Rheumatic Paraneoplastic Syndromes and Malignancies With Rheumatic Manifestations

Relationship Between Cancer and Rheumatic Diseases

• Cancer and rheumatic diseases have a complex and bidirectional relationship.
• Persistent inflammatory states from rheumatic diseases or therapies may increase malignancy risks.
• Conversely, malignancies or their treatments may induce autoimmunity or rheumatic manifestations.

Rheumatic Paraneoplastic Syndromes

• Rare syndromes with clinical importance for early detection of occult malignancies.
• Mediated by soluble factors (hormones, cytokines) or immune mechanisms.
• Clinical manifestations can involve joints, fasciae, muscles, vessels, and bones, occurring distant from the malignancy.
• To classify as paraneoplastic, a causal relationship needs to be established (Bradford Hill Criteria).

Key Features of Paraneoplastic Syndromes

• Symptoms typically appear within 3 years of cancer detection.
• Remission of rheumatic symptoms can occur after successful elimination of the tumor.
• Important for clinicians to be aware of these syndromes for timely treatment.

Common Rheumatic Paraneoplastic Syndromes

Paraneoplastic Arthritis

• Associated Malignancy: Various tumors.
• Features: Seronegative, more common in males, asymmetric polyarthritis with elevated inflammation markers.
• Pathogenesis: Possible recognition of cytotoxic tumor neo-antigens.
• Treatment: Corticosteroids, DMARDs.

Palmar Fasciitis and Polyarthritis Syndrome (PFPAS)

• Associated Malignancy: Ovarian and other urogenital cancers.
• Features: Fibrosis of palms, flexion contractures, “woody” texture of hands.
• Treatment: Physical therapy, ineffective immunosuppression.

Remitting Seronegative Symmetric Synovitis with Pitting Edema (RS3PE)

• Associated Malignancy: Solid tumors, hematologic malignancies.
• Features: Pitting edema primarily in hands, excellent corticosteroid response.
• Malignancy Rate: 16-31% in various studies.

Pancreatic Panniculitis and Polyarthritis (PPP)

• Associated Malignancy: Pancreatic cancer.
• Features: Symmetric polyarthritis with panniculitis.
• Prognosis: Generally poor, minimal response to NSAIDs.

Erythromelalgia

• Associated Malignancy: Myeloproliferative disorders.
• Features: Severe burning pain, warmth, and redness in extremities.
• Management: Aspirin, topical therapies like lidocaine.

Paraneoplastic Vasculitis

• Associated Malignancy: Myelodysplasia, non-Hodgkin lymphoma.
• Features: Usually cutaneous, may involve joints and organs.
• Proposed Pathogenesis: Immune complex formation.

Hypertrophic Osteoarthropathy (HOA)

• Associated Malignancy: Lung cancer or other thoracic malignancies.
• Features: Distal phalange clubbing, inflammatory periostitis leading to bone/joint pain.
• Pathogenesis: PDGF and VEGF production by tumors.
• Treatment: Bisphosphonates may be effective.

Eosinophilic Fasciitis

• Associated Malignancy: Hematologic malignancies.
• Features: Skin induration, myalgia, possible persistent eosinophilia.
• Treatment: Corticosteroids, methotrexate if steroid tapering is difficult.

Tumor-Induced Osteomalacia (TIO)

• Features: Bone pain, muscle weakness due to hypophosphatemia.
• Pathophysiology: High FGF23 from mesenchymal tumors.
• Resolution: Surgery to remove tumor often cures symptoms.

Cancer-Associated Myositis and Scleroderma

• Features: Paraneoplastic presentation with associated malignancies; specific autoantibodies are indicators of risk.

Malignancies Associated With Musculoskeletal Symptoms

• Bone pain in malignancies, particularly multiple myeloma and lymphomas, often presents to rheumatologists.
• Treatment-related symptoms due to cancer therapies (
• Aromatase Inhibitors: Commonly cause joint pain.
• Chemotherapy: Association with various inflammatory rheumatic manifestations.
• BCG Therapy: Can induce reactive arthritis.
• Radiation Therapy: Can lead to rheumatic symptoms confounding existing diseases.

Conclusion

• Awareness of paraneoplastic rheumatic manifestations can facilitate early cancer diagnosis. Successful cancer management usually results in symptom subsidence, although some symptoms may persist affecting quality of life. Understanding these mechanisms enhances management strategies for concurrent rheumatic diseases.