Diagnostic criteria for hyper-IgE syndrome
Question:
3/20/2019
I have a patient who is 13 years-old and presents with a history of mild intermittent asthma, chronic nasal allergies, atopic dermatitis, and recurrent staph infections of her upper extremities, with no pulmonary abscess or pneumonia in the past. Allergy blood test is positive to environmental allergens and IgE count of 7,314 IU/ml. considering hyper IgE syndrome.
Answer:
The case you describe above is compatible with the classic triad of atopic dermatitis, allergic, rhinitis, and asthma. This case does not meet the diagnostic criteria for either type of hyper-IgE syndrome.
Reference:
Schimke LF, Sawalle-Belohradsky J, Roesler J, Wollenberg A, Rack A, Borte M, Rieber N, Cremer R, Maass E, Dopfer R, Reichenbach J, Wahn V, Hoenig M, Jansson AF, Roesen-Wolff A, Schaub B, Seger R, Hill HR, Ochs HD, Torgerson TR, Belohradsky BH, Renner ED. Diagnostic approach to the hyper-IgE syndromes: immunologic and clinical key findings to differentiate hyper-IgE syndromes from atopic dermatitis. J Allergy Clin Immunol. 2010 Sep;126(3):611-7.e1.
Please see the Abstract below:
Background: Hyper-IgE syndromes (HIES) are primary immunodeficiency disorders characterized by Staphylococcus aureus abscesses, recurrent pneumonia, increased serum IgE levels, and eczema. The association of heterozygous signal transducer and activator of transcription 3 (STAT3) mutations with autosomal dominant (AD)–HIES allows the differentiation of AD-HIES from disorders associated with eczema and increased serum IgE levels, such as other primary immunodeficiencies and atopic dermatitis.
Objective: To facilitate early diagnosis of AD-HIES to initiate appropriate therapy.
Methods: The clinical phenotype (suggested by a National Institutes of Health [NIH] score of >_40 points), STAT3 genotype, and TH17 cell counts were compared in a cohort of 78 patients suspected of having HIES. Results: Heterozygous STAT3 missense mutations and in-frame deletions were identified in 48 patients, all but 2 with an NIH score >_40 points. Patients with STAT3 mutations with HIES showed significantly lower TH17 cell counts compared with patients with wild-type STAT3 and control subjects. Only 1 patient with wild-type STAT3 had both an NIH score >or=40 points and abnormal T(H)17 cell counts.
Conclusion: We expanded the number of STAT3 mutations and validated that the NIH score sensitively identifies patients with HIES. Based on our patient cohort, we propose key findings that, when combined with T(H)17 cell numbers, predict patients with AD-HIES with STAT3 mutations, supporting early diagnosis of AD-HIES.
I hope this information is of help to you and your patient.
Regards,
Eric Macy MD MS FAAAAI