What Is Lymphopenia?

Even though it may look like one, our blood is not just a liquid; it is a suspension of millions of cells. Cells of different types perform different functions- the red blood cells (RBCs) transport oxygen throughout your body, platelets help in clotting and much more. There are also the white blood cells (WBCs), which form the natural defence of your body- the immune system. Some of these WBCs are called lymphocytes. What happens if these lymphocytes are drastically reduced in number?

Lymphopenia or lymphocytopenia is a condition where the lymphocyte count is extremely low (1,500 cells per microlitre or lower in adults). This is usually the result of severe malnutrition or an underlying condition affecting the immune system. Lymphopenia is an indicator of a compromised immune system, and most of its symptoms relate to this decrease in immunity.

Lymphopenia is a condition that can stem from a variety of causes, and a lymphopenia diagnosis can lead a medical professional to discover further some of the more severe causes of the disease- including HIV/AIDS and lymphomas. Therefore, knowing the warning signs and what to watch out for is of utmost importance. Read on to know more below!

Overview

Lymphopenia, also known as lymphocytopenia, is a disorder where there is a marked reduction in the number of lymphocytes (white blood cells) in the blood. Lymphocytes are cells that result in immune system activity and help fight against infections and diseases. However, not all white blood cells are lymphocytes. The two main subclasses of white blood cells that are categorised as lymphocytes are T-lymphocytes and B-lymphocytes. T-lymphocytes, also known as T-cells, aid in the identification and killing of infected cells in the body. B-lymphocytes, also known as B-cells, help in what is known as an adaptive immune response (the immunity developed against a new pathogen). There are receptors on the cell surface of B-cells, which get released as substances commonly known as antibodies that fight against infection. A drastic reduction in the number of lymphocytes can result in an impaired immune system. This can make a seemingly benign infection turn life-threatening.¹

Causes of lymphopenia

Lymphopenia refers to a low lymphocyte count, so there can be a wide variety of causes affecting these white blood cells that can lead to a deficiency.

Two major categories of causes can lead to a low white blood cell count:

1. Acquired causes - as the word “acquired” suggests, a few medical conditions can result in lymphopenia.² A few conditions that can lead to lymphopenia are:
   • Malnutrition or protein deficiency (most common cause) 
   • HIV/AIDS or other viruses targeting the immune system, HIV in particular specifically targets T-cells  
   • Other autoimmune conditions like lupus or rheumatoid arthritis 
   • COVID-19 or other viral infections 
   • General bacterial and viral infections
   • Stress response 
   • Blood and bone marrow transplant treatments 

2. Inherited causes - certain genetically inherited disorders and conditions can lead to lymphopenia. These are most frequently immunodeficiency disorders as one of the mechanisms of these conditions is an attack on lymphocytes, reducing the lymphocyte count. A few inherited conditions leading to lymphopenia are:
   • Wiskott-Aldrich syndrome
   • Severe-combined immunodeficiency syndrome
   • WHIM syndrome
   • DiGeorge syndrome
   • Ataxia telangiectasia³  

Signs and symptoms of lymphopenia

The following are common symptoms associated with lymphopenia:

• Absent or shrunken tonsils or any other tonsil abnormality 
• Shrunken lymph nodes 
• Certain skin abnormalities (alopecia, eczema, frequent warts, jaundice, mouth sores or open sores on the skin surface² 
• Frequent infections and disease, an indicator of immunodeficiency associated with lymphopenia 
• Recurrent long-lasting diseases 
• Swollen lymph nodes⁴ 

Consult a general practitioner as soon as possible if you are facing any of these symptoms, as immunodeficiency-related conditions need prompt medical treatment to prevent long-term frequent infections.

Management and treatment for lymphopenia

As lymphopenia can have a wide variety of underlying causes ranging from malnutrition to HIV/AIDS, management and treatment are dependent upon the cause. Mild lymphopenia arising from deficiencies in diet and stress usually resolves itself through consuming a properly balanced diet and without the need for treatment.⁵ As a low lymphocyte count leads to an added severity of viral and bacterial infections, these infections are treated to avoid complications. If the cause of lymphopenia is an autoimmune condition like HIV/AIDS, lupus, or Wiskott-Aldrich syndrome, amongst others, treatment of the condition can lead to an improvement in the low lymphocyte count. Immunoglobulin infusions may be used to strengthen the immune system in a patient with lymphopenia.⁶ Long-term treatment options are being researched currently, for example, bone marrow stem cell transplants.

Diagnosis

A lymphopenia diagnosis is dependent upon an analysis of family history towards various genetic disorders, physical exams, and other screenings. The following procedures are usually carried out to arrive at a diagnosis:

1. Medical history and physical symptoms

A general practitioner will first look for fever and physical symptoms like swollen spleen or lymph nodes. They may also question you regarding your medical history to consider any autoimmune condition, blood transfusions, or any other courses of infection. 

2. Complete blood count 

This is a test that provides counts per unit volume for the various types of cells suspended in the blood. This includes red blood cells, neutrophils, basophils, and lymphocytes. Low levels of white blood cells (specifically B- and T-cells) indicate lymphopenia.

Normal lymphocyte levels in a healthy adult are 1,000-4,800 per microlitre of blood. A lymphopenia diagnosis occurs at levels of less than 1,500 lymphocytes per microlitre.

3. Flow cytometry

This is used to analyse blood for different types of lymphocytes and their frequency (B- and T-cells and subtypes of T-cells like helper T-cells and cytotoxic T-cells). This is used to gain insight into the cause of lymphopenia.

4. Immunoglobulin tests

B-cells have molecules on their surface called B-cell receptors. When a virus or other pathogen invades the body, these receptors are shed off and turn into molecules we know as antibodies that neutralise these viruses. Some of these antibodies belong to a class called immunoglobulins. Their levels in the blood give a good indication of the extent to which B-cells have been affected by the underlying cause.⁷

FAQs

How can I prevent lymphopenia?

Lymphopenia has a high chance of developing if you have an autoimmune condition or any comorbidities that result in reduced efficacy of the immune system. However, it may be prevented in otherwise healthy individuals by consuming a healthy, balanced diet. People who have HIV/AIDS or other conditions that can lead to lymphopenia can also benefit from a nutritious diet.

How common is lymphopenia?

Statistics among the general population are not well documented. However, almost 80% of adults and 50% of children with some form of AIDS also have lymphopenia.⁸ Since the SARS-CoV-2 pandemic, it was observed that around 6.9% of COVID-19 patients had lymphopenia at some point.⁹

Who is at risk of lymphopenia?

Anyone with autoimmune conditions like HIV/AIDS, lupus, rheumatoid arthritis, miliary tuberculosis, cancers like leukaemia, or anyone generally with malnutrition or poor diet is at an extremely high risk of lymphopenia.

What can I expect if I have lymphopenia?

Symptoms like fatigue, skin abnormalities, and swollen lymph nodes can be expected. Abnormalities in the tonsils are also reported. Lymphopenia treatment depends on the underlying cause, so an investigation into the said cause by a general practitioner is an optimal course of treatment.

When should I see a doctor?

If you continuously have long-term infections, tonsil and skin abnormalities, fatigue, cold sores, or any other symptoms of reduced immunity, contact a general practitioner as soon as possible.

Summary

Lymphopenia is a condition where the lymphocyte count in the blood is low. Your blood is a suspension of many different cell types performing diverse functions, and lymphocytes are one of them. These are the cells involved in the immune system. There are two major types of lymphocytes: B-cells, which produce antibodies against viruses and other pathogens (also known as humoral immunity), and T-cells, which help in killing infected cells and activating B-cells to produce antibodies against a pathogen. 

Lymphopenia often occurs as a symptom of an autoimmune condition like HIV/AIDS or lupus. It can also occur as a side effect of malnutrition. Generally, in adults, a lymphocyte count of less than 1,500 cells per microlitre is considered lymphopenic. It is diagnosed via total blood cell count, and other tests like immunoglobulin level analysis are carried out to gain insight into the underlying cause. Symptoms range from fatigue, shrunken tonsils, and skin conditions to long-term frequent infections. Treatments are often carried out based on the underlying cause. Immunoglobulin infusions are carried out to compensate for the loss of antibodies due to fewer B-cells. New treatments like bone marrow stem cell transfers are being researched to offer a long-term solution for those with lifelong conditions resulting in lymphopenia.