What is malignancy-related arthropathy in a patient with anemia of chronic disease and new onset joint pains?

Malignancy-Related Arthropathy

Malignancy-related arthropathy is a paraneoplastic syndrome characterized by new-onset inflammatory polyarthritis that occurs as a direct manifestation of an underlying malignancy, typically presenting before the cancer diagnosis is made and resolving with successful cancer treatment. 1, 2

Clinical Presentation

The arthropathy presents with distinctive features that should raise suspicion for underlying malignancy:

• Symmetric polyarthritis affecting predominantly the wrists and hands (85% of cases), mimicking rheumatoid arthritis in distribution 2
• Acute onset in patients without prior rheumatic disease history, particularly in males and smokers 2
• Poor response to NSAIDs, which distinguishes it from typical inflammatory arthritis 1
• Extra-articular symptoms are frequent (84% of cases), including constitutional symptoms and systemic manifestations 2

The joint involvement typically includes MCPs and PIPs, following a pattern similar to rheumatoid arthritis, though the clinical context differs significantly 3.

Temporal Relationship to Cancer

The timing between arthritis onset and cancer diagnosis is critically important:

• Mean delay of 3.6 months between rheumatic symptoms and cancer diagnosis 2
• Articular symptoms precede cancer diagnosis in 88.5% of cases, making this a true paraneoplastic phenomenon rather than a consequence of known malignancy 2
• The arthritis serves as an early warning sign, often leading to cancer detection at earlier, more treatable stages 2

Associated Malignancies

Specific cancer types are most commonly associated:

• Adenocarcinoma of the lung is the most frequent solid tumor (60% of solid cancers) 2
• Solid tumors account for approximately 77% of cases (20 of 26 patients) 2
• Hematological malignancies comprise the remaining 23% (6 of 26 patients) 2
• Small cell lung cancer and colon adenocarcinoma have been specifically documented 1

Diagnostic Approach in Context of Anemia

When evaluating a patient with anemia of chronic disease and new-onset joint pains, consider:

• Anemia is present in 40-64% of cancer patients and may be the first manifestation alongside arthropathy 4
• The combination of unexplained anemia and new polyarthritis should prompt aggressive cancer screening, particularly in males, smokers, and chronically ill patients 5, 2
• Standard rheumatologic markers (RF, ANA) are typically negative, distinguishing this from primary rheumatoid arthritis 1
• No specific radiographic features exist early in the disease course 2

Prognosis and Treatment Response

The response to cancer treatment is the defining characteristic:

• Spontaneous resolution of arthritis occurs after successful cancer treatment (chemotherapy or tumor resection) 1
• Significantly higher resolution rates in solid tumors (75%) compared to hematological malignancies (p = 0.007) 2
• Arthritis does not recur in 75% of patients even if the tumor relapses, suggesting the paraneoplastic mechanism may be distinct from tumor burden 2
• Median survival of 1.21 years reflects earlier cancer detection through the arthropathy presentation 2

Key Clinical Pitfalls

Several critical distinctions must be made:

• Do not assume anemia of chronic disease without investigation—10% of anemic RA patients had established malignancy and another 10% had premalignancy in one cohort 5
• Failure to respond to NSAIDs is a red flag that should prompt cancer screening rather than escalation to DMARDs 1
• The arthropathy differs from cancer pain syndromes described in NCCN guidelines, which address pain management in known cancer patients rather than arthritis as a presenting sign 6
• Unlike Adult-Onset Still's Disease, which can mimic malignancy-related arthropathy, there is no characteristic quotidian fever pattern or salmon-pink rash 6

Recommended Workup

When malignancy-related arthropathy is suspected:

• Immediate chest imaging given the high prevalence of lung adenocarcinoma 2
• Age-appropriate cancer screening with particular attention to gastrointestinal sources (colonoscopy if indicated) 1, 2
• Investigation of anemia etiology including iron studies, peripheral smear, and consideration of bone marrow examination if unexplained 5, 4
• Avoid empiric DMARD therapy until malignancy is excluded, as the arthropathy should resolve with cancer treatment 1

The diagnosis requires high clinical suspicion, particularly in patients over 50 years with new-onset symmetric polyarthritis, smoking history, constitutional symptoms, and concurrent anemia who fail to respond to initial anti-inflammatory therapy 2.