Holger A Haenssle

Georg-August-Universität Göttingen, Göttingen, Lower Saxony, Germany

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Publications (55)127.28 Total impact

  • Journal der Deutschen Dermatologischen Gesellschaft 02/2014; · 1.40 Impact Factor
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    ABSTRACT: Optimized delivery of antigens combined with sustainable maturation of dendritic cells (DCs) is crucial for generation of effective antitumoral immune responses. Multiple approaches for ex vivo antigen loading and improvement in immunogenicity have been described. We have recently established a single-step protocol consisting of a fusion peptide (a sequence of the melanoma antigen Melan-A and a cationic cell-penetrating HIV TAT domain) bound in complexes with a toll-like receptor agonist. As the exact cellular uptake mechanisms of TAT-coupled antigens have been a matter of considerable debate and significantly depend on cell type, cargo and concentrations, we evaluated internalization routes into human immature DCs in comparison with non-phagocytic cell lines. We found that Melan-A-TAT fusion peptide uptake by DCs is mainly energy dependent, superior compared with polylysine-coupled Melan-A and significantly higher in DCs as compared with Jurkat cells or HUVECs. Furthermore, we could track the uptake of the fusion peptide exclusively through early endosomes to lysosome compartments after 90 min by fluorescence microscopy and immunoelectron microscopy. Specific endocytosis inhibitors revealed major internalization of the fusion peptide by DCs via clathrin-mediated endocytosis, whereas uptake by non-phagocytic HUVECs differed significantly, involving macropinocytosis as well as clathrin-mediated endocytosis. As our understanding of the processes involved in internalization of TAT-coupled cargos by human DCs broadens, and DC activation becomes available by single-step procedures as described, further development of simultaneous DC maturation and intra-cellular peptide targeting is warranted.
    Experimental Dermatology 01/2014; 23(1):20-6. · 3.58 Impact Factor
  • Der Hautarzt 12/2013; 64(12):946-948. · 0.50 Impact Factor
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    ABSTRACT: Background: D-dimer analysis and clinical probability scoring (Wells-score) show a high sensitivity and negative predictive value for the exclusion of deep vein thrombosis (DVT). Objective: To identify the diagnostic performance of D-dimer testing and Wells-score in hospitalized patients with dermatologic conditions. Methods: In this retrospective cohort study, 109 examinations in 102 patients were performed by Wells-score, Tina-quant(®) D-dimer testing and whole-leg duplex ultrasonography or phlebography. Results: DVT was confirmed in 14 patients. The Wells-score alone allowed no discrimination of DVT and non-DVT patients. D-dimer testing identified all cases of DVT (100% sensitivity). Only 16 patients showed D-dimers within normal limits and none was diagnosed with DVT (100% negative predictive value). A high rate of false-positive D-dimer results (72%) led to a low specificity (17%). The number needed-to-test to exclude one DVT was 6.8. Based on multivariate statistical analysis, increased D-dimer levels were significantly associated with the dermatologic main diagnosis (p = 0.008), age (p = 0.001) and with the presence of DVT (p = 0.011). The highest D-dimer values were found in non-DVT patients with metastasized or systemic malignancies (median 2.48 mg/L) or inflammatory skin conditions (e.g. generalized psoriasis, median 2.22 mg/L). Conclusions: Wells-score and D-Dimer testing were of limited diagnostic value because of many false-positive results. Required imaging procedures were reduced by only 16 cases (15%). Therefore, we suggest directly investigating hospitalized dermatologic patients with suspected DVT and skin diseases associated with high D-Dimer levels, by whole-leg compression ultrasonography.
    European journal of dermatology : EJD. 11/2013;
  • Journal der Deutschen Dermatologischen Gesellschaft 10/2013; · 1.40 Impact Factor
  • M Jantke, C Has, H A Haenssle, M P Schön, S Emmert
    Clinical and Experimental Dermatology 06/2013; · 1.33 Impact Factor
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    ABSTRACT: Plasma in the sense of ionized gas can be referred to as the fourth state of matter following solids, liquids, and gases in view of their energy content. Application of high voltages across small gas filled spaces results in ionization of the air. Generally, two types of cold plasma can be discerned: direct plasma (e.g. dielectric barrier discharge—DBD) and indirect plasma (plasma torch, plasma jet). In indirect plasma treatment, the plasma is produced in a remote cavity and ejected by gas flow onto the skin in the form of an effluent. In direct plasma treatment, the skin itself acts as the counter electrode. Advantageous features of direct plasma treatment include the higher plasma density as well as the induced high frequency electric current onto the skin. In plasma treatment antiinflammatory, antipruritic, antimicrobial, tissue stimulation, stimulation of microcirculation, and other therapeutic effects are achieved in a single treatment due to the combined action of ultraviolet radiation, reactive oxygen species (e.g. ozone), reactive nitrogen species, and electric fields. In line with other reports, we have already demonstrated the use of direct plasma treatment in skin disinfection, in atopic eczema (superinfected dermatitis), in modulating the epidermal barrier, as well as in chronic wound treatment. We as well as others did not notice any side effects of plasma treatment so far. In summary, cold atmospheric pressure plasma constitutes a new and innovative treatment option especially for superinfected skin diseases. These promising relatively new clinical applications warrant further carefully conducted translational research to delineate the modes of actions of plasma as well as potential long term side effects. This should lead to norms for the technical devices to allow a standardized treatment of given diseases in the mid-term.
    Clinical Plasma Medicine. 06/2013; 1(1):24–29.
  • Clinical and Experimental Dermatology 05/2013; · 1.33 Impact Factor
  • Sophie Luise Kraus, Holger Andreas Haenssle
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    ABSTRACT: The early diagnosis and excision of cutaneous melanoma is essential for an improved prognosis of the disease. Besides the investigation of pigmented lesions with the unaided eye and conventional dermatoscopy, long-term sequential digital dermatoscopy has been shown to improve the sensitivity of melanoma detection, especially in high-risk patients. In addition to the static clinical and dermatoscopic assessment, the sequential digital dermatoscopy strategy helps to detect changes over time. This review summarizes the latest developments in the field of sequential digital dermatoscopy, describes current strategies for the selection of patients and lesions to monitor, and suggests objective criteria that should lead to an excisional biopsy.
    Journal der Deutschen Dermatologischen Gesellschaft 03/2013; · 1.40 Impact Factor
  • Holger Andreas Haenssle
    Journal der Deutschen Dermatologischen Gesellschaft 03/2013; 11(3):197-8. · 1.40 Impact Factor
  • Archives of dermatology 10/2012; 148(10):1210-2. · 4.76 Impact Factor
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    ABSTRACT: No abstract available.
    Dermatology 09/2012; · 2.02 Impact Factor
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    ABSTRACT: BACKGROUND Therapy with vemurafenib, an inhibitor of mutated BRAF, yields a response rate of approximately 50% in patients with metastatic melanoma harboring a BRAF V600E mutation. As an adverse effect of vemurafenib, proliferative disorders of keratinocytes, including squamous cell carcinoma, have been described. Low concentration of vemurafenib as present in the epidermis were found to activate wild-type RAF, which, in combination with a preexisting RAS mutation, can promote keratinocyte proliferation. While activating BRAF mutations occur in approximately 50% of melanomas, they are even more frequently observed in melanocytic nevi. OBSERVATION We present the case of a patient with dynamic changes of melanocytic nevi well documented by sequential digital dermoscopy during vemurafenib therapy. A variety of dermoscopic changes were observed. First, nevi involuted, and all of these originally showed a centrally elevated papillomatous and predominant globular pattern. Second, preexisting nevi increased in size, and pigmentation that rendered them atypical. Such lesions were flat and showed a predominant reticular pattern at baseline. Third, multiple new nevi occurred. One example of each of the latter 2 categories was excised and showed wild-type BRAF. CONCLUSION Our findings of changing nevi in a patient treated with vemurafenib highlight the need for sequential skin examinations, including dermoscopy.
    Archives of dermatology 08/2012; · 4.76 Impact Factor
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    Franziska Brehmer, Martina Ulrich, Holger A Haenssle
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    ABSTRACT: Cutaneous melanoma is a highly aggressive malignant tumor of skin melanocytes with an increasing incidence in most countries of the world, especially in the fair-skinned populations. Despite all preventive and therapeutic efforts, malignant melanoma is still the most lethal skin cancer. A delayed diagnosis results in an advanced stage and worsened prognosis. Once distant metastases are present, the five-year survival rate is less than 10 percent. At the same time, patients may be cured by an early diagnosis of cutaneous melanoma followed by a wide excision. Therefore, the early detection of melanoma at curable stages is crucial for the patients' survival. Besides the investigation of pigmented lesions with the unaided eye, a wide range of examination techniques for improved diagnostic accuracy have been developed and validated in clinical trials. However, none of these techniques are able to provide a definite and final diagnosis or to replace an excisional biopsy of suspicious lesions followed by histological analysis. This review provides a concise overview of general principles as well as current and future strategies for an improved early diagnosis of cutaneous melanoma.
    Dermatology practical & conceptual. 07/2012; 2(3):203a06.
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    ABSTRACT: Availability of large quantities of functionally effective dendritic cells (DC) represents one of the major challenges for immunotherapeutic trials against infectious or malignant diseases. Low numbers or insufficient T-cell activation of DC may result in premature termination of treatment and unsatisfying immune responses in clinical trials. Based on the notion that cryopreservation of monocytes is superior to cryopreservation of immature or mature DC in terms of resulting DC quantity and immuno-stimulatory capacity, we aimed to establish an optimized protocol for the cryopreservation of highly concentrated peripheral blood mononuclear cells (PBMC) for DC-based immunotherapy. Cryopreserved cell preparations were analyzed regarding quantitative recovery, viability, phenotype, and functional properties. In contrast to standard isopropyl alcohol (IPA) freezing, PBMC cryopreservation in an automated controlled-rate freezer (CRF) with subsequent thawing and differentiation resulted in significantly higher cell yields of immature and mature DC. Immature DC yields and total protein content after using CRF were comparable with results obtained with freshly prepared PBMC and exceeded results of standard IPA freezing by approximately 50 %. While differentiation markers, allogeneic T-cell stimulation, viability, and cytokine profiles were similar to DC from standard freezing procedures, DC generated from CRF-cryopreserved PBMC induced a significantly higher antigen-specific IFN-γ release from autologous effector T cells. In summary, automated controlled-rate freezing of highly concentrated PBMC represents an improved method for increasing DC yields and autologous T-cell stimulation.
    Cancer Immunology and Immunotherapy 04/2012; · 3.64 Impact Factor
  • British Journal of Dermatology 03/2012; 167(4):944-6. · 3.76 Impact Factor
  • H A Haenssle
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    ABSTRACT: A 75-year-old man presented after recurrence of a pigmented macule on his left cheek. Approximately 8 month before a seborrheic keratosis had been diagnosed clinically and treated with cryosurgery and curettage. Dermatoscopy of the recurrent lesion revealed a number of criteria associated with lentigo maligna including asymmetric pigmented follicular openings, streaks, rhomboidal structures, and homogeneous slate-gray areas. Histopathology confirmed a lentigo maligna melanoma with a Breslow tumor thickness of 0.3 mm.
    Der Hautarzt 02/2012; 63(2):143-4. · 0.50 Impact Factor
  • Journal of the American Academy of Dermatology 08/2011; 65(2):e58-60. · 4.91 Impact Factor
  • T Buhl, H A Haenssle
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    ABSTRACT: A 16-year-old boy with multiple nevi presented with an enlarging pigmented lesion on his right chest. Previously excised nevi were all benign. Dermoscopy of the symmetrical lesion revealed a trizonal globular-homogeneous pattern. A peripheral rim of brown globules was followed by a zone with homogeneous pigmentation. The centre of the lesion showed black dots and globules. Histopathology confirmed a dysplastic compound nevus and found no diagnostic aspects of pigmented spindle cell nevus (Reed).
    Der Hautarzt 06/2011; 62(8):625-6. · 0.50 Impact Factor
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    ABSTRACT: Sequential digital dermatoscopy identifies dynamic changes in melanocytic lesions. However, no algorithm exists that systematically weights dynamic changes regarding their association with melanoma. We sought to identify relevant dynamic changes and to integrate these into a novel diagnostic algorithm. During follow-up (mean 44.28 months) of 688 patients at high risk, 675 pigmented lesions with prospectively documented dynamic changes were excised. The association between specific changes and melanoma was assessed. We detected 61 melanomas (38 invasive, median thickness 0.42 mm) with dynamic changes. Multivariate logistic regression analyses revealed a significant association between the diagnosis of melanoma and 5 dynamic criteria. According to the observed odds ratios we defined two dynamic major criteria (2 points each: asymmetric-multifocal enlargement and architectural change) and 3 dynamic minor criteria (1 point each: focal increase in pigmentation, focal decrease in pigmentation, and overall decrease in pigmentation when not accompanied by a lighter pigmentation of the adjacent skin). The DynaMel score was generated by addition of dynamic and 7-point checklist scores with a threshold for excision of 3 or more points. Including information about dynamic changes increased the sensitivity of the 7-point checklist from 47.5% (29 of 61 melanomas detected) to 77.1% (47 of 61 melanomas detected). The specificity slightly decreased from 99.0% to 98.1%. Before broad application the DynaMel algorithm needs to be validated using data from a different prospective study. The DynaMel algorithm integrates a scoring system for dynamic dermatoscopic changes into the 7-point checklist for dermatoscopy and thereby increased the sensitivity of melanoma detection.
    Journal of the American Academy of Dermatology 06/2011; 66(1):27-36. · 4.91 Impact Factor

Publication Stats

282 Citations
127.28 Total Impact Points

Institutions

  • 2003–2013
    • Georg-August-Universität Göttingen
      Göttingen, Lower Saxony, Germany
  • 2002–2012
    • Universitätsmedizin Göttingen
      • Department of Dermatology, Venereology and Allergology
      Göttingen, Lower Saxony, Germany
  • 2008
    • Universität Heidelberg
      • University Hospital of Dermatology
      Heidelberg, Baden-Wuerttemberg, Germany