Amoebiasis (amoeba cutis, acanthamoebiasis, entamoebiasis)
amoeba cutis, acanthamoebiasis, entamoebiasis; ICD-9 006.6
Are You Confident of the Diagnosis?
What to be alert for in the history
Amoebiasis, in particular, amoeba cutis is a rare and unusual disease that exists chiefly as a disease of the tropics. The condition is extraordinarily unusual in the United States except in a returning traveler, and the infection should be suspected principally in a patient who has spent time abroad. Exceptions to this rule would be men having sex with men (MSM) population (where it can occur as a sexually transmitted disease), the immunocompromised patient, or in occasional outbreaks among day care centers (due to fecal-oral communicability).
Characteristic findings on physical examination
Ameobiasis in the skin manifests principally as an ulceration. In the immunocompromised, infections by the genus Acanthamoeba may begin as erythematous papules or nodules, which ultimately drain purulent material leading to ulceration. In patients infected by the genus Entamoeba often ulceration occurs in the genital area or upon the abdominal wall as direct extension of a hepatic abscess.,
Expected results of diagnostic studies
For acanthamoebiasis the diagnosis is typically made through skin biopsy of the raised and advancing border. Characteristic trophozoites (double walled; 15-20 um diameter) are identified in the areas of suppuration. Culture and specialized immunohistochemistry may confirm the diagnosis.
For entamoebiasis, which is generally a gastrointestinal and/or hepatic disease with only rare cutaneous involvement, serological testing is sensitive and specific, but it cannot distinguish between active and past infection.Skin biopsy specimens taken from the ulceration may afford visualizations of trophozoites (eccentric nuclei, prominent pink nucleoli, often with phagocytosed erythrocytes; 20-50 um diameter). Motile trophozoites have been described in skin scrapings taken from the edge of an ulceration.
Who is at Risk for Developing this Disease?
All forms of cutaneous amoebiasis are rare. The population at risk for cutaneous amoebiasis varies with the particular species involved. For example, while the genus Acanthamoeba is ubiquitous in the environment, and it can occasionally cause necrotizing keratitis in otherwise healthy persons, particularly in wearers of contact lenses; when this species does cause skin disease, it is generally in the immunocompromised, including organ transplant patients.
Entamoeba histolytica is a species from an entirely different genus that causes principally gastrointestinal infection in tropical regions. It may rarely cause cutaneous disease, either due to direct extension from a hepatic abscess, or as an ulceration in the genital area, likely from contact with contaminated fecal material. In fact, entamoebiasis may also present as a sexually transmitted disease among men having sex with men, or in occasional outbreaks among day care centers. Mexico has the highest known incidence of cutaneous entamoebiasis and only two cases have been reported in the United States.
What is the Cause of the Disease?
Amoebiasis is caused by Entamoeba histolytica. This disease is acquired principally by fecal-oral transmission; an amoebic cyst begins the infective stage upon ingestion and ultimately yields the characteristic trophozoite. This trophozoite then invades intestinal epithelium and causes amoebic colitis with bloody diarrhea. Amoebic liver abscess may occur and is 10 times more common in men than women; such patients often present with fever and right upper quadrant pain.
Cutaneous disease may occur from either direct extension of a liver abscess through the abdominal wall, or as extension of a rectal amoebiasis to the anus or perineum. Rarely, primary cutaneous disease has been described (particularly contamination of pre-existing wounds), and sexual transmission may occur, particularly in the MSM population.
Acanthamoebiasis is caused by different Acanthamoeba species. These species are ubiquitous in the environment, and have been isolated from normal human secretions and from contaminated contact lens solution. It may cause corneal ulceration and keratitis in immunocompetent patients.
Cutaneous disease is uncommon in healthy patients, and while still rare, is perhaps more common in immunosuppressed patients. In immunocompromised patients, there may be multiple subacute cutaneous lesions, tender or asymptomatic, that are typically papulonodular early in the course of disease, but lead ultimately to poorly healing or nonhealing ulcers.
Balamuthiasis, caused by the free-living amoeba, Balamuthia mandrillaris, is sufficiently unique and distinguishable, both in cutaneous presentation, epidemiology and otherwise, that is best discussed separately, but suffice to say that this species almost always (51/52 cases in the largest series) causes an ill-defined plaque upon the central facial region, and also may lead, disastrously, to granulomatous amoebic encephalitis. It is exquistely rare for balamuthiasis to present anywhere other than the central face (1/52 in the largest series of which this author is aware).
Primary amoebic encephalitis is caused by Naegleria fowleri, a pathologic amoeba usually acquired from swimming in contaminated water amoebic encephalitis. It does not have significant cutaneous manifestations and is beyond the scope of this review.
Systemic Implications and Complications
Entamoebiasis is initially a gastrointestinal infection. While this disease may be subclinical and unnoticed, it typically leads to diarrhea (typically bloody and/or with mucous) and may result in weight loss. Dissemination through the portal circulation may lead to liver abscesses, a phenomenon that is 10 times more common in men than women. Alcoholism is a risk factor for development of liver abscesses. Dissemination to organ systems other than the liver is extremely rare, but has been described.
Through direct extension from rectal disease the skin of the anus or perineum may be involved. Cutaneous involvement in these areas typically produces tender, oval ulcerations with irregular borders and a white-grey base that is friable and easily bleeds.These cutaneous ulcers fail to respond to common antimicrobial therapy, and if verrucous reactive features are present, the lesions may be confused with squamous cell carcinoma.
The principal concern in infections caused by Acanthamoeba species is that of granulomatous amoebic encephalitis (GAE). In this condition, the amoeba invades the central nervous system, where treatment is generally ineffective, and death is a frequent outcome. Other symptoms of GAE include seizures, paralysis, and other neurological problems.Symptoms are caused both by frank necrosis of brain tissue and by the inflammatory infiltrates engendered by the amoebic infiltrates. Resultant amoebic abscesses within the CNS may mimic a brain tumor and confuse the diagnosis.
Asymptomatic amebic colitis is treated with a luminal agent (iodoquinol, paromomycin, diloxanide furoate) to eradicate infection, both to prevent progression to invasive disease and to reduce amoebic shedding, a public health concern.
Amebic colitis is first treated with a nitroimidazole derivative (metronidazole or tinidazole), followed by a luminal agent to eradicate colonization.
Amebic liver abscess can be cured without surgical drainage and with metronidazole, followed by a luminal agent to eradicate gut colonization. Failure to improve is an indication for surgical intervention.
Cutaneous amebiasis should be treated with metronidazole or tinidazole, followed by a luminal agent to eradicate probable gut colonization.
Because of the risk of granulomatous amoebic encephalitis, this is a medical emergency and liberal consultation with specialists in dermatopathology, infectious disease, neurology, and neurological surgery is advised.
Use of multiple and concomitant antimicrobial agents, including nitroimidazole derivatives (metronidazole, tinidazole), polyenes and azoles(amphotericin B, itraconazole and voriconazole), antiprotozoal agents (albendazole, thiabendazole), and sulfonamides may be employed.
Recovery depends not only upon use of multiple antimicrobial agents but also upon the underlying host defenses, the virulence of the amoebic species, and the timeliness of the diagnosis and commencement of therapy.
Optimal Therapeutic Approach for this Disease
Asymptomatic amoebic colitis or luminal agents to be used concomitantly with invasive colitis or cutaneous disease (choose one) -Iodoquinol 30-40mg/kg/day (with a maximum of 650mg/dose) orally divided three times a day for 20 days.
-Paromycin 25-35mg/kg/day orally divided three times a day for 7 days.
Symptomatic amoebic colitis or cutaneous disease
-Metronidazole 30-50mg/kg/day orally divided three times a day for 14 days.
-Consider adding promethazine 1 hour prior to minimize nausea.
-Counsel to avoid alcohol during treatment (disulfiram-like reactions may result).
-Add a luminal agent as well.
-Chloroquine 600mg (1g of chloroquine phosphate) daily for 2 days, followed by 300 mg (500 mg of chloroquine phosphate) once daily for at least 2-3 weeks, may be substituted or added in patients intolerant of metronidazole, or who are not responding to therapy, respectively.
-Other forms of disease - consult infectious disease experts.
-Consult an infectious disease specialist.
-There is no proven therapeutic regimen.
-Anticipate combination use of nitroimidazole derivatives (metronidazole, tinidazole), polyenes and azoles(amphotericin B, itraconazole and voriconazole), antiprotozoal agents (albendazole, thiabendazole), and sulfonamides.
-Even use of combination regimens reported (anecdotally) to be successful may be ineffective in otherwise similar cases.
-The situation is impacted greatly by the patient's underlying disease status, co-morbidities, and the timeliness of diagnosis and therapy
As the disease is spread principally by fecal-oral and/or fecal-oral-genital contact, patients, family members, and, if applicable, sexual partners should be educated with regard to proper handwashing and the avoidance of high-risk behaviors.
Patients and/or family members should be informed of the gravity of the situation and the high risk of treatment failure (even treatments that have been reported in others to be effective) because of comorbidities and variance in host defenses.
Once granulomatous amoebic encephalitis has set in, it is unlikely to be effectively treated, irrespective of the management strategy.
Unusual Clinical Scenarios to Consider in Patient Management
While it duly noted that amoebiasis is a rare infection in the United States, it should be considered in the differential diagnosis for chronic nonhealing ulcers, particularly those occurring in the perianal area and perineum. This is particularly in certain demographic groups, such as men having sex with other men, and the immunocompromised, and admittedly these same patients may have other reasons for similar appearing chronic ulcerations (such as syphilis, chronic HSV, chronic CMV, and other ailments) even the brief consideration of the possibility of cutaneous amebiasis is important.
What is the Evidence?
Young, AL, Leboeuf, NR, Tsiouris, SJ, Husain, S, Grossman, ME. "Fatal disseminated Acanthamoeba infection in a liver transplant recipient immunocompromised by combination therapies for graft-versus-host disease". Transpl Infect Dis.. vol. 12. 2010. pp. 529-37.(Recent report highlighting the occurrence of Acanthamoeba infection in an immunocompromised patient with brief review of appropriate therapy.)
Verma, GK, Sharma, NL, Shanker, V, Mahajan, VK, Kaushik, R, Verma, S. "Amoebiasis cutis: clinical suspicion is the key to early diagnosis". Australas J Dermatol.. vol. 51. 2010. pp. 52-5.(Report of Entamoeba infection in a non-HIV infected person that involved the buttocks, perianal/perineal area, and part of the left thigh that discusses appropriate diagnostic techniques and therapeutic approach.)
Galarza, C, Ramos, W, Gutierrez, EL, Ronceros, G, Teran, M, Uribe, M. "Cutaneous acanthamebiasis infection in immunocompetent and immunocompromised patients". Int J Dermatol. vol. 48. 2009. pp. 1324-9.(Recent series of five patients with cutaneous Acanthamoeba infections in both immunocompetent and immunosuppressed patients, with suggestion that those patients with less than intact immunity may suffer a greater risk for catastrophic disease.)
Abdolrasouli, A, McMillan, A, Ackers, JP. "Sexual transmission of intestinal parasites in men who have sex with men". Sex Health. vol. 6. 2009. pp. 185-94.(Review that highlights fact that amoebiasis can be a sexually transmitted disease, particularly in men having anal sex with other men, due to the increased potential for fecal-oral contamination.]
Magaña, ML, Fernández-Díez, J, Magaña, M. "Cutaneous amebiasis in pediatrics". Arch Dermatol. vol. 144. 2008. pp. 1369-72.(Series of 26 patients from Mexico with cutaneous amoebiassis (22 adults and 4 children). which discusses the diagnosis as it pertains to perianal ulceration, acquired via direct and indirect routes, and discusses means of diagnosis and appropriate therapy.)
Lin, M, Giusto, D, Jakate, S, Proia, L. "A man with a chronic painful perianal ulcer". Clin Infect Dis. vol. 46. 2008. pp. 637-9.(Case report of a homosexual man who acquired cutaneous amoebiasis and presented with perianal ulceration. with strong clinical and histopathologic photographs, and for which the full-text is freely accessible.)
Walia, R, Montoya, JG, Visvesvera, GS, Booton, GC, Doyle, RL. "A case of successful treatment of cutaneous Acanthamoeba infection in a lung transplant recipient". Transpl Infect Dis.. vol. 9. 2007. pp. 51-4.(Discusses treatment of Acanthamoeba infection with successful treatment with amphotericin and voriconazole, and reviews current treatment options for cutaneous amoebiasis in general.)
Kenner, BM, Rosen, T. "Cutaneous amebiasis in a child and review of the literature". Pediatr Dermatol. vol. 23. 2006. pp. 231-4.(Discusses the importance of amoebiasis in the differential diagnosis of immigrants from endemic areas, like Mexico, and reviews the appropriate means of diagnosis and treatment.)
Paltiel, M, Powell, E, Lynch, J, Baranowski, B, Martins, C. "Disseminated cutaneous acanthamebiasis: a case report and review of the literature". Cutis. vol. 73. 2004. pp. 241-8.(Report of case of multiple perianal ulcers caused by Entamoeba in a homosexual male that were responsive to combined therapy with tetronidazole and chloroquine.)
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