Immunodeficiency is an immune system defect that increases a person's susceptibility to infection and is classified as a primary or secondary disorder.1,2 Primary immunodeficiency (PID) diseases, sometimes called inborn errors of immunity, are rare genetic defects in one or more immune system components resulting in infections that may be severe, persistent, recurrent, and present with unusual complications or organisms.3-5
Secondary immunodeficiency (SID) is more common than PID. It results from an impairment of immune function associated with medical conditions or variables extrinsic to the immune system, thereby predisposing a person to infection.2 This article presents the signs, symptoms, and management of adults with PID and SID.
Epidemiology and prevalence
PID encompasses more than 450 single gene defects classified by the International Union of Immunological Societies according to the specific gene(s) affected and clinical presentation.1,5-7 PID is suspected when a person has severe recurrent infections involving multiple body areas and are resistant to treatment, particularly pneumonia, bronchitis, sinusitis, and gastroenteritis.1,8-11
Cutaneous manifestations of immunodeficiency may include eczema, human papillomavirus infection, abscesses, oral and esophageal candidiasis, oral ulcers, and periodontitis.1,8-11
SID is far more common than PID.2,8 People with SID have a loss of immune function secondary to medical conditions or immunosuppressive medications, rather than a genetic defect, resulting in infection.2,8
Malnutrition-related SID impacts approximately 50% of people in the poorest countries.2,8,12 More than 6 million people globally, including 350,000 to 700,000 in the US, have PID.1-5 In 2022, 2.7% of the US population was immunocompromised (7 million people), of whom more than 6 million were affected by SID.12
The prognosis of PID depends on the underlying etiology.12-15 Most people are expected to have an average lifespan if they receive aggressive treatment and maintain a healthy lifestyle.1,6 The prognosis for SID is generally favorable when an underlying medical condition is controlled.2,8
Primary immunodeficiency
PIDs are classified according to the defective innate or adaptive part of the immune system.8,16,17 The innate immune system comprises barriers that prevent infectious agents from entering the body or spreading throughout body tissues.8,16,17 Such barriers include the skin, body hair, eyelashes, respiratory tract, gastrointestinal tract, tears, sweat, saliva, mucus, gastric acid, bile, neutrophils, macrophages, natural killer (NK) cells, and complement.8,16,17 The latter consists of more than 30 proteins produced by the liver and macrophages that target, bind, and opsonize an antigen until its contents leak and are destroyed by phagocytosis.16,18,19 The complement system is so named because it "complements" antibody production in the adaptive immune response.16,18,19
Adaptive immunity, also called acquired immunity, is a component of the immune system that becomes more efficient after infection and vaccination.16,20 Adaptive humoral defenses include the production of immunoglobulins, including immunoglobulin (Ig) G (IgG), IgM, IgA, and IgE.16,20 These antibodies are mediated by a cluster of differentiation (CD)-19 and CD-20 positive B lymphocyte produced in the bone marrow.16,20 Adaptive cellular defenses include T lymphocytes that are CD-4 (T helper cells) and CD-8 (killer T cells) positive.16,20 T lymphocytes are produced in the bone marrow, travel to the thymus to mature and help B lymphocytes produce antibodies.16,20
Thymic aplasia or hypoplasia leads to PID.3-5 Most of a person's T lymphocytes are produced before birth.16,20 Since B-lymphocyte antibody production requires proper T-lymphocyte functioning, most T-lymphocyte immunodeficiencies cause a dual B-lymphocyte and T-lymphocyte PID disorder.14
Examples of PID disease classifications include B-lymphocyte immunodeficiency (adaptive), T-lymphocyte immunodeficiency (adaptive), severe combined immunodeficiency deficiency (adaptive), phagocyte disorders (innate), and complement defects (innate).6,13-15 The type of infection and clinical presentation will vary based on a specific PID.6,13-15 Bacterial infections are common with B-lymphocyte deficiencies, while viral, fungal, and bacterial infections are common in dual B-lymphocyte and T-lymphocyte deficiencies.6,13-15 Cytopenia and autoimmune diseases are features of complement deficiency.17-19
Some PIDs cause an uncontrolled production of lymphocytes (lymphoproliferation), leading to lymphadenopathy, hepatomegaly, splenomegaly, and bone marrow infiltration (see PID disorders).1,3-5,21,22 These lymphocytes may attack healthy body tissues, organs, and blood cells, leading to autoimmune disease, anemia, thrombocytopenia, lymphoma, and leukemia (see Noninfectious manifestations of PID).1,3-5,21,22 PID may manifest as an infected mass (granuloma) involving the bone, skin, brain, lungs, liver, and intestines.6,23-25 Food allergies, asthma, and dermatitis are features of T-lymphocyte deficiency.3
Secondary immunodeficiency
SID occurs from a chronic or transient impairment of T lymphocytes, B lymphocytes, phagocytosis, and antibody production and losses affecting immune function.2,12,13,26 The most frequent causes of SID include malnutrition, immunosuppression medications, and chronic infections.2,12,13,26 Malnutrition from a protein-calorie deficiency accounts for more than 50% of SID cases globally, particularly in impoverished communities, leaving a person especially prone to chronic diarrhea and respiratory tract infections.2,12,13,26
A deficiency in protein and micronutrients such as iron, folate, vitamin A, vitamin C, vitamin D, and zinc results in decreased macrophage function resulting in infections. Macrophages are white blood cells that engulf and destroy pathogens.
Many medications to treat malignancies, autoimmune conditions, and solid-organ transplantation may cause immunosuppression, predisposing a person to opportunistic infections.2,12,13,26 Chronic infections may cause SID syndromes.2,12,13,26 AIDS from the HIV is the most common cause of SID syndromes from the depletion of CD4-positive T lymphocytes.2,12,13,26
A primary infection, such as HIV, viral hepatitis, influenza, Epstein-Barr virus, cytomegalovirus, varicella zoster virus, and COVID-19, impairs innate or adaptive immune responses predisposing a person to additional infections (secondary).27,28 Splenectomy, diabetes mellitus, liver disease, nephropathy, malignancies, severe trauma, and severe burns are frequent causes of SID.2,12,13,26 SID may also result from severe stress; UV light; radiotherapy; prematurity; aging; and antiepileptic medications, including carbamazepine, valproate, and phenytoin.2,12,13,26
Clinical manifestations
The signs and symptoms of PID and SID may be indistinguishable and need to be carefully assessed, including comorbidities and medication regimens.2,6,8,29,30 For example, a child might have frequent ear infections from a genetic defect (PID) or immunosuppression medications (SID) to control a systemic autoimmune disease.2,6,11 Both situations predispose the child to systemic opportunistic infections and malignancy.
A health history will help determine if the patient's signs and symptoms are related to a primary or secondary etiology.8,10,11 The nurse should perform a head-to-toe physical assessment for evidence of recurrent and severe infections anywhere in the body, including the ears, sinuses, lungs, and skin.8,10,11,17
For example, does the patient have a cough, difficulty breathing, crackles or wheezing when auscultating the lungs, fever, fatigue, malaise, rash, or drainage from the nose or ears? Deep abscesses of the skin and internal organs; oropharyngeal candidiasis; viral infections including colds, human papillomavirus, and herpes simplex virus; fungal infections; chronic diarrhea; weight loss; poor dentition; and malignancy may occur.2,6
A patient with PID or SID may not always look or feel sick. Patients may present with fatigue, malaise, pallor, and various rashes.1,2,6 Patients should be assessed for genetic (PID) or extrinsic immune system factors (SID) when they have recurrent infections or when they are not responding to treatment, such as antibiotic therapy, effectively.1,2,6 Assessing for easy bruising and bleeding is a priority because of possible thrombocytopenia.2,3,6,8
Lab testing
Nurses should correlate the patient's signs and symptoms with priority lab data. A complete blood cell count may reveal neutropenia and lymphopenia, indicators of immunodeficiency.2,3,6,17 Flow cytometry is a specialized lab test for quantifying and assessing the function of T lymphocytes, B lymphocytes, and NK lymphocytes in a few hours to establish a diagnosis of PID.31 Genetic testing takes weeks to months.32
Anemia is characteristic of chronic inflammatory conditions and autoimmune hemolytic anemia.2,3,6,8 Howell-Jolly bodies in peripheral blood smears are remnants of red blood cell nuclei, and their presence indicates asplenia or poorly functioning spleen causing immunodeficiency.3-6,14 Low Ig levels are a characteristic marker of immunodeficiency.2,6 Low complement levels may indicate an inherited complement deficiency, particularly in the classical pathway (CH50), alternative pathway (AP50), C3, and C4.6,18,19 A reduction in complement may also indicate active inflammation in autoimmune disease.18,19 Elevated C-reactive protein levels and erythrocyte sedimentation rate indicate inflammation and possible infection.10,11 Renal panels, liver panels, and serum electrolytes should be assessed to evaluate disease processes, including comorbidities and adverse reactions of treatment, such as Ig replacement therapy.2,6,10,11,33
Additional diagnostic testing
Allergy skin testing is an approach to evaluating immune function.2,6,8 Skin prick testing for IgE hypersensitivity may be delayed in immunodeficiency due to a weak immune system.2,6,8 An active immune system should produce an allergic reaction. Patients may receive a pneumococcus, tetanus, or diphtheria vaccination challenge in which antibody production is measured in response to the vaccination. Patients with immunodeficiency may not mount measurable antibodies to the vaccination.2,6,8
Imaging studies may indicate the impact of immunodeficiency on body organs and systems, including the brain, thymus, heart, lymph nodes, blood vessels, lungs, sinuses, liver, spleen, kidneys, gastrointestinal tract, muscles, bones, and joints.2,6,8 Infants with suspected immunodeficiency should be screened through a blood test called T-cell receptor excision circle screening.14,15 T lymphocytes (T cells) may be reduced from thymic dysfunction, causing SCID, predisposing the infant to life-threatening infection.14,15
Management
Treatment for immunodeficiency includes preventing infection, managing infection, replacing the absent immune system component, and controlling medical conditions and adverse reactions of medications in SID.2-6,17,27,28 Infection is prevented by closely monitoring a patient's signs and symptoms.17 Acute infection should be treated promptly after an evaluation of blood cultures.8-11 People most prone to severe infection, such as in SCID and asplenia, may receive prophylactic antibiotics.14,15 Intravenous immune globulin or subcutaneous immune globulin is the standard replacement therapy in patients with PID and SID.2,6,33
Hematopoietic cell transplantation should be considered in severe T-lymphocyte disorders, including SCID.14,15 A deficiency of adenosine deaminase (ADA) is responsible for most cases of SCID.34
ADA deficiency is a rare, autosomal-recessive genetic disorder caused by pathogenic variants in the ADA1 gene. Without functional ADA, there is an intracellular accumulation of adenosine and deoxyadenosine. These products are toxic to lymphocytes and lead to dysfunction of T, B, and NK cells that can range in severity from T-B-NK SCID to milder phenotypes.
ADA deficiency usually occurs in infants but may also affect adults.34 Enzyme replacement therapy (ERT) with ADA is an effective treatment.34
Clinical trials with gene therapy show promising results when stem cell transplant or ERT does not sufficiently improve immune function.32 Gene therapy is effective in SCID by replacing a person's defective gene with a reprogrammed gene using a patient's cells.32 Parents of children with PID may explore genetic testing when planning future pregnancies.30
Protein- and nutrient-rich feeding formulas and diets enhance immunity and reduce the incidence of complications, such as severe respiratory infections, sepsis, and poor wound healing.6,9,17,30
Nursing considerations
Nurses must teach the patient and their family that an interprofessional approach is necessary and includes physicians, advanced practice clinicians (APCs), nurses, physical therapists, occupational therapists, counselors, dietitians, and school teachers (see Interventions and teaching points).17,30
Conclusions
PID causes various severe infections that may include dermatitis, eczema, gastrointestinal syndromes, autoimmunity, and malignancy. Early immunologic screening is warranted when immunodeficiency is suspected and aggressive treatment instituted to achieve the best outcomes.
Management of PID has advanced significantly; most people will survive through adulthood. SID is suspected when a person has recurrent infections and abnormal lab results indicating immunodeficiency from a medical condition or medications. The use of immunosuppressive medications in cancer chemotherapy and inflammatory autoimmune diseases is a common cause of SID.
Maintaining disease control or remission, managing medications prudently, and teaching healthy lifestyle habits will help the patient to achieve optimal quality of life.
Interventions and teaching points
When working with patients who are immunocompromised, nurses should include the following interventions and patient teaching points:1,2-6,8,10-12,17,29,30,34
* Ensure that the home, school, and work environments are clean to prevent infection. Parents may need to visit with school officials about a child's special needs. In addition, the work environments may need to be adjusted for adults. The following are selected examples: (1) Work space in a separate area or cubicle away from others, (2) Air purifier and cleaning unit in the workplace, (3) Work from home or virtually if possible, and (4) Computer terminals need to be cleaned frequently.
* Limit or restrict contact with others, stay home when they are sick, avoid others who are sick, and wear an N95 or KN95 mask as indicated. In addition, it is wise to avoid large crowds, such as in shopping areas, malls, and movie theaters. Drink water in purchased water bottles and not from a public fountain.
* Maintain good body hygiene. Engage in regular hand hygiene before and after eating and toileting. Wipe the rim of a cup or glass served in restaurants with a napkin before drinking. Special germicide soaps may be prescribed.
* Avoid smoking and environments where others smoke. Nicotine is an irritant to the respiratory tract and predisposes a patient to respiratory infections.
* Practice respiratory hygiene/cough etiquette, including covering the mouth and nose when coughing or sneezing, followed by hand hygiene.
* Rinse sinuses daily with saline solutions to remove allergens and potential infectious organisms.
* Avoid vaccination with live viruses because they may induce infections. Inactive vaccines should be explored. Household members should be fully vaccinated as well.
* Probiotics may be prescribed to promote healthy intestinal bacteria flora, especially in patients prescribed antibiotic therapy.
* Dental care is essential. Proper toothbrushing, flossing, and regular dental checkups will help promote tooth and gum health.
* Exercise regularly to promote physical and mental health. Partake in activities such as yoga, walking, running, and riding a bike.
* Getting sufficient rest and sleep (8 hours each night) is essential to mental and physical health, including optimal immune system function.
* Reduce stress as much as possible. Chronic illnesses and life events are known to suppress immune function.
* Have regular clinical follow-ups. Patients should report new symptoms to the physician or APC. A cough, sinus drainage, malaise, fatigue, and a new rash or lesion in the oral mucous membranes and perineal region might be early signs of a developing infection. Restlessness and tugging at the ear are signs of ear infections in children. Fever is always a concern.
* Physical growth and cognitive development are assessed in all children, especially in those with DiGeorge syndrome.
* Join a support group to engage with others with immunodeficiency.
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