Immunosuppression And Infection

The hallmark of the acquired immunosuppression appearing after infection with HIV is the occurrence of life-threatening infections by organisms that are usually opportunistic or nonpathogenic. A range of orbital infections has been seen, which may be bacterial, fungal, parasitic, or protozoan. These are listed in Table 3.2.

Invasive Aspergillosis

The commonest orbital infection seen in association with HIV/AIDS is invasive aspergillosis.30 Risk factors for invasive aspergillosis apart from HIV/AIDS include other causes of decreased cellular immunity, neutropenia below 1000/mm3, defects of phagocytosis, hematological malignancy, steroids or other im-munosuppressive agents, and diabetes mellitus.31 As-pergillus is a ubiquitous fungus found especially in soil and in decaying vegetable matter. A. fumigatus and A. flavus are the species most commonly seen in orbital and paranasal sinus disease. A range of patterns of disease may be associated with this organism, broadly divided into noninvasive and invasive forms. In nonimmunocompromised patients, two forms, both less aggressive, may occur. Aspergillus sinusitis may cause a chronic form of sinusitis in patients with atopy whose immune systems are otherwise normal. The sinuses may expand dramatically, with resultant telecanthus and structural changes in the facial skeleton. A fungus ball (aspergilloma) may occur in poorly aerated sinuses. Both these types of infection are characterized by a lack of tissue reaction, invasion, or necrosis. By contrast, in immunocompromised individuals, infection with Aspergillus may take the form of an invasive granulomatous inflammation with concomitant fibrosis, or a more fulminant necrotizing form characterized by vascular invasion and associated tissue necrosis.

When invading the orbit, aspergillosis usually spreads from the adjacent paranasal sinuses but may spread hematogenously from distant sites of infection, most commonly, the lung. The posterior orbit is commonly involved, presenting as an orbital apex syndrome, with loss of vision, ophthalmoplegia, loss of sensation in the first division of the trigeminal nerve and proptosis, often with pain.32 In the early phases of the process, single nerves may be affected before progression to a full orbital apex syndrome. The cavernous sinus is usually also involved by the process. All too often, spread occurs to the cranial cavity and brain, with cerebral infarction or subarachnoid hemorrhage being terminal events. The diagnosis of invasive aspergillosis is aided by clinical imaging. Computed tomography (CT) images often show opaci-fication of adjacent paranasal sinuses, with enhancing soft tissue masses usually invading the posterior orbit, with or without bone destruction. Intraluminal calcification visible on CT images is said to be characteristic but is present in less than 50% of cases.33 Magnetic resonance imaging often shows more widespread enhancement than is seen on CT, showing involvement of adjacent dura or optic nerve, for exam-ple.34 The definitive diagnosis of invasive aspergillosis is made by examination of affected tissue, both for his-topathology and microbiology. If the condition is suspected, tissue should be obtained as soon as possible. It is important to alert the laboratory to the suspicion of fungal infection. Tissue may be obtained by fine needle aspirate,35 or biopsy via an endoscopic or open approach. Frozen sections should be requested, since the establishment of an immediate diagnosis may allow the surgeon to proceed to appropriate debridement.

Treatment of invasive aspergillosis is difficult. Reversal of any immunosuppression, if possible, is important. In AIDS patients, in whom invasive as-pergillosis is often fatal, treatment with antiretroviral drugs, including protease inhibitors, may prolong survival for extensive periods, even in the presence of invasive aspergillosis.36 The role of wide surgical debridement is unclear.37 Systemic and local antifungal therapy is the mainstay of treatment, with the less toxic liposomal form of amphotericin B most widely used.38

Mucormycosis

Mucormycosis is usually a fulminant form of fungal infection occurring in a group of patients somewhat different from those who are susceptible to invasive aspergillosis (see also Chapter 27). Often referred to as phycomycosis or zygomycosis, mucormycosis is a dis

TABLE 3.2. Infectious Diseases of the Orbit Occurring in HIV/AIDS Patients.

Bacterial

Orbital cellulitis/abscess

Syphilitic periostitis

Fungal

Invasive aspergillosis

Mucormycosis (uncommon)

Parasitic/protozoan

Infection with Pneumocystis carinii

Toxoplasmosis

ease caused by a variety of fungi from the order Muco-rales in the class Zygomycetes. These organisms are widespread molds that we are exposed to regularly in daily life, but disease is rare because of their low virulence and because of host defenses. The people most susceptible are the debilitated, injured, and diabetic (especially ketoacidotic, poorly controlled diabetics), and those who are immunocompromised, most commonly by corticosteroids. Renal dialysis patients have also been commonly affected possibly because of the previous widespread use of deferoxamine in these patients to treat aluminum or iron overload.39 Iron overload of itself may be a risk factor also,40 with some evidence that the acidosis found in diabetics alters iron metabolism and enhances the ability of the Mucor organisms to grow in tissues.41 AIDS patients do not appear to have an increased susceptibility to mucormycosis. This is probably because of the vital role of polymorphonuclear neutrophils (PMNs) in the prevention of the disease and the relatively normal function of PMNs in AIDS.42

Spores enter the airways, and for rhino-orbital-cerebral mucormycosis, the infection begins in the paranasal sinuses, or nasal airway, then spreading to the orbit and cranial cavity. The organism causes isch-emic necrosis and invades blood vessels, including major arteries. The disease process is usually more fulminant than in invasive aspergillosis, with time from onset of symptoms to death often measured in days. The predisposed patient presents with pain, headache, swelling of the lids, ophthalmoplegia, and visual loss, occasionally with a central retinal artery occlusion. The classic black eschar due to tissue necrosis, which may be seen in the skin, nasal mucosa, or palate, is a late sign. Signs of intracranial involvement usually occur within a short period, with death resulting from cerebral infarction or subarachnoid and intracerebral hemorrhage. Early diagnosis is essential in mucormycosis. The tissue required for diagnostic purposes can be obtained from the sinuses or the orbit and processed both for histopathology (frozen section) and microbiology. Reversal of any immunosuppression and reversal of acidosis improves survival significantly. Widespread surgical debridement has a clearer role in mucormyco-sis than in aspergillosis and often involves orbital ex-enteration and widespread removal of affected paranasal sinuses.43 Antifungal therapy, both local and systemic, is critical. There may be a role for adjunctive hyperbaric oxygen therapy.44 Despite these measures, mortality rates remain high in mucormycosis.

Other Infections and Orbital Inflammation in AIDS Patients

Fulminant bacterial infections of the orbit have been reported in AIDS patients. Francis et al. reported a case of orbital streptococcal gangrene (necrotizing fasciitis) in an AIDS patient with extensive tissue necrosis and visual loss secondary to infection with group A 3-hemolytic Streptococcus.45 Kronish et al. also documented a variety of bacterial infections in AIDS patients, including cases caused by low virulence organisms such as Propionibacterium acnes.30 Parasitic orbital infections have also been reported, including cases of Toxoplasma orbital cellulitis.46 Orbital infection from Pneumocystis carinii is rare,47 but Pseudomonas orbital cellulitis has been reported by several authors.30,48

Noninfectious Orbital Inflammation in AIDS

A small number of cases of apparently noninfectious inflammation of the orbit have been described in AIDS patients. This includes a case of "pseudotumor"49 and one of "ocular myositis" that responded to high doses of corticosteroids.50 Extreme caution needs to be exercised in accepting such a diagnosis and then treating with further immunosuppression. If the diagnosis is erroneous and the condition is, for example, a fungal infection, the addition of the steroids may accelerate the process.

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