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Dermatologic Therapeutics 2015 Lecture Notes Teresa O’Sullivan, PharmD, BCPS Learning Goal Attainment of a basic level of comfort with the choice of agent, vehicle/route, directions, and duration of therapy for common skin diseases. Learning objectives At the end of this lecture, you should be able to: Select an appropriate agent for dermatology lesions you diagnose. Assess patient information to determine likelihood of a drug allergy label being correct. General Information Module 1 (online) General Information Fun facts about skin The single largest organ in the body (17% of body weight). The top layer of the skin is the epidermis. Keratinocytes originate in the bottom layer of epidermis and migrate upward, dying near the top layer and forming a semi-permeable keratin layer that is sloughed off. Cycle (differentiation, migration, death, sloughing) takes ~26 days (3-4 days with psoriasis). The dermal layer is the thickest part of the skin. Capillary network supplies nutrients for keratinocyte growth, generally regulates temperature, and introduces topically applied drugs into the general circulation. Sweat glands, sebaceous glands, and hair follicles protect epidermis and facilitate temperature control. Nerves enable touch, itch, and pain sensations. Lymphocytes and macrophages combat entry of pathogens. The dermis is also a water storage organ. The subcutaneous layer serves as a fat storage area, providing cushioning and facilitating temperature control. Choosing vehicles Baths. Good for widespread eruptions: chicken pox, lichen planus, pityriasis rosea, viral or drug-induced itchy maculopapular rashes, crusting eczemas. For itchiness: one packet of colloidal oatmeal (regular oatmeal will not work) or two cups of cornstarch to a tub of lukewarm water q2-4hours prn. For dry skin: there is a large variety of bath oils with main ingredient usually mineral oil. Generic fine; watch additives if sensitive skin. Main concern with all bath products: slippery tub (hazard for falling), skin maceration (loss of protective keratin layer) with prolonged soaking. Wet dressings. Good for acutely-inflamed, oozing lesions, erosions, and ulcers. These cause vasoconstriction by evaporative cooling, promoting cleaning and drainage, and decreasing itching. 15-30minute soaks 3-6x/day. Saline or Burow’s solution the standards. Burow’s solution is OTC with directions for use printed on package. Normal saline irrigation is legend drug so patient will need prescription or can make at home by mixing 1/4 tsp table salt in 2/3 cup of water. Witch hazel is used for the same purpose on hemorrhoids. Solutions/gels. Drug dissolved is either a water or alcohol base. Best for very hairy areas, such as the scalp, since solutions and gels are not oily and do not leave a residue. Sprays. Only useful if mechanical contact with skin causes intolerable pain for the patient. Otherwise, sprays tend to be the most expensive of the dosage forms. Lotions. Suspensions of powder in a water or alcohol base. Good for slightly oozy lesions or widespread lesion areas (e.g., tinea versicolor). Generally not preferred for dry, flaky, calloused, or hairy areas. Creams. Soft emulsion of drug in a water base. Medicated creams should be used sparingly; their soft texture means that once rubbed in well they will “vanish.” Best for lesions that are not oozy. Emollient creams will be thicker and waxier than medicated creams. Ointments. Emulsion of drug in an oleaginous (oil) base. Best for dry, scaly, brittle, or thickened skin. Since these are stiffer than creams, spreading is more controlled and thus about 5-10% less ointment is needed for any given area. Ointments also block evaporation, increasing drug delivery (compared to cream or lotion) to the dermis. A paste is a very thick ointment so the same rules apply. Powders. Are drying and cooling, but the most important function is the ability of the particles to slip off each other, decreasing friction in areas where rubbing occurs. Good for athlete’s foot, jock itch, diaper rash, pressure/friction sores. DERM-1 Summary of vehicle choice Widespread itchy rash or dry skin bath q4-6h Wet, oozy lesion or ulcer wet dressing x 15-30 minutes q4-8h Red lesion that is not dry but has little to no oozing cream Red, dry, excoriated lesion ointment Itchy lesion in hairy area gel or solution Itchy lesion in area where skin is rubbing against skin powder Lesion too painful or itchy to touch spray Choosing amounts In general, BID dosing is fine for most topical agents (exceptions noted in text, as with baths and wet dressings above). Therefore, you will need: area size amt for each application amt to prescribe for 7 days small lesion or collective lesion 1g cream or ointment 15g cream or ointment group no more than 2” x 2” 2ml lotion/solution 30ml lotion/solution many small lesions: collective size > 2g cream or ointment 30g cream or ointment 2” x 2” 3ml lotion/solution 60ml lotion/solution area equal to one forearm 3g cream or ointment 45g cream or ointment 4ml lotion/solution 90ml lotion/solution area equal to front or back of trunk 4g cream or ointment 60g cream or ointment 5ml lotion/solution 120ml lotion/solution whole body 45g cream or ointment 21oz cream or ointment 60ml lotion/solution 750ml lotion/solution Most creams and ointments come in 15g or 20g, 30g, and 60g tubes; many creams come in 45g tubes. Most lotions come in 30ml or 60ml bottles. Tip: You may not know the available sizes of tubes for many products. Some pharmacists feel comfortable choosing the closest available size, but some pharmacists do not and will interrupt you with a (unnecessary) phone call. Options to avoid this: Note on the prescription the desired amount and then in parentheses write “(or closest larger available size)” Write “amount per pharmacy” if your interactions with the pharmacist likely to dispense the medication make you feel comfortable that the pharmacist can determine a reasonable amount. Application area and systemic absorption Studies have examined mainly absorption of topical corticosteroids ≤1% absorption: soles, palms, tops of forearms 2-15% absorption: scalp, face, legs, undersides of forearms >20% absorption: genitalia, axilla Many other factors will affect rate and extent of systemic absorption including presence of inflammation or desquamation (enhance absorption), use of occlusion (enhances absorption), type of vehicle (ointment enhances absorption versus cream), and whether the drug is in salt or ionized form (e.g., ionized drug generally poorly absorbed) It’s all in a name... Reasons to use trade name: Easier to remember and (usually) to pronounce. The name most likely to be used by patients (and many health care professionals). Reasons to use generic name: The name of the drug that will be on the prescription vial, any time a generic is dispensed. The generic name ending can often provide a clue to the class of the drug (e.g., “pril” for ACE inhibitors, “olol” for betablockers) so easier to identify a drug’s probable use and effects. Trade names do not provide such a clue and thus all trade names need to be individually memorized. Every time trade name is used, it’s free advertising for the company. DERM-2 Fact Sheet: Multiple-use Agents Module 2 (online) Protectants/keratotic agents Used for dry skin (xerosis), otitis externa, diaper dermatitis prophylaxis, acne, corns Mechanism: Various; many will slow fluid loss from skin, increasing hydration of area; keratolytics decrease skin thickness Effect: Immediate relief for dry skin with emollients, improvement over days to weeks for acne and corns/calluses with keratolytic agents; the keratolytic and cauterizing agents for warts will be covered in the antiviral section Agents: product comments Emollients for dry skin: Dry skin is often an inherited trait, particularly in Read ingredient list for product. Ingredient 1 will atopic families; it typically worsens in winter, always be water. Ingredient 2 should be mineral oil, a when humidity is low fat (e.g., cetyl alcohol), a wax (e.g., cetyl palmitate, Gloves are the most important investment for lanolin), or oil (e.g., cocoa butter, shea butter). Ureaperson with dry skin, especially if that person containing products more effective than non-urea routinely washes dishes or uses cleansers containing, but more expensive. Use lubricants daily; the best time to apply is Avoid product with glycerin as ingredient #2. after showering—pat skin dry and apply Baby oil just out of shower helpful for dry extremities. Emollients for diaper dermatitis prophylaxis: Zinc-oxide based products will discharge heavy Options: zinc oxide and non-zinc oxide products. metal into wastewater or landfill so non-zinc Apply after each diaper change. Use single application oxide-based product friendlier for the of hydrocortisone 1% cream if skin very inflamed. environment. Keratolytics for acne: For cystic-type acne only Tretinoin (Retin A), tazarotene (Tazorac), adapalene ADEs of topical retinoid products: local (Differin); apply once daily at bedtime irritation, price, potential for teratogenicity Isotretinoin (Accutane®) only for severe cases (consent Isotretinoin available in 10mg, 20mg, 40mg form + pregnancy test); 0.25mg/kg BID to start, capsules. Bone loss, mucous membranes increase to 0.5mg/kg at one month if patient not irritation, hypertriglyceridemia are worries. responding; treatment duration: 15-20 weeks; can do Suicide risk?? Causality not established. second course of therapy after ≥ 2 months off therapy Keratolytics for corns, calluses: Soak foot in warm water for 5 minutes before Salicyclic acid 40% in plaster cut to size of thickened application. area; put in place with waterproof tape; remove at 48 hours; max 5 applications in 2-week period . Drying agents for otitis externa: Swimmer’s ear symptoms include itching, Swimmer’s ear: options include commercial OTC watery discharge, mild pain, and muffled products (e.g., Auro-Dri) and compounded Burowshearing. glycerin solution. Otitis externa infection symptoms include pain Itching with no redness or pain: try hydrocortisone and visualization of a red and tender ear canal; cream on a cotton tip applicator, but only in ear canal need to cover Pseudomonas (11% of people are entry. colonized with this in outer ear canal) plus Staph so need agent to cover both. Options are double If otitis externa infection: triple antibiotic + HC otic or triple antibiotic (product will include HC 1%) suspension 3-4 drops to fill ear canal, put in cotton to or otic quinolone (ciprofloxacin, ofloxacin: $$$) hold solution x 10 mins, then drain ear, TID x 5 days. Antipruritics Used for topical relief of itching Mechanism: block histamine receptors in skin mast cells or block fast sodium channels in “itch” nerves. Effect: onset 45 min – 1 hr after application with peak at 1-2 hours; re-emergence of itching at 4-8 hours after application. Agents: Topical: combo product containing diphenhydramine 1-2%; prescription-only product is doxepin 5% cream (Zonalon) which comes in a 30g tube. Oral: q4-6h: diphenhydramine 25mg po prn itching; q12h dosing: fexofenadine (Allegra) 60mg po; q24h dosing: cetirizine (Zyrtec) 5-10mg, levocetirizine (Xyzal) 5mg, loratidine (Claritin) 10mg, desloratidine (Clarinex) 5mg Side effects sedation, dry mouth, constipation with diphenhydramine; mild sedation with other oral agents DERM-3 Topical pain relievers Used for relief of skin pain and itching, muscular pain, neurogenic pain, hemorrhoids Mechanism: slowing/blocking of nerve pain conduction (‘caines), depletion of substance P (capsicum), anti-inflammatory effect (salicylates), counterirritant (menthol, camphor) Effect: ‘caines will begin working within minutes, salicylates and counterirritants can take 1-2 hours before symptom relief apparent, capsaicin may take several days to reach peak effect Agents: topical: capsaicin, ‘caines, counterirritants (e.g., menthol); oral: NSAIDs, opiates Antiinflammatory agents – topical corticosteroids Used for all inflammatory and itchy eruptions, such as allergic contact dermatitis, atopic dermatitis (eczema), alopecia areata, hypertropic scars and keloids, lichen planus, psoriasis flares, seborrheic dermatitis, and varicose eczema. If lesions worsen, consider alternate diagnosis such as bacterial, fungal, or viral skin infection or sensitivity/allergy to corticosteroid agent. Mechanism: block intracellular production of interleukins and other inflammatory mediators such as TNF, stabilize the membranes of lysosomes within the cell and thus prevent the release of histamine, kinins, and proteoglycans. Effect: Itching can begin to decrease within 2-4 hours (stabilization of lysosomal membranes) and the immune response attenuation will be noticeable by around 6-8 hours after application. Full effect of decreased inflammation will not be seen for 18-24 hours after therapy is begun. It will be 3-7 days before decreased excoriation/hyperkeratosis becomes apparent. Agents. There are a lot of agents in a lot of strengths and a lot of vehicles—see appendix. In an effort to simplify this list, the following recommendations are made: product description comments low potency: use in all areas where skin is thinnest: face, groin, axillae hydrocortisone cream 0.5%, use in all lesions on any part of body for children (0.5% on face, groin, 1%, lotion 1% axillae) use for acute discrete mild lesions, prophylaxis for chronic lesions medium potency use for confluent, hyperkeratotic dermatitis lesions fluocinolone acetonide 0.01% use for discrete lesions on elbows, knees, palms, soles ointment, 0.025% cream, or once confluent lesions become discrete, or discrete lesions look benign, triamcinolone acetonide 0.1% switch back to hydrocortisone 1% cream, 0.025% ointment can use these with occlusive covering (plastic wrap) for very severe dermatitis or for psoriatic lesions if higher potency corticosteroid is too expensive for patient; occlusive dressing on 3-4 hours after application; stop occlusion if itching increases high potency good for psoriatic flares; allow several weeks between successive courses betamethasone diproprionate of therapy to minimize tolerance development 0.05% cream, ointment, or use for max of 2 weeks before switching to lower potency agents lotion monitor for signs of HPA axis suppression if large area being covered; if these appear, need to taper agent All of these products are available generically and are thus the least expensive options for prescribing. In general, avoid combination steroid–antiinfective products. They are expensive and not usually necessary Brand vs. generic. There is a lot of variability in activity of generic formulations. Side effects of topical corticosteroids nearly non-existent with low-potency agents such as hydrocortisone). Adrenal axis suppression, dermal atrophy and striae, and adrenal hyperglycemia can occur when agents are high potency (or moderate potency applied to a thinned-skin area) and used for more than 2 weeks. Antiinflammatory agents – topical calcineurin inhibitors product description comments topical tacrolimus (Protopic) inhibit Th1 and Th2 cytokine production 0.03% (kids) or 0.1% (adults) very effective agents; not atrophic like corticosteroids ointment BID expensive; use for people with non-responding atopic dermatitis or if pimecrolimus (Elidel) 1% patients intolerant to steroids BID Side effects are burning/pruritis at application site which usually resolves within a week after starting. Some but not all studies have shown an increased incidence of upper respiratory tract infections, folliculitis, or chicken pox, so patients should be counseled to report any viral or dermal infections; minimize sunlight exposure as topically immunosuppressed patients at theoretically higher risk of developing skin cancer. DERM-4 Fact Sheet: Dermatitis and Similar Use Agents Epidemiology Prevalence 10-20% children, 1-3% adults Prevalence higher in industrial areas, lower in agricultural areas Etiology Often family history of atopy; 70-80% of patients have extrinsic IgE-mediated sensitization (usually childhood-onset); 20-30% have intrinsic non-IgE-mediated sensitization (usually adult-onset) Th1 and Th2 cell mutations cause dominance of Th2 functions and a shift from production of IgM to IgE Previously it was thought that defects in immune response caused the characteristic inflammatory skin lesions. More recently, the focus has shifted to primary dysfunction of filaggrin and filaggrin-like substances, proteins produced by keratinocytes that bind keratin, forming the fibrous matrix of the epidermis. Most individuals with eczema display nonsense mutations in the gene coding for filaggrin and so produce an ineffective or less-effective stratum corneum. The defect in the skin’s normal barrier function allows better allergen penetration, activating dendritic cells, and promoting inflammation. So it appears that the characteristic inflammatory skin lesions of eczema are secondary to a defective skin formation, rather than a defective immune response. Features The family of diseases called dermatitis generally includes Eczema/atopic dermatitis: An inflammatory skin condition characterized by dry skin, erythematous papular (red and raised) lesions in the acute form, and keratinization (thick or thin), lichenification and/or scales (chronic, non-acute form) in the chronic form. Also called atopic dermatitis. Infant dermatitis/eczema: lesions usually papular and in clusters ranging in size from small to large, and is most often seen on the face and crawling surfaces. By age of 2, lesions will begin to look more like adult lesions and will be commonly seen in the trunk, extremities, and sub-facial areas. Contact dermatitis: papular erythematous lesions, initially; occur at point of contact with allergen. Nummular/discoid eczema: small disc-shaped eczema lesions usually occurring on the lower extremities; often occurs in winter; herald lesion frequently near area of recent leg trauma; can be hard to get under control. Seborrheic dermatitis: mild seborrhea produces dandruff while moderate to severe lesions characterized by waxy secretions; occurs primarily in the face (eyebrows, lashes, facial hair) and scalp, but also seen in hairy areas of the back, chest, extremities, and groin. The lipophilic Malassezia genus of fungus may play a role. HIV+ patients seem to be more susceptible to this kind of dermatitis. +/ Perioral dermatitis: small papular lesions clustering about but not immediately adjacent to the mouth; sometimes extending onto the area of the cheeks alongside the nose and below the eyes Varicose, asteatotic, or stasis dermatitis: lesions on one or both lower extremities occurring as a consequence of impaired oxygen delivery. Usually due to arterial atherosclerosis or impaired venous drainage due to venous valve failure. Very different in appearance from other kinds of dermatitis, with the exception of dry, roughened skin. Triggers Food, aerogens (house dust mites, pollens, animal dander, mold); auto-allergens; Staph aureus ( #s in skin lesions; cause or effect?); cold or dry weather (many forms of dermatitis worsen in winter) Chemicals will exacerbate dryness, excoriation, lichenification Use of corticosteroid creams on face associated with perioral dermatitis Resources National Eczema Association: http://nationaleczema.org/ American College of Allergy, Asthma, and Immunology: http://acaai.org/ Staging Mild disease: a few small lesions Moderate disease: multiple small clusters of lesions in several locations Severe exacerbation: extensive clusters of lesions in more than one body area Severe cases with suboptimal response to therapy, patient needs referral to dermatologist. Consider: for Staph infection overlaying eczematous lesions and treat with either topical mupirocin or systemic Staph aureus agent like cephalexin or dicloxacillin; adding phototherapy (PUVA) helps some patients DERM-5 systemic corticosteroids, interferon-, cyclosporin, mycophenoloate, methotrexate, or azathioprine can all help with resistant cases, but have adverse effects needing careful monitoring Treatments Avoidance of identified triggers, where possible. Antihistamines for acute pruritis; non-sedating during day (although less effective at relieving itch than diphenhydramine), diphenhydramine at night when itching often worsens Emollients for all forms of eczema or dermatitis condition Infant dermatitis Mild atopic dermatitis Moderate atopic dermatitis Severe atopic dermatitis Refractory atopic dermatitis Numular/discoid dermatitis Contact dermatitis Seborrheic dermatitis Stasis dermatitis Perioral dermatitis therapy description HC 0.5% or 1% applied once or once daily x a few days will often be enough to get recession of lesion HC 1% cream apply BID until lesion gone; use emollient on arms and legs after every shower. Fluocinolone acetonide 0.01% ointment applied BID prn to reduce size and number of acute lesions until at mild stage or completely disappear. If this therapy x 2 weeks has not brought lesions to mild stage, patient should consult provider for re-evaluation. Emollient use daily or after each showering if done every other day. Betamethasone diproprionate 0.05% ointment applied BID to the area for a maximum time of 2 weeks. At this time, patient should return for re-evaluation. Severe atopic dermatitis that is unresponsive to 2 weeks of therapy with highpotency agent. Refer to dermatologist. Fluocinolone acetonide 0.01% ointment applied BID. Emollient use daily. This needs to be done until lesions are nearly or totally resolved, which may take from 2-4 weeks. HC 1% cream can be adequate, however may need 1 week of medium potency steroid (fluocinolone actonide 0.01% ointment applied twice daily). Treatments will not cure the disease and will only ameliorate symptoms. Ketoconzole 2%, selenium sulfide 2.5%, ciclopirox 1%, and fluocinolone acetonide 0.01% shampoos are effective for scalp seborrhea and probably useful for treatment of hairy areas in the groin. Lesions on the face, trunk, and/or extremities can be treated with a low-potency topical corticosteroid or topical calcineurin inhibitor cream if mild disease and with moderate-potency corticosteroid or antifungal such as miconazole 2% (OTC) or econazole 1% (Rx) cream once or twice daily if moderate disease. Shaving (in men with facial hair) may help control this condition. Daily cleansing of the area with Cetaphil or similar mild cleanser. Daily to twice daily application of relatively occlusive emollient. Apply fluocinolone or triamcinolone cream or ointment once or twice daily to erythematous areas that are itchy, vesicular, or mildly oozy. Apply wet dressings (saline or Burow’s solution) to exudative lesions Withhold application of any topical steroid for at least a few weeks as this may exacerbate lesions. DERM-6 Fact sheet: Psoriasis Epidemiology prevalence 1-3%; Scandinavians have highest incidence; 1% incidence in North America most cases not severe and are treatable by primary care provider Etiology genetic; 40% of patients have a family history of disorder in first degree relative; gene or group of genes have been identified on the short arm of chromosome 6 appears to involve Th1 lymphocyte cytokines: interferon-, TNF-, and IL-2 Features psoriasis is a papulosquamous (papules and scale formation) eruption characterized by discrete (bordered) lesions and increased epidermal cell turnover cells on the top layer of the skin still have intact nuclei and function (so no protective keratin surface) plaque psoriasis: “classic” psoriasis; patients present with plaque-type lesions on scalp, extensor elbows and knees, and back; often appears in young adulthood guttate psoriasis: abrupt appearance of multiple small psoriatic lesions, usually < 1cm in diameter; typically occurs in child or young adult; are located primarily on the trunk; often associated with recent streptococcal infection pustular psoriasis: the most severe form (can be life-threatening): widespread erythema, scaling, sheets of superficial pustules with erosions; associated with malaise, fever, diarrhea inverse psoriasis: presentation involving intertriginous areas; called “inverse” because in opposite areas of classic plaque psoriasis; differential diagnosis of fungal or bacterial infection, atopic dermatitis (lack of pruritis can help delineate) nail psoriasis: nail involvement not usually isolated, but deserves mention because of troubling nature for patients; nails have a few to multiple tiny pits scattered over the nail plate, can also develop a localized colour change—tan-brown like new motor oil; severe nail involvement can resemble onychomycosis; psoriatic nails generally resistant to treatment psoriatic arthritis: seen in about 30% of psoriasis patients; arthritis can precede skin involvement in small fraction of cases; different clinical patterns exist, some which resemble RA and others which resemble OA increasing evidence that psoriasis is a multisystem inflammatory disorder. In addition to arthritis, people with psoriasis are at higher risk for obesity, metabolic syndrome, diabetes, cardiovascular disease, malignancies, and psychiatric disorders. Triggers HIV infection any other infection alcohol consumption several drugs: beta-blockers, lithium, antimalarial drugs, ACEIs, NSAIDs, terbinafine all have been documented to worsen flares in some individuals Treatment principles hydration and emollients beneficial to everyone; apply after bath; Eucerin, petrolatum, or any thick creams are most effective. topical corticosteroids for flares: medium potency steroid BID for moderate lesions on extensor surface fluocinonide 0.05% BID on scalp lesions hydrocortisone 1% BID for intertriginous lesions for thick plaques on extensor surfaces, betamethasone 0.05% BID with added plastic wrap occlusion may be needed acutely topical calcipotriene for maintenance once flare under control; anthralin or tazarotene or coal tar is second-line methotrexate for extensive involvement or if patient has psoriatic arthritis may also help with nail disease (give folic acid 1mg daily to prevent stomatits) phototherapy with UVB light can enhance drug therapy (psoralens + UVA light—PUVA—is second-line phototherapy) refer to dermatologist if these don’t work; severe pustular psoriasis: acitretin or etretinate, cyclosporine; etanercept (Enbrel®) and infliximab (Remicade®) useful; alefacept (Amevive®)—some patients may have sustained clinical response after cessation of therapy Antipsoriatics DERM-7 Used for chronic psoriatic lesions during and after topical steroid therapy has attenuated flare. Oral agents used for advanced disease refractory to topical steroids. Mechanism: most inhibit DNA synthesis or cell division in some way, in an effort to slow the rapidly-dividing and migrating keratinocytes. Effect: patients should notice an effect from these products within 1-2 days (since skin cell turnover is rapid, effect is seen more rapidly than with other skin conditions) product description calcipotriene (sometimes called calcipotriol) 0.005% vitamin D analog but less effect on bone compared cream or ointment (Dovonex); apply thin layer and rub to natural calcitriol; convenient, well-tolerated, in gently BID for up to 8 weeks expensive agent of choice for mild-moderate plaque psoriasis once flare is controlled with steroid coal tar 2-10%, available in a variety of creams, liquids, convenient, inexpensive, less irritating than steroids lotions, ointments, soaps and gels (T-gel, Z-tar, Pentrax, or anthralin Ionil T, T-derm) messy, smelly, stains clothes so second-line agent anthralin (called dithranol in Europe) 0.1%, 0.25%, good for scalp; apply to lesions BID. leave on for 20 0.5%, 1% ointment; 0.25%, 1% cream applied once minutes, then remove; use daily until clearing daily achieved, then twice weekly irritant, staining, probably less effective than calcipotriene, so second-line tazarotene (Tazorac) 0.05%, 0.1% gel; apply qHS to clinical trials have examined up to 12 months of psoriatic lesions continuous use; second-line after calcipotriene in non-reproductive individuals vitamin A analog, so usual warnings about teratogenicity, skin irritation; expensive methotrexate 2.5mg tablets; 10-20mg given as single the gold standard for patients with advanced joint dose, once weekly and skin disease; effective, prompt, relatively nontoxic liver biopsy at 2-4 months into therapy, once efficacy established, then again when cumulative dose reaches 1.5g and every 1g thereafter etretinate (Tegison) 10mg, 20mg capsules; 1 mg/kg qd expensive, teratogenic, lots of systemic adverse until response seen, then decrease to 0.5mg/kg/day effects; reserve for severe cases unresponsive to acitretin (Soriatane) 10mg, 25mg capsules; start at methotrexate; terminate therapy when lesions 25mg/day, increase as needed improved single daily dosing for both agents alefacept (Amevive) 15mg (0.5mL) IM or IV once suppresses CD2+ T-lymphocytes weekly both products will produce a ≥ 75% improvement in efalizumab 1 or 2 mg/kg SC once weekly about 20% of patients; relapse at therapy cessation occurs in > 50% of patients ADRs: lymphopenia (get baseline WBC and have patient report any infections), chills 6%, injection site reaction 2%, pharyngitis infliximab 5 mg/kg IV; repeat at 2 and 6 weeks block tumor-necrosis factor activity etanercept 25 or 50mg SC twice weekly x 3 months black box warning for increased risk of severe skin infections cyclosporine ≥ 5 mg/kg/day Both moieties have about 70% incidence of clearing PUVA or almost clear for moderate - severe plaque UV-B (narrow band) psoriasis. Side effects as noted above. Any topical product can cause stinging. DERM-8 Fact Sheet: Bacterial Skin Infections Suggested gram positive agents Topical Bacitracin 500 units/gm; spectrum: Strep, MSSA Mupirocin (Bactroban®, generic) 2% cream and ointment; spectrum: Strep, MRSA Azelaic acid 20% cream, 15% gel; spectrum: Staph epi, propionibacterium Oral Cephalexin (Keflex®, generic); spectrum: Strep, MSSA; adult dose 500mg po BID, TID, or QID depending on severity of infection Trimethoprim/sulfamethoxazole (Bactrim DS®, generic); spectrum: MRSA; adult dose 160/800 po q12h Clindamycin (generic); spectrum: Strep, many anaerobes; adult dose 300mg po TID Amoxicillin (generic); spectrum: Strep, some respiratory gram negative organisms, some anaerobes; 500mg po BID or TID Parenteral Cefazolin; spectrum: Strep, MSSA; adult dose 1 g IV q8h Nafcillin; spectrum: Strep, MSSA; adult dose 500mg IV q4h Suggested gram negative agents Topical Neomycin-polymyxin; spectrum: most gram-negative organisms Oral Ofloxacin (generic); spectrum: MSSA, most gram-negative pathogens; adult dose 400mg po q12h, ophthalmic solution 0.3% Parenteral Gentamicin; spectrum: most gram-negative organisms; dose by weight (1 mg/kg IV q8h common starting dose) Suggested broad spectrum agents Topical Chlorhexidine gluconate (Hibiclens®, generic, Peridex®) 2%, 4% liquid scrub solution, 0.12% mouthwash); spectrum: most gram positive organisms, including MRSA; many gram negative organisms, including Pseudomonas; facultative anaerobes, including mouth flora; and some fungi Oral Levofloxacin (Levaquin®, generic); Strep, MSSA, most gram negative pathogens; adult dose 500-750mg po daily Amoxicillin-clavulante (Augmentin®, generic); spectrum: Strep, MSSA, selected gram negative (including respiratory pathogens), anaerobes; adult dose extended release 1 g/62.5mg po q12h Doxycycline; spectrum: spotty gram positive (Strep pneumo and some MRSA) and gram negative (respiratory pathogens) coverage Parenteral Levofloxacin (Levaquin®, generic); Strep, MSSA, most gram negative pathogens; adult dose 500mg or 750mg IV daily Piperacillin-tazobactam (Zosyn®, generic); Strep, MSSA, most gram negative pathogens; adult dose 3.375mg IV q6-8 hours DERM-9 condition For superficial dermal infections, dermal infection prophylaxis: bacitracin ointment (OTC) polymixin/bacitracin/±neomycin ointment, cream; called triple antibiotic, but read ingredient list— some products have only bacitracin + polymixin mupirocin 2% cream, ointment (Bactroban®) gentamicin cream, ointment (Rx) silver sulfadiazine (Rx–Silvadene) 1/16 inch applied qd-BID until eschar formation well underway; 20g tube only for very small burn, 50g for burn < 2”x2”, 400g for larger burns, and 1kg tubs for big bad burns. For cellulitis, lymphadenitis: cellulitis (warm, tender, red area of the skin; Staph or Strep is usually the cause) that is larger than a fingerprint will need oral antibiotics (cephalexin 500mg po QID) and IV antibiotics if larger than a handprint (will need consult here but want pip-tazo or 2nd - 3rd gen ceph) lymphadenitis characterized by a red streak extending up a limb from a site of skin trauma; may be accompanied by fever, tachycardia, or headache; Strep pyogenes is the most common cause if symptoms appear within a day or two after a skin wound, but other bacterial and nonbacterial organisms can also cause For acne, rosacea: erythromycin 2% gel, topical solution; clindamycin 1% gel, solution, lotion benzoyl peroxide 2.5%, 5%, and 10% available generically in lotions, creams, gels, washes doxycycline 100mg po BID, erythromycin 500mg po BID for acne metronidazole 0.75% gel (MetroGel) metronidazole 250mg po BID initially, can increase to 500mg po BID if more control needed tea tree oil 5% applied daily found as effective as benzoyl peroxide in one study azelaic acid (Azelex, Finevin) 20% cream BID For bacterial conjunctivitis sodium sulfacetamide 10% solution will cover Staph effectively gentamicin 0.3% solution or ofloxacin 0.3% will cover gm (-) organisms and may effectively cover gm (+) organisms For bacterial vaginosis: metronidazole 500mg po BID x 7 days is cheapest; don’t use during 1st trimester Side effects as noted above. comments bacitracin spectrum: gm (+), so good for infection prophylaxis of cuts, scrapes and for mildly infected dermal insult; inexpensive polymixin, neomycin add gm (-) activity, so triple antibiotic cream is good for mild infection where mixed flora is likely e.g., diabetic foot mupirocin broad spectrum; hits MRSA so excellent for catheter-related localized redness, erythema; expensive; not related to other anti-MRSA agents so unlikely to acquire resistance gentamicin good for Strep, Staph, also gm (-) spectrum; no advantage over triple antibiotic preps one study found less scarring with triple antibiotic ointment on dermabrasion wound healing Can track effectiveness of cellulitis therapy by using Sharpie to mark edges of inflammed (red) area at start of therapy. If border recedes, antibiotic is working. If not border extends will need to reevaluate therapy Lymphadenitis often called “blood poisoning” by lay individuals who can interpret it as a lifethreatening disease and then propose treatment with home remedies. These remedies may appear to work both because the body’s immune system responds to the infection and warm compresses may enhance migration of immune system responders to the area (it’s all we had prior to antibiotics…) many benzoyl peroxide products available OTC; start use qOd for 1-2 weeks, then move to qd, then BID in order to decrease initial irritation oral agents for acne only if topical treatment failure or nonadherence due to ADR; low-dose OCs (for women) often effective for rosacea, start with topical metronidazole daily or BID – should see improvement within 3 weeks; go to oral if no improvement by 8 weeks www.rosacea.org is a good source of information for your patients doxycyline 40mg po qd only approved doxy product for rosacea 85% bacterial conjunctivitis caused by Staph, which is covered by sodium sulfacetamide 15% caused by gm (-) organism metronidazole vag gel is expensive clindamycin vag cream qHS x 7 days for 1 st trimester DERM-10 Fact Sheet: Acne and Rosacea Focus skin condition: acne (a.k.a. acne vulgaris) epidemiology 85-100% of adolescents, 8% of 25-34-year-olds, 3% of 35-44 year-olds; affects more than 17 million Americans accounts for over 10% of all patient encounters with primary care providers; 4.8 million visits/year has psychosocial effects; scars can be permanent etiology follicular hyperkeratination is earliest change; due to increased keratinocyte production and decreased desquamation androgens (e.g., dehydroepiandrosterone sulfate—DHEA-S) trigger increased sebum production; sebum overproduction more likely due to hyperresponsiveness of sebaceous gland than androgen overproduction hyperkeratination meets excess sebum product; result: plug in hair follicle Propionibacterium acnes (anaerobic diphtheroid which is part of normal skin flora) thrives in this oxygen-poor, lipidrich environment (these organisms dine on triglycerides); hyperproliferation of P. acnes and localized irritation from free fatty acids liberated from triglyceride hydrolysis causes localized inflammation inflammation attracts neutrophils which release chemokines, cytokines, lysosomal enzymes; these and keratin extrude into surrounding dermis, forming a papule or nodule the degree of follicular hyperkeratinization, sebum production, P. acnes growth, and inflammation will determine whether the lesion evolves into a whitehead (closed comedome), blackhead (open comedome), inflamed papule, or cyst/nodule features: the following is one type of classification type 1: mainly comedones with occasional small inflamed papule or pustule; no scarring (mild) type 2: comedomes and more numerous papules and pustules (mainly facial); mild scarring (moderate 1) type 3: numerous comedomes, papules, and pustules; spread to back, chest, shoulders; occasional cyst or nodule; moderate scarring (moderate 2) type 4: numerous large cysts on face, neck, upper trunk; severe scarring (severe) triggers cosmetics and warm humid environments can exacerbate foods do not influence production of sebum; do not recommend diet modification treatment mild to moderate acne: benzoyl peroxide 2.5% (if available) BID (use 5% otherwise), increase to 5% if suboptimal effect; most people won’t like the skin irritation (stinging, burning) from this product—apply 5% qOd x 1st two weeks, then qd, x 2 weeks, then BID if too irritating next step: topical erythromycin or clindamycin; other options at this point are tea tree oil and azelaic acid (no published evidence on topical dapsone) moderate to severe acne: oral antibiotics are often effective (doxycycline, erythromycin, TMP-SMX) and can be used concomitantly with benzoyl peroxide oral contraceptives (OCs) are often quite effective in women desiring contraception (no, Tri-Levlen is probably not significantly better for acne than any other OC, despite what the commercials imply) spironolactone 50mg or 100mg po daily; little evidence to support use for acne (Cochrane Database System Rev 2009 Apr 15;(2):CD000194) topical tretinoin is an option, although most people will notice skin irritation similar to that with benzoyl peroxide oral isotretinoin use should be reserved only for severe, cystic acne and needs two negative initial and then monthly pregnancy tests in women, informed consent documentation, and birth control for female patients and partners of male patients resources http://www.rosacea.org/ DERM-11 Focus skin condition: rosacea (a.k.a acne rosacea) epidemiology A chronic acneiform inflammatory facial skin disorder of middle-aged and older adults. It most commonly occurs in patients between the ages of 30 an 60 years. Relatively common among individuals with fair skin and light hair and eye color. Also common among those who experience frequent blushing or flushing. Many people experience flares starting in spring. etiology The cause of the vascular dilation is unknown. One theory is that hair follicle mites Demodex folliculorum and Demodex brevis play a role in the condition. This idea is supported by studies showing increased numbers of mites in the kin of patients with rosacea compared to unaffected controls. It is also supported by a small study of 63 patients from Turkey who had papulopustular rosacea. Patients were randomized to permethrin 5% cream, metronidazole 0.75% gel., or placebo, and were evaluated at days 15, 30, 45, and 60 of therapy. ITT analysis showed that permethrin was as effective as metronidazole for rosacea. Another postulation is that Helicobacter pylori plays a role, as a higher prevalence of infections has been reported in rosacea patients. For the most part, current literature does not support this hypothesis. It seems likely that genetics plays a role (direct? indirect?) in this condition. In one National Rosacea Society survey, 33% of respondents reported Irish heritage and 27% were of English descent. Rosacea also seems to be associated with Scandinavian, Scottish, Welsh and eastern European descent. features: Hallmark: vascular dilation of the central face, including the nose, cheeks, and forehead. Rosacea subtypes: Erythematotelangiectatic rosacea. Characterized by noticeable persistent flushing, sometimes producing a burning or stinging feeling. Can occur in response to triggers or without known stimuli. Patients with this subtype seem to have lower threshold for topically-applied irritants, which can produce skin roughness and scaling. Papulopustular (“classic”) rosacea. Characterized by episodic or persistent small papules that may or may not have pinpoint pustules, and (generally) sparing of periorbital skin. Telangiectases may be present. Skin not usually sensitive to irritants. Edema around papules present in more severe form. Phymatous rosacea. Characterized by noticeable skin thickening, nodule development over most of the face. Hyperplasia of the nose (rhinophyma; think W.C. Fields) seems to occur almost exclusively in males. Ocular rosacea. Characterized by blepharitis, conjunctivitis, and (less frequently) chalazions (meibomian gland cysts). Can occur in conjunction with or separately from (often preceding) the other subtypes. triggers hot or spicy foods (including hot beverages); alcohol ingestion (do not, however, assume that patients with rosacea drink alcohol excessively) emotional reactions, heavy exercise, some skin care products heat, sunlight (UV light), wind treatment facial erythema Avoiding triggers reduces flare-ups; mild cleanser (Cetaphil, Dove) and broad-spectrum sunscreen use important. Brimonodine tartrate (Mirvaso) 0.33% gel applied once daily to affected facial areas; a topical vasoconstrictor papules/pustules Initial therapy: topical antibiotics (metronidazole 1% cream, 0.75% cream, lotion, and gel; not yet available generically) BID for papular/pustular stage; one study found qd dosing also effective. Azelaic acid 20% cream BID also useful for treatment. Use for 4-6 weeks. Back-ups: sodium sulfacetamide 10% lotion; sulfur 5% cream or 10% lotion; clindamycin 1% solution, gel, or lotion; erythromycin 2% solution, all can be used BID and all are a little less effective than metronidazole or azelaic acid. Next step if initial therapy not providing adequate effect: oral antibiotics (tetracycline 250 or 500mg po BID, erythromycin 250mg BID, metronidazole 250mg BID, doxycycline 100mg po qd; TMP/SMX DS qd; taper oral abx within 3 mos after skin clears) or topical tretinoin cream (0.025%, 0.05%, 0.1%) 2-3x/week initially and increasing to qPM. dermatologist: surgical intervention; pulsed vascular laser therapy; isotretinoin (not as effective in rosacea) DERM-12 Fact Sheet: Antifungal agents Used for athlete’s foot, ringworm, jock itch, onychomycosis, fungal dermal rash, vaginal yeast infection, thrush Mechanism: alteration of fungal cell membrane permeability; some agents also interfere with fungal mitochondrial activity Effect: Symptom relief should start within 2-3 days after therapy begins, but clinical resolution may require 2-4 weeks of therapy Agents: product comments For athlete’s foot, ringworm, jock itch, fungal dermal clotrimazole and miconazole also come in rash: prescription for those patients whose insurance clotrimazole or miconazole topical creams are covers Rx but not OTC agents; if large area, use available OTC (Lotrimin AF, Micatin); apply to vaginal cream preparation - more spreadable plus affected area BID; 15g, 30g tubes larger tube (45g) tolnaftate (Tinactin) and undecylenic acid challenge: fungal infection versus diaper dermatitis (Desenex) are also reasonable agents to recommend (more common); fungal infections usually erosions; (both OTC) not sure? have mom apply 0.5% hydrocortisone at bedtime – if diaper dermatitis then rash will if therapeutic failure: fluconazole 100mg po qd attenuate overnight for tinea versicolor: selenium sulfide 2.5% shampoo tinea versicolor often not spotted until summer, applied undiluted to all involved areas at bedtime where it appears as hypopigmented, mildly scaly and washed off in morning for 3-4 days; oral spots on the chest, neck, and abdomen; most imidazole for 7 days will also work commonly diagnosed in young adults; often recurrent For vaginal yeast infection: a small amount of cream applied BID to vaginal miconazole or clotrimazole OTC vaginal cream for vestibule will help decrease itching patients who can pay – directions on package eating yogurt daily may also be effective for butaconazole (Femstat) or terconazole (Terazol 3) prevention of recurrent vaginal yeast infections and are Rx-only products and involve 3 days of vaginal is worth a try in patients taking birth control pills or administration; easiest prescription option is qd doxycline for acne (both increase risk of vaginal fluconazole 150mg po as single dose yeast infection) For thrush: nystatin and miconazole also available as troches nystatin suspension 5ml swish and swallow QID x which are to be dissolved in mouth; this dosage 14 days is gold standard form is more expensive than the genericallyavailable nystatin suspension fluconazole 100mg po qd if topical nystatin doesn’t work oral nystatin for baby + topical for mother is standard for breastfeeding infant thrush For onychomycosis: caution! triazoles (ketoconazole, fluconazole, terbinafine 250mg po qd x 12 weeks AOC, but itraconazole) are CYP 3A4 enzyme inhibitors; your expensive pharmacist will assist you in scanning for 3A4 substrates in the patient's other meds; terbinafine is itraconazole 200mg po qd x 12 weeks (ketoconazole a CYP 2D6 inhibitor, so look for concurrent opioid, 200mg po qd has also been used and may be beta-blocker, antidysrhythmic, or TCA therapy cheaper than itraconazole; griseofulvin ultramicrosize 330mg po BID less expensive but not as effective as newer agents Side effects are rare with topical agents; oral agents most commonly cause tummy upset; can see hepatotoxicity with oral agents, so get baseline LFTs if patient to be on > 1 month DERM-13 Fact Sheet: Antiviral agents Used for warts, cold sores, shingles, chicken pox, ocular viral infections Mechanism: inhibits viral thymidine kinase (‘clovirs) or viral mitosis (podophyllum & co.) Effect: onset of symptom relief should occur within 24-48 hours of initial administration Agents: product comments For warts: calluses can be mistaken for warts: keep this in cryotherapy in your office usual AOC mind; a callus will have skin lines on the surface whereas a wart will not OTC: salicylic acid lotions for plantar and common warts, cryotherapy in a can: dimethyl ether, propane cryotherapy with liquid nitrogen by you is the most products include Dr. Scholl's Freeze Away®, frequently-used treatment for warts; repeat visit for Wartner®; use single application cryotherapy reapplication often necessary; painful alternative home treatment: cut duct tape to the size “cryotherapy in a can” produces a reaction that of the wart and place over the top; leave in place for lowers temperature to around - 60°C (although one 6 days, remove, soak in water for 5-10 minutes, study measured temp of only -20°C). For debride with emery board; repeat process on day 7 comparison, cryotherapy with liquid nitrogen lowers and continue until wart gone; most warts will temperature to more than -100°C resolve within 28 days with this therapy skin irritation and damage to healthy surrounding patient can use at home podofilox (Condylox®) for tissue is the main ADR with any wart treatment genital warts applied BID x 3 days, withhold 4 days, (except duct tape) then repeat cycle until wart tissue gone; female will need help with administration For chicken pox or shingles: for chicken pox, probably more effective for pre acyclovir 800mg po CID (5x/day) x 7-10 days for school age child to be vaccinated prior to chicken adults; 20mg/kg po QID for kids under 90 pounds pox season (Jan-Mar) For ocular viral infections: viral eye infections often diagnosed by exclusion trifluridine (Viroptic®) one drop on cornea of i.e., antibacterial therapy doesn’t work affected eye q2h WA; continue for 7 days beyond therapeutic alternative: vidarabine (Vira-A), thin corneal ulcer re-epithelialization; max 21 days of strip of ointment to conjunctival sac 5x/day; chronic therapy. blurry vision For cold sores: wash hands after application to decrease interperson acyclovir or penciclovir ointment applied to transmission lesion(s) q2-3 hours while awake some patients swear by OTC products (e.g., Abreva®) ; they’re cheaper and it’s worth a try Side effects mostly noted above; oral acyclovir can cause tummy upset DERM-14 Fact Sheet: Antipediculocides Used for scabies, head lice, pinworms Mechanism: act on the critter’s nervous system to paralyze it, causing parasite suffocation Effect: lice and scabies absorb pediculocide right away; killing takes hours to days. pinworm killing takes longer (slower incubation) Agents: product comments For lice: eggs (nits) laid at hairline and take 10 days to hatch permethrin 1% (OTC - Nix) cream rinse (97-99% (eggs > 1mm from scalp are non-viable), the infant cure rate). Single application (left on the hair for 10 nymphs 7 days to mature, and adult lice live about minutes) is pediculocidal and 60-70% ovacidal, due 30 days. Female lice will lay 6-7 eggs daily. to residual persistence (up to 10 days after a single lice can move fairly quickly on dry hair, but application). A follow-up application at 7-10 days is movement slows when the hair is wet. Use only often recommended anyway. water to wet hair when doing lice checks. Start Spinosad 0.9% suspension an alternative to behind ears and include nape of neck. permethrin. More effective? More expensive. Rx conditioners coat hair and protect lice from only pediculocide penetration, so avoid use of Many cases of resistance are due to poor package conditioners during lice infestations. directions: review steps with your patients. diagnosis by combing is 4 times more reliable than Pediculocide shampoo should always go on dry diagnosis by observation. Wipe comb on white hair. tissue to better observe tan/brown lice. Combing is crucial! Mechanical removal of lice pediculocidal shampoo needs to go on dry hair. eggs should always accompany pediculocide Wait 10 minutes, then rinse. Begin combing treatment; only method of treatment for kids < 2 and immediately afterward. Wait 2-3 days after eggs (pediculocide penetrates egg shell poorly); use treatment before hair is next shampooed. fine metal comb from pet store if hair too thick for lice products don’t penetrate nit shells well, so plastic comb that comes with OTC product pediculocide needs to have residual activity of vacuum rooms; soak combs and brushes x 1 hour in several days for best effect; reapplication after 1 isopropyl alcohol; wash sheets, blankets, week also best. pillowcases, clothes in hot water. Tell your patients if lice are dead or moving slowly at 12-24 hours not to be overzealous about this. Lice don’t live after treatment, it is probably effective. long off a host; within about 12 hours, lack of food if resistance suspected: combing crucial; one group induces dehydration and non-viability, even if they of researchers recommend leaving permethrin on for are still able to move. longer period of time (several hours) if resistance Malathion (Ovide – Rx) and lindane (Kwell®) less seems to be occurring effective and more toxic than permethrin No mayonnaise, please. Messy and ineffective. For scabies: scabies mite rarely lives outside the human body for permethrin 5% cream (Rx – Elimite®, Acticin® more than 30 minutes; it is transmitted by both come in 60g tubes) has efficacy rate of 91%; prolonged, still skin-to-skin contact – holding hands apply from neck to toes and wash off after 8-14 is the most common way to become infested and hours; < 2% of dose absorbed so toxicity not a explains why mites are most often found on the problem hands and fingers backup: lindane (Rx – Kwell) has efficacy rate of the characteristic scabies rash is an allergic reaction 86%; same directions; crotamiton (Rx- Eurax) has to the mite, its eggs, or its feces; rash appears 10-30 60% efficacy rate days after infestation (time to build hypersensitivity response) same laundry information as for lice; no evidence scabies lives when off hosts For pinworms: best to treat everyone in the household at the same pyrantel 50mg/ml oral suspension (OTC) is AOC; time, since highly transmissable single dose of 11 mg/kg (5 mg/lb); can repeat wash hands well after bathroom and before eating, another dose in 2 weeks, if desired; efficacy 96% otherwise no unusual cleansing procedures needed DERM-15 Fact Sheet: Actinic Keratosis and Skin Cancer epidemiology actinic keratosis (AK) has prevalence rates ranging from 11-26%, depending upon which study you examine; prevalence rates are highest in Australia and New Zealand (sun exposure + heritage). About 1/1000 AK lesions develop into squamous cell carcinoma, annually. estimates are that 550,000 new skin cancers diagnosed each year, currently; about 75% (>400,000) are basal cell carcinoma (BCC), 20% (~100,000) squamous cell carcinoma (SCC) and 5% (25,000-55,000) are melanoma. Incidence is increasing among older adults and decreasing in younger adults. risk factors: sun exposure is the strongest risk factor for AK and all skin cancers. Cumulative exposure is biggest predictor, but exposure specifically in childhood or adolescence increases risk. Usual: fair skin, light hair and eye colour; Scandanavian, Celt descent. etiology and features: etiology features “classic” location prognosis AK sun-induced; develop only on sun-exposed skin small oval nodule with erythematous border sometimes will scab may appear as fissure in lip or like a cold sore, except the sore doesn’t heal backs of hands face lower lip ear scalp occasionally metastasize good prognosis if detected early grayish-brown, dicrete, raised, scaly lesions if scale removed, small superficial ulcer can develop often erythematous edge around scaly portion of lesion all sun-exposed areas cosmetically bothersome but conversion to SCC rare SCC sun-induced BCC sun-induced can also be arsenic and radiation therapyinduced small papule which spreads outwards, leaving central ulcer edges are raised and pearlcoloured once lesion ulcerates these often bleed and give patients a persistent scab that fails to heal face, particularly on nose and below eyes rarely metastasize slow growing good prognosis melanoma sun-influenced (not sun-induced) genetic component hormone influenced? solitary pigmented lesions looks like a mole, but often not round unlike mole, it will spread unlike mole, can ulcerate or bleed anywhere females have more commonly on legs males: more commonly on back can metastasize the deeper the lesion, the poorer the prognosis treatment Non-chemo treatment. surgical excision is treatment of choice for BCC, SCC, early (not thick) melanoma (cure rate > 90%); radiation therapy for BCC, SCC if pt not candidate for surgical tx AK: 5-FU, masoprocol, imiquimod, diclofenac superficial BCC, SCC: excision and/or topical 5-FU and topical imiquimod metastatic disease will require systemic chemotherapy (outlined on next page) and lymph node dissection DERM-16 Topical chemotherapy Used for: actinic keratosis and treatment of skin cancer Mechanism: as noted in chart below Effect: resolution of lesions; avoid sun with all agents; don’t occlude lesions—cover with light gauze dressing only Agents: product description 5-flurorouracil (5-FU; Efudex) applied qPM inhibits DNA synthesis 1% cream, 1%, 2% solution for actinic little systemic absorption keratosis stages: 1. early inflammation , erythema x several days 5% cream, 5% solution for superficial 2. inflammation increases in severity, burning, stingin, basal cell carcinoma vesiculation 3. disintegration with erosion, ulceration, necrosis (DC 5-FU at this time), pain, crusting, beginning of re-epithelialization 4. healing with residual erythema x 1-2 weeks; length of stages 2 and 3 will depend upon severity of lesions, but usually last several weeks masoprocol 10% cream (Actinex), massage into derived from the creosote bush area of actinic keratosis BID x 2-4 weeks a 5-lipoxygenase inhibitor, so IL production; also appears to inhibit DNA synthesis, possibly through free radical production; inhibits keratinocyte growth may stain clothing; wash hands after application up to 70% reduction in lesion number no data comparing effectiveness to 5-FU imiquimod 5% cream (Aldara), apply BID for an immunomodulator; MOA not precisely known actinic keratosis and superficial basal cell approved for treating genital and perianal warts carcinoma diclofenac 3% gel (Solaraze)apply to lesion areas diclofenac gel mechanism of action (MOA) is unknown BID x 60-90 days little systemic absorption Side effects: skin irritation (erythema, excoriation, erosion, contact dermatitis) and fungal infection most common ADRs with these agents Systemic chemotherapy Used for: metastatic disease Mechanism: cell cycle disruption Agents: cancer product SCC platin therapy ± bleomycin cetuximab BCC melanoma platin therapy ± bleomycin vismodegib first FDAapproved hedgehog inhibitor surgical excision can be curative if not metastatic for metastatic disease: high-dose IL-2 or IFN ipilimumab 3 mg/kg IV q3 wks vemurafenib 960mg po BID dacarbazine 1000 mg/m2 q2-4 wks comments SCC metastatic disease is rare case reports suggest that cetuximab has activity against SCC metastatic disease BCC metastatic disease is rare tolerance of high-dose IL-2 is low For malignant disease remissions are partial and shortlived, so the goal is to give the patient a few additional months of life. vemurafenib used in pts w/V600 BRAF mutation temozolamide not FDA-approved but has been used DERM-17 Fact Sheet: Drug Allergies Drug eruptions allergic drug rashes are usually bright red, very itchy, confluent, and show up within a couple of days of starting the drug viral exanthems tend to be more pink or brownish, discrete, and the patient will often have a history of an upper respiratory infection within a week preceding appearance of the rash amoxicillin non-allergic rashes show up later in therapy than allergic rashes (e.g., > day 3 of amoxicillin), are often not very itchy and may or may not be raised; the rash will fade over around 3 days whether or not amoxicillin is continued; the patient unlikely to experience rash upon amoxicillin readministration a maculopapular rash will not “turn into” an anaphylactic reaction if drug readministered a maculopapular rash that blisters and peels should be considered Stevens-Johnson syndrome and patient should be labeled “allergic” Important information to obtain from patient who claims allergy to drug (the most important information to get is in bold): name of drug reason patient was taking drug complete description of physical symptoms of reaction (DISCERN - Distribution, Itchiness, Shape, Colour, Elevation, Running together (confluency), Number). Conduct physical assessment if ADR currently in progress. timing of reaction with regard to administration of drug "How many days into therapy were you when this reaction occurred?" “What was the length of time between ingestion of the most recent dose of the drug and your detection of the reaction?” “How many times had you previously taken this drug?” (this is important - if the patient has received the suspected drug 2-3 times in the past and nothing happened, you should be less than enthusiastic about labeling the patient as allergic) amount of drug taken concomitant disease state(s) Be particularly interested in diagnosis of mononucleosis around the time of drug ingestion – reaction between penicillin-type drug and Epstein-Barr virus causes a rash ≈80% of the time; has also been reported with cephalexin) name of other drugs that patient took around the same time reaction occurred occurrence of same reaction when other medications in the same drug class administered any non-drug allergies that occur; family or personal history of asthma or other allergies Cross-sensitivity of drugs between penicillins: reasonable cross-sensitivity; consider skin-testing with expired pen G, ampicillin, cefazolin, saline control: skin tests have 70% sensitivity and 95% specificity; if positive skin test, avoid penicillins if skin test positive, supervised challenge with low oral dose penicillin if skin test negative between cephalosporins: reasonable cross-reactivity amongst first-gen cephs, but third gen cephs have been used with sequelae by pts with reported allergy to first-gen ceph between penicillins and cephalosporins: traditional number is 7-10% cross-reactivity. These numbers are based on two poorly-done “studies” published in the ‘70s. Bottom line: there may be cross-sensitivity between the penicillin-related drug and a cephalosporin with a similar side chain (think first-generation cephs), but cross-sensitivity approaches 0% if the side chains of the ceph are different. This only a worry with anaphylactic reactions. sulfonamide antibiotics and other sulfonamides (e.g., hydrochlorothiazide, glyburide, celecoxib): no good evidence of cross-sensitivity n-4 amino group thought to be responsible for maculopapular rashes in vitro evidence that 5-methyl-3-isoxazolyl ring causes anaphylactic reaction “All patients, regardless of allergy status, should be supervised when they take their first dose of any medication, particularly an antibiotic.” DERM-18 Corticosteroid Products Product Strength Vehicle Trade Name 0.05% ointment Diprolene 0.05% 0.05% 0.05% ointment, cream, gel, lotion ointment ointment, cream Temovate, generic Florone, Maxiflor Ultravate 0.1% 0.05% 0.1% 0.25% 0.05% 0.2% 0.05% 0.1% 0.5% ointment ointment, cream ointment ointment, cream cream, ointment cream ointment, cream, gel, lotion ointment, cream ointment, cream Cyclorcort Diprosone Valisone, generic Topicort, generic Psorcon, Florone, Maxiflor Synalar, generic Lidex, generic Halog Kenalog, Aristocort, generic 0.1% 0.05% 0.1% 0.1% 0.05% 0.025% 0.025,0.05% 0.05,0.005% 0.1% 0.2% 0.1% 0.025,0.1% cream, gel, lotion lotion cream cream cream ointment, cream ointment, cream, lotion, tape cream, ointment ointment, cream, solution ointment, cream ointment, cream, lotion ointment, cream, lotion Cyclorcort Diprosone Valisone, generic Cloderm Topicort, generic Synalar, generic Cordran, generic Cutivate Locoid Westcort, generic Elocon Kenalog, Aristocort, generic 0.05% 0.05% 0.1-0.4% 0.01% 0.5,1,2.5% ointment, cream cream spray, cream cream, solution, shampoo ointment, cream, lotion Aclovate Tridesilon, generic Decadron Synalar, generic generic; 0.5%, 1% OTC very high potency—do not use longer than 2 weeks augmented betamethasone diproprionate clobetasol proprionate diflorasone diacetate halobetasone proprionate high potency—switch to medium potency when exacerbation controlled amcinonide betamethasone diproprionate betamethasone valerate desoximetasone diflorasone diacetate fluocinolone acetonide fluocinonide halocinonide triamcinlone acetonide medium potency—for moderate exacerbations amcinonide betamethasone diproprionate betamethaseon valerate clocortolone pivalate desoximetasone fluocinolone acetonide fluradrenolide fluticasone proprionate hydrocortisone butyrate hydrocortisone valerate mometasone furoate triamcinolone acetonide low potency—for chronic use in adults and children and on thin skin alclometasone diproprionate desonide desametasone (and NaP salt) fluocinolone acetonide hydrocortisone (plain and acetate) DERM-19