How should a middle-aged adult with recurrent unexplained illness, weight loss, jaundice, confusion, hemoptysis, leukocytosis, esophageal varices, and anemia be managed?

Management of Middle-Aged Adult with Recurrent Illness, Weight Loss, Jaundice, Confusion, Hemoptysis, Leukocytosis, Esophageal Varices, and Anemia

This constellation of symptoms—particularly the combination of jaundice, confusion (hepatic encephalopathy), esophageal varices, and anemia—strongly suggests decompensated cirrhosis with portal hypertension, and this patient requires immediate ICU admission for resuscitation, airway protection, urgent endoscopy within 12 hours, and simultaneous initiation of vasoactive drugs, antibiotics, and lactulose. 1

However, the presence of hemoptysis, leukocytosis, and recurrent unexplained illness in a middle-aged patient also raises critical concern for Wilson disease, which must be excluded urgently as it can present with acute liver failure, hemolytic anemia, neuropsychiatric symptoms (confusion), and cirrhosis with portal hypertension. 2

Immediate Life-Threatening Management (First 12 Hours)

ICU Admission and Airway Protection

• Admit immediately to ICU given the combination of active bleeding (presumed variceal), hepatic encephalopathy (confusion), and hemodynamic instability. 1
• Perform emergent tracheal intubation for airway protection prior to endoscopy, as aspiration of blood is a significant risk with active bleeding and altered mental status. 1

Hemodynamic Resuscitation

• Use restrictive transfusion strategy: transfuse packed red blood cells only when hemoglobin falls below 7 g/dL, targeting 7-9 g/dL. 1
• Avoid excessive fluid resuscitation with crystalloids, as vigorous resuscitation increases portal pressure and worsens variceal bleeding. 1

Immediate Pharmacological Therapy (Before Endoscopy)

• Initiate vasoactive drug therapy immediately upon suspicion of variceal hemorrhage: options include octreotide, terlipressin, or somatostatin. 1
• Start prophylactic antibiotics immediately (ceftriaxone or norfloxacin) to decrease bacterial infections, early rebleeding, and mortality. 1
• Initiate lactulose immediately for hepatic encephalopathy, titrating to achieve 2-3 soft bowel movements per day. 1

Urgent Diagnostic Endoscopy

• Perform upper endoscopy within 12 hours once hemodynamic stability is achieved and airway is protected. 1
• Endoscopic variceal ligation (EVL) is the preferred endoscopic therapy for esophageal varices. 1

Critical Diagnostic Workup for Underlying Etiology

Exclude Wilson Disease (Priority)

Wilson disease must be excluded in any patient with unexplained liver disease along with neurologic symptoms (confusion), hemolysis (which can cause jaundice and anemia), and age between 3-55 years. 2

Specific Tests Required:

• Slit-lamp examination for Kayser-Fleischer rings (present in virtually all patients with neurologic Wilson disease). 2
• Serum ceruloplasmin (typically <20 mg/dL in Wilson disease). 2
• 24-hour urinary copper (typically >40 μg/day or >0.6 μmol/day in Wilson disease). 2
• Liver biopsy with quantitative hepatic copper if above tests are equivocal. 2
• Coombs-negative hemolytic anemia with acute renal failure is characteristic of acute liver failure presentation of Wilson disease. 2

Investigate Hemoptysis Source

• The hemoptysis in this context is unusual and requires specific attention:
  • Chest CT with contrast to evaluate for pulmonary vascular abnormalities, as systemic collateral veins from portal hypertension can rarely cause hemoptysis. 3
  • Consider bronchoscopy if hemoptysis is significant or recurrent.
  • Evaluate for aspiration pneumonia given altered mental status.

Evaluate Anemia and Leukocytosis

• Complete blood count with differential: leukocytosis may indicate infection (spontaneous bacterial peritonitis), hemophagocytic syndrome, or inflammatory process. 2
• Reticulocyte count and peripheral smear to assess for hemolysis (Wilson disease) versus chronic blood loss. 2
• Serum ferritin and iron studies to evaluate for iron deficiency anemia from chronic GI blood loss. 2, 4
• Direct Coombs test to confirm Coombs-negative hemolysis if Wilson disease is suspected. 2

Additional Liver Disease Workup

• Hepatitis B and C serologies, HIV testing. 2
• Autoimmune hepatitis panel: ANA, anti-smooth muscle antibody, anti-LKM, immunoglobulins (IgG elevation). 2
• Celiac disease screening (tissue transglutaminase antibody), as celiac disease is found in 3-5% of cases with anemia and can cause malabsorption. 2, 4
• Liver function tests: bilirubin, albumin, INR, AST, ALT. 2
• Abdominal ultrasound or CT to assess liver morphology, splenomegaly, ascites, and portal vein patency. 5

Consider Adult-Onset Still's Disease

Given the constellation of recurrent fever (implied by "recurrent unexplained illness"), leukocytosis, weight loss, and potential liver involvement with jaundice:

• Serum ferritin levels (extremely elevated levels 4,000-30,000 ng/mL or higher suggest Adult-Onset Still's Disease). 2
• ESR and CRP (typically markedly elevated). 2
• However, this diagnosis is less likely given the presence of esophageal varices, which indicate portal hypertension from chronic liver disease. 2

Secondary Prevention and Long-Term Management

After Acute Episode Control

• Initiate non-selective beta-blockers (propranolol or nadolol) for secondary prophylaxis of variceal bleeding. 1
• Consider rifaximin for prevention of recurrent hepatic encephalopathy. 1
• Regular endoscopic surveillance and hepatic venous catheterization to monitor varices. 5

Liver Transplant Evaluation

• Refer urgently for liver transplant evaluation given decompensated cirrhosis with variceal bleeding and hepatic encephalopathy. 1
• This is particularly urgent if Wilson disease is confirmed, as it is potentially curable with transplantation. 2

Iron Replacement if Indicated

• If iron deficiency anemia is confirmed after excluding hemolysis, initiate iron replacement therapy with monitoring of hemoglobin at 3,6,12, and 24 months. 2
• Long-term iron replacement may be appropriate when the cause of recurrent anemia is irreversible (chronic variceal bleeding). 2

Critical Monitoring Parameters

• Hemodynamic status, hemoglobin, mental status, renal function, signs of rebleeding, and infection require close ICU monitoring. 1
• Avoid NSAIDs as they can worsen both portal hypertension and cause GI bleeding. 2

Common Pitfalls to Avoid

• Do not delay Wilson disease workup: this is a treatable cause of liver failure that can present with this exact constellation of symptoms, and missing it has catastrophic consequences. 2
• Do not attribute all symptoms to cirrhosis alone: the hemoptysis and leukocytosis require specific investigation as they may indicate concurrent pathology. 3
• Do not perform endoscopy without airway protection in a patient with altered mental status and active bleeding. 1
• Do not over-resuscitate with fluids: this worsens portal pressure and variceal bleeding. 1