Q:

3/11/2013
I have a 13 year old patient with CVID who has done well for several years on IVIG. Over the past year he has reverted to a pattern of frequent febrile illnesses despite q 28 day IVIG, with trough levels well within the limit of normal on his current dose. He "knows" that he is due for his IVIG at 3 weeks, but measured gamma levels are still good then. He is a non responder to the pneumovax (did not develop good antibody levels when he was immunized while off IVIG). Is there any utility to trying q 3 weeks on IVIG?

Re: another patient: Is there any literature supporting IvIG in a patient with normal IVIG levels, but no response to pneumovax given twice, and a history of recurrent pneumonia? Or does he need a better pulmonary/immunology eval? He is otherwise well, save for the pneumonias.

A:

Thank you for your inquiry.

In answer to your question regarding the 13 year old patient, it would certainly not in any way be harmful to institute an empiric trial of replacement at every three weeks or increase his dose administered every four weeks. However, I think that it would also be important to look at other “noninfectious” potential causes of his febrile illnesses. These would include granulomatous/lymphoid infiltrative disease. These granulomatous/lymphoid infiltrations occur most commonly in the lungs, spleen, and lymph nodes, but they can occur elsewhere including the liver, bone marrow, gastrointestinal tract, and other sites. It can be associated with febrile episodes.

Also, as you know, autoimmune complications can occur in patients with common variable immunodeficiency. Usually these are associated with other manifestations, but early on, fever can occur without an obvious autoimmune source. And finally, there is cancer of various types including lymphomas, and also lymphoid hyperplasia and splenomegaly. Since you did not mention specifically that these viral episodes were accompanied by clear-cut infections (e.g., pneumonia), I believe it would be important for you to look for other possible causes before assuming that they are infectious related, and increasing the frequency of infusions empirically.

If, however, none of these complications are present, as noted, a trial of more frequent infusions would certainly be without harm, and I would proceed in doing so.

The issue of the administration of immunoglobulin replacement therapy to a patient with normal immunoglobulin levels but poor response to pneumococcal vaccine is controversial. However, clearly, in some cases it is indicated. The best source for a discussion of this issue is the Working Group Report of the American Academy of Allergy, Asthma, and Immunology on the use of immunizations in the diagnosis of immunodeficiency disorders recently published in the Journal of Allergy and Clinical Immunology (1). I have copied for you below Summary Statement 30 taken from this document:

“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)”

However, in my opinion, the clinical situation should be fairly consistent with immunoglobulin deficiency, and the patient should show clear-cut manifestations of bacterial infections. Such manifestations would include hyperplastic sinusitis, bronchiectasis, and recurrent documented bacterial pneumonia.

Also, there is an excellent reference available to you regarding noninfectious febrile complications of common variable immunodeficiency. You can access this reference online without charge. It is entitled “How I Treat Common Variable Immunodeficiency” and is written by Dr. Charlotte Cunningham-Rundles.

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

Reference:
1. Orange JS, 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 (September); 130(3): Supplement, Pages S1-S24.

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology