Introduction

Monocytes are a type of white blood cell in the body. White blood cells are part of the immune system. In a healthy adult, monocytes make up 1-9% of the total white cell blood count. In adults, normal monocyte count is between 0.2-0. x10⁹ /L. They are produced in the bone marrow and then stay in the blood for a period of a few days before they move into different tissues/organs in the body. Once they enter the tissues, they differentiate (meaning monocytes turn into different, more specialised types of white blood cells. The main types that monocytes differentiate into are macrophages and dendritic cells.³

Monocytes have different functions. They engulf foreign cells, dead or abnormal cells that may be circulating in the body. They can present the antigens of the foreign cells on their own surface to alert other cells of the immune system (cells that do this are known as antigen-presenting cells). Monocytes can also produce cytokines, which are molecules part of the inflammatory process. These functions enable monocytes to help the body fight off infections and help also to prevent infections from happening.³ 

Monocytosis is a condition where the number of monocytes in the blood is abnormally high. The World Health Organization (WHO) defines persistent monocytosis as a monocyte count of over 1 × 10⁹/L with monocytes comprising over 10% of white blood cells, persisting for more than 3 months. In neonates (newborns), monocytosis is a count of over 3.5 × 10⁹/L. On the other end of the spectrum, monocytopenia (having too few monocytes) is defined as the monocyte count of less than 0.2 × 10⁹/L, which is a very rare finding.^{2, 3}

Causes of monocytosis

The causes of monocytosis can broadly be divided into persistent or transient. 

Transient causes are usually because of an infection or a stressful event that then resolves. Examples of this can include a myocardial infarction (heart attack) or removal of the spleen (splenectomy). Patients who have had cytotoxic chemotherapy have also been shown to have monocytosis.  

Persistent causes can be varied. These can be from chronic infections such as endocarditis (where the inside of the heart is inflamed), malaria (a parasitic disease which is carried by mosquitoes) or tuberculosis (a bacterial infection which usually affects the lungs, but can affect other parts of the body too).

Certain chronic autoimmune conditions can cause monocytosis like inflammatory bowel disease (primarily Crohn's disease and ulcerative colitis), rheumatoid arthritis (inflammation of the joints) and systemic lupus erythematosus (aka lupus).

Respiratory conditions of pulmonary fibrosis, COPD (chronic obstructive pulmonary disease) and COVID-19 also have elevated monocyte levels. Coronary heart disease and atherosclerosis also have monocytes as part of their disease processes. 

Certain cancers are also linked with elevated monocyte levels - Hodgkin's and non-Hodgkin’s lymphoma, certain leukaemias CMML (chronic myelomonocytic leukaemia) and AML (acute monocytic leukaemia). Leukaemias are cancers of the blood-forming tissues (bone marrow), which produce abnormal cells in high numbers. CMML and AML are two types of leukaemia which involve abnormal production of monocytes (there are more common forms of leukaemia which involve different white blood cells). Both CMML and AML mainly affect adults. 

Lymphoma is a cancer of the lymphatic system, which comprises the lymph nodes, spleen, thymus gland also bone marrow which produces lymphocytes, another white blood cell type. Lymphoma usually starts in the lymph nodes. The difference between Hodgkin’s and non-Hodgkin's lymphoma is that Hodgkin’s lymphoma has the presence of cells known as Reed Sternberg cells, and non-Hodgkin’s lymphoma does not.   

Malignancies and chronic infections create a chronic inflammatory environment in the body, and this can increase the white cell count (amount of white blood cells produced) and therefore increase the number of monocytes too.^2,3 

Medications can induce monocytosis too. Granulocyte colony-stimulating factor, olanzapine, ziprasidone, radiation therapy, and anti-thymocyte globulin have all been shown to cause monocytosis. 

Obesity in both adults and children has been shown to have higher levels of monocytes circulating in the blood. This is because obesity creates a chronic inflammatory state and accumulation of visceral adipose tissue (fat deposits around the organs). Obesity is associated with infiltration of a different type of white blood cell—macrophages— into the adipose tissue, which gives rise to type II diabetes (insulin resistance).⁵ 

However it is worth noting that the finding of monocytosis is not something usually looked for in itself, nor will there be any particular symptoms of monocytosis itself. It is more so a non-specific finding that will be part of others. Whilst some conditions may present with monocytosis (some research showed certain respiratory infections can present with monocytosis), as like an initial sign. Most, if not all, of these conditions will have other signs and symptoms which will be much more evident. It is important to have further investigations to identify the root cause.³ 

Risk factors 

• Age is one of the main risk factors for monocytosis. Age is associated with a decline in the function of the immune system, and increased vulnerability to infections and cancers, which can cause monocytosis
• Sex has a mild influence over monocyte count. People assigned male at birth have a slightly higher normal monocyte count than those assigned female at birth, and this is likely due to differences in the sex hormones
• Differences between different ethnic backgrounds were generally not statistically significant. Although not directly related, lifestyle factors can have an influence over the risk of acquiring certain illnesses, which can then cause monocytosis
• Obesity—and specifically the monocytosis found in obese people—is one established risk factor for coronary heart disease. Likewise, obesity is a risk factor for monocytosis. Genetic predisposition can increase risk of autoimmune conditions of IBD, lupus and rheumatoid arthritis, so someone would be at an increased risk if they have a family history of any of these diseases. However, it isn’t always the case that a family history is present^3,4

Diagnostic tests 

• Monocyte levels can be detected on a full blood count. In the situation of an acute cause of monocytosis, levels should return to normal once the acute cause has resolved
• Bone marrow biopsies can also detect monocyte levels. These involve a needle taking a sample of cells (also called a fine needle aspirate) to look under a microscope. Biopsies are part of the diagnostic process for cancers
• Another test that can identify monocytosis is a peripheral blood smear. This involves a small drop of blood being analysed under a microscope. A high number of white cells or abnormal-looking monocytes can be an indication of an underlying malignancy
• Flow cytometry is another test used in identifying leukaemias and lymphomas. It involves marking cells from a blood sample or bone marrow biopsy with fluorescent markers to detect abnormal cells⁴ 

Patient prognosis

Prognosis means the possible development of any medical condition based on how the disease is progressing. Patients who have monocytosis would have some other medical condition as their main diagnosis. Based on a report, in which researchers studied patients with monocytosis, their diagnoses included congestive heart failure, COPD, cancer, renal failure, and diabetes but not dementia. The study found that the length of the duration of a hospital stay and 30-day mortality was much higher in those with monocytosis. This shows that the prognosis was poor, but it is worth remembering monocytosis alone does not provide a complete picture of the patient's disease patterns.^1,3 

Summary 

Monocytosis is a condition where a type of white blood cell—monocytes—are in higher than usual numbers. Causes of monocytosis can be categorised as either acute or persistent. Acute causes are usually because of an acute infection like COVID-19 or a condition with a fast onset like a heart attack. Persistent causes refer to when the monocyte levels are elevated over a period of at least 3 months. This can be caused by chronic infections such as endocarditis, tuberculosis or malaria. Some cancers can cause monocytosis- Hodgkin's and non-Hodgkin's lymphoma, chronic myelomonocytic leukaemia and acute monocytic leukaemia. 

The high level of monocytes is indicative of a state of inflammation in the body and if detected, is a sign that something is wrong. Monocytosis is rarely the main diagnosis and in only some cases, is the main symptom on presentation. Usually, monocytosis is one finding amongst many others that are in most cases, more evident. It is important that whichever presenting issue is investigated to have the correct diagnosis and management.