Q:

4/24/2013
I've looked up elevated IgE for an adult patient with chronic sinusitis, but negative for atopy or asthma, whose total IgE is 150-200, and he also had a pyogenic granuloma removed from his frontal sinus. Intradermals also negative. I looked on the AAAAI site for Ask the Expert Q/A, but in one of them you referred to older entries that are no longer posted, i.e. 7-6-09 and 3-31-08. Can I get those entries emailed to me? Thank you!

A:

Thank you for your inquiry.

Copied below you will find the previous entries you requested.

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

7/6/2009: Elevated IgE in a non-allergic asthmatic
Question:
I have a 58 year old patient who has developed rather severe asthma over the last 6 months. He has an IgE level of 893 (<114) but no evidence of allergy to any current outdoors or any routine indoor allergens. Do you have any thoughts on the elevated IgE or the clinical situation?

Thanks

Answer:
Thank you for your recent inquiry.

Asthma with an onset in later adulthood is, in the vast majority of cases, "intrinsic" or non-allergic asthma as defined by the presence of this illness in the absence of detectable specific IgE against a relevant allergen. In my experience, it is not unusual for intrinsic asthmatics to have elevated IgE values, but I have personally never been able to find a cause for these elevated levels. Nonetheless, when elevated IgE levels are present, the potential cause should be sought.

When you stated there was "no evidence of allergy," I assume that this patient has been evaluated by an allergist (preferably with allergy skin tests). One cannot completely rule out the presence of allergy without such an evaluation. In vitro tests, although valid, are less sensitive than tests performed in vivo. If such has been done, then the next step would be to rule out an elevation unrelated to the presence of asthma. Although such an unrelated etiology would be unexpected, one would be obligated to pursue other possible causes. These would include quite a number of illnesses, most of which would not fit the clinical picture you describe. However, in terms of broad categories of diseases, you should consider the following:

1. Parasitic diseases
2. Allergic bronchopulmonary aspergillosis
3. Churg-Strauss/polyarteritis nervosa

In addition, rarer causes such as an IgE myeloma can be worked up quite easily (immunoelectrophoresis or immunofixation).

As noted, in my experience, in most instances, the cause of the elevated IgE in patients with late onset (intrinsic) asthma remains undetected. If no other condition can be found, and the patient is clearly not allergic, the elevated IgE would not affect your approach to therapy. However, there may be one exception to this. The use of omalizumab should be considered in a patient with elevated IgE and with any detectable specific IgE which may be clinically relevant. Thus, again, I would clearly make sure that the patient has had in vivo tests to detect specific IgE, since even if a single relevant antigen can be found, the patient may be a candidate for omalizumab treatment.

3/31/2008: Elevated IgE of Unknown Cause
I have seen several patients in the last several years with highly elevated IgE levels with negative inhalant and select food allergy skin tests and RAST. Today I saw a 4 year old with an IgE of 1716 IU/ml with negative skin test and RAST to inhalant and food allergens including aspergillus. He has no history of any immune or pulmonary problems. How can I explain his markedly elevated IgE level?

I am really loathed to mention the standard causes of elevated IgE because I know you are well aware of them. Nonetheless, I will mention them because other readers looking up this query may not be aware of these disorders. They include the following:

1. The atopic diseases of allergic rhinitis, asthma, and allergic dermatitis.

2. Parasitic disease including the following:
a. Cestodes (Echinococcus).
b. Trematodes (Schistosoma).
c. Nematodes.
d. Ascaris.
e. Strongyloides.
f. Ancylostoma.
g. Capillaria.
h. Toxocara.

3. Hyper-IgE syndrome (parenthetically discussed in detail in the following New England Journal article reference: Holland SM, et al. STAT3 Mutations in the Hyper-IgE Syndrome. New England Journal of Medicine, October 18, 2007; 357:1608.)

4. IgE myeloma.

5. Various immunodeficiency states including the following:
a. Wiskott-Aldrich.
b. DiGeorge.
c. Nezelof.

6. Cystic fibrosis with the presence of atopy.

7. Kawasaki's.

8. Bronchopulmonary aspergillosis (some cases of aspergilloma as well).

9. Leprosy.

Obviously the vast majority of these entities are in no way relevant to your patient and would not be germane to any evaluation that you would perform. However, I mention them for the sake of completeness since, as noted, this may be viewed by other readers.

Looking over this list, none of these causes seem likely in your patient. However, most likely will of course be parasitic disease. Therefore one thing that you might do is proceed with a workup for parasitosis. This may seem somewhat exotic, but we have seen a number of patients over the years who presented with eosinophilia due to parasitosis, mainly ascaris and strongyloides.

Unfortunately, as you know, stools for ova and parasites are not particularly sensitive in making such a diagnosis. However, serology can be helpful for strongyloides, ascaris, and another one, not mentioned above, trichinosis.

On occasion, even when tests have been negative, empiric treatment with antiparasite therapy (e.g., mebendazole) has been successful in eliminating the eosinophilia.

I also, in adults, do an immunofixation or immunoelectrophoresis, looking for monoclonality (although this is obviously quite rare and would not normally apply to a 4-year-old).

From the above discussion, you can easily see that none of these examples clearly apply to your young patient, but I think it is the best we can offer at this time. It should also be mentioned that in many instances where I have seen an elevated IgE, we have not been able to find a cause and are simply left with either empiric treatment for parasitosis and/or simple observation to monitor the level over the years.

Although I have not given you a definitive answer, I hope this information is helpful to you in your evaluation, and would greatly appreciate a follow-up if you do find the cause. I would personally benefit by such a follow-up, and would like to share it with our readers as well.

Sincerely,
Phil Lieberman, M.D.

Dr Lieberman, Thanks for all your responses and taking the time to answer all these questions as a great public service to the allergy community.

In regards to eosinophilia workup that I wrote to you about in this patient below, I have perused the Ask the Expert question and answers, including the one you responded to me below. This may sound like a silly question, but when checking serology for parasites is it IgE or IgG? You have written: 'Unfortunately, as you know, stools for ova and parasites are not particularly sensitive in making such a diagnosis. However, serology can be helpful for strongyloides, ascaris, and another one, not mentioned above, trichinosis.'

For the pt below, I did order stool and serology and results came back + IgE for Echinococcus 18 ku/L by Quest (class 4), with negative stool for ova and parasites and Schistosoma IgG was negative. She denies overseas travel. Eosinophils are 2800 with IgE 400s. Repeat CT chest, abdomen /pelvis, sinus are all negative. ANCAs negative.

Any input would be appreciated.

Thank you for your help!
 
Phil Lieberman, M.D. response:
Thank you for your follow-up and also for your kind words.

The significance of IgE and IgG anti-Echinococcus is the same in that they both indicate that the patient has been exposed. The difference between the two in terms of Echinococcus is that, having an IgE anti-Echinococcus means your patient would be subject to an immediate hypersensitivity reaction to a release of Echinococcal antigen from, for example, a hydatid cyst. However, in terms of making the diagnosis, they are both identical in terms of significance.

At this point in time, I believe that there is strong indication your patient does have Echinococcal infection. Echinococcal infection is a complex disease with many different presentations, and a number of different species causing these presentations. I am not an expert in its diagnosis or management, and I would suggest at this point in time contacting an Infectious Disease specialist. You could also go ahead and order a test for Echinococcal antigen. This is performed in a number of different ways. It is not very sensitive, but its presence would confirm the diagnosis.

Thank you again, and I would greatly appreciate a follow-up on your patient.

Sincerely,
Phil Lieberman, M.D.

 

AAAAI - American Academy of Allergy Asthma & Immunology