In April 2022, a 62-year-old man was admitted to the Department of Infectious Diseases at the University Clinical Centre in Pristina due to a high fever that had been initially intermittent and later on had become persistent for two weeks prior to hospitalization. The patient had been seen by several physicians, including a family physician, gastroenterologist, pulmonologist, and urologist, but the cause of the high fever could not be identified.
On admission, the patient had a fever of 38.5  C and slightly enlarged spleen. Blood tests were performed and showed the following results: erythrocyte sedimentation rate (ESR) = 5 mm/h, leukocytes = 4.0 x 109/L, erythrocytes = 4.02 x 1012/L, hemoglobin = 11.5 g/dL, platelets = 123 x 103/mm3, hematocrit = 31.3 %, C-reactive protein (CRP) = 54.9 mg/dL, procalcitonin (PCT) = 0.35 ng/mL (< 0.25), serum albumin = 44.1 g/L (34-54), direct bilirubin = 2.85 micromol/L (< 5.1), total bilirubin = 9.4 micromol/L (< 20.5), aspartate aminotransferase (AST) = 25 UI/L (8-33), alanine aminotransferase (ALT) = 43 UI/L (4-36), gamma-glutamyl transferase (GGT) = 153 UI/L (5-40), lactate dehydrogenase (LDH) = 288 U/L (105-333), D-dimer = 16 (0.5), PT = 10.5 s (11-15), INR = 0.98 (< 1.1), PTT = 30 s (24-39), TT = 16 s, anti CCP = 7.0 U/mL (< 500), C3 = 100 mg/dL (80-178), C4 = 19 mg/dL (12-42), IL 6 = 13.9 pg/mL (< 5.90), CK-MB = 35 ng/mL (< 25), AFP = 13.24 IU/mL < 40), CEA = 2.06 ng/mL (< 10), Anti ENA = negative, ANA = negative, ANCA = negative, Anti DSDNA = 4.58 IU/mL (< 30), PSA = 1.50 ng/dL (< 4.1), Fr PSA = 0.123 ng/dL (< 0.87), FrT3 = 4.6 pg/mL (1.5-6.0), T4 = 11.61 microg/dL(4.5-12.5), TSH = 2.29 mIU/mL (0.4-4.5).
Several serologic tests were also performed, including Leptospira IgM/IgG, Lyme Borreliosis IgM/IgG, Wright, Widal,TORCH, HBsAg and Anti HCV. All results were negative except for Toxoplasma IgG and Rubella IgG, which were positive. The patient also underwent additional examinations, including lumbar puncture, bone marrow aspiration, urine culture, blood culture, smear of peripheral blood, QuantiFERON TB gold test, echocardiography, bone scintigraphy, and CT scans of the brain, head, chest, abdomen, and pelvis. However, except of QuantiFERON TB gold test which was positive, and splenomegaly (170 mm) on CT scan of the abdomen, none of other tests revealed any other pathological findings.
Due to the positive result of the QuantiFERON TB gold test and the lack of any other identifiable cause for the patient's fever, treatment with four antituberculous drugs was started. However, this treatment had to be interrupted after several weeks due to severe toxic hepatitis.
During the patient's two-month stay at the hospital, laboratory tests demonstrated a progressive multilineage cytopenia and increased values of inflammation markers, despite several courses of different antibiotics used as single agents or in combination (ceftriaxone, gentamycin, vancomycin, meropenem, azithromycin, and levofloxacin) (Table 1). The patient was subsequently discharged from the department at the end of June 2022 and referred for further treatment abroad with a diagnosis of fever of unknown origin (FUO).
The patient was admitted to the LIV Hospital Vadi Haematology Department in Istanbul, Turkey, on June 26, 2022, where examinations revealed splenomegaly and pancytopenia. Abdominal MRI showed an abscess in the left psoas muscle with dimensions of 68 x 45 mm, which expanded the muscle. The material provided by the abscess biopsy revealed MRSA, which was eventually drained. After six days on antibiotics (Tigecycline), the patient became afebrile, and acute phase inflammatory reactants regressed to normal levels. The antibiotic was given for three weeks, but the patient's pancytopenia persisted throughout the follow-up period, until July 19, 2022.
The biopsy material from the bone marrow taken in Kosovo was reexamined in the Istanbul hospital, and the findings were interpreted as bone marrow findings secondary to infection, medications, and immune system-mediated pathologies. 18-FDG-PET (18-fluorodeoxyglucose positron emission tomography) showed a prominent spleen with involvement of the liver and bone marrow. A diagnostic splenectomy was recommended, but the patient declined the procedure.
In January 2023, six months after hospitalization in Istanbul, the patient was hospitalized for the third time, this time at the University Clinical Centre in Pristina, Haematology Department, due to fever, chills, weight loss, and night sweats. Repeated tests showed persistent anemia/pancytopenia, and peripheral blood smear examination was again without pathological changes. Abdominal and pelvic scan revealed an enlarged spleen and liver. Repeated puncture of the bone marrow was performed, and light microscopic examination of a Giemsa-stained bone marrow specimen finally revealed the presence of amastigotes of Leishmania infantum within the macrophages (Fig. 1).
The microscopic findings were corroborated by a positive serological test for Leishmania IgG = 2.783 (IgG cut-off 0.481). As a result, the patient was referred to the Department for Infectious Diseases of the University Clinical Centre in Pristina for further assessment and management. Treatment with liposomal amphotericin B (LAMB) 1.5 mg/kg/day for 14 days was administered to the patient. Following the treatment, the patient's fever subsided, and their overall health condition improved. The laboratory results obtained three weeks after the treatment indicate a significant improvement (Table 1).