From the Guidelines
Elevated lymphocytes, known as lymphocytosis, are most commonly caused by viral infections, bacterial infections, certain chronic conditions, and other factors that trigger an immune response. The causes of elevated lymphocytes can be varied, including:
- Viral infections such as mononucleosis, cytomegalovirus, or hepatitis
- Bacterial infections like tuberculosis or pertussis
- Certain chronic conditions including some cancers (leukemia, lymphoma), autoimmune disorders (lupus, rheumatoid arthritis), and endocrine disorders (hyperthyroidism)
- Medications like antibiotics and anti-seizure drugs that can cause lymphocytosis as a side effect
- Stress, both physical and psychological, that can temporarily increase lymphocyte levels as part of the body's natural immune response 1. It is essential to evaluate the underlying cause of persistent lymphocytosis, especially if accompanied by symptoms like fever, fatigue, swollen lymph nodes, or unexplained weight loss, as recommended by the American Society of Clinical Oncology clinical practice guideline 1. The diagnostic work-up should include a history and physical examination, evaluation of nutritional state, spleen size, CBC with differential and reticulocyte counts, CXR for evaluation of presence of thymoma, and bacterial cultures and evaluation for infection (fungal, viral, bacterial, specifically CMV/HIV) 1. In the context of chronic lymphocytic leukemia (CLL), the clinical diagnosis requires an absolute lymphocytosis with a lower threshold of greater than 5,000 mature-appearing lymphocytes/µL in the peripheral blood, and the presence of certain phenotypic features such as CD5 antigen, monoclonal B-cell markers, and low-density surface immunoglobulin 1. The most critical step in managing elevated lymphocytes is to determine the underlying cause and develop an appropriate treatment plan, prioritizing the patient's morbidity, mortality, and quality of life.
From the Research
Causes of Elevated Lymphocytes
Elevated lymphocytes can be caused by various factors, including:
- Infections such as infectious mononucleosis, which is caused by the Epstein-Barr virus (EBV) 2, 3, 4, 5
- The EBV infection can lead to an increase in lymphocytes, particularly B-lymphocytes, as the virus infects and transforms these cells 2, 3
- Other factors such as inflammation, autoimmune disorders, and certain types of cancer can also cause elevated lymphocytes
Relationship Between Acyclovir and Lymphocytes
Acyclovir, an antiviral medication, has been shown to reduce the shedding of EBV in patients with infectious mononucleosis 2, 3, 5
- However, the effect of acyclovir on lymphocyte counts is not well established, and more research is needed to understand its impact on elevated lymphocytes
- Some studies suggest that acyclovir may have a beneficial effect on reducing the duration of fever and hospitalization in patients with EBV infection, but its effect on lymphocyte counts is not clear 4
Limitations of Current Research
The current research on the causes of elevated lymphocytes and the relationship between acyclovir and lymphocytes is limited to studies on EBV infection and infectious mononucleosis
- More research is needed to understand the effects of acyclovir on lymphocyte counts and to explore other potential causes of elevated lymphocytes
- The use of acyclovir in the treatment of herpes viruses, such as HSV-1 and HSV-2, is well established, but its effects on lymphocytes in these contexts are not well understood 6