Localized Leishmanial Lymphadenopathy: An Unusual Manifestation of Leishmaniasis in a Traveler in Southern Europe

Introduction

L eishmaniasis comprises a diversity of clinical manifestations caused by different species of Leishmania parasites, which are transmitted by phlebotomine sandflies. Visceral leishmaniasis is characterized by fever, hepatosplenomegaly, pancytopenia, and weight loss. Cutaneous leishmaniasis manifests as papular, nodular, and ulcerative skin lesion, whereas in mucocutaneous/mucosal leishmaniasis the mucosa of the nose and throat are affected, sometimes with devastating tissue destruction (Murray et al. 2005).

Here, we describe a case of localized lymph node enlargement due to leishmanial infection without visceral or cutaneous manifestation.

Case Report

In October 2009, a 38-year-old man presented with enlarged, indolent, cervical lymph nodes, which he had noticed since around 1 month ago. On physical examination, a small nuchal and a sinistral supraclavicular lymph node were palpable; ultrasonography detected some more enlarged lymph nodes in the left neck region. No further symptoms such as fever, appetite or weight loss, night sweats, or fatigue existed. No skin abnormalities were detected. Laboratory investigations including numbers of leukocytes and erythrocytes, differential blood count, C-reactive protein (CRP), liver enzymes, lipase, and electrolytes were in the normal range. He was not immunocompromised. The patient's travel history included trips to India (1993 and 2002), Ecuador/Peru (1994), Kenya/Tanzania (1995), South Africa (1998), Bali (2003), Spain (2006), and Sicily (2008), and he had encountered insect bites at most locations.

To rule out a primary hematological disorder, the enlarged nuchal lymph node was excised and examined histologically. Numerous intracellular amastigotes of Leishmania species were detectable in both hematoxylin–eosin- and Giemsa-stained slides (Fig. 1A, B). To verify the diagnosis, a Leishmania-specific PCR was performed and a species belonging to the Leishmania (Leishmania) donovani complex (comprising L. (L.) donovani and L. (L.) infantum/chagasi) was determined by RFLP analysis of the PCR product (Schönian et al. 2003). Sequencing confirmed Leishmania (L.) infantum as the causative species of the complex. IgG antibodies to Leishmania (L.) infantum were detected at low concentrations by enzyme immunoassay (14 U, cutoff: 11 U; IBL International GmbH) and an indirect immunofluorescence test yielded a borderline titer (1:20). Hepatosplenomegaly was excluded by abdominal ultrasonography, and because of absence of further symptoms, more invasive investigations to exclude visceral involvement were not performed.

OPEN IN VIEWER

FIG. 1.

Numerous Leishmania amastigotes in lymph node sample following hematoxylin–eosin (A) and Giemsa staining (B). Color images available online at www.liebertonline.com/vbz

The patient was treated with liposomal amphotericin B (AmBisome^®). As he developed a mild allergic reaction upon the first administration, he received 1.5 mg/day for 3 weeks. At the end of treatment, no lymph nodes were palpable. No further symptoms or signs were noted during a period of 15 months after treatment.

Discussion

Lymph node involvement may accompany all forms of leishmaniasis. In Northeast Brazil, for example, cutaneous leishmaniasis due to L. (Viannia) braziliensis is constantly accompanied by an extensive lymphadenopathy (Harms et al. 2005). Localized lymphadenopathy without any cutaneous or systemic manifestation is, however, a rare manifestation of leishmaniasis (Vera-Alvarez et al. 1999, Harms et al. 2001, Kumar et al. 2001, Daneshbod et al. 2007, Cardot-Leccia et al. 2009). The enlarged lymph node is usually indolent and most frequently located in the neck region (supraclavivular, cervical, or nuchal), but other localizations, mainly postauricular, submental, axillary, and inguinal, have been also observed (Vera-Alvarez et al. 1999, Kumar et al. 2001, Daneshbod et al. 2007, Cardot-Leccia et al. 2009). In most reported cases, lymph node enlargement affected the left neck region. In the presented case, one enlarged lymph node was located in the left supraclavicular region at the junction of the ductus thoracicus (Virchow's lymph node). As the ductus drains the lymph system of the organs, this might indicate a potential visceral involvement.

Patients are often referred to hematology/oncology units to exclude malignancies, especially tumor metastases, lymphoma, and leukemia. Other important differential diagnoses of isolated lymphadenopathy are toxoplasmosis, tuberculosis (acid-fast bacilli), and histoplasmosis. The key to the diagnosis is the detection of intracellular Leishmania amastigotes containing a nucleus and a kinetoplast (Fig. 1A, B).

The infection was most probably acquired in the European Mediterranean area, Spain or Sicily, where L. (L.) infantum, a species of the L. (L.) donovani complex, is the causative agent of leishmaniasis. The absence of further symptoms and laboratory abnormalities suggests that the patient was able to control the infection. Notably, in Iran, the syndrome of localized leishmanial lymphadenopathy is regarded as a self-limited condition, which does not require treatment (Kumar et al. 2001, Daneshbod et al. 2007). As confinement of the infection depends on functioning cell-mediated immunity and parasites may disseminate with a change of immunocompetence, treatment should be considered. Liposomal amphotericin B, a drug that concentrates in the macrophages, where the parasites reside, is highly effective in the treatment of visceral leishmaniasis due to L. (L.) infantum (Bern et al. 2006). It is usually applied at a dose of 3–4 mg/kg on days 1–5 and 10, but longer regimens at a lower dose may be given in patients with preexisting conditions or to avoid side effects. Our patient was treated with liposomal amphotericin B 1.5 mg/kg for 3 weeks with good response. No further symptoms appeared during the 15-month posttreatment period.

In conclusion, Leishmaniasis is an uncommon cause of localized lymph node enlargement but should be considered in the differential diagnosis of unexplained lymphadenopathy in returnees from endemic countries including southern Europe.