Cutaneous Infectious Diseases Reviewed and Updated

Ted Rosen, MD Professor and Vice‐Chair of Dermatology Baylor College of Medicine Houston, Texas Conflict of Interest Disclosure

• Dr. Rosen has disclosed that he has no actual or potential conflict of interest in relation to this topic. Infectious Diseases Include….

Bacteria Fungi Viruses Ectoparasites Parasites Goal

• There are way too many organisms to cover all the myriad of possibilities • I will just review select diseases which you might or are very likely to see B

28 yo febrile female

35 yo febrile female

C 35 yo afebrile male transvestite B

28 yo febrile female

35 yo febrile female

C 35 yo afebrile male transvestite B

28 yo febrile female

35 yo febrile female

C 35 yo afebrile male transvestite B

28 yo febrile female

35 yo febrile female

C 35 yo afebrile male transvestite B

28 yo febrile female Atypical PG w/ AML

35 yo febrile female Angiosarcoma

C 35 yo afebrile male transvestite Granuloma w/ self‐injection silicone Message • Just because it “looks” infectious, doesn’t mean that it is! Clinical mimics! • Always attempt to confirm infection by using the laboratory: Pathology, microbiology, serology, PCR • PS: It is incumbent upon you to provide the laboratory enough information to help them decide what they need to do! General Approach to Infection

1. Listen to the patient; take a good history! (travel, animals) 2. Confirm infectious nature 3. Get help: Micro lab, pathologist, ID consultant 4. Think infection if treatment for “non‐infection” fails Consult: “Subacute Lupus Refractory to Plaquenil” Tinea from new kitten; Response to Naftifine Cream General Approach to Infection 1. Listen to the patient; take a good history! (travel, animals) 2. Confirm infectious nature 3. Get help: Micro lab, pathologist, ID consultant 4. Think infection if treatment for “non‐infection” fails 5. Think infection if you stare at something and are puzzled 6. Why did it happen? Predisposition that can be changed? 7. Could anyone else have it? (Ping‐Pong effect) 8. Could it have prevented from happening again/to others? Bacteria Impetigo • Impetigo contagiosum: Highly contagious • Superficial erosion covered by honey‐colored crust • May be mild itch, sting, burn, pain; one or more spots • Children > Adults • > 70% Staph, < 30% Strep • Renal complication now rare Impetigo Impetigo • CHOICE: Topical versus Oral Rx • TOPICAL Therapy • Mupirocin oint TID x 7d (RESISTANCE is now an issue) • Retapamulin oint BID x 5 d • Ozenoxacin cream BID x 5d • ORAL Therapy • Cephalexin or Dicloxacillin • If MRSA: know local susceptibilities Staphylococci

• According to the Texas State Dept. of Health, the proportion of Staph isolates that are MRSA rather than MSSA, statewide, has steadily increased • In some counties, MRSA comprises >90% of all isolates • MRSA is more virulent, with more complication

https://www.dshs.texas.gov/idcu/health/antibiotic_resistance/mrsa/ MRSA • Boil (Furuncle) most common manifestation • Tender, fluctuant nodule • Most important Rx intervention is incision and drainage • Antibiotics may or may not be required, but…. • I usually DO give them • Gram negatives may cause boils! N Engl J Med. 2017;376(26):2545‐255

N Engl J Med. 2017;376(26):2545‐255 MRSA Boil • Gram negatives may cause boils! • E. coli, Proteus, Klebsiella, Pseudomonas • Delafloxacin, et al MRSA or NON‐MRSA? • Recent hospitalization OR 7.5 • HIV/AIDS OR 4.0 • Prior MRSA skin infection OR 2.8 • IVDU OR 2.8 • Recent (90 days) Abx OR 2.6 • Renal disease/dialysis OR 1.4 • Diabetes w/obesity OR1.1

Int J Antimicrob. Agents 2018;51:43‐46

Acute Bacterial “Run Around” Ligament

Tendon • VERY dangerous • Closed space • Quickly involves bone • May lead to amputation • OPEN UP ABSCESS! • Then: Antibiotics MRSA/Boil • I & D paramount • Parenteral options (IV) • Know your own local • Fever, very high WBC, MRSA antibiogram! immunocompromised, • Doxycyline 100mg BID failed oral therapy • Minocycline 100mg BID • Daptomycin 4 mg/kg IV q 24h • TMP‐SMX DS BID • Linezolid 600 mg IV q 12h • Clindamycin 300mg TID • Ceftaroline 600mg IV q12h • Linezolid 600mg BID • Omadacycline 100mg IV QD after one 200mg loading dose

JAMA 2019;322:457‐58 What about RECURRENT BOILS?

• Address hygiene • Address environment MRSA: Sources….Environment • Investigation 346 households w/ proven index case of MRSA • Los Angeles and Chicago • High rates of initial and persistent (3 mos) MRSA colonization were: Landline phone, bathroom toilet and sink faucet, hairbrush Less: Kitchen faucet & counter, television remote, refrigerator door handle • MRSA300 58% initial and 63% at 3 mo • “Persistent reservoir placing all household members at risk for MRSA infection”

Infect Control Hosp Epidemiol 2014;35:1373‐82 What about RECURRENT BOILS? • Address hygiene • Address environment • Address and treat close household contacts, sexual partners, sports teammates • Address and treat pets (“superficial pyoderma”) • Nasal de‐colonization (mupirocin BID x 5 days) • Body de‐colonization (dilute bleach baths: careful!) • Nasopharyngeal de‐colonization (chlorhexidine)

Clin Cosmet Investig Dermatol. 2014;7:59‐64 Uncomplicated Cellulitis • Swollen, red and tender: Strep • Predisposition: Diabetes, obesity • Cefalexin 500mg QID • Dicloxacillin 500mg QID • Clindamycin 600mg Q8h • IV drugs for severe • Vancomycin if MRSA • Recurrent: Look for portals of entry, such as tinea pedis BEWARE! • Looks like cellulitis, but its not! • Allergic contact dermatitis • Stasis dermatitis • Peripheral edema (CHF) • Lymphedema • Error in diagnosis: About 1/3 cases!

JAMA Dermatol. 2018;154:529‐536 JAMA Dermatol. 2018;154:537‐543 Erysipelas: Facial Cellulitis (Group A beta‐hemolytic Strep pyogenes)

Portal of entry Older adults Fever/chills precede Sepsis is rare, but blood culture IC/IS, cardiac valves, IVDU Pen VK 5‐10d Hospitalize?

Note: Sharp borders

Infect Dis. 2018;50:27‐34 Erythrasma • Red‐brown, scaly in groin, axilla • Looks like tinea cruris (NO central clearing) • KOH, fungal culture negative • Wood’s lamp: “Coral red” • Corynebacterium minutissimum • Topical: Clindamycin 1% or Erythromycin 2% • Oral: Clindamycin 300mg TID Erythromycin 250mg QID Amoxicillin‐clavulanate 500/125mg TID Erythrasma (Groin, Axilla, Toewebs) Cat Bites

• 3‐5 x 106 US animal bites/year • Pasteurella multocida oral flora • 5‐15% animal bites due to cats • Rapid tissue destruction • 50% in children/50% adults • Especially bad if hands, feet • 675,000 cat bites seek aid • Treat asap; oral OK to start, but • 50% of all cat bites infected if progressive, hospitalize for IV

Am Fam Physician. 2014;90:239‐43 Cat Bites • Amoxicillin‐clavulanate 875/125mg BID**** • Doxycycline 100mg BID (second choice) • Cefuroxime 500mg BID (third) • (IV for severe) • (Hand surgery consult) • New: May become Rx of choice Omadacycline 300mg QD after 450mg QD x 2d loading dose

Antimicrob Agents Chemother. 2018 Mar 27;62(4). pii: e02551‐17 Cat Bites

• Immediate Rx urgent • Hand bites: Risk of septic arthritis high, also osteomyelitis • May need open debridement, cleansing of region and drain placed Surgical Wound Infection

• Removal some/all sutures to allow: • Purulent drainage • FOR: Erythema, pain and induration >5cm wound edge • FOR: Fever >38.5oC (101oF) • FOR: WBC > 12,000 • FOR: Tachycardia > 110/min • Adjunctive oral antibiotics • Doxycycline 100mg BID likely best PRE‐Rx

7 Days

2 Days Primary/Secondary/ELI Syphilis: Texas

Rank by rate #18 Rate 8.0/100,000 Rank by cases #3 Cases 2233 (↑14%)

Cases: Dallas ~700 > Houston ~400 > Austin = San Antonio ~325 Syphilis: Resurgent Incubation 9‐90 days (21 avg.) • Texas among top states by # • Chancre: Solitary, indurated painless, shallow ulceration Microbes Don’t Read Textbooks! Syphilis: Resurgent • Texas among top states by # • Chancre: Solitary, indurated painless, shallow ulceration • 5% may be extragenital • Rash: Palms & soles • Chancre + Rash of 2o concurrent: Patient HIV+ • 3‐7% present with alopecia • Oral mucous patches Extragenital Chancre Concurrent Primary + Secondary Lues = HIV+

Clin Infect Dis. 2015;61:281‐7 Concurrent Primary + Secondary Lues = HIV+

Clin Infect Dis. 2015;61:281‐7 Alopecia of Secondary Syphilis

13‐Year‐old boy Mucous Patch Syphilis: Resurgent Chancre of 1o Lues • Benzathine PCN 2.4MU IM x 1 • Alternate Rx: • Doxycycline 100mg BID x 14d • Minocycline 100mg BID x 28d • Tetracycline 500mg QID x 14d • Everything else inferior • (Erythromycin, Ceftriaxone, Azithromycin) Syphilis

• Test for HIV • Encourage barrier protection (condom) • But… • Condom only protects what it covers! Gonorrhea

Rank by rate #22 Rate 170.2/100,000 Rank by cases #2 Cases 47,409 “Bull Head” Clap Soft, ASx swelling In and behind coronal sulcus Minimal to no dysuria Minimal to no discharge Post‐Exposure Bacterial Prophylaxis? • French study; MSM who have condom‐less sexual contact • All receiving PRE‐exposure HIV prophylaxis antiretroviral • Randomized: Single dose doxycycline 200mg within 24 hours vs. no antibiotic within 24 hours of sexual contact (n=116/group) • 10 months; Occurrence of chlamydia, GC, syphilis • 22% presented with bacterial STD in prophylaxis group versus 42% presenting with bacterial STD in NO prophylaxis group (p =0.007); AEs equal (GI) • Message: Single dose doxy effective post‐exposure STD Fungi Fungi: Unique Organisms • Reproductive mechanisms • Dimorphic growth • Nutritional requirements • Cell wall containing chitin, glucan • Cell membrane rich in ergosterol • Size (larger than virus/bacteria) • No photosynthesis • No response to antibiotics Fungi: Unique Organisms • Reproductive mechanisms • Dimorphic growth • Nutritional requirements • Cell wall containing chitin, glucan • Cell membrane rich in ergosterol** • Size (larger than virus/bacteria) • No photosynthesis • No response to antibiotics Cell Membrane MOA

Terbinafine, Naftifine, Butenafine

Clotrimazole, Miconazole, Econazole, Oxiconazole, Sertaconazole, Luliconazole, Ketoconazole Fungi • Superficial disease: Dermatophytes and yeast • “Tinea” & “Monilia” Most treated topically • Trichophyton rubrum 90%, Candida albicans • Onychomycosis (NAIL) and Tinea capitis (HAIR) best Rx systemic, though nails may be either • T. tonsurans major culprit for tinea capitis • Deep fungal disease: Various endemic fungi • Require systemic therapy; May be life‐threatening • Histoplasmosis, Coccidioidomycosis, Sporo • Cryptococcosis, NA/SA Blastomycosis • Mucormycosis, Chromomycosis • Aspergillosis, Candida sepsis Deep Fungal Infection HIV+/Histo • Non‐specific morphology • Febrile abnormal host: HIV+, diabetic, immunosuppressed • Biopsy and culture • Amphotericin‐B • Azoles: Itraconazole, fluconazole, posaconazole, DM/Fusarium voriconazole Cryptococcosis in HIV Small=Resemble MC; Large=Resemble Skin Cancer Deep Fungi NA Blastomycosis Coccidioidomycosis Sporotrichosis Penetrating injury Cats, Rose bushes, Moss NOTE: Sporotrichoid spread = Sporotrichosis

Sporotrichosis Atypical mycobacteria Leishmaniasis Norcardia Tularemia Sporotrichosis Terbinafine vs. Itraconazole • Terbinafine 250mg/d (n = 55) • Itraconazole 100mg/d (n = 249) • Ages 18‐70, all culture positive • Rx duration to healing: ~3 months • Cure rate: Terb 92.7% Itra 92.0% THERMOTHERAPY • Two patients in each group required twice normal dose escalation (500mg/d, 200mg/d) • Adverse events nearly identical 7% Mycopathologia. 179:349, 2011 Hyperthermia

Sporotrichosis Chromoblastomycosis Leishmaniasis Atypical mycobacteria HSV‐1, HSV‐2

J Am Acad Dermatol. 2010;62:909‐27 Hyperthermia and Molluscum

• Small (n=21) Chinese prospective study; patented IR heating unit • 440C (1110F) for 30 minutes, once weekly x 12 weeks • 13 children, 8 sexually active adults (ages 21‐28) • Average # lesions = 59 (i.e. Bad molluscum) • 12/18 complete clearance 12 weeks (children & adults) • Facial lesions relatively resistant compared to other sites • Use heating pad for thermotherapy!!!!

Br J Dermatol. 2017;176:809‐812 Tinea This ’n Tinea That; Dermatophytes Tinea This ’n Tinea That; Dermatophytes

Itchy Scaly Annular Tinea and Systemic Disease

• Cushing’s Disease • Diabetes mellitus • Leukemia/Lymphoma • AIDS Therapy: Cutaneous Tinea • Skin only – topical therapy; Many agents to choose from and all work; be aware of dosing, which varies from agent to agent • Vehicle important (cream, gel, lotion, foam) • Azole: Clotrimazole, econazole, miconazole, ketoconazole, luliconazole, oxiconazole, sertaconazole • Allylamine: Butenafine, naftifine, terbinafine • Hydroxypyridone: Ciclopirox

Br J Dermatol. 2012;166:927‐33 Therapy: Cutaneous Tinea

• Skin only – topical therapy; Many agents to choose from and all work; be aware of dosing, which varies from agent to agent • Vehicle important (cream, gel, lotion, foam) • Azole: Clotrimazole, econazole, miconazole, ketoconazole, luliconazole, oxiconazole, sertaconazole • Allylamine: Butenafine, naftifine, terbinafine • Hydroxypyridone: Ciclopirox

Br J Dermatol. 2012;166:927‐33 Vehicle Importance! Lotion, Foam

GEL Ketoconazole? Oxiconazole? Butenafine? Sertaconazole? Terbinafine? Clotrimazole? Ciclopirox? Econazole? Naftifine?

Luliconazole?

Tinea pedis, manum, corporis, faciei, cruris Br J Dermatol. 166:927, 2012

Meta‐analysis: 135 studies, 15,795 patients NO difference between groups; efficacy NO difference between groups; safety NO difference between groups; tolerability

Allylamines are faster in onset (↓Symptoms) SYSTEMIC ANTIFUNGAL DRUGS

DRUG PO Dermatophytes Saprophytes and Yeast Drug‐Drug or IV? Deep Griseofulvin PO ++ ‐ ‐ EtOH, OCP Fluconazole Both ++ ‐ +++ 2C9, 2C19 Itraconazole Both +++ ++ ++ 3A4 Posaconazole Both ++ +++ +++ 3A4 Voriconazole Both ++ +++ +++ 2C9, 2C19 Isavuconazole IV ? +++ +++ 3A4 Amphotericin IV ? +++ +++ Toxic Terbinafine PO +++ ‐ ‐ 2D6 Caspofungin IV ‐ Aspergillus +++ Cyc‐A Micafungin IV ‐ Aspergillus +++ Sirolimus Anidulafungin IV ‐ Aspergillus +++ None “Yeast” Infection of the Akin: C. Albicans • Bright red, w/ satellite • KOH and/or culture • Stinging, burning, itching • Pustules: rupture • Intertriginous areas • Groin, Axilla, Inframammary • Excessive moisture • Post‐op laying on back • Diabetes • Immunocompromise Candidiasis: Any Azole Topical ‐OR‐ Fluconazole po (150mg QOD x 3 Doses) Tinea Versicolor (“Many Colored”) Summer Months, Mild Itch, Recurrent July, 2013

Oral ketoconazole should not be used as first-line therapy for ANY fungal infection Ketoconazole should be used only for treatment of life-threatening mycoses when the potential benefits outweigh the risks and alternative therapeutic options are not available or not tolerated Oral ketoconazole is no longer indicated for dermatophyte or Candida infections Oral ketoconazole is not indicated for fungal infections of the skin or nails Contraindicated in any individual with liver disease Tinea (Pityriasis) Versicolor

• 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;50:311‐13 Onychomycosis Onychomycosis: KEY POINTS • 4% General population; > DM, aged, HIV • ONLY 50% abn nails fungal**** • KOH, culture, PCR • 90% T. rubrum • Candida: fingernails; WATER • Rarely soil fungi (abn host) • Treat early: better outcome • Treat feet concurrently • Autosomal dominant! • Prevention measures Onychomycosis Rx Itraconazole • 400mg/d x 7d; Repeated monthly 2 Pulses (fingers); 3 Pulses (toes) Terbinafine **** • 250mg daily 6 wks (fingers); 12 wks (toes) Fluconazole • 300mg/week until clear (Off Label*) • Topical agents: Ciclopirox lacquer Efinaconazole, Tavaborole solutions (QDx48wk) • Debridement helps; Laser therapy?

Dermatol Therapy. 2012;25:582‐93 Onychomycosis: Topical Therapy

COMPLETE CURE AGENT MYCOLOGIC CURE (Almost Complete Cure)

Ciclopirox 8% 7.0% (9.3%) 33.0% Efinaconazole 10% 16.5% (24.9%) 54.3% Tavaborole 5% 7.8% (16.6%) 33.5%

Almost complete cure is: < 5%‐10% residual abnormal nail with mycologic cure cure

All data based on package insert

Efinacolnazole: J Am Acad Dermatol. 2013;68:600-608 Tavaborole: J Clin Aesthet Dermatol. 2014;7:13-21 Onychomycosis: Preventing Recurrence

• Wash feet • Changes socks • Alternate shoes • Do NOT go barefoot in hotels, gym locker rooms, pools • Ozone cabinet (shoes)

• Shoe UVC inserts daily J Drugs Dermatol. 2016;15:279‐82 • ?Periodic oral/topical drug? Proximal Subungual KEY POINT

Proximal Onychomycosis Due to HIV, until proven otherwise Viruses Estimated HIV Incidence among Persons Aged ≥13 Years, by Area of Residence 2016—United States Total = 38,700

Note. Estimates were derived from a CD4 depletion model using HIV surveillance data. Estimates rounded to the nearest 100 for estimates >1,000 and to the nearest 10 for estimates ≤1,000 to reflect model uncertainty. 90% HIV+ Have Related Skin Disorders

• Acute retroviral syndrome • Molluscum contagiosum • Itchy face or arms/trunk rash • Bacillary angiomatosis • Psoriasis • Kaposi sarcoma • Seborrhea • Oral warts • Severe cold sores (HSV‐1) • Hypertrophic genital HSV‐2 • Ulcerative genital HSV‐2 90% HIV+ Have Related Skin Disorders

HIV+ Molluscum Contagiosum

• Core removal, curettage, tape stripping, cryosurgery w/ LN2, podophyllin and podofilox, cantharidin, iodine solution, salicylic acid plaster, tretinoin, cimetidine, 10‐15% potassium hydroxide, 3.75‐5% imiquimod cream, 1‐3% cidofovir, interferon‐alpha, candida antigen, thermotherapy, and pulsed dye laser Molluscum Contagiosum

• Core removal, curettage, tape stripping, cryosurgery w/ LN2, podophyllin and podofilox, cantharidin, iodine solution, salicylic acid plaster, tretinoin, cimetidine, 10‐15% potassium hydroxide, 3.75‐5% imiquimod cream, 1‐3% cidofovir, interferon‐ alpha, candida antigen, thermotherapy, and pulsed dye laser Molluscum Contagiosum

• Core removal, curettage, tape stripping, cryosurgery w/ LN2, podophyllin and podofilox, cantharidin, iodine solution, salicylic acid plaster, tretinoin, cimetidine, 10‐15% potassium hydroxide, 3.75‐5% imiquimod cream, 1‐3% cidofovir, interferon‐ alpha, candida antigen, thermotherapy, and pulsed dye laser Common Viral Diseases

Cold Sores HSV‐1

Shingles

Genital Herpes VZV

HSV‐2 Acyclovir, Penciclovir: Same MOA Triphosphorylated and incorporated into DNA polymerase, terminating chain elongation, DNA production and viral replication.

ACV HSV Thymidine kinase ACV-P Cellular kinases (2) ACV-tri P

HSV DNA HSV DNA polymerase X HSV‐1 (Cold Sores) Therapeutic Decision • Episodic therapy • Topical • Oral HSV‐1 (Cold Sores) Therapeutic Decision • Episodic therapy • Topical • Oral • Continuous suppression • Oral • Not very effective Episodic v. Suppressive • Infrequent outbreaks: Episodic • Mild‐Moderate severity: Episodic • Very frequent: Suppressive • Very severe: Suppressive • Eczema (self/child): Suppressive! • EM‐associated: Suppressive! • Surgery, Sunburn: Prophylactic suppression • No prodrome: Suppressive? (If desired) • Patient preference: Either Episodic Rx Seems Reasonable Suppression Seems Reasonable Topical Rx Seems Reasonable Systemic Rx Seems Reasonable Topical Episodic Therapy

Topical Decrease in Decrease in Agent Miscellaneous resolution time pain duration

Vehicle type Acyclovir 0.5-2.0 days None important

OK to apply later Penciclovir 0.7-1.2 days 0.6-1.0 day (papule)

Docosanol Increase in attacks 0.75-1.6 days 0.56 day (OTC) that are aborted

Acyclovir-HC Fewer lesions 1.4 days 1 day progress to ulceration

Arch Intern Med. 2008;168:1137 Newest Rx HSV‐1 • Mucoadhesive Buccal acyclovir 50mg • Single tablet = one dose • Releases massive amounts of acyclovir in oral cavity, to diffuse through mucosa • Reduces time until resolution of outbreak by about 1 day (on par with other agents) • Unique: Reduces future number of outbreaks J Drugs Dermatol. 2016 Jun 1;15(6):775‐7 Oral Episodic Therapy

Oral Decrease in Increase in Agent Miscellaneous Dose resolution time aborted lesion

Acyclovir 14% Must Rx within 1.0 day 48 hours 400mg 5x/5d > placebo Not approved

Valacyclovir 10-22% Must Rx within 1.0 day 48 hours 2gm x 2, 1d > placebo FDA-approved

Famciclovir 2.4-15.4% Must Rx within 1.0 day 48 hours 1.5gm x 1 > placebo FDA-approved

Acta Derm Venereol. 90:122, 2010 Evid B Dent. 9:117, 2008 Arch Intern Med. 168:1137, 2008 J Antimicrob Chemother. 53:703, 2004 Oral Suppressive Therapy

Agent Decreased number Time Miscellaneous of overt outbreaks studied Dose

Acyclovir Not FDA 53% (RTC) 4 mo 400mg BID Approved

Not FDA Valacyclovir 50% (RTC) 4 mo Approved 500mg-1g/QD

Not FDA Famciclovir Short Data very soft Approved 500mg BID term

J Evid Based Dent Pract. 2013;13:16 Oral Surg Oral Med Oral Pathol Oral Radiol. 2012;113:618 Arch Intern Med. 2008;168:1137 J Drugs Dermatol. 2007;6:400 Cutis. 2003;71:239 Derm Surg. 1999;25:242 HSV‐2 (Genital Herpes) Therapeutic Decision

• Episodic therapy • Oral (mild, infrequent) • Continuous suppression • Oral (severe, frequent) HSV‐2 (Genital Herpes) Oral Therapy

DRUG EPISODIC SUPPRESSIVE COMMENT

Acyclovir 400mg TID x 5d 400mg BID Least costly 800mg TID x 2d 800mg BID x 5d Valacyclovir 500mg BID x 3d 500 or 1000mg QD Very effective 1g QD x 5d

Famciclovir 125mg BID x 5d 250mg BID Less effective 500mg, 250mg BID suppression x 2 1000mg BID x 1 Genital Herpes: Chronic Suppression Valacyclovir 500‐1000mg QD

• Reduces overt outbreaks (~75%) increasingly so with longer duration of suppressive Rx • Reduces frequency of viral (73%) shedding, including ASx shedding • Reduces transmission to seronegative partners (>50%)

N Engl J Med. 2004;350:11‐20. Acyclovir Resistance • Rare in normal hosts with community acquired infection with either HSV‐1 or HSV‐2 • Incidence: about 1‐1.5% of new infections • In HIV+ or immunocompromised, may be 5‐10% of isolates lack viral TK, thus resistant • Less often: TK is present, but not very functional or viral DNA polymerase altered to resist drug • Trifluorothymidine, Imiquimod, Cidofovir: Topical • Foscarnet, Vidarabine, Cidofovir: IV • For details, see… Dermatol Clin. 2003;21:311‐20 HSV and Pregnancy

• Attempt to protect newborn baby from neonatal herpes • At week 36 of gestation, CDC now recommends: • Acyclovir 400mg TID • Valacyclovir 500mg BID

2015 CDC STD Rx Guidelines Genital Herpes in HIV+ (Immunocompromised) VZV Therapy (Herpes Zoster, “Shingles”)

DRUG EPISODIC COMMENT

Acyclovir 800mg 5x daily x 7 days IV for severe disease 10mg/kg IV Q8h x 7 days Start in first 72hr

Valacyclovir 1000mg TID x 7days Start in first 72hr

Famciclovir 500mg TID x 7 days Start in first 72hr VZV Therapy (Herpes Zoster, “Shingles”)

DRUG EPISODIC COMMENT

Acyclovir 800mg 5x daily x 7 days IV for severe disease 10mg/kg IV Q8h x 7 days Start in first 72hr

Valacyclovir 1000mg TID x 7days Start in first 72hr

Famciclovir 500mg TID x 7 days Start in first 72hr

Simultaneous initial Rx with gabapentin (+ antiviral) may actually PREVENT post‐ herpetic neuralgia Arch Dermatol. 2011;147:901‐7 VZV Therapy: LARGE DOSES OF ACYCLOVIR

DRUG EPISODIC COMMENT Acyclovir 800mg 5x daily IV for severe x 7 days disease Start in first 72hr Valacyclovir 1000mg TID x Start in first 7days 72hr 8-12 OZ WATER PER DOSE Prevents drug ppt renal tubules ~2% HIV: presents w/ HZ CD4+ T‐cells <50 Severe or Disseminated Young (unexpected) age

19‐year‐old AA Female Genital Warts (HPV 6, 11) Therapeutic Options

Patient-applied Provider-administered6,7

Imiquimod cream1,2 Trichloroacetic acid Bichloroacetic acid

Cryotherapy Podofilox gel/solution3,4 Podophyllin resin

Sinecatechins ointment5 Laser therapy/surgery

1. Aldara Cream, 5% [package insert]. Bristol, TN: Graceway Pharmaceuticals; November 2007. 2. Zyclara Cream, 3.75% [package insert]. Bristol, TN: Graceway Pharmaceuticals; March, 2011 3. Condylox gel, 0.5% [package insert]. Corona, CA: Watson Pharmaceuticals; November 2007. 4. Condylox topical solution, 0.5% [package insert]. Corona, CA: Watson Pharmaceuticals; November 2007. 5. Veregen ointment, 15% [package insert]. Melville, NY; PharmaDerm, a division of Sandoz US, Inc.; September 2008. 6. Beutner KR, Ferenczy A. Am J Med. 1997;102:28-37. 7. Workowsky KA, Berman SM. MMWR Recomm Rep. 2006;55:No.44-11. Rx EGW

DRUG MECHANISM OF ACTION (presumed)

Imiquimod 5% Immunostimulatory (TNF, IL12, Interferon)

Imiquimod 3.75% Same

Podofilox 0.5% Infected cell necrosis (?microtubule)

Sinecatechins Ointment 15% Immunostimulatory, Apoptosis, Antiviral Green tea derivative Patient‐Applied Therapies: Dosing and Administration

Treatment Application/Dose Duration of therapy

Imiquimod cream1 Apply thin layer at bedtime 3 nights/week, Up to 16 weeks 5% wash off after 6-10 hours

Imiquimod cream2 Apply thin layer at bedtime daily for 2 Up to 8 weeks 3.75% months

3 days followed by Podofilox3,4 Apply BID (max, 0.5 mL/d) 4-day rest; repeat for up to 4 cycles

Apply thin layer to each Up to 16 weeks Sinecatechins4 15% wart TID (D/C when clear)

1. Aldara Cream, 5% [package insert]. Bristol, TN: Graceway Pharmaceuticals; November 2007. 2. Zyclara Cream, 3.75% [package insert]. Birstol, TN: Graceway Pharmaceuticals; March, 2011. 3. Condylox gel, 0.5% [package insert]. Corona, CA: Watson Pharmaceuticals; November 2007. 4. Condylox topical solution, 0.5% [package insert]. Corona, CA: Watson Pharmaceuticals; November 2007. 5. Veregen ointment, 15% [package insert]. Melville, NY; PharmaDerm, a division of Nycomed US, Inc.; September 2008.

“OLD” Shingles Vaccine • LIVE Attenuated Oka‐strain of VZV • 14x concentration of chickenpox vaccine • SQ administration, one dose • Overall efficacy: Reduces risk of shingles by 51%, but better when given in younger pt • Nov, 2011: Lowered age of administration to > 50, where shingles risk reduced by 70% • AE: Erythema, pain, swelling or itching at vaccination site

N Engl J Med. 352: 2271, 2005 Clin Infect Dis. 54:922, 2012 “NEW” Shingles Vaccine

• Recombinant subunit (GP‐E) • IM administration, two doses • Overall efficacy: reduces risk of shingles by 90‐97%, equally at all ages (even >70); Reduces PHN 88% • Approved > 50 • AE: erythema, pain, swelling at vaccination site, and/or GI distress, fever, arthralgia, myalgia (common) but only lasts 1‐3 days

Med Lett Drugs Ther. 2017;59:195‐196 N Engl J Med. 2016; 15;375(11):1019‐32 MMWR Morb Mortal Wkly Rep. 2019 Feb 1;68(4):91‐94 HPV Vaccines • Bivalent: HPV 16, 18 • Quadrivalent: HPV 6,11,16,18 • Nanovalent: HPV 6,11,16,18,31,33,45,52,58 • Series of three SQ injections (0,2,6 months) • ONLY TWO (0 and <6mo) if patient <15 years old • Protection: 75% (anal SCCA) to 99% (EGW) • AEs: Rare (syncope) • Indicated for males and females aged 9‐45 • Recently extended to age 45 Ectoparasites

US Tick Borne Diseases • Anaplasmosis Outside US Tick Borne Diseases • Babesiosis • African Tick Bite Fever • Colorado tick fever • European and Asian Lyme • Ehrlichiosis • Tickborne encephalitis • Heartland (?Bourbon Virus) • Boutonneuse Fever • Lyme (and B. miyamotoi) • Crimean‐Congo Hemorrhagic fever • Powassan virus • Omsk Hemorrhagic fever • RMSF • Kyasansur Forest Disease & • STARI Alkhurma fever • Tickborne relapsing fever • Severe Fever and Thrombocytopenia • Tularemia Syndrome in Asia • Summer monthsTick‐Borne Diseases • Common: Headache, myalgia, fever • Erythema migrans: Lyme, STARI • Centripetal spread rash: RMSF • GI symptoms: Ehrlichiosis, Anaplasmosis & Babesiosis • Confusion, Emotional lability: Ehrlichiosis & Babesiosis • Doxycycline for all but Babesiosis Submit a Tick: Identification and Screening

• Department of State Health • Questions about ticks and Services tick‐related illnesses: • ATTN: Zoonosis Control – MC 1956 • (512) 776‐7255 • 1100 W 49th St • Austin, TX 78756 Tick! Ticks! Tick Removal Scabies • Sarcoptes scabiei • Direct skin‐to‐skin contact Most often sexual contact Transmitted by healthcare workers • Incubation to Sx: 4‐6 weeks Shorter w/ subsequent attacks • Total mites on body 10‐12 Only 5‐6 w/ subsequent attacks • Pruritus major symptom • Cutaneous findings Burrow: Fingerwebs, wrists, genitalia Rash: generalized, eczema‐like Scabies Diagnosis • #15 Scalpel blade + Mineral oil • Scrape (interdigital web, wrist, peno‐scrotal skin) Scabies Rx

Drug MOA Administered Comment Ivermectin Neurotoxin PO; 200ug/kg x 2 Not FDA approved (Chloride gated channels)

Permethrin 5% Cr Neurotoxin Topical (12 hr) x 2 Equal to (Sodium gated channels) Ivermectin

Sulfur 10% pet GI toxin Topical QHS x 3d Compounded Crotamiton 10% Cr Unknown Topical QD x 2‐3d Not as effective Lindane 1% Lot Neurotoxin Topical 8‐12 hr x 1 Toxic to humans (GABA neurotransmission) Benzyl benzoate Uncertain Topical x 24 hr (x1‐2) Not in USA Scabies Rx

Drug MOA Administered Comment Ivermectin Neurotoxin PO; 200ug/kg x 2 Not FDA approved (Chloride gated channels)

Permethrin 5% Cr Neurotoxin Topical (12 hr) x 2 Equal to (Sodium gated channels) Ivermectin

Sulfur 10% pet GI toxin Topical QHS x 3d Compounded Crotamiton 10% Cr Unknown Topical QD x 2‐3d Not as effective Lindane 1% Lot Neurotoxin Topical 8‐12 hr x 1 Toxic to humans In Europe, topical and oral therapy used concurrently(GABA neurotransmission) Benzyl benzoateMeta‐analysis of 52 RCT, 9917 patients, supports this Uncertain Topical x 24 hr (x1‐2) Not in USA

J Am Acad Dermatol. 2019 May;80(5):1435‐1444 Br J Dermatol. 2019 Apr;180(4):888‐893 Crusted (“Norwegian”) Scabies

• Immunocompromised, including HIV+, steroids • VERY contagious • Fissures: bacterial sepsis • Best Therapy: • Ivermectin 200ug/kg given on days 1,2,8,9,15 • Permethrin 5% QD x 7, then BIW Lice (Pediculosis)

Head and Body Lice Pubic Lice (Crabs) Pubic Louse Rx

Drug MOA Administered Comment Permethrin 1% or 5% Cr Neurotoxin Topical (10 min) May re‐treat in 7‐10 days (Sodium gated channels)

Pyrethrins + Piperonyl Neurotoxin Topical (10 min) May re‐treat in 7‐10 days butoxide (Sodium gated channels) Ivermectin Neurotoxin PO; 200ug/kg x 2 Not FDA approved (Chloride gated channels)

Malathion 0.5% Lot Neurotoxin Topical 8‐12 hours May re‐treat in 7‐10 days (Binds to cholinesterase) (Resistance Rare) Head Louse Rx Drug MOA Administered Comment Permethrin 1% Neurotoxin Topical (10 min) Must re‐treat in 7‐10 days Crème rinse (Sodium gated channels)

Pyrethrins + Piperonyl Neurotoxin Topical (10 min) Must re‐treat in 7‐10 days butoxide (Sodium gated channels) Ivermectin 0.5% Lotion Neurotoxin Topical (10 min) One application (Chloride gated channels)

Malathion 0.5% Lot Neurotoxin Topical 8‐12 hours Must re‐treat in 7‐10 days (Binds to cholinesterase) Spinosad 0.9% Neurotoxin Topical (10 min) Must re‐treat in 7‐10 days Suspension (nicotinic acetylcholine rec) Benzyl alcohol 5% Lotion Asphyxiation Topical (10 min) Must re‐treat in 7‐10 days in Mineral Oil Resistance common NUVO Method (Head Lice)

• Saturate scalp with a Gentle Skin Cleanser • Hair dryer: totally dry scalp • Material remains in place 8 hours • Washed out (May need dish detergent) • Repeated once weekly x 3 • Asphyxiates lice • >90% cure rate • Cheap, OTC, Safe, Effective Parasites Dog or cat Larval Migrans hookworm • Cryosurgery looking for a home! • Topical thiabendazole • Oral thiabendazole • Oral ivermectin • Oral albendazole • 200mg BID x 7 days • MOA: binds to tubulin in GI tract, impairs glucose absorption • Transient ↑LFTs, Headache, each 10% • 78/78 cured w/ regimen J Dermatol Treat. 23:189, 2012 Leishmaniasis Endemic US Leishmaniasis

JAMA Dermatol. 2018;154:1032‐1039

• Median age 61 (range 3‐89) • 68% Female • 100% Leishmania mexicana • ALL in Texas, Southern OK JAMA Dermatol. 2018;154:1032‐1039 OK

JAMA Dermatol. 2018;154:1032‐1039 JAMA Dermatol. 2018;154:1032‐1039 Traditional Therapy

Pentavalent Antimony Thermotherapy • Enhances ROS and NO • Denatures critical production in parasite enzymes histiocytes • Destroys parasite • Enhances T‐cell nucleic acid function and TH1 • ~1300F response • Blistering, Scarring • Inhibits parasite energy production Miltefosine

• Lecithin derivative; MOA ? • 2.5mg/kg/day orally; AEs: 10% inc LFTs • Visceral leishmaniasis and Cutaneous leishmaniasis (New World) • Variable response depending on type and location (Mucosal > Cutaneous) • One course = $32,000 Clin Infect Dis. 38:1266, 2004 Expert Opin Pharmacother. 6:1381, 2005 Clin Infect Dis. 44:350, 2007 & Am J Trop Med Hyg. 82:1, 2010 I hope you are now ready for the next skin infection you see… Audience Polling Question #1

The most important therapeutic intervention for a boil is? 1. Administration of antibiotics 2. Application of heat 3. Incision and drainage 4. Application of cold 5. Application of mupirocin Audience Polling Question #2

Endemic U.S. leishmaniasis is found in? 1. Texas and Oklahoma 2. Texas and Louisiana 3. Texas and Arkansas 4. Texas and New Mexico 5. Florida and Louisiana Audience Polling Question #3

Drug of choice for most tick‐borne illnesses is? 1. Minocycline 2. Azithromycin 3. Levofloxacin 4. Cephalexin 5. Doxycycline Audience Polling Question #4

Drug of choice for an infected cat bite is? 1. Minocycline 2. Azithromycin 3. Amoxicillin/Clavulanate 4. Cephalexin 5. Trimethoprim‐Sulfamethoxazole Audience Polling Question #5

Oral drug of choice for scabies is? 1. Permethrin 2. Ivermectin 3. Malathion 4. Albendazole 5. Thiabendazole