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A case of atopic dermatitis (AD), recurrent infections, and elevated immunoglobulin E (IgE) level is presented. Clinical characteristics, pathophysiology, diagnosis, and management in this patient are reviewed. Clinical pearls and pitfalls include the following: (1) deep-seeded Staphylococcus aureus infections occur rarely in AD and should raise the possibility of immunodeficiency syndromes such as hyper-IgE syndrome (HIES); (2) HIES is characterized by a clinical triad consisting of elevated serum IgE levels, recurrent staphylococcal skin abscesses, and pneumonia with pneumatocele formation; (3) although serum IgE levels in AD have been noted to be as high as 10,000 IU/mL, severe cases of AD such as that presented here can exceed this range; (4) the efficacy of anti-IgE therapy in AD or HIES is unknown and may be limited by dosing requirements.

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