Skin Diseases Flashcards

Question

What causes chronic wound?

Answer 1

Neuropathy in diabetes mellitus, spinal injuries Ischemia in atherosclerosis, PVD, microangiopathy DM Peripheral oedema DVT, Varicose veins, renal or cardiac failure Pressure Poor stability, spinal cord injuries, Dementia, diabetes mellitus, old age, terminal illness. Other connective tissue disorders leading to vasculitis, systemic diseases, malignancy, smoking, drugs such as corticosteroids and hydroxyurea.

Answer 2

Presence of necrotic and unhealthy tissue Excess exudate and slough Lack of adequate blood supply Absence of healthy granulation tissue Failure of re-epithelialisation Cyclical or persistent pain Recurrent wound breakdown Clinical or sub clinical infection.

Answer 3

There can be motor/sensory or autonomic neuropathy If there is motor neuropathy damage to neurons and neuron message signal is terminated this results in muscle atrophy. This causes a change in gait (new pressure distribution) and leads to ulcers. Motor neuropathy can also cause bone changes which leads to deformed foot and ulcers Sensory neuropathy you can’t detect pain if injury occurs you get painless trauma. If body is injured no pain is detected so could lead to wound and ulcers and complications of ulcer is infection and gangrene (localized death and decomposition of body tissue, resulting from obstructed circulation or bacterial infection.) Autonomic neuropathy: Decreased sweating so excess drying of skin occurs. Cracks in skin can cause chronic ulcers.

Answer 4

Eczema (dermatitis) both terms used interchangeably. Eczema inflammation of the epidermis and dermatitis inflammation of the dermis but both occur simultaneously. Group of skin conditions that cause dry, irritated, inflamed skin. Inflammatory reaction of the skin: _Erythema, oedema, oozing, papeles, crusting, thickening and slacking. _Itching, burning.

Answer 5

Atopic dermatitis Contact dermatitis Seborrhoeic dermatitis Dyshidrotic dermatits Nummular dermatitis Neurodermatitis Stasis dermatitis

Answer 6

Chronic disorder with flare ups and remissions-May clear up for long periods Most common form of eczema 1-2% adults, 15-20% school children 30% of skin problems in general practise Manley’s and femalesbequally affected Type IV hypersensitivity reaction Often occurs with asthma or hay fever (atopic triad) Commonly affects knees, elbows, wrists, neck, face.

Answer 7

Genetic predisposition-atopic families Defects in the skin barrier-repair and maintain Lack of anti-microbial peptides Defect in the fliaggrin gene-important for maintaining the skin barrier-in most eczema patients. Abnormalities in the normal inflammatory and allergy responses Barrier defects makes the skin in affected patients m uh more susceptible to infection and to irritation and allow allergy inducing substances to enter the skin, causing itch abs inflammation. Abnormalities in the normal inflammatory and allergy responses Barrier defects makes the skin in affected patients much more susceptible to infection and to irritation and allows allergy inducing substances if enter the skin, causing itch and inflammation. Immunology of eczema: Allergen in the skin gets taken up by the dendritic cells are the langerhans cells in epidermis and dermis. Dendritic cells present antigens to the T-cells, there is a change in the balance of TH1&2 cells so expansion occurs in TH2 cells and this secretes IL-4 activates B-cells to change antibody class and they start to produce IgE, this travels in the blood to mast cells it gets taken up by high affinity receptors on the surface of mast cells and this allows allergens to be taken up, this causes a release of pro-inflammatory mediators that cause the inflammation.

Answer 8

Often age specific: Felxural eczema in children Hand eczema in adults Dry skin Itching, May be severe, especially at night Red to brownish grey patches in affected areas become lichenified Raw, sensitive, swollen skin from scratching skin infections and sores can occur when scratching breaks the skin.

Answer 9

Moisturisers to prevent drying of the skin Identify and avoid triggers if possible Mild soaps and short showers/baths

Answer 10

Emollients to keep skin moisturised Topical corticosteroids work locally to inhibit the inflammation Antibiotics if eczema infected Phototherapy Next step in treatment: Systemic corticosteroids if patient doesn’t respond or experiences s/e next step is to use Topical calcineurin inhibitors TCIs eg pimecrolimus and tacrolimus. These inhibit T-cell response so prevents T helper cells from releasing IL-4. Next step in treatment is immunosuppressants- ciclosporine, Azathioprine Dupilimumab-mAb inhibiting IL4/IL13 signalling, inviting switching of classes from b-cells to T-cells. Alitretinoin-for chronic hand eczema refractory to steroids (retinoids)

Answer 11

Contact dermatitis cause by many substances in the home or work place responsible Usually exposed parts of the body 2types of contact dermatitis: •Irritant contact sue to toxic insult or accumulative exposure to some type of toxin or just long term use of water •Allergic contact Can distinguish between irritant and allergic contact via a patch test More common in adults than children Common in wet work- healthcare, hairdressers, catering, labs, cleaners, industrial factory workers. Atopic eczema patients have increased susceptibility to both types

Answer 12

75% of cases Exposure to acute toxic insult or cumulative damage from irritants Detergents and solvents which strip skin of natural oils Amount of exposure important Excessive hand washing, dribble rashes or nappy rashes Occurs under rings Diagnosis by knowing which substances irritate

Answer 13

•Majority of occupational skin disorders •Type IV hypersensitivity reaction •Over time of exposure, immune response builds up •Nickel, rubber, perfumes, preservatives in cosmetics, dyes •Diagnosis by patch testing

Answer 14

•Atopic dermatitis: Allergen gets taken up by dendritic cells which then presents allergens to T-cells in the lymph node T cells cause B-cells to have IgE class switching; triggers mast cells to produce many pro-inflammatory mediators which switches on many cells involved in this adaptive immune response, increases production of lots of different cytokines that will disturb epithelial barrier and causes more water loss. •Irritant contact dermatitis: Innate immune twosome occurs in ICD. The irritant will directly affect the keratinocytes and this will switch on and secrete many Pro-inflammatory cytokines such as TNF, IL-1, IL-8, GM-CSF and it will switch on dendritic cells via IL-1 secretion. This activates the up regulation of endothelial cells this allows vasodilation to occur and this allows cellular recruitment in the skin area eg recruitment of neutrophil followed by monocytes which become macrophages, lymphocytes and mast cells. This causes a local inflammatory response. This is innate immunity •Allergic contact dermatitis: Consists of a combination of both adaptive and innate immune response Allergic contact dermatitis is a type of delayed hypersensitivity reaction that occurs when the skin comes into contact with an allergen. The pathogenesis of allergic contact dermatitis involves both adaptive and innate immune responses. 1. Sensitization Phase: - Allergen Penetration: The allergen, such as nickel or fragrance, penetrates the skin and is taken up by dendritic cells (DCs) present in the epidermis. - Presentation to T-Cells: The DCs migrate to the nearby lymph nodes, where they present the allergen to T-cells. This interaction leads to activation and differentiation of allergen-specific T-cells. - B-Cell Activation: Activated T-cells produce cytokines that promote B-cell class switching to IgE production. B-cells then produce allergen-specific IgE antibodies. - IgE Production: The IgE antibodies bind to high-affinity receptors (FcεRI) on mast cells and basophils, sensitizing them to the specific allergen. 2. Elicitation Phase: - Re-Exposure to Allergen: Upon re-exposure to the allergen, it binds to the IgE antibodies on mast cells and basophils. - Mast Cell Activation: Cross-linking of IgE receptors on mast cells triggers the release of various pro-inflammatory mediators, including histamine, leukotrienes, and cytokines. - Inflammatory Response: The released mediators cause vasodilation, increased vascular permeability, and recruitment of inflammatory cells, such as neutrophils, monocytes/macrophages, lymphocytes, and additional mast cells. - Epithelial Barrier Dysfunction: The pro-inflammatory cytokines released by mast cells and other immune cells disrupt the epithelial barrier, leading to increased water loss and further inflammation. The combination of mast cell activation, release of pro-inflammatory mediators, and recruitment of immune cells results in the characteristic symptoms of allergic contact dermatitis, including redness, swelling, itching, and skin lesions. It's important to note that the pathogenesis of allergic contact dermatitis may vary depending on the specific allergen and individual immune response.

Answer 15

Avoid irritants and allergens Use emollients Topical corticosteroids Oral corticosteroids Alitretinoin (vitA form) for chronic hand contact dermatitis refractory to steroids (retinoid)

Answer 16

1-3% uk population More common in males bd over age of 20 Common harmless rash wig skin flakes, itchy and sore inflamed red skim with greasy looking white or yellow scales Ranges from mild dandruff to severe on the scalp Sebaceous skin zones- face, scalp, chest, ears, skin folds, acúlale, groin Sue to overgrowth of malassezia yeasts, which are part of the normal skin flora but trigger inflammatory response Not contagious, aggravated by stress

Answer 17

Infants aged 3-8 months Yellow, waxy, scales ok scalp, thick and difficult to remove Pink flaky patches on forehead, eyebrows, behind ears, nappy area. Due to developing sebum glands.

Answer 18

Infants: Emollients or minerals for scalp Topical steroids with antifungal for body Adults Shampoos with ketoconazole, Zn pyrithione, Se sulfide (anti-yeast) Steroid scalp lotions/mousses Topical mild corticosteroids with salicylic acid for scalp Topical mild corticosteroids with anti-yeast creams-ointments (clotrimazole, miconazole and nystatin) In severe cases and if above treatment fail use Oral antifungals ( severe cases)

Answer 19

•Nummular (discoid) dermatitis: Round oval blistered dry lesions Usually lower legs/ trunk arms Affects males and females equally Unknown cause Treat with emollients, steroids, antibiotics and phototherapy. •Neurodermatitis: 12% of the population, commonly mid to late adulthood esp 30-50yesrs Localised area caused by repeated rubbing it scratching. Possibly due to compressed nerve or presence of other dermatitis. Very persistent and recurring Treat with emollients and topical steroids. •Stasis dermatitis: Adults with varicose veins, DVT, or ulcers or where increased pressure in the veins of the leg. Other risk factors- overweight, standing up More common in women Often associated with signs of venous hypertension Skin become fragile, thin, shiny, inflamed, itchy abs flaky. Treat with emollients, steroids, compression stocking, exercise, weight loss, elevation of the legs and surgery for varicose veins. •Dishydrotic dermatitis Common in people with atopic eczema under the age of 40 Affects hands and feet Unknown cause but aggravated by heat and stress Tiny itchy blisters Treat with emollient, steroids, antibiotics, systemic immunosuppressants and phototherapy.

Answer 20

Chronic autoimmune disease, inflammatory skin disease with periods of remission and relapse. Affects 2-3% of uk population Equally in men and women at any age Peaks in late teens-early 30s and 50-60 Normal skin cells produced faster than they are shed resulting in itchy, skin lesions/plaques—pink/red with white scales variety of shapes and sizes- can split-painful. Can develop psoriatic arthritis.

Answer 21

Plaque psoriasis Scalp psoriasis Guttate psoriasis Pustular psoriasis Nail psoriasis Psoriatic arthritis Psoriasis in sensitive areas- armpits, genitals and skinfolds.

Answer 22

Is most common type of psoriasis can occur alone or in combination with other types. Red, itchy, sores plaques with white or silvery scales-well demarcated. Occurs anywhere on body- usually different type of on palms or soles or where skin touches skin.

Answer 23

•Scalp psoriasis similar to other parts of body but thick build up of scaly skin leading to dandruff like flakes Also visible around the hairline, forehead, neck and ears If severe can cause thinning of hair •Guttate psoriasis Bring the pink or red on fair skin less red and more darkening on dark skin Widespread across torso, back, limbs Usually eventually clears up m common in children and younger adults Often triggered by strep throat •Pustular Small white or yellow fluid filled blisters pustules on top of red or darkened skin m—turn crusty when burst Palms of hands or soles of feet Can become generalised Can be painful and require dermatologist for treatment •Nail psoriasis Up to 50% of psoriasis and 80% of psoriatic arthritis patients Can affect only the nails Fingernails and or toenails Mild to severe and often mistaken for fungal infection Nail discolouration, putting, crumbling, cracking m, splitting, detaching

Answer 24

Bring the pink or red on fair skin less red and more darkening on dark skin Widespread across torso, back, limbs Usually eventually clears up m common in children and younger adults Often triggered by strep throat

Answer 25

Genetic predisposition Complex inheritance but 1in4 children of affected parent Several susceptibility loci Keratinocytes normally take 3-4 weeks from basal layer to shedding but this occurs in 3-4 days in psoriasis. Inflammatory cells increased in all layers Trigger often outside event—eg throat infection (streptococcal), stress or injury to skin, virus (HIV or HPV) or withdrawal of corticosteroids.

Answer 26

Genetic predisposition of the genotype PSORS-1 or IL-23R, IL-12B in combination with environmental stress eg microorganisms, trauma, drugs or stress combined can cause stress in the keratinocytes cells, this triggers production of pro-inflammatory cytokines that will activate dermal dendritic cells. At the same time keratinocytes breakup so their DNA is released. Keratinocytes also produce anti microbial peptides including LL-37, the DNA that is released and LL-37 combine to form complexes and our immune system doesn’t recognise these complexes and classifies them as foreign these then are taken up by dendritic cells and they present them to T-cells. Dendritic cells also release IL-23 and IL-12 this switches on T cells and clinal expansion occurs resulting in formation of TH1&17 helper cells. These T-cells produce cytokine we get TH1 cells response means we get production of interferon gamma and TNF-a and they activate the dendritic cells again and the keratinocytes which causes more inflammation as keratinocytes produce chemokine and these chemokine offer a chemokine gradient that allows T-helper cells and our macrophages to get into keratinocytes layer. We get local expansion of T-cells and also the cytotoxic T-cells play a role here and we get more production of pro-inflammatory cytokines that help keratinocytes to grow more so all the growth factors KGF, EGF, TGF cytokine. Hyper proliferation of the keratinocytes layer and also get activation of fibroblasts. All of this means more production of collagen So keratinocytes made too quickly and body doesn’t have enough time to shed them off.

Answer 27

Unique to each individual Topical treatment •Moisturisers and emollients to prevent water loss and drying or flaking. •Vitamin-D derivatives (calcipotriol) tacalcitol, calcitriol) inhibit proliferation of cells and induced differentiation of keratinocytes and that slows down the excess growth. •Dovobet (betamethasone, and vitD derivatives) •Coal tar preps-scalp anti inflammatory and anti-scaling •Dithranol for well defined plaques not in sensitive areas •Topical calcineurin inhibitors which inhibit T-cell responses. However if these don’t work we can use •Phototherapy *Systemic treatments: •Immunosuppressants-methotrexate and Ciclosporin •Vitamin A derivative (Acitretin) •Apremilast-inhibits phsophodiesterase 4 which causes local inflammation •Dimethyl fumarate- activates Nrf2 which is involved in modifying responses against oxidative stress and inhibits inflammation too. •Anti-TNF (infliximab, adalimumab, etanercept, certolizumab) •Anti-IL23 (Ustekinumab (anti-IL12&23), guselkumab, rizankizumab, tildrakizumab) •Anti-IL17/IL17A ( secukinumab, brodalumab, ixekizumab)

Answer 28

Inflammatory joint diseas affecting north joints (eg knees, hand and feet) and tendons (eg heel and lower back) Relapsing band remitting Generally occurs after skin lesions Not linked to severity of psoriasis Joints become tender, swollen and stiff—worse in the morning and ease with exercise. Inflammation of tendons without joints Often associated with nail psoriasis

Answer 29

Painkillers NSAIDs eg ibuprofen, Diclofenac, COX-2 inhibitors Corticosteroids DMARDs Leflunomide Biologicals Anti-TNF adalimumab, etanercept, certolizumab Aprémielast—anti-PDE4 Tofacitinib-JAK inhibitor

Answer 30

•Acne •Skin cancer •Infections: Warren Verrucas Impetigo Fungal infections •Pigmentation changes Vitiligo

Answer 31

Acne is very common and it is Characterised by blackheads abs whiteheads and pustules. Mostly affects face, upper part of chest, and the back where most sebaceous follicles. Severe acne results in inflammation but acne can also manifest in non-inflammatory forms. Lesions are caused by excess oil and dead skin cells clogging up follicles- propionibacterium acne grow, triggering inflammation and pus. In adolescence, acne is usually caused by an increase in testosterone, which accrues during puberty. Acne scars are the results of inflammation within the dermis brought by acne (1 in 5 suffered have scarring) Benzoyl peroxide, antiseptics m, antibiotics, hormonal treatment and retinoids.

Answer 32

Basal cell carcinoma Squamous cell carcinoma Malignant melanoma

Answer 33

Slow growing and locally invasive tumours 4times more common than other skin cancers Caused by UV exposure and proliferation of basal keratinocytes Commonly on head and neck Morbidity related to local tissue invasion and destructions Imiquimod cream treatment enhances the immunity in the area which tries to kill off cancer cells.

Answer 34

Malignant invasive proliferation of epidermal keratinocytes. Second most common skin cancer More common in men abs the elderly Caused by UV exposure Common in white skins that burns easily Also caused by topical carcinogens-arsenic or chronic immunosuppression With treatment overall remission rate is 90%

Answer 35

Malignant melanoma is an aggressive form of skin cancer due to changes in the melanocytes. Malignant proliferation of melanocytes. Incidence and mortality are increasing with highest incidence in Australia and New Zealand. It caused by UG exposure Mortality rate of 25% Limited treatment options Recent high profiles successes of immune system modulation

Answer 36

UV exposure Intense short exposure in childhood Fair skin Red and blonde hair Blue eyes Difficulty to tan Freckles Benign naevi/dysplasia naevi Signs of melanoma: Asymmetry Boarder is irregular Colour variegation Diameter >6mm Evolving-any changes in size, shape, colour, elevation bleeding, itching crusting. Increasing rates in both men and women peak incidence at 40-60yrs of age In women it affects in legs and in men it is more common in trunk

Answer 37

In the epidermis we have melanocytes at the basal layer, proliferation occurs that can turn into benign moles or benign nevus that is fine but sometimes it can grow out of control and form a dysplastic nevus and these cause asymmetrical moles The next phase is called the radial growth phase. During this phase, the cancer cells grow horizontally along the surface of the skin in the epidermis but then we get vertical growth and start to expand in the terminal layer and eventually become metastatic because they reach the blood vessel in the area and they can leave the area and move to other areas to form metastasis in the brain bone or liver.

Answer 38

<1mm: 5-year survival is 95-100% 1-2mm: 5-year survival is 80-96% 2-1-4mm: 5-year survival is 60-75% >4mm: 5-year survival is 37-50%

Answer 39

Surgery: Simple or wide Sentinel node biopsy Take biopsy of the nearest lymph node and look for cancerous cells shows if cancer has left area or not. Chemotherapy Cytotoxic drugs such as Dacarbazine iv infusion which patients become resistant to quickly or Temozolomide oral. Taxanes (docetaxel, paclitaxel) and platinum agents. More recently: Target therapy Interferon alpha 2b IL-2 Ipilimumab (anti-CTLA4) Anti-BARF Anti-PD1

Answer 40

Melanoma cells grow due to growth factors epidermal growth factors stimulate these cells through receptor tyrosine kinases to stimulate RAS then BRAF then MEK then ERK. BRAF in melanoma cells about 40-50% of patients have BRAF mutations you can target this and this actually reduces the growth of melanoma cells. Another target is targeting protein to protein interactions which is the CTLA4 which is present on T-cells and B7 on melanoma cell or Pd-1 on T-cells and PD-L1 on melanoma cell. These block if you use antibodies to these protein to protein interactions they block the immunological check points that would result in adaptive immune resistance so the melanoma cells don’t become resistant to T-cells that try to kill it off.

Answer 41

Small, rough growth, typically hands or feet. Several different types and shapes Common-rebound, firm, raised, knuckles Verrucas- white, soles of feet, flat Plan- clusters-yellowish, smooth, young Filiforme-long, slender, neck and face Periungual-nails, change shape, painful Mosaic-tile-like clusters, palms and soles.

Answer 42

Caused by human papillomavirus-causes excess keratin production on epidermis. Virus can spread through close skin to skin contact, contaminated objects eg towels, shoes, communal changing areas, more likely to spread if skin wet, soft and in contact with rough surface. Clear up after 2 years. Salicylic acid containing creams, gels and paints Cryosurgery Genital warts- very common, sexually transmitted Months or eve after years to develop after HPV infection. Liquids and creams eg lmiqumoid, topical cream that stimulates the immune system to fight papillomavirus by encouraging interferón production. Keratolysis and cryosurgery.

Answer 43

Common highly contagious skin infection causing sores and blisters_often Streptococcus/Staphylococcus infections. 2 types: •Non-bullous-most common- nose and mouth, sores quickly burst- leave yellow brown crust. •Bullous-trunk, fluid-filled blíster that burst after few days- leave yellow crust. Very common in young 1/35 children in uk aged 0-4 Topical antibiotics, stay away from other people Severe cases-systemic antibiotics (eg flucloxacillin)

Answer 44

Several types of infections eg dermatophytes and Yeats, results in inflammation. Fungi invade abs grow in dead keratin Dermatophytes Athletes foot Ringworm growing between toes Itchy flaky red skin Contaminated floors Nail infections usually toenails—start from edge to base Ringworm-body, scalp, groin Small areas treated with topical applications of imidazole 2% Severe cases with systemic antifungal agents (griseofulvin, itraconazole) Immunocompromised patients (Candida, and aspergillus) m

Answer 45

Hypopigmentation: Vitiligo Decreased production of melanin Albinism Infection, blisters Burns Phototherapy Hyperpigmentations: Enhanced melanin production Pregnancy, Addisons disease UV exposure Antibiotics and anti-malarials Hydroquinone

Answer 46

Vitiligo also called leucoderma Loss of skin colour in patches-discoloured areas usually get bigger with time. Affects any parts of the body, hair and inside the mouth but more around the eyes, nostrils, mouth, navel, knees, and elbows. Melanocytes die or stop functioning leading to loss of melanin Affects people of all races and all skin types 95% develop it before age 40 Not contagious or life threatening and not linked to cancer No cure 3 types: Focal, segmental, generalised Aetiology Auto immune component 30% of patients have a family history 15-24% have autoimmune disease Immune system attacking its own melanocytes Trigger stress, skin damage, hormonal m changes, chemical exposures (phenol) m, liver/renal disease. Pathogenesis: Auto immune component Body makes autoantibodies to tyrosine hydroxylase in non-segmental vitiligo Increase in ROS production also in mitochondria of affected cells.

Answer 47

Important target for drug therapy and cosmetics, lotions and other agents. Cosmeceuticals-huge market, many with no proof of efficacy. Reasons vary from beauty, anti-ageing. Skin vital route of drug administration in dermatology Topical applications of drugs onto skin not only for skin disorders but can be used as systemic route of administration eg NSAIDs applied to underlying inflamed joints and connective tissue.

Answer 48

Advantage: drug can be applied directly to diseases tissue Disadvantage: skin is a highly effective barrier, so can prevent entry of medicines. Site of action-often lower layer if epidermis or dermis so has to pass through lipid rich layers of epidermis—leads to special issues with transdermal delivery. Special formulations required to promote skin penetration: Eg glucocorticoids derivatised with fatty acid esters to enhance absorption Eg waterproof occlusion dressing to cover skin after drug application to keep epidermis hydrated.

Answer 49

To skin: Manipulate the barrier function of the skin. Infection use topical antibiotics and antibacterial UV Protection: sunscreen and emollient preparation to restore pliability to dry stratum corneum layer Via skin: Skin delivery for systemic treatment Transdermal patch for treatment of motion sickness Transdermal patch fit systemic delivery in angina.

Answer 50

Topical: Intended for external use Localised action on one or more layers of the skin. But some little bit of drug still reaches systemic circulation (Reach systemic circulation in sub-therapeutic drug concentration) Skin softening emollient Examples of topical formulation: Solutions (erythromycin) Collodion (salicylic acid) Suspensions (selenium sulfide) Emulsions (lotion) Semisolids (ointment, pastes, gels, and creams) Solids (powders, aerosols) Spray (lidocaine) Transdermal patches: Intended for external use, skin is not the primary target Drugs transport through percutaneous route to systemic circulation. Nicotine patch, hormones.

Answer 51

•Cream/ointments: Formulations tailored to specific drugs-be bile for dissolving drug important. Water in oil emulsion for Ciclosporin as hydrophobic Oil in water for NSAIDs as hydrophilic Appearance and odour important. Agents to protect skin abs promote repair: Emollients-rehydrate the skin Barrier creams-prevent damage from irritants •Novel technologies-nano carriers •Ointment: semi-solid Hydrophobic ointment bases eg paraffin, fats and fixed oil bases eg caster oil, silicones, emulsifying bases eg aqueous cream m, water soluble bases eg polyethylene glycols. •Creams-semi-solid of O/W or W/O •Pastes-semi-solid eg dental paste •Gels-liquids gelled eg Ibugel •Others eg poultices, medicated plasters, powders, aerosols.

Answer 52

1-Surface treatment •protective layer, insect repellent, anti-microbial, anti-fungal, sunscreen. 2-Stratum Corneum •emollient, keratosis 3-Skin appendage •Acne, antibiotics, antiperspirant 4-Viable Epidermis-Dermis •anti-inflammatory, anaesthetics, antihistamine , antipruritic 5-Systemic treatment •transdermal

Answer 53

Delivering drugs across the stratum corneum and into the systemic circulation. Crossing epidermis, dermis till reaches vascular system in the dermis layer. Greatest advance in transdermal drug delivery Transdermal therapeutic system TTS: designed to release drug at a rate below the maximal rate for controlled systemic therapy. Advantages: Avoids first-pass metabolism of drug liver Consistent site of absorption ie no missing gut absorption window Can give constant drug input rate Can stop dosing by removing patch Examples: Transdermal scopolamine (hyoscine)-motion sickness Transdermal nitroglycerin GTN-angina Transdermal estradiol-HRT and menopause Transdermal contraceptives-Ethinyl estradiol and noregestromin Transdermal nicotine Transdermal testosterone Transdermal fentanyl Drug penetration across the stratum corneum occurs via two routes intracellular route (between cells) or transcellular route (through the cells) Transdermal drug delivery market is worth 2billion per year In 2000 only eight drugs were in the market: Scopolamine, nitroglycerin, clonidine, estradiol, nicotine, testosterone, fentanyl and notethisterone. Why can’t all drugs be administered via the skin? Complex process only few micrograms per hour can reach systemic circulation so drugs have to be potent and need to be in right formulation. Maximal steady flux in the order of micro grams per hour. Identifying candidate drugs for transdermal delivery? Choice of drug candidate depends on: Physicochemical nature if the drug Potency of the drugs Timescale of drug exposure Site and condition of skin Formulation Alteration of skin barrier by formulation Skin hydration Potency of drug: Low amounts of drugs crossing the skin means that most drugs delivered transdermally are potent I.e have ver low minimum effective concentration. Transdermal drug delivery involves the administration of medications through the skin. Since the skin acts as a barrier, only a small amount of drug is able to cross into the bloodstream. Therefore, drugs delivered transdermally are often formulated to be potent, meaning they have a low minimum effective concentration. This ensures that even a small amount of the drug can produce the desired therapeutic effect.

Answer 54

•Time scale of drug exposure Creams lotions ointments applied OD,BD,TDS Patches applied OD or every 72hrs •Site and condition of skin SC thickness varies across body Hirsute skin may be more permeable (especially to hydrophilic drugs that diffuse slowly through SC but faster through hair follicles) •Skin hydration state Hydrated skin is generally more permeable to drugs Through to be due to looser packing of SC lipids. Less restrictive path to drug diffusion. Open up the SC and can increase SC penetration 10-folds. Formulations factors Ointment, cream, lotion, gel Aim is to maximise drug concentration gradient across SC Use formulation techniques to achieve supersaturated concentrations Alteration of skin barrier by formulation: Can include penetration enhancers Ointments are greasy and restrict loss from skin—> stratum corneum become more permeable

Answer 55

Many also used to treat other diseases and mechanisms of action are the same: Antimicrobial agents: antibiotics, antifungals, antivirals for infections. Glucocorticoids eg hydrocortisone Antihistamines- puritis, eg eczema, insect stings eg crotamiton. Drugs used to control hair growth-co-cyprindol (acne, hirsutism in women) finasteride (alopécica(, elfornithine (hirsutism), minoxidil (alopecia) Retinoids-acne, eczema, psoriasis Vitamin-D analogous psoriasis,dermatitis Salicylic acid-keratolytic Imiquimod-immune modifier for genital warts and basal cell cancer-possibly increases immune surveillance. Biologicals anti-TNF treatments eg adalimumab and infliximab.

Answer 56

Target inflammation in the skin-psoriasis,eczema, pruritis Classified as: _Mild-hydrocortisone _Moderate-alclomethasone dipropionate, clobetasone butyrate flusroxycortide, fluocortolone. _Potent beclomethasone dipropionate, betamethasone esters. _Very potent clobetasol propionate, diflucortolone valerate. Choice depends on severity of disease and location (different skin thicknesses) Used in combinations with antimicrobials in infection. Mechanism of action Inhibits release of inflammatory mediators, NF Kappa B, neutrophils activation and emigration, mast cell release, immune cell activation. Side effects: Short term, low potency generally safe Prolonged usage can lead to: Steroid rebound Skin atrophy Systemic effects Spread of infection Steroid rosacea in face Stretch marks and superficial dilated blood vessels

Answer 57

Disturbances in vitamin A metabolism disrupt skin Retinoids acid has potent effects on skin homeostasis Retinoid drugs include: Tretinoin, isotretinoin, alitretinoin, tazarotene, adápalene. Acne, eczema, psoriasis Usually topical applications, oral in severe cases. Mechanism of action: Bind to RXR retinoid X or A receptor and RAR nuclear receptors in keratinocytes and sebaceous glands to decrease cell proliferation and sebum production. Anti-inflammatory effects through pleiotropic actions on immune system Side effects Dry skin Stinging Burning sensation Joint pains Teratogenic VitD analogues: Mixture of related substances-calcitriol biologically active molecule Act via VDR vitamin D receptors to modulate gene transcription in keratinocytes, fibroblasts, langerhans cells and sebaceous glands. Anti-proliferative and pro-differentiative effects in keratinocytes. Inhibit T cell production Calcitriol, calcipotriol and tacalcitol are main analogues-psoriasis Given topically Side effects possible effects on bone and potential skin irritation.

Answer 58

Remove allergen/irritant if possible Emollients-hydrate skin Topical steroids Topical calcineurin inhibitors- reduce inflammation through T-cell inhibiton Phototherapy severe eczema Oral corticosteroids severe eczema Immunosuppressants chronic severe eczema Antibiotics Topical localised infection Oral visibly infected skin

Answer 59

Emollients- hydrate skin Vitamin D derivatives-maturation if epidermal cells Topical steroids reduce epithelial turnover Coal tar Dithranol anti-proliferative Keratolytics removes scale Phototherapy moderate to sever psoriasis Oral corticosteroids severe Immunosuppressants methotrexate, Ciclosporin Severe Accitretin if immunosuppressants ineffective Anti-TNF antibodies last resort

Answer 60

Topical corticosteroids adverse effects Systemic side effects More likely with potent corticosteroids Long treatment duration > 2weeks Large area Localised side effects Skin thinning Within 1-3 weeks of starting a potent topical corticosteroids Select lowest potency likely to work within 7-14days based upon: Severity of inflammation Response to previous treatment Review in 7days Stop or step up as necessary •Mild eczema: Manage trigger Emollients Mild topical steroids •Moderate eczema Manage trigger Eminente Moderate topical steroids Topical calcineurin inhibitors Bandages •Severe eczema Manage triggers Emollients Moderate topical steroid Topical calcineurin inhibitors Bandages Phototherapy Oral corticosteroids

Answer 61

Tacrolimus Pimecrolimus Reduce inflammation through suppression of T-lymphocytes responses. Suitable for use on face because they don’t cause skin atrophy like glucocorticoids but they cause local skin irritation redness. Suitable for children aged over 2-years

Answer 62

Occluding thr area Prevent scratching Keeps creams in contact with skin Medicated or dry dressing Over emollient of chronic lichenified eczema. Over emollient and topical steroid for flare ups. Maximum use of 7-14 days

Answer 63

Down regulation of inflammatory pathway

Answer 64

Corticosteroids e.g. Prednisolone: Short term measure in severe or widespread eczemas Gain control very rapidly Not recommended for children Immunosuppressants: Ciclosporin-not recommended for children Extremely effective in chronic severe eczema.

Answer 65

Antibiotics oral: Treat visibly infected skin with oral antibiotics. Flucloxacillin first line therapy Erythromycin if penicillin allergic or resistant Clarithromycin if erythromycin not tolerated Treat with 1-2 week course Staphylococci aureus 90% colonised Swab from infected lesion if resistance suspected or not Staph.aureus infection. Use topical antibiotics if localised small infection Maximum of 2 weeks treatment Advise general measures to prevent infection: Not to leave tub open Use clean spoons to remove cream Reorder new pot of cream after an infection

Answer 66

Not for routine use only for pruritus most distressing feature Trial with non sedating antihistamine 4weeks Short term use of sedating antihistamine at night eg chlorphenamine, promethazine. Promote sleep and reduce scratching Topically cause sensitisation and have no place in management

Answer 67

Describe the incidence of psoriasis and its precipitating factors. Explain the pathogenesis of psoriasis List the clinical features and different types of psoriasis Describe the rationale behind treatment of psoriasis State the treatment used for the management of psoriasis.

Answer 68

Common type >80% Plaques raised scaly sliver white flakes affects the elbows and knees

Answer 69

Red glazed plaques confined to flexures Groin, natal cleft, sun-mammary area Usually no scale Lesions are shiny and smooth Skin very tender Infection risk

Answer 70

Raindrop like Common in children and young adults Small circular plaques on trunk 2 weeks after streptococcal sore throat.

Answer 71

Most severe types: Widespread intense inflammation of the skin Maybe associated with malaise, pyrexia and circulatory disturbance Can be life threatening: Widespread skin shedding

Answer 72

•To hydrate the skin Emollients •To promote normal maturation of epidermal cells Vitamin D derivatives •To reduce epidermal cell turnover Corticosteroids and cytotoxic agents •To remove scale Keratolytics •To reduce inflammation and the immunological skin reaction Immunosuppressants

Answer 73

•First line Emollients Vitamin D analogues Topical corticosteroids Dithranol Coal Tar •Second line UVB and PUVA Systemic non biological agents •Third line Systemic biological agents

Answer 74

Smooth and smooth and hydrate Apply regularly and liberally Creams used as a soap substitute Bath or shower emollients Add to bath water Apply to wet skin and rinse

Answer 75

Inhibit T-cell activation Antiproliferative effect & improved differentiation Interfere with cytokine release Anti-inflammatory Calcipotriol (Dovonex) Tacalcitol (Curatoderm) Calcitriol (Silkis) Cream and ointment apply OD or BD Colourless, odourless and does not stain Not for use on the face, flexures or genitals

Answer 76

Moderate potency topical corticosteroids Eg Clobetasone butyrate 0.05% Stronger agents on palms and soles of feet Reduce epidermal cell turnover •Anti-inflammatory and antiproliferative May lead to rebound exacerbation on discontinuation Inappropriate for: Widespread psoriasis Long term use (max 8-weeks)

Answer 77

Anti-proliferative effect on epidermal keratinocytes Starts with low conc 0.05% increase gradually depending on tolerance max 3% Proprietary preparations eg Dithrocream usually washed off after 50-60min (short contact) Specialist intensive treatment overnight Very irritant Careful to avoid the normal skin Difficult to use with many small lesionan Stains skin, clothing and bath fittings Unsuitable for face, flexures or acutely inflamed psoriasis. Anti-proliferative effect inhibits thiamine thymidine from incorporating in the DNA and ATP supply to normal cells so it inhibits cell turnover.

Answer 78

Anti-inflammatory and keratolytic activity Effective for inducing remission Used for many years Mostly used scalp psoriasis Tar based shampoos available eg poly tar Efficacy enhanced when used with UVB Known carcinogen

Answer 79

UVB and PUVA Methotrexate and Ciclosporin Acitretin UVB Slows cell proliferation Light of wavelengths 290-320nm Responsible for sunburn Used alone or with emollients Dose give 3X a week until clear Usually for 4-6 weeks PUVA Psoralen UVA Activated by UVA to interfere with DNA synthesis Reduces epidermal cell turnover Allows deeper penetration of UVA lightning Eye protection Dark goggles worn during and 8hours after treatment to prevent cataract Skin cancers Ci if genetic risk of melanoma

Answer 80

Systemic preparations Methotrexate Most effective treatment for psoriatic arthritis 1st line systemic agent Antipoliferative ( antifoalte effect) and T cell suppressor Ciclosporin T-cell suppression Renal function and blood pressure monitored Avoid over exposure to the sun and should it receive concurrent UV therapy

Answer 81

If methotrexate and Ciclosporin unsuccessfull Oral vitamin D analogue Buen to nuclear retinoid acid receptors Involved in controlling development and maturation of cells Induce keratinocytes differentiation and reduce epidermal hyperplasia Teratogenic effects Enhances the action of PUVA allowing a reduction in dose

Answer 82

TNF antagonists Reduce T cell mediated effects Monoclonal antibodies Adalimumab and infliximab Fusion proteins Etanercept Most effective 60-80% having at least 75% improvement within 12 weeks Long term side effects unknown Infection Increased malignant disease Restricted use Severe psoriasis only Failed to respond to or can’t tolerate conventional systemic treatments

Answer 83

Genetic pre-disposition Cause and Pathophysiology unknown Trigger factors exacerbate Psychologicallly distressing condition Treatment is symptomatic Remove scale Reduce over production of cells Reduce inflammation Improve maturation and hydrate

Skin Diseases Flashcards

(108 cards)