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Notes: Chronic ulcerative stomatitis (CUS) has recently been described as a new disease entity characterized by chronic ulceration of oral mucosa which responds to treatment with hydroxychloroquine. It has a particular type of stratified epithelium-specific, antinuclear autoantibody as an immunological marker. Twelve cases have been reported in the literature. We present a 40-year-old woman with an 11-year history of chronic oral ulcerations. Other dermatological diseases, including oral lichen planus, pemphigus vulgaris and cicatricial pemphigoid, as well as bullous lupus erythematosus, were excluded. The clinical diagnosis of CUS was confirmed on the ground of the immunological and ultrastructural findings. The lesions initially responded to high doses of systemic corticosteroids but relapsed promptly after dose reduction. Dapsone was ineffective. Hydroxychloroquine, given at a dosage of 200–400 mg/day, led to a complete and longlasting remission.

Notes:   Topical Calcineurin Inhibitors (TCIs) used for the treatment of atopic eczema modify the immune regulatory function of the skin and may have the potential to enhance immunosuppressive ultraviolet (UV) effects. Current recommendations on UV protection in eczema patients treated with PCIs are inconsistent and have given rise to uncertainty and anxiety in patients. Therefore, the European Dermatology Forum (EDF) developed a position statement which reviews critically the available data with regard to the problem, especially analysing and commenting the limitations of rodent models for the human situation. There is no conclusive evidence from rodent trials to indicate that long-term application of TCIs is photococarcinogenic. There is a need for further studies to investigate the validity of mouse models as well as long-term cohort studies in patients using TCIs. Available data suggest that long-term application of TCIs is safe, that there is no evidence of increased skin cancer risk and that it is ethical to treat patients with TCIs when indicated.

Notes: Abstract: These results demonstrate for the first time that human keratinocytes under in vivo-like conditions have the capacity of the enzymatic hydroxylation of vitamin D3 to hormonally active calcitriol (1α,25(OH)2D3). Supplementation of the culture medium with bovine serum albumin (BSA) up to 1.5% (w/v) amplifies the conversion of vitamin D3 to 1α,25(OH)2D3. The maximum turnover rate of this reaction at 780 nM vitamin D3 in presence of 1.0% (w/v) BSA amounts to approximately 3 pmol 1α,25(OH)2D3 per 106 cells after 6 h of incubation. The hydroxylation of vitamin D3 to 1α,25(OH)2D3 is inhibited by the P-450 oxidase inhibitor ketoconazole. The generation of 1α,25(OH)2D3 from vitamin D3 has an apparent Michaelis constant (Km) of 2.3×10−6 M. The intrinsic conversion of vitamin D3 to biologically active 1α,25(OH)2D3 may be of importance for the regulation of proliferation and differentiation of keratinocytes.

Notes: UVB irradiation of cultured human keratinocytes induces both the conversion of 7-dehydrocholesterol (7-DHC) to calcitriol (1α,25(OH)2D3) and the release of tumor necrosis factor-a (TNF-α) in these cells. Calcitriol synthesis in human keratinocytes was reduced in the presence of a neutralizing polyclonal antibody directed against human TNF-α. On the other hand, we found a 1.7-fold higher stimulatory effect of UVB on liberation of TNF-α in cultured keratinocytes enriched with 7-DHC compared with irradiated cell cultures in absence of 7-DHC. These observations argue in favor of a synergetic relationship between generation of TNF-α and calcitriol in UVB irradiated keratinocytes. In addition, we found that TNF-α potently increases the conversion rate of vitamin D3(cholecalciferol) to calcitriol this cell system. The UVB-triggered formation of both TNF-α and calcitriol in cultured keratinocytes as wavelength-, time- and dose-dependent. Maximum formation of TNF-α and calcitriol was found at 300 nm and UVB doses of 30 mJ/cm2. The enhancement of both, the formation of TNF-α and calcitriol in keratinocytes by UVB may be of relevance for regulation of growth and apoptosis in light-exposed epidermal cells and, in addition, may play a role in the UVB treatment of deseased skin, including psoriasis.

Notes: Summary Chronic graft-versus-host disease after bone marrow transplantation presents, in a few cases, as mild to severe scleroderma-like changes. Patients with chronic graft-versus-host disease with and without sclerodermatous skin changes were analysed for antinuclear autoantibodies (ANA) and antinucleolar autoantibodies (ANoA) and the results correlated with disease symptoms and histocompatibility locus antigen (HLA) pattern. Nineteen patients with chronic graft-versus-host disease and scleroderma-like skin changes. 18 with chronic graft-versus-host diseae without scleroderma. and 17 controls on immunosuppressive treatment were screened for ANA and ANoA using enzyme-linked immunosorbent assay, immunodiffusion and immunoblot techniques. Four patients with severe scleroderma had antibodies to topoisomerase I. two had antibodies against PM-Scl. both characteristic serological findings in idiopathic systemic scleroderma. One patient had La/SSB antibodies and, in three cases, antibodies to the nucleolar antigen C23 (nucleolin) could be identified. A possible correlation between antinucleolin antibodies and disease activity was observed. HLA-Al. -B1. and -B2 were found significantly more often in patients with scleroderma-like symptoms in comparison to patients without scleroderma-like symptoms. Chronic graft-versus-host disease with seleroderma-like manifestations can be associated with the occurrence of ANA specific for idiopathic scleroderma. The development of seleroderma after bone marrow transplantation might have a HLA-linked genetic background.

Notes: Summary Using a direct immunogold technique, we studied the level of immunological events in the skin basement membrane in a patient with herpes gestationis during blister formation. Within the lamina lucida. IgG and C3 were localized bencath the basement membrane of basal keratinocytes, 30–40 nm above the lamina densa. In many areas of blister formation sub-basal dense plates. but probably also the upper parts of the hemidesmosomes were separated from the roof of the blister. In the perilesional lamina lucida and in the blister. lgG and C3 containing amorphous grains. Most probably immunocomplex aggregates, were detected. They covered the basement membrane of keratinocytes and left free a 30–40 nm band above the lamina densa. Our study indicates that in herpes gestationis the cleavage, accompanied by IgG, C3 and immunocomplex deposition, occurs at the level of the subbasal dense plate, However, cleavage through upper hemidesmosomal structures can occur in parallel. These data further support the involvement of hemidesmosmes in the pathogenesis of the disease and therefore in its relationship to bullous pemphigoid.

Notes: Background  There are very few data regarding sun exposure behaviour of patients with basal cell carcinoma (BCC) in central Europe.Objectives  A case–control study of patients with sporadic BCC was conducted to assess the risk of occupational and leisure-time sun exposure behaviour, precursor lesions for skin cancer and phenotypic factors on the development of sporadic BCC in Ulm and Dresden, Germany.Methods  A comparison was made of 213 patients with BCC (128 from Ulm, 85 from Dresden; 103 men and 110 women; median age at diagnosis 69 years) and 411 controls (237 from Ulm, 174 from Dresden; 197 men and 214 women; median age 58 years). Crude odds ratios (ORs) and corresponding 95% confidence intervals for all of 64 possible risk factors revealed strong associations in 33 items. Selection of important risk factors was performed in a multiple logistic regression.Results  For sporadic BCC, an increased risk was shown for persons with actinic cheilitis (OR 7·1), actinic keratosis (OR 2·7) and solar lentigo (OR 2·5). The only phenotypic factor indicating risk of sporadic BCC was hair colour, with a higher risk for red/fair than brown/black hair (OR 4·3). There was an increased risk for persons with BCC in first-degree relatives (OR 5·1) and those with sunburn 20 years before sporadic BCC was diagnosed (OR 3·6). Additionally, occupational ultraviolet (UV) exposure appeared to be a risk factor (OR 2·4). In contrast, clinical actinic elastosis showed a protective effect (OR 0·1).Conclusions  In contrast to earlier reports, clinical actinic elastosis turned out to be the only protective factor for sporadic BCC. A special relationship between wrinkling and BCC risk could not be shown. For basic research, future work should be aimed at elucidating further the different forms of collagen repair processes after intermittent and/or chronic UV exposure. The data strongly support the recommendation that a change in recreational UV exposure habits in individuals, and sunburn avoidance in particular, are necessary not only because of the increased long-term risk of melanoma, but also because of the risk of other skin cancers such as sporadic BCC.

Notes: Thirty-seven men (36 homosexual or bisexual and one heterosexual) with epidemic Kaposi's sarcoma and underlying HIV infection were followed up over a period of up to 32 months. Fourteen patients (38%) died, with a median survival time of 7.2 months after the diagnosis of AIDS. Seventeen patients (46%) presented with one or more opportunistic infections, mostly Pneumocystis carinii pneumonia. Eighteen patients (49%) had lymphadenopathy syndrome according to the definition of the CDC. Using the Laubenstein-classification of Kaposi's sarcoma, all patients either remained stable or deteriorated, improvement was never observed. Absolute T4 lymphocyte counts and the T4/T8 ratio were not related to the disease stage. With the onset of B symptoms (systemic symptoms), however, the absolute T4 numbers and the T4/T8 ratio markedly decreased. Delayed type hypersensitivity also showed no relationship to the clinical stages of Kaposi's sarcoma. Thus, the clinical progression of Kaposi's sarcoma lesions seems to be largely independent of the immunological parameters investigated. However, the onset of B symptoms was observed to be related to changes in immune status.

Notes: A group of 191 patients with systemic scleroderma and 12 patients with silicosis-associated scleroderma were investigated for connective tissue turnover. The serum levels of type III collagen aminopropeptide (P-III-P), the laminin P1 (Lam P1) fragment and the acid lysosomal β-galactosidase (β-Gal) were determined by specific radioimmunoassays and spectrofluorometry, respectively. Increased levels of type III collagen aminopropeptide strongly correlated with enhanced activity of β-galactosidase. Both parameters correlated with the clinical course in idiopathic systemic scleroderma and in silicosis-associated scleroderma. Serum levels of Lam P1 were also found to be elevated in both groups, although there was no correlation with the severity of the disease. Autoantibodies directed against the DNA topoisomerase Scl-70 and against centromeric proteins were found in a similar range in patients with idiopathic systemic and silicosis-associated scleroderma. These results suggest that P-III-P, Lam P1 and β-Gal are useful serological markers of fibrotic activity and demonstrate similarities between idiopathic systemic scleroderma and scleroderma associated with silica-dust exposure.