Introduction
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 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.
An immunodeficiency disorder may be present at birth (congenital, or primary) or may develop later in life, often as a result of another disorder (acquired, or secondary). Congenital immunodeficiency disorders are usually hereditary. They typically become evident during infancy or childhood. There are more than 70 congenital immunodeficiency disorders; all are relatively rare. Acquired immunodeficiency disorders are much more common. Some immunodeficiency disorders shorten lifespan, others persist throughout life but do not affect lifespan, and a few resolve with or without treatment.
Immunodeficiency disorders are grouped by which part of the immune system (see Section 16, Chapter 183) is affected. They may involve problems with antibodies (due to abnormalities in B lymphocytes, a type of white blood cell), T lymphocytes (a type of white blood cell that helps identify and destroy foreign or abnormal cells), both B and T lymphocytes, phagocytes (cells that ingest and kill microorganisms), or complement proteins. The affected component of the immune system may be missing, reduced in number, or abnormal and malfunctioning.
 See the table Some Congenital Immunodeficiency Disorders.
Causes
Congenital immunodeficiency disorders are caused by a genetic abnormality, which is often X-linked (see Section 1, Chapter 2). That is, boys are more likely to be affected than girls. As a result, about 60% of affected people are male.
Acquired immunodeficiency disorders may result from almost any prolonged serious disorder. Examples are cancer, blood disorders (such as aplastic anemia, leukemia, and myelofibrosis), kidney failure, diabetes, liver disorders, and spleen disorders. Diabetes can result in an immunodeficiency disorder because white blood cells do not function well when the blood sugar level is high. Infections can also cause immunodeficiency disorders. 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 usually impaired. A decrease to less than 70% usually results in severe impairment.
Use of certain drugs called immunosuppressants may result in an acquired immunodeficiency disorder. These drugs are intentionally used to suppress the immune system. For example, immunosuppressants are used to prevent rejection of a transplanted organ or tissue (see Section 16, Chapter 187), and corticosteroids, a type of immunosuppressant, are used to suppress inflammation due to various disorders. However, immunosuppressants also suppress the body's ability to fight infections and perhaps to destroy cancer cells. Chemotherapy and radiation therapy can also result in immunodeficiency disorders.
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. Skin infections by bacteria or viruses are also common. Bacterial infections (with staphylococci, for example) may cause pyoderma, in which the skin is covered with pus-filled sores. Warts (caused by viruses) may occur.
Many people lose weight. Children tend to develop slowly. Other symptoms vary depending on the severity and duration of the infections.
Diagnosis
Doctors first establish that an immunodeficiency exists. Then they identify the abnormality in the immune system.
Doctors suspect immunodeficiency when a severe or an unusual infection recurs often or when an organism that normally does not cause infection (such as pneumocystis or cytomegalovirus) causes infection. The results of a physical examination may also suggest immunodeficiency. Evidence of recurring infections--such as rashes, hair loss, many skin infections, chronic cough, weight loss, and an enlarged liver and spleen--is often present.
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 lymphocytes. Infections in older children usually indicate an abnormality in B lymphocytes 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 Section 17, Chapter 199).
Laboratory tests are needed to confirm the diagnosis of immunodeficiency and 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 performed.
A laboratory test using a chemical to stimulate lymphocytes or skin tests may be performed if the immunodeficiency is thought to be due to a T-lymphocyte 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 lymphocytes are functioning normally. No reaction suggests a T-lymphocyte abnormality. These skin tests are not useful in children younger than 2 years.
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 are of having an affected child. Genetic counseling before testing is helpful. Several immunodeficiency disorders, such as X-linked agammaglobulinemia, Wiskott-Aldrich syndrome, severe combined immunodeficiency disease, 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.
Prevention and Treatment
Some of the disorders that can cause immunodeficiency disorders can be prevented or treated. For example, the spread of HIV infection can be reduced by following safe sex guidelines and by not sharing needles to inject drugs. Successful treatment of cancer usually restores the function of the immune system. Treatment with antiviral drugs can help improve white blood cell function, thus preventing additional infections due to immunodeficiency. Good control of diabetes can help white blood cells function better and thus prevent infections.
Strategies for reducing the risk of and for 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. Periodic treatment with immune globulin given intravenously and good personal hygiene (including conscientious dental care) reduce this risk, as does not eating undercooked food, drinking bottled water and 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.
For people who have an immunodeficiency disorder that increases the risk of viral infections (particularly immunodeficiency due to a T-lymphocyte abnormality, such as AIDS), antiviral drugs, such as amantadine for influenza or acyclovir for herpes, are promptly given at the first sign of infection.
People who can produce antibodies are vaccinated. However, people who have a B- or T-lymphocyte 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 oral poliovirus vaccine, measles-mumps-rubella vaccine, chicken pox (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 Section 16, Chapter 187) can correct some immunodeficiency disorders, particularly severe combined immunodeficiency disease. 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 is being studied.
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