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High IgE

Question:

10/23/2018
A 7 year-old child was referred to me 10 months ago for hives as patient had total IgE levels of 1265 kU/L, with class 2 level of IgE to milk, dust mite and class one to shrimp, walnut and almond. However, she had IgE to wasp 15.30, and hornet and other and yellow jacket between 1.5 to 2.9. Negative to Bees. The patient has never been stung by the above insects but no problem with fire ants and mosquitos.

Patient had done well with hydroxyzine and zantac as far as hives are concerned and had been medication free and symptoms free for 3 to 4 months. The repeat IgE is still very high 1250 kU/L repeated after 8 months of original test and she has started itching again. She does not have a history of insect stings since the original test done. Patient has been consuming all the foods including milk and seafood without any obvious symptoms.

How should I proceed? What other test can be done to evaluate the elevated IgE? What is the relevance of high IgE to venoms of hymenoptera in absence of the history of insect stings?

Answer:

Clinically as the patient has never been stung then there is indication for venom skin testing. As you know, random venom skin testing of patients with no clinical history of venom allergy will result in a small percent of patients who will react. In general, these patients can be followed expectantly.

The differential for an elevated IgE is quite broad and has been reviewed previously in Ask the Expert and I am copying a previous response below:

Q: 2/20/2013
Differential diagnosis of elevated IGE and normal eosinophylia.

A: We have numerous entries on our website regarding the differential diagnoses of an elevated IgE (with or without eosinophilia). I have copied for you below one example of these.

However, this is such a broad differential that our website alone is not sufficient to actually do it justice or put it into clinical perspective. There are excellent standard medical textbook chapters on this topic; perhaps the one most pertinent would be found in the latest edition of Middleton’s Allergy: Principles and Practice (1). I would suggest that you consult that chapter if your question regards a specific patient.

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

Ask The Expert 3/31/2008:
Elevated IgE of Unknown Cause

Q: 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?

A: 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, here in the, 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.

Reference:
1. Middleton’s Allergy: Principles and Practice, 7th Edition, edited by Atkinson F, Bochner B, Busse W, Holgate S, Lemanske R, and Simons FER (Publisher Mosby, an affiliate of Elsevier, Inc.) 2009.

Sincerely,
Phil Lieberman, MD, FAAAAI

I hope this is helpful.
Andrew Murphy, MD, FAAAAI