Skin Manifestations in AIDS Patients Dr. Robert A. Norman President and CEO Dermatology Healthcare T

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Skin Manifestations in AIDS Patients Dr.
Robert A. NormanPresident and CEODermatology
HealthcareTampa, Florida Associate Clinical
ProfessorNova Southeastern University President
International Society of Geriatric Dermatology
www.drrobertnorman.com
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Disclosure of Financial Relationships

• This speaker has no significant financial
  relationships with commercial entities to
  disclose.

This slide set has been peer-reviewed to ensure
that there areno conflicts of interest
represented in the presentation.
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• Increases in
• chlamydia 5.5
• gonorrhea 5.6
• syphilis (1o/2o) 13.8

• 50 of STD in 15-24 y/o
• Blacks 6-18x higher rates
• Two-thirds of syphilis occurred in MSM

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STDs

• Viral
• Herpes
• HPV
• HIV
• Protozoal/Infestations
• Scabies
• Pubic Lice
• Trichomonas

• Bacterial
• Syphilis
• Chlamydia/LGV
• Gonorrhea
• Chancroid
• Granuloma inguinale

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Herpes Simplex Virus

• Two viral subtypes
• HSV-1, HSV-2
• Worldwide distribution
• 1 cause genital ulcers
• Ubiquitous in adults
• 57 HSV-1
• 17 HSV-2
• Latency in ganglia
• leads to recurrent disease

Xu F, et al. JAMA 2006 29696473.
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HSVClinical Lesions
Dew drops on a rose petal Scalloped
ulcerations
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HSV Diagnosis

• Tzanck sensitive in experienced hands, no
  typing
• DFA rapid, allows for diff. of HSV subtypes
• Culture fastidious technique, 5 days for
  results
• Antibodies IgG not present in primary infection
• PCR 4x more sensitive (?), increasing in
  popularity

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Biopsy or Tzanck Findings
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DFA Results
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We have discontinued culture for these viruses

• Performed on swabs from lesions
• Same day results with rapid PCR
• Cost is around 120.00 (v. 36.02 164.95 cx.)

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Treatment Primary Recurrent

• ACV (cheap, frequent dosing) 14.99
• Primary 200 mg 5x/d or 400 mg TID x 7-10 d
• Recurrent 400 mg TID x 5 d
• 800 mg TID x 2 d
• Suppress 400 mg BID
• Valacyclovir (expensive, convenient) 159.99
• Primary 1 gm BID x 7-10 d
• Recurrent 500 mg BID x 5 d
• 500 mg TID x 3 d
• Suppress 500 mg qd (or 1 gm qd if / 10 /yr)
• Famciclovir (expensive, convenient) 164.15
• Primary 250 mg TID x 7-10 d
• Recurrent 125 mg BID x 5 d
• 1 gm BID x 1 d
• Suppress 250 mg BID

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HSVImportant Developments

• USA, Canada, EU with ? genital HSV-1
• Genital herpes ? risk of HIV 3x
• HSV-2
• MOST cases subclinical (70-80)
• MOST cases acquired from asx. shedding
• asx. shedding on up to 25 of days with HSV-2
• TK-resistant HSV in
• HIV (5)
• bone-marrow transplant recipients (10-12)

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Condyloma

• 150 HPV subtypes
• 40 cause anogenital infections
• HPV 6, 11 90 condyloma
• HPV 16, 18 cervical cancer
• Integrative forms interrupt function of p53 and
  Rb

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Penile
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Vulvar
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• Examined
• 29 vulvar verruca in girls (
• HPV 2 in 41, HPV 6/11 in 59
• 275 vulvar verruca in women
• HPV 6/11 in 94, HPV 2 in 3, other HPV 3

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Treatments for Condyloma

• Classic destructive
• LN2
• TCA
• podophyllin
• laser
• surgical removal (some lesions)

• Imiquimod (Aldara)
• upregulates IFN-a (TLR-7)
• erythema and tenderness
• initial trial of 109 patients
• overall response 76
• complete response 50
• of those that cleared, 83 improved in 4
  weeks

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New Vaccines

• Gardasil (Merck)
• HPV 6, 11, 16, 18 (quadrivalent)
• prevents genital warts/cervical CA
• aluminum adjuvant
• Cervarix (GlaxoSmithKline)
• HPV 16/18 (bivalent)
• prevention of cervical cancer
• proprietary adjuvant AS04
• longer lasting or therapeutic use (?)

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Currently in USA

• Gardasil -- FDA approved
• Basis non-infectious virus-like particles (VLP)
• Indications
• prevention of genital warts/cervical cancer
• protects against HPV 6, 11, 16, and 18
• girls and women 9-26 years of age
• Three IM injections in deltoid over 6 mos.
• Cost is point of contention (300-500.00)

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Bacterial STDs
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Gonorrhea

• Gram neg. diplococci
• Neisseria gonorrhoeae
• Common cause of purulent d/c in men
• Often asymptomatic cervicitis
• May also involve
• Oropharynx
• Conjunctiva
• Pelvic inflammatory disease (20)
• Disseminated disease (1)

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• Diagnosis
• Smear
• Culture (gold std.)
• NAATs (very good sensitivity/specificity)
• Perform on 1st voided urine
• Increased detection but no abx. sensitivity
  information

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Trends in GC Treatment

• CDC surveillance
• 16 resistance PCN/tetracycline
• 13 resistance to fluoroquinolones in
  Hawaii/California/MSM
• Still little resistance to ceftriaxone or
  cefixime

MMWR, April 13, 2007
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Case 1

• 19 y/o woman with recent menses and recent
  contact with an STD. She has arthritis
  periarticular lesions.

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Disseminated Gonococcemia

• Occurs in 0.5 3 of cases of gonorrhea
• Usually days to weeks after infection, after
  menses
• 70 with migratory polyarthritis (1-3 joints)
• Gunmetal pustules, often periarticular on the
  distal extremities (5-50 lesions)
• Lesions asymptomatic resolve in 4-7 days
• Culture of the lesions positive in
• Ceftriaxone IV with transition to cefixime PO

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Chlamydia

• Intracellular GN organism
• C. trachomatis
• Different serovars may yield
• non-gonococcal urthrethritis (D-K)
• lymphogranuloma venereum (L1-3)
• Cannot be easily cultured
• Treatment of NGU
• azithromycin 1 gm OTD
• doxycycline 100 mg BID x 7 days (21 days for
  LGV)

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• Demonstrated cross-serovar protection (D-L)
• Animals demonstrated increased recovery and
  decreased shedding of organisms
• Disappointing protection against re-infection

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LGV with Groove Sign
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Saxophone Penis
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Case 2

• 23 y/o man. Two week history of rash on penis and
  sore knee. Last partner reported an STD.

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Reactive Arthritis (Reiters Syn.)

• Classic triad
• arthritis, NGU, conjunctivitis
• Rare (3.5-4.6 cases/100k/yr)
• Often HLA-B27 positive
• MF 101
• Arthritis lasts 6 wks to 6 mos.
• 15-50 recurrent episodes
• Circinate balanitis, keratoderma blenorrhagicum
• Tx. long term abx, corticosteroids, NSAIDS

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Kataria et al. AAFP, 2004.
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Syphilis

• First European epidemic thought to be around
  1493-94
• French Disease
• Italian Disease
• Pre-Colombian v. Post-Colombian v. Combination
  theory

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Syphilis in the United States 2004
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Primary Syphilis

• Treponema pallidum
• Usually single, painless, clean chancre
• 90 with LAD
• Dx - RPR FTA-ABS
• Dark field microscopy
• Highly sensitive to PCN
• Benzathine PCN 2.4 M units OTD
• Doxy 100 mg PO BID x 14 days

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Primary Syphilis Chancre
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Primary Syphilis Chancre
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Secondary Syphilis

• Dissemination of spirochete
• Usually 4-8 weeks after chancre resolves
• Boiled ham or copper penny rash
• Often with palmoplantar involvement
• Confirmed with RPR FTA-ABS

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Secondary Syphilis
High WA. Papulosquamous eruption following a
spider-bite on the penis. Medscape Derm Clinics
2003 (http//www.medscape.com/viewarticle/465134)
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Unusual presentations as well
Jarisch-Herxheimer Reaction
Rupioid Secondary Syphilis
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• Series of 19 cases of secondary syphilis
• superficial and deep perivascular pattern (9)
• lichenoid pattern (4)
• combined pattern (6)
• All cases demonstrated plasma cells, sparse in 4
  cases
• Granulomas were noted in 53 of cases
• Papillary edema and plump endothelial cells
  common
• Perineural infiltrate was seen in 74 of cases
• Variable acanthosis and dyskeratosis in the
  epidermis

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Chancroid
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Chancroid

• Haemophilus ducreyi (GN coccobacillus)
• Multiple, painful, ragged ulcerations
• Can have buboe formation
• Most common in sub-Saharan Africa
• Typically diagnosed with Gram stain
• schools of fish or railroad tracks
• Treatment azithromycin, fluoroquinolones

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Immune-effector cells in chancroid show increased
expression of CCR5 and CXCR4 than do cells in
other ulcers. (these receptors are involved in
entrance of HIV into cells)
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Case 3

• Prostitute presents for evaluation S/P NSVD
• Heaped and beefy plaque of 6 years duration on
  perineum
• Still working in the Callao community!!!

Courtesy of Francisco Bravo, MD
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The Crush Prep

• Tissue transferred to slide
• Crushed with second slide
• Parasitized macrophages and white blood cells.

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Granuloma Inguinale

• AKA - Donovanosis
• Calymmatobacterium granulomatis
• Intracellular GNB (actually Klebsiella spp.)
• Treat with long term doxycyline (also TMP/SMX,
  cipro, azithro, EES)
• Use a prolonged course of 21 days
• Relapse may occur up to 18 months later

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Protozoa Arthropod Infestations
ScabiesSarcoptes scabiei var hominis

• Arachnid (8 legs)
• Ubiquitous
• First visualized in 1687 in Italy
• Often occurs in 30 year epidemics
• Last epidemic began in 1960s (? Continuing)

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ScabiesPathogenesis

• Female burrows into stratum corneum
• Imbibes fluid, lays eggs, and defecates
• Allergy to mite/products leads to tremendous itch
• Associated with rheumatic fever

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Scabies Clinical
Penile Nodules
Wrist area
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Real world results of agood scabies prep
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ScabiesCrustedVariant (HIV patient)
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• 23 persons with crusted scabies over 6 months
• HTLV-I infection in 16 (69.6) patients
• Other co-morbidities corticosteroid therapy
  (8.6), malnutrition (8.6), and Downs syndrome
  (4.3)
• 13 tested for HIV NO positive results (none)

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Scabies Treatment

• Topical - 5 permethrin (Elimite?) 19.80
• Neck to toes for 8-14 hours then wash-off
• Often repeat in 1 week
• Clean all linens bag anything not laundered
• Ivermectin (Stromectol?) 31.20
• 150-200 mcg/kg (5 or 6 3 mg tabs)
• /- repeat in 1 week
• Personal favorite for crusted scabies (/-
  topical)
• Lindane resistance, neurotoxicity
• FDA issued stern warning letter Jan. 15, 2008

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Pubic Lice

• Pthirus pubis
• Visible to the naked eye
• Blood meals from pubic area
• Secondary changes from scratching
• Maculae cerulea from lice saliva

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Pubic Lice Clinical
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How do I diagnose pubic lice?

• CAREFULLY
• Cut hair, place on slide with mineral oil
  coverslip

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Pubic Lice Also Effect Eyelashes
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Pubic Lice Treatment

• Topical meds
• permethrin 1-5 (short contact)
• malathion 0.5 ( vehicle with 78 isopropyl
  alcohol)
• lindane (again, falling out of favor)
• Oral meds
• ivermectin 200 mcg/kg OTD
• For eyelashes
• smother with white petrolatum (ophtho. grade)
• anti-cholinesterase eye drops reported abroad

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MRSA
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Report of a Case   A 60-year-old Caucasian male
presented to our office for a follow up visit to
discuss the results of cultures from the left jaw
line and left upper thigh abscesses. The
patient arrived for a follow-up appointment
stating that a week earlier he went to the urgent
care center concerned about acutely tender
abscesses that had developed on his left jaw line
and left upper thigh. The pus-filled abscesses
were lanced, cleaned, and packed to prevent
another reinfection of the wound area. Cultures
of the areas were then sent to a reference lab
for identification and sensitivity. The
physician at the urgent care center prescribed
cephalexin.      
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The culture of the abscess reveled colonies of
Methicillin resistant Staphylococcus aureus
(MRSA) present. The sensitivity demonstrated a 0.5/9.5 sensitivity to Trimethoprim-sulfamethoxazo
le. The patient was then instructed to return
at a later date to determine the efficiency of
the antibiotics and to monitor the healing
process. An infection with MRSA is a very
serious matter and his prompt treatment saved
himself potentially harsh physical discomfort and
disfigurement.   Diagnosis Methicillin Resistant
Staphylococcus aureus
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Discussion   Gram positive bacteria are bacteria
that stain purple under the microscope due to its
thick outer cell wall which is made of
peptidoglycan. The thick peptidoglycan cell wall
is constructed by the enzyme transpeptidase
(penicillin-binding protein). Transpeptidase
enzyme cross-links the peptidoglycan chains
forming the bacterial cell wall. This is the
last step in the cell wall synthesis.
Staphylococcus aureus has this thick cell wall
and thus is classified as gram positive. It has
a round shape (cocci), which grow in grape-like
clusters. This is due to the bacterial cell
dividing in more than one plane. S. aureus is
the most virulent of all 33 staphylococcal
species, which causes both toxin mediated and
non-toxin mediated disease.    
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S. aureus was discovered in pus from surgical
abscesses by the surgeon Sir Alexander Ogston in
Aberdeen, Scotland in 1880. Staphylococcus
aureus literally translates to "Golden Cluster
Seed". When S. aureus is grown on blood agar it
takes on a yellow-gold appearance. They are
catalase positive (causes H2O2 to break down into
oxygen and water) due to the bacterias ability
to produce the enzyme catalase. S. aureus is
also coagulase positive, which converts
fibrinogen to fibrin forming a clot. These two
enzymes, catalase and coagulase, are both used to
identify the bacteria.
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Antibiotics such as penicillin, that are used to
kill these gram positive bacteria, bind to the
enzyme transpeptidase to prevent the bacteria
from synthesizing its cell wall. S. aureus
produces an enzyme called penicillinase (a beta
lactamase) that is secreted from the bacteria and
hydrolizes the beta-lactam ring on the penicillin
thus inactivating penicillin. Methicillin is
used to treat bacteria that produce
penicillinase. This drug is a penicillinase
resistant drug that is used to treat bacteria
(such as S. aureus) that produce the
penicillinase enzyme.  
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There are increasing strains of S. aureus that
are resistant to methicillin. These
methicillin-resistant staphylococci (MRSA)
synthesize an additional penicillin binding
protein that has a much lower affinity for
beta-lactam antibiotics than the normal
penicillin binding proteins. This enables cell
wall synthesis when its other penicillin binding
proteins are inhibited. MRSA strain of S.
aureus usually develops around the hospital where
there is the use of broad-spectrum antibiotics.
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MRSA is resistant to many antibiotics and
intravenous vancomycin is one of the few
antibiotics useful in treatment. Since this
patient came to our clinical office and not to a
hospital, intravenous medications would not be
practical. Trimethoprim-sulfamethoxazole
(TMP-SMX) was found to be effective against this
particular patients MRSA strain. TMP-SMX is a
two-drug combination that results in the
sequential blockade of folate synthesis. Since
TMP-SMX can be taken orally, it was a more
practical antibiotic to prescribe. The patient
returned in two weeks and his healing reflected
that the antibiotic and his immune system had
worked effectively.
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Bacillary angiomatosis (Bartonella ) nodules
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Eosinophilic folliculitis
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Candidiasis Chronic Mucocutaneous
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Candidiasis Chronic Mucocutaneous
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Herpes Immunocompromised
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Herpes Buttocks
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Herpes Type 1 Recurrent
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Herpes Type 1 Recurrent
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Candidiasis Mouth
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Warts Immunocompromised
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Warts Immunocompromised
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Warts Immunocompromised
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Cholinergic Urticaria
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Axillary seborrheic dermatitis
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DRUG RASHES
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Drug eruptions are around 100 times more common
in people living with HIV, and drug reactions are
the most common reason that people need to change
their anti-viral therapy in HIV. Most drug
associated rashes begin in the first few weeks
after starting a new drug. Sulfonamides and
other antibiotics were the main cause of
drug-rashes in the past. More recently rashes
associated with anti-viral medications have
become a greater problem. It can sometimes be
difficult to be sure exactly which drug is
responsible for a rash, as many drugs are usually
started at the same time to gain better viral
control. Nevirapine, efavirenz, delavirdine,
amprenavir and abacavir are more common causes of
rash.
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A rash can occur in isolation with just skin
changes or be part of a major hypersensitivity
reaction or 'allergy' with involvement of the
bodies internal organs as well. More concerning
drug-reactions are usually associated the new
onset of any or all of the following fever,
tiredness, sore-throat, loss of appetite,
swelling of the glands, feeling light-headed and
faint, or just feeling unwell. Other features of
a drug-rash that warn of a major potentially
life-threatening reaction are involvement of the
mouth or eyes, tenderness of the skin
particularly if blisters are present, or if there
is associated swelling of the face and
neck. These drug-rashes range from minor red
lumpy rashes to widespread redness through to
occasional cases with blistering and even
shedding of the skin (see picture of
Stevens-Johnson Syndrome).
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If you develop a rash in the first few weeks
after starting a new medication it is important
to contact your doctor. Some minor rashes without
fever, mouth or eye involvement, or other new
symptoms may settle with continuation of the drug
while other potentially serious reactions
necessitate prompt cessation of the associated
drug. A topical cortisone cream, cool baths with
oil and oatmeal, and an antihistamine can be used
to reduce itch. This reaction occurs slowly,
over months or years. Regular (moderate) exercise
and a balanced diet can help reduce some of these
changes. Fat redistribution can also be
associated with changes in the level of
cholesterol and other blood fats along with dry
irritable skin.
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Thank you.

• Questions or Comments?