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Background and objectives It has been postulated that psoriasis is associated with tongue lesions and geographic tongue might be "oral psoriasis". However, reports are inconclusive, prevalence rates vary and data for Europe are sparse. In this prospective case-control study we investigated the point-prevalence of tongue conditions in an Austrian cohort. Patients and methods Psoriasis patients and healthy volunteers were assessed regarding tongue and skin lesions, age, sex, smoking habits, allergies, onset of psoriasis, PASI scores and anti-psoriatic treatment. Results We included 173 psoriasis patients, 58 women, 115 men (median age: 50 [37-60] years), and 173 volunteers, 79 women, 94 men (median age: 54 [43-64] years). Overall, 95 subjects had allergies, 64 psoriasis patients and 50 volunteers were smokers. Median age at onset of psoriasis was 26 (12-40) years, the median PASI score was 2 (0-4.1), most patients received ustekinumab (n = 47). Fissured tongue was significantly associated with psoriasis (25 [14.4 %] psoriasis patients, 13 [7.5 %] volunteers; P = 0.04). Geographic tongue was present in four individuals of each group (2.3%) and associated with smoking (P = 0.01) but not with psoriasis. Conclusions Overall, we found a low point-prevalence of tongue lesions in this Austrian cohort. Psoriasis was associated with fissured tongue but not with geographic tongue. Thus, we cannot corroborate the hypothesis that geographic tongue is an oral manifestation of psoriasis.

BACKGROUND Bullous pemphigoid (BP) is the most frequent autoimmune blistering disease mainly affecting elderly patients. Among several published risk factors, a recent post hoc analysis linked anti-BP180 autoantibodies (AABs) to fatal outcomes in BP. To date, this finding has not been confirmed independently. OBJECTIVE To investigate the potential of anti-BP180-AAB levels as a marker of prognosis and to identify a cut-off level indicative of an increased risk for early death. Secondly, to characterize parameters associated with mortality. METHODS Retrospective, single-centre study of BP patients diagnosed between 2001 and 2012. Analyses included epidemiological and patient- and disease-specific characteristics as well as immunological parameters at diagnosis and during follow-up. Standardized mortality ratios as well as uni- and multivariate regression analyses were calculated. RESULTS One hundred patients (56 women, 44 men) with a median age of 81 years (interquartile range 74-86) were followed up for a median of 775 days (interquartile range 162-1617). One-year mortality rates were 25.0% implying a 2.4-fold increased risk of death compared with the general population. High anti-BP180 autoantibody levels at diagnosis (CI95 1.30-2.89; P = 0.001), dementia (CI95 1.13-6.72; P =0.03), length of hospitalization (CI95 1.16-2.41; P = 0.01) and age (CI95 1.23-4.19; P = 0.009) correlated significantly with 1-year mortality. BP180-AAB concentrations of ≥61 U/mL characterized a subgroup of patients with a particular higher risk for early death compared with the general population (CI95 1.81-3.81; P

Topical cyclosporine (CSA) has been reported as an alternative treatment in steroid-refractory oral lichen planus (OLP), but evidence is limited and conflicting. An N-of-1 trial setting could be appropriate to evaluate interindividual differences in treatment response. We studied a series of 21 open-label, biphasic single-patient observations. Patients (15 women, 6 men) with OLP recalcitrant to topical steroids received four weeks of CSA mouth rinse (200 mg/twice daily) followed by four weeks of drug withdrawal. Pain (visual analogue scale (VAS) score), disease extent (physicians’ global assessment (PGA) score) and quality of life (Dermatology Life Quality Index (DLQI) score,) were assessed at baseline (T0), after four weeks of treatment (T1) and after another four weeks without treatment (T2). Median age was 58 years (interquartile range/IQR = 52–67) and median disease duration was 18 months (IQR = 12–44). Median baseline VAS score decreased significantly at T1 (p = 0.0003) and increased at T2 (p = 0.032) (T0 = 5 (IQR = 3–6.5); T1 = 2 (IQR = 0.5–3.4); T2 = 3 (IQR = 2–4.8)). Similarly, median baseline PGA score decreased significantly at T1 (p = 0.001) and increased at T2 (p = 0.007) (T0 = 2 (IQR = 1.3–2.5); T1 = 1 (IQR = 1–2); T2 = 2 (IQR = 1–2)). Median baseline DLQI score also decreased significantly at T1 (p =.027) but did not change at T2 (p = 0.5) (T0 = 2.5 (IQR = 1–5.8); T1 = 1 (IQR = 0–3); T2 = 1 (IQR = 1–4)). CSA responders (n = 16) had significantly higher median baseline VAS scores (5.2 (IQR = 5–6.5)) than nonresponders (n =5) (2 (IQR = 2–3.5) (p = 0.02). In our study, pain, disease extent and quality of life of patients with OLP improved significantly during therapy with low-dose CSA mouth rinse and exacerbated after drug withdrawal. Remarkably, patients with high initial VAS scores seemed to profit most.

Background Apremilast is a novel oral phosphodiesterase-4 inhibitor approved for psoriasis treatment. Randomized trials have documented its efficacy and safety, but data on real-world patients are scarce. Objectives We aim to characterize psoriasis patients treated with apremilast in a real-world setting and calculate drug survival as an important measure of efficacy and compliance. Methods All psoriasis patients that received apremilast between April 1st 2015 and January 19th 2017 were evaluated every 4 weeks and we documented: age, weight, height, smoking status, family history of psoriasis, joint involvement, previous treatments, psoriasis area severity index (PASI) scores, and the onset and duration of adverse events (AE). Efficacy was analyzed by PASI50, PASI75, and PASI90, reflecting the improvement of skin lesions compared to the PASI-baseline. Kaplan-Meier statistics were used for drug survival estimates. Results Forty-eight patients were included. The median apremilast drug survival was 12.5 weeks (range 1-87). Three patients (6.3%) reached PASI90, nine (18.8%) PAIS75 and eight patients (16.7%) PASI50. Patient weight inversely correlated with a PASI50 response (p 30.0, n=6) reached PASI75, compared to 32% of the non-obese patients (BMI

ZusammenfassungHintergrund und Ziele Biologika werden haufig zur Behandlung der Psoriasis eingesetzt und wurden in zahlreichen klinischen Studien getestet. Allerdings konnen sich Wirkungen und Nebenwirkungen (AEs) bei „real-world“-Patienten unterscheiden, da diese keiner solch strengen Auswahl und Uberwachung unterzogen werden. Wir haben Therapieadharenz („Medikamenten-Uberlebenszeit“), Wirksamkeit und AEs (Qualitat, Zeitpunkt des Auftretens) bei „real-world“-Psoriasis-Patienten, die mit Etanercept, Adalimumab oder Ustekinumab behandelt wurden, untersucht. Patienten und Methoden Retrospektive Datenanalyse (1. Januar 2004 bis 30. Juni 2015) an Patienten, die an einer Psoriasis-Klinik in einem osterreichischen Krankenhaus behandelt wurden. Alle Patienten, die mindestens eine Dosis von Etanercept, Adalimumab oder Ustekinumab erhalten hatten, wurden in die Analyse einbezogen. Wir analysierten Demographie, Therapieadharenz, den Psoriasis Area and Severity Index (PASI) sowie Qualitat und Zeitpunkt des Auftretens von AEs. Ergebnisse In 209 Behandlungsreihen variierte die geschatzte mittlere Therapieadharenz zwischen den verschiedenen Behandlungen: 21 Monate (SE: 6,9) fur Etanercept, 61 Monate (SE: 9,4) fur Adalimumab und 65 Monate (SE 1,4) fur Ustekinumab. Mannliches Geschlecht und Vorbehandlung mit einem Biologikum waren positive Pradiktoren fur langere Therapie mit Adalimumab. Wir fanden keinen signifikanten Unterschied in der am PASI gemessenen Arzneimittelwirksamkeit. Schlussfolgerungen Die meisten AEs treten wahrend des ersten Jahres der Behandlung auf. Adalimumab und Ustekinumab zeichnen sich im Vergleich zu Etanercept durch eine langere Therapieadharenz aus.

SummaryBackground and objectives Widely used in the treatment of psoriasis, biologics have been tested in numerous clinical trials. However, drug efficacies and adverse events (AEs) may differ in ‘real-world’ patients as they do not undergo as rigorous selection and monitoring. Our objective was to examine drug survival, efficacy, and AEs (quality, time of onset) in ‘real-world’ psoriasis patients treated with etanercept, adalimumab, and ustekinumab. Patients and methods Retrospective data analysis (Jan 1, 2004 to Jun 30, 2015) of patients treated at a psoriasis clinic in an Austrian hospital. All patients who had received at least one dose of etanercept, adalimumab, or ustekinumab were included in the analysis. We analyzed: demographics, drug survival, Psoriasis Area and Severity Index (PASI), as well as quality and time of onset of AEs. Results In 209 treatment series, the estimated median drug survival varied among the various treatments: 21 months (SE: 6.9) for etanercept, 61 months (SE: 9.4) for adalimumab, and 65 months (SE 1.4) for ustekinumab. Male gender and pretreatment with a biologic were positive predictors of longer drug survival in adalimumab. We found no significant difference in drug efficacy as determined by PASI. Conclusions Most AEs occur during the first year of treatment. Adalimumab and ustekinumab are marked by longer drug survival compared to etanercept.

Up to 18% of melanomas harbor mutations in the neuroblastoma rat-sarcoma homolog (NRAS). Yet, decades of research aimed to interfere with oncogenic RAS signaling have been largely disappointing and have not resulted in meaningful clinical outputs. Recent advances in disease modeling, structural biology, and an improved understanding of RAS cycling as well as RAS signaling networks have renewed hope for developing strategies to selectively block hyperactive RAS function. This review discusses direct and indirect blocking of activated RAS with a focus on current and potential future therapeutic approaches for NRAS mutant melanoma.

Aim of study Incidence rates of melanoma, generated by cancer registries (CRs), are susceptible to reporting inconsistencies due to increasing decentralisation of diagnosis. We therefore independently assessed the burden of melanoma in Austria. Methods We collected histopathological reports on melanoma of all patients diagnosed in Austria in 2011. Demographic and clinical characteristics, histopathological tumour stages were assessed. Their regional distributions and incidence rates were analysed and compared with data of national and international CRs. Results A total of 5246 patients were diagnosed with 1951 in-situ and 3295 invasive melanomas in Austria in 2011 (population 8.4 million). Age, sex and anatomic distribution corresponded to findings in other European countries, however, the incidence of 25/100,000 (world age-standardised rate) for invasive melanomas was two-fold higher than published by the Austrian CR (12/100,000). Varying frequencies in diagnosing thin melanomas (≤1 mm; n = 4415) accounted exclusively for significant regional disparities, while advanced tumours (>1 mm; n = 761) were evenly distributed. Western Austria showed the highest rates (36/100,000). Patients from eastern Austria whose melanomas were diagnosed in laboratories in western Austria (n = 76) showed significantly higher proportions of in-situ lesions (n = 43; 57%) compared to those whose tumours were diagnosed in eastern Austria (n = 4014; in-situ = 1369; 34%) (p Conclusions In Austria, the melanoma burden and its potential socio-economic implications are significantly underestimated. Similarities of incidences indicate this could affect other European countries with well-established CRs and compromise international comparability of data. Austrian regional disparities suggest overdiagnosis of thin melanomas due to the variability of pathologists' thresholds for the diagnosis of early stage tumours.

Zusammenfassung Hintergrund und Ziele: Frauen, die sich einem bariatrisch-chirurgischen Eingriff unterzogen haben, sind bei spateren Schwangerschaften anfallig fur Nahrstoffmangelzustande. Wir beleuchten die wichtige Rolle der Dermatologen bei der Fruherkennung von Hautsymptomen infolge von Mangelernahrung in dieser speziellen klinischen Situation. Patienten und Methoden: Wir vergleichen die klinischen Merkmale zweier junger Frauen mit dermatologischen Symptomen kombinierter postnataler Nahrstoffmangelzustande nach einer Magenbypass-Operation nach Roux-en-Y. Ergebnisse: Patientin 1 zeigte follikulare Papeln an den Extremitaten, perianale Ekzeme, Perleche, Haarausfall und Depigmentierung der Haare. Patientin 2 wies erythematose Plaques im Genitoanalbereich und an den Akren, Perleche, diffusen Haarausfall und Depigmentierung der Haare auf. Auf der Grundlage der klinischen und histopathologischen Befunde und des erniedrigten Vitamin-A- (Patientin 1) oder Zink-Spiegels (Patientin 2) diagnostizierten wir ein Phrynoderm beziehungsweise eine erworbene Acrodermatitis enteropathica. Bei beiden Patientinnen war, (i) nach der Magenbypass-Operation keine Nachbeobachtung erfolgt, (ii) entwickelten sich Hautlasionen als primare Symptome, (iii) traten aufgrund kombinierter Nahrstoffmangelzustande verschiedene klinische Manifestationen auf und (iv) traten die Symptome erstmals beim Stillen auf, was auf einen kausalen Zusammenhang hinwies. Schlussfolgerungen: Unsere Beobachtungen weisen darauf hin, dass Frauen nach einem bariatrisch-chirurgischen Eingriff ein erhohtes Risiko fur postnatale dermatologische Manifestationen einer Mangelernahrung haben konnten. Sind sich Dermatologen dieser neuen anfalligen Patientengruppe bewusst, kann dies dazu beitragen, Schaden fur Mutter und Kind zu vermeiden. Summary Background and objectives: Women who have undergone bariatric surgery are susceptible to nutritional deficiencies in subsequent pregnancies. We highlight the importance of dermatologists in the early recognition of cutaneous signs of malnutrition occurring in this specific clinical setting. Patients and methods: We compare clinical characteristics of two young women with dermatological signs of combined post-gestational nutritional deficiencies following Roux-en-Y gastric bypass surgery. Results: Patient 1 exhibited follicular papules on the extremities, perianal eczema, perleche, alopecia, and depigmentation of hair. Patient 2 showed erythematous plaques in genitoanal and acral areas, perleche, diffuse alopecia, and depigmentation of hair. Based on clinical and histopathological findings, decreased vitamin A (patient 1) and zinc levels (patient 2), we diagnosed phrynoderma and acquired acrodermatitis enteropathica, respectively. Comparison of the two patients revealed that both (i) were lacking follow-up after gastric bypass surgery, (ii) developed skin lesions as primary symptoms with (iii) mixed clinical manifestations due to combined deficiencies, and (iv) experienced initial symptoms during lactation suggesting a causal relationship. Conclusions: Our observations highlight the potentially increased risk of women to develop post-gestational dermatological manifestations of malnutrition following bariatric surgery. The awareness of dermatologists with respect to this emerging, susceptible patient group may help avert damage to mother and child.

Summary Background and objectives Women who have undergone bariatric surgery are susceptible to nutritional deficiencies in subsequent pregnancies. We highlight the importance of dermatologists in the early recognition of cutaneous signs of malnutrition occurring in this specific clinical setting. Patients and methods We compare clinical characteristics of two young women with dermatological signs of combined post-gestational nutritional deficiencies following Roux-en-Y gastric bypass surgery. Results Patient 1 exhibited follicular papules on the extremities, perianal eczema, perleche, alopecia, and depigmentation of hair. Patient 2 showed erythematous plaques in genitoanal and acral areas, perleche, diffuse alopecia, and depigmentation of hair. Based on clinical and histopathological findings, decreased vitamin A (patient 1) and zinc levels (patient 2), we diagnosed phrynoderma and acquired acrodermatitis enteropathica, respectively. Comparison of the two patients revealed that both (i) were lacking follow-up after gastric bypass surgery, (ii) developed skin lesions as primary symptoms with (iii) mixed clinical manifestations due to combined deficiencies, and (iv) experienced initial symptoms during lactation suggesting a causal relationship. Conclusions Our observations highlight the potentially increased risk of women to develop post-gestational dermatological manifestations of malnutrition following bariatric surgery. The awareness of dermatologists with respect to this emerging, susceptible patient group may help avert damage to mother and child.

Background The aim of the present study was to evaluate the validity of the German version of the Oral Health Impact Profile (OHIP-G) in comparison with the Visual Analogue Scale (VAS) and to evaluate whether gender has a potential influence on OHIP scores and dimensions in oral lichen planus (OLP) patients.

The aim of this study was to assess the relationship between oral health-related quality of life, the nature of mucosal disease, and personality traits. One hundred forty-nine patients seeking care for oral mucosal disease were recruited in this cross-sectional study conducted at the University Clinic of Dentistry in Vienna from June to December 2013. All participants agreed in answering two questionnaires: the Oral Health Impact Profile German version (OHIP-G), which assessed the perceived limitations of oral health-related quality of life and the Neuroticism Extraversion Openness Five-Factor Inventory (NEO-FFI), which evaluated five personality domains. A multiple linear regression was applied to examine the potential influence on OHIP scores. Bullous/erosive mucosal diseases and oral lichen planus patients (n = 73, 49 % of total) reported the highest impact on oral health-related quality of life (OHIP total score 49.3 ± 35.7, p = 0.02). A highly significant influence of neuroticism, as a personality trait, was observed on oral health-related quality of life (p = 0.001). Women had significantly more restrictions (OHIP score 45.3 ± 32.2) compared to men (32.6 ± 30.1, p = 0.009). Psychosocial factors such as personality traits, especially neuroticism, are significantly associated with quality of life ratings in patients with mucosal disease. Since mucosal diseases impact patient’s daily living and quality of life while affected by their psychological profiles, this should be considered when formulating a therapeutic approach.

Background Evidence for the efficacy of various therapies of livedoid vasculopathy (LV) is limited. Objective We sought to determine efficacy and tolerability of 2 g/kg of intravenous immunoglobulins (IVIG) every 4 weeks in patients with LV. Methods This was a long-term follow-up study of 11 patients with LV treated with 2 g/kg of IVIG assessing the clinical characteristics, disease course, and quality of life. Results The treatment regimen led to complete remission of ulcerations and pain in 17 of 29 disease episodes (59%) after 3 cycles and in 25 of 29 episodes (86%) after 6 cycles. Two disease episodes showed remission after 7 and 8 cycles, resulting in a total number of remissions of 27 (93%). Subscore analysis showed resolution of pain in 80% after 2 IVIG cycles. Disease severity and quality of life were significantly improved after 6 cycles. Median duration of remissions was 26.7 months after initial and 7.5 months after subsequent disease episodes. Limitations This was a retrospective study that did not include the comparison of IVIG efficacy and its impact on quality of life with treatment options. Conclusions In our patients with LV, high-dose IVIG led to fast and complete resolution of pain and ulcerations and to substantial improvement in quality of life.

Background: Interleukin-2 (IL-2) treatment for patients with metastatic melanoma has shown remarkable durable responses. Systemic administration of IL-2 may cause severe side effects, whereas local administration is considered to be a safe alternative. The lungs are common sites of metastases in melanoma patients causing considerable respiratory problems. We sought to evaluate the potential antitumoral effect of a low-dose inhalative IL-2 (lh-IL-2) regimen for patients with melanoma lung metastases. In addition, we explored the prophylactic potential of Ih-IL-2 after surgical removal of lung metastases in a study carried out in an outpatient setting. Methods: Twenty patients with American Joint Committee on Cancer stage-IV (M1b and M1c) melanoma were enrolled in this study and treated with 3 × 3 million IU inhalative IL-2 q.d. together with monthly dacarbazine bolus injections. Five patients received lh-IL-2 after surgical resection of lung metastases to prevent recurrence of the disease (prophylaxis group, N=5). All other patients were enrolled in the treatment group (N=15). Clinical evaluations were carried out monthly and radiological follow-up was performed every third month. Results: Nine patients in the treatment group had a clinical benefit with partial regression (27%) or stable disease (33%). Four patients had progression of lung metastases (26.7%) and two patients were not evaluable (13.3%). In the prophylaxis group, none of the patients developed new lung metastases during lh-IL-2 therapy. The median follow-up period was 7.8 months in the treatment group and 25.7 months in the prophylaxis group. In the majority of patients, treatment was well tolerated. Conclusions: Low-dose IL-2 inhalation might offer an effective and safe treatment option for lung metastases in melanoma patients. In addition, lh-IL-2 may have a prophylactic potential to prevent recurrence in the lungs after pulmonary melanoma metastasectomy. Administration can easily be performed in an outpatient setting, thus offering an attractive treatment option.

Effective medical treatment for patients with severe hidradenitis suppurativa (HS) is limited.We sought to measure the impact of wide local excision on quality of life in HS Hurley grade III patients and to examine the rate of postoperative complications, disease recurrences, and satisfaction with the cosmetic results.Seventy-four patients were enrolled. Outcome measures included Dermatology Life Quality Index responses, disease duration, recurrence, previous therapies, postoperative complications, and satisfaction with cosmetic results.Most patients had inguinogenital/gluteal disease (68.9%, P .001). Involvement of both the axillary and the inguinogenital/gluteal areas were pronounced in male patients (P = .018). None of the patients was treated with tumor necrosis factor-α inhibitors. Most patients (71.6%) had a disease history of5 years at the time of presentation and multiple unsuccessful attempts with systemic and local therapeutic interventions. Wide local excision improved Dermatology Life Quality Index scores from initially 27.89 to 5.31 after surgery (P .001), independent of localization (P = .195). Forty-seven percent of patients had postoperative complications, most frequently pain and scarring. The vast majority of patients (70.3%) were satisfied with the cosmetic results.The retrospective nature of the study was a limitation.Wide local excision significantly improves the quality of life of HS patients. Local recurrence rates are low, and satisfaction with the cosmetic results is high.

Summary Animal-type melanoma (ATM) represents a rare subtype within the wide spectrum of melanocytic tumors. Clinically, ATM lesions appear as sharply demarcated, brown, black and dark blue pigmented nodules, which show grey-white surface elements on dermatoscopy. The tumor is restricted to the dermis and arranged in irregular fascicles, which are composed of spindle-shaped and epithelioid melanocytes. Moderate tumor cell pleomorphism, mitoses and apoptotic cells all suggest a malignant process. Abundant, finely dispersed melanin pigment within tumor cells as well as numerous melanophages are strongly suggestive of ATM. Even though locoregional lymph node metastases are frequently found at diagnosis, the course of ATM is generally benign. Specific molecular changes may be detected in melanocytes from lesions and lymph nodes on fluorescence in situ hybridization (FISH). Such findings strongly indicate the malignant potential of ATM. The peculiar biology of ATM, as a moderately malignant tumor, is reflected in a new histopathological classification within the spectrum of dermal borderline melanocytic tumors (BMT).

Background Pyoderma gangrenosum (PG) is a rare, ulcerating neutrophilic dermatosis of unknown aetiology; PG during pregnancy is particularly rare. The disease is frequently associated with immune-mediated, inflammatory diseases. Objective Diagnosis of PG can be challenging and relies upon exclusion of other causes such as traumas, infections, vascular diseases or neoplasms. Treatment options during pregnancy are limited. Methods To evaluate current treatment options for PG during pregnancy, we present a case of multilocular PG during the patient's first trimester. In conjunction with a comprehensive review of previously published cases of PG during gravidity, we discuss available treatment modalities including immunosuppressants and TNFα inhibitors. Results Our patient highlights the importance of including PG as a potential differential diagnosis of cutaneous ulcers during gravidity. Treatment with systemic glucocorticoids is effective and safe for the health of the mother and the unborn. Conclusion In pregnant females, it is particularly important to diagnose PG and control disease activity due to the risk of pathergy and wound healing deficiencies during delivery and post-partum. A limited number of treatment options are available to date, which require a precise risk–benefit evaluation.

Women who have undergone bariatric surgery are susceptible to nutritional deficiencies in subsequent pregnancies. We highlight the importance of dermatologists in the early recognition of cutaneous signs of malnutrition occurring in this specific clinical setting.We compare clinical characteristics of two young women with dermatological signs of combined post-gestational nutritional deficiencies following Roux-en-Y gastric bypass surgery.Patient 1 exhibited follicular papules on the extremities, perianal eczema, perlèche, alopecia, and depigmentation of hair. Patient 2 showed erythematous plaques in genitoanal and acral areas, perlèche, diffuse alopecia, and depigmentation of hair. Based on clinical and histopathological findings, decreased vitamin A (patient 1) and zinc levels (patient 2), we diagnosed phrynoderma and acquired acrodermatitis enteropathica, respectively. Comparison of the two patients revealed that both (i) were lacking follow-up after gastric bypass surgery, (ii) developed skin lesions as primary symptoms with (iii) mixed clinical manifestations due to combined deficiencies, and (iv) experienced initial symptoms during lactation suggesting a causal relationship.Our observations highlight the potentially increased risk of women to develop post-gestational dermatological manifestations of malnutrition following bariatric surgery. The awareness of dermatologists with respect to this emerging, susceptible patient group may help avert damage to mother and child.

// Igor Vujic 1, 2 , Martina Sanlorenzo 1, 3 , Rosaura Esteve-Puig 1 , Marin Vujic 1, 2 , Andrew Kwong 1 , Aaron Tsumura 1 , Ryan Murphy 1 , Adrian Moy 1 , Christian Posch 2, 4 , Babak Monshi 2 , Klemens Rappersberger 2 , Susana Ortiz-Urda 1 1 Department of Dermatology, Mt. Zion Cancer Research Center, University of California San Francisco, San Francisco, CA, USA 2 Department of Dermatology, The Rudolfstiftung Hospital, Academic Teaching Hospital, Medical University Vienna, Vienna, Austria 3 Department of Medical Sciences, Section of Dermatology, University of Turin, Turin, Italy 4 Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA Correspondence to: Igor Vujic, e-mail: igor.vujic.md@gmail.com Keywords: NRAS, APT-1, melanoma, palmostatin B, acyl protein thioesterase Received: August 30, 2015 Accepted: November 22, 2015 Published: January 13, 2016 ABSTRACT Oncogenic NRAS mutations are frequent in melanoma and lead to increased downstream signaling and uncontrolled cell proliferation. Since the direct inhibition of NRAS is not possible yet, modulators of NRAS posttranslational modifications have become an area of interest. Specifically, interfering with NRAS posttranslational palmitoylation/depalmitoylation cycle could disturb proper NRAS localization, and therefore decrease cell proliferation and downstream signaling. Here, we investigate the expression and function of NRAS depalmitoylating acyl protein thioesterases 1 and 2 (APT-1, APT-2) in a panel of NRAS mutant melanoma cells. First, we show that all melanoma cell lines examined express APT-1 and APT-2. Next, we show that siRNA mediated APT-1 and APT-2 knock down and that the specific APT-1 and -2 inhibitors ML348 and ML349 have no biologically significant effects in NRAS mutant melanoma cells. Finally, we test the dual APT-1 and APT-2 inhibitor palmostatin B and conclude that palmostatin B has effects on NRAS downstream signaling and cell viability in NRAS mutant melanoma cells, offering an interesting starting point for future studies.

Arterial aneurysm, despite its rarity, is a characteristic feature of Behcet's disease. Although involvement of different arteries has been reported in the literature, few cases of carotid or subclavian aneurysms have been reported. We present here a 22-year-old Iranian man with Behcet's disease presenting with neurological problems (such as headache, seizure, hemiparesis, internuclear ophthalmoplegia, dysarthria and mental problems), and absent left radial pulse. He was diagnosed by digital subtraction angiography, as having multiple ischemic lesions in the brainstem, as well as multiple aneurysms in the territory of carotid and subclavian arteries. To our best knowledge this is the first case of multiple aneurysms of these arteries in a patient with Behcet's disease. Its unusual presentation as a neuro-Behcet case, associated with hand pulselessness is the outstanding feature of this case.

Background There are conflicting data on markers of disease progression and outcome of Merkel cell carcinoma. Objective We suggest to review histological and various immunohistochemical features of Merkel cell carcinoma specimens, in order to identify prognostic markers of clinical relevance. Methods We collected paraffin-embedded blocks from primary tumours from 26 patients diagnosed with Merkel cell carcinoma and determined the following: type and size of the tumour, number of mitoses, proliferation rate (Ki-67 antibody), (anti)-apoptosis rate (bcl-2, p53, p63 antibodies) and lymphatic vessel invasion (D2-40 antibody for podoplanin). Two authors blinded to clinical outcome, independently assessed and scored all samples. The findings were correlated with tumour progression, which was determined by local recurrence, lymph node- or distant metastases. Results During the average follow-up period of 63.4 months 12 (46%) patients had disease progression. Statistical analysis revealed Ki-67-staining (P = 0.005) as a marker of disease progression, high number of mitoses (P = 0.026) correlated with lymph node metastasis, while a tendency for increased Bcl-2 expression (P = 0.064) was found in patients with local recurrence. A higher number of invaded lymphatic capillaries showed a tendency in correlation with metastases (P = 0.072). Conclusion The findings indicate that high numbers of mitoses, proliferation and survival of tumour cells as marked by Ki-67- and Bcl-2-staining, and infiltration of lymphatic vessels, might correlate with the biological behaviour of Merkel cell carcinoma.

Background Mycoplasma pneumoniae, a bacterium known to be a common cause of pneumonia, has been documented to cause complications such as debilitating mucositis previously described as an atypical Stevens-Johnson syndrome without skin lesions. However, in the spectrum of epidermal dermatopathies, the condition is increasingly recognized as a separate entity, now termed M. pneumoniae-associated mucositis (MPAM). Objectives We present a case of MPAM and systemically review the literature to discuss diagnostic and therapeutic options. Methods A systematic literature search was performed to find studies reporting MPAM in adults. We extracted and analysed patient demographics, disease symptomatology, diagnostic testing and treatment. Results Eleven articles, describing 12 patients and our own patient met the predefined criteria and were analysed. Respiratory, ocular and oral symptoms were present in all patients. Therapies predominantly included antibiotics (10 of 13) and immunosuppressive treatment (9 of 13) leading to complete resolution of symptoms in all patients. Conclusion Our findings highlight that MPAM should be recognized as a distinct disease entity within the spectrum of epidermal dermatopathies. We discuss and show in our patient why M. pneumoniae IgA serum levels could prove to be more reliable diagnostic tools in the MPAM diagnosis than the widely used IgG and IgM titre levels.

Animal-type melanoma (ATM) represents a rare subtype within the wide spectrum of melanocytic tumors. Clinically, ATM lesions appear as sharply demarcated, brown, black and dark blue pigmented nodules, which show grey-white surface elements on dermatoscopy. The tumor is restricted to the dermis and arranged in irregular fascicles, which are composed of spindle-shaped and epithelioid melanocytes. Moderate tumor cell pleomorphism, mitoses and apoptotic cells all suggest a malignant process. Abundant, finely dispersed melanin pigment within tumor cells as well as numerous melanophages are strongly suggestive of ATM. Even though locoregional lymph node metastases are frequently found at diagnosis, the course of ATM is generally benign. Specific molecular changes may be detected in melanocytes from lesions and lymph nodes on fluorescence in situ hybridization (FISH). Such findings strongly indicate the malignant potential of ATM. The peculiar biology of ATM, as a moderately malignant tumor, is reflected in a new histopathological classification within the spectrum of dermal borderline melanocytic tumors (BMT).

Summary Background: Immunoapheresis/immunoadsorption is a specific tool to remove immunoglobulins and immune complexes from the circulation. Immunoapheresis is successfully used in various autoantibody-mediated diseases (such as autoimmune renal disease and others). In dermatology immunoapheresis is increasingly applied as an adjuvant treatment for severe autoimmune bullous diseases. Case report: We successfully employed adjuvant immunoapheresis to treat a 57-year-old man with life-threatening pemphigus vulgaris and a 30-year-old pregnant woman with severe pemphigoid gestationis. Immunoapheresis induced a rapid improvement and almost complete clearance of clinical symptoms without notable side effects. The clinical improvement was paralleled by a decline of the pathologic circulating autoantibodies. Following stabilization of his disease with immunoapheresis, the pemphigus vulgaris patient was continued on rituximab and remained almost free of symptoms for the next 12 months. The patient with pemphigoid gestationis was subsequently treated with systemic corticosteroids until the symptoms of her self-limited disease ceased. Conclusion: Immunoapheresis might represent an excellent therapy for certain patients with severe pemphigus vulgaris or pemphigoid gestationis, unresponsive to conventional treatment regimens. We observed rapid improvement of clinical symptoms and no notable side effects.

A patient with painful erosions of the oral cavity and the labia minora developed multifocal blisters in inter-triginous areas. These blisters eroded and evolved into papillomatous erosive vegetations. Histopathology and immunopathological investigations confirmed the diagnosis of pemphigus vegetans, mediated by IgG autoantibodies. The circulating IgG1 and IgG4 autoantibodies were exclusively directed against desmoglein 3, as shown by ELISA and indirect immunofluorescence studies. These IgG1 and IgG4 isotypes were also in vivo bound, as demonstrated with immunoperoxidase staining of perilesional skin. Our clinical, biochemical and immunopathological observations confirm the hypothesis that pemphigus vegetans is a variant of pemphigus vulgaris.

ejd.2013.2175 Auteur(s) : Igor Vujic1,2 igor.vujic@wienkav.at, Leo Richter1, Katrin Bartsch1, Babak Monshi1, Klemens Rappersberger1 1 Department of Dermatology, Rudolfstiftung Hospital, Juchgasse 25, 1030 Vienna, Austria 2 Department of Dermatology, Mount Zion Cancer Research Center, San Francisco, CA 94115, USA Pityriasis rubra pilaris (PRP) is a rare, inflammatory, papulosquamous disease of unknown etiology. It is classified into 6 different types [1-3]. Type 1 PRP accounts for 50% of cases, the onset [...]