Hyper Ig-E Syndrome: A Diagnostic Challenge

Abstract

INTRODUCTION: Hyper Ig-E syndrome (HIES) is a rare multi system disorder characterized by hyperimmunoglobinemia E, eosinophilia, chronic eczema, recurrent skin and pulmonary infections. CASE PRESENTATION: 52 year old female with long standing history of severe eczema since childhood, asthma, environmental allergies, multiple hospitalizations for MRSA/fungal infections (soft tissue, pneumonia, osteomyelitis), eosinophilia, failure to thrive, who presented to the pulmonologist with complaints of recurrent bronchitis and pneumonia. She was previously seen by an allergist and dermatologist few years ago for the management of severe eczema and allergies. IgE levels were found to be >54000 at that time but she wasn't conclusively diagnosed with HIES and placed on omalizumab trial. Since then, patient clinically deteriorated and began to exhibit the classic manifestation of the disease including the presence of characteristic facies, recurrent MRSA infections/pneumonias, fungal infections, osteoporosis and failure to thrive. Lab work this time revealed IgE levels > 3000 units with normal IgA, G levels. ANA, ANCA, RF, HIV and hepatitis panel were negative. Spiral CT scan of chest revealed new finding of pneumatocele in right upper lobe as compared to prior imaging. PFTs showed restrictive disease pattern with mild decrease in diffusion capacity. At this time, patient was diagnosed with HIES based on elevated Ig E levels, weighted score of > 30 based on NIH scoring system. Prophylactic antibiotic therapy with Bactrim was precluded due to severe sulfa allergy. She is scheduled to receive IVIG therapy as well as Bactrim desensitization. DISCUSSION: HIES is a rare primary immuno-deficiency disorder inherited in autosomal dominant and recessive patterns. The classic Autosomal Dominant HIES presents with immune abnormalities as mentioned above as well as non immune manifestations which include facial, dental and skeletal abnormalities. Diagnosis is based on NIH scoring and definitive diagnosis requires STAT 3 genetic testing. Management is largely supportive based on prophylactic antibiotic, antifungal therapy and aggressive treatment of infections. Other treatment modalities include IFN gamma, IVIG, cycloscoprine and stem cell transplantation. CONCLUSIONS: HIES is a diagnostic challenge with broad spectrum of clinical features which can often be attributed to other diagnoses. Although the patient had childhood eczema, hyperimmunoglobunemia and asthma, she presented insidiously with the more classic features of recurrent infections along with presence of pneumatocele at a later age leading to delayed diagnosis. Therefore, it becomes important to have a high index of suspicion along with multidisciplinary team approach to ensure early diagnosis and treatment.