Infantile visceral leishmaniasis disguised as Kawasaki disease

Dear Sir, We report the first paediatric case of visceral leishmaniasis in an 8-month-old boy from Singapore. He presented with pyrexia of unknown origin and was initially managed as atypical Kawasaki disease with coronary artery dilatation. When secondary haemophagocytic lymphohistiocytosis (HLH) was suspected, bone marrow aspiration revealed the diagnosis. There was a travel history to Sicily, Italy, albeit 5 months ago, but no insect bites were recalled. The patient was a resident born in Singapore. He was first admitted because of a 9-day febrile illness associated with signs of upper respiratory infection and cervical lymphadenopathy with no mucosal inflammation. On palpation, the liver was firm and non-tender and the spleen was 3 cm below the costal margins. Laboratory investigations showed pancytopenia (haemoglobin 7.8 g/dL; white blood cells 9.26 × 109/L; neutrophils 1.02 × 109/L; platelets 85 × 109/L), hyperferritinaemia (1601 ng/mL, normal <322), mild transaminasaemia (aspartate transaminase 61 U/L, normal <40; alanine transaminase 50 U/L, normal <40), with normal bilirubin level. Cultures from the blood, stool and urine were negative. Human rhinovirus/enterovirus DNA was positive on the nasopharyngeal swab. As the patient manifested digital swelling and echocardiography showed aneurysms of the left main and left descending coronary arteries, atypical Kawasaki disease was thought to be the primary event. Fever persisted despite treatment with intravenous (IV) immunoglobulin and oral prednisolone. On the third day, high-dose IV methylprednisolone (30 mg/kg for 3 days) was used. As no clinical improvement was seen, treatment was switched to IV infliximab (10 mg/kg), oral dexamethasone (6 mg/m2/day) and a second infusion of IV immunoglobulin. He was discharged on Day 12 of admission with oral dexamethasone when the fever apparently resolved. Transaminasaemia and cytopenia persisted. He was readmitted 6 days later with swinging fever again, persistent hepatosplenomegaly and pancytopenia. During the second admission, a thorough haematological evaluation was carried out as secondary HLH was suspected. The peripheral blood smear revealed an unusual cytoplasmic inclusion in a monocyte [Figure 1a]. Bone marrow aspiration revealed multiple histiocytes and occasional erythrocytes laden with intracytoplasmic organisms consistent with Leishmania amastigotes [Figure 1b and c], and haemophagocytosis [Figure 1d]. Confirmation of Leishmania infantum infection was made at the National Public Health Laboratory, a tertiary reference laboratory, by multiple polymerase chain reactions and sequencing of a fragment of the cytb gene (sequence GenBank accession number OQ446692). The final diagnoses were visceral leishmaniasis and secondary HLH. The patient was treated with liposomal amphotericin 3 mg/kg/day for 10 days.[1] No specific treatment for HLH was used. The child remained well with normal cardiac and haematological findings 1 year after completion of treatment.Figure 1: Photomicrographs of the peripheral blood film (Wright’s stain) and bone marrow aspirate (Giemsa’s stain). (a) A peripheral monocyte with a single amastigote in the cytoplasm, characterised by an eccentric nucleus and a rod-shaped kinetoplast (arrow) (×4000). (b) A bone marrow histiocyte with numerous amastigotes in the cytoplasm (×1000). (c) An occasional erythrocyte containing amastigotes in the bone marrow (arrow) (×4000). (d) Multilineage haemophagocytosis in the bone marrow (circle) (×1000).Distinguishing Kawasaki disease from other paediatric hyperinflammatory syndromes, such as multisystem inflammatory syndrome of childhood and HLH, can be challenging in the post-coronavirus disease era.[2] Leishmaniasis in children is notoriously associated with HLH.[3] Although coronary artery abnormalities are pivotal in the diagnosis of Kawasaki disease, especially in atypical variants, they can also be found in the other conditions. Paediatricians should keep an open mind when managing hyperinflammatory conditions and search for alternative diagnoses when patients do not respond well to the initial treatment or when new clinical signs develop. At least six cases of visceral leishmaniasis have previously been reported in Singapore since 1982.[4,5,6,7,8] All were adult cases, and five of them were migrant workers originating from endemic regions. None of the infections was acquired in Singapore. However, the incubation period is typically long, from 2 weeks to several months and up to 3 years,[9] and a travel history may not be recalled immediately. As the disease is usually fatal unless treated appropriately, clinicians should be aware of the diagnosis of leishmaniasis in patients of any age presenting with prolonged fever, even when a history of travel to an endemic area appears remote. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.