I have a patient with chronic cough and marked peripheral eosinophilia as follows:

58 year-old female patient with chronic cough since January of this year. Cough is non-productive. Symptoms did not improve with z-pack and medrol dose pack prior to my evaluating her. Since I have seen her, serial spirometry have been largely unimpressive without frank obstruction. Two chest x-rays have been normal. Skin testing was negative to prick tests with mildly reactive intradermal tests only to dust mites and a few molds. Her cough has had only modest improvement with trials of various inhaled steroids (most recently advair 250/50).

Her PCP recently checked labs and found that she had a marked eosinophilia of 46% (6026 absolute count) with WBC of 13.1, normal hemoglobin and platelets. BMP normal. LFT's with mildly decreased albumin (3.1) and mildly elevated Alkalaine Phosphatase (259). Total protein 7.4 and LFT's otherwise normal.

I repeated her CBC, and her WBC is 16.8 with 41% eos (6888 absolute count). IgE 420. Stool O&P pending, and srongyloides antibody negative. ANCA's pending. ANA negative. ESR was elevated at 63 and CRP elevated at 2.16. Aspergillus precipitins pending.

Besides awaiting the pending ANCA results, what additional work up/consultation would you recommend? I am considering obtaining a CT scan of her chest and sending her for a hem/onc consult.


Thank you for your inquiry.

I think that you are doing due diligence in pursuit of the cause of your patient’s symptom complex. Basically we are looking at a patient with a moderate elevation in IgE and a marked elevation in eosinophil count. Both have occurred in a patient with an unexplained chronic cough not responsive to inhaled corticosteroids in combination with a long-acting beta-adrenergic agent.

Obviously, the differential diagnosis in this symptom complex is lengthy and, in its totality, not possible to convey in this venue. So before going further, I would like to mention three excellent references which should be available to you and which can guide you through the details of further evaluation.

There are two superb sources on the evaluation of patients with hypereosinophilia. The senior author on both is Weller. One of these references is in The Journal of Allergy and Clinical Immunology (July 2010), Volume 126 (Issue 1), Pages 39-44. The second article by Weller is in Middleton’s Allergy: Principles and Practice (2009), Pages 859-877. Also in this edition of Middleton, there is an excellent article on the evaluation of patients with elevated IgE by Smith and Ownby, Pages 845-857.

With these references in mind, I will try and help by mentioning some suggestions:
1. Clearly you have thought of the most likely diagnosis (a parasitic infection) and have done a workup in this regard. You have already done what is most important, and that is rule out the presence of strongyloides as best one can. This will allow you to consider a trial of corticosteroid therapy to see if your patient has corticosteroid-responsive eosinophilia without the worry of exacerbating a strongyloides infection. However, the workup is, to date, incomplete as far as the evaluation of a potential parasitic infection. There are serologic tests for several other parasites which I would consider ordering. These include, but are not limited to, ascariasis and echinococcus. If you prefer, since you are also considering an Infectious Disease consult, you may consider turning that part of the workup over to the consult. Clearly, however, I believe performing these studies is indicated.

2. You mentioned a consult with a hematologist/oncologist. You may wish also to turn this part of the workup over to this physician, but I believe that any patient with an eosinophil count of this level should have a mutational assessment for FIP1L1-PDGFR mutation. You can order this as a standard blood test.

3. I do not know how symptomatic your patient is in any other regard except for the cough, and I do not know how bad this cough is affecting quality of life. But the failure to respond to a Medrol Dosepak and probably even to a combination inhaled steroid and LABA may not indicate that the cough is not steroid-responsive. Now that you have ruled out strongyloidosis, a trial of oral steroids beginning at 60 mg and tapering over two weeks might be considered to see if your patient does respond to steroid therapy. I think this of course depends on your further workup (that is, whether or not you can find the cause) and how badly her cough is bothering her.

4. We do not know how long your patient has had this level of eosinophilia, but levels of 1,500 for six months indicate the possible diagnosis of idiopathic hypereosinophilic syndrome. There are clinical trials going on that are looking at the use of anti-IL5 in such patients, and if you do not find a cause of the eosinophilia in your patient, it would be advisable to go to “clinicaltrials.gov” where you will find a list of such trials. Your patient may be a candidate for one of these.

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

Phil Lieberman, M.D.

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