Causes of death in hyper-IgE syndrome

Background: Hyper-IgE syndrome (HIES) is characterized by recurrent pyogenic infections, eczema, increased serum IgE levels, and a variety of connective tissue and skeletal system abnormalities. Little has been published regarding the causes of death in these patients or pathologic findings. Objective: To identify the cause of death in patients with HIES and to describe pathologic findings in fatal HIES. Methods: We reviewed the medical records and autopsy slides of 6 patients with HIES with autopsies performed at our institution. Results: All 6 patients with HIES were women and ranged in age from 24 to 40 years. All patients had a history of cystic lung disease and had pneumonia at the time of death, with Pseudomonas aeruginosa and fungal organisms predominating. Pulmonary fungal vascular invasion with fatal hemorrhage was observed in 3 patients, and metastatic fungal disease to the brain was observed in 2 patients caused by Aspergillus fumigatus and Scedosporium prolificans. Four patients had evidence of renal tubular injury, which was likely from amphotericin B toxicity; 3 patients had glomerulosclerosis; and I patient had 2 kidney angiomyolipomas. Conclusions: Our series highlights the important role Pseudomonas and Aspergillus species play in patients with HIES with cystic lung disease. Intensified antifungal and gram-negative bacterial prophylaxis need evaluation as possible strategies to prevent these infectious complications in patients with cystic lung disease. Clinical implications: Fungal and Pseudomonas infection of cystic lung disease in HIES may be life threatening, and the proper management and prevention of these infections need continued investigation.