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Genital amebiasis: historical perspective of an unusual disease presentation

1999; Elsevier BV; Volume: 54; Issue: 6 Linguagem: Inglês

10.1016/s0090-4295(99)00343-x

1527-9995

Suresh J. Antony, Patricia Lopez-Po,

Gallbladder and Bile Duct Disorders

Amebiasis is a disease with a worldwide distribution, especially in the tropics. An extraintestinal manifestation of this disease, genital amebiasis, is a rare presentation, often missed by clinicians because of the similarity of its presentation to genital carcinoma. This retrospective study of 148 cases of genital amebiasis was performed to define its clinical features and management. Using a MEDLINE search (all languages), reports of 148 cases of genital amebiasis were identified in published reports between 1924 and 1997. Cases were included if the diagnosis was made by biopsy or direct smear for Entamoeba histolytica. The data were analyzed for patient demographics, clinical features, risk factors, mode of transmission, and clinical outcome. Of the 148 patients identified with genital amebiasis, 85% were women (n = 126) and 15% were men (n = 22). The average age of those patients for whom data were available was 39 years for the women and 44 years for the men. The country of origin included Mexico (n = 16) and New Guinea (n = 3), with the remainder from Asia and the United States. There were 116 Hispanic, 15 Asian, 13 African, and 2 white patients; in 2 patients, race was not reported. Of the patients analyzed, 7.4% had associated ailments, such as genital cancer (n = 8), condyloma acuminatum (n = 1), syphilis (n = 1), and phimosis (n = 1). Seven cancers occurred in the cervix and one in the labia. All were squamous cell cancers. In all female patients with genital amebiasis, a foul-smelling bloody vaginal discharge was the predominant presentation. In addition, approximately 37% presented with abdominal pain, 8.1% had ulcerative genital lesions, and 2.8% had weight loss (Table I). The diagnosis of genital amebiasis was made by direct smear (Papanicolaou smear) in 92% of the cases and by biopsy of the ulcerative lesions in the rest of the cases.TABLE IClinical presentation of genital amebiasisWomen%Men%Vaginal discharge100Painful penile ulcers86Abdominal pain37Dysuria and urethral14Genital ulcers8.1dischargeWeight loss2.8Cervical squamous cell cancer5.5Labial squamous cell cancer0.79 Open table in a new tab Eighty-six percent of the male patients presented with a penile ulcer; the remainder had dysuria and urethral discharge (Table I). Biopsy of the ulcerative lesions was necessary to make the diagnosis in 92% of the 22 patients, and culture, direct smear (Papanicolaou smear), or wet preparation for E. histolytica of urethral discharge was done in 2 patients. Ninety-two percent of the patients were treated with antibiotics (metronidazole and other agents) alone and 4.8% received a combination of both medical and surgical treatment. In 3.2% of the patients, the treatment was not noted in the report. Of the 28 patients in whom the outcome could be documented, 26 were clinically cured (96%). One died of unknown causes and the other was lost to follow-up. The risk factors for these cases included homosexual and heterosexual contact with infected partners and concomitant intestinal amebic infection, poor genital hygiene, rectosigmoid amebic infection, and vulvovaginitis. E. histolytica, once more prevalent in the tropics, has now become increasingly common in the subtropical regions as well. In the United States, the incidence is higher in the immigrant populations from Asia, Africa, and Central and South America. Residents of the southeastern and southwestern United States appear to have a higher incidence of amebiasis, presumably because of the influx of immigrants from Mexico and South America.1Centers for Disease Control: Intestinal Parasite Surveillance. Annual Summary, 1978.Google Scholar It was estimated in 1986 that approximately 480 million people or 12% of the population are infected with amebiasis and that the annual mortality is 40,000 to 110,000 persons.2Walsh J.A. Problems in recognition and diagnosis of amoebiasis estimation of global magnitude of morbidity and mortality.Rev Infect Dis. 1986; 8: 228-238Crossref PubMed Scopus (528) Google Scholar The incidence is widely variable in the population studied, from around 1% in industrialized countries to 50% to 70% in the tropics. People who are at recognized high risk include travelers, immigrants, migrant workers, immunocompromised individuals, sexually active homosexual men,3Markell E.K. Havens R.F. Kuritsubo R.A. Intestinal protozoa in homosexual men of the San Francisco Bay area. Prevalence and correlates of infection.Am J Trop Med Hyg. 1984; 33: 239-245PubMed Google Scholar institutionalized patients, and possibly children in day care centers. In homosexual men, the increase appears to be in the nonpathogenic strains.4Gathiram V. Jackson T.F.G.H. Frequency distribution of Ehistolytica zymodemes in a rural South African population.Lancet. 1985; 1: 719-721Abstract PubMed Scopus (88) Google Scholar Transmission occurs by the fecal-oral route and from food and water contamination.5Farthing MJG, Cevallos A, and Kelly P: Intestinal protozoa, in Mansens Tropical Diseases, 20th ed. Philadelphia, WB Saunders, 1996, pp 1255–1298.Google Scholar In our study, the age ranged from 39 to 44 years, with women predominant. The latter may be because of the increased vigilance in the detection of pelvic diseases in women or because the presence of a vaginal discharge alerts physicians to an underlying disease process. Seven percent of the patients in this review were thought to have acquired the disease sexually.6Thomas J.A. Antony A.J. Amoebiasis of the penis.Br J Urol. 1976; 48: 269-273PubMed Google Scholar, 7Chantarakul N. Sook-Anek M. Tantiwonse A. et al.Amebiasis of the penis on top of giant condyloma acuminata report of a case.J Med Assoc Thailand. 1979; 62: 387-393PubMed Google Scholar, 8Veliath A.J. Bansal V. Rajaram P. et al.Genital amoebiasis.Int J Gynecol Obstet. 1987; 25: 249-256Abstract Full Text PDF PubMed Scopus (15) Google Scholar, 9Purpon I. Jimenez D. Engelking R.L. Amoebiasis of the penis.J Urol. 1967; 98: 372-374PubMed Google Scholar, 10Parkarsh S. Ananthkrishnan N. Ramakrishnan K. et al.Amoebic ulcer of the penis.Postgrad Med J. 1982; 58: 375-377Crossref PubMed Scopus (6) Google Scholar, 11Mylius R.E. Ten Seldam R.E. Venereal infection caused by Entamoeba histolytica in a New Guinea native couple.Trop Geogr Med. 1962; 14: 20-26PubMed Google Scholar There is an increasing body of evidence supporting sexual transmission of E. histolytica in the homosexual community in the United States, as well as in other countries.1Centers for Disease Control: Intestinal Parasite Surveillance. Annual Summary, 1978.Google Scholar, 6Thomas J.A. Antony A.J. Amoebiasis of the penis.Br J Urol. 1976; 48: 269-273PubMed Google Scholar, 8Veliath A.J. Bansal V. Rajaram P. et al.Genital amoebiasis.Int J Gynecol Obstet. 1987; 25: 249-256Abstract Full Text PDF PubMed Scopus (15) Google Scholar, 11Mylius R.E. Ten Seldam R.E. Venereal infection caused by Entamoeba histolytica in a New Guinea native couple.Trop Geogr Med. 1962; 14: 20-26PubMed Google Scholar, 12Munguia H. Franco E. Valenzua P. Diagnosis of genital amoebiasis in women by standard Papanicolaou technique.Am J Obstet Gynecol. 1966; 94: 181-188PubMed Scopus (14) Google Scholar This might possibly be due to direct oral/anal contact or anal intercourse, although clear evidence regarding this mode of transmission was not available. E. histolytica has the capacity of destroying almost all tissues of the human body, including bone and cartilage. It does this by means of several virulence factors such as adhesion molecules, toxins, contact-dependent cytolysis, protease, and phagocytic activity.13Adams S.A. Robson S.C. Gathiram V. Immunological similarity between the 170KD amoebic adherence glycoprotein and human B2 integrans.Lancet. 1993; 341: 17-19Abstract PubMed Google Scholar, 14Guillen N. Cell signaling and motility in Entamoeba histolytica.Parasitol Today. 1993; 9: 364-369Abstract Full Text PDF PubMed Scopus (16) Google Scholar Damage is produced by the trophozoites, which adhere to the colonic mucosa after colonization (Fig. 1). The presence of bacteria is essential for the colonization, as they provide an environment low in oxygen tension and a supply of other metabolic needs. The trophozoites then penetrate the mucosa and adhere to the host cells. The trophozoites possess several receptors that recognize proteins in the extracellular matrix and induce the release of protease and collagenase. This substance then degrades the cellular attachment and produces a cytolytic effect.15Reed S.L. Keene W.E. McKerrow J.H. Thio protease expression and pathogenicity of Entamoeba histolytica.J Clin Microbiol. 1989; 27: 2772-2777Crossref PubMed Google Scholar, 16Munoz M. Lamoyi E. Leon G. Antigens in electron dense granules from Entamoeba histolytica as possible markers for pathogenicity.J Clin Microbiol. 1990; 28: 2418-2424PubMed Google Scholar, 17Schulte W. Scholze H. Action of the major protease from Entamoeba histolytica on proteins of the extracellular matrix.J Protozool. 1989; 36: 538-543Crossref PubMed Scopus (75) Google Scholar In the heterosexual population, other factors that could be responsible for the spread of genital amebiasis include perineal trauma during anal intercourse and anal and vaginal intercourse with partners who have active genital ulcers.6Thomas J.A. Antony A.J. Amoebiasis of the penis.Br J Urol. 1976; 48: 269-273PubMed Google Scholar, 8Veliath A.J. Bansal V. Rajaram P. et al.Genital amoebiasis.Int J Gynecol Obstet. 1987; 25: 249-256Abstract Full Text PDF PubMed Scopus (15) Google Scholar, 12Munguia H. Franco E. Valenzua P. Diagnosis of genital amoebiasis in women by standard Papanicolaou technique.Am J Obstet Gynecol. 1966; 94: 181-188PubMed Scopus (14) Google Scholar, 18Grigsby W.P. Surgical treatment of amoebiasis.Surg Gynecol Obstet. 1969; 128: 609-625PubMed Google Scholar, 19Hingorini V. Mahapatra L.N. Amoebiasis of the vagina and cervix.J Int Coll Surg. 1964; 42: 662-667PubMed Google Scholar Veliath et al.8Veliath A.J. Bansal V. Rajaram P. et al.Genital amoebiasis.Int J Gynecol Obstet. 1987; 25: 249-256Abstract Full Text PDF PubMed Scopus (15) Google Scholar noted in their patients that cervical amebiasis was possible after vaginal intercourse, adding more support to this mode of transmission. In women, the exact incidence and prevalence of genital amebiasis is unknown.12Munguia H. Franco E. Valenzua P. Diagnosis of genital amoebiasis in women by standard Papanicolaou technique.Am J Obstet Gynecol. 1966; 94: 181-188PubMed Scopus (14) Google Scholar, 20Fentenes E.F. Bribiesca L.B. Cytological detection of vaginal parasitosis.Acta Cytol. 1973; 17: 252-257PubMed Google Scholar, 21Fentenes E. Benitez L. Amoebiasis en eltracto genital femenino.Rev Inst Nal Cancerol Mex. 1969; 21: 654-656PubMed Google Scholar Predisposing factors for genital amebiasis in women include vulvovaginitis, rectosigmoid infection, perianal trauma, and poor hygiene.12Munguia H. Franco E. Valenzua P. Diagnosis of genital amoebiasis in women by standard Papanicolaou technique.Am J Obstet Gynecol. 1966; 94: 181-188PubMed Scopus (14) Google Scholar, 18Grigsby W.P. Surgical treatment of amoebiasis.Surg Gynecol Obstet. 1969; 128: 609-625PubMed Google Scholar, 20Fentenes E.F. Bribiesca L.B. Cytological detection of vaginal parasitosis.Acta Cytol. 1973; 17: 252-257PubMed Google Scholar, 21Fentenes E. Benitez L. Amoebiasis en eltracto genital femenino.Rev Inst Nal Cancerol Mex. 1969; 21: 654-656PubMed Google Scholar The ulcers produced by the trophozoite are deep and penetrating, allowing easy spread and transmission of the disease. Another postulated method of transmission is venous embolization by way of an anastomosis between perirectal and perivaginal veins.18Grigsby W.P. Surgical treatment of amoebiasis.Surg Gynecol Obstet. 1969; 128: 609-625PubMed Google Scholar, 20Fentenes E.F. Bribiesca L.B. Cytological detection of vaginal parasitosis.Acta Cytol. 1973; 17: 252-257PubMed Google Scholar It appears that local external spread from the gastrointestinal tract to the genital tract is more feasible as a mode of transmission in women. The largest series of genital amebiasis (n = 40) cases in women was reported by Fentenes and Bribiesca.20Fentenes E.F. Bribiesca L.B. Cytological detection of vaginal parasitosis.Acta Cytol. 1973; 17: 252-257PubMed Google Scholar In their series, the diagnosis was made by cytologic examination, with 18 cases confirmed by histologic examination. The lesions appearing in the cervix often resemble large carcinomatous ulcers,8Veliath A.J. Bansal V. Rajaram P. et al.Genital amoebiasis.Int J Gynecol Obstet. 1987; 25: 249-256Abstract Full Text PDF PubMed Scopus (15) Google Scholar, 12Munguia H. Franco E. Valenzua P. Diagnosis of genital amoebiasis in women by standard Papanicolaou technique.Am J Obstet Gynecol. 1966; 94: 181-188PubMed Scopus (14) Google Scholar, 19Hingorini V. Mahapatra L.N. Amoebiasis of the vagina and cervix.J Int Coll Surg. 1964; 42: 662-667PubMed Google Scholar, 22Weinstein B.B. Weed J.C. Amoebic vaginitis.Am J Obstet Gynecol. 1948; 56: 180-183PubMed Scopus (5) Google Scholar, 23Bhaduri K.P. Entamoeba histolytica in leukorrhea and salpingitis.Am J Obstet Gynecol. 1957; 74: 434-435PubMed Scopus (3) Google Scholar, 24Jayaweera F.R.B. Amoebic ulceration of the cervix uteri and penis.Ceylon Med J. 1975; 20: 117-121PubMed Google Scholar, 25Carter B. Jones C.P. Thomas M.L. Invasion of squamous cell carcinoma of the cervix uteri by Entamoeba histolytica.Am J Obstet Gynecol. 1954; 68: 1607-1610PubMed Scopus (4) Google Scholar, 26Heinz K.P.W. Amoebic infection of the female genital tract.S Afr Med J. 1973; 47: 1795-1798PubMed Google Scholar, 27Majumder B. Chaiken M.L. Amoebiasis of the clitoris mimicking carcinoma.JAMA. 1976; 236: 1145-1146Crossref PubMed Scopus (16) Google Scholar which can lead to diagnostic difficulties. The diagnosis of genital amebiasis in women can occasionally be made by standard Papanicolaou smear; only a small percentage require biopsy of the lesions for definitive diagnosis.12Munguia H. Franco E. Valenzua P. Diagnosis of genital amoebiasis in women by standard Papanicolaou technique.Am J Obstet Gynecol. 1966; 94: 181-188PubMed Scopus (14) Google Scholar Eight percent of the female patients in this series had coexistent genital amebiasis and malignancy (Table I). The clinical presentation was similar to the patients who had only amebiasis. The average age of this group was 46 years. All these patients had squamous cell carcinoma of the cervix, with the exception of one who had labial involvement. No predisposing factors were clearly documented, but all of these patients were sexually active. In men, the classic presentation is painful penile ulcers that progress rapidly with a mucopurulent discharge. The best differentiating feature between penile cancer and amebic ulcer appears to be the absence of pain in the patients with cancer.6Thomas J.A. Antony A.J. Amoebiasis of the penis.Br J Urol. 1976; 48: 269-273PubMed Google Scholar, 7Chantarakul N. Sook-Anek M. Tantiwonse A. et al.Amebiasis of the penis on top of giant condyloma acuminata report of a case.J Med Assoc Thailand. 1979; 62: 387-393PubMed Google Scholar, 9Purpon I. Jimenez D. Engelking R.L. Amoebiasis of the penis.J Urol. 1967; 98: 372-374PubMed Google Scholar, 18Grigsby W.P. Surgical treatment of amoebiasis.Surg Gynecol Obstet. 1969; 128: 609-625PubMed Google Scholar, 28Cooke R.A. Rodriguee R.B. Amoebic balanitis.Med J Aust. 1964; 1: 114-115PubMed Google Scholar, 29Camacho B.S. Bierana L. Amebiasis cutanea genital.Dermatologica. 1959; 3: 127-133Google Scholar, 30Herman H.B. Berman L.S. Penile ulcer caused by Entamoeba histolytica.JAMA. 1942; 120: 827-828Crossref Scopus (4) Google Scholar, 31Velasco D.J. Engleking R.L. Purpon I. et al.Amibiasis de pene, presentacio de un caso.Rev Mex Urol. 1965; 24: 527-534PubMed Google Scholar, 32Talwalker G.V. Amoebiasis of the penis.J Ind Med Assoc. 1962; 39: 103-104PubMed Google Scholar, 33O'Leary R.K. Posen J. Amoebiasis of the penis.S Afr Med J. 1984; 65: 113PubMed Google Scholar, 34Quevedo A.M. Dib E.J. Un caso de amoebiasis del pene.Medicina. 1963; 43: 240-243PubMed Google Scholar, 35Shih H.E. Wu Y.K. Lieu V.T. Amoebiasis of the penis.Chin Med J. 1939; 55: 139-145Google Scholar, 36Lee S.W. Amoebiasis of the penis.Chin Med J. 1932; 46: 1096Google Scholar, 37Straub M. Amoebiasis penis (venerica).Geneeskundig Tijdschrift Voor Nederlandssch Indie. 1922; 64: 989-990Google Scholar Predisposing factors in men include homosexual and heterosexual contact and possibly concomitant intestinal infection. The diagnosis was made by biopsy in 91% of the patients and with direct examination of the Papanicolaou smear in the rest. Laboratory findings of extraintestinal amebiasis include leukocytosis, the absence of eosinophilia, and the presence or absence of pathogens in the stools. More recently, the presence of antibody against E. histolytica may prove to be more useful in the diagnosis because an antibody response is present in 80% to 90% of patients with invasive disease. Some of the serologic tests include immunofluorescent antibody test, radioimmunoassay, countercurrent immunoelectrophoresis, and enzyme-linked immunosorbent assay. The enzyme-linked immunosorbent assay is the most sensitive and does not give false-negative results in patients with amebic abscesses. It is also specific, giving only 3.6% false-positive results in controls living in endemic areas. One must interpret these results with caution, as patients may remain positive for more than 10 years after infection.5Farthing MJG, Cevallos A, and Kelly P: Intestinal protozoa, in Mansens Tropical Diseases, 20th ed. Philadelphia, WB Saunders, 1996, pp 1255–1298.Google Scholar, 38Patterson M. Healy G.R. Shabot J.M. Serological testing for amoebiasis.Gastroenterology. 1980; 78: 136-141PubMed Scopus (80) Google Scholar, 39Proctor E.M. Laboratory diagnosis of amoebiasis.Clin Lab Med. 1991; 11: 829-859PubMed Google Scholar Culture of the tissue is 100% sensitive and 100% specific. The more recently developed polymerase chain reaction is around 87% sensitive and specific in detecting E. histolytica. The treatment of this unusual disease appears to be either metronidazole or a combination of metronidazole and an intraluminal agent such as puromycin or iodoquinol. Surgical treatment such as skin grafts may occasionally be required in severely deformed cases. The clinical outcome appears to be excellent in patients treated with medical treatment alone and should probably be instituted empirically while awaiting results of diagnostic studies. An early Papanicolaou smear in addition to the other routine studies could be an option in both sexes. If metronidazole therapy fails, then biopsy of lesion is necessary. The relationship between genital amebiasis and cancer is unclear. However, Leroy et al.40Leroy A. Mareel M. De Bruyne G. et al.Metastasis of Entamoeba histolytica compared to colon cancer one more step in invasion.Invasion Metastasis. 1994; 14: 77-91Google Scholar recently found indications that in the mucosa of the colon, there were molecules released by the trophozoites immediately after adhesion to epithelial monolayers that bind to elements of the epithelial intracellular junctions. This phenomenon may lead to functional disturbances of this junction. Down-modulation of cell-to-cell adhesion molecules promotes invasion of colon cancer cells as well.40Leroy A. Mareel M. De Bruyne G. et al.Metastasis of Entamoeba histolytica compared to colon cancer one more step in invasion.Invasion Metastasis. 1994; 14: 77-91Google Scholar Other studies have noted that trophozoites cause a decrease of transfilter electrical resistance, resulting in the formation of holes in the enteric cell layer and transfilter migration of trophozoites.41Leroy A. De Bruyne G. Verspeelt A. et al.Bacterium assisted invasion of Entamoeba histolytica through human enteric epithelia in 2 compartment chambers.Invasion Metastasis. 1997; 17: 38-48Google Scholar In light of the above data, it is possible that the trophozoites cause disruption of the genital epithelium, with possible invasion by cancer cells as well. This disease process is difficult to diagnose and must be distinguished from genital cancer, especially in countries in which the incidence of amebiasis is high. The risks factors for the development of the disease are unclear, but appear to be related to sexual activity, poor hygiene, and intestinal amebiasis. The reason for the coexistence of genital amebiasis and cancer is not well understood. The diagnosis is made with cytologic or histopathologic examination or a combination of both, looking for active trophozoites. Medical treatment is almost 100% effective, but surgery may be required when there is coexistent carcinoma or deformity.