Diseases & Conditions


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Immunodeficiency Disorders


Immunodeficiency disorders involve malfunction of the immune system, resulting in infections that develop and recur more frequently, are more severe, and last longer than usual. Immunodeficiency disorders usually result from use of a drug or from a long-lasting serious disorder (such as cancer) but occasionally are inherited. People usually have frequent, unusual, or unusually severe infections. Doctors suspect immunodeficiency based on symptoms and do blood tests to identify the particular disorder. People are given antibiotics to prevent and treat infections. Immune globulin may be given if antibodies (immunoglobulins) are missing. If the disorder is severe, stem cell transplantation may be done.

Immunodeficiency disorders impair the immune system's ability to defend the body against foreign or abnormal cells that invade or attack it (such as bacteria, viruses, fungi, and cancer cells). As a result, unusual bacterial, viral, or fungal infections and rare cancers may develop.

There are two types of immunodeficiency disorders: Congenital (primary): These disorders are present at birth and are usually hereditary. They typically become evident during infancy or childhood. There are more than 200 congenital immunodeficiency disorders. All are relatively rare. Acquired (secondary): These disorders develop later in life and often result from use of a drug or from another disorder, such as diabetes or human immunodeficiency virus (HIV) infection. They are more common than congenital immunodeficiency disorders.

Some immunodeficiency disorders shorten life span. Others persist throughout life but do not affect life span, and a few resolve with or without treatment.

Causes

Congenital immunodeficiency: These disorders are caused by a genetic abnormality, which is often X-linked (see Genetics: X-Linked Inheritance ). That is, only boys are affected. As a result, about 60% of people with congenital immunodeficiency disorders are male.

Congenital immunodeficiency disorders are classified by which part of the immune system (see Biology of the Immune System: Introduction ) is affected: B cells (lymphocytes), a type of white blood cell that produces antibodies (immunoglobulins) T cells (lymphocytes), a type of white blood cell that helps identify and destroy foreign or abnormal cells B and T cells Phagocytes (cells that ingest and kill microorganisms) Complement proteins (proteins with various immune functions, such as killing bacteria and other foreign cells and making foreign cells easier for other immune cells to identify and ingest—see Biology of the Immune System: Complement System )

The affected component of the immune system may be missing, reduced in number, or abnormal and malfunctioning. Problems with B cells are the most common congenital immunodeficiency disorders, accounting for more than half.

Some Congenital Immunodeficiency Disorders

Classification

Disorder

Problems with B cells (lymphocytes) and their production of antibodies

Common variable immunodeficiency Deficiency of a specific antibody (immunoglobulin), such as IgA deficiency Transient hypogammaglobulinemia of infancy X-linked agammaglobulinemia

Problems with T cells (lymphocytes)

Chronic mucocutaneous candidiasis DiGeorge syndrome X-linked lymphoproliferative syndrome

Problems with B and T cells

Ataxia-telangiectasia Hyperimmunoglobulinemia E syndrome Severe combined immunodeficiency Wiskott-Aldrich syndrome

Problems with the movement or killing activity of phagocytes

Chédiak-Higashi syndrome (rare) Chronic granulomatous disease Leukocyte adhesion defects

Problems with complement proteins

Complement component 1 (C1) inhibitor deficiency (hereditary angioedema) C3 deficiency C6 deficiency C7 deficiency C8 deficiency

Acquired immunodeficiency disorders: These most commonly result from drugs (mainly immunosuppressants, which are used to treat serious disorders). Immunosuppressants are used to intentionally suppress the immune system. For example, some are used to prevent rejection of a transplanted organ or tissue (see Transplantation: Drugs Used to Prevent Transplant Rejection ). Corticosteroids, a type of immunosuppressant, are used to suppress inflammation due to various disorders, such as rheumatoid arthritis. However, immunosuppressants also suppress the body's ability to fight infections and perhaps to destroy cancer cells. Chemotherapy and radiation therapy can also suppress the immune system, sometimes leading to immunodeficiency disorders.

What Can Cause Immunodeficiency?

Type

Examples

Drugs

Anticonvulsants

Carbamazepine Some Trade Names TEGRETOL Phenytoin Some Trade Names DILANTIN Valproate Some Trade Names DEPARENE

Immunosuppressants

Azathioprine Some Trade Names IMURAN Mycophenolate mofetil Some Trade Names CELLCEPT Cyclosporine Some Trade Names SANDIMMUNE NEORAL Sirolimus Some Trade Names RAPAMUNE Tacrolimus Some Trade Names PROGRAF

Corticosteroids

Methylprednisolone Some Trade Names MEDROL Prednisone Some Trade Names DELTASONE METICORTEN

Chemotherapy drugs

Alemtuzumab Some Trade Names CAMPATH Busulfan Some Trade Names MYLERAN Cyclophosphamide Some Trade Names CYTOXAN Melphalan Some Trade Names ALKERAN

Monoclonal antibodies (substances that target and suppress specific parts of the immune system)

Muromonab (OKT3)

Disorders

Blood

Aplastic anemia Leukemia Myelofibrosis Sickle cell disease

Cancer

Brain cancer Intestinal cancer Lung cancer

Chromosomal

Down syndrome

Infections

Cytomegalovirus infections Epstein-Barr virus infections Human immunodeficiency virus (HIV) infection Measles Varicella

Hormonal

Diabetes mellitus

Kidney

Build up of toxic substances in the blood (uremia) Nephrotic syndrome

Liver

Hepatitis

Musculoskeletal

Rheumatoid arthritis Systemic lupus erythematosus (lupus)

Spleen

Removal of spleen

Other

Alcoholism Burns Undernutrition

Immunodeficiency disorders may result from almost any prolonged serious disorder. For example, diabetes can result in an immunodeficiency disorder because white blood cells do not function well when the blood sugar level is high. Human immunodeficiency virus (HIV) infection results in acquired immunodeficiency syndrome (AIDS), the most common severe acquired immunodeficiency disorder.

Undernutrition—whether of all nutrients or only one—can impair the immune system. When undernutrition causes weight to decrease to less than 80% of recommended weight, the immune system is often impaired. A decrease to less than 70% usually results in severe impairment.

Symptoms

People with an immunodeficiency disorder tend to have one infection after another. Usually, respiratory infections develop first and recur often. Most people eventually develop severe bacterial infections that persist, recur, or lead to complications. For example, sore throats and head colds may progress to pneumonia. However, having many colds does not suggest an immunodeficiency disorder.

Infections of the skin and the membranes lining the mouth, eyes, and digestive tract are common. Thrush, a fungal infection of the mouth, may be an early sign of an immunodeficiency disorder. Sores may form in the mouth. Ear infections and skin infections by bacteria or viruses are also common. Bacterial infections (for example, with staphylococci) may cause pus-filled sores to form (pyoderma). Warts (caused by viruses) may form.

Many people lose weight.

Infants or young children may have chronic diarrhea and may not grow and develop as expected (called failure to thrive). The earlier symptoms begin in children, the more severe the immunodeficiency.

Other symptoms vary depending on the severity and duration of the infections.

Diagnosis

Doctors must first suspect that an immunodeficiency exists. Then they do tests to identify the specific immune system abnormality.

Doctors suspect immunodeficiency when a severe or an unusual infection recurs often or when an organism that normally does not cause severe infection (such as Pneumocystis or cytomegalovirus) causes severe infection. The results of a physical examination may also suggest immunodeficiency. Rashes, hair loss, chronic cough, weight loss, and an enlarged liver and spleen are often present. Lymph nodes and tonsils may be extremely small in some forms of immunodeficiency, whereas in other types the lymph nodes may be swollen. Certain symptoms may suggest a particular disorder to doctors.

To help identify the type of immunodeficiency disorder, doctors ask at what age the person began to have recurring or unusual infections. Infections in infants younger than 6 months usually indicate an abnormality in T cells. Infections in older children usually indicate an abnormality in B cells and antibody production. The type of infection may also help doctors identify the type of immunodeficiency disorder.

Doctors ask the person about risk factors, such as diabetes, use of certain drugs, exposure to toxic substances, and the possibility of having close relatives with immunodeficiency disorders (family history). The person is asked about past and current sexual activity and use of intravenous drugs to determine whether HIV infection could be the cause (see Human Immunodeficiency Virus HIV Infection ).

Tests: Laboratory tests are needed to confirm the diagnosis of immunodeficiency and to identify the type of immunodeficiency disorder. A blood sample is taken and analyzed to determine the total number of white blood cells and the percentages of each main type of white blood cell. The white blood cells are examined under a microscope for abnormalities. Antibody levels, the number of red blood cells and platelets, and the levels of complement proteins are determined. If any results are abnormal, additional tests are usually done.

Skin tests may be done if the immunodeficiency is thought to be due to a T-cell abnormality. The skin test resembles the tuberculin skin test, which is used to screen for tuberculosis. Small amounts of proteins from common infectious organisms such as yeast are injected under the skin. If a reaction (redness, warmth, and swelling) occurs within 48 hours, the T cells are functioning normally. No reaction suggests a T-cell abnormality.

People whose families are known to carry a gene for a hereditary immunodeficiency disorder may wish to have genetic testing to learn whether they carry the gene for the disorder and what the chances of having an affected child are. Talking with a genetic counselor before testing is helpful. Several immunodeficiency disorders, such as X-linked agammaglobulinemia, Wiskott-Aldrich syndrome, severe combined immunodeficiency, and chronic granulomatous disease, can be detected in a fetus by testing a sample of the fluid around the fetus (amniotic fluid) or the fetus's blood (prenatal testing). Such testing may be recommended for people with a family history of an immunodeficiency disorder when the mutation has been identified in the family.

Prevention and Treatment

Some of the disorders that can cause immunodeficiency disorders can be prevented or treated. The following are examples: HIV infection: Following safe sex guidelines and not sharing needles to inject drugs can reduce the spread of this infection. Cancer: Successful treatment usually restores the function of the immune system unless people need to continue taking immunosuppressants. Diabetes: Good control of blood sugar levels can help white blood cells function better and thus prevent infections.

Strategies for preventing and treating infections depend on the type of immunodeficiency disorder. For example, people who have an immunodeficiency disorder due to a deficiency of antibodies are at risk of bacterial infections. The following can help reduce the risk: Being treated periodically with immune globulin (antibodies obtained from the blood of people with a normal immune system) given intravenously Practicing good personal hygiene (including conscientious dental care) Not eating undercooked food Drinking only bottled water Avoiding contact with people who have infections

Antibiotics are given as soon as a fever or another sign of an infection develops and before surgical and dental procedures, which may introduce bacteria into the bloodstream.

If an immunodeficiency disorder increases the risk of viral infections (as immunodeficiency due to a T-cell abnormality does), antiviral drugs, such as amantadine Some Trade Names SYMMETREL for influenza or acyclovir Some Trade Names ZOVIRAX for herpes or chickenpox, are promptly given at the first sign of infection. Such treatment may be lifesaving.

If a disorder (such as severe combined immunodeficiency) increases the risk of developing serious infections or particular infections, people may be given antibiotics in advance to prevent these infections.

If the immunodeficiency disorder does not prevent antibody production, people are vaccinated. However, people who have a B- or T-cell abnormality are given only killed viral and bacterial vaccines rather than live vaccines. Live viruses may cause an infection in such people. Live vaccines include rotavirus vaccines, oral poliovirus vaccine, measles-mumps-rubella vaccine, chickenpox (varicella) vaccine, and bacille Calmette-Guérin (BCG) vaccine. An influenza vaccine given once a year is recommended for people who can produce antibodies and for their immediate family members.

Stem cell transplantation (see Transplantation: Stem Cell Transplantation ) can correct some immunodeficiency disorders, particularly severe combined immunodeficiency. Stem cells are usually obtained from bone marrow but occasionally from blood (including umbilical cord blood). Stem cell transplantation, which is available at some major medical centers, is usually reserved for severe disorders.

Transplantation of thymus tissue is sometimes helpful. Gene therapy for a few congenital immunodeficiency disorders has been successful, but it is not widely used because leukemia is sometimes a risk.

Source: The Merck Manual Home Edition