HIV / AIDS – dermatological aspects of this problem.

1. HIV/AIDS – dermatological aspects of this problem. Lector: Shkilna M.

2. AIDS patients

3. 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

4. Human 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 5

6. 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.

7. 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.

8. Modes of Transmission: • Sexual • Parenteral • Perinatal

9. The population groups at risk: • 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.

10. 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.

11. 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

12. Clinical features: Group 1 Acute infection (Seroconversion Illness). Group 2 Asymptomatic infection. Group 3 Persistent generalized lymphodenopathy. Group 4A: Constitutional upset. B: Neurological disturbances. C: Secondary infectious disease. D: Malignancy features (Secondary Neoplasms). E: Other conditions.

13. Dermatological Manifestations of HIV-infection • Infectious coetaneous conditions. • Inflammatory skin conditions. • Kaposi’s sarcoma.

14. 1. Infectious coetaneous conditions: • Staphylococcus aureus infections. • Herpes simplex infection. • Varicella Zoster infection. • Molluscum contagiosum. • Human papillomavirus (warts). • Acute HIV exanthema and anathema. • Syphilis. • Dermatophytosis. • Candidiasis.

15. Varicella Zoster infection

16. Varicella Zoster infection

17. Varicella Zoster infection

18. Candidiasis of mucous membranes

19. Inflammatory skin conditions • Eosinophilic folliculitis. • Drug reactions. • Scabies. • Psoriasis. • Atopic dermatitis. • Seborhoeic dermatosis.

20. Seborhoeic dermatitis

21. Seborhoeic dermatitis

22. Staphylococcus aureus infections • Bullous impetigo. • Ecthyma. • Folliculitis: a. Folliculitisdue 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.

23. Molluscum contagiosum • Molluscum contagiosum is manifesting as flesh-colored 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.

24. Molluscum contagiosum

25. Molluscum contagiosum

26. 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.

27. 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 rosea-like, 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.

28. Syphilis • Coetaneous presentation of primary and secondary syphilis in HIV-infected persons are usually similar to those in now-HIV-infected 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.

29. 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.

30. Oral hairy leucoplakia

31. 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.

32. Kaposi’s sarcoma

33. Kaposi’s sarcoma

34. Kaposi’s sarcoma

35. Kaposi’s sarcoma

36. Kaposi’s sarcoma

37. 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%).

38. Investigations Tests to Diagnosis HIV Infection: • Screening tests. • Supplement tests. • Confirmatory tests.

39. ELISA for HIV antibody Microplate ELISA for HIV antibody: colored wells indicate reactivity

40. 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

41. TreatmentSpecific treatment • Based on mechanisms of action, two classes of anti-retroviral drugs are available: • Reverse transcriptase inhibitors which are of two types: • Nucleoside reverse transcriptase inhibitors (NRTIs). • Non-nucleoside reverse transcriptase inhibitors (NNRTIs).

42. 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)

43. 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 4-8 G + pyrimethamine 200-400 mg x 6 weeks.

44. IMMUNOPROPHYLAXIS Types of HIV vaccines 1.Attenuatedvaccines 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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