Do patients with secondary immunodeficiency (acquired immunodeficiency) have an increased risk for developing lymphoma or autoimmune diseases?

From the Guidelines

Patients with secondary immunodeficiency are at increased risk for both lymphoma and autoimmune diseases. This is because secondary immunodeficiencies, which result from external factors like medications, infections, or other medical conditions, can disrupt normal immune surveillance and regulation. For lymphoma risk, the impaired immune system fails to properly control proliferation of lymphocytes and may not effectively eliminate potentially malignant cells, particularly those infected with oncogenic viruses like Epstein-Barr virus, as seen in studies such as 1. Regarding autoimmune diseases, the dysregulation of immune responses in secondary immunodeficiency can paradoxically lead to autoimmunity through several mechanisms: impaired regulatory T cell function, persistent antigen stimulation, molecular mimicry from infections, and disruption of normal immune tolerance, as discussed in 1 and 1. The specific risk varies depending on the underlying cause of immunodeficiency, with certain conditions like HIV infection and immunosuppressive therapies carrying particularly high risks, as noted in 1. Some key points to consider include:

• The degree of immune impairment in patients with primary or secondary immunodeficiency is variable, with certain conditions like combined primary immunodeficiency disorder, cancer chemotherapy, and HIV infection with a CD4 T-lymphocyte count <200 cells/mm3 for adults and adolescents, being associated with high-level immunosuppression, as defined in 1.
• Regular monitoring for both malignancies and autoimmune manifestations is essential in managing patients with secondary immunodeficiency, as emphasized in 1.
• The management of patients with secondary immunodeficiency may involve vaccination, as outlined in 1, as well as other treatments aimed at preventing and managing complications. Overall, the increased risk of lymphoma and autoimmune diseases in patients with secondary immunodeficiency highlights the importance of careful monitoring and management of these patients, as supported by the evidence from 1, 1, and 1.

From the Research

Secondary Immunodeficiency and Risk of Lymphoma or Autoimmune Disease

• Patients with secondary immunodeficiency may be at increased risk for lymphoma or autoimmune disease, as their immune system is compromised due to various factors such as underlying conditions, medications, or infections 2, 3.
• The risk of hematological cancer, including lymphoma, is increased in patients with primary immunodeficiency, and this risk may also apply to secondary immunodeficiency 2, 4.
• Secondary immunodeficiencies can be caused by various factors, including malnutrition, metabolic disorders, use of immunosuppressive medications, chronic infections, malignancies, severe injuries, and exposure to adverse environmental conditions 3, 5.
• The use of biological agents, such as rituximab, can lead to persistent hypogammaglobulinemia, a type of secondary immunodeficiency, which may increase the risk of infections and other complications 2, 3.
• Lymphoproliferative disorders, including lymphoma, can occur in patients with primary or acquired immunodeficiencies, and the risk of these disorders may be increased in patients with secondary immunodeficiency 4, 6.
• The lymphomas that occur in immunodeficient patients are often driven by viruses, such as Epstein-Barr virus, and may have distinct clinical characteristics, such as a high frequency of extranodal disease 4, 6.