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Immunoglobulin Replacement Therapy in Children

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Immunoglobulin replacement therapy has many benefits in children with primary antibody deficiencies.

Medically reviewed by

Dr. Veerabhadrudu Kuncham

Published At September 8, 2023
Reviewed AtMay 30, 2024

Introduction:

Many congenital disorders present earlier in life; hence, this therapy is often first enforced in children. For many of these children, immunoglobulin infusions will remain a necessity. No other therapy is confirmed as efficacious as immunoglobulin replacement therapy in lowering the number and severity of contagious complications in affected children with antibody deficiency. The pediatric immunologists will combine close clinical monitoring and punctual and appropriate immunoglobulin replacement, which could ultimately extend the life expectancy of affected young children.

What Is Immunoglobulin Replacement Therapy?

Immunoglobulin replacement therapy is the infusion of immunoglobulin (antibodies) into people with primary or secondary immunodeficiencies. Immunodeficiencies comprise a weakened or absent immune response that makes children vulnerable to recurrent infections. Immunodeficiencies can be inherited or acquired because of certain medical conditions, medications, or treatments.

What Are the Causes of Low Immunoglobulin in Children?

Low immunoglobulins in children can be due to multiple causes, such as the following,

1. Decreased Immunoglobulin Production:

  • Primary antibody defects.

  • X-linked agammaglobulinemia.

  • Transient hypogammaglobulinemia of infancy.

  • Autosomal recessive agammaglobulinemia.

  • Hyper IgM syndrome.

  • Ataxia-telangiectasia.

  • Severe combined immunodeficiency.

  • Common variable immunodeficiency.

  • Prematurity.

  • Malignancy.

  • Post-organ transplant.

  • Drugs.

  • Chemotherapy.

  • Immune thrombocytopenia.

  • Kawasaki disease.

2. Increased Loss of Immunoglobulins:

3. Increased Catabolism (Breakdown of the Molecule) Of Immunoglobulins:

  • FcRN mutations.

  • Myotonic dystrophy.

  • Sepsis.

What Are the Indications of Immunoglobulin Replacement Therapy in Children?

Immunoglobulin replacement therapy is generally indicated for children with primary or secondary autoimmune deficiency only if they suffer from recurrent or severe infections and impaired antibody production. Currently, there are six clinical indications for immunoglobulin replacement therapy in the USA that the Food and Drug Administration (FDA) has approved:

  1. For treatment of primary immunodeficiencies.

  2. Preventing bacterial infections in individuals with hypogammaglobulinemia and recurrent infection from B-cell chronic lymphocytic leukemia.

  3. Preventing coronary artery aneurysms in case of Kawasaki disease.

  4. Preventing infections, acute graft versus host disease, and pneumonia after bone marrow transplantation.

  5. Reducing severe bacterial infection in kids with HIV (human immunodeficiency virus).

  6. To increase platelet count in idiopathic thrombocytopenic purpura to prevent or control bleeding.

Immunoglobulin replacement therapy is used as a treatment for many disorders in children. Some of the common conditions in which it is indicated the following:

1. Neurological Conditions:

  • Chronic inflammatory demyelinating polyradiculopathy (CIDP).

  • Guillain Barre syndrome.

  • Dermatomyositis and inflammatory myopathies.

  • Myasthenia gravis.

  • Opsoclonus myoclonus ataxia.

  • Rare childhood epilepsy (Landau Kleffner seizure, Lennox gastaut seizure).

  • Opsoclonus myoclonus ataxia.

  • Pediatric autoimmune neuropsychiatric disorders of streptococcal infection include obsessive-compulsive disorder, anxiety, depression, and emotional lability.

2. Hematological Conditions:

  • Idiopathic thrombocytopenic purpura.

  • Pure white cell aplasia.

  • Pure red cell aplasia.

  • Immune neutropenia.

  • Immune hemolytic anemia.

3. Immunological Conditions:

  • Primary antibody deficiencies include XLA, CVID, WAS, HIGM, and others.

  • Secondary antibody deficiencies.

4. Dermatological Conditions:

  • Kawasaki syndrome.

  • Dermatomyositis.

  • Blistering diseases.

  • Toxic epidermal necrolysis.

  • Immune urticaria.

  • Pyoderma gangrenosum.

  • Atopic dermatitis.

5. Neonatological Conditions:

  • Hemolytic disease in newborns because of Rh and ABO incompatibility.

  • Bacterial sepsis in preterms.

  • Neonatal alloimmune thrombocytopenic purpura.

6. Other Conditions:

  • Myocarditis.

  • Systemic lupus erythematosus.

  • Autoimmune uveitis.

  • Streptococcal toxic shock syndrome.

What Are the Benefits of Immunoglobulin Replacement Therapy in Children?

  • Infection Prevention: One of the main benefits of immunoglobulin replacement therapy is its ability to strengthen the child's immune system, decreasing the frequency and severity of infections. Immunoglobulin Replacement Therapy also helps as Immunoglobulin antibodies neutralize bacterial toxins, viruses, and superantigens, ultimately decreasing the risk of serious infections. It activates, complements, and boosts phagocytosis and antibody-mediated cytotoxicity. Additional benefits are due to its anti-inflammatory and immunomodulatory properties.

  • Long-Term Health Benefits: Effective immunoglobulin replacement therapy can improve long-term health outcomes for children with immunodeficiencies. Immunoglobulin replacement therapy maintains optimal immunoglobulin levels, which helps prevent organ damage caused due to recurrent infections, including pneumonia or meningitis. It also reduces the risk of acquiring chronic lung diseases in children.

  • Improved Quality of Life: Regular immunoglobulin replacement therapy can significantly improve a child's quality of life by decreasing the number of infections, hospitalization, and other complications. With better health, children can attend school regularly, experience social activities, and lead a more fulfilling life.

What Are the Methods of Administration of Immunoglobulin Replacement Therapy?

The doctor may administer Immunoglobulin replacement therapy in different ways, depending on the condition of the affected child and particular conditions:

  • Intravenous Immunoglobulin: It is the most common method of administering immunoglobulin. It involves the intravenous infusion of immunoglobulins every three to four weeks. The duration of each infusion session may range from two to six hours. The regular dose of intravenous preparation for antibody replacement ranges between 181.44 mg/lb and 272.16 mg/lb every two to four weeks. The dose is modified so the trough level before the next infusion stands at least 500 mg/dl.

  • Subcutaneous Immunoglobulin: It is an alternative method of administering immunoglobulins. It is particularly appropriate for children who cannot attend the hospital for therapy every three to four weeks. In such cases, parents can administer or children can self-administer subcutaneous immunoglobulin. It involves the injection of immunoglobulins under the skin using a syringe or an infusion pump. It can also be used more frequently, such as once or twice a week, with shorter infusion times. Other advantages to the subcutaneous infusion are the more restricted fluid load and no connection with renal failure, which is a concern for sucrose-containing intravenous preparations. In addition, higher steady-state IgG levels can be achieved by subcutaneous infusion. However, it also has some limitations, such as the volume of fluid delivered subcutaneously being limited, mandating the concentration of the immunoglobulin preparation, and requiring infusion in multiple sites.

What Are the Side Effects and Risks of Immunoglobulin Replacement Therapy?

Immunoglobulin replacement therapy is usually safe. However, there are some possible side effects associated with it, as mentioned below,

  • After the infusion, some children may encounter local reactions at the injection site, including redness, swelling, and pain. However, these reactions are generally mild and temporary.

  • Some of the severe adverse effects of immunoglobulin infusion are renal failure, convulsions, thrombosis, stroke, pulmonary edema, hemolysis, and anaphylaxis which require immediate medical intervention.

  • In rare cases, children may get mild to moderate systemic symptoms, including headache, fever, chills, nausea, flushing, headache, back pain, chest pain, bronchospasm, nausea, myalgia, aseptic meningitis, transaminitis, and increased creatinine.

  • Allergic reactions to immunoglobulin infusions can rarely occur. Signs of an allergic condition may include rash, itching, wheezing, or difficulty breathing. Such cases require immediate medical intervention.

Conclusion:

Immunoglobulin replacement therapy is a leading treatment modality for children having immune disorders, which significantly improves their immune response, prevents infections, and enhances their overall quality of life. Through intravenous or subcutaneous administration, immunoglobulin replacement therapy provides the necessary antibodies that the immune system of the affected child lacks.

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Dr. Veerabhadrudu Kuncham
Dr. Veerabhadrudu Kuncham

Pediatrics

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