A new test for Stevens Johnson Syndrome
Published: Tuesday, 23 August 2011 23:50
All emergency physicians have made the dreaded consult call to the dermatologist: "Patient with drug eruption, rule out Stevens-Johnson syndrome." Although adverse cutaneous drug eruptions are common, Stevens-Johnson syndrome (SJS) and its more severe variant, toxic epidermal necrolysis (TEN), are fortunately rare. These extensive mucocutaneous blistering drug eruptions are associated with significant morbidity, even death. In the case of TEN, mortality rates may exceed 20%.
In the past, the condition was easy to miss, and the consequences were often catastrophic. Many a medical malpractice lawsuit has been filed on account of this missed diagnosis. Medical expert witnesses from the fields of emergency medicine and dermatology have testified for and against plaintiffs whose families survived them, or who were left with dire and permanent health effects. The diagnosis is not always apparent, but unfortunately the condition is often fulminant. Less than a day can pass between discharge home and a full blown desquamating rash.
Now for the first time, there is a new test that will diagnose the condition before it has advanced to a critical stage.
Intervention for full-blown SJS and TEN consists primarily of supportive measures such as management in a burn unit (for TEN), prophylaxis against infections, correction of fluid and electrolyte imbalances, and prevention of stricture formation and ocular complications. Recently, intravenous immunoglobulin therapy has shown promise as an early intervention, potentially arresting progression of SJS and TEN if administered early enough. In this context, early detection of SJS/TEN might greatly improve clinical outcomes.
Granulysin, a cytotoxic lipid-binding protein that induces cell apoptosis, is found in high concentrations in blister fluid from patients with SJS/TEN. Recently, Abe and colleagues found significantly elevated serum granulysin levels in patients with SJS/TEN. Intriguingly, these elevated levels occurred before the development of skin and mucosal detachment and dropped rapidly within 5 days of disease onset, suggesting that serum granulysin may be a useful marker for the early phase of SJS/TEN.
Inspired by these preliminary data, Fujita and colleagues developed a simple rapid immunochromatographic test for elevated serum granulysin. This test is completed in only 15 minutes and yields a clinically visible result line at a threshold of 10 ng/mL of serum granulysin.
In order to gauge the sensitivity and specificity of this novel screening test, Fujita and colleagues tested serum samples from 5 patients with clinically confirmed SJS/TEN. The samples were taken early in the disease progression (ie, 2-4 days before development of mucocutaneous erosions). For comparison, serum samples were taken from 24 patients with non-SJS/TEN drug eruptions, defined in this study as "ordinary drug-induced skin reactions" (ODSRs), and 31 healthy controls. Interestingly, 4 of the 5 serum samples from SJS/TEN patients showed positive bands, whereas only 1 of the 24 samples from patients with ODSRs and none of the controls showed positive bands. Test sensitivity was 80% and specificity was 95.8% for SJS/TEN vs other drug eruptions.
If future larger studies confirm that this screening test is both sensitive and specific for SJS/TEN, then it should see immediate clinical use.
Of note, because serum granulysin levels peak before the onset of mucocutaneous erosions and decline as the disease progresses, the absence of a positive test will not be enough to rule out SJS/TEN. Hence, the serum granulysin rapid screening test should be most useful in identifying the subset of drug eruptions that are most likely to progress to SJS/TEN. Once this subgroup is identified, closer clinical monitoring and a lower threshold for initiating intravenous immunoglobulin therapy may be warranted.