Q:

1/14/2013
I saw a 50 year old white female who presented with a diagnosis of panhypogammaglobulemia. She is otherwise in good general health. A recent lab work up showed a good IgG response to pertussis, rubella and tetanus. She had a fair response to pneumoccal. She had normal T cells, however her B cells were 5 and her IgG was 550. Please advise as to the best way to proceed. Thank you.

A:

Thank you for your inquiry.

I hope that we will be able to help you, but I believe to give us our best chance, we will need a little more information. It would be very helpful if you would supply us with the following:

1. There is a range of “normal” in B cell determinations between labs. Could you send us the “normal” value for the lab you used?
2. What were the levels of her other immunoglobulins?
3. Which pneumococcal vaccine did you use? Was it Prevnar or Pneumovax?
4. Could you be more explicit regarding the results to pneumococcal immunization? Could you give us the pre and post titers for each serotype or at least the number of serotypes tested and the number which increased significantly as well as the number that reached a protective level of 1.3?
5. Finally, and perhaps more importantly, you said she was referred because of panhypogammaglobulinemia, and that she was in general good health. But what would be very important is a more detailed history of the infections she has shown. How many upper respiratory tract infections per year? Any episodes of pneumonia and Is there any evidence whatsoever of secondary bacterial infections with end-organ damage such as bronchiectasis, chronic hyperplastic sinusitis, or decline in lung function?

The decision to begin immunoglobulin replacement therapy (for example compared to antibiotic prophylaxis) is one of clinical judgment in a case such as yours, and one cannot make a very accurate clinical decision without the above information.

I will do my best to get back with you with either my opinion or someone else's who is perhaps more expert in this area, as soon as we receive the information noted above. I hate to put you to the extra work, but I believe it will greatly enhance our response to you.

Thank you again for your inquiry, and for your interest in our website.

Sincerely,
Phil Lieberman, M.D.

Thank you for the additional information.

I am referring your question to Dr. John Routes, who is a nationally recognized expert in immunodeficiency disorders and has a tremendous amount of experience in dealing with common variable immunodeficiency and patients requiring immunoglobulin replacement therapy. As soon as I receive a response from Dr. Routes, I will forward it to you.

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

Sincerely,
Phil Lieberman, M.D.

Below is the response that we received from Dr. John Routes. Thank you again for your inquiry and we hope this response is helpful to you.

Sincerely,
Phil Lieberman, M.D.

Response from Dr. John Routes:
As you know the decision to give IVIG is not totally based on lab findings. In this case, I believe the immunological findings are almost normal---the international guidelines (which are currently under revision) for the diagnosis of CVID require a low IgG (I believe a consensus will be reached on a level and almost certainly <400mg/dl) and/or low IgA or IgM and a poor specific Ab response. In this case you have an IgG of 550 mg/dl (not in the worrisome range ), normal IgA/IgM, normal response to protein Ags and protective response to 6/14 capsular antigens to pnuemovax (which despite the AAAAI guidelines, I believe is completely normal)---as far as the flow cytometry----I don't worry about a borderline low B cell count---the patient has near normal immunoglobulin levels and normal specific Ab response, so she has good B cell function-----flow cytometry results are VERY lab dependent---we run a CLIA certified flow cytometry lab in our division and I read/sign off on the results daily---so I would be very particular about where I send my lymphocyte subsets---in this case, David should consider sending his lymphocyte subset analysis to National Jewish as they have an excellent flow lab----regardless, the low numbers of B cells would not influence my decision to treat in this case.

Finally, when I see an isolated low IgG, I always think about secondary causes for this abnormality such as drugs (corticosteroids, rituximab) and protein losing states (protein losing enteropathy, proteinuria).

I hope this is helpful.

John M. Routes, MD

AAAAI - American Academy of Allergy Asthma & Immunology