Abstract

Toxic shock syndrome and sepsis-induced cholestasis are the foremost common causes of jaundice in the intensive care unit. A rare cause of jaundice is autoimmune haemolytic anaemia (AIHA). We present a case in which recurrent Escherichia coli sepsis induced a Coombs-positive AIHA leading to jaundice. Although AIHA induced by Gram-negative shock is rare, it needs to be considered in the absence of alternative causes to prevent delay of treatment.

Introduction

Jaundice in the intensive care unit (ICU) has a broad differential diagnosis, with toxic shock syndrome (i.e. hepatic hypoxia) and sepsis-induced cholestasis, predominantly linked to infections with Gram-negative bacteria, being the foremost common causes.[1, 2] Using the SOFA score, sepsis-induced liver dysfunction is quantified by measuring serum total bilirubin, with levels ≥20 µmol/l indicating some degree of hepatic involvement.[3] Sepsis-induced liver dysfunction is frequent and associated with increased mortality, although it is uncertain if elevated serum bilirubin during sepsis truly reflects a pathological condition or is just a mere reflection of altered bile production and transport into the systemic circulation.[4] A rare cause of jaundice is autoimmune haemolytic anaemia (AIHA).[5] In Coombs-positive AIHA, antibodies directed against red blood cells are produced, leading to haemolysis. Coombs-positive AIHA has a broad differential diagnosis, with viral and mycoplasmal infections being the leading cause of secondary AIHA.[6] We present a patient who was admitted to the ICU in whom Escherichia coli septic shock induced hyperbilirubinaemia as a result of AIHA.

Case Report

A 71-year-old man, with a history of ischaemic cerebrovascular disease, unexplained anaemia, choledocholithiasis, cholecystectomy, urolithiasis and recurrent orchiditis with recent use of fluoroquinolones (ciprofloxacin and levofloxacin) for epididymitis, presented to the emergency department (ED) with severe abdominal pain and discoloured urine. Physical examination showed jaundice, elevated respiratory rate (22 breaths/min), hypotension (84/52 mmHg) and tachycardia (100 beats/min) in the absence of fever or altered mentation. Abdominal examination revealed painful percussion, tenderness and guarding. Scrotal examination showed status after unilateral orchidectomy and no sign of orchiditis or epididymitis. Laboratory investigations revealed anaemia (haemoglobin 6.7 mmol/l, N: 8.5-11.0) with sign of haemolysis (haptoglobin 95% neutrophils, no fragmentocytes), prolonged prothrombin time (38 sec, N: 12-15) and prolonged activated partial thromboplastin time (64 sec, N: 26-36) with only mildly impaired antithrombin (65%, N: 80-120). Blood platelets were normal (249 x 109 /l, N: 150-400) whereas lactate dehydrogenase could not be determined due to haemolysis. Renal function was impaired (eGFR CKD-epi 29 ml/min/1.73 m², N: >90) with severe hyperbilirubinaemia (unconjugated bilirubin 408 µmol/l, N: 0-16), low albumin (28 g/l, N: 35-50), mildly elevated liver enzymes (ALT 137 U/l, N: 0-44; gamma-glutamyltransferase 104 U/l, N: 0-54), raised inflammatory markers (C-reactive protein 80 mg/l, N: 0-8; procalcitonin >75 ng/ml, N: 0-0.5) with normal serum glucose (4.5 mmol/l, N: 4.0-7.7) and ammonia levels (32 µmol/l, N: 10-35). In the ED, we performed abdominal radiography and ultrasonography, both of which were unremarkable, excluding urolithiasis, and single doses of cefuroxime, metronidazole and tobramycin were given. He was admitted to our ICU under the diagnosis of severe septic shock with multiorgan failure combined with disseminated intravascular coagulation and haemolysis without evident cause (Apache II score 31; Apache IV score 103; SOFA score 15).

Table 1. Differential diagnosis of jaundice at the intensive care unit