Non-Hodgkin Lymphoma and Autoimmune Diseases

The exact cause of non-Hodgkin lymphoma (NHL) is not fully understood. Several risk factors, including autoimmune disease, have been identified that may increase the likelihood of developing NHL. While the link between autoimmune disease and NHL has been well established, exactly how or why they are linked is an area of ongoing research. 

Can Autoimmune Diseases Be Mistaken for Lymphoma?

There is some overlap between the symptoms of autoimmune disease and NHL. The majority of autoimmune diseases have the potential to cause lymph node swelling, which is also one of the main symptoms of NHL. In particular, rheumatoid arthritis, systemic lupus erythematosus, and Sjögren’s syndrome are associated with swollen lymph nodes. A lymph node biopsy may be used to confirm whether the swelling is a result of NHL. 

Can Autoimmune Diseases Cause Lymphoma?

Several autoimmune diseases are considered risk factors for NHL. One analysis of almost 30,000 patients with NHL demonstrated an association between autoimmune disease and subtypes of NHL, including:

• Sjögren’s syndrome
• Systemic lupus erythematosus
• Hemolytic anemia
• Celiac disease
• Psoriasis
• Rheumatoid arthritis

Patients with Sjögren’s syndrome were 6.6 times more likely to develop NHL than those without. Sjögren’s syndrome was specifically associated with marginal zone lymphoma, diffuse large B-cell lymphoma, and follicular lymphoma. Sjögren’s syndrome had a very strong association with parotid gland marginal zone lymphoma, with patients with Sjögren’s syndrome 1000 times more likely to develop parotid gland marginal zone lymphoma than those without. 

Patients with systemic lupus erythematosus were 2.7 times more likely to develop NHL, with a particular association with marginal zone lymphoma and diffuse large B-cell lymphoma. 

Patients with hemolytic anemia were 2.6 times more likely to develop NHL, especially diffuse large B-cell lymphoma. 

Celiac disease was not associated with NHL overall, but patients diagnosed with celiac disease over the age of 32 did have an increased risk. Patients with celiac disease had a substantially higher risk of developing enteropathy-associated T-cell lymphoma and anaplastic large-cell lymphoma. Patients with celiac disease were also 30 times more likely to develop small intestinal NHL. 

Psoriasis was not associated with NHL overall, but there was an increased risk of developing T-cell NHL, particularly anaplastic large-cell lymphoma. 

Rheumatoid arthritis was not associated with an increased risk of NHL overall, but the results did vary. Patients who received treatment for rheumatoid arthritis with corticosteroids or immunosuppressants did have an increased risk of NHL. 

How Does Autoimmune Diseases Cause Lymphoma?

While the exact reason autoimmune disease may cause NHL is unknown, several factors may explain the connection.

The immune system's reaction to autoimmune disease may cause long-term inflammation and increased activation of B-cells and T-cells. Treatment for autoimmune diseases, such as immunosuppressants, may also contribute to the increased risk of NHL. Shared environmental risk factors for autoimmune disease and NHL may also play a role. An overlap in genetic mutations associated with autoimmune disease and NHL has also been suggested as a potential mechanism, although one study found this association to be weak. 

Does Autoimmune Diseases Affect Prognosis in Patients with Lymphoma?

An analysis of patients treated at the Mayo Clinic found that a history of autoimmune disease did not affect the outcomes of patients with lymphoma. However, autoimmune diseases involving B-cells (such as rheumatoid arthritis, Sjögren’s syndrome, or systemic lupus erythematosus), particularly rheumatoid arthritis, were associated with a worse prognosis in patients with mantle cell lymphoma and Hodgkin lymphoma. 

Key takeaways

• Some symptoms of autoimmune disease and NHL overlap, particularly swollen lymph nodes.
• Several autoimmune diseases have been linked to an increased risk of developing NHL.
• The exact way in which autoimmune diseases contribute to the development of NHL is not fully understood. 

Join the HealhTree community to learn more about your disease and attend our next free webinar!

EXPLORE HEALTHTREE EDUCATION

Sources: 

• Autoimmune disorders and risk of non-Hodgkin lymphoma subtypes: a pooled analysis within the InterLymph Consortium
• Clinical mimics of lymphoma
• Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes
• History of autoimmune conditions and lymphoma prognosis