Disseminated Cutaneous Acanthamebiasis: A Case Report and Review of the Literature
The genus Acanthamoeba includes species of free-living soil and water ameba that have been implicated in a small number of human diseases. Acanthamoeba species have been identified as the etiologic agents in 2 well-defined clinical entities, amebic keratitis and granulomatous amebic encephalitis (GAE). Less commonly, Acanthamoeba species have been identified as the cause of disseminated disease in debilitated and immunocompromised patients. Cutaneous acanthamebiasis, often a reflection of disseminated disease, is an increasingly recognized infection since the emergence of acquired immunodeficiency syndrome (AIDS) and the use of immunosuppressive drugs. The disease portends a poor prognosis and is uniformly fatal if the infection involves the central nervous system (CNS). We describe a patient with advanced AIDS who presented with disseminated cutaneous lesions, headache, and photophobia, and in whom a diagnosis of cutaneous acanthamebiasis was made based on the results of a skin biopsy. A multidrug therapeutic regimen was begun that included sulfadiazine; the patient responded favorably to treatment. This paper also reviews 36 previously reported cases of cutaneous acanthamebiasis with delineation of clinical, diagnostic, histologic, and prognostic features, as well as discusses treatment options.
Cutaneous lesions are present in 90% of patients with disseminated acanthamebiasis, making it the most common sign of disseminated disease. The primary cutaneous lesions in patients with acanthamebiasis are polymorphic and are commonly described as intradermal6 or subcutaneous6,18,26 nodules that are erythematous6,10,11,16 or violaceous,10,22 ranging from a few millimeters to several centimeters in diameter. In addition, papules,7,8,16 pustules,14 plaques,12 cellulitis,28 and intramuscular abscesses23 all have been described. Lesions can be pruritic,14 tender,6,11 or nontender,10,18 and they typically evolve through a course of enlargement, suppuration, and ulceration. A necrotic eschar may develop and then slough, thereby deepening the ulcer.16 The differential diagnosis of nodular and ulcerative cutaneous lesions is broad and includes deep fungal or mycobacterial infections, pyoderma gangrenosum, and vasculitis.
The histologic findings of the cutaneous lesions in acanthamebiasis may show granulomatous inflammation, which is notably absent in immunocompromised patients with severe disease and CNS involvement.19,27 Other reported histopathologic features include leukocytoclastic5,7 or necrotizing10,11 vasculitis, panniculitis,14,22,27 and acute and/or chronic inflammation.9,16,20,21,23,30 The diagnosis of Acanthamoeba infection requires visualization of amebic trophozoites and/or cysts, which may be found perivascularly. Ideally, a culture should be performed on the organisms with subsequent morphologic examination. Trophozoites and cysts both contain a single nucleus and a nucleolus. Acanthamoeba cysts vary in size depending on the species, but commonly range from 13 to 30 mm in diameter. Trophozoites contain slender projections termed acanthopodia, which aid in motitility.34 A finding of Acanthamoeba requires a high index of suspicion because the ameba have been mistaken for macrophages, Rhinosporidium seeberi, Cryptococcus neoformans, Prototheca wickerhamii, and Blastomyces dermatitides.11,24 An incorrect diagnosis of a deep fungal infection is sometimes made when histologic evaluation is done with Gomori methenamine silver or periodic acid–Schiff stains. The amebic cyst wall picks up those stains in a pattern reminiscent of a fungal cell wall, leading to the missed diagnosis.24
Among the 37 reported cases of cutaneous acanthamebiasis, 27 patients were HIV positive (aged 8 months–60 years; mean, 34 years).5-23 A history of AIDS-defining illnesses was reported in 74% of patients, and CD4 counts ranged from 0 to 566 cells/mm-3 (median, 28 cells/mm-3). In addition to cutaneous involvement, patients with HIV/AIDS also presented with concomitant amebic sinusitis (13/27), osteomyelitis (3/27), uveitis (2/27), pneumonitis (2/27), and infection of the CNS (confirmed in 2/27; suspected but unconfirmed in 4/27). Involvement of the nasal septum (5/27) and palate (4/27) was not uncommon. Symptoms on presentation often included fever,5,7,11,20 nasal congestion/discharge,8,9,13,21 epistaxis,13,14 and cough.14 Patients with presumed or confirmed CNS involvement developed headaches,17,21 fever,20 altered mental status,17,20 hemiparesis,19 lethargy,17 spasticity,21 and seizures.14
The mortality rate for cutaneous acanthamebiasis in the setting of HIV/AIDS without evidence of CNS involvement is at least 75%. Of the patients who died, the duration of illness until death ranged from 9 weeks to 2 years (average, 7.5 months). The development of CNS symptoms in HIV-positive patients with cutaneous acanthamebiasis resulted in death in all patients within days to weeks of the appearance of symptoms.17,19,25,27,30
In addition to patients with HIV/AIDS, cutaneous acanthamebiasis has been described in 7 non-HIV, immunosuppressed patients aged 7 to 61 years (mean, 35 years). Six of the patients were transplant recipients,24-29 and one patient was receiving long-term steroid therapy.30 Five patients died from their infections, and 2 patients were treated successfully (resolution of all lesions). In one successfully treated case, immunosuppression was lowered, and the patient was given pentamidine with 5-flourocytosine.29 In another successfully treated case, immunosuppression was maintained, and the patient responded to pentamidine and topical chlorhexidine and ketoconazole cream.26
In exogenously immunocompromised patients with cutaneous acanthamebiasis, additional sites of involvement included CNS (3/7), lungs (2/7), adrenal glands (2/7), kidney (1/7), pancreas (1/7), and bone (1/7). In the 3 patients with CNS involvement, cutaneous lesions preceded neurological symptoms in 2 patients,27,30 and the lesions occurred after the expression of focal neurological symptoms in one patient.25 This suggests that cutaneous lesions can be either an initial or late manifestation of disseminated acanthamebiasis.
Although cutaneous acanthamebiasis is largely a disease of immunocompromised patients, 3 patients with this disease (aged 5 years, 24 years, and unknown) were apparently healthy.31-33 In one patient, the history of illness could not be elicited33; in the other 2 patients, lesions developed at a site of prior trauma.32,33 In these otherwise healthy patients, the course of the illness was more protracted than in the immunocompromised patients. Lesions remained localized from 6 months to more than a year prior to involvement of other sites. In 2 cases, the symptoms were exacerbated after the patients received systemic steroids.32,33 All 3 patients died after infection spread to the CNS.31-33
In any patient with disseminated cutaneous acanthamebiasis presenting with neurological symptoms, a diagnosis of GAE, meningitis, or meningoencephalitis is often made postmortem.19,20,27,30 Premortem diagnosis may be facilitated by a brain biopsy because radiographic or CSF analyses are often nonspecific or nondiagnostic. There are case reports of patients with disseminated disease and CNS involvement whose CSF never yielded amebic organisms. However, there also are reports of 3 patients with strictly localized CNS involvement who had amebic organisms on CSF wet mounts.35,36 In patients with disseminated acanthamebiasis and extensive CNS involvement documented at autopsy, premortem CSF findings were within reference range20 or showed intermediate elevation in white blood cell count and protein.19,27,30 Radiographic findings in patients with GAE may show hypodense lesions on CT scans, which may enhance on T2-weighted magnetic resonance imaging.37,38 Isodense or hyperdense lesions also are seen on brain CT scans of patients with GAE; however, CT findings are normal in up to 12% of patients with GAE.38 Normal magnetic resonance imaging findings in patients with CNS involvement also have been reported.36 In the present case, no definitive evidence of CNS infection was noted on CSF or radiographic analysis.
The treatment for acanthamebiasis has not been well established and is based largely on in vitro sensitivity of the organism to a number of chemotherapeutic agents, and on a small number of reports of successfully treated cases. The Table lists common antimicrobial agents used in the treatment of patients with disseminated cutaneous acanthamebiasis and their reported response. The Table includes only immunocompromised patients with disseminated cutaneous acanthamebiasis without evidence of CNS involvement. Patients with CNS involvement were excluded because the rapid course of illness in those patients makes evaluation of therapy difficult.
