Immunoglobulins in Pediatric Disease: Diagnostic and Therapeutic Applications
Primary Diagnostic Role
Immunoglobulin measurement is fundamental for diagnosing primary immunodeficiencies, with serum IgG, IgA, and IgM levels serving as essential screening tests alongside assessment of specific antibody responses to vaccine antigens. 1
Key Diagnostic Applications
- Measurement of serum immunoglobulin levels (IgG, IgA, IgM) is essential for global assessment of immune development and identifying humoral immunodeficiencies 1
- Evaluation of specific antibody responses to vaccine antigens is critical for assessing functional immunity beyond just measuring total immunoglobulin levels 1
- Agammaglobulinemia (both X-linked Bruton and autosomal forms) presents with extremely low or absent B cells and requires immunoglobulin measurement for diagnosis 1
- Common variable immunodeficiency shows variable reduction in two or more major immunoglobulin classes with impaired specific antibody responses 1
- Milder antibody deficiencies including selective IgA deficiency, IgG subclass deficiency, and transient hypogammaglobulinemia of infancy require immunoglobulin measurement for identification 1
Therapeutic Applications: Replacement Therapy
For primary immunodeficiencies with agammaglobulinemia or common variable immunodeficiency, IgG replacement therapy is the cornerstone of treatment, either alone or combined with antibiotic prophylaxis. 1
Indications for Replacement Therapy
- Severe combined immunodeficiency (SCID) requires immediate supportive therapy with antimicrobials and IgG replacement while awaiting definitive hematopoietic stem cell transplantation 1
- Syndromic immunodeficiencies (Wiskott-Aldrich syndrome, DiGeorge syndrome, ataxia-telangiectasia, hyper-IgE syndromes) often require supportive therapy with polyclonal human IgG 1
- Milder antibody deficiencies are most often managed with antibiotic prophylaxis, though IgG therapy can be applied in selected cases 1
Therapeutic Applications: Immunomodulation in Immune Thrombocytopenia (ITP)
For children with newly diagnosed ITP and non-life-threatening mucosal bleeding or diminished quality of life, IVIG 0.8-1 g/kg as a single dose is the preferred first-line treatment. 1, 2
ITP Treatment Algorithm
First-Line Options for Moderate Bleeding:
- IVIG 0.8-1 g/kg as single dose raises platelet count in more than 80% of children and acts more rapidly than corticosteroids 1, 2
- Alternative: Prednisone 4 mg/kg/day for 3-4 days is effective in 72-88% of children (platelet count ≥50×10⁹/L within 72 hours) 1, 2
- For Rh(D)-positive children with intact spleens, IV anti-D immunoglobulin can be given as a short infusion, though it carries risk of hemolysis (RR for no hemolysis 0.72; 95% CI 0.64-0.92) 1, 2
Emergency Treatment for Severe Bleeding:
- For organ- or life-threatening bleeding, immediately administer 2-3 fold larger-than-usual platelet transfusion combined with IV high-dose corticosteroids (methylprednisolone 30 mg/kg/day) and IVIG 1, 2
- Add fresh frozen plasma if coagulation studies are prolonged 2
- Never delay treatment for severe bleeding while awaiting complete diagnostic workup 2
Critical ITP Management Pitfalls
- Avoid prolonged corticosteroid therapy in children due to significant toxicities including intolerable short-term side effects with higher doses 1, 2
- Anti-D immunoglobulin has a black box warning for fatal intravascular hemolysis, though this is rare; it requires Rh-positive status and intact spleen to be effective 1
- Anti-D immunoglobulin is not acceptable to some populations (e.g., Jehovah's Witnesses) who refuse blood products 1
- Do not assume isolated ITP when fever and bicytopenia are present—this combination mandates exclusion of malignancy and bone marrow failure 2
Therapeutic Applications: Kawasaki Disease
For Kawasaki disease, IVIG 2 g/kg as a single infusion combined with aspirin should be administered within the first 10 days of illness, preferably within 7 days, to reduce coronary artery abnormalities. 1
Kawasaki Disease Treatment Specifics
- High-dose IVIG (2 g/kg single infusion) demonstrates dose-response efficacy, with higher doses having greatest effectiveness in preventing coronary artery abnormalities 1
- Peak adjusted serum IgG levels are inversely related to fever duration and inflammation markers; lower peak IgG levels correlate with worse outcomes 1
- Treatment before day 5 of illness appears no more effective than treatment on days 5-7 but may increase need for IVIG retreatment 1
- IVIG should also be given to children presenting after day 10 if they have persistent unexplained fever or aneurysms with ongoing systemic inflammation (elevated ESR or CRP) 1
- Measles and varicella immunizations must be deferred for 11 months after high-dose IVIG administration 1
Therapeutic Applications: Other Pediatric Conditions
IVIG demonstrates proven efficacy in Guillain-Barré syndrome and juvenile dermatomyositis, though most use in pediatric rheumatology beyond Kawasaki disease remains off-label. 3, 4, 5
Evidence for Additional Indications
- Guillain-Barré syndrome: IVIG targets inflammation from aberrant immune activation underlying myelinotoxic effects 3, 4
- Juvenile dermatomyositis: Literature supports IVIG use, though it remains unclear whether use should be limited to severe or refractory disease 5
- Autoimmune thrombocytopenia secondary to lupus: IVIG appears efficacious but responses may be transient 5
- Neonatal sepsis: Despite theoretical promise, IVIG shows no clear clinical benefit in prophylaxis or treatment, likely due to limitations in research design and unique neonatal immunologic environment 3
- Childhood epilepsy: IVIG exerts anti-epileptic effects through targeting upregulated cytokine pathways and antibodies contributing to epilepsy 3
Practical Considerations and Monitoring
When prescribing immunoglobulin therapy, consider product availability, cost-effectiveness, patient-specific factors, and establish appropriate monitoring protocols. 1
Important Clinical Factors
- Corticosteroid use is substantially less expensive than anti-D immunoglobulin or IVIG 1
- Anti-D immunoglobulin availability is limited in many locations and requires Rh-positive status with intact spleen 1
- IVIG is a biological product from pooled donor plasma with potentially important manufacturing differences between products 1
- Transient side effects with IVIG (fever, headache, nausea/vomiting) are highest with 1 g/kg given on consecutive days 1
- Children with persistent/refractory ITP may stabilize with adequate platelet counts (20-30×10⁹/L) without symptoms unless injured, and spontaneous remission may occur over time 1
- Families should carry emergency information cards and consider medical alert bracelets for children with persistent coagulation disorders 1, 2