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A 61-year-old man is described with sclerodactyly of the hands and syndactyly of the second and third toes. Hereditary sclerodactyly is a rare condition, beginning in early youth with flexion contracture of the fingers. In this patient the skin of the fingers was sclerotic and thickened, and the dorsal skin of the hands was atrophic and dry. The condition did not progress nor did it show signs of Raynaud's phenomenon. Both feet showed syndactyly of the second and third toes. The family tree suggested autosomal dominant inheritance, with reduced penetrance since the grandfather of our patient was reported to have had a similar disease.

The combination of different antipsoriatics or treatment regimens should increase the therapeutic effect and reduce the adverse reactions. The combination of dithranol and tar (cignolin-salicyl-vaseline + tar, CSVT) reduces dithranol erythema and increases the antipsoriatic effect. CSVT treatment is highly effective, but patients tend to accept it less than other treatment regimens. On the other hand, Goeckerman therapy (tar + UV irradiation) is more accepted but less effective. Combinations of dithranol with UV irradiation or with tar and UV irradiation (Ingram regimen) are not advantageous. Dithranol and Goeckerman therapy are relatively secure treatment regimens, as they have been applied for more than 50 years without knowledge of significant late defects. PUVA therapy, although highly effective, is not superior to dithranol therapy. Even though PUVA therapy is more easily accepted than dithranol treatment, PUVA therapy should be applied only in severe cases. The combinations of aromatic retinoid with (selective) UVB irradiation (ReSUP) or with PUVA therapy (RePUVA) are highly effective. Retinoids can reduce the UV doses and most likely limit the risk of late damage. For routine treatment, ReSUP is preferable to RePUVA therapy.

The effect of oral aromatic retinoid Ro 10-9359 in a high dosage (25 mg/kg/day) on guinea pig epidermis was investigated by light and electron microscopy. The induced morphological alterations showed two different stages: (a) In the injury stage, seen aftr one week of retinoid administraion, the epidermis was mainly characterized by lack of the horny layer and vacuolar cytoplasmic disintergration of the malpighian layer with intracellular edema and accumulation of some PAS-positive material. Tonofilaments and desmosomes were markedly reduced, keratinosomes were increased in number. (b) In the recovery stage, seen after 3 weeks of administration, the horny layer had reappeared, the edematous and vacuolar changes were diminished and the epidermis became slightly acanthotic. Hypergranulosis with numerous spongiform keratohyalin granules was a prominent feature. The number of tonofilaments, desmosomes, and keratinosomes showed a clear tendency to normalization. In conclusion, high systemic doses of aromatic retinoid initially exert a cytotoxic, keratolytic, and mucoplastic effect on the normal guinea pig epidermis. Nevertheless, the affected keratinocytes adapt themselves, despite the further administration of the drug, showing a gradual restoration of these changes and a stimulation of epidermal proliferation, leading to acanthosis.

In this review the general structure and the properties of the plasma membrane are described with respect to the recent findings on the membrane of the keratinocyte. A structural and functional model of the plasma membrane of the keratinocyte is proposed based on biochemical, electron microscopic and fluorescence microscopic findings. The plasma membrane is obviously involved in the control of intercellular adhesion, growth and differentiation of normal epidermal cells. Under pathological conditions an alteration of the plasma membrane of the keratinocyte may affect the intercellular communication and/or the cellular control by mediators.

Five patients with T-cell lymphoma of the skin (mycosis fungoides; Sézary syndrome) were given parenterally arotinoid ethyl ester (Ro 13-6298) at a daily dose of 0.5-4.0 micrograms/kg body weight, to a total dose of 20 mg over maximally 31 weeks. In three patients, among them one with tumourous mycosis fungoides, there was complete regression of the cutaneous lesions. In another patient the cutaneous changes, some of them with ulceration, regressed so that there were only residual infiltrates. In the case of the Sézary syndrome there was no response. Most important side-effects of treatment were cheilitis, moist and sticky skin, paronychia and dry mucosae. The most serious side-effect was pain in muscles, joints and bones. There were no significant changes in biochemical values during the treatment.

The effect of long-term ultraviolet irradiation on the connective tissue of the skin was investigated in 25 naked (Ng/-) mice which received a total daily radiant dose of 40 +/- 2 J/cm2 for a period of 8.5 months. The produced alterations were very similar to those found in actinic elastosis of humans, as assessed by histologic and electron-microscopic criteria.

Regarding the keratin pattern of non-exposed skin, we found no significant qualitative or quantitative differences between 6 old persons (mean age 85 years) and 4 young adults (mean age 20 years). There was, however, a slight increase of proliferation keratins (K6, K16) in aged skin. In non-exposed skin taken from 6 old (mean age 70 years) and 5 young persons (mean age 37 years), longterm primary submersion cultures of keratinocytes did not show any significant differences as far as the classical parameters of growth behavior were concerned (i.e. plating efficiency, cell count, and labeled thymidine incorporation). In accordance with these findings, daily measurements of the thymidine kinase activity in the supernatants revealed discrete but not significant differences between keratinocytes in aged people and those in young persons.

T-lymphocytes and their subsets were determined in three patients with classical Kaposi's sarcoma. A reduction of pan-T-lymphocytes, including both a reduction of T-helper and T-suppressor cells, was found in one patient. None of the patients showed a reduction of the T-helper/T-suppressor cell ratio, as described in the lymphadenopathic disseminated type of Kaposi's sarcoma. Intradermal testing with tuberculin and trichophytin gave no indication of humoral immunodeficiency or anergy. In addition to electron beam irradiation, one female patient was treated with rIFN-alpha-interferon, 6 X 10(6) IU 3 times a week over a period of 3 months, and 18 X 10(6) IU 3 times weekly over 1 month. Under this therapy, irradiated as well as nonirradiated lesions become flatter, reduced in size and faded. The number of T-suppressor cells diminished.

Epithelial sheets can be cultivated from isolated epidermal cells; in this way, it is possible to increase the cell number considerably. H. Green and co-workers were the first to make use of such epithelia for the autologous covering of burn wounds. We modified this method and report on our experiences with this technique in a patient with small skin defects.

Eight benign and three malignant granular cell tumors were characterized by means of antibodies and antisera against keratin, desmin, epithelial membrane antigen, factor VIII-related protein, lysozyme, myelin basic protein, myoglobin, neurone-specific enolase, S 100 protein, myelin-associated protein (Leu 7), glial fibrillary acidic protein, vimentin, and neurofilament. All benign granular cell tumours showed positive staining of the tumor cells to antibodies against vimentin, S 100 protein, and neurone-specific enolase; myelin-associated protein (Leu 7), in contrast, was only detectable in a few tumor sections. Histogenetically the granular cells may be classified as Schwann's cells which lost their expression of laminin. The three malignant granular cell tumors showed a staining pattern significantly different from that of the benign tumours. Thus, only neurone-specific enolase was detectable in all the tumors, whereas S 100 protein and vimentin could not be demonstrated but in one and two, resp., out of three tumors.

In the psoriatic skin, nexus were most prominent in the upper layers of the viable epidermis, using the Alcian blue-Lanthanum technique. There, they reached double and manifold the length (giant nexus) of those in normal epidermis. According to the villous transformation of the epidermal cell surface in psoriasis, the nexus showed a great variation in their shape. Undulating nexus were seen beside invagination--and anular nexus. On ther other hand, nexus were lacking in the deepest layers of the psoriatic epidermis in contrast to normal epidermis. From these findings it seems that the intercellular communication by specialized low resistant junctions is reduced in the deepest layers of the psoriatic epidermis. In the upper epidermal layers, however, the extensive formation and the variable configuration of the nexus express a high synthetic activity and a well developed intercellular information in these areas of the psoriatic epidermis.

Three cell surface parameters of epidermal cells have been studied by immunofluorescence, pemphigus antigens, concanavalin-A binding sugars, and beta 2 microglobulin. Biopsy specimens were taken from a total of 59 patients with psoriasis, seborrheic and solar keratosis, squamous cell carcinoma, and basal cell epithelioma. We found a loss of demonstrability of all parameters in dedifferentiated tumors or tumor areas in squamous cell carcinoma, premonitory changes in solar keratosis, and no changes in seborrheic keratosis. In the psoriatic epidermis a granular redistribution of the cell surface parameters was occasionally observed in circumscribed areas of the epidermis. A selective loss of the demonstrability of beta 2 microglobulin was the prominent feature in basal cell epithelioma. Our findings demonstrate that the alterations of the cell surface differ in malignant and premalignant skin tumors, in basal cell epithelioma, and in benign psoriatic hyperplasia.

We report on two female patients (30 and 33-year-old) suffering from bowenoid papulosis (BP) which showed HPV-16-DNA (E.-M. de Villiers, DKFZ, Heidelberg). Both patients developed cutaneous invasive squamous cell carcinoma in the perineal and vulvar region, resp. In the first patient, the microinvasive part of the tumor was excised. Subsequent therapy with interferon-gamma resulted in complete clinical and histological remission of the BP within 4 months; 6 months after discontinuation of the therapy with interferon, however, we observed a relapse of BP. In the second case, which showed more prominent BP alterations and deeper tumor invasion, interferon-gamma did not bring on any improvement within 3 weeks of therapy; thus radical operation was performed. To our knowledge, this is the first report on the transition of BP of the outer ano-genital region into invasive squamous cell carcinoma.

Microtubules (MT) occur in the keratinocytes as 20 nm broad tubular structures with an electron-lucent core surrounded by an electron-dense wall. The number and the length of the MT increased to the upper epidermal layers. In the normal keratinocytes the MT were relatively short (maximal length 2.2 microns) and slightly tortuous. Their outline was tenuous and irregular. Sometimes the MT were interrupted indicating a high fragility. In the upper layers of the psoriatic epidermis the MT reached a maximal length of 3.1 microns, showing a greater elongation than in the normal epidermis. The MT were stright and distinctly limited, most likely resulting from a higher grade of stabilization or polymerisation. By their interaction with the tonofilaments the MT may contribute to the stability of the cell shape, delaying the flattening of the psoriatic keratinocytes in the upper epidermal layers. Nowhere did the MT make direct contact with the cell membrane. At some places they did gain access to the cell membrane by short microfilaments.

Thirty-nine skin tumors of epithelial, mesenchymal, and neuroectodermal origin were studied using antibodies against intermediate filaments and other cell proteins. Formol-fixed and paraffin-embedded material was reconstituted and stained with antibodies against epithelial cells (keratin, epithelial membrane antigen, carcinoembryonic antigen), mesenchymal and histiocytic cells (vimentin, alpha-1-antichymotrypsin, alpha-1-antitrypsin, lysozyme), nerve tissue (neurofilament, glial fibrillary acidic protein, myelin basic protein, myelin-associated protein, neuron-specific enolase), vessels (factor-VIII-related protein), basal cell lamina (laminin) and S-100 protein. Tumor cells displayed the same antibody pattern found in the normal cell type. It is recommended that immunotyping be started with three antibodies to allow gross classification into epithelial (keratin positive), mesenchymal (vimentin positive) and neuroectodermal (vimentin and S-100 protein positive) tumors; then, in a second step, the tumors can be subclassified by the other more specific antibodies listed above. All antibodies used in this study are commercially available and provide reliable results.

We report on two female patients suffering from mycosis fungoides, tumorous type but without systemic involvement, who have been treated with 400 mg Zovirax (Acyclovir) 3 times daily (about 15 mg/kg/day) for 12 days. The follow-up period amounted to 11 and 14 days, respectively. This therapy did not result in regression of the disease; one patient even showed progression of her skin tumors.

We report on a 17-year-old patient suffering from generalized mottled hyperpigmentation and multiple telangiectatic lesions of the skin. The subcutaneous fatty tissue was lacking or deficient. The patient showed a bird-like face. The cutaneous changes had been present since birth. X-ray studies revealed acro-osteolysis of the hands and feet. The metabolic and endocrine data were within normal ranges except of latent hypothyroidism. The clinical picture presented all criteria of metageria. The patient's mother and sister showed similar cutaneous changes, however, restricted to the distal parts of the extremities. We diagnosed acrogeria Gottron. The incidence of both metageria and acrogeria in one family makes metageria as an independent entity doubtful.

A 54-year-old woman had a six-months history of a scarring blistering disease with clinical signs of dermatitis herpetiformis and bullous pemphigoid. Direct immunofluorescence examination showed homogeneously linear deposits of IgA along the dermo-epidermal junction. Electron microscopic studies revealed blistering above and beneath the lamina densa. Referring to this new case of a scarring linear IgA disease we discuss some other forms of scarring bullous diseases in adults.

Fifty-one patients with psoriasis were treated with 1% anthralin for 1 h (1-h treatment) and UV-light. Seven of 11 out-patients treated with anthralin and UV-B showed a good response. In 40 in-patients the 1-h regimen was administered in right-left side comparison to evaluate (1) whether UV-A or UV-B combined with anthralin was more effective than anthralin alone and (2) whether anthralin was photoactivated by UV-A or UV-B. As to the latter, one body side of the patients was exposed to UV radiation before and the other body side after application of anthralin. In in-patients the response to therapy was monitored by a defined score system. We did not find any significant differences in the paired comparisons. We therefore summarized the different treatment regimens and rated 42% with very good or good, 26% with fair, and 32% with poor. The results show that the 1-h treatment with 1% anthralin seems to be advantageous especially for the treatment of out-patients with circumscribed chronic psoriatic lesions. UV-light did not improve considerably the therapeutic effect of anthralin in the regimen of this study.

Lanthanum has been used as a tracer for the intercellular space and the surface coats in different epithelia including human epidermis, however, lanthanum compounds may or may not penetrate into skin specimes and reaction product may or may not be present in the intercellular space. After treatment with alcian blue prior exposure to lanthanum the trilaminar plasma membrane was more regularly stained and a thin coat of reaction product corresponding to superficial glycoconjugates outlined the cell surface and filled the narrow intercellular space in normal epidermis. In psoriatic epidermis the quantity of superficial membrane-bound glycoconjugates was rather reduced, their distribution and compartmentalization was profoundly changed and the outer leaflet of the trilaminar plasma membrane was not always clearly seen, having a "moth-eaten appearance" in some places. These findings show once more that alterations of the cell membranes and their surface architecture are present in psoriasis. They may play a major role in the pathogenesis of the disease, influencing the activities of membrane-bound enzymes and the flow of the epidermal growth control mechanism. The glycocalyx may serve in this mechanism as an accumulator of energy rich compounds or as a receptor site of membrane-bound ezymes. According to our views it represents a "ground substance" of epidermal origin, which controls the social behaviour of the keratinocytes in tissue.

This article deals with the immediate effect of infra-red (IR) irradiation on human skin. The cutaneous response to IR significantly differed from that to polychromatic UV rays. The IR erythema showed a reticular pattern and was monophasic. Minimal erythema (ME) appeared without latency and faded a few minutes later. Induction of IR-ME required a radiation doses about 15,000 times higher (187-295 J/m2) than was needed for UVB erythema. The maximum erythema also occurred immediately after exposure to IR and faded away within one to four hours. The response was biphasic in only one of 28 test persons. Histological studies revealed dilated vessels and perivascular accumulation of degranulated mast cells.

Eight patients with T-cell-lymphoma of the skin (6 mycosis fungoides, 2 parapsoriasis variegata) were treated with Tigason in combination with PUVA-therapy. The daily dose of Tigason was 50-100 mg. There was complete regression of skin lesions in three patients, partial regression in three patients, and an improvement in two patients.

A variety of immunologic staining techniques were compared in a quantitative study of antigen expression by human epidermal cells. Virtually all nucleated epidermal cells express beta 2-microglobulin, which is associated with HLA-A, -B, and -C antigens, whereas only about 4% expressed T6, an antigen expressed by Langerhans cells but not other cells in the skin. With the fluorescence-activated cell sorter (FACS), epidermal cell suspensions were selectively enriched 10- to 15-fold for T6-positive Langerhans cells. An average of 6.5% of cells were specifically stained by anti-HLA-DR antibody. When dispersed cells stained with anti-DR plus peroxidase were examined with the technique of immunoelectron microscopy, only mononuclear leukocytes (probably Langerhans cells) were stained. After separating HLA-DR positive skin cells with the FACS, the DR-positive population but not the DR-negative population stimulated proliferation of allogeneic responder lymphocytes, indicating that sorted cells are metabolically active. We conclude that HLA-DR antigen is not expressed by keratinocytes in normal human skin cell suspensions and that the FACS can be used to selectively enrich or deplete skin cell suspensions of antigenically distinct subpopulations such as Langerhans cells.

Cheilitis glandularis simplex is a rather rare disease which has to be differentiated from cheilitis granulomatosa. The histological characteristics of cheilitis glandularis simplex are hypertrophy and hyperplasia of mucous and/or heterotopic salivary glands. The therapy is the excision of the tumor.

To extend our initial observations that recombinant gamma-interferon (r gamma IFN) influences the growth and differentiation of normal cultured human keratinocytes, we studied the electron microscopic changes induced by r gamma IFN. Treatment of cultured human keratinocytes with 10(3) units/ml (7.1 nM) of r gamma IFN produced a shift toward an increasing percentage of attached cells that had a mature-type, differentiated appearance rather than a basal type of proliferating cell, as observed in control, untreated cultures. This report extends the number of cell types that can be influenced by r gamma IFN at the ultrastructural level and supports the notion that r gamma IFN can influence both growth and maturation of normal cultured human keratinocytes.

Sixteen patients - 12 with cutaneous T cell lymphoma (CTCL), 1 with Sézary syndrome, 1 with actinic reticuloid, and 2 with parapsoriasis variegata - were treated with either a new, potent arotinoid alone or with combined etretinate (Tigason) and PUVA therapy (Re-PUVA). 92% of all patients showed a minor up to a distinct response of their skin lesions within 12.6 +/- 7.4 weeks. More than 50% of the skin lesions cleared in 67% of the patients. After discontinuation of the retinoid therapy, relapses occurred in all cases within 3-10 weeks. There was no difference between the therapeutic efficacy of arotinoid alone and the Re-PUVA regimen, but the latter was less toxic.

We report on a patient suffering from striate palmoplantar keratoderma (Wachters' type). Ultrastructural findings are presented for the first time. There was orthohyperkeratosus without alterations indicating a specific disturbance of keratinisation.

We report on a 17-year-old patient suffering from generalized verrucosis. This diagnose had been confirmed by means of light microscopy, electron microscopy, and DNA hybridisation (HPV type 2). The study of immunological parameters revealed reduced numbers of T-lymphocytes, especially of helper-T-cells. Skin tests with recall antigens were normal. Three brothers of our patient showed slight reduction of helper-T-cells. Treatment with topical retinoic acid was not effective. Treatment with alpha-interferon i.m. intralesionally was effective in the beginning, but two weeks after onset of therapy no further improvement could be achieved. Discontinuation of therapy was followed by a relapse. Tigason which was given thereafter led to flattening of the warts but failed to bring about complete regression within the following four months.

Epidermal cells taken from guinea pigs were cultured on collagen in order to study the processes comparable to reepithelialization of wounds by means of time-lapse cinematography and electron microscopy. Attachment and spreading of the cells are essential for the following cell proliferation. Immediately after seeding, the cells move in streams and rotate around their axes. Flattened cells show cytoplasmic streaming and ameboid movement as they continuously alter their shapes (10-25 microns/h). The cells actively form intercellular bridges, which favor the confluence of the cells. In the present study, the phases of attachment, intercellular association, and formation of colonies have been classified and related to the activity of the DNA synthesis, as it was indicated by 3H-thymidine incorporation.