TY - JOUR A1 - Bauer, Boris A1 - Goebeler, Matthias A1 - Weissbrich, Benedikt A1 - Kerstan, Andreas T1 - Kerinokeratosis papulosa of childhood JF - Dermatology N2 - 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. KW - Waxy papulosis of childhood KW - Human papillomavirus KW - EVER1 KW - EVER2 KW - Kerinokeratosis papulosa Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-198997 SN - 1018-8665 SN - 1421-9832 N1 - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively. VL - 231 IS - 1 SP - 1 EP - 4 ER - TY - JOUR A1 - Almanzar, Giovanni A1 - Klein, Matthias A1 - Schmalzing, Marc A1 - Hilligardt, Deborah A1 - El Hajj, Nady A1 - Kneitz, Hermann A1 - Wild, Vanessa A1 - Rosenwald, Andreas A1 - Benoit, Sandrine A1 - Hamm, Henning A1 - Tony, Hans-Peter A1 - Haaf, Thomas A1 - Goebeler, Matthias A1 - Prelog, Martina T1 - Disease Manifestation and Inflammatory Activity as Modulators of Th17/Treg Balance and RORC/FoxP3 Methylation in Systemic Sclerosis JF - International Archives of Allergy and Immunology N2 - 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. KW - methylation KW - systemic sclerosis KW - suppression KW - Tregs KW - Th17 Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196577 SN - 1018-2438 SN - 1423-0097 N1 - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively. VL - 171 IS - 2 ER - TY - JOUR A1 - Vaman V. S., Anjana A1 - Poppe, Heiko A1 - Houben, Roland A1 - Grunewald, Thomas G. P. A1 - Goebeler, Matthias A1 - Butt, Elke T1 - LASP1, a Newly Identified Melanocytic Protein with a Possible Role in Melanin Release, but Not in Melanoma Progression JF - PLoS One N2 - 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. KW - cell membranes KW - vesicles KW - melanoma cells KW - melanomas KW - melanocytes KW - membrane proteins KW - melanin KW - cell staining Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125994 VL - 10 IS - 6 ER - TY - JOUR A1 - Steinke, Sabine I. B. A1 - Peitsch, Wiebke K. A1 - Ludwig, Alexander A1 - Goebeler, Matthias T1 - Cost-of-Illness in Psoriasis: Comparing Inpatient and Outpatient Therapy JF - PLOS ONE N2 - 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. KW - plaque-type psoriasis KW - health-care costs KW - patient preferences KW - disease severity KW - United States KW - moderate KW - life KW - multicenter KW - biologics KW - Germany Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128235 SN - 1932-6203 VL - 8 IS - 10 ER - TY - JOUR A1 - Behr, Daniel S. A1 - Peitsch, Wiebke K. A1 - Hametner, Christian A1 - Lasitschka, Felix A1 - Houben, Roland A1 - Schönhaar, Kathrin A1 - Michel, Julia A1 - Dollt, Claudia A1 - Goebeler, Matthias A1 - Marx, Alexander A1 - Goerdt, Sergij A1 - Schmieder, Astrid T1 - Prognostic value of immune cell infiltration, tertiary lymphoid structures and PD-L1 expression in Merkel cell carcinomas JF - International Journal of Clinical and Experimental Pathology N2 - 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. KW - CD8(+) KW - PD-L1 KW - tertiary lymphoid structures KW - immune cell infiltration KW - polymavirus KW - survival KW - lymphocytes KW - responses KW - lung cancer KW - B-cells KW - breast cancer KW - antitumor immunity KW - T-antigens KW - Merkel cell carcinoma Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117720 SN - 1936-2625 VL - 7 IS - 11 ER - TY - JOUR A1 - Buder, Kristina A1 - Gesierich, Anja A1 - Gelbrich, Götz A1 - Goebeler, Matthias T1 - Systemic treatment of metastatic uveal melanoma: review of literature and future perspectives JF - Cancer Medicine N2 - 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. KW - Clinical trials KW - drug therapy KW - metastatic KW - review KW - uveal melanoma Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-97175 VL - 2 IS - 5 ER - TY - JOUR A1 - Buder, Kristina A1 - Lapa, Constantin A1 - Kreissl, Michael C. A1 - Schirbel, Andreas A1 - Herrmann, Ken A1 - Schnack, Alexander A1 - Bröcker, Eva-Bettina A1 - Goebeler, Matthias A1 - Buck, Andreas K. A1 - Becker, Jürgen C. T1 - "Somatostatin receptor expression in Merkel cell carcinoma as target for molecular imaging" N2 - 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. KW - Merkel cell carcinoma KW - Molecular imaging KW - Somatostatin receptor expression KW - Positron emission tomography Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-110326 ER - TY - JOUR A1 - Ueberschaar, Simon A1 - Goebeler, Matthias A1 - Kneitz, Hermann T1 - CD10-Positive Cutaneous PEComa: An Extremely Rare Skin Tumour JF - Case Reports in Dermatology N2 - 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. KW - PEComa KW - cutaneous PEComa KW - Skin KW - CD10 KW - perivascular epitheloid cell tumour Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236151 VL - 12 ER - TY - JOUR A1 - Kolb-Mäurer, Annette A1 - Goebeler, Matthias A1 - Mäurer, Mathias T1 - Cutaneous adverse events associated with interferon-\(\beta\) treatment of multiple sclerosis JF - International Journal of Molecular Sciences N2 - 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. KW - autoimmune diseases KW - psoriasis KW - cutaneous adverse events KW - utaneous adverse events KW - interferon-\(\beta\) KW - multiple sclerosis KW - lesions KW - therapy KW - experience KW - skin reactions KW - improvement Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148451 VL - 16 ER - TY - JOUR A1 - Martin, Eva A1 - Mauer, Isabell A1 - Malzahn, Uwe A1 - Heuschmann, Peter Ulrich A1 - Goebeler, Matthias A1 - Benoit, Sandrine T1 - Comorbid diseases among bullous pemphigoid patients in Germany: new insights from a case-control study JF - Journal der Deutschen Dermatologischen Gesellschaft N2 - 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 Würzburg, 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). KW - bullous pemphigoid KW - comorbid diseases KW - Germany Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318395 VL - 20 IS - 6 SP - 798 EP - 805 ER - TY - JOUR A1 - Kneitz, Hermann A1 - Rose, Christian A1 - Glutsch, Valerie A1 - Goebeler, Matthias T1 - Recurrence of a cellular blue nevus with satellitosis — a diagnostic pitfall with clinical consequences JF - Dermatopathology N2 - 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. KW - common blue nevus KW - cell rich blue nevus KW - satellitosis KW - immunohistochemistry KW - skin Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-297436 SN - 2296-3529 VL - 9 IS - 4 SP - 361 EP - 367 ER - TY - JOUR A1 - Rak, Katrin A1 - Hamm, Henning A1 - Kerstan, Andreas A1 - Kolb-Mäurer, Annette A1 - Goebeler, Matthias T1 - Severe and prolonged liver damage in pityriasis rubra pilaris treated with acitretin: a case report JF - SN Comprehensive Clinical Medicine N2 - 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. KW - acitretin KW - pityriasis rubra pilaris KW - drug-induced liver injury (DILI) KW - adverse event Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-323982 VL - 4 IS - 1 ER - TY - JOUR A1 - Wobser, Marion A1 - Schummer, Patrick A1 - Appenzeller, Silke A1 - Kneitz, Hermann A1 - Roth, Sabine A1 - Goebeler, Matthias A1 - Geissinger, Eva A1 - Rosenwald, Andreas A1 - Maurus, Katja T1 - Panel sequencing of primary cutaneous B-cell lymphoma JF - Cancers N2 - 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. KW - B-cell lymphoma KW - primary cutaneous follicular B-cell lymphoma KW - targeted sequencing Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-290330 SN - 2072-6694 VL - 14 IS - 21 ER - TY - JOUR A1 - Schön, Michael P. A1 - Berking, Carola A1 - Biedermann, Tilo A1 - Buhl, Timo A1 - Erpenbeck, Luise A1 - Eyerich, Kilian A1 - Eyerich, Stefanie A1 - Ghoreschi, Kamran A1 - Goebeler, Matthias A1 - Ludwig, Ralf J. A1 - Schäkel, Knut A1 - Schilling, Bastian A1 - Schlapbach, Christoph A1 - Stary, Georg A1 - von Stebut, Esther A1 - Steinbrink, Kerstin T1 - COVID‐19 and immunological regulations – from basic and translational aspects to clinical implications JF - JDDG: Journal der Deutschen Dermatologischen Gesellschaft N2 - 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. KW - COVID-19 KW - SARS-CoV-2 KW - immunology Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218205 VL - 18 IS - 8 SP - 795 EP - 807 ER - TY - JOUR A1 - Wendlinger, Simone A1 - Wohlfarth, Jonas A1 - Kreft, Sophia A1 - Siedel, Claudia A1 - Kilian, Teresa A1 - Dischinger, Ulrich A1 - Heppt, Markus V. A1 - Wistuba-Hamprecht, Kilian A1 - Meier, Friedegund A1 - Goebeler, Matthias A1 - Schadendorf, Dirk A1 - Gesierich, Anja A1 - Kosnopfel, Corinna A1 - Schilling, Bastian T1 - Blood eosinophils are associated with efficacy of targeted therapy in patients with advanced melanoma JF - Cancers N2 - 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. KW - melanoma KW - eosinophils KW - biomarker Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-275137 SN - 2072-6694 VL - 14 IS - 9 ER - TY - JOUR A1 - Buhl, Timo A1 - Beissert, Stefan A1 - Gaffal, Evelyn A1 - Goebeler, Matthias A1 - Hertl, Michael A1 - Mauch, Cornelia A1 - Reich, Kristian A1 - Schmidt, Enno A1 - Schön, Michael P. A1 - Sticherling, Michael A1 - Sunderkötter, Cord A1 - Traidl‐Hoffmann, Claudia A1 - Werfel, Thomas A1 - Wilsman‐Theis, Dagmar A1 - Worm, Margitta T1 - COVID‐19 and implications for dermatological and allergological diseases JF - JDDG: Journal der Deutschen Dermatologischen Gesellschaft N2 - 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. KW - COVID-19 KW - dermatology KW - allergies Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-217860 VL - 18 IS - 8 SP - 815 EP - 824 ER - TY - JOUR A1 - Benoit, Sandrine A1 - Scheurlen, Michael A1 - Goebeler, Matthias A1 - Stoevesandt, Johanna T1 - Structured diagnostic approach and risk assessment in mucous membrane pemphigoid with oesophageal involvement JF - Acta Dermato-Venereologica N2 - 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 Würzburg. 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. KW - cicatricial pemphigoid KW - mucous membrane pemphigoid KW - oesophagogastroduodenoscopy KW - laminin 332 Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176191 VL - 98 ER - TY - JOUR A1 - Huttelmaier, Johanna A1 - Benoit, Sandra A1 - Goebeler, Matthias T1 - Comorbidity in bullous pemphigoid: up-date and clinical implications JF - Frontiers in Immunology N2 - 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. KW - bullous pemphigoid KW - autoimmune skin blistering disease KW - comorbidity KW - neurologic disease KW - metabolic disease KW - malignancy KW - inflammatory disease Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-321671 VL - 14 ER - TY - JOUR A1 - Frings, Verena Gerlinde A1 - Schöffski, Oliver A1 - Goebeler, Matthias A1 - Presser, Dagmar T1 - Economic analysis of the costs associated with Hidradenitis suppurativa at a German University Hospital JF - PLoS One N2 - 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 Würzburg, 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. KW - inpatients KW - outpatients KW - health insurance KW - dermatology KW - surgical and invasive medical procedures KW - health economics KW - psoriasis KW - indirect costs Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-261668 VL - 16 IS - 8 ER - TY - JOUR A1 - Glutsch, Valerie A1 - Wobser, Marion A1 - Schilling, Bastian A1 - Gesierich, Anja A1 - Goebeler, Matthias A1 - Kneitz, Hermann T1 - PRAME expression as helpful immunohistochemical marker in rhabdoid melanoma JF - Dermatopathology N2 - 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. KW - PRAME KW - rhabdoid differentiation KW - rhabdoid melanoma KW - immunohistochemistry KW - melanocytic markers Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284115 SN - 2296-3529 VL - 9 IS - 2 SP - 148 EP - 157 ER -