Q:

12/24/2013
I have a 4 y.o. Caucasian female patient with eosinophilic esophagitis who has had significant peripheral eosinophilia since 9 months age. This has decreased after treatment with oral viscous budesonide and dietary elimination and I'm wondering if I need to pursue diagnosis of Hypereosinophilic syndrome and investigate involvement of other organs (Echo, e.g.).

Patient initially referred by pediatrician at 15 months age for atopic dermatitis since 2 weeks age worsening progressively after 6 months age and elevated ImmunoCAP to several foods at 9 months age. Absolute eos at 9 months age were 2280. ImmunoCAP significantly elevated to milk, egg above cut-offs predicting >95% probability of reaction. Soy, wheat, peanut were at indeterminate levels.

She was exclusively breastfed and started solids at 6 months. She had already been avoiding milk, egg and had not been introduced to peanut at the recommendation of pediatrician. Skin tests positive to milk, egg, wheat at initial evaluation by me at 15 months. She underwent supervised oral food challenge to wheat (ImmunoCAP 16.6 kU/L, skin test 3 mm wheal) which she failed: After a cumulative dose of one half of a slice of wheat bread, developed single hive on left shoulder and one on right upper back. Projectile vomiting. Nasal congestion, Mild retractions and prolonged expiratory phase. Therefore she was avoiding milk, egg, wheat, and peanut (and tree nuts). Soy was continued in the diet (neg skin prick test, ImmunoCAP 1.94 kU/L). She also had aggressive treatment of atopic dermatitis which improved signficantly though she always had an appearance of mottled skin and I wondered about dermal infiltration of eosinophils.

Repeat AEC at 16 months was 2036. I had attributed this to her atopy but remained unnerved. Her mother had not reported any concerns for reflux and she was already avoiding several major food allergens due to documented or suspected immediate hypersensitivity.

She was subsequently followed by another allergist due to health insurance change and returned to continue her care with me at 3 1/2 years of age. At that point, mom reported that she had started having vomiting episodes and complaints of recurrent abdominal pain which were attributed to various food ingestions (not known food allergens which were avoided). I started her on omeprazole and referred her to pediatric GI for evaluation of eosninophilic esophagitis. After 8 weeks of PPI therapy, her EGD revealed esophagitis with increased eos of 83 per hpf in the mid esophagus and upto 76 per hpf in the upper esophagus. She had already been eliminating milk, egg, wheat, peanut, and tree nuts before this EGD due to immediate hypersensitivity concerns and her parents were diligent about her diet. She had been on INHALED QVAR via spacer for her persistent asthma prior to the EGD and was also on daily antihistamines for itching due to her atopic dermatitis and also development of perennial allergic rhinitis with sensitization to dog. I elected to treat her with oral viscous budesonide. Her parents also elected to add soy elimination to her dietary restrictions.

She was evaluation by dietician to make sure her nutritional needs were being met. After 12 weeks of oral viscous budesonide and added soy elimination (as well as continuing her PPI), her EGD looked significantly improved with no eosinophilic infiltration in the distal or proximal esophagus and clinically she was improved with resolution of vomiting and significantly improved abdominal pain. At this point, her peripheral eosinophil count has decreased to an AEC of 1136. My question is whether her esophageal eosinophilia represents organ involvement of hypereosinophilic syndrome or whether she just has eosinophilic esophagitis with signficant peripheral eosinophilia. If HES workup to be done, then what to pursue diagnostically? Or do I just follow the AEC and if it declines further then avoid additional workup.

A:

Thank you for your inquiry.

Pediatric hypereosinophilic syndrome is rare and you certainly have enough other causes of eosinophilia to explain the elevated eosinophil count in your patient. In addition, the recent eosinophil count of 1,136 would be inconsistent with a diagnosis of hypereosinophilic syndrome in which the counts are above 1,500. In addition, you would not expect the count to go down with the treatment that you instituted if your patient had hypereosinophilic syndrome. For these reasons, in my opinion, the eosinophilia in your patient is not due to hypereosinophilic syndrome. Therefore, I would have little concern about simply following her with appropriate treatment for her allergic disease.

Having said this, there may be disagreement regarding this opinion, and therefore if you do decide to pursue a diagnosis of hypereosinophilic syndrome, the link to an excellent reference online copied below, plus the two references copied below will be excellent resources for you in terms of what workup might be indicated. In addition, we have several entries on our Ask the Expert website which have discussed the issue of the evaluation of an elevated eosinophil count.

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

Pediatric Hypereosinophilic Syndrome Workup

M. van Grotela, M. de Hoogb, R.R. de Krijger c, H.B. Beverlood, M.M. van den Heuvel-Eibrinka Hypereosinophilic syndrome in children
Leukemia Research 36 (2012) 1249– 1254
abstract
Recently, according to the Hypereosinophilic Diseases Working Group of the International Eosinophil Society, six variants of hypereosinophilic syndrome have been proposed, i.e. (1) myeloproliferative, (2)lymphoproliferative, (3) idiopathic/undefined, (4) overlapping, (5) associated and (6) familial variant.Hypereosinophilic syndrome is a rare disorder in children and can occur at any age during childhood. Corticosteroids are the treatment of choice, whereas other treatment options are hydroxyurea, IFN, imatinib, vincristine, mepolizumab. We present a fulminant fatal case of hypereosinophilic syndrome in a teenager with an initial presentation of an idiopathic thrombocytopenia (ITP) and present a narrative review of literature.

Indian J Pediatr. 2013 Feb;80(2):124-7. doi: 10.1007/s12098-012-0821-x. Epub 2012 Jun 28.
Idiopathic hypereosinophilic syndrome in children: 3 cases with review of literature.
Kanthila J, Bhaskaranand N.
Author information
Department of Pediatrics, Kasturba Medical College, A-14, A Block, KMC Staff Quarters, Light House Hill Road, Mangalore, 575003, India.
Abstract
Objectives: To highlight the varied clinical manifestations and management of idiopathic hypereosinophilic syndrome, a rare disorder in children.
Methods: Retrospective review of case records of 3 patients who were diagnosed to have idiopathic hypereosinophilic syndrome (IHES) in a tertiary referral centre between 1997 and 2010 was performed. These 3 children presented with different symptoms and the first case had cardiac involvement. All had very high absolute eosinophil count (cells/mm(3)) 43,206, 9,082, 2,925, respectively. Diagnosis was confirmed by bone marrow biopsy in all three cases and supported by liver biopsy in the first two cases and inguinal lymphnode biopsy in the last case. All 3 children responded to treatment with steroids, with only second patient requiring hydroxyurea to control disease.
Results: Case 1 and 2 are on follow up for 13 y and 10 y respectively and both are asymptomatic. Case 3 expired due to sepsis 1 mo after diagnosis.
Conclusions: Treatment with steroids with or without hydroxyurea gave good response in all 3 cases. Hence, they still remain the gold standard for the treatment of IHES in children.

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology