Immunosuppression: Causes and Risk Factors

Immunosuppression means that your immune system is not functioning as it should. This can be caused by disease, but it is more often induced by medications such as chemotherapy and immunosuppressants. Some procedures can cause immunosuppression too.

The immune system is the collection of all the cells, tissues, and organs that help the body stave off infection. Without an intact immune system, infections can become very aggressive, and may even be fatal. Immunosuppression also increases the risk of cancer, because the immune system helps protect the body from cancer.

There are a number of medications that reduce inflammation or suppress the immune system. Immunosuppressants are used for treating a variety of inflammatory and autoimmune diseases, such as lupus and arthritis. Human immunodeficiency virus (HIV) can cause AIDS, another cause of immunosuppression.

Because steroids reduce inflammation, they are prescribed for a variety of autoimmune, allergic, and inflammatory conditions, such as rheumatoid arthritis, inflammatory bowel disease, asthma, and atopy. Taking a high dose of steroids makes you susceptible to infections from a variety of organisms, such as Pneumocystis jirovecii, which causes deadly Pneumocystis pneumonia, as well as Strongyloides, a potentially deadly roundworm infection. Corticosteroids can also increase the risk of reactivation of tuberculosis or other latent infections.

Chemotherapy is used to shrink cancer cells. There are a number of different chemotherapeutic medications. Sometimes treatment of cancer requires a combination of several different chemotherapeutic agents. Cancer cells rapidly reproduce and chemotherapeutic agents work by targeting cells that rapidly reproduce. Hair and skin cells rapidly reproduce and this is why hair loss is such a common (and visible) side effect of chemotherapy.

Unlike skin cells, immune cells are hidden inside the body. They tend to be substantially reduced during treatment with chemotherapy, resulting in a high risk of infection.

These medications target disease-causing cells in the body. Rituximab is an example of a monoclonal antibody used to treat non-Hodgkin lymphoma, rheumatoid arthritis, and chronic lymphocytic leukemia. It is linked to rare illnesses such as progressive multifocal leukoencephalopathy (PML), which is caused by JC virus, and pure red cell aplasia, which is associated with parvovirus infection. Furthermore, immunosuppression secondary to rituximab administration can lead to reactivation of hepatitis B infection.

These medications are cytokines; cytokines are usually produced by immune cells. TNF-α inhibitors include drugs like infliximab and certolizumab pegol and are used to treat autoimmune conditions like rheumatoid arthritis and Crohn's disease. Of note, immunosuppression resulting from the administration of these drugs opens the door to infection with Listeria monocytogenes, a foodborne pathogen that can cause fetal death in pregnant women.

HIV is a virus that can be transmitted by sexual contact, intravenous (IV) drug use with contaminated needles, or from a pregnant mother to her infant. The virus may destroy a large number of immune cells called helper T cells, which are necessary to mount an immune response.

The progression of HIV to AIDS is marked by severe immunocompromise. Once the infection advances to the AIDS stage, a person can develop opportunistic infections, including:

• Candidiasis
• Coccidioidomycosis
• Cryptococcosis
• Cytomegalovirus disease
• Encephalopathy, HIV-related
• Herpes simplex
• Histoplasmosis
• Kaposi's sarcoma (a type of cancer)
• Tuberculosis
• Pneumocystis carinii pneumonia
• Toxoplasmosis of brain

There are several procedures that result in immunosuppression, either directly or indirectly. Removal of the spleen, bone marrow ablation, and organ transplant are all associated with immunosuppression.

Asplenia, the loss of splenic function, can occur due to conditions like sickle cell anemia, which can damage the spleen. Surgical removal of the spleen, called splenectomy, may be necessary for treatment of cancer, trauma, or blood disorders (like refractory idiopathic thrombotic purpura).

People with asplenia are at increased risk of infection with encapsulated organisms, such as Streptococcus pneumoniae, Haemophilus influenzae, and some forms of Neisseria meningitides. These infections are more likely to occur within the first few years of developing asplenia or of having a splenectomy.

After receiving a solid organ transplant, such as a kidney, liver, heart, or pancreas, lifelong treatment with immunosuppressant medications is needed to decrease the risk of rejecting the organ.

Six months after transplant and beyond, recipients are most susceptible to community-acquired infections like those caused by encapsulated organisms such as Streptococcus pneumoniae and Haemophilus influenzae.

Prior to a stem cell transplant, a bone marrow transplant, or treatment for leukemia or lymphoma, the suppression of the cells in the bone marrow involves the use of radiation or powerful medications. The immune system becomes very weak during this time and there is a high risk of infection.

Radiation can be used as a treatment for cancer, or as preparation for certain procedures, such as bone marrow transplant. Radiation therapy can be targeted to certain areas of the body, so it does not always result in immunosuppression. However, radiation targeted to the bone marrow results in immunosuppression.

Inherited immune diseases, called primary immunodeficiencies, are rare. These conditions, such as severe combined immunodeficiency and chronic granulomatous disease, are diagnosed at an early age. Common variable immunodeficiency (CVID) and immunoglobulin A deficiency may begin to cause infections during adolescence and young adulthood, with a later diagnosis.

With CVID, the immune cells fail to produce immunoglobulins necessary to mount an immune response. Consequently, people with CVID are more likely to suffer from respiratory infections as well as infections of the gastrointestinal system like Giardia lamblia. 

The treatment of CVID is complicated and requires specialist care in part because people with this condition don't respond to immunization and instead require an infusion of immunoglobulin in a hospital setting.

Chemotherapy, HIV, and bone marrow ablation are examples of severe immunosuppression that can make a person susceptible to fatal infections. If you have any of these types of immunosuppression, you need to avoid contact with people who could carry contagious illnesses, such as schoolchildren and toddlers. You may need to avoid public places or wear a mask when out in public to protect yourself from common community infections.

There are several other causes of more mild immunosuppression, such as malnutrition, cytomegalovirus (CMV) infection, alcoholism, diabetes, and kidney failure. Having a suppressed immune system can expose you to more frequent infections which may take longer than usual to recover from. Be sure to talk to your doctor about preventing infections if you have one of the risk factors of immunosuppression.