Acanthamoeba sinusitis with subsequent dissemination in an AIDS patient.

Abstract

Otolaryngologists can play an important role in the care of patients with acquired immunodeficiency syndrome (AIDS) and/or human immunodeficiency virus infection. We present the case of an AIDS patient who was hospitalized for dehydration and who was soon found to have sinusitis and subsequent disseminated infection caused by Acanthamoeba. To treat the Acanthamoeba infection, the patient was started on oral itraconazole and intravenous metronidazole; IV pentamidine was added 2 days later. Despite aggressive therapy, on the eleventh day of hospitalization, the patient was obtundent and provided minimal response to noxious stimuli. He died on the sixteenth day of hospitalization.

This case is one of only six reported cases of Acanthamoeba associated with sinusitis. Current therapeutic regimens have not been successful for most of these patients, and the prognosis is poor.

Introduction

The first documented cases of acquired immunodeficiency syndrome (AIDS), which is caused by the human immunodeficiency virus (HIV), were described in 1981. The World Health Organization has estimated that the combined number of cases of HIV infection and AIDS will reach 40 million in 2000. [1]

With the increasing prevalence of HIV infection and AIDS, it is essential that otolaryngologists be aware of the ENT manifestations of HIV infection. Otolaryngologists can play an important role in the care of HIV patients and are often asked to evaluate them. The otolaryngologic manifestations of AIDS are varied; they include otorrhea, hearing loss, otitis media and externa, rhinologic symptoms (including sinusitis), nasopharyngeal masses, parotid cysts, and cervical lymphadenopathy, as well as other manifestations of conditions unique to the AIDS condition, such as Kaposi's sarcoma and Pneumocystis carinii infection. [2] Although sinusitis is not unique to the AIDS setting, otolaryngologists should be aware of the wide range of possible infectious etiologies in the HIV patient.

Many cases of HIV sinusitis are caused by common organisms. At least one study has shown that Streptococcus pneumoniae and Streptococcus viridans are the two most common causes of sinusitis in both the immunocompromised and immunocompetent patient populations. [3] However, the same study has also shown that HIV patients are more likely to suffer from sinusitis caused by the more atypical agents, such as Pseudomonas aeruginosa, Hemophilus influenzae, Staphylococcus aureus, coagulase-negative staphylococcus, Candida albicans, Klebsiellapneumoniae, Listeria monocytogenes, and Torulopsis (Candida) glabrata. In addition, rare atypical agents have also been described in the literature: cytomegalovirus, [4] microsporidia, [5] aspergillus [6] and other fungi, [7] cryptosporidia, [8] and amoebae. [9]

We present the case of an AIDS patient who had sinusitis and subsequent disseminated infection caused by Acanthamoeba. To date, this is only the sixth reported case of sinusitis caused by this protozoan and the first described in the otolaryngology literature. Members of the Acanthamoeba genus are free-living protozoans. These organisms are common in the environment, and humans often make contact with them, usually without any ill effects. However, they have recently received much attention as a cause of Acanthamoeba keratitis in otherwise healthy individuals and opportunistic infections in immunocompromised patients. [10] Sinusitis is one example of an opportunistic infection that can be caused by Acanthamoeba; it is actually thought to be one of the predisposing conditions that might lead to a more serious disseminated disease state.

Case report

A 42-year-old man with AIDS (CDC subcategory C3) was admitted for dehydration secondary to intractable diarrhea of 3 days' duration. Prior to admission, the patient had experienced nasal congestion and discharge. Earlier examinations had revealed a pink, edematous nasal mucosa and left facial swelling. Computed tomography (CT) showed evidence of sinusitis in the left maxillary and ethmoid sinuses as well as an abscess in the left buccal soft tissues (figure 1). The abscess and sinusitis were addressed surgically. Using the Caldwell-Luc approach, biopsies and cultures of the left maxillary sinus tissue were collected and found to be positive for Acanthamoeba (figure 2). In addition, the patient had a history of Kaposi's sarcoma, toxoplasmosis, Shigella enteritis, cytomegaloviral retinitis, and peripheral neuropathy.

The patient's medications on admission included zalcitabine, lamivudine, saquinavir, trimethoprim/ sulfamethoxazole, clindamycin, ciprofloxacin, ganciclovir, senna, naproxen, beclomethasone dipropionate, oxymetazoline HCl, morphine, potassium chloride, warfarin, and zolpidem.

On admission, the patient had a temperature of 100.2[degrees] F, a pulse rate of 117 beats per minute, and a blood pressure of 123/68 mm Hg with orthostatic changes. The physical examination was significant for left facial swelling, some erythematous lesions in the oral cavity with slight exudate, and multiple violaceous plaques on his skin that were consistent with Kaposi' s sarcoma. The rest of the examination was normal.

Laboratory studies showed a sodium level of 136 mmol/ L, a potassium of 4.9 mmol/L, a chloride of 99 mmol/L, a bicarbonate of 23 mmol/L, a BUN of 6 mg/dl, a creatinine of 0.5 mg/dl, and a glucose of 94 mg/dl. The patient had a white blood cell count of 11.6 x [10.sup.3][micro]1, a hemoglobin of 8.7 g/dl, a hematocrit of 25.2%, and a platelet count of 508 x [13.sup.3]/[micro]1. His serum and urine osmolalities were 259 and 351 mOsm/kg, respectively. His prothrombin time was 14.4 seconds, and his activated partial thromboplastin time was 73 seconds. The albumin level was 3 g/dl, total bilirubin was 0.6 mg/dl, and alkaline phosphatase was 147 IU/L. Assays for Clostridium difficile toxins were negative.

To treat the Acanthamoeba infection, the patient was started on 200mg of oral itraconazole twice a day and 450 mg of metronidazole intravenously every 6 hours. Six stool samples (two for bacteriology, two for parasitology, and two for acid-fast staining) were negative. On the third day of hospitalization, the patient began to spike fevers as high as [103[degrees] F. Blood, urine, and Mycobacterium avium intracellulare cultures were negative. At this point, IV pentamidine was added to the anti-Acanthamoeba regimen. A CT scan of the head and sinuses obtained on the fifth day of hospitalization revealed changes consistent with early progressive multifocal leukoencephalopathy.

On the eleventh day of hospitalization, the patient was obtundent and provided minimal response to noxious stimuli. His chest x-ray at the time showed multiple rounded densities in both lung fields (figure 3). An arterial blood gas sample showed a pH of 7.52, [Pco.sub.2] of 32 mm Hg, a [Po.sub.2] of 53 mm Hg, a bicarbonate of 28 mmol/L, and an [O.sub.2] saturation of 90%. At this point, a decision was made with the family to pursue less aggressive management, and a standing order of DO NOT RESUSCITATE was posted. The patient died on the sixteenth day of hospitalization. The hospital obtained consent for an autopsy limited to the patient's lung nodules, the results of which were consistent with an Acanthamoeba infection, according to the pathology report.

Discussion

Causes. At least three factors help explain the predisposition of HIV patients to sinusitis.

Acquired atopy. These patients are thought to have an acquired atopic state, and sinusitis is included in this condition. [11] It is believed that this atopic state is caused, at least in part, by the elevated levels of immunoglobulin E seen in HIV patients. Thus, atopic sinusitis might help to create a condition favorable to an infectious process.

Diminished mucociliary clearance. These patients experience a reduction in the mucociliary clearance of their sinuses. [12] This decreased clearance contributes to the obstruction of the sinus ostia. The obstructed ostia ultimately help create an environment that is favorable to pathogenic overgrowth. Although the exact mechanism has not been elucidated, other groups of immunocompromised patients (such as those who receive chemotherapy, irradiation, or bone marrow transplantation) have shown a similar decrease in mucociliary clearance. [13] These other immunocompromised patients, unlike HIV patients, regain their mucociliary clearance after their immune systems return to normal.

Low CD4 cell counts. It has been shown that the general depletion of CD4 T lymphocytes in HIV patients occurs in the nasal mucosa as well as elsewhere. [14] The T lymphocyte is the predominant intraepithelial cell in normal nasal mucosa. [15] As the number of CD4 cells declines, the HIV patient incurs a greater risk of developing an infection in the sinus and/or respiratory tract.

These three factors help to explain the higher prevalence--up to 70% [16]--of sinusitis and its atypical etiologies seen in HIV patients.

The disease process. Our patient was diagnosed with Acanthamoeba sinusitis by culture and biopsy. Species of the Acanthamoeba genus are protozoans who, during their life cycles, exist as two entities: the trophozoites and the cyst. The sizes of the trophozoites and cysts vary among the different species. [17] These ubiquitous pathogens have been found not only in the air, but in fresh water, sea water, tap water, bottled mineral water, industrial cooling water, medicinal pools, chlorinated swimming pools, frozen swimming water, ocean sediment, air conditioners, dental treatment units, gastric lavage tubing, dialysis units, contact lenses, sewage, soil, and compost. [18] One study of healthy active-duty soldiers who were stationed in a dry, windy, and dusty region found that 15% of them had Acanthamoeba in their nasal mucosa. [19] This finding is consistent with beliefs about the proposed spread of infection in immunocompromised patients. It is thought that after Acanthamoeba is first introduced into the skin and/or respiratory tract, it subsequently disseminates. [20] This is what happened to our patient, whose cultures were positive for Acanthamoeba in the left maxillary sinus before the pathogen spread to the lungs.

One uncommon, but almost always fatal, consequence of dissemination is multifocal encephalitis (granulomatous amebic encephalitis). [20] The CT scan of our patient's head suggests that such a central nervous system (CNS) infection was occurring at the time of his death.

Treatment. There is no single regimen that is believed to be effective against disseminated Acanthamoeba infections, and the prognosis is usually poor. There have been only two reports of successful treatment--one with a combination of IV pentamidine and oral itraconazole and the other with 5-fluorocytosine. [21, 22] Both patients were immunocompromised with disseminated infection, but with no CNS involvement.

The regimen for our patient--pentamidine, itraconazole, and metronidazole--was not successful in eradicating the infection. Although in vitro studies have yielded varying results, they have provided us with a list of effective and possibly effective anti-Acanthamoeba medications. These drugs include neomycin sulfate, paromomycin, natamycin, ketoconazole, ciclopirox olamine, [23] pentamidine isethionate, propamidine isethionate, stilbamidine isethionate, [24] amphotericin B, sulfadiazine, sulfisoxazole, sulfamethoxazole, polymyxin B and E, [25] and clotrimazole. [26]

Treatment for the sinusitis component of HIV infection is important and consists of eradicating the infection and providing symptomatic relief. Our patient was given beclomethasone and oxymetazoline for relief of nasal congestion. Long-term use of topical steroids has not increased the rates of opportunistic infections and it is safe when used properly. [27] Although topical decongestants are generally not recommended for chronic sinusitis, [27] our patient experienced symptomatic relief with oxymetazoline during an acute exacerbation. Some patients with HIV sinusitis might benefit from a mucolytic agent such as guaifenesin, owing to the thick and tenacious nature of their mucus. [28]

When conventional methods fail to relieve symptoms, endoscopic sinus surgery can often offer palliation. Although sinus surgery has not been as successful in curing sinus disease in HIV patients as it is in the normal population, it definitely improves their quality of life. [27] The refractory nature of HIV sinusitis to surgery was evident in our patient, who still had sinus disease following sinus surgery.

As the number of cases of AIDS and HIV infection continues to increase, active research for better treatment options is ongoing. This research will undoubtedly result in longer survival and less morbidity.

Acknowledgment

The authors would like to express gratitude for the aid and support of Dr. Jerome Meyers of the Department of Pathology at the Madigan Army Medical Center in Tacoma, Wash.

From the Department of Surgery, Madigan Army Medical Center, Tacoma, Wash. (Dr. Kim), the Department of Surgery, Tripler Regional Medical Center, Tripler AMC, Honolulu (Dr. Syms and Dr. Holtel), and the Department of Pathology, Brooke Army Medical Center, San Antonio, Tex. (Dr. Nauschuetz).

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