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).

[Mobile teledermatology in the treatment of chronic ulcers]. / Mobile Teledermatologie in der Behandlung chronischer Ulzera.

BACKGROUND: Treatment of chronic ulcers is challenging. Advanced age, comorbidities, and a lack of medical knowledge of the caretaker's relatives are additional burdens. This study analyses if patient driven teledermatology could support them in the treatment of leg ulcers. Another purpose was the evaluation of savings in time and costs through telemedicine. PATIENTS AND METHODS: Over a period of approximately 6 months, 50% of the patients were treated in an ambulant setting, the other 50% used mainly teledermatology. The tele-group used an application to upload their pictures, clinical results, and history. After examination, the expert sent back a treatment plan and a date for the next teleconsultation. RESULTS: In all, 40 patients-20 in the tele-group and 20 in the control group-(18 women, 22 men; median age: 75 years [39-88 years]) were included in the study. A total of 4 patients managed the teleconsultation on their own, while 3 patients were supported by relatives and 11 by nurses. Overall, 196 outpatient treatments took place in the control group (1.6 visits/patient/month), compared to 97 outpatient treatments (0.6 visits/patient/month) and 182 teledermatology consults (1.3/patient/month) in the tele-group. Six patients were only treated in the teledermatology setting. CONCLUSIONS: Results from this study suggest that teledermatology is well qualified for the treatment of chronic ulcers; at the same time teledermatology is able to reduce the number of outpatient treatments, in some cases teleconsultation alone is possible. This decreases waiting time and travel costs for patients. Mobile teledermatology for treatment of ulcers was well-accepted among the patients.

Lebensqualität und Behandlungsziele bei Psoriasis aus Patientensicht: Ergebnisse eines österreichweiten Querschnitt-Survey.

HINTERGRUND: Patienten mit Psoriasis sind mit einer krankheitsbedingten Einschränkung ihrer Lebensqualität konfrontiert, weshalb einer hochqualitativen dermatologischen Versorgung ein besonderer Stellenwert zukommt. PATIENTEN UND METHODIK: Wir führten einen bundesweiten Querschnitt-Survey in Österreich (BQSAustria Psoriasis 2014/2015) mit dem Schwerpunkt auf Lebensqualität und Therapiezufriedenheit bei Patienten mit Psoriasis in dermatologischer Behandlung vorwiegend an Zentren mit überwiegend tertiären Versorgungsaufgaben durch. ERGEBNISSE: 70,2 % der 1184 befragten Patienten berichtete über eine eingeschränkte Lebensqualität (DLQI 2-5: 29,4 %; 6-10: 19,3 %; 11-15: 11,5 %; 16-20: 5,2 % und > 20: 4,9 %) trotz Behandlung innerhalb der letzten vier Wochen (mit lokaler Therapie in 88,2 % und/oder systemischer Therapie in 38,7 % der Fälle). Mit den verabreichten Therapien konnte im Durchschnitt kein einziges von 25 definierten subjektiven Behandlungszielen im gewünschten Ausmaß erreicht werden. So litten 82,2 % der Patienten trotz Behandlung weiter unter Juckreiz, wobei statistisch hochsignifikante Assoziationen mit einem schlechten Gesundheitszustand in der letzten Woche (Spear-man-Rangkorrelation; p = 1.1e-45), dem Ausmaß des psoriatischen Körperoberflächenbefalls (p = 3.2e-11) und Kopfhautbefalls (p = 3.2e-11) sowie Schmerzen (p = 2.3e-22) vorlagen. Die Behandlung mit einem Biologikum war mit einer signifikant höheren Patientenzufriedenheit verbunden (Wilcoxon-Test, p = 2.0e-16). SCHLUSSFOLGERUNGEN: Die Lebensqualität der meisten österreichischen Patienten mit Psoriasis in dermatologischer Versorgung ist krankheitsbedingt beeinträchtigt, und es besteht ein Verbesserungspotenzial bei der Umsetzung von Behandlungszielen.

Quality of life and treatment goals in psoriasis from the patient perspective: results of an Austrian cross-sectional survey.

BACKGROUND: Patients with psoriasis experience impairment in quality of life. Thus, high-quality dermatological care is of particular importance. PATIENTS AND METHODS: We performed a nationwide cross-sectional survey in Austria (BQSAustria Psoriasis 2014/2015) with a special focus on quality of life and satisfaction with treatment among psoriasis patients predominantly treated at tertiary care centers. RESULTS: Overall, 70.2 % of 1,184 patients reported impaired quality of life (DLQI 2-5: 29.4 %; 6-10: 19.3 %; 11-15: 11.5 %; 16-20: 5.2 % and > 20: 4.9 %) despite treatment over the preceding four weeks (topical treatment in 88.2 % of cases and/or systemic treatment in 38.7 %). On average, none of the 25 defined subjective treatment goals was achieved to a sufficient degree. In particular, 82.2 % of patients continued to have pruritus despite treatment, which was highly significantly associated with a poor general health status over the preceding week (Spearman's rank correlation; p  =  1.1e-45), the extent of body surface area (p  =  3.2e-11) and scalp area (p  =  3.2e-11) affected, as well as pain (p  =  2.3e-22). Treatment with a biologic was significantly correlated with higher patient satisfaction (Wilcoxon-Test, p  =  2.0e-16). CONCLUSIONS: Despite dermatological care, the majority of Austrian psoriasis patients continues to experience impaired quality of life; there is potential for improvement in the achievement of treatment goals.

Mineral Depositions of Calcifying Skin Disorders are Predominantly Composed of Carbonate Apatite.

Subcutaneous calcifications can lead to complications, including pain, inflammation, ulceration and immobilization. Studies on the pathophysiology of mineral compositions and effective treatment modalities are limited. We therefore studied 14 patients with subcutaneous calcifications. Mineral material was collected and analysed by Fourier transform infrared spectrometry. Blood analyses were run to evaluate systemic alterations of mineral metabolism. Carbonate apatite (CAP) was found to be the single constituent in the majority of patients (n = 9, 64.3%), 3 cases (21.4%) had a composition of CAP and calcium oxalate dihydrate and one case had a combination of CAP and magnesium ammonium phosphate, whereas CAP was the major component in all 4 cases. Only one case showed predominantly calcium oxalate. Thus, CAP was found to be the only or predominant component in most cases of subcutaneous calcifications. Chemical analyses of the mineral compositions may aid in the development of new treatment regimes to improve the solubility of mineral components and to decrease extraosseous calcifications.

Survival and Effectiveness of Tumour Necrosis Factor-alpha Inhibitors in the Treatment of Plaque Psoriasis under Daily Life Conditions: Report from the Psoriasis Registry Austria.

This retrospective multicentre analysis from the Psoriasis Registry Austria (PsoRA) was conducted to determine drug effectiveness and survival of anti-tumour necrosis factor alpha (anti-TNF-α) agents in patients with moderate-to-severe chronic plaque psoriasis over a 9-year period. Data on 1,019 treatment cycles with adalimumab (n = 460), etanercept (n = 501), and/or infliximab (n = 58) administered to 827 patients (272 women, 555 men) were available for analysis. Compared with etanercept, adalimumab and infliximab showed superior short-term effectiveness. Intention-to-treat-calculated median drug survivals for adalimumab (1,264 days) and etanercept (1,438 days) were similar to each other (p = 0.74), but significantly superior to that of infliximab (477 days) (p = 7.0e-07 vs. adalimumab and p=2.2e-07 vs. etanercept, respectively). Their drug survival rates at 36 months were 51.6%, 56.0%, and 22.6%, respectively. Survival rates correlated significantly with effectiveness for adalimumab and etanercept, but not for infliximab.

Childhood generalized pustular psoriasis: longtime remission with combined infliximab and methotrexate treatment.

An 8-year old boy with generalized pustular psoriasis unresponsive to several topical and systemic treatments responded dramatically with long-lasting remission to infliximab in combination with methotrexate. Combined therapy might offer a new therapeutic strategy yielding long-term remission.

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.

Mast cells express IL17A, IL17F and RORC, are activated and persist with IL-17 production in resolved skin of patients with chronic plaque-type psoriasis.

Little is known about IL-17 expression in psoriasis and the actual cellular source of IL-17 remains incompletely defined. We show that high numbers of IL-17 + mast cells persisted in resolved lesions after treatment (anti-IL-17A, anti-IL-23, UVB or topical dithranol) and correlated inversely with the time span in remission. IL-17 + mast cells were found in T cell-rich areas and often close to resident memory T cells (Trm) in active psoriasis and resolved lesional skin. Digital cytometry by deconvolution of RNA-seq data showed that activated mast cells were increased in psoriatic skin, while resting mast cells were almost absent and both returned to normal levels after treatment. When primary human skin mast cells were stimulated with T cell cytokines (TNFα, IL-22 and IFNγ), they responded by releasing more IL-17A, as measured by ELISA. In situ mRNA detection using padlock probes specific for transcript variants of IL17A, IL17F, and RORC (encoding the Th17 transcription factor RORγt) revealed positive mRNA signals for IL17A, IL17F, and RORCin tryptase + cells, demonstrating that mast cells have the transcriptional machinery to actively produce IL-17. Mast cells thus belong to the center of the IL-23/IL-17 axis and high numbers of IL-17 + mast cells predict an earlier disease recurrence.

Pilot study on the acceptance of mobile teledermatology for the home monitoring of high-need patients with psoriasis.

BACKGROUND/OBJECTIVES: The willingness to be educated is one of the highest desires among patients with psoriasis. Therefore, a collaborative model of management would appear to be essential in enhancing patient satisfaction in this challenging condition. The present study aimed at examining the applicability of a mobile teledermatology service in this regard and assessing the association between patient acceptance and perceived health-related quality of life. METHODS: High-need patients with psoriasis performed visits over 12 weeks transmitting clinical images together with some relevant clinical information via mobile phones to teledermatologists, who provided treatment instructions. Ten patients and two teledermatologists completed 20-item patient (weeks 6 and 12) and 10-item physician (at week 12) acceptance questionnaires. In addition, patients answered the dermatology life quality index (DLQI) at weeks 0, 6 and 12. RESULTS: Both patients and teledermatologists were pleased with the service with high acceptance rates (patients: 81.0% at week 6 and 82.9% at week 12; teledermatologists: 74.0%). In addition, 80% of the patients considered the service an alternative to in-person consultation and 90% felt they were in good hands but had achieved a more flexible and empowered lifestyle. No significant correlations were found between patient acceptance and DLQI. Both teledermatologists found the service a convenient and reliable tool for patient monitoring. Neither patients nor teledermatologists thought further in-person consultations necessary. CONCLUSION: Mobile teledermatology is a valuable tool for the home monitoring of patients with psoriasis that makes a meaningful difference in their lives. It is well accepted by both patients and the physicians involved.

Neonatal lupus erythematosus and its clinical variability.

Neonatal lupus erythematosus (NLE) is a rare disease affecting newborns that is caused by maternal autoantibodies transmitted across the placenta. The disease may affect the skin, the heart, and rarely the hepatobiliary or hematological systems. A serious complication affecting some patients with NLE is atrioventricular heart block (AV block). The clinical picture of cutaneous NLE varies considerably. NLE presents with confluent, scaly, periorbital erythema, or erythematous infiltrated plaques with central vesicles and lesions resembling seborrheic eczema or fungal infection. In any newborn with such skin lesions, NLE should be included in the differential diagnosis. Dermatologists play an important role in the diagnosis. We review different skin lesions occurring in neonatal lupus erythematosus based on five patients from our own clinic.

Teledermatological monitoring of psoriasis patients on biologic therapy.

Patients with psoriasis who are being treated with biologics require intensive monitoring. However, the monitoring tool teledermatology is not commonly used. We investigated the applicability of a mobile phone based teledermatological system for monitoring psoriasis patients on biologic therapy. Nineteen patients were given mobile phones with built-in cameras, in order to transmit health status data and images (mobile visits) weekly for a 6-month period. Face-to-face visits were carried out at weeks 0, 4, 12 and 24. Image quality, the Psoriasis Area and Severity Index (PASI), the handling of adverse events, and patients' feedback questionnaires were evaluated. Ninety-five percent of the images were of sufficient quality to enable accurate assessment of the PASI. The distance between the interpolated face-to-face PASIs and the corresponding mobile visit PASIs was 0.46 ± 2.15 (median ± interquartile range). All 155 adverse events were handled correctly by the system. This teledermatological system represents a reliable tool for management of psoriasis patients who are on systemic treatment.

Tele-assessment of Psoriasis Area and Severity Index: a study of the accuracy of digital image capture.

BACKGROUND: The implementation of remote Psoriasis Area and Severity Index (PASI) determinations would greatly enhance the delivery of specialist dermatological care to patients with severe psoriasis unable to attend face-to-face dermatological consultations. Here we investigate the feasibility of the remote determination of PASI scores by comparing the results of face-to-face with digital image assessment. METHODS: Twelve patients with confirmed psoriasis were recruited for the study. Initially, two dermatologists scored the PASI at the patients' usual scheduled face-to-face visits, at which time standardized digital images were obtained. PASI scoring based on digital images was then performed on two separate occasions by three dermatologists with a time-interval period between assessments, facilitating an assessment of score reproducibility. Linear weighted kappa statistics were applied to the PASI scores to ascertain agreement between sets of observations. RESULTS: While we found a moderate (κ = 0.51) agreement between the face-to-face scores, there was very good (κ = 0.83) agreement between the first round of telescores and moderate (κ = 0.60) agreement between the second round of telescores. Comparison between the face-to-face and telescores revealed good (κ = 0.67 and 0.63) agreement for the scorers respectively. CONCLUSION: We demonstrate that PASI scores can be determined with moderate to good accuracy by dermatologists using standardized digital images. Our results imply the implementation of a tele-PASI service may be a practical and effective adjunct to the dermatological care of patients with severe psoriasis where incapacity or distance prevent the realisation of face-to-face consultations.

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.

Biological anti-psoriatic therapy profoundly affects high-density lipoprotein function.

Psoriasis is a common chronic inflammatory skin disease linked to increased cardiovascular risk. Functional impairment of high-density lipoprotein (HDL) may contribute to excessive cardiovascular mortality in psoriasis patients. Anti-cytokine therapies with biologics have been efficiently used for the management of psoriasis, however little data is available on the effects of biologic anti-psoriatic therapies on the composition and functionality of HDL. Blood samples were taken from 17 healthy volunteers and from 27 real-world psoriasis patients at baseline (no therapy with biologics) and after short-term (3 to 6 months) and intermediate-term (1 to 2 years) therapy. The biologics used included anti-interleukin (IL)-12/23p40 (ustekinumab), anti-IL17A (secukinumab) or anti-tumor necrosis factor-α (etanercept or adalimumab) antibodies. We observed that in psoriasis patients at baseline, metrics of HDL function including cholesterol efflux capacity of apolipoprotein B-depleted serum (p = 0.021), paraoxonase (p < 0.001) and lecithin-cholesterol acyltransferase (p < 0.001) activities were impaired, when compared to controls. Unexpectedly, we observed that short- and especially intermediate-term therapy with biologics markedly reduced HDL cholesterol efflux capacity (p < 0.001) and rendered HDL pro-inflammatory (p < 0.001), but increased paraoxonase (p = 0.009) and lecithin-cholesterol acyltransferase (p = 0.019) activities. All biologics caused similar changes in HDL composition, subclass distribution and cholesterol efflux capacity. Our results provide evidence that anti-psoriatic therapy with biologic agents is associated with changes in HDL functionality, particle composition and subclass distribution.

Exercise Pulmonary Resistances Predict Long-Term Survival in Systemic Sclerosis.

BACKGROUND: Pulmonary hemodynamics during exercise may reveal early pulmonary vascular disease and may be of clinical and prognostic relevance in systemic sclerosis (SSc). We aimed to assess the prognostic relevance of exercise pulmonary resistances in patients with SSc with no or mildly increased mean pulmonary arterial pressure (mPAP). RESEARCH QUESTION: Are pulmonary resistances at peak exercise independent predictors of mortality in systemic sclerosis? STUDY DESIGN AND METHODS: All SSc patients with resting mPAP < 25 mm Hg and at least one year of follow-up data who underwent symptom-limited exercise right heart catheterization between April 2005 and December 2018 were analyzed retrospectively. Age-adjusted Cox regression analysis was used to evaluate the association between pulmonary resistances and all-cause mortality. RESULTS: The cohort consisted of 80 patients: 73 women and 7 men with a mean age of 57 years (interquartile range [IQR], 47-67 years) and a mean follow-up time of 10.4 years (IQR, 8.5-11.8 years). At baseline, resting mPAP of ≤ 20 mm Hg and 21 to 24 mm Hg was found in 68 and 12 patients, respectively. Pulmonary vascular resistance (PVR) and total pulmonary resistance (TPR) at peak exercise were associated significantly with mortality (P = .006 [hazard ratio (HR), 2.20; 95% CI, 1.26-3.87] and P = .026 [HR, 1.56; 95% CI, 1.06-2.29]), whereas resting PVR and TPR were not (P = .087 [HR, 2.27; 95% CI, 0.89-5.83] and P = .079 [HR, 1.88; 95% CI, 0.93-3.80]). The mPAP per cardiac output (CO) and transpulmonary gradient (TPG) per CO slopes were associated significantly with mortality (P = .047 [HR, 1.14; 95% CI, 1.002-1.286] and P = .034 [HR, 1.34; 95% CI, 1.02-1.76]) as well. The area under the receiver operating characteristic curve for exercise PVR to predict 10-year mortality was 0.917 (95% CI, 0.797-1.000). INTERPRETATION: PVR and TPR at peak exercise, mPAP/CO slope, and TPG/CO slope are predictors of age-adjusted long-term mortality in SSc patients with no or mildly increased pulmonary arterial pressure.

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.