What is the diagnosis and treatment for an alcoholic patient with fever for more than one week, right upper quadrant (RUQ) abdominal pain, leukocytosis, hyperbilirubinemia, jaundice (icterus), and a positive Treponema pallidum hemagglutination assay (TPHA) test?

Diagnosis and Treatment for Alcoholic Patient with Fever, RUQ Pain, Leukocytosis, Hyperbilirubinemia, Jaundice, and Positive TPHA

The most likely diagnosis is severe alcoholic hepatitis with possible concurrent spontaneous bacterial peritonitis (SBP), and the positive TPHA represents either coincidental syphilis or a false-positive result; immediate treatment requires third-generation cephalosporin antibiotics (cefotaxime 2g IV every 8 hours), complete alcohol abstinence, aggressive nutritional support, and consideration of corticosteroids if Maddrey Discriminant Function ≥32 after infection is excluded. 1, 2

Primary Diagnostic Considerations

Severe Alcoholic Hepatitis (Most Likely)

The constellation of prolonged fever (>1 week), RUQ pain, leukocytosis, hyperbilirubinemia, and jaundice in an alcoholic patient strongly suggests severe alcoholic hepatitis, which presents with progressive jaundice, fever (even without infection), tender hepatomegaly, and laboratory findings showing AST >50 IU/L with AST/ALT ratio >1.5-2.0, neutrophilia, and elevated bilirubin >50 μmol/L. 1, 2

Critical pitfall: Alcoholic hepatitis patients commonly have fever and leukocytosis that can masquerade as infection, but they do NOT develop false-positive elevated ascitic fluid PMN counts—an elevated PMN count must be presumed to represent SBP until proven otherwise. 1

Concurrent Infection (Must Be Excluded Immediately)

Infection occurs in 20-30% of patients with severe alcoholic hepatitis and is a major cause of mortality. 1 The combination of fever >1 week, leukocytosis, and RUQ pain mandates immediate investigation for:

• Spontaneous bacterial peritonitis (SBP): Perform diagnostic paracentesis immediately if ascites is present; ascitic fluid PMN count ≥250 cells/mm³ indicates SBP requiring empiric antibiotics. 1
• Other bacterial infections: Obtain blood and urine cultures before starting antibiotics. 1, 2

Syphilitic Hepatitis (Less Likely but Must Consider)

While the positive TPHA suggests syphilis exposure, syphilitic hepatitis is extremely rare (incidence 0.2-38% of syphilis cases) and typically presents with cholestatic pattern (predominantly elevated alkaline phosphatase) rather than the hepatocellular pattern expected in alcoholic hepatitis. 3, 4, 5 The evidence for T. pallidum as a liver pathogen in early syphilis is not convincing, and coincidental viral hepatitis is more likely in jaundiced patients. 6

Immediate Diagnostic Workup

Laboratory Assessment

• Calculate severity scores immediately: Maddrey Discriminant Function (MDF) and MELD score to determine if severe alcoholic hepatitis (MDF ≥32 or MELD >20) is present, as these patients have high 28-day mortality requiring treatment. 1, 2, 7
• Obtain complete hepatic panel: AST, ALT, bilirubin (total and fractionated), alkaline phosphatase, albumin, INR/PT, creatinine, and CBC with differential. 1, 2, 8
• Confirm syphilis diagnosis: Obtain RPR titer and FTA-ABS or treponemal IgG/IgM to confirm active syphilis versus past exposure. 4, 5

Infection Screening

• Obtain cultures immediately: Blood, urine, and ascitic fluid (if ascites present) cultures BEFORE starting antibiotics. 1, 2
• Perform diagnostic paracentesis: If ascites is present, measure ascitic fluid PMN count, protein, albumin, and send for culture. 1

Imaging

• Abdominal ultrasound: First-line imaging to assess liver parenchyma, exclude biliary obstruction, evaluate for ascites, and assess for complications. 1, 8

Immediate Treatment Protocol

Empiric Antibiotic Therapy (Start Immediately)

Cefotaxime 2g IV every 8 hours is the treatment of choice for suspected SBP and covers 95% of flora including E. coli, Klebsiella pneumoniae, and pneumococci. 1 This broad-spectrum third-generation cephalosporin should be started immediately in any patient with convincing signs of infection (fever, abdominal pain, unexplained deterioration) regardless of PMN count until culture results are available. 1, 2

• Duration: Continue for 5 days if SBP is confirmed (as effective as 10 days). 1
• Discontinuation criteria: If ascitic fluid, blood, and urine cultures show no bacterial growth after 48 hours, antibiotics can be discontinued. 1

Universal Interventions for Alcoholic Hepatitis

• Complete alcohol abstinence: Mandatory and immediate; this is the cornerstone of treatment improving both short-term and long-term survival. 7
• Thiamine 500 mg IV three times daily for 3-5 days: Administer BEFORE any glucose-containing solutions to prevent Wernicke's encephalopathy. 7
• Aggressive nutritional support: Provide 35-40 kcal/kg ideal body weight daily and 1.2-1.5 g/kg/day protein, as protein-calorie malnutrition is present in almost every patient with severe alcoholic hepatitis. 2, 7
• Avoid nephrotoxic agents: Discontinue diuretics and other nephrotoxic drugs immediately, as acute kidney injury is an early manifestation of multi-organ failure syndrome with very high mortality. 2, 7

Corticosteroid Therapy (If Severe Disease and No Contraindications)

Prednisolone 40 mg daily for 28 days should be prescribed for patients with MDF ≥32 or MELD >20 if no contraindications exist (active infection, GI bleeding, renal failure). 1, 7

• Critical timing: Do NOT start corticosteroids until infection is excluded or adequately treated. 1
• Response assessment: Calculate Lille score at day 7; if Lille score ≥0.45, stop corticosteroids immediately as non-responders have increased risk of infection and death. 1, 7

Treatment of Syphilis (If Confirmed Active)

If RPR is reactive with positive treponemal antibodies confirming active syphilis:

• Benzathine penicillin G 2.4 million units IM as a single dose for early syphilis. 9, 4
• Alternative if penicillin-allergic: Doxycycline 100 mg PO twice daily for 14 days. 9

Important note: Syphilitic hepatitis, if present, responds rapidly to penicillin therapy with normalization of liver enzymes within 1-2 weeks. 4, 10 However, given the clinical presentation more consistent with alcoholic hepatitis, syphilis treatment should not delay management of the primary hepatic condition.

Monitoring and Follow-Up

• Daily assessment: Monitor vital signs, mental status, urine output, and laboratory values (bilirubin, creatinine, INR) daily. 2
• Lille score calculation: At day 7 of corticosteroid therapy to assess response. 1, 7
• Liver transplant evaluation: If MELD >26, refer for early liver transplantation evaluation as 90-day mortality is very high. 7

Critical Pitfalls to Avoid

• Do not delay antibiotics: Waiting for culture results in suspected infection may result in death from overwhelming sepsis. 1
• Do not assume fever is from alcoholic hepatitis alone: Always exclude infection first, as 20-30% of severe alcoholic hepatitis patients have concurrent bacterial infections. 1
• Do not continue corticosteroids in non-responders: Lille score ≥0.45 at day 7 mandates stopping steroids to avoid increased infection risk. 1, 7
• Do not use diuretics: These are nephrotoxic and precipitate acute kidney injury in this vulnerable population. 2, 7