A Japanese case of Kindler syndrome
Authors: Suga Yasushi , Tsuboi Ryoji , Hashimoto Yukiko , Yaguchi Hitoshi , Ogawa Hideoki 
Published: March 2003

A 25‐year‐old Japanese woman presented with contracture of the fingers and toes, and difficulty in opening her mouth. Her grandparents are first cousins, but none of the other members of the family are affected. Bulla formation started at birth on areas of the skin that received pressure, and in infancy and early childhood the lesions were limited only to the acral areas. She also had bilateral, incomplete syndactylies involving all web spaces ( Fig. 1a). The formation of blisters ceased after the age of 15 years, but a generalized progressive poikiloderma then appeared with accompanying cutaneous atrophy of the skin of the neck, trunk, and extremities (
Fig. 1b). The patient experienced mild photosensitivity of the face and neck. At age 18 years, surgical removal of the webbing of all her fingers was performed. Oral examination showed atrophy of the buccal mucosa, and an inability to fully open the mouth. The patient also suffered from poor dentition and easily bleeding gums, but had no symptoms of esophageal dysfunction.

Clinical manifestations of the patient with Kindler syndrome. (a) Dorsal surface of the patient's hands. Note the marked cutaneous atrophy with a severely wrinkled appearance on the dorsal surface of the hands, as well as the proximal fusion of the fingers. (b) Lower left leg of the patient. Atrophic thinning of the skin and poikiloderma with reticular pigmentation are evident

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Histology of separate biopsy specimens, taken from the poikilodermatous pretibial and trunk skin, showed classical features of poikiloderma, namely epidermal atrophy with flattening of the rete ridges, vacuolization of basal keratinocytes, pigmentary incontinence, and mild dermal perivascularization ( Fig. 2a). Interestingly, dyskeratotic cells (
Fig. 2b) and eosinophilic rounded bodies (colloid bodies) (
Fig. 2c) were frequently found at the basal keratinocyte layer and in the upper dermis, respectively. Pigment was also present in the upper epidermis.

Hematoxylin and eosin staining of a biopsy specimen taken from pretibial skin. (a) Epidermal atrophy with flattening of the rete ridges. Note the dyskeratotic cells (arrowheads) and vacuolar degeneration of the basal layer in the epidermis. Bar = 50 μm. (b) Higher magnification of dyskeratotic cells (arrowheads). Bar = 10 μm. (c) Higher magnification of colloid bodies (arrowheads) in the superficial dermis. Bar = 10 μm

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To rule out the possibility of a congenital epidermolysis bullosa, ultrastructural and immunofluorescence studies were performed. Ultrastructural studies demonstrated the reduplication of the basal lamina with branching structures within the upper dermis and cleavage between the lamina densa and the cell membrane of the keratinocytes ( Fig. 3a). The numbers of associated anchoring fibrils did not seem to be reduced, and colloid bodies and dyskeratotic cells were detected. Immunofluorescence studies with the antibody against type VII collagen (LH 7 : 2) were subsequently carried out. The results showed extensive broad bands with intermittently discontinuous and reticular staining at the dermo‐epidermal junction (DEJ) (
Fig. 3b), whereas a linear distribution is typically seen in healthy tissue (data not shown). Interestingly, direct immunofluorescence studies revealed intracellular accumulation of immunoglobulin G (IgG), IgM, IgA, and C3 in colloid bodies under the basement membrane (
Fig. 3c).

Ultrastructural and immunohistochemical findings of the patient with Kindler syndrome. (a) Ultrastructural study of the dermo‐epidermal junction. The branching structures of the lamina densa (arrowheads) were frequently seen. The asterisks show the cleavage in the lamina lucida. Bar = 1 μm. (b) Immunohistochemical studies with the antibody to type VII collagen (LH 7 : 2). An extensive broad band with reticular patterns is evident. Bar = 50 μm. E, epidermis; D, dermis. (c) Direct immunofluorescence study. Intracytoplasmic deposition of IgM in the basal keratinocytes is evident (arrowheads). Bar = 50 μm. E, epidermis; D, dermis

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