Evolution of characteristics and biologic treatment effectiveness in patients of the Austrian psoriasis registry from 2004-2022.

BACKGROUND AND OBJECTIVES: This study analyzed the extent to which the recent introduction of more effective treatments has led to an improvement in real-world psoriasis patients. PATIENTS AND METHODS: Patient characteristics and the first-year treatment effectiveness in biologic-naive patients have been analyzed since 2004 until now, irrespective of treatment switches. RESULTS: Data from 2,729 patients were eligible for this analysis. The proportion of female patients increased significantly over the years from 29.9% to 36.2% (p < 0.028), while the number of patients with psoriatic arthritis declined from 36.6% to 30.0% (p < 0.001). Moreover, the duration of psoriatic disease and PASI at the start of the treatment significantly decreased. Last observation carrief forward (LOCF) analysis indicated that PASI 90 response increased from 18.9 to 44.6% at 3 months and from 32.9 to 66.8% at 12 months after treatment started. Similary, the PASI ≤ 3 rates increased from 33.2% to 66.0% at 3 months and from 41.9% to 78.9% at 12 months after the treatment started. CONCLUSIONS: The continuous introduction of more efficient biologics has led to significant improvements in patient care and clinical outcomes. Though one out of three to five patients, depending on the endpoint selected, nowadays still does not achieve an entirely satisfactory treatment response (i.e., PASI 90 or PASI ≤ 3).

Pityriasis rosea in pregnancy: A case series and literature review.

BACKGROUND AND OBJECTIVE: Pityriasis rosea (PR), a common skin disease in young adults, may adversely affects the course of pregnancy and the unborn child. PATIENTS AND METHODS: Data from forty-six pregnant women with PR seen in the dermatological university clinic between 2003 and 2018 were analyzed and compared with patient data (n = 53) from previously published studies to determine the incidence and risk factors for an unfavorable pregnancy outcome after PR infection. RESULTS: Unfavorable pregnancy outcomes (defined as miscarriage, preterm delivery before week 37 of gestation, or birth weight < 2,500 g) were significantly less frequent in our study population than in a pooled cohort obtained from previously published studies (10.9 % vs. 39.6 %; P = 0.0012). Analysis of pooled data from our study and from previous studies revealed that the week of pregnancy at onset of PR was inversely associated with an unfavorable outcome (odds ratio [OR] = 0.937; 95 % CI 0.883 to 0.993). In addition, duration of PR (OR = 1.432; 95 % CI 1.129 to 1.827), additional extracutaneous symptoms (OR = 4.112; 95 % CI 1.580 to 10.23), and widespread rash distribution (OR 5.203, 95 % CI 1.702 to 14.89) were directly associated with unfavorable outcome. CONCLUSION: In most cases, PR does not influence pregnancy or birth outcomes.

Generation of Red-Shifted Cameleons for Imaging Ca²âº Dynamics of the Endoplasmic Reticulum.

Cameleons are sophisticated genetically encoded fluorescent probes that allow quantifying cellular Ca2+ signals. The probes are based on Förster resonance energy transfer (FRET) between terminally located fluorescent proteins (FPs), which move together upon binding of Ca2+ to the central calmodulin myosin light chain kinase M13 domain. Most of the available cameleons consist of cyan and yellow FPs (CFP and YFP) as the FRET pair. However, red-shifted versions with green and orange or red FPs (GFP, OFP, RFP) have some advantages such as less phototoxicity and minimal spectral overlay with autofluorescence of cells and fura-2, a prominent chemical Ca2+ indicator. While GFP/OFP- or GFP/RFP-based cameleons have been successfully used to study cytosolic and mitochondrial Ca2+ signals, red-shifted cameleons to visualize Ca2+ dynamics of the endoplasmic reticulum (ER) have not been developed so far. In this study, we generated and tested several ER targeted red-shifted cameleons. Our results show that GFP/OFP-based cameleons due to miss-targeting and their high Ca2+ binding affinity are inappropriate to record ER Ca2+ signals. However, ER targeted GFP/RFP-based probes were suitable to sense ER Ca2+ in a reliable manner. With this study we increased the palette of cameleons for visualizing Ca2+ dynamics within the main intracellular Ca2+ store.

Psoriasis and its impact on close relatives and partners of patients - A cross-sectional questionnaire study.

Background: Little is known about the exact impact of psoriasis on the disease burden of close relatives and partners of those affected by the disease. Objectives: The aim of this single-centre cross-sectional study was to evaluate the quality of life in psoriasis patients and the impact of disease on partners and close relatives. Methods: 250 plaque-type psoriasis patients (58.4% males and 41.6% females) with mostly treatment-controlled disease (mean PASI of 1.7 and Dermatology Life Quality Index (DLQI) of 4.1) were recruited from the Psoriasis Registry Austria (PsoRA) and their close relatives and partners were invited to participate in the study. Patient Family Impact Score (PFIS) was calculated from the FamilyPso questionnaire data to establish categories of disease burden in close relatives and partners. Results: Valid FamilyPso questionnaires were returned from 153 (61.2%) close relatives and partners. Correlation analysis revealed a significant association between PASI and DLQI (r = 0.512, p < 0.001), PASI and PFIS (r = 0.228, p = 0.006), and DLQI and PFIS (r = 0.210, p = 0.014). An at least small or larger impairment of life quality (DLQI ≥ 2) was observed in 46.7% of psoriasis patients, despite treatment. A small or larger disease burden was detected in nearly 78.7% of the male and 77.3% of the female relatives and partners quantified with categorized PFIS. Conclusions: The study revealed a significant impact of patients' psoriasis on the disease burden of close relatives and partners, depending on the severity of PASI and extent of quality of life disruption in patients. The gender of the relatives and partners had no impact on the PFIS.

Blocking STAT3/5 through direct or upstream kinase targeting in leukemic cutaneous T-cell lymphoma.

Leukemic cutaneous T-cell lymphomas (L-CTCL) are lymphoproliferative disorders of skin-homing mature T-cells causing severe symptoms and high mortality through chronic inflammation, tissue destruction, and serious infections. Despite numerous genomic sequencing efforts, recurrent driver mutations have not been identified, but chromosomal losses and gains are frequent and dominant. We integrated genomic landscape analyses with innovative pharmacologic interference studies to identify key vulnerable nodes in L-CTCL. We detected copy number gains of loci containing the STAT3/5 oncogenes in 74% (n = 17/23) of L-CTCL, which correlated with the increased clonal T-cell count in the blood. Dual inhibition of STAT3/5 using small-molecule degraders and multi-kinase blockers abolished L-CTCL cell growth in vitro and ex vivo, whereby PAK kinase inhibition was specifically selective for L-CTCL patient cells carrying STAT3/5 gains. Importantly, the PAK inhibitor FRAx597 demonstrated encouraging anti-leukemic activity in vivo by inhibiting tumor growth and disease dissemination in intradermally xenografted mice. We conclude that STAT3/5 and PAK kinase interaction represents a new therapeutic node to be further explored in L-CTCL.

Furin Expression in Patients With Psoriasis-A Patient Cohort Endangered to SARS-COV2?

Background: SARS-Cov2 has raised concerns among dermatologists regarding psoriasis and its respective treatments. Comorbidities, which induce the expression of the proprotease furin have been associated with severe course of COVID-19. Furin and angiotensin converting enzyme 2 (ACE2) play a major role in viral host cell entry of SARS-Cov2. Objective: To evaluate mRNA expression of Furin and ACE2 from blood cells in psoriasis patients, and whether systemic or topical treatment reduces expression levels. Methods: This observational translational study analyzed blood samples from patients from a clinical trial and samples retrieved from the biobank of the Psoriasis Registry Austria (PsoRA). Furin and ACE2 expression levels were analyzed prior to as well as 3 and 12-24 months after start of biologic treatment with either ustekinumab or secukinumab. Additionally, the study analyzed expression levels prior to, 6 days after start of dithranol treatment and 4-6 weeks after end of dithranol treatment. Results: Furin mRNA expression was significantly increased at baseline in the biologic (4.9 ± 2.6 fold, p < 0.0001) and in the dithranol group (2.7 ± 1.4 fold, p < 0.001) compared to controls. There was a trend for arthritis patients to express more furin than patients with psoriatic skin involvement only (5.26 ± 2.30 vs. 3.48 ± 2.27, p = 0.078). Analyzing furin mRNA expression after treatment initiation with secukinumab or ustekinumab revealed a normalization of levels after 3 and 12 to 24 months. Similar findings were obtained for patients treated with dithranol, with significantly decreased expression levels 6 days after start of dithranol treatment and also at follow-up, (4-6 weeks after dithranol treatment had been terminated). ACE2 expression levels did not differ from controls at any timepoint, regardless of biologic or topical treatment. Conclusion: Significantly overexpressed levels of furin were observed in untreated patients, and, thus, these patients may be at risk for infection and a severe course of COVID-19. However, the data indicate that successful therapeutic intervention in psoriasis, by systemic biologic or topical treatment, can efficiently reduce furin levels in blood cells, possibly limiting the risk of psoriasis patients for a severe COVID-19 course. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT02752672.

Long-Term Course of Polymorphic Light Eruption: A Registry Analysis.

Background: Little is known about the long-term course of polymorphic light eruption (PLE). Objective: To predict disease course, a questionnaire was sent to patients whose PLE had been diagnosed between March 1990 and December 2018 and documented in the Austrian Cooperative Registry for Photodermatoses. Methods: In January 2019, 205 PLE patients were contacted by mail and asked to complete a questionnaire on their disease course, including whether the skin's sun sensitivity had normalized (i.e., PLE symptoms had disappeared), improved, stayed the same, or worsened over time. Patients who reported normalization of sun sensitivity were asked to report when it had occurred. Results: Ninety-seven patients (79 females, 18 males) returned a completed questionnaire. The mean (range) duration of follow-up from PLE onset was 29.6 (17-54) years for females and 29.4 (16-47) years for males. The disease disappeared in 32 (41%) females after 17.4 (2-41) years and in 4 (24%) males after 11.8 (5-26) years. Twenty-nine (37%) females and 6 (35%) males reported improvement of symptoms over time; 15 females (19%) and 7 males (41%) reported no change; and 3 females (4%) and no males reported worsening of symptoms. Kaplan-Meier analysis revealed that after 20 years 74% (95%CI, 64-82%) of patients still suffered from PLE. PLE lesion persistence (>1 week) tended to predict a prolonged course of PLE. Conclusions: PLE usually takes a long-term course over many years though in most patients its symptoms improve or disappear over time. How improvement relates to the pathophysiology of the disease remains to be determined.

Effectiveness and clinical predictors of drug survival in psoriasis patients receiving apremilast: A registry analysis.

BACKGROUND: Little is known about the effectiveness and drug survival associated with apremilast under real-world conditions. OBJECTIVE: To investigate the influence of patient and disease characteristics on drug survival associated with apremilast and to elucidate clinical effectiveness with regard to the psoriasis area and severity index (PASI) reduction. METHODS: This was an observational, retrospective, multicenter analysis from the Austrian Psoriasis Registry. RESULTS: Data from 367 patients were eligible for analysis. The 12-month drug survival rate associated with apremilast (ie, the proportion of patients on the drug) was 57.3% and decreased significantly in patients younger than 40 years (relative hazard ratio = 1.49, P = .007918). Sex; concomitant arthritis; previous biologic therapy; obesity; and palmoplantar, scalp, nail, and intertriginous involvement did not significantly affect drug survival. At 12 months, the response rates in patients receiving apremilast per protocol with a PASI of 50, 75, 90, and 100 were 80.0%, 56.4%, 38.2%, and 22.7%, respectively. LIMITATIONS: Inclusion of a substantial number of patients with no record of absolute PASI at study entry and lack of PASI reduction follow-up data of 103 patients (28.1%) after starting apremilast treatment. CONCLUSION: Apremilast is a robust antipsoriatic drug for which the drug survival is not strongly influenced by most patient- or disease-related factors except age. Drug survival is significantly shorter in patients younger than 40 years.

Quality of Life, Anxiety, and Depression in Patients With Early-Stage Mycosis Fungoides and the Effect of Oral Psoralen Plus UV-A (PUVA) Photochemotherapy on it.

Background: Little is known about psychological discomfort and quality of life (QoL) in early stage mycosis fungoides (MF) and the effect of psoralen plus UV-A (PUVA) on it. Objective: To evaluate QoL, anxiety, and depression with validated instruments in early stage MF patients and whether PUVA treatment improves it. Methods: Patients with stage IA to IIA MF were treated with PUVA twice weekly for 12-24 weeks, followed by maintenance treatment or not, in a prospective randomized clinical trial. Patients completed a questionnaire on DLQI as well as the Hospital Anxiety and Depression Scale (HADS) prior to therapy, after their last PUVA exposure, and after the PUVA maintenance or observance phase. Results: For 24 patients with early stage MF, completed questionnaires were available and analyzed. Prior to treatment, 17% reported strong (DLQI > 10) and 29% moderate impairment (DLQI 6-10) in QoL; 33% of patients reported HADS scores indicating anxiety, and 21% reported scores indicating depression. PUVA significantly improved overall QoL by reducing mean DLQI scores by 58.6% (p = 0.003), HADS-A by 30% (p = 0.045), and HADS-D by 44% (p = 0.002). Improvements in QoL and psychological well-being seemed to be sustained, irrespective of maintenance treatment or not. Limitations: Small sample size. Conclusions: PUVA sustainably improves QoL and psychological well-being in patients with early stage MF. Clinical trial registration: ClinicalTrials.gov identifier: NCT01686594.