3D surface roughness measurement for scaliness scoring of psoriasis lesions

Psoriasis is an incurable skin disorder affecting 2–3% of the world population. The scaliness of psoriasis is a key assessment parameter of the Psoriasis Area and Severity Index (PASI). Dermatologists typically use visual and tactile senses in PASI scaliness assessment. However, the assessment can be subjective resulting in inter- and intra-rater variability in the scores. This paper proposes an assessment method that incorporates 3D surface roughness with standard clustering techniques to objectively determine the PASI scaliness score for psoriasis lesions. A surface roughness algorithm using structured light projection has been applied to 1999 3D psoriasis lesion surfaces. The algorithm has been validated with an accuracy of 94.12%. Clustering algorithms were used to classify the surface roughness measured using the proposed assessment method for PASI scaliness scoring. The reliability of the developed PASI scaliness algorithm was high with kappa coefficients>0.84 (almost perfect agreement).     

Mean Platelet Volume Is Elevated in Patients with Psoriasis Vulgaris

Purpose

This retrospective study was done to investigate the mean platelet volume (MPV) level in patients with psoriasis vulgaris and its relationship with disease severity.

Materials and Methods

We undertook a cross-sectional study on 176 patients and 101 healthy controls to examine the association between MPV and psoriasis. Various clinical and laboratory parameters were analyzed and compared.

Results

Platelet distribution width and MPV were significantly higher in patients with psoriasis than controls. In addition, there was positive correlation between Psoriasis Area Severity Index (PASI) and MPV. When psoriasis patients were grouped into mild psoriasis (PASI<10) and moderate to severe psoriasis (PASI≥10), the MPV of the latter group was significantly elevated. Nevertheless, patients with higher MPV level (MPV≥10.4 fL) did not show higher PASI than lower MPV level (MPV<10.4 fL). MPV levels significantly decreased after improvements of psoriasis with various treatments. The variations of MPV and PASI also showed significant correlation.

Conclusion

We have shown that MPV is increased in psoriasis patients and correlates with disease severity. Therefore, MPV levels may be considered as a marker of disease severity of psoriasis.     

Secukinumab (AIN457) for the treatment of psoriasis

Psoriasis is a chronic inflammatory disease with a multifactorial origin that appears in patients with genetic predisposition and is induced by environmental factors, and characterized by alterations in the innate and adaptive immunity. IL-17A is one of the specific cytokines involved in the pathogenesis of psoriasis and its inhibition is highly effective in the treatment of patients with moderate and severe psoriasis. Secukinumab is a monoclonal antibody that specifically binds to IL-17A and inhibits the interaction to its receptor, and it has demonstrated its efficacy and safety in the treatment of psoriasis. Phase II and III clinical trials indicate that > 80% of the patients receiving secukinumab achieve Psoriasis Area Severity Index (PASI) 75 at week 12. In the Phase III efficacy of response and safety of two fixed secukinumab regimens in psoriasis trial, PASI 75 rates were 81.6% with 300 mg secukinumab, 71.6% with 150 mg secukinumab and 4.5% with placebo, and responses were maintained up to 52 weeks in the majority of patients. In the Phase III Full Year Investigative Examination Of Secukinumab versus Etanercept Using Two Dosing Regimens To Determine Efficacy in Psoriasis study, the efficacy of secukinumab was compared to etanercept. The results indicate that both doses of secukinumab (150 and 300 mg) showed superior efficacy compared with etanercept throughout the study; PASI 75 rates at week 12 were 77.1% with 300 mg secukinumab, 67% with 150 mg of secukinumab, 44% with etanercept and 4.9% with placebo. PASI 90 and PASI 100 were 54 and 24% with secukinumab 300 mg and 21 and 4% with etanercept at week 12. At week 52, PASI 90 continued to be higher in the secukinumab group (65%) compared with the etanercept group (33%). Regarding safety, the most common side effects were nasopharyngitis and headache. The rate of infections was higher with secukinumab than placebo. This was especially the case for Candida infections, which were more common in the secukinumab group (4.7% with secukinumab 300 mg and 2.3% with secukinumab 150 mg), but all cases were resolved with conventional treatment. Secukinumab is a well-tolerated treatment that has demonstrated efficacy in treating moderate-to-severe plaque psoriasis. Nevertheless, long-term studies are necessary to confirm Phase II and Phase III data.     

Oxidant / antioxidant status in patients with psoriasis

Psoriasis is a common, chronic inflammatory skin disease with unknown etiology. Recently it has been suggested that increased ROS production and deficient function of antioxidant systems activities may be involved in the pathogenesis of the disease. Although there are several studies investigating oxidant/antioxidant systems in psoriatic patients, the data obtained from these studies is not concordant. In this study, superoxide dismutase (SOD) enzyme activity, and malondialdehyde (MDA) and antioxidant potential (AOP) levels in thirty-five patients with psoriasis were investigated and compared with those of twenty-four control subjects. Clinical severity of the disease was determined according to the Psoriasis Area and Severity Index (PASI) scores in the patients. Plasma SOD activity and MDA levels were significantly higher (p=0.012 and p=0.005 respectively), whereas AOP levels were lower, in patients than controls (p=0.001). There was no correlation between PASI scores and plasma SOD, MDA, and AOP levels. Our findings may provide some evidence for a potential role of increased ROS production and decreased antioxidant activity in psoriasis.     

Decreased expression levels of L-selectin on subsets of leucocytes and increased serum L-selectin in severe psoriasis

L-selectin is a leucocyte adhesion molecule involved in leucocyte interactions with vascular endothelial cells. Following leucocyte activation L-selectin is endoproteolytically released from the cell surface. To assess whether psoriasis vulgaris results in systemic leucocyte activation, we examined expression levels of L-selectin on subsets of peripheral blood leucocytes from patients with psoriasis (n = 25) and normal control subjects. Serum levels of soluble L-selectin were quantified by ELISA in patients with psoriasis (n = 75), pustulosis palmaris et plantaris, and contact dermatitis, as well as normal control subjects. Psoriasis severity was evaluated by psoriasis area and severity index (PASI). L-selectin expression levels on CD4+ T cells, B cells, monocytes, and neutrophils from patients with severe-type psoriasis (PASI > or = 15) was significantly decreased compared with leucocytes from normal control subjects. Furthermore, L-selectin expression on CD4+ T cells showed good inverse correlation with PASI scores. Monocyte L-selectin expression was restored when the skin lesions of psoriasis were remitted. The frequencies of L-selectin+ CD4+ T cells or L-selectin+ CD8+ T cells from patients with psoriasis were almost normal. Serum L-selectin levels in patients with severe-type psoriasis were significantly higher than those in normal control subjects. These results suggest that subsets of leucocytes may be activated in psoriasis, and that L-selectin expression levels on some leucocyte subsets, especially CD4+ T cells, tend to correlate with disease severity of psoriasis.     

Ustekinumab for the treatment of psoriasis

Management of psoriasis over the last decade has changed significantly with the introduction of biological therapies. Ustekinumab is a first-in-class biological agent, inhibiting the action of IL-12 and IL-23, and has provided further evidence for the role of Th1 and Th17 lymphocytes in the pathogenesis of psoriasis. Efficacy has been clearly demonstrated in three Phase III clinical trials. Week 12 Psoriasis Area and Severity Index (PASI) 75 was observed in 66.4–75.7% of patients with PASI 90 achieved in 36.7–50.9%. This marked clinical response is also reflected in a significant improvement in quality of life. The most recent Phase III clinical trial has demonstrated the superior efficacy of ustekinumab (regardless of dosing regimen) compared with high-dose etanercept at week 12. Long-term efficacy has been demonstrated over 148 weeks with 64–76% of patients maintaining PASI 75. The role of ustekinumab in the treatment of psoriatic arthritis has shown some benefit in Phase II clinical trials. Phase III clinical trials are pending and will provide further guidance on management of concurrent disease. The currently available safety data are on the whole reassuring, although ongoing vigilance remains central to the detection of rare or late sequelae.     

Ustekinumab for the treatment of psoriasis

Management of psoriasis over the last decade has changed significantly with the introduction of biological therapies. Ustekinumab is a first-in-class biological agent, inhibiting the action of IL-12 and IL-23, and has provided further evidence for the role of Th1 and Th17 lymphocytes in the pathogenesis of psoriasis. Efficacy has been clearly demonstrated in three Phase III clinical trials. Week 12 Psoriasis Area and Severity Index (PASI) 75 was observed in 66.4-75.7% of patients with PASI 90 achieved in 36.7-50.9%. This marked clinical response is also reflected in a significant improvement in quality of life. The most recent Phase III clinical trial has demonstrated the superior efficacy of ustekinumab (regardless of dosing regimen) compared with high-dose etanercept at week 12. Long-term efficacy has been demonstrated over 148 weeks with 64-76% of patients maintaining PASI 75. The role of ustekinumab in the treatment of psoriatic arthritis has shown some benefit in Phase II clinical trials. Phase III clinical trials are pending and will provide further guidance on management of concurrent disease. The currently available safety data are on the whole reassuring, although ongoing vigilance remains central to the detection of rare or late sequelae.     

Classification of depressive illness. Clinico-psychological correlates

347 patients with primary depressive illness were studied. Patients were classified on the Newcastle Diagnostic Scale and their depression was rated on the Hamilton Rating Scale for Depression (HRS) and self-rated on the Beck Depression Inventory (BDI). Clinical and personality factors were studied in relation to classification. Personality was measured by the Eysenck Personality Questionnaire, Fould's Personality Deviance Scale, the Marke-Nyman Temperament Scale and the Crown-Crisp Experimental Index. The frequency distribution of the Newcastle scores of all 347 patients was unequivocally unimodal. Significant positive correlations were obtained between patients' Newcastle scores, age, and HRS scores but not with BDI scores. Patients with non-endogenous depression showed clinical and personality differences compared with those with endogenous depression, and with a group of bipolar depressives.     

Evaluation of safety and clinical activity of multiple doses of the anti-CD80 monoclonal antibody, galiximab, in patients with moderate to severe plaque psoriasis

Background: Reduction in lesional, activated T cells induces improvement in psoriatic plaques. Galiximab (IDEC-114), an IgG(1) anti-CD80 antibody, binds to CD80, a costimulatory molecule involved in T-cell activation. Objective: A Phase I/II, multidose, multischedule, dose-finding study of galiximab to evaluate safety, pharmacokinetics, and clinical activity was conducted in 35 patients with moderate to severe plaque psoriasis. Methods: Seven cohorts of five patients received galiximab intravenously on three different schedules at different dose levels. Results: Adverse events (AEs) commonly occurred as mild and self-limiting. Improvements were observed in most cohorts without evidence of a dose response in Psoriasis Area and Severity Index (50% or greater reduction in PASI score in 40% of patients), Physician's Global Psoriasis Assessment (PGA rating of Good or above in 57% of patients), and Psoriasis Severity Scale (PSS, baseline mean of 7.6 decreased by Study Day 127 to 5.0). An association was observed between reduction in CD3(+) cell count in histologic studies and reduction in PASI score. No antibodies to galiximab were detected. Conclusion: Galiximab appears to be safe and well tolerated with preliminary evidence of clinical and histologic response.     

Am I (hyper)aroused or anxious? Clinical significance of pre‐sleep somatic arousal in young adults

Self‐reported somatic arousal remains a challenging clinical construct, particularly because only a subset of patients report symptoms such as racing heart, palpitations or increased body temperature interfering with their sleep. It is unclear whether self‐reported somatic arousal is a marker of hyperarousal or co‐morbid clinical anxiety in individuals with insomnia. Participants included 196 young adults aged 20.2 ± 1.0 years old who were predominantly females (75%). About 39% of the sample reported subthreshold insomnia, and about 8% reported clinically significant insomnia, based on their Insomnia Severity Index. Participants completed the Pre‐Sleep Arousal Scale, Beck Anxiety Inventory, Beck Depression Inventory, Arousal Predisposition Scale, and Ford Insomnia Response to Stress Test. Multivariable stepwise regression assessed which factors were independently associated with pre‐sleep cognitive (Pre‐Sleep Arousal Scale‐Cognitive) and somatic (Pre‐Sleep Arousal Scale‐Somatic) arousal. Receiver‐operating characteristic analysis assessed the predictive value to identify clinically significant anxiety (Beck Anxiety Inventory ≥ 20), insomnia (Insomnia Severity Index ≥ 15) and arousability (Arousal Predisposition Scale ≥ 32). Beck Anxiety Inventory (β = 0.42) was the best single correlate of Pre‐Sleep Arousal Scale‐Somatic, while Insomnia Severity Index (β = 0.33) was of Pre‐Sleep Arousal Scale‐Cognitive. A Pre‐Sleep Arousal Scale‐Somatic score of 12 or more identified those with clinically significant anxiety with 65% specificity and 65% sensitivity, while a cut‐off score of 14 increased its sensitivity (86%). Self‐reported pre‐sleep somatic arousal may be an index of co‐morbid clinical anxiety in individuals with insomnia. These findings aid clinicians with assessment and treatment, particularly in the absence of clinical guidelines indicating when somatically focused relaxation techniques should be included as part of multicomponent cognitive behavioural treatment of insomnia.     

Ustekinumab

? Ustekinumab is a fully human monoclonal antibody that binds with high specificity and affinity to the cytokines interleukin (IL)-12 and IL-23, thereby suppressing IL-12- and IL-23-mediated inflammation associated with psoriasis. ? In two large, phase III trials in patients with moderate to severe plaque psoriasis, significantly more subcutaneous ustekinumab 45 or 90 mg recipients (administered as two injections 4 weeks apart) than placebo recipients achieved a 75% improvement on the Psoriasis Area and Severity Index (PASI 75) score at 12 weeks. ? Other efficacy measures, including the physician’s global assessment of clinical response at week 12, also favored ustekinumab over placebo. Psoriatic symptom control was maintained during ustekinumab maintenance therapy (administered once every 12 weeks) for up to 76 weeks. ? In a phase II trial in patients with active plaque psoriasis and psoriatic arthritis, signs and symptoms of arthritis and psoriatic symptom control were improved to a greater extent with ustekinumab than with placebo at 12 weeks, based on the proportion of patients achieving a 20% improvement in American College of Rheumatology response criteria (arthritis) or PASI 75 (skin symptoms). ? Health-related quality of life, assessed using the Dermatology Life Quality Index and the Health Assessment Questionnaire disability index, was improved to a significantly greater extent with ustekinumab than with placebo at week 12. ? Subcutaneous ustekinumab was generally well tolerated in clinical trials, with most treatment-emergent adverse events being of mild severity.     

Association of Disease Severity with IL‐1 levels in Methotrexate‐treated Psoriasis Patients

Interleukin‐1 plays a key role in inflammation and keratinocyte activation. It is an important mediator in the initiation and maintenance of psoriatic plaques and may represent an attractive therapeutic target. The aim of this study is to evaluate the effect of Methotrexate (MTX) on IL‐1 α and IL‐1 β levels in both plasma and skin biopsy of patients with psoriasis and to investigate their association with clinical disease activity. Forty‐five control subjects and 58 patients with psoriasis were recruited for this study. The patients were treated with 7.5 mg of MTX per week for 12 weeks. Folic acid was given at 5 mg once daily except on the day of MTX for 12 weeks. Blood samples and lesional skin biopsy were taken. Disease severity was assessed by Psoriasis Area Severity Index (PASI) score. IL‐1 levels in plasma and skin biopsy were analysed using ELISA. PASI score declined significantly (P < 0.001) from day 0 to 12 weeks of MTX treatment. IL‐1 α level in plasma and skin biopsy was reduced at day 0 sample and elevated significantly (P < 0.001) after MTX treatment. IL‐1β level in plasma and skin biopsy was higher at day 0 sample and reduced significantly (P < 0.001) after MTX treatment. IL‐1α levels and PASI score showed inverse correlation score before and after treatment with MTX. Whereas IL‐1β levels showed positive correlation before and after treatment with MTX. Decreasing IL‐1β levels by MTXs in psoriasis may block the Th17 differentiation. This shows the therapeutic effect of MTX in controlling the immunopathogenesis of psoriasis.     

银屑病患者外周血单个核细胞CCR5的表达及其意义

目的研究银屑病患者外周血单个核细胞趋化因子受体5（CCR5）的表达及其与银屑病皮损面积和严重程度指数（PASI）的关系。方法分离35例中重度寻常型银屑病患者及30例健康对照者外周血单个核细胞（PBMCs）,用RT-PCR法测定PBMCs培养前后CCR5 mRNA的表达水平,免疫荧光标记-流式细胞仪检测CCR5阳性细胞比率。结果治疗前银屑病患者外周血单个核细胞中CCR5 mRNA表达水平明显高于治疗后及健康对照组,并与PASI呈正相关（r=0.516,P〈0.05）。结论 CCR5可能通过活化与趋化单个核细胞到银屑病皮损而参与了银屑病的发病。     

Changes in numbers of epidermal cell adhesion molecules caused by oral cyclosporin in psoriasis.

AIM--To determine the effects of a three month course of low dose cyclosporin on the expression of epidermal cell adhesion molecules. METHODS--Eighteen patients with psoriasis were treated for 12 weeks with either 2.5 or 5 mg/kg/day of oral cyclosporin. Biopsy specimens taken from skin before, during, and after cyclosporin treatment were stained immunohistochemically for CD 54 (ICAM-1), CD 29 (beta-1 integrins), and CD18 (beta-2 integrins). RESULTS--There was a highly significant (p < 0.01) clinical response after 12 weeks of cyclosporin as assessed by the Psoriasis Area and Severity Index (PASI) score. The staining of CD 29 on keratinocytes of affected and unaffected psoriatic skin was not affected by cyclosporin. Epidermal CD54 was variably expressed in active psoriatic plaques and changed unpredictably after cyclosporin (p = NS). Staining for CD18 on large epidermal dendritic cells was reduced after cyclosporin (p < 0.02). The expression of CD18 by large epidermal dendritic cells during treatment correlated strongly with the PASI score at that time and one month after stopping cyclosporin (p < 0.02). CONCLUSIONS--Persistence of epidermal staining for CD 54 in psoriasis is compatible with a good clinical response to cyclosporin. Residual staining for CD 18 on large epidermal dendritic cells may be a useful marker for early clinical relapse.     

Objective assessment of psoriasis erythema for PASI scoring

Skin colour is vital information in dermatological diagnosis as it reflects the pathological condition beneath the skin. It is commonly used to indicate the extent of diseases such as psoriasis, which is indicated by the appearance of red plaques. Although there is no cure for psoriasis, there are many treatment modalities to help control the disease. To evaluate treatment efficacy, the current gold standard method, PASI (Psoriasis Area and Severity Index), is used to determine severity of psoriasis lesion. Erythema (redness) is one parameter in PASI and this condition is assessed visually, thus leading to subjective and inconsistent results. Current methods or instruments that assess erythema have limitations, such as being able to measure erythema well for low pigmented skin (fair skin) but not for highly pigmented skin (dark skin) or vice versa. In this work, we proposed an objective assessment of psoriasis erythema for PASI scoring for different (low to highly pigmented) skin types. The colour of psoriasis lesions are initially obtained by using a chromameter giving the values L*, a*, and b* of CIELAB colour space. The L* value is used to classify skin into three categories: low, medium and highly pigmented skin. The lightness difference (ΔL*), hue difference (Δh_ab), chroma (ΔC*_ab) between lesions and the surrounding normal skin are calculated and analysed. It is found that the erythema score of a lesion can be distinguished by their Δh_ab value within a particular skin type group. References of lesion with different scores are obtained from the selected lesions by two dermatologists. Results based on 38 lesions from 22 patients with various level of skin pigmentation show that PASI erythema score for different skin types i.e. low (fair skin) to highly pigmented (dark skin) skin types can be determined objectively and consistent with dermatology scoring.     

Depressive symptoms and neurocognitive test scores in patients passing symptom validity tests.

This study examined the effect of depression on neurocognitive performance in patients who passed symptom validity testing. The Beck Depression Inventory (BDI) was used to assess depression in 420 patients with heterogeneous referral diagnoses (more than half of these cases were head injury or neurological disease). All patients had demonstrated satisfactory effort by passing two symptom validity tests. No differences were found on objective cognitive and psychomotor measures in groups sorted based on their self-reported depression. In contrast, on the self-report measures [i.e., Minnesota Multiphasic Personality Inventory-2 (MMPI-2), Symptom Checklist-90-Revised (SCL-90-R), and Memory Complaints Inventory (MCI)], differences were found indicating that patients with depression report more emotional, somatic, and cognitive problems. Contrary to expectation, these data suggest that depression has no impact on objective neurocognitive functioning.     

Depression scales in rheumatoid arthritis: criterion contamination in interpretation of patient responses

Self-report depression scales include items concerning somatic symptoms, such as fatigue, pain, and inability to work, which may be symptoms of depression in individuals who do not have a chronic disease. However, in patients with somatic diseases such as rheumatoid arthritis, these symptoms may reflect disease rather than depression. Interpretation of responses to these items in patients with chronic disease as indicating depression is known as “criterion contamination”. Criterion contamination has been described in responses of patients with rheumatoid arthritis on many widely-used depression scales, including the Minnesota Multiphasic Personality Inventory (MMPI), the Beck Depression Inventory, and the Center for Epidemiologic Studies Depression Index (CES-D). Evidence for criterion contamination in responses of patients with rheumatoid arthritis on these depression scales is summarized in this essay.     

骨肉瘤患者的疼痛、负性情绪、睡眠和生活质量及其相互关系

目的：探讨骨肉瘤患者的疼痛、负性情绪、睡眠和生活质量及其相互关系。方法：应用简式McGill疼痛问卷(SF-MPQ)、疼痛自我效能感问卷（PSEQ）、贝克抑郁量表（BDI）、贝克焦虑量表（BAI）、阿森斯失眠量表（AIS）、简式健康相关生活质量问卷（SF-12）对139名骨肉瘤患者和139名健康者的疼痛、情绪、睡眠和生活质量进行评估。结果：61.2%的骨肉瘤患者有中等以上强度的疼痛,PSEQ分与疼痛强度呈明显负相关（P<0.001）;骨肉瘤组在情绪、睡眠、生活质量等量表上的得分均明显高于正常对照组（P<0.01）;骨肉瘤组在疼痛、情绪、睡眠、生活质量等量表上的得分之间存在相关关系（P<0.05）。结论：骨肉瘤导致患者存在疼痛、抑郁、焦虑和睡眠问题,且这些问题相互影响,使得骨肉瘤患者生活质量降低。     

Psychological Symptoms Following Smoking Cessation in Pregnant Smokers

This study examined the relationship between smoking status and psychological symptoms in pregnant women across pregnancy. Participants were 45 women who quit smoking early in pregnancy (early quitters), 22 who quit later in pregnancy (later quitters), and 84 who smoked throughout pregnancy (never quitters). Assessments of smoking status and psychological symptoms (Brief Symptom Inventory and Beck Depression Inventory) occurred near first prenatal visit, second visit, and end of pregnancy. Results indicated that scores on the Global Severity Index of the Brief Symptom Inventory, several Brief Symptom Inventory subscales, and on the Beck Depression Inventory were highest among never quitters, lowest among early quitters, and intermediate for later quitters. Scores decreased across pregnancy, especially between first and second assessments. We found no evidence that quitting smoking increased psychological symptoms either in the immediate post-withdrawal period or later in pregnancy. These findings should temper concerns that quitting smoking may have detrimental psychological consequences during pregnancy.     

Dental outpatients: health locus of control correlates

Examined relationships between the Multidimensional Health Locus of Control (MHLC) Scales, Beck Depression Inventory, Trait subscales of the State-Trait Personality Inventory, and dental ratings of oral hygiene and presence of periodontal disease with dental outpatients (N = 101) at a Veterans Administration Medical Center Dental Clinic. Results indicated that this sample of outpatients scored comparably on MHLC Health Internality and Health Externality to a sample reported by Wallston and Wallston. Older dental patients, in the present sample, scored significantly higher on Powerful Others Externality in contrast to younger Ss, which suggests greater reliance on health professionals for dental health. Confirmatory evidence is presented on the negative correlations of depression, anger, and anxiety with Health Internality. Differential approaches to dental treatment are discussed.