What is the investigation and management of low Immunoglobulin A (IgA) in a pediatric patient with Hypoimmunoglobulinemia?

From the Guidelines

For a pediatric patient with low IgA (0.76g/L), I recommend watchful waiting with regular monitoring rather than immediate intervention, as this level represents a mild deficiency that may normalize with age. Initial evaluation should include a complete history focusing on recurrent infections, autoimmune conditions, and family history of immunodeficiencies. Physical examination should assess for lymphadenopathy, growth parameters, and signs of chronic infection. Laboratory workup should include complete blood count, comprehensive metabolic panel, and assessment of other immunoglobulin classes (IgG, IgM, IgE) 1. No specific medication is indicated for isolated mild IgA deficiency unless the child has recurrent infections or other complications. Follow-up IgA levels should be checked annually as many children will normalize their IgA levels with age. Parents should be educated about increased vigilance for infections but reassured that most children with mild IgA deficiency remain healthy. If the child develops recurrent sinopulmonary infections, prophylactic antibiotics might be considered on a case-by-case basis. The rationale for this approach is that IgA deficiency is the most common primary immunodeficiency, with many individuals remaining asymptomatic throughout life, and intervention is generally only needed if clinical symptoms develop 1.

Some key points to consider in the management of low IgA in pediatric patients include:

• The definition of selective IgA deficiency (SIGAD) is restricted to very low or absent circulating IgA concentrations, and patients with serum IgA levels of less than the normal range for age but greater than 7 mg/dL should not be given a diagnosis of IgA deficiency 1.
• Patients with SIGAD should be monitored over time for the occurrence of complications, such as respiratory and gastrointestinal tract infections, atopy, autoimmune diseases, celiac disease, and malignancy 1.
• The general principles of management of Good syndrome, a form of adult-onset hypogammaglobulinemia associated with thymoma, are the same as for common variable immunodeficiency (CVID), including IgG replacement and monitoring of lung, liver, gastrointestinal, and kidney function 1.

Overall, the approach to managing low IgA in pediatric patients should prioritize watchful waiting and regular monitoring, with intervention only if clinical symptoms develop or if the child has recurrent infections or other complications.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Investigation of Low IgA in Paediatric Patients

• Low IgA levels in children can be due to various reasons, including transient impairment of immunoglobulins, maturation of the child's immune system, or serious illnesses 2.
• In children younger than 4 years, transient impairment of immunoglobulins is common, and the IgA levels may improve as the child's immune system matures 2.
• In older children, decreased IgA levels may lead to serious illnesses, and appropriate diagnostic methods are necessary to recognize and acknowledge these conditions 2.

Management of Low IgA in Paediatric Patients

• Selective IgA deficiency is defined as absolute or partial when serum IgA level is < 7 mg/dl or 2 SD below normal for age, respectively 3.
• Symptomatic patients with selective IgA deficiency may have similar clinical, immunological, and genetic features, regardless of whether they have absolute or partial IgA deficiency 3.
• Monitoring of symptomatic patients with selective IgA deficiency is recommended over time to promptly identify and treat associated diseases 3.
• Reversal of IgA deficiency has been observed in some children, especially in pediatric patients, and the average age of reversal is around 9-10 years 4.

Diagnostic Approach

• Quantitative serum immunoglobulin tests are used to detect abnormal levels of IgG, IgA, and IgM, and can help diagnose various conditions and diseases that affect the levels of these immunoglobulin classes 5.
• Secretory IgA deficiency in pediatric patients has been studied, and a direct statistical correlation was found between patients who normalize their secretory IgA levels and their course in an asymptomatic state 6.
• The relative risk of disease decreases in patients with normal secretory IgA levels, and strict environmental control should be established to avoid allergens in patients with repeated episodes of bronchial obstruction and lacking secretory IgA 6.

IgA Deficiency Diagnosis and Outcome

• The definition of IgA deficiency should not be made before the early teens using 0.07 g/L of IgA in serum as a cut-off, as some children may experience reversal of IgA deficiency 4.
• The prevalence of TNFRSF13B mutations has been assessed in patients with selective IgA deficiency, and no significant differences were observed between absolute and partial selective IgA deficiency patients 3.
• A significant difference in the rate of IgA normalization was detected between partial and absolute selective IgA deficiency patients, with 33% of partial selective IgA deficiency patients experiencing normalization compared to 9% of absolute selective IgA deficiency patients 3.