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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. Figure 1. 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 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. Figure 2. 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 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). Figure 3. 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

We present two Japanese cases of involutional lipoatrophy. The first case is that of a 30-year-old woman, who first appeared at our hospital complaining of a localized, well-demarcated depression, approximately 3 × 4 cm in size, normal to slightly erythematous in coloration, on the lateral side of the left upper arm (Fig. 1a). The condition was asymptomatic, and she had noticed this anomaly a month prior to consultation. She received intramuscular injections of corticosteroids of unknown dosage at the affected site for the treatment of allergic rhinitis 4 months prior to her present consultation. Figure 1. Clinical, histological and immunohistological findings in two cases of localized involutional lipoatrophy. Loss of subcutaneous tissue in the left upper arm is seen both in the first (a) and second (b) cases. Arrowheads indicate the depressed region. (c) The involved regions showed a decrease in the size of individual lipocytes in the first case (bar = 10 µm). (d) Immunoperoxidase staining for CD68 in the first case. Scattered macrophages (arrowheads) were identified within the affected adipose tissue and surrounding connective tissue (bar = 10 µm) Download figure to PowerPoint The second patient, a 23-year-old woman, appeared at our hospital complaining of a similar macule 4 × 4 cm in size, which she noticed several weeks prior to her most recent consultation. She had no history of injury or injection at the site before the development of the condition (Fig. 1b). She had been under treatment for atopic dermatitis since early childhood and was treated only with topical applications of white petrolatum containing 2% salicylic acid for the past several years. In order to rule out the possibility of acquired partial lipodystrophy associated with localized scleroderma, lupus profundus and the other connective tissue diseases, a histological examination was performed for both patients. Histopathological analysis of the region exhibited a well-defined fat lobule composed of numerous small adipocytes (Fig. 1c) embedded in hyaline connective tissue. Edema and dilated capillaries were noticeable in the subcutaneous tissue surrounding the area. Inflammatory cells were not prominent, although mononuclear cells were observed in both patients. No epidermal change was seen in either patient. Direct and indirect immunofluorescence studies revealed no deposits of immunoreactants in the skin of either patient. Immunohistochemical studies with the antibody against macrophage (anti-CD68 antigen; DAKO.) showed that positive cells were scattered around blood vessels and shrunken lipocytes in the subcutaneous tissues (Fig. 1d). Most of these cells in the fat lobules were also positive for mucin stains such as Alcian blue. No abnormal findings came to light in the ordinary hematological and blood chemistry examinations of both patients. The autoantibody screening tests using antinuclear, anti-DNA, anticentromere, and anti-Scl-70 antibodies were negative in both patients.