Q:

6/6/2012
I am currently following 10 year old boy with a history recurrent "colds" and coughing. He was experiencing 4-5 episodes/year of a chronic cough that persisted for 3 or more weeks. When I saw him the first time in 2009, he was being treated with inhaled corticosteroids which seemed to help the cough but not the nasal symptoms. IgA at that time was 45 mg/dL, IgG- 702 mg/dL(normal for age), IgM- 65 mg/dL, IgE- 11 kU/L, Hib titers 0.63 mcg/mL and streptococcus titers showed 13/14 below 1.3 mcg/mL. He had a few bouts of sinus infections with culture positive per ENT which responded nicely to antibiotics in 2009 -2010. He was lost to follow up in 2011 and the mother reported that the patient had done well that year.

Since December 2011, the patient has had 3 episodes of sinus infections with significant purulent nasal discharge that have responded to antibiotics. Repeat labs showed IgG- 709 mg/dL (low for age), IgA- 80 mg/dL and IgM- 70 mg/dL, tetanus antibody 2.28 IU/mL, post vaccination Hib of 6.12 mcg/mL and post-Pneumovax strep titers with only 3/14 below 1.3 mcg/mL, IgG1- 480 mg/mL (low), IgG2- 156 mg/mL, IgG3- 66 mg/mL and IgG4- 15.7 mg/mL. Recent CT scan this month was negative. Total IgE of 17 kU/mL and ImmunoCAP to aeroallergens was negative.

The patient is being treated nasal corticosteroids and antihistamines for his chronic rhinitis. He no longer has a chronic cough and is off inhaled corticosteroids.

1. Given the patient's history with a good response to Pneumovax and Hib vaccinesbut with chronic rhinitis and sinus symptoms, do think this patient is a candidate for IVIG with the current level of 709 mg/dL (per Stiehm 4th edition, IgG range for this age is 1124+ 235)

2. If he is a candidate, would you try prophylactic antibiotics first before considering IVIG?

3. Is there any other evaluation that you would suggest before pursuing a treatment such as IVIG?

4. Is the low IgG1 significant?

Thank you for your time and expertise.

A:

Thank you for your inquiry.

I am going to ask Dr. Ricardo Sorensen, a nationally known expert in pediatric immunodeficiency disease, to respond to your inquiry. As soon as we receive his response, we will forward it to you.

Thank you again for your inquiry.

Sincerely,
Phil Lieberman, M.D.

We received a response from Dr. Ricardo Sorensen regarding your recent Ask the Expert inquiry. Thank you again for your inquiry and we hope this response is helpful to you.

Sincerely,
Phil Lieberman, M.D.

Response from Dr. Ricardo Sorensen:
Let me start by answering each one of your questions and then ask you some questions to better define you patient and complement my initial answers. The response to your questions and my inquires are as follows:

1. Given the patient's history with a good response to Pneumovax and Hib vaccines but with chronic rhinitis and sinus symptoms, do think this patient is a candidate for IVIG with the current level of 709 mg/dL (per Stiehm 4th edition, IgG range for this age is 1124+ 235)

Answer: No. His IgG concentrations are slightly decreased according to the values given in Dr. Stiehm's book but they would be normal according to our normal values. It also needs to be remembered that normal values usually are expressed as 2SD, including 95% of all values; 2,5% of values are somewhat lower and 2,5% are higher that two SD in a normal population.  

2. If he is a candidate, would you try prophylactic antibiotics first before considering IVIG?

Answer: Yes, with the following qualifications: it seems that chronic rhinitis may have been a major risk factor for his sinus infections. Since it now is well controlled on antihistamines and inhaled steroids, antibiotic prophylaxis does not seem necessary.

If he needs prophylactic antibiotics for URI, you should start with regular nasal mupiricin rather than oral antibiotics. The last choice before IgG replacement should be oral antibiotics.

3. Is there any other evaluation that you would suggest before pursuing a treatment such as IVIG?

Answer: Yes. First, you need to put together an exact timetable of immunizations and tests performed giving the results for each of the serotype antibodies measured. It is notable that before pneumococcal immunization this patient had protective antibodies to only 1 pneumococcal serotype, despite a history of recurrent infections. This is not defined as an immunodeficiency in itself, but it is unusual at that age. It would be suggestive of a poor memory for specific antibodies if the patient was immunized with Prevnar as a child. Furthermore, which bacteria was cultured by the ENT? Was it a S. Pneumo strain or something else?

Based on these considerations, you should:

a. Check for possible fast loss of protective antibody concentrations after pneumococcal immunization

b. Culture his nasopharynx for colonization with antibiotic resistant pathogens that should no be there

c. Assess memory B cells by flow cytometry. Low levels would suggest that the patient has a mild immunological abnormality, although the patient may be losing protective antibody concentrations over time even without having low memory B cells.

4. Is the low IgG1 significant?

Answer: No, same comments as for total IgG concentrations.

If this patient's immunity is normal and there is no evidence for an allergic rhinitis, what is the cause for his chronic rhinitis? Local conditions created by a chronic rhinitis may be the predisposing factor for his recurrent infections. Low grade infections with a resistant bacteria, environmental irritants, drugs, anatomic factors, reflux, etc, need to be considered.

Hope this helps,
Ricardo Sorensen, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology