Tracey C. Vlahovic, DPM FFPM RCPS (Glasg) Clinical Professor, Dept of Podiatric Medicine, Temple Univ School of Podiatric Medicine, Philadelphia, PA

Tracey C. Vlahovic, DPM FFPM RCPS (Glasg) Clinical Professor, Dept of Podiatric Medicine, Temple Univ School of Podiatric Medicine, Philadelphia, PA

None for this presentation Ortho Dermatologics, Bako

Stratum corneum forms the skin barrier Corneocytes filled with keratin Extracellular matrix - lipid enriched Protective wall Regulates homeostasis TEWL Prevents the entry of foreign particles and pathogens into the body Epidermis in Palm/Sole

Xerosis Hyperkeratosis Eczema/dermatitis Atopic dermatitis Lichen simplex chronicus Dyshidrotic eczema Wet to dry foot syndrome Psoriasis Lichen planus Contact dermatitis Stasis edema/dermatitis/ulcer Dermatophyte infection = Skin Barrier Dysfunction

Lies within choosing the proper topical and active ingredient (Wolverton 2001) The old rule in dermatology is If a lesion is dry, wet it; if a lesion is wet, make it dry BUT!!!! A vehicle can retard TEWL, increase flexibility of the skin, and stabilize the compound as well as drive it into the skin A vehicle can make or break a formulation especially if sub-optimal vehicle used

A Vehicle is the nonactive ingredient, but impacts how the patient tolerates the medicine An IDEAL Vehicle is odorless, non greasy, easy to apply, non irritating, inexpensive, stable, cosmetically elegant, and doesn t leave a residue Powder Gel Lotion Cream Foam Spray Tape Emulsion Solution Lacquer Topical Suspension

Ointment most potent Cream Emollient cream Gel Lotion most diluted Spray Tape Foam *Traditional thinking was that drugs had to be occlusive (ointment) in order to get the best penetration and efficacy *Newer vehicles have changed our mindset *Changing vehicles can affect efficacy

Steps of percutaneous absorption of a topical: A concentration gradient is initiated Active drug moves out of the vehicle and into the skin Active drug moves deeper into the skin and blood stream

By: Controlling the partition characteristic between skin and vehicle The vehicle itself may enter the skin and may affect diffusion The vehicle may cause occlusion and drive the medication s penetration The release of the drug from the vehicle to the skin may control the rate of delivery D Piacquadio and A Kligman, JAAD, 1998

SC E D SC E D H&E 10 µm Untreated 10 µm SC E D SC E D Vaseline 10 µm Dimethicone 10 µm SC E SC D E D Proderm 10 µm Proderm Ghadially R., abstract presented at 7th Annual Caribbean Dermatology Symposium, St Thomas, US Virgin Islands, 2008 10 µm

Pairing the correct vehicle/drug combination for the type of skin targeted as well as these factors: Anatomy: interdigital vs hair baring skin vs large BSA vs plantar surface WE DEAL WITH A MULTITUDE OF SKIN TYPES ON THE LOWER EXTREMITY: plantar, dorsal, hair bearing, interdigital, nails Severity of skin disease (barrier disruption): Class 1 topical steroid vs the lower classes vs condition of the affected skin vs type of lesions present Wet lesion vs dry lesion Patient occupation, knowledge, and abillity

Palms and Soles need a topical with greater potency = ointment >>> solution, but not the most cosmetically elegant; also foam Leg dermatitis: spray for spread-ability or lotion Macerated interdigital = gel but what about a cream? Moccassin tinea = cream/emollient/emulsion/spray? Interdigital and Moccasin tinea = a combination of gel and cream or a topical suspension Inflamed skin = increased absorption, so can use a less potent vehicle (ie liquid or cream)

Male vs. female preferences Men may prefer gel, spray, or foam for their feet because of applying socks Women may prefer creams for moisturizing Age related preferences Younger patients may prefer gels, foams, sprays and perceive it as a newer concept than cream Which will lead to the best patient compliance??

What do you see?

If it is psoriasis, DO NOT USE oral steroids!! Thou shalt not use Medrol Dose Packs If acute eczema, use prednisone taper If you can t tell it s psoriasis, biopsy Don t use a combination of antifungal and corticosteroid! Thou shalt not use Lotrisone (clotrimazole and betamethasone) Tinea incognito

What is it: fungal, bacterial, inflammatory? Use the appropriate drug What stage is it: acute, sub-acute, chronic? Use the appropriate level of steroid Other medical factors? A reason to use topical over systemic? Require topical or systemic therapy? Chronic vs acute, severity If you don t know or treatment fails, biopsy!!!

The first line is a topical corticosteroid: Class I drugs should be used for 2 weeks to 1 month with NO refills, remember side effects! Titrate down Prepare for flares Add a barrier function cream Goal: use little to no topical steroid ultimately Class I steroids: Clobetasol (Clobex, Olux, Temovate) Betamethasone (Diprolene) Diflorasone (Psorcon) Halobetasol (Ultravate) Fluocinonide (Vanos)

Class 1 Super Potent: Clobex Lotion/Spray/Shampoo, 0.05% Cormax Cream/Solution, 0.05% Diprolene Ointment, gel, lotion, 0.05% Olux E Foam, 0.05% Olux Foam, 0.05% Temovate Cream/Ointment/Solution, 0.05% Clobetasol propionate Clobetasol propionate Betamethasone dipropionate Clobetasol propionate Clobetasol propionate Clobetasol propionate Class 2 Potent: Diprolene Cream AF, 0.05% Betamethasone dipropionate Class 3 Upper Mid-Strength: DFD-01 emollient Spray, 0.05%* Betamethasone dipropionate Stein Gold L et al, J Drugs Dermatol. 2016 Mar 1;15(3):334-42.

Tazarotene Gel 0.1% T + Diflorasone reduced atrophy by 37% Ammonium lactate (AL) AL + Clobetasol 35% decrease, 15% decrease occluded Calcipotriene ointment CP + BP Minimized atrophy in animal model Kaidbey K, Int J Dermatol. 2001 Jul;40(7):468-71. Lavker RM J Am Acad Dermatol. 1992 Apr;26(4):535-44. S. Kurdykowski et al, poster EADV, 2012

Ointment (8 weeks) 70% marked improvement Skin irritation 10-15% 11% clear Cream 50% marked improvement Skin irritation 10-15% 4% clear Solution 31% marked improvement Skin irritation 1-5% 14% clear Foam 41% clear/almost clear scalp Skin irritation 2% 14-27% clear/almost clear body J Drugs Dermatol. 2016 Aug 1;15(8):951-7

Size, shape, charge, keratin binding, hydrophobicity Nature of vehicle, ph, drug concentration Nail properties: extent of hydration and disease condition Kobayashi looked at 5-fluorouracil (hydrophilic) vs tolnaftate (lipophilic): tolnaftate had a low nail permeation because of its high molecular weight and low solubility in water Urea in an aqueous solvent system denatured keratin and allowed permeation of the drug (swells the nail plate, too) Chem Pharm Bull 46 (11) 1797-1802, 1998

Nail permeability decreases as the molecular weight of the drug increases BUT Nail hydration facilitates diffusion: reduces resistance of a slightly larger molecular weight, but shouldn t go above 350g/mol J Control Release. 2015 Feb 10;199:132-44.

Nail is a hydrogel; with permeation depending upon solubility in water or in a hydrated keratin matrix Solvents that promote diffusion through the skin, don t seem to work for the nail The Above azoles are insoluble in water remember you need something hydrophilic!! Adding urea to the mixture did not promote passage of the azoles through Drug Development and Industrial Pharmacy, Volume 24, Issue 7, January 1998, pages 685-690

Vehicles not only drive in the active ingredient, but can affect the skin barrier and efficacy of the medication Choosing the right vehicle involves: anatomy, pt preference, skin lesion, etc With the lower extremity, we are dealing with hair bearing, plantar, interdigital, nails which makes choosing the best topical more complicated It s about the steroid class, not the percentage! Moisturizers should be part of your regimen The nail is a hydrogel that is hydrophilic, so the same vehicles that are proven for the skin, may be ineffective for the nail

THANK YOU!!!! traceyv@temple.edu