NONE 7/3/2018 MY MANTRA: SIMPLE, SAFE, CHEAP TWO ITCHY PEARLS ZINC! CONFLICT OF INTEREST DISCLOSURE

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1 TOTALLY RADICAL SYSTEMIC THERAPEUTIC PEARLS {SOMETIMES BASED ON BASICS} {Sometimes Based on Faith} Radical Pearls Hong Kong Jade Market 2014 CONFLICT OF INTEREST DISCLOSURE NONE Ninguno Nessuno Aucun Keiner Ни один 無なし없음 MY MANTRA: SIMPLE, SAFE, CHEAP 70% Psoriasis patients itch ¾ of them itch daily ASPIRIN relieves PsO itch TWO ITCHY PEARLS No-reason itch Negative work up Paroxetine 20mg QD Aropax, Brisdelle, Deroxat, Paxil, Pexeva, Paxtine, Paxetin, Paroxat, Paraxyl, Sereupin, and Seroxat. Skin Therapy Lett 13:6, 2008 ZINC! ZINC: FAST FACTS: LOW ZINC LEVELS ASSOCIATED WITH Immune deficiency: macrophage and neutrophil function, lymphocyte activation / proliferation, complement activity; loss of modulation of TNFα and NO species Delayed wound healing: decreased matrix metalloproteinase activity, decreased keratinocyte migration, increased keratinocyte apoptosis Autoimmun Rev. 2015;14: Wound Repair Regen. 2007;15(1):2-16 1

2 ZINC RX FOR MOLLUSCUM? Open label trial (Korea; n=59) Zinc sulfate 10mg/kg/day (maximum 600mg) Rx done up to 6 months (Mean to success only 4 mo) COMPLETE clearance 47.5% PARTIAL clearance 25.4% CR + PR = 73% Well tolerated (constipation 3%, nausea 1%) ZINC RX FOR VERRUCA? Multiple trials (Korea and Brazil) Zinc sulfate 10mg/kg/day (maximum 600mg) Rx done up to 3 months? MOA; Maybe increases APC activity % success rate reported Failures ascribed to too low a dose, noncompliance due to GI symptoms, or too short treatment regimen Patients do better when serum Zn levels rise by end 1-2mo J Am Acad Dermatol 2016;74(Suppl1):AB162 Br J Dermatol 2002;146:423-31; JAAD 2009;60: ; Ann Bras Dermatol 2009;84:23-29 Clin Exp Dermatol 2009;34:e984-85; J Dermatol 2011;38: ZINC: CAUTION! Warts From Hell Gastritis to gastric perforation; To avoid this. Always give in divided doses Always give after meal Do not exceed mg elemental zinc per day Zinc sulfate: Multiple mg x 23% = elemental Zn Zinc gluconate: Multiply mg x 13% = elemental Zn Six children 9-11yo Recalcitrant warts: palmar or plantar or both Failed: Salicylic acid, Duct tape, Cryo LN 2, Imiquimod, 5-FU, CO 2 laser, Cimetidine 4vHPV x 3 shots (full series) Appropriate age timing for vaccine! Approved and recommended ALL clear non-genital warts (6 of 6) QUADRIVALENT HPV VACCINE EXTRAGENITAL CUTANEOUS WARTS Acta Derm Venereol. 95:1017-9, 2015 HPV VACCINE AND COMMON WARTS 17-yo with idiopathic neutropenia/lymphopenia Multiple common and plantar warts Resistant to cryosurgery, imiquimod, OTCs Given 4vHPV vaccine: after third injection: all warts gone Message: Administration of HPV vaccine (indicated > age 9) may lead to resolution of common/plantar warts Clin Exp Dermatol. 2017;42:

3 HYPERTHERMIA Vasodilation: increased immune cells Upregulates TSLP: recruits immune cells Increased activity T- and B- cells Increased phagocytosis pmn s Increased cytokine release Direct toxic effect on microbes HYPERTHERMIA Sporotrichosis Chromoblastomycosis Leishmaniasis Atypical mycobacteria HSV-1, HSV-2 J Am Acad Dermatol. 2010;62: J Am Acad Dermatol. 2010;62: HYPERTHERMIA AND HSV-1 OR HSV-2 Small handheld device Approved everywhere but USA Emits C heat x 4 seconds 1-2 applications shortens HSV-1 course to 1.85 days (mean) 1-2 applications shortens HSV-2 ~$100; need refills of heat generating cartridge E-Bay, Amazon Praktische Dermatologie. 2011;17: Clin Cosmet Investig Dermatol Jun 5;6:163-6 HYPERTHERMIA AND MOLLUSCUM HEATING PAD Small (n=21) Chinese prospective study; patented IR heating unit 44 0 C (111 0 F) for 30 minutes, once weekly x 12 weeks 13 children, 8 sexually active adults (ages 21-28) Average # lesions = 59 (ie. Bad molluscum) 12/18 complete clearance 12 weeks (children & adults) Facial lesions relatively resistant compared to other sites Br J Dermatol. 2017;176:

4 TINEA VERSICOLOR Stronger warning issued ; Don t use ketoconazole! Alternative orals (off label) Itraconazole 400mg/d x 3d or 200mg/d x 5d J Dermatolog Treat 2002;13:185-7 Fluconazole 300mg QWk x 2 Mycoses 2007;50: VITAMIN D AND INFLAMMATION Vitamin D attaches to both nuclear receptors and transmembrane receptors Alters transcription pattern within cell In general (macrophage/monocyte/lymphocytes) Decreases TNFα, IL-12 Increases IL-4, IL-10 Interaction with mast cells: decreases inflammatory mediator release (histamine, leukotrienes) Histamine, Leukotrienes From mast cells.. HIVES! Int J Biochem Cell Biol. 2011;43:41-6 Exp Dermatol. 2009;18: VITAMIN D RX FOR CHRONIC IDIOPATHIC URTICARIA? Vitamin D levels often low (deficient/insufficient) in CIU IF Vitamin D level < 30ug/L, consider Vitamin D therapy How much? ,000 IU Vitamin D3 daily in literature I give 10,000 IU daily ADJUNCT to typical high dose antihistamine therapy Better response Quicker response Response rates 70+% to 90+% J Dermatolog Treat. 2016;27:163-6 World Allergy Organ J Jun 4;8(1):e15 Dermatoendocrinol Jul 16;6:e29727 Simple, Safe and Cheap Ann Allergy Asthma Immunol. 2014;112: ALOPECIA AREATA 4

5 ALOPECIA AREATA?FEXOFENADINE? Widely utilized in Japan as an adjunctive or even as primary monotherapy Mechanism of action: may prevent mast cell degranulation;? part of AA etiology Simple, safe, cheap: Can be used long term Dose: mg/d (adult) 15-30mg/d (child > 6mo) Available: 30, 60,180mg tab, 30mg/5cc susp and 30mg dissolving tab J Dermatol 39:1063, 2012 J Dermatol 36:323, 2009 J Dermatol 34:852, 2007 COMMON PROBLEM: SENILE (SOLAR) PURURA J Drugs Dermatol 10:718-22, 2011 Arnica montana Ascorbic acid Hesperidin Rutoside Eriocitrin CITRUS BIOFLAVENOIDS Inhibits hyaluronaidase Decreases capillary permeability Collagen synthesis Capillary strength Capillary stability Inhibits elastase Decreases capillary permeability Antioxidant SARCOIDOSIS IF ANTI-MALARIALS, MTX AND STEROIDS FAIL SARCOIDOSIS AND MINOCYCLINE REFERENCE RESPONDED? COMMENT Dermatol Online J 2014 Aug 17;20(8) 1 of 1 Skin only JAMA Dermatol 2013;149: of 27 Skin only J Drugs Dermatol 2012;11: of 1 Hypopigmented Clin Rheumatol 2008;27: of 1 Ocular + Lung Arch Ophthalmol 2007;125: of 1 Ocular + Skin Arch Dermatol 2001;137: of 12 Skin only All at dose of 200mg/day Multiple mechanisms whereby minocycline might be anti-inflammatory in sarcoid (such as TNF-alfa and others), it also directly inhibits granuloma formation Arch Derm 1994;130:

6 SARCOIDOSIS AND INFLIXIMAB Inlfiximab is a chimeric monoclonal antibody which exerts its therapeutic effects by binding to TNF-alfa Infliximab not only binds to free cytokine, but also binds to tissue-bound TNF-alfa (That s why we worry about reactivation of TB, because TNF-alfa is necessary for granuloma formation and maintenance) Logical to administer to a non-infectious disease composed of granulomata STASIS ULCERS SIMVASTATIN AND STASIS ULCERS RCT of Rx chronic ( years) stasis ulcers n= 62 Divided equally: Simvastatin 40mg QD vrs placebo QD Both groups: adequate compression, elevation Ulcers < 5cm: Active Rx 100% versus placebo 50% healed Ulcers > 5cm: Active Rx 67% versus placebo 0% healed Large ulcers took about 9-10 weeks to heal MOA: unknown (?accelerated wound healing) Br J Dermatol 170:1151, 2014 CHONDRODERMATITIS NODULARIS HELICIS Standard therapy: Surgical removal; Topical/IL steroids Open label study (n=11) CNH Nitroglycerin patches 5mg/24hr, 12 hours daily, x 2 months 7/11 (63.6%) complete resolution 2 (18%) stopped Rx due to headache; 1(9%) non-responder MOA: Reversal of ischemia due to vasodilation? Supports prior work w/ nitroglycerin gel (2011) Dermatol Ther 27:278, 2014 HIDRADENITIS: METFORMIN Dermatol Ther 27:278, 2014 Refractory to Rx 25 patients (non-diabetic) Metformin 500mg BID to TID maximum, for 6 mo Majority (18/25) had improved Sartorious score, DLQI and PGA JEADV 27: , 2013 I often add finasteride (men) 5mg/d J Dermatol Treat 16:75-8,

7 HIDRADENITIS: OTHER Refractory to Rx n= 20 patients Open label, prospective 6mo Minocycline 100mg QD Colchicine 0.6mg BID Maintenance only colchicine at prior dosage (3mo) All cleared or improved! Aphthous Ulcers from Hell Int J Dermatol. 2017;56: VITAMIN B12 RCT with 58 patients Minimum 6 attacks/yr 1000mcg sublingual B12 QD vs placebo, 6 mo Active Rx: decreased number aphthae per month, decreased duration of each ulcer, decreased pain associated w/ ulcer By 6 mo, 74% ulcer-free Simple, Safe, Cheap J Am Board Fam Med 22:9, 2009 NICOTINE RAS rare in smokers, maybe because nicotine decreases cytokine and IL production and induces keratinization of oral mucosa Med Hypoth 77:185, 2011 Case report: 39 yo female w/ lifelong severe RAS Failed corticosteroids, colchicine, Abx Thalidomide worked, but developed neuropathy 4.5mg nicotine (lozenges) QD x 14 days, followed by 1.5mg lozenges TID x 6 mo (Australia) RAS-free In USA: 4mg and 2mg lozenges available OTC Australas J Dermatol 56:143, 2015 Hurricane Harvey Hurricane Irma Hurricane Maria HURRICANES AND FLOODS! HOUSTON 7

8 Int J Environ Res Public Health Jun 3;14(6). pii: E594. LEPTOSPIROSIS: CHEMOPROPHYLAXIS Comprehensive review and meta-analysis Doxycycline most widely used drug Single dose 200mg OR 200mg/week for 2-4 weeks PRE-exposure dosage significantly reduces morbidity and mortality POST-exposure dosage trends toward benefit but not statistically significant Int J Environ Res Public Health Jun 3;14(6). pii: E594. FLOOD COMING? TAKE 200MG DOXYCYCLINE! Lancet Infect Dis Dec 8. pii: S (17) Road to my office! POST-EXPOSURE BACTERIAL PROPHYLAXIS? French study; MSM who have condomless sexual contact All receiving PRE-exposure HIV prophylaxis Randomized: Single dose doxycycline 200mg within 24 hours versus no antibiotic within 24 hours of sexual contact (n=116 per group) Followup: 10 mos; Occurrence: chlamydia, GC, syphilis 22% presented with bacterial STD in prophylaxis group 42% presenting with bacterial STD in NO prophylaxis group (p =0.007) Adverse GI events: 53% PEP vs. 41% NO PEP (not stat signif) Lancet Infect Dis Dec 8. pii: S (17) RADICALLY DIFFERENT PEARLS THINK OUTSIDE THE BOX! USE RADICALLY DIFFERENT PEARLS Ted Rosen, MD Professor of Dermatology Baylor College of Medicine Houston, Texas 8