Overview  

Monocytes are one type of blood cells. Their count can be elevated, a state known as monocytosis, in various conditions ranging from physiological, infectious, cancerous, endocrine and inflammatory conditions. Understanding the differential diagnosis allows the physician to identify the cause and the most suitable treatment plan. This article provides a comprehensive overview of the various causes of monocytosis.  

What is monocytosis? 

The monocytes

Produced from the bone marrow, monocytes are a type of white blood cells responsible for the production of other kinds of blood cells. They function as a part of the immune system, helping to protect the body from foreign microbial invasion (infection) and remove dead cells. 

When an external substance enters the body, a signal is transmitted into the bone marrow causing the monocytes to enter the bloodstream and migrate to the target area where they help ingest microbes, toxic materials and damaged cells. Moreover, monocytes recruit more cells to further increase the scale of the inflammation which means more destruction of the disruptive agent. Monocytes can also be found in clusters in many organ tissues like the brain, liver and bones.¹ ​

Monocytosis  

Monocytosis is defined as a phenomenon where the count of monocytes is more than 1000 cells per microliter of blood (normal value is between 200 and 800) or when monocytes constitute more than 10% of the total white blood cell count.² ​ 

Elevated monocyte count is detected in blood analysis when a test sample is taken for any reason. It is non-serious in most of the cases; however, it can also indicate a more sinister underlying cause especially if this elevation is prolonged or unexplained.¹ 

Physiological causes 

Some causes of monocytosis are physiological, resulting in the body responding to events by elevating the monocyte count. Examples of such events are: 

Stress 

Psychological conditions like depression, anxiety and other stressful disorders, either for short or prolonged periods, can lead to significant changes in the body’s immune system, including a rise in monocyte count. This results from the action of stress hormones like adrenaline and cortisol.³ 

Post-splenectomy

The spleen is a major organ of the immune system responsible for the elimination of dead and dysfunctional blood cells as well as microbes. Surgical removal of the spleen, for any reason, results in monocytosis to compensate for its function.⁴ ​

Post-infection 

After the resolution of any acute infection, there is usually a transient increase of monocytes in the blood to aid in the removal of dead organisms, blood cells, and debris.² ​  

Infection  

An infectious disease is an inflammatory condition caused by infectious agents, such as bacteria, viruses, parasites and fungi, entering the body. Monocytes migrate to the area of entry of the invading microbe to contain the infection and kill the microorganisms.  

Bacterial infections 

Certain chronic bacterial infections are known to cause monocytosis. They cause a state of prolonged immune response leading to elevated monocyte count. Examples are: 

• Tuberculosis 
• Brucellosis  
• Typhoid fever 
• Syphilis 

Viral infections 

Monocytosis can also be evident in some viral diseases like: 

• Infectious mononucleosis (glandular fever) 
• Cytomegalovirus infection 
• Covid-19 

Parasitic infections  

Parasitic invasion can also induce a response of raised monocyte count to regulate the immune response and eliminate the organisms. They include: 

• Malaria 
• Leishmaniasis 
• Toxoplasmosis 
• Trypanosomiasis (sleeping sickness)

Fungal infections 

Yeast and moulds infection that results in monocytosis are: 

• Aspergillosis 
• Cryptococcosis^2,5 ​ 

Malignant conditions 

Monocytosis can be an early indicator when assessing an individual for cancerous blood disorders. The doctor will suspect a malignant cause for monocytosis in cases of persistent elevation of monocyte count or when all other benign causes have been excluded. Such conditions include: 

Leukaemia 

Leukaemia is one of the cancerous blood diseases in which there is rapid uncontrolled overgrowth of abnormal white blood cells. Those cells have defective function and structure in most cases and cause symptoms like fatigue, pallor (state of being pale), recurrent infections and bleeding tendency. Types of leukaemia which are characterised by marked monocytosis are: 

• Acute myeloid leukaemia with monocytic differentiation 
• Chronic myelomonocytic leukaemia 

Lymphoma  

Lymphoma is another type of blood-related malignancy. It affects the lymphatic system, which is part of the body’s defence system, and has two types: Hodgkin and non-Hodgkin lymphoma. Individuals with lymphoma are expected to show higher monocyte numbers in blood samples.⁶ 

Autoimmune conditions 

The body’s normal immune response is against harmful invading organisms, however, in autoimmune disease the body mistakenly attacks its own cells. Different organs are targeted in each disease such as the joints, kidneys, lungs and pancreas.  

Autoimmune diseases associated with monocytosis include: 

• Rheumatoid arthritis
• Inflammatory bowel disease
• Systemic lupus erythematosus

Rheumatoid arthritis 

Rheumatoid arthritis is a chronic condition in which there is inflammation and destruction of the joints resulting in swelling, pain and limited movement, particularly in the small joints of the hands and feet. Monocytes play an important role in the inflammatory process in rheumatoid arthritis therefore their count is usually raised.⁷ ​

Inflammatory bowel disease (IBS) 

In IBS, the inflammation involves the small and large bowel leading to abdominal pain and diarrhoea, which can be mixed with blood. It encompasses two conditions: Crohn's disease and Ulcerative colitis.  

Monocytosis is not only evident in IBS but it can also predict the severity and extent of the disease; the higher the monocyte count, the worse the outcome.⁸ ​

Systemic lupus erythematosus (SLE) 

An additional chronic autoinflammatory disease is SLE, it can affect any organ in the body although it mainly affects the kidneys, joints and the skin. Monocytosis reflects the exaggerated immune response found in SLE.⁷  ​

Drug-induced monocytosis 

Medications can also cause monocytosis as a side effect. For example:

• Corticosteroids (steroids): anti-inflammatory drugs 
• Ziprasidone: an antipsychotic medication used to treat several mental health conditions² ​

Miscellaneous   

Other medical conditions associated with monocytosis include:

• Bone marrow recovery: chemotherapy is a well-known cause of bone marrow suppression, after stopping the treatment there is a reactive rise in blood cells including monocytes. 
• Myocardial infarction (heart attack)  
• Exercise²

How can doctors identify the cause of monocytosis? 

Doctors usually follow the steps below when a patient's test result shows an abnormal increase in monocyte figures.  

Confirming monocytosis 

The first step when evaluating monocytosis is to confirm its presence. This is done by taking blood samples for analysis of:

• Count monocytes > 1000 cells/microliter or > 10% of total white blood cell count. 
• Morphology: looking at the structure and shape of the different blood cells. This can help in distinguishing malignant from benign causes as abnormal monocytes raise the suspicion of malignancy. 
• Other blood components: like red blood cells, platelets and microorganisms. 

History and clinical examination 

The doctor will perform a thorough investigation of the possible causes by asking the patient about the symptoms and past history information relevant to each condition like the duration, presence of fever, other coexisting conditions, travel history, family history and medications. 

The history will guide the physical examination, searching for clues like signs of infections, autoimmune diseases and malignancies. 

Many doctors reach a diagnosis by this step and either prescribe medications or reassure their patient if the cause is found to be benign and self-limiting. However, if no definitive diagnosis has been made, the patient doesn’t recover or if the monocytosis remains for a prolonged period, the doctor may conduct further tests to rule out more serious illnesses. 

Further tests 

• Bone marrow examination: a biopsy is taken from the site of monocyte production within the bones. It is able to detect a wide range of conditions like leukaemia, lymphoma, infections, and drug toxicity. 
• Monocyte population assessment: tests such as flow cytometry and immunohistochemistry are performed to evaluate which type of monocyte is causing the problem.
• Disease-related investigations:  imaging, autoimmune screens, and genetic testing are conducted when a certain disease is suspected.⁹ ​

Summary 

Monocytosis, a condition of elevated monocyte count in the blood, is a frequently encountered phenomenon. It has a wide variety of causes ranging from simple physiological reactions to stress and splenectomy to infections like glandular fever, malaria, and drug reactions, or harder-to-manage autoimmune diseases, lymphoma and leukaemia. Proper history and physical examination, with the aid of relevant investigations, help doctors to reach a definitive diagnosis.