Immune-complex-like disease in the course of Enterobacter cloacae sepsis due to cholelithic cholecystitis preceded by influenza vaccination

Abstract

This case report describes a 52-y-old male patient who, one week after influenza vaccination, presented with abdominal symptoms: pain in the right epigastrium followed by liver dysfunction and pyrexia, as well renal failure, muscles pain and consciousness disorders. Immune-complex-like disease and Enterobacter cloacae sepsis due to cholelithic cholecystitis were diagnosed. In this case, a correlation between vaccination and immune complex–like-disease was suspected based on the onset of symptoms a few days after vaccination and clinical improvement after plasmapheresis. The etiopathogenesis of immune-complex–like disease in this case possibly could relate to the similarity of the vaccine antigens and E. cloacae antigens as well a genetic predisposition.

Keywords: :

• Enterobacter cloacae
• cholelithic cholecystitis
• immune-complex-like disease
• influenza vaccination
• sepsis

Patient Presentation

A 52-y-old man was admitted to the emergency room due to fever up to 39°C accompanied by headache, vomiting, jaundice, passing dark urine, and fits of dry cough. A week before these complaints started, the patient had been vaccinated against influenza. Patient reported no effects of having taken antibiotics, and denied overusing alcohol or paracetamol. Physical examination on admission revealed jaundice, right epigastrium tenderness and no peritoneal signs. Allopsychic orientation was distorted with fresh memory defects. Lab tests showed hyperactivity of aminotranspherases (AST 3004 U/l, ALT 4182 U/l) and GGT (162 U/l); elevated levels of: bilirubin (8.3 mg/dl with direct bilirubin prevalence: 7.75 mg/dl), creatinine (3.08 mg/dl), CPK (603 U/l), procalcitonine (3.65 ng/ml), ferritin (>100,000 ng/ml) and d-dimers (6.52 μg FEU/ml), and depleted numbers of platelets (75 × 10³/μl) and leukocytes (2.81 × 10³/μl), with normal values of INR,^1,2 albumins (3.2 g/dl) and CRP (3.86–5.11 mg/l). Tests for hepatotropic viruses (HBV, HCV and CMV) were negative. The repeated abdominal ultrasound examinations indicated acute cholelithic cholecytitis. Echocardiography was normal. Influenza vaccination was taken into consideration as possible etiology. The blood culture was positive for Enterobacter cloacae, and the patient received a suitable antibiotic.

Considering the disproportionately increased biochemical parameters in relation to the patient’s relatively good general condition and well-preserved liver function, as well the 2-fold decrease in aminotransferases activity after i.v. steroids administration, a suspicion of septicaemia with immune complexes disease appeared.

In the next step, the patient was transferred for cholelithic cholecystitis surgery. The inflamed gall bladder was removed, and infiltrated liver and liver hilar lymphadenopathies were noted. The patient showed no cardio–pulmonary impairments during the surgical procedure, but then prolonged respiratory failure occurred. In the intensive care unit, plasmapheresis was performed for three consecutive days, leading to gradual normalization of renal and hepatic function, excluding cholestatic parameters with increase in GGT (482 U/l) and bilirubin (14 mg/dl).

The biliary duct prosthesis was endoscopically inserted, and the duct was decompressed. Gradually, the general condition of the patient improved, and biliary leaks and cholestasis receded (bilirubin fell to 7.0 mg/dl). After 8 weeks, the prosthesis was removed, and lab biochemistry test data were normal. The patient recovered totally, although his weight decreased by 11 kg.

Discussion

The probable initial causal factor for the pyrexia was an exacerbation of chronic cholecystitis, although due to oral antibiotic therapy the symptoms were atypical. On admission, the patient presented with symptoms of immune-complex-like disease and multi-organ injury that initially masked the signs of cholecystitis. At the beginning, various toxic causes (paracetamol, fungi, occupational exposures) or the previous influenza vaccination were taken into consideration. Inadequately high activity of aminotransferases compared with normal liver function (e.g., intact INR) and renal defect as well as improvement of general condition and biochemical parameters after administration of steroids led to a diagnosis of sepsis originating in the gall bladder, complicated by immune complex disease. Blood cultures revealed the Gram-negative bacteria E. cloacae, and a significant improvement in the postoperative period was achieved by applying the plasmapheresis.

The Gram-negative bacteremia with onset in the abdominal cavity may lead to immune complexes disease with crescentic glomerulonephritis,¹ which could have occur in this reported case. The occurrence of immune complexes during sepsis has been described in the literature.^2,3

Theoretically, three options can be considered:

1. The influenza vaccination could have induced the immune-complex-like disease, in the course of which an exacerbation of chronic cholecystitis occurred.

2. The influenza vaccination induced an exacerbation of chronic cholecystitis followed by septicaemia and immune-complex-like disease.

3. Influenza vaccination was a simple coincidence, and the exacerbation of cholecystitis was followed by septicemia and immune-complex-like disease in its course.

The question about the initiating factor—was it the vaccination inducing the immune complexes-like, or cholecystitis with immune-complex-like disease in the course of sepsis—will remain unanswered. Regarding the fact that influenza vaccination can be complicated by serum sickness or serum sickness-like disease,^4-6 the impact of the vaccination on the clinical course of the reported case cannot be ruled out. The possibility of serum sickness symptoms occurring after various vaccinations is reported in literature.^6-15 Immune complex deposition and adjuvant effects are potential pathogenic mechanisms of such immune complex-like diseases.^8,16,17

Shoenfeld et al.¹⁶ have recently proposed that post-vaccination immune-mediated disease, belonging to the new syndrome ASIA “Autoimmune (Auto-inflammatory) Syndrome Induced by Adjuvants,” could be linked with previous exposure to the adjuvants,, silicone, aluminum salts and others.

In the case described, the suspected correlation between vaccination and immune-complex, like disease resulted mainly from two reasons, the onset of symptoms after only a few days after vaccination, and clinical improvement after the plasmapheresis.

In the etiopathogenesis of this specific case, the similar immunogenicity of vaccine antigens and E. cloacae antigens¹⁸ could be considered.

Furthermore, according to Münz et al.,¹⁹ genetic factors should not be excluded because they affect the immune system sensitivity and might induce autoimmunity triggered by environmental factors, which include not only viral infections but also the provision of viral antigens that specifically stimulate immune responses, which might cross-react with self-antigens and lead to autoreactive immunopathology.