Clinical Features

2.6.1 Immunosuppressed Patients

Cytomegalovirus is the most common life-threatening opportunistic viral pathogen in patients with AIDS,(Jacobson and Mills, 1988) and in one autopsy series, over half of patients dying from any AIDS-related complication had CMV infection o f at least one organ.(Morinelli et al. 1992) As prophylaxis regimens against P. carinii pneumonia have become widespread, CMV infection has emerged as the most frequent initial AIDS-related illness.(Hoover et al. 1993) In the post-HAART era the incidence of CMV disease, as with other opportunistic infections, has been declining in the USA(Palella et al. 1998) and other developed countries.

It is estimated that up to 20% of patients with AIDS will develop CMV related-gastrointestinal disease.(Dieterich et al. 1993) Cytomegalovirus oesophagitis is a common cause o f dysphagia in patients with AIDS and colitis/ileitis has been estimated to develop in 10% of patients with AIDS in the pre-HAART era. Cytomegalovirus is an infrequent cause o f hepatitis and biliary tract disease.(Blanchard, 1992)

Cytomegalovirus can be detected in culture from a high proportion of lung tissue or bronchial fluids obtained from patients with AIDS; in one study, 43% of specimens were culture positive.(Broaddus et al. 1985) Cultures cannot distinguish between colonization by CMV and clinically significant infection, however.(Millar et al. 1990) Furthermore, the presence of inclusion bodies in the lung does not

necessarily implicate CMV as the cause o f clinical disease, unless other causes have been excluded.(McKenzie et al. 1991) Only 4% of patients with AIDS and

pneumonitis have been found to have CMV as the sole pathogen.(Murray et al. 1984) In contrast, CMV pneumonitis in immunosuppressed solid organ or bone marrow transplant recipients is common, and isolation of CMV from lung tissue or bronchial fluids is associated with a poor prognosis in bone marrow transplant

recipients.(Meyers et al. 1982)

Cytomegalovirus infection o f the nervous system in patients with AIDS may cause a number of disorders, including meningoencephalitis, polyradiculomyelitis, and peripheral neuropathy.(de Cans et al. 1990; Masdeu et al. 1988; Said et al.

1991) The role o f CMV in the AIDS dementia complex is uncertain, but it is probable that HIV itself, rather than CMV, is the main causal agent.(Navia et al. 1986)

Other disorders attributed to CMV in patients with AIDS have included adrenalitis,(Glasgow et al. 1985) thyroiditis,(Frank et al. 1987)

epididymitis,(Randazzo et al. 1986) and dermatitis.(Thiboutot et al. 1991)

2.6.2 Ocular Disease

Ocular CMV infection is primarily a disease o f the retina, although there have been isolated reports of infection involving other ocular structures, as described at the end o f this subsection. Detailed information about CMV retinitis is derived almost exclusively from patients with AIDS; possible differences in CMV retinitis between patients with AIDS and others at risk are identified in the discussion below.

The diagnosis of CMV retinitis is usually based on clinical findings.

Untreated disease can have a variety o f clinical presentations, with variable amounts of retinal whitening or opacification (due to oedema and necrosis), retinal

haemorrhage, and vascular sheathing. Two distinct clinical types o f CMV retinitis have been described, based on retinal characteristics. The "fulminant/oedematous" variant corresponds to the classic appearance of disease, which was recognized before the AIDS epidemic. These lesions tend to have the following characteristics: dense confluent areas of retinal opacification (through which choroidal details cannot be seen) involving both the border and central areas of the lesions; and the absence of clear central atrophic areas (unless the lesions are large, involving 25% or more o f the retina), (see Figure 2.1)

Other suggestive, but not definitive, characteristics of fulminant/oedematous lesions are the following: location along vessels; haemorrhage sufficient to obscure underlying choroidal or retinal detail; and inflammatory vascular sheathing.

The "indolent/granular" variant is defined by the following characteristics: only faint, grainy opacification of the retina (through which choroidal details can be seen); only trace (punctate) or no haemorrhage; and no inflammatory vascular sheathing, (see Figure 2.2)

Other suggestive, but not definitive, characteristics o f indolent/granular lesions are the following: circular or oval shape; location not overlying arterioles or venules; and opacification o f the lesion border only, with the presence o f a clear atrophic central area.

Both lesion variants have an irregular, dry-appearing, granular border, which is the most characteristic feature of CMV retinitis. There can be a variable number of distinct "satellite” lesions, which are considered to be encompassed within the lesion border, (see Figure 2.3)

Other clinical features that suggest a diagnosis of CMV retinitis include relatively slow enlargement of lesions and minimal vitreous humor and anterior chamber inflammatory reactions. These two variants seem to exist at the ends of a disease spectrum, and many lesions cannot be classified as one clinical type or the other; they are considered to be "indeterminant" in type.

In occasional patients, severe retinal periphlebitis has been the most prominent feature of AIDS-related CMV retinitis.(Geier et al. 1992; Spaide et al. 1992) Such patients have foci of CMV retinitis typical of the fulminant/oedematous variant somewhere in the fundus, but also have dense inflammatory sheathing of vessels throughout the retina, even remote from the site of infection. Perivascular

inflammatory cells remote from foci o f CMV-induced retinal necrosis can be found in many patients,(Holland et al. 1983) however, and those who appear to have frosted branch angiitis can be thought of as having an extreme form o f the

fulminant/oedematous variant o f disease. In the post-HAART era patients may present with very indolent CMV retinitis lesions, with mild or no clinically evident border opacity that may gradually enlarge. With immune reconstitution,

inflammatory complications may become present such as epiretinal membranes, cystoid macula oedema and vitritis.(Karavellas et al. 1998; Zegans et al. 1997)

Figure 2.1

Fulminant/oedematous variant of untreated CMV retinitis following the major retinal vessels in the right eye of a patient with AIDS.

Figure 2.2

Figure 2.2

CMV retintitis in the superior right eye. There are a number of satellite lesions at the border between infected and normal retina (arrow).

Figure 2.4

Active CMV retinitis (left figure below) and inactive CMV retinitis following treatment (right figure below). The boreder of the lesion has no opacity. The central portion of the lesion is characterised by gliosis and mild pigment stippling.