Morphological assessment of the effects of cyclosporin A on mast cell--nerve relationship in atopic dermatitis.

There is considerable clinical and experimental evidence that cyclosporin A has powerful therapeutic effects on severe, therapy-resistant atopic dermatitis. To further clarify the mechanism of beneficial action of cyclosporin A for atopic dermatitis, we assessed its effects on mast cell morphology and on the topographical relationship between mast cells and cutaneous nerves in lesional skin of atopic dermatitis. The ultrastructural features of mast cell-specific granules in cyclosporin A-treated skin compared with those in the pretreated skin included an increase in the stable granule population and the disappearance of signs of granule exocytosis. The close apposition of mast cells to peripheral nerve fibres in the upper dermis and an invasion of mast cells into nerve bundles in the lower dermis were immunohistochemically noted, and an intimate association between mast cells and unmyelinated dermal nerves or Schwann cells was observed ultrastructurally in the pretreated lesional skin. After cyclosporin A therapy, the close interrelation of mast cells and cutaneous nerves was not seen. These findings suggest that cyclosporin A may exert its therapeutic efficacy by inhibiting mast cell activation, and by affecting the interaction between mast cells and nerves, which may explain the beneficial therapeutic action of cyclosporin A in the management of the disease.