Pennsylvania Academy of Family Physicians Foundation & UPMC 43rd Refresher Course in Family Medicine CME Conference March 10 13, 2016

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1 Pennsylvania Academy of Family Physicians Foundation & UPMC 43rd Refresher Course in Family Medicine CME Conference March 10 13, 2016 Disclosures: Dermatology Potpourri Authur Huen, MD Speaker has no disclosures and there are no conflicts of interest. The speaker has attested that their presentation will be free of all commercial bias toward a specific company and its products. The speaker indicated that the content of the presentation will include discussion of unapproved or investigational uses of products or devices. This activity was funded in part by an educational grant from Bayer HealthCare Pharmaceuticals at the Pittsburgh CME Conference, which had no control over the content.

Dermatology Potpourri 2016 Combined PAFP CME Conference and UPMC 43RD REFRESHER COURSE IN FAMILY MEDICINE Disclosures I have no financial conflicts of interest I have no financial affiliation with

2 Dermatology Potpourri 2016 Combined PAFP CME Conference and UPMC 43RD REFRESHER COURSE IN FAMILY MEDICINE Disclosures I have no financial conflicts of interest I have no financial affiliation with the companies that manufacture medications or products presented in this presentation The content of this presentation will include discussion of unapproved or investigational uses or devices as indicated. Kollias, Helen. Research Review: Research, big food, and science. Precision Nutrition, n.p. n.d. 27 Aug For severe alopecia areata, which of the following are potential treatments? A. Systemic steroids B. DMARDs C. Photochemotherapy D. Topical diphenylcyclopropenone E. All of the above 3 1

3 The best complete cure rate of topical antifungals for onychomycosis is similar to which of the following 2016 NFL team win-loss percentage? A. Carolina Panthers 93.8% B. Denver Broncos 75% C. Indianapolis Colts 50% D. Dallas Cowboys 25% E. Tennessee Titans 18.8% 4 For systemic steroids, treatment efficacy is dependent on which of the following A. Dose B. Vehicle C. Potency D. Class E. All of the above 5 alopecia areata and use of immune modulators steroid formulation selection onychomycosis treatments 6 2

4 Base References Springer K, Brown M, Stulberg DL. Common hair loss disorders. Am Fam Physician Jul 1;68(1): Review. PubMed PMID: Ference JD, Last AR. Choosing topical corticosteroids. Am Fam Physician Jan 15;79(2): PubMed PMID: Westerberg DP, Voyack MJ. Onychomycosis: Current trends in diagnosis and treatment. Am Fam Physician Dec 1;88(11): Review. PubMed PMID: Alopecia areata 8 Alopecia areata Autoimmune condition causing non-scarring alopecia 9 3

5 Alopecia areata Autoimmune condition causing non-scarring alopecia Classified by degree Alopecia areata (patchy loss of hair) Alopecia totalis (loss of facial and scalp) Alopecia universalis (loss of all hair) 10 Alopecia areata

13 Alopecia areata: systemic therapies Systemic steroids Prednisolone 200 mg Q weekly x 3 months 30+% regrowth in 40% of patients vs 0% 60+% regrowth in 10% of patients vs 0% NOTE: study only

6 13 Alopecia areata: systemic therapies Systemic steroids Prednisolone 200 mg Q weekly x 3 months 30+% regrowth in 40% of patients vs 0% 60+% regrowth in 10% of patients vs 0% NOTE: study only included patients with at least 40% hair loss or at least 10 patches Kar BR, Handa S, Dogra S, Kumar B. Placebo-controlled oral pulse prednisolone therapy in alopecia areata. J Am Acad Dermatol. 2005;52(2): Intralesional steroids 5-20 mg/ml injected into lesions Q 4-6 weeks (63% complete regrowth) Deposit 0.1mL in cm intervals 14 Sulfasalazine Hair growth in 55% of patients 60+% regrowth in 26% of patients moderate regrowth in 31% of patients 500 mg PO BID x 1 month 1000 mg PO BID x 1 month 1000 mg PO TID x 1 month ADR: GI distress, dizziness, headache, allergy to sulfa Monitor: CBC/diff/PLT, LFT, Cr, G6PD screen 15 5

7 Methotrexate Methotrexate mg PO Q weekly With or without mg prednisone PO daily 20/22 had hair regrowth 6/20 had incomplete hair regrowth 14/20 had complete hair regrowth NOTE: pts included had totalis- or universalis-type AA Joly P. The use of methotrexate alone or in combination with low doses of oral corticosteroids in the treatment of alopecia totalis or universalis 16 Oral cyclosporine and azathioprine No randomized controlled trials Reported efficacy is similar to methotrexate however, side effect profile is not preferred Cyclosporine Hypertension Renal toxicity Hyperkalemia Hirsuitism Azathioprine Hepatic toxicity GI upset Bone marrow suppression 17 Alopecia areata: systemic therapies Topical sensitizers In a nutshell Replace a Th1 immune response (alopecia areata) with a Th2 response (allergic contact dermatitis) Diphenylcyclopropenone (DPCP) Week 1: sensitization phase apply 2% solution to a 4 cm x 4 cm area (in clinic) Week 3 6 months: treatment phase Apply 0.001% solution weekly to scalp for 48 hours (at home). ADR: allergic contact dermatitis 18 6

8 Alopecia areata: systemic therapies Antidepressants Imipramine 75 mg PO daily x 6 months 71% of patients had any regrowth vs 0% of placebo patients No significant difference in complete regrowth (1/7 vs 0/6) Cipriani R, Perini GI, Rampinelli S. Paroxetine in alopecia areata. Int J Dermatol. 2001;40(9): Paroxetine 20 mg PO daily x 3 months 75% had any regrowth vs 20% of placebo patients No difference in complete regrowth (2/8 vs 1/5) Perini G, Zara M, Cipriani R, Carraro C, Preti A, Gava F, Coghi P, Peserico A. Imipramine in alopecia areata. A double-blind, placebo-controlled study. Psychother Psychosom. 1994;61(3 4): Photochemotherapy with UVA (PUVA) Success rate 15-70% depending upon method of drug delivery Systemic 8-methoxypsoralen 20 mg PO 2-4 hours prior to UVA exposure Topical 8-methoxypsoralen Typically 0.1% cream 1-4 hours prior to exposure OR Bath-PUVA: 3 mg/l soak 1-4 hours prior to exposure PUVA-Turban: % (1 mg/ L) solution in damp towel wrapped on scalp for 20 minutes prior to exposure Behrens-Williams SC, Leiter U, Schiener R, Weidmann M, Peter RU, Kerscher M. The PUVA-turban as a new option of applying a dilute psoralen solution selectively to the scalp of patients with alopecia areata. J Am Acad Dermatol Feb;44(2): It rubs the lotion on its skin The Silence of the Lambs. Dir. Jonathan Demme. Perf. Jodie Foster, Anthony Hopkins, Scott Glenn. Orion, Film. 21 7

9 Topical Steroids can be categorized in several ways Potency class Vehicle Structural Class 22 Topical Steroids can be categorized in several ways Potency class Vehicle Structural Class Steroid allergies exist! There are some cross-reactivities among classes 23 Class VII least potent (includes OTC) Class VI low potency Class IV and V medium potency Class III medium/high potency Class II - high Class I ultra high potency 24 8

10 Class VI and VII least potent (includes OTC) Safest choice for thin or occluded skin Dermatitis (diaper) Dermatitis (eyelids) Dermatitis (face) Intertrigo Perianal inflammation 25 Class VI and VII least potent (includes OTC) 26 Class VI and VII least potent (includes OTC) For 15 g ointment $17-28 $17-20 $14-23 $29-49 $

11 28 Class IV and V medium potency Safest choice for truncal/extremity skin Anal inflammation (severe) Asteatotic eczema Atopic dermatitis Lichen sclerosus (vulva) Nummular eczema Scabies (after scabicide) Seborrheic dermatitis Severe dermatitis Severe intertrigo (short-term) Stasis dermatitis Class IV and V medium potency 29 Class IV and V medium potency For 15 g ointment $30-50 ($62-64) $29-46 ($60-62) $6-10 $

12 31 Class I III: high potency Best choice for acral skin or severe inflammation Alopecia areata Atopic dermatitis (resistant) Discoid lupus Hyperkeratotic eczema Lichen planus Lichen sclerosus (skin) Lichen simplex chronicus Poison ivy (severe) Psoriasis Severe hand eczema 32 For 15 g ointment $30-37 $30-60 $ ($ ) $47-94 ($ ) $47-94 ($ ) $

13 Vehicle For the same dose, the potency changes with type of vehicle (usually) Can affect compliance. Male patients often dislike ointment vehicle Cream or lotion vehicle can burn or sting if skin is broken Gels can leave a white residue after drying 34 Onychomycosis How do I know what is the best treatment? 35 Onychomycosis How do I know what is the best treatment? First, consider that it might NOT be onychomycosis

14 Onychomycosis How do I know what is the best treatment? First, consider that it might NOT be onychomycosis. 50% of nail disorders are onychomycosis Nail matrix trauma Psoriasis Chronic paronychia 37 Onychomycosis How do I know what is the best treatment? First, consider that it might NOT be onychomycosis. 50% of nail disorders are onychomycosis Nail matrix trauma Psoriasis Chronic paronychia Second, know what you are treating 38 Onychomycosis How do I know what is the best treatment? First, consider that it might NOT be onychomycosis. 50% of nail disorders are onychomycosis Nail matrix trauma Psoriasis Chronic paronychia 39 Second, know what you are treating Good clinical exam: appearance, Laboratory analysis KOH Culture (up to 4 weeks) H&E analysis 13

Maybe more than onychomycosis Most common Maybe just mechanical debridement Maybe workup is needed 40 Onychomycosis How do I know what is the best treatment?

15 Maybe more than onychomycosis Most common Maybe just mechanical debridement Maybe workup is needed 40 Onychomycosis How do I know what is the best treatment? Mycological cure culture negative or KOH negative Clinical cure appearance of nail Complete cure combination of mycologic and clinical cure Gold standard is systemic terbinafine, 12 week continuous treatment 41 Onychomycosis Terbinafine 76% (22-64% complete cure) Pulse therapy 2 pulses 250 mg/day x 4 weeks, 4weeks off, 4 weeks on Comparable to continuous therapy (250 mg PO daily for 6-12 weeks 42 14

16 Onychomycosis Terbinafine 76% (22-64% complete cure) Pulse therapy 2 pulses 250 mg/day x 4 weeks, 4weeks off, 4 weeks on Comparable to continuous therapy (250 mg PO daily for 6-12 weeks Itraconazole 63-70% clinical/mycotic cure Pulse seems to be better than continuous therapy (complete cure was not assessed). 400 mg/day x 1 month, off 3 months, for 3 or 4 pulses 400 mg/day x 1 week per month 2-3 months 200 mg PO daily x 6-12 weeks 43 Onychomycosis Fluconazole 41-48% clinical-mycotic cure mg PO q weekly for 3-6 or 6-12 months 20% complete cure 450 mg once weekly at least 6 months Ketoconazole not recommended Multitude of drug interactions Hormonal effects Hepatotoxicity 44 Topical antifungal treatments Ciclopirox (nail lacquer) 33% clinical cure 7% complete cure Urea 40% ointment Under occlusion QHS with mechanical debridement 45 15

17 Topical antifungal treatments Ciclopirox 8% solution (nail lacquer) 33% (9%-91%) clinical cure 7% (0%-22%)complete cure Urea 40% ointment (no RCT) Under occlusion QHS with mechanical debridement Efinaconazole 10% solution 54%(17%-87%) mycologic cure 17% (5.5%-26%) complete cure Piraccini BM, Bruni F, Alessandrini A, Starace M. Evaluation of efficacy and tolerability of four weeks bifonazole treatment after nail ablation with 40% urea in mild to moderate distal subungual onychomycosis. G Ital Dermatol Venereol Feb;151(1):32-6. Lipner SR, Scher RK. Efinaconazole in the treatment of onychomycosis. Infect Drug Resist Jun 1;8: Gupta AK, Daigle D, Foley KA. Topical therapy for toenail onychomycosis: an evidence-based review. Am J Clin Dermatol Dec;15(6): doi: /s Review 46 Topical antifungal treatments Ciclopirox 8% solution (nail lacquer) 33% (29%-91%) clinical cure* 7% (3.2%-22%)complete cure Tavaborole 5% solution % clinical cure** Urea 40% ointment (no RCT) % complete cure Under occlusion QHS with mechanical debridement Efinaconazole 10% solution 54%(17%-87%) mycologic cure 17% (5.5%-26%) complete cure Piraccini BM, Bruni F, Alessandrini A, Starace M. Evaluation of efficacy and tolerability of four weeks bifonazole treatment after nail ablation with 40% urea in mild to moderate distal subungual onychomycosis. G Ital Dermatol Venereol Feb;151(1):32-6. Lipner SR, Scher RK. Efinaconazole in the treatment of onychomycosis. Infect Drug Resist Jun 1;8: Gupta AK, Daigle D, Foley KA. Topical therapy for toenail onychomycosis: an evidence-based review. Am J Clin Dermatol Dec;15(6): doi: /s Review 47 Name Dosing Price Efinaconazole 4 ml of 10% solution $ Ciclopirox 6.6 ml of 8% solution $10-36 Penlac brand ciclopirox 6.6 ml of 8% nail lacquer $1,147-1,161 Terbinafine Thirty 250 mg tablets $6-10 Tavaborole 4 ml of 5% solution $

18 For severe alopecia areata, which of the following are potential treatments? A. Systemic steroids B. DMARDs C. Photochemotherapy D. Topical diphenylcyclopropenone E. All of the above 49 The best complete cure rate of topical antifungals for onychomycosis is similar to which of the following 2016 NFL team win-loss percentage? A. Carolina Panthers 93.8% B. Denver Broncos 75% C. Indianapolis Colts 50% D. Dallas Cowboys 25% E. Tennessee Titans 18.8% 50 For systemic steroids, treatment efficacy is dependent on which of the following A. Dose B. Vehicle C. Potency D. Class E. All of the above 51 17

19 Summary Alopecia areata - Systemic corticosteroids is still the gold standard - Many DMARDs may also reach up to 60+% hair regrowth - Some additional options reviewed (immuno-, phototherapy) - Vehicle choice is important for drug delivery and compliance - However, drug prices often limit choices Onychomycosis - pulsed terbinafine and itraconazole remain most effective - slightly better topicals are available, however, price is an issue 52 Questions? Arthur C. Huen MD/PhD Instructor Department of Dermatology UPMC / University of Pittsburgh huenac@upmc.edu 53 18

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