Background: Due to similarities, the distinction between generalized pustular psoriasis (GPP) and acute generalized exanthematous pustulosis (AGEP) has been a matter of debate for a long time. Objectives: Our aim was to define the molecular features of GPP and AGEP. Methods: We analyzed skin biopsy samples and clinical data from 125 patients with AGEP, GPP, palmoplantar pustulosis (PPP), plaque psoriasis (PSO), and nonpustular cutaneous adverse drug reactions (ADRs), as well as from healthy skin controls using RNA-sequencing and blinded histopathologic analyses. Results: The transcriptome and histopathologic features of AGEP and GPP samples exhibited significant overlap (177 differentially expressed genes [DEGs] in GPP and AGEP compared to healthy skin, only 2 DEGs comparing AGEP and GPP). Yet, they displayed marked differences from those of PPP, PSO, and ADR samples, with a notable number of DEGs (131 DEGs comparing AGEP and PSO, 75 DEGs comparing AGEP and PPP, and 52 DEGs comparing AGEP and ADR). A transcriptome profile subgroup evaluation of >13,000 analyzed genes did not reveal any DEGs in drug-induced GPP and AGEP. Moreover, the immune response pattern and immune cell composition did not differ between drug-induced GPP and AGEP, whereas non-drug-induced GPP had higher expression of T(H)17-cell-related genes and a higher neutrophil count than AGEP. Conclusions: We propose that AGEP is a drug-induced variant of GPP and therefore part of IL-36-related pustulosis. A key signature overarching this spectrum was identified, thereby opening the therapeutic approach of IL-36 inhibition to all subtypes of the disease.

Ammonia oxidizing archaea (AOA) have been repeatedly detected in the human skin microbiome through molecular and biochemical analyses, yet their persistence, physiology, and adaptations remain poorly understood. Here, we describe two cultivated strains, Candidatus Nitrosocosmicus epidermidis and Ca. Nitrosocosmicus unguis, enriched from human skin samples. These autotrophic strains grow on ammonia and urea as sole energy sources. Genomic islands and expanded gene families in their genomes testify to the capacity of colonizing skin, including specific interactions with host proteins and signaling cascades that distinguish these AOA from their close relatives from soil. Molecular signatures of Nitrosocosmicus ssp. were consistently identified on individuals in cross-sectional and longitudinal cohorts (n=47) with a higher prevalence in sebaceous areas. Co-occurrence network patterns with specific bacteria reinforce the observation that AOA of the genus Nitrosocosmicus form a stable component of the healthy skin and represent emerging commensals in the human microbiome. ### Competing Interest Statement The authors have declared no competing interest.

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.

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).

ZusammenfassungHintergrund und ZieleIn dieser Studie wurde untersucht, inwieweit die Einführung wirksamerer Medikamente in jüngster Zeit zu einer Verbesserung der Behandlungsergebnisse von Psoriasis‐Patienten im klinischen Alltag geführt hat.Patienten und MethodikEs wurden Patientencharakteristika und die Wirksamkeit der Therapie im ersten Behandlungsjahr bei Biologika‐naiven Patienten von 2004 bis heute analysiert, unabhängig von Therapiewechseln.ErgebnisseDie Daten von 2729 Patienten eigneten sich für die Analyse. Der Anteil der weiblichen Patienten stieg über die Jahre signifikant von 29,9% auf 36,2% (p < 0,028), während der Anteil der Patienten mit einer Psoriasis‐Arthritis von 36,6% auf 30,0% sank (p < 0,001). Außerdem nahm die Dauer der Psoriasis‐Erkrankung und der PASI‐Wert zu Beginn der Behandlung in Verlauf der Zeit signifikant ab. Die „letzte Beobachtung übernommen“ (LOCF)‐Analyse zeigte, dass das PASI‐90‐Ansprechen drei Monate nach Therapiebeginn von 18,9% auf 44,6% und 12 Monate nach Therapiebeginn von 32,9% auf 66,8% anstieg. Ebenso stiegen die PASI<3 Befunde von 33,2% auf 66,0% 3 Monate und von 41,9% auf 78,9% 12 Monate nach Behandlungsbeginn.SchlussfolgerungenDie kontinuierliche Einführung wirksamerer Biologika hat zu einer deutlichen Verbesserung des klinischen Ansprechens und der Patientenversorgung geführt. Dennoch erreicht auch heute noch, je nach gewähltem Endpunkt, jeder dritte bis fünfte Patient kein vollständig zufriedenstellendes Behandlungsergebnis (d.h. PASI 90 oder PASI ≤ 3).

JDDG: Journal der Deutschen Dermatologischen GesellschaftVolume 21, Issue 6 p. 697-698 FORUM-ÖGDV Preisträger stellen sich vor: Thomas Graier erhält den Versorgungsforschungspreis der ÖGDV 2022 Thomas Graier, Corresponding Author Thomas Graier [email protected] Korrespondenzanschrift Dr. Thomas Graier, Medizinische Universität Graz, Universitätsklinik für Dermatologie und Venerologie, Auenbruggerplatz 8, 8036 Graz. Email: [email protected]Search for more papers by this author Thomas Graier, Corresponding Author Thomas Graier [email protected] Korrespondenzanschrift Dr. Thomas Graier, Medizinische Universität Graz, Universitätsklinik für Dermatologie und Venerologie, Auenbruggerplatz 8, 8036 Graz. Email: [email protected]Search for more papers by this author First published: 20 June 2023 https://doi.org/10.1111/ddg.15138_gRead the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. LITERATUR 1Purzycka-Bohdan D, Kisielnicka A, Zabłotna M, et al. Chronic plaque psoriasis in Poland: Disease severity, prevalence of comorbidities, and quality of life. J Clin Med. 2022; 11(5): 1-16. 2Yeung H, Takeshita J, Mehta NN, et al. Psoriasis severity and the prevalence of major medical comorbidity: A population-based study. JAMA Dermatol. 2013; 149(10): 1173-9. 3Mason KJ, Barker J, Smith C, et al. Comparison of drug discontinuation, effectiveness, and safety between clinical trial eligible and ineligible patients in BADBIR. JAMA Dermatol. 2018; 154(5): 581-8. 4Masson Regnault M, Castañeda-Sanabria J, Diep Tran MHT, et al. Users of biologics in clinical practice: Would they be eligible for phase III clinical studies? Cohort study in the French Psoriasis Registry PSOBIOTEQ. J Eur Acad Dermatology Venereol. 2019; 293-300. 5Graier T, Salmhofer W, Jonak C, et al. Biologic drug survival rates in the era of anti-interleukin-17 antibodies: A time-period-adjusted registry analysis. Br J Dermatol. 2021; 184(6): 1094-105. Volume21, Issue6June 2023Pages 697-698 ReferencesRelatedInformation

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.

Pityriasis rosea (PR), a common skin disease in young adults, may adversely affects the course of pregnancy and the unborn child.

ZusammenfassungHintergrund und ZielsetzungPityriasis rosea (PR), eine häufige Hauterkrankung bei jungen Erwachsenen, kann den Verlauf der Schwangerschaft und das ungeborene Kind nachteilig beeinträchtigen.Patienten und MethodikSechsundvierzig schwangere Frauen mit PR, die zwischen 2003 und 2018 an der dermatologischen Universität vorstellig waren, wurden analysiert und die Daten mit Patientendaten aus früher veröffentlichten Studien (n = 53) verglichen, um die Inzidenz und die Risikofaktoren für einen ungünstigen Schwangerschaftsausgang nach einer PR‐Infektion zu bestimmen.ErgebnisseUngünstige Schwangerschaftsausgänge (definiert als Fehlgeburt, Frühgeburt vor der 37. Schwangerschaftswoche oder Geburtsgewicht < 2500 g) waren in unserer Studienpopulation signifikant seltener als in der gepoolten Kohorte aus zuvor veröffentlichten Studien (10,9 % gegenüber 39,6 %; P = 0,0012). Die Analyse der gepoolten Daten aus unserer und früheren Studien ergab, dass die Schwangerschaftswoche bei Beginn der PR invers mit einem ungünstigen Ausgang assoziiert war (Odds Ratio [OR] = 0,937; 95 %‐KI 0,883 bis 0,993). Darüber hinaus waren die Dauer der PR (OR = 1,432; 95 %‐KI 1,129 bis 1,827), extrakutane Manifestationen (OR = 4,112; 95 %‐KI 1,580 bis 10,23) und ein großflächiges Exanthem (OR = 5,203; 95 %‐KI 1,702 bis 14,89) direkt mit einem ungünstigen Schwangerschaftsausgang assoziiert.SchlussfolgerungIn den meisten Fällen hatte die PR keinen Einfluss auf die Schwangerschaft oder die Geburt.

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.

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.

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.

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.

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.