When children present with recurrent infections, treatment of the specific infection is typically paramount in the clinician’s mind. While obviously necessary, such focus on resolving the infection may distract from considering an underlying condition, such as allergies or immunodeficiencies, that may be occasioning the recurrent infections.
“Some immunodeficiency disorders are not picked up as early as they might be because pediatricians are so focused on treating, for example, an ear infection from crisis to crisis with antibiotics that they may not get at the real cause, which might be an immunodeficiency,” says Stuart L Abramson, MD, PhD, FAAP, director, Allergy/Immunology Services, Shannon Medical Center/Shannon Clinic, San Angelo, Texas.
It is estimated that primary immunodeficiencies (PIs) occur in about 1:2000 live births.1 Unlike secondary immunodeficiencies that occur in connection with other conditions (for example, viral infections, malignancies, or malnutrition), PIs are inherited disorders affecting the functioning of the immune system. Children and adults with PIs are predisposed to infection, autoimmune disease and aberrant inflammatory response, and malignancy.
A key presenting feature of all immunodeficiency disorders is an increased susceptibility to infection. Therefore, children who present with frequent infections should be on the clinician’s radar as potentially having immunodeficiency disorders. This is the first step in recognizing and managing what could be a life-altering condition if not caught and treated early. Early diagnosis and treatment are critical to preventing or reducing the significant morbidity and mortality that can result if PIs are left undiagnosed and untreated.2
“’Chance favors the prepared mind,’” says Abramson, quoting the French scientist Louis Pasteur. “If you don’t think about it, you aren’t going to make the diagnosis and help these patients. So just thinking about the problem, being alert to the early warning signs, and getting the proper testing and referral can make all the difference.”
In a presentation at the 2017 American Academy of Pediatrics (AAP) meeting in Chicago, Illinois, titled “Recurrent infections: Is it immunodeficiency?” Abramson discussed the warning signs suggestive of a PI, a stepwise approach to making the diagnosis, and management issues in the care of children with PI disorders.3
Abramson opened his talk with a description of the different types of immunodeficiency disorders, focusing specifically on PI disorders. All PIs stem from the failure of one or more of the body’s defensive mechanisms to properly function. The type of PI depends on the specific defect of the immune system—whether it is characterized by a humoral (antibody) deficiency, cellular deficiency, or a combination of both humoral and cellular deficiencies.1
Fifty percent of PIs are primary B-cell disorders: both more-common PIs (eg, selective immunoglobulin A [IgA] deficiency disorders) and uncommon PIs (eg, X-linked agammaglobulinemia). Other types of PIs are categorized as combined B-cell and T-cell immunodeficiencies (20%), phagocyte immunodeficiencies (18%), T-cell immunodeficiencies (10%), and complement immunodeficiencies (2%).1 Abramson provided a brief description of several common and uncommon PIs and their clinical presentations (Table 1).
To help clinicians recognize when a child may have a PI, Abramson referred to a quick checklist of 10 warning signs developed by the Jeffrey Modell Foundation.2 As noted in Table 2, a child who presents with 2 or more of these warning signs should undergo further assessment to make the differential diagnosis. Some of these symptoms also may indicate an underlying undiagnosed and untreated allergy, so making the correct diagnosis is crucial.
Abramson emphasized the importance of pediatricians knowing these 10 warning signs because “they are often the first line of defense in terms of picking up these patients and getting them to the proper specialists.”
1. Bonilla FA, Khan DA, Ballas ZK, et al; Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma, and Immunology; American College of Allergy, Asthma, and Immunology; and Joint Council of Allergy, Asthma, and Immunology. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol. 2015;136(5):1186-1205.
2. Modell V, Gee B, Lewis DB et al. Global study of primary immunodeficiency diseases (PI)—diagnosis, treatment, and economic impact: an updated report from the Jeffrey Modell Foundation. Immunol Res. 2011;51(1):61-70.
3. Abramson SL. Recurrent infections: Is it immunodeficiency? F1120. Presented at: American Academy of Pediatrics National Conference and Exhibition; September 16-19, 2017; Chicago, IL.
4. Yong PL, Boyle J, Ballow M, et al. Use of intravenous immunoglobulin and adjunctive therapies in the treatment of primary immunodeficiencies: a working group report of and study by the Primary Immunodeficiency Committee of the American Academy of Allergy, Asthma, and Immunology. Clin Immunol. 2010;135(2):255–263.
5. Orange JS, Ballow M, Stiehm ER, et al. Use and interpretation of diagnostic vaccination in primary immunodeficiency: a working group report of the Basic and Clinical Immunology Interest Section of the American Academy of Allergy, Asthma, and Immunology. J Allergy Clin Immunol. 2012;130(3 suppl):S1-S24.