
ustekinumab (Stelara) |
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Definition
MONOCLONAL ANTIBODY targeting the cytokines IL12 and IL23
abundant in psoriasis skin and are thought to promote accumulation of psoriasis causing T cells
ustekinumab works by selectively targeting the cytokines IL12 and IL23
IL12/23 are also cytokines that mediate inflammation
the PASI score stands for Psoriasis Area and Severity Index
this tool allows researchers to put an objective number of what would otherwise be a very subjective idea: how bad is a person's psoriasis
to make up the score, the 3 features of a psoriatic plque (redness), scaling, and thickness are each assigned a number from 0 to 4 with 4 being the worst
then the extent to involvement of each region of the body is scored for 0 to 6
adding up the scores give a range of 0 to 72 |
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Term
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Definition
the major active ingredients of available sunscreens include chemical agents that absorb incident solar radiation in the UVB and/or UVA ranges and physical agents that contain particulate material that can block or reflect incident energy and reduce its transmission to the skin
many of the sunscreens available are mixtures of organic chemical absorbers and particulate physical substances
ideal sunscreens provide a broad spectrum of protection and are formulations that are photostable and remain intact for sustained periods on the skin
they also should be nonirritating, invisible, and nonstaining to clothing
no single sunscreen ingredient possesses all of these desirable properties but many are quite effective nonetheless
photoprotection from the acute and chronic effects of sun exposure is readily available with sunscreens
ultraviolet radiation:
UVC - caught by ozone layer of atmosphere
UVB - outer layer of skin; MAJOR contributor to skin damage
UVA - deeper skin penetration
associated with: wrinkles, aging, sunburn, cancer
sunlight has a profound effect on the skin causing premature skin aging, skin cancer, and a host of skin changes
exposure to UV light (UVA or UVB) from sunlight accounts for 90% of the symptoms of premature skin aging
many skin changes that were commonly believed to be due to aging, such as easy bruising are actually a result of prolonged exposure to UV radiation
UVA:
UVA was once thought to have a minor effect on skin damage, but now studies are showing that UVA is a major contributor to skin damage
UVA penetrates deeper into the skin and works more efficiently
the intensity of UVA radiation is more constant than UVB without the variations during the day and throughout the year
UVA is also not filtered by glass
UVB:
UVB affects the outer layer of skin, the epidermis, and is the primary agent responsible for sunburns
it is the most intense between the hours of 10AM and 2PM when the sun is brightest
it is also more intense in the summer months accounting for 70% of a person's yearly UVB dose
UVB does not penetrate glass
UVC:
UVC radiation is almost completely absorbed by the ozone layer and does not affect the skin
UVC radiation can be found in artifical sources such as mercury arc lamps and germicidal lamps
UV radiation and wrinkles:
both UVA AND UVB radiation cause wrinkles by breaking down collagen, creating free radicals, and inhibiting the natural repair mechanisms of the skin
a popular classification system of sun sensitivity is the skin phototype (SPT) classification
people with skin types I and II are at the highest risk for photoaging effect including wrinkles and skin cancer
the proper use of sunscreen to block both UVA and UVB radiation is an important weapon in the battle against wrinkles
SUN PROTECTION FACTOR (SPF):
a ratio of the minimal dose of incident sunlight that will produce redness (sunburn) on skin with the sunscreen in place (protected) and the dose that evokes the same reaction on the skin without the sunscreen (unprotected)
valuable for UVB only
reduced risk of actinic keratoses (dry, scaly, rough textured patches or lesions that form on the outermost layer of the skin after years of exposure to UV light) and squamous cell carcinomas of the skin
except for total sun avoidance, sunscreens are the best single method of protection from UV induced damage to the skin
there is a need for more definitive answers to questions related to the efficacy of sunscreens in reducing skin cancer risk
prospects for more effective photoprotection are excellent as better sunscreens components are developed and as more careful evaluations are preformed
applying: 20-30 minutes, quantity, daily
reapplying: frequency and activity
insect repellent combo: lowers effective SPF
picking the proper sunscreen:
the SPF measures the amount of UVB absorption, but there is no method of reporting the UVA absorption
the only way to determine if a sunscreen protects against UVA and UVB radiation is to look at the ingredients
a good broad spectrum sunscreen should have an SPF of at least 15 and also contain a UVA agent
applying sunscreen properly:
most people use sunscreen improperly by not applying enough
they apply only 25-50% of the recommended amount
sunscreen should be applied liberally enough to all sun exposed areas that it forms a film when initially applied
it takes 20-30 minutes for suncreen to be absorbed by the skin, so it should be applied at least a half hour before going out in the sun
sunscreen should also be the last product applied especially on the face since some sunscreens can break down in the presence of water contained in water based foundations and moisturizers
reapplying sunscreen:
most instructions on sunscreen labels recommend reapplying sunscreen "frequently", but the definition of "frequently" is vague
a common instruction is to reapply sunscreen after 2-4 hours in the sun
however, one study has shown that reapplying sunscreen 20-30 minutes after being in the sun is more effective than waiting 2 hours
it is possible that this time period is more effective b/c most people do not apply enough sunscreen initially, and this second application approximates the actual amount needed
sunscreen should be reapplied after swimming, excessive sweating, or toweling
daily sunscreen:
sunscreen should be applied daily
the daily use of a low SPF sunscreen (15) has been shown to be more effective in preventing skin damage than the intermittent use of higher SPF sunscreen
sunscreen and insect repelletns:
insect repellents reduce the sunscreen's SPF by up to 1/3
when using sunscreen and insect repellent together, a higher SPF should be used and reapplied more often |
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Term
| botulinum boxin (Botox, Dysport) |
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Definition
Clostridium botulinum
blocks neuromuscular conduction
inhibits acetylcholine vesicle docking and release - SNAP-25
denervation of muscle, muscle atrophy
botulinum toxin type A is an intramuscular toxin produced from fermentation of Clostridium botulinum type A
it is one of seven toxic serotypes of botulinum (A through G) that have been purified
2 of the serotypes are available commercially in the US, type A and B
botulinum toxin type A is more potent and longer acting than type B
botulinum toxin type A blocks neuromuscular conduction by binding to receptor sites on motor nerve terminals, entering nerve terminals, and inhibiting the release of ACh
INHIBITION OCCURS AS THE NEUROTOXIN CLEAVES A PROTEIN (SNAP-25) INTEGRAL TO THE SUCCESSFUL DOCKING AND RELEASE OF ACH FROM VESICLE SITUATED WITHIN NERVE ENDINGS
after intramuscular injection of atherapeutic dose, botulinum toxin type A produces partial chemical denervation of the muscle resulting in a localized reduction in muscle activity
additionally, the muscle may atrophy, axonal sprouting may occur, and extrajunctional ACh receptors may develop
evidence exists that suggest that reinnervation of the muscle may occur thereby slowing reversing muscle denervation produced by the neurotoxin |
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