Fatal hemophagocytic lymphohistiocytosis due to visceral leishmaniasis in a patient with Wegener granulomatosis.

A 45-year-old man was admitted to our hospital for a 2-month history of fatigue and fever. His clinical history war remarkable for Wegener granulomatosis diagnosed 11 years earlier. On admission the patient denied use of alcohol and illicit drugs. He was taking low-dose glucocorticoids as maintenance therapy for the vasculitidis. Physical examination was normal, except for a temperature of 38.6 °C and conjunctival icterus. In the next few days the patient became critically ill, and the laboratory exams revealed pancytopenia (hemoglobin 7.0 g/dl, normal values 13–17; Leucocytes 700/mm3, normal values 4.000–11.000; Platelets 72.000/mm3, normal values 150.000–450.000), AST 3421 U/L, ALT 1692 U/L (normal values for both 5–55), total bilirubin 12 mg/dl (direct fraction 7 mg/dl) (normal value 0.4–1.2), Procalcitonin 23 ng/ml (normal values < 0.09) CPR 93 mg/L (normal values 0–5), ferritin 1200 ng/ml (normal values 11–307) and fibrinogen 133 mg/dl (normal values 150–450). Blood and urine cultures showed no growth, and results of serologic testing for hepatitis B, C, HIV, CMV,EBV, HSV, rickettsia, as well as serum antibodies anti-leishmania, were negative. Anti-neutrophil cytoplasmic antibodies were also normal. A chest and abdomen CT showed splenomegaly. To rule-out hematologic malignancies a bone marrow biopsy was performed. An empirical course of antibiotic and anti-mycotic treatment was unsuccessful. In the suspicion of hemophagocytic lymphohistiocytosis (HLH), steroidal therapy (Methylprednisolone 60 mg per day) was started, and subsequently, due to lack of clinical improvement, cyclosporine (250 mg per day) was added. Slight clinical and serological improvement was observed. After three days this latter treatment was discontinued because the bone marrow biopsy confirmed the HLH, but also showed numerous small bodies typical for leishmaniae (Fig. 1, Fig. 2).

Fig. 1

Bone marrow biopsy section showing a macrophage (black arrow) that has ingested leishmania bodies (red arrow) and a lymphocyte’s nucleus (yellow arrow). Giemsa stain, x 400.

Fig. 2

Bone marrow biopsy section showing numerous intra-cellular and extra-cellular leishmania bodies (arrows). Hematoxylin-eosin stain, x 400.

Intravenous liposomal amphotericin b was started, but the conditions of the patient continued to worsen with the occurrence of multi-organ failure, and he died on hospital day 14. LHL is a life-threatening disorder that can be primary or secondary to infectious, autoimmune or malignant diseases. It is characterized by fever and systemic inflammatory features, and our case met the criteria for its diagnosis [1]. Visceral leishmaniasis (VL) can mimic or cause LHL [2], [3], as can do Wegener granulomatosis [4]. The treatment of VL associated to HLH rely on intravenous liposomal amphotericin b and often glucocorticoids [1], [2]. In our unfortunate patient the negativity of antibodies anti-leishmania delayed the diagnosis and the therapy of the leishmaniasis.

Ethical approval

This case report has obtained approval from the head of the Internal Medicine Unit at the Department of Internal Medicine of the Azienda Ospedaliera di Cosenza (Italy).

Consent

Patient consent was not obtained as no patient identifiers were used.

Funding

This case report has been undertaken by the authors without any form of sponsorship or support from any individual or institution.

CRediT authorship contribution statement

C. Bova, R. De Stefano, M. Ruvio: Conception and design of study. C. Bova: Drafting the manuscript. All authors read and approved the final manuscript.

Conflict of Interest

Each author declares that he or she has no commercial associations (e.g. consultancies, stock ownership, equity interest, patent/licensing arrangement etc.) that might pose a conflict of interest in connection with the submitted article.