A 42-year-old Saudi male from Jizan, with a comorbidity of hypertension and type 2 diabetes mellitus diagnosed 6 years prior (well controlled by oral antidiabetic agents: metformin 1000 mg twice daily and gliclazide 30 mg once daily), presented with impaired renal function and hematuria. After basic laboratory investigations, kidney biopsy was performed. Histological examination with light microscope revealed a global sclerosed glomeruli, minimal interstitial fibrosis and tubular atrophy [Figure 1]. A diagnosis of glomerulonephritis of unknown etiology was made and treatment with mycophenolate (1 g PO twice daily) and prednisone (20 mg PO once daily) was initiated.
After 3 months, the patient presented with a 3-week history of fever, abdominal pain and fatigue. The fever was subjective, intermittent, associated with chills and rigors, especially at night, and not relieved by paracetamol. The abdominal pain was intermittent, diffuse and colicky in nature and was associated with nausea and vomiting without blood (2-3 times/day). During these 3 weeks, the patient's appetite decreased, owing to which he lost 7 kg in weight. In addition, the patient reported a history of animal contact (goat and sheep), ingestion of raw goat milk and swimming in the valley water. There was no history of rash, cough, hemoptysis, jaundice, diarrhea, constipation, dysuria, change in urine color, arthralgia, visual disturbances, oral ulcers, genital rash, discharge or contact with tuberculosis patients.
On physical examination, the patient was found to be obese, sweating, not jaundiced or cyanosed. He was conscious, alert and oriented to time, place and person. His vital signs were as follows: body temperature, 38.6 C; pulse rate, 98 beats/min; respiratory rate, 24 breaths/min; blood pressure, 125/85 mmHg; and oxygen saturation, 100% on room air. He was pale, with normal jugular venous pressure and no oral ulcers or thrush. Abdominal examination revealed mild epigastric tenderness and a palpable liver 4 cm below the costal margin with a 15-cm liver span. The rest of the examinations were within normal limits.
Laboratory investigations on admission revealed a white blood cell (WBC) count of 2.65/mcL (neutrophils, 72.1%; lymphocytes, 23.2%; monocytes, 4%; and eosinophils, 0.7%). Results of other hematological examinations were as follows: hemoglobin level, 8.8 g/L; erythrocyte sedimentation rate, 88 mm/h; platelet count, 87,000/mcL; and reticulocyte count, 1.28%. Level of ferritin was 1000 ng/mL, with a transferrin saturation of 11.22 mg/dL. Estimation of electrolytes showed sodium 138 mEq/L, potassium 3.2 mEq/L and bicarbonate 25 mmol/L. Liver function tests showed that total protein was 6.1 g/dL, albumin 3.2 g/dL, total bilirubin 1.2 mg/dL, alanine transaminase 71 IU/L, aspartate transaminase 42 IU/L, alkaline phosphatase 179 IU/L and gamma-glutamyl transferase 447 IU/L. International normalized ratio was 0.8. Renal function tests showed that blood urea nitrogen was 12 mg/dL and creatinine 2.15 mg/dL. Level of lactate dehydrogenase was 732 U/L and C-reactive protein 53 mg/L. Urine analysis showed 2-5 WBCs/high-power field and 10-25 red blood cells/high-power field with no nitrites. Sickling test and direct/indirect Coombs test were negative, and the stool test result was normal.
Chest X-ray and electrocardiogram were normal. Abdominal ultrasound showed an enlarged liver (16.2-cm liver span) and a mildly enlarged spleen (14 cm in length). Kidneys were normal in size, with a mild increase in the echogenicity of renal parenchyma, but no hydronephrosis or ascites.
The serological tests for viral hepatitis, human immunodeficiency virus, Epstein-Barr virus, cytomegalovirus, Toxoplasma and Brucella were negative. Rheumatoid factor, antinuclear antibody, antineutrophil cytoplasmic antibody, antiglomerular basement membrane antibody, anti-Sjogren's syndrome A and B antibodies and cryoglobulin were negative. Malaria smear and blood cultures were also negative.
The patient's condition continued to deteriorate and he developed continuous fever of up to 40.5 C. Repeated tests after 5 days revealed the following: WBC, 1.4/mcL; hemoglobin, 6.7 g/dL; platelet, 55,000/mcL; creatinine, 3.3 mg/dL; C-reactive protein, 151 mg/L; total bilirubin, 2.9 mg/dL; alkaline phosphatase, 460 IU/L; alanine aminotransferase, 80 IU/L; aspartate aminotransferase, 138 IU/L; gamma-glutamyl transferase, 651 IU/L; albumin, 2.5 g/dL; and lactate dehydrogenase, 1400 U/L.
Bone marrow aspirate showed mild hypocellular marrow with no evidence of dysplasia or malignancy. Bone marrow culture for Brucella was negative. Further, Leishman-Donovan bodies were not detected by light microscope. Polymerase-chain reaction test for the diagnosis of tuberculosis, serological tests for dengue fever and Q fever as well as beta-D-Glucan and galactomannan antigen tests were all negative. Liver biopsy showed granulomatous hepatitis with extramedullary hematopoiesis. After 1 week of admission, the patient was treated empirically with broad-spectrum antibiotic (meropenem intravenously, 1 g every 8 h for 6 days); however, there was no improvement.
Additional serological testing using enzyme-linked immunosorbent assay (ELISA) releveled the presence of anti-Leishmania antibodies. Based on this, the patient was started on liposomal amphotericin B course as a treatment for VL (4 mg/kg intravenous on Days 1-5, 10, 17, 24, 31 and 38), despite the lack of a definitive diagnosis. After 1 week, the patient improved clinically, the fever subsided, the laboratory parameters began to improve and at the end of liposomal amphotericin B course, all tests returned to normal.