[Peri-Operative Anaphylaxis - Antiquated Customs and News Towards the Culprits]. / Perioperative Anaphylaxie ­ alte Zöpfe und Neues zu den Auslösern.

Perioperative anaphylaxis occurs in about 1:6000 of all surgical procedures. Recently, the pathophysiology of anaphylactic reactions via mast cell related G-protein und complement-activated pseudo-allergy have been added to the "old" IgE mediated etiology. New culprits for anaphylactic reactions are chlorhexidine or gelatine as hemostypticum or blue surgical dyes to mark the situs. Biphasic anaphylactic reactions should be kept in mind. In the meantime, propofol use is allowed in egg and soybean allergic patients.

[Polyethylengylcole - Friend or Foe?] / Polyethylenglycol ­ Freund oder Feind?

Anaphylactic reactions following vaccination are rare. However, anaphylactic reactions towards the Pfizer-BioNTech Covid-19 vaccine were first reported in two patients in the UK and another 19 in the USA. Pegylation with polyethylene glycol (PEG) was thought to be the possible culprit. Pegylation is a common process in the manufacture of vaccines in order to prevent early degradation by the immune system. PEG is a polyether like e. g. Laureth-9, polidocanol, thesit and macrogol and is found in foodstuffs, cosmetics and personal care products as well as in liposomes and nanoparticles, as drug-delivery-system and as osmotic laxans for gastroscopies/coloscopies. Given the widespread use of PEG, reactions to vaccinations are rare and therefore no reason to exclude allergic patients in principle or indeed those who know the exact cause of a former anaphylaxis. In Germany, medical doctors are obliged to report any severe adverse reactions following vaccination; it is hoped that this procedure will help to resolve any remaining questions.

[Topical hormonal treatment in anti-aging of the skin]. / Topische Hormontherapie im Anti-Aging der Haut.

Topical hormonal treatment allows anti-aging of the skin when used during and after the menopause without an increase in the blood level of hormones. Natural hormones are only prescribed by medical doctors. In controlled clinical studies versus placebo and application for months, an increase in skin quality parameters, reduction of dryness, increase of glycosaminoglycanes, increase in elastic fibers und increase of collagen precursers and collagen fibers on the mRNA and protein level could be shown, the latter proven by biopsies. Skin with dramatic sun-damage does not respond to this treatment option. Patients with melasma or seborrhoe should not be treated with hormonal topical preparations. Compared to the natural hormones, phytotherapeutics do not bind to hormone receptors in relevant levels. Growth hormones should not be used in anti-aging treatment due to a potential carcinogenic effect.

Honeybee and wasp venom allergy: Sensitization and immunotherapy.

Hymenoptera venom allergy is the most common cause of anaphylactic reactions in adults. In children, it is the second most common cause after food-related anaphylaxis. Such reactions are primarily due to stings by honeybees (Apis) and certain social wasps (Vespula vulgaris and Vespula germanica in particular). Especially in adults, stings are frequently associated with severe anaphylaxis. Established diagnostic methods including molecular tests allow for greater success rates in terms of determining the insect actually responsible for triggering the anaphylactic reaction. Sensitization to both venoms, or a history of systemic sting reaction without any evidence of sensitization, complicate the decision regarding treatment. Venom immunotherapy (VIT) is a safe and effective causal treatment.

A 12-Month Follow-up, Randomized Comparison of Effectiveness and Safety of Two Hyaluronic Acid Fillers for Treatment of Severe Nasolabial Folds.

BACKGROUND: Hyaluronic acid (HA) filler injection is an increasingly popular aesthetic procedure. OBJECTIVE: To compare the effectiveness and safety of two HA fillers (HAED and HAPER) for the treatment of severe nasolabial folds (NLFs). MATERIALS AND METHODS: This was an evaluator-blinded and subject-blinded split-face study. At baseline, HAED or HAPER was randomly assigned to the left or right NLF. The follow-up period was 12 months. Effectiveness was assessed using the wrinkle severity rating scale (WSRS) and subject preference. Safety was assessed by adverse events and local tolerability symptoms recorded by subjects during 3 weeks after the treatment. RESULTS: At 6 months, HAED was noninferior to HAPER (assessed by mean change from baseline in WSRS score). There was a significant difference in mean WSRS score change from baseline in favor of HAED at 3 to 12 months, and a majority of subjects preferred HAED over HAPER at 12 months. However, the overall responder rate was similar between products, and it remained high throughout the study. At 12 months, approximately 80% of subjects were still responders. Both products were well tolerated and associated with a few treatment-related adverse events. CONCLUSION: To conclude, HAED was at least as effective and well tolerated for the treatment of severe NLFs as HAPER.

An 18-Month Follow-up, Randomized Comparison of Effectiveness and Safety of Two Hyaluronic Acid Fillers for Treatment of Moderate Nasolabial Folds.

BACKGROUND: Hyaluronic acid (HA) filler injection is a popular nonsurgical aesthetic procedure. OBJECTIVE: To compare the effectiveness and safety of 2 hyaluronic acid fillers (HAEC and HARES) for treatment of moderate nasolabial folds (NLFs). MATERIALS AND METHODS: This was an evaluator- and subject-blinded split-face study. HAEC or HARES was randomly assigned to the left or right NLF at baseline. Retreatment was performed after 9 months; follow-up extended to 18 months after baseline (9 months after retreatment). Effectiveness assessments included the Wrinkle Severity Rating Scale (WSRS) and subject preference. Safety assessments included adverse events (AEs) and local tolerability symptoms recorded by subjects during 3 weeks after treatment. RESULTS: HAEC was noninferior to HARES measured as mean change from baseline in WSRS score at 6 months. Mean WSRS score change from baseline was similar between products up to 18 months. A majority of subjects (>70%) were still responders at 18 months (after retreatment at 9 months). The volume required at retreatment was approximately two-thirds of that at baseline. There was no difference in subject preference between products. Both fillers were well tolerated and associated with few treatment-related AEs. CONCLUSION: HAEC and HARES were effective and well tolerated for treatment of moderate NLFs.

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. METHODS: A standardized questionnaire evaluated the available diagnostic methods i. e. direct immunofluorescence microscopy (IFM), indirect IFM, commercial ELISA systems, and non-commercial serological tests as well as the number of samples per year in all 34 university and 39 non-university dermatology departments. RESULTS: The overall return rate was 89 %, 100 % and 79 % for the university and non-university departments, respectively. Direct IFM was the most frequently used method and was applied in 98 % of the responding departments. In 74 % of the responding departments, indirect IFM was used mainly on monkey esophagus and human salt-split skin. Commercial ELISA systems were employed in 58 % of the clinics; all of them used anti-desmoglein ELISA, while anti-BP180 and anti-BP230 ELISA were established in 49 % and 48 % of departments, respectively. Non-commercial analytic methods were only performed in 22 % of the departments. CONCLUSIONS: The high return rate of this survey allows a relatively precise description of the current diagnostic methods used in German dermatology departments. Standard diagnostic tests are available nationwide and in bullous pemphigoid and pemphigus, the antigen-specific detection of autoantibodies is routinely performed in half of the departments. Rare disorders may be diagnosed by cooperation with some specialized centers.

Efficacy and safety of a new hyaluronic acid dermal filler in the treatment of moderate nasolabial folds: 6-month interim results of a randomized, evaluator-blinded, intra-individual comparison study.

BACKGROUND: Hyaluronic acid (HA) fillers such as Restylane(®) are frequently used for the correction of facial soft tissue defects. OBJECTIVE: To compare the efficacy and safety of a novel HA filler, Emervel(®) Classic, with those of Restylane in the treatment of moderate nasolabial folds. METHODS: This was a split-face, randomized and evaluator-blinded comparison study. Subjects were randomized to receive an injection of Emervel Classic or Restylane on their left or right side. Efficacy was evaluated based on the change in Wrinkle Severity Rating Score (WSRS) from baseline. Local tolerability was assessed based on subject diary, which recorded the severity of erythema, oedema/swelling, bruising, pain/tenderness and pruritus during the first 3 weeks after injection. RESULTS: The interim results 6 months after injection are reported. At week 24, the mean improvement in WSRS from baseline was 0.83 ± 0.51 for Emervel Classic, similar to that for Restylane (0.90 ± 0.57). A similar volume of both fillers was injected. Most local tolerability events were mild and transient. Erythema, oedema/swelling and pain/tenderness were significantly less severe and disappeared faster with Emervel Classic than with Restylane (at least p < 0.05). CONCLUSION: Emervel Classic provides similar efficacy and better overall local tolerability compared with Restylane 6 months after treatment of moderate nasolabial folds.

Drug survival rates and reasons for drug discontinuation in patients with atopic dermatitis: a retrospective study of adult outpatients.

BACKGROUND: Treatment of moderate-to-severe atopic dermatitis (AD) can be challenging and little is known about the sustainability of on- and off-label prescribed systemic therapies. OBJECTIVES: To compare drug survival (DS) rates and reasons for drug discontinuation of cyclosporine A (CyA), dupilumab (DUP), azathioprine (AZA), methotrexate (MTX) and mycophenolate mofetil (MMF) prescribed under real-world conditions. MATERIALS & METHODS: In this retrospective study, 139 treatment courses for 94 adults with AD treated at two German dermatology departments were analysed. RESULTS: Based on Cox regressions with CyA as reference category, hazard ratios for treatment discontinuation were 0.10 for DUP, 0.87 for MTX, 0.98 for MMF, and 1.18 for AZA. CyA, AZA, and MTX were most frequently interrupted due to adverse events, and MMF due to non-compliance. Only one patient (6.3%) discontinued DUP before the end of the observation period, which was due to ineffectiveness. CONCLUSION: Systemic therapies for AD differ with regards to DS and reasons leading to treatment withdrawal; this should be considered in real-life practice.

Patterns of care and follow-up care of patients with uveal melanoma in German-speaking countries: a multinational survey of the German Dermatologic Cooperative Oncology Group (DeCOG).

PURPOSE: Uveal melanoma (UM) is an orphan cancer of high unmet medical need. Current patterns of care and surveillance remain unclear as they are situated in an interdisciplinary setting. METHODS: A questionnaire addressing the patterns of care and surveillance in the management of patients with uveal melanoma was distributed to 70 skin cancer centers in Austria, Germany and Switzerland. Frequency distributions of responses for each item of the questionnaire were calculated. RESULTS: 44 of 70 (62.9%) skin cancer centers completed the questionnaire. Thirty-nine hospitals were located in Germany (88.6%), three in Switzerland (6.8%) and two in Austria (4.5%). The majority (68.2%) represented university hospitals. Most patients with metastatic disease were treated in certified skin cancer centers (70.7%, 29/41). Besides, the majority of patients with UM were referred to the respective skin cancer center by ophthalmologists (87.2%, 34/39). Treatment and organization of follow-up of patients varied across the different centers. 35.1% (14/37) of the centers stated to not perform any screening measures. CONCLUSION: Treatment patterns of patients with uveal melanoma in Germany, Austria and Switzerland remain extremely heterogeneous. A guideline for the treatment and surveillance is urgently needed.

[Adjuvant dermato-cosmetic acne therapy]. / Adjuvante dermatokosmetische Aknetherapie.

Adjuvant dermato-cosmetic therapy in acne is an essential part of the concept of treating acne after initiation and during maintenance therapy. Those are mechanical peeling, chemical peeling and its combination. It needs supervision by an experienced dermatologist.

[S2k-guideline for therapy of acne]. / 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.

Trauma experience in individuals with idiopathic environmental intolerance and individuals with somatoform disorders.

OBJECTIVE: Results from previous studies suggest that past trauma experience increases the risk for medically unexplained somatic symptoms and somatoform disorders (SFD). This cross-sectional study examined the link between various lifetime traumas, idiopathic environmental intolerance (IEI), and SFD. METHODS: Two clinical groups of 54 subjects with IEI and 44 subjects with SFD were compared to 54 subjects (comparison group, CG) free from both IEI and SFD regarding self-reported traumas. The subjects were mainly recruited via advertisements in local newspapers. From 970 individuals screened for IEI and multiple somatic symptoms, 152 were included through a two-step selection procedure consisting of screening questionnaires, a medical examination, and structured interviews for IEI and mental disorders. RESULTS: In all three groups at least one potential traumatic event was reported rather frequently (CG: 70%; IEI: 82%; SFD: 73%). But contrary to our expectation, significant group differences were neither found in regard to the proportion of subjects with any trauma, nor traumas fulfilling DSM-IV criteria (CG: 41%; IEI: 48%; SFD: 59%), nor multiple traumas (CG: 43%, IEI: 56%, SFD: 39%). Only two trauma categories were endorsed more frequently by the two clinical groups than by the CG: the unspecified 'other' category (IEI, SFD>CG) and 'life-threatening illness' (IEI>CG). CONCLUSION: No clear evidence was found for increased rates of trauma experience in IEI and SFD. However, the results of this exploratory study should be considered as preliminary. Comparing larger IEI and SFD groups with a representative population-based sample may yield different results.

Evidence for overlap between idiopathic environmental intolerance and somatoform disorders.

OBJECTIVE: Idiopathic environmental intolerance (IEI), also known as multiple chemical sensitivity, is a chronic, polysymptomatic condition that cannot be explained by an organic disease. Physical and psychological complaints are believed to be sustained by low levels of chemically unrelated substances in the environment. At present, it is unclear whether IEI is an environmental illness or a variant of somatoform disorders (SFD). This study examined whether IEI can be distinguished from SFD with respect to self-reported symptoms, trait anxiety, body-related cognitions, and symptom attributions. METHODS: We compared 54 subjects with IEI, 54 subjects with SFD but without IEI, and 44 subjects with neither IEI nor SFD on symptom scales, psychological questionnaires, and structured interviews for IEI, depression, anxiety, and SFD. RESULTS: More than half of the IEI subjects met Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria of SFD. This group shared both symptoms and psychological features of somatization with the SFD group. IEI subjects who did not fulfill criteria for a specific SFD were less impaired by their chemical sensitivity but differed nevertheless from nonsomatoform controls by significantly higher symptom scores, higher trait anxiety, a focus on autonomic sensations, and more pronounced somatic symptom attributions. These psychological features were significantly associated with the burden of somatic symptoms in both SFD and IEI. Furthermore, self-reported allergy but not total immunoglobulin E correlated with symptom burden in the total sample. CONCLUSIONS: The similarity of IEI and SFD regarding symptoms and psychological features of somatization support the hypothesis that IEI is a variant of SFD.

Targeting TGF-beta1 increases hepatocyte growth factor (HGF/SF) levels in external auditory canal cholesteatoma (EACC) epithelial cell culture.

OBJECTIVE: The transforming growth factor (TGF)-beta 1 is known to have pro- and anti-angiogenic actions. Hepatocyte growth factor/scatter factor (HGF/SF) antagonizes TGF-beta1 by stabilizing SMAD transcriptional co-repressor TGIF. HGF/SF is a multifunctional polypeptide with morphogenic, motogenic, angiogenic, and proliferative capabilities. We assume HGF to be a pivotal factor during the pathogenesis of the external auditory canal cholesteatoma (EACC). In this study, we investigate the effect of antisense targeting TGF-beta1 on HGF/SF levels in the epithelial EACC-culture. MATERIALS: For 48 h, epithelial EACC cell culture was incubated with 3 and 6 mumol antisense targeting TGF-beta1, respectively. Levels of HGF/SF were determined and normalized to cellular protein. Untreated EACC cell culture and scrambled TGF-beta1-antisense served as control. In the second experiment, EACC cells were incubated with rh TGF-beta1 (2 and 4 ng/ml) for 48 h and HGF/SF was determined. RESULTS: After incubation with 3 mumol TGF-beta1-antisense, the average level of HGF/SF was measured at 43.68 pg/ml. Incubation with 6 micromol TGF-beta1-antisense showed 64.95 pg/ml. In untreated EACC (control), the average level of HGF/SF after 48 was 34.55 pg/ml. Incubation with scrambled TGF-beta1 oligonucleotide showed an average HGF/SF level of 34.41 (3 micromol) and 35.66 (6 micromol), respectively. The difference between the scrambled antisense and the targeting antisense TGF-beta1 was significant (p<0.05). After incubation with 2 ng/ml TGF-beta1, the HGF/SF levels were at 22.16 pg/ml. TGF-beta1, 4 ng/ml, resulted in 15.33 pg/ml of HGF/SF. The difference of the levels of HGF/SF after incubation with exogenous TGF-beta1 was significant (p<0.05). CONCLUSION: In this study, levels of HGF/SF increased in the epithelial EACC cell culture after incubation with 3 and 6 mumol antisense TGF-beta1 oligonucleotides depending on the concentration of the antisense. In reverse, TGF-beta1 acted as inhibiting cytokine on HGF/SF levels. In conclusion, TGF-beta1 may be a useful therapeutic agent for managing EACC.

Effect of vascular endothelial growth factor on fibroblasts from external auditory canal cholesteatoma.

BACKGROUND: EACC is a disease of the external auditory canal resulting in destruction of adjacent tissue. However, the role of the surrounding mesenchymal fibroblasts of the perimatrix still remains unclear. In this study we treat isolated fibroblasts of EACC with VEGF and determine FGF-2 levels. We also treat the fibroblast cultures with FGF-2 and measured VEGF levels. METHODS: All EACC cell cultures were obtained from five patients undergoing surgery and used at passage 3. After 1-4 days incubation with 50 ng/mL FGF-2, and 1-8 days incubation with 50 pg/mL VEGF incubation, the expression of the FGF-2 and VEGF protein in the supernatants of the HGF/SF-treated and -untreated culture cell lines was analyzed, respectively. RESULTS: After 8 days of incubation with 50 ng/mL VEGF, the levels of FGF-2 decreased. However, after 4 days of incubation with FGF-2 the VEGF levels increased significantly in treated tissue culture (p <0.05) in comparison to untreated EACC fibroblasts. The total protein concentration showed no significant difference in both cultures (p >0.05). CONCLUSIONS: In summary, exogenous FGF-2 increased fibroblast expression of VEGF, which is a major autocrine mediator of FGF-2-induced angiogenesis and proliferation. However, incubation with VEGF resulted in decrease of FGF-2 levels. Regarding the slow growth of the fibroblasts, they may not be as likely to exhibit a reactive or invasive phenotype as seen in middle ear cholesteatoma fibroblasts.

Up-regulation of beta-catenin in external auditory canal cholesteatoma.

The external auditory canal cholesteatoma (EACC) is a rare disease with hyperproliferation and destructive growth in the adjacent structures. Down-regulation of beta-catenin (key component of the zonula adherens) is a pivotal factor for loose tissue integrity and invasiveness. Transforming growth factor beta1 (TGF-beta1) was reported to decrease beta-catenin in mammary epithelium. We investigated the abrogation of TGF-beta1 and beta-catenin expression in EACC culture cells. Cultured EACC-specimens were incubated with 6 micromol TGF-beta1 antisense. After 48 h, expression of beta-catenin was determined by means of immunohistochemistry. The cells showed an increased mural reactivity to beta-catenin, and intracellular reactivity was unchanged. The untreated cells showed a loss of beta-catenin expression at the membranes. The predominant membranous location after treatment with TGF-beta1 antisense suggests increased tendency of the cells for tissue formation and strong cell-cell adhesion rather than migratory and invasive character, and thus TGF-beta1 antisense application is a useful therapeutical strategy.

Hepatocyte growth factor/scatter factor induces VEGF in human external auditory canal cholesteatoma cell culture.

Human external auditory canal cholesteatoma (EACC) is not often seen in otolaryngology. Some authors have noted circulatory disorders of the local blood vessels as the etiologic factor for establishing EACC. Diminished oxygen supply results in the attempt to establish angiogenesis. Hepatocyte growth factor/scatter factor (HGF/SF) and vascular endothelial growth factor (VEGF) are the most important angiogenic factors in this process. In a recent study we described strong expression of VEGF and HGF in EACC. All EACC and normal AMS cell cultures were obtained from 5 patients undergoing surgery and used at passage 3. After 16 to 72 h of incubation with 20 ng/ml HGF/SF, the expression of the VEGF protein in the supernants of the HGF/SF-treated and untreated culture was analyzed. EACC-culture cells showed a stronger baseline expression of VEGF. After 72 h of incubation with 20 ng/ml HGF/SF of HGF/SF, the expression of VEGF in normal keratinocytes was 173.4 pg/ml. The expression level of VEGF in the EACC culture was 275.73 pg/ml. We observed a 2.5-fold induction of VEGF in EACC after 72 h, which started with 1.5-fold baseline VEGF concentrations of normal keratinocytes. Our analysis showed that, in the EACC culture, VEGF was elevated after treatment with HGF/SF. HGF/SF appears to activate cellular pathways inducing release of VEGF. After purification, no fibroblasts were present in our EACC culture so as to exclude possible paracrine effects by fibroblasts.