Christian Andres

Intraindividual genome expression analysis reveals a specific molecular signature of psoriasis and eczema

Signatures from patients with both psoriasis and eczema contribute to understanding disease pathogenesis and diagnosis. Discrimination That’s Skin Deep A molecular signature may be able to aid in the differential treatment of psoriasis from eczema. Quaranta et al. examined a group of individuals affected by both psoriasis and eczema and compared molecular signatures from psoriasis and eczema lesions on the same individual. This approach limited noise from interindividual variability, allowing the authors to focus on genes involved in disease pathogenesis. They found that psoriasis-specific genes involved not only immune mediators but also regulators of metabolism. In contrast, eczema-related genes included those related to the epidermal barrier and inflammasome activation. These insights provide not only new targets for disease-specific therapies but also an independently verified classifier that can be used in difficult to diagnose patients. Previous attempts to gain insight into the pathogenesis of psoriasis and eczema by comparing their molecular signatures were hampered by the high interindividual variability of those complex diseases. In patients affected by both psoriasis and nonatopic or atopic eczema simultaneously (n = 24), an intraindividual comparison of the molecular signatures of psoriasis and eczema identified genes and signaling pathways regulated in common and exclusive for each disease across all patients. Psoriasis-specific genes were important regulators of glucose and lipid metabolism, epidermal differentiation, as well as immune mediators of T helper 17 (TH17) responses, interleukin-10 (IL-10) family cytokines, and IL-36. Genes in eczema related to epidermal barrier, reduced innate immunity, increased IL-6, and a TH2 signature. Within eczema subtypes, a mutually exclusive regulation of epidermal differentiation genes was observed. Furthermore, only contact eczema was driven by inflammasome activation, apoptosis, and cellular adhesion. On the basis of this comprehensive picture of the pathogenesis of psoriasis and eczema, a disease classifier consisting of NOS2 and CCL27 was created. In an independent cohort of eczema (n = 28) and psoriasis patients (n = 25), respectively, this classifier diagnosed all patients correctly and also identified initially misdiagnosed or clinically undifferentiated patients.

Successful ultraviolet A1 phototherapy in the treatment of localized scleroderma: a retrospective and prospective study

Background  Ultraviolet (UV) A1 phototherapy is an effective anti‐inflammatory treatment modality that influences fibroblast functions.

Sinonasal, genital and acrolentiginous melanomas show distinct characteristics of KIT expression and mutations.

KIT aberrations predict the outcome of targeted therapies in acrolentiginous (ALM) and mucosal (MM) melanoma patients. KIT immunoreactivity and mutation status was assessed in 41 ALM and 25 MM patients. Of these, 19 ALM and 15 MM patients had matched primary and metastatic lesions. P-ERK was investigated in a subset of 9 ALM and 7 MM matched primary/metastatic pairs by immunohistochemistry. Heterogeneous KIT immunoreactivity was observed in both primary and metastatic lesions. Mutations were present in four of 41 ALM (10%) and five of 25 MM (20%) patients. Only vulvar mucosal samples carried KIT mutations in contrast to sinonasal lesions (p = 0.0109). In KIT-mutated tumours, the mutations were present in KIT expressing as well as KIT negative cells, as shown by Laser Capture Microdissection (LCM). P-ERK expression was preferentially found in metastases. KIT mutations predict treatment outcome with KIT inhibitors. Therefore, especially vulvar melanoma patients should be screened for activating KIT mutations.

Pyoderma gangrenosum and concomitant hidradenitis suppurativa--rapid response to canakinumab (anti-IL-1β).

ejd.2013.2018 Auteur(s) : Teresa JAEGER1,2, Christian ANDRES1, Martine GROSBER1, Michael ZIRBS1, Rudiger HEIN1, Johannes RING1, Claudia TRAIDL-HOFFMANN1,2 Traidl-Hoffmann@lrz.tu-muenchen.de 1 Department of Dermatology and Allergy Biederstein, Technische Universitat Munchen, Biedersteiner Str. 29, 80802 Munchen, Germany 2 Center of Allergy and Environment (ZAUM), Technische Universitat Munchen and Helmholtz Center, Munich, Germany A classic ulcerative pyoderma gangrenosum (PG) lesion most commonly [...]

Re: Clinical Factors Associated With Merkel Cell Polyomavirus Infection in Merkel Cell Carcinoma

Sihto et al. ( 1 ) recently analyzed 114 formalinfixed and paraffin-embedded Merkel cell carcinoma (MCC) samples from a Finnish cohort for the presence of Merkel cell polyomavirus (MCPyV) DNA. They reported that the prevalence of MCPyV DNA in MCC was 79.8% and, surprisingly, that MCPyV DNA – positive MCCs were preferentially located on the limbs compared with MCPyV DNA – negative MCCs. Their data also suggested that patients with MCPyV DNA – positive tumors had a better prognosis and fewer regional nodal metastases at time of diagnosis compared with patients with MCPyV DNA – negative tumors. We asked if the fi ndings of Sihto et al. could be replicated in an independent cohort of MCC patients. We previously investigated 35 MCC tissue samples from 31 German patients for the presence of MCPyV DNA. We detected MCPyV DNA by polymerase chain reaction amplifi cation in 22 samples (63%) and in 21 patients (68%) ( 2 ) using two sets of primers. Polymerase chain reaction amplifi cation with these two primer sets resulted in a 138-base pair product (MCV138 forward: 5 ′ -GGTTAGAGAT GCTGGAAATGACC-3 ′ ; reverse: 5 ′ C A A A T A A G C A G C A G T A C C A GGC-3 ′ ) and a 191-base pair product (MCV191 forward: 5 ′ -CCACTTTATT ATCTTAGCCCAT-3 ′ ; reverse: 5 ′ -TCCT TTTGGCTAGAACAGTGTC-3 ′ ) that target the large and small T-antigen regions, respectively. The exact locations for the primer pairs are forward 2185 – 2207 and reverse 2301 – 2322 (MCV138) and forward 1994 – 2015 and reverse 2163 – 2184 (MCV191) and are based on reference sequences in the National Center for Biotechnology Information Entrez Nucleotide database (gb|EU375803.1, MCPyV isolate MCC350). All positive polymerase chain reaction results were confi rmed by Southern blot analysis as previously described ( 2 ). Of the 31 primary tumor tissue samples from the German MCC patients, 21 were positive for MCPyV DNA and 10 Table 1 . Clinicopathological data *

Novel immunological approaches in the treatment of atopic eczema

Purpose of reviewAtopic eczema is a common inflammatory skin disease showing chronically relapsing eczema and high association with elevated serum IgE levels. A subgroup of atopic eczema patients requires systemic immunomodulatory treatment for long time periods. However, beyond cyclosporine A and azathioprine, only limited consent exists on systemic treatment options. Recent findingsTimely published systemic treatment modalities include studies on efalizumab (anti-CD11a antibody), infliximab, adalimumab, and etanercept (anti-TNF-α treatment), omalizumab (an anti-IgE antibody), rituximab (an anti-CD20 antibody), specific immunotherapy, leflunomide, and leukotriene receptor antagonists with varying clinical results and with particular safety profiles. SummaryAlthough there is not yet a treatment modality reaching clinical efficacy of cyclosporine A as gold standard of systemic therapy, limitation in its application duration as in its side effect profile as well as the search for alternatives has set a focus on the new alternatives of which especially B-cell-directed therapies might be promising candidates.

Phosphohistone‐H3 and Ki‐67 immunostaining in cutaneous pilar leiomyoma and leiomyosarcoma (atypical intradermal smooth muscle neoplasm)

The mitotic index is important in the assessment of tumors such as leiomyoma (LM) and leiomyosarcoma (LMS), which may exhibit a range of cytological atypia. The mitotic marker phosphohistone‐H3 (PHH3) was shown to improve interobserver and intraobserver variability in many tumors.

Detection of Merkel cell polyomavirus DNA in atypical fibroxanthoma in correlation to clinical features.

A clear etiopathogenetic concept for atypical fibroxanthoma (AFX) is not established yet. Nevertheless, AFX is known as a pleomorphic but indolent tumor primarily of the elderly and/or immunosuppressed patient occurring in severely sun- or radiation-damaged skin. These risk factors are almost identical to those of Merkel cell carcinoma (MCC), a highly malignant skin tumor being thought to be pathogenetically associated with the recently discovered Merkel cell polyomavirus (MCPyV). Because AFX and MCC share risk factors, the aim of this study was to evaluate presence of MCPyV DNA in 23 cases of AFX by PCR and direct DNA sequencing. Subsequently, we correlated clinical features with MCPyV DNA status in AFX. We detected MCPyV DNA in 4 of 23 AFX. All patients with MCPyV DNA-positive tumors were men. The mean age of patients with MCPyV DNA-positive AFX was 84.8 ± 8.7 years (vs. 75.2 ± 7.8 years of MCPyV DNA-negative AFX), the mean duration of tumor growth was 4.5 ± 2.3 months (vs. 5.1 ± 2.8 months) and the mean tumor diameter was 1.2 ± 0.3 cm (vs. 1.3 ± 0.7 cm). Ulceration was present in 75% of MCPyV DNA-positive tumors (vs. 65.2%). In conclusion, MCPyV DNA is present in 17% of AFX, in this cohort affecting predominantly male patients with higher age (>80 years). Clinical features seem to be independent of MCPyV DNA status. Although the role of MCPyV is unclear in this setting, it may act as a cofactor in the tumorigenesis of AFX in a subset of cases.

Prevalence of Merkel cell Polyomavirus DNA in Cutaneous Lymphomas, Pseudolymphomas, and Inflammatory Skin Diseases

Several groups confirmed Merkel cell polyomavirus (MCPyV) as the likely causative agent of Merkel cell carcinoma. Hematolymphoid disorders are known to be a substantial risk factor for Merkel cell carcinoma, and vice versa. The association between MCPyV and hematologic neoplasms is poorly analyzed, as well as the speculation that lymphocytes may serve as reservoir for MCPyV. Therefore, we investigated the prevalence of MCPyV DNA in primary cutaneous T- and B-cell lymphomas, pseudolymphomas (PLs), and inflammatory skin diseases with dominant lymphocytic infiltrate. We performed a molecular pathology study in 22 tissue samples and 1 blood sample of different cutaneous lymphomas from 19 patients (17 mature T-cell neoplasms, 5 mature B-cell neoplasms, and 1 immature hematopoietic malignancy), 13 PLs from 12 patients, and 25 various inflammatory skin diseases from 23 patients. All tumors were analyzed for the presence of MCPyV DNA by polymerase chain reaction, confirmed by Southern blot hybridization of polymerase chain reaction products. We detected MCPyV DNA in 4 of 23 (17.4%) cutaneous lymphoma tissue samples (3 of 17 mature T-cell neoplasms and 1 of 5 mature B-cell neoplasms), in 2 of 13 (15.4%) PL tissue samples, and 2 of 25 (8%) inflammatory skin conditions (1 drug reaction and 1 erythema multiforme). We conclude that MCPyV DNA is infrequently, but consistently present in lesional tissue from patients with primary cutaneous lymphomas, PLs, and inflammatory skin diseases; prevalence is in the range of 8%-17%. Our results suggest that MCPyV does not play a significant role in the pathogenesis of cutaneous lymphoproliferative disorders.

Pyoderma gangrenosum, acne, psoriasis, arthritis and suppurative hidradenitis (PAPASH)‐syndrome: a new entity within the spectrum of autoinflammatory syndromes?

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