Clinical and immunologic aspects of the hyperimmunoglobulin E syndrome

The HIE syndrome is a rare disorder characterized by extremely high serum IgE levels; recurrent serious infections, primarily involving the skin and sinopulmonary tract; and chronic eczematoid dermatitis dating from early infancy. The most common organisms that infect these patients are S. aureus and C. albicans. In addition, they have increased susceptibility to infection with H. influenzae, S. pneumoniae, enteric gram-negative rods, herpesviruses, and a variety of fungal organisms. The infections are frequently deep-seated, with abscess formation in the case of skin infection and pneumatocele formation in the case of pneumonias. Osteomyelitis, septic arthritis, and visceral abscesses are also seen but less frequently. Associated features of this syndrome are coarse facies, growth retardation, osteoporosis, keratoconjunctivitis, and eosinophilia. The immunologic basis of the HIE syndrome is still speculative. It is believed that the elevated IgE levels reflect a T-cell imbalance characterized by T-cell activation and a deficiency of suppressor T cells to inhibit IgE production. The propensity for recurrent infection may be related to a unique abnormality in the humoral immune system: excessive production of IgE directed to S. aureus and other infectious organisms with a concurrent deficit in their ability to synthesize protective IgG antibody against the same organisms. The fluctuating neutrophil chemotactic abnormality found in these patients may be secondary to the underlying T-cell defect with secretion of chemotactic inhibitor substances from mononuclear cells. Alternatively, the interaction of infectious agents with IgE on the surface of Fc epsilon R-bearing immune effector cells results in the release of inflammatory mediators that impair local host immune response. Activation of the immune system may also contribute to the associated features in this syndrome via the secretion of mediators that regulate connective tissue production and bone mineralization. Further studies will be needed before we completely understand the pathogenesis of HIE syndrome. Therapy primarily involves use of prophylactic anti-S. aureus antibiotics and the use of intravenous antibiotics, antifungal agents, or antiviral agents during acute infections. Surgical drainage or resection of deep-seated infections are frequently indicated. In patients who do not respond to conservative management, there may be a role for intravenous gammaglobulin and/or plasmapheresis.