Overview

Lymphocytosis (lim-foh-sigh-TOH-siss) is when there is an increase in lymphocyte count, a type of white blood cell, within the blood. Lymphocytosis is most notably linked to viral infections, as infections in the body induce an immune response and thus the increased production of white blood cells. However, it can also occur in response to certain bacterial infections or medical conditions such as blood cancers. There is a range of bacterial infections that often result in lymphocytosis, including Bordetella pertussis, Bartonella henselae, Mycobacterium tuberculosis, Brucella species and Treponema pallidum.¹

What are lymphocytes?

Lymphocytes are a type of white blood cell that can be further classified into B cells, T cells and natural killer (NK) cells. These cells all play a vital role in the body’s immune response. When the immune system encounters a threat, such as bacteria or any other foreign object, it stimulates the production of cells called antigen-presenting cells (APCs). 

These cells trigger adaptive immune responses and stimulate the quick proliferation of lymphocytes in the bloodstream to combat the danger. Consequently, the count of lymphocytes in the bloodstream rises. Recognising and differentiating the various bacterial infections leading to lymphocytosis is essential for determining the best treatment options.²

Bacterial infections that are known to cause lymphocytosis

Bordetella pertussis

Bordetella pertussis is the bacterium that causes whooping cough. The disease produces a toxin called pertussis toxin (PT) that disrupts lymphocyte communication in the body by inhibiting particular chemical signals that instruct the cells on when and where to move. In their monitoring roles, lymphocytes typically circulate between the blood, lymph nodes, and tissues.¹ As a result of the inhibition, lymphocytes are unable to reach areas of infection and assist in combating the bacteria, leading to their accumulation in the blood.³

Bartonella henselae

Bartonella henselae is the bacterium that is associated with cat scratch disease, an infection caused by a scratch or bite from an infected cat. It usually results in swollen lymph nodes, inflammation around the wound, fevers and tiredness. The infection sets off an immune response so powerful that it often results in lymphocytosis. To contain the infection and prevent it from spreading, the immune system activates particular lymphocyte types, such as T cells, that work directly to kill the infected cells. The lymphocytosis associated with cat scratch disease is usually mild and transient; it can still be a cause for concern. 

Mycobacterium tuberculosis

Mycobacterium tuberculosis is the bacterium responsible for Tuberculosis (also known as TB). TB is an infectious condition that primarily affects the lungs but can spread to other regions of the body. Lymphocytosis arises during the initial phases of infection because of extensive T-cell activation, serving as the primary defence against Mycobacterium. However, as TB progresses, chronic patients are commonly likely to experience a severe weakening of the immune response and lower lymphocyte counts (lymphopaenia) instead.⁶

Brucella species

The Brucella species of bacteria is zoonotic. It infects a range of species that come into contact with it, including cattle, dogs, goats, sheep and pigs, causing a disease called Brucellosis. Generally, people contract the disease by ingesting unpasteurised dairy products, directly interacting with infected animals or inhaling airborne bacteria present in animal living areas. Brucella has been known to survive within host cells for a prolonged time, which often results in sustained lymphocyte activation and accumulation.^7,8,9,10

Treponema pallidum

Treponema pallidum is the bacterium that causes syphilis. This is a sexually transmitted infection that, if left untreated, can result in organ damage. Although lymphocytosis is not a typical or distinctive symptom of syphilis, it can manifest during this infection and, when combined with other symptoms like rash and enlarged lymph nodes, may help confirm the diagnosis.¹¹

Diagnosis and clinical considerations

Following a patient consultation and blood tests, which have identified lymphocytosis, a meticulous and comprehensive clinical evaluation is necessary. The length of symptoms, recent travel, animal exposure, immunisation history, and new medication use are important components of the patient history. 

For instance, close contact with cats or a recent trip to an area where TB is prevalent may raise suspicions of the infectious conditions associated with lymphocytosis. Determining the cause can also be aided by the chronology and progression of symptoms, whether they are acute or chronic. Additionally, many healthcare professionals request laboratory diagnostic testing to help identify the severity of lymphocytosis as well as the specific bacterial species responsible for their increase. 

A healthcare professional may conduct a complete blood count (CBC) that measures the numbers of every type of white blood cell in a blood sample.¹² Subsequently, blood culture testing would most likely be done to grow and identify the bacteria present in the bloodstream.¹³ 

An alternative test is serological testing, which is used to test for specific antibodies that are released into the bloodstream following bacterial infection. This could help diagnose infectious conditions like cat scratch disease.^14,15 

Lastly, molecular testing like polymerase chain reaction (PCR) testing can be done to identify bacterial DNA; it is a rapid and effective method which has been used in syphilis and TB diagnosis.^16,17

In specific cases, supplementary imaging techniques such as computed tomography (CT) or X-ray scans may be an appropriate tool for diagnosing bacterial infections. For example, imaging tests are widely used in TB diagnosis as they permit healthcare professionals to see signs of infection typical of Mycobacterium tuberculosis.

Management of bacteria-induced lymphocytosis

The management of bacteria-induced lymphocytosis relies on treating the underlying cause of the infection. This means that once the exact bacterial species is identified through laboratory testing, healthcare professionals can start prescribing medication to treat the infection, as well as ultimately lower the lymphocyte count in the bloodstream. Once the infection is over, lymphocyte counts usually return to normal. Persistent lymphocytosis following antibiotic treatment may necessitate further testing to rule out underlying blood disorders.¹

Summary

Lymphocytosis is the term used when there is an increased number of lymphocytes, a type of white blood cell, in the blood. Lymphocytes are crucial for the immune response and include B cells, T cells, and natural killer (NK) cells. When the immune system detects infection, it produces antigen-presenting cells that spur the growth of lymphocytes, leading to higher lymphocyte counts in the blood. This condition is often associated with viral infections, but can also arise from certain bacterial infections or medical conditions like blood cancers. Various bacterial infections known to cause lymphocytosis include Bordetella pertussis, Bartonella henselae, Mycobacterium tuberculosis, Brucella species, and Treponema pallidum. 

Bordetella pertussis causes whooping cough, producing a toxin that disrupts lymphocyte communication, preventing them from reaching infection sites and causing their accumulation in the bloodstream. Bartonella henselae causes cat scratch disease, triggering a strong immune response that often leads to mild, temporary lymphocytosis. Mycobacterium tuberculosis causes tuberculosis, where lymphocytosis occurs in early infection but may decrease in advanced stages. Brucella species cause brucellosis, leading to prolonged lymphocyte activation. Treponema pallidum, which causes syphilis, may also cause lymphocytosis, but it is not a common symptom. Diagnosis of lymphocytosis involves thorough clinical evaluation and various tests, like complete blood counts and bacterial cultures. Treatment focuses on addressing the underlying infection, and once resolved, lymphocyte counts typically return to normal. Persistent lymphocytosis after antibiotic treatment may require further investigation for possible blood disorders.