Acanthamoebae are free-living protozoa that are present ubiquitously in the environment. They are found in water, soil, and air samples throughout the world and have been cultured from the throats of both healthy and immunocompromised asymptomatic individuals.1,2 The life cycle of Acanthamoeba consists of a feeding and replicating trophozoite stage and a resilient, dormant cystic stage.1 At least 16 species of Acanthamoeba have been identified, of which several have been associated with human disease.1,2
The pathogenic potential of Acanthamoeba was established in animal models by Culbertson et al in 1959.3 The earliest report of human infection by Acanthamoeba may have been reported by Kernohan et al4 in 1960 when they attributed a brain granuloma to an Iodamoeba butschlii infection. The organism was later identified as Acanthamoeba. Since then, more than 100 cases of granulomatous amebic encephalitis (GAE) and hundreds of cases of amebic keratitis have been reported.2 GAE is a slowly progressive, fatal central nervous system (CNS) infection primarily affecting immunocompromised patients.1-9 Amebic keratitis is a sight-threatening infection that affects the general population of developing countries, as well as healthy individuals worldwide who wear contact lenses.1 Cutaneous acanthamebiasis, often a manifestation of disseminated extracerebral disease, is extremely rare, with only 37 cases, including the present report, described to date.5-33 Dissemination of the ameba is postulated to occur by hematogenous spread from a primary focus within the skin or the upper or lower respiratory tract.14 The prognosis of cutaneous acanthamebiasis is dismal, with a mortality rate of at least 74% in patients without CNS involvement and 100% in patients with CNS involvement.
We present a patient with acquired immunodeficiency syndrome (AIDS) and disseminated cutaneous acanthamebiasis with possible involvement of the CNS whose general condition and cutaneous lesions improved with a prompt antiparasitic therapeutic regimen that included sulfadiazine and antiretroviral therapy.
Case Report
A 51-year-old woman with AIDS, a history of cytomegalovirus retinitis, and multiple episodes of Pneumocystis carinii pneumonia was admitted to the hospital with numerous pruritic, painful cutaneous nodules that had developed over a 2-week period. The initial skin lesion appeared as a small papule on her right forearm that slowly enlarged as other nodules appeared in a generalized distribution over the next 5 to 7 days. Some of the nodules ulcerated, draining purulent fluid and forming necrotic eschars. On admission, the patient reported no chills or fever but complained of photophobia and a 1-week history of severe headache localized to the right frontal region.
On physical examination, the patient was cachectic, photophobic, oriented yet drowsy, and in mild respiratory distress. Multiple intradermal and subcutaneous nodules (0.5–2 cm in diameter), some with overlying erythema, were present on her face, arms, chest, back, legs, and thighs. A deep ulcer covered by a 3x4-cm eschar was noted on the dorsum of her right forearm and an additional ulcer was noted on her leg (Figure 1). Ophthalmologic examination revealed no evidence of active disease and neurologic examination was nonfocal.
The patient's most recent CD4 count and viral load were 3 cells/mm-3 and 34,875 copies/mL-1, respectively. A deep incision biopsy of a skin nodule on the patient's right thigh was performed. Bacterial tissue cultures of the thigh nodule grew Enterococcus faecalis. Mycobacterial, fungal, and viral culture results of the tissue were negative. Blood culture results were negative for bacterial, mycobacterial, and fungal growth. Serum cryptococcus and histoplasma antigens were negative, as was the urine histoplasma antigen.
Histologic sections of the skin biopsy showed an intense inflammatory infiltrate of lymphocytes within the deep dermis, subcutis, and fascia, admixed with neutrophils, plasma cells, and eosinophils. Diffuse areas of collagen and fat necrosis were noted throughout the areas of inflammation. Numerous Acanthamoeba trophozoites measuring 10 to 15 µm were scattered throughout the inflammatory infiltrate. These structures, best visualized on hematoxylin-eosin (H&E) staining, contained a centrally located nucleus and clear nucleolus surrounded by copious vacuolated cytoplasm. Fewer encysted forms were present, and they contained a scalloped inner endocystic wall surrounded by a less ruffled outer ectocyst wall (Figure 2). Culture of the tissue sample was performed in a medium inoculated with Escherichia coli as a nutrient source; results of the culture demonstrated trophozoite forms with acanthopodia formation, confirming the organism to be Acanthamoeba.
Computed tomography (CT) of the brain was unremarkable; however, magnetic resonance imaging of the brain showed cerebral volume loss and nonspecific foci of increased signal intensity in the periventricular and subcortical white matter, basal ganglia, and posterior fossa with no abnormal enhancement. These findings were interpreted to be secondary to human immunodeficiency virus (HIV) infection. Cerebrospinal fluid (CSF) analysis showed one mononuclear leukocyte and 2 erythrocytes. The CSF glucose and protein levels were 50 mg/dL and 17 mg/dL, respectively (reference ranges, 50–75 mg/dL and 15–45 mg/dL, respectively). CSF culture results were sterile and were negative for cryptococcus antigen. Results of microscopic examination showed no evidence of amebic organisms in the CSF.
Three days after admission, the patient was prescribed a therapeutic regimen of pentamidine 160 mg intravenously once a day and oral 5-flucytosine 1 g every 6 hours. Unfortunately, new nodules continued to appear, and some of the existing nodules enlarged and ulcerated forming necrotic eschars. Because of the patient's poor response, sulfadiazine and highly active antiretroviral therapy (HAART) were added to the therapeutic regimen. The appearance of new nodules subsequently ceased, and the patient experienced slow regression of existing nodules. The patient's general well being also improved as her photophobia resolved and her severe headaches, which initially required intravenous narcotic analgesia, diminished.
After completing a 14-day course of intravenous pentamidine, the patient was discharged in stable condition on a therapeutic regimen of 5-flucytosine 1 g every 6 hours, sulfadiazine 1 g every 6 hours, and HAART therapy consisting of tenofovir 300 mg/d, lamivudine 300 mg/d, and abacavir 600 mg/d. Three months after discharge, no evidence of CNS decline was noted. Improvement in the patient's general condition and in her cutaneous lesions continues despite less than optimal compliance with the treatment regimen.
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