Page 470 - Clinical Immunology_ Principles and Practice ( PDFDrive )

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Approach to the Evaluation of the Patient

With Suspected Immunodeficiency

Javier Chinen, Mary E. Paul, William T. Shearer

Clinical immunologists are often consulted to evaluate patients KEY CONCEPTS
for suspected immune defects, usually because such patients
have an unusual frequency or severity of infectious illnesses. Secondary Immunodeficiencies
Indeed, immunodeficiency presents with increased susceptibility Immunodeficiency is often secondary or transient, caused by nonimmune
to infection but may also manifest with conditions that reflect factors, including:
dysregulation of the immune response, such as allergies, autoim- • Previous use of high-dose steroids, or other immunosuppressive
munity, or lymphoproliferation. Prompt diagnosis is essential to medications
reduce the risk of organ damage caused by preventable severe • Previous use of monoclonal antibodies (mAbs), such as rituximab
infections. Primary immunodeficiencies (PIDs) are congenital (anti-CD20)
diseases that might affect any aspect of the immune response and • Immunoglobulin losses via the gastrointestinal or urinary tract
• Severe illness requiring critical care
are often diagnosed in childhood. Examples of PIDs include severe • Malnutrition
combined immune deficiencies (SCIDs), complete DiGeorge • Human immunodeficiency virus (HIV) infection
syndrome, and chronic granulomatous disease (CGD). In
contrast to PIDs, secondary immunodeficiencies (Chapters 38,
39) present at any age, as a result of a wide variety of factors
that affect the immune function, such as environmental factors, increase the frequency of infections include allergic inflammation,
metabolic disease, anatomical abnormalities, or infectious agents. HIV infection, and the use of immunosuppressive drugs. Examples
The most known and significant secondary immunodeficiency of nonimmunological conditions include those that disrupt the
is caused by human immunodeficiency virus (HIV). The assess- usual mucosal clearance mechanisms, such as posterior urethral
ment of a patient for PID should include history and physical valves or urethral stenosis in a patient with recurrent urinary
examination to direct immunology laboratory testing to confirm a tract infection, or cystic fibrosis in individuals who have recurrent
diagnosis. sinusitis or pneumonia and/or diarrhea. Disruption of natural
barriers can lead to increased risk of infection, for example, in
EPIDEMIOLOGY—PRIMARY patients with skin lesions caused by eczema or burns or in
IMMUNODEFICIENCIES ARE NOT UNCOMMON individuals with cerebrospinal fluid (CSF) leaks following bony
injury to the cranium. Patients presenting with low Ig levels
Estimates of the incidence of PIDs or congenital immuno- might have loss of antibodies as a result of a protein-losing
deficiencies varies from selective immunoglobulin A (IgA) enteropathy, nephropathy, or massive protein loss through skin,
1
5
deficiency, a relatively common condition, (1/223–1/1000 people) such as in severe eczema or burns. Secondary immunodeficiency
to the less common SCID. Recent analysis from 11 state programs can also result from other conditions affecting cell metabolism
established for universal newborn screening for T-cell deficiencies (e.g., malnutrition, diabetes mellitus, and sickle cell anemia) or
in the United States reported an incidence of SCID of 1/58 000 could be secondary to predictable or idiopathic adverse effects
2
live births, comparable with childhood leukemia. A household- of drugs. Optimal management of these conditions often results
based telephone survey suggested that 1 in 1200 persons in the in improved immunity.
3
United States has been diagnosed with a PID. Although significant
progress has been made to stop the acquired immunodeficiency EVALUATING PATIENTS FOR IMMUNODEFICIENCY
syndrome (AIDS) epidemic, HIV infection continues to be the
most prevalent cause of immunodeficiency worldwide, with an The evaluation of patients for immunodeficiency is based on a
estimated 36.9 million people living with HIV. 4 careful assessment of patient history and physical examination,
with very limited initial laboratory testing. With this information,
PRIMARY VERSUS SECONDARY the clinician can often tell patients (or parents) whether their
IMMUNODEFICIENCY (or their child’s) immune system is significantly compromised.
The immunologist must take on a role of counselor and advisor
Because of their common occurrence, acquired and nonim- of patients and explain the many factors that may result in
munological causes for recurrent infections should be first increased frequency of infections (Fig. 32.1). The limitations of
considered in the differential diagnosis of the patient with a available clinically validated testing need to be considered, as
suspected immune disorder. Acquired conditions that might such tests may not be sensitive or specific to identify uncommon

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