Cutaneous Amebiasis in Pediatrics

OBSERVATION Cutaneous Amebiasis in Pediatrics

Mario L. Maganã, MD; Jorge Fernańdez-Dıéz, MD; Mario Maganã,MD

Background: Cutaneous amebiasis (CA), which is still Conclusions: Cutaneous amebiasis always presents with a health problem in developing countries, is important painful ulcers. The ulcers are laden with amebae, which to diagnose based on its clinical and histopathologic are relatively easy to see microscopically with routine features. stains. Erythrophagocytosis is an unequivocal sign of CA. Amebae reach the skin via 2 mechanisms: direct and in- Observations: Retrospective medical record review of direct. Amebae are able to reach the skin if there is a lac- 26 patients with CA (22 adults and 4 children) treated from eration (port of entry) and if conditions in the patient 1955 to 2005 was performed. In addition to the age and are favorable. Amebae are able to destroy tissues by means sex of the patients, the case presentation, associated ill- of their physical activity, phagocytosis, enzymes, secre- ness or factors, and method of establishing the diagnosis, tagogues, and other molecules. clinical pictures and microscopic slides were also analyzed. Arch Dermatol. 2008;144(10):1369-1372

UTANEOUS AMEBIASIS (CA) ria, are opportunistic organisms that act as can be defined as damage pathogens, usually in the immunocompro- to the skin and underly- mised host, who can develop disease in any ing soft tissues by tropho- organ, such as the skin and central ner- zoites of Entamoeba histo- vous system. This kind of amebiasis has be- lytica, the only pathogenic form for humans. come more common during the last few C 8-18 Cutaneous amebiasis may be the only ex- years. To determine the forms of presen- pression of the disease or may involve other tation of CA in pediatric patients and the organs, usually the gastrointestinal tract.1,2 mechanisms by which amebae reach the The liver, lungs, and especially the central skin, we performed a retrospective study of nervous system may also be involved. patients cared for during the last 50 years Other species of Entamoeba, such as Ent- at 2 major hospitals in Mexico City, Mexico. amoeba hartmanni, Entamoeba coli, and Ent- amoeba gingivalis, are nonpathogenic.3 In- METHODS terestingly, another species, Entamoeba dispar, identified by Brumpt in 1925,4 has been recognized as being responsible for All patients with an unequivocal diagnosis of CA many cases of CA in patients previously in- based on the clinical and histopathologic iden- terpreted as “healthy carriers.” Entamoeba tification of trophozoites were retrieved from our dispar is morphologically indistinguish- files at the Clinic for Pediatric Dermatology of able from E histolytica but genetically and the Hospital General de Me´xico and from the De- 5,6 partment of Pathology of the Hospital de Espe- serologically different. cialidades of the Centro Me´dico Nacional, IMSS, Entamoeba moshkovskii, which is mor- from 1955 to 2005. The clinical information was phologically indistinguishable from E his- collected from the clinical records and/or by histolytica and E dispar but biochemically and topathologic request. Paraffin-embedded blocks Author Affiliations: Hospital genetically different, has been considered that housed skin specimens were recut and General de Me´xico and School until recently to be primarily a free-living stained with hematoxylin-eosin. Slides were pre- of Medicine, Universidad (nonpathogenic) ameba. The early isolates pared to be read under the microscope. Nacional Autońoma de Me´xico of E moshkovskii were free-living forms Bacteriologic studies from ulcers and ne- (Drs M. L. Magan˜ a and crotic edges and parasitoscopic analysis from M. Magan˜ a), and Centro found in sewage, but human isolates have stool samples were performed at the time of pre- Me´dico Nacional Siglo XXI, now been detected in North America, Africa, sentation for care. Results of these tests were 7 Instituto Mexicano del Seguro Australia, and some parts of Europe. The retrieved from patient records. Clinical pic- Social (Dr Fernańdez-Dıéz), group of amebae known as free-living ame- tures of all patients were taken before and af- Mexico City, Mexico. bae, Acanthamoeba, Balamuthia, and Naegle- ter treatment.

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©2008 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/26/2021 Figure 3. A trophozoite with a red cell inside among inflammatory cells in a cutaneous amebiasis (hematoxylin-eosin, original magnification ϫ400).

The 4 pediatric patients were all toddlers using diapers. All these patients had amebic colitis and developed amebic diarrhea. The diaper maintained contact of Figure 1. A male child with multiple ulcers by amebiasis in the diaper area. the trophozoites with the skin. Therefore, the anatomi- cal sites of the ulcers were in the diaper area: anus and perianal area, buttocks, perineal, inguinal folds, and pu- bis. Patient 1 has been previously described by 1 of us (M.M.) as an example of this disease in children.19 Diagnosis was clinically suspected and confirmed by skin biopsy. Trophozoites of E histolytica were identified as round or oval unicellular basophilic structures, measuring 20 to 50 µm, often surrounded by a clear halo, which is assumed to be tissue retraction due to dehydra- tion,20 and with a nucleus measuring 4 to 7 µm (Figure 3). By performing a smear from the edge of the ulcers, we were to show the amebae in 2 of our patients (patients 1 and 3). At least 1 ulcer that involved the epidermis and dermis to a variable depth was seen. Often there were wide areas of necrosis, with fine granular and eosinophilic bland material with nuclear debris. Surrounding the ulcers was a mixed inflammatory infiltrate of neutrophils, lympho- cytes, and eosinophils, generally in association with ex- travasated erythrocytes. Erythrophagocytosis by amebae was a constant feature in CA and represents a microscopic sign of its pathogenicity. No granulomas are seen in amebiasis. In all 4 pediatric patients, microscopic examination of the stool sample showed a cyst of E histolytica; cultures of the ulcers yielded Staphylococcus epidermidis and Escherichia coli. Cultures from blood and cerebrospinal fluid yielded no growth of bacteria. In 2 patients (patients 1 and 4), we were able to perform serologic tests in which an enzyme-linked immunosorbent assay reac- tion was positive for E histolytica. Chest radiographs from the 4 pediatric patients showed Figure 2. A female child with amebic dysentery showing 1 painful ulcer. right hemidiaphragm elevation in 2 of them and abdominal radiography confirmed hepatomegaly in those 2, but RESULTS no other alterations were seen in the 4 pediatric patients. All these children were treated with dehydroemetine, There were 22 adults and 4 children (all Ͻ2 years old) iden- 1 mg/kg daily for 10 days, and metronidazole, 30 mg/kg tified with CA. The constant and common clinical de- daily for 21 days. Escharotomy, cleaning, and dressing nominator of the 4 children was a putrid, painful ulcer, changes were performed daily for all patients. This regi- which ranged from 1 to several perineal ulcers. Ulcers men produced rapid improvement in days to weeks, with showed a gray-white necrotic base, with red edges, that all ulcers healing by the second week of care. Patient 1, extended rapidly in diameter and depth, during a period who had the most severe case of CA, was referred to the of weeks, at the rate of approximately 1 cm/wk. The ul- plastic surgery service for reconstruction of the vulva and cer measured from a few millimeters to several centime- perineum. The other 3 children healed without the need ters (Figure 1 and Figure 2). for reconstruction.

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Patient No./Sex/Age Reference(s) Location Associated Factors Method of Diagnosis Treatment Outcome 1/F/8 mo 22 Vulvar Dysentery, pneumonia, Cytologic testing Medical Died meningitis 2/M/10 mo 22 Inguinal Dysentery, Cytologic testing Medical Healed pneumonia 3/F/13 mo 22 Vulvar Dysentery Cytologic testing Medical Healed 4/M/9 mo 23 Abdomen Dysentery Postmortem histopathologic None Died analysis 5/F/4 mo 24 Vulvar Liver abscess, dysentery Histopathologic analysis Medical Healed 6/F/14 mo 25 Anal, rectal, perineal, Dysentery Histopathologic analysis Medical, Healed vaginal surgical 7/F/12 mo 26 Vulvar Liver abscess, Serologic testing Medical Healed dysentery 8/F/17 mo 27 Right orbita Dysentery Cytologic testing, Medical, Healed histopathologic analysis surgical 9/M/9 y 28 Perianal Dysentery Cytologic testing Medical Healed 10/F/7 mo Present and 19 Vulvar, perineal Dysentery Cytologic testing, histopathologic Medical, Healed analysis, serologic testing surgical 11/F/5 mo Present Vulvar Dysentery Histopathologic analysis Medical Healed 12/F/9 mo Present Anal, perianal Dysentery Cytologic testing, Medical Healed histopathologic analysis 13/M/8 mo Present Entire diaper area Dysentery Histopathologic analysis, Medical Healed serologic testing

COMMENT treatment (emetine, dehydroemetine, metronidazole, or diiodohydroxyquinoline) is initiated, CA responds soon Historically, the first patient with amebiasis seems to have and well; however, because of the destructive character been treated in Mexico by Mateo Alema´n, the physician of of the disease, surgical repair is often needed. the then archbishop and viceroy of New Spain, who in 1611 To better understand the pathogenesis of CA, it is con- presented with “diarrhea followed a few days later by he- venient to briefly review the life cycle of E histolytica.It patic suppuration.”20 Nevertheless, Hippocrates recog- consists of 2 stages: the cyst or infective stage and the tro- nized that “dysenteries in association with inflammation phozoites or tissue-invasive stage. The disease is usually of the liver are bad,” and in 1875 Lösch described amebic acquired by ingesting food or water contaminated with trophozoites in the stool and colonic ulcerations of a man cysts, which are 10 to 25 µm and have 4 nuclei; they are with fatal dysentery.21 However, other authors20 state that capable of surviving for days outside the body and are also the first identification of the parasite associated with di- able to survive the acidic environment of the stomach and arrhea was made in children by Lamb and that Lösch re- excyst in the ileum. Each cyst gives origin to 8 trophozo- produced the intestinal disease in a dog by means of the ites, which live in the lumen of the colon, where they mul- feces from an individual with dysentery. tiply by binary fission and from where they may invade In children CA is rare; when it occurs, it usually, if not the intestinal wall and eventually penetrate a blood ves- always, develops in the anal and perianal area and the geni- sel and spread though the bloodstream, most often to the talia, usually in association with amebic dysentery, as can liver, or they may encyst and produce quadrinucleated cysts be deduced from our 4 patients and 9 others mentioned after 2 successive nuclear divisions.3,29 Therefore, ame- in the literature (Table). Biagi and Martuscelli22 de- bae reach the skin and develop any of the patterns described 3 patients: a male with inguinal involvement and scribed herein through 2 mechanisms: direct and indirect 2 females with vulvar ulcers, 1 of whom died of CA and transmission of the trophozoites.2 the other 2 who healed in a 10-day period after treatment Direct infestation results with the spread from the co- with emetine hydrochloride. A 9-month-old boy with le- lon and rectum to anal, perianal, perineal, pubic, or geni- sions on the abdomen died without treatment—the diag- tal skin, which is the mechanism of CA in infants (and is nosis was obtained post mortem.23 Alvarez Chacon,24 the most common form in adults) and thus deserves spe- Wynne,25 and Rimsza and Berg26 each published articles cial mention not only for its rareness but also because all 4 describing a girl with ulcers on the vulva, which healed of our pediatric patients share the same clinical picture with with medical treatment after approximately 10 days. Two those previously described: they are all younger than 2 years. other children with CA were exceptional because of where Cutaneous amebiasis is preceded or accompanied by di- it developed on one child (on the right periorbital skin27) arrhea. Because of these patients wear diapers, trophozo- and in the other because of the child’s age (a 9-year-old) ites are able to remain in contact for a longer time with and where it developed (perianal ulcers and diarrhea in the skin surface and, surely the association of diapers with the diaper area on child who did not wear diapers).28 Both humidity and ammonia due to urine and bacteria due to responded well to medical treatment. feces may play an adjuvant role. In general, all these children presented with dysen- Indirect transmission results when the trophozoites tery, fever (body temperatures, 39°C-40°C), irritability, invade the intestinal wall, penetrate a vessel, and reach weight loss, anemia, and leukocytosis. When medical the liver; rarely, trophozoites invade other organs, such

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©2008 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/26/2021 as the lung and/or chest wall, and migrate to the skin. port: M. L. Magan˜ a, Fernańdez-Dıéz, and M. Maganã.Study However, any other area of the body may be infected via supervision: M. L. Magan˜ a, Fernańdez-Dıéz and M. Maganã. a contaminated hand by scratching. Financial Disclosure: None reported. Although CA is not a common disease, it certainly is Role of the Sponsors: The sponsors had no role in the still a public health problem in many areas. In Mexico, it design and conduct of the study, in the collection, analy- was more frequent from 1960 to 1980, when its incidence sis, and interpretation of data, or in the preparation of was estimated to be 1 of every 300 dermatologic patients the manuscript, review, or approval of the manuscript. (children and adults) at the Hospital General de Mexico.30 Most cases observed in Mexico have been treated in this REFERENCES institution, which assists mostly indigent people. Now, it may be less common because metronidazole, emetine, and 1. Maganã ML, Maganã GM. Cutaneous amoebiasis. In: Canizares O, Harman R, dehydroemetine are readily and widely available. eds. Clinical Tropical Dermatology. 2nd ed. Boston, MA: Blackwell Scientific Pub- lications; 1992:278-282. Amebiasis is an even more important public health 2. Maganã M, Maganã LM, Alcańtara A, Pe´rez-Martıń MA. Histopathology of cuta- problem than CA. There are 500 million individuals in- neous amebiasis. Am J Dermatopathol. 2004;26(4):280-284. fected with Entamoeba. Although most people are colo- 3. Martìnez-Palomo A, Ruiz-Palacios G. Amebiasis. In: Warren KS, Mahmoud AAF, eds. Tropical and Geographical Medicine. New York, NY: McGraw-Hill; 1991:327-344. nized with E dispar, which is not pathogenic, many of 4. Brumpt ME. 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