Transient Hypogammaglobulinemia of Infancy - Clinical Presentation, Diagnosis, and the Associated Complications

Introduction:

Transient hypogammaglobulinemia (THI) is when the baby has low levels of immunoglobulins. The unborn baby does not produce an immunoglobulin G antibody (IgG). However, it begins to receive the antibody from the mother within six months of pregnancy, which increases during the last trimester of pregnancy. The immunoglobulin G is the only antibody that crosses the placenta. The baby will have only the immunoglobulin G in its circulation at birth. The presence of immunoglobulin M (Ig M) in the baby may indicate the presence of infection during intrauterine life.

Transient hypogammaglobulinemia is a temporary drop in the levels of immunoglobulin G, which usually begins between 5 to 24 months. This automatically returns to its normal reference range by two to six years of age in a healthy baby. This article explains the clinical features, its diagnosis, and the management of transient hypogammaglobulinemia.

What Is Immunoglobulin G And How Is It Important?

Immunoglobulin G is a type of antibody produced by the body’s immune system. It produces special proteins called “antibodies” to fight against the invasion of microorganisms or foreign bodies. This immunoglobulin G (IgG) is found in the blood and extracellular fluid.

What Causes Hypogammaglobulinemia?

Despite several pieces of research and advancements in medicine, the actual cause of transient hypogammaglobulinemia is hypothetical and still not clear. However, there are few mechanisms that are thought to cause transient hypogammaglobulinemia. They are:

1. The malfunctioning of the T cells may fail to stimulate the production of B cells.

2. The maternal (Ig G ) immunoglobulin G suppresses the production of immunoglobulin G in the infant.

3. The production of critical cytokine levels is lower.

4. Inherited immunodeficiencies that run in families.

5. The presence of immature and abnormal B lymphocyte cells.

What Is the Incidence of Transient Hypogammaglobulinemia?

• It is not a common condition that occurs in about 0.05 to 1 in 1000 live births.

• It has a male predilection and a 2:1 male to female ratio.

• It is more prone in immune-compromised individuals and affects about two percent of immune-deficient children.

What Is the Physiologic Alteration That Happens in the Body?

• The transient hypogammaglobulinemia (THI) is considered a physiological (normal) change that occurs in the baby. The maternal immunoglobulin G (IgG) is important to the baby as it is the only immunoglobulin that crosses the placenta, and it protects from infection during the first few months of life. They may also get additional antibodies through breast milk. This material or the transplacental immunoglobulin G slowly begins to decrease, and by six months of life, it is almost gone. So the baby begins to produce its own IgG antibody. During the first six months of life, as the maternal antibodies have decreased and the baby has begun its own production, the baby will have lesser levels of antibodies.

• Also, the immunosuppressive antibodies from the mother cross the placenta and result in decreased levels of antibodies in the baby.

• However, the number of B lymphocytes is normal with a temporary impaired T cells function.

What Is the Clinical Presentation of Transient Hypogammaglobulinemia?

• Most often, the patients may be asymptomatic.

• The main symptom that is specific to transient hypogammaglobulinemia (THI) is a frequent and recurrent middle ear infection, sinusitis, and bronchial infection.

• Loss of weight and failure to thrive.

• Some present with recurrent upper and lower respiratory tract infections.

• Gastrointestinal disorders, diarrhea, and persistent vomiting.

• They are more prone to allergic diseases, asthma 25%, eczema (a skin condition that appears red, dry, and itchy) 15%, and food allergy 12%.

• Aphthous ulcers (sores present in the mouth).

• More frequent bacterial, viral and fungal infections (candidiasis).

• Nasal and throat infections and recurrent tonsillitis are very common.

• Purulent conjunctivitis (eye disease causing pain and swelling) and pyodermatitis (a rare skin condition).

What Are Other Complications Associated?

The other possible complications are:

• Septicemia (infection in the blood) and bacteremia (viable bacteria seen in the blood circulation).

• They are more prone to serious infections such as pneumonia, meningitis, and typhoid.

• In rare and severe cases, urinary tract infections, gastroenteritis, and opportunistic infections are seen.

• Anaphylaxis (a severe allergic reaction that is life-threatening).

• Neutropenia (a decrease in the number of circulating neutrophils, a type of white blood cell).

• Oral candidiasis fungal infection.

How to Diagnose Transient Hypogammaglobulinemia?

Transient hypogammaglobulinemia is most often asymptomatic, and its diagnosis requires certain investigative procedures. By definition, transient hypogammaglobulinemia is when the immunoglobulin G(IgG) levels are lower than 200mg/dL, and values less than 100mg/dL are defined as permanent immunodeficiency.

What Are the Investigations Done to Rule Out Transient Hypogammaglobulinemia?

• Complete Blood Count (CBC): It helps to rule out primary immunodeficiency.

• Total Lymphocyte Count, T4 Lymphocytes ( Cd3, Cd4, And Cd 8 Count), And Cd4/Cd8 Ratio.

• Chest And Sinus X-Ray: To diagnose chronic respiratory tract infections.

• DNA Testing: A genetic test to detect any mutations in the genes.

• Diagnostic Ultrasound: It is a noninvasive procedure that uses sound waves to visualize the inside of the body.

• Computed Tomography (CT Scan): A computerized X-ray imaging that gives detailed information regarding the disease condition.

• Microbiological Studies: The following examinations are done to evaluate the infection present and the causative organism.

• Cerebrospinal Fluid: Culture, chemistry, and histopathology.

• Blood Culture: The blood sample is collected and viewed for the presence of microorganisms.

• Stool Culture: The feces or stool is collected and examined for the presence of microorganisms.

• Sputum Examination: The respiratory secretions are collected to identify the cause of the infection.

Is There Any Similar Condition Like Transient Hypogammaglobulinemia?

There is one such condition that mimics the symptoms of transient hypogammaglobulinemia and is often misinterpreted. It is X-linked agammaglobulinemia or Bruton’s syndrome, where the child presents with recurrent bacterial infection with bronchitis that commonly affects male children.

What Is the Management of Transient Hypogammaglobulinemia?

• If your child is asymptomatic, then no specific treatment is required. All that you have to do is take your child for regular follow-ups, and clinical evaluation of the Immunoglobulin G is repeated every four to six months.

• In case of recurrent infections, then,

  • Prophylactic antibiotic therapy is given.

  • Allergic rhinitis is treated with topical Corticosteroids and antihistamines.

• In some cases where the child does not respond to antibiotic therapy, then intravenous immunoglobulin G(IVIG) is indicated.

• Regular immunization protocols are mandatory in order to prevent the risks of life-threatening infections.

1. Conjugated heptavalent Pneumococcal vaccine is initiated at two months of age.

2. Inactivated vaccines against diphtheria, tetanus, pertussis, and Haemophilus influenzae.

3. Killed vaccines against polio, hepatitis A and B are also included.

4. Live viral vaccines against measles, mumps, rubella, and rotavirus should be delayed.

• Surgical Management:

• Tympanostomy tubes are placed to prevent recurrent middle ear infections.

• Functional endoscopic sinusitis surgery (FESS) may also be indicated in cases of chronic sinusitis.

What Is the Prognosis of This Condition?

The outcome depends on the severity of the condition. In cases of asymptomatic and mild cases, the outcome is generally good. Severe cases often suffer from opportunistic infections, and immunoglobulin therapy has improved the condition in many children. Only in extremely rare cases do the intravenous immunoglobulin G and antimicrobials indicate lifelong.

Conclusion:

Most children with transient hypogammaglobulinemia (THI) return to normal levels by the age of three. However, it is important to educate the parents on the health condition of their children, and proper measures have to be taken. As these children are more prone to infections and have the least ability to resist foreign body invasions, preventive measures should be taken in order to keep them away from sick individuals. Avoid food substances that provoke allergic reactions. The majority of the children respond well to the treatment and return to their normal state, so do not get stressed about the child’s health. Follow regular check-ups that will improve your child’s health.