Visceral Leishmaniasis in a Patient with Hyper-IgM Syndrome Secondary to PIK3CD Mutation: A Case Report

Background: Visceral leishmaniasis is rare in patients with primary immunodeficiencies, especially, in patients with hypogammaglobulinemia. Recently, gain of function in PI3CKD have been related to a hyper-IgM syndrome, characterised by autoimmunity and lymphoproliferative disease, apart from hypogammaglobulinemia and predisposition to infections. As PI3CKD is part of the mTOR pathway, its treatment is based on blocking of different steps of it, with drugs such as sirolimus.

We present a case of visceral leishmaniasis in a 14-year-old boy with hyper-IgM syndrome secondary to PIK3CD mutation.

Case Presentation: Our patient is a 14-year-old boy with hyper-IgM syndrome secondary to PIK3CD mutation treated with immunoglobulin, sirolimus, cotrimoxazole, pantoprazole and calcium.
He had developed previous outbreaks of lymphoproliferative disease, consisting mainly of enlarged lymph nodes and tonsils, but they were controlled with sirolimus.

He referred a 6-week history of daily fever associated to headache and pain of his lymphadenopathies, more intense after the administration of immunoglobulin. On physical examination, he was pale and his lymphadenopathies were as usual, but slight splenomegaly was present. Laboratory tests showed a progressive pancytopenia (minimum values: haemoglobin 5 g/dL, WBC 1120/μL, neutrophils 610/µL, lymphocytes 290/µL, platelets 95000/µL). Sirolimus blood levels were higher than previous controls, without dosage changes nor renal disturbances. Sirolimus was discontinued, but there was not improvement of the symptoms and pancytopenia. Studies performed because of the pancytopenia were negative, except for positive PCR for Leishmania infantum in blood. PCR for Leishmania infantum was also positive in the bone marrow biopsy, although amastigotes were not visualized. Patient was treated with liposomal amphotericin B for 10 days, followed by additional doses at days 14 and 21. Progressively, fever, splenomegaly and analytic disturbances disappeared. After recovery, he received monthly suppressive therapy with liposomal amphotericin B for 6 months.

Conclusions: Visceral leishmaniasis should be considered as a possible cause of lasting fever in patients with immunodeficiencies, regardless of the type of immunodeficiency. Mainly, when fever is associated with pancytopenia and splenomegaly.