What is the diagnosis and treatment for a patient presenting with maculopapular (maculopapular) rashes and right upper quadrant pain?

Maculopapular Rash with Right Upper Quadrant Pain: Diagnosis and Management

Primary Diagnosis

The combination of maculopapular rash and right upper quadrant pain most likely represents drug-induced liver injury (DILI) with cutaneous manifestations, particularly DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms), which requires immediate discontinuation of the offending agent and urgent specialist evaluation. 1

This presentation demands immediate recognition of potentially life-threatening conditions before pursuing standard RUQ pain workup, as the combination of systemic rash and hepatobiliary symptoms suggests a systemic process rather than isolated biliary disease.

Critical Initial Assessment

Immediate Red Flag Evaluation

• Assess for severe cutaneous adverse reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, or DRESS syndrome, which necessitate immediate drug discontinuation and specialist consultation 1
• Examine for mucosal involvement (oral, ocular, genital ulcerations), skin detachment, or bullous lesions that indicate severe reactions requiring hospitalization 1
• Obtain detailed medication history including all drugs started 2-12 weeks prior (though onset can occur after one year), over-the-counter medications, and herbal supplements 2

Specific Clinical Features to Document

• Maculopapular rash characteristics: distribution (photo-exposed areas, trunk, extremities), presence of eosinophils on examination, associated pruritus, and timeline relative to medication initiation 1
• RUQ pain characteristics: relationship to meals (postprandial suggests biliary), fever presence, Murphy sign, and associated symptoms (nausea, vomiting, jaundice) 1
• Systemic symptoms including fever, lymphadenopathy, facial edema, and organ dysfunction suggesting DRESS syndrome 1

Diagnostic Algorithm

Laboratory Workup (Immediate)

• Complete metabolic panel with liver function tests including AST, ALT, alkaline phosphatase, total and direct bilirubin, and GGT to assess hepatobiliary injury pattern 2
• Complete blood count with differential to evaluate for eosinophilia (>1000 cells/μL suggests DRESS) and leukocytosis (suggests cholecystitis) 1, 2
• Calculate conjugated versus unconjugated bilirubin if total bilirubin elevated to differentiate cholestatic from hepatocellular injury 2

Imaging Approach

Right upper quadrant ultrasound remains the first-line imaging study (rated 9/9 by ACR) even in the presence of rash, as it rapidly identifies or excludes acute cholecystitis and other hepatobiliary pathology with 96% accuracy for gallstones 1

• Ultrasound should specifically evaluate for: gallbladder wall thickening, pericholecystic fluid, bile duct dilatation, hepatic parenchymal abnormalities, and sonographic Murphy sign 1, 3
• Do not skip ultrasound and proceed directly to CT, as ultrasound avoids radiation exposure and is more appropriate for initial biliary evaluation 3, 4

Algorithmic Next Steps Based on Findings

If ultrasound shows acute cholecystitis:

• Proceed to surgical consultation for cholecystectomy while managing drug reaction concurrently 3
• If ultrasound equivocal for cholecystitis, obtain cholescintigraphy (HIDA scan) with 96% sensitivity and 90% specificity 1, 3

If ultrasound negative but cholestatic liver enzymes elevated:

• Consider CT abdomen with IV contrast to evaluate for alternative diagnoses including hepatic abscess, mass, or vascular pathology 1, 3
• MRCP may be indicated if bile duct pathology suspected but not visualized on ultrasound 3

If drug-induced liver injury suspected:

• Immediately discontinue suspected offending medication 1
• Obtain skin biopsy if diagnosis uncertain, which typically shows lymphocytic CD4+ infiltrates with eosinophils and papillary edema in maculopapular rashes 1

Management Strategy

For Confirmed DRESS or Severe Drug Reaction

• Immediate discontinuation of all potentially causative medications is the single most important intervention 1
• Initiate systemic corticosteroids (prednisone 0.5-1 mg/kg/day) for moderate to severe reactions with systemic involvement 1
• Hospitalize patients with extensive skin involvement (>30% body surface area), mucosal involvement, or organ dysfunction 1

For Concurrent Biliary Pathology

• Uncomplicated acute cholecystitis: proceed with urgent cholecystectomy as standard treatment 5
• Complicated cholecystitis (perforation, abscess): initial supportive measures with antibiotics and percutaneous drainage, followed by delayed cholecystectomy 5

For Mild Maculopapular Rash Without Systemic Features

• If isolated mild rash (<10% body surface area) without systemic symptoms and normal liver enzymes, may continue monitoring with topical corticosteroids 1
• However, maintain high suspicion and low threshold for drug discontinuation if symptoms progress 1

Critical Pitfalls to Avoid

• Never dismiss the combination of rash and RUQ pain as coincidental without excluding DRESS syndrome, which has mortality risk if not recognized early 1
• Do not attribute all RUQ pain to biliary disease when systemic drug reaction is present; over one-third of RUQ pain has non-biliary causes 5, 6
• Avoid ordering CT as initial imaging for RUQ pain, as it has only 75% sensitivity for gallstones and exposes patients to unnecessary radiation when ultrasound is diagnostic 2
• Do not assume maculopapular rash is benign without evaluating for mucosal involvement, which indicates severe reaction requiring immediate intervention 1
• Remember that pathological examination showing lymphocytic infiltrates with eosinophils confirms drug reaction, but clinical diagnosis should not be delayed awaiting biopsy results 1