Which liver function tests (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma‑glutamyl transferase, total and direct bilirubin, serum albumin, prothrombin time/INR) and renal function tests (blood urea nitrogen, serum creatinine, estimated glomerular filtration rate, basic electrolyte panel, and urinalysis with microscopy) should be ordered for a patient with suspected cutaneous drug eruption before initiating systemic therapy?

Laboratory Testing for Suspected Cutaneous Drug Eruption

For patients with suspected cutaneous drug eruption before initiating systemic therapy, order a comprehensive metabolic panel (including ALT, AST, alkaline phosphatase, bilirubin, BUN, and creatinine), complete blood count with differential, and urinalysis with microscopy to assess for organ involvement and guide treatment decisions. 1, 2, 3

Essential Laboratory Tests

Liver Function Assessment

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are mandatory to detect hepatic involvement, with ALT >2 times the upper limit of normal indicating significant liver dysfunction in DRESS syndrome 1, 3
• Alkaline phosphatase and total/direct bilirubin should be included in the comprehensive metabolic panel to evaluate for cholestatic patterns and severity of hepatic injury 1, 3
• Gamma-glutamyl transferase (GGT) can provide additional information about hepatobiliary involvement, though it is less specific than ALT for liver injury 4, 5
• Prothrombin time/INR and serum albumin are important markers of hepatic synthetic function but are typically reserved for cases with confirmed liver involvement or severe reactions 6

Renal Function Assessment

• Serum creatinine and blood urea nitrogen (BUN) are essential baseline tests, with creatinine >1.5 times baseline indicating nephritis in DRESS syndrome 1, 3
• Estimated glomerular filtration rate (eGFR) should be calculated to assess renal function, particularly important before initiating systemic therapies like methotrexate or cyclosporine that require renal dosing 6
• Basic electrolyte panel (sodium, potassium, chloride, bicarbonate) is necessary to detect metabolic derangements and guide fluid management 1, 2
• Urinalysis with microscopy is critical to evaluate for nephritis, proteinuria, and hematuria that may indicate renal involvement 1, 2, 3

Hematologic Assessment

• Complete blood count with differential is mandatory to assess for eosinophilia (>700/μL or >10% of white blood cells), which is a hallmark feature of DRESS syndrome 1, 3
• The CBC also evaluates for leukopenia, thrombocytopenia, and atypical lymphocytes that may indicate severe drug reactions 6

Clinical Context and Timing

When to Order These Tests

The latency period for severe cutaneous drug eruptions like DRESS syndrome is typically 2-6 weeks after drug exposure, distinguishing it from immediate reactions 1, 3. Laboratory testing should be performed:

• Immediately upon suspicion of a cutaneous drug eruption, particularly if fever, constitutional symptoms, or signs of organ involvement are present 1, 2
• Before initiating systemic corticosteroids or other immunosuppressive therapy, as baseline values are essential for monitoring treatment response and toxicity 6

Risk Stratification

Certain findings predict severity and guide management intensity 1, 3:

• Elevated serum creatinine and ferritin at presentation predict fatal outcomes
• Higher lymphocyte counts indicate the need for systemic corticosteroids
• Eosinophilia >700/μL or >10% strongly suggests DRESS syndrome

Common Pitfalls to Avoid

Testing Errors

• Do not delay laboratory testing while waiting for dermatology consultation, as organ involvement may progress rapidly in severe reactions like DRESS syndrome 1, 2
• Do not order only ALT and AST without a comprehensive metabolic panel, as renal dysfunction and electrolyte abnormalities are common and clinically significant 1, 3
• Do not omit urinalysis, as nephritis may be present even with normal serum creatinine early in the disease course 1, 2

Interpretation Pitfalls

• AST is less liver-specific than ALT and can be elevated from cardiac or skeletal muscle injury 4, 5
• Mild transaminase elevations may warrant re-evaluation before extensive workup, but persistent elevation with clinical suspicion for drug eruption requires comprehensive testing 5
• Blood cultures should be obtained if the patient is febrile to rule out infectious mimics before attributing symptoms to drug reaction 1, 3

Additional Considerations for Specific Scenarios

Before Initiating Methotrexate or Cyclosporine

If systemic therapy with these agents is planned for the underlying condition, additional baseline testing is required 6:

• Lipid profile (fasting) for cyclosporine due to risk of hypertriglyceridemia 6
• Pregnancy testing in women of childbearing potential 6
• Hepatitis B and C serologies if not previously documented 6

Monitoring During Treatment

Once systemic therapy is initiated 6:

• Repeat CBC and liver function tests every 2 weeks initially, then every 3-6 months if stable
• Monitor renal function and electrolytes monthly for cyclosporine
• Urinalysis periodically, especially in patients at increased risk for proteinuric renal disease