Dermal eosinophils in atopic dermatitis undergo cytolytic degeneration.

BACKGROUND: Immunofluorescent staining for eosinophil granule proteins in lesional skin of patients with atopic dermatitis shows extensive extracellular deposition throughout the upper dermis with relatively few intact eosinophils. OBJECTIVE: This study was carried out to determine whether eosinophil granule protein deposition in atopic dermatitis occurs by classical exocytosis, by piecemeal degranulation, or as a result of cytolysis. METHODS: Skin biopsy specimens from 10 patients with atopic dermatitis were examined by electron microscopy. RESULTS: The biopsy specimens showed varying degrees of dermal eosinophil granule major basic protein deposition by indirect immunofluorescence. Specimens from seven patients showed striking alterations of eosinophils by electron microscopy including intact eosinophils with granule alterations (reversal of core staining and/or core lucency) and with uropod processes. Biopsy specimens from six patients showed evidence of eosinophil degeneration with disruption of nuclear and/or plasma membranes. In four patients' specimens, membrane-bound eosinophil granules were present near degenerating eosinophils or were present in the absence of recognizable eosinophils. Evidence of classical exocytotic degranulation was not observed. Two of the specimens were also examined by immunoelectron microscopy for major basic protein localization. In these, major basic protein appeared to be lost from the granule core and distributed in the eosinophil cytoplasm as granules disintegrated and the cell disrupted. CONCLUSION: These findings support the hypothesis that eosinophils undergo cytolysis with release of granule contents and membrane-bound granules; this is likely the usual mechanism of eosinophil granule protein release in atopic dermatitis.

Assessment of eosinophil and neutrophil participation in atopic dermatitis: comparison with the IgE-mediated late-phase reaction.

We hypothesized that repeated IgE-mediated late-phase reactions are critical in the pathogenesis of atopic dermatitis (AD). Prior studies have shown that extracellular deposition of eosinophil granule major basic protein (MBP) occurs in lesional AD skin, despite a paucity of infiltrating eosinophils, and that deposition of both neutrophil and eosinophil granule proteins occurs in the IgE-mediated late-phase reaction. We evaluated the participation of both eosinophil and neutrophil granule proteins in AD. Cutaneous biopsy specimens and serum and urine samples were obtained from 22 patients with AD. Lesional tissue was examined by means of immunofluorescence for neutrophil elastase and lactoferrin and for eosinophil granule MBP, eosinophil-derived neurotoxin (EDN), and eosinophil cationic protein (ECP). Serum levels of elastase, MBP, EDN, and ECP and urine levels of MBP, EDN, and ECP were measured. Marked extracellular deposition of at least one of the eosinophil granule proteins was present in the dermis of 15 of the 22 AD skin specimens, but minimal or no extracellular neutrophil elastase or lactoferrin deposition was observed in any specimens. Serum and urine levels of MBP, EDN, and ECP in the patients were elevated when compared with those of normal controls, whereas serum levels of neutrophil elastase were not elevated. Serum MPB levels correlated with extent of body surface involvement. These results suggest that eosinophil degranulation occurs in AD but that neutrophil degranulation does not. Although eosinophil degranulation is prominent in both the late-phase reaction and in AD, the lack of neutrophil degranulation in AD demonstrates differences in the inflammatory reactions.

Childhood sinusitis.

Childhood sinusitis is difficult to diagnose. It is classified on the basis of duration of inflammation--acute or chronic--and cause of inflammation--infectious or noninfectious. Infectious sinusitis is often a result of obstruction of the osteomeatal complex. Inflammation in noninfectious sinusitis is similar to the inflammatory changes detected in respiratory mucosa of patients with asthma. Acute sinusitis is primarily an infectious process similar to a prolonged infection of the upper respiratory tract. Plain radiography has limited value for the diagnosis of acute sinusitis in children. The most effective treatment of acute sinusitis is administration of a beta-lactamase-resistant antibiotic. Chronic sinusitis may be infectious, noninfectious, or both. Coronal computed tomography of the sinuses and nasal endoscopy are the preferred methods for determining the presence of chronic sinusitis. When physicians prescribe therapy for chronic sinusitis, they need to consider whether the underlying cause is infectious, noninfectious, or both. Treatment of chronic infectious sinusitis is most effective when a beta-lactamase-resistant antibiotic is administered. Chronic noninfectious sinusitis may respond to topically intranasally applied corticosteroids. If medical treatment fails to resolve the disease within 3 months, surgical intervention may be necessary. Finally, although an association between asthma and sinusitis exists, a cause-and-effect relationship has not been established.