Begin by thinking about this diagnosis. If you don’t consider immunodeficiency during your routine evaluations, you are likely to miss one of these relatively rare conditions. Screening is of the utmost importance with more than 175 pediatric primary immunodeficiencies identified.
Considering immunodeficiencies appropriately is important – they represent sharp needles in the pediatrician’s haystack. You might be thinking: How am I going to recognize these important needles in my busy practice? My advice is to look for the hallmarks – infections that are recurrent, severe, or unusual.
I use a Statue of Liberty analogy. Give me your five sickest kids – the ones who hound your triage nurse, the ones who always page you after hours – and then think about immunodeficiency as a possible diagnosis. A child with recurrent infections who requires and responds to antibiotics frequently is a likely candidate.
Upper and lower respiratory tract infections are common in this patient population. About half of children with an immunodeficiency will have antibodies and will most typically present with involvement of the sinuses and/or the ears, including in some cases, bronchitis or pneumonia.
Severe combined immunodeficiency syndrome (SCIDS) is particularly alarming. If you practice in one of the states that require newborn screening for this condition – California, Louisiana, Massachusetts, New York, or Wisconsin – you are likely to receive a call at some point from your state laboratory. The number of calls you get alerting you to a positive result will vary by the size of your practice: SCIDS affects about 1 in 50,000 live births. There was a case in Wisconsin where a baby with SCIDS was identified quickly and cured (J. Allergy Clin. Immunol. 2011;127:535-38).
A newborn with SCIDS lacks the capacity to make functional T cells, and there is a movement to expand this screening to all 50 states.
As with any confirmed immunodeficiency, working in concert with an immunologist becomes essential. Expertise is important because there are therapeutic options for almost every patient with a primary immunodeficiency diagnosis. A subspecialist can help you devise an effective management plan. It is a matter of pediatricians feeling empowered, not feeling that children with primary immunodeficiencies are too complex to manage.
I am fine with a pediatrician calling for a direct referral. It is appropriate not to manage the diagnostic evaluation of these children if you feel uncomfortable. With that said, there are opportunities for pediatricians to manage these patients as well. I know some pediatricians are as adept at this as I am.
For example, you can screen a child with a suspected immunodeficiency for the presence of antibodies. Keep quantity and quality in mind. Quantity is a check of how full the tank is; for example, assess their levels of IgG, IgM, and IgA.
Quality assessment can be more challenging, but there are appropriate, point-of-contact screenings you can perform without too much effort. Most importantly these would include checking the antibody titers against vaccines you have provided, such as a tetanus titer or pneumococcal titers.
A complete blood count with differential, for example, provides important information, including the percentage and number of lymphocytes and neutrophils. If the absolute levels are low, then it becomes relevant to think: Why? Viral suppression is a true cause, but it’s overrated, so be sure to reevaluate a low count and remember to consider immunodeficiency if a low value persists.
If you suspect immunodeficiency in a baby, for example, check the infant’s lymphocyte count against the age-specific normal value. This varies, but the lower limit for normal for a healthy child under 1 year of age is about 3,500/mcL.
This might surprise you, but a child with low or no lymphocytes can quickly require emergency medical attention.
Other tests are more in the domain of the specialist or more appropriate in specific situations. In addition, the assay order forms and specialty laboratories can be tricky. Right next to IgG, for example, the IgG subclasses are often listed. These subclass evaluations are expensive and of little value in routine clinical assessment.
The bottom line is: Think about primary immunodeficiency. If you are uncomfortable in carrying forward a diagnostic evaluation – call an immunologist. We are happy to help. Statistically speaking, the needle is in your haystack. A pediatric practice looking after 10,000 children should be following 5 with primary immunodeficiency. Do you know who yours are?
This column, "Subspecialist Consult," appears regularly in Pediatric News, an Elsevier publication. Dr. Orange is a pediatric immunologist in the division of allergy and immunology at Children’s Hospital of Philadelphia. He disclosed that he is a medical adviser to the Immunodeficiency Foundation and a consultant to three manufacturers of immunoglobulin therapies: Baxter Healthcare, Talecris Biotherapeutics, and CSL Behring. He also receives research grants from Octapharma USA.