Recent biochemical and morphological investigations have provided evidence for a heterogeneous composition of keratohyalin in human skin. A major component is filaggrin. In interfollicular epidermis the heterogeneity of keratohyalin is not directly visible, whereas in normal ridged skin bicomponent keratohyalin is revealed by electron microscopy. Skin biopsies of ridged and non-ridged skin of normal individuals and patients with autosomal dominant ichthyosis vulgaris (ADI)--characterized by defective keratohyalin synthesis and lack of filaggrin--were investigated by routine transmission electron microscopy and immunogold postembedding techniques using a commercial monoclonal anti-filaggrin antibody. In normal interfollicular epidermis filaggrin labelling was demonstrated on keratohyalin granules and in the lowermost cornified cells, whereas in ADI patients crumbly keratohyalin granules were present that did not show specific labelling for filaggrin. In normal ridged skin only the major (more electron-dense) component reacted with anti-filaggrin, whereas the attached (less electron-dense) component did not react. Ridged skin of ADI patients contained globular keratohyalin that did not react with anti-filaggrin, thus corresponding to the attached keratohyalin component in normal ridged skin. Our results provide a visible counterpart to the recent biochemical investigations of keratohyalin protein heterogeneity and contribute to the understanding of terminal differentiation in human skin and of the defective keratohyalin synthesis in ADI.

Filaggrin, a basic protein of the stratum corneum, was named as such because of its capability to aggregate keratin intermediate filaments in vitro. To investigate its filament-aggregating capability in vivo, we performed immunoelectron microscopy in three autosomal dominant genodermatoses serving as in vivo models of abnormalities of keratin filament aggregation. In bullous congenital ichthyosiform erythroderma Brocq and epidermolytic palmoplantar keratoderma Voerner suprabasal clumping of keratin filaments prevents the normal spreading of keratohyalin between keratin filaments. Keratohyalin granules, either isolated or attached to clumped keratins, were specifically labelled by the anti-filaggrin antibody, whereas tonofilament clumps did not show any reaction. In epidermolysis bullosa herpetiformis Dowling-Meara the abnormal filament aggregation occurred in basal cell keratins where no reaction of the anti-filaggrin antibody was detected. In high level keratinocytes with normal distribution of tonofilaments, normal stellate keratohyalin reacted specifically. In all instances keratin filament clumping occurred independently of, and spatially separated from, the first signs of profilaggrin synthesis and keratohyalin granule formation. Thus, in these disorders, filaggrin is not involved in filament aggregation.

We report on a 61-year-old patient with sclerodermiform skin lesions of the extremities and polyneuropathy. Borrelia (B.) burgdorferi DNA was detected in lesional skin by the polymerase chain reaction. Serological testing revealed IgG antibodies to B. burgdorferi. Histology revealed an inflammatory stage of a sclerotic reaction in the lesional skin. The admixture of plasma cells and the perineural distribution of the cellular infiltrate was suggestive for a borrelia infection. Immunohistochemical staining for the B. burgdorferi flagellin (41 kDa) revealed a positive staining reaction in the epidermis of lesional skin. The improvement of both the dermatological and the neurological symptoms upon antibiotic treatment with ceftriaxone was taken as further support for the diagnosis of a. B. burgdorferi infection.