What is the most consistent diagnosis for a 66-year-old female with diffuse itching, normal aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, and elevated alkaline phosphatase levels?

Primary Biliary Cholangitis (PBC)

The most consistent diagnosis for this 66-year-old woman with diffuse pruritus, normal AST/ALT, and isolated elevated alkaline phosphatase is primary biliary cholangitis (PBC).

Clinical Presentation Matches PBC

This patient's presentation is classic for PBC, which characteristically presents with:

• Cholestatic pattern with isolated elevated alkaline phosphatase while aminotransferases remain normal or only mildly elevated 1
• Pruritus as a presenting symptom in the absence of jaundice, which occurs in approximately 73.5% of PBC patients at some point in their disease course 2
• Middle-aged to older women as the predominant demographic (average age at diagnosis is 60 years, with 91% being female) 3
• Normal dermatologic examination because the pruritus is cholestatic in origin, not dermatologic 1

Biochemical Pattern Strongly Supports PBC

The laboratory findings are pathognomonic for cholestatic liver disease:

• Elevated alkaline phosphatase (279 U/L) is the most common biochemical abnormality in PBC, present in approximately 75% of patients 1
• Normal AST and ALT levels do not exclude PBC—aminotransferases are typically normal or only mildly elevated (2-3 times upper limit of normal) in early disease 1
• Normal bilirubin (1.1 mg/dL) is typical at diagnosis in the majority of PBC patients, as bilirubin elevation occurs later in disease progression 1
• In early-stage PBC, up to 29.2% of patients may have normal ALP levels, but when elevated, it is the hallmark finding 4

Differential Diagnosis Considerations

While PBC is most likely, other cholestatic conditions should be considered but are less probable:

• Primary sclerosing cholangitis (PSC) also presents with elevated ALP and pruritus, but typically affects younger men (not 66-year-old women) and is strongly associated with inflammatory bowel disease (60-80% of cases), which is not mentioned here 1
• Drug-induced cholestasis is possible given her daily alcohol consumption (15 oz wine), but the pattern and demographics favor PBC 1
• Intrahepatic cholestasis would be relevant only in pregnancy, which does not apply to this 66-year-old patient 1

Recommended Diagnostic Workup

To confirm PBC diagnosis, the following tests should be ordered immediately:

• Anti-mitochondrial antibody (AMA) testing—positive in 95% of PBC cases, with AMA-M2 being highly specific 1, 4
• If AMA is negative, check anti-nuclear antibody (ANA), particularly ANA centromere pattern, which has a 92.3% positivity rate in AMA-negative early PBC 4
• Confirm hepatic origin of elevated ALP with gamma-glutamyl transferase (GGT) or ALP isoenzyme fractionation, as ALP can originate from bone in postmenopausal women 1
• IgM and IgG levels, which are modestly elevated in approximately 60% of PBC patients 1
• Abdominal ultrasound to exclude biliary obstruction and assess for structural abnormalities 1

Important Clinical Pitfalls

Several critical considerations must be addressed:

• Pruritus in PBC is significantly undertreated—only 37.4% of patients with persistent pruritus receive cholestyramine, and only 11% receive rifampicin despite guideline recommendations 2
• Do not wait for jaundice to develop before investigating cholestatic disease, as bilirubin elevation is a late finding and marker of poor prognosis 1
• Younger age at diagnosis and higher ALP levels at 12 months are associated with persistent severe pruritus, requiring more aggressive antipruritic management 2
• Exclude secondary causes of sclerosing cholangitis including choledocholithiasis, surgical biliary trauma, IgG4-associated cholangitis, and ischemic cholangitis before finalizing the diagnosis 1

Treatment Implications

Once PBC is confirmed:

• Ursodeoxycholic acid (UDCA) 13-15 mg/kg/day is first-line therapy and should be initiated promptly to slow disease progression 5
• For pruritus management, start with cholestyramine, then consider rifampicin if inadequate response 2
• Monitor ALP and bilirubin levels as surrogate endpoints for disease progression and treatment response 1
• Screen for inflammatory bowel disease, as there is overlap between PBC and IBD in some patients 1