Dermatology for Pharmacists Module 4 PC6 PDF

Overview of Dermatology for Pharmacists Cary Mobley  Objectives Describe important features of the anatomy and physiology of skin. Describe the effects of ultraviolet light on skin and the use of photoprotective measures, including sunscreens. Describe common dosage forms and vehicle...

Overview of Dermatology for Pharmacists Cary Mobley  Objectives Describe important features of the anatomy and physiology of skin. Describe the effects of ultraviolet light on skin and the use of photoprotective measures, including sunscreens. Describe common dosage forms and vehicle selection for topical therapy. Describe the pharmacology and therapeutics of topical corticosteroids. Describe the evaluation of dermatological conditions 2 Introduction Dermatological problems are among the most common complaints seen by pharmacists in the community setting There are numerous skin conditions that a pharmacist is likely to encounter. Among the most common are: – Psoriasis, seborrheic dermatitis, acne vulgaris, rosacea, atopic dermatitis, allergic disorders (including urticaria), skin cancer, skin infections (bacterial, fungal, and viral), wound care, pigmentation disorders 3 Review of Skin Structure and Function Review of Skin Structure and Function Human skin consists of three layers ((1) epidermis, (2) dermis, (3) subcutaneous fat) The skin also has several appendages nair follicle Sweat gland It is our largest organ, weighing about 3-4 kg in adults and varying in thickness throughout the ↳ important w choosing body topical meds Its main function is that of a barrier UV light – Microbiological, chemical, radiation, electrical, and mechanical It also serves important roles in temperature regulation and excretion /some drugs can exit through the skin) It is physiologically and biochemically very complex 5  The Epidermis * don' need to know s A continuously renewing stratified squamous epithelium – Keratinocytes comprise 80% of the cells imacrophages Others: Langerhans cells, melanocytes, Merkel cells fine > - touch sensation – It matures progressively from the viable cells in the stratum basale (SB) to the stratum spinosum (SS), stratum secretes feature of> cell above it granulosum (SG) to the dead cells in the stratum corneum (SC) > what's shede Thickness varies: About 0.06 mm (e.g., eyelids) to 0.1 mm thick over most of the body (though about 1.5 mm in palms and soles) thinner= - penetration ↑ADE ↳ 6 Stratum Corneum * shredding constantly ↳ losing cells ↳ would physically see if had dry skin The most important barrier component of the skin 15 to 25 layers of flattened, enlarged, UV barrier ↳ espwl Melanin overlapping, dead cells (corneocytes) ↑ brick + mortar Connected corneocytes interspersed with a I prevent water from leaving continuous sheets of intercellular lipids 2 N ~ things getting through preventative factor of leaving skin-water skin maintain Turnover via desquamation is about 2 -4 hydration helps keep it intact weeks ~ – Important for preventing colonization with pathogens 7  Stratum Corneum – Corneocytes The cytoplasm is filled with an insoluble protein complex composed of keratin, filaggrin, and their degradation products important↳ in atopic dermatitis Encapsulated within a cell envelope unlike bilayer in normal cell made of non-keratin proteins very unusual membrane Held together by corneodesmosomes, spot welds : Important for keeping which are degraded by proteases to ↳ want to ↑ those cells together - contributes facilitate orderly desquamation ↳ leads to turnover get rid of cells T to this – The proteases are co-extruded along with lipids, by the SG – Abnormal corneodesmosome proteolysis can lead to dry flaky skin L – Protease function is affected by water proteins tertiary amount and pH (SG) : structures ↳ amino acid can dependent on H2O + pH be ionized Barrier dysfunction in the skin allergy - Scientific Figure on ResearchGate. Available from: 8 https://www.researchgate.net/figure/The-structures-of-the-cornified-envelope-and-corneodesmosome-Involucrin-forms- the_fig3_321164595 [accessed 27 Oct, 2020]  Stratum Corneum – Intercellular Lipid Matrix Help hold the corneocytes together and are critical to limit permeation inside of substances and limit transepidermal water loss f rom out to inside - to out important to maintaining integrity r + hydration of SC A roughly equimolar combination of three lipid components thatj moisturizers that utilize these lipids originate from stratum granulosum cell secretions: – Ceramides – 13 different ceramides from enzymatically processed* ou glucosylceramides and sphingomyelin produced ↳ by so – Free fatty acids – several, long chain FFAs from enzymatically processed* phospholipids – Cholesterol – incorporated without enzymatic processing Exists as lamellae between the corneocytes blicheda I water * The processing enzymes are also secreted by the SG cells orderly fashion sheet-like nature to have 9 JAMA. 2013;310(22):2443-2450. doi:10.1001/jama.2013.282023  Stratum Corneum – Water Content Normal water content is about 15-20% Most water is within corneocytes aided by the presence of natural moisturizing factor (NMF) didstowata – A complex “soup” of small hygrosopic, water-soluble compounds key hold: onto water molecules ↳ polar functional groups & "When – Filaggrin is proteolyzed to produce a significant portion of " important be of ↳ it's protein a breakdown product NMF problems w/ filaggrin problemswI = hydration skin – Mostly amino acids, pyrrolidone carboxylic acid, lactate, sugars, urea, and others – Tightly bind a portion of SC water SC can take up significant water during bathing and under occlusion Water content can be affected by relative humidity ↓ humidity ↓ water content in skin = 10 Some Factors Affecting SC Water Content V radiation Low humidity ( - SC glycerol (glycerin) content is critical – A natural humectant Restoring and maintaining – Important for many skin properties including flexibility, hydration, and corneodesmosome degradation > - turnover SC hydration is an important Hot baths and showers ] leachesoutNMe therapeutic element for Detergents, harsh soaps, solvents Repeated water contact leaches NMF many skin conditions 11  Consequences of Low Water Content ① Desquamation defects – Proteases that degrade desmosomes and thus release corneocytes are inactive if the skin dries ] corneocytes remaining connected together be desmosomes have to be broken down – Corneocytes remain connected and pile up at the surface instead of detaching and invisibly shedding, leading to: roughness and scaling dull, white, or ashy appearance Other manifestations of low water content – cracking ↓ normal water content need plasticizer be water is – feeling of tightness (contract) ↳ something makes softer – T pruritis· neurons sense changes inskin + itching manifest – increased permeation of xenobiotics and potential allergens https://www.lybrate.com 12 Sebaceous Glands Found throughout the body except the palms and soles Associated with hair follicles and exist in certain hairless areas Produce sebum – Composition includes triglycerides, free fatty ~ I some have surfactant property acids, wax esters, squalene, and cholesterol – Combines with water to form a hydrolipid film L on skin that lubricates and waterproofs skin and hair – Helps to produce the acid mantle that contributes to the naturally low skin pH (acidic) affects protease +x Advances in Colloid and Interface Science 264 (2019) 11–27 13 The Acidic pH of the Skin Approximately pH 4.5-6.2 in the acid mantle and acidic upper SC layers more in acidic upper layers – The pH transitions to neutral pH in the lower layers of the SC Contributions to acidic pH of skin – Acid mantle on the skin surface - from sebaceous fatty acids and lactic acid in sweat – Other endogenous sources: Na/proton antiporter at SG/SC creates inner lamallae sheet interface, FAs from lipid processing, certain acids from filaggrin breakdown, melanin granules at SG/SC interface FA = fatty acids 14 The Importance of Acidic Skin pH creates lamallae > - Lipid processing enzymes – function best at an acidic pH important protective lipids for fx of intercellular – Permeability barrier integrity, TEWL = limiting transepidermal water Corneodesmosome-degrading enzymes (members of kallikrein family) – activity lessens 1 over pH(more acidic) at acidic pH lowers activity of proteases important be – Prevents desquamation from occurring too rapidly 2 Antimicrobial properties – e.g., an acidic pH is antibacterial for certain pathogenic bacteria (e.g., S. aureus) – An acidic pH is important for the normal skin microbiome 15  Commensal skin microbiota The skin is home to a variety of bacterial and fungal communities – residing on the surface, as well as in the appendages important a in a Different sites of the body have different microbe populations – The type of microbes depend on if the area is moist, dry, or sebaceous ( – For example, sebaceous sites are dominated by don'tnea Propionibacterium species, while Staphylococcus and Corynebacterium species are abundant in moist areas It significantly interacts with and affects our skin’s immune system – e.g., can affect production of cytokines and antimicrobial peptides Science 21 Nov 2014:Vol. 346, Issue 6212, pp. 954-959 16 Antimicrobial peptides More than 100 AMPs in and on the skin Produced by numerous cells in the skin – are also produced by commensal microbiota Among the best-known AMPs are cathelicidins, defensins, and psoriasin Functions: – Antimicrobial action – Immunomodulation – Wound healing Important factors in many skin conditions 17 Immune function of the skin Within the skin, there is a full complement of cells and cytokines important for immunity and inflammation Semin Immunopathology (2016) 38:3–10 18 Changes in Aged Skin Defect in lipid processing (>50 yo) and reduced lipid synthesis and secretion (>80 yo) – Greater potential for skin dehydration Reduced sebaceous secretions changes put ↓ waterproofing Reduced number of cell layers & thin skin Disorganization of collagen and elastin in the. 9 dermis – UV radiation (UVR) is a significant contributing factor – Contributes to flattening of the rete ridges ↑ skin tears important for maintaining epidermis on top of dermis Less effective barrier repair https://www.azurlis.com/pages/aging-skin 19 Melanocytes and melanin Melanocytes are located at the level of the SB Produce melanin, two types: – Eumelanin - a less soluble black-brown form Very important for protection from UV damage – Pheomelanin - a cysteine-rich red–yellow form The phenotype of fair skin, freckling, and carrot- red hair is associated with large amounts of pheomelanin and small amounts of eumelanin – The major producer of our skin color Other contributors: carotenoids, hemoglobin, connective tissue basal 20  Melanocytes and melanin Each melanocyte actively transfers its melanosomes Differences between individuals: – light- and dark-skinned individuals have similar numbers of melanocytes – melanosomes are larger, more numerous, and more pigmented in darker skin compared to lighter skin Melanin (eumelanin) – Accumulates within keratinocytes and melanocytes in the perinuclear area Forms supranuclear caps that are thought to shield DNA from UVR L – Scatters and absorbs UVR, thereby reducing penetration larger in of UVR through the epidermis & arker skin More effective at reducing UVB penetration than UVA Estimated natural SPF in darker skin of about 1.5-4 ↳ dendrite help connect w/ 21 peratinocyte  Fitzpatrick Skin Phototype Scale A scale originally develop to optimize UVR doses in phototherapy Commonly used to categorize acute and chronic effects of UVR, including skin cancer risk ↓ melanin Color of ↓ & - higher loweronscale ↑ on scale - - burning Burning and Tanning Reactions Susceptibility Protected or upon Exposure to Sun to Skin Cancer Unexposed Skin ↑ melanin I Pale white Always burns, never tans Very high ↓ susceptibility of skin cancer II White Always burns, then tans Very high III White Sometimes burns, can tan High without prior burn IV White to light Usually does not burn, tans easily Moderate brown; olive and deeply V Brown Rarely burns, tans easily and Low substantially VI Dark brown to Burns only with very high UVR Low black doses, tans readily and profusely Fitzpatrick's Dermatology, 9e > Cutaneous Photobiology. Sewon Kang, et al. Figure 17-3 22 Young AR, Claveau J, Rossi AB. J Am Acad Dermatol. 2017;76(3S1):S100-S109. UV Light and Its Effects UVC filtered by ozone lower wavelength light UVB (290-320nm) – absorbed mainly in the epidermis exposure to sun doesn't always Peak exposure between 10AM and 3PM throughout afternoon cause carcinogenesis since we have repair mechanism ↳ more efficient in darker skin Direct damage of keratinocyte DNA => carcinogenesis (major UVR-cause of keratinocyte carcinomas) nucleotide absorb vvB- > changes nature ↳ mutation - > cancer Damage to DNA and to other chromophores => inflammatory response of manifestation of DNA damage sunburn and delayed tanning days 2-3 later => Vitamin D3 synthesis Immunosuppression UVA (UVA2 320-340nm, UVA1 340-400nm) - penetrates into the dermis Ros generation is balanced continues Peak exposure between 8AM and 5PM throughout day w/ anti-oxidation ↳ more ROS bad = Indirectly damages DNA through the generation of ROS => carcinogenesis Contributes to photoaging of the skin by damaging the structural proteins of the dermis[(i.e. collagen and elastin)& degrade both ↳ wrinkle , thinning of skin spots/lentigines) melanocyte ↳ dark > - due to effect on Can cause hyperpigmentation, esp. FST III-VI patients (VL can also contribute to ↳ light visible this in these patients) Immunosuppression This Photo by Unknown Author is licensed under CC BY-ND  * don't need to knowAs new melanin don't need to know ↓ further harm caused by or light didn't talk about Bens, G. (2014). Sunscreens. In: Sunlight, Vitamin D and Skin Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0437-2_25 24 Sunscreens and Photoprotection Sunscreens and Photoprotection Everyone, regardless of skin phototype, but especially types I to III, are susceptible to UV radiation effects and can benefit from photoprotection Recommendations by American Academy of Dermatology: – Seek shade when outdoors – Wear sun-protective clothing – Use a water-resistant, broad-spectrum sunscreen with an SPF of at least 30 UV protection don't ↑ much after SPF 30 26 Sunscreens Protection – SPF Calculated by dividing the Minimum Erythema Dose (MED) on protected skin by the MED on unprotected skin – Based on an application of 2 milligrams of sunscreen per square centimeter (Note: Patients commonly underapply.) Want apply liberally to * – Focused on UVB All sunscreens with SPF values of 15 and above must satisfy broad spectrum requirements – Must protect against both UVB and UVA penetration – Broad spectrum test is based on applying sunscreen to glass plates and calculating the critical wavelength the wavelength below which 90% of the area under the absorbance curve resides (=370nm) Final Administrative Order OTC000006_M020-Sunscreen Drug Products for OTC Human Use (https://dps- admin.fda.gov/omuf/omuf/sites/omuf/files/primary-documents/2022-09/Final%20Administrative%20Order%20OTC000006_M020- 27 Sunscreen%20Drug%20Products%20for%20OTC%20Human%20Use.pdf )  Explaining SPF to Patients ↑ reduction in penetration of uV light SPF 15 SPF 30 SPF 50 SPF 100 93% 97% 98% 99% Marginal increase in % UV blocked beyond SPF 30 SPF indicates the amount of time skin is protected from sunburn* – Example: SPF 30: If sunburn on unprotected skin normally appears with 10 min exposure, then 300 minutes with SPF 30 protection assumingone reapplication – * As long as it is applied with the proper 7 amount and reapplied with proper frequency Bens, G. (2014). Sunscreens. In: Sunlight, Vitamin D and Skin Cancer. Springer, New (q2h) – more frequent with sweating/water York, NY. https://doi.org/10.1007/978-1-4939-0437-2_25 exposure  Organic (chemical) sunscreens Aromatic compounds that absorb UV radiation and convert it to a negligible amount of heat – Oil-soluble – formulated as emulsions or with solvents/cosolvents (e.g., ethanol) Must apply 15-30 min before UVR exposure Common examples: Avobenzone – The only chemical sunscreen approved for UVA protection – It is an unstable compound (photolabile) important absorption radiation conjugation for UV < results in release of heat When excited stabilizers such as vitamin E and C, and octocrylene (a weak UVB absorber) a nti-oxidants to limit its degradation bad ↳ sunscreen ↳ bodyguard for arobenzone Jancrease Common UVB-protective organic sunscreens [ many products will be free – Octinoxate – concerns about being toxic to coral reefs Of these – Oxybenzone – UVB and UVA absorber; the most common cause of photoallergic reaction among UV filters, some systemic absorption – Salicylates (Homosalate, Octisalate) - weak UVB absorbers, can reduce degradation of other organic sunscreens (primarily used in combination with other organic absorbers) 29 Inorganic (physical, mineral) sunscreens Zinc oxide (ZnO) and titanium dioxide (TiO2) Reflect, scatter, and absorb UVR Effective immediately upon application Degree of UVB/UVA protection depends on particle size – Formulations with large ZnO particle size that form an opaque film offers UVB/UVA/visible protection – Micronized zinc oxide (ZnO) micronized is Good UVA protection, less UVB protection than titanium dioxide more desirable for pt – Micronized titanium dioxide (TiO2) Good UVB protection, not effective against long-wave UVA radiation They tend to leave a whitish coat on the skin – Can be aesthetically unacceptable – Formulations with smaller particles are generally more aesthetically acceptable Jo 30 McSweeney PC. The safety of nanoparticles in sunscreens: An update for general practice. Aust Fam Physician. 2016;45(6):397-399. UVR Protection by Inorganic Sunscreens Zu0 ↳ not micronized Bens, G. (2014). Sunscreens. In: Sunlight, Vitamin D and Skin Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0437-2_25 31 Commercial Sunscreen Products Regulated by FDA as OTC products – Recent monograph posted Sept. 2021* – Specifies labelling requirements and maximum concentrations for each ingredient Water-resistant products – Tested for either 40 minutes or 80 minutes resistance Two or more sunscreen active ingredients are usually combined with each other in a single product * Final Administrative Order OTC000006_M020-Sunscreen Drug Products for OTC Human Use (https://dps- admin.fda.gov/omuf/omuf/sites/omuf/files/primary-documents/2022-09/Final%20Administrative%20Order%20OTC000006_M020- 32 Sunscreen%20Drug%20Products%20for%20OTC%20Human%20Use.pdf ) Sun Protection – OTC Monograph – Labeling Requirements for Uses and Warnings Uses: – All sunscreens: “helps prevent sunburn” – Products with a Broad Spectrum SPF value of 15 or higher: “If used as directed with other sun protection measures (see Directions), decreases the risk of skin cancer and early skin aging caused by the sun.” Warnings: – SPF 2 to - application regardless Water resistant NOT – immediately after towel drying or – at least every 2 hours". X For products that do not satisfy the water resistance test: “Reapply at least every 2 hours. Use a water resistant sunscreen if swimming or sweating". Other Information to prevent degradation 34 “Protect the product in this container from excessive heat and direct sun". of product Sunscreens and Photoprotection – Additional Recommendations Compensating for underapplication – Use an SPF > 30 (e.g., SPF 50) – If a thin film applied - Apply second thin film a few minutes after the first Lip sunscreen – Apply generously to cover the whole lip Infants – Avoid sunscreen use in infants younger than six months (AAD) – If adequate clothing and shade are not available, a minimal amount of sunscreen with at least 15 SPF can be applied to small areas, such as the infant's face and the back of the hands. NOT to entire body 35 Sunscreens and Photoprotection – Additional Recommendations Clothing – UV protective clothing (with UVP ratings) is preferred to regular clothing – Regular clothing - choose clothing with tighter weaves, increased fabric thickness, darker colors moisture, fabric stretching, and fabric degradation can decrease UV protection Sunglasses - Wear sunglasses providing UV absorption up to 400 nm Hats – Hats should be wide-brimmed (at least 7.5 cm) Do not use past the expiration date 36  Overview of Psoriasis, Acne Vulgaris, Rosacea, and General Skin Review Care of Topical Dosage Forms and Drug Delivery Review of Topical Dosage forms and Drug Delivery Dosage Form Properties Ointments greasyones Upon application to the skin, an Anhydrous ointment will form an adherent, aseline ~ Oleaginous continuous, greasy, water-repellant Anhydrous film. stays on skin very well Water-in-Oil Good occlusiveness block TEWL + maintain hydration Absorption This can have an emollient effect and This Photo by Unknown Author is licensed under CC BY-NC-ND ~ Base aquanor can enhance drug permeation expanding lipid lamella STAYS LONGER Prolonged contact with the skin Good protection This Photo by Unknown Author is licensed under CC BY-NC-ND 38  Review of Topical Dosage forms occlusive + greasy scale : and Drug Delivery oint> who cream > olw cream Dosage Form Properties interal external Creams Water-in-Oil Eucerin or cold cream droplet Water-in-oil Less occlusive and less greasy than anhydrous Oil-in-water ointments be presence of of water ↳vanishing most pp cream More occlusive and greasier than o/w creams l like internal external Oil-in-water easily (negative) Notbest choice i - will come off more semi an is A MORE PT Opaque, soft solids or thick liquids PREFERRED Upon application, the external phase evaporates This Photo by Unknown and the application shrinks to a thin film Author is licensed under CC BY-NC-ND Less occlusive than ointments and w/o creams They blend with water (including our own o il in water water lotion secretions) This Photo by Unknown TRICK to tell diff : if you stirred up oil-in-water it Author is licensed under CC , 39 into a lotion be water's external phase BY-NC-ND easily transforms · Eucerin would Not transform  Review of Topical Dosage forms and Drug Delivery Dosage Form Properties Lotions These are fluid emulsions or suspensions for Suspensions external application Oil-in-water Upon application, the continuous phase emulsions (which is aqueous) evaporates, leaving a thin depending on formulation uniform film of powder or liquid ↳ glycerin prevent complete evaporation ↳ can maintain drug in soln good in terms of spreading The fluidity allows fast application to broad areas and facilitates application to difficult ↳ like hairy areas areas This Photo by Unknown Author 40 is licensed under CC BY-ND  Review of Topical Dosage forms and Drug Delivery Dosage Properties Form I Gels Upon application, the solvent evaporates, GOOD FOR often leaving a porous matrix film for RELEASING DRUG drug to diffuse through Tend to be very good at releasing the ↳ biggest advantages drug Most are water-washable and greaseless Solvents: & ↳ propylene glycol or ethanol Can have a drying effect L Can enhance drug penetration due to disruption of lipid lamallae 41  Considerations for vehicle (dosage form) selection The type of dermatosis - want something to match – Wet or oozy lesions – creams or lotions water – Dry and scaly skin – ointments or oils will stick + around moisturizes – Inflamed – wet compress or soaks, followed by creams or ointments to decrease inflamm S– Cracks and sores – bland preparations, no Sc barrier is alcohol or acids breached ↳ can irritate 42 Considerations for vehicle · · cream inflamed : wet oozy lesions or · · ointment inflamed : dry + scaly skin lotion wet or · : oozy Skin folds lesions (dosage form) selection paims + soles palms hairy · · + soles areas skin folds · Skin site occlusive arug penetration ↑ – Palms and soles – ointment or cream thickest part of skin – Skin folds – cream or lotion (ointments are too skin touches & skin-naturally occlusive occlusive) & helps we spread drug of – Hairy areas – lotion, solution, gel, or foam ↑ drug release Patient preference + penetration – For example, even though an ointment may be more effective for some conditions, for patient compliance, a cream may be a better choice 43 Considerations for Topical Drug Delivery to Newborns If full term, skin barrier function nearly the same as an adult – But susceptibility to inflammatory conditions > in 1st yr SA is proportionally much greater than that of an adult ↑ SA ↳ vol ratio more drug in smaller volume If premature, skin barrier function can be significantly impaired 44  Review of Topical Drug Delivery Important Considerations When a Drug Is Applied to the Skin: - only onsurfacea red about penetration What are the intended pharmacological targets? where's the target? I drug ↳ down have to assure deep into epidermis ? ↳ can penetrate to What is the application site and coverage area? into dermis? ↳ Often the case that level thinness/thicknessvaries from diff sitesI ↳ larger areaa risk of systemic IVIS What are the absorption pathways of intact and diseased skin? ↳ less SC-through drug get more readily How does the chemistry of the drug affect the penetration? lipophilic : better chance of getting through vs hydrophilic. How does the vehicle and formulation affect ethanol/propylene glycol penetration enhancers penetration? : ↳ improve pene How much of the drug penetrates the skin? dangerous is that ? 45 Overview of Psoriasis, Acne Vulgaris, Rosacea, and General Skin Drug Care Focus – Topical Corticosteroids  Topical Corticosteroids - Background Endogenous glucocorticoids regulate immune and inflammatory reactions Their topical use began in the 1950s with hydrocortisone used for eczema They are among the most common topical 1 ofs of skin conditions have dermatological medications inflam as a component 47 Topical Corticosteroids - Pharmacology The clinical effects of TC are the result of their binding and activating glucocorticoid receptors (GCR) Steps: has to penetrate into cell to work – Diffusion into cytoplasm – Binding to GCR – creating a TC-GCR complex – Conformational change of complex – Activated complex binding to DNA – Gene regulation that produces anti- inflammatory effects and adverse effects 48  Topical Corticosteroids - Pharmacology Anti-inflammatory effects of TC – appear to affect all aspects of cutaneous inflammation Reduce activity or number of numerous cells 1 angerhan cells involved with inflammationPMNs monocytes Reduce the synthesis and secretion of cytokines Reduced phospholipase A2 ( arachidonic acid and associated inflammatory mediators) These anti-inflammatory effects are useful for inflammatory conditions such as atopic dermatitis, but can be harmful where the inflammatory response is useful Not used in fungal infection 49 Topical Corticosteroids - Pharmacology Antiproliferative effects of TC important for psoriasis – Reduced mitotic activity in the epidermis, causing flattening of the basal layer and thinning of the SC and SG – Reduced levels of enkephalins that ↓ turnover modulate epidermal differentiation and psoriasis has a turnover inflammation important for psoriasis quick turnover of cells be have Reduced fibroblast activity leadtoMajor AO – e.g., causing reduced collagen synthesis 50 Topical Corticosteroids – Potency The most common measure of TC potency is the Stoughton Vasoconstriction Assay – The test corticosteroid is applied to the volar (inside) surface of the forearm, followed by the application of an occlusive dressing for 16 hr. – The area is washed off, then vasoconstriction is measured as blanching 2 hr later whitening ↳ a of skin whitening ↑ potency V. P. Shah et al. (eds.), Topical Drug Bioavailability, Bioequivalence, and 51 Penetration, DOI 10.1007/978-1-4939-1289-6_9  Topical Corticosteroids – Potency Classes (see table) Super-high potency (group 1) High potency (group 2) High potency (group 3) Medium potency (group 4) Lower-mid potency (group 5) Low potency (group 6) Least potent (group 7) 52 Topical Corticosteroids – PK / PD Topical corticosteroid pharmacokinetics and pharmacodynamics depend on: – the physicochemical properties : lipophilicity – the vehicle : eg.. gels are good at releasing > - a potency IVI – the concentration of drug in the vehicle ↑ Conc ↑ will go thru-faster – the nature of skin where the drug is applied intact skin , thinness thickness = important for , pene 53 Topical Corticosteroid Potency – Structural Factors - The removal, replacement, or masking of hydroxyl groups can alter solubility, lipophilicity, percutaneous absorption, and glucocorticoid receptor binding Common modifications to increase ester lipophilic = potency include esterification (e.g., Hydrocortisone betamethasone-17-valerate), double- un bond in the 1 position (e.g., = triamcinolone acetonide) acetonide addition (e.g., triamcinolone Triamcinolone acetonide acetonide), halogenation (e.g., fluorination (e.g., fluocinolone acetonide), chlorination (e.g., clobetasol propionate) 54 Clobetasol propionate Topical Corticosteroid Potency – Effect of Vehicle Properties Based on a combination of properties including the occlusiveness of the vehicle, its ability to release the drug, and the presence of excipients that affect drug solubility or penetration through the skin mostly in get – Example: [Propylene glycol and ethanolJ affect the drug maintains in soln corticosteroid solubility 4 drug readily in molecular form - > absorbed = ↑ potency e.g.., Example: Betamethasone dipropionate ointment (augmented) ↳ be of propylene glycol Ointments - because of their occlusiveness, are generally more potent than creams or lotions of the same concentration Gels - because of the presence of cosolvents and because of their ability to release the drug, they tend to yield greater potency than creams or lotions 55 Topical Corticosteroid Potency– Effect of Concentration Follows Fick’s Law – The greater the concentration gradient, the better the flux across a barrier Whether the drug is in solution or suspension in the vehicle can be significant if powder- > have to dissolve to allow absorption into skin 56 Topical Corticosteroids - Relevance of Skin Properties Penetration inversely correlated with SC thickness terms of thickness Penetration increases with compromised SC NOT intact General Order of Penetration barrier 1. Eyelids and genitals thin apply win bathing 3 min after 2. Face SC hydration level can affect penetration 3. Armpit occlusive 4. Forearm SC can act as a drug reservoir for up to 5 5. Palm 6. Sole thick days Int J Endocrinol.2012;2012:561018. Epub 2012 Nov 5 57 Topical Corticosteroids – Adverse Effects Skin atrophy Most common adverse effect Involves thinning of the epidermis, dermis, and potentially the hypodermis Caused by: – Decreased proliferation rate of keratinocytes – Inhibition of collagen synthesis – Vasoconstriction Considered reversible can take wks Risk factors – TC potency – Duration of use – Age – e.g., the elderly already thin skin – Occlusion disallowing drug get thru more to – Body site – e.g., sites with thinner skin and intertriginous sites 58 Topical Corticosteroids – Adverse Effects Striae A common form of dermal scarring that appear on the skin as linear striations Typically begin as red striations (striae rubra) and can progress over time to hypopigmented (white) striations (striae alba) Thought to be caused by cross-linking of immature collagen in the dermis, resulting in intradermal tears Occurs in areas of mechanical stress likethighs Considered irreversible if not caught early enough 59  Topical Corticosteroids – Adverse Effects Telangiectasia featureof rosacea Small dilated blood vessels near the surface of the skin or mucous membranes Caused by stimulation of dermal microvascular endothelial cells Tachyphylaxis A reduction in efficacy over time has been reported for topical corticosteroids Evidence for this in clinical trials is lacking – adherence issue? Others Hypopigmentation corticosteroid ache Acne or rosacea-like eruption Allergic contact dermatitis Exacerbation of skin infections (e.g., fungal/yeast and bacterial) 60 Topical Corticosteroids – Adverse Effects Systemic adverse effects High and super-high potency TC can be absorbed well enough to cause systemic adverse effects, though they are uncommon Hypothalamic-pituitary-adrenal suppression, If applied to eye glaucoma, hyperglycemia, hypertension, and others have been reported Greatest risk: When ultrahigh- or high-potency corticosteroids are used for > 4 weeks over a >20% BSA or under occlusion ↑ ability of drug to get thru 61 Topical Corticosteroids - Selection Factors General guideline – Choose the appropriate potency product to achieve disease control – Continue with a lower potency product after a sufficient response 62 Topical Corticosteroids - Selection Factors Location of lesions / SC thickness Areas of thin skin such as the face and Least to low potency TCS for a axilla (especially eyelids and genitals) limited duration > naturally occlusive - Intertriginous areas such groin, under breasts, and diaper areas apply don't oint Severity of dermatosis Severe nonfacial/nonintertriginous Super high-potency TCS dermatoses Mild to moderate Medium- to high-potency TCS nonfacial/nonintertriginous dermatoses Extent of area to be treated Large body areas ↑ sys circulation ADE Low to medium potency TCS 63 Topical Corticosteroids - Selection Factors Age of patient – Children have a higher ratio of BSA to BW and are more likely to have systemic adverse effects; lower potency corticosteroids recommended – Low- to mid-potency corticosteroids are recommended in elderly adults with thin and/or fragile skin 64 Topical Corticosteroids – Usage Frequency – Once to twice a day application is the usual recommendation ↑ freq wI OTC limited – May be optimal to apply within first 3 minutes after a bath or shower ↳ conditions use ↳ be skin hydrated Thick vs thin applications ↳ drug in soln – Apply a thin layer opposite (apply lot) of sunscreen a – A thicker application can result in longer time of drug release and a modest increase in amount of drug absorbed. It is generally wasteful Quantity of corticosteroid – The finger-tip unit method can be used to approximate the amount needed (1 FTU = 0.5 g; covers both sides of one-hand (2% BSA) Adjusted down for children (e.g., infants- 1/5, children- 2/5, adolescents- 2/3) Note: To avoid confusion, avoid using the phrase “apply sparingly to the affected area”. Rather state: “apply enough to cover the affected area with a thin layer” 65 Topical Corticosteroids - Usage Duration of treatment, in general: – Super high potency: treat for no longer than 4 weeks – High and Medium potency: 1cm, usually located in the dermis or subcutaneous tissue. The greatest portion may be beneath the skin. Papule An elevated, solid, palpable lesion that is 1 cm or less in diameter Pustule A circumscribed lesion that contains pus 70 Evaluation of Dermatological zesipeppe manonpa Disorders - Lesion Types = vesicles wheal = circumscribedelevated circumscribed elevatedircumscribed fatedfa * KNOW Lesion Definition Vesicle A circumscribed lesion 1 cm or less in diameter that contains liquid (clear, serous, or hemorrhagic) Plaque A circumscribed, palpable lesion > 1cm in diameter. Most plaques are elevated. Wheal A rounded or flat-topped, pale red papule or plaque that commonly disappears within 24 to 48 hours 71  don't have to memorize Classification of Topical Corticosteroids WHO potency group Classification Super-potent Class 1 1. Augmented betamethasone dipropionate 0.05% oint, gel Ultrahigh 2. Clobetasol propionate 0.05% oint, gel, cream, lotion, foam, solution, spray 3. Desoximetasone 0.25% spray 4. Augmented diflorasone diacetate 0.05% oint 5. Fluocinonide 0.1% cream 6. Flurandrenolide 4 mcg/cm2 tape 7. Halobetasol propionate 0.05% oint, cream High Class 2 1. Amcinonide 0.1% oint 2. Betamethasone dipropionate 0.05% oint 3. Augmented betamethasone dipropionate 0.05% cream, lotion 4. Desoximetasone 0.25% oint, cream 5. Desoximetasone 0.05% gel 6. Augmented diflorasone diacetate 0.05% cream 7. Diflorasone diacetate 0.05% oint 8. Fluocinonide 0.05% oint, gel, cream, solution 9. Halcinonide 0.1% oint, cream 10. Mometasone furoate 0.1% oint 11. Triamcinolone acetonide 0.5% oint Class 3 1. Amcinonide 0.1% cream, lotion 2. Betamethasone dipropionate 0.05% cream, foam 3. Betamethasone valerate 0.1% oint 4. Betamethasone valerate 0.12% foam 5. Diflorasone diacetate 0.05% cream 6. Fluticasone propionate 0.005% oint 7. Triamcinolone acetonide 0.1% oint 8. Triamcinolone acetonide 0.5% cream Moderate (medium) Class 4 1. Betamethasone valerate 0.12% foam 2. Desoximetasone 0.05% cream 3. Fluocinolone acetonide 0.025% oint 4. Flurandrenolide 0.05% oint 5. Hydrocortisone valerate 0.2%a oint 6. Mometasone furoate 0.1% cream, lotion 7. Triamcinolone acetonide 0.1% cream, Kenalog oint 8. Triamcinolone acetonide 0.2% lotion Class 5 1. Betamethasone dipropionate 0.05% lotion 2. Betamethasone valerate 0.1% cream, lotion 3. Clocortolone pivalate 0.1% cream 4. Fluocinolone acetonide 0.025% cream 5. Fluocinolone acetonide 0.01% oil, shampoo 6. Fluticasone propionate 0.05% cream, lotion 7. Flurandrenolide 0.05% cream, lotion 8. Hydrocortisone butyrate 0.1% oint, cream, lotion, solution 9. Hydrocortisone probutate 0.1% cream 10. Hydrocortisone valerate 0.2% cream  11. Prednicarbate 0.1% oint, cream 12. Triamcinolone acetonide 0.025% oint 13. Triamcinolone acetonide 0.01% lotion Low Class 6 1. Alclometasone dipropionate 0.05% oint, cream 2. Betamethasone valerate 0.05% lotion 3. Desonide 0.05% oint, gel, cream, lotion, foam 4. Fluocinolone acetonide 0.01% cream, solution 5. Triamcinolone acetonide 0.025% cream, lotion Class 7 1. Dexamethasone sodium phosphate 0.1% cream 2. Hydrocortisone 0.5%-2.5%a,b,c,d,foint, gel, cream, lotion, solution, 3. Methylprednisolone acetate 0.25% cream J Am Acad Dermatol 2021;84:432-70. Psoriasis Cary Mobley Psoriasis “a complex, chronic, multifactorial, systemic inflammatory, autoimmune disease that involves hyperproliferation of the keratinocytes in the epidermis, with an increase in the epidermal cell turnover rate” (Medscape - http://emedicine.medscape.com/article/1943419-overview) I createssee Psoriasis a systemic condition that results from an interplay of genetic, environmental, and immune factors lifelong, chronic and recurrent ↓ or curable can have a significant negative physical, psychological, and social effects Psoriasis - Epidemiology About 3.1% U.S. adults (about 5 million) Males females Hispanic ( 1.6%), African American ( 1.9%), Caucasian ( 3.6%) Onset – About 75% before 40 yo (average age of onset between 25- 33); another peak between 50-60 y will manifest at younger age – About 10% before 10 yo Genetics – About 41% chance if both parents affected, about 14% if one parent Psoriasis Types – Pustular and Guttate Neutrophils collect in enough quantity to form pustules May be localized Pustular or generalized a risk of death ↳ Small papules Associated with beta-hemolytic streptococci URI Guttate think drops Psoriasis Types – Inverse and Erythrodermic Smooth, shiny Often plaques in skin misdiagnosed folds as fungal or Usually scaling Inverse bacterial is minimal infection Severe, Possible relatively rare desquamation Widespread in sheets erythema over Potentially life- Erythrodermic at least 90% of threatening the body Psoriasis Types – Nail Psoriasis = Psoriatic onychodystrophy – Nails (fingers > toes) can be affected in all subtypes of psoriasis – Nails changes include pitting, onycholysis, subungual lifting Nail hyperkeratosis (Fitzpatrick's Dermatology in General Medicine, 8e) – Can resemble onychomycosis (Tinea unguium) 7 Psoriasis Types – Plaque Psoriasis (PP) - psoriasis vulgaris The most common type j Characterized by well-defined, irregular, sharply demarcated, erythematous plaques covered by dry, thin, silvery- white scales – most often located in scalp, trunk, buttocks, limbs (especially elbows and knees) – Vary in size from one to several cm PP- Pathophysiology Complexity Psoriasis: Targets and Therapy 2016, 6:7-32 https://doi.org/10.2147/PTT.S64950 PP - Pathogenesis Primarily a T-lymphocyte mediated systemic inflammatory disease Genetics (innate immune response) - Rapid turnover (3-5 days) Abnormal immune - Immature cells fail to response T-lymphocytes release lipids properly Dendritic cells leads to initial lesions => poorly adherent with keratinocyte TNF- , IL23, corneocytes and flaking hyperproliferation IL17 and chronic scales Precipitating inflammation) factors (adaptive immune response) 10 PP – Genetic factors Numerous potential susceptibility loci – Example: Psoriasis susceptibility locus 1 (PSORS1) on chromosome 6P up to 50% of the heritability of non late-onset – About 40 other loci may be involved 11  PP – Triggers, and exacerbating factors Many theories exist about triggers including infections, traumatic insult, or stressful life event – Koebner phenomenon – lesion formation at site of trauma Skin injury (e.g., from scratching, piercings, tattoos, etc.) – Phototoxic reactions CMAJ April 16, 2013 185 (7) 585 – Chemical irritants – Infection – e.g., viral, streptococcal – Drugs – e.g., Beta blockers, lithium, antimalarials, NSAIDs, immune checkpoint inhibitors – Smoking, alcohol, psychogenic stress, winter weather PP - Treated and resolved plaques remain prone to recurrence Lancet. 2021 Apr 3;397(10281):1301-1315. doi: 10.1016/S0140-6736(20)32549-6. 13  PP – Clinical Presentation Lesions (plaques) – Erythematous Pink, red in lighter skin Psoriasis in skin of color. Dermatology Times.July 8, 2015 Violaceous, possibly hyperpigmented in darker skin –Typically covered by silver, flaking scales –At least 0.5 cm in diameter, larger plaques from coalescence –Well demarcated –Common locations: scalp, elbows, knees, and gluteal cleft (lesions in intertriginous areas are call inverse psoriasis) Pruritus – > 50% of patients – May be severe in some patients and may require treatment to minimize excoriations from constant scratching Psoriasis – Comorbidities and Complications Obesity, insulin resistance, metabolic syndrome, atherosclerosis, HF Crohn’s disease, ulcerative colitis Psychological illnesses (anxiety, depression, alcoholism) Psoriatic arthritis (30-33 % of patients) If severe, a 3-4 year reduction in lifespan This Photo by Unknown Author is licensed under CC BY-SA-NC Psoriasis – Comorbidities and Complications – Psoriatic Arthritis An inflammatory arthritis Can be associated with enthesitis and dactylitis Associated with a greater risk for clinical and subclinical diabetes and cardiovascular disease “Appropriate education about the signs and symptoms of PsA and the potential consequences of delay in diagnosis and management is imperative” (J Am Acad Dermatol 2019;80:1073-113) This Photo by Unknown Author is licensed under CC BY-SA-NC PP – Impact on QOL Can cause significant psychosocial morbidity Problems with work, activities of daily living, and socialization Many feel unattractive Many experience stress and depression Many report frustration with effectiveness of treatment => adherence issues Quality-of-life scores tend to improve with age This Photo by Unknown Author is licensed under CC BY-SA PP – Patient Evaluation Psoriasis Area and Severity Index (PASI) – Evaluates lesion erythema, thickness, and scaling in different body areas – Commonly used for assessment in clinical trials Dermatology Life Quality Index (DLQI) – Evaluates how psoriasis is affecting a patient’s quality of life – Issues addressed: symptoms, embarrassment, shopping and home care, clothes, social and leisure, sport, work or study, close relationships, sex, treatment Screen for comorbidities – e.g., Be alert to complaints of joint pain or stiffness PP – Evaluation – Severity Levels Assessed based on body surface area, PASI, and DLQI Mild - National Psoriasis Foundation) – Usually in isolated plaques on scalp, elbows, hands, knees, and/or feet Moderate -10% BSA - National Psoriasis Foundation) – Plaques are often on scalp, torso, arms, legs, and other areas Severe – Plaques may be extensive and pustules and erythroderma may be present PP Therapy Outcomes Reduce or eliminate visual signs (e.g., plaques, scales) Decrease pruritis and prevent associated excoriations Reduce frequency of flare-ups Improve QOL BSA-Based Treatment Targets for Plaque Psoriasis Preferred assessment BSA instrument in clinical practice Acceptable response Either BSA 3% or less; or BSA after treatment improvement of 75% or more from initiation baseline at 3 mo after treatment initiation Ideal Target response BSA 1% or less at 3 mo after after treatment treatment initiation initiation Target response during BSA 1% or less at every 6 mo maintenance therapy assessment intervals 21 PP - Therapeutic Strategies Monotherapy – Can limit side effects and improve adherence – Long-term use of some agents may lead to toxicity Combination therapy – Often more effective than each agent individually – Can allow for lower doses compared to monotherapy Sequential therapy – Use stronger agent(s) initially to rapidly clear the lesions, followed by less toxic agent(s) for maintenance 22 PP – Steps for Mild-to- Moderate Disease Topical Agents + Topical Systemic Agents + Therapy Topical Phototherapy Agents + Moisturization When controlled, reduce therapy intensity to least potent, least toxic agents needed to maintain control PP – Steps for Moderate-to-Severe Disease Biological Response Modifier +/- Other More Potent Agents Systemic Agent or 2 Systemic Agent +/- or more systemic Topical Agent or agents in rotation Phototherapy. +/- Topical Agent. Consider BRM Consider BRM biologic response modifiers + Moisturization When controlled, reduce therapy intensity to least potent, least toxic agents needed to maintain control Plaque Psoriasis (PP) Therapy – Selection Criteria Severity level Body site Thickness and scaling of the lesions Comorbid conditions (e.g., psoriatic arthritis) Age of the patient Patient preference – Effect on the patient’s quality of life – Patient goals – Motivation and ability to adhere to therapeutic strategy – Vehicle preferences of the patient if a topical Cost This Photo by Unknown Author is licensed under CC BY-NC-ND 25  PP Therapy Topical Agents Phototherapy Systemic Agents - Corticosteroids - UVA / PUVA - Retinoids - Retinoids - UVB (Broadband - Methotrexate and other - Vitamin D analogs narrowband) immune-modulators - Calcineurin - Goeckerman (tar + - Calcineurin inhibitor inhibitors UVB) (cyclosporine) - Aryl hydrocarbon - Excimer laser - Phosphodiesterase 4 receptor agonist inhibitor - Phosphodiesterase - Tyrosine kinase 2 4 inhibitor inhibitor - Combination - Biologics products - Coal tar - Salicylic acid PP Topical Pharmacotherapy – Possible Exclusion Criteria Extensive coverage (e.g., > 3 to 5% BSA) Plaque location(s) – Topical treatment of certain areas can be difficult (e.g., scalp, genital, palmar, plantar, facial, or scattered plaques) Associated psoriatic arthritis Severe symptoms Severe psychosocial impact Inability to apply topical therapy Patient preference  PP Topical Pharmacotherapy – Glucocorticoids A mainstay: Anti-inflammatory, antiproliferative, immunosuppressive, and vasoconstrictive effects Potency Examples Role in Therapy Class High to Betamethasone dipropionate 0.05% Oint for use on localized areas of thick Super High Clobetasol propionate 0.05% Oint plaques on extremities and trunk BID Fluocinonide 0.1% Crm initially for 2-4 weeks and then alternate with calcipotriene or calcitriol. Medium Triamcinolone acetonide 0.1% Crm for chronic use on widespread plaques ↳ most common mid potency on extremities and trunk BID Low Desonide 0.05% Crm for use on face, groin, axillae in adults Hydrocortisone 1% Crm or psoriasis in children BID PP Topical Pharmacotherapy – Topical Glucocorticoids – Potential adverse effects Skin atrophy Striae Telangiectasis  PP Topical Pharmacotherapy – Vitamin D3 Analogs Upon binding to the VDR (Vitamin D Receptor), the drug-receptor complex associates with the RXR- (retinoid x receptor) and binds to vitamin D response elements on DNA. => Genes that modulate epidermal differentiation and inflammation are subsequently expressed Major effect: reduce hyperproliferation Calcipotriol Dovonex Cream, solution 0.005% Apply twice daily to affected areas. (calcipotriene) Sorilux Foam 0.005% Typically used in combination therapy with TCS in adults. Calcitriol Vectical Ointment 0.0003% - Can be steroid-sparing Approved for mild to Adverse effects: moderate plaque Possible irritant contact dermatitis psoriasis in adults and in pediatric patients 2 years Rarely hypercalcemia: Weekly dose and older. should not exceed 100 g Irritation if used in face or genital area PP Topical Pharmacotherapy – Combination Vit.D3 analog/corticosteroid Calcipotriene 0.005% and betamethasone dipropionate 0.064% broad hairy & good for or areas Taclonex Suspension, Ointment good ↳ for Applied once daily to affected areas 12 years and older t nick plaques Up to 4 weeks Should not be used on face, axillae, Enstilar Foam hairy - areas groin, or armpits 12 years and older Up to 4 weeks Weekly dose should not exceed 100 g (hypercalcemia) Wynzora Cream 18 years and older Up to 8 weeks  PP Topical Pharmacotherapy – Retinoid Bind to cytoplasmic retinoic acid receptors (RARs) and retinoid X receptors (RXRs). The drug-receptor complex regulates gene transcription Normalizes keratinocyte differentiation and reduces hyperproliferation and inflammation Applied once daily to affected areas Tazarotene Tazorac Cream, gel 0.05%, 0.1% For use in thick plaques in adults in combination with topical steroids. Adverse effects: Irritation in lesional and perilesional skin may be reduced by: - use of the cream, lower concentration, application on alternate days, use with moisturizers, use with topical corticosteroid Photosensitizing (Use sun protection) Pregnancy category X (Contraindicated) PP Topical Pharmacotherapy – Combination retinoid/corticosteroid halobetasol propionate-tazarotene lotion, 0.01 percent/0.045 percent Duobrii Lotion Apply once daily to cover only affected areas and rub in gently. Avoid application on the face, groin, or in the axillae If a bath or shower is taken prior to application, the skin should be dry before applying the lotion. Total weekly dose: 50g max (potential HPA-axis suppression) Possible AEs: atrophy, striae, telangiectasias, folliculitis and contact dermatitis Teratogenic risk: Do not use in pregnancy  PP Topical Pharmacotherapy – Calcineurin Inhibitors Calcineurin upregulates the expression of multiple cytokines and costimulatory molecules necessary for full activation of T cells (calcineurin inhibitors inhibit this) Normalize keratinocyte differentiation and reduce hyperproliferation and inflammation Tacrolimus Protopic Ointment Used off-label 0.1% - Tacrolimus for psoriasis on face and inverse psoriasis up to 8 weeks Pimecrolimus Elidel Cream 1% - Pimecrolimus for inverse psoriasis for 4-8 weeks Can be less irritating than calcipotriol and also avoids corticosteroid adverse effects Can be used for psoriasis on face, axillae, groin, and genitals BID Main adverse effects are burning and itching - Reduces with repeated usage - Can be mitigated by not applying immediately after bathing PP Topical Pharmacotherapy – aryl hydrocarbon receptor agonist Tapinarof (Vtama) Aryl hydrocarbon receptor agonist- Downnregulates IL-17: promotes skin barrier normalization, antioxidant activity For patients with mild, moderate, or severe plaque psoriasis A once-daily topical cream (1%) More tolerable than TCS, but expensive Bissonnette, R et al. Tapinarof in the treatment of psoriasis: A review of the unique mechanism of action of a novel therapeutic aryl hydrocarbon receptor–modulating agent. Journal of the 35 American Academy of Dermatology, Volume 84, Issue 4, 1059 - 1067 PP Topical Pharmacotherapy - Phosphodiesterase-4 inhibitor Zoryve (roflumilast) Phosphodiesterase-4 inhibitor => reduces production of multiple cytokines A once daily 0.3% cream indicated for topical treatment of plaque psoriasis, including intertriginous areas, in patients 6 years of age and older An alternative to TCS, but expensive 36  PP Pharmacotherapy – Topical Salicylic Acid May reduce keratinocyte cohesion and stratum corneum pH, with the net effect of increasing desquamation, reducing scaling, and softening of the plaques Keratolytic Keralyt 6% Gel, Dermarest For use in thick plaques in Salicylic acid combination with topical steroids 3% gel (OTC), MG217 3% cream (OTC), T-Sal 3% Adverse effects: shampoo (OTC) Systemic toxicity - Rare, but risk increases when commonly used applied to greater than 20% BSA or - UVB = most to patients with hepatic or renal phototherapy can be important component of impairment. Should avoid this psoriasis # If salicylates are applied to an 1 Decreases efficacy of UVB therapy area that applied afterwards UVB therapy that can will be due to a filtering effect, thus apply reduce the effect of UVB therapy afterwards  PP Pharmacotherapy – Topical Medications Other Coal tar products Mechanism unknown - antiproliferative Coal tar Shampoos, Adjunct to topical steroids NOTuseda products and creams, lotions, Use has diminished preps ointments, and AEs: Contact dermatitis, folliculitis, oils photosensitivity to UVA Stains and odiferous Goeckerman Combines 2-4% regimen crude coal tar in a An effective, synergistic combination petrolatum base with UVB phototherapy  PP - Phototherapy Mechanisms (speculative) – Suppression of DNA synthesis (may explain effect on diseases with epidermal hyperproliferation) – Selective immunosuppression (may explain effect for autoimmune skin diseases) An effective option for patients who: – require more than topical medications – wish to avoid systemic medications – seek an adjunct to a failing regimen Either UVA or UVB – UVB more effective, safer, and used more often than UVA https://www.psoria sis.org/sites/default Home units are available /files/light_therapy 39