A retired 60 year-old Caucasian female with SLE was admitted to the Rheumatology Department in our hospital with persistent low-grade fever, night sweats, malaise, weakness and weight loss. She had no neurologic, respiratory, gastrointestinal or urinary symptoms, and no cutaneous lesions or joint pain, although she had a sensation of abdominal fullness. The symptoms had started approximately one year earlier, had shown progressive worsening, and she had lost 30 kg (approximately 1/3 of her previous body weight). During that time she was seen by her primary care physician (PCP) on several occasions and had several consultations with her rheumatologist. The investigation performed had been negative for common pathogens associated with chronic febrile illnesses, such as tuberculosis and brucellosis, and progression of immunosuppression had not stalled the symptoms. The patient had been treated for presumptive tuberculosis for 6 months, having shown no signs of improvement.
The patient had been diagnosed with SLE in her late 20s, had consultations with a rheumatologist in our hospital since 2003, and was being treated with a daily dose of 5 mg prednisolone and a weekly 10 mg dose of methotrexate. She also had diabetes mellitus and hypertension, both being treated by her PCP. Her SLE had been deemed controlled until these symptoms started, and she had no past history of confirmed tuberculosis or any chronic febrile infection. An HIV screening performed by her PCP had been negative. She had no past surgeries and no family history of cancer. The patient lived in a farm, in a town located in the region of the Douro river basin, in the north of the country. She had no history of smoking or of any drug use.
On admission, the only abnormalities were a low-grade fever (37.5  C), marked pallor and a palpable, non-tender hepatosplenomegaly. Her blood pressure was 105/63 mmHg, heart and respiratory rates were 84/min and 18/min, respectively. There were no abnormalities on cardiac or lung auscultation, no rash, and her neurologic examination was unremarkable. A careful examination revealed no swelling, redness or pain of any joint.
Preliminary analytical study revealed pancytopenia, with a hemoglobin of 8.0 g/dL, white blood cell count (WBC) of 3020/mm3, and platelet count of 98,000/mm3, erythrocyte sedimentation rate (ESR) of 116 mm/h, lactic dehydrogenase (LDH) of 2331 U/L, low serum albumin (18 g/L) with increased total proteins (90 g/L). Hepatic aminotransferases were slightly elevated, bilirubin, blood urea nitrogen and creatinine were normal. Blood was also collected for culture of bacteria, mycobacteria and fungi, and for serologic study. Chest X-ray showed no opacities, nodules or effusions; abdominal ultrasound revealed massive hepatosplenomegaly, with a liver and spleen of 35 cm and 16 cm, respectively. The first diagnostic hypothesis was a hematologic malignancy, although subacute infections such as brucellosis or tuberculosis were also considered. A differential protein analysis with electrophoresis, antibody search, and full body computerized tomography (CT) scan were performed. A Hematology consultation was requested.
The patient had marked hypergammaglobulinemia, with a total gamma globulin count of 7580 mg/L, and a polyclonal gamma curve was seen on electrophoresis; gamma globulin differential was normal. There was no complement consumption, anti-nuclear antibodies (ANA), anti-extractable nuclear antigens (ENA), and anti-double stranded DNA (anti-dsDNA) antibodies were negative. Full-body CT confirmed the hepatomegaly and homogeneous splenomegaly, but did not show any other relevant abnormalities. Serial blood cultures for bacteria, mycobacteria and fungi were persistently negative. The serologic study revealed multiple positive IgG and IgM for Coxiella burnetti, Mycoplasma pneumoniae and for Rickettsia conorii. IgM for Epstein-Barr virus (EBV), cytomegalovirus (CMV) and parvovirus B-19 were negative. Blood and bone marrow cultures for bacteria and fungi were negative. Bone marrow aspirate and biopsy were performed and sent for histologic and microbiologic study (culture for bacteria and mycobacteria). The patient and the preliminary results of the marrow smear were seen by an experienced hematologist who considered the patient had no consistent signs of hematologic malignancy. Amoxicillin/clavulanate and ciprofloxacin were empirically administered, but showed to be ineffective.
On day 18 of admission, an infectious diseases (ID) consultation was requested. The clinical history and the physical examination were those previously described, but the patient revealed for the first time that she lived next to livestock and that her husband was a sports hunter, had a pack of dogs, and one had died recently of an undiagnosed consumptive disease. The hypothesis of visceral leishmaniasis was considered: the patient had an appropriate background, prolonged fever and constitutional symptoms, pancytopenia, and increased protein count with low albumin and hypergammaglobulinemia. The multiple positive antibodies were interpreted as resulting from increased gamma globulin production. Polymerase chain reaction (PCR) for L. infantum was positive both in the blood and in the bone marrow.
The patient was transferred to the ID Department and was treated with liposomal amphotericin B (AmB), in a dosing of 3 mg/kg. She received one daily dose during the first 5 days, another one on day 10, and then once weekly until she completed 10 doses. A prolonged regimen was chosen due to her long standing immunosuppression, long duration of disease, and overall poor clinical condition. She was discharged on day 29 of admission (10 days after being transferred to the ID department), after completing her sixth dose of AmB. She showed great improvement, sustained normal body temperature once she started treatment, and recovered some of the analytical anomalies. The patient completed therapy in our department's ambulatory clinic. A histologic review of the bone marrow biopsy showed histiocytes infected with amastigotes, confirming our diagnosis, without any signs of primary hematologic disease.
Six months later, on her second appointment after discharge, the patient was completely asymptomatic, had recovered 10 kg, and had an overall normal physical examination. Hemoglobin rose to 11.7 g/dL, WBC to 7340/mm3, platelet count to 164,000/mm3, total serum protein was 81 g/L, serum albumin rose to 34 g/L and globulin count decreased to 5460 mg/L; abdominal ultrasound no longer showed signs of organ enlargement.