@article{SchaeferBauerDonhauseretal.2017, author = {Sch{\"a}fer, Kristina and Bauer, Boris and Donhauser, Julian and Kerstan, Andreas and Hamm, Henning}, title = {Becker Naevus Syndrome of the Lower Body: A New Case and Review of the Literature}, series = {Acta Dermato-Venereologica}, volume = {97}, journal = {Acta Dermato-Venereologica}, number = {4}, doi = {10.2340/00015555-2589}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171057}, pages = {499-504}, year = {2017}, abstract = {Becker naevus syndrome is a rare epidermal naevus syndrome defined by the co-occurrence of a Becker naevus with various cutaneous, muscular and skeletal anomalies. In the majority of cases, abnormalities exclusively consist of ipsilateral hypoplasia of the breast, areola and/or nipple in addition to the naevus. Here, we report on a 42-year-old woman with an extensive Becker naevus reaching from the left buttock to the left calf verified on histological examination. In addition, there was marked hypoplasia of the fatty tissue of the left thigh confirmed by magnetic resonance imaging in contrast to hyperplasia of the fatty tissue of the left gluteal area. Underlying muscles and bones were not affected. There was no difference in leg lengths. In addition, we review and discuss the features of Becker naevus syndrome with emphasis on 10 reported cases with involvement of the lower body.}, language = {en} } @article{PanayotovaDimitrovaFeoktistovaPloesseretal.2013, author = {Panayotova-Dimitrova, Diana and Feoktistova, Maria and Ploesser, Michaela and Kellert, Beate and Hupe, Mike and Horn, Sebastian and Makarov, Roman and Jensen, Federico and Porubsky, Stefan and Schmieder, Astrid and Zenclussen, Ana Claudia and Marx, Alexander and Kerstan, Andreas and Geserick, Peter and He, You-Wen and Leverkus, Martin}, title = {cFLIP Regulates Skin Homeostasis and Protects against TNF-Induced Keratinocyte Apoptosis}, series = {Cell Reports}, volume = {5}, journal = {Cell Reports}, doi = {10.1016/j.celrep.2013.09.035}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-122155}, pages = {397-408}, year = {2013}, abstract = {FADD, caspase-8, and cFLIP regulate the outcome of cell death signaling. Mice that constitutively lack these molecules die at an early embryonic age, whereas tissue-specific constitutive deletion of FADD or caspase-8 results in inflammatory skin disease caused by increased necroptosis. The function of cFLIP in the skin in vivo is unknown. In contrast to tissue-specific caspase-8 knockout, we show that mice constitutively lacking cFLIP in the epidermis die around embryonic days 10 and 11. When cFLIP expression was abrogated in adult skin of cFLIP(fl/fl)-K14CreER(tam) mice, severe inflammation of the skin with concomitant caspase activation and apoptotic, but not necroptotic, cell death developed. Apoptosis was dependent of autocrine tumor necrosis factor production triggered by loss of cFLIP. In addition, epidermal cFLIP protein was lost in patients with severe drug reactions associated with epidermal apoptosis. Our data demonstrate the importance of cFLIP for the integrity of the epidermis and for silencing of spontaneous skin inflammation.}, language = {en} } @article{ThomannSchneiderCyranetal.2021, author = {Thomann, Anna Sophie and Schneider, Theresa and Cyran, Laura and Eckert, Ina Nathalie and Kerstan, Andreas and Lutz, Manfred B.}, title = {Conversion of Anergic T Cells Into Foxp3\(^-\) IL-10\(^+\) Regulatory T Cells by a Second Antigen Stimulus In Vivo}, series = {Frontiers in Immunology}, volume = {12}, journal = {Frontiers in Immunology}, issn = {1664-3224}, doi = {10.3389/fimmu.2021.704578}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-241429}, year = {2021}, abstract = {T cell anergy is a common mechanism of T cell tolerance. However, although anergic T cells are retained for longer time periods in their hosts, they remain functionally passive. Here, we describe the induction of anergic CD4\(^+\) T cells in vivo by intravenous application of high doses of antigen and their subsequent conversion into suppressive Foxp3\(^-\) IL-10\(^+\) Tr1 cells but not Foxp3\(^+\) Tregs. We describe the kinetics of up-regulation of several memory-, anergy- and suppression-related markers such as CD44, CD73, FR4, CD25, CD28, PD-1, Egr-2, Foxp3 and CTLA-4 in this process. The conversion into suppressive Tr1 cells correlates with the transient intracellular CTLA-4 expression and required the restimulation of anergic cells in a short-term time window. Restimulation after longer time periods, when CTLA-4 is down-regulated again retains the anergic state but does not lead to the induction of suppressor function. Our data require further functional investigations but at this stage may suggest a role for anergic T cells as a circulating pool of passive cells that may be re-activated into Tr1 cells upon short-term restimulation with high and systemic doses of antigen. It is tentative to speculate that such a scenario may represent cases of allergen responses in non-allergic individuals.}, language = {en} } @article{CyranSerflingKirschneretal.2022, author = {Cyran, Laura and Serfling, Julia and Kirschner, Luisa and Raifer, Hartmann and Lohoff, Michael and Hermanns, Heike M. and Kerstan, Andreas and Bodem, Jochen and Lutz, Manfred B.}, title = {Flt3L, LIF, and IL-10 combination promotes the selective in vitro development of ESAM\(^{low}\) cDC2B from murine bone marrow}, series = {European Journal of Immunology}, volume = {52}, journal = {European Journal of Immunology}, number = {12}, doi = {10.1002/eji.202149663}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312448}, pages = {1946 -- 1960}, year = {2022}, abstract = {The development of two conventional dendritic cells (DC) subsets (cDC1 and cDC2) and the plasmacytoid DC (pDC) in vivo and in cultures of bone marrow (BM) cells is mediated by the growth factor Flt3L. However, little is known about the factors that direct the development of the individual DC subsets. Here, we describe the selective in vitro generation of murine ESAM\(^{low}\) CD103\(^{-}\) XCR1\(^{-}\) CD172a\(^{+}\) CD11b\(^{+}\) cDC2 from BM by treatment with a combination of Flt3L, LIF, and IL-10 (collectively named as FL10). FL10 promotes common dendritic cell progenitors (CDP) proliferation in the cultures, similar to Flt3L and CDP sorted and cultured in FL10 generate exclusively cDC2. These cDC2 express the transcription factors Irf4, Klf4, and Notch2, and their growth is reduced using BM from Irf4\(^{-/-}\) mice, but the expression of Batf3 and Tcf4 is low. Functionally they respond to TLR3, TLR4, and TLR9 signals by upregulation of the surface maturation markers MHC II, CD80, CD86, and CD40, while they poorly secrete proinflammatory cytokines. Peptide presentation to TCR transgenic OT-II cells induced proliferation and IFN-γ production that was similar to GM-CSF-generated BM-DC and higher than Flt3L-generated DC. Together, our data support that FL10 culture of BM cells selectively promotes CDP-derived ESAM\(^{low}\) cDC2 (cDC2B) development and survival in vitro.}, language = {en} } @article{GrundmeierHammWeissbrichetal.2012, author = {Grundmeier, Natalie and Hamm, Henning and Weissbrich, Benedikt and Lang, Sabrina Christine and Br{\"o}cker, Eva-Bettina and Kerstan, Andreas}, title = {High-risk human papillomavirus infection in Bowen's disease of the nail unit: report of three cases and review of the literature}, series = {Dermatology}, volume = {223}, journal = {Dermatology}, number = {4}, issn = {1018-8665}, doi = {10.1159/000335371}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196638}, pages = {293 -- 300}, year = {2012}, abstract = {Background: Bowen's disease (BD) of the nail unit is associated with human papillomavirus (HPV) infection. Objective: This study aimed to investigate the frequency of high-risk HPV infection, gender, age and digital distribution in this condition. Methods: Biopsy specimens of 3 consecutive cases with periungual BD were investigated for the presence of HPV DNA by in situ hybridization and by polymerase chain reaction (PCR). Furthermore, 74 cases of ungual BD conducted with HPV genotyping as reported in the literature were reviewed. Results: PCR of biopsy specimens revealed in 2 cases infection with HPV-16 and in 1 case with HPV-73. Additionally, in 1 HPV-16-positive case HPV-31/33 was detected by in situ hybridization. In line, review of the literature demonstrated a clear association of HPV-positive BD with high-risk HPV types. Interestingly, age at diagnosis was significantly lower in women. Whereas in both genders the second to fourth fingers on both hands were commonly diseased, only in men the thumbs were also prominently affected. Conclusions: Infection with high-risk HPV types is common in BD of the nail unit suggesting the aetiological cause. Therefore, patients and partners should be closely followed up for digital and genital HPV-associated lesions.}, language = {en} } @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{IckrathStoevesandtSchulmeyeretal.2021, author = {Ickrath, Franziska and Stoevesandt, Johanna and Schulmeyer, Lena and Glatzel, Caroline and Goebeler, Matthias and Kerstan, Andreas}, title = {Metastatic Crohn's disease: an underestimated entity}, series = {Journal of the German Society of Dermatology}, volume = {19}, journal = {Journal of the German Society of Dermatology}, number = {7}, doi = {10.1111/ddg.14447}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258435}, pages = {973-982}, year = {2021}, abstract = {Cutaneous metastatic Crohn's disease (MCD) is a rare but challenging dermatologic manifestation of Crohn's disease. It is histologically defined as the presence of non-caseating granulomas at skin sites separated from and non-contiguous to the gastrointestinal tract. Cutaneous metastatic Crohn's disease should be distinguished from the much more frequent contiguous cutaneous manifestations of Crohn's disease that present at perianal or, less common, peristomal sites with direct extension from the intestine to the adjacent skin. Versatile clinical presentation and the fact that occurrence can predate the initial diagnosis of Crohn's disease may lead to misdiagnosis, delayed treatment and underreporting. As case numbers are small and randomized controlled studies on management are lacking, the therapeutic approach remains challenging and is often unsatisfactory. We here performed a systematic literature search identifying 264 published pediatric and adult cases of MCD and additionally report three of our own cases. Our review summarizes clinical characteristics, putative etiopathology, histologic findings, differential diagnoses and treatment options for MCD.}, language = {en} } @article{AlrefaiMuhammadRudolfetal.2016, author = {Alrefai, Hani and Muhammad, Khalid and Rudolf, Ronald and Pham, Duong Anh Thuy and Klein-Hessling, Stefan and Patra, Amiya K. and Avots, Andris and Bukur, Valesca and Sahin,, Ugur and Tenzer, Stefan and Goebeler, Matthias and Kerstan, Andreas and Serfling, Edgar}, title = {NFATc1 supports imiquimod-induced skin inflammation by suppressing IL-10 synthesis in B cells}, series = {Nature Communications}, volume = {7}, journal = {Nature Communications}, doi = {10.1038/ncomms11724}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173053}, year = {2016}, abstract = {Epicutaneous application of Aldara cream containing the TLR7 agonist imiquimod (IMQ) to mice induces skin inflammation that exhibits many aspects of psoriasis, an inflammatory human skin disease. Here we show that mice depleted of B cells or bearing interleukin (IL)-10-deficient B cells show a fulminant inflammation upon IMQ exposure, whereas ablation of NFATc1 in B cells results in a suppression of Aldara-induced inflammation. In vitro, IMQ induces the proliferation and IL-10 expression by B cells that is blocked by BCR signals inducing NFATc1. By binding to HDAC1, a transcriptional repressor, and to an intronic site of the Il10 gene, NFATc1 suppresses IL-10 expression that dampens the production of tumour necrosis factor-α and IL-17 by T cells. These data indicate a close link between NFATc1 and IL-10 expression in B cells and suggest NFATc1 and, in particular, its inducible short isoform, NFATc1/αA, as a potential target to treat human psoriasis.}, language = {en} } @article{HeitmannFringsGeieretal.2021, author = {Heitmann, Johanna and Frings, Verena G. and Geier, Andreas and Goebeler, Matthias and Kerstan, Andreas}, title = {Non-alcoholic fatty liver disease and psoriasis - is there a shared proinflammatory network?}, series = {Journal der Deutschen Dermatologischen Gesellschaft}, volume = {19}, journal = {Journal der Deutschen Dermatologischen Gesellschaft}, number = {4}, doi = {10.1111/ddg.14425}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258424}, pages = {517-528}, year = {2021}, abstract = {Psoriasis is an immune-mediated systemic inflammatory disease that is not limited to the skin but may be associated with arthritis, cardiovascular diseases, metabolic syndrome including diabetes and obesity and, as identified more recently, non-alcoholic fatty liver disease (NAFLD) that occurs in approximately 50 \% of all patients with psoriasis. NAFLD is characterized by accumulation of fat in hepatocytes in the absence of excessive alcohol consumption. Over the last two decades, NAFLD has developed to the most common chronic liver disease with an estimated prevalence of 25 \% in the Western population. NAFLD ranges from non-inflammatory or bland hepatic steatosis to inflammation of hepatic tissue (non-alcoholic steatohepatitis, NASH) and consecutive liver fibrosis. It is controversial whether the underlying systemic inflammation of psoriasis is contributing to development of NAFLD or if comorbid diseases such as obesity enhance NAFLD development. Recent findings indicate that cytokine-mediated inflammation through TNFα, interleukin (IL)-6 and IL-17 might be the common link between psoriasis and NAFLD. Considering the shared inflammatory pathways, IL-17 pharmacological blockade, which is already well-established for psoriasis, may be a promising strategy to treat both psoriasis and NAFLD. Therefore, early detection of NAFLD and a better understanding of its pathophysiology in the context of the systemic inflammation in psoriasis is important with regard to individualized treatment approaches.}, language = {en} } @article{StoevesandtHospKerstanetal.2017, author = {Stoevesandt, Johanna and Hosp, Christine and Kerstan, Andreas and Trautmann, Axel}, title = {Safety of 100 µg venom immunotherapy rush protocols in children compared to adults}, series = {Allergy, Asthma \& Clinical Immunology}, volume = {13}, journal = {Allergy, Asthma \& Clinical Immunology}, number = {32}, doi = {10.1186/s13223-017-0204-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157830}, year = {2017}, abstract = {Background: There is a paucity of studies examining the safety of venom immunotherapy (VIT) in children. We aimed to assess the incidence of anaphylactic side effects during rush VIT in a cohort of pediatric patients and adult controls. Methods: 72 consecutive cycles of VIT-buildup in 71 children/adolescents aged 7-17 years were retrospectively evaluated and compared to an adult control group (n = 981) with regard to baseline parameters (sex, causative venom, severity of index sting reaction, results of allergy testing, comorbidities) and the incidence of anaphylactic adverse reactions. Results: Compared to adults, severe index sting-induced anaphylaxis was significantly less common in children (P = .001). Children were more likely to suffer from bee venom allergy (P < .001) and showed higher levels of bee venom-specific IgE (P = .013), but lower serum tryptase concentrations (P = .014). The overall rate of VIT-induced anaphylactic reactions was higher in children than in adults (6.9\% vs 2.5\%, P = .046 by univariate analysis). In the final binary logistic regression model, however, only bee VIT (P = .039; odds ratio 2.25; confidence interval 1.04-4.87) and 5-day compared to 3-day buildup protocols (P = .011; odds ratio 2.64; confidence interval 1.25-5.57) were associated with an increased risk of treatment-induced anaphylaxis. All pediatric patients finally reached and tolerated the target maintenance dose of 100 µg. Conclusions: The higher anaphylactic reaction rate observed in pediatric patients may be attributed to a greater prevalence of bee venom allergy. VIT-induced anaphylaxis in children is usually mild and does not affect further updosing and maintenance of VIT.}, language = {en} }