What is the differential diagnosis for a 47-year-old female with intense pruritis, taking celecoxib (celecoxib) 200 mg twice daily (bid) and rosuvastatin (rosuvastatin) 20 mg once daily (qd), and garlic supplements, without a rash?

Immediate Management: Get LFTs and Bili First, ER Not Needed Unless Unstable

For a 47-year-old woman with intense pruritus without rash on celecoxib and rosuvastatin, obtain liver function tests, bilirubin, and serum bile acids immediately in the outpatient setting—ER triage is not necessary unless she develops signs of systemic instability (hypotension, altered mental status, or severe abdominal pain). 1, 2

Why Outpatient Workup is Appropriate

• Pruritus without rash is rarely an emergency unless accompanied by systemic signs of anaphylaxis, severe hepatic failure, or hemodynamic instability 1
• The absence of rash makes acute allergic reactions (urticaria, angioedema, anaphylaxis) less likely, though celecoxib can rarely cause anaphylaxis with pruritus as an early symptom 3
• Both celecoxib and rosuvastatin can cause hepatotoxicity, making drug-induced cholestatic liver disease a key consideration that requires laboratory confirmation, not emergent imaging 1, 4, 5

Essential Immediate Laboratory Workup

The British Association of Dermatologists provides the most comprehensive evidence-based initial panel for generalized pruritus without rash 1, 2:

• Liver function tests (AST, ALT, alkaline phosphatase) to assess hepatocellular vs. cholestatic injury 1, 6
• Total bilirubin to evaluate severity of hepatic dysfunction 1, 6
• Serum bile acids (most important test for cholestatic pruritus—levels >10 μmol/L are diagnostic) 1, 6
• Complete blood count with differential to screen for eosinophilia (drug reaction), anemia, or hematologic malignancy 1, 2, 7
• Ferritin level (iron deficiency causes 25% of systemic pruritus cases and is highly treatable) 1, 2, 7
• Urea and electrolytes to rule out uremic pruritus from renal dysfunction 1, 2
• Antimitochondrial antibodies if cholestatic pattern emerges (to evaluate for primary biliary cholangitis) 1, 7

Differential Diagnosis: Prioritized by Likelihood

1. Drug-Induced Cholestatic Hepatitis (Most Likely)

• Rosuvastatin causes cholestatic hepatitis in 1.1% of patients, with pruritus as a cardinal symptom 1, 4, 5
• Rosuvastatin-induced pruritus typically develops within 2 weeks of initiation and resolves within 2 weeks of discontinuation 5
• Celecoxib can cause hepatotoxicity, though less commonly than statins 1, 8
• Garlic supplements can potentiate statin toxicity through cytochrome P450 interactions, though rosuvastatin undergoes minimal CYP metabolism 4

2. Drug-Induced Hypersensitivity Reaction (Less Likely Without Rash)

• Celecoxib can cause pruritus as part of anaphylaxis (with urticaria, angioedema, respiratory distress) 3
• Acute Generalized Exanthematous Pustulosis (AGEP) from celecoxib presents with pustular rash, fever, and leukocytosis—absence of rash makes this unlikely 8
• Rosuvastatin rarely causes isolated pruritus without hepatic involvement 5

3. Primary Hepatobiliary Disease

• Primary biliary cholangitis (check antimitochondrial antibodies) 1, 7
• Viral hepatitis (if risk factors present—check hepatitis A, B, C serology) 1, 2

4. Systemic Causes of Pruritus Without Rash

• Iron deficiency anemia (25% of systemic pruritus cases) 2, 7
• Chronic kidney disease/uremic pruritus (check creatinine, BUN) 1, 2, 7
• Polycythemia vera (aquagenic pruritus triggered by water—check JAK2 mutation if suspected) 2, 7
• Hodgkin lymphoma (nighttime pruritus with B symptoms—weight loss, fevers, night sweats) 2, 7
• Thyroid dysfunction (only test if clinical features suggest thyroid disease—do NOT routinely screen) 1, 2, 7

5. Neuropathic Pruritus (Unlikely Without Localized Distribution)

• Small fiber neuropathy can cause pruritus, but typically localized (not generalized) 1, 2

Immediate Management Algorithm

Step 1: Obtain Laboratory Tests (Same Day or Next Day)

• LFTs, bilirubin, bile acids, CBC, ferritin, creatinine 1, 2, 6

Step 2: Medication Review and Trial Discontinuation

• Discontinue rosuvastatin immediately (most likely culprit for cholestatic pruritus) 4, 5
• Consider discontinuing celecoxib if rosuvastatin cessation does not improve symptoms within 2 weeks 8, 3
• Stop garlic supplements (potential drug interaction) 4

Step 3: Symptomatic Treatment While Awaiting Results

• Emollients and moisturizers (first-line for all pruritus) 1
• Non-sedating antihistamines (fexofenadine 180 mg or loratadine 10 mg daily) for symptomatic relief, though efficacy is limited in cholestatic pruritus 1
• Avoid sedating antihistamines (hydroxyzine) except in palliative settings 1

Step 4: Interpret Results and Adjust Management

If LFTs/Bile Acids Elevated (Cholestatic Pattern):

• Rifampin 150 mg twice daily (first-line for hepatic pruritus, increase to 600 mg twice daily if needed) 1
• Cholestyramine 9 g daily (second-line, binds bile salts) 1
• Sertraline 75-100 mg daily (third-line) 1
• Refer to hepatology if significant hepatic impairment or persistent elevation 1

If Ferritin Low (Iron Deficiency):

• Iron replacement therapy (complete cessation of pruritus occurs shortly after treatment) 2, 7

If Creatinine Elevated (Uremic Pruritus):

• Refer to nephrology for dialysis optimization and management 1

If All Tests Normal (Generalized Pruritus of Unknown Origin):

• Consider gabapentin 300-900 mg daily, paroxetine, or mirtazapine 1
• Refer to dermatology if symptoms persist despite initial management 1

Critical Pitfalls to Avoid

• Do NOT delay bile acid testing—this is the definitive test for cholestatic pruritus and should be ordered immediately 6
• Do NOT routinely order thyroid function tests unless clinical features suggest thyroid disease (weight changes, palpitations, heat/cold intolerance) 1, 2, 7
• Do NOT omit ferritin—iron deficiency is the most common treatable cause of systemic pruritus 1, 2, 7
• Do NOT continue rosuvastatin while awaiting results—the risk-benefit analysis favors immediate discontinuation given high likelihood of drug-induced cholestasis 4, 5
• Do NOT assume pruritus is benign—while ER triage is unnecessary, delayed workup can miss serious underlying conditions (cholestasis, malignancy, renal failure) 1, 2

When to Escalate to ER

Send to ER immediately if any of the following develop 1, 3:

• Hypotension, tachycardia, or respiratory distress (anaphylaxis) 3
• Severe abdominal pain with jaundice (acute cholangitis, biliary obstruction) 1
• Altered mental status (hepatic encephalopathy) 1
• Rash with fever and mucosal involvement (Stevens-Johnson syndrome, though rare with these drugs) 8