Christiane Bayerl

Prostaglandin-H-synthase isozyme expression in normal and neoplastic human skin

Expression of prostaglandin‐H‐synthase (PGHS) isozymes was analyzed in 50 biopsies of normal human skin and of pre‐malignant and malignant skin lesions, by means of quantitative RT‐PCR, immunoprecipitation and Western blotting, as well as immunohistochemistry. Normal skin constitutively expressed PGHS‐1 in all cell layers of the epidermis, in endothelial cells of small blood vessels and in sweat‐gland epithelium. PGHS‐2 expression was very low and restricted to a few keratinocytes of the interfollicular and follicular epidermis. Steady‐state concentrations of PGHS‐1 and PGHS‐2 mRNA were similar in normal skin and in basal‐cell carcinomas, but PGHS‐1 mRNA was reduced and PGHS‐2 mRNA was elevated in actinic keratoses, squamous‐cell carcinomas and keratoacanthomas. PGHS‐1 protein was detected in all tumor biopsies, being occasionally increased in basal‐cell carcinomas. High amounts of PGHS‐2 protein were found in actinic keratoses, squamous‐cell carcinomas and keratoacanthomas, but not in basal‐cell carcinomas. Four malignant melanomas included in this study contained PGHS‐1 but no PGHS‐2 protein. Immunohistochemical analysis of the biopsies identified keratinocytes, in addition to cells of inflammatory infiltrates and of dendritic morphology, as the major PGHS‐expressing cell types. PGHS‐2‐specific signals were spread throughout the epidermal part of actinic keratoses and squamous‐cell carcinomas. These data suggest that constitutive up‐regulation of PGHS‐2 expression is a consistent pre‐malignant event in squamous‐cell cancer development in man, as it is in animal models of skin carcinogenesis. Thus, pre‐cancerous lesions such as actinic keratoses present a likely target for chemoprevention of skin cancer by selective PGHS‐2 inhibitors. Int. J. Cancer 82:648–656, 1999.

Characterization of sunburn cells after exposure to ultraviolet light

Sunburn cells (SBCs) appear in the epidermis shortly after acute UV damage, especially after exposure to UVB light. As yet, the mode of their formation remains to be satisfactorily elucidated. In order to characterize these cells, the expression of various markers of epidermal differentiation following UV exposure was investigated using immunhistochemical procedures. These were applied to paraffin‐embedded (microwave technique) and frozen specimens of human skin 24 h after irradiation with 4 times the minimal erythema doses(MED). Normal nonirradiated skin without irradiation served as the control. We used a battery of antibodies directed against the following: cytokeratins (CKs) 5, 10, 17, and 19, actin, cell‐adhesion proteins (desmoplakins, desmogleins), markers of terminal epidermal differentiation (filaggrin, involucrin and loricrin), markers of proliferation (PCNA, MIB, K6,16), a marker of endocytosis (clathrin) and markers of cell growth, (transforming growth factor [TGF‐α]) and B‐cell leukemia/lymphoma‐2 [bcl‐2]. After UV irradiation it was found that CK 5, which is typically confined to basal keratinocytes, was also expressed in suprabasal keratinocytes. The CKs 1 and 10/11 exhibit a normal suprabasal localization, but suprisingly, SBCs were negative for these CKs. Although CK 6,16, and 17 are not usually found in normal epidermis, UVB exposure induced their expression in suprabasal keratinocytes, but again failed to elicit their expression in SBCs. Antibodies specific for markers of late epidermal differentiation (filaggrin, involucrin and loricrin), cell‐junction proteins (desmogleins, desmoplakins), proliferation (PCNA and MIB), and endocytosis (clathrin) also failed to produce positive staining of SBCs. Even though TGF‐α immunoreactivity became detectable in most keratinocytes after UV exposure, this was not the case for SBCs. The number of basally located dendritic cells, most probably melanocytes, exhibiting bcl‐2 staining was markedly reduced 6 and 12 h after irradiation as compared with normal skin. SBCs do not express any late differentiation markers, but they do contain proteins typical of basal keratinocytes (CK 5). It can be concluded that SBCs do not develop beyond a more basal‐like differentiation pattern, probably as a result of cell death and migration through the epidermis.

CUTANEOUS REACTIONS TO ANTICOAGULANTS. RECOGNITION AND MANAGEMENT

Anticoagulant-induced skin reactions appear as allergic or necrotic responses to vitamin K antagonists or heparins. Cutaneous allergy has been reported with danaparoid sodium and flush reactions have been seen with hirudins. The pathogenesis of the reactions differs between drugs. Generally, they occur between days 3 to 10 after the start of treatment, but may also occur later. In patients experiencing necrosis with a vitamin K antagonist, concomitant protein C deficiency, protein S deficiency or lupus anticoagulant has been described, whereas the precise mechanism of the other reactions is unknown. In patients with allergic reactions to heparins, cutaneous tests may help to identify alternative anticoagulants. Such a test cannot be performed in patients with skin necrosis.In patients with heparin-induced skin reactions danaparoid sodium may be used after negative intracutaneous testing in some patients and a hirudin may be used without testing in all patients. Heparin-induced skin necrosis has been reported to be mediated by immunologic mechanisms and to be associated with a high frequency of heparin-induced thrombocytopenia type II. Surgical excision of the necrosis may be required. If further anticoagulation is indicated in any patient, extreme caution has to be taken when restarting oral anticoagulants. Because a large number of anticoagulants available today, safe treatment of all patients experiencing anticoagulant-induced skin reactions is feasible.

S2k-Leitlinie zur Therapie der Akne

To optimize the treatment of acne in Germany, the German Society of Dermatology (DDG) and the Association of German Dermatologists (BVDD) initiated a project to develop consensus-based guidelines for the management of acne. The Acne Guidelines focus on induction therapy, maintenance therapy and treatment of post-acne scarring. They include an evaluation of the most commonly used therapeutic options in Germany. In addition, they offer detailed information on how to administer the various treatments and on contraindications, adverse drug reactions, and drug interactions, taking into account gender and special conditions such as pregnancy and lactation. The Acne Guidelines were developed following the recommendations of the Association of Scientific Medical Societies in Germany (AWMF). The treatment recommendations were developed by an expert group and finalized by an interdisciplinary consensus conference. The first choice treatments for acute acne according to acne type are as follows: 1) comedonal acne: topical retinoids; 2) mild papular/pustular acne: fixed or sequential combinations of BPO and topical retinoids or of BPO and topical antibiotics; 3) moderate papular/pustular acne: oral antibiotic plus BPO or plus topical retinoid, or in a fixed combination 4) acne papulo-pustulosa nodosa and acne conglobata: oral antibiotic plus topical retinoid plus BPO or oral isotretinoin. For maintenance treatment: topical retinoid or its combination with BPO. Particular attention should be paid to compliance and quality of life. Additional treatment options are discussed in the main body of the text.

Hypersensitivity to the pentasaccharide fondaparinux in patients with delayed-type heparin allergy

Hypersensitivity to the pentasaccharide fondaparinux in patients with delayed-type heparin allergy -

Predominant telangiectatic erythema in linear atrophoderma of Moulin: novel variant or separate entity?

Linear atrophoderma of Moulin is a distinctive disease originally described in 1992 and characterized by acquired, mildly atrophic, non-sclerotic, slightly hyperpigmented lesions following the lines of Blaschko. Here, we describe a 15-year-old girl with a 13-year history and a 29-year-old male with a 6-year history of prominent linear telangiectatic erythema and mild atrophoderma following the lines of Blaschko that involved the right leg and hip, and both legs, the trunk and both arms, respectively. As pronounced telangiectatic erythema within lesions of atrophoderma of Moulin has not hitherto been described, we propose that the disease in our patients represents a novel variant of linear atrophoderma of Moulin. Due to considerable overlap, we do not favour the notion that our cases constitute an entity entirely separate from linear atrophoderma of Moulin.

Meloxicam in acute UV dermatitis — a pilot study

The non‐steroidal anti‐inflammatory drug (NSAID) meloxicam is a preferential cyclooxygenase‐2 (COX‐2) antagonist. The UV protective potential of this drug was studied to compare it with the reported beneficial effects of such preferentially COX‐1 specific NSAIDs as indomethacin and acetylsalicylic acid in the literature. In a pilot study (open‐label, non‐randomized, non‐controlled, unblinded), 10 patients received UV irradiation with the minimal erythema dose (MED), first with meloxicam (7.5 mg/die) to reduce post‐operative pain and second without ingestion of meloxicam. The factor of UV protection was evaluated. In six of ten patients meloxicam showed no benefit, whereas four of ten patients had a 1.3‐ up to 3‐fold UV protection. In this study, the benefit in UV protection of meloxicam as a prefential COX‐2 antagonist was not above the reported benefit of the “old” COX‐1 inhibiting NSAIDS.

Diagnostics of autoimmune bullous diseases in German dermatology departments.

Background: No consistent data are available on the currently employed diagnostic tools for autoimmune bullous diseases in Germany. The aim of this survey was to describe currently performed diagnostic methods for bullous autoimmune diseases in German dermatology departments.

Immunohistochemical characterization of HSP, α-MSH, Merkel cells and neuronal markers in acute UV dermatitis and acute contact dermatitis in vivo

Abstract.Objective: To study the immunoneurocrine network in inflammatory dermatoses, we investigated histochemically acute UV and acute contact dermatitis.¶Methods: Antibodies were applied to frozen and paraffin specimens of human skin after irradiation (n = 10), to positive patch tests (n = 10) and controls (n = 10) against: HSP 70, 72, 27, neuronal polypeptides (α-MSH, NSE, bombesin, PGP 9.5, NGF, NGF-R) and intermediate filaments (peripherin, NF 200, CK 19, 20).¶Results: HSPs and α-MSH were upregulated in UV dermatitis in the epidermis compared to contact dermatitis and normal skin. Sunburn cells did not express HSPs or α-MSH in UV dermatitis. Neuronal markers and HSP 27 labeled more nerve fibers in UV than in contact dermatitis, except the increased staining for NGF, NGF-R and α-MSH in nerve fibers in contact dermatitis. In UV dermatitis, 50% of Merkel cells were suprabasal, but in contact dermatitis, basal, rounded and reduced in number.¶Conclusions: Merkel cells, HSPs and markers of neuroinflammation are of different importance in UV and contact dermatitis in vivo.

A three-year randomized trial in patients with dysplastic naevi treated with oral beta-carotene.

Ultraviolet irradiation provokes the development of new melanocytic naevi, or changes in existing naevi, leading to repeated surgery of atypical naevi and becoming a continual burden for individuals with many of these lesions. To determine the influence of long-term medication with the radical scavenger beta-carotene on newly developing atypical naevi, a single-centre, randomized, placebo-controlled study, prospective over 3 years, was started double-blind in 62 patients with numerous clinically atypical naevi. Beta-carotene (25 mg) was given twice daily for 36 months in the treatment group (n = 30) and saccharose capsules as placebo in the control group (n = 32). The total number of newly developed naevi in the beta-carotene group (n = 18) was 68 versus 88 in the placebo group (n=21) (not significant). Of 12 different locations on the human body evaluated separately, only in two, the lower arm (p = 0.03) and the feet (p = 0.03), was there a difference for the beta-carotene group in the quantification of naevi. Overall, it is concluded that beta-carotene does not reduce the development of new naevi in patients with numerous atypical naevi.