Characteristic immunohistochemical and ultrastructural findings indicate that Kindler's syndrome is an apoptotic skin disorder.
BACKGROUND
Kindler's syndrome is a rare genodermatosis mainly characterized by the onset of skin blistering in early childhood, web formation of fingers and toes, photosensitivity, and progressive poikiloderma. There is still debate whether this disease represents a distinctive entity in the spectrum of congenital bullous poikilodermas or a variant of dystrophic epidermolysis bullosa.


OBJECTIVE
To evaluate the recently proposed and debated characteristic immunohistochemical and ultrastructural features of Kindler's syndrome.


METHODS
Immunofluorescence (IF) antigen mapping and transmission electron microscopy (TEM) were performed on a skin specimen from non-sun-exposed inner aspect of the upper arm of a 49-year-old patient with characteristic clinical features of Kindler's syndrome.


RESULTS
IF studies revealed focally an extensively broadened, partly reticular staining pattern in the dermoepidermal basement membrane zone (BMZ) with antibodies against laminin-5 and type IV as well as type VII collagen. Anti-alpha6 and beta4 integrin staining revealed small gaps in the linear reactivity in the BMZ. Abundant keratin bodies, as detected by anti-immunoglobulin M (IgM) staining, were focally present in the dermis, indicating prominent epidermal apoptosis. This was verified by a histochemical apoptosis stain [terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) reaction]. Transmission electron microscopic examination showed manifold reduplications of the lamina densa (with attached anchoring fibrils) as well as a keratin body surrounded by a fibroblast in the upper dermis.


CONCLUSIONS
We present characteristic immunohistochemical and ultrastructural features of Kindler's syndrome identical to those described by Shimizu et al. and provide evidence that Kindler's syndrome might primarily be an apoptotic disorder of basal keratinocytes.
D017209:Apoptosis / Q000502:physiology*; D001485:Basement Membrane / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D024141:Collagen Type IV / Q000378:metabolism; D024143:Collagen Type VII / Q000378:metabolism; D004820:Epidermolysis Bullosa / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D016023:Integrins / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure*; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D000097794:Kalinin
D015815:Cell Adhesion Molecules; D024141:Collagen Type IV; D024143:Collagen Type VII; D016023:Integrins; D000097794:Kalinin