[Reality of inpatient vasoactive treatment with prostacyclin derivatives in patients with acral circulation disorders due to systemic sclerosis in Germany]. / Versorgungsrealität der stationären vasoaktiven Therapie mit Prostazyklinderivaten bei Patienten mit akralen Durchblutungsstörungen bei systemischer Sklerose in Deutschland.

BACKGROUND: Raynaud's phenomenon and the frequently ensuing digital ulcerations represent an early and very distressing symptom in patients with systemic sclerosis (scleroderma, SSc) causing significant limitations in the ability to work and quality of life. The use of vasoactive drugs (especially intravenous prostacyclin derivatives) is recommended to reduce the risk of hypoxic tissue damage up to the loss of fingers. METHODS: In order to obtain information about the current state of treatment of patients with prostacyclin derivatives in routine clinical life in Germany, a survey was conducted among the centers affiliated to the German Network for Systemic Scleroderma (DNSS). In addition, a separate patient survey was conducted by the schleroderma self-help group (Sklerodermie Selbsthilfe e. V.), which only covered the symptoms Raynaud's syndrome, digital ulcers and the use of intravenous prostacyclin derivatives. RESULTS: Of the 433 patients surveyed 56% stated that they had already been treated with prostacyclin derivatives (iloprost/alprostadil) because of their illness and symptoms. A total of 61% received the treatment for severe Raynaud's phenomenon and 39% for digital ulcerations. Most respondents not only experienced an improvement in Raynaud's phenomenon and digital ulcers but also a significant improvement of limitations in everyday life. They also needed significantly less outside help and absenteeism from work was much lower. CONCLUSION: Patients consistently reported a positive effect of treatment with prostacyclin derivatives on Raynaud's phenomenon, acral ulcerations, pain and daily restrictions and felt well and safely cared for during inpatient treatment. These positive effects in the patients' perceptions provide crucial information supporting and confirming the current European and international treatment recommendations.

Challenging a paradigm: skin sensitivity to sodium lauryl sulfate is independent of atopic diathesis.

BACKGROUND: Sodium lauryl sulfate (SLS) is the best-studied detergent in irritant contact dermatitis. In atopic dermatitis, the two major pathophysiological abnormalities concern skin barrier function and regulation of cutaneous immune responses. The probability of atopic skin diathesis can be assessed by comprehensive analysis of patient history, as well as clinical and laboratory findings, resulting in the Erlangen Atopy Score (EAS). OBJECTIVES: To investigate the impacts of (i) atopic skin diathesis according to the EAS and (ii) the physician-assessed diagnoses 'atopic dermatitis', 'allergic rhinitis' and 'allergic asthma' on SLS skin reactions. METHODS: This is a retrospective analysis of data from 2030 consecutive patients patch tested with SLS (0·25% aqueous) from two tertiary referral centres in Germany, from 2008 to 2014. RESULTS: Patients with a high probability of atopic skin diathesis showed no significant increase in positive SLS reactions compared with patients without atopic skin diathesis (14·2% vs. 16·8%). The grading of positive SLS skin reactions (1-4) revealed no differences in patients with or without atopic skin diathesis. Furthermore, diagnoses of atopic dermatitis, allergic rhinitis or allergic asthma had no impact on positive SLS skin reactions in multivariate logistic regression analysis. CONCLUSIONS: We found no association of increased skin irritability to SLS with atopic skin diathesis, atopic dermatitis, allergic rhinitis or allergic asthma in a large patient cohort. It therefore seems that the test of skin irritability with SLS, which is currently common practice in many centres, does not allow prediction of susceptibility to irritant eczematous inflammation in atopic vs. nonatopic individuals. What's already known about this topic? Irritant contact dermatitis and atopic skin diathesis share impaired skin barrier function as a pathophysiological pattern. Sodium lauryl sulfate (SLS) is tested at 0·25% aqueous as an irritant control in patch testing, and hence the results might be affected by atopic skin diathesis. What does this study add? Challenging a long-standing paradigm, we found no association of increased reactivity to SLS patch tests in individuals with atopic skin diathesis, atopic dermatitis, allergic rhinitis or allergic asthma in a large patient cohort. Thus, irritant control testing with SLS, which is useful in interpreting doubtful allergen patch test results, does not depend on individual atopy status.

Assessment of occupational exposure and spectrum of contact sensitization in metalworkers with occupational dermatitis: results of a cohort study within the OCCUDERM project.

BACKGROUND: Metalworkers occupationally exposed to metals, tools, metalworking fluids (MWFs), technical oils, gloves, skin care products etc. frequently suffer from occupational dermatitis (OD). OBJECTIVES: To investigate occupational exposure and to identify relevant occupational sensitizers in metalworkers with OD, and to evaluate suitability of current German patch test recommendations for this occupational group. PATIENTS AND METHODS: As part of the OCCUDERM project, occupational exposure of 230 metalworkers with suspected OD patch tested in the departments of dermatology in Göttingen and Osnabrück (both Lower Saxony, Germany) in 2012-2017 was recorded by questionnaire. These data, as well as results, of patch testing with standardized allergens and with workplace material were analysed. RESULTS: Metalworking fluids and skin care products were the most important exposures. Among MWF allergens, most frequently sensitizations to formaldehyde and formaldehyde releasers, colophony/abietic acid and monoethanolamine were observed. Sensitization to methylisothiazolinone (MI) was frequent, probably as part of the general European epidemic of contact allergy to MI in leave-on cosmetics. Sensitization to glove ingredients only played a minor role. CONCLUSIONS: The known occupational allergen spectrum could largely be confirmed. In order not to miss relevant sensitizations, patch testing with material from the patients' workplaces in parallel to baseline and MWF series is recommended. Sensitizations diagnosed could not always be linked to particular occupational exposures.

The volume of postoperative drainage fluid as a potential early predictor of lymphedema after lymph node excision for metastatic melanoma.

Lymphedema (LE) following lymph node dissection is a major problem for cancer patients, and radiation therapy, extended surgery, groin dissection, obesity, and older age are well-established risk factors of LE. We studied whether these risk factors are further associated with high volumes of postoperative drainage fluid after complete lymph node dissection (CLND) for melanoma metastases. Moreover, we examined whether a high amount of drainage fluid after sentinel lymph node biopsy (SLNB) can predict a high amount of drainage fluid after subsequent CLND. Using descriptive statistics and regression analyses, we analyzed the cumulative volumes of postoperative drainage fluid for 836 melanoma patients with lymph node excision in the axilla or groin. In multiple regression analyses, the well-established risk factors of LE, i.e., increased body mass index, older age, and ilioinguinal versus inguinal versus axillary dissection predicted a high drainage volume after CLND. Of note, a high drainage fluid volume after SLNB also predicted a high drainage volume after subsequent CLND. In patients with groin dissections, who are particularly susceptible to swelling, extended iliac dissection, age above 60, and a cumulative drainage volume of more than 100 ml in the preceding SLNB were predictors of the cumulative drainage volume. We find that common risk factors predict the volume of postoperative drainage fluid after CLND and postoperative LE. Further, high postoperative drainage volume may therefore function as a potential early predictor of LE following CLND.

Neutrophil extracellular traps: protagonists of cancer progression?

Neutrophil extracellular traps (NETs) are a defense mechanism first described to trap and kill bacteria and other pathogens. Increasingly, however, their involvement in the pathogenesis of inflammatory and malignant diseases is being recognized. Several recent studies have suggested important roles of NETs in tumor progression, metastasis and tumor-associated thrombosis. Although systematic studies to address the role of NETs in tumor development are still scarce, we will explore the emerging evidence for NETs as potential protagonists in malignant disease and highlight the mechanisms through which these effects may be exerted. Future questions arising from our current knowledge of direct and indirect interactions between NETs and cancer cells will be outlined and we will explore NETs as candidate pharmaceutical targets in cancer patients.

Nd:YAG and pulsed dye laser therapy in infantile haemangiomas: a retrospective analysis of 271 treated haemangiomas in 149 children.

BACKGROUND: Infantile haemangiomas (IH) are common benign tumours in infancy. Most IH resolve spontaneously, but some require treatment due to ulceration, functional impairment or cosmetic disfiguration. While systemic propranolol is effective in many cases, laser therapy may be a safe topical alternative. OBJECTIVE: To assess the efficacy of combined Nd:YAG/pulsed dye laser (PDL) or PDL alone for therapy of IH. PATIENTS AND METHODS: A total of 271 IH in 149 infants were treated with combined Nd:YAG/PDL or PDL alone. Based on photographs before and 4-6 weeks after the last treatment, the results were evaluated independently by three physicians. Remissions were categorized as 0-25% (I), 26-50% (II), 51-75% (III) and 76-100% (IV). RESULTS: In total, 472 laser treatments were performed. In 137 of 149 infants (91.9%) laser therapy was performed during a short sevoflurane mask anaesthesia, while 12 of 149 infants (8.1%) received topical anaesthetic gel. Combined Nd:YAG/PDL was applied in 187 of 271 IH (69.0%), while PDL alone in 84 of 271 IH (31.0%). On average, 1.74 treatments per IH were necessary (Nd:YAG/PDL: 1.95, PDL: 1.26). Moderate or strong (III/IV) improvement was observed in 92.4% of all IH treated. No serious adverse effects were observed. CONCLUSION: Combined Nd:YAG/PDL therapy is an effective and well-tolerated local treatment option for IH of any classification, in any phase of development and at any age. With regard to the systemic use of propranolol, combined Nd:YAG/PDL therapy seems a safe and promising alternative in many cases.

[Pathogenesis of psoriasis]. / Pathogenese der Psoriasis vulgaris.

Psoriasis is an inflammatory T cell-mediated autoimmune disease of skin and joints that affects 2-4 % of the adult population and 0.1-1 % of children. Genetic susceptibility, environmental triggering factors, and innate immune processes initiate psoriasis pathogenesis that results in an adaptive autoreactive response. The T cell response is orchestrated by CD 8(+) T cells in the epidermis and by CD 4(+) T cells in the dermis that predominantly produce interleukin-17 (IL­17). Research of the past 15 years unraveled cellular and molecular mechanisms as well as cytokines like TNF-α or IL­23 that contribute to psoriatic inflammation. This knowledge has been translated into clinical practice and a number of antipsoriatic small molecules and immunobiologics are now available. Here, we discuss the current principles of psoriasis pathogenesis in the context of modern therapies.

A pro-apoptotic function of iASPP by stabilizing p300 and CBP through inhibition of BRMS1 E3 ubiquitin ligase activity.

The p53 family and its cofactors are potent inducers of apoptosis and form a barrier to cancer. Here, we investigated the impact of the supposedly inhibitory member of the apoptosis-stimulating protein of p53, iASPP, on the activity of the p53 homolog TAp73, and its cofactors p300 and CBP. We found that iASPP interacted with and stabilized the histone acetyltransferase p300 and its homolog CBP upon cisplatin treatment. Vice versa, iASPP depletion by shRNA resulted in decreased amounts of p300 and CBP, impaired binding of p300 and TAp73 to target site promoters, reduced induction of pro-apoptotic TAp73 target genes, and impaired apoptosis. Mechanistically, we observed that the p300-regulatory E3 ubiquitin ligase BRMS1 could rescue the degradation of p300 and CBP in cisplatin-treated, iASPP-depleted cells. This argues that iASPP stabilizes p300 and CBP by interfering with their BRMS1-mediated ubiquitination, thereby contributing to apoptotic susceptibility. In line, iASPP overexpression partially abolished the interaction of BRMS1 and CBP upon DNA damage. Reduced levels of iASPP mRNA and protein as well as CBP protein were observed in human melanoma compared with normal skin tissue and benign melanocytic nevi. In line with our findings, iASPP overexpression or knockdown of BRMS1 each augmented p300/CBP levels in melanoma cell lines, thereby enhancing apoptosis upon DNA damage. Taken together, destabilization of p300/CBP by downregulation of iASPP expression levels appears to represent a molecular mechanism that contributes to chemoresistance in melanoma cells.

[Development of curly hair under systemic therapy with alitretinoin]. / Haarkräuselung unter Systemtherapie mit Alitretinoin.

BACKGROUND: The retinoid alitretinoin is a therapeutic option for chronic refractory hand eczema. Dryness of skin and mucosa, erythema, pruritus and alopecia are typical cutaneous side effects. CASE REPORT: We report the case of a 44-year-old man whose head hair became curly while taking alitretinoin. Other causes could not be elicited as the patient was otherwise healthy, did not take any other drugs, and denied any specific physical or mental stress. RESULTS: Until now there has been no report about hair curling under alitretinoin. Case reports exist for the retinoids acitretin, isotretinoin and etretinate and for other drugs such as valproat or EGFR tyrosine-kinase inhibitors. The underlying pathogenetic mechanisms are still unclear. With regard to retinoids, an influence on the keratinisation of the inner root sheath has been speculated; however further investigation will be needed to better understand the processes.