What is the recommended evaluation and treatment for shoulder pain in a patient with autoimmune hepatitis receiving prednisone and azathioprine?

Bilateral Shoulder Pain in Autoimmune Hepatitis

Corticosteroid-Induced Musculoskeletal Complications

Bilateral shoulder pain in a patient with autoimmune hepatitis on prednisone and azathioprine is most likely steroid-induced osteoporosis, avascular necrosis, or myopathy—all well-documented complications of long-term corticosteroid therapy. 1, 2

Immediate Evaluation Required

• Obtain plain radiographs of both shoulders as the initial imaging study to assess for fractures, joint space narrowing, or signs of avascular necrosis 1
• Order MRI of both shoulders if radiographs are negative or equivocal, as MRI is the gold standard for detecting early avascular necrosis before radiographic changes appear 1
• Perform DEXA bone mineral density scanning of the lumbar spine and hip if not done within the past year, as this should be monitored at 1-2 yearly intervals in all patients on corticosteroids 1, 2, 3
• Check serum calcium, vitamin D (25-OH), phosphate, alkaline phosphatase, and creatine kinase to evaluate for metabolic bone disease and steroid myopathy 1

Common Steroid-Related Causes

Long-term corticosteroid therapy causes severe complications including osteoporosis, vertebral compression fractures, avascular necrosis, and myopathy, typically developing after 18 months of treatment at doses >10 mg/day 2, 4. The cosmetic changes occur in 80% of patients after 2 years, but the severe skeletal complications are the most concerning for bilateral shoulder pain 2.

Management Strategy

If osteoporosis or osteopenia is confirmed:

• Initiate bisphosphonate therapy immediately 1, 3
• Ensure adequate calcium (1000-1500 mg daily) and vitamin D (800-1000 IU daily) supplementation, which should have been started at treatment initiation 1, 2, 3
• Consider reducing prednisone to the lowest effective dose by tapering 2.5 mg monthly while monitoring liver enzymes 1
• Maintain azathioprine at 2 mg/kg/day as monotherapy if possible to minimize cumulative steroid exposure, as 87% of patients remain in remission on azathioprine alone 1, 5

If avascular necrosis is confirmed:

• Refer urgently to orthopedic surgery for consideration of core decompression (early stage) or joint replacement (advanced stage) 1
• Attempt to minimize or eliminate prednisone by transitioning to azathioprine monotherapy at 2 mg/kg/day 1, 5

If steroid myopathy is suspected (elevated CK, proximal weakness):

• Reduce prednisone dose aggressively while maintaining disease control with azathioprine 1, 2
• Initiate physical therapy for strengthening exercises 1

Alternative Diagnoses to Consider

Azathioprine-related arthralgia occurs in 63% of patients on long-term azathioprine maintenance and typically presents as withdrawal arthralgia when the drug is stopped or dose-adjusted 1. However, this is less likely to cause bilateral shoulder pain specifically and usually affects multiple joints.

Optimization of AIH Treatment to Minimize Steroid Exposure

The combination regimen of prednisone plus azathioprine achieves similar efficacy to prednisone monotherapy with significantly fewer corticosteroid-related side effects (10% vs 44%) 2, 4. Your patient is already on combination therapy, which is appropriate.

Consider the following steroid-sparing strategies:

• Taper prednisone to ≤10 mg daily or less (median effective dose is 7.5 mg daily) while maintaining azathioprine at 2 mg/kg/day 1
• Monitor serum aminotransferases monthly during dose reduction, as small decrements in prednisone can cause marked increases in liver enzymes 1
• In non-cirrhotic patients with early-stage disease, consider switching to budesonide 9 mg/day plus azathioprine, which produces fewer steroid-related side effects than prednisolone 1, 3, 4
• Never use budesonide in cirrhotic patients due to impaired first-pass metabolism 3, 4

Monitoring Requirements Going Forward

• Perform DEXA scanning every 1-2 years while on corticosteroids 1, 2, 3
• Conduct periodic eye examinations for cataracts and glaucoma, which are additional long-term steroid complications 1, 2
• Check complete blood count regularly to monitor for azathioprine-induced myelosuppression 1

Critical Pitfall to Avoid

Do not attribute musculoskeletal symptoms to "normal aging" or "arthritis" in patients on chronic corticosteroids—these are red flags for serious steroid-induced complications that require immediate evaluation and intervention. The goal should always be to minimize cumulative steroid exposure while maintaining hepatic remission 2, 4.