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Journal: Journal of the European Academy of Dermatology and Venereology : JEADV

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Psoriasis is a common, chronic, inflammatory skin disease with the majority of individuals having limited disease, treated with topical medication. However, special attributes of topical treatments like galenic/cosmetic properties or an inconvenient treatment schedule may result in low preference for topical treatments. Hence, there is strong medical need for a topical medication, which is highly efficacious, easy-to-use and preferred by both physicians and patients.

Concepts: Randomized controlled trial, Topical, Antibiotic, Medical terms, Medicine

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Background  Patient preferences for psoriasis treatments can impact treatment satisfaction and adherence and may therefore influence clinical outcome. Objective  To assess the impact of treatment experience (satisfaction with current treatment, number of prior visits, disease duration, number of preceding therapies and currently prescribed treatment modalities) on treatment preferences. Methods  A computer-based conjoint analysis experiment was conducted to analyse preferences of patients with moderate or severe psoriasis (n = 163) treated at a German University Medical Center for outcome (probability, magnitude and duration of benefit; probability, severity and reversibility of side effects) and process attributes (location, frequency, duration, delivery method, individual cost) of psoriasis treatments. Relative importance scores (RIS) were calculated for each attribute and compared using anova, post hoc test and multivariate regression analysis. Results  Participants with longer disease duration attached significantly greater importance to duration of benefit (β = 0.206, P = 0.018), whereas participants on oral therapy were more concerned about magnitude of benefit by trend (β = 0.218, P = 0.058). Participants receiving injectables not only set higher value to probability of benefit (RIS = 32.80 vs. 21.89, P = 0.025) but also to treatment location (RIS = 44.74 vs. 23.03, P = 0.011), delivery method (RIS = 43.75 vs. 19.29, P = 0.019), treatment frequency (RIS = 31.24 vs. 16.89, P = 0.005) and duration (RIS = 32.54 vs. 16.57, P = 0.003) when compared with others. Treatment satisfaction was significantly higher in participants on infusions or injections compared with those on phototherapy and mere topical therapy. Conclusions  Treatment preferences may change over time course and with treatment experience. Participants on injectables attach great importance to efficiency and convenience of therapies, and are highly satisfied with their treatment.

Concepts: Multivariate statistics, Attribute, Attached, Injection, Therapy, Statistics, Regression analysis, Psoriasis

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Background  Recently, the updated EAACI/GA(2) LEN/EDF/WAO guidelines for urticaria have been published. Objective  To examine how chronic spontaneous urticaria (csU) patients in Germany are diagnosed and treated, and to compare the outcome to the guideline recommendations. Methods  During this cross-sectional survey study, most dermatologists, paediatricians and 5149 general practitioners in private practice in Germany were asked to participate. All physicians who agreed were requested to complete a standardized questionnaire about their diagnostic and therapeutic management of csU. Results  A total of 776 questionnaires were available for analysis. Most physicians (82%) were attempting to identify underlying causes in their csU patients, but with only limited success. More than 70% reported to check for total serum IgE and to do skin prick testing (not suggested in first line by guideline). In contrast, only 10% applied the autologous serum skin test. The most common first-line treatments were non-sedating antihistamines in standard or higher doses (as recommended). However, many physicians reported still using first generation sedating antihistamines (23%) (not recommended) or systemic steroids (18%). Experience with alternative options was low. Less than one-third of the participants reported to be familiar with the guidelines. Those who did, were found to be more likely to check for underlying causes, to be more experienced with antihistamine updosing and to be more reluctant to use sedating antihistamines or systemic steroids. Conclusion  The diagnostic and therapeutic management of csU by private practice physicians does not sufficiently comply with the guidelines. Awareness of the guidelines can lead to improved care.

Concepts: Questionnaire, Physician, General practitioner, Medicine, Histamine, H1 antagonist, Antihistamines, Histamine antagonist

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Background  Paget’s disease is an intraepidermal adenocarcinoma that is difficult to diagnose clinically as it mimics inflammatory or infectious diseases. As a consequence, it may be clinically misdiagnosed resulting in a delay in appropriate management. Reflectance confocal microscopy allows the visualization of the upper layers of the skin and mucosa at cellular resolution. Paget’s disease is characterized histologically by the presence of neoplastic cells scattered throughout all layers of the epidermis in a pattern similar to that also observed in melanoma (and termed Pagetoid spread). Objective  In vivo confocal microscopy is an excellent diagnostic tool for detecting Pagetoid spread and for diagnosing melanoma. We therefore hypothesized that it may also assist in the diagnosis of Paget’s disease. Methods  In this study, we describe the confocal features of nine cases of extramammary Paget’s disease and one case of mammary one. Results  Large atypical Pagetoid cells were present singly and in clusters in all 10 cases and were readily visualized on ex vivo and in vivo confocal microscopy. The presence of Pagetoid spread and other confocal features, in the appropriate clinical context, is suggestive Paget’s disease and should allow distinction from other inflammatory diseases that may appear similar clinically. Conclusion  The use of confocal microscopy is likely to facilitate earlier diagnosis of Paget’s disease and the instigation of appropriate management with concomitant improvement in clinical outcomes.

Concepts: James Paget, In vivo, Disease, Epidemiology, Infectious disease, Infection, Cancer, Diagnosis

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Background  Adult pityriasis rubra pilaris (PRP) type 1 is a rare chronic papulosquamous disorder with clinical and histological parallels with psoriasis. Treatment is challenging and recent case reports suggest a potential role for tumour necrosis factor (TNF) antagonists. Objectives  Our objective was to systematically review the literature for evidence of efficacy of TNF antagonists in the treatment of adult PRP. Methods  We performed a systematic search of the Cochrane library, EMBASE, Pubmed and MEDLINE databases. We defined diagnosis of PRP, classified clinical response and whether this was clearly attributed to TNF-antagonists. We also reviewed disease, treatment duration and follow up. Results  Sixteen articles were selected for detailed review. From these, 12 articles (13 cases) met our predefined criteria and were included in the systematic review. The authors identified two more cases from their personal archive. A total of 15 evaluable cases were included for analysis. Twelve showed complete response (CR) (80%) to TNF-antagonists with a mean time to maximal response of 5 months. In 10 of the CR cases (83%) this was clearly attributable to TNF antagonist therapy. Conclusion  These data indicate that TNF-antagonists may be of value in treating adult type 1 PRP refractory to other systemic agents but selective reporting bias, together with the lack of standard diagnostic criteria and established spontaneous resolution in PRP, prevent any firm recommendations on their place in management.

Concepts: Cochrane Collaboration, Agonist, Diagnosis, Pityriasis rubra pilaris, Evidence-based medicine, Cochrane Library, MEDLINE, Tumor necrosis factor-alpha

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Background  A disintegrin and metalloprotease (ADAM) 12 is one of the metalloproteinase-type ADAMs and possesses extracellular metalloprotease and cell-binding functions. ADAM12 is expressed in two alternative forms, such as a membrane-anchored form (ADAM12-L) and a short secreted form (ADAM12-S). Objective  To investigate the clinical significance of serum ADAM12-S levels in systemic sclerosis (SSc). Methods  Serum ADAM12-S levels were determined by a specific enzyme-linked immunosorbent assay in 61 SSc patients and 18 healthy controls. Results  Serum ADAM12-S levels were significantly increased in diffuse cutaneous SSc (dcSSc) patients than in healthy controls (0.417 ± 0.389 vs. 0.226 ± 0.065 ng/mL; P < 0.05), while being comparable between limited cutaneous SSc (0.282 ± 0.258 ng/mL) and healthy controls. Serum ADAM12-S levels significantly elevated in dcSSc patients with disease duration of ≤6 years (0.537 ± 0.449 ng/mL, P < 0.05), but not in dcSSc with disease duration of >6 years (0.225 ± 0.049 ng/mL), compared to healthy controls. Furthermore, in dcSSc patients with disease duration of ≤6 years, serum ADAM12-S levels correlated positively with modified Rodnan total skin thickness score, ground glass score, and serum C-reactive protein values, while showed inverse correlation with fibrosis score. Conclusion  Elevated serum ADAM12-S levels are associated with elevated serum inflammatory marker, severity of skin fibrosis, and activity of interstitial lung disease in dcSSc, suggesting the possible contribution of ADAM12-S to the pathological events in this disorder.

Concepts: Inflammation, Eva Engvall, Systemic scleroderma, Assay, Skin, ELISPOT, ELISA, Scleroderma

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Background  Scleroderma is a connective tissue disease that includes localized and systemic forms. Our recent encounter with a morphea case exhibiting prominent perineural inflammation microscopically prompted us to assess the features of all patients diagnosed with morphea/scleroderma at our institution. Objective/methods  To describe the clinicopathological features of all patients diagnosed with morphea/scleroderma at American University of Beirut Medical Center (AUB-MC) between 1999 and 2010, and compare our findings with those published in the literature. Results  A total of 81 cases (63 women and 18 men) were identified, of which 73 were localized (morphea) and eight were systemic scleroderma. Clinically, plaque type morphea was the most common variant both in adults and children, and seven (9%) cases of morphea were associated with lichen sclerosis et atrophicus (LSA). Histopathologically, perineural inflammation was observed in 49% of cases, and may serve, in addition to other features including lichen sclerosis-like changes (observed in exclusively nine cases of morphea), more diffuse dermal and less subcutaneous sclerosis, and intense inflammation, as clues favouring diagnosis of morphea over systemic sclerosis. Conclusion  The features of morphea/scleroderma patients in this study are generally comparable to those published in the literature, with few differences. Clinically, plaque type morphea was the most common variant both in adults and children and LSA was a frequent association. Histopathologically, perineural inflammation was commonly observed and may serve in addition to lichen sclerosis-like changes and intense inflammation as clues favouring diagnosis of morphea over systemic sclerosis.

Concepts: Lichen sclerosus, Systemic scleroderma, Rheumatology, Scleroderma

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BACKGROUND: Psoriasis is a chronic, inflammatory skin disease with a significant impact on health-related quality of life (HRQoL). Tofacitinib (CP-690,550) is a novel, oral Janus kinase inhibitor that is being investigated as a targeted immunomodulator. OBJECTIVE: This Phase 2b study assessed three tofacitinib dosage regimens vs. placebo to characterize the efficacy and safety of tofacitinib in patients with moderate-to-severe chronic plaque psoriasis. We report the patient-reported outcome (PRO) data. METHODS: A total of 197 patients were randomized to tofacitinib 2, 5, 15 mg twice daily or placebo for 12 weeks. Six PRO questionnaires were completed during the study: Dermatology Life Quality Index, Itch Severity Score (ISS), Short Form-36 questionnaire, version 2 (SF-36), Pain/Discomfort Assessment (PDA), Patient Satisfaction with Study Medication (PSSM) item and Patient Global Assessment of psoriasis. RESULTS: Treatment with tofacitinib resulted in significant, dose-dependent improvements in several PROs vs. placebo from week 2 onwards. At week 12, least squares mean changes from baseline for Dermatology life quality index, ISS and SF-36 mental component scores were significantly greater for all active drug arms vs. placebo (P < 0.05), and significantly greater for tofacitinib 5 and 15 mg for SF-36 physical component scores vs. placebo (P < 0.05). At week 12, all dose groups had significantly greater numbers of patients reporting 'Clear' or 'Almost clear' on the PtGA vs. placebo. CONCLUSION: In patients with moderate-to-severe chronic plaque psoriasis, short-term (12-week) treatment with oral twice-daily tofacitinib improves HRQoL outcomes and patient assessment of disease severity and symptoms, with an early onset noted.

Concepts: Hospital, Medical terms, Quality, Assessment, Psoriasis, Quality of life, Quality-of-life index

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Background  Mycetoma is a chronic granulomatous inflammation of the subcutaneous tissue and usually results due to traumatic implantation of soil organisms. Mycetoma can be eumycotic or acinomycotic in origin. Actinomycetoma is susceptible to a large number of chemotherapeutic agents, but the response is variable and affected by various factors such as extent of involvement, duration of disease, presence or absence of bony involvement and drugs used for treatment. Aims and objectives  To describe our experience of various treatment regimens used for actinomycetoma. Material and methods  It was a prospective, open label study of actinomycetoma. Ten patients who were diagnosed clinically as mycetoma were included in this study. All patients were completely evaluated and investigated including skin biopsy, Gram staining of grains and discharge, Ziehl -Nielson stain, KOH preparation, fungal and bacterial cultures and CT scan/Magnetic resonance imaging (MRI), if required. Patients were treated with different treatment regimens, for example, Ramam regimen, modified Ramam regimen, Welsh regimen and its modification. Results  Ten patients (eight males, two females) age ranging from 9 to 55 years (mean 29.6 years) were included in this study. Six patients were successfully treated with Ramam regimen, three patients were treated with our modified Welsh regimen (one of these three patients (case 7) initially failed to respond to Ramam regimen), and one patient was treated with modified Ramam regimen. Conclusion  Ramam regimen was found to be quite effective in treating patients of actinomycetoma with only minimal bony involvement, while Welsh regimen and its modification should be used in case of severe disease due to amikacin being more sensitive than gentamicin in treating resistant organisms. Intensive phase of Modified Welsh regimen can be extended to five cycles in case of extensive bony involvement.

Concepts: DNA, Chemotherapy, Immune system, Biology, Cancer, Staining, Gram staining, Chemotherapy regimens

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There is a very limited amount of data available regarding the relationship between alopecia areata (AA) and psychiatric morbidity and quality of life (QoL) in children and adolescents.

Concepts: Quality-of-life index, Life, Quality of life, Quality, Alopecia areata