eMedicine Specialties > Pediatrics: General Medicine > Allergy & Immunology
Transient Hypogammaglobulinemia of Infancy: Treatment & Medication
Updated: Jun 20, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
Transient hypogammaglobulinemia of infancy (THI) treatment is conservative and depends on the severity of infections and the patient's response to therapy. Appropriate antibiotic treatment may be sufficient. However, given emerging evidence that THI is an intrinsic B-cell immunodeficiency, with antibody deficiencies to polysaccharide and conjugated-polysaccharide immunizations (eg, S pneumoniae), treatment with prophylactic antibiotics is reasonable.
Furthermore, in patients with THI who develop severe life-threatening infections or who develop recurrent respiratory tract infections despite antibiotic therapy, a trial of antibody replacement therapy in the form of intravenous immunoglobulin (IVIG) is indicated. Investigators have recommended IVIG for 6-12 months using the usual therapeutic dose of IVIG of 400-800 mg/kg intravenously every 3-4 weeks.3,4 A subcutaneous form of gammaglobulin (Vivaglobin) has become available as an alternative to IVIG. The usual therapeutic dose is 100-200 mg/kg subcutaneously per week.
Allergic rhinitis contributes to recurrent otitis media and sinusitis. If allergic rhinitis occurs, the child should be aggressively treated with topical nasal corticosteroids and antihistamines.
Routine immunizations are continued in children with THI. Recently, a conjugated heptavalent pneumococcal vaccine has been recommended for routine immunization in children beginning at age 2 months. Whether this immunization can significantly reduce otitis media in children with THI is unclear. The conjugated heptavalent pneumococcal vaccine covers approximately 85% of the serotype responsible for invasive pneumococcal infection in children.
In studies of healthy children, the pneumococcal vaccine significantly eliminated invasive infections but reduced the frequency of otitis media by only 20%. Sorensen et al have reported that a significant percentage of children with a selective antibody deficiency to bacterial polysaccharide antigens following immunization with the unconjugated vaccine (Pneumovax) develop protective antibody levels following immunization to the conjugated vaccine (Prevnar), with a reduction in infections.13
Surgical Care
Many of these children are referred to otolaryngologists for placement of tympanostomy tubes for recurrent otitis media and functional endoscopic sinus surgery (FESS) for chronic sinusitis. Tympanostomy tubes are of uncertain benefit in the prevention of recurrent otitis media, and the potential adverse anatomic and audiologic sequelae of tube placement must be considered. Likewise, some have suggested that FESS is not the cure for chronic sinusitis but that the underlying immunodeficiency disease must be appropriately treated.
Consultations
These children need to be referred to an allergist, immunologist, or both to evaluate for THI and to ascertain that another immunodeficiency is not present. A definitive diagnosis of THI is a retrospective diagnosis when the immunodeficiency resolves. These patients need to be evaluated over time.
Atopic diseases associated with THI need to be looked for and treated.
Diet
No special diet is required unless a food allergy is present.
Activity
The child should not attend a daycare center to reduce his or her increased susceptibility to infections. However, physicians need to consider each family's dynamics and economic situation when giving this recommendation.
Medication
Choose antibiotics to cover S pneumoniae, H influenzae, and Moraxella catarrhalis (eg, amoxicillin, second-generation cephalosporins, clarithromycin). Often, prophylactic antibiotics decrease infections. IVIG is rarely needed and is used only when the patient continues to have infections despite antibiotics.
Immunoglobulins
IVIG or subcutaneous immune globulin is used for antibody replacement therapy.
Immune globulin, intravenous (Carimune, Gammagard S/D, Gammagard liquid, Gammar-P, Gamunex, Optigam Polygam S/D)
Purified preparation of gamma globulin derived from large pools of human plasma. Comprises 4 antibody subclasses.
Potential adverse effects include allergic reactions (eg, anaphylaxis, urticaria) because of IgE or anti-IgA antibodies. In a risk-benefit analysis, allergic reactions with IVIG administration in THI probably warrant discontinuation of IVIG. In severe B-cell immunodeficiency diseases in which IVIG is critical to care, premedication with corticosteroids and antihistamines (diphenhydramine) is usually successful in avoiding a reaction. In addition, the different IVIG preparations contain different amounts of IgA. Select an IVIG preparation with the least amount of IgA (eg, Gammagard SD). Contact manufacturer for specific lots low in IgA.
Adult
Pediatric
300-800 mg/kg IV q3-4wk; begin at slow infusion rate and gradually increase
Globulin preparation may interfere with immune response to live virus vaccine (MMR) and reduce efficacy (do not administer within 3 mo of vaccine)
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
More common adverse reactions include infusion-related reactions, such as fever, chills, muscle aches, nausea, and vomiting, probably because of complement activation; infusion-related reactions are treated by decreasing the infusion rate; fever and chills are treated with acetaminophen or ibuprofen; check serum IgA before IVIG (use an IgA-depleted product such as Gammagard SD); infusions may increase serum viscosity and thromboembolic events; infusions may increase risk of migraine attacks, aseptic meningitis (10%), urticaria, pruritus, or petechiae (2-5 d postinfusion to 30 d)
Immune globulin, subcutaneous (Vivaglobin)
IgG antibodies that neutralize a wide variety of bacterial and viral agents. Neutralizes circulating myelin antibodies through anti-idiotypic antibodies; downregulates proinflammatory cytokines, including INF-gamma; blocks Fc receptors on macrophages; suppresses inducer T and B cells and augments suppressor T cells; blocks complement cascade. Peak serum IgG levels are lower and trough IgG levels are higher than those achieved with IVIG. SC administration results in stable steady-state IgG levels when administered weekly. Available as a 16% (ie, 160-mg/mL) SC injectable.
Adult
Pediatric
<2 years: Limited data available; recommended dose is 100-200 mg/kg SC qwk
>2 years: 100-200 mg/kg/SC qwk
Globulin preparation may interfere with immune response to live-virus vaccine (MMR) and reduce efficacy (do not administer within 3 mo of vaccination)
Documented hypersensitivity; intravenous administration; selective IgA deficiency (serum IgA level <0.05 g/L) with known antibody against IgA
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Common adverse effects include swelling, redness, and itching at injection site; for SC administration only; preferred SC administration sites include abdomen, thighs, upper arms, or lateral hip; initiate 1 wk after regularly scheduled IVIG infusion; does not contain preservative (discard unused portion); may cause fever, chills, nausea, or vomiting when switching from one immune globulin product to another or if >8 wk since last administered; do not shake product
Vaccines
These agents are used to induce active immunity.
Pneumococcal 7-valent conjugate vaccine (Prevnar)
Sterile solution of saccharides of capsular antigens of S pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F individually conjugated to diphtheria CRM197 protein. These 7 serotypes have been responsible for >80% of invasive pneumococcal disease in children <6 years in the United States. Also accounted for 74% of penicillin-nonsusceptible S pneumoniae (PNSP) infections and 100% of pneumococci infections with high-level penicillin resistance. Customary age for first dose is 2 mo, but can be given as young as 6 wk.
Preferred sites of IM injection include the anterolateral aspect of the thigh in infants or deltoid muscle of upper arm in toddlers and young children. Do not inject vaccine in gluteal area or areas where there may be a major nerve trunk or blood vessel.
Number of 0.5 mL doses for series initiated at age 7-11 mo is 3 (4 wk apart; third dose after first birthday), at age 12-23 mo is 2 doses (2 mo apart), for age 2-9 y is one dose.
Minor illnesses, such as a mild upper respiratory tract infection, with or without low-grade fever are not generally contraindications.
Adult
Not established
Pediatric
Initiate series at age 2 months: 3 doses of 0.5 mL IM at 4-8 wk intervals, followed by a fourth dose of 0.5 mL at age 12-15 mo; administer fourth dose 2 mo or later following the third dose
If series initiated at age 7-11 months: 2 doses of 0.5 mL IM at 4 wk intervals, followed by a third dose after first birthday; separate second and third dose by at least 2 mo
If series initiated at age 12-23 months: 2 doses of 0.5 mL IM administered 2 mo apart
If initiated at age 2-9 years: 0.5 mL IM once
Effects may decrease with immunosuppressive agents (immunosuppressive doses of corticosteroids, antimetabolites, alkylating agents, cytotoxic agents); pneumococcal 7-valent conjugate vaccine may increase effects of anticoagulant therapy; globulin preparations may interfere with immune response to pneumococcal vaccine and reduce efficacy (do not administer within 3 mo of vaccine)
Documented hypersensitivity to any component or diphtheria toxoid; severe or moderate febrile illness; infants or children with thrombocytopenia or coagulation disorder contraindicating IM injection (unless benefits outweigh risks of administration)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
For IM use only, do not administer IV under any circumstances; take special care to prevent injection into or near a blood vessel or nerve; caution in patients with possible history of latex sensitivity (packaging contains dry natural rubber); use of pneumococcal conjugate vaccine does not replace use of 23-valent pneumococcal polysaccharide vaccination in children >24 mo with sickle cell disease, asplenia, HIV infection, chronic illness, or those who are immunocompromised; caution in coagulation disorders
More on Transient Hypogammaglobulinemia of Infancy |
| Overview: Transient Hypogammaglobulinemia of Infancy |
| Differential Diagnoses & Workup: Transient Hypogammaglobulinemia of Infancy |
 Treatment & Medication: Transient Hypogammaglobulinemia of Infancy |
| Follow-up: Transient Hypogammaglobulinemia of Infancy |
| References |
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References
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Further Reading
Keywords
transient hypogammaglobulinemia of infancy, THI, decreased immunoglobulin A, IgA, decreased immunoglobulin G, IgG, immunoglobulin M, IgM, common variable immunodeficiency, CVID, Bruton's agammaglobulinemia, hyper-IgM syndrome, HIGM, B-cell defect, dysgammaglobulinemia, upper respiratory tract infections, otitis media, sinusitis, pneumonia, severe combined immunodeficiency, SCID, bronchial infections, polysaccharide-encapsulated bacteria, varicella, oral candidiasis, sepsis, meningitis, food allergy, asthma, allergic rhinitis, acute lymphocytic leukemia, ALL, X-linked infantile agammaglobulinemia
