Therapeutics of Skin Disease

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  • Created by: LBCW0502
  • Created on: 30-01-20 10:43
What are the aims of therapy?
Control extent and severity of the disease so that it has minimal impact on the patient's QOL. Remove/minimise triggers/disease state. Reassure patient (treatment will take time to become effective). Cure is not always possible
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Describe features of emollients (1)
All patients should use regularly for treatment and maintenance (regardless of whether or not it controls disease state). MOA - forms a oily layer over skin to prevent evaporation of water. Hydrates skin, softens plaques, reduces shedding of scales
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Describe features of emollients (2)
Reduces itch, reduces cracking/bleeding. Oily barrier on skin prevents evaporation of water from skin surface (prevent dry skin)
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What are the types of emollients? (1)
Creams (water miscible, for moist/weeping lesions, E45, Diprobase). Ointments (greasier/more effective/less acceptable to patient, for dry/lichenified skin, WSP, emulsifying ointment, 50:50 WSP/LP ointment). Use creams/day, ointments/night
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What are the types of emollients? (2)
Lotions (water based liquids, doesn't help to retain water, useful for hairy areas, cooling effect when stored in the fridge/also for creams, QV, Dermol). Bath oils (add to bath water/not too hot, take care/makes surfaces slippery, Oilatum, Balneum)
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What are the types of emollients? (3)
Soap substitutes (use instead of soap, apply to dry skin then wash off, Dermol 500, Hydromol). Scalp (olive oil, almond oil, compound coconut ointment, hair masks)
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Describe features of topical corticosteroids (1)
Important that they are not over/underused. OD recommended, max BD. Up/down titration based on symptoms, stop once flare has resolved. Use different strengths for different parts of the body e.g. Dermovate (clobetasol prorionate) to body
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Describe features of topical corticosteroids (2)
Eumovate (clobetasone butyrate) to face/neck. Some products contain antimicrobial - should have defined treatment course (avoid resistance). S/E - skin atrophy, local/systemic, allergies, thin skin, adrenal suppression, systemic absorption, rebounds
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Describe features of topical corticosteroids (3)
Topical corticosteroids are used if emollients are not effective after a month. Ask patients to titrate medication based on symptoms. Stop corticosteroids once flare has resolved (go back to using emollients). Weaker steroids used on face/neck
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Describe features of steroid potency (1)
Mild (when skin is inflamed but not aggressive), hydrocortisone 0.1-2.5%, + antimicrobial - Canestan HC, + Crotamition - Eurax HC. Moderate (skin under reasonable control but still active), betnovate RD (betamethasone 0.025%), Haelan, Synalar 1 in 4
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Describe features of steroid potency (2)
Eumovate (clobetasone butyrate 0.05%), + antimicrobial - Trimovate. Potent (bad skin condition), betamethasone 0.1%, mometasone 0.1%, + antimicrobial - betnovate N or C, Fucibet, Synalar N or C, + salicylic acid - Diprosalic
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Describe features of steroid potency (3)
Very potent (very bad skin condition), Dermovate (clobetasol proprionate 0.05%), + antimicrobial dermovate NN
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Describe features of fingertip units (1)
Patient counselling - apply to affected area only, 1 finger tip unit give 500 mg. Per hand (1), per foot (2), per arm (3), front (7), back and buttocks (7), per leg (6). Apply emollients first, wait 30 mins, then apply steroids to affected areas
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Describe features of fingertip units (2)
This avoids steroids being applied all over/rebound effects/steroid potency. Cannot overdose with emollients (use generous amount)
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What does the treatment of psoriasis depend on?
Severity, site and type
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What are the patient factors to consider for the treatment of psoriasis?
Lifestyle, self treatment, hospital out-patient, hospital in-patient. Response to previous treatment. Co-morbidities. Anti-inflammatory medicines likely to reduce patient's immune system (e.g. diabetes, immunocompromised)
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Outline the schematic of psoriasis treatment ladder (1)
Topical (corticosteroids, calcipotriol, dithanol, coal tar), photo (PUVA, UVB), systemic (biologics, cyclosporin, MTX, retinoids). With each step up the ladder (increasing toxicity but increasing effectiveness)
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Outline the schematic of psoriasis treatment ladder (2)
Add on therapy, modifications for each patient but also adding on S/E. Cyclosporin - used for immediate response (if required), then step down ladder when symptoms improve
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What are the topical treatments for psoriasis and their targets?
Emollients (moisturise). Vitamin D analogues, coal tar, dithranol (anti-mitotic - inhibits cel division). Steroids (anti-inflammatory). Salicylic acid (keratolytic - breaks down outer keratin layer of skin). Treatments make skin feel better (no cure)
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Describe features of vitamin D analogues (1)
Calcipotriol, tacalcitol, calcitriol, anti-mitotic (inhibits epidermal cell proliferation). 1st line for chronic plaque psoriasis. Advantages - no smell, no staining, no skin atrophy, more effective than dithranol/coal tar
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Describe features of vitamin D analogues (2)
As effective as potent steroid and longer period of remission after discontinuation. Disadvantages - irritation/cannot use on face/flexures, except calcitriol. Applied OD/BD (cream/day, ointment/night), 1 finger tip unit per 100 cm2
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Describe features of vitamin D analogues (3)
Max dose to avoid hypercalcaemia (100g/week, systemic absorption). If not responded after 8 weeks add steroid. Some patients allergic
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Describe features of coal tar (1)
Used for decades to treat psoriasis. MOA unclear (keratolytic, anti-mitotic, anti-inflammatory). Applied BD, shower off after 15 mins, concentration 1-10% in soft paraffin base. Disadvantages - safety/increased risk of skin cancer
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Describe features of coal tar (2)
Stains clothing/skin, smells unpleasant, less effective than vitamin D analogues, can cause folliculitis, contact allergy, bronchospasm (inhalation of particles)
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Describe features of dithranol (1)
Use for decades to treat psoriasis. Anti-mitotic, oxidises/forms free radicals thought to inhibit DNA synthesis. Short contact dithranol therapy - 8-15% applied for 15-30 mins. Weaker concentration applied for 12-24 h
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Describe features of dithranol (2)
Increased every few days as tolerated. Temporary staining of skin, permanent staining of clothing/bathroom fittings. Messy unpleasant odour. Highly irritant, must avoid contact with surrounding skin, not used on face/flexures
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Describe features of dithranol (3)
Incorporated in lassar's paste (doesn't smudge, increases viscosity, placed on affected skin, not healthy skin). Dithrocream (0.1-2%), short (up to 1 hr) or long (overnight) contact. Apply sparingly once every 24 h, easy to apply and wash off
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Describe features of salicylic acid (1)
Keratolytic. Softens scales and eases removal. Can increase penetration/efficiency of other topical treatments, especially corticosteroids. Usually used on pals, soles and scalp. Disadvantages - irritant, use on large areas (salicylate toxicity)
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Describe features of salicylic acid (2)
Breaks down top thick layer of skin, allows emollients/steroids to penetrate the skin, synergistic effect with other treatments, gateway drug, large amounts/very frequent use – leads to systemic absorption
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Summarise features of topical treatment (1)
First line (emollients and vitamin D analogues). Scalp (mild - coal tar shampoo, emollient, salicylic acid to remove excessive scale). Face and flexures (emollient and steroid)
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Summarise features of topical treatment (2)
Trunk and limbs (emollient and steroid/specialist use and advice, vitamin D analoges, dithranol/coal tar)
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Describe features of phototherapy (1)
Uses - refractory to topical treatment, extensive disease, can combine with topical treatments (increased efficacy/faster results), C/I in malignancy or lupus erythema. MOA - anti-mitotic, immunosuppressant, anti-inflammatory
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Describe features of phototherapy (2)
UVB - light wavelength 290-320 nm. Dose adjusted to match skin type to avoid burning. 3x/week until psoriasis clears (4-6 weeks), treatment takes a few minutes. Narrowband UVB - light of wavelength 300-313 nm, reduced risk of burning,
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Describe features of phototherapy (3)
Increased effect of plaque clearance and length of remission time
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Describe features of phototherapy (4)
PUVA (UVA light wavelength 320-400 nm) causes psoralen to form cross links between complementary strands of DNA causing cell death, reducing proliferation. Psoralen must be present in skin at time UVA treatment is given
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Describe features of phototherapy (5)
PO tablets 1-2h before irradiation or topical lotion/paint/bath solution just before irradiation. UVA dose determined by skin type. Treatment twice a week, until psoriasis clears, max 250 treatments, after 20-30 treatments, 90% patients see clearance
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Describe features of phototherapy (6)
Adverse effects - sunburn, skin cancer, skin ageing, pigmentation. PO psoralens take 12-24h to clear form body (must protect skin from natural sunlight during this time, wear sunglasses to avoid cataracts, nausea - take with food)
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Describe features of phototherapy (7)
When topical therapy is not effective, can be used with topical therapy, not used in skin cancer (UV light used)
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Describe features of phototherapy (8)
Band of UV therapy depends on pigment of patient’s skin – to prevent burning, increase effect of plaque clearance, fewer sessions/longer remission time
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Describe features of systemic therapy (1)
Initiated in hospital setting, severe disease unresponsive to topical treatment and phototherapy. Immunosuppressants (MTX, cyclosporin, acitretin)
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Describe features of systemic therapy (2)
Biologics (etanercept, infliximab, ustekinumab, adalimumab, secukinumab, ixekizumab, certolizumab, risankizumab, tildrakizumab). Combine with other treatment - increase efficacy, disadvantages - S/E, C/I
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Describe features of systemic therapy (3)
Oral immunosuppressants e.g. MTX. Biologics – monthly, weekly, every 8 weekly injections. Immunosuppressants, then biologic, then second biologic, try combination of immunosuppressant and biologic. Difficult to predict S/E
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Describe features of systemic therapy (4)
2 biologics not used at the same time. Increased risk of infection
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Describe features of acitretin (1)
Oral retinoid, reverse hyperkeratotic and metaplastic skin changes, for pustular and erythrodermic psoriasis. Problems (teratogenic, hepatotoxicity, hyperlipidaemia, dry lips, mucous membranes, sticky skin, hair thinning
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Describe features of acitretin (2)
Can use with PUVA, increase effect and decrease dosage needed (reduces S/E). Max effect seen after 4-6 weeks
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Describe features of acitretin (3)
Requires a negative pregnancy test from female patients, also need to be on oral contraception (teratogenic), causes sticky skin (due to affecting lipids)
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Describe features of methotrexate (1)
Can be used for psoriasis and eczema. MOA - immunosuppression, folate antagonist, blocks DNA synthesis and production of new cells. Once a week dose (7.5-20 mg, PO/IM/SC). Treatment/maintenance with regular monitoring,
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Describe features of methotrexate (2)
Folate – involved in mitochondria, inhibiting folate in every cell in the body, not able to function. MTX used weekly, folic acid co-prescribed
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Describe features of methotrexate (3)
Problems - bone marrow suppression, neutropenia, teratogenicity, hepatotoxicity, nausea, mouth ulcers, pneumonitis, multiple drug interactions, avoid/minimise alcohol intake
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Describe features of methotrexate (4)
Renally cleared, need to monitor renal function. Check HIV, hep B, unknown underlying infections. TB infections, chest x-rays, FBC, rule out any infections prior to starting MTX.
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Describe features of methotrexate (5)
If there is an infection – treatment needs to control infection (MTX will reduce the immune system e.g. could allow HIV to develop). Negative pregnancy test every 3 months. First four weeks of treatment, high risk of infection compared to public
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Describe features of cyclosporin (1)
MOA - immunosuppressant, blocks calcineurin dependent factor (makes IL-2), inhibits T-cell proliferation. Rapid acting (within 4 weeks) but use for 1 year maximum due to adverse effects. Dosage 2.5-5 mg/kg/day. Blood monitoring every 2-8 weeks
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Describe features of cyclosporin (2)
Problems - nephrotoxicity, HTN, increased risk of malignancy, hyperlipidaemia, tremor, headache
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Describe features of cyclosporin (3)
If not effective in 4 weeks/titration, chance of not being effective, used for a maximum of 1 year (prevent damage to kidneys/liver, S/E are reversible if used for 1 year, reduced risk of cancer)
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Describe features of cyclosporin (4)
Blood monitoring, every 2 weeks, every 4 weeks then every 8 weeks, then every other month
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Describe features of biologics (1)
Last line (very expensive). MOA - disrupts inflammatory cascade. Ustekinumab – reduces cytokines, blocks IL-12, IL-23 and decreases activation of T-cells. Guselkumab, risankizumab and tildrakizumab – block IL-23 and decrease T- cell activation
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Describe features of biologics (2)
Secukinumab and ixekizumab– block IL-17 and decrease T-cell activation. Etanercept, adalimumab, infliximab, certolizumab – inhibit TNF alpha
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Describe features of biologics (3)
NICE recommendations - severe disease only, not responded to standard treatments (cyclosporin, MTX, PUVA or can't tolerate/CI), if not responded adequately, stop
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Describe features of biologics (4)
If patient doesn't meet NICE criteria e.g. requires dose more frequently - individual funding required
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Describe features of biologics (5)
Last line, MOA (inhibition of IL, TNFa), pregnant women usually use biologics (skip treatment with MTX/ciclosporin due to being teratogenic), low threshold for stopping. 6 week interval between injections
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What are the general principles for eczema and dermatitis treatment?
Identify/avoid allergen/irritant. Moisturise skin/prevent further drying. Reduce inflammation. Dry up weeping/prevent crusting. Treat secondary infection. Reduce itching
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Outline the treatment pathway for eczema/dermatitis (1)
Topical corticosteroids -> immunomodulation e.g. topical tacrolimus -> immunosuppressants (e.g. MTX, cyclosporin) -> biologics (e.g. dupilumab). + control pruitis (e.g. antihistamines) and control infection (e.g. antibiotics).
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Outline the treatment pathway for eczema/dermatitis (2)
Can always be on medicines to control pruitis or infection
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Describe features of topical tacrolimus/pimecrolimus
Immunosuppressants. Considered if topical corticosteroid treatment has failed and there is a risk of skin atrophy from further use. S/E - skin burning and pruitis. Started only on advice of specialist
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Describe features of dry lotions (1)
Prevents weeping. Potassium permanganate soaks. 1/10,000 solution (0.01%) - 1 tablet dissolved in 4 L. Cleansing/deodorising discharging eczematous reactions/wounds. Irritant to mucus membrane. Stains skin/clothing. Not for oral administration.
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Describe features of dry lotions (2)
Dries out the skin, cleans wounds, only used for weeping eczema, doesn’t further dry out skin
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Describe features of antihistamines (1)
Sedating histamines (e.g. promethazine, hydroxyzine, chlorphenamine), effective, unclear if they reduce itch or if itch is reduced because of drowsiness, used at night
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Describe features of antihistamines (2)
Non-sedating antihistamines (e.g. cetirizine, loratidine), much less effective, daytime use. Itch frequently causes insomnia. Keep children's nails short, wear mittens
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Describe features of antibiotics
Used to treat secondary infections with S. aureus. Flucloxacillin (QDS on an empty stomach)/erythromycin to treat S. aureus
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What are the options when treatment has failed?
Narrow band UVB or PUVA. Immunosuppressants e.g. cyclosporin. PO steroids (prednisolone, use short term), Alitretinoin – oral retinoid for chronic hand dermatitis 12 – 24 week courses, Dupilumab
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Describe features of acne treatment (1)
Mild/moderate non-inflammatory acne (topical retinoid, topical benzoyl peroxide or azelaic acid if not tolerated)
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Describe features of acne treatment (2)
Mild/moderate inflammatory acne (topical benzoyl peroxide, topical antibiotic if ineffective/not tolerated, +/- topical retinoid or PO tetracycline, oxytetracycline or doxycycline if topical therapy fails/high potential for scarring/back affected
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Describe features of acne treatment (3)
+/- topical retinoid. Severe acne (PO tetracycline or doxycycline, +/- topical retinoid, minocycline if 1st line antibiotic fails, PO isotretinoin)
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Describe features of acne treatment (4)
Topical retinoids (redness/peeling initially, use every 3/7, photosensitivity, teratogenic). Benzoyl peroxide (redness/peeling initially - gradually increase concentration and frequency of application, dryness, bleaching)
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Describe features of acne treatment (5)
Topical antibiotics (tetracycline can stain skin and clothing yellow). PO isotretinoin - significant adverse effects - dry skin/mucous membranes, myalgia, arthralgia, arthritis, headaches, malaise, depression
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Describe features of acne treatment (6)
Pregnancy prevention programme - teratogenic, female patients need to be on two forms of contraception
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