Recurrent infection in immunologically deficient children is associated with pathology at sites of infection resulting in substantial morbidity, such as scarring tympanic membranes leading to hearing loss or chronic lung disease due to recurrent pneumonia. Height and weight percentiles, nutritional status, and presence of subcutaneous fat should be assessed. Oral thrush, purulent nasal or otic discharge, and chronic rales may be evidence of repeated or persistent infections. Absence of lymphoid tissue (e.g., tonsils) suggests agammaglobulinemia or SCID, whereas increased size of lymphoid tissue suggests CVID, CGD, or human immunodeficiency virus (HIV) infection. Cerebellar ataxia and telangiectasia indicate ataxia-telangiectasia. Severe eczema and inflammatory bowel disease are seen in some disorders of immune regulation with polyendocrinopathy and enteropathy that is X-linked (IPEX), whereas eczema and petechiae or bruises suggest Wiskott-Aldrich syndrome.
There are many secondary causes of immunodeficiency that should be considered, particularly if the immunologic testing is nonrevealing (Table 72-4). In patients with primary immunodeficiencies, infections develop at multiple sites (e.g., ears, sinuses, lungs, skin), whereas in individuals with anatomic problems (e.g., sequestered pulmonary lobe, ureteral reflux), infections are confined to a single anatomic site. Asplenia is associated with recurrent and severe infections, even in the presence of protective antibody titers. Infection with HIV should be considered in any patient presenting with a history suggesting a T-cell immunodeficiency.
The diagnosis of patients with primary immunodeficiency diseases depends on early recognition of signs and symptoms, followed by laboratory tests to evaluate immune function. Recognizing the patient who may have an immunodeficiency disease prompts an evaluation and referral to an immunologist (see Table 72-3).
A diagnosis of primary immunodeficiency disease cannot be established without the use of laboratory tests based on the clinical history (Table 72-5). A complete blood count with differential should always be obtained to identify patients with neutropenia or lymphopenia (SCID) as well as the presence of eosinophils (allergic disease) and anemia (chronic disease). Serum immunoglobulin levels are essential to the workup of suspected primary immunodeficiency. Antibody levels vary with age, with normal adult values of IgG at full-term birth from transplacental transfer of maternal IgG, a physiologic nadir occurring between 3 and 6 months of age, and a gradual increase to adult values over several years. IgA and IgM are low at birth, and levels increase gradually over several years, with IgA taking the longest to reach normal adult values. Low albumin levels with low immunoglobulin levels suggest low synthetic rates for all proteins or increased loss of proteins, as in protein-losing enteropathy. High immunoglobulin levels suggest intact B-cell immunity and can be found in diseases with recurrent infections, such as CGD, immotile cilia syndrome, cystic fibrosis, HIV infection, and autoimmune diseases. Elevated IgE levels can be found in a number of immune deficiencies such as hyper-IgE syndrome, as well as in atopic dermatitis.