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Lingual Leishmaniasis Complicating Visceral Disease Shirin A. Mazumder, MD,∗ Soumya Pandey, MD,† Susan C. Brewer, MD,∗ Vickie S. Baselski, MD,† Peter J. Weina, MD,‡ Mack A. Land, MD,∗ and James M. Fleckenstein, MD∗§ ∗ Division
of Infectious Diseases, Department of Medicine and † Department of Pathology, University of Tennessee Health Science Center, Memphis, TN, USA; ‡ Veterans Affairs Medical Center, Infectious Diseases Division, Memphis, TN, USA; § Walter Reed Army Medical Center, Department of Infectious Disease, Washington, DC, USA
DOI: 10.1111/j.1708-8305.2010.00403.x
Leishmania species are obligate intracellular parasites transmitted by various types of female sand flies. The clinical syndrome that results depends on a number of factors including the Leishmania species and immune response of the host. Here, we report successful treatment of lingual leishmaniasis complicating visceral disease in an immunocompetent patient.
Case Report A 50-year-old National Guardsman with no significant medical problems presented with a 2-week history of a painful central tongue ulcer preceded by 2 weeks of tongue edema. He was deployed to Saudi Arabia during Operation Desert Storm in 1991 and to Iraq and Kuwait during Operation Iraqi Freedom (2002–2003). The lesion appeared 6 years after he returned from his last deployment. A 1.5-cm central cavitary lesion extending to the circumvallate papillae with surrounding erythema, a smaller 0.5 cm lesion lateral to the midline, and oral candidiasis were noted on examination. Physical examination did not reveal any hepatosplenomegaly, lymphadenopathy, or abnormal skin findings. The platelet count was 115,000 μL but the white blood cell count and hemoglobin level were normal. Aspartate aminotransferase and alanine aminotransferase were 113 U/L and 132 U/L, respectively. The alkaline phosphatase level was 571 U/L, but the measurements of the total bilirubin, albumin, total protein, and renal function were normal. Incisional biopsy of the central tongue cavity done at presentation revealed squamous papilloma with candidiasis. The patient received nystatin suspension but no systemic antifungal therapy. During the subsequent 15 weeks, four additional lateral lesions
Corresponding Author: Shirin A. Mazumder, MD, 1211 Union Ave., Suite 340, Memphis, TN 38104, USA. E-mail:
[email protected] © 2010 International Society of Travel Medicine, 1195-1982 Journal of Travel Medicine 2010; Volume 17 (Issue 3): 212–214
developed and the central lesion enlarged. Laser excision biopsy of the central lesion was done to determine a definitive etiology of the ulcers. Histopathologic evaluation showed marked non-caseating granulomas. The lesions continued to worsen, and 2 weeks later a partial glossectomy was done. Histopathologic examination revealed the presence of numerous intracellular amastigotes (Figure 1A and B). After the amastigotes were discovered, the previous biopsies were reexamined and were also noted to contain amastigotes. Review of additional history revealed that the patient had experienced intermittent night sweats and an unintentional 40-pound weight loss over the last 5 years. While serving with the US military in Saudi Arabia in 1991, he had developed pruritic white and red macules on his arms, neck, and back. These lesions eventually waned and never became ulcerative. Punch biopsy of the back performed in 2004 revealed only a perivascular lymphocytic infiltrate. Since 2000, he had been noted to have thrombocytopenia. Liver function tests were noted to be abnormal in 2004 and liver biopsy demonstrated non-necrotizing granulomas, but no specific diagnosis was made. He recalled being bitten by various insects and had contact with various animals including dogs during both deployments. He lived in Tennessee and denied any additional travel history. Serum antibodies against human immunodeficiency virus (HIV), and hepatitis viruses A, B, and C were negative. The presence of HIV RNA was not detected by polymerase chain reaction (PCR). The absolute CD4 was found to be 465 cells/μL
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Figure 1 (A and B) Biopsy specimen of the tongue lesion seen under oil immersion revealing numerous intracellular organisms consistent with Leishmania amastigotes. (A) 60× magnification. (B) 100× magnification. Arrow is pointing to an amastigote.
(normal 395–1601 cells/μL) and may have accounted for the development of oral candidiasis. Angiotensinconverting enzyme and immunoglobulin levels were normal. Rapid plasma reagin and tuberculin skin test were nonreactive. Computed tomography of the chest, abdomen, and pelvis was remarkable only for splenic lesions consistent with granulomatous disease. Bone marrow biopsy also demonstrated granulomas. Additional confirmatory testing performed by the Leishmania Diagnostic Laboratory at Walter Reed Army Institute of Research included a positive Leishmania genus-specific PCR of the tongue sample and rK39 dipstick assay was strongly positive. The PCR was unable to make an identification at the species level. Cultures done on the tissue from the tongue and bone marrow remained negative. Following definitive diagnosis, the patient received lipsomal amphotericin B 3 mg/kg intravenously on days 1 to 5, followed by additional doses on days 9 and 16. On last follow-up 1 week after the final amphotericin infusion, the patient was doing remarkably well with complete resolution of his night sweats and a 10-pound weight gain. In addition, the tongue was healing well, the liver enzymes had nearly normalized, and the platelet count had increased. Discussion Commonly classified into Old World and New World disease, the World Health Organization estimates that presently 12 million people are infected with leishmaniasis worldwide and 2 million new cases occur annually. The spectrum of clinical disease is classically divided into cutaneous, mucocutaneous, and visceral leishmaniasis. Mucocutaneous disease typically occurs in the New World, and 90% of visceral disease is found in eastern India, Bangladesh, the Sudan, and Brazil.1 Cutaneous and visceral illness has been well described
in US military personnel serving in Afghanistan, Iraq, Saudi Arabia, and Kuwait.2 – 4 Leishmaniasis of the tongue is not commonly reported. It has been described primarily among immunocomprimised patients with HIV, malignancy, organ transplant, and corticosteroid use.5 – 8 Only rare cases of lingual leishmaniasis have been reported as occurring in immunocompetent hosts.9 – 11 Various laboratory abnormalities can be seen with visceral disease including thrombocytopenia, anemia, leukopenia, elevated liver function tests, hypoalbuminemia, and hypergammaglobulinemia.1 Definitive diagnosis of leishmaniasis requires demonstration of the organism by histology, culture, or PCR. In our case, definitive diagnosis of mucocutaneous involvement was made by the visualization of amastigotes and positive PCR from the tongue biopsy. Visceral involvement was suggested by the presence of granulomas in both the liver and the bone marrow. Prolonged constitutional symptoms and the various laboratory abnormalities such as thrombocytopenia and elevated liver function tests, as seen in this case, are also likely indicative of visceral disease. The rK39 dipstick assay, which was strongly positive in our patient, detects antibodies against a recombinant antigen found in Leishmania infantum-chagasi.1 The test is highly suggestive of visceral leishmaniasis with an overall sensitivity of 93.9% and specificity of 90.6%.12 L infantum, which is closely related to Leishmania donovani, is a common cause of visceral leishmaniasis. The species has also been implicated in cases of lingual leishmaniasis and is typically found in the Middle East and parts of Africa. Incubation periods for leishmaniasis vary. Cutaneous disease may be seen weeks to months after infection while visceral disease may not appear for several years.1 In members of the US military with viscerotropic disease caused by Leishmania tropica, the incubation period ranged from 2 to 14 months,2 however, a more J Travel Med 2010; 17: 212–214
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prolonged incubation time of up to 2 years has been reported for visceral disease caused by the same organism in a veteran returning from Saudi Arabia.3 This case highlights some unique features of Leishmania infection. Oral lesions acquired in the Old World and occurring in an immunocompetent host is unusual and rarely reported. In addition, mucocutaneous disease complicating probable visceral illness in our case is also atypical. To our knowledge, ours is the first reported case of lingual leishmaniasis in a member of the US military. Clinicians should be informed of nontraditional presentations of leishmaniasis and the potential prolonged incubation period in returning travelers and military troops. Declaration of Interests
Mazumder et al.
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The authors state they have no conflicts of interest to declare. 10.
References 1. Pearson RD, Sousa AQ. Clinical spectrum of leishmaniasis. Clin Infect Dis 1996; 22:1–13. 2. Magill AJ, Grogl M, Gasser RA, et al. Visceral infection caused by Leishmania tropica in veterans of Operation Desert Storm. New Eng J Med 1993; 328:1383–1387. 3. Magill AJ, Grogl M, Johnson SC, Gasser RA. Visceral infection due to Leishmania tropica in a veteran of
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