Updated evidence-based (S2e) European Dermatology Forum guideline on topical corticosteroids in pregnancy.

BACKGROUND: Topical corticosteroids may be needed for treating skin conditions in pregnancy. Nevertheless, only limited data on the fetal effects of topical corticosteroids are available. OBJECTIVE: To update an evidence-based guideline on the safe use of topical corticosteroids in pregnancy. METHODS: A guideline subcommittee of the European Dermatology Forum updated the guideline by adding and appraising new evidence. RESULTS: The current best evidence from 14 observational studies with 1 601 515 study subjects found no significant associations between maternal use of topical corticosteroids of any potency and some adverse pregnancy outcomes including mode of delivery, birth defect, preterm delivery and fetal death. However, maternal use of potent/very potent topical corticosteroids, especially in large amounts, is associated with an increase in the risk of low birthweight. CONCLUSION: Mild/moderate topical corticosteroids should be preferred to potent/very potent ones in pregnancy. The well-known topical side-effects of corticosteroids on the mother's side need to be considered as well.

Evidence-based (S3) guideline on topical corticosteroids in pregnancy.

Women with skin conditions may need topical corticosteroids during pregnancy. However, little is known about the effects of topical corticosteroids on the fetus. A guideline subcommittee of the European Dermatology Forum was organized to develop an evidence-based guideline on the use of topical corticosteroids in pregnancy (http://www.euroderm.org/edf/images/stories/guidelines/EDF-Guideline-on-Steroids-in-Pregnancy.pdf). The evidence from a Cochrane Review suggested that the major possible adverse effects on the fetus of topical corticosteroids were orofacial clefts when used preconceptionally and in the first trimester of pregnancy, and fetal growth restriction when very potent topical corticosteroids were used during pregnancy. To obtain robust evidence, a large population-based cohort study (on 84,133 pregnant women from the U.K. General Practice Research Database) was performed, which found a significant association of fetal growth restriction with maternal exposure to potent/very potent topical corticosteroids, but not with mild/moderate topical corticosteroids. No associations of maternal exposure to topical corticosteroids of any potency with orofacial cleft, preterm delivery and fetal death were found. Moreover, another recent Danish cohort study did not support a causal association between topical corticosteroid and orofacial cleft. The current best evidence suggests that mild/moderate topical corticosteroids are preferred to potent/very potent ones in pregnancy, because of the associated risk of fetal growth restriction with the latter.

ALDEN, an algorithm for assessment of drug causality in Stevens-Johnson Syndrome and toxic epidermal necrolysis: comparison with case-control analysis.

Epidermal necrolysis (EN)--either Stevens-Johnson syndrome (SJS) or toxic EN (TEN)--is a severe drug reaction. We constructed and evaluated a specific algorithm, algorithm of drug causality for EN (ALDEN), in order to improve the individual assessment of drug causality in EN. ALDEN causality scores were compared with those from the French pharmacovigilance method in 100 cases and the case-control results of the EuroSCAR study. Scores attributed by ALDEN segregated widely. ALDEN pointed to a "probable" or "very probable" causality in 69/100 cases as compared to 23/100 with the French method (P < 0.001). It scored "very unlikely" causality for 64% of medications vs. none with the French method. Results of ALDEN scores were strongly correlated with those of the EuroSCAR case-control analysis for drugs associated with EN (r = 0.90, P < 0.0001), with probable causality being reported in 218/329 exposures. ALDEN excluded causality in 321 drugs that the case-control analysis had described as "probably not associated" and in 22/233 drugs that had been described as inconclusive exposures. Being more sensitive than a general method, ALDEN, which correlates well with case-control analysis results, can be considered a reference tool in SJS/TEN.

[Generation of reactive oxygen species in vitro by Malassezia yeasts]. / Bildung von reaktiven Sauerstoffspezies in vitro durch Malassezia-Hefen.

BACKGROUND AND METHODS: Free oxygen species are able to destroy cells due to their cytotoxic effect, which is based on lipid peroxidation, enzyme oxidation and protein oxidation. We analyzed the ability of six different Malassezia (M.) species to generate reactive oxygen species (ROS), using the lucigenin-amplified chemiluminescence. Further investigations showed the effect of different concentrations of terbinafine on ROS generation by M. furfur and M. pachydermatis after 10, 30 and 60 minutes. RESULTS: All of the investigated Malassezia species (M. furfur, M. globosa, M. sympodialis, M. slooffiae, M. obtusa, M. pachydermatis) was able to generate reactive oxygen species. Terbinafine inhibited free radical production by M. furfur and M. pachydermatis. CONCLUSION: Dependent on their cell concentrations, M. species have the ability to generate ROS. The ability of the different Malassezia species to produce ROS should be considered as one further virulence factor of this yeast. The antifungal agent terbinafine (concentrations from 100 microg to 1 microg ml -1) reduced ROS production by M. furfur and M. pachydermatis. Terbinafine acts as oxygen species scavenger. This could be an additional mechanism supporting the classic antifungal effect of this agent, the inhibition of ergosterol synthesis.

[Species differentiation of yeasts of the genus Malassezia with Fourier transform infrared spectroscopy]. / Speziesdifferenzierung von Hefen der Gattung Malassezia mittels Fourier-Transform-Infrarot-Spektroskopie.

BACKGROUND: 83 Malassezia strains (65 wild isolates and 18 reference strains) were differentiated to the species level using conventional methods including morphological and biochemical features. These strains were further analyzed by Fourier transform infrared spectroscopy (FT-IRS). RESULTS: FT-IRS analysis allowed a clear separation of Malassezia strains according to species-specific cluster formation. The main differences were found between Malassezia furfur and other Malassezia species. In addition, within the species Malassezia furfur, a separation in two similar groups could be demonstrated. A disadvantage of FT-IRS is the relatively expensive apparatus. A great advantage is the speed and simplicity of the procedure, producing results within minutes. CONCLUSION: In pityriasis versicolor, Malassezia globosa was the dominant species found in 62% of cases. In addition, Malassezia furfur was found in 60% of dandruff cases.

Activity of nadifloxacin (OPC-7251) and seven other antimicrobial agents against aerobic and anaerobic Gram-positive bacteria isolated from bacterial skin infections.

BACKGROUND AND METHODS: The in vitro activity of nadifloxacin (OPC-7251), a novel topical fluoroquinolone, was assessed and compared with those of ofloxacin, oxacillin, flucloxacillin, cefotiam, erythromycin, clindamycin, and gentamicin against 144 Gram-positive bacteria: 28 Staphylococcus aureus, 10 Streptococcus spp., 68 coagulase-negative staphylococci (CNS), 36 Propionibacterium acnes, and 2 Propionibacterium granulosum strains. All strains originated from bacterial-infected skin disease and were isolated from patients with impetigo, secondary infected wounds, folliculitis and sycosis vulgaris, and impetiginized dermatitis. In vitro susceptibility of all clinical isolates was tested by agar dilution procedure and minimum inhibitory concentrations (MICs) were determined. RESULTS: Nadifloxacin was active against all aerobic and anaerobic isolates. MIC(90) (MIC at which 90% of the isolates are inhibited) was 0.1 microg/ml for S. aureus, 0.78 microg/ml for both Streptococcus spp. and CNS, and 0.39 microg/ml for Propionibacterium spp. On the other hand, resistant strains with MICs exceeding 12.5 mug/ml were found in tests with the other antibiotics. For both CNS and Propionibacterium acnes, MIC(90) values > or =100 microg/ml were demonstrated for erythromycin. Ofloxacin, cefotiam, erythromycin, clindamycin and gentamicin exhibited MIC(90) values < or =1 microg/ml for some bacterial species tested. Both oxacillin and flucloxacillin were active against all investigated bacterial species with MIC(90) values < or =1 microg/ml. CONCLUSION: In summary, nadifloxacin, a topical fluoroquinolone, was found to be highly active against aerobic and anaerobic bacteria isolated from patients with infected skin disease, and seems to be a new alternative for topical antibiotic treatment in bacterial skin infections.

[Topically applied arginine hydrochloride. Effect on urea content of stratum corneum and skin hydration in atopic eczema and skin aging]. / Topisch appliziertes Argininhydrochlorid. Einfluss auf den Harnstoffgehalt des Stratum corneum und die Hautfeuchtigkeit bei atopischem Ekzem und Altershaut.

BACKGROUND AND OBJECTIVE: Currently, there are no data on how the topical application of amino acids influences the complex moisture retaining system of the skin in vivo. PATIENTS/METHODS: An open study was performed to investigate the effects of topical application of arginine hydrochloride on epidermal stratum corneum urea content, transepidermal water loss, skin hydration, and clinical status of patients with atopic dermatitis and dry elderly skin. RESULTS: Treatment of patients with atopic dermatitis with 2.5% arginine hydrochloride ointment over 4 weeks showed a significant increase in urea in the stratum corneum as well as a continuous increase in skin moisture. CONCLUSIONS: The urea deficit in the stratum corneum in atopic dermatitis and elderly skin was corrected not by applying the moisturizer urea itself but instead by using arginine - its precursor in the Krebs-Henseleit urea cycle. This topical treatment also improved the clinical symptoms of dry skin.

Systemic sclerosis-scleroderma.

Systemic sclerosis is a clinically heterogeneous, systemic disorder which affects the connective tissue of the skin, internal organs and the walls of blood vessels. It is characterized by alterations of the microvasculature, disturbances of the immune system and by massive deposition of collagen and other matrix substances in the connective tissue. This review discusses epidemiology and survival, clinical features including subsets and internal organ involvement, pathophysiology and genetics, microvasculature, immunobiology, fibroblasts and connective tissue metabolism and environmental factors. Early diagnosis and individually tailored therapy help to manage this disorder, which is treatable, but not curable. Therapy involves immunomodulation as well as the targeting of blood vessel mechanics and fibrosis. Physical therapy and psychotherapy are also important adjunctive therapies in this multifactorial disease.

[Multiple lentigines (LEOPARD) syndrome. Case reports and review of the literature]. / Multiple-Lentigines (LEOPARD)-Syndrom. Kasuistiken und Literaturübersicht.

The rarely occurring multiple lentigines (LEOPARD) syndrome represents a complex of skin, heart, skeleton and other malformations and is described in a 36-year-old male and his 9-year-old daughter. With the occurrence of multiple lentigines, the diagnostic search for further malformations should always be undertaken. Its differential diagnosis and its pathogenetic and clinical aspects are discussed in this paper.

The Thy-1/Thy-1 ligand interaction is involved in binding of melanoma cells to activated Thy-1- positive microvascular endothelial cells.

The expression of adhesion molecules on endothelial cells as well on tumor cells regulates and directs adhesion and transmigration of tumor cells through the endothelial cell barrier as one prerequisite to the formation of metastasis. Thy-1 is an inducible activation-associated cell-adhesion molecule on human dermal microvascular endothelial cells (HDMECs). In this study we investigated whether the Thy-1/Thy-1 ligand interaction may also play a role in adhesion of melanoma cells to endothelial cells. In situ, a strong Thy-1 expression on endothelial cells in melanoma and melanoma metastases was observed. In vitro, Thy-1 expression was stimulated by melanoma-cell-derived soluble factors, reflecting that Thy-1 expression in melanoma is not only due to a nonspecific inflammatory response. TNFalpha and bFGF were not responsible for this effect. In vitro and in situ a Thy-1 ligand was detected on melanoma cells. In cell-adhesion assays we showed the involvement of the Thy-1/Thy-1 ligand interaction in adhesion of melanoma cells to HDMECs. In summary, the data support that the study of the Thy-1/Thy-1 ligand interaction might give a more detailed insight into the regulation and direction of adhesion of melanoma cells to endothelial cells as one critical step in the formation of tumor metastasis.

[Sports-induced infections--an overview]. / Sport-induzierte Infektionen--eine Ubersicht.

Sportive activities are playing an increasing role for the spare time in our society. Subsequently, practicing of various kinds of sport can lead to direct and indirect exposures to and transmission of microorganisms between athletes and also passive observers. As a result, different microbial pathogens can be transmitted and might lead predominantly to cutaneous or mucosal infections. These include both bacteria--Staphylococcus aureus, streptococci and gram-negative bacteria, like Pseudomonas, viruses--herpes simplex virus, human papilloma virus--and, last but not least, also dermatophytes--e.g. Trichophyton tonsurans as particular pathogenic agent of tinea gladiatorum. Beside single cases of infections outbreaks through various virus-, bacteria- and dermatophytes-induced infections might happen and have indeed been reported. Surprisingly, there is only limited knowledge among physicians concerning sport-induced infections. Therefore, sport-induced infections are reviewed giving details about their route of transmission. Awareness of these infections might facilitate implementation of early treatment and preventive measures.

Juvenile papular-purpuric gloves and socks syndrome.

Papular-purpuric gloves and socks syndrome (PPGSS) occurs mainly in young adults, but it should also be considered in the differential diagnosis of childhood exanthems. The case presented here is the youngest patient hitherto reported with PPGSS and supports the concept of a viral genesis.

Cutaneous breast angiosarcoma after conserving treatment of breast cancer.

Cutaneous angiosarcoma is a rare malignancy that sometimes occurs as a late sequela of breast conservation therapy. We report on a 79-year-old female who developed well-differentiated angiosarcoma in a lymphedematous left breast 5.5 years after surgery and radiotherapy for early invasive ductal breast cancer. The initial appearance was very similar to late radiation dermatitis, and histologically interpreted as scar tissue with atypical vascular lesion. The lesion progressed further, and was clinically suspicious for angiosarcoma. Thus, a second biopsy was taken which confirmed the diagnosis. A complete mastectomy removed all the tumor with clear margins. However, within a period of 16 months she presented four local recurrences which were treated by wide local excision. At present, the patient is free of locally recurrent tumour for 7 months. The few cases of breast angiosarcoma after breast conservation therapy reported so far demonstrate that these lesions are difficult to diagnose due to their rarity and their highly variable and benign appearance, which sometimes may mimic radiation-induced cutaneous changes. Since chronic lymphedema possibly contributes to the development of angiosarcoma, long-term clinical surveillance of these patients is recommended. Biopsies should be taken if new skin lesions occur.

IgG and IgE immune response against the surface glycoprotein gp200 of Saccharomyces cerevisiae in patients with atopic dermatitis.

The heat-stable and soluble glycoprotein gp200 (molecular weight 200 kDa) is part of the cell wall of S. cerevisiae. Recently, an association was shown between IgA and IgG against gp200 and inflammation in Crohn's disease. Gp200 is able to induce a proliferation of human lymphocytes in vitro, together with a natural killer cell associated cytotoxicity. Specific IgE against Saccharomyces cerevisiae (baker's or brewer's yeast) may be detected in approximately 73%, against Candida albicans in 68% of those patients suffering from severe atopic dermatitis. The aim of this study was to elucidate the possible role of an anti-gp200 immune response for the pathogenesis of atopic dermatitis by immunoblot analysis. Anti-gp200 IgE was found in 55% of healthy individuals, in 67% of individuals with atopic predisposition without eczema, in 63% of the patients with mild atopic dermatitis, and in 86% of patients with severe atopic dermatitis, respectively. On the contrary, anti-gp200 IgG could be shown in 55% of healthy individuals, in 89% of individuals with atopic predisposition but without eczema, in 100% of patients with mild atopic dermatitis, and in 79% with severe atopic dermatitis, respectively. No immunoreactivity was found when an extract of Arxula adeninivorans was used as antigen. These results underline the specificity of the immunoblot results with gp200 from Saccharomyces cerevisiae. It can be concluded that occurrence of specific IgE against Saccharomyces cerevisiae cannot be explained by a cross reactivity, e.g., against Candida albicans allergens. Further investigations with the recombinant gp200 will give information on the role of this glycoprotein both in atopic dermatitis and Morbus Crohn.

Systemic sclerosis-related Raynaud's phenomenon: effects of iloprost infusion therapy on serum cytokine, growth factor and soluble adhesion molecule levels.

Microvascular damage occurs in systemic sclerosis and is associated with increased serum levels of endothelial adhesion molecules and endothelium-associated cytokines, including vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), E-selectin, endothelin-1 and vascular endothelial growth factor (VEGF). Iloprost, a prostacyclin analogue, induces clinical benefit in patients suffering from scleroderma-related Raynaud's phenomenon. This study was performed to investigate the effect of iloprost infusions on endothelium activation. Serum samples from 12 patients with systemic sclerosis were examined using specific enzyme-linked immunoassays. The serum levels of sICAM-1, sVCAM-1 and soluble E-selectin were initially elevated and significantly reduced after iloprost infusions. The serum concentrations of VEGF and endothelin-1 revealed decreased levels after therapy too. These results indicate that the well-known clinical benefit of iloprost infusions on Raynaud's phenomenon is serologically detectable by a reduction of serum levels of endothelium-associated adhesion molecules, cytokines and growth factors reflecting an improvement in endothelial function.