@article{BauerGoebelerWeissbrichetal.2015, author = {Bauer, Boris and Goebeler, Matthias and Weissbrich, Benedikt and Kerstan, Andreas}, title = {Kerinokeratosis papulosa of childhood}, series = {Dermatology}, volume = {231}, journal = {Dermatology}, number = {1}, issn = {1018-8665}, doi = {10.1159/000381539}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-198997}, pages = {1 -- 4}, year = {2015}, abstract = {Background: Kerinokeratosis papulosa (KP) is considered an extremely rare genodermatosis presenting usually as waxy papules on the trunk in childhood. Objective: To describe and analyze the clinical, histological and potential etiopathological aspects of KP. Methods: The dermatoscopic features of a new case of KP of childhood are investigated. The presence of human papillomavirus (HPV) DNA in lesional skin was studied by polymerase chain reaction. Furthermore, all cases of KP of childhood reported so far were reviewed. Results: As a diagnostic tool, we describe for the first time a dermatoscopic feature, namely a cribriform pattern of KP, in an 11-year-old boy. In addition, we detected HPV (type 57) in his KP lesions. Conclusions: Dermatoscopic examination might be a useful tool to distinguish KP from other skin lesions, e.g. common warts. The detection of HPV type 57 might hint to an etiological role of HPV for KP.}, language = {en} } @article{AlmanzarKleinSchmalzingetal.2016, author = {Almanzar, Giovanni and Klein, Matthias and Schmalzing, Marc and Hilligardt, Deborah and El Hajj, Nady and Kneitz, Hermann and Wild, Vanessa and Rosenwald, Andreas and Benoit, Sandrine and Hamm, Henning and Tony, Hans-Peter and Haaf, Thomas and Goebeler, Matthias and Prelog, Martina}, title = {Disease Manifestation and Inflammatory Activity as Modulators of Th17/Treg Balance and RORC/FoxP3 Methylation in Systemic Sclerosis}, series = {International Archives of Allergy and Immunology}, volume = {171}, journal = {International Archives of Allergy and Immunology}, number = {2}, issn = {1018-2438}, doi = {10.1159/000450949}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196577}, pages = {141-154}, year = {2016}, abstract = {Background: There is much evidence that T cells are strongly involved in the pathogenesis of localized and systemic forms of scleroderma (SSc). A dysbalance between FoxP3+ regulatory CD4+ T cells (Tregs) and inflammatory T-helper (Th) 17 cells has been suggested. Methods: The study aimed (1) to investigate the phenotypical and functional characteristics of Th17 and Tregs in SSc patients depending on disease manifestation (limited vs. diffuse cutaneous SSc, dcSSc) and activity, and (2) the transcriptional level and methylation status of Th17- and Treg-specific transcription factors. Results: There was a concurrent accumulation of circulating peripheral IL-17-producing CCR6+ Th cells and FoxP3+ Tregs in patients with dcSSc. At the transcriptional level, Th17- and Treg-associated transcription factors were elevated in SSc. A strong association with high circulating Th17 and Tregs was seen with early, active, and severe disease presentation. However, a diminished suppressive function on autologous lymphocytes was found in SSc-derived Tregs. Significant relative hypermethylation was seen at the gene level for RORC1 and RORC2 in SSc, particularly in patients with high inflammatory activity. Conclusions: Besides the high transcriptional activity of T cells, attributed to Treg or Th17 phenotype, in active SSc disease, Tregs may be insufficient to produce high amounts of IL-10 or to control proliferative activity of effector T cells in SSc. Our results suggest a high plasticity of Tregs strongly associated with the Th17 phenotype. Future directions may focus on enhancing Treg functions and stabilization of the Treg phenotype.}, language = {en} } @article{VamanVSPoppeHoubenetal.2015, author = {Vaman V. S., Anjana and Poppe, Heiko and Houben, Roland and Grunewald, Thomas G. P. and Goebeler, Matthias and Butt, Elke}, title = {LASP1, a Newly Identified Melanocytic Protein with a Possible Role in Melanin Release, but Not in Melanoma Progression}, series = {PLoS One}, volume = {10}, journal = {PLoS One}, number = {6}, doi = {10.1371/journal.pone.0129219}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125994}, pages = {e0129219}, year = {2015}, abstract = {The LIM and SH3 protein 1 (LASP1) is a focal adhesion protein. Its expression is increased in many malignant tumors. However, little is known about the physiological role of the protein. In the present study, we investigated the expression and function of LASP1 in normal skin, melanocytic nevi and malignant melanoma. In normal skin, a distinct LASP1 expression is visible only in the basal epidermal layer while in nevi LASP1 protein is detected in all melanocytes. Melanoma exhibit no increase in LASP1 mRNA compared to normal skin. In melanocytes, the protein is bound to dynamin and mainly localized at late melanosomes along the edges and at the tips of the cell. Knockdown of LASP1 results in increased melanin concentration in the cells. Collectively, we identified LASP1 as a hitherto unknown protein in melanocytes and as novel partner of dynamin in the physiological process of membrane constriction and melanosome vesicle release.}, language = {en} } @article{SteinkePeitschLudwigetal.2013, author = {Steinke, Sabine I. B. and Peitsch, Wiebke K. and Ludwig, Alexander and Goebeler, Matthias}, title = {Cost-of-Illness in Psoriasis: Comparing Inpatient and Outpatient Therapy}, series = {PLOS ONE}, volume = {8}, journal = {PLOS ONE}, number = {10}, issn = {1932-6203}, doi = {10.1371/journal.pone.0078152}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-128235}, pages = {e78152}, year = {2013}, abstract = {Treatment modalities of chronic plaque psoriasis have dramatically changed over the past ten years with a still continuing shift from inpatient to outpatient treatment. This development is mainly caused by outpatient availability of highly efficient and relatively well-tolerated systemic treatments, in particular BioLogicals. In addition, inpatient treatment is time-and cost-intense, conflicting with the actual burst of health expenses and with patient preferences. Nevertheless, inpatient treatment with dithranol and UV light still is a major mainstay of psoriasis treatment in Germany. The current study aims at comparing the total costs of inpatient treatment and outpatient follow-up to mere outpatient therapy with different modalities (topical treatment, phototherapy, classic systemic therapy or BioLogicals) over a period of 12 months. To this end, a retrospective cost-of-illness study was conducted on 120 patients treated at the University Medical Centre Mannheim between 2005 and 2006. Inpatient therapy caused significantly higher direct medical, indirect and total annual costs than outpatient treatment (13,042 (sic) versus 2,984 (sic)). Its strong influence on cost levels was confirmed by regression analysis, with total costs rising by 104.3\% in case of inpatient treatment. Patients receiving BioLogicals produced the overall highest costs, whereas outpatient treatment with classic systemic antipsoriatic medications was less cost-intense than other alternatives.}, language = {en} } @article{BehrPeitschHametneretal.2014, author = {Behr, Daniel S. and Peitsch, Wiebke K. and Hametner, Christian and Lasitschka, Felix and Houben, Roland and Sch{\"o}nhaar, Kathrin and Michel, Julia and Dollt, Claudia and Goebeler, Matthias and Marx, Alexander and Goerdt, Sergij and Schmieder, Astrid}, title = {Prognostic value of immune cell infiltration, tertiary lymphoid structures and PD-L1 expression in Merkel cell carcinomas}, series = {International Journal of Clinical and Experimental Pathology}, volume = {7}, journal = {International Journal of Clinical and Experimental Pathology}, number = {11}, issn = {1936-2625}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-117720}, pages = {7610-7621}, year = {2014}, abstract = {Merkel cell carcinoma (MCC) is an aggressive, virus-associated, neuroendocrine tumor of the skin mainly affecting immunocompromised patients. Higher intratumoral infiltration with CD3 and CD8 positive T-cells is associated with a better prognosis, highlighting the relevance of the immune system for MCC development and progression. In this study 21 primary MCCs were stained with immune cell markers including CD3, CD4, CD8, CD68, CD20, and S100. Furthermore, tumor-infiltrating neutrophils, tertiary lymphoid structures and PD-L1 expression were analyzed and correlated with overall and recurrence free survival. All MCCs were Merkel Cell Polyomavirus positive. Overall and recurrence-free survival did not correlate with intra-and peritumoral CD3 and CD8 T-cell infiltration. In addition, no significant association regarding prognosis was found for tumor-associated neutrophils, tumor-associated macrophages or PD-L1 positivity in MCCs. Interestingly, the presence of tertiary lymphoid structures (TLS) in the tumor microenvironment significantly correlated with recurrence-free survival (P=0.025). In addition, TLS were significantly associated with a higher CD8/CD4 ratio in the tumor periphery (P=0.032), but not in the center of the tumor (P > 0.999). These results demonstrate for the first time that TLS, easily assessed in paraffin-embedded tissue in the tumor periphery of MCCs, may be a valuable prognostic factor indicating prolonged recurrence free survival.}, language = {en} } @article{BuderGesierichGelbrichetal.2013, author = {Buder, Kristina and Gesierich, Anja and Gelbrich, G{\"o}tz and Goebeler, Matthias}, title = {Systemic treatment of metastatic uveal melanoma: review of literature and future perspectives}, series = {Cancer Medicine}, volume = {2}, journal = {Cancer Medicine}, number = {5}, doi = {10.1002/cam4.133}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97175}, pages = {674-686}, year = {2013}, abstract = {Up to 50\% of patients with uveal melanoma develop metastatic disease with poor prognosis. Regional, mainly liver-directed, therapies may induce limited tumor responses but do not improve overall survival. Response rates of metastatic uveal melanoma (MUM) to systemic chemotherapy are poor. Insights into the molecular biology of MUM recently led to investigation of new drugs. In this study, to compare response rates of systemic treatment for MUM we searched Pubmed/Web of Knowledge databases and ASCO website (1980-2013) for "metastatic/uveal/melanoma" and "melanoma/eye." Forty studies (one case series, three phase I, five pilot, 22 nonrandomized, and two randomized phase II, one randomized phase III study, data of three expanded access programs, three retrospective studies) with 841 evaluable patients were included in the numeric outcome analysis. Complete or partial remissions were observed in 39/841 patients (overall response rate [ORR] 4.6\%; 95\% confidence intervals [CI] 3.3-6.3\%), no responses were observed in 22/40 studies. Progression-free survival ranged from 1.8 to 7.2, median overall survival from 5.2 to 19.0 months as reported in 21/40 and 26/40 studies, respectively. Best responses were seen for chemoimmunotherapy (ORR 10.3\%; 95\% CI 4.8-18.7\%) though mainly in first-line patients. Immunotherapy with ipilimumab, antiangiogenetic approaches, and kinase inhibitors have not yet proven to be superior to chemotherapy. MEK inhibitors are currently investigated in a phase II trial with promising preliminary data. Despite new insights into genetic and molecular background of MUM, satisfying systemic treatment approaches are currently lacking. Study results of innovative treatment strategies are urgently awaited.}, language = {en} } @article{BuderLapaKreissletal.2014, author = {Buder, Kristina and Lapa, Constantin and Kreissl, Michael C. and Schirbel, Andreas and Herrmann, Ken and Schnack, Alexander and Br{\"o}cker, Eva-Bettina and Goebeler, Matthias and Buck, Andreas K. and Becker, J{\"u}rgen C.}, title = {"Somatostatin receptor expression in Merkel cell carcinoma as target for molecular imaging"}, doi = {10.1186/1471-2407-14-268}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-110326}, year = {2014}, abstract = {Background Merkel cell carcinoma (MCC) is a rare cutaneous neoplasm with increasing incidence, aggressive behavior and poor prognosis. Somatostatin receptors (SSTR) are expressed in MCC and represent a potential target for both imaging and treatment. Methods To non-invasively assess SSTR expression in MCC using PET and the radiotracers [68Ga]DOTA-D-Phe1-Tyr3-octreotide (DOTATOC) or -octreotate (DOTATATE) as surrogate for tumor burden. In 24 patients with histologically proven MCC SSTR-PET was performed and compared to results of computed tomography (CT). Results SSTR-PET detected primary and metastatic MCC lesions. On a patient-based analysis, sensitivity of SSTR-PET was 73\% for nodal metastases, 100\% for bone, and 67\% for soft-tissue metastases, respectively. Notably, brain metastases were initially detected by SSTR-PET in 2 patients, whereas liver and lung metastases were diagnosed exclusively by CT. SSTR-PET showed concordance to CT results in 20 out of 24 patients. Four patients (17\%) were up-staged due to SSTR-PET and patient management was changed in 3 patients (13\%). Conclusion SSTR-PET showed high sensitivity for imaging bone, soft tissue and brain metastases, and particularly in combination with CT had a significant impact on clinical stage and patient management.}, language = {en} } @article{UeberschaarGoebelerKneitz2020, author = {Ueberschaar, Simon and Goebeler, Matthias and Kneitz, Hermann}, title = {CD10-Positive Cutaneous PEComa: An Extremely Rare Skin Tumour}, series = {Case Reports in Dermatology}, volume = {12}, journal = {Case Reports in Dermatology}, doi = {10.1159/000510718}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236151}, pages = {192-198}, year = {2020}, abstract = {We here present the case of a 67-year-old woman with a history of a slowly progressive, polypous nodule on her left wrist. The lesion was excised, and the histological analysis revealed a clear cell tumour that was relatively sharply demarked from the surrounding tissue extending into the subcutaneous tissue. The tumour showed a characteristic trabecular pattern in which the tumour cells were arranged around numerous vessels. The neoplastic cells had a predominantly epithelioid shape, granular eosinophilic to clear cytoplasm and prominent centrally located nucleoli. The histological differential diagnosis included a metastatic clear-cell renal cell carcinoma and a primary cutaneous perivascular epithelioid cell tumour (PEComa). Immunohistochemically, the tumour cells revealed homogenous expression of HMB-45, MiTF and CD10, whereas MART-1 and S100 were negative. Antibodies against actin marked the trabecularly arranged vessels, and the neoplastic cells yielded a patchy positivity against actin and desmin. Additional immunohistochemical stains against pan-cytokeratin, CAIX, PAX-8 and EMA were negative. Based on the morphologic and immunophenotypic findings, the histological diagnosis of a CD10-positive cutaneous PEComa was made.}, language = {en} } @article{KolbMaeurerGoebelerMaeurer2015, author = {Kolb-M{\"a}urer, Annette and Goebeler, Matthias and M{\"a}urer, Mathias}, title = {Cutaneous adverse events associated with interferon-\(\beta\) treatment of multiple sclerosis}, series = {International Journal of Molecular Sciences}, volume = {16}, journal = {International Journal of Molecular Sciences}, doi = {10.3390/ijms160714951}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148451}, pages = {14951-14960}, year = {2015}, abstract = {Interferons are widely used platform therapies as disease-modifying treatment of patients with multiple sclerosis. Although interferons are usually safe and well tolerated, they frequently cause dermatological side effects. Here, we present a multiple sclerosis (MS) patient treated with interferon-\(\beta\) who developed new-onset psoriasis. Both her MS as well as her psoriasis finally responded to treatment with fumarates. This case illustrates that interferons not only cause local but also systemic adverse events of the skin. These systemic side effects might indicate that the Th17/IL-17 axis plays a prominent role in the immunopathogenesis of this individual case and that the autoimmune process might be deteriorated by further administration of interferons. In conclusion, we think that neurologists should be aware of systemic cutaneous side effects and have a closer look on interferon-associated skin lesions. Detection of psoriasiform lesions might indicate that interferons are probably not beneficial in the individual situation. We suggest that skin lesions may serve as biomarkers to allocate MS patients to adequate disease-modifying drugs.}, language = {en} } @article{MartinMauerMalzahnetal.2022, author = {Martin, Eva and Mauer, Isabell and Malzahn, Uwe and Heuschmann, Peter Ulrich and Goebeler, Matthias and Benoit, Sandrine}, title = {Comorbid diseases among bullous pemphigoid patients in Germany: new insights from a case-control study}, series = {Journal der Deutschen Dermatologischen Gesellschaft}, volume = {20}, journal = {Journal der Deutschen Dermatologischen Gesellschaft}, number = {6}, doi = {10.1111/ddg.14738}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318395}, pages = {798 -- 805}, year = {2022}, abstract = {Background and objectives Bullous pemphigoid (BP) is associated with neuropsychiatric disorders. Other comorbid diseases are discussed controversially. We evaluated the prevalence of comorbidity in BP patients in a representative area of Germany. Patients and methods Medical files of all BP patients treated at the Department of Dermatology, University Hospital W{\"u}rzburg, Germany, between June 2002 and May 2013 were retrospectively reviewed. Bullous pemphigoid was diagnosed based on established criteria. For each patient, two controls were individually matched. Records were evaluated for age, sex, laboratory values, concomitant medication and comorbidity. Conditional logistic regression, multivariable regression analysis and complex regression models were performed to compare results. Results 300 BP patients were identified and compared to 583 controls. Bullous pemphigoid was associated with neuropsychiatric disorders as well as laboratory abnormalities including leukocytosis and eosinophilia. Importantly, a highly significant association of BP with anemia (OR 2.127; 95 \% CI 1.532-2.953) and renal impairment (OR 2.218; 95 \% CI 1.643-2.993) was identified. No association was found with malignancy and arterial hypertension. Conclusions Our data revealed an increased frequency of anemia and renal impairment in BP patients. In accordance with previous studies the strong association for neuropsychiatric disorders was confirmed (p < 0.0005).}, 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} } @article{WobserSchummerAppenzelleretal.2022, author = {Wobser, Marion and Schummer, Patrick and Appenzeller, Silke and Kneitz, Hermann and Roth, Sabine and Goebeler, Matthias and Geissinger, Eva and Rosenwald, Andreas and Maurus, Katja}, title = {Panel sequencing of primary cutaneous B-cell lymphoma}, series = {Cancers}, volume = {14}, journal = {Cancers}, number = {21}, issn = {2072-6694}, doi = {10.3390/cancers14215274}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-290330}, year = {2022}, abstract = {Background: Primary cutaneous follicular B-cell lymphoma (PCFBCL) represents an indolent subtype of Non-Hodgkin's lymphomas, being clinically characterized by slowly growing tumors of the skin and common cutaneous relapses, while only exhibiting a low propensity for systemic dissemination or fatal outcome. Up to now, only few studies have investigated underlying molecular alterations of PCFBCL with respect to somatic mutations. Objectives: Our aim was to gain deeper insight into the pathogenesis of PCFBCL and to delineate discriminatory molecular features of this lymphoma subtype. Methods: We performed hybridization-based panel sequencing of 40 lymphoma-associated genes of 10 cases of well-characterized PCFBCL. In addition, we included two further ambiguous cases of atypical B-cell-rich lymphoid infiltrate/B-cell lymphoma of the skin for which definite subtype attribution had not been possible by routine investigations. Results: In 10 out of 12 analyzed cases, we identified genetic alterations within 15 of the selected 40 target genes. The most frequently detected alterations in PCFBCL affected the TNFRSF14, CREBBP, STAT6 and TP53 genes. Our analysis unrevealed novel mutations of the BCL2 gene in PCFBCL. All patients exhibited an indolent clinical course. Both the included arbitrary cases of atypical B-cell-rich cutaneous infiltrates showed somatic mutations within the FAS gene. As these mutations have previously been designated as subtype-specific recurrent alterations in primary cutaneous marginal zone lymphoma (PCMZL), we finally favored the diagnosis of PCMZL in these two cases based on these molecular findings. Conclusions: To conclude, our molecular data support that PCFBCL shows distinct somatic mutations which may aid to differentiate PCFBCL from pseudo-lymphoma as well as from other indolent and aggressive cutaneous B-cell lymphomas. While the detected genetic alterations of PCFBCL did not turn out to harbor any prognostic value in our cohort, our molecular data may add adjunctive discriminatory features for diagnostic purposes on a molecular level.}, language = {en} } @article{SchoenBerkingBiedermannetal.2020, author = {Sch{\"o}n, Michael P. and Berking, Carola and Biedermann, Tilo and Buhl, Timo and Erpenbeck, Luise and Eyerich, Kilian and Eyerich, Stefanie and Ghoreschi, Kamran and Goebeler, Matthias and Ludwig, Ralf J. and Sch{\"a}kel, Knut and Schilling, Bastian and Schlapbach, Christoph and Stary, Georg and von Stebut, Esther and Steinbrink, Kerstin}, title = {COVID-19 and immunological regulations - from basic and translational aspects to clinical implications}, series = {JDDG: Journal der Deutschen Dermatologischen Gesellschaft}, volume = {18}, journal = {JDDG: Journal der Deutschen Dermatologischen Gesellschaft}, number = {8}, doi = {10.1111/ddg.14169}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218205}, pages = {795 -- 807}, year = {2020}, abstract = {The COVID-19 pandemic caused by SARS-CoV-2 has far-reaching direct and indirect medical consequences. These include both the course and treatment of diseases. It is becoming increasingly clear that infections with SARS-CoV-2 can cause considerable immunological alterations, which particularly also affect pathogenetically and/or therapeutically relevant factors. Against this background we summarize here the current state of knowledge on the interaction of SARS-CoV-2/COVID-19 with mediators of the acute phase of inflammation (TNF, IL-1, IL-6), type 1 and type 17 immune responses (IL-12, IL-23, IL-17, IL-36), type 2 immune reactions (IL-4, IL-13, IL-5, IL-31, IgE), B-cell immunity, checkpoint regulators (PD-1, PD-L1, CTLA4), and orally druggable signaling pathways (JAK, PDE4, calcineurin). In addition, we discuss in this context non-specific immune modulation by glucocorticosteroids, methotrexate, antimalarial drugs, azathioprine, dapsone, mycophenolate mofetil and fumaric acid esters, as well as neutrophil granulocyte-mediated innate immune mechanisms. From these recent findings we derive possible implications for the therapeutic modulation of said immunological mechanisms in connection with SARS-CoV-2/COVID-19. Although, of course, the greatest care should be taken with patients with immunologically mediated diseases or immunomodulating therapies, it appears that many treatments can also be carried out during the COVID-19 pandemic; some even appear to alleviate COVID-19.}, language = {en} } @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{HuttelmaierBenoitGoebeler2023, author = {Huttelmaier, Johanna and Benoit, Sandra and Goebeler, Matthias}, title = {Comorbidity in bullous pemphigoid: up-date and clinical implications}, series = {Frontiers in Immunology}, volume = {14}, journal = {Frontiers in Immunology}, doi = {10.3389/fimmu.2023.1196999}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-321671}, year = {2023}, abstract = {Bullous pemphigoid is the most common autoimmune blistering disease in industrialized countries and particularly affects the elderly. In this patient population, comorbid diseases are frequent and may complicate management and treatment of bullous pemphigoid. A better understanding why distinct diseases are more frequent in bullous pemphigoid patients may lead to new pathophysiological insights and - as a consequence - result in better patient care. The association of bullous pemphigoid with neurological and psychiatric diseases is well known and confirmed by several case-control studies. Association with further diseases such as malignancy and metabolic diseases are still discussed controversially. In recent years new relationships between bullous pemphigoid and autoimmune as well as inflammatory skin diseases have been reported. This review provides a systematic overview on studies addressing comorbidity in bullous pemphigoid patients. Increasing the awareness of both, common and rare comorbid diseases, may enable clinicians to optimize patient support and individualized treatment of bullous 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} }