We report a case of a 64-year-old male patient, with a history of left nephrectomy due to lithiasis, chronic kidney disease (baseline serum creatinine levels: 1.7 mg/dl) and in situ papillary urothelial carcinoma (2017) treated with transurethral resections and six BCG instillations in 2019. He presented to our emergency department with a fever up to 39 C, with concomitant shudder and mild dysuria symptoms, a few hours after the last intravesical instillation of bacillus Calmette-Guerin (BCG), fifteen days prior. He was receiving ciprofloxacin for the previous two days, without remission of his symptoms.
On admission he was oriented, febrile (38.5 C), normotensive, with sinus tachycardia (115 bpm) and normal pulse oximetry (SpO2:98%). He also showed a petechiae non-palpable rash on both legs, and his liver was mildly enlarged. Laboratory tests revealed neutropenia (neutrophils: 1,000 K/muL) and severe thrombocytopenia (platelets: 8 K/muL); normal haemoglobin levels; acute kidney injury (urea:59 mg/dL, serum creatinine:2.01 mg/dL); abnormal liver function tests (AST:177U/L, ALT:94U/L, ALP:201U/L, GGT:380U/L);high LDH levels (604U/L), triglycerides (282 mg/dl) and d-dimers (5.5 mug/ml). There were also significantly elevated inflammation markers (CRP: 229 mg/L, ferritin: 5,596 ng/ml), with normal erythrocyte sedimentation rate (12 mm/hr) and coagulation tests (PT and PTT). Serologic tests were negative for hepatitis B, C, HIV, parvovirus B19, EBV and CMV viruses, as well as for Leishmania and Brucella. Multiple urine and blood cultures with specific cultures for mycobacteria were sterile. Serum complement levels, serum immunoglobulins, antinuclear and antineutrophil cytoplasmic autoantibodies were also negative. A peripheral blood smear was evaluated suggesting platelets with characteristics of peripheral consumption. The chest radiography was normal, and the abdomen ultrasound revealed an enlarged liver (23 cm) and spleen (16.8 cm). Whole-body computed tomography (CT) also revealed hepatomegaly and splenomegaly, without focal lesions or lymphadenopathy and emphysematous lesions in the right upper lobe.
The patient was immediately treated with broad-spectrum antibiotics (piperacillin-tazobactam and amikacin) and empiric anti-tuberculosis treatment with isoniazid 300 mg, rifampicin 600 mg and ethambutol 1,200 mg three times weekly, and levofloxacin 750 mg. Immune thrombocytopenic purpura (ITP) was also considered due to the peripheral blood smear analysis, so the patient also received prednisone 1 mg/kg and intravenous immunoglobulin (IVIG) 400 mg/kg/day for five days, without clinical or laboratory improvement. The patient remained febrile in the sixth day with a further decrease in neutrophils, platelets and haemoglobin levels. Antibiotic treatment was upgraded to meropenem, but the patient showed no signs of improvement, and as a result it was discontinued three days later. Haemophagocytic lymphohistiocytosis (HLH) was suspected due to cytopenia, organomegaly, high ferritin and triglycerides levels and persistent fever above 38.5 C. The patient underwent bone marrow aspiration, which confirmed the diagnosis showing marked phagocytosis of platelets by histiocytes (Fig. 1). Bone marrow PCR for TBC, Ziehl-Neelsen stain and TBC cultures all came back negative. Unfortunately, we were not able to measure NKcell activity and soluble IL-2 receptor levels. Dexamethasone 10 mg/m2 was immediately started and the patient showed gradual clinical and laboratory improvement. Etoposide was not administered because of the abnormal liver and kidney biochemistry, and the severe cytopenia the patient suffered. Finally, a liver biopsy was performed, showing multiple parenchymal non-necroticising granulomas, composed of epithelioid histiocytes (Fig. 2) and Ziehl-Neelsen histochemical staining revealed a small number of acid-fast bacilli (Fig. 3).