What is the significance of a normal white blood cell (WBC) count with elevated C-reactive protein (CRP) in a patient with cholangitis?

From the Guidelines

In patients with suspected cholangitis, a normal white blood cell count does not rule out the diagnosis, and elevated C-reactive protein (CRP) levels should be considered a significant indicator of inflammation and potential infection, as suggested by the EASL clinical practice guidelines on sclerosing cholangitis 1.

Key Considerations

• CRP is a more sensitive marker of inflammation that can increase within 4-6 hours of an inflammatory stimulus, while white blood cell elevation may take longer or be affected by factors like immunosuppression, antibiotic use, or the body's ability to mount a leukocyte response.
• The diagnosis of cholangitis should be based on the complete clinical picture including fever, right upper quadrant pain, jaundice (Charcot's triad), imaging findings showing biliary obstruction, and other laboratory markers like elevated liver enzymes and bilirubin, rather than relying solely on white cell count.
• Prompt treatment is essential even with normal white cell counts, as cholangitis can rapidly progress to sepsis and has significant mortality if not properly managed.

Treatment Approach

• Patients with suspected cholangitis should receive appropriate treatment, typically including broad-spectrum antibiotics (such as piperacillin-tazobactam 4.5g IV every 8 hours or ceftriaxone 2g IV daily plus metronidazole 500mg IV every 8 hours) and biliary drainage procedures if indicated.
• The use of antibiotics should be guided by the EASL-EAGE guidelines, which recommend routine use of antibiotics in patients with PSC and high-grade strictures, as well as in patients undergoing ERCP, especially with stenting 1.

Clinical Context

• The clinical presentation of cholangitis can be variable, and a high index of suspicion is necessary to make the diagnosis, especially in patients with primary sclerosing cholangitis (PSC) or other underlying biliary diseases.
• The role of endoscopy in PSC, including ERCP and colonoscopy, is critical in the diagnosis and management of cholangitis, as outlined in the European Society of Gastrointestinal Endoscopy (ESGE) and European Association for the Study of the Liver (EASL) clinical guideline 1.

From the Research

Normal White Cell Count but High CRP in Cholangitis

• A normal white cell count with high CRP (C-reactive protein) levels can be observed in patients with cholangitis, as seen in various studies 2, 3, 4.
• High CRP levels are often associated with inflammation and infection, which are common in cholangitis 3.
• The study by 3 found that high CRP levels were an independent risk factor for acute suppurative cholangitis (ASC), a severe form of cholangitis.
• Another study by 4 evaluated the pharmacokinetic-pharmacodynamic comparison of ceftriaxone regimens in acute cholangitis and found that clinical efficacy was evaluated by body temperature, white blood cell count, and serum levels of C-reactive protein.
• It is essential to note that the diagnosis and treatment of cholangitis should be based on a comprehensive evaluation of clinical symptoms, laboratory results, and imaging studies, rather than relying solely on white cell count or CRP levels 5, 6.

Laboratory Results and Cholangitis

• Laboratory results, including white cell count and CRP levels, can help diagnose and monitor cholangitis 2, 3, 4.
• A study by 5 found that fever-based antibiotic therapy for acute cholangitis was safe and effective when resolution of fever was achieved following endoscopic biliary drainage.
• The study by 6 provides an update on the clinical and pathological features of various forms of cholangitis, including the role of laboratory results in diagnosis and treatment.

Treatment and Management of Cholangitis

• The treatment and management of cholangitis typically involve a combination of antibiotic therapy and biliary drainage 2, 5, 6, 4.
• The choice of antibiotic therapy should be based on the severity of the disease, the presence of biliary obstruction, and the results of bacterial cultures 2, 4.
• Biliary drainage procedures, such as endoscopic retrograde cholangiopancreatography (ERCP), are often necessary to control the progression of cholangitis 5, 6.