J. Tyler Lonergan MD of UC San Diego Owen Clinic presents "Owen Clinic Case" at AIDS Clinical Rounds

1. The UC San Diego AntiViral Research Center sponsors weekly
presentations by infectious disease clinicians, physicians and
researchers. The goal of these presentations is to provide the most
current research, clinical practices and trends in HIV, HBV, HCV, TB
and other infectious diseases of global significance.
The slides from the AIDS Clinical Rounds presentation that you are
about to view are intended for the educational purposes of our
audience. They may not be used for other purposes without the
presenter’s express permission.
AIDS CLINICAL ROUNDS

2. J.#Tyler#Lonergan,#MD#
Clinical#Professor#of#Medicine#
UCSD#Health#Systems#
April#24,#2015#

3. 60#yo#HIVHinfected#
(CD4=264/13%,#VL<40#
on#ART)#man,#w/#hx#of#
anal#dysplasia/#
condyloma,#anogenital#
HSV,#and#squamous#cell#
carcinoma#of#lip#who#
presents#with#this#
enlarging,#painful,#
exophyUc#scrotal#lesion#
for#two#months#

4. 1. Condyloma#acuminatum##
2. Squamous#cell#carcinoma#
3. Lymphoma#
4. Herpes#simplex#
5. Syphilis#(Condyloma#lata)#

5. 1997:#HIV##
Nadir#CD4#=#10#(‘99),#MDR,#due#to#past#poor#
adherence,#suppressed#now#with#DRV/r/RAL/ETR#
1999:#Cryptosporidiosis#
1999:#Cryptococcal#meningiUs##
2000:#Primary#CNS#lymphoma,#s/p#whole#brain#
XRT#
2003:#Squamous#cell#carcinoma#of#lower#lip,#s/p#
excision#and#XRT#

6. Recurrent#oral,#anal#and#genital#HSV#on#
acyclovir#suppression#
Anal#dysplasia/condyloma#
OHL#
Oral#candidiasis#
Recurrent#C.#difficile#coliUs#
CogniUve#impairment#related#to#HIV,#brain#
radiaUon#
Depression/Anxiety#
Hypertension#
LUTS#

7. Legally#immigrated#from#Cuba#as#a#teenager#in#
1960s#
Worked#for#US#postal#service#for#several#years#
unUl#became#ill#and#qualified#for#disability#in#
late#90s#
Lives#alone#in#SecUon#8#apartment#in#Hillcrest,#
has#SW#and#IHSS#worker,#meals#on#wheels#
MSM,#not#sexually#acUve#for#years#
Former#smoker#
No#history#of#substance#abuse#

8. 2001H2014:#Recurrent,#painful,#large#(2H5#cm),#
ulceraUve,#hypertrophic#lesions#on#scrotum#and#
R#chin/lower#lip#area#
IniUally#episodes#infrequent#(once#every#1H2#
years)#but#became#frequent#(new#lesions#within#
a#week#of#compleUng#therapy)#and#then#
refractory#to#treatment#and#persistent#
20#hospital#admissions#for#treatment;#one#
lasted#over#4#months#

10. MulUple#biopsies#from#chin/lip#and#scrotal#
lesions#at#different#Umes#to#confirm#previous#
diagnosis#and#rule#out#alternaUve#ones##

17. Swabs#from#chin#and#genital#lesions#grew#HSV#
from#cultures##
HSV#PCR#tesUng#idenUfied#HSV#type#2#from#chin#
and#scrotal#lesions#

18. Oral#Acyclovir/Valacyclovir/Famciclovir:#
ineffecUve#for#hypertrophic#lesions#irrespecUve#
of#dose#or#duraUon.###Typical#HSV#ulcers#
remained#responsive.##Prescribed#acyclovir#for#
suppression#but#adherence#poor#unUl#recently#

19. Hypertrophic#lesions#presumed#to#be#acyclovir#
resistant#based#on#lack#of#clinical#response.#
AnUviral#suscepUbility#tesUng#in#2012.##From#
same#HSV#culture:##
ARUP#phenotypic#assay#demonstrated#HSV#
resistance#to#acyclovir#and#ganciclovir#and#
suscepUbility#to#foscarnet##
ViroMed#assay#showed#suscepUbility#to#acyclovir###
Repeat#test#requested#but#not#done#
TK#genotypic#resistance#tesUng#ordered#but#never#
done##

20. ARUP%
ViroMed%

21. 1. Intravenous#Acyclovir#
2. Intravenous#Foscarnet#
3. Intravenous#Cidofovir#
4. Topical#Imiquimod#
5. Topical#Cidofovir#
6. Surgery#

22. Acyclovir:#high#dose#parenteral#@10#mg/kg/
Q8hr#used#twice;#once#x#8#days#and#other#for#2+#
weeks#without#response###
Foscarnet:#IniUally#responsive#to#2H3#weeks#of#
therapy#but#over#Ume#less#effecUve.##As#
outbreaks#became#more#frequent,#a#lower#dose#
of#daily#foscarnet#prescribed#for#suppression#
but#strategy#ineffecUve#due#to#logisUcal#issues,#
poor#adherence,#line#infecUons#

23. IV#cidofovir#discussed#but#considered#too#
nephrotoxic#(pt#had#chronic#CKD#with#Cr#
1.4H2.0)#
Topical#cidofovir:#unable#to#get#as#outpaUent#
because#of#cost#(~$900/2#weeks#of#therapy)#and#
not#covered#by#insurance.##Used#as#inpaUent#
twice#for#several#weeks#with#IV#foscarnet;#
parUal#response##
Thalidomide:#considered#but#determined#too#
risky#with#his#underlying#cogniUve#impairment#
and#mental#illness#
Cryotherapy#used#twice#on#lip#lesions#but#

24. Surgery:#scrotal#lesions#refractory#to#medical#
therapy#excised#in#OR#three#Umes.##Last#surgery#
June#2014.##Wound#dehisced#but#eventually#
healed#without#recurrence#of#lesions#

26. Imiquimod:#tried#twice#as#inpaUent#in#2012#but#
disconUnued#aner#brief#periods#because#
thought#to#be#irritaUng#lesions.##Used#as#
outpaUent#in#September#’14#when#he#
developed#new#chin#lesion.##Aner#a#month#
lesion#started#to#respond#and#within#3#months#
resolved#

30. 1. 40%#
2. 80%#
3. 20%#
4. 60%#
#

31. Leading#cause#of#genital#ulcer#disease#
worldwide#
Higher#prevalence#in#HIVHinfected#persons#
In#a#prospecUve#cohort#of#700#HIVHinfected#persons#
in#the#US,#60%#of#HIV#infected#paUents#were#HSVH2#
seroposiUve#compared#to#20%#in#general#US#
populaUon*#
*Patel#et#al.#Sex#Transm#Dis#2012;39:154#

32. As#HIV#progresses#and#CD4#counts#decline#HSV#
infecUons#more#severe#and#frequent,#with#
delayed#healing#and#prolonged#shedding#
Not#clear#whether#ART#reduces#HSV#outbreaks#
and#shedding#because#of#conflicUng#results#from#
small#observaUonal#studies#
#

33. UlceraUve#disease:##
#
Well#controlled#HIV:#
HSV#outbreaks#similar#
to#HIV#negaUve#
persons#
#
Poorly#controlled#HIV#
and#low#CD4#counts#
(<100):#ulcers#are#onen#
deeper,#larger,#more#
painful#and#can#be#
persistent##

34. Hypertrophic#masses,#pseudotumors,#nodular#or#
plaqueHlike#lesions#and#most#with#superficial#
ulceraUons#
Only#associated#with#HSVH2#
Rare;#most#cases#described#in#HIVHinfected#paUents#
but#also#cases#reported#in#other#immunoH
compromised#individuals#
More#common#in#persons#with#current#or#previous#
diagnosis#of#AIDS#

35. Most#have#history#of#typical#recurrent#ulceraUve#
anogenital#HSV#outbreaks#but#hypertrophic#form#can#
be#iniUal#presentaUon##
Almost#all#cases#report#anogenital#lesions#but#few#
reports#of#ectopic#locaUons#(e.g.,#tongue,#tonsil,#face,#
endobronchial#tree)#
Lesions#typically#large#
Single#lesion#at#one#site#most#commonly#reported#but#
mulUple#lesions#and#involvement#of#2#different#sites#
occurs##
Usually#grow#slowly#over#months#but#a#few#reported#
rapidly#growing#over#a#couple#of#weeks#
#

36. Case#reports#of#lesions#misdiagnosed#most#commonly#
as#condyloma#acuminata#or#squamous#cell#carcinoma#
Possible#misdiagnosis#of#our#paUent’s#lip#lesion#as#squamous#
cell#carcinoma#in#situ#in#2003;#Derm#path#Bx#Report:##
Clinical#History:#12#month#hx#of#enlarging#len#lower#lip#12#x#
13#mm#verrucous#plaque.##No#response#to#LN###
Dermatopath:#epidermis#irregularly#acanthoUc#and#
demonstrates#mild#papillomatosis.##Epithelium#covered#
with#densely#compacted#orthoH#and,#focally,#parakeratoUc#
scale.##Throughout#the#epithelium#there#is#evidence#of#
dysplasia,#with#many#mitoUc#figures#located#well#above#
the#basilar#layer##
Plan#to#obtain#slides#stored#offsite#to#review#
#

37. Some#but#not#all#paUents#exposed#to#acyclovir#prior#to#
development#of#hypertrophic#lesions#
About#half#of#cases#reported#as#acyclovir#resistant#
Case#reports#with#longer#term#followHup#report#
recurrences#usually#within#a#year#

39. Neoplasms:#squamous#cell#carcinoma,#
lymphoma#
Bacteria:#Treponema#pallidum,#mycobacteria##
Viruses:#HPV#

40. HSV#PCR#of#lesion#surface#
HSV#Culture#(if#PCR#unavailable)#
Biopsy#

41. Epidermis:#foci#of#ulceraUon#with#epithelial#
hypertrophic#changes#(if#marked:#
pseudoepitheliomatous#hyperplasia)#
Dermis:#dense#inflammatory#infiltrate#consisUng#
mostly#of#plasma#cells#mixed#with#lymphocytes,#
neutrophils#and#eosinophils#
MulUnucleated#keraUnocytes#with#moulded#
ground#glass#nuclei#and#eosinophilic#inclusions#
typical#of#HSV##

42. Underlying#mechanism#for#exaggerated#tumor#
like#response#to#HSV#has#not#been#elucidated#
Polyclonal#lymphoplasmocyUc#B#cells#in#lesion#
infiltrate#supports#hypothesis#of#dysregulated#
anUgenHdriven#immune#reacUon,#likely#directed#
at#HSVH2##
Scarcity#of#T#cells#in#the#lesional#mononuclear#
infiltrate#support#a#hypothesis#that#a#funcUonal#
deficit#of#HSVH2#specific#T#cells###

43. IRIS#proposed#as#eUology#of#exaggerated#
inflammatory#response#leading#to#epithelial#
hyperplasia#but#several#cases#described#in#
paUents#not#on#ART#and#others#presenUng#aner#
2#years#of#effecUve#ART.##Also#occurs#in#HIV#
negaUve#immunocompromised#paUents###
Acyclovir#resistance#thought#to#play#a#role#but#
some#lesions#are#responsive#and#suscepUble#to#
acyclovir##

44. Some#respond#to#oral#or#intravenous#acyclovir#
Those#refractory#to#acyclovir#had#mixed#
responses#to#topical#or#parenteral#foscarnet#or#
cidofovir#which#have#been#more#successfully#
used#for#acyclovir#resistant#ulcers#
Other#cases#have#reported#beser#and#more#
sustained#response#to#immunomodulatory#
agents#such#as#imiquimod#and#thalidomide#

45. Imiquimod#,#a#TollHlike#receptor#7#agonist,#
boosts#both#innate#and#adapUve#anUviral#
immunity#and#may#overcome#deficiency#of#
anUherpeUc#immunity##
Imiquimod#advantage#of#low#adverse#effects,#
relaUvely#inexpensive,#topical,#no#risk#of#
resistance,#and#self#administered#

46. Hypertrophic#HSV#is#a#rare#manifestaUon#of#
HSVH2#in#HIVHinfected#paUents#
Include#in#differenUal#diagnosis#of#a#mass#lesion#
in#the#anogenital#or#oral#areas#
Diagnosis#can#be#made#by#HSV#tesUng#of#
lesion’s#surface#but#may#require#a#biopsy#
(especially#at#iniUal#presentaUon)#to#confirm#
diagnosis#and#rule#out#other#mimicking#
condiUons##
Acyclovir#should#be#tried#iniUally#but#if#lesion#is#
unresponsive#then#test#for#acyclovir#resistance#
and#try#imiquimod##