| Proposed mechanism | Example(s) |
| Cancer secondary to rheumatic disease |
| Chronic inflammation and damage from rheumatic disease | - Sjögren's: Disease activity, severity, and duration predictive of non-Hodgkin lymphoma risk
- RA: Elevated ESR and CRP associated with increased cancer risk; long-term glucocorticoid therapy associated with lower lymphoma risk
- SSc: Pulmonary scar associated with lung cancer
|
| Cytotoxic or biologic therapies | - Cyclophosphamide: Higher cumulative doses associated with an increased risk of lymphoproliferative and bladder cancers
- Mycophenolate: Possible increase in nonmelanoma skin cancer and CNS lymphoma
- TNF inhibitors: An increased risk of nonmelanoma and possibly melanoma skin cancer
|
| Inability to clear oncogenic infections | - SLE: Risk higher for virus-associated cancers (eg, cervical, vaginal/vulvar, and anal cancers associated with HPV)
|
| Rheumatic disease secondary to cancer |
| Cancer-induced autoimmunity | - SSc: An increased risk of cancer at disease onset among patients with RNA polymerase III autoantibodies; genetic abnormalities of POLR3A in cancers associated with mutation-specific T-cell immune responses and crossreactive autoantibodies
- Dermatomyositis: Striking clustering of cancer diagnosis with disease onset; an increased risk of CAM in patients with unique autoantibodies (NXP-2 and TIF-1 gamma); clinical improvement in dermatomyositis with cancer therapy
|
| Immunotherapy or chemotherapy | - IL-2 therapy or immune checkpoint inhibitors: Inflammatory arthritis and other autoimmune phenomena have been reported
- Bleomycin and gemcitabine: Associated with skin sclerosis, development or exacerbation of the Raynaud phenomenon and ischemic digits
|
| Radiation therapy | - Localized scleroderma may develop in radiation port
|
| Shared etiology |
| Common inciting exposure | - Silica, solvents, organic chemicals, pesticides, smoking, infections, and hormonal state
|
| Shared genetic susceptibility | - Increased risk of Hodgkin lymphoma in patients with a personal or family history of multiple autoimmune conditions
|
