Can individuals with lymphoma experience joint pain?

Can Individuals with Lymphoma Experience Joint Pain?

Yes, individuals with lymphoma can experience joint pain, though it is not a typical presenting feature of the disease itself. Joint pain in lymphoma patients most commonly occurs as a consequence of treatment with immune checkpoint inhibitors or as a rare manifestation of extranodal disease, rather than as a direct symptom of the lymphoma 1.

Primary Mechanisms of Joint Pain in Lymphoma Patients

Treatment-Related Arthralgia (Most Common)

Musculoskeletal symptoms including arthralgia are extremely common in lymphoma patients receiving immune checkpoint inhibitor (ICPi) therapy, reported in up to 40% of patients in clinical trials 1. This represents the most frequent cause of joint pain in this population.

• Inflammatory arthritis secondary to ICPi can present in multiple patterns:

  • Oligoarthritis affecting large joints (knees, ankles, wrists) with features resembling reactive arthritis 1
  • Symmetrical polyarthritis resembling rheumatoid arthritis with possible autoantibodies 1
  • Polymyalgia-like syndrome with severe myalgia and arthralgia, particularly in proximal extremities 1

• These immune-related adverse events occur more frequently with PD-1/PD-L1 inhibitors than CTLA-4 antagonists, and are most common with combination therapy 1

• Arthritis can develop at any time during treatment, including many months after ICPi initiation 1

Extranodal Lymphoma Presentation (Rare)

While lymphoma typically presents as painless adenopathy 2, rare cases of extranodal soft tissue lymphoma can cause pain and tenderness in affected areas 3. However, this represents soft tissue involvement rather than true articular joint pain.

Clinical Presentation Patterns

ICPi-Related Arthritis Characteristics

Inflammatory markers (ESR, CRP) are usually markedly elevated in patients with ICPi-induced arthritis, which helps differentiate these events from other rheumatic syndromes 1.

• Joint involvement can affect both large and small joints 1
• Some patients develop sicca symptoms (dry eyes, dry mouth) alongside arthritis 1
• Patients may be seronegative despite clinical arthritis 1

Polymyalgia-Like Syndrome

• Severe myalgia in proximal upper and lower extremities with severe fatigue 1
• Arthralgia present but typically without definite synovitis 1
• Pain without true weakness (distinguishing from myositis) 1
• CK levels remain within normal limits 1

Diagnostic Evaluation

When joint pain occurs in lymphoma patients, diagnostic workup should include:

• Serum inflammatory markers (ESR, CRP) 1
• Autoantibody evaluation (ANA, RF, anti-CCP) 1
• Imaging as indicated (x-rays, ultrasound, and/or MRI) 1

Important differential diagnoses to exclude include:

• Degenerative joint disease or osteoarthritis 1
• Crystal arthropathies (gout and pseudogout) 1
• Septic arthritis 1
• Soft tissue rheumatic disorders 1

Management Approach

Grade 1 (Mild) Symptoms

• Continue ICPi therapy 1
• Initiate analgesia with acetaminophen and/or NSAIDs if no contraindications 1

Grade 2 (Moderate) Symptoms

• May hold ICPi and resume upon symptom control when prednisone <10 mg; if worsens, escalate to grade 3 management 1
• Initiate prednisone 20 mg/day or equivalent 1
• If symptoms improve, taper after 3-4 weeks 1
• Consider rheumatology referral 1

Grade 3-4 (Severe) Symptoms

• Hold ICPi and may resume only in consultation with rheumatology if symptoms recover to grade 1 or less 1
• Mandatory rheumatology referral 1
• Initiate prednisone 20 mg/day or equivalent 1
• If no improvement or need for higher dosages for prolonged time, consider corticosteroid-sparing agents such as methotrexate or IL-6 inhibition with tocilizumab 1
• Consider hospital admission for pain control 1

Critical caveat: IL-6 inhibition can cause intestinal perforation and should NOT be used in patients with colitis or GI metastases 1.

Treatment Response and Prognosis

• NSAIDs alone are usually insufficient to control ICPi-induced arthritis symptoms 1
• Corticosteroids and synthetic or biologic DMARDs are frequently required 1
• Intra-articular corticosteroid injections are effective when only one or two joints are affected 1
• Approximately one-quarter to one-third of patients require additional immunosuppressive therapy beyond corticosteroids 1

Important Clinical Pitfalls

Cases of toxicity returning upon ICPi rechallenge have been reported, so resumption of therapy requires careful consideration and rheumatology consultation 1. The quality of life impact can be substantial due to effects on function and daily activities 1, making aggressive symptom management essential even when it requires holding cancer therapy temporarily.