What rheumatology disease is likely to cause liver and kidney involvement with cholestasis in an elderly female patient with early cirrhosis, impaired renal function, and cholestatic symptoms?

Primary Biliary Cholangitis (PBC) with Systemic Lupus Erythematosus (SLE)

Primary Biliary Cholangitis (PBC) is the rheumatology-associated disease most likely causing liver and kidney involvement with cholestasis in this elderly female patient, particularly when occurring as a rare overlap syndrome with Systemic Lupus Erythematosus (SLE). 1, 2, 3

Key Diagnostic Features

The combination of cholestatic liver disease with renal impairment in an elderly female with autoimmune features points strongly toward PBC, especially given:

• PBC predominantly affects women and commonly presents with cholestatic symptoms including elevated alkaline phosphatase and bilirubin 4
• Osteoporosis is particularly common in cholestatic disorders like PBC, especially in postmenopausal women, which aligns with your patient population 4
• The rare coexistence of SLE and PBC has been documented in elderly women, with several case reports describing this overlap syndrome in patients aged 65-70 years 1, 2, 3

Diagnostic Workup Algorithm

First-line testing should include:

• Antimitochondrial antibodies (AMA) - high-titer AMA (≥1:40) with cholestatic enzyme profile establishes PBC diagnosis with confidence 4
• PBC-specific antinuclear antibodies (ANA) if AMA is negative 4
• Ultrasound to exclude extrahepatic biliary obstruction as the initial imaging modality 4

If AMA and PBC-specific ANA are negative:

• MRCP should be performed to evaluate for primary sclerosing cholangitis or other biliary pathology 4
• Liver biopsy with ≥10 portal fields is indicated when diagnosis remains unclear, looking specifically for nonsuppurative destructive cholangitis characteristic of PBC 4

Renal Function Assessment

The hepatorenal syndrome must be differentiated from other causes of acute kidney injury in this cirrhotic patient 4:

• Severe cholestasis can directly impair renal function by worsening inflammation and macrocirculatory dysfunction 4
• Estimated GFR using MDRD6 formula should be calculated, though conventional biomarkers like serum creatinine have significant limitations in cirrhotic patients 4, 5
• Consider inulin clearance or renal biopsy if GFR is <30 ml/min or if hepatorenal syndrome requiring renal replacement therapy persists >8-12 weeks, as this may indicate need for combined liver-kidney transplantation 4

Critical Pitfall: SLE-PBC Overlap Syndrome

The coexistence of SLE and PBC is extremely rare but well-documented 1, 2, 3:

• SLE can present with cholestatic liver disease that mimics PBC, particularly in late-onset cases 6
• Check for SLE criteria including cutaneous lesions, photosensitivity, anti-dsDNA antibodies, pancytopenia, and arthritis 3
• Antimitochondrial M2 antibodies distinguish true PBC from lupus hepatitis 3
• Autoimmune mechanisms, environmental and genetic factors contribute to susceptibility for both diseases, with osteopontin potentially playing an important role 1

Management Considerations

For confirmed PBC without decompensated cirrhosis:

• Ursodeoxycholic acid (UDCA) is first-line therapy for PBC and has been shown to stabilize liver dysfunction in SLE-PBC overlap cases 1
• Obeticholic acid is contraindicated in patients with decompensated cirrhosis, prior decompensation events, or compensated cirrhosis with portal hypertension 7

For renal impairment:

• Terlipressin plus albumin should be considered if hepatorenal syndrome is diagnosed, with careful cardiovascular screening via electrocardiogram before initiation 4
• Baseline creatinine and degree of inflammation are the most relevant factors impairing response to vasoconstrictors 4

Monitor closely for:

• Evidence of portal hypertension (ascites, varices, persistent thrombocytopenia) which would contraindicate certain therapies 7
• Progression to hepatic decompensation requiring consideration for liver transplantation 4
• Bone density given high risk of osteoporosis in cholestatic disease 4