Q:

7/1/2013
A 69 yo female with history of allergic rhinitis, food allergy, chronic lymphocytic leukemia, was seen for recurrent infections including multiple episodes of bronchitis, sinusitis, and pneumonia. She does have exposure to sick contacts working in a daycare. Immunoglobulins on 4-30-2013 were IgA 25 (68-378), IgG 1210 (694-1618), IgM 78 (53-334) and on 6-19-2013 were IgA 26 (82-453), IgG 1250 (751-1600), IgM 80 (46-304). She had very decreased antibody titers to tetanus and diphtheria and does not remember when she was vaccinated. She had extremely decreased antibody titers to strep pneumonia despite vaccination with pneumovax 7 months ago.

Although her Immunoglobulins are normal, she has notable decreased titers to strep pneumonia. In the workup for selective antibody deficiency, IgG subclasses should be checked; however, what is the value of checking subclasses given the controversy in whether or not to check subclasses as far as diagnosis and management with IVIG. I am planning to vaccinate with conjugated vaccine prevnar as well. Additionally, how if at all does the CLL possibly affect the workup and change findings? Thank you.

A:

Thank you for your inquiry.

Unfortunately, the issue brought up by your inquiry is controversial. According to the best of my knowledge, different opinions exist regarding whether a poor response to pneumococcal vaccination alone in a patient with relatively normal immunoglobulins can determine the need for immunoglobulin replacement therapy. In the final analysis, clinical judgment is used to make the decision as to whether or not to administer immunoglobulin in such cases. But our practice parameter does allow for a liberal interpretation in cases where there is clinical indication for replacement therapy in such instances.

As you can see in Summary Statement 30 copied below, from a recent practice parameter(1), one can make a diagnosis of specific antibody deficiency based upon a poor response to pneumococcal immunization alone in spite of the fact that both the response to immunization with protein antigens and total immunoglobulin levels are normal. This clearly indicates that hypogammaglobulinemia is not a sine qua non for the diagnosis of specific antibody deficiency.

The presence of documented chronic bacterial infection (eg chronic sinusitis, bronchiectasis) would strengthen the case for replacement. You might therefore consider doing imaging studies to look for the presence of these complications. The diagnosis of Chronic lymphocytic leukemia strengthens the case a bit. This would be especially true if there was a monoclonal antibody present. So I would do an immuno-electrophoresis if it hasn't been done. I don't think subclass determinations would offer any help.

Thank you again for your inquiry and we hope this response is helpful to you.

(1) The Journal of Allergy and Clinical Immunology
Volume 130, Issue 3, Supplement , Pages S1-S24, September 2012
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 & Immunology
"Summary "Statement 30: A diagnosis of specific antibody deficiency (SAD) can be made if the response to PPV23 is deficient but the responses to protein antigens(eg, tetanus toxoid or diphtheria toxoid), conjugate vaccines (Haemophilus influenzae type b, PCV7, or PCV13), or both are intact and total immunoglobulin levels are normal. (III C)"

Warm Regards
Phil Lieberman MD

AAAAI - American Academy of Allergy Asthma & Immunology