Transcript 09. HIV AIDS

HIV/AIDS – dermatological aspects
of this problem.
Lector: Shkilna M.
AIDS
patients
Content
1. Causative Agent
2. Modes of Transmission
3. Incubation period
4. Clinical features
5. Dermatological Manifestations of HIV-infection:
 Infectious coetaneous conditions.
 Inflammatory skin conditions.
 Kaposi’s sarcoma.
6. Investigations:
 Screening tests.
 Supplement tests.
 Confirmatory tests.
7. Treatment:
 Specific treatment
 Drug for Opportunistic Infections
Human Immunodeficiency Virus
Human Immunodeficiency Virus
Knob engages CD4 receptor on lymphocyte; virus carries preformed RT and
integrase enzymes; 107 particles/mL; 0 billion made per day as opposed to 2
billion CD4 cells/day
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Causative Agent:
• HIV is a simple virus with only 9 genes encoding
15 proteins.
• HIV is a retrovirus, with a 9.2 kilobase RNA
genome that is copied into DNA by reverse
transcriptase.
• The dsDNA copy is then inserted into the host
genome.
Causative Agent:
On the basis of serological properties and
sequence analysis of molecularly cloned viral
genomes, two types of HIV viruses infecting
human beings have been identified:
 HIV1 and HIV2 are retroviruses containing
reverse transcriptase, which allows
incorporation of the virus into a cell’s DNA.
 Both infect the same target cells (CD4+T
cells, monocytes, macrophages, dendrite
cells, Langerhans cells) through the same
CD4 receptors.
Modes of Transmission:
Sexual
Parenteral
Perinatal
The population groups at
risk:
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Homosexuals;
Parenteral drug abusers;
Haemophilics;
Those receiving repeated blood products
transfusions;
 Heterosexual partners of AIDS victims;
Other contacts of AIDS victims, like the
laboratory technicians and doctors.
Incubation period:
 In general, it is though to vary
from 15 to 28 month. In
infants, it is found to be
shorter ( 8 month). Acute HIV
infection is now getting more
and more recognizable.
PATHOGENESIS
Incubation period: In general, it is
though to vary from 15 to 28 month. In
infants, it is found to be shorter ( 8
month).
1) PRIMARY INFECTION
2) LYMPHOID INFECTION
3) ACUTE SYNDROME
4) IMMUNE RESPONSE
5) LATENCY
6) AIDS
Clinical features:
Group 1
Acute infection (Seroconversion
Illness).
Group 2
Group 3
Asymptomatic infection.
Persistent generalized
lymphodenopathy.
Group 4
A: Constitutional upset.
B: Neurological disturbances.
C: Secondary infectious disease.
D: Malignancy features (Secondary
Neoplasms).
E: Other conditions.
Dermatological Manifestations
of HIV-infection
 Infectious coetaneous conditions.
 Inflammatory skin conditions.
 Kaposi’s sarcoma.
1. Infectious coetaneous conditions:
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Staphylococcus aureus infections.
Herpes simplex infection.
Varicella Zoster infection.
Molluscum contagiosum.
Human papillomavirus (warts).
Acute HIV exanthema and anathema.
Syphilis.
Dermatophytosis.
Candidiasis.
Varicella Zoster infection
Varicella Zoster infection
Varicella Zoster infection
Candidiasis of mucous membranes
Inflammatory skin conditions
 Eosinophilic folliculitis.
 Drug reactions.
 Scabies.
 Psoriasis.
 Atopic dermatitis.
 Seborhoeic dermatosis.
Seborhoeic dermatitis
Seborhoeic dermatitis
Staphylococcus aureus infections
 Bullous impetigo.
 Ecthyma.
 Folliculitis:
a. Folliculitis due to S. aureus.
b. Often the follicular lesions of the trunk
are intensely pruritic and may be mistaken
for scabies. About 50 % of HIV-infection
persons with scabies have coexistent S.
aureus folliculitis.
Molluscum contagiosum
 Molluscum contagiosum is manifesting as fleshcolored hemispheric papules. A faint whitish core
usually is visible at the centre of each papule,
some of which may be slightly umbilicated. This
eruption is seen commonly in immunocompetent
young children (ages 3 to 8 years), whose lesions
are scattered widely over the face, arms, and
trunk.
 In adults, this mild infection is usually sexually
transmitted and occurs in the pubic area
.
Molluscum contagiosum
Molluscum contagiosum
Human papillomavirus (warts)
Relapse of warts after treatment is common
especially in advanced HIV disease. Liquid
nitrogen cryotherapy can be applied every 2
to 4 weeks. Topical “anti-wart” medications
containing salicylic and lactic acids are
applied daily under occlusion and may lead
to complete disappearance of the lesions.
The treatment outlook for warts is poor in
immunosuppressed patients.
Acute HIV exanthema and anathema
In acute primary HIV infection, a rash may develop
along with a mononucleosis-like illness. The rash
may be exanthematous or pityriasis rosealike, usually does not itch, is distributed over
the upper trunk and proximal limbs, and may
involve palms and soles. An associated exanthema
of oral erythema or superficial erosions may be
present. Spontaneously resolve within 1 to weeks.
Detection of HIV antigen by enzyme immunoassay
may confirm the diagnosis of acute HIV infection
in HIV-antibody-negative persons.
Syphilis
 Coetaneous presentation of primary and
secondary syphilis in HIV-infected persons
are usually similar to those in now-HIVinfected persons. HIV may delay
development of serological evidence of
Treponema pallidum, resulting in negative
tests. In the HIV- infected person, a
negative serological test may not be
adequate to rule out rule out secondary
syphilis.
Dermatophytosis
In patients who are positive for the AIDS virus has a
presentation similar to that of dermatophyte in
non-HIV-infected patients. It has a tendency to
present in a more widespread fashion.
Onychomycosis, or nail fungal infection, may
present with either the common distal subungual
onychomycosis pattern or as proximal subungual
onycholysis.
Oral hairy leucoplakia
Kaposi’s sarcoma
 Kaposis’s sarcoma is a neoplasm of endothelial
cells with the skin and other organs. Most KS
patients are homosexual men. KS may be present
in up to 46% of homosexual me with advanced
HIV disease at initial diagnosis. The incidence in
heterosexual injection drug users is only 3.8%.
Herpes virus 8 (HHV-8) has been associated with
KS most individuals with KS have generalized
with KS. Most individuals with KS have
generalized , slowly progressive disease; others
have stable KS.
Kaposi’s sarcoma
Kaposi’s sarcoma
Kaposi’s sarcoma
Kaposi’s sarcoma
Kaposi’s sarcoma
Kaposi’s sarcoma
KS may effect any portion of the coetaneous surface.
Initially, it appears as red-to brown flat
macules. Papules, nodules, and tumors may
also be present or develop later. Numbering from
one to hundreds, they range in size from several
millimeters to over 10 cm and may be widespread,
grouped, or zosteriform. KS may affect mucosal
surfaces and internal organs. Visceral
involvement occurs in 71% of patients with
advanced HIV disease and KS, most often
affecting the gastrointestinal tract (50%), lymph
nodes (50%), and lungs (37%).
Investigations
Tests to Diagnosis HIV
Infection:
 Screening tests.
 Supplement tests.
 Confirmatory tests.
ELISA for HIV antibody
Microplate ELISA for HIV antibody: colored wells indicate
reactivity
Western blot for HIV antibody
 There are different
criteria for the
interpretation of
HIV Western blot
results e.g. CDC,
WHO, American
Red Cross.
 The most important
antibodies are
those against the
envelope
glycoproteins
gp120, gp160, and
gp41
 p24 antibody is
usually present but
may be absent in
the later stages of
HIV infection
Treatment
Specific treatment
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Based on mechanisms of action, two
classes of anti-retroviral drugs are
available:
 Reverse transcriptase inhibitors which are
of two types:
1. Nucleoside reverse transcriptase inhibitors
(NRTIs).
2. Non-nucleoside reverse transcriptase
inhibitors (NNRTIs).
Therapy of HIV Infection:
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Nucleoside-Analog Reverse Transcriptase Inhibitors (NRTI). These drugs
inhibit viral RNA-dependent DNA polymerase (reverse transcriptase) and are
incorporated into viral DNA (they are chain-terminating drugs).
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Zidovudine (ZDV, Retrovir) first approved in 1987
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Didanosine (ddI, Videx)
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Zalcitabine (ddC, Hivid)
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Stavudine (d4T, Zerit)
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Lamivudine (3TC, Epivir)
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs). In contrast to
NRTIs, NNRTIs are not incorporated into viral DNA; they inhibit HIV
replication directly by binding non-competitively to reverse transcriptase.
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Nevirapine (Viramune)
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Delavirdine (Rescriptor)
Protease Inhibitors. These drugs are specific for the HIV-1 protease and
competitively inhibit the enzyme, preventing the maturation of virions capable
of infecting other cells.
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Saquinavir (Invirase) first approved in 1995
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Ritonavir (Norvir)
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Indinavir (Crixivan)
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Nelfinavir (Viracept)
 Fusion inhibitors e.g. Fuzeon (IM only)
Drug for Opportunistic Infections
 Herpes simplex virus – Acyclovir 2 G x
2weeks,
 Herpes zoster – Acyclovir 4 G x 2weeks,
 Candidiasis – Fluconasole 100-200 mg
daily x 3 weeks,
 Toxoplasma encephalitis – Sulphadiazine 48 G + pyrimethamine 200-400 mg x 6
weeks.
IMMUNOPROPHYLAXIS
Types of HIV vaccines
1. Attenuated vaccines are made from genetically engineered
strains lacking some crucial genes, so that the resulting virus causes
a harmless infection. This approach has been tried successfully with
simian immunodeficiency virus (SIV)
2. Killed virus vaccines. In humans, it has been proposed that
vaccination with low doses of killed HIV enhances cellular immunity
and favors (lie development of cell-mediated cytotoxicity. Evaluation
is difficult because the end-point is a disease-free interval that is
long and variable.
3. Recombinant viral particles made by inserting HIV
glycoprotein genes in, for example, vaccinia-virus genomes
induce neutralizing antibodies in animals.
4. Component vaccines have been prepared from isolated
gpl20, polymerized gpl20, or gpl20 peptides representing more
conserved regions (such as the CD4-binding domain)
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