Essentials of Diagnosis

· Prominent systemic complaints

o Sweats, diarrhea, weight loss, and wasting.

· Opportunistic infections

o Diminished CMI - often life-threatening.

· Aggressive cancers

o Kaposi's sarcoma and extranodal lymphoma.

· Neurologic manifestations

o Dementia, aseptic meningitis, and neuropathy.

· When AIDS was first recognized in the USA in 1981, cases were

identified by finding severe opportunistic infections such as

Pneumocystis carinii pneumonia that indicated profound defects in

cellular immunity in the absence of other causes of immunodeficiency.

When the syndrome was found to be caused by the human

immunodeficiency virus (HIV), it became obvious that severe

opportunistic infections and unusual neoplasms were at one end of a

spectrum of disease, while healthy seropositive individuals were at the

other end.

· 1993 CDC definition includes

o 23 opportunistic infections (eg: pneumocystis pneumonia,

candidiasis, cryptococcosis)

o Neoplasms (eg: Kaposi's sarcoma)

· 1987 definition

o Includes as AIDS cases: persons with documented weight loss,

diarrhea, or dementia and a positive HIV serology.

o There remain criteria for both definitive and presumptive

diagnoses.

o The “expansion” in the definition refers to:

· “Immunodeficiency” identified as the defining characteristic of AIDS.

· Cutoff point at 200 cells/mL

o Several cohort studies show that over 80% of persons with

counts below this level will develop AIDS within 3 years.

· 1993 definition also expanded to include Positive HIV serology plus

o Pulmonary tuberculosis

o Recurrent pneumonia

o Invasive cervical cancer

· By expanding definition HIV-infected persons are diagnosed with AIDS

an average of 1.6 years earlier in the course of the disease.

AIDS Related Complex (ARC)

· All symptomatic HIV cases that do not fit into the CDC definition

o Serology positive for HIV

o CD4 count may be > 200 cells/mL

o CD4 lymphocyte % may be >14%

Definitive AIDS Diagnosis

(with or without laboratory evidence of HIV infection)

· Candidiasis

o Esophagus, trachea, bronchi, or lungs

· Cryptococcosis

o Extrapulmonary

· Cryptosporidiosis

o Diarrhea for >1 month

· Cytomegalovirus disease

o Other than liver, spleen, or lymph nodes.

· Herpes simplex virus infection

o A mucocutaneous ulcer for >1 month

o Bronchitis, pneumonitis, or esophagitis of any duration.

o Kaposi's sarcoma

· Lymphoma of the brain (primary) in a patient <60 years of age

o Mycobacterium avium complex or Mycobacterium kansasii disease

·Disseminated (at a site other than or in addition to lungs, skin, or

cervical or hilar lymph nodes).

· Pneumocystis carinii pneumonia

· Progressive multifocal leukoencephalopathy.

· Toxoplasmosis of the brain.

· Receptive anal intercourse is the riskiest

· From a needle stick with infected blood

o Risk is approx 1:300

· Between 13% and 40% of children born to HIV-infected mothers

contract HIV infection

· The current risk of contracting HIV from a screened unit of blood is

1:100,000

· The most common mode of transmission is bidirectional heterosexual

spread

· The best available estimates indicate that the risk of HIV transmission

with

o Receptive anal intercourse is between 1:100 and 1:30,

o Insertive anal intercourse 1:1000,

o Receptive vaginal intercourse 1:1000,

o Insertive vaginal intercourse 1:10,000,

o Receptive fellatio with ejaculation 1:1000.

· The risk of acquiring HIV infection from illicit drug use with sharing of

needles from an HIV-infected source is estimated to be 1:150.

· When blood transfusion from an HIV-infected donor occurs, the risk of

transmission is 95%

o Not directly oncogenic

· HTLV-I

o Associated with lymphoma

· The HIV genomes contain genes for 3 basic structural proteins

o Gag codes : For group antigen proteins

o Pol codes : For polymerase

o Env codes : For the external envelope protein

· The greatest variability in strains of HIV occurs in the viral envelope

· The hallmark of symptomatic HIV infection is immunodeficiency caused

by continuing viral replication. The virus can infect all cells expressing

the T4 (CD4) antigen, which HIV uses to attach to the cell

· Once it enters a cell, HIV can replicate and cause cell fusion or death.

· The cell principally infected is the CD4 (helper-inducer) lymphocyte,

which directs many other cells in the immune network. With increasing

duration of infection, the number of CD4 lymphocytes falls

· Other cells in the immune network that are infected by HIV include

o B lymphocytes

o Macrophages

· Can lead to generalized hypergammaglobulinemia

· The immunodeficiency of HIV is mixed

· Macrophages

o Act as a reservoir for HIV

o Serve to disseminate it to other organ systems (eg, CNS).

· Glial cells and oligodendrocytes express CD4 antigen

· Neuropathology - results from the release of cytokines and other

neurotoxins by the macrophages.

· Low incidence of certain infections:

o Listeriosis and Aspergillosus

· Autoimmunity:

o Lymphocytic interstitial pneumonitis

o Immunologic thrombocytopenia

· HIV infected individuals appear to have higher rates of allergic

reactions to unknown allergens as seen with eosinophilic pustular

folliculitis (“itchy red bump syndrome”) as well as increased rates of

hypersensitivity reactions to medications

Clinical Findings

· Mean time of approximately 10 years between exposure and

development of AIDS

· Predictive of HIV infection

o Hairy leukoplakia of the tongue

o Disseminated Kaposi's sarcoma

o Cutaneous bacillary angiomatosis

· Systemic complaints: Fever, night sweats, weight loss - TNF (cachectin)

· TNF (cachectin)

o Cause for weight loss

o Seconadry infections such as Pneumocystis pneumonia

o Decreases lipoprotein lipase activity

o Decreases synthesis of fatty acids

o Promotes breakdown of fat

· High alpha interferon levels

o Decreased clearance of triglycerides

· CD4 count 250-750

o Bacterial infections

o Tuberculosis

o Herpes simplex

o Herpes zoster

o Hairy leukoplakia

o Kaposi’s sarcoma

o Vaginal candidiasis

· CD4 count 50-250

o Pneumocystosis

o Toxoplasmosis

o Cryptococcosis

o Coccidioidomycosis

o Cryptosporidiosis

· CD4 count < 50

o Disseminated MAC infection

o Histoplasmosis

o CMV retinitis

o CNS lymphoma

· CD4 count 250-750

o Bacterial infections

o Tuberculosis

o Herpes simplex

o Herpes zoster

o Hairy leukoplakia

o Kaposi’s sarcoma

o Vaginal candidiasis

· CD4 count 50-250

o Pneumocystosis

o Toxoplasmosis

o Cryptococcosis

o Coccidioidomycosis

o Cryptosporidiosis

· CD4 count < 50

o Disseminated MAC infection

o Histoplasmosis

o CMV retinitis

o CNS lymphoma

· Cachexia and Weight loss

o Anabolic steroid oxandrolone - increases body mass

· Nausea and Vomiting

· 2 potentially treatable causes of weight loss

o Depression

o Adrenal insufficiency (due to TB in India)

Sinopulmonary disease

Pneumocystis pneumonia

· Most common site - lungs

· Most common opportunistic infection - 75%

· Hypoxemia may be severe - Type I failure

o PO2 < 60 mm Hg.

· Chest radiograph

o Diffuse or perihilar infiltrates are most characteristic

· Apical infiltrates

o In patients with pneumocystis pneumonia receiving aerosolized

pentamidine prophylaxis

· Large pleural effusions

o Uncommon with pneumocystis pneumonia and suggest:

· Isolated elevation of serum LDH in HIV

o Pneumocystis pneumonia

o Lymphoma

o Disseminated histoplasmosis

o Long-term treatment with zidovudine

· Definitive diagnosis can be obtained by Wright-Giemsa stain of induced

sputum in 50-80% of cases

· Bronchoalveolar lavage

· Elevation of serum LDH occurs in 95% of cases of pneumocystis

pneumonia

· Specificity of this finding is at best 75%

· Against diagnosis of Pneumocystis pneumonia

o Low LDH (<220 units/L)

o Low ESR (<50 mm/hr)

o CD4 count >250 cells/mL within 2 months prior

to respiratory symptoms

· Recurrent pneumothoraces

o Sclerosis with bleomycin or talc

· Other infectious pulmonary diseases :

o Bacterial, mycobacterial, and viral pneumonias

o Pneumococcal pneumonia with septicemia

o Haemophilus influenzae pneumonia

o Pseudomonas aeruginosa

o Multi-drug resistant tuberculosis

· Distinguish between Mycobacterium tuberculosis and atypical

mycobacteria

o DNA probes allow for presumptive identification usually within

days of a positive culture.

o Risk of atypical mycobacteria is very high - CD4 count under 50

cells/mL

· CMV

o Isolation of cytomegalovirus from bronchoalveolar lavage fluid

occurs commonly in AIDS patients

o Does not establish a definitive diagnosis

o Diagnosis of cytomegalovirus pneumonia requires biopsy

o Response to treatment is poor.

· Noninfectious causes of lung disease

o Kaposi's sarcoma

o Non-Hodgkin's lymphoma

o Interstitial pneumonitis

· Pulmonary involvement by HIV directly

o Lymphocytic interstitial pneumonitis

o Chest X-ray: Interstitial infiltrates

o Corticosteroids may be helpful in some cases

References- Harrison's Principles of Internal Medicine