Precision medicine?

In 1877, the physician, Jean Martin Charcot, described the triad of jaundice, fever and abdominal pain that bears his name. It has since become pathognomonic of acute cholangitis. It is taught to both undergraduates and registrars and forms the basis of many examination questions. Charcot’s original description of the triad was largely based on a single patient, a 68-year-old man, who experienced the symptoms for 3 months before being found at autopsy to have an obstructed bile duct from a single gallstone. It is important to note that in 1877 jaundice was assessed by clinical examination along with pain, and temperature was measured using mercury thermometers. That the patient died indicates both a premorbid uncertainty surrounding the diagnosis and an inability to intervene with the surgical resources available at the time. Eighty-two years later, Benedict Reynolds, a surgeon from New York, described Reynolds’ pentad for the diagnosis of acute cholangitis. This included Charcot’s triad in addition to hypotension and altered mental state, clinical findings that would today be considered as markers of multiple organ failure. In the current issue of the journal, Rumsey et al. present a systematic review of the diagnostic accuracy of Charcot’s triad based on the analysis of 16 publications including 4288 patients. The overall sensitivity of Charcot’s triad for the diagnosis of acute cholangitis was 36.3% (range: 7.7–72%), with specificity measured in only three studies for an overall value of 93.2%. Put simply, the results indicate that if you present with the triad there’s a fair chance you have cholangitis but if you don’t have the triad you still might. The sensitivity of Reynolds’ pentad was even lower at 4.82% and the specificity was not assessed. This creates a quandary. In an age when medicine is driven to increasing precision in both diagnosis and treatment, should Charcot’s triad and many of the other eponymously named clinical pearls in surgery (Courvoisier’s law, Cullen’s sign, Grey Turner’s sign, Murphy’s sign, etc) be cast aside, particularly if they have not been formerly evaluated in rigorous clinical studies? Most date from a time when presenting pathology was more extreme than now and diagnosis could only be made by clinical observations repeated over time. Radiological investigations were not yet available and medical laboratories were restricted in scope and without the ability to quantify serum measures of organ function. But contemporary expectations of patients and their doctors have also become more refined. Clinical diagnosis nearly always requires objective confirmation (for cholangitis an endoscopic bile duct decompression would require an initial confirmatory biliary ultrasound demonstrating bile duct dilatation as well as a full panel of liver function tests, coagulation studies and full blood count). The implicit expectation is that the diagnosis will be rapid and certainly occur sometime prior to the hypotension and mental alterations of Reynolds’ pentad. The internist/epidemiologist David Sackett was the first to highlight this issue. Sackett believed the question of whether to retain or discard clinical pearls such as Charcot’s triad was unanswerable and debate would ‘generate far more heat than light’. Rather it was a stimulus to re-evaluate clinical methods. Under his stewardship, CARE (Clinical Assessment of the Reliability of the Examination) was established. This multicentre, clinician-led group systematically reviewed the accuracy of individual and constellations of examination findings. Using this approach, nine elements of history and physical examination findings in patients with suspected deep venous thrombosis were found to be as accurate as the gold standard of compression ultrasound. Similarly, when four items of a quick history and physical examination were present or absent significant airflow limitation was invariably present in patients with chronic obstructive airway disease. CARE became an advocacy body for the maintenance and improvement of clinical examination rather than an agent of its demise. Rumsey et al. now provide a similar level of scrutiny of surgical examination findings to that provided by CARE in internal medicine and establish that Charcot’s triad is not as accurate as we thought. Really it never was and nothing has changed except our ability to objectively evaluate clinical findings and our expectation that medicine must be unfailingly precise and faultless. Charcot’s triad should continue to be used and discussed and recognized as the aphorism it is with the pearl of wisdom it contains (biliary infection occurs with biliary obstruction so treat the obstruction). The Tokyo Guidelines now represent a more accurate, although more complex, tool for the diagnosis of acute cholangitis and are derived from a comprehensive review of the available clinical evidence – celestial navigation progressively replaced by global positioning system.