HIV-Dermatology Concepts in 2011 Toby Maurer, MD Dept of Dermatology University of California, San Francisco Skin disease that is catalyst for HIV testing and indication for starting EARLY antiretrovirals (ARV s) How does the skin in HIV demonstrate chronic inflammation and premature aging and what can you do about that? Any problems associated with starting ARV s early? Early Detection of KS-pt placed on meds in spite of having high CD4 count 1
CLUES-look for high yield locations KS drives down CD4 counts Can occur in CD4 s in the 800 s IAS guidelines: start meds whenever KS is seen in HIV irrespective of CD4 count 2
Widespread KS with Declining CD4 counts Widespread KS with low CD4 Often have other concomitant disease like toxoplasmosis, PCP CD4 s under 100 Non-adherent patients At risk for Immune reconstitution syndrome 25-30% mortality rate even with best of treatment Treatment These guys are sick-too sick for doxil? Too well for doxil-so just start ARV s? High burden of KS-might die from KS immune reconstitution ANSWER: start doxil and ARV s and support through NO PREDNISONE-would be nice to turn off the associated inflammation but prednisone exacerbates KS 3
KS started with low CD4-pt now with High CD4-KS persisted Diagnosed with KS long ago with low CD4 s Have been ARV adherent for years VL undetectable, high CD4 s for years KS NEVER went away KS usually involving lymph channels Maintained on doxil, taxol, etc-now shortage of these drugs! NEED new meds-clinical trials AIDS Malignancy Consortium Aroused quiescent KS/HHV8 Stable KS patients with few lesions Well controlled KS patients Some are HIV negative but with KS Sudden exacerbation of KS with steroids in all forms-potent topical, intrarticular injections, inhalers BEWARE.. Treatment: stop steroids, check for other strange ingredients like growth stimulants?follow?, XRT, doxil? 4
Psoriasis Antiretrovirals have a direct effect on the inflammation, on those cytokines Act immediately even before the CD4 cells have a chance to stabilize CD4 cells stabilize after 12-16 weeks on HIV meds 5
TNF blockers Don t want to use in pts who have latent TB Don t want to use in pts with Hepatitis B-deaths Being explored in HIV to turn off cytokines before cytokines have a chance to damage the patient Worry about turning off TNF alpha in HIV-may be good but may be bad Lessons Learned KS and Psoriasis-look for it-start ARV s at any CD4 count Eczema Antiretrovirals(ART) have turned HIV infection into a chronic disease Starting to see pts who are fatigued taking ART s And with adherence, we are seeing some interesting long term effects: Chronic Inflammation Premature aging Inflammation is chronic if CD4 was ever lower than 200 Mirmirani-Women s Interagency Health Survey-JAAD 2001? Irreparable damage to CD4 functionality if meds started too late? 6
Treatment of Eczema Mid-potency steroids (triamcinolone 0.1% ) ointment Emollients Is malnutrition a component? Is photoexposure a component? Keep down the staph aureus 7
Pruritic Papular Eruption Recurrent episodes in 2 years of followup even in patients who started antiretrovirals at CD4 ave = 350 with full adherence (UARTO cohort in Uganda) and undetectable viral load Reservoir effect? Chua 2011 8
Buttock/flank Acne Looks like folliculitis Occasionally grows out staph Usually sterile pustules, boils, cysts Does not respond to antibiotics Long term ARV controlled patients with high CD4 counts Treatment Low dose isotretinoin for chronic acne BUT Prevent chronic inflammation Start effective ARV s before chronic inflammation can set in 9
Chronic Activation of the Immune system Not good over the long-haul: Chronic Inflammation-Eczema, acne?premature Aging? How does chronic inflammation age the immune system? Evidence from patients that have had HIV for 20 years HIV has been well controlled but starting to see premature aging as marked by: Heart disease-mi s around the age of 50 Carotids with plaques CRP s that are sky high Kidney function declining 50 yr olds have kidney function of 60-65 year olds Dementia occuring in 50 year olds Indolent KS with High CD4 (KS eliters) Reminiscent of Classical KS (older Mediterranean man with few lesions on lower legs) Not old and not Mediterranean 50 year olds HIV since the beginning (ave. duration of HIV 17 years) Adherent to every new drug that came along Viral load undetectable for years, high CD4 count 10
Something s happening here; what it is ain t exactly clear Seeing SCC s RECURRING in greater number and in half the time in wellcontrolled HIV infected pts -Chren M at UCSF? Premature aging characterized by problems with immune surveillance? Have noted this clinically-eruptive SCC s and aggressive SCC s in pts in their 50 s 11
What happens when you start ART at high CD4 count? Drug reaction-rare Eosinophilic folliculitis-with underlying concomitant disease Molluscum immune reconstitution Acne immune reconstitution Epidermodysplasia verruciformis exacerbation Epidermodysplasia verruciformis Specific wart type 5 and 8 Commonly seen in HIV infected children in Africa See it in our HIV infected population in SF presents as flat warts around neck and on arms Exacerbation with ART Have never seen malignant transformation into SCC 12
Molluscum Immune Reconstitution Nadir around 200 Rapid rise in CD4 count Sterile pus All biopsies c/w molluscum with surrounding inflammatory cells 13
Immune reconstitution Acne Not necessarily at low CD4 counts In fact, need some CD4 cells to mount this response Tx with oral antibiotics,? prednisone,? isotretrinoin 14
Eosinophilic Folliculitis Eosinophilic Folliculitis 15
Penicilliosis All had concomitant disease-systemic fungal, TB All had CD4 counts that were around 200 Started ARV s and got a severe TH2 type inflammatory response (eosinophilic) that was immediate and severe Left with significant scarring indicating that this was a severe inflammatory condition 16
Lessons Learned Should systemic steroids be started? Don t do it in pts with systemic fungus Don t do it in IRIS wart reactions, don t do it in KS-makes disease worse Can thalidomide be used? Borrowing ideas from leprosy where we use it in type and type 2 reactions. Look for skin diseases that clue you in to HIV status Start ARV s when you see skin diseaseindication that immune system is dysregulated Start ARV s early so chronic imflammation/ premature aging does not set in Might set off some immune reconstitution in the skin even with high CD4 counts-patience, treat through, beware of systemic steroids! Thanks Happy Holidays 17