Hyper IgE Syndrome Associated With Warts: A First Case of Dedicator of Cytokinesis 8 Deficiency in the Philippines.

Jose Carlo Miguel M Villanueva,Koon-Wing Chan,Yu-Lung Lau,Hirokazu Kanegane,Agnes G Andaya,Remedios C Ong,Menno C Van Zelm

doi:10.3389/fped.2020.604725

Abstract

Hyper IgE syndrome (HIES) encompasses a group of primary immunodeficiency diseases (PIDs) that is characterized by severe atopy, and recurrent infections and markedly elevated serum IgE levels. The majority of HIES cases suffer from autosomal dominant mutations in the signal transducer and activator of transcription 3 gene. A minority of cases display autosomal recessive inheritance, and one form is caused by mutations in the dedicator of cytokinesis 8 (DOCK8) gene. Here we describe the first recognized and diagnosed case of DOCK8 deficiency in the Philippines. A 14 year-old-girl was referred due to recalcitrant atopic dermatitis, recurrent sinopulmonary infections, with widespread warts on the face, trunk and extremities. She had no coarse facial features or retained primary teeth, whereas she presented with widespread viral skin infections and multiple allergic diseases. Laboratory examinations revealed elevations in eosinophil count and serum IgE. The level of T-cell receptor excision circles was undetectable. The patient was suspected to have HIES with a probable DOCK8 deficiency. Genetic analysis disclosed a large genomic deletion involving exons 2-4 in the DOCK8 gene. A combination of recalcitrant atopic dermatitis, asthma, food allergies, with viral skin infections should increase the physician's consideration of a PID. Patients with HIES accompanied by warts and T-cell deficiency can be strongly suspected to have DOCK8 deficiency.

Highlights

Primary immunodeficiencies (PIDs) are a heterogeneous group of inherited disorders characterized by poor or absent function in one or more components of the immune system [1]
Hyper IgE syndrome (HIES) is heterogenous syndromic form of PID that presents with severe dermatitis and recurrent infections, with a characteristic markedly elevated serum IgE level
The majority of HIES cases are caused by autosomal dominant (AD) mutations in the signal transducer and activator of transcription 3 (STAT3) gene [4, 5]; a minority of patients suffer from an autosomal recessive (AR) form

Summary

INTRODUCTION

Primary immunodeficiencies (PIDs) are a heterogeneous group of inherited disorders characterized by poor or absent function in one or more components of the immune system [1]. The patient was born to a 34-year-old primigravida, and the mother and the father are first-degree cousins, she was born from a consanguineous union (Supplementary Figure 1) Her younger brother who had severe molluscum infection died of brain abscess at 5 years old. She presented with dry erythematous skin and pruritic scales from 3rd day of life, and was diagnosed with atopic dermatitis. Yellowish purulent discharges were noted from both eyes Her condition was complicated by severe atopic dermatitis, persistent allergic rhinitis, asthma, suspected multiple food and drug allergies, recurrent sinopulmonary infections, recurrent skin and soft tissue abscesses, mucocutaneous fungal lesions, and extensive giant molluscum contagiosum lesions. She died of severe sepsis at the age of 14 years

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ETHICS STATEMENT