A 21-year-old woman developed the photosensitive facial rash depicted along with polyarticular arthralgias. Laboratory investigation revealed anemia, leukopenia, a positive antinuclear antibody test (1:1024), and the presence of anti-double-stranded DNA antibodies. A skin biopsy shows dense lymphocytic infiltrate at the dermo-epidermal junction and around hair follicles. She smokes one pack of cigarettes per day and drinks socially. Family and past medical histories are non-contributory.
C. Follicular thyroid carcinoma
This patient demonstrates the classic malar eruption associated with systemic lupus erythematosus (SLE), and her laboratory studies support that diagnosis. The association between neoplasia and lupus has been investigated for decades using differing methodologies. Nonetheless, recent reviews and meta-analyses present convincing aggregate evidence that such an association does, indeed, exist. The relative risk of cancer in a Swedish lupus cohort of over 5000 was 1.25 times that in the general population. A larger (N = 9547) multinational SLE cohort study demonstrated a 1.15 relative risk (95% CI 1.05-1.27) of cancer. While the foregoing risk ratios appear to be modest, when individual types of cancer are investigated, the relative risk increases dramatically. Specifically, SLE is associated with a considerably increased incidence of non-Hodgkin lymphoma (NHL), bronchogenic adenocarcinoma, and possibly cervical dysplasia (CIN).[1,4,5] In the multinational cohort study, for example, the risk ratio for NHL was 3.64 (95% CI of 2.63-4.93), and the risk ratio for lung cancer was 1.37 (95% CI 1.05-1.76). However, among SLE patients who smoke, the risk of lung cancer is four times greater, and the ultimate prognosis is much worse, underscoring the urgent necessity of smoking cessation in patients with SLE. The data from the multinational study also revealed greater than twice the overall risk of mortality due to cancer in SLE patients compared with the general population.
One might also consider the converse situation; that is, among patients with certain types of cancer, is there an increased incidence of SLE? In a population-based case-control study, the frequency of SLE among NHL patients compared with matched cancer-free controls was found to be 4.6 times greater. This study and others have indicated that among SLE patients, NHL often carries a poor prognosis because it frequently presents with extra-nodal involvement.
A final study worth mentioning addressed the concurrence of cervical dysplasia with SLE. A group of women with SLE and normal baseline cervical cytology were followed for three years. The incidence of high-grade CIN during that time period was 9.8%, significantly higher than expected. Exposure to cyclophosphamide was felt to be responsible, although other studies have shown the presence of oncogenic HPV in cervical specimens obtained from patients with SLE regardless of the type/duration of therapy.
The most critical question from a clinical perspective—the mechanism of an SLE-cancer association—is largely unanswered, and the relative importance of the disease state compared to chronic exposure to immunosuppressive therapy remains elusive. However, in most cases, the potential for adequate SLE control and/or prevention of important long-term sequelae justify immunosuppressive therapy, far outweighing the small absolute risk of facilitating cancer development.
1. Kiss E, Kovacs L, Szodoray P. Malignancies in systemic lupus erythematosus. Autoimmun Rev. 2010;9:195-199.
2. Bjornadal L, Lofstrom B, Yin L, et al. Increased cancer incidence in a Swedish cohort of patients with systemic lupus erythematosus. Scand J Rheumatol. 2002;31:66-71.
3. Bernatsky S, Boivin JF, Joseph L, et al. An international cohort study of cancer in systemic lupus erythematosus. Arthritis Rheum. 2005;52:1481-1490.
4. Gayed M, Bernatsky S, Ramsey-Goldman R, et al. Lupus and cancer. Lupus. 2009;18:479-485.
5. Bernatsky S, Ramsey-Goldman R, Clarke A. Malignancy in systemic lupus erythematosus: What have we learned? Best Prac Res Clin Rheumatol. 2009;23:539-547.
6. Bin J, Bernatsky S, Gordon C, et al. Lung cancer in systemic lupus erythematosus. Lung Cancer. 2007;56:303-306.
7. Bernatsky S, Boivin JF, Manzi S, et al. Mortality in systemic lupus erythematosus. Arthritis Rheum. 2006;54:2550-2557.
8. Smedby KE, Hjalgrim H, Askling J, et al. Autoimmune and chronic inflammatory disorders and the risk of non-Hodgkin lymphoma by subtype. J Natl Cancer Inst. 2006;98:51-60.
9. Ognenovski VM, Marder W, Somers EC, et al. Increased incidence of cervical intraepithelial neoplasia in women with systemic lupus erythematosus treated with intravenous cyclophosphamide. J Rheumatol. 2004;31:1763-1767.