Didactic Series. HIV related Dermatologic Manifestations. Ankita Kadakia, MD UC San Diego, Owen Clinic April 26, 2018

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Didactic Series HIV related Dermatologic Manifestations Ankita Kadakia, MD UC San Diego, Owen Clinic April 26, 2018 1

Learning Objectives 1) Recognize common dermatologic manifestations associated with HIV and underlying disorders 2) Understand diagnosis and treatment of dermatologic manifestations 3) Review immunologic factors related to skin manifestations 2

HIV Dermatology Presenting sign of HIV infection is skin manifestations HIV positive individuals due to defects in cell immunity are predisposed to certain bacterial, fungal, viral, and mycobacterial disease with skin manifestations Skin diseases which are common in general population are exacerbated in HIV with increased prevalence American Academy of Dermatology 3

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Infectious Dermatoses Bacterial Mycobacterial Fungal Viral Parasitic Noninfectious Dermatoses Classifications Systemic and Cutaneous Malignancy Drug reactions Epidermal disorders Papular and follicular eruptions Pigment disorders 5

https://www.aids.gov.hk/pdf/g190htm/21.htm 6

Infectious Dermatoses Bacterial Fungal Viral Parasitic 7

Case Presentation 50 y homeless M, CD4 22, VL 110K, not on ARVs, living in a tent under a bridge, recently took in a female cat and her kittens. He presents to the ER 3 months later with fever, weight loss, and dark red papules on his arms and trunk. 8

Left: P. Volberding, MD, UCSF Center for HIV Information Image Library Right: G. Beatty, MD; A. Lukusa, MD, HIV InSite 9

Poll Question What could the lesions be due to? A. Syphilis B. Kaposi s sarcoma C. Sporotrichosis D. Bacillary angiomatosis (Bartonellosis) 10

CD4 <50 Bacillary Angiomatosis Bartonella henselae / Bartonella quintana kitten scratches and fleas Systemic lesions in Liver, spleen, bone, lymph nodes Bartonella PCR or blood culture Doxycyline, macrolides have activity MAC prophylaxis is protective 11

Bacterial Dermatoses Staph aureus (skin abscess,folliculitis, carbuncles) Syphilis ( secondary syphilis, gumma, chancre) Bacillary angiomatosis Nocardia Mycobacterial TB and NTM 12

52 participants, HIV +/-, MRSA+/-,measured MRSA-specific CD4 T-cell responses including IFN-gamma in skin biopsies and blood Lower frequency of IFNγ+ producing CD4 memory T cells compared to HIV-uninfected participants with MRSA SSTIs Increasing CA-MRSA causing skin and soft tissue infections MRSA colonizes 8.8% PLWHIV in North America PLWHIV were 18-fold more likely to have CA-MRSA infections than uninfected and twice as likely to have recurrences Lower CD4 counts and low nadir CD4 Higher peak RNA levels Not on ART Close contact in MSM and multiple sex partners 13

Fungal Dermatoses Primary Cutaneous Candidiasis Seborrheic dermatitis of scalp and face Tinea/onychomycosis Acute pseudomembranous candidiasis (thrush): The classic multiple white-flecks on the tongue, buccal mucosa, and palate Muco-cutaneous Oropharyngeal candidiasis Chronic hyperplastic candidiasis: Thick white plaques on the buccal mucosa Invasive Fungal with cutaneous lesions Cryptococcus Histoplasma Acute atrophic (erythematous) candidiasis: Erythematous patches on the palate Penicillium Cocci Blastomycosis Sporotrix 14

Pearly flesh colored papules indicate disseminated cryptococcosis Raised red papules of disseminated Histoplasmosis Courtesy of Dr.Stephen Raffanti 15

Poll Question 35y M with HIV, CD4 250, VL ND, on ART c/o of recurrent painful ulcerations in the anal cleft. Took acyclovir 5x s/day for 10 days with no relief. Similarly 3 months ago did not respond to acyclovir. You confirm HSV by PCR of a lesion. What should you do next? A. Test for Thymidine Kinase mutation and empirically start Valganciclovir B. Test for VZV Ab and give IVIG C. Start Foscarnet immediately 16

Viral Dermatoses HSV VZV/Herpes Zoster Molluscum contagiosum CMV HPV Vesicles- grouped in HSV and VZV Umbilicated in Molluscum Ulcerations in HSV, CMV Verrucous growth in HPV 17

Parasitic Dermatoses Scabies Norwegian (Crusted) Scabies webmd.com 18

Scabies Superinfestation in Norwegian scabies occurs in advanced AIDS, HTLV coinfection Permethrin 5% cream once, can reapply after 14 days Need to treat household contacts Ivermectin 200 mcg/kg oral, at least 2 doses taken 7 days apart 19

Non-Infectious Dermatoses Systemic and Cutaneous Malignancy Drug Reactions Epidermal Disorders Papular and Follicular Eruptions Pigment Disorders 20

Most Common Non-infectious Dermatoses Psoriasis Eosinophilic Folliculitis Seborrheic Dermatitis Atopic Dermatitis Xerosis Prurigo nodularis Drug reaction 21

Cedeno-Laurent et al. Journal of the International AIDS Society 2011, 14:5 22

Systemic and Cutaneous Malignancy Kaposi s sarcoma Lymphoma Melanoma Basal cell carcinoma Squamous cell Carcinoma 23

Kaposi s Sarcoma http://visualsonline.cancer.gov 24

Kaposi s Sarcoma Decreased prevalence with more ART Associated with HHV-8 More extensive disease at low CD4 counts ART can prevent / regress lesions unless extensive cutaneous disease Extensive cutaneous disease requires adjunct chemo with Doxorubicin Radiation therapy for localized lesions 25

Kaposi s Sarcoma Have to look for mucocutaneous lesions- Oral and rectal exam MC visceral site is GI tract followed by pulmonary Workup for visceral lesions includes EGD/Colonoscopy, CT Chest Steroids worsen KS so avoid systemic steroids including steroid inhalers and topical 26

Poll Question 45 y M, new HIV diagnosis, CD4 255, VL 55K, starts Triumeq. 3 days later he develops painful blisters on his arms and trunk, 5 days later the skin starts to peel near the blisters and he feels like he has a bad sunburn. What do you do? A. Prescribe Acyclovir for Herpes Zoster since he is likely reconstituting his immune system B. Test for HLA B5701, if negative then continue Triumeq C. Stop Triumeq immediately and give fluids and steroids D. Treat for MRSA skin infection with Bactrim 27

Drug Eruption Increased due to ART, 20 to 100 times more common Can occur with any ART or OI prophylaxis ( Nevirapine/sulfa) Mild form: Maculopapular exanthem or morbiliform rash Toxic epidermal necrolysis Stevens Johnson syndrome DRESS ( drug reaction with eosinophilia and systemic symptoms) 28 Dermatol Res Pract. 2017; 2017: 6216193.

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SJS <10% BSA TEN >30% BSA HLA types like B5701 with abacavir hypersensitiviy syndrome Drug specific CD8+ cytotoxic lymphocytes can be detected in the early blister fluid. They have some natural killer cell activity and can probably kill keratinocytes by direct contact. Cytokines implicated include perforin/granzyme, Fas-L and tumour necrosis factor alpha (TNFα). Dermnet NZ 31

Epidermal Disorders Psoriasis Xerosis ( severe generalized itching and dryness) Seborrheic dermatitis 32

Psoriasis Any CD4 count Worsening of psoriasis with HIV Increase prevalence of psoriatic arthritis Inverse psoriasis occurs in body folds, smooth shiny red lesions Topical steroids, retinoids, vitamin D replacement not as effective in HIV Responsive to ART 33

Cedeno-Laurent et al. Journal of the International AIDS Society 2011, 14:5 34

Inverse Psoriasis http://psoriasismedication.org/flexural-or-inversepsoriasis/ 35

Classic Psoriasis American Academy of Dermatology Well circumscribed erythematous plaques with silver scaling 36

Papular and Follicular Eruptions Eosinophilic folliculitis Prurigo nodularis- pruritic nodules on extremities Pruritic Papular Eruption- papular and pustular eruptions on extensor surfaces and dorsum of hands 37

Eosinophilic Folliculitis Raised pruritic nodules with pustular head on erythematous base Courtesy of Dr.Stephen Raffanti 38

Eosinophilic Folliculitis Elevated IgE, peripheral eosinophilia CD4 < 300 Inflammatory condition and often diffuse Th2 cytokine response to an unknown antigen (Pityrosporum ovale or Demodex folliculorum) elevation of IL-4, IL-5 and chemokines that mediates chemotaxis, recruits eosinophils in the allergic late phase reaction 39

Eosinophilic Folliculitis Skin biopsy: Intense infiltration of eosinophils around sebaceous glands/hair follicles, no PMNS or organisms Improves with ART Topical steroid creams,oral antihistamines for mild disease Isotretinoin, Itraconazole, Phototherapy, moderate to severe disease 40

Prurigo nodularis http://bestpractice.bmj.com/topics/en-gb/855 41

Pigment Disorders Hyperpigmentation ( Zidovudine) Vitiligo- unknown pathogenesis but thought to be autoimmune and possibly viral trigger to melanocytes Vitiligo treatment: topical corticosteroids, vitamin-d derivatives, calcineurin inhibitors, photochemotherapy 42 https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4360494/

Vitiligo https://en.wikipedia.org/wiki/vitiligo#/media/file:vitiligo2.jpg 43

References American Academy of Derm- HIV module Mandel, Douglas and Bennet s Principles and Practice of Infectious Disease ed.2011 aidsetc.org Cedano et.al, New Insights into HIV-1 Primary Skin Disorders; Journal of the International AIDS Society 2011, 14:5 44