Eczema and possible hyper-IgE syndrome
Question:
12/4/2017
I saw a 16 year-old male with history of diffuse eczema since birth, allergic rhinitis and asthma. He reported staph infections for which he has received several antibiotics. He denies abscess formation but has received several course of antibiotics for skin infections. He has received prednisone several times from walk in clinics and most recently has achieved better control with oral antihistamines and topical steroids from the allergy clinic. However, he continues to have severe flare-ups of eczema. Blood work was positive to peanut, almond, hazelnut, pistachio, sesame seed, shrimp, lobster, and oyster which he has avoided without much improvement in symptoms. Blood Rast was very low positive to milk (0.36) and egg white (0.35). He did not notice much improvement with avoidance, so these foods were continued given questionable significance of very low values. His IgE was elevated at 24,000 and repeat value was 26,000. His eosinophil count was 1300 with WBC of 7500. While IgE can be elevated in atopic dermatitis, his levels are concerning. Given the severity of his symptoms, history of infections, and elevated IgE level, there is concern for hyper IgE syndrome which can be associated with dysregulation in many genes such as STAT3, TYK2, and DOCK8. Is there utility in testing for all three genes at once rather than STAT3 alone. If so, is there a commercially available test that you would recommend. Additionally please advise on any additional workup you would recommend other than quantitative immunoglobulins and lymphocyte subsets.
Answer:
The hype-IgE syndrome with autosomal dominant inheritance, also known as Job’s syndrome, is an immunodeficiency syndrome with multisystem disorder with nonimmunologic abnormalities of dentition, bone and connective tissue. From your description I suspect your patient has severe eczema with bacterial infection of the skin due to barrier defects and innate immune defects, particularly decreases in anti-microbial peptides. Before considering genetic testing, I would suggest you score your patient with the validated instrument available in the article by Grimbacher et al ((http://www.sciencedirect.com/science/article/pii/S0002929707623258). A score of ≥ 15 is highly suggestive of hyper-IgE syndrome whereas a score of < 10 points makes the diagnosis highly unlikely.
If you remained concerned that your patient has the hyper-IgE syndrome, I referred your question to Dr. Jolan Walter, the Robert A. Good Chair of Immunology, at the University of South Florida Morsani College of Medicine. Her response is as follows:
“I recommend genetic testing with Invitae https://www.invitae.com/en/physician/tests/08113/?cat=CAT000075 that covers DOCK8 PGM3 SPINK5 STAT3.
The company free of charge upgrades to the 207 PID gene panel that includes Tyk2. If needed that panel can be order upfronthttps://www.invitae.com/en/physician/tests/08100/
I also recommend testing for the fraction of memory B cells. HIES patient had low fraction of switched memory B cells.https://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/88800
TH17 differentiation is also decreased in HIES. This could be tested in Wisconsin or Mayo, although low yield.”
In summary, I do not suspect your patient to have hyper-IgE syndrome but the above resources may help in your assessment.
1. 2Bonilla FA, Khan DA et al. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol 2015;136: 1186-
2. Grimbacher B, Schäffer AA, Holland SM et al. Genetic linkage of hyper-IgE syndrome to chromosome 4. American J Human Genetics 1999;65:735-44 (http://www.sciencedirect.com/science/article/pii/S0002929707623258)
I hope this information is of help to you and your patient.
All my best.
Dennis K. Ledford, MD, FAAAAI