48 yo M presented referred from PCP for worsening of his exercise induced asthma and low IgM 26 (30-180) for evaluation of immunodeficiency. Reports 6 sinusitis and 2 otitis, no pneumonia in his adult life, most recent sinusitis 1/2012. Subsequently immunodeficiency workup performed, with pneumococcal titers > 1.0 for only 2 of 23 serotypes, ie serotype 20 was 1.1, serotype 57 was 1.9. Hib titer not protective at 0.14. Pneumovax given and post titers only > 1.0 for 5 types without two fold increase for any. Prevnar and HIB vaccines then given with 7 of 23 serotypes > 1.0 without two fold increase for any. HIB titer protective now; IgM still decreased at 30. IgG 1023; IgA 200. This workup may not have been necessary considering lack of significant infections but was done due to request. He responds to conjugated HIB vaccine only. None of this seems clinically relevant. I have looked for undetected infection perhaps as explaining his labs and sudden worsening of exercise induced asthma. CT sinus and CXR are normal. Questions: 1. How can we explain these findings of lack of response to Prevnar in such a patient. He wants an explanation. 2. Would he warrant a diagnosis as 'specific antibody deficiency'? He also continues to have low IgM. 3. Any other thoughts with someone whose exercise induced asthma is not controlled with premedication with Symbicort 160 and Singulair? (Admittedly he sometimes , but not always, takes immediately before since he runs 5-10 miles at 5 am upon awakening)


Thank you for your inquiry.

Let me start with your third question first. I would be reluctant to accept a diagnosis “offhand” of exercise-induced asthma in your patient if he runs 5 to 10 miles daily. It would be very unusual for a patient with exercise-induced asthma taking Symbicort and Singulair (and I assume albuterol?) to be able to run 5 to 10 miles. In addition, it would be unusual for a patient on this type of pretreatment with exercise-induced asthma who did not experience asthma to other triggers. You might consider further workup with an exercise challenge under observation or perhaps a mannitol challenge to further elucidate whether or not this patient truly has exercise-induced asthma.

I agree with you in regards to the probable lack of clinical significance at this time of his low IgM, and I refer you to several entries that we have had on our website regarding isolated hypogammaglobulinemia M. You can pull up each one of these by simply going to our Ask the Expert website and typing “IgM” in the search box.

These entries reflect the statements in your inquiry that your “workup may not have been necessary considering the lack of significant infections” and that “none of this seems clinically relevant.” I would agree with both comments, and based upon his clinical status and the observations in the previously posted entries, I would suggest observation at this time without consideration of instituting any therapy for the IgM.

Unfortunately, your patient may well have an underlying immunodeficiency based on the lack of a response to Prevnar, and certainly could develop clinically significant manifestations over time. But my advice at this time, as noted above, would be watchful waiting since your only other options would be to start immunoglobulin replacement or to treat with prophylactic antibiotics. And, as you stated, there appears to be no clinical indication for this in the absence of any detectable chronic bacterial infection.

You did not state over what period of time his “six sinusitis” and two “otitis” episodes occurred. However, considering the fact that two to three upper respiratory tract infections (commonly called sinusitis) per year is not abnormal for a 48 year-old, there is very little evidence to support the institution of preventive therapy at this time.

I empathize with your desire to give your patient an explanation for his failure to respond to Prevnar. And I also empathize with his need to know the underlying reason for this lack of response. However, as you know, we face such requests for many of the conditions we treat. And in fact, quite often we simply do not have explanations. In these instances, it is not unreasonable simply to tell the patient that we do not have an answer for her/him at this time.

In summary:
1. From a clinical standpoint, I would not proceed with any further workup in your patient nor consider instituting any preventive therapy in regards to his low IgM. It is possible, based upon his lack of response to Prevnar that something will “show up later,” and I would simply advise following him.
2. Unfortunately, I do not believe you can give your patient a trustworthy answer as to why he did not respond to Prevnar. A frank discussion with your patient regarding our inability to give such answers on occasion is indicated.
3. Parenthetically, you might consider evaluating his exercise-induced symptoms further. If he runs 5 to 10 miles at a time, I would not be concerned about this shortness of breath, but it may be that his use of asthma prophylactic therapy is really not indicated.

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

Phil Lieberman, M.D.

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