What is the recommended pre-operative workup for patients with IgG4 (Immunoglobulin G4) disease?

Pre-operative Workup for Patients with IgG4-Related Disease

For patients with IgG4-related disease, a comprehensive pre-operative workup should include serum IgG4 levels, confirmatory histological diagnosis, assessment of other organ involvement, and evaluation for malignancy before proceeding with surgery. 1

Essential Pre-operative Assessments

Laboratory Evaluations

• Serum IgG4 levels: Elevated levels support the diagnosis but cannot be relied upon for definitive diagnosis 1
• Complete IgG panel: Measure total IgG and calculate IgG4/IgG ratio (>40% is supportive) 1
• Liver function tests: To assess hepatobiliary involvement
• Inflammatory markers: ESR, CRP to evaluate disease activity

Histological Confirmation

• Tissue biopsy: Attempts should be made to obtain confirmatory histological diagnosis before surgery 1
  • Look for lymphoplasmacytic infiltration with IgG4-positive plasma cells (>10 per high power field)
  • Evaluate for storiform fibrosis and obliterative phlebitis
  • Perform IgG4 and IgG immunostaining on biopsies with lymphoplasmacytic infiltration 1

Imaging Studies

• Cross-sectional imaging (CT/MRI): To assess extent of disease and identify other organ involvement
• MRCP: For evaluation of biliary involvement patterns in IgG4-related sclerosing cholangitis
• 18F-FDG PET/CT: Helps map sites of inflammation, evaluate disease extent, and guide biopsy decisions 2

Multi-organ Assessment

• Pancreatic evaluation: Assess for autoimmune pancreatitis, which is present in >80% of IgG4-related sclerosing cholangitis cases 1
• Salivary and lacrimal glands: Evaluate for involvement as these are common sites
• Retroperitoneum, kidneys, aorta: Check for additional organ involvement 2

Malignancy Exclusion

• Biliary brush cytology/biopsy: To rule out cholangiocarcinoma in cases with biliary strictures 1
• EUS-guided FNA: For pancreatic lesions to exclude malignancy 1
• Papanicolaou guidelines: Should be used for reporting biliary lesion cytology results 1

Pre-operative Management Considerations

Steroid Trial

• Consider pre-operative steroid trial (prednisolone 40mg daily for 2-4 weeks) 1
• Assess objective improvement in radiological abnormalities at 4-8 weeks
• Lack of response suggests either incorrect diagnosis or fibrotic phase of disease 1

Multidisciplinary Team Discussion

• MDT review: Patients with complex IgG4-SC and suspected malignancy should be referred to a specialist MDT 1
• Surgical planning: Complete staging and assessment of operability should be done before deciding on drainage 1

Biliary Drainage Considerations

• If biliary obstruction is present, consider preoperative biliary drainage in cases of:
  • Cholangitis
  • Jaundice (bilirubin >50 μmol/L)
  • Need for extensive surgery (>50% of liver parenchyma) 1

Pitfalls and Caveats

• Diagnostic challenges: IgG4-related disease can mimic malignancy, infection, and other immune-mediated disorders 3
• Serum IgG4 limitations: Up to 30% of patients with IgG4-RD may have normal serum IgG4 levels 1
• Histopathological interpretation: Requires clinical correlation for accurate diagnosis 4
• Disease relapse: High relapse rates (60%) after cessation of steroid treatment should be considered in perioperative planning 1
• Malignancy risk: Careful exclusion of malignancy is essential, as IgG4-RD can be associated with or mimic various cancers 5

By following this structured pre-operative workup, clinicians can better prepare patients with IgG4-related disease for surgery, minimize complications, and optimize outcomes.