@article{WendlingerWohlfarthKreftetal.2022, author = {Wendlinger, Simone and Wohlfarth, Jonas and Kreft, Sophia and Siedel, Claudia and Kilian, Teresa and Dischinger, Ulrich and Heppt, Markus V. and Wistuba-Hamprecht, Kilian and Meier, Friedegund and Goebeler, Matthias and Schadendorf, Dirk and Gesierich, Anja and Kosnopfel, Corinna and Schilling, Bastian}, title = {Blood eosinophils are associated with efficacy of targeted therapy in patients with advanced melanoma}, series = {Cancers}, volume = {14}, journal = {Cancers}, number = {9}, issn = {2072-6694}, doi = {10.3390/cancers14092294}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-275137}, year = {2022}, abstract = {Background: Eosinophils appear to contribute to the efficacy of immunotherapy and their frequency was suggested as a predictive biomarker. Whether this observation could be transferred to patients treated with targeted therapy remains unknown. Methods: Blood and serum samples of healthy controls and 216 patients with advanced melanoma were prospectively and retrospectively collected. Freshly isolated eosinophils were phenotypically characterized by flow cytometry and co-cultured in vitro with melanoma cells to assess cytotoxicity. Soluble serum markers and peripheral blood counts were used for correlative studies. Results: Eosinophil-mediated cytotoxicity towards melanoma cells, as well as phenotypic characteristics, were similar when comparing healthy donors and patients. However, high relative pre-treatment eosinophil counts were significantly associated with response to MAPKi (p = 0.013). Eosinophil-mediated cytotoxicity towards melanoma cells is dose-dependent and requires proximity of eosinophils and their target in vitro. Treatment with targeted therapy in the presence of eosinophils results in an additive tumoricidal effect. Additionally, melanoma cells affected eosinophil phenotype upon co-culture. Conclusion: High pre-treatment eosinophil counts in advanced melanoma patients were associated with a significantly improved response to MAPKi. Functionally, eosinophils show potent cytotoxicity towards melanoma cells, which can be reinforced by MAPKi. Further studies are needed to unravel the molecular mechanisms of our observations.}, language = {en} } @article{BuhlBeissertGaffaletal.2020, author = {Buhl, Timo and Beissert, Stefan and Gaffal, Evelyn and Goebeler, Matthias and Hertl, Michael and Mauch, Cornelia and Reich, Kristian and Schmidt, Enno and Sch{\"o}n, Michael P. and Sticherling, Michael and Sunderk{\"o}tter, Cord and Traidl-Hoffmann, Claudia and Werfel, Thomas and Wilsman-Theis, Dagmar and Worm, Margitta}, title = {COVID-19 and implications for dermatological and allergological diseases}, series = {JDDG: Journal der Deutschen Dermatologischen Gesellschaft}, volume = {18}, journal = {JDDG: Journal der Deutschen Dermatologischen Gesellschaft}, number = {8}, doi = {10.1111/ddg.14195}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-217860}, pages = {815 -- 824}, year = {2020}, abstract = {COVID-19, caused by the coronavirus SARS-CoV-2, has become pandemic. A further level of complexity opens up as soon as we look at diseases whose pathogenesis and therapy involve different immunological signaling pathways, which are potentially affected by COVID-19. Medical treatments must often be reassessed and questioned in connection with this infection. This article summarizes the current knowledge of COVID-19 in the light of major dermatological and allergological diseases. It identifies medical areas lacking sufficient data and draws conclusions for the management of our patients during the pandemic. We focus on common chronic inflammatory skin diseases with complex immunological pathogenesis: psoriasis, eczema including atopic dermatitis, type I allergies, autoimmune blistering and inflammatory connective tissue diseases, vasculitis, and skin cancers. Since several other inflammatory skin diseases display related or comparable immunological reactions, clustering of the various inflammatory dermatoses into different disease patterns may help with therapeutic decisions. Thus, following these patterns of skin inflammation, our review may supply treatment recommendations and thoughtful considerations for disease management even beyond the most frequent diseases discussed here.}, language = {en} } @article{BenoitScheurlenGoebeleretal.2018, author = {Benoit, Sandrine and Scheurlen, Michael and Goebeler, Matthias and Stoevesandt, Johanna}, title = {Structured diagnostic approach and risk assessment in mucous membrane pemphigoid with oesophageal involvement}, series = {Acta Dermato-Venereologica}, volume = {98}, journal = {Acta Dermato-Venereologica}, doi = {10.2340/00015555-2938}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176191}, pages = {660-666}, year = {2018}, abstract = {Oesophageal involvement in mucous membrane pemphigoid is considered rare, but it may be underdiagnosed. To assess the incidence of oesophageal involvement in a group of patients with newly diagnosed mucous membrane pemphigoid we retrospectively analysed the medical records of 30 consecutive patients with mucous membrane pemphigoid diagnosed between 2006 and 2016 at the Department of Dermatology, University Hospital W{\"u}rzburg. Twenty-one patients (70\%) reported symptoms indicative of oesophageal mucous membrane pemphigoid. Twelve patients (40\%) underwent oesophagogastroduodenoscopy, and oesophageal pathology compatible with mucous membrane pemphigoid was endoscopically found in 9 cases (30\%). In all patients indirect and direct immunofluorescence were performed. Patients with and without oesophageal involvement did not differ with regard to the results of indirect immunofluorescence on salt-split human skin and monkey oesophagus. Study results demonstrate the necessity of a standardized diagnostic work-up, including adequate tissue samples for direct immunofluorescence, to prevent underdiagnosis of oesophageal mucous membrane pemphigoid.}, language = {en} } @article{FringsSchoeffskiGoebeleretal.2021, author = {Frings, Verena Gerlinde and Sch{\"o}ffski, Oliver and Goebeler, Matthias and Presser, Dagmar}, title = {Economic analysis of the costs associated with Hidradenitis suppurativa at a German University Hospital}, series = {PLoS One}, volume = {16}, journal = {PLoS One}, number = {8}, doi = {10.1371/journal.pone.0255560}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-261668}, year = {2021}, abstract = {Background and objectives Hidradenitis suppurativa (HS) significantly affects the patient`s quality of life and leads to multiple medical consultations. Aim of this study was to assess the utilization of medical care of HS patients. Patients and methods All patients presenting in 2017 for an outpatient, day patient and / or inpatient treatment with leading claim type HS at the Department of Dermatology, University Hospital W{\"u}rzburg, were included. Primary outcome was the economic burden of HS patients, measured by resource utilization in €. Results The largest share of the direct medical costs for HS were the inpatient costs with a leading surgical diagnosis-related group (DRG). Antiseptics were the predominant topical prescription. While doxycycline was the most frequently prescribed systemic therapy, adalimumab was the main cost driver. The difference between in-patient (€ 110.25) and outpatient (€ 26.34) direct non-medical costs was statistically significant (p < 0.001). With regards to indirect medical costs, a statistically significantly higher loss of gross value added (inpatient mean € 1,827.00; outpatient mean € 203.00) and loss of production (inpatient mean € 1,026.00; outpatient mean € 228.00) could be noted (p < 0.001), respectively. Conclusions The present study on disease-specific costs of HS confirms that the hospital care of patients with this disease is cost-intensive. However, the primary goal of physicians is not and should not be to save costs regarding their patients`treatment, but rather the premise to utilize the existing resources as efficient as possible. Reducing the use of costly therapeutics and inpatient stays therefore requires more effective therapy options with an improved cost-benefit profile.}, language = {en} } @article{GlutschWobserSchillingetal.2022, author = {Glutsch, Valerie and Wobser, Marion and Schilling, Bastian and Gesierich, Anja and Goebeler, Matthias and Kneitz, Hermann}, title = {PRAME expression as helpful immunohistochemical marker in rhabdoid melanoma}, series = {Dermatopathology}, volume = {9}, journal = {Dermatopathology}, number = {2}, issn = {2296-3529}, doi = {10.3390/dermatopathology9020019}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284115}, pages = {148 -- 157}, year = {2022}, abstract = {Background: Rhabdoid melanoma is a rare variant of malignant melanoma with characteristic cytomorphologic features. Due to the potential loss of conventional melanocytic markers, histopathologic diagnosis is often challenging. We hypothesize that immunostaining for PReferentially expressed Antigen in MElanoma (PRAME) might have the potential to uncover the melanocytic origin of these dedifferentiated tumors. Methods: Four cases of rhabdoid primary melanomas were assessed by immunohistochemistry for expression of PRAME and conventional melanocytic markers. Immunohistochemical expression patterns were analyzed in the rhabdoid primaries and, if available, associated metastases. Results: All four cases of rhabdoid primary melanomas showed a strong nuclear positivity for PRAME, while the expression of conventional melanocytic markers S100, MART-1, SOX-10 and HMB-45 was variable between the analyzed cases. Conclusions: In summary, we report four cases of rhabdoid primary melanoma with high to intermediate expression of PRAME despite the partial and variable loss of other melanocytic markers. Hence, PRAME might facilitate the recognition of this highly aggressive entity to avoid misdiagnosis due to histopathologic pitfalls.}, language = {en} } @article{WobserGoebeler2023, author = {Wobser, Marion and Goebeler, Matthias}, title = {Special Issue "Cutaneous Lymphomas"}, series = {Cancers}, volume = {15}, journal = {Cancers}, number = {5}, issn = {2072-6694}, doi = {10.3390/cancers15051481}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304180}, year = {2023}, abstract = {No abstract available}, language = {en} } @article{GlutschGraenWeberetal.2019, author = {Glutsch, Valerie and Gr{\"a}n, Franziska and Weber, Judith and Gesierich, Anja and Goebeler, Matthias and Schilling, Bastian}, title = {Response to combined ipilimumab and nivolumab after development of a nephrotic syndrome related to PD-1 monotherapy}, series = {Journal for ImmunoTherapy of Cancer}, volume = {7}, journal = {Journal for ImmunoTherapy of Cancer}, doi = {10.1186/s40425-019-0655-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201214}, pages = {181}, year = {2019}, abstract = {Background High response rates of metastatic melanoma have been reported upon immune checkpoint inhibition by PD-1 blockade alone or in combination with CTLA-4 inhibitors. However, the majority of patients with a primary resistance to anti-PD-1 monotherapy is also refractory to a subsequent combined checkpoint inhibition. In BRAF wildtype patients with a primary resistance to PD-1 inhibitors, therapeutic options are therefore limited and immune-related adverse events (irAE) have to be taken into consideration when discussing a subsequent immunotherapy. Case presentation We report the case of a 68-year-old male patient with metastatic melanoma who experienced an acute renal failure with nephrotic syndrome due to a minimal change disease developing after a single dose of the anti-PD-1 antibody pembrolizumab. A kidney biopsy revealed a podocytopathy without signs of interstitial nephritis. Renal function recovered to almost normal creatinine and total urine protein levels upon treatment with oral steroids and diuretics. Unfortunately, a disease progression (PD, RECIST 1.1) was observed in a CT scan after resolution of the irAE. In a grand round, re-exposure to a PD-1-containing regime was recommended. Consensually, a combined immunotherapy with ipilimumab and nivolumab was initiated. Nephrotoxicity was tolerable during combined immunotherapy and a CT scan of chest and abdomen showed a deep partial remission (RECIST 1.1) after three doses of ipilimumab (3 mg/kg) and nivolumab (1 mg/kg). Conclusion This case illustrates that a fulminant response to combined checkpoint inhibition is possible after progression after anti-PD-1 monotherapy and a severe irAE.}, language = {en} } @article{HoeslFroehlichPoschetal.2021, author = {Hoesl, Christine and Fr{\"o}hlich, Thomas and Posch, Christian and Kneitz, Hermann and Goebeler, Matthias and Schneider, Marlon R. and Dahlhoff, Maik}, title = {The transmembrane protein LRIG1 triggers melanocytic tumor development following chemically induced skin carcinogenesis}, series = {Molecular Oncology}, volume = {15}, journal = {Molecular Oncology}, number = {8}, doi = {10.1002/1878-0261.12945}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-238925}, pages = {2140 -- 2155}, year = {2021}, abstract = {The incidence of melanoma and nonmelanoma skin cancer has increased tremendously in recent years. Although novel treatment options have significantly improved patient outcomes, the prognosis for most patients with an advanced disease remains dismal. It is, thus, imperative to understand the molecular mechanisms involved in skin carcinogenesis in order to develop new targeted treatment strategies. Receptor tyrosine kinases (RTK) like the ERBB receptor family, including EGFR/ERBB1, ERBB2/NEU, ERBB3, and ERBB4, are important regulators of skin homeostasis and their dysregulation often results in cancer, which makes them attractive therapeutic targets. Members of the leucine-rich repeats and immunoglobulin-like domains protein family (LRIG1-3) are ERBB regulators and thus potential therapeutic targets to manipulate ERBB receptors. Here, we analyzed the function of LRIG1 during chemically induced skin carcinogenesis in transgenic mice expressing LRIG1 in the skin under the control of the keratin 5 promoter (LRIG1-TG mice). We observed a significant induction of melanocytic tumor formation in LRIG1-TG mice and no difference in papilloma incidence between LRIG1-TG and control mice. Our findings also revealed that LRIG1 affects ERBB signaling via decreased phosphorylation of EGFR and increased activation of the oncoprotein ERBB2 during skin carcinogenesis. The epidermal proliferation rate was significantly decreased during epidermal tumorigenesis under LRIG1 overexpression, and the apoptosis marker cleaved caspase 3 was significantly activated in the epidermis of transgenic LRIG1 mice. Additionally, we detected LRIG1 expression in human cutaneous squamous cell carcinoma and melanoma samples. Therefore, we depleted LRIG1 in human melanoma cells (A375) by CRISPR/Cas9 technology and found that this caused EGFR and ERBB3 downregulation in A375 LRIG1 knockout cells 6 h following stimulation with EGF. In conclusion, our study demonstrated that LRIG1-TG mice develop melanocytic skin tumors during chemical skin carcinogenesis and a deletion of LRIG1 in human melanoma cells reduces EGFR and ERBB3 expression after EGF stimulation.}, language = {en} } @article{KneitzRoseGlutschetal.2022, author = {Kneitz, Hermann and Rose, Christian and Glutsch, Valerie and Goebeler, Matthias}, title = {Recurrence of a cellular blue nevus with satellitosis — a diagnostic pitfall with clinical consequences}, series = {Dermatopathology}, volume = {9}, journal = {Dermatopathology}, number = {4}, issn = {2296-3529}, doi = {10.3390/dermatopathology9040042}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-297436}, pages = {361 -- 367}, year = {2022}, abstract = {Blue nevus is a benign melanocytic lesion, typically asymptomatic and of unknown etiology. Several histologic and clinical variants have been distinguished, the most frequent being common blue nevus, cellular blue nevus, and combined blue nevus. Although melanocytic nevi with a satellite lesion are usually suggestive of locally advanced malignant melanoma, very few cases of blue nevi with satellite lesions have been reported. The diagnosis of common or cellular blue nevi is generally straightforward; however, the presence of structures such as irregular edges or satellitosis are highly suggestive for malignancy, and differential diagnoses such as locally advanced malignant melanoma and malignant blue nevus should be considered. Recurrent blue nevi can display atypical features not seen in the primary lesion, such as pleomorphism and mitotic activity. They usually tend to follow a benign course; however, in some cases, recurrence may indicate malignant transformation. We here report the unique case of a 64-year-old woman with a recurrent cellular blue nevus accompanied by satellite lesions. Such a biological behavior resulting in a clinical presentation as a melanoma-like lesion is a rarity in blue nevus and has not been described before.}, language = {en} } @article{RakHammKerstanetal.2022, author = {Rak, Katrin and Hamm, Henning and Kerstan, Andreas and Kolb-M{\"a}urer, Annette and Goebeler, Matthias}, title = {Severe and prolonged liver damage in pityriasis rubra pilaris treated with acitretin: a case report}, series = {SN Comprehensive Clinical Medicine}, volume = {4}, journal = {SN Comprehensive Clinical Medicine}, number = {1}, doi = {10.1007/s42399-022-01309-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323982}, year = {2022}, abstract = {Acitretin is a systemic retinoid that is used in dermatology for treatment of various inflammatory and especially hyperkeratotic diseases. Elevation of liver enzymes may occur occasionally but normally resolves spontaneously, at the latest after termination of acitretin. However, it can very rarely develop into a life-threatening adverse event including drug-induced liver injury (DILI). A 45-year-old man with classical pityriasis rubra pilaris, a frequently severe, inflammatory skin disease, was started on acitretin. After a seemingly harmless elevation of transaminases, a few weeks after initiation of acitretin, the patient experienced a dramatic course of liver injury with hepatic jaundice though acitretin was stopped immediately. Eventually, laboratory values recovered upon high-dose oral prednisolone therapy. Prescribing physicians should keep in mind that acitretin might induce severe liver injury. Even after termination of acitretin laboratory values should be monitored for a while in order to recognize symptomless but harmful drug-induced liver injury in time.}, language = {en} }