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Please cite this paper as: Enhanced T-cell activation by immature dendritic cells loaded with HSP70-expressing heat-killed melanoma cells. Experimental Dermatology 2010; 19: 108–116. Vaccination protocols that utilize dendritic cells (DCs) to elicit therapeutic immunity against tumors are the subject of intense research. Given that the capacity of DCs to cross-present antigens is physiologically low, there is considerable interest to develop strategies that enhance that pathway. In order to best exploit the enhanced cross-presentation of antigens bound to heat shock protein 70 (HSP70), we analysed melanoma cell preparations for their HSP70 expression. Western blotting revealed strong upregulation of HSP70 after heat-killing in contrast to UV-B irradiation. When the uptake of heat-killed necrotic cells by DCs at various levels of maturation was assessed, 61 ± 7% of immature DCs (iDCs) internalized fluorescence-labelled necrotic material. Apoptotic material from UV-B-irradiated cells was internalized by only 48 ± 5% of iDCs. Maturation-inducing cytokines did not affect the uptake when added simultaneously with the tumor cell preparations. Loading DCs with heat-necrotic or apoptotic melanoma cells slightly reduced CD83 expression while leaving CD208 (DC-LAMP) expression unchanged. As determined by IFN-γ-detecting enzyme-linked-immunospot assays, iDCs loaded with heat-killed melanoma cells activated autologous T cells most effectively when used without any further maturation, whereas DCs loaded with apoptotic material required maturation. In conclusion, HSP70-expressing melanoma cells could be generated by heat-killing. Loading iDCs with heat-killed melanoma cells resulted in a superior priming of autologous T cells in vitro. [ABSTRACT FROM AUTHOR]

Based on their role for the induction of T-cell responses, dendritic cells (DCs) are popular candidates in cancer vaccine development. We established a novel single-step intracellular delivery of peptide/poly(I:C) complexes for antigen loading and Toll-like receptor-3 (TLR3)-mediated maturation of human DCs using a cell-penetrating peptide (tat49–57: RKKRRQRRR) as delivery vector. Towards this end, a cationic tat-sequence was fused with an antigenic, major histocompatibility complex (MHC) class I-binding melanoma epitope (Melan-A/Mart-1 sequence: ELAGIGILTV) and then mixed with negatively charged poly(I:C) dsRNA to form peptide/nucleic acid complexes. Flow cytometry and confocal laser scanning microscopy confirmed intracellular localization of TLR3 in monocyte-derived immature DCs (iDCs). Peptide/poly(I:C) complexes were readily internalized by iDCs without negatively affecting cell viability. They induced DC maturation and secretion of bioactive interleukin (IL)-12p70. When peptide/poly(I:C) complex-loaded DCs were used for autologous T cell stimulation, epitope-specific interferon-gamma secretion was quantitatively superior in comparison to peptide-loaded DCs matured by a cytokine cocktail, as detected by enzyme-linked immunospot assays. Thus, complexes of cationic antigenic peptides and poly(I:C) might be of great utility for a TLR3-mediated DC maturation and intracellular peptide targeting in a single step. Resulting DCs induce a strong expansion/activation of antigen-specific T cells in the context of an IL-12p70 secretion. [ABSTRACT FROM AUTHOR]

Background: Irritant contact dermatitis (ICD) is caused by the acute locally toxic effect of a strong irritant, or the cumulative exposure to various weaker physical and/or chemical irritants. Objectives: To describe the characteristics of patients with ICD in the population patch tested in the European Surveillance System on Contact Allergies (ESSCA; www.essca-dc.org) database. Methods: Data collected by the ESSCA in consecutively patch tested patients from January 2009 to December 2018 were analyzed. Results: Of the 68 072 patients, 8702 were diagnosed with ICD (without concomitant allergic contact dermatitis [ACD]). Hand and face were the most reported anatomical sites, and 45.7% of the ICD was occupational ICD (OICD). The highest proportions of OICD were found in metal turners, bakers, pastry cooks, and confectionery makers. Among patients diagnosed with ICD, 45% were found sensitized with no relevance for the current disease. Conclusions: The hands were mainly involved in OICD also in the subgroup of patients with contact dermatitis, in whom relevant contact sensitization had been ruled out, emphasizing the need for limiting irritant exposures. However, in difficult-to-treat contact dermatitis, unrecognized contact allergy, or unrecognized clinical relevance of identified allergies owing to incomplete or wrong product ingredient information must always be considered. [ABSTRACT FROM AUTHOR]

Background: The use of disinfectants is part of the everyday life of people, especially in the medical profession. During the coronavirus disease 2019 (COVID-19) pandemic, the use of disinfectants continues to increase and is of fundamental importance in infection control. Objectives: To determine the frequency of sensitization and the value of patch testing to didecyldimethylammonium chloride (DDAC) and the alcohols ethanol, 1-propanol, and isopropanol. Methods: Clinical patch test data of 145 patients with suspected contact allergy to disinfectants were retrospective analysed. Results: Among the 145 patients patch tested with the different alcohols, only one nurse was detected with a possible allergy to 1-propanol. Additional patch testing in 84 patients with DDAC 0.05% resulted in five patients with weakly positive reactions only, without clinical relevance. Patch testing with DDAC 0.03% showed no positive reactions at all on day 3 readings. Conclusions: DDAC and alcohols are rarely responsible for allergic contact dermatitis. The accused products of the patients should be checked for other allergens and further additives with skin-irritating properties. Individual susceptibility and mishandling of the disinfectants should be considered. [ABSTRACT FROM AUTHOR]

Background: In about half of the patients reacting positive to fragrance mix I (FM I), breakdown testing remains negative. This raises the question of whether the reaction to FM I is false‐positive, or the breakdown test is false‐negative. Objectives: To identify characteristics and sensitization patterns of patients positive to FM I, but not to its fragrance constituents. Patients and Methods: Retrospective analysis of data from the Information Network of Departments of Dermatology (IVDK) between 2005 and 2019. Three patient groups were defined according to their reaction pattern: Group I, FM I positive and ≥1 single fragrance positive in the breakdown test (n = 1912); Group II, FM I positive and breakdown test negative (n = 1318); Group III, FM I negative (n = 19 790). Results: Regarding the pattern of concomitant reactions to other fragrances, Group II had an intermediate position between Group I and Group III. In other respects (age and sex distribution, frequency of sensitization to non‐fragrance baseline series allergens), Group II rather resembled Group I. Conclusions: Not every positive reaction to FM I in patients with negative breakdown tests is false‐positive. There may be false‐negative reactions to the single fragrance components when patch tested at 1% pet. Raising patch concentrations of some single fragrances is recommended. [ABSTRACT FROM AUTHOR]

Background: Allergy evaluation by patch testing with povidone‐iodine (PVP‐I) or iodine remains challenging, because current patch test preparations frequently lead to false‐positive or irritant skin reactions. Objectives: To investigate different preparations for iodine patch tests and to assess their clinical relevance with repeated open application tests (ROATs). Methods: We monocentrically analyzed 95 patients with suspected allergy to disinfectants in retrospect who underwent parallel iodine patch testing with four preparations: PVP‐I 2% aq., 5% aq., 10% aq., and iodine 0.5% pet. Results: In 27 of 95 patients (28.4%), we found positive reactions to one of the four test preparations. After ROATs in 22 of these 27 positively tested individuals, only one patient was diagnosed with iodine allergy. In contrast, 31 of 95 patients (32.6%) showed irritant or questionable patch test reactions on day 2 (D2) and/or D3 and/or D7 to one or more test preparations. Testing with PVP‐I 2% aq. resulted in the lowest number of doubtful skin reactions while detecting the single allergic patient. Conclusion: PVP‐I 2% aq. was found to be the optimal patch test preparation. In general, iodine allergy appears to be substantially overestimated, and positive patch test responses to iodine should prompt an urgent ROAT for confirmation before diagnosing iodine allergy. [ABSTRACT FROM AUTHOR]

Background: Clinical surveillance of the prevalence of contact allergy in consecutively patch tested patients is a proven instrument to continually assess the importance of contact allergens (haptens) assembled in a baseline series. Objectives: To present current results from the European Surveillance System on Contact Allergies, including 13 countries represented by 1 to 11 departments. Methods: Anonymized or pseudonymized patch test and clinical data from various data capture systems used locally or nationally as transferred to the Erlangen data centre were pooled and descriptively analysed after quality control. Results: In the 4 years (2015‐2018), data from 51 914 patients patch tested with the European baseline series (EBS) of contact allergens were analysed. Contact allergy to nickel was most frequent (17.6% positive), followed by contact allergy to fragrance mix I (6.9%), methylisothiazolinone (MI; 6.2%), and Myroxylon pereirae resin (balsam of Peru; 5.8%). Conclusions: While the prevalence of MI contact allergy decreased substantially following regulatory intervention, the persistently high levels of allergy to metals, fragrances, other preservatives, and rubber chemicals point to problems needing further research and, potentially, preventive efforts. Results with national additions to the baseline series provide important information on substances possibly to be considered for inclusion in the EBS. [ABSTRACT FROM AUTHOR]

Background: Metalworkers are exposed to a variety of contact allergens by handling tools, metals, metalworking fluids (MWFs), oils and greases, rubber materials, and so on. Most large‐scale reports on contact allergy due to MWFs are more than 10‐years‐old, and there are only few studies on contact allergy in mechanics and other metal workers not exposed to MWFs. Objectives: To describe a current spectrum of contact sensitization in metalworkers with occupational dermatitis (OD). Patients and Methods: Retrospective analysis of patch test data collected by the Information Network of Departments of Dermatology (IVDK; 2010–2018), stratifying for 804 cutting metalworkers, 2197 mechanics, and 355 other metalworkers. Results: Cutting metalworkers were most frequently sensitized to monoethanolamine (12.6%), colophonium/abietic acid (11.4%) and formaldehyde releasers (up to 8.5%) from the MWF series, and formaldehyde (4.6%) and iodopropynyl butylcarbamate (4.6%) from the baseline series. Sensitization among mechanics and other metalworkers indicates possible occupational exposure to MWFs, glues, and resins, although this may not be expected from their job titles. Conclusions: The spectrum of MWF contact allergens remained largely unchanged during the last years. Taking a comprehensive occupational history is indispensable in order to not miss relevant allergen exposures. Highlights: There have been largely no significant changes in the spectrum of contact sensitizations in cutting metalworkers with occupational dermatitis (OD); leading allergens are monoethanolamine, resin acids, formaldehyde (releasers), and iodopropynyl butylcarbamate.Mechanics and other metalworkers may be occupationally exposed to metalworking fluids, glues, and resins, although this may not be expected from their job titles.Two formaldehyde releasers—Bioban P1487 and Bioban CS 1135—are outdated, and should no longer be patch tested in a metalworking fluid series. [ABSTRACT FROM AUTHOR]

Background: Studies on patch testing with workplace materials and evaluation of current occupational relevance of positive patch test reactions are scarce in patients with occupational dermatitis (OD). Objectives: To identify frequent sensitizations with occupational relevance and to determine the value of patch testing with workplace materials in OD patients. Patients and Methods: Results and clinical data of 654 patients with suspected OD patch tested between 2013 and 2017 were analysed. Results: Occupational allergic contact dermatitis was diagnosed in 113 (17.3%) patients. Mechanics had the widest range of occupational sensitizations. Sensitization to epoxy resin was rated occupationally relevant in almost all handicraft trades. Among positive patch test reactions to workplace products, those to water‐based metal working fluids and leave‐on cosmetic products were most frequent. Despite frequent testing, protective gloves only rarely elicited positive reactions. Preservatives and rubber compounds were most frequently identified as currently occupationally relevant. Conclusions: Rubber allergy is occupationally relevant especially in healthcare workers and cleaners. Generally, preservatives including formaldehyde releasers are important allergens in OD patients. Leave‐on cosmetic products must not be forgotten as allergen sources. Patch testing both workplace materials and standardized test preparations has a complementary value and is beneficial for the diagnostic work‐up of OD patients. Highlights: Patch testing of workplace materials and standardized test preparations has a complementary value in the diagnostic work‐up of occupational dermatitis patients.Mechanics should be patch tested in a broad fashion, including rubber, metal working fluids, epoxy resin systems, and leave‐on products.Epoxy resin systems exhibit current occupational relevance in almost all high‐risk professions of the handicraft sector. [ABSTRACT FROM AUTHOR]

We report two patients with contact allergy to diclofenac and subsequent tolerance in oral challenge tests. Allergic contact dermatitis (ACD) after topically applied diclofenac1,2 and type IV reactions after oral intake are rarely reported.3 To date, no study exists on possible oral tolerance in patients with contact allergy to topical diclofenac. Keywords: allergic contact dermatitis; case report; diclofenac; systemic tolerance EN allergic contact dermatitis case report diclofenac systemic tolerance 41 43 3 12/17/21 20220101 NES 220101 Diclofenac (CAS 15307-86-5) is a widely used non-steroidal anti-inflammatory drug (NSAID). [Extracted from the article]

Keywords: allergic contact dermatitis; clinical epidemiology; commerce; contact sensitization; export; import; propolis; trade EN allergic contact dermatitis clinical epidemiology commerce contact sensitization export import propolis trade 722 724 3 11/18/21 20211201 NES 211201 Propolis is a natural product that consists of more than 100 compounds and shows great compositional variation depending on its origin.1 The most common poplar-type propolis is produced by honeybees in China, Europe, and North America, and is characterized by several caffeates as major allergens.2 The Information Network of Departments of Dermatology (IVDK) and others recently observed increasing rates of propolis sensitization.3,4 We aimed to identify causes of increasing sensitization to propolis using IVDK and German trade data. Since 2016, increased import and decreased export of propolis to and from Germany, respectively, probably indicate increased propolis use and exposure, which most likely explains the upward trend of propolis sensitization. [Extracted from the article]

Background: Metal work apprentices (MWAs) frequently develop work‐related hand eczema (HE). Objectives: To evaluate the effect of health education on incidence of work‐related HE in MWAs and to assess confounding factors. Materials/methods: In a prospective controlled intervention study, 131 MWAs received educational training on prevention of HE, whereas 172 MWAs and 118 office work apprentices served as controls. At baseline and during three yearly follow‐ups, questionnaires were completed and hands were examined. Saliva samples were collected for assessment of filaggrin (FLG) null mutations and an explorative genome‐wide association study (GWAS), and levels of various cytokines were assessed from stratum corneum samples. Results: The 2‐year and 3‐year incidence of HE in the metalwork control group was 20.9% and 32.6%, respectively, which was significantly higher than in the intervention group (odds ratio [OR] 2.63, 95% confidence interval [CI] 1.31 to 5.28, P <.01 and OR 3.47, 95% CI 1.88 to 6.40, P <.0001). The knowledge score was higher in unaffected MWAs (P <.05). Other factors significantly associated with developing HE in MWAs were smoking cigarettes (P <.01) and FLG mutations (P <.001). No significant associations were found regarding epidermal cytokine levels and GWAS. Conclusions: Health education is effective in primary prevention of HE in MWAs. Individual factors should be considered in targeted counseling. [ABSTRACT FROM AUTHOR]

Background: Sensitization to methylisothiazolinone (MI) has seen an exceptional epidemic, mainly attributed to its use in cosmetics. Objectives: To trace the epidemic of MI allergy (2009–2018), and to analyze a possible change of patients' characteristics. Methods: Informationsverbund Dermatologischer Kliniken‐data of patients patch tested between 2009 and 2018 with MI (0.05% aq.) were analyzed concerning anamnestic items and sensitization frequencies. Results: Overall, 4.9% reacted positive to MI. Comparing sensitization to MI in three periods (2009, 2013/14, and 2017/18), there was an increase to 7% in 2013 and a decrease to 3.4% in 2018. The MOAHLFA Index (M=Men, O=Occupational Dermatitis, A=Atopic Dermatitis, L=Leg Dermatitis, F=Face Dermatitis, A= Age > 40) for the period 2013/14 is characterized by a lower proportion of occupational dermatitis and a higher proportion of face dermatitis. The period 2017/18 is characterized by increases of occupational dermatitis and hand dermatitis, and a decrease of face dermatitis. Painters, personal care workers, and hairdressers were particularly affected. Sensitization in hairdressers and personal care workers (mostly cosmeticians) decreased after the peak in 2013/14, whereas sensitization to MI in painters continued to increase. Conclusions: After an unprecedented epidemic of MI allergy, mainly caused by its use in cosmetics, the continuous use of MI in industrial applications, for example, paints, and subsequent sensitization remain a matter of concern. Highlights: After an epidemic of MI allergy mainly caused by its use in cosmetics, the continuous use of MI in industrial applications, for example, paints, and subsequent sensitization remain a matter of concern. [ABSTRACT FROM AUTHOR]

However, there is still a considerable need for effective targeted therapies for other melanoma subgroups with constitutive MAPK activation, such as RAS- and NF-1-mutated tumors, as well as for therapeutic options targeting MAPK pathway inhibitor resistant BRAF-mutated melanomas, which commonly exhibit a striking reactivation of this pathway. Based on that, our work "Inhibition of RSK family members can effectively target malignant melanoma cells with MAPK pathway hyperactivation" assessed a potential functional role of the p90 ribosomal S6 kinases and their inhibition in different MAPK pathway-driven genetic melanoma subgroups. In line with a pronounced reactivation of the MAPK pathway in the case of MAPK pathway inhibitor resistance, we observed a further increase in RSK activity in BRAF-mutated melanoma cells with acquired MAPK pathway inhibitor resistance both in an in vitro model system and in tumor biopsies from stage IV melanoma patients which progressed under MAPK pathway inhibitor therapy. We found that IL-9-producing TH cells are better described as a subpopulation of TH2 cells that express IL-9 transiently post activation, rather than as a bona fide TH cell lineage. [Extracted from the article]

Background: Filaggrin (Flg) and hornerin (Hrnr) share similar structural and functional features. Both proteins have been implicated as essential proteins for skin barrier maintenance. Loss‐of‐function mutations of these genes constitute a risk factor for atopic dermatitis and eczema‐related asthma. Furthermore, both FLG and HRNR protein levels are downregulated in patients with atopic dermatitis. Thus, mice deficient for Flg and Hrnr provide a novel model to study skin barrier impairment and the susceptibility for cutaneous inflammation. Methods: By using appropriate targeting vectors and breeding strategies, we established a homozygous FlgHrnr double‐deficient (FlgHrnr−/−) mouse model lacking both genes including the intergenomic sequence. Results: Neonates appeared normal, but developed a transient scaly phenotype with overall flaky appearance, but no overt skin phenotype in adulthood, thereby reflecting a subclinical barrier defect seen in humans. Structurally, FlgHrnr−/− mice displayed a markedly reduced granular layer and a condensed cornified layer. Functionally, FlgHrnr−/− mice showed permeability abnormalities and metabolic aberrations regarding the production of natural moisturizing factors (NMFs) in the stratum corneum. Surprisingly, although the immune system revealed no aberrations under steady‐state conditions, FlgHrnr−/− mice are predisposed to mount an allergic contact dermatitis, especially at hapten threshold levels eliciting allergic reactions. Conclusions: Together, our FlgHrnr−/− mouse model nicely reflects the epicutaneous sensitization susceptibilities and inflammatory reactions to environmental insults in humans with impaired skin barrier functions. [ABSTRACT FROM AUTHOR]

The article presents a case study of a contact dermatitis caused by diltiazem cream and cross-reactivity with other calcium channel blockers. Topics include a 47-year-old healthy man, without a history of atopic disease, experienced a generalized papular rash starting from the anogenital area, and he developed an eczematous eruption in the anogenital area, and this was followed by rapid dissemination of the skin lesions to the trunk and extremities.

The article presents a case study of 55-year-old White non-atopic metalworker with the medical history of work-related hand eczema. It notes the allergic contact dermatitis caused by the emulsifying agent 2-Amino-2-methyl-1-propanol (AMP), which is used in metalworking fluids (MWF), and AMP used in cosmetics like hair dyes.

The article presents the case study of 31-year-old non-atopic toolmaker being exposed to a concentrated solution with an oligomeric reaction product, with diphenylmethane and tripropyleneglycol. It states that the patient wore protective gloves and goggles, his right forearm and face that were contaminated. It focuses application of topical corticosteroids in the affected are.

The article discusses research which patch tested didecyldimethylammonium chloride (DDAC) in patients with suspected contact sensitization to surface or instrument disinfectants after observing a case of a geriatric nurse with airborne occupational allergic contact dermatitis caused by DDAC. Topics covered include the clinical relevance of patch testing, test concentrations which shows strong and weak positive reactions, and ideal concentrations for suspected allergic contact dermatitis.

The article offers information on a study related to the concentration of povidone-iodine in patch test. Topics discussed include use of povidone-iodine (PVP-I) as a skin disinfectant in wound care and preparation for surgery; medical examination of suspected allergic contact dermatitis (ACD) caused by antiseptics; and administration of iodine-containing contrast media.