HIVHIV//AIDS – dermatological aspects AIDS – dermatological aspects

of this problem.of this problem.

Lector: Shkilna M. Lector: Shkilna M.

AIDS patients

ContentContent1. Causative Agent1. Causative Agent2. Modes of Transmission2. Modes of Transmission3. Incubation period3. Incubation period4. Clinical features4. Clinical features5. Dermatological Manifestations of HIV-infection:5. Dermatological Manifestations of HIV-infection: Infectious coetaneous conditions.Infectious coetaneous conditions. Inflammatory skin conditions.Inflammatory skin conditions. Kaposi’s sarcoma.Kaposi’s sarcoma.6. Investigations:6. Investigations: Screening tests.Screening tests. Supplement tests.Supplement tests. Confirmatory tests.Confirmatory tests.7. Treatment:7. Treatment: Specific treatmentSpecific treatment Drug for Opportunistic InfectionsDrug for Opportunistic Infections

Human Immunodeficiency VirusHuman Immunodeficiency Virus

5

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

• 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:Causative Agent:

Causative Agent:Causative Agent:On the basis of serological properties and On the basis of serological properties and

sequence analysis of molecularly cloned viral sequence analysis of molecularly cloned viral genomes,genomes, two types of HIV viruses infecting two types of HIV viruses infecting human beings have been identified:human beings have been identified:

HIV1 and HIV2 are retroviruses containing HIV1 and HIV2 are retroviruses containing reverse transcriptase, which allows reverse transcriptase, which allows incorporation of the virus into a cell’s DNA.incorporation of the virus into a cell’s DNA.

Both infect the same target cells (CD4+T Both infect the same target cells (CD4+T cells, monocytes, macrophages, dendrite cells, monocytes, macrophages, dendrite cells, Langerhans cells) through the same cells, Langerhans cells) through the same CD4 receptors.CD4 receptors.

Sexual

Parenteral

Perinatal

Modes of Transmission:Modes of Transmission:

The population groups at The population groups at risk:risk:

Homosexuals;Homosexuals; Parenteral drug abusers;Parenteral drug abusers; Haemophilics;Haemophilics; Those receiving repeated blood products Those receiving repeated blood products

transfusions;transfusions; Heterosexual partners of AIDS victims;Heterosexual partners of AIDS victims;

Other contacts of AIDS victims, like the Other contacts of AIDS victims, like the laboratory technicians and doctors.laboratory technicians and doctors.

Incubation period:Incubation period:

In general, it is though to vary In general, it is though to vary from 15 to 28 month. In from 15 to 28 month. In infants, it is found to be infants, it is found to be shorter ( 8 month).shorter ( 8 month). Acute HIV Acute HIV infection is now getting more infection is now getting more and more recognizable. and more recognizable.

PATHOGENESISIncubation periodIncubation period: : In general, it is In general, it is though to vary from 15 to 28 month. In though to vary from 15 to 28 month. In infants, it is found to be shorter ( 8 infants, it is found to be shorter ( 8 month).month).

1) PRIMARY INFECTION

2) LYMPHOID INFECTION

3) ACUTE SYNDROME

4) IMMUNE RESPONSE

5) LATENCY

6) AIDS

Clinical features:Clinical features:

Group 1Group 1 Acute infection (Seroconversion Acute infection (Seroconversion Illness).Illness).

Group 2Group 2 Asymptomatic infection. Asymptomatic infection.

Group 3Group 3 Persistent generalized Persistent generalized lymphodenopathy.lymphodenopathy.

Group 4Group 4 AA: Constitutional upset: Constitutional upset..

B:B: Neurological disturbances Neurological disturbances.. C:C: Secondary infectious disease Secondary infectious disease.. D:D: Malignancy features (Secondary Malignancy features (Secondary

Neoplasms). Neoplasms). E:E: Other conditions. Other conditions.

Dermatological Manifestations Dermatological Manifestations of HIV-infectionof HIV-infection

Infectious coetaneous conditions.Infectious coetaneous conditions. Inflammatory skin conditions.Inflammatory skin conditions.

Kaposi’s sarcoma.Kaposi’s sarcoma.

1. Infectious coetaneous conditions:1. Infectious coetaneous conditions:

Staphylococcus aureus infections.Staphylococcus aureus infections.

Herpes simplex infection.Herpes simplex infection. Varicella Zoster infection.Varicella Zoster infection. Molluscum contagiosum.Molluscum contagiosum. Human papillomavirus (warts).Human papillomavirus (warts). Acute HIV exanthema and anathema.Acute HIV exanthema and anathema. Syphilis.Syphilis. Dermatophytosis.Dermatophytosis. Candidiasis.Candidiasis.

Varicella Zoster infectionVaricella Zoster infection

Varicella Zoster infectionVaricella Zoster infection

Varicella Zoster infectionVaricella Zoster infection

Candidiasis of mucous membranesCandidiasis of mucous membranes

Inflammatory skin conditionsInflammatory skin conditions

Eosinophilic folliculitis.Eosinophilic folliculitis. Drug reactions.Drug reactions. Scabies.Scabies. Psoriasis.Psoriasis. Atopic dermatitis.Atopic dermatitis. Seborhoeic dermatosis.Seborhoeic dermatosis.

Seborhoeic dermatitisSeborhoeic dermatitis

Seborhoeic dermatitisSeborhoeic dermatitis

Staphylococcus aureus infectionsStaphylococcus aureus infections

Bullous impetigo.Bullous impetigo. Ecthyma.Ecthyma. Folliculitis:Folliculitis: a. a. FolliculitisFolliculitis due to S. aureus.due to S. aureus.

b. b. Often the follicular lesions of the trunk Often the follicular lesions of the trunk are intensely pruritic and may be mistaken are intensely pruritic and may be mistaken for scabies. About 50 % of HIV-infection for scabies. About 50 % of HIV-infection persons with scabies have coexistent S. persons with scabies have coexistent S. aureus folliculitis.aureus folliculitis.

Molluscum contagiosumMolluscum contagiosum Molluscum contagiosum is manifesting as Molluscum contagiosum is manifesting as flesh-flesh-

colored hemispheric papulescolored hemispheric papules. A faint whitish core . A faint whitish core usually is visible at the usually is visible at the centre of each papule, centre of each papule, some of which may be slightly umbilicatedsome of which may be slightly umbilicated. This . This eruption is seen commonly in immunocompetent eruption is seen commonly in immunocompetent young children (ages 3 to 8 years), whose lesions young children (ages 3 to 8 years), whose lesions are scattered widely are scattered widely over the face, arms, and over the face, arms, and trunk.trunk.

In adults, this mild infection is usually sexually In adults, this mild infection is usually sexually transmitted and occurs in the transmitted and occurs in the pubic areapubic area..

Molluscum contagiosumMolluscum contagiosum

Molluscum contagiosumMolluscum contagiosum

Human papillomavirus (warts)Human papillomavirus (warts)

Relapse of warts after treatment is common Relapse of warts after treatment is common especially in advanced HIV disease. Liquid especially in advanced HIV disease. Liquid nitrogen cryotherapy can be applied every 2 nitrogen cryotherapy can be applied every 2 to 4 weeks. Topical “anti-wart” medications to 4 weeks. Topical “anti-wart” medications containing salicylic and lactic acids are containing salicylic and lactic acids are applied daily under occlusion and may lead applied daily under occlusion and may lead to complete disappearance of the lesions. to complete disappearance of the lesions. The treatment outlook for warts is poor in The treatment outlook for warts is poor in immunosuppressed patients.immunosuppressed patients.

Acute HIV exanthema and anathemaAcute HIV exanthema and anathema

In acute primary HIV infection, a rash may develop In acute primary HIV infection, a rash may develop along with a mononucleosis-like illness. The rash along with a mononucleosis-like illness. The rash may be may be exanthematous or pityriasis rosea-exanthematous or pityriasis rosea-like, usually does not itchlike, usually does not itch, is distributed over , is distributed over the upper trunk and proximal limbs, and may the upper trunk and proximal limbs, and may involve palms and soles. An associated exanthema involve palms and soles. An associated exanthema of oral erythema or superficial erosions may be of oral erythema or superficial erosions may be present. Spontaneously resolve within 1 to weeks.present. Spontaneously resolve within 1 to weeks.

Detection of HIV antigen by enzyme immunoassay Detection of HIV antigen by enzyme immunoassay may confirm the diagnosis of acute HIV infection may confirm the diagnosis of acute HIV infection in HIV-antibody-negative persons.in HIV-antibody-negative persons.

SyphilisSyphilis Coetaneous presentation of primary and Coetaneous presentation of primary and

secondary syphilis in HIV-infected persons secondary syphilis in HIV-infected persons are usually similar to those in now-HIV-are usually similar to those in now-HIV-infected persons. HIV may delay infected persons. HIV may delay development of serological evidence of development of serological evidence of Treponema pallidum, resulting in negative Treponema pallidum, resulting in negative tests. In the HIV- infected person, a tests. In the HIV- infected person, a negative serological test may not be negative serological test may not be adequate to rule out rule out secondary adequate to rule out rule out secondary syphilis.syphilis.

DermatophytosisDermatophytosis

In patients who are positive for the AIDS virus has a In patients who are positive for the AIDS virus has a presentation similar to that of dermatophyte in presentation similar to that of dermatophyte in non-HIV-infected patients. It has a tendency to non-HIV-infected patients. It has a tendency to present in a more widespread fashion. present in a more widespread fashion. Onychomycosis, or nail fungal infection, may Onychomycosis, or nail fungal infection, may present with either the common distal subungual present with either the common distal subungual onychomycosis pattern or as proximal subungual onychomycosis pattern or as proximal subungual onycholysis.onycholysis.

Oral hairy leucoplakiaOral hairy leucoplakia

Kaposi’s sarcomaKaposi’s sarcoma Kaposis’s sarcoma is a neoplasm of endothelial Kaposis’s sarcoma is a neoplasm of endothelial

cells with the skin and other organs. Most KS cells with the skin and other organs. Most KS patients are homosexual men. KS may be present patients are homosexual men. KS may be present in up to 46% of homosexual me with advanced in up to 46% of homosexual me with advanced HIV disease at initial diagnosis. The incidence in HIV disease at initial diagnosis. The incidence in heterosexual injection drug users is only 3.8%. heterosexual injection drug users is only 3.8%. Herpes virus 8 (HHV-8) has been associated with Herpes virus 8 (HHV-8) has been associated with KS most individuals with KS have generalized KS most individuals with KS have generalized with KS. Most individuals with KS have with KS. Most individuals with KS have generalized , slowly progressive disease; others generalized , slowly progressive disease; others have stable KS.have stable KS.

Kaposi’s sarcomaKaposi’s sarcoma

Kaposi’s sarcomaKaposi’s sarcoma

Kaposi’s sarcomaKaposi’s sarcoma

Kaposi’s sarcomaKaposi’s sarcoma

Kaposi’s sarcomaKaposi’s sarcoma

Kaposi’s sarcomaKaposi’s sarcoma

KS may effect any portion of the coetaneous surface. KS may effect any portion of the coetaneous surface. Initially, it appears as Initially, it appears as red-to brown flat red-to brown flat macules. Papules, nodules, and tumorsmacules. Papules, nodules, and tumors may also be present or develop later. Numbering may also be present or develop later. Numbering from one to hundreds, they range in size from from one to hundreds, they range in size from several millimeters to over 10 cm and may be several millimeters to over 10 cm and may be widespread, grouped, or zosteriform. KS may widespread, grouped, or zosteriform. KS may affect affect mucosal surfaces and internal organsmucosal surfaces and internal organs. . Visceral involvement occurs in 71% of patients Visceral involvement occurs in 71% of patients with advanced HIV disease and KS, most often with advanced HIV disease and KS, most often affecting the gastrointestinal tract (50%), lymph affecting the gastrointestinal tract (50%), lymph nodes (50%), and lungs (37%).nodes (50%), and lungs (37%).

InvestigationsInvestigations

Tests to Diagnosis HIV Tests to Diagnosis HIV Infection:Infection:

Screening tests.Screening tests. Supplement tests.Supplement tests. Confirmatory tests.Confirmatory tests.

ELISA for HIV antibody

Microplate ELISA for HIV antibody: colored wells indicate Microplate ELISA for HIV antibody: colored wells indicate reactivityreactivity

Western blot for HIV antibody

There are different There are different criteria for the criteria for the interpretation of HIV interpretation of HIV Western blot results Western blot results e.g. CDC, WHO, e.g. CDC, WHO, American Red American Red Cross.Cross.

The most important The most important antibodies are those antibodies are those against the envelope against the envelope glycoproteins gp120, glycoproteins gp120, gp160, and gp41 gp160, and gp41

p24 antibody is p24 antibody is usually present but usually present but may be absent in may be absent in the later stages of the later stages of HIV infectionHIV infection

TreatmentTreatmentSpecific treatmentSpecific treatment

Based on mechanisms of action, two Based on mechanisms of action, two classes of anti-retroviral drugs are classes of anti-retroviral drugs are available:available:

Reverse transcriptase inhibitors which are Reverse transcriptase inhibitors which are of two types:of two types:

1.1. Nucleoside reverse transcriptase inhibitors Nucleoside reverse transcriptase inhibitors (NRTIs).(NRTIs).

2.2. Non-nucleoside reverse transcriptase Non-nucleoside reverse transcriptase inhibitors (NNRTIs).inhibitors (NNRTIs).

Therapy of HIV Infection: 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).

Zidovudine (ZDV, Retrovir) first approved in 1987 Didanosine (ddI, Videx) Zalcitabine (ddC, Hivid) Stavudine (d4T, Zerit) 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.

Nevirapine (Viramune) 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.

Saquinavir (Invirase) first approved in 1995 Ritonavir (Norvir) Indinavir (Crixivan) Nelfinavir (Viracept) Fusion inhibitors e.g. Fuzeon (IM only)

Drug for Opportunistic InfectionsDrug for Opportunistic Infections

Herpes simplex virus – Acyclovir 2 G x Herpes simplex virus – Acyclovir 2 G x 2weeks,2weeks,

Herpes zoster – Acyclovir 4 G x 2weeks,Herpes zoster – Acyclovir 4 G x 2weeks, Candidiasis – Fluconasole 100-200 mg Candidiasis – Fluconasole 100-200 mg

daily x 3 weeks,daily x 3 weeks, Toxoplasma encephalitis – Sulphadiazine 4-Toxoplasma encephalitis – Sulphadiazine 4-

8 G + pyrimethamine 200-400 mg x 6 8 G + pyrimethamine 200-400 mg x 6 weeks.weeks.

IMMUNOPROPHYLAXIS

Types of HIV vaccines1. 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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