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A review on SLE and malignancy

https://doi.org/10.1016/j.berh.2017.09.013Get rights and content

Abstract

Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune disease characterized by autoantibody production, complement activation, and immune complex deposition. It predominantly affects young and middle-aged women. While improvements in the diagnosis and treatment of SLE have altered prognosis, morbidity and mortality rates remain higher than the general population. In addition to renal injury, cardiovascular disease, and infection, malignancy is known to be a significant cause of death in this population. There is increasing evidence to suggest that patients with SLE have a slightly higher overall risk of malignancy. The risk of malignancy in SLE is of considerable interest because the immune and genetic pathways underlying the pathogenesis of SLE and the immunosuppressant drugs (ISDs) used in its management may mediate this altered risk. Our current understanding of these and other risk factors and the implications for treating SLE and screening for malignancy is still evolving.

This review summarizes the association between SLE and malignancy. The first section discusses the risk of overall and site-specific malignancies in both adult- and pediatric-onset SLE. Next, we evaluate the risk factors and possible mechanisms underlying the link between malignancy and SLE, including the use of ISDs, presence of certain SLE-related autoantibodies, chronic immune dysregulation, environmental factors, and shared genetic susceptibility. Finally, we review guidelines regarding cancer screening and vaccination for human papilloma virus.

Section snippets

Overall risk of malignancy

Over the last four decades, there have been numerous studies examining the risk of malignancy in adult patients with systemic lupus erythematosus (SLE) compared to a matched general population. These studies are based either on observational clinical cohorts [1] or cohorts identified through administrative data such as hospital discharge [2] and national health insurance databases [3]; they are summarized in Table 1, and additional details are provided in Supplementary Table 1. In most of these

Immunosuppressive therapy and SLE disease activity

It remains unclear whether ISDs influence susceptibility to malignancy in patients with SLE. Mechanistically, ISDs may theoretically lead to the development of cancer by causing direct mutagenesis and cytotoxicity and by increasing susceptibility to or decreasing clearance of oncogenic viruses. The evidence on the risk of overall and site-specific malignancies, notably hematological and cervical neoplasia, with ISD exposure is summarized in Table 3.

As the use of ISDs is highly correlated with

Malignancy screening and HPV vaccination in SLE

Tessier-Cloutier et al. [110] recently reviewed the evidence regarding malignancy screening in SLE. Of the 25 research articles that suggested some form of screening strategy, most recommendations were rudimentary and based on cancer incidence data from observational cohort studies or a case–control design and none compared the value of alternative screening strategies. Eleven of these 25 studies promoted following the general population cancer screening guidelines, while the remaining 14

Summary

There is increasing evidence supporting the association between malignancy and adult-onset SLE. There is an increased risk for malignancy overall as well as for lung, liver, head and neck, thyroid, vulvar/vaginal, and anal malignancies and cervical dysplasia; a substantially increased risk for hematologic malignancies, particularly NHL, has been consistently observed. In contrast, a decreased risk of hormone-sensitive cancers such as breast and prostate has also been reported. Little is known

Conflict of interest

Dr. Clarke has received consulting fees from AstraZeneca/MedImmune and Exagen Diagnostics (less than $10,000).

Dr. Ramsey-Goldman has received consulting fees from Seattle Genetics, AstraZeneca, and Eli Lilly (less than $10,000).

Acknowledgments

Grant support: Dr. Clarke holds The Arthritis Society Research Chair in Rheumatic Diseases at the University of Calgary.

Dr. Ramsey-Goldman's work was supported by the NIH (grants 5UL1TR001422-02 formerly 8UL1TR000150 and UL-1RR-025741, K24-AR-02318, and P60AR064464 formerly P60-AR-48098).

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