TOPIC 24: Immunodeficiency Findings – Recognize findings that would suggest an immunodeficiency and plan the initial evaluation
OFFICIAL ABP TOPIC:
Recognize findings that would suggest an immunodeficiency and plan the initial evaluation
BACKGROUND
Primary immunodeficiencies (PIDs) represent inborn defects in immunity and affect 1 in every 1,200 to 2,000 individuals. More than 300 PIDs have been identified, with growing prevalence due to increased recognition. PIDs commonly involve humoral or combined humoral and cellular defects. Recognizing findings that suggest a PID is essential for timely evaluation and management.
CLINICAL FEATURES SUGGESTIVE OF IMMUNODEFICIENCY
Infections:
- Recurrent, severe, or atypical infections: More frequent, prolonged, severe, or caused by unusual organisms compared with a normal child.
- Infections requiring IV antibiotics or hospitalization, or failing to respond to standard treatments.
- Multiple (≥6) ear or sinus infections, ≥2 pneumonias, or ≥2 deep-seated infections (e.g., sepsis, meningitis) in one year.
- Recurrent skin or organ abscesses.
- Persistent fungal infections, such as oral thrush or cutaneous candidiasis.
INFECTIONS WITH OPPORTUNISTIC OR SIGNATURE PATHOGENS
|
PATHOGEN |
ASSOCIATED IMMUNE DEFECT |
|
Pneumocystis jirovecii |
Profound T-cell deficiencies (e.g., SCID). |
|
Staphylococcus aureus |
Phagocyte defects (e.g., CGD); STAT3 deficiency. |
|
Neisseria species |
Terminal complement deficiencies (C5-C9). |
|
Atypical mycobacteria |
IFN-γ/IL-12 axis defects. |
|
Candida species |
T-cell defects, chronic mucocutaneous candidiasis. |
|
Severe/persistent herpes viruses |
Natural killer cell deficiency. |
Family History:
Family history is one of the most predictive factors for identifying PIDs. Consider:
- Family history of immunodeficiency or unexplained early deaths, especially before age 30.
- Consanguinity, which increases the risk for autosomal-recessive PIDs.
- Family members with recurrent or unusual infections.
Failure to Thrive:
Poor weight gain or growth often related to recurrent infections, chronic diarrhea, or nutritional deficiencies.
Atypical Vaccine Reactions:
Disseminated infection following live vaccines.
Absent Lymphoid Tissue:
Lack of palpable lymph nodes, tonsils, or adenoids, particularly in children with recurrent respiratory infections.
Autoimmune Features:
These may precede infections in some immunodeficiencies:
- Cytopenias (e.g., thrombocytopenia, anemia).
- Arthritis.
- Lupus-like syndromes.
- Vasculitis.
Other:
- Delayed umbilical cord detachment (>30 days).
CHARACTERISTICS ASSOCIATED WITH CERTAIN GENETIC SYNDROMES
|
SYNDROME |
KEY CLINICAL FEATURES |
|
Ataxia-Telangiectasia |
Ataxia, oculocutaneous telangiectasias, sinopulmonary infections, lymphoma. |
|
Wiskott-Aldrich |
Eczema, thrombocytopenia (<70k), recurrent infections, bleeding. |
|
STAT3 Deficiency |
Eczema, staphylococcal abscesses, bone fractures, facial features. |
|
DiGeorge (22q11.2 Deletion) |
Hypocalcemia, cardiac defects, abnormal facies, cognitive delay. |
|
Chronic Granulomatous Disease |
Recurrent bacterial/fungal infections, granulomas, gingivitis. |
|
Chédiak-Higashi |
Partial oculocutaneous albinism, neutropenia, neurologic deficits. |
FINDINGS ASSOCIATED WITH DIFFERENT IMMUNE DEFICIENCIES
|
IMMUNODEFICIENCY TYPE |
KEY FINDINGS |
|
Antibody Deficiencies |
Recurrent sinopulmonary infections, meningitis, sepsis with encapsulated organisms; low immunoglobulins and/or vaccine titers. |
|
Combined Immune Deficiencies |
Opportunistic infections, failure to thrive, absent lymphoid tissue, lymphopenia, rash, diarrhea. |
|
Phagocyte Defects |
Recurrent skin/organ abscesses, gingivitis, delayed wound healing, CGD+ on DHR flow cytometry test. |
|
Complement Deficiencies |
Recurrent meningococcal or encapsulated bacterial infections, angioedema, SLE-like disease, abnormal CH50. |
EVALUATING SUSPECTED IMMUNODEFICIENCY
Initial Laboratory Tests in Children Suspected to Have Immunodeficiency:
- CBC with manual differential: Evaluate for lymphopenia (<2,500 cells/μL in infants; <1,500 cells/μL in older children) or neutropenia.
- Immunoglobulin levels: IgG, IgA, IgM, and IgE.
- Specific antibody titers: Measure response to vaccines (e.g., tetanus, diphtheria, pneumococcus). Obtain baseline titers, administer vaccine, and measure postimmunization titers.
- Total serum hemolytic complement assay (CH50): Detect any deficiencies in the classic complement pathway.
Additional Tests Based on Clinical Suspicion:
- CXR: Look for an absent thymic shadow in infants, as in SCID or DiGeorge.
- Serial CBCs with differential: For children suspected to have cyclic neutropenia.
- DHR flow cytometry assay: Screen for chronic granulomatous disease.
- Serum alpha-fetoprotein levels: Elevated in children with ataxia-telangiectasia.
If screening tests suggest immunodeficiency or clinical suspicion remains high, refer to immunology for advanced testing (e.g., lymphocyte subsets, flow cytometry, genetic testing).
Secondary Immunodeficiencies
Secondary causes of immunodeficiency should be ruled out during the evaluation. Common causes include:
- Chronic Illness: Diabetes, renal failure, chronic lung disease.
- Medications: Corticosteroids, chemotherapy, immunosuppressants.
- Infections: HIV, measles (causes B- and T-cell suppression).
- Malnutrition: Severe protein-calorie malnutrition impairs immune function.
- Other Causes: Prematurity, asplenia, protein-losing states.
REFERENCES
https://publications.aap.org/pediatricsinreview/article/40/5/229/35282/Immunodeficiency-Disorders
https://www.uptodate.com/contents/approach-to-the-child-with-recurrent-infections