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Background: Although subclinical enthesopathy is a well-established diagnostic criterion for psoriatic arthritis (PsA), it is frequently overlooked, as many patients are asymptomatic. The possibility of finding a clinical clue predicting enthesopathy would help clinicians establish an early diagnosis of PsA., Material and Methods: A prospective single-center study of a total of 90 patients with psoriasis was conducted to assess the presence of entheseal abnormalities as detected by ultrasound, and to determine any correlation with nail involvement., Results: Entheseal abnormalities were found in 23 patients (25.5 %), 19 (82.6 %) of whom showed nail involvement, whereas four (17.4 %) individuals did not. Enthesopathy was present in 31.1 % (19/61) of patients with onychopathy compared to 13.8 % (4/29) of those without nail involvement (p  =  0.07). There was a significant correlation between target NAPSI score and evidence of enthesopathy. In addition, the number of nails affected also showed a significant correlation with the presence of enthesopathy (p  = 0.035)., Conclusions: Clinical evidence of onychopathy may be the clue to an early diagnosis of enthesopathy in psoriasis patients., (© 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.)

Hintergrund: Obwohl subklinische Enthesiopathie ein gut etabliertes diagnostisches Merkmal der Psoriasisarthritis (PsA) ist, wird sie häufig übersehen, da viele Patienten asymptomatisch sind. Gäbe es klinische Hinweise auf das Vorliegen einer Enthesiopathie, würde dies den Klinikern die Möglichkeit eröffnen, eine PsA frühzeitig zu diagnostizieren., Material Und Methoden: Es wurde eine monozentrische prospektive Studie mit insgesamt 90 Psoriasis-Patienten durchgeführt, um mittels Ultraschall das Vorliegen von Enthesenanomalien zu untersuchen und eine Korrelation mit dem Befall der Nägel festzustellen., Ergebnisse: Enthesenanomalien wurden bei 23 Patienten (25,5 %) gefunden, von denen 19 (82,6 %) Nagelbefall aufwiesen. Bei 4 Patienten waren die Nägel nicht betroffen. Enthesiopathie lag bei 31,1 % (19/61) der Patienten mit Onychopathie vor, von den Patienten ohne Nagelbefall litten nur 13,8 % (4/29) an Enthesiopathie (p = 0,07). Zwischen dem Target-NAPSI-Score und dem Vorliegen einer Enthesiopathie bestand eine signifikante Korrelation. Eine signifikante Korrelation bestand darüber hinaus auch zwischen dem Vorliegen einer Enthesiopathie und der Anzahl der betroffenen Nägel (p = 0,035)., Schlussfolgerungen: Klinische Belege für eine Onychopathie können der Schlüssel für die frühe Diagnose einer Enthesiopathie bei Psoriasis-Patienten sein., (© 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.)

Derailed endolysosomal trafficking is emerging as a widespread feature of aggressive neoplasms. However, the oncogenic signals that alter membrane homeostasis and their specific contribution to cancer progression remain unclear. Understanding the upstream drivers and downstream regulators of aberrant vesicular trafficking is distinctly important in melanoma. This disease is notorious for its inter- and intra-tumoral heterogeneity. Nevertheless, melanomas uniformly overexpress a cluster of endolysosomal genes, being particularly addicted to the membrane traffic regulator RAB7. Still, the underlying mechanisms and temporal determinants of this dependency have yet to be defined. Here we addressed these questions by combining electron microscopy, real time imaging and mechanistic analyses of vesicular trafficking in normal and malignant human melanocytic cells. This strategy revealed Class I PI3K as the key trigger of a hyperactive influx of macropinosomes that melanoma cells counteract via RAB7-mediated lysosomal degradation. In addition, gain- and loss-of-function in vitro studies followed by histopathological validation in clinical biopsies and genetically-engineered mouse models, traced back the requirement of RAB7 to the suppression of premature cellular senescence traits elicited in melanocytes by PI3K-inducing oncogenes. Together, these results provide new insight into the regulators and modes of action of RAB7, broadening the impact of endosomal fitness on melanoma development.