ResearchGate See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/43340220 Cutaneous acanthamebiasis infection in immunocompetent and immunocompromised patients Article in Internationaljournal of Dermatology- December 2009 301:10-1111/J-1365-4632-2008-03786-X • Source: PubMed CITATIONS 32 READS 515 8authors, including: WillyCesar Ramos Munoz Universidad Ricardo Palma 103 PUBLICATIONS 692 CITATIONS SEE PROFILE Ericson L Gutierrez National Institute of Health of Peru 74 PUBLICATIONS 397 CITATIONS SEE PROFILE Gerardo Ronceros 46 PUBLICATIONS 263 CITATIONS SEE PROFILE Alex Ortega Universidad Iberoamericana deCiencia yTecnologfa 97 PUBLICATIONS 1,116 CITATIONS SEE PROFILE Some of the authors of this publication are also working on these related projects: pr0j«t Chapter an article View project Pr^t Estudiodel riesgo cardiometabölicoen personascon peso normal yen obesos View project All content following this page was uploaded by Ericson L Gutierrez on 13 February 2019. The user has requested enhancement of the downloaded file. Tropical medicine rounds Cutaneous acanthamebiasis infection in immunocompetent and immunocompromised patients Carlos Galarza1, MD, Willy Ramos1, MD, Ericson L. Gutierrez1, MD, Gerardo Ronceros1, MD, Maria Teran2, MD, Martha Uribe1, MD, Marcos Navincopa3, MD, and Alex G. Ortega-Loayza4, MD From the11nstituto de Investigaciones Clinicas de la Facultad de Medicina, Universidad Nacional Mayor de San Marcos, 2Servicio de Dermatologia, Hospital EsSaluddeEmergenciasGrau, 3Serviciode Enfermedades Infecciosasy Tropicales. Hospital Nacional Dosde Mayo, Lima, Peru, and department of Medicine, University of North Carolina at Chapel Hill, North Carolina Correspondence AlexG. Ortega-Loayza, md Department of Medicine University of North Carolinaat Chapel Hill 99 Manning Dr, Campus Box 7075 Chapel Hill, NC 27599 E-mail: aortega@med.unc.edu Abstract Background Cutaneous acanthamebiasis is a rare infection and few patients have been reported worldwide. Methods Observational and descriptive study carried out from March 1996 to February 2006 in patients with diagnosis of cutaneous free-living amebic infection caused by Acanthamoeba spp. The patients were diagnosed atthe Dos deMayo National Hospital (Lima-Peru) where skin biopsies, histopathologic studies and cultures were performed. The clinical and epidemiologic characteristics, diagnosis, treatment and evolution were recorded in asurvey. Results Five patients with cutaneous free-living amebic infection caused by Acanthamoeba spp. were identified. Skin lesions were ulceronecrotic (four patients), an infiltrative bluish plaque (one patient), and a periorbital tumor (one patient). Three patients were positive for human immunodeficiency virus (HIV), had only cutaneous involvement, and died of opportunistic infections. The two immunocompetent patients developed Acanthamoeba granulomatous encephalitis and meningoencephalitis that progressed to intracranial hypertension and death. Conclusion The clinical manifestations of cutaneous free-living amebic infection caused by Acanthamoeba spp. appear to vary according to the underlying immunologic status. Introduction Free-living amebae (FLA) are amphizoic protozoa. The three genera of medical importance are Acanthamoeba, Naegleria, and Balamuthia, but Sappinia cerebral infection has also been reported.1 These organisms have been classified under two supergroups: Amoebozoa and Excavata.z The life cycle of FLA has two stages: trophozoite and cyst. Naegleria has an additional, flagellar stage.3 In 1958, Culbertson etal.4 found that FLA were pathogenic in experimental animals. Fowler and Carter5 subsequently reported the first human case of amebic meningoencephalitis; the etiologic agent, first thought to be Acanthamoeba, was later identified as Naegleria. The first human infection with Acanthamoeba was described by Jager and Stamm6 in 1972. Patients with Balamuthia7 and Sappinia diploidea1 infection have since been reported. FLA can affect the central nervous system and typically produce two types of lesion: Acanthamoeba, Balamuthia, and Sappinia cause amebic granulomatous encephalitis (AGE); Naegleria induces primary amebic meningoencephalitis (PAM).8 The entry point for Acanthamoeba infection is the skin or upper respiratory tract via airborne cysts.3 The organism has been isolated from contact lens solutions3 and from secretions of 1324 healthy individuals.9 International Journal of Dermatology 2009, 48, 1324-1329 Acanthamoeba and Balamuthia cause ocular abnormalities, such as keratitis10 and corneal ulcers, as well as primary cutaneous lesions.3 Acanthamoeba produces AGE, cutaneous infections, sinusitis, and amebic keratitis. In contrast with PAM, which is characterized by sudden onset, the clinical presentation of AGE is insidious (weeks, months, or years).11 Involvement of the central nervous system develops after hematogenous spread from a primary cutaneous or respiratory tract lesion.8-14'16-2'1 PAM caused by Naegleria fowleri usually affects healthy children and young adults with a recent history (7-10 days) of exposure, particularly during the summer months, to contaminated water in lakes, swimming pools, ponds, streams, or mud.8 Options for treatment of PAM, AGE, cutaneous infections, nasopharyngeal infections, and amebic keratitis include combinations of antimicrobials and azoles. Naegleria fowleri is highly sensitive to antifungal agents, such as amphotericin B. Nevertheless, because of the insidious onset of the disease and typically delayed diagnosis, the mortality rate is high. The use of multiple antimicrobials is recommended to avoid resistance;12 however, recovery depends not only on antimicrobial therapy, but also on the underlying host defense, virulence of the amebic strain, and early diagnosis and therapy. © 2009 The International Society of Dermatology Galarza et al. Cutaneous acanthamebiasis infection Tropical medicine rounds 1325 (a) © 2009 The International Society of Dermatology Our study sought to determine the clinical, epidemiologic, and histopathologic characteristics of cutaneous free-living amebic infections in immunocompetent and immunocompromised patients at the Dos de Mayo National Hospital, Lima, Peru. Materials and Methods Patients with cutaneous acanthamebiasis infection, who were seen atthe Dos de Mayo National Hospital by the Teaching Division of Dermatology from March 1996 to February 2006, were studied. Patients were evaluated by a multidisciplinary medical group. Skin biopsyspecimens were obtained for histopathologic examination and culture. Specimens were processed by the Institute of Tropical Medicineofthe Universidad Nacional Mayorde San Marcos, Lima, Peru. If abnormal neurologic signsorsymptoms were detected, fundoscopy and computed tomography (CT) (with and without contrast) of the brain were performed. All patients had human immunodeficiency virus (HIV) testing by enzyme-linked immunosorbent assay; when positive, HIV infection was confi rmed by Western blot. Results Five patients with FLA infection caused by Acanthamoeba spp. were identified during the n-year period. Cutaneous involvement was mainly in young adult men (four of five patients; average age, 28.4 ±5.4 years) with an illness lasting for 4.8 ± 2.2 months. Only two patients gave a history of exposure to pond or swimming pool water, which occurred during the year prior to the onset of their disease. Two patients were from outside the capital (Arequipa and Madre de Dios) (Table 1). Three patients were HIV positive and were thus considered to be immunocompromised. The cutaneous lesions had the following features: ulceronecrotic (four patients), an infiltrative bluish plaque (one patient), and a cellulitis/abscess-like periorbital tumor (one patient) (Fig. ia). Four patients presented with multiple lesions that predominantly involved the lower limbs (three patients) and upper limbs (two patients). Skin lesions were also located in the thoracic, abdominal, and periorbital areas. Two patients (one immunocompetent and one immunocompromised) had lymphadenopathy. None had amebic keratitis. In all cases, histopathologic Figure 1 (a) Ulceronecrotic cutaneous lesions caused by free-living Acanthamoeba spp. in patients with human immunodeficiency virus (HIV), (b) Histologic description: ulcerated epidermis, necrosis of keratinocytes. The dermis shows an intense inflammatory reaction with a predominance of histiocytes, plasmocytes, and neutrophils. Presence of Acanthamoeba spp. trophozoite. Light microscopy; hematoxylin and eosin stain, X400 International journal of Dermatology 2009, 48, 1324-1329 Table 1 Characteristics of patients with cutaneous acanthamebiasis infection Epidemiology Immune status Cutaneous lesions Sex Duration Pt Age of illness (years) (months) Origin Pond/ swimming Previous pool diagnosis Systemic HIV disease Number/type of lesion Location Lymphadenopathy Course Histopathology 1 25 M 2 31 3 22 M 3 4 28 5 36 M 7 Coast No (Lima) Cutaneous tuberculosis Yes Pulmonary Multiple/ Thorax tuberculosis ulceronecrotic No Coast No (Lima) Amazonia No (Madre de Dios) Andes Yes (Arequipa) Leukocytoclastic Yes No vasculitis Leishmaniasis Yes No Lymphoma No No Coast (Lima) Yes Lymphoma No No Multiple/ Lower Yes ulceronecrotic limbs/upper limbs Multiple/ Lower No ulceronecrotic limbs/upper limbs Single/cellulitis Periorbital Yes abscess-like area Multiple/ Abdomen infiltrative and lower bluish plaque limbs and ulceronecrotic No Partial remission Ulcerated epidermis, necrosis of keratinocytes. Dermis with intense inflammatory reaction with predominance of histiocytes, plasmocytes, and neutrophils. Presence of FLA trophozoite. A few tuberculoid granulomas Partial remission Ulcerated epidermis, necrosis of keratinocytes. Dermis with intense inflammatory reaction with predominance of histiocytes, plasmocytes, and neutrophils. Presence of FLA trophozoite Remission Ulcerated epidermis, necrosis of keratinocytes. Dermis with intense inflammatory reaction with predominance of histiocytes, plasmocytes, and neutrophils. Presence of FLA trophozoite Acanthamoeba Epidermis: acanthosis with irregular meningoencephalitis papillomatosis. Dermis: intense inflammatory reaction with lymphocytes, histiocytes, and plasmocytes involving blood vessels. A focal point of tuberculoid granuloma. Presence of trophozoites and some cysts of FLA AGE Flattened epidermis. Dermis with intense mixed inflammatory infiltrate. Focal points of tuberculoid granuloma. A few trophozoites of FLA O AGE, amebic granulomatous encephalitis; F, female; FLA, free-living amebae; HIV, human immunodeficiency virus; M, male; Pt, patient. Galarza et al. Cutaneous acanthamebiasis infection Tropical medicine rounds 1327 Figure 2 (a) Amebic granulomatous encephalitis (AGE) in an immunocompetent patient, (b) Trophozoites of Acanthamoeba spp. in brain tissue, (c) Ferric hematoxylin stain, X400 study of the cutaneous lesions showed trophozoites and cysts of Acanthamoeba spp. (Fig. ib), and cultures were positive for this organism. The patients had been given a different diagnosis prior to evaluation at our hospital: cutaneous tuberculosis, leishmaniasis, leukocytoclastic vasculitis, and, in two cases, lymphoma. The immunocompromised patients received treatment with itraconazole and amphotericin B, with good clinical response and partial remission of the lesions, but they succumbed to opportunistic infections (disseminated cryptococcosis and miliary tuberculosis). At the time of diagnosis, the two immunocompetent patients had suffered from a longer duration of illness than those who were immunocompromised (7.0 ± 1.4 months vs. 3.3 ± 0.6 months); they developed Acanthamoeba AGE (Fig. 2a-c) and meningoencephalitis. In the patient with AGE, who had a 7-month history of cutaneous lesions and a i-month history of progressive and intense headache, CT scan showed a cerebral tumor-like mass that shifted the midline. The second patient presented with a papulonodular lesion of the right eyelid that, within 6 months, had evolved into a periorbital tumor and was accompanied by progressive sensory loss, psychomotor agitation, and meningoencephalitis. Both patients developed intracranial hypertension and died despite medical intervention. Discussion The present study shows that the clinical characteristics of cutaneous free-living amebic infection caused by Acanthamoeba spp. differ according to the underlying immunologic competence. Immunocompromised patients tend to have multiple subacute cutaneous lesions, without central nervous system involvement and with a good response to therapy. In contrast, immunocompetent patients present with an insidious onset of chronic cutaneous lesions, followed by central nervous system compromise and death. In general, cutaneous lesions are late manifestations of disseminated acanthamebiasis, especially in patients with AGE. Cutaneous lesions are typically papulonodular, exhibit purulent drainage, and ultimately develop into poorly healing/ nonhealing ulcers.13 Papules, pustules, plaques, cellulitis, and intramuscular abscesses have also been described. The lesions may be pruritic, tender, or nontender.14 The broad spectrum of diseases in the differential diagnosis may be misleading, including other types of infection, pyoderma gangrenosum, and vasculitis.13 Patients from Amazonia, who have papulonodular and eventually ulcerative lesions, most often are thought to have a deep mycosis. In developing countries, cutaneous tuberculosis or atypical mycobacteria should be considered. The latter is more common in immunocompromised patients. Cytomegalovirus (CMV) and herpes simplex virus (HSV) infection frequently present as chronic periorificial ulceration.13 © 2009 The International Society of Dermatology International Journal of Dermatology 2009, 48, 1324-1329 1328 Tropical medicine rounds Cutaneous acanthamebiasis infection Galarza et al. Infection caused by acanthameba is rare, and few patients have been reported from Peru. Worldwide, approximately 200 cases of systemic acanthamebic infection and more than 3000 patients with keratitis have been reported.3 In Peru, some previously described cases resemble those described here; however, the immunologic condition of these patients was not compared with the clinical manifestations. In 1979, Arce and Asato15 reported a case of Acanth'amoeba encephalitis, and, in 1996, Narvaez16 reported four cases olAcantha-moeba encephalitis. The Institute of Tropical Medicine of the Universidad Nacional Mayor de San Marcos described 10 patients with isolated cutaneous ulcers caused by acanthamebiasis. In 2000, a patient with cutaneous acanthamebiasis17 was presented and, in 2002, two with cutaneous involvement and one with ocular compromise were described.18 In the Peruvian National Institute of Health, from 1995 to the present, three cases of acanthamebiasis have been evaluated, all with ocular involvement (Maria Beltran, Coordinator of the Laboratory of Enteroparasites, Instituto Nacional de Salud, personal communication). Between April and May T999-> I5 samples from patients at the Department of Ophthalmology, Cayetano Heredia Hospital, Peru were positive for Acanthamoeba.19 The international literature contains several reported cases2'0-2'5 of Acanthamoeba meningoencephalitis, with characteristics similar to those of our patients. In contrast with the clinical presentation described for Naegleria sp. (PAM), we found that Acanthamoeba spp. infection presented an insidious course with neurologic signs and symptoms developing 6 months after cutaneous infection of the right eyelid. Only two patients presented with a history of bathing in a pond/pool. Therefore, the absence of such a history should not eliminate the diagnosis if the clinical characteristics are compatible with free-living amebic infection. The clinical characteristics of cutaneous free-living amebic infection caused by Acanthamoeba spp. appear to vary according to the underlying immunologic status. Acknowledgments Humberto Chia and Alicia Barquinero provided the clinical photographs, and Kristin E. Thompson assisted with a critical review of the manuscript. References 1 Gelman BB, Rauf SJ, Nader R, et al. Amoebic encephalitis due to Sappinia diploidea. J Am Med Assoc 2001; 285: 2450-2451. 2 Visvesvara GS, Moura H, Schuster FL. Pathogenic and opportunistic free-living amoebae. Acanthamoeba spp., Balamuthia mandrillaris, Naegleria fowleri, and Sappinia diploidea. FEMS Immunol Med Microbiol 2007; 50: 1-26. International Journal of Dermatology 2009, 48, 1324-1329 3 Schuster FL, Visvesvara GS. 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Acanthamoeba meningoencephalitis in a patient with AIDS. / Infect Dis 1987; i55: 130-133- © 2009 The International Society of Dermatology ew publication stats International Journal of Dermatology 2009, 48, 1324-1329