What is the best course of action for a 56-year-old female patient with hypothyroidism, taking Hydroxychloroquine Sulfate and Prednisone, who has been experiencing knee pain for 3 months?

Management of Knee Pain in a Patient on Hydroxychloroquine and Prednisone

Discontinue hydroxychloroquine immediately, as it has no efficacy for osteoarthritis and should not be used for knee pain. 1

Immediate Medication Changes

• Stop hydroxychloroquine: The 2019 American College of Rheumatology/Arthritis Foundation guidelines strongly recommend against hydroxychloroquine for knee osteoarthritis, as well-designed randomized controlled trials demonstrate no efficacy. 1

• Taper prednisone: While prednisone may provide short-term relief, chronic use at doses >20 mg/day carries significant morbidity risks including bone loss, metabolic complications, and infection risk. 1 The patient should be tapered to the lowest effective dose or discontinued if being used for knee pain alone.

Diagnostic Clarification Needed

Before proceeding with treatment, determine the underlying cause of knee pain:

• If bilateral knee osteoarthritis (most likely given age and bilateral presentation): Proceed with OA-specific management below. 1

• If inflammatory arthritis (less likely but important to exclude): Look for morning stiffness >30 minutes, joint swelling/warmth, elevated inflammatory markers (ESR, CRP), and consider rheumatology referral. 1

• If the hydroxychloroquine was prescribed for systemic lupus erythematosus or rheumatoid arthritis: Do NOT discontinue hydroxychloroquine, as it is effective for these conditions and prevents disease flares. 2, 3 The knee pain would then require separate evaluation for coexisting osteoarthritis.

First-Line Treatment for Knee Osteoarthritis

Non-pharmacological interventions should be initiated immediately as they provide sustained benefit:

• Quadriceps strengthening exercises: These reduce pain with an effect size of 1.05 and improve function long-term (up to 18 months). 1 Referral to physical therapy is strongly recommended. 1

• Aerobic exercise: Low-impact aerobic conditioning is equally efficacious to strengthening exercises for pain and function. 1

• Weight reduction: If BMI ≥25 kg/m², weight loss reduces risk of symptomatic knee OA progression. 1, 4

• Patient education: Structured education programs reduce pain and improve coping skills. 1

Pharmacological Management

For pain control, use the following stepwise approach:

1. Acetaminophen (paracetamol): First-line oral analgesic for mild-to-moderate pain. 1, 5

2. Topical NSAIDs: If acetaminophen inadequate, topical NSAIDs (e.g., diclofenac gel) are preferred over oral NSAIDs due to lower systemic side effects, particularly important given her prednisone use. 1

3. Oral NSAIDs: If topical NSAIDs insufficient and no contraindications (consider GI protection given prednisone use). NSAIDs show better efficacy than acetaminophen (effect size 0.32-0.45) but with increased gastrointestinal risk. 1

4. Intra-articular corticosteroid injection: For acute exacerbations, especially if effusion present. Provides short-term benefit (1-7 days with effect size 1.27). 1 However, use cautiously given she's already on systemic prednisone.

Treatments to Avoid

Do NOT use the following, as they lack efficacy:

• Glucosamine and chondroitin: Strongly recommended against by ACR/AF guidelines; highest quality evidence shows no benefit over placebo. 1, 4, 5

• Intra-articular hyaluronic acid: Conditionally recommended against for knee OA; when limited to low-risk-of-bias trials, effect size approaches zero. 1

• Bisphosphonates: Strongly recommended against; no improvement in pain or function. 1

Critical Pitfall to Avoid

The most common error is continuing hydroxychloroquine for osteoarthritis pain. While one small Iranian study from 2013 suggested benefit 6, this contradicts multiple high-quality randomized controlled trials specifically in erosive hand OA that showed no efficacy. 1 The ACR/AF guidelines are based on the highest quality evidence with lowest risk of bias and should take precedence. 1

Exception: If hydroxychloroquine was prescribed for an underlying autoimmune condition (SLE, RA), it must be continued to prevent disease flares, but it will not treat the knee pain itself. 2, 3

Monitoring and Follow-up

• Reassess pain and function at 4-6 weeks after initiating non-pharmacological interventions and appropriate analgesics. 1
• If inadequate response after 3 months of optimal conservative management, consider referral to orthopedic surgery for evaluation of joint replacement candidacy. 1