Severe Congenital Generalized Exfoliative Erythroderma in Newborns and Infants: A Possible Sign of Netherton Syndrome

Abstract

We examined skin biopsy specimens from 17 of 19 newborns or infants with generalized ichthyosiform, exfoliative, seborrheic, or psoriasiform erythroderma. The specimens showed similar characteristic but nonspecific and therefore, at first sight, uninformative histologic features. Morphologically, the skin was affected overall with a persistent outbreak of eczema-like eruptions of subacute or chronic dermatitis. Pronounced dermal inflammatory processes were obvious by their perivascular and interstitial presence as well as exocytosis of lymphocytes, macrophages, and neutrophils. Epidermal barrier function was Impaired by the highly suppressed terminal differentiation, with thin or in part completely absent stratum corneum, decrease of keratin filaments, decrease or lack of keratohyalin granules, and of keratinosomes containing stacks of lipid membranes. As a result, the formation and discharge of epidermal barrier lipids from the keratinosomes that normally provide intercellular lamellar sheets at the granular-horny layer interface contributing to the epidermal barrier, was highly disturbed. The concomitant loss of water, electrolytes, and proteins by fluid exudation caused the patients severe metabolic problems and recurrent infections. The suspicion of Netherton syndrome was eventually confirmed in 18 patients by light microscopic demonstration of bamboo hairs (trichorrhexis invaginata), mostly from the scalp, but also in vellus hairs and eyelashes. Atopy actually belongs to the symptom triad defining Netherton syndrome and is, in our opinion, primarily responsible for the pathologic events within the skin and of the keratinizing parts of the growing hair shafts. Differential expression of the atopic condition determines the appearance of the keratinization disorder of the skin, namely, severe, generalized, exfoliative erythroderma or milder forms of ichthyosis linearis circumflexa Comèl. Retinold treatment seems to be contraindicated in these conditions since their biopharmacologic effects involve suppression of terminal differentiation, which is the proper pathognomonic event. In six patients the condition had a fatal course within months because of hypernatremia, recurrent infections, failure to thrive, and sepsis. Our aim is to call attention to and reaffirm that in congenital or early infantile cases of generalized exfoliative erythroderma. Netherton syndrome should be suspected as the underlying disease.

SPINK5 knockdown in organotypic human skin culture as a model system for Netherton syndrome: effect of genetic inhibition of serine proteases kallikrein 5 and kallikrein 7

“…The thicker and parakeratotic stratum corneum, frequently detached from the underlying epidermis (Fig. 1c), is also observed in the skin of patients with Netherton syndrome (10,11).…”

Clinico-Immunological Heterogeneity in Comèl-Netherton Syndrome

“…The affected children are often erythrodermic at or shortly (1 or 2 days) after birth [3, 4]. The erythroderma may persist or evolve after 1–2 years into erythematous, slightly scaly, annular or polycyclic, migrating, flat lesions with an incomplete advancing double edge of peeling scale [3, 5]. This lamellar collarette desquamation may also be present at birth.…”

“…This lamellar collarette desquamation may also be present at birth. Erythroderma is not necessarily the only first manifestation of CN but mostly seems to represent the persistent form with the worst prognosis and does not often convert to ILC [5]. …”

“…The skin abnormalities may be due to an alteration in the extracellular processing of lamellar body (keratinosome) contents contributing to the defective permeability barrier [5]. This profound disturbance of epidermal barrier function may explain problems such as xerosis, exfoliation, tendency to hypernatraemic dehydration, temperature instability, failure to thrive and renal dysfunction.…”

“…As mentioned above, the atopic diathesis is not only an essential part of CN but is crucial in mediating the aetiopathological process of the skin changes and hair shaft abnormalities [5]. …”