Early diagnosis, treatment critical
Diagnosis of a PI disorder is based on stepwise approach involving 4 stages. Table 3 lists the stepwise approach to diagnosis recommended by the Jeffrey Modell Centers Network. Abramson said that most PIs (about 75%) can be diagnosed by obtaining a complete blood count (CBC) and quantitative immunoglobulin levels (stage 1).
If either test is abnormal, he emphasized, it is important to repeat the test to ensure that the first reading was not a lab error and that the positive test truly reflects a persistent problem.
“Unless you get a follow-up test, for example, of an initial test that showed either a low or high white blood cell count, you don’t know whether the blood cell count has normalized,” Abramson said. “In the case of a very low lymphocyte count that remains low, that could be indicative of a cellular immunodeficiency and not just a viral infection.”
“Viral infections can lower the white blood count, but if it doesn’t go away, it may be a persistent cellular deficiency,” he reiterated.
If a positive test persists after repeat testing, further diagnosis is indicated. For any diagnosis required after stage 1, Abramson suggests pediatricians consider referral to an allergist or immunologist for further workup. In addition to a potential diagnosis of a PI, some of these children with recurrent infections (eg, recurrent otitis) may have an underlying allergy that needs to be diagnosed or ruled out to make the correct differential diagnosis.
Following this stepwise diagnostic approach and referring children to specialists when warranted are critical to ensuring an accurate and early diagnosis.
“Early diagnosis is very important for some of these disorders because if the patient goes for a long period of time with recurrent infections, this can sometimes cause more chronic problems,” said Abramson, citing the potential for, among other conditions, the development of bronchiectasis if the underlying PI goes undetected and untreated.
In addition, Abramson said that early detection is critical for children who have a severe PI because they can be candidates for bone marrow transplantation. These children typically have an immunodeficiency that poses serious, life-threatening outcomes if immune reconstitution is not achieved. “If you wait too long and the infection becomes too difficult to treat or becomes chronic, it’s much riskier to do a bone marrow transplant because you have to immunosuppress the patient as you don’t want them to develop a graft-versus-host reaction,” he said. Characteristics for transplantation for PI disorder are listed in Table 4.
Currently, most children diagnosed with PI disorders are treated with immunoglobulin therapies that can be delivered either intravenously in the clinic or subcutaneously at home.4 Table 5 describes a standard intravenous immunoglobulin therapy. For some children, subcutaneous therapy at home may be a better option. When compared with intravenous therapy, the benefits of subcutaneous therapy include improved quality of life, lower costs, and lower systemic adverse effects. However, disadvantages may include the need for more frequent treatments and local reactions at infusion sites.
Children presenting with recurrent infections may have underlying immunodeficiency disorders. Pediatricians should be alert to the warning signs indicating the potential for a PI disorder. Diagnosis includes a stepwise approach that begins with analysis of a CBC and quantitative immunoglobulin levels. If the results are positive after repeat testing, children should be referred to a specialist for further workup.
For most children diagnosed with a PI disorder, intravenous or subcutaneous immunoglobulin therapy is the standard treatment if specific antibody production is deficient.4,5 Bone marrow transplantation is indicated for children with severe PI disorders. For all patients, early detection and treatment are critical to avoid long-term adverse effects of an untreated PI disorder.
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.