Intracytoplasmic retention of type VII collagen and dominant dystrophic epidermolysis bullosa: reversal of defect following cessation of or marked improvement in disease activity.

It has been recently shown that the presence of perinuclear "stellate bodies" within the epidermis in patients with a form of dominant dystrophic epidermolysis bullosa named "transient bullous dermolysis of the newborn" corresponds to collections of type VII collagen. To determine the temporal relationship of this unique immunohistochemical defect with course of clinical disease activity, we have longitudinally studied the expression of two epitopes of type VII collagen (LH 7:2; L3d) in nine patients in four such kindreds by immunofluorescence and immunoelectron microscopic technique. In every infant so studied at the time of active blistering, type VII collagen was detectable primarily within basilar and, to a lesser extent, suprabasilar keratinocytes. In contrast, type VII collagen was detectable solely in linear array along the dermoepidermal junction in skin from each patient following complete cessation or at least marked diminution of visible clinical disease activity. These findings support the hypothesis that the temporary mechanical fragility and blistering of the skin in infants with this rare subset of dominant dystrophic epidermolysis bullosa reflect the presence of reduced amounts of type VII collagen along the dermoepidermal junction, and that this diminution may be the result of either a delay in transport and integration of type VII collagen from basilar keratinocytes into the skin basement membrane or excessive phagocytosis of type VII collagen.