Association of Autoimmune Disorders and Lymphoma: A Population-Based Cohort Study

Background

Autoimmune disorders present as exaggerated responses to self antigens. The chronic inflammatory state, with its underlying immune overstimulation, is associated with development of a variety of Lymphoid malignancies. Furthermore, multiple studies have attempted to explore environmental factors, such as toxic and UV exposures, for a possible association with NHL, albeit with mixed results. In this article, we seek to further elucidate the relationship between a number of autoimmune disorders (Sjögren's syndrome, Rheumatoid Arthritis, Hashimoto Thyroiditis, Systemic Lupus Erythematosus, Type 1 Diabetes Mellitus) and Lymphoid malignancies in a population-based study of Texas residents.

Methods

We used publicly available, de-identified, and state-wide data to conduct a population-based cohort study of hospitalizations aged ≥ 18 years admitted to acute care hospitals in Texas during 2016-2022. The target population was identified using International Classification of Diseases, Tenth Revisions, Clinical modification codes for Mantle Cell Lymphoma, Small B-cell lymphoma, Chronic lymphocytic leukemia, Follicular lymphoma, Marginal zone lymphoma and diffuse large B-cell lymphoma selected from Clinical Classification Software Refined category NEO058: Non-Hodgkin lymphoma and C18x and C20 selected from Clinical Classification Software Refined category NEO015: Gastrointestinal cancers - colorectal. The exposure variable was diagnosis of lymphoma with hospitalizations diagnosed with only colon cancer used as the reference group. The response variable was diagnosis of the autoimmune disorders Sjogren's syndrome, Rheumatoid arthritis, Hashimoto thyroiditis, Systemic lupus erythematosus, or Type 1 diabetes mellitus. Three methods were used to measure the association of lymphoma and autoimmune disorders. Propensity score matching was the primary analysis approach with propensity adjusted multilevel logistic regression, and propensity score overlap weighting applied as alternative analysis procedures. Subgroup analyses included sex, age, and race/ethnicity. Results are reported as adjusted odds ratios and 95% confidence intervals (aOR [95% CI]).

Results

A total of 222,496 hospitalizations were included in the study of which 85,701 (38.5%) had a diagnosis of lymphoma and 136,795 (61.5%) had a diagnosis of colon cancer and no diagnosis of lymphoma. Propensity score matching resulted in 63,516 pairs of hospitalizations. Hospitalizations with lymphoma were older (62.6 % vs 49.7% aged ≥ 65 years), had lower Deyo comorbidity index (mean 3.54 SD [2.05] vs 5.49[3.22]), more often had COVID-19 (3.8% vs 0.4%), and more frequently were diagnosed with substance use disorders, (27.4% vs 11.3%); p < 0.0001 for all comparisons. Autoimmune disorder was more frequently diagnosed in hospitalizations with lymphoma (3.3% vs 1.9%). Four of the five autoimmune disorders were higher in the lymphoma group, rheumatoid arthritis (2.2% vs 1.2%), systemic lupus erythematous (0.5% vs 0.3%), Sjogren's syndrome (0.3% vs 0.1%), and Hashimoto thyroiditis (0.2% vs 0.1%); p ≤ 0.0010 for each comparison. Type 1 diabetes mellitus was not associated with lymphoma (0.3% vs 0.3% p = 0.6121). On adjusted analysis using propensity score matching, autoimmune disorders remained associated with lymphoma (aOR 1.75, [95% CI 1.63 to 1.87]). Similar results were found using the alternative analysis procedures and on subgroup analysis.

Conclusions

There is a significant association between four of the five autoimmune diseases and Lymphoid malignancy, especially Sjogren's syndrome, Rheumatoid Arthritis, and Hashimoto Thyroiditis, with the strongest association observed with Sjögren's syndrome. This is consistent with previous literature, reinforcing the relationship between autoimmune disorders and lymphoid malignancies. Furthermore, there seems to be negligible geographic or environmental contribution to variability in the relative prevalence of autoimmune disorders within this patient group.

No relevant conflicts of interest to declare.