Altered lamellar body secretion and stratum corneum membrane structure in Netherton syndrome - Differentiation from other infantile erythrodermas andpathogenic implications

Background: The infant with Netherton syndrome (NS) typically displays a ge neralized erythroderma covered by fine, translucent scales, which can be di fficult to distinguish clinically from erythrodermic psoriasis, nonbullous congenital ichthyosiform erythroderma, or other infantile erythrodermas. So me infants with NS develop progressive hypernatremic dehydration, failure t o thrive, and enteropathy. Such complications can be fatal. Diagnosis is ty pically delayed until the appearance of a pathognomonic hair shaft anomaly, trichorrhexis invaginata (bamboo hair). To facilitate the early diagnosis of NS, we obtained biopsy specimens from 7 patients with erythrodermic NS a nd compared their morphologic findings to those of 3 patients with erythrod ermic psoriasis and 2 with congenital ichthyosiform erythroderma. Biopsy sp ecimens were processed for light and electron microscopy using postfixation with osmium tetroxide and ruthenium tetroxide. Observation: In NS, and often in congenital ichthyosiform erythroderma and erythrodermic psoriasis, the stratum corneum layer was largely replaced by parakeratotic cells. A distinctive feature-premature secretion of lamellar body contents-occurred only in NS. Furthermore, lamellar body-derived extra cellular lamellae and stratum corneum lipid membranes were separated extens ively by foci of electron-dense material. Finally, transformation of lamell ar body-derived lamellae into mature lamellar membrane structures was distu rbed in NS. Conclusions: Premature lamellar body secretion and foci of electron-dense m aterial in the intercellular spaces of stratum corneum, features not observ ed in other erythrodermic disorders, appear to be frequent and relatively s pecific markers for NS. These ultrastructural features could permit the ear ly diagnosis of NS before the appearance of the hair shaft abnormality. The se abnormalities could explain the impaired permeability barrier in NS, and account for hypernatremia and dehydration in infants with NS.