Characteristics and management of generalized pustular psoriasis (GPP): Experience from the Central and Eastern Europe (CEE) GPP Expert Network.

BACKGROUND: Generalized pustular psoriasis (GPP) is a rare, inflammatory skin disease characterized by widespread eruption of sterile pustules with or without systemic symptoms. OBJECTIVES: This study aimed to describe the demographics of patients with GPP in Central and Eastern Europe (CEE), present the clinical characteristics of individual GPP flares and explore the current treatment landscape. METHODS: Patient demographics were collected at the times of last observation and previous treatment. Characteristics of a patient's last (most recent) and most severe (from all documented episodes) flare were provided at clinician's discretion. RESULTS: Fifty-eight patients were recruited from 12 centres in nine CEE countries; median (range) age was 61 (16-92) years and 60.3% (35 out of 58) were female. The most common comorbidities were hypertension (43.1% [25 out of 58]) and hyperlipidaemia (32.8% [19 out of 58]). Thirty-four patients (58.6%) presented with concomitant plaque psoriasis before or during the course of GPP. Data from two separate flares were recorded in 26 individuals; in 32 patients, the most recent flare was reported as the most severe. Over 90% of patients with a flare episode classified as most severe by clinicians were hospitalized, with >75% of these individuals having a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) total score of 3 or 4. Systemic symptoms were more common in patients with a GPPGA score of 3 or 4 but were also manifest in individuals with a GPPGA score ≤2. A significant correlation was observed between a combined systemic disease score of clinical and laboratory features and both GPPGA total score (r = 0.385, p < 0.001) and GPPGA pustulation subscore (r = 0.305, p < 0.05). CONCLUSIONS: Considerable heterogeneity in the presentation of GPP flares was observed, both between patients and within-patient. All GPP flares were associated with a significant clinical burden, highlighting the unmet need for accurate and early diagnosis.

Drug survival in patients with psoriasis is associated with the availability of biologic medications.

BACKGROUND: Drug survival rates in patients with psoriasis had been described extensively. Different survival rates of TNF-α inhibitors (TNFIs), ustekinumab and secukinumab were reported. OBJECTIVES: To investigate drug survival rates of TNFIs, ustekinumab and secukinumab, with particular emphasis on the difference between ustekinumab and secukinumab. METHODS: Survival analysis was performed in patients with moderate-to-severe psoriasis who received adalimumab, infliximab, etanercept, ustekinumab and secukinumab treatment in 2002-2018, using the Clalit Health Services database. Stratified analysis was performed according to biologic treatment lines. Multivariate analysis was performed adjusting for demographic variables, calendar year, metabolic syndrome, psoriatic arthritis, biologic treatment line, biologic naivety, co-administration of oral treatments and previous oral systemic treatment exposure. RESULTS: Among 1459 patients treated with 3070 biologic medication courses, ustekinumab had a significantly higher crude survival as compared with TNFIs and secukinumab. The mean drug survival of ustekinumab, adalimumab, etanercept, infliximab and secukinumab was 43.5 (CI: 39.7-47.2), 38.2 (CI: 34.8-41), 33.9 (CI: 30.8-37.1), 28.2 (CI: 22.5-33.8) and 17.1 (CI: 15.6-18.6) months, respectively, with significant statistical differences for all comparisons (P < 0.001). The differences between ustekinumab and secukinumab were not significant following adjustment to factors that included treatment line (hazard rate 1.16, CI: 0.93-1.43). CONCLUSION: Different drug survival rates between ustekinumab and secukinumab are determined by the treatment line and calendar year, reflecting the availability of biologic medications, and not only by the biologic attributes of each medication.

Psychological stress and psoriasis: a systematic review and meta-analysis.

BACKGROUND: Psychological stress has long been linked with the exacerbation/onset of psoriasis. OBJECTIVES: To determine if antecedent psychological stress is associated with the exacerbation/onset of psoriasis. METHODS: A search of the PubMed, PsycINFO, Cochrane library and ClinicalTrials.gov databases was performed. Surveys evaluating beliefs about stress reactivity were analysed separately. Suitable studies were meta-analysed. RESULTS: Thirty-nine studies (32 537 patients) were included: 19 surveys, seven cross-sectional studies, 12 case-control studies and one cohort study. Forty-six per cent of patients believed their disease was stress reactive and 54% recalled preceding stressful events. Case-control studies evaluating stressful events rates prior to the exacerbation (n = 6) or onset (n = 6) of psoriasis varied in time lag to recollection (≤ 9 months to ≥ 5 years). Pooling five studies evaluating stressful events preceding onset of psoriasis gave an odds ratio (OR) of 3·4 [95% confidence interval (CI) 1·8-6·4; I2 = 87%]; the only study evaluating a documented stress disorder diagnosis reported similar rates between patients and controls (OR 1·2, 95% CI 0·8-1·8). Four studies evaluating stressful events prior to psoriasis exacerbation reported comparable rates with controls, whereas two found more frequent/severe preceding events among patients with psoriasis. A small prospective cohort study reported a modest association between stress levels and exacerbation of psoriasis (r = 0·28, P < 0·05). CONCLUSIONS: The association between preceding stress and exacerbation/onset of psoriasis is based primarily on retrospective studies with many limitations. No convincing evidence exists that preceding stress is strongly associated with exacerbation/onset of psoriasis.

Narrow band UVB: is it effective and safe for paediatric psoriasis and atopic dermatitis?

BACKGROUND: Phototherapy has a time-honoured place in the treatment of variety of skin diseases in adults. The use of this modality in children is limited mainly due to concerns about long-term carcinogenic potential. Only a few clinical trials have been performed on the efficacy and safety of phototherapy in children. OBJECTIVES: To determine the efficacy and safety of NB-UVB phototherapy in children with atopic dermatitis (AD) and psoriasis. METHODS: This is a retrospective review of the treatment outcomes of 129 children with psoriasis and AD, who were treated with NB-UVB between 1998 and 2006 at our institute. RESULTS: Fifty per cent of the psoriatic patients and 25% of patients with AD achieved clearance by the end of the treatment. NB-UVB phototherapy was well-tolerated, with no serious adverse effects except one doubtful case of melanoma in situ. CONCLUSIONS: NB-UVB may be considered as a viable therapeutic option in children with psoriasis and AD. Children who are treated by phototherapy should remain under annual dermatologic observation. To determine true carcinogenic risk of UV therapy, longer follow-up is essential.

Trends in pemphigus research over 15 years.

BACKGROUND: Although pemphigus is a rare autoimmune blistering disease, it attracts the attention of physicians of many disciplines. OBJECTIVE: This study aims to assess the number of articles on pemphigus that have been published over 15 years in dermatology vs. non-dermatology medical journals, and to evaluate the quality of available evidence. METHODS: PubMed was searched for articles on pemphigus published between 1 January 1993 to 31 December 2007 using the search word pemphigus. Articles were characterized by publication type and journal type per year. Regression analysis was used to determine the effect of year of publication on number of publications of each type. RESULTS: The search yielded 2032 publications on pemphigus during the evaluation period. Sixty-one per cent were published in dermatology journals. Overall, the number of publications increased linearly with time. Most of this increase was accounted for by publications in non-dermatology journals. There was an increase in clinical trials over the course of the study period. The number of certain publications with lower quality of evidence, mainly case reports and letters to the editor, increased significantly in the last few years. There was no increase in publications with high quality of evidence. CONCLUSIONS: The increase on data from non-dermatology disciplines is a welcome contribution. Nevertheless, high-quality evidence on pemphigus is still lacking. We trust that the current trend towards evidence-based dermatology will impact future research on this severe disease.

From basic research to biological treatments: psoriasis publications over the past 15 years.

In the past few decades, great progress has been made in psoriasis research, culminating with the development of new, biological treatments. We designed this study to test the hypothesis that there is a linear increase in psoriasis publications over time. We evaluated all PubMed articles from 1 January 1993 to 31 December 2007. We categorized the search into basic science, traditional therapy and new biological treatments. We used regression analysis to determine the effect of year of publication upon number of publications of each type. There was a significant quadratic increase in the number of all types of psoriasis publications, with basic science-related publications being greatest, followed by relevant clinical publications. We conclude that better understanding of psoriasis immunopathology has led to a significant yearly increase in clinical studies, contributing approximately 60% of studies in the entire field of dermatology reports.

Cholinergic excitation induces activity-dependent electrophysiological and transcriptional responses in hippocampal slices.

To explore the correlations between short-term neurophysiological events initiated by over-activation of acetylcholine receptors, and long-lasting changes in brain function, we combined electrophysiology and PCR-based measurements in hippocampal slices or live mice subjected to stress or drug-induced cholinergic activation. Our findings reveal a common cascade of neuronal events resulting in delayed suppression of cholinergic transmission.