Bacterial Infections

Mycobacteriosis (atypical, e.g., M. avium-intracellulare, disseminated or extrapulmonary; M. tuberculosis, pulmonary or extrapulmonary)

Nocardiosis (pneumonia, meningitis, disseminated)

Salmonella infections, disseminated

Viral Infections

Cytomegalovirus (pulmonary, intestinal, retinitis, or CNS infections)

Herpes simplex virus (localized or disseminated)

Varicella-zoster virus (localized or disseminated)

Progressive multifocal leukoencephalopathy)

NEOPLASMS

Kaposi sarcoma

B-cell non-Hodgkin lymphomas

Primary lymphoma of the brain

Invasive cancer of uterine cervix

CNS, central nervous system.

atypical and typical mycobacteria, Cryptococcus neoformans, Toxoplasma gondii, Cryptosporidium, herpes simplex virus, papovaviruses, and Histoplasma capsulatum.

Candidiasis is the most common fungal infection in patients with AIDS. Candida infection of the oral cavity (thrush) and esophagus are the two most common clinical manifestations of

candidiasis in HIV-infected patients. In asymptomatic HIV-infected individuals, oral candidiasis is a sign of immunologic decompensation, and it often heralds the transition to AIDS.

Invasive candidiasis is not common in patients with AIDS, and it usually occurs when there is drug-induced neutropenia or use of indwelling catheters. Cytomegalovirus may cause

disseminated disease, although, more commonly, it affects the eye and gastrointestinal tract. Chorioretinitis was seen in approximately 25% of patients pre-HAART, but this has decreased

by over 50% after the intiation of HAART. Cytomegalovirus retinitis occurs almost exclusively in patients with CD4+ cell counts below 50/μl. Gastrointestinal disease, seen in 5% to 10%

of cases, manifests as esophagitis and colitis, the latter associated with multiple mucosal ulcerations. Disseminated bacterial infection with atypical mycobacteria (mainly M. aviumintracellulare)

also occurs late, in the setting of severe immunosuppression. Coincident with the AIDS epidemic, the incidence of tuberculosis has risen dramatically. [153] Worldwide,

almost a third of all deaths in AIDS patients are attributable to tuberculosis; in the United states, about 5% of patients with AIDS develop active tuberculosis. Patients with AIDS have

reactivation of latent pulmonary disease as well as outbreaks of primary infection. In contrast to infection with atypical mycobacteria, M. tuberculosis manifests itself early in the course of

AIDS. As with tuberculosis in other settings, the infection may be confined to lungs or may involve multiple organs. The pattern of expression depends on the degree of

immunosuppression; dissemination is more common in patients with very low CD4+ cell counts. Most worrisome are reports indicating that a growing number of isolates are resistant to

multiple drugs.

Cryptococcosis occurs in about 10% of AIDS patients. Among fungal infections that prey on HIV-infected individuals, it is second only to candidiasis. As in other settings with

immunosuppression, meningitis is the major clinical manifestation of cryptococcosis. In contrast to Cryptococcus, T. gondii, another frequent invader of the central nervous system in

AIDS, causes encephalitis and is responsible for 50% of all mass lesions in the central nervous system. JC virus, a human papovavirus, is another important cause of central nervous system

infections in HIV-infected patients. It causes progressive multifocal leukoencephalopathy ( Chapter 28 ). Herpes simplex virus infection is manifested by mucocutaneous ulcerations

involving the mouth, esophagus, external genitalia, and perianal region. Persistent diarrhea, so common in patients with AIDS, is often caused by infections with protozoans such as

Cryptosporidium, Isospora belli, or microsporidia. These patients have chronic, profuse, watery diarrhea with massive fluid loss. Diarrhea may also result from infection with enteric

bacteria, such as Salmonella and Shigella, as well as M. avium-intracellulare. Depressed humoral immunity renders AIDS patients susceptible to severe, recurrent bacterial pneumonias.

Patients with AIDS have a high incidence of certain tumors, especially Kaposi sarcoma (KS), non-Hodgkin B-cell lymphoma, cervical cancer in women, and anal cancer in men.[154] [155]

It is estimated that 25% to 40% of HIV-infected individuals will eventually develop a malignancy. A common feature of these tumors is that they are all believed to be caused by oncogenic

DNA viruses, that is, Kaposi sarcoma herpesvirus (Kaposi sarcoma), EBV (B-cell lymphoma), human papillomavirus (cervical and anal carcinoma). The increased risk of malignancy is

thus mainly a consequence of increased susceptibility to infections by these viruses and decreased immunity against the tumors.

KS, a vascular tumor that is otherwise rare in the United States, is the most common neoplasm in patients with AIDS. The morphology of KS and its occurrence in patients not infected

with HIV are discussed in Chapter 11 . At the onset of the AIDS epidemic, up to 30% of infected homosexual or bisexual men had KS, but in recent years, with use of HAART there has

been a marked decline in its incidence, from 15 cases per 1000 person years to less than 5 cases.

The lesions of KS are characterized by the proliferation of spindle-shaped cells that express markers of both endothelial (vascular or lymphatic) and smooth muscle lineages. There is also a

profusion of slit-like vascular spaces, suggesting that the lesions may arise from primitive mesenchymal precursors of vascular channels. In addition, KS lesions display chronic

inflammatory cell infiltrates. There is still some debate about whether the lesions represent an exuberant hyperplasia or a malignant neoplasm, but the weight of evidence favors the former.

For instance, spindle cells in many KS lesions are polyclonal or oligoclonal, although more advanced lesions occasionally show monoclonality.[156] Moreover, spindle cells in many KS

lesions are diploid, dependent on growth factors for their proliferation, and do not form tumors in immunodeficient mice.[157] When KS cells are implanted subcutaneously in such mice,

they transiently induce slit-like new blood vessels and inflammatory infiltrates in the surrounding tissue; these elements recall features of human KS, but interestingly are of murine origin.

When the human KS cells involute, these elements also regress. These observations suggest that KS pathogenesis involves a complex web of paracrine signaling interactions among

different types of cells, no one of which is fully autonomous. One popular view envisions that spindle cells produce pro-inflammatory and angiogenic factors, recruiting the inflammatory

and neovascular components of the lesion, while the latter components supply signals that aid in spindle cell survival or growth[157] ( Fig. 6-51 ).

But what initiates this cycle of events? Clues to this came from the observation that not all HIV patients are at equal risk for KS development. AIDS-related KS is twenty times more

frequent in individuals who acquire HIV by sexual routes compared to those who acquire it parenterally. This observation suggested that a sexually transmitted agent other than HIV might

be implicated in KS etiology and prompted a search for new viruses in KS. This search yielded a novel herpesvirus, aptly labeled KS herpesvirus (KSHV), or human herpesvirus 8.[158]

Epidemiologic studies strongly link KSHV to KS development. Infection is uncommon in the general population and strikingly increased in prevalence in groups in which KS is common.

In individual patients, KSHV infection precedes KS development and is highly correlated with increased KS risk. KSHV DNA is found in virtually all KS lesions, including those that

occur in HIV-negative populations. In the lesions, KSHV is strikingly localized to the spindle cells, which display predominantly latent infection.[159] Thus,

Figure 6-51Proposed role of HIV, KSHV (HHV8), and cytokines in the pathogenesis of Kaposi sarcoma. Cytokines are produced by the mesenchymal cells infected by KSHV, or by HIVinfected

CD4+ cells. B cells may also be infected by KSHV; their role in the disease is unclear.

Figure 6-52Amyloidosis. A, A section of the liver stained with Congo red reveals pink-red deposits of amyloid in the walls of blood vessels and along sinusoids. B, Note the yellow-green

birefringence of the deposits when observed by polarizing microscope. (Courtesy of Dr. Trace Worrell and Sandy Hinton, Department of Pathology, University of Texas Southwestern

Medical School, Dallas TX.)

Figure 6-53Structure of an amyloid fibril, depicting the b-pleated sheet structure and binding sites for the Congo red dye, which is used for diagnosis of amyloidosis. (Modified from

Glenner GG: Amyloid deposit and amyloidosis. The b-fibrilloses. N Engl J Med 52:148, 1980. By permission of The New England Journal of Medicine.)

TABLE 6-15-- Classification of Amyloidosis

Date: 2016-04-22; view: 684