Pharmacotherapy ofPharmacotherapy ofCommon Skin DiseasesCommon Skin Diseases

John Zic, MDJohn Zic, MD

Dermatologic Therapy Dermatologic Therapy Lecture OutlineLecture Outline

I. Acne Vulgaris and RosaceaII. PsoriasisIII. Eczema

Acne Vulgaris and RosaceaAcne Vulgaris and Rosacea

Defined: Chronic papulopustular eruption Defined: Chronic papulopustular eruption affecting the pilosebaceous units of the face affecting the pilosebaceous units of the face and trunk.and trunk.

Types: Comedonal, Papulopustular, Types: Comedonal, Papulopustular, Nodulocystic, Conglobata, Fulminans, Nodulocystic, Conglobata, Fulminans, Rosacea.Rosacea.

Primary Lesion: red papule/nodule, pustule, Primary Lesion: red papule/nodule, pustule, comedones (white and black heads).comedones (white and black heads).

Keys to Dx: Age, Flushing?Keys to Dx: Age, Flushing?

Acne Pathophysiology Acne Pathophysiology The Formation of the ComedoThe Formation of the Comedo

Early microcomedo: sebaceous canal Early microcomedo: sebaceous canal distends with sticky corneocytes.distends with sticky corneocytes.Late microcomedo: colonization with Late microcomedo: colonization with Propionibacterium acnes.Propionibacterium acnes.Mature closed comedo (white head): Mature closed comedo (white head): densely packed corneocytes, solid masses densely packed corneocytes, solid masses of of P. acnes P. acnes, few small hairs., few small hairs.Open comedo (black head): sticky Open comedo (black head): sticky corneocytes, bacteria, oxidized lipidscorneocytes, bacteria, oxidized lipids

The Fate of the Closed ComedoThe Fate of the Closed Comedo

Closed comedo (“Time bomb of acne”)

Rupture and Inflammation Open Comedo

Potent chemoattractantfor neutrophils

Acne: Natural History Acne: Natural History

Comedonal: closed and open comedonesComedonal: closed and open comedones

Papular: + red inflamed papulesPapular: + red inflamed papules

Papulopustular: + pustulesPapulopustular: + pustules

Nodulocystic: + inflamed nodules/cystsNodulocystic: + inflamed nodules/cysts

Acne Vulgaris Therapeutic AgentsAcne Vulgaris Therapeutic AgentsClasses of topical agentsClasses of topical agents

Retinoids: tretinoin, adapalene (micro gels, gels, Retinoids: tretinoin, adapalene (micro gels, gels, creams, solutions)- comedolytic, shrink creams, solutions)- comedolytic, shrink sebaceous glandssebaceous glands

Should not be used in pregnant womenShould not be used in pregnant womenAntibiotics: Antibiotics: – Clindamycin & Erythromycin (solution, gel, pads, Clindamycin & Erythromycin (solution, gel, pads,

lotion)- antibacterial lotion)- antibacterial – Sulfur-containing products (lotion, cream)- Sulfur-containing products (lotion, cream)-

antibacterialantibacterial

Benzoyl Peroxide (cream, gel)- antibacterial, Benzoyl Peroxide (cream, gel)- antibacterial, comedolyticcomedolytic

Acne Vulgaris Therapeutic AgentsAcne Vulgaris Therapeutic AgentsClasses of oral agents Classes of oral agents

AntibioticsAntibiotics

Retinoid (Isotretinoin)Retinoid (Isotretinoin)

SpironolactoneSpironolactone– Uncommonly usedUncommonly used

Oral contraceptives (low progesterone)Oral contraceptives (low progesterone)– Yasmin, OrthotricyclenYasmin, Orthotricyclen– Only for adjunctive therapyOnly for adjunctive therapy

Acne Vulgaris Therapeutic AgentsAcne Vulgaris Therapeutic AgentsOral AntibioticsOral Antibiotics

Tetracycline: 500mg bid - tid Tetracycline: 500mg bid - tid (Photosensitivity, GI upset- empty stomach) (Photosensitivity, GI upset- empty stomach)

Doxycycline: 100mg qd - bid Doxycycline: 100mg qd - bid (Photosensitivity, $$)(Photosensitivity, $$)

Minocycline: 100mg qd Minocycline: 100mg qd (Dizziness, skin pigmentation, $$$)(Dizziness, skin pigmentation, $$$)

Erythromycin: 500mg bid-tid (GI upset)Erythromycin: 500mg bid-tid (GI upset)

Trimethoprim/sulfamethoxazole: 800/160mg Trimethoprim/sulfamethoxazole: 800/160mg (1 DS tab) bid (Photosensitivity, renal effects) (1 DS tab) bid (Photosensitivity, renal effects)

Acne Vulgaris Therapeutic AgentsAcne Vulgaris Therapeutic AgentsOral IsotretinoinOral Isotretinoin

Nodulocystic acne or refractory acneNodulocystic acne or refractory acne1.0 mg/kg/d with food for 16 to 20 wks.1.0 mg/kg/d with food for 16 to 20 wks.TeratogenicityTeratogenicity, extreme xerosis, increased liver , extreme xerosis, increased liver function tests & triglycerides, etc.function tests & triglycerides, etc.March 1, 2006: FDA iPledge BeginsMarch 1, 2006: FDA iPledge Begins– To prevent use in pregnant women To prevent use in pregnant women – Pt, MD, & Pharmacist must register with FDAPt, MD, & Pharmacist must register with FDA– All women of child bearing age must list 2 forms of All women of child bearing age must list 2 forms of

contraception to registercontraception to register

No evidence to support increased risk of No evidence to support increased risk of depression and suicidedepression and suicide

Acne Vulgaris TherapyAcne Vulgaris TherapyComedonal Acne Comedonal Acne

Topical tretinoin cream or gel at bedtimeTopical tretinoin cream or gel at bedtime* Apply a small amount (pea-sized) to * Apply a small amount (pea-sized) to affected regions of face.affected regions of face.* Apply to dry face, not wet.* Apply to dry face, not wet.* Try applying every other night if irritating* Try applying every other night if irritating

Consider adding a topical antibiotic or Consider adding a topical antibiotic or topical benzoyl peroxide in the morning.topical benzoyl peroxide in the morning.

Acne Vulgaris TherapyAcne Vulgaris TherapyPapular Acne Papular Acne

As per Comedonal AcneAs per Comedonal Acne

Add oral antibiotic if moderately severe or Add oral antibiotic if moderately severe or if chest and back are involved.if chest and back are involved.* Continue oral antibiotic for at least 6 to 8 * Continue oral antibiotic for at least 6 to 8 weeks then slowly decrease daily dose to weeks then slowly decrease daily dose to avoid flare-ups.avoid flare-ups.* Do not abandon a given therapy until a 6 * Do not abandon a given therapy until a 6 week trial has been completed.week trial has been completed.

Acne Vulgaris Therapy Acne Vulgaris Therapy Papulopustular/Nodulocystic Acne Papulopustular/Nodulocystic Acne

As per Papular AcneAs per Papular Acne

If severe consider Isotretinoin If severe consider Isotretinoin * Recommend Dermatology referral.* Recommend Dermatology referral.* All other acne treatment is stopped.* All other acne treatment is stopped.* Contraceptive counseling important. Oral * Contraceptive counseling important. Oral contraceptives are safe with isotretinoin.contraceptives are safe with isotretinoin.

Pitfalls of Therapy for Pitfalls of Therapy for Acne Vulgaris Acne Vulgaris

Not waiting 6-8 weeks to establish a Not waiting 6-8 weeks to establish a response to starting therapy.response to starting therapy.Ignoring the impact of cosmetics, skin Ignoring the impact of cosmetics, skin cleansers, hair lubricants, picking, OCPs, cleansers, hair lubricants, picking, OCPs, occupational exposures, stress, and occupational exposures, stress, and hormones on a patient’s acne.hormones on a patient’s acne.Poor patient education on how to Poor patient education on how to counteract the drying effects of topical counteract the drying effects of topical therapy.therapy.

Acne RosaceaTherapeutic Considerations Therapeutic Considerations

NO COMEDONES: No place for topical NO COMEDONES: No place for topical comedolytics (tretinoin, benzoyl peroxide).comedolytics (tretinoin, benzoyl peroxide).

P. acnesP. acnes bacteria not important: Topical bacteria not important: Topical erythromycin and clindamycin not helpful.erythromycin and clindamycin not helpful.

Vascular instability leads to flushing.Vascular instability leads to flushing.

Therapy of Acne RosaceaTherapy of Acne Rosacea

Topical metronidazole cream or gel bidTopical metronidazole cream or gel bid

If moderately severe add oral antibioticsIf moderately severe add oral antibiotics* Tetracycline , Doxycyline, Minocycline* Tetracycline , Doxycyline, Minocycline* Erythromycin* Erythromycin

Topical sulfur containing lotions/creams Topical sulfur containing lotions/creams are occasionally helpful.are occasionally helpful.

Pitfalls of Acne Rosacea Therapy Pitfalls of Acne Rosacea Therapy

Not waiting 6-8 weeks to establish a Not waiting 6-8 weeks to establish a response to starting therapy.response to starting therapy.

Ignoring the impact of cosmetics, skin Ignoring the impact of cosmetics, skin cleansers, skin care products, topical cleansers, skin care products, topical steroids, stress, and other steroids, stress, and other triggerstriggers on a on a patient’s rosacea.patient’s rosacea.

Psoriasis

Psoriasis

Defined: A chronic eruption of scaly plaques on Defined: A chronic eruption of scaly plaques on the extensor surfaces that may involve the scalp the extensor surfaces that may involve the scalp and nails.and nails.

Types: Vulgaris, Guttate, Pustular, Types: Vulgaris, Guttate, Pustular, Erythrodermic, Scalp, Palmoplantar, Nail.Erythrodermic, Scalp, Palmoplantar, Nail.

Primary Lesion: well-defined plaque with thick Primary Lesion: well-defined plaque with thick silvery scale.silvery scale.

Keys to Dx: Distribution; Pitting of nails.Keys to Dx: Distribution; Pitting of nails.

Plaque-type Psoriasis Vulgaris

Plaque-type Psoriasis Vulgaris

Guttate Psoriasis

Scalp Psoriasis

Palmoplantar Psoriasis

Erythrodermic Psoriasis

Pustular Psoriasis

Pustular Psoriasis

Pitted Nails of Psoriasis

Psoriatic Nail Disease

Clinical features of psoriatic arthritis

Clinical features of psoriatic arthritis

Histopathology of psoriasis

Psoriasis: Pathophysiology

Etiology unknown: possible genetic, Etiology unknown: possible genetic, environmental, physical factors? environmental, physical factors?

Main defect: rapid turnover of epidermal Main defect: rapid turnover of epidermal maturation (differentiation).maturation (differentiation).***Normal epidermal transit time = 30 days***Normal epidermal transit time = 30 days***Psoriasis epidermal transit time = 7-14 ***Psoriasis epidermal transit time = 7-14 daysdays

T cell mediated cytokine release (eg. TNFa)T cell mediated cytokine release (eg. TNFa)

Psoriasis: Therapeutic Modalities Psoriasis: Therapeutic Modalities

Topical steroid creams and ointmentsTopical steroid creams and ointments

Topical calcipotriene cream and ointmentTopical calcipotriene cream and ointment

Topical tazarotene (retinoid) gelTopical tazarotene (retinoid) gel

Topical tar containing ointmentsTopical tar containing ointments

Phototherapy (UVB & PUVA)Phototherapy (UVB & PUVA)

Oral methotrexate, acitretin (retinoid), or Oral methotrexate, acitretin (retinoid), or cyclosporinecyclosporine

Injectable biologic response modifiersInjectable biologic response modifiers– etanercept, efalizumab, adalimumab, infliximab, etanercept, efalizumab, adalimumab, infliximab,

Topical Steroid Potency RankingsI= Strongest, VII= Weakest

Class I*Class I*-Betamethasone diproprionate 0.05 % oint (Diprolene)-Betamethasone diproprionate 0.05 % oint (Diprolene)-Clobetasol propionate 0.05% oint & cream (Temovate)-Clobetasol propionate 0.05% oint & cream (Temovate)Class II*Class II*-Flucinonide 0.05% oint (Lidex)-Flucinonide 0.05% oint (Lidex)-Amcinonide 0.1% oint (Cyclocort)-Amcinonide 0.1% oint (Cyclocort)

*NEVER ON FACE OR SKIN FOLDS*NEVER ON FACE OR SKIN FOLDSClass IIIClass III -Triamcinolone acetonide 0.1% oint (Aristocort)-Triamcinolone acetonide 0.1% oint (Aristocort) -Amcinonide 0.1% cream (Cyclocort)-Amcinonide 0.1% cream (Cyclocort) -Halcinonide 0.1% oint (Halog)-Halcinonide 0.1% oint (Halog)

Topical Steroid Potency RankingsI= Strongest, VII= Weakest

Class IVClass IV -Hydrocortisone valerate 0.2% oint (Westcort)-Hydrocortisone valerate 0.2% oint (Westcort) -Halcinonide 0.1% cream (Halog)-Halcinonide 0.1% cream (Halog)Class VClass V-Triamcinolone acetonide 0.025% oint (Aristocort)-Triamcinolone acetonide 0.025% oint (Aristocort)-Betamethasone valerate 0.1% cream (Valisone)-Betamethasone valerate 0.1% cream (Valisone)Class VIClass VI-Desonide 0.05% oint & cream (Desowen)-Desonide 0.05% oint & cream (Desowen)-Triamcinolone acetonide 0.025% cream (Aristocort)-Triamcinolone acetonide 0.025% cream (Aristocort)Class VII*Class VII* -Hydrocortisone 0.5%, 1%, 2.5% oint and cream-Hydrocortisone 0.5%, 1%, 2.5% oint and cream* Safe for the face and skin folds* Safe for the face and skin folds

Partially cleared psoriasis

Limited Plaque Psoriasis TherapyLimited Plaque Psoriasis Therapy

Topical SteroidsTopical Steroids* Class I or II for short term (14 days) control.* Class I or II for short term (14 days) control.* Class III-IV for daily maintenance therapy.* Class III-IV for daily maintenance therapy.

Topical calcipotriene 0.005% cream/ointment (Dovonex)Topical calcipotriene 0.005% cream/ointment (Dovonex)* Apply twice daily +/- topical steroids* Apply twice daily +/- topical steroids

Topical tazarotene 0.1%, 0.05% gel (Tazorac): Topical tazarotene 0.1%, 0.05% gel (Tazorac): Should not Should not be used in pregnant women.be used in pregnant women.* Apply once daily +/- topical steroids* Apply once daily +/- topical steroids

Topical tar containing ointments Topical tar containing ointments * short contact therapy to bid applications* short contact therapy to bid applications

Eczema

Defined: Inflamed, pruritic skin (dermatitis) Defined: Inflamed, pruritic skin (dermatitis) not due, exclusively, to external factors not due, exclusively, to external factors (allergens, sunlight, cold, heat, fungus, (allergens, sunlight, cold, heat, fungus, etc.).etc.).Types: Atopic, Asteatotic, Hand, Types: Atopic, Asteatotic, Hand, Nummular, Stasis (Dermatitis).Nummular, Stasis (Dermatitis).Primary Lesion: ill-defined scaly red patch.Primary Lesion: ill-defined scaly red patch.Keys to Dx: Rule out external factors as Keys to Dx: Rule out external factors as the sole cause of the eruption.the sole cause of the eruption.

Hand eczema

Atopic dermatitis

Face involvement in atopic dermatitis

Nummular eczema

Nummular eczema

Eczema: Pathophysiology Eczema: Pathophysiology

Etiology unknown: genetic and Etiology unknown: genetic and environmental factors play a strong role.environmental factors play a strong role.

Histology: Spongiosis = intercellular edema Histology: Spongiosis = intercellular edema within the epidermis. Acute and chronic within the epidermis. Acute and chronic inflammatory cells.inflammatory cells.

T cell mediated cytokine release (TH2 type)T cell mediated cytokine release (TH2 type)

Atopic eczema

Therapy of Mild to Moderate Eczema Therapy of Mild to Moderate Eczema

Correct diagnosis! Rule out allergic or Correct diagnosis! Rule out allergic or irritant contact dermatitis, dermatophyte irritant contact dermatitis, dermatophyte infections, drug reactions, etc.infections, drug reactions, etc.

Good skin care: Mild superfatted skin Good skin care: Mild superfatted skin cleanser (unscented Dove, Basis, etc.), cleanser (unscented Dove, Basis, etc.), lukewarm not hot showers, lubricate skin lukewarm not hot showers, lubricate skin frequently with unscented lotions/creams.frequently with unscented lotions/creams.

Topical steroids only for flaresTopical steroids only for flares– Class I or II for short term (14 days) control of severe Class I or II for short term (14 days) control of severe

flares in adults. Class III or IV for children.flares in adults. Class III or IV for children.– Class IV - VII for mild flares in adults. Class VI or VII Class IV - VII for mild flares in adults. Class VI or VII

in children.in children.

Consider topical or oral antibiotics if crustedConsider topical or oral antibiotics if crustedConsider topical tacrolimus or topical Consider topical tacrolimus or topical pimecrolimus ($$$) for refractory disease.pimecrolimus ($$$) for refractory disease.– Both are calcineurin inhibitors that inhibit T cell Both are calcineurin inhibitors that inhibit T cell

proliferationproliferation– NO SKIN ATROPHYNO SKIN ATROPHY– FDA is concerned about long term use (Skin cancers, FDA is concerned about long term use (Skin cancers,

lymphomas ???)lymphomas ???)– Dermatologists are not concernedDermatologists are not concerned

Therapy of Mild to Moderate Eczema Therapy of Mild to Moderate Eczema

Intense pruritus in atopic dermatitis

Therapy of Severe and Therapy of Severe and Widespread Eczema Widespread Eczema

Dermatology referralDermatology referral

Oral or intramuscular steroidsOral or intramuscular steroids

PhototherapyPhototherapy

Oral methotrexateOral methotrexate

Questions?Questions?