Lymphocytosis: What it is, Causes, Signs, Symptoms & Treatment

What causes lymphocytosis?

Lymphocytosis is an elevation of the number of lymphocytes (one of the white blood cells) in the blood. Lymphocytes play a critical role in the immune system and consist of T cells, B cells, and natural killer (NK) cells.

Causes of Lymphocytosis

Lymphocytosis can be categorized as either:

• Reactive (secondary) – secondary to infections or other non-cancerous causes
• Clonal (primary) – secondary to cancers of the blood or disorders of the bone marrow

Infections (Most frequent cause)

Viral Infections:

• Epstein-Barr virus (EBV) – Infectious mononucleosis
• Cytomegalovirus (CMV)
• Hepatitis viruses
• HIV (early stages)
• Varicella-zoster virus
• Mumps, measles, rubella

Bacterial Infections:

• Pertussis (whooping cough)
• Tuberculosis
• Brucellosis

Parasitic Infections:

• Toxoplasmosis
• Malaria

Chronic Inflammatory Conditions

• Autoimmune diseases (e.g., rheumatoid arthritis, Graves' disease)
• Inflammatory bowel disease

Hematologic Malignancies (Clonal Lymphocytosis)

• Chronic lymphocytic leukemia (CLL) – most common adult leukemia
• Acute lymphoblastic leukemia (ALL) – more prevalent in children
• Lymphomas (particularly those spilling into the blood)
• Hairy cell leukemia

Stress-Related or Physiologic Causes

• Acute physical/emotional stress
• Post-surgery or trauma
• After intense exercise

Smoking

• Persistent lymphocytosis is commonly found in chronic smokers.

Drug responses

• Lymphocytosis is sometimes caused by drugs (e.g., phenytoin).

Post-splenectomy

• Spleen removal can result in mild persistent lymphocytosis.

Lymphocytosis symptoms

If due to a Viral or Bacterial Infection

• Fever
• Fatigue
• Sore throat
• Swollen lymph nodes (especially in the neck)
• Runny nose or cough
• Muscle aches
• Enlarged spleen or liver (e.g., in EBV infections)

If due to Hematologic Cancer (like CLL or ALL)

• Persistent fatigue
• Unexplained weight loss
• Night sweats
• Fever without infection
• Painless swollen lymph nodes
• Easy bruising or bleeding
• Frequent infections
• Bone pain (especially in acute leukemia)

If due to Autoimmune Disease

• Joint pain or swelling
• Rashes
• Dry eyes or mouth
• General inflammation signs

Is lymphocytosis cancer?

Lymphocytosis is not necessarily cancer, but cancer can cause it in certain situations.

When Lymphocytosis is not Cancer:

In most individuals, particularly children and young adults, lymphocytosis is reactive — that is, it's due to the body's normal reaction to:

• Viral infections (such as Epstein-Barr virus, influenza, COVID-19)
• Bacterial infections (such as pertussis, tuberculosis)
• Inflammatory or autoimmune conditions
• Stress or smoking
• This type of lymphocytosis is temporary and typically clears once the underlying condition is treated or resolves.

When Lymphocytosis may be a Sign of Cancer:

Lymphocytosis may be a manifestation of blood cancers that include lymphocytes, namely:

• Chronic Lymphocytic Leukemia (CLL)
• Most often in adults aged 60 and above
• Causes chronic high levels of lymphocytes for months
• Often with no initial symptoms, or with fatigue, enlarged lymph nodes, or infections

Acute Lymphoblastic Leukemia (ALL)

• More common in children
• Rapid onset with extremely elevated white cell counts
• Symptoms: tiredness, bruising, pyrexia, bone ache

Other Lymphoid Cancers

• Some lymphomas can present with lymphocytosis when malignant lymphocytes leak into the blood

Red Flags That Suggest Cancer

• Lymphocytosis that persists longer than 2 months
• Extremely elevated lymphocyte level (most often > 5,000–10,000 cells/μL)
• Presence of abnormal (atypical or immature-appearing) lymphocytes in the blood

Association with:

• Night sweats
• Weight loss
• Unexplained fever
• Enlarged lymph nodes or spleen

Treatment for lymphocytosis

Treatment for lymphocytosis relies solely on its cause. Lymphocytosis is not a disease but a symptom that the immune system is responding to something — an infection, inflammation, or in some cases a cancer.

If Due to an Infection (Most Common Cause)

• No treatment for the lymphocytosis itself
• The body typically normalizes lymphocyte levels after an infection resolves.

Viral Infections (e.g., EBV, CMV, influenza):

• Rest, hydration, control of fever
• No antiviral medications unless severe (e.g., HIV)

Bacterial Infections (e.g., pertussis, tuberculosis):

• Antibiotics as indicated
• Lymphocyte count typically returns to normal in weeks following resolution of infection.

If Due to Hematologic Cancer (e.g., CLL, ALL, lymphoma)

• Clonal lymphocytosis requires targeted therapy

Chronic Lymphocytic Leukemia (CLL):

• Typically monitored (watchful waiting) if asymptomatic

Treatment options (if required):

• Targeted therapies (e.g., ibrutinib, venetoclax)
• Immunotherapy
• Chemotherapy (less frequently now)

Acute Lymphoblastic Leukemia (ALL):

• Requires prompt treatment
• Chemotherapy
• Stem cell transplant in high-risk

Lymphoma-associated lymphocytosis:

• Managed according to lymphoma type and stage

If Due to Autoimmune Disease or Chronic Inflammation

• Treat the underlying autoimmune disease (e.g., lupus, rheumatoid arthritis)
• Corticosteroids
• Immunosuppressants

If Due to Physiologic or Temporary Causes

Stress-associated or smoking-associated lymphocytosis:

• Treatment not necessary
• Will resolve by stress management or smoking cessation

Post-splenectomy lymphocytosis:

• Mild, chronic lymphocytosis is normal
• No treatment necessary

Signs of lymphocytosis in adults

Viral Infection–Related Lymphocytosis

• Fatigue or malaise
• Fever
• Sore throat
• Swollen lymph nodes (especially in the neck)
• Runny nose, cough
• Enlarged spleen or liver (especially with EBV)

Bacterial Infection (e.g., Pertussis, TB)

• Persistent cough (often whooping-type in pertussis)
• Fever and chills
• Night sweats
• Weight loss (common in tuberculosis)

Hematologic Cancers (e.g., CLL, ALL, Lymphoma)

These cancers can cause persistent or unexplained lymphocytosis, often with systemic symptoms:

Red Flag Symptoms in Adults:

• Unexplained weight loss
• Persistent fatigue
• Night sweats
• Fever without infection
• Painless, swollen lymph nodes (neck, armpits, groin)
• Frequent infections
• Enlarged spleen or liver
• Bruising or bleeding easily (especially in leukemia)

Autoimmune or Inflammatory Conditions

• Joint pain or swelling
• Skin rashes
• Mouth ulcers
• Dry eyes/mouth (e.g., in Sjögren's syndrome)
• Generalized inflammation signs

Other Signs (Less Common Causes)

• Post-splenectomy: mild persistent lymphocytosis without symptoms
• Stress or Smoking: usually asymptomatic and found incidentally

Lymphocytosis in children causes

Lymphocytosis in children — increased numbers of lymphocytes in the blood — is normal and harmless, particularly when caused by infections. It does, however, on occasion, signal more severe conditions such as leukemia.

Common Causes:

Viral Infections (most common cause)

Children's immune systems tend to react vigorously to viruses with elevated lymphocytes.

Examples:

• Epstein-Barr virus (EBV) – mononucleosis
• Cytomegalovirus (CMV)
• Adenovirus
• Measles
• Mumps
• Rubella
• Influenza
• Hepatitis viruses
• COVID-19

Bacterial Infections (less common)

Some bacterial infections, especially chronic or atypical infections, are responsible for causing lymphocytosis.

Examples:

• Pertussis (whooping cough) – classically associated with significant lymphocytosis
• Tuberculosis (TB)

Hematologic Malignancies

Recurrent or extremely high lymphocyte counts may be suspicious for childhood leukemia.

Examples:

• Acute lymphoblastic leukemia (ALL) – most common childhood cancer
• Chronic lymphocytic leukemia (CLL) – unusual in children
• Consider fatigue, bruising, infections, weight loss, or swollen lymph nodes.

Autoimmune or Inflammatory Conditions

Less common in children, but could occur.

Examples:

• Juvenile idiopathic arthritis
• Lupus (SLE)
• Sarcoidosis

Other Causes

• Post-splenectomy (following spleen removal)
• Stress response (physical/emotional stress)
• Smoking exposure (in teens or older children)

Lymphocytosis and viral infection

Lymphocytosis — a rise in the number of lymphocytes (a form of white blood cell) in the blood — is most often caused by viral infections, particularly among children and young adults. It's typically a normal reaction to infection and will often clear up once the infection has passed.

Why Do Viral Infections Cause Lymphocytosis?

• Lymphocytes (predominantly T cells, B cells, and NK cells) are the body's first line of immune defense against viruses.
• Once a virus enters the body, it triggers both the bone marrow and lymphoid tissues to make and release additional lymphocytes into the circulatory system.
• This can result in reactive (or benign) lymphocytosis.

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