The Association between Lymphedema and Autoimmunity: A Large Case Control Study
Stav Brown, Catherine Ly, Raghu Kataru, Michelle Coriddi, Andrea Barrio, Joseph Dayan, Babak J. Mehrara
Plastic and Reconstructive Surgery, Memorial Sloan Kettering Cancer Center, USA
Despite the emerging evidence highlighting the role of immune responses in the development of cancer related lymphedema, there is lack of data on the role of autoimmune reactions in the pathophysiology of lymphedema. The purpose of this large case control study was to investigate the association between a wide range of autoimmune diseases and lymphedema development after axillary lymph node dissection (ALND).
Patients who received ALND at a tertiary cancer center between 1995 and 2023 were included. Demographic data, chemotherapy and radiation history, lymphedema development after ALND, and history of preexisting autoimmune disorders were analyzed.
A total of 13,670 patients aged 49.0±10.2 with a mean follow-up time of 88.9±65 months were included. 1381 patients had one or more preexisting autoimmune disorders (10.1%) and lymphedema developed in 1056 patients (7.7%). Lymphedema development after ALND was significantly associated with one or more autoimmune diseases (OR 1.9, 95% CI 1.6-2.2, p<0.0001). The association was strongest for autoimmune disorders involving the skin (OR 2.4, 95% CI 1.5-3.7, p<0.0001), endocrine disorders (OR 2.0, 95% CI 1.6-2.5, p<0.0001) and rheumatic disorders (OR 1.5, 95% CI 1.1-2.0, p=0.006). Preexisting diagnoses of atopic dermatitis (OR 5.5, 95% CI 2.4-12.0, p<0.0001), diabetes (OR 2.2, 95% CI 1.7-2,8, p<0.0001), grave's disease (OR 1.9, 95% CI 1.1-2.9, p=0.009) and rheumatoid arthritis (OR 1.5, 95% CI 1.0-2.2, p=0.042) were highly predictive of lymphedema development following ALND. These findings remained stable in multivariable analyses after adjustment for age, gender, ethnicity, BMI, radiation and chemotherapy history.
This is the first and largest study to date to investigate the link between preexisting autoimmune conditions and lymphedema development. Our analysis demonstrated significant autoimmune comorbidity of patients with cancer-related lymphedema, suggesting that autoimmunity might play a role in the pathophysiology of lymphedema development after ALND.
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