Immune deficiency disorders should be considered once the more common causes of recurrent infection have been excluded. The initial approach to a child or adult with recurrent infections is described separately.
Immune dysregulation can result in disorders other than recurrent infections, including:
- Autoimmune disorders, such as autoimmune hemolytic anemia
- Inflammatory disorders, such as inflammatory bowel disease or inflammatory arthritis
- Malignancies, such as lymphoma
- Allergic disease, such as atopic dermatitis, food allergy, and allergic rhinosinusitis and asthma Before initiating immunologic testing, the clinician should perform a thorough clinical history and
physical examination. In infants and children, height and weight records should be reviewed, as failure to thrive and poor growth are consistent with immunodeficiency. In patients with possible immunodeficiency, important elements of the clinical presentation include:
- The nature of the infections: This should include the frequency, chronicity, severity, and response to Other considerations include what organ system(s) is involved and what type of organism has been identified in the past (ie, viral, bacterial, fungal, opportunistic), since patterns of infections can suggest specific immune defects
- Age of onset of illness, since different immune problems present in infancy, childhood, and adulthood
- The patient’s sex, because X-linked defects are mostly or exclusively seen in boys
- Any associated nonimmunologic symptoms and signs, as revealed by a complete review of systems
Initial screening laboratory tests. In patients of any age, the laboratory evaluation of the immune system begins with general studies, including:
- Complete blood count with differential: Lymphopenia is characteristic of a variety of combined cellular and antibody deficiency Lymphopenia is defined as an absolute lymphocyte count <1500 cells/microliter in adults or <2500 cells/microliter in infants. Neutropenia can be found in primary phagocyte disorders, as well as in neutrophil disorders that lead to secondary immunodeficiency. Leukocytosis is sometimes noted and suggests chronic infection.
- Chemistry panels to assess for metabolic disorders (diabetes mellitus, renal disease) that might cause secondary immune Hypoalbuminemia or low serum proteins suggest malnutrition or protein loss. Markedly elevated globulin levels may be seen in gammopathies or chronic infections.
- Urinalysis for proteinuria, casts, or cells, which suggest
- Tests to evaluate for specific infections, if indicated by the presentation (eg, appropriate cultures, chest and/or sinus imaging): Sinus films may uncover extensive chronic sinusitis in patients with immune Children or adolescents with nasal polyposis (although not adults) should beevaluated for cystic fibrosis, which is a cause of frequent sinopulmonary infections. Chest radiographs of an infant showing absence of a thymic shadow should prompt an emergent evaluation for severe forms of immunodeficiency. In older children and adults, chest radiographs may show scarring from past infections, interstitial lung disease, or bronchiectasis. Hyperinflated lung fields suggest chronic obstructive lung disease or chronic asthma.
- Erythrocyte sedimentation rate and/or C-reactive protein: Nonspecific elevations in acute phase reactants can be seen with infectious and inflammatory disorders and suggest the need for further
Referral. More advanced immunologic tests require varying degrees of expertise to perform and interpret, may not be widely available, and are often costly. In addition, knowledge about the possible diagnoses in question is invaluable in deciding the type of testing to pursue first. Thus, immunologic testing is best performed in a graded fashion, and referral to an allergist/immunologist should be sought early in the process, when possible.
Ultimately, definitive diagnosis may require specialized flow cytometric or molecular methods available in reference laboratories.
CATEGORIES AND PREVALENCE OF IMMUNE DEFICIENCIES — Immune deficiency
disorders may be grouped into categories based upon the part of the immune system that is predominantly affected. The prevalence of each group of disorders in the population has been estimated to include:
- Antibody deficiencies and defects account for approximately 65 percent of identified immunodeficiency disorders
- Combined antibody and cellular deficiencies: 15 percent
- Disorders of phagocytes: 10 percent
- Isolated cellular defects: 5 percent
- Disorders of the complement system: 5 percent
- Other disorders of innate immunity: <1 percent
Each of these categories of disorders has characteristic clinical manifestations, although there are varying degrees of overlap among the clinical presentations of the groups.
