Expression of integrins in junctional and dystrophic epidermolysis bullosa.

Recently, monoclonal antibodies (MoAb) have been raised against a family of adhesive membrane receptors (R) for extracellular matrix molecules known as integrins. In order to ascertain whether these adhesive proteins are normally expressed in inherited epidermolysis bullosa (EB) dermal epidermal junction, we studied the reactivity of MoAb recognizing receptors for VLA-1 (R for unknown ligand), VLA-2 (R for collagen), VLA-3 (R for collagen, laminin, fibronectin), VLA-4 (R for unknown ligand), VLA-5 (R for fibronectin), VLA-6 (R for laminin), VNR alpha, and VNR beta (R for vitronectin) on cryostat skin sections from EB patients and normal controls and on cytospins of normal epidermal cell suspensions with indirect immunohistochemical methods. Two cases of junctional EB (EBj) (lethal and non-lethal), three cases of dominant dystrophic EB (EBdd), two cases of recessive dystrophic EB (EBdr), and two normal controls skin sections and cell suspensions entered the study. No significant modification of the distribution of these adhesive receptors was observed in junctional and dystrophic EB skin. Both in normal and EB specimens MoAb against VLA-2, VLA-3, and VNR alpha determinants showed reactivity with the total cytoplasmic membrane of basal keratinocytes and basement membrane zone. Interestingly, anti-VLA-6 MoAb was characterized by an intense linear staining of the dermal-epidermal junction with the same localization on the roof of the blisters in EBj, EBdd, and EBdr as bullous pemphigoid (BP) serum. On the basis of these results we suggest that anti-VLA-6 MoAb could be used instead of BP serum for immunohistochemical detection of the cleavage of blisters in EB.

Prenatal testing in a fetus at risk for autosomal dominant polycystic kidney disease and autosomal recessive junctional epidermolysis bullosa with pyloric atresia.

Amniocentesis and fetal skin biopsies were performed at 18 weeks of gestation in a fetus at risk for autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive junctional epidermolysis bullosa (EBJ) with pyloric atresia. A previous son of the couple under investigation had died at 3 months of EBJ. The mother of the propositus has ADPKD. Genetic linkage studies were carried out in 11 relatives (4 with ADPKD), and on fetal DNA obtained from cultured amniocytes, using 8 flanking DNA markers tightly linked to the PKD1 locus on chromosome 16p, and a DNA marker linked to another putative ADPKD locus on chromosome 2p. The linkage results indicated that the fetus had not inherited the ADPKD chromosome from the affected mother, with a diagnostic accuracy of > 99%. Ultrastructural and immunohistochemical analyses of multiple fetal skin biopsies showed no EBJ-associated abnormalities. Thus, combining recent morphological and molecular diagnostic methods, we could show that the fetus was free from both diseases. After 40 weeks of gestation, a normal male infant was delivered.

Very late antigen (VLA) expression in various forms of epidermolysis bullosa simplex.

The very late antigen (VLA) glycoproteins are a family of adhesion membrane receptors involved in cell-cell and cell-matrix interactions. In order to investigate the expression of these molecules in inherited epidermolysis bullosa (EB), we studied the reactivity of monoclonal antibodies directed against VLA-1, -2, -3, -4, -5, and -6, and VLA beta receptors in skin sections from patients affected by several types of EB simplex (EBs) using indirect immunofluorescence. Skin samples were obtained from six patients with generalized type (Koebner), one patient with localized type (Weber-Cockayne) and one patient with Dowling-Meara EBs type and also from two normal controls. No significant modification of the expression of these adhesion receptors was observed. Anti-VLA-2 and anti-VLA-3 stained the whole cytoplasmic membrane of basal keratinocytes and allowed the detection of focal areas of cytolysis in unblistered skin from the Koebner and Dowling-Meara type. In Koebner type blisters anti-VLA-3 stained the cell remnants at the roof of the blister with a linear staining along the epidermal basement membrane on the dermal side. In Dowling-Meara type blisters anti-VLA-3 also stained cell remnants at the bottom of the cavity. Anti-VLA-6 stained the bottom of the blister cavity with the same distribution of bullous pemphigoid serum but with a stronger and more constant reactivity. Our data show that anti-VLA-3 and anti-VLA-6 can usefully be utilized in diagnostic immunomapping studies of EBs.

Ichthyosis revealing coeliac disease.

We describe the case of a twenty-nine year-old woman presenting a lamellar desquamation on the abdomen, submammary folds and on the limbs. During recent years the patient suffered neither from bowel disorders, nor from dryness of the skin. Laboratory tests revealed high values of parathormone and a high level of antiendomysial antibodies. The total bone-mineral density was about 78% of normal levels. A duodenal mucous membrane specimen showed total atrophy of the villi. Skin biopsy revealed an acquired ichthyosis mimicking an ichthyosis vulgaris. The patient underwent a gluten-free diet, supported by folic acid and vitamin D and six months later, after the regression of secondary hyperparathyroidism, a remarkable improvement of the cutaneous symptoms was obtained.

[Dermatologic manifestations of tuberous sclerosis in children. A study of 6 cases]. / Le manifestazioni dermatologiche della sclerosi tuberosa in età pediatrica. Studio di 6 casi.

Typical cutaneous findings in tuberous sclerosis are present in over 90% of cases and represent one of the earliest markers of the syndrome. Our study, based on 6 pediatric cases, underlines how the skin manifestations vary with the patient's age. Hypopigmented maculae were usually present at birth and remained often the only clinical sign during the first few years of age. Angiofibromas on the face appeared later and were followed by orange-peel patches and then by periungual fibromas. The high spontaneous new mutation rate of tuberous sclerosis seems to be confirmed by our study in which clinical evaluation of first-degree relatives of all patients was negative.

Cutaneous myiasis caused by larvae of Cordylobia anthropophaga (Blanchard).

BACKGROUND: Cordylobia anthropophaga (Blanchard) is a nonhematophagous dipteron belonging to the Calliphoridae family. It produces a myiasis called "tumbu fly" or "ver de Cayor" or "mango fly" or "skin maggot fly". CASE REPORTS: We describe two women, 24 and 23 years of age, affected by cutaneous myiasis caused by the larva of Cordylobia anthropophaga. In both cases the myiasis was contracted in Senegal and was characterized by a single lesion localized to the flank and the thigh respectively. From each of these lesions a single larva was extracted. DISCUSSION: This myiasis represents a typical example of tropical disease that in the past was unknown to Western dermatologists.

Acrokeratoelastoidosis of Costa: a primary disease of the elastic tissue?

A 24-year-old black woman from Uganda was seen for treatment of multiple papules on her hands and feet. The lesions corresponded microscopically to foci of hyperkeratosis and acanthosis. Acid orcein stain revealed marked elastic fiber fragmentation. Acrokeratoelastoidosis of Costa (AKE) was diagnosed. The same damage to the elastic fibers was also present in an additional specimen from grossly uninvolved skin. On electron microscopy there were pronounced changes of the elastic fibers with elastolysis in both specimens. This case with generalized damage of the dermal elastic tissue supports the view that elastorrhexis is the key feature of AKE. Accordingly, the disease could be regarded as a primary elastic tissue disorder. The marginal acral keratoderma that is seen in AKE patients could represent epidermal changes secondary to chronic trauma.

Ichthyosis congenita type IV: a new case resembling diffuse cutaneous mastocytosis.

The wide phenotypical heterogeneity within the ichthyosis congenita group of diseases is well known. We report a case of a very rare and unusual autosomal recessive ichthyosis congenita, type IV, according to the ultrastructural classification. Our case presented the triad clue for the diagnosis, characterized by follicular hyperkeratosis, prematurity and perinatal complications, but the clinical diagnosis was further complicated by hypereosinophilia and a strongly positive Darier's sign suggesting diffuse cutaneous mastocytosis. The diagnosis was provided only by electron microscopy, which showed the pathognomonic markers of ichthyosis congenita type IV, namely a large number of membrane structures in the stratum corneum and stratum granulosum. As a consequence, correct genetic counselling for the parents was carried out, and they were informed about the benign course of the disease after the complications of the perinatal period. This case is a further example of the reliability of ultrastructural markers in the diagnosis of inherited keratinization disorders, especially those with an unusual clinical appearance.

Localized peeling skin syndrome: case report with ultrastructural study.

We report a young woman in whom the history, clinical features, histopathological and ultrastructural findings led to a diagnosis of peeling skin syndrome (PSS). PSS is a rare and not well classified genodermatosis, mainly characterized by the spontaneous separation of the stratum corneum from the stratum granulosum. The unusual feature in our patient was the strict localization to the palm. PSS has been described as a more generalized disease frequently sparing palms and soles. We propose the diagnosis label of 'localized PSS' for this previously undescribed variant of a rare keratinization defect.

Uncommon clinical presentations of juvenile xanthogranuloma.

Two unusual clinical presentations of juvenile xanthogranuloma (JXG), the most common non-Langerhans cell histiocytosis, are described: a flat 'plaque-like' and a 'paired' form. This report confirms the great variability of JXG. Besides representing a dermatological curiosity, the recognition of these atypical forms of presentation should facilitate the clinical diagnosis of the disorder.

Proteus syndrome. Ultrastructural study of linear verrucous and depigmented nevi.

Proteus syndrome is a rare hamartomatous disorder characterized by multifocal overgrowths that can involve any structure of the body. Clinical manifestations include macrodactyly, hemihypertrophy, subcutaneous masses, exostosis, cerebroid thickening of palms and soles, and linear skin lesions. About 50 cases have been described, but the ultrastructural features of the linear skin lesions have not been characterized. We describe the clinical, histologic, and ultrastructural findings for a 30-year-old patient who had a mild form of Proteus syndrome with linear lesions characterized by a mixed pattern of hyperkeratosis and depigmentation. Light microscopy of the linear nevus showed acanthosis and hyperorthokeratosis. Electron microscopy revealed extensive vacuolation at the interface between melanocytes and keratinocytes, with large aggregations of densely packed granules in the intercellular space. Melanocytes showed only slight degenerative changes. An immunohistochemical study of the expression of epidermal growth factor receptors revealed no significant abnormalities.

Pityriasis rotunda: report of a familial occurrence and review of the literature.

Pityriasis rotunda is an uncommon dermatosis characterized by multiple, widely distributed, strikingly circular hypopigmented or hyperpigmented patches that are slightly scaly. It has been described in Oriental and black patients, usually in association with certain infective or malignant systemic diseases. Pityriasis rotunda is rare in white patients and does not act as a marker of malignancy. Our ultrastructural and histologic findings demonstrated that pityriasis rotunda is more closely related to congenital ichthyoses than ichthyosis vulgaris, contrary to previous reports. On the basis of our studies and a review of the literature, it seems that two types of pityriasis rotunda exist with significant prognostic differences.

A case of congenital reticular ichthyosiform erythroderma--ichthyosis 'en confettis'.

We describe the third case of congenital reticular ichthyosiform erythroderma (CRIE), a rare inherited keratinization disorder, the second with the peculiar reticulate skin pattern. The same case had been previously described and defined, for the clinical appearance, as ichthyosis 'en confettis'. An 18-year-old girl was born with the clinical features of an erythrodermic lamellar ichthyosis. Patches of normal skin enclosed by erythematous-ichthyotic skin in a reticular arrangement appeared on the trunk at the age of 10 years, and they enlarged slowly during 6 years. The treatment with etretinate, started 2 years ago, further increased this process. Another peculiar clinical feature is a remarkable hypertrichosis. At the ultrastructural level, perinuclear deposits of filamentous material in vacuolized keratinocytes of the upper epidermis, pathognomonic for CRIE, were demonstrated. This suggests that CRIE and ichthyosis 'en confettis' are the same disorder. In addition the peculiar clinical presentation of this rare genodermatosis develops only during late childhood and puberty. The identification of three sporadic cases only leaves the problem of inheritance still unsolved.

Unusual hyperpigmentation developing in congenital reticular ichthyosiform erythroderma (ichthyosis variegata).

We present an unusual new clinical feature which developed in a patient with congenital reticular ichthyosiform erythroderma. This rare ichthyotic disorder is characterized by erythematous ichthyotic skin surrounding slowly enlarging areas of normal skin, and by a pathognomonic ultrastructural pattern, namely perinuclear deposits of a filamentous material in vacuolized keratinocytes. At the age of 18 years, a 23-year-old woman developed several irregular hyperpigmented macules on her limbs, which were almost black in colour. These lesions have not been observed in the other patients affected by the disease nor, to our knowledge, in other ichthyotic disorders. Electron microscopy and immunohistochemistry demonstrated that the lesions were strictly related to the ichthyotic skin and that their dark colour was especially due to melanosome accumulation in activated dendritic melanocytes. An unusual postinflammatory hyperpigmentation, in which the lack of pigment deposition in the keratinocytes is due to a transfer defect in pathological cells, is hypothesized. A characteristic hyperplastic stimulation of the epidermis is also taken into consideration to explain the lack of a similar picture in other erythrodermic ichthyotic disorders with a continuous inflammatory process.

Familial occurrence of isolated accessory tragi.

Three sibs were affected by numerous accessory tragi. On clinical examination, no other associated developmental defects, such as the Goldenhar syndrome, were detected.

Multiple pilomatricomas in Rubinstein-Taybi syndrome: a case report.

Rubinstein-Taybi syndrome is a multisystem developmental disorder due to an autosomal dominant mutation. It is clinically defined by the presence of peculiar facies, mental retardation, and broad thumbs and first toes. Important dermatologic findings include hirsutism, keloids, hemangiomas, and dermatoglyphic abnormalities. We report a 12-year-old girl with the typical phenotype of Rubinstein-Taybi syndrome, associated with numerous pilomatricomas. These are benign epithelial neoplasms with hair cell differentiation that may have a familial transmission. Pilomatricomas have not been reported in patients with Rubinstein-Taybi syndrome, although their association with myotonic dystrophy, another autosomal dominant disorder, is well known. Possibilities to explain the association include contiguous gene syndrome, the action of a pleiotropic gene, predisposition to malformations, and mere coincidence.