Chapter 19: Immune Dysfunction

Chapter 19 INTRODUCTION The immune system protects against microorganisms through three lines of defense; mechanical barriers, inflammation, and acquired or adaptive immunity. The first-line barriers and the inflammatory response are part of innate immunity that reacts to an initial exposure to an...

Chapter 19 INTRODUCTION The immune system protects against microorganisms through three lines of defense; mechanical barriers, inflammation, and acquired or adaptive immunity. The first-line barriers and the inflammatory response are part of innate immunity that reacts to an initial exposure to an antigen or microbe in a rapid, nonspecific fashion. Subsequent exposure activates the adaptive response that specifically reacts to the microbe and creates lasting immune memory (lifelong immunity). Additionally, the immune system prevents the proliferation of cancer cells and initiates the healing of damaged tissue. Immune disorders may be due either to a deficiency or overactivity and may involve one or more components of the immune system. Deficiency can result in disease processes; overactivation can result in reactions that may include anaphylaxis and autoimmune disorders. OVERVIEW OF PRIMARY AND SECONDARY IMMUNE DYSFUNCTION Primary immune dysfunction occurs in persons born with an immune system that is deficient or limited in its ability to function. In this case, there is an intrinsic (inborn), congenital, or genetic cause. Most primary immune dysfunctions are inherited diseases, but some are the result of the interaction of predisposing genetic and environmental factors. These primary immunodeficiencies result from defects in T lymphocytes, B lymphocytes, natural killer cells, phagocytic cells, or the complement system. There are more than 200 primary immune deficiency diseases identified, many of which are rare. Examples of these are chronic granulomatous disease and hyperimmunoglobulin M (HIGM) syndromes. Although the majority are diagnosed in childhood, there are a few primary immune dysfunctions that take years for symptoms to manifest and so do not present in early childhood. Table 19.1 lists warning signs that a primary immune dysfunction is present. Secondary immune dysfunction, or acquired immune deficiency, occurs after birth when there is damage to the immune system caused by an extrinsic or external environmental factor or agent. This arises secondary to another disease process or exposure to medications or chemicals. Examples of secondary immune dysfunction include immune deficiency caused by HIV disease, irradiation, chemotherapy, malnutrition, or burns. Secondary immune dysfunction comprises the majority of deficiencies presented in the adult clinical setting. PRIMARY IMMUNE DYSFUNCTION: B-CELL DEFICIENCIES One classification of primary immune dysfunction involves B-cell deficiencies. B cells are involved in producing a humoral immune response, which is the antibody response. An antibody, or immunoglobulin, is produced in response to a foreign substance known as an antigen. B cells mature into plasma cells that produce antibodies and immunoglobulins (IgG, IgA, and IgM). These antibodies and immunoglobulins bind to the invading organism, alter them, and make them more susceptible to phagocytosis. B cells are also a part of lifelong-immunity that occurs from responding to infection(s) and immunizations. B-cell deficiencies involve a lack of differentiation of B-cell precursors into mature B cells or a lack of differentiation of B cells into plasma cells. One example of a B-cell deficiency is X-linked agammaglobulinemia (XLA). X-LINKED AGAMMAGLOBULINEMIA Epidemiology Agammaglobulinemia is an X-linked recessive inherited or congenital primary immune deficiency. The term X-linked recessive means that the gene that causes this disease is located on the X chromosome. Humans have 46 pairs of chromosomes. One pairing identifies sex. Females have two X chromosomes; males have an X and a Y. XLA primarily affects males because it is unlikely that females will inherit two X chromosomes carrying the altered gene. Males get only one X chromosome. If their one X chromosome carries an altered or disease-carrying gene, they will have symptoms of the disease. Females may inherit one altered gene, which makes them a carrier of the disease. Figure 19.1 illustrates the genetic inheritance of XLA. An individual with a family history of the disorder has the potential of inheriting XLA which occurs at a frequency of about 1 in 250,000 male newborns. There is no ethnic predisposition. Prevalence is three to six per million males in all racial and ethnic groups. Symptoms do not appear until between 6 and 12 months of age because there is initial protection from the mother's antibodies. Many children die before their sixth birthday because of infection if the disorder is not identified and treated. Pathophysiology XLA is the result of a mutation of the BTK gene. The BTK gene is present on the long arm of the X chromosome, and its defect results in a deficiency of Bruton's tyrosine kinase, which is essential for the development of B lymphocytes. B cells are specialized white blood cells (WBCs) that, when mature, produce special proteins called antibodies or immunoglobulins. The BTK protein transmits chemicals that alert B cells to mature and produce antibodies. This type of B-cell deficiency is one in which immature B cells are present in normal numbers but are unable to mature, which means they cannot produce antibodies or immunoglobulins. The inability to produce antibodies in response to the invasion of an antigen leaves the patient vulnerable to severe bacterial infections. Clinical Manifestations Clinical manifestations include infections of the ears, lungs, skin, conjunctiva, and central nervous system. The presence of recurrent bacterial infections of the respiratory tract in childhood is the first indicator of the possibility of this disease. Chronic respiratory infections such as sinus infections and pulmonary disease are common clinical manifestations. Serious or systemic infections can develop in the bloodstream and affect internal organs. Patients can have a history of recurrent pneumonia, meningitis, and septicemia caused by organisms such as Streptococcus pneumoniae and Haemophilus influenzae. They may also develop autoimmune diseases such as leukemia or lymphoma. Patients tend to cope well with most short-term viral infections (like upper respiratory tract infections; URIs) but are very susceptible to chronic viral infections such as hepatitis, polio, and enterovirus viruses. Interprofessional Management Medical Management Diagnosis Obtaining a detailed family history and history of infections is an important first step in the care of a patient suspected to have an abnormal immune response. Diagnostics should begin with a blood test that will count the number of mature B lymphocytes; this is called a Lymphocyte Surface Marker Analysis or B cell count. This is a general test that can aid in the diagnosis of primary immunodeficiency disorders. If abnormal numbers and percentages of B lymphocytes are found, more specific diagnostics will be ordered based upon the patient's history and assessment. In XLA, the patient's blood tests will indicate a lack of circulating B cells and low levels of immunoglobulins. A Western blot test should be done to determine if the BTK protein is being expressed thus determining if the effects of the gene are appropriately manifested in a person. BTK expression is reported as present, absent, partial deficiency, or mosaic. Mosaic BTK expression indicates a genetic carrier. Genetic testing can confirm the diagnosis. Women with a family member with XLA should seek genetic counselling before pregnancy. Periodic radiographs of the chest or sinuses in a child at risk are utilized to detect any signs of infection in its early stages. Treatment Treatment includes giving IV immune globulin (IVIG) to provide short-term passive immunity (see Geriatric/Gerontological Considerations). IV immune globulin is a sterilized solution made from human plasma. It contains the antibodies, mostly immunoglobulin G (IgG) or gamma globulin, to help protect against infection from various diseases. The dosage and the schedule are individualized, but typically IV immune globulin is given every 3 or 4 weeks. Gamma globulin can also be given by weekly subcutaneous injections. Both routes provide therapeutic concentrations of serum IgG. Patients with immunodeficiencies may also take a low dose of prophylactic broad-spectrum antibiotics regularly, even when feeling well, if the episodes of infection are frequent. The aim of prophylactic antibiotics is to prevent an infection from starting. Aggressive treatment with microorganism-specific antibiotics is initiated when the patient exhibits overt signs of infection. Patients should have an antibiotic course at least twice as long as that used in healthy individuals. Immunization with killed viral and bacterial vaccines is sometimes done to aid in the development of T-cell-mediated immune response, which may augment the protection that is obtained through immunoglobulin replacement. Vaccination with live viruses is contraindicated. Complications Children with XLA are prone to complications. Approximately 60% of individuals with XLA develop a severe, life-threatening bacterial infection, such as pneumonia, empyema, meningitis, sepsis, cellulitis, or septic arthritis. They may also develop a chronic viral enterovirus. When IV gamma globulin became available in the mid-1980s, the incidence of chronic enteroviral infection markedly decreased in individuals with XLA. However, some patients still develop enteroviral encephalitis, and some have neurological deterioration of unknown etiology. Nursing Management Assessment and Analysis Many of the clinical manifestations observed in the patient with XLA are directly related to infections of the respiratory tract, skin, conjunctiva, or ears. Common findings include: General: Fever Changes in behavior: the social outgoing person is too tired to go out, inconsolable crying, irritability, decreased activity Change in appetite Fatigue and lethargy Respiratory: Increased respiratory rate Poor quality of respirations (shallow vs deep) Absent, decreased, or adventitious lung sounds Skin: Rash Lesions Wounds that heal slowly or not at all Conjunctiva: Redness and/or drainage Ear: Pulling at the ears Pain in ears Complaints of muffled sounds Decrease in hearing ability (listening to the TV with volume loud) It is important to note the nurse must consider the entire patient; most of the assessment findings listed are nonspecific and will not immediately lead to the conclusion of an immune dysfunction. In immune dysfunction evaluation, both the history and the physical are extremely relevant. Nursing Diagnosis/Problem List Risk for infection related to compromised host defenses secondary to B-cell immunodeficiency Nursing Interventions Assessments General Survey The patient may "appear ill". Pallor Fatigued Periorbital hyperpigmentation (dark circles under eyes) Erythema around nose and mouth from increased secretions Dry mucous membranes (cracking, chapped lips) Lack of interest in environment (they may only give one-word answers or close their eyes when they are not speaking) Poor eye contact Vital signs Increased temperature may indicate the presence of infection. Respiratory rate may increase with respiratory infections in an effort to increase oxygenation. Respiratory rate may decrease if patient has been sick for some time and the body is beginning to become ineffective at fighting the infection. Respiratory effort may change, i.e., shallow breathing, labored breathing, or the use of accessory muscles to assist in breathing and ventilation. Oxygenation levels may drop (decrease in pulse oximetry) due to ineffective gas exchange. Carbon dioxide levels may increase due to decreases in ventilation. Heart rate may be increased due to fever and/or the body's response to infection. Changes in blood pressure due to the body's response to infection, fever, or shock. Assess lung sounds. Decreased, absent, or adventitious breath sounds may be present, with excessive secretions. Cough may be present (both productive and nonproductive). Inspect eyes and ears, skin and nails, and rashes and lesions. Red, inflamed ears may indicate an ear infection. Recurrent ear infections in children are the most common infection prior to diagnosis. Red conjunctiva with drainage indicates conjunctivitis, a common manifestation. Skin rashes and infections are frequently seen. Evaluate the patient's behavior and eating patterns. Irritability, decreases in activity, decreased interest, or change in personality can indicate fatigue due to the increased metabolic demand of the body while trying to maintain homeostasis. Poor appetite and decreased fluid intake can be signs of infection and illness. Actions Prevent exposure to other infections. The nurse must view their patient as vulnerable to all other infections and implement nursing measures to protect the patient. These may include protective isolation, limited visitors, and consideration that the patient's assigned nurse is not caring for other patients with infectious diseases that can be transmitted to the immunocompromised patient. Administer IV or PO gamma globulin as ordered. Immune globulin contains antibodies to protect against infection, providing short-term immunity. Administer prophylactic antibiotic therapy as ordered. Prophylactic antibiotics may prevent infections. Anticipate prompt treatment with antibiotics when infection is present. Aggressive organism-specific treatment with antibiotics should begin as quickly as possible to prevent the development of extensive and more severe infections. Teaching Teach patients to advise family members about the 10 warning signs of primary immunodeficiency, and instruct them to speak to their provider if there are more than one of the conditions listed in Table 19.1. Prompt detection of XLA is essential to manage infections and initiate proper treatment to avoid life-threatening complications. Institute precautions to prevent infection and minimize any source of infection in the environment at home related to: Foods Raw foods may contain microorganisms that cause infection in the immunocompromised patient. Teach safe food handling and storage. Water Many drinking sources of water are not tested routinely for microorganisms or parasites such as well or spring water. These present as high risk for life-threatening infection in immunocompromised patients. Domestic Animals Many animals, especially reptiles, carry diseases that can easily infect an immunocompromised patient. Unsanitary Conditions General household cleaning promotes an environment that is free of microorganisms. Examples of reservoirs of infection in the home are: sites that accumulate stagnant water (such as sinks, toilets, waste pipes, cleaning tools, and facecloths), dirty dishes, moist dirty laundry, household trash, and expired food. Potential sources of infection should be identified and controlled as much as possible. Protect the patient from any direct contact with anyone with a contagious illness. This helps to prevent infection from others. Identify signs and symptoms of infection and when to seek medical attention, particularly any temperature 100.5°F (38°C) or greater. Infection requires immediate treatment, and the patient should not wait to report fever or symptoms of infection. Good hand washing This helps prevent infection. Information regarding genetic disorders and community support groups Support for the family regarding understanding of genetic disorders and peer support are useful to cope with the disorder and manage the care of the patient. Evaluating Care Outcomes Appropriate antibiotic therapy and treatment with IVIG can help patients with XLA lead normal, active lives. The family and patient should be provided with information regarding the genetic transmission of XLA, the importance of preventing infection, and when to contact their healthcare provider. Most patients have a good prognosis if they start antibody replacement early OTHER B-CELL DEFICIENCIES Common Variable Immune Deficiency Common variable immune deficiency (CVID) is another type of B-cell deficiency. It is due to a lack of differentiation of B cells into plasma cells. This results in low levels of circulating antibodies (gamma globulin levels). Patients with CVID have normal levels of B cells, but they fail to differentiate into antibody-secreting cells. CVID can also cause alterations in the number and function of T cells. It is similar to XLA in that it manifests with recurrent bacterial infections, but the infections tend to be less severe. Unlike XLA, a genetic link is not found in most patients and this deficiency is usually not diagnosed until adulthood. It occurs equally in men and women. Patients with CVID can also have autoimmune disorders that affect the components of the blood, endocrine disorders, gastrointestinal disorders such as nausea, vomiting, chronic diarrhea, abdominal pain, and weight loss. Some patients with CVID may develop granulomas in the lungs and lymph nodes and some cancers such as skin, lymphoid, and gastrointestinal cancers. Treatment is similar to that of XLA. Selective Immunoglobulin A Deficiency Selective immunoglobulin A deficiency (SIgAD) is the most common type of immunoglobulin deficiency. This disorder is diagnosed by measuring IgA in the blood. Affected individuals will have low levels of IgA but normal levels of other immunoglobulins. SIgAD affects 1 in 150 to 1 in 1,000 persons depending on geographic region. It occurs most commonly in Whites or people of European descent. However, these statistics are thought to be inaccurate because many individuals with SIgAD are asymptomatic. The pattern of occurrence is random or inherited with no defined pattern of inheritance. SIgAD is usually diagnosed after 4 years of age, but symptoms may present as early as infancy. This is another example of the second type of B-cell deficiency, affecting proliferation, maturation of B cells, and immunoglobulin production. Patients with this disorder may be diagnosed due to routine blood work or they can present with recurrent sinus or pulmonary disorders caused by Streptococcus pneumoniae or Haemophilus influenzae. Around 20% to 30% of patients will also have an autoimmune disorder. Immunoglobulin G Subclass Deficiency Immunoglobulin G subclass deficiency affects one or more of the IgG subtypes but does not affect the overall levels of IgG. Because antibodies directed against carbohydrate and polysaccharide antigens are primarily IgG2, those with IgG2 deficiency are at greater risk for the development of sinusitis, otitis media, and pneumonia that is caused by polysaccharide-encapsulated microorganisms such as S. pneumoniae, H. influenzae type B, and Neisseria meningitides. Those with mild forms can be treated with prophylactic antibiotics. Those with more severe symptoms can be treated with IVIG. PRIMARY IMMUNE DYSFUNCTION: T-CELL DEFICIENCIES T lymphocytes include subtypes CD4 helper and CD8 cytotoxic T cells. They are responsible for the cell-mediated immune response that protects against fungal, protozoan, viral, and intracellular bacterial infections. They are also responsible for controlling malignant cell proliferation and coordination of the immune response. T-cell deficiencies lead to infections and other problems that are more severe than B-cell deficiencies. An example of a T-cell deficiency is DiGeorge syndrome. DIGEORGE SYNDROME Epidemiology DiGeorge syndrome, or congenital thymic hypoplasia, is an autosomal-dominant genetic condition that arises from the 22nd chromosome. Autosomal dominant means that the presence of only one altered gene is required for the disease to be present. Figure 19.2 illustrates the genetic inheritance of DiGeorge syndrome. This disorder arises spontaneously and is present at birth. It is hard to identify anyone at risk for this disorder, but gestational diabetes is implicated in increasing risk. A population-based study conducted by the Centers for Disease Control and Prevention (CDC) found a prevalence of about 1 in 6,000 in White, Black, and Asian populations, and 1 in 3,800 in Hispanic populations. Pathophysiology DiGeorge syndrome arises from a disturbance of the normal embryological development of the pharyngeal pouches occurring between the 6th and 10th weeks of gestation. Pharyngeal pouches are the embryonic precursors to specific organ systems in the head, neck, and chest. For example, the third and fourth pharyngeal pouches develop into the thymus, parathyroid gland, and aorta. The pulmonary artery arises from the sixth pharyngeal pouch. The effects of DiGeorge syndrome are dependent on which pharyngeal pouch is affected but typically involve dysfunction of the thymus gland and parathyroid, facial deformities such as cleft palate, and heart anomalies. The thymus gland is responsible for T-cell production and differentiation. Thymus dysfunction results in T-cell deficiencies. The deficiencies vary depending on the amount of thymus that is affected. Because T cells help B cells mature, the lack of T cells usually affects B-cell activity also. T-cell function may improve with age depending on the severity of involvement. This chapter will explore how DiGeorge syndrome affects the immune system. Clinical Manifestations Immune dysfunction caused by T-cell deficiencies, such as DiGeorge syndrome, results in recurrent infections. For those affected by DiGeorge syndrome there are variations in the type and severity of dysfunction due to the variation in extent of the body system(s) affected. If the patient has some thymic function, infections may be frequent but not necessarily severe. Typical infections in those with poor immunity include yeast, fungal, protozoan, and viral illnesses such as chickenpox, measles, and rubella, which can be fatal. Candida albicans is almost always seen in patients with T-cell deficiencies. Frequent colds and ear infections are common. The type of infections that frequently occur in an immunocompromised patient are referred to as "opportunistic infections" because they utilize the hosts poor defense (poor immunity) to invade the host. Generally, those with a fully functioning immune system are not affected or have very minor symptoms if infected with these microorganisms. Other disorders that occur in DiGeorge syndrome are related to the specific body systems affected (Box 19.1). The acronym CATCH is formed by the first letter of each of these disorders. Because the disorder is caused by the deletion of a small piece of chromosome 22, the healthcare community sometimes refers to DiGeorge syndrome as CATCH-22. Other clinical manifestations of DiGeorge syndrome may include: General Weakness or tiring easily Failure to thrive Failure to gain weight (in children) Small stature Difficulty feeding (in babies) Respiratory Frequent infections---many of which become severe, difficult to treat, or require hospitalization Shortness of breath Bluish skin due to low oxygen-rich blood Clubbing of fingernails Other Twitching or spasms around the mouth, hands, arms, or throat Poor muscle tone Delayed achievement of developmental milestones Delayed speech development Learning delays or difficulties, emotional and behavioral problems Cleft palate or other problems with the palate Certain facial features, such as low-set ears, wide-set eyes, or a narrow groove in the upper lip Interprofessional Management Medical Management Diagnosis Diagnosis of the disorder is primarily done by genetic testing. DiGeorge syndrome is determined with a finding of submicroscopic deletion of chromosome 22. Treatment General treatment includes pharmacological therapy, such as calcium supplements to prevent tetany and seizures, which could be caused by hypocalcemia from hypoparathyroidism if the parathyroid gland is affected. Specific treatment of the T-cell immune deficiency may include: Aggressive treatment of infections. IVIG to provide short-term passive immunity; usually given every 3 or 4 weeks with individualized dosage and the scheduling. Prophylactic antibiotics. Bone marrow transplantation in severe cases Surgical Management Surgery such as thymus tissue transplantation is an option if the thymus is absent. This is usually discovered at birth, and the child is extremely vulnerable to infections. Ideally, the procedure is performed within 3 to 6 months of age, prior to the onset of multiple infections and the loss of the mother's immunity. The tissue for this transplantation is obtained from other infants having cardiac surgery. In cardiac surgery, to successfully visualize the heart, portions of the thymus gland are excised. With parental consent, that tissue can be saved for use in thymus transplantation for children with DiGeorge syndrome. Surgery may also be an option to correct the cardiac defects of DiGeorge syndrome, such as tetralogy of Fallot. Complications Those affected by DiGeorge syndrome with a poor immune system due to the small thymus, may have an increased risk of autoimmune disorders, such as rheumatoid arthritis (RA) and Graves' disease. Patients with T-cell dysfunction are also at risk for graft-versus-host disease. This is manifested when T cells in grafted tissue such as transfused blood attack and destroy the host's tissues. DiGeorge syndrome may cause other complications such as in the development and function of the brain, resulting in learning, social, developmental, or behavioral problems. Delays in speech development are common. Common disorders found in those with DiGeorge syndrome include attention deficit-hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). In later life, the patient is at increased risk of mental health problems, including depression, anxiety disorders, schizophrenia, and other psychiatric disorders. Nursing Management Assessment and Analysis The clinical manifestations of DiGeorge syndrome are related to the disturbance of normal embryonic development of the pharyngeal pouches that leads to the eventual development of the thymus and parathyroid gland, facial structures, and cardiac structures. Table 19.2 summarizes the assessment data for DiGeorge syndrome. Nursing Diagnoses/Problem List Risk for infection related to compromised host defenses secondary to T-cell immunodeficiency (inadequate function of B cells secondary to T-cell deficiencies) Risk for complications of opportunistic infections Deficient knowledge related to condition, prognosis, treatment, self-care, and discharge Nursing Interventions Assessments General Survey Decreased level of consciousness, pallor, ill appearing, and cachectic may indicate overall poor health. Vital signs Increased temperature may indicate infection; respiratory rate may increase with respiratory infections in an effort to increase oxygenation, increased or decreased blood pressure will indicate infection, shock and organ involvement. Lung sounds Decreased or adventitious breath sounds may be present with a respiratory infection. Calcium levels Calcium levels may be decreased because of hypoparathyroidism. Tetany Lack of plasma calcium due to hypoparathyroidism leads to increased neuromuscular activity such as sustained contractions Monitor WBCs. An increase or decrease in WBC count is an indication of infection. Trending these values helps determine the presence of infection and evaluate the response to treatment. Actions Administer calcium supplements as ordered. A low serum calcium concentration requires calcium supplementation to prevent complications such as tetany or bronchospasm. Infection control precautions and standard precautions, including thorough hand hygiene Prevent infection: Implementation of hygiene practices is the best infection-preventive measure. Strategies for addressing feeding difficulties include modification of spoon placement when eating; treatment for gastroesophageal reflux with acid blockade, prokinetic agents, and postural therapy; and medication to treat gastrointestinal dysmotility and facilitate bowel evacuation. Feeding difficulties can occur with this syndrome in 30% of patients. Interprofessional collaboration and care management An interprofessional evaluation involving healthcare providers from many specialties is often necessary. Specialties that may be consulted are: genetics, immunology, plastic surgery, speech pathology, otolaryngology, audiology, dentistry, cardiology, neurology, and mental health. Teaching Overview of the disease process It is important that the patient and family are able to both detect early signs of infection and prevent infection. Additionally, they need to understand the genetic disease. Growth and development milestones, need for early assessment for learning disabilities, need for ongoing medical care and evaluation The family needs to know the normal developmental milestones to evaluate their child's development. Information and emotional support to include peer support groups and respite care for caregivers if necessary. The family needs to have community resources to provide support with their child's diagnosis. Evaluating Care Outcomes The patient with DiGeorge syndrome that compromises their immune system will be compliant with their individualized protocol (plan of care) to promote improved immunity, recognize the early symptoms of infection/illness notifying their provider immediately, and will have no life-threatening infections. This is accomplished through on-going care management with an interprofessional team that supports the patient and family to achieve optimal health. OTHER T-CELL IMMUNE DEFICIENCIES DiGeorge syndrome provid es one example of a T-cell deficiency. Other T-cell deficiencies include chronic mucocutaneous candidiasis and hyper-IgM (HIGM) syndrome. Chronic Mucocutaneous Candidiasis Chronic mucocutaneous candidiasis is a T-cell disorder that is autosomal recessive. It involves the thymus and other endocrine glands, resulting in an autoimmune disorder with endocrine failure and immunodeficiency. This disorder is evidenced by recurrent Candida infections of the skin, nails, and mucous membranes. Other problems include hypocalcemia and tetany due to hypofunction of the parathyroid glands. Morbidity is high because of endocrine dysfunction, specifically hypofunction of the adrenal cortex. Hyper-IgM Syndrome HIGM syndrome is an X-linked immunodeficiency with low IgG and IgA serum levels, normal or high IgM and IgD levels, and absent IgG-specific antibodies. This was previously designated as a B-cell defect but is now known to be a T-cell defect. In this disorder, T cells do not have the ability to signal B cells to undergo switching to IgG and IgA and can produce only IgM. Although it is identified by the levels of antibodies, its cause is a defect in cell-mediated immunity. The estimated prevalence of HIGM is 2:1,000,000 males of European, African, and Asian descent. The diagnosis of HIGM is based on clinical findings, family history, and molecular genetic testing of CD40LG, the only gene known to be associated with HIGM. As with XLA, clinical manifestations in boys are seen in the first 2 years of life. Recurrent infections include sinusitis, otitis media, tonsillitis, and pneumonia. Patients are also susceptible to opportunistic infections, especially Pneumocystis jiroveci, because of the cell-mediated immunity defect. Complications include the development of an autoimmune disease of the blood, such as hemolytic anemia, thrombocytopenia, and neutropenia PRIMARY IMMUNE DEFICIENCY OF BOTH T AND B CELLS One type of primary immune deficiency that affects both T and B cells is severe combined immune deficiency (SCID). This disorder is a potentially fatal primary immunodeficiency and involves a combined absence of T-lymphocyte and B-lymphocyte function. There are at least 13 different genetic defects that can cause SCID. David Vetter, who was born with SCID, was known as the boy in the bubble. When he was born in 1971, a bone marrow transplant from an exactly matched donor was the only cure, and no one in his family was a match. For 12 years, David lived in a protected, germ-free environment at Texas Children's Hospital. In 1984, after receiving a bone marrow transfusion, David died from lymphoma, a cancer that was introduced into his system by the Epstein--Barr virus. Today, the outcomes and treatment of SCID are different. Read about David's story here: (https://primaryimmune.org/story-david-vetter). Another primary immunodeficiency disorder is Wiskott--Aldrich syndrome, which results from a combined B- and T-cell defect; its characteristics include recurrent infection, eczema, and thrombocytopenia. The bleeding problems are unique to this primary immunodeficiency disorder and are the result of unusually small, dysfunctional platelets. The inheritance is X-linked recessive. SECONDARY IMMUNE DYSFUNCTION: THERAPY-INDUCED DEFICIENCIES Epidemiology Secondary immune deficiencies are caused by a variety of factors, such as medication-induced immunosuppression, radiation, and surgery. The most common is medication-induced immunosuppression. Two of the most common reasons immunosuppressive therapy is prescribed are the treatment autoimmune disorders and prevention of transplant rejection. Immunosuppression is also a side effect of chemotherapy in the treatment of cancer. Chemotherapy can lead to leukopenia. This results in decreased cell-mediated and humoral responses. Another type of medication that suppresses the immune system is corticosteroids. Radiation therapy can also cause secondary immunodeficiency by destroying dividing and resting cells. With increased radiation, there is increased pancytopenia, which is a decreased number of all types of blood cells---red blood cells (RBCs), WBCs, and platelets. This causes a further suppression of the immune system function. Finally, surgical removal of organs of the immune system, such as the lymph nodes, thymus, or spleen, also suppresses immune response. Pathophysiology Chemotherapeutic medications used to treat cancer are cytotoxic, which means they target rapidly dividing cancer cells. Cells of the immune system are naturally rapidly dividing and so are inadvertent targets of chemotherapy. Cells such as WBCs, including lymphocytes and phagocytes, are also destroyed by chemotherapy. The result is a decrease in the number of circulating lymphocytes and phagocytes. Additionally, chemotherapy causes general immunosuppression because remaining lymphocytes are unable to release antibodies and lymphokines, which are substances that bind to receptors on target cells, facilitating a directed immune response. Immunosuppressive therapy, such as corticosteroid administration, is used to treat autoimmune disorders (discussed later in this chapter) or prevent transplant rejection by specifically targeting the immune system. The immunosuppressive medications interfere with cell-mediated immunity or the production of antibodies. Corticosteroids have anti-inflammatory effects in addition to immunosuppressive effects. The anti-inflammatory effects include stabilizing blood vessel membranes, decreasing permeability, and blocking the movements of neutrophils and monocytes. Immunosuppressive effects include decreased serum T cells because corticosteroids keep T cells in the bone marrow. This results in the suppression of cell-mediated immunity and lymphopenia as well as a decrease in the inflammatory response. There is also decreased IgG production and decreased antibody to antigen binding. Interprofessional Management Medical Management Management of patients with secondary immune dysfunction is primarily preventive. Good hand washing is the first step. Avoiding contact with people who have obvious infections, such as a cough or cold, is recommended. Regular check-ups and communication with the provider is necessary. Prompt action with any signs of infection, such as fever, chills, or cough, is essential. Any signs of urinary tract infection, such as dysuria, hematuria, urgency, frequent urination, or lower back pain, should be reported immediately. Nursing Management Assessment and Analysis The goal of managing secondary immune deficiency is to protect the patient from infection. The nurse assesses for signs of infection, such as a fever over 100°F (37.8°C), chills, nasal congestion, rhinorrhea, cough, sore throat, or cloudy and foul-smelling urine. Nursing Diagnoses/Problem List Risk for infection related to compromised host defenses secondary to therapy-induced immunodeficiency Risk for complications of opportunistic infections Nursing Interventions Assessments Vital signs Increased temperature, hypotension, and tachycardia all indicate infection. The temperature increases in an attempt to kill organisms. Hypotension results because of increased permeability causing fluid shifts and dehydration. Tachycardia occurs in an attempt to compensate for the hypotension. Signs of infection: Monitor WBC and differential. Increased WBCs and leukocytes are part of the body's natural response to infection. Respiratory Decreased or adventitious breath sounds may be present with a respiratory infection. Increase in respiratory rate and rhythm, increased secretions, and pain upon percussion of sinuses and cough can indicate infection. Genitourinary Cloudy or foul-smelling urine, frequency and urgency, hematuria, and fever may indicate a urinary tract infection. Costovertebral angle (CVA) tenderness often indicates a kidney infection. Skin Skin rashes or lesions indicate skin infections, which may occur with immunodeficiency. Actions Practice good hand washing and encourage patient to screen family and others for potential symptoms of infections. Hand washing is the first step in preventing infections. A minor cold or cough in an immunocompromised patient can progress to a life-threatening infection. Treat infection with antibiotics or antivirals as ordered. Antibiotics or antivirals specifically targeting the organism help control the infection. The full course of antibiotics or antiviral medications must be consumed to prevent resistant infections and recurrence. Anticipate changing or discontinuing the immunosuppressive medication if possible. If possible, a change in medication will remove the cause of the secondary immune deficiency. This is considered only if the infection is deemed a greater risk than the primary problem being treated with the immunosuppressive medications and if an effective alternative medication is available. Teaching Avoid crowds or large gatherings, and avoid exposure to anyone with an obvious illness. This helps to avoid exposure to infections. Do not change cat litter boxes. Litter boxes expose the patient to toxoplasmosis. Avoid turtles and reptiles as pets. Turtles and reptiles carry diseases and bacteria such as Salmonella. Eat a low-bacteria diet. Avoid salads; raw fruit and vegetables; and undercooked meat, fish, and eggs including uncooked fish in sushi. These foods can carry bacteria and parasites that can cause infection. Report/contact a provider for any of the following: Temperature greater than 100°F (37.8°C) Cough/upper respiratory infection (URI) symptoms Cloudy urine A wound that is slow to heal, warm to touch, is swollen or has drainage Knowing the signs of infections and reporting them early to the healthcare provider can minimize infections and complications. Evaluating Care Outcomes A well-managed patient has a good understanding of their immune disorder and accompanying risks. This patient takes all appropriate precautions, practices good hand washing, and knows when to contact the provider. If an infection does occur, it is treated promptly with the appropriate antibiotic or antiviral therapy. EXCESSIVE IMMUNE RESPONSE In contrast to the immune deficiencies, when the immune system is initiated inappropriately or when it overreacts, autoimmunity and hypersensitivity disorders occur. Autoimmunity is when the body initiates an immune response against self; antibodies are formed that respond to normal healthy cells and tissue. The body fails to recognize these normal cells as self, which causes an immune reaction to occur against the perceived antigen, the healthy cell. The cause of autoimmune diseases is still not completely known. Theories of causation include the inheritance of susceptible genes that may contribute to the failure of self-tolerance. Even with a genetic predisposition, some trigger is required for the initiation of autoreactivity. This may include an infectious agent such as a virus, medications, hormones, or environmental factors. Autoimmune diseases are often classified as systemic or organ specific. A hypersensitivity reaction is when the immune response is overreactive to a foreign antigen. An antigen is a foreign protein that stimulates an immune response in a susceptible individual. Hypersensitivity reactions can be damaging to the body, may cause discomfort, and may also be fatal, as in anaphylaxis. There are several categories of hypersensitivity reactions. They can be divided into five types---type I, type II, type III, type IV, and type V---as illustrated in Table 19.4. These types are based on the specific mechanisms and mediators that are involved in the process, the source of the antigen, and the length of time for the reaction to occur. This chapter discusses all of these hypersensitivity reactions but focuses on type I and type IV. Hypersensitivity reactions and autoimmunity overlap. Many autoimmune diseases have hypersensitivity as part of their pathogenesis. Graves' disease is an autoimmune disorder that is a result of a type V hypersensitivity reaction. Systemic lupus erythematosus (SLE) is the result of a type III hypersensitivity reaction. Goodpasture's syndrome is an example of a type II hypersensitivity reaction. Similarly, most but not all hypersensitivity reactions are manifested in autoimmune disorders, but one that does not manifest as autoimmune is a type I hypersensitivity reaction---a typical allergic reaction. TYPE I HYPERSENSITIVITY REACTION: IMMEDIATE Epidemiology Type I hypersensitivity reaction is a rapid or immediate allergic reaction. There can be a local (atopic) reaction or a systemic reaction. The most common is allergic rhinitis also called seasonal allergies or hay fever, a local reaction. The most severe form is anaphylaxis, a systemic reaction. A genetic predisposition exists for the development of allergic diseases. If both parents have allergies, there is an 80% chance the child will have allergies. If the mother is allergic, the child is likely to also have allergies. Approximately 20% of the population is atopic, which means having an inherited tendency to become sensitive to environmental allergens, the substances that cause an allergic response. Potential allergens include food (e.g., peanuts, tree nuts, seafood), medications (e.g., penicillin, sulfa), insect bites (e.g., bees, fire ants, hornets, yellow jackets, and wasps) and biting insects (e.g., mosquitoes), diagnostic testing substances (e.g., radiocontrast media), and blood (via blood transfusions) In Western countries, between 10% and 25% of people annually are affected by allergic rhinitis. Allergic rhinitis affects 35.9 million individuals, which is about 11% of the population in the United States. It can be perennial or seasonal. Perennial rhinitis is caused by dust, molds, and animal dander. Seasonal rhinitis is caused by pollens from trees, weeds, or grasses. The person's immune system responds to the harmless material as though it were a real threat. An accurate incidence of anaphylaxis is not known because of the differentiation between a full-blown anaphylactic response and milder cases. Milder forms are more common. There are up to 1,500 fatal cases of anaphylaxis annually. There are at least 40 deaths per year due to insect venom, about 400 deaths due to penicillin anaphylaxis, approximately 220 cases of anaphylaxis and 3 deaths per year due to latex allergy, and an estimated 150 people die annually from anaphylaxis due to food allergy. A recent review concluded that the lifetime prevalence of anaphylaxis is 1% to 2% of the population as a whole. The incidence of anaphylaxis appears to be increasing, especially cases in children attributed to food allergy. Pathophysiology The primary mediator of type I hypersensitivity reactions is immunoglobulin E (IgE). The first time a patient is exposed to an allergen, IgE is produced. The IgE antibodies attach to mast cells. The next time the patient is exposed to that specific allergen, it binds to the IgE antibodies attached to the mast cells. This causes the mast cell to degranulate, releasing histamine and other chemicals such as leukotrienes and prostaglandins that cause smooth muscle contraction, vasodilation, increased vascular permeability, bronchoconstriction, and edema. This results in the symptoms associated with the allergy. The allergic reaction is illustrated in Figure 19.3. Anaphylaxis is the most severe form of type I hypersensitivity reaction that exhibits the extremes of the symptoms. Table 19.5 indicates the specific mediator of a type I hypersensitivity reaction, its pathophysiological activity, and the symptoms it produces. Anaphylaxis can occur when these mediators are released systemically. Clinical Manifestations The signs and symptoms associated with an allergic reaction may be local or systemic. Clinical manifestations of allergic rhinitis, which is considered a local reaction, include nasal discharge, sneezing, inflammation of the nasal passages, pruritus of the upper airways and itchy, watery eyes with stringy mucous discharge that may be inflamed or appear bloodshot (allergic conjunctivitis). The patient may also complain of headache or sinus pressure. In anaphylaxis, a systemic response, there is an immediate response to an allergen. The patient complains of dyspnea and shortness of breath. Audible wheezes and/or crackles are present. A skin reaction or rash may appear. Patients may experience nausea, vomiting, or diarrhea. They complain of anxiety and often state they feel a flush of heat. Angioedema, swelling just below the surface of the skin, typically around the mouth and eyes, may also be present. In an extreme anaphylactic reaction, there is a severe and rapid onset of symptoms. They include bronchospasm with extreme dyspnea and shortness of breath and wheezing. The patient may have hoarseness and stridor, a high-pitched crowing sound, which indicates narrowing of the airways. Severe or untreated reactions result in anaphylactic shock with hypotension and tachycardia due to the vasodilation and capillary leak Interprofessional Management Medical Management Diagnosis Diagnostics include a WBC count and differential. This test reveals an increase in eosinophils, which indicates the presence of an allergic response. Eosinophils are the key inflammatory cells seen in allergic rhinitis. As eosinophils increase, the symptom severity increases. A normal count is 1% to 2%. Someone with severe seasonal allergic rhinitis may have an eosinophil count as high as 12%. Skin testing is performed to determine the specific allergen. Various allergens are introduced via a scratch test to determine which produce a positive reaction that indicates an allergy. The results are used to determine the causes of the allergic rhinitis, urticaria or hives, and asthma (airway symptoms). A localized reaction or wheal indicates a positive result within 15 to 20 minutes. When preparing for allergy testing, glucocorticoids and antihistamines are discontinued 5 days prior to testing if possible. NSAIDs may also be discontinued. The forearm(s) and the back are the most common sites used as sites for scratch testing. Treatment Allergy management includes the identification, treatment, and prevention of allergic responses. Treatment of type I hypersensitivity reactions also depends on the severity. This means the responder must assess the patient and determine if the reaction is local or systemic as well as how quickly the symptoms are progressing. Avoidance therapy can be successful when the allergies have been identified. If a reaction does occur but is mild, merely removing the offending agent may be the only necessary action. If symptoms persist, antihistamines are utilized (Table 19.6). Diphenhydramine hydrochloride (Benadryl), an antihistamine, decreases edema and constriction of smooth muscle in the respiratory tract and blood vessels; however, it is sedating for most patients. This is because it is a first-generation antihistamine and crosses the blood--brain barrier. Often, diphenhydramine is avoided and second-generation antihistamines such as cetirizine (Zyrtec), loratadine (Claritin), or fexofenadine (Allegra) are used on a daily basis. Steroids may be indicated to decrease the inflammatory response and decrease mast-cell degradation. Short- and long-acting beta-agonist bronchodilators may aid in easing respiratory distress by causing respiratory smooth muscle relaxation. In severe cases of anaphylaxis, prompt recognition and treatment are necessary to avoid death (see Evidence-Based Practice). Emergency intervention and cardiopulmonary resuscitation may be necessary. Nursing Management Assessment and Analysis The clinical manifestations associated with a type I hypersensitivity reaction are caused by the release of histamine and other chemical mediators from mast cells upon exposure to the antigen. Typical results from histamine release include bronchoconstriction and increased capillary permeability. A runny nose, itching, red eyes, and rash are common. In extreme cases, the patient complains of shortness of breath and dyspnea. Wheezes may be audible or heard on auscultation. Nursing Diagnoses/Problem List Risk for ineffective breathing pattern, airway clearance, and gas exchange related to bronchial inflammation, increased upper airway secretions, and inflammation Risk for impaired adjustment related to lifestyle changes necessary to avoid and manage allergic reactions Risk for complications of allergic reaction: wheals, itching, light-headedness, hypotension, wheezing, dyspnea, chest tightness, decreased level of consciousness, respiratory distress, and shock Nursing Interventions Assessments General Survey: Determine if the patient is experiencing a local or systemic reaction. Assess for anxiety or confusion, position (sitting comfortably or in a tripod position trying to catch their breath), notice facial edema or cyanosis. This will help the nurse determine if this is a local or systemic reaction and then plan actions including calling for additional help. Monitor respiratory rate, depth, and quality; lung sounds; pulse oximetry; cyanosis; and arterial blood gases (ABGs). Because of bronchoconstriction produced by the histamine release, the respiratory rate may be increased and ineffective. Wheezing, dyspnea, stridor, and chest tightness may be present indicating and causing impaired ventilation. Decreased SpO2 and ABGs demonstrating hypoxemia indicate impaired oxygenation. Blood pressure/pulse If anaphylaxis occurs, hypotension may be present because of vasodilation and capillary leak seen in distributive shock (discussed in detail in Chapter 14). Tachycardia is present as a compensatory response to the hypotension. Irregular and increased pulse and decreased blood pressure are also due to leukotriene release, which constricts airways and coronary vessels. General systems assessment Initial symptoms caused by the histamine release may be a rash and itching followed by watery red eyes, runny nose, and sneezing. Angioedema may be present. The patient may complain of feeling faint and diaphoretic. Diarrhea, stomach cramps, and abdominal pain may be present because of increased acid production due to histamine release. Actions Discontinue offending agent ASAP; if the offending agent is in an IV infusion, stop the IV medication, change the IV tubing, and hang normal saline. If the reaction is from a food or environmental trigger, remove if possible (e.g., remove the food tray, have the person with a perfume that triggered the reaction removed). The medication causing the allergic reaction needs to be stopped to prevent any further reaction. The tubing has to be changed to prevent any further medication being infused. If the trigger is not removed, it may cause an increased and continued reaction). Anticipate STAT medication administration of IM epinephrine if reaction is severe (intravenous \[IV\] dose if IM ineffective). Epinephrine is the medication of choice to counteract anaphylactic shock by causing blood vessel constriction, raising blood pressure, and improving cardiac output through inotropic and chronotropic activity. It also acts as a beta-2 agonist to promote bronchial smooth muscle relaxation. Administer oxygen as ordered via 100% nonrebreather. The vasodilation, capillary leak, and other shock responses are interfering with oxygenation and tissue perfusion. Starting oxygen enhances oxygen delivery to the tissues, especially the brain cells and cardiac muscle cells. Elevate the head of the bed as able; care is taken if hypotension is present. To improve ventilation, elevate the head of the bed, but do not compromise blood pressure if low. Administer further medications as ordered. Administer diphenhydramine hydrochloride (Benadryl) as ordered. Diphenhydramine hydrochloride (Benadryl) is a histamine-receptor blocker; histamine is the main mediator in type I hypersensitivity reaction. Administer corticosteroids as ordered. This inhibits the inflammatory response exacerbating the allergic response. Administer bronchodilators as ordered. Beta agonists or bronchodilators facilitating bronchial smooth muscle relaxation may be indicated to ease bronchoconstriction. Administer H2 blockers as ordered. In severe reactions, H2 blockers are ordered to assist the H1 blocker (antihistamine) to help stop the reaction. Administer vasopressors as needed. If anaphylaxis occurs, vasoactive medications may be indicated to constrict blood vessels and increase blood pressure. Have emergency resuscitation equipment available (endotracheal intubation or tracheostomy) for possible progression to anaphylactic shock. As anaphylaxis progresses, there may be complete circulatory and ventilatory collapse requiring resuscitation. Maintain careful monitoring of the patient. Continuous monitoring is crucial as nursing assessment will recognize early signs of a new or worsening reaction allowing intervention as necessary. Also, because medications have half-lives and will eventually "wear off", patients may require repeated doses of these medications over time to ensure a rebound reaction does not occur. Stay with the patient and provide reassurance. Provide support to the patient who is anxious and fearful. Teaching Educate patient regarding potential causes (triggers) in the environment and ways to avoid exposure to the allergen. Minimizing any potential allergen exposure can prevent any future allergic or anaphylactic reaction. Educate the patient regarding the signs and symptoms of an initial reaction: rash and itching. The patient should know the possible signs and symptoms of a reaction to be able to react in a timely manner and prevent a more serious reaction. Educate the patient on the use of devices that are manufactured to be used in an emergency to give IM epinephrine such as an EpiPen. These devices inject a dose of epinephrine when the patient has been exposed to an allergen and is at risk for or experiencing anaphylaxis. Advise patient to obtain a Medic Alert bracelet or pendant and ensure that healthcare professionals are aware of any potential allergies. A Medic Alert bracelet alerts others to a patient's allergies. Healthcare professionals should be aware of any potential reactions to guard against potentially dangerous food or medication exposure. Review allergies with patient and caregivers. Ensuring the patient record is up to date will help to prevent future reactions. Evaluating Care Outcomes A well-managed patient is free of symptoms of the allergic reaction and has a normal oxygen level. With the removal of the offending agent and appropriate treatment of the allergic reaction with antihistamines, steroids, bronchodilators, and epinephrine, if necessary, there will be resolution of symptoms. The patient is discharged when respiratory and cardiovascular assessment criteria have returned to baseline. After a severe allergic reaction for which the cause is not known, a trigger should be identified if possible. An allergist/immunologist should perform an evaluation, which may include a detailed history, physical examination, skin testing, in vitro testing, and challenges when indicated. Future avoidance of the identified triggers should prevent subsequent anaphylactic episodes TYPE II HYPERSENSITIVITY REACTION: CYTOTOXIC Type II antibody-mediated hypersensitivity reactions include three subtypes: Complement and antibody-mediated cell destruction Complement and antibody receptor-mediated inflammation Antibody-mediated cellular dysfunction Epidemiology One example of a type II hypersensitivity reaction that causes cell destruction is erythroblastosis fetalis, which is due to Rh sensitization (Fig. 19.4). Rh sensitization occurs in approximately 1 in 1,000 births to Rh-negative women. The incidence of Rh-negative blood type is approximately 15% to 20% of individuals of European descent, 5% to 10% of individuals of African descent, and less than 5% of individuals of Chinese and American Indian descent. An example of type II hypersensitivity that causes inflammation is Goodpasture's syndrome, which is rare. It is more common in European populations, in which there is approximately one case present per million people per year. This syndrome is most common between ages 18 and 30 and again between 50 and 65. It is more common in males by a 6:1 ratio. An example of type II hypersensitivity that causes cell dysfunction is myasthenia gravis. This disease affects approximately 2 out of 100,000 people. It can occur at any age but is most common in female individuals who are 18 to 25 years of age and male individuals who are 60 to 80 years of age. Pathophysiology and Clinical Manifestations The pathophysiology for each of the three subtypes of type II hypersensitivity has a basic component of complement and antibody-mediated cell involvement. Subtype 1: Complement- and Antibody-Mediated Cell Destruction Hypersensitivity Complement- and antibody-mediated cell destruction hypersensitivity reaction is cytotoxic and antibody dependent. Complement is a series of proteins that distinguishes the individual's own cells from foreign substances: self-tolerance or self-recognition. When this function is not working, the individual is susceptible to autoimmune diseases as a result of the hypersensitivity reaction. The antibodies involved in this hypersensitivity reaction are immunoglobulin M (IgM) and immunoglobulin G (IgG). In subtype 1, the targeting of cells for deletion by antibodies is mediated by the complement system or by antibody-dependent cell-mediated cytotoxicity (ADCC). Destruction of cells by the complement-mediated system involves opsonization of cells or coating them with molecules that attract the phagocytes. ADCC does not require complement. With ADCC, cells are coated with IgG antibody and are killed by various effector cells that bind to their target by the receptors for IgG; cell lysis results without phagocytosis. Examples of subtype 1 are blood transfusion reactions that occur when incompatible blood is transfused (Fig. 19.5; see Safety Alert), hemolytic disease of the newborn due to blood type (ABO) or Rh incompatibility, and certain medication reactions. In the example of medication reactions, medications or metabolites of medications bind to the surface of either RBCs or WBCs. This action causes an antibody response that lyses the medication-coated cell. Subtype 2: Complement- and Antibody-Mediated Inflammation Complement- and antibody-mediated inflammation causes inflammation rather than destruction. An example of this type is Goodpasture's syndrome, also known as anti-glomerular basement membrane antibody disease. Goodpasture's syndrome is an autoimmune disease triggered when the patient's immune system attacks the Goodpasture's antigen, an antigen in the glomerular basement membrane. The exact cause and trigger agent are not known. The antibody-mediated autoimmune reaction involves the glomerular and alveolar basement membranes. The antibodies combine with tissue antigen to activate complement. This causes deposits of IgG to form along the basement membranes of the lungs or kidneys. This disease is characterized by glomerulonephritis and hemorrhaging of the lungs and results in damage to the kidney and lungs. This is a rapidly progressing disorder. Subtype 3: Antibody-Mediated Cellular Dysfunction Antibody-mediated cellular dysfunction is a hypersensitivity reaction where the antibodies bind to cell-surface receptors. An example is myasthenia gravis. In myasthenia gravis, autoantibodies to acetylcholine receptors on the neuromuscular endplates are formed. The autoantibodies either block the action of acetylcholine or mediate the destruction of receptors. Either of these situations leads to decreased neuromuscular function and weakness. See Chapter 38 for more information on myasthenia gravis. Interprofessional Management Medical Management As in type I hypersensitivity reactions, treatment of type II reactions requires removal of the medication or blood product that is causing the reaction. In addition, there are procedures to remove the offending blood components from the plasma. Plasmapheresis involves filtering the plasma to remove substances that precipitated the cytotoxic reaction. In this procedure, blood is removed via a catheter, RBCs and plasma are separated, and the RBCs are returned to the patient. In traditional plasmapheresis, the plasma is treated and returned to the patient. In plasma exchange, the patient's plasma is discarded and replaced by donor plasma. Plasmapheresis is covered in more detail in Chapter 20. Goodpasture's syndrome is treated with corticosteroids and immunosuppressive medications in addition to plasmapheresis to slow the progression. Some patients require intravenous immunoglobulin (IVIG), a solution made from human plasma containing mostly IgG antibodies, to maintain antibody protection. Depending on the amount of renal involvement, dialysis may be necessary. Renal transplantation is an option for some patients. Complications Complications of immune system reactions such as renal failure or hemolytic reaction may be life-threatening. Renal function can be completely lost in a matter of days in a condition known as rapidly progressive glomerulonephritis. Lung damage, occurring as rapidly as the renal damage, may cause severe impairment of oxygenation requiring artificial ventilation. The patient may be anemic because of loss of blood through lung hemorrhaging over a long period. In Goodpasture's syndrome, lung hemorrhaging most often occurs in smokers and those with damage from lung infection or exposure to fumes. Medication reactions causing hemolytic reactions that cause cell lysis can produce transient anemia, leukopenia, or thrombocytopenia. Once the medication has been removed, these effects are corrected. TYPE III HYPERSENSITIVITY REACTION: IMMUNE COMPLEX Type III hypersensitivity reactions are immune complex--mediated reactions. These immune complex allergic disorders are mediated by the formation of antigen--antibody complexes. Similar to type I hypersensitivity reactions, there are two categories of type III reactions: systemic and local immune complex reactions. Examples of systemic immune complex reactions are SLE, RA, and serum sickness. A local immune complex reaction is Arthus reaction. Epidemiology SLE may be caused by genetic, environmental, or unknown factors. In the United States, the prevalence of SLE is estimated to be about 53 per 100,000. SLE occurs more frequently and with greater severity among those of non-European descent, and the prevalence is higher in those of Afro-Caribbean descent. SLE occurs more often in female than male persons at a rate of 9 to 1, which is similar to other autoimmune diseases. RA affects all ethnic groups, and it affects female individuals 2.5 times more often than male individuals. Arthus reaction is considered to be rare, and no specific prevalence is known. Pathophysiology and Clinical Manifestations A type III hypersensitivity reaction involves the formation of an antigen--antibody immune complex. IgG is the immunoglobulin involved. These immune complexes are large molecules of antibody combined with antigen and, due to their size, are difficult for the body to remove. Disease results when they are not removed but lodge in the tissues. Systemic Immune Complex Disorders Manifestations of RA are caused by the immune complexes that are lodged in joint spaces. When there are too many immune complexes, too much complement is activated, and an acute inflammatory response develops. Complement attracts neutrophils to the area of inflammation and stimulates the release of lysosomal enzymes. This release causes tissue damage, especially in small blood vessels where the immune complexes tend to lodge and the lack of blood supply causes tissue necrosis. This is followed by destruction of tissue, scarring, and fibrous changes. SLE produces antibodies against virtually any organ or tissue in the body. It forms immune complexes that lodge in the vessels, causing vasculitis; in the glomeruli, causing nephritis; and in the joints, causing arthralgia (joint pain) and arthritis. It affects connective tissues and multiple organs, resulting in cardiovascular, renal, or neurological complications. Serum sickness is an immune system reaction to certain kinds of medications, most commonly penicillin and other antibiotics or injected proteins (antiserum) used to treat immune conditions. Antiserum is given to enhance immunity, most commonly after a snake bite. Serum sickness occurs when the body mistakenly identifies a protein from the antiserum or medication as harmful and activates the immune system to fight it off. This results in the collection of immune complexes in blood vessel walls of the skin, joints, and kidney. The deposited complexes activate complement. This then increases vascular permeability, and phagocytic cells are recruited to the area that causes tissue damage and edema. Serum sickness usually develops within 7 to 12 days after initial exposure but sometimes can take as long as 3 weeks. If the patient is exposed to the substance a second time, serum sickness tends to develop faster (within 1 to 4 days), and a very small amount may cause an intense response. Serum sickness is less common currently because vaccines are made with human proteins rather than being animal based. Clinical manifestations include fever, arthralgia, lymphadenopathy (swollen lymph nodes), malaise, and possibly polyarthritis (arthritis in multiple joints), nephritis (inflammation of the nephrons in the kidney), urticaria (hives), a patchy or generalized rash, or extensive edema involving the face (angioedema), neck, and joints. The symptoms may last only a few days, and damage is temporary, but if there is prolonged exposure, it may lead to irreversible damage. In extreme cases, serum sickness may be fatal. Local Immune Complex Reactions Arthus reaction is a localized vasculitis due to the deposit of immune complexes in dermal vessels after intradermal or subcutaneous injections, typically vaccinations. Within 4 to 10 hours, a red raised lesion develops at the site of the injection. An ulcer forms in the center. This is due to the in-situ formation of antigen--antibody complexes. Interprofessional Management Medical Management Removal of the offending agent is the first treatment. Symptom treatment for systemic immune complex reactions includes aspirin for joint pain and antihistamines for the pruritus. For the severe reactions, epinephrine or systemic corticosteroids may be utilized as well. Epinephrine is used for symptomatic relief of serum sickness, urticaria, and angioedema. Corticosteroids such as prednisone have been used to reduce the inflammation associated with serum sickness. TYPE IV HYPERSENSITIVITY REACTIONS Epidemiology Type IV is a delayed-type hypersensitivity. Examples are poison ivy, the Mantoux test for tuberculosis, and latex allergy. Some patients may experience a mixed type I and type IV reaction. Latex allergy may be an immediate, rapid type I hypersensitivity reaction or a type IV delayed hypersensitivity reaction. The prevalence of latex allergy in the general population is approximately 2%. People at high risk for developing a latex allergy include healthcare workers who are routinely exposed to latex; patients who have undergone multiple surgical procedures, especially patients with spina bifida; people with a previous history of atopic dermatitis or pre-existing hand dermatitis; and people who are female. Pathophysiology and Clinical Manifestations Type IV cell-mediated/delayed-type hypersensitivity is also known as cell-mediated immune memory response or antibody independent. This reaction is different from the previous reactions in that it is mediated by cells rather than antibodies. This type of hypersensitivity reaction is delayed and is regulated by T lymphocytes that are damaging to cells or cytotoxic. The reaction usually occurs 24 to 72 hours after exposure to the antigen. Sensitized T lymphocytes are the cells that attack the antigens and release cytokines and thus mediate the reaction. The macrophages and enzymes released by macrophages are responsible for most of the tissue destruction. In the delayed hypersensitivity reaction, it takes 24 to 48 hours for a response to occur. Clinical manifestations of a local reaction typical of a positive TB test include a wheal and flare reaction. This reaction is a raised area containing edematous fluid surrounded by red flare. The clinical manifestations of a latex allergy may range from local contact dermatitis, rhinitis, and conjunctivitis to pharyngeal edema and severe systemic reaction such as anaphylactic shock. The following Medical and Nursing Management section focuses on latex allergy. Interprofessional Management Medical Management As in other hypersensitivity reactions, treatment is based on prevention, such as avoiding products that contain latex. If exposure does occur, antihistamines may help with a less severe reaction. Skin creams containing steroids help with the contact dermatitis but cannot be used for long periods of time. More severe reactions occur with repeated exposure and may require a trip to the hospital to receive oxygen, epinephrine, and IV corticosteroids to reduce the inflammatory response. Nursing Management Assessment and Analysis The clinical manifestations seen with type IV hypersensitivity latex reaction are typically due to the tissue damage caused by the inflammatory response mediated by sensitized T cells. Mild reactions include: Local skin reactions, typically on the hands in relation to latex gloves (or can be on any area repeatedly exposed to latex) Conjunctivitis Rhinitis More severe reactions can include severe respiratory distress related to pharyngeal edema and anaphylactic shock as described previously under type I hypersensitivity reactions. Nursing Diagnoses/Problem List Risk for localized tissue damage related to hypersensitivity reaction secondary to latex allergy Risk for impaired oxygenation related to pharyngeal edema secondary to hypersensitivity reaction Nursing Interventions Assessments Assess vital signs. A severe latex allergy reaction may produce clinical manifestations of anaphylaxis: respiratory distress with decreased oxygenation, hypotension, and tachycardia. Assess the skin. Mild reactions may include rashes, especially on the hands from latex gloves (or other areas exposed to latex). Assess for previous history of latex allergy. A secondary exposure to latex after an allergic reaction may cause a more severe anaphylactic response because of already sensitized T cells. Assess for allergies for any of the following: avocado, chestnut, mango, papaya, passion fruit, tomato, raw potato, peach, banana, kiwi. Allergies to these substances may also indicate a sensitivity to latex. Assess for history of repeated surgical procedures or adverse reaction or complication related to surgery. Patients having repeated surgical procedures resulting in multiple exposures to latex are more likely to become sensitized and suffer an allergic response to latex. Actions Administer medications as ordered. Steroid skin creams and/or IV corticosteroids may be necessary to decrease inflammation. IM or IV epinephrine may be necessary to relieve respiratory distress and increase blood pressure in a severe reaction. Eliminate exposure to latex products by using nonlatex alternatives: vinyl or neoprene gloves. The best treatment is prevention. A secondary exposure may lead to anaphylaxis. Protect patients from exposure to latex by: Knowing if your institution is "Latex Free" Reading labels to look for items containing latex Covering skin with cloth before applying a latex blood pressure cuff Not allowing rubber stethoscope tubing to touch the patient, if it contains latex Not injecting through rubber ports on IV tubing, if it contains latex As stated, overexposure to latex can exacerbate the hypersensitivity reaction. Avoidance of exposure is the best treatment. Teaching Teach the patient to avoid exposure to products that are commonly made of latex: Healthcare equipment: wheelchair cushions, tourniquets, airways, endotracheal tubes, masks for anesthesia, electrode pads Office/household products: erasers, rubber balls, tires, shoe soles, rubber bands, hot water bottles, cycle grips, baby bottle nipples, carpeting Any exposure can result in an anaphylactic reaction. Instruct the patient to wear a Medic Alert bracelet and inform healthcare providers of allergy. It is essential that the patient identify latex allergies to avoid exposure as much as possible and aid in the response should a reaction occur and the patient is unable to articulate the problem. Instruct the patient on the use and necessity of having ready-to-use IM epinephrine. These devices deliver a dose of epinephrine to counteract an allergic response, decreasing respiratory distress and increasing blood pressure. Evaluating Care Outcomes Patients can avoid the complications related to latex allergy by maintaining a heightened awareness of products in the environment that contain latex. Carrying IM epinephrine and wearing a Medic Alert bracelet are necessary in the case of an inadvertent exposure to latex. TYPE V HYPERSENSITIVITY: STIMULATED The type V designation can be noted as a distinct subcategory but is sometimes included in type II hypersensitivity reactions. This is an antibody-mediated cellular dysfunction that leads to a change in cell function but does not lead to cell death as in type II hypersensitivity reactions. This reaction is also called a stimulatory reaction. There is an excessive stimulation of a normal cell-surface receptor by an autoantibody. This stimulation results in a continuous turned-on state for the cell. An example of this is Graves' disease, which is a form of hyperthyroidism. An autoantibody binds to the thyroid-stimulating hormone receptor sites on the thyroid gland. The action of the binding results in a continual stimulation of thyroid cells to produce thyroid hormone. The normal negative feedback system is no longer working to stop the overproduction of thyroid hormones.