Metal implants are widely utilized in orthopedics and dentistry but can occasionally trigger allergic reactions, presenting diagnostic and therapeutic challenges. In vitro testing has become a pivotal tool for evaluating metal hypersensitivity, employing methods such as the lymphocyte transformation test (LTT), enzyme-linked immunosorbent assay (ELISA), and cytokine profiling to detect immune responses to common allergens like nickel, cobalt, and chromium. Additionally, genetic testing on certain polymorphisms is emerging as a complementary approach, identifying predispositions to hypersensitivity by analyzing polymorphisms in genes related to immune regulation, such as cytokine- and inflammation related genes. While these techniques offer significant insights, they face challenges, including variability in test sensitivity, specificity, and a lack of standardized protocols. The clinical relevance of positive in vitro results or genetic markers remains complex, necessitating integration with patient history and clinical observations. Advances in these in vitro testing methods and studies with expanded genomic databases, hold potential to improve diagnostic precision. We want to show the current capabilities and limitations of in vitro and genetic testing in metal implant allergy diagnostics, highlighting their combined potential to enhance patient care, personalized risk assessment, and implant biocompatibility.

Antibiotic-loaded polymethylmethacrylate (PMMA) bone cement is a cornerstone in knee arthroplasty, providing mechanical stability and infection prophylaxis. However, hypersensitivity reactions to its constituents, including methylmethacrylate monomer, benzoyl peroxide, and incorporated antibiotics like gentamicin, are an emerging concern. Gentamicin, a commonly used additive, has been implicated in allergic reactions, with studies reporting positive patch test results in up to 2–5% of tested patients. Such reactions can present as dermatitis, chronic pain, implant loosening, or systemic symptoms, complicating postoperative recovery. Clinical data indicate that revision surgery without gentamicin-containing cement often results in significant symptom resolution and favorable outcomes. Diagnosis of hypersensitivity remains challenging and requires a multidisciplinary approach, including detailed patient history, patch testing, and occasionally in vitro immune response assays like lymphocyte transformation tests. To minimize risks, preoperative screening for antibiotic hypersensitivity in cases of reasonable suspicion of an allergy and the use of alternative cement formulations or antibiotics are good possibilities for a better outcome. Advances in materials with reduced allergenic potential and personalized therapeutic strategies promise improved patient care. In this work, we want to show the frequencies and pathways of a possible bone cement allergy and present ways in which better patient care and treatment can be achieved after knee arthroplasty.

Knee Implants are usually made of CoCr28Mo6 or TiAl6V4 alloys or combinations of both materials in modular junctions. Particles and metal ions from knee implants are always released after implantation, either as a result of mechanical (wear) or electrochemical processes (corrosion). Total knee arthroplasties (TKA) are very effective treatment options for advanced osteoarthritis of the joints with overall low revision rates [1–4]. However, biological reactions in patients (allergy, inflammatory response), caused by the release of metal particles and ions, have been reported [4–8]. An overview will be given about alternative implant materials and their biotribological properties, biological reactions and clinical results to substantially reduce metal ion release in knee arthroplasty. Methods. Implant materials are usually well tolerated, but if a critical metal ion concentration is exceeded, local or systemic reactions can occur. The released metal particles and metal ions accumulate around affected joints as well as in body fluids and distant organs. Local tissue reactions to metal particles around joint arthroplasties have been described by the term “adverse reactions to metal debris”. Based on the alloy composition of established implant materials their biotribological behaviour with release of metal debris and Co, Cr, Mo, Ni, Ti ions will be demonstrated in meaningful examples with a focus on adverse biological reactions, clinical findings in patients with suspected metal ion hypersensitivity and implant registry results. If patients present with a confirmed metal allergy, in TKA a ZrN-multilayer-coated or oxidized zirconium implant is currently the best option [5,6,8]. To address hyper-sensitivity reactions to bone cement constituents [9], up-coming innovative implant technologies based on ceramic-coated 3D-printed TiAl6V4-alloy with cementless bone fixation represent a future perspective.

BackgroundAlthough rare, allergic reactions to metal implants represent a diagnostic challenge in view of missing guidelines.ObjectivesTo develop an European expert consensus on characteristics of metal allergy reactions and the utility of various diagnostic tools in suspected metal implant allergy.MethodsA nominal group technique (NGT) was applied to develop consensus statements. Initially an online literature database was created on a secure server to enable a comprehensive information. Twenty-three statements were formulated on potential aspects of metal implant allergy with a focus on diagnostics and grouped into five domains. For the consensus development, the panel of 12 experts initially did refine and reformulate those statements that were ambiguous or had unclear wording. By face-to-face (9/12) or virtual participation (3/12), an anonymous online voting was performed.ResultsConsensus (>= 80% of agreement) was reached in 20/23 statements. The panel agreed that implant allergy despite being rare should be considered in case of persistent unexplained symptoms. It was, however, recommended to allow adequate time for resolution of symptoms associated with healing and integration of an implant. Obtaining questionnaire-aided standardized medical history and standardized scoring of patient outcomes was also considered an important step by all experts There was broad consensus regarding the utility/performance of patch testing with additional late reading. It was recognized that the lymphocyte transformation test (LTT) has to many limitations to be generally recommended. Prior to orthopaedic implant, allergy screening of patients without a history of potential allergy to implant components was not recommended.ConclusionsUsing an expert consensus process, statements concerning allergy diagnostics in suspected metal implant allergy were created. Areas of nonconsensus were identified, stressing uncertainty among the experts around topics such as preoperative testing in assumed allergy, histological correlate of periimplant allergy and in vitro testing, which underscores the need for further research.

Background Allergies against implant materials are still not fully understood. Despite controversies about its relevance, some patients need treatment with hypoallergenic implants. This study compared coated and standard total knee arthroplasty (TKA) regarding inflammatory response and patient-reported outcome measures (PROMs). Methods 76 patients without self-reported allergies against implant materials were included in a RCT and received a coated or standard TKA of the same cemented posterior-stabilized knee system. 73 patients completed the 3-year follow-up. Two patients died and there was one revision surgery. Serum levels of cytokines with a possible role in implant allergy were measured in patient`s serum (IL-1beta, IL-5, IL-6, IL-8, IL-10, IFN γ, TNF α) prior to, one and three years after surgery. Furthermore, PROMs including knee function (Oxford Knee Score, Knee Society Score) and health-related quality of life (QoL, EuroQuol questionnaire) were assessed. Additionally, 8 patients with patch-test proven skin allergy against implant materials who received the coated implant were assessed similarly and compared to a matched-pair group receiving the same implant. Results There were no differences in function and QoL between the assessed groups at any follow-up. The majority of patients demonstrated no elevation of the measured blood cytokines. Cytokine patterns showed no differences between study groups at any follow-up. The allergy patients demonstrated slower functional improvement and minor differences in cytokine pattern. Yet these results were not significant. There were no differences in the matched-pair analysis. Conclusion We observed no relevant increase in serum cytokine levels in any group. The inflammatory response measured seems limited, even in allergy patients. Furthermore, there were no differences between coated and standard TKA in non-allergy patients in the 3-year Follow-Up period. Trial registration The study protocol was registered in the US National Institutes of Health’s database ( http://www.clinicaltrials.gov ) registry under NCT03424174 on 03/17/2016.

Background In contrast to infection or mechanical issues joint replacement failure following inflammatory adverse reactions is poorly understood. Objective To assess the association of IL-1β polymorphisms and history of allergy with aseptic non-mechanical complications following arthroplasty. Methods In 102 patients with aseptic non-mechanically caused symptomatic knee or hip arthroplasty (SA) and 93 patients with asymptomatic arthroplasty (AA) questionnaire-based history, patch test with at least standard series, lymphocyte transformation test (LTT) with nickel, cobalt and chromium and interleukin-1 polymorphism analysis were done. Three polymorphisms of the IL1B gene [IL-1b -3954 (rs1143634), IL-1b -511 (rs16944) and IL-1b -31 (rs1143627)] and one polymorphism of the IL1RN gene [IL1RN intron 2, variable number of tandem repeats, VNTR (rs2234663)] were assessed by PCR and gel electrophoresis. Results We found no significant difference in smoking history and atopy but 25% versus 10% of self-reported metal allergy in SA versus AA; the patch test (respective, LTT) for metal sensitivity was more often positive in SA patients. The allele 498 bp of the IL1RN polymorphism occurred significantly more often in the SA group (37% versus 11%; p < 0.0001). Upon additional presence of atopy, the difference was even greater (60% vs 10%) (p < 0.000001). There was no association of IL-1 polymorphisms with metal allergy. Conclusion The IL1RN VNTR allele 498 bp was strongly associated with SA. In patients with a history of atopy, presence of the IL1RN VNTR allele 498 bp led to a four-fold higher SA prevalence compared to patients without this allele.

Purpose Allergy against implant materials is discussed controversially and still not fully understood. Despite these controversies, a relevant number of patients receive hypoallergenic knee implants. The aim of this study was to compare a new coating system with the standard implant in total knee arthroplasty (TKA). Additionally, the influence of proinflammatory cytokines on patient-reported outcome measures (PROMs) was investigated. Methods 120 patients without known metal allergy and without previous metal implants were included. The patients were randomized to receive a coated or standard TKA of the same knee system. 105 patients completed the 5 year follow-up. Patient-reported outcome measures (PROMs) including knee function (Oxford Knee Score, OKS), quality of life (SF36) and UCLA activity scale were assessed. Additionally, several cytokines with a possible role in implant allergy were measured in patient`s serum (IL-1beta, IL-5, IL-6, IL-8, IL-10, IP-10, IFN γ, TNF α). Group comparison was performed using Mann–Whitney U test for continuous values and chi-square test for categorical values. Results There were no differences in PROMs between both groups at any follow-up. The majority of patients demonstrated no elevation of the measured blood cytokines. The blood cytokine pattern after 5 years demonstrated no differences between study groups. There was a significant association between elevated IL-8 values and worse results in the overall OKS ( p = 0.041), the OKS function component ( p = 0.004), the UCLA activity scale ( p = 0.007) and the physical component of SF36 ( p = 0.001). Conclusion There were no problems with the new coating during mid-term follow-up and no differences in PROMs between coated and standard TKA. Patients with an increased inflammatory response demonstrated worse functional results, regardless of the implant. Level of evidence I. Clinical trial registration The study protocol was registered in the US National Institutes of Health’s database ( http://www.clinicaltrials.gov ) registry under NCT00862511.

BACKGROUND:Little is known about sensitization to iron (Fe) in private, occupational, and medical settings, particulary implantology.OBJECTIVES:To investigate sensitization to metals, particularly to Fe, both in pre-implant individuals with presumed metal allergy and in patients with suspected metal implant allergy. To further characterize Fe-sensitized individuals.METHODS:Analysis of patch test reactions to an Fe (II) sulfate-containing metal series in 183 consecutive patients (41 pre-implant, 142 metal implant bearers). Test readings were on day (D)2, D3, and D6. Evaluation of questionnaire-aided history of metal reactivity patterns and demographics of Fe reactors.RESULTS:Metal reactivity in pre-implant/implant/total group was: to nickel 39%/30%/32%; to cobalt 17%/15%/15%; and to chromium 7%/13%/11%. Co-sensitizations cobalt/nickel (19/58) and cobalt/chromium (11/21) were significant at P < .001; co-sensitizations Fe/nickel (4/10) and chromium/knee arthroplasty (11/73) at P = .03. Ten of 183 (5.5%) reacted to Fe (2 of 41 pre-implant patients, 8 of 142 implant bearers), with 10 reacting only on D6. Fe reactivity was highest in complicated knee arthroplasty (7/73). Further peculiarities of Fe reactors included frequent isolated Fe reactivity (6/10), occupational metal exposure (7/10), previous (par)enteral Fe substitution (6/10).CONCLUSIONS:The 5.5% prevalence of Fe reactions suggests a potentially underestimated role of this metal allergen in general and in implant bearers. The latter also shows a distinct metal sensitization pattern.

Metal implants are increasingly important in many medical fields, including orthopedic surgery, dentistry, and ophthalmology. Their use is almost part of daily life. Metal implant allergy is a rare but important-diagnosis of exclusion. The clinical pictures encompass both cutaneous and extracutaneous manifestations. The diagnostic work-up is done in several steps by integrating patient history, clinical picture, and results of medical examinations, which requires interdisciplinary cooperation. In case of confirmed implant allergy, alternative materials are available. Their application may lead to complete disappearance of symptoms in the affected patients.

The effect of Actovegin® was investigated on PMA- and LPS-induced human peripheral blood mononuclear cells (PBMCs). PBMCs (1 × 106 cells/ml) from five blood donors (2 f, 3 m; 45–55 years) were grown in medium and exposed to Actovegin® in the presence or absence of PMA or LPS. Supernatants were collected to assess the concentration of cytokines (TNF-α, IL-1beta, IL-6 and IL-10). The reactive oxygen species (ROS) were assessed by a ROS-GloTM H2O2 assay. Stimulation of cells by PMA or LPS (without Actovegin®) significantly increased the secretion of IL-1beta, IL-6, IL-10 and TNF-α from PBMCs, compared to controls. Pre-treatment of cells with Actovegin® (1, 5, 25, 125 µg/ml) plus PMA significantly decreased the secretion of IL-1beta from PBMCs, compared to controls (PMA without Actovegin®). In contrast, addition of Actovegin® (1, 5, 25, 125 and 250 µg/ml) plus LPS did not alter the IL-1beta production, compared to controls (LPS without Actovegin®). TNF-α, IL-6 and IL-10 do not contribute to the reduction of inflammatory reactions with Actovegin®. Actovegin® can reduce the PMA-induced IL-1beta release and the ROS production from PBMCs. These findings may help to explain the clinically known positive effects of Actovegin® on athletic injuries with inflammatory responses (e.g., muscle injuries, tendinopathies).

OBJECTIVE:The objective of the present study was to examine the clinical and immunological parameters in samples collected from the peri-implant crevicular fluid (PICF) of machined titanium (M) abutments compared to titanium abutments with a laser-microtextured surface (LMS) on dental implants.MATERIAL AND METHODS:A total of 40 patients with one titanium implant, half of them (n=20) provided with a M abutment (control group) and the other half (n=20) with LMS abutments (test group), were included in the study. Clinical parameters pocket probing depth (PD), full-mouth plaque score (FMPS), radiographic bone loss (RBL), clinical attachment level (CAL), mucosal recession (MR), bleeding on probing (BOP), and width of keratinized mucosa (KM) were evaluated. The peri-implant sulcus fluid was analyzed for cytokines IL-1α, IL-1β, IL-6, IL-8, and IL-10 via flow cytometry.RESULTS:Clinical evaluation demonstrated no significant difference of PD (mean LMS = 3.50 mm/SD 0.95 mm vs mean M = 3.45 mm/SD 0.76 mm (p=0.855)), MR (mean LMS = 0.30 mm/SD 0.57 mm vs mean M = 0.35 mm/SD 0.67 mm (p=0.801)), CAL (mean LMS = 3.60 mm/SD 1.14 mm vs mean M = 3.55 mm/SD 0.89 mm (p=0.878)), and KM (mean LMS = 2.03 mm/SD 1.08 mm vs mean M = 2.13 mm/SD 0.92 mm (p=0.754)) between LMS and M abutments. LMS abutments showed less BOP than M abutments (26.7% vs 30.8%), but statistically not significant (p = 0.2235). Radiographic bone loss (mean LMS = 0.22 mm/SD 0.44 mm vs mean M = 0.59 mm/SD 0.49 mm) was reduced in the test group in comparison with the control group (p=0.016). In the collected PICF, the levels of pro-inflammatory cytokines IL-1α (median LMS = 180.8 pg/ml vs M = 200.9 pg/ml (p=0.968)) and IL-1β (median LMS = 60.43 pg/ml vs M = 83.11 pg/ml (p=0.4777)) were lower, and the levels of IL-6 (median LMS = 180.8 pg/ml vs M = 200.9 pg/ml (p<0.0001)) were significantly lower in the test group. In contrast, the levels of IL-8 (median LMS = 255.7 pg/ml vs M = 178.7 pg/ml (p=0.3306)) were higher in the test group, though not significantly. The levels of anti-inflammatory IL-10 were significantly increased in the test group (LMS median = 0.555 pg/ml vs M median = 0.465 pg/ml (p=0.0365)). IL-1β showed a significant correlation to radiologic bone loss (p=0.0024). The other variables IL-1α, IL-6, IL-8, and IL-10 had no significant correlation to radiological bone loss.CONCLUSION:Within the limitations of this study, titanium implants provided with laser-microtextured surface abutments seem to demonstrate less pro-inflammatory and more anti-inflammatory activity and to show reduced radiographic bone loss compared to machined titanium abutments.CLINICAL RELEVANCE:The use of laser-microtextured surface abutments might have the potential to support peri-implant tissue health.

Background Antibiotic-loaded (particularly gentamicin) bone cement (BC) is widely used in total joint arthroplasty (TJA) to prevent periprosthetic infections (PPIs), but may itself cause implant failure. In light of a complete lack in literature, the objective was to assess the clinical relevance of gentamicin allergy for failure of cemented total knee arthroplasties in 25 out of 250 patients with positive patch test reactions to gentamicin and otherwise unexplained symptoms by evaluating benefits from revision with change to gentamicin-free cement. Methods Fifteen of these 25 patients and their treating orthopaedic surgeons agreed to a re-assessment. They were surveyed regarding interim course of therapy and symptoms, including re-assessment of the Knee Injury and Osteoarthritis Outcome Score (KOOS), and underwent follow-up clinical and radiographic investigations. The initial use of gentamicin-loaded BC was reaffirmed by review of the primary implantation operative reports and respective implant passports. Primary and follow-up KOOS scores were analyzed regarding benefits from revision surgery by comparing nine patients with revision to six without revision. Results Mean follow-up time was 38 months. The entirety of patients experienced an improvement of self-reported symptoms, with revision surgery (i.e., switching to gentamicin-free BC or uncemented total knee arthroplasty) yielding significantly greater improvement ( p = 0.031): the nine revised patients reported a significant symptom relief ( p = 0.028), contrary to the six unrevised patients ( p = 0.14). Interestingly, the decision to proceed with revision surgery was significantly correlated with higher symptom severity ( p = 0.05). Conclusion In symptomatic total knee arthroplasty with gentamicin allergy, uncemented revision arthroplasty or change to gentamicin-free BC provides significant symptom relief.

AbstractBackgroundOften concomitant patch test (PT) reactivity to palladium (Pd) and nickel (Ni) is found.ObjectivesTo determine whether lymphocyte transformation test (LTT) could be useful in discrimination between cross‐reacting or distinct PT results, and to compare the results with in vitro cytokine production upon Pd or Ni stimulation.Materials and MethodsThe study population consisted of two groups: 13 individuals with Pd PT reactions (10 with concomitant Ni PT reaction, 3 individuals with only Pd PT reactivity) and 10 Ni/Pd PT negative individuals. LTT and assessment of cytokine release (interferon‐gamma, interleukin‐5 [IL‐5], IL‐8, IL‐17A, tumor necrosis factor alpha) by cytometric bead assay were performed.ResultsAll 10 patients with positive PT to Ni and Pd showed positive LTT to Ni (P < .05) as compared with the 10 Pd/Ni PT negative patients—but had no significant LTT reaction to Pd. In all, 9 out of 10 Pd/Ni PT negative patients were also LTT negative to Ni and 10 out of 10 to Pd. In the 3 only Pd PT reactors 2 out of 3 remained LTT negative to Ni and 0 out of 3 to Pd. As a major finding, cytokine production gave clearly enhanced IL‐5 response to Ni in Ni PT positive individuals (P < .05), whereas Pd PT reactivity was not linked with such enhanced IL‐5 production in vitro to Pd.ConclusionsPd and Ni sensitization are mostly found concomitantly, and cross‐reactivity is questioned. By different LTT reactions and particularly IL‐5 production in vitro, predominant Ni sensitization becomes more evident.

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Journal of the European Academy of Dermatology and VenereologyVolume 33, Issue 7 p. e265-e267 Letter to the Editor Nickel contact dermatitis evaluated by means of optical coherence tomography: first impressions C. Ruini, Corresponding Author C. Ruini cristel.ruini@med.uni-muenchen.de Department of Dermatology and Allergology, University Hospital of the Ludwig Maximilian University, Frauenlobstr.9-11, 80337 Munich, Germany Department of Dermatology, München Klinik GmbH – Munich Municipal Hospital, Thalkirchnerstrasse 48, 80337 Munich, GermanyCorrespondence: C. Ruini. E-mail: cristel.ruini@med.uni-muenchen.deSearch for more papers by this authorD. Wittmann, D. Wittmann Department of Dermatology and Allergology, University Hospital of the Ludwig Maximilian University, Frauenlobstr.9-11, 80337 Munich, GermanySearch for more papers by this authorB. Summer, B. Summer Department of Dermatology and Allergology, University Hospital of the Ludwig Maximilian University, Frauenlobstr.9-11, 80337 Munich, GermanySearch for more papers by this authorT. von Braunmühl, T. von Braunmühl Department of Dermatology and Allergology, University Hospital of the Ludwig Maximilian University, Frauenlobstr.9-11, 80337 Munich, GermanySearch for more papers by this authorL.E. French, L.E. French Department of Dermatology and Allergology, University Hospital of the Ludwig Maximilian University, Frauenlobstr.9-11, 80337 Munich, GermanySearch for more papers by this authorP. Thomas, P. Thomas Department of Dermatology and Allergology, University Hospital of the Ludwig Maximilian University, Frauenlobstr.9-11, 80337 Munich, GermanySearch for more papers by this author C. Ruini, Corresponding Author C. Ruini cristel.ruini@med.uni-muenchen.de Department of Dermatology and Allergology, University Hospital of the Ludwig Maximilian University, Frauenlobstr.9-11, 80337 Munich, Germany Department of Dermatology, München Klinik GmbH – Munich Municipal Hospital, Thalkirchnerstrasse 48, 80337 Munich, GermanyCorrespondence: C. Ruini. E-mail: cristel.ruini@med.uni-muenchen.deSearch for more papers by this authorD. Wittmann, D. Wittmann Department of Dermatology and Allergology, University Hospital of the Ludwig Maximilian University, Frauenlobstr.9-11, 80337 Munich, GermanySearch for more papers by this authorB. Summer, B. Summer Department of Dermatology and Allergology, University Hospital of the Ludwig Maximilian University, Frauenlobstr.9-11, 80337 Munich, GermanySearch for more papers by this authorT. von Braunmühl, T. von Braunmühl Department of Dermatology and Allergology, University Hospital of the Ludwig Maximilian University, Frauenlobstr.9-11, 80337 Munich, GermanySearch for more papers by this authorL.E. French, L.E. French Department of Dermatology and Allergology, University Hospital of the Ludwig Maximilian University, Frauenlobstr.9-11, 80337 Munich, GermanySearch for more papers by this authorP. Thomas, P. Thomas Department of Dermatology and Allergology, University Hospital of the Ludwig Maximilian University, Frauenlobstr.9-11, 80337 Munich, GermanySearch for more papers by this author First published: 28 February 2019 https://doi.org/10.1111/jdv.15536Citations: 4Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume33, Issue7July 2019Pages e265-e267 RelatedInformation

Contact DermatitisVolume 79, Issue 1 p. 48-49 CONTACT POINT Titanium hypersensitivity causing painful intra-abdominal oedema after staple-fixed inguinal hernia repair Silke C. Hofmann, Corresponding Author Silke C. Hofmann silke.hofmann@helios-gesundheit.de orcid.org/0000-0002-4221-386X Centre for Dermatology, Allergy and Dermatosurgery, Helios University Hospital Wuppertal, University Witten/Herdecke, Wuppertal, Germany Correspondence Dr. Silke C. Hofmann, Department of Dermatology, Allergy and Dermatosurgery, HELIOS University Hospital Wuppertal, Heusnerstr 40, 42283 Wuppertal, Germany. Email: silke.hofmann@helios-gesundheit.deSearch for more papers by this authorMaria Plett, Maria Plett Centre for Dermatology, Allergy and Dermatosurgery, Helios University Hospital Wuppertal, University Witten/Herdecke, Wuppertal, GermanySearch for more papers by this authorStefan Jansen, Stefan Jansen Centre for Visceral Surgery, Helios University Hospital Wuppertal, University Witten/Herdecke, Wuppertal, GermanySearch for more papers by this authorPeter Thomas, Peter Thomas Department of Dermatology and Allergy, Ludwig-Maximilians-University, Munich, GermanySearch for more papers by this authorKarisa F. M. Thölken, Karisa F. M. Thölken Centre for Dermatology, Allergy and Dermatosurgery, Helios University Hospital Wuppertal, University Witten/Herdecke, Wuppertal, GermanySearch for more papers by this author Silke C. Hofmann, Corresponding Author Silke C. Hofmann silke.hofmann@helios-gesundheit.de orcid.org/0000-0002-4221-386X Centre for Dermatology, Allergy and Dermatosurgery, Helios University Hospital Wuppertal, University Witten/Herdecke, Wuppertal, Germany Correspondence Dr. Silke C. Hofmann, Department of Dermatology, Allergy and Dermatosurgery, HELIOS University Hospital Wuppertal, Heusnerstr 40, 42283 Wuppertal, Germany. Email: silke.hofmann@helios-gesundheit.deSearch for more papers by this authorMaria Plett, Maria Plett Centre for Dermatology, Allergy and Dermatosurgery, Helios University Hospital Wuppertal, University Witten/Herdecke, Wuppertal, GermanySearch for more papers by this authorStefan Jansen, Stefan Jansen Centre for Visceral Surgery, Helios University Hospital Wuppertal, University Witten/Herdecke, Wuppertal, GermanySearch for more papers by this authorPeter Thomas, Peter Thomas Department of Dermatology and Allergy, Ludwig-Maximilians-University, Munich, GermanySearch for more papers by this authorKarisa F. M. Thölken, Karisa F. M. Thölken Centre for Dermatology, Allergy and Dermatosurgery, Helios University Hospital Wuppertal, University Witten/Herdecke, Wuppertal, GermanySearch for more papers by this author First published: 09 March 2018 https://doi.org/10.1111/cod.12985Citations: 4Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume79, Issue1July 2018Pages 48-49 RelatedInformation