General Approach to Immune Workup
Summarized from Kliegman. Practical Strategies in Diagnosis and Therapy. 1996

Possible step-wise lab eval. If each step is normal, proceed to next step. Also consider B-cell subsets. Red flags: absent lymphoid tissue, FTT, chronic diarrhea, prolonged infections, infections w/ unusual organisms, eczematous dermatitis, family hx of early childhood deaths or other dz with incr risk of infection (sickle cell anemia, malignancy, asplenia)

• Initial Screening
  • CBC, retic , cultures, leukocyte morphology
    • Looking for anemia, chediak higashi, howell jolly bodies (functional asplenia), Wiskott-Aldrich, neutropenia (<1500)
• If neutropenic do BM bx, antineutrophil antibodies, serial CBC to establish cyclic neutropenia
• Immunoglobin/Complement workup
• hypoglammglobulinemia syndromes, selective IgA deficiency, IgG subclass deficiency; specific polysaccharide unresponsiveness; HyperIgE >2000)
• IgG, IgM, IgA levels. IgE levels
• antibody titers to vaccine antigens, tetanus, diphtheria, rubeola, Haemophilus influenza polysaccharide
• Delayed hypersensitivity skin tests (Candida, tetanus toxoid, mumps, trichoplyton, streptokinase-streptodornase)
• IgG subclass levels for IgG1, igG2, IgG3, IgG4
• Chest and sinus XR studies
• Total T cells, and t-cell subsets: T helper cells, T-suppressor cells and the ratio between T-helpers::T-suppressors (SCID, AIDS, DiGeorge, mucocutaneous candidiasis, Wiskott-Aldrich; ataxia telangiectasia)
• C3, C4, CH50
• Phagocyte evaluation
• NBT test, superoxide assay (Chronic Granulomatous Disease, Neutrophil G6PD deficiency; GSH pathway d/o)
• Chemotaxis assays (complement deficiency, acquired humoral defects, leukocyte adhesion deficiency, chediak higashi)
• Rebuck skin window
• In vitro assay with patient and control sera
• Further phagocyte evaluation
• Myeloperoxidase stain (myeloperoxidase deficiency)
• Flow cytometry to measure CD11/CD18 surface glycoproteins on neutrophils (leukocyte adhesion deficiency)
• Quantitative ingestion assays (patient and control sera as opsonins) (Neutrophil actin dysfunction)
• Flow cytometry to measure L-selectin on neutrophil (LAD, opsonin defect)

Approach to immune workup

Children with recurrent infections can fall into 4 categories

• The probably well child
• The atopic or allergic child
• The chronically ill child with a non-immunologic defect in host defense
• The immunodeficient child with a neutrophil defect, lymphocyte abnormality, antibody deficiency, or complement deficiency

The probably well child

• 50% of children with complaint of recurrent infections are probably well
• Brief history of recurrent infections (or) Single prolonged illness from which recovery has been delayed
• Most resp infections last < 7 days. Unusual if  >14 days.
• Most children under 1 y/o get 6-10 resp/GI infections in a year
• Normal growth and development, normal tonsils and LN
• Consider: CBC, ESR, CRP, to screen for rheum.,  culture/XR of affected area

The allergic patient

• In addition to characteristic history, look for these on PE:
• Pallor, circles under eyes, open mouth with dry lips
• evid of nasal obstr, transverse nasal crease, boggy nasal mucosa, postnasal drip
• Coated tongue, mucus in the pharynx, posterior pharyngeal cobblestoning
• Cervical LAD, increase in chest AP diameter, pectoral hypertrophy, chest asymmetry, chronic sinusitis, chronic resp obstru, dry skin, eczema, dermatographism
• Lab eval of allergic child:
• CBC, ESR
• Nasal smear for eosinophils
• Spirometry before and after bronchodilators
• Sinus XR +/- CXR
• Quantitative Immunoglobins (QUIGs), including IgE level (If >100 IU/mL, suggests allergic d/o; use threshold of 40 IU/mL if under age 1.)

The Chronically ill patient with an anatomic or obstructive abnormality

• 10% of children with recurrent infections have an underlying chronic disease or a structural defect that predisposes
• Examples:
• chronic illnesses, malnutrition and vitamin deficiencies, protein lositn enteropathies (decr complement, gammaglobulins)
• Eustachian tube abnormalites (i.e. cleft palate), CHD, posterior urethral valves, TE fistula or sequestration, foreign body aspiration, BPD, GER
• CF, immotile cilia syndrome, anti-trypsin deficiency
• Consider:
• CBC, CXR, sweat test, cultures of involved site
• QUIG’s

The immunodeficient patient

• Usually present in the second half of the first year.

  Summarized from Kliegman. Practical Strategies in Diagnosis and Therapy. 1996