Nemolizumab with concomitant topical therapy in adolescents and adults with moderate-to-severe atopic dermatitis (ARCADIA 1 and ARCADIA 2): results from two replicate, double-blind, randomised controlled phase 3 trials.

BACKGROUND: Nemolizumab, an interleukin (IL)-31 receptor subunit α antagonist, inhibits the IL-31 pathway of itch and skin inflammation in atopic dermatitis. Two international phase 3 studies were done to assess the efficacy and safety of nemolizumab in atopic dermatitis. In this Article we report results for the 16-week initial treatment period of both trials. METHODS: ARCADIA 1 and ARCADIA 2 were identical 48-week randomised, double-blind, placebo-controlled phase 3 trials in adult and adolescent participants (aged ≥12 years) with moderate-to-severe atopic dermatitis, associated pruritus, and inadequate response to topical steroids. Participants were enrolled from 281 clinics, hospitals, and academic centres in 22 countries across both trials, and were randomly assigned (2:1) to receive nemolizumab 30 mg subcutaneously (baseline loading dose 60 mg) or matching placebo once every 4 weeks with background topical corticosteroids (TCS) with or without topical calcineurin inhibitors (TCI; ie, TCS-TCI background treatment). Randomisation was done via interactive response technology and stratified by baseline disease and pruritus severity. Study staff and participants were masked throughout the study, with outcome assessors masked until database lock. Coprimary endpoints at week 16 post-baseline were Investigator's Global Assessment (IGA) success (score of 0 [clear skin] or 1 [almost clear skin] with a ≥2-point improvement from baseline) and at least 75% improvement in Eczema Area and Severity Index score from baseline (EASI-75 response). Outcome rates were compared between groups with the Cochran-Mantel-Haenszel test adjusting for randomisation strata. The key secondary endpoints were the proportion of participants with Peak Pruritus Numerical Rating Scale (PP-NRS) score improvement of at least 4 points at weeks 1, 2, 4, and 16; PP-NRS score below 2 at weeks 4 and 16; Sleep Disturbance Numerical Rating Scale score improvement of at least 4 points at week 16; EASI-75 response plus PP-NRS score improvement of at least 4 points at week 16; and IGA success plus PP-NRS score improvement of at least 4 points at week 16. Efficacy analyses were done on an intention-to-treat basis; safety analyses included all participants who received one dose of nemolizumab or placebo. Both studies are completed (ClinicalTrials.gov: ARCADIA 1, NCT03985943 and ARCADIA 2, NCT03989349). FINDINGS: Between Aug 9, 2019, and Nov 2, 2022, 1728 participants were enrolled across both trials: 1142 were allocated to nemolizumab plus TCS-TCI (620 in ARCADIA 1 and 522 in ARCADIA 2) and 586 to placebo plus TCS-TCI (321 in ARCADIA 1 and 265 in ARCADIA 2). ARCADIA 1 included 500 (53%) male participants and 441 (47%) female participants, and ARCADIA 2 included 381 (48%) male participants and 406 (52%) female participants. Mean age ranged from 33·3 (SD 15·6) years to 35·2 (17·0) years across the treatment groups. Both trials met the coprimary endpoints; at week 16, a greater proportion of participants receiving nemolizumab plus TCS-TCI versus placebo plus TCS-TCI had IGA success (ARCADIA 1: 221 [36%] of 620 vs 79 [25%] of 321, adjusted percentage difference 11·5% [97·5% CI 4·7-18·3], p=0·0003; ARCADIA 2: 197 [38%] of 522 vs 69 [26%] of 265, adjusted difference 12·2% [4·6-19·8], p=0·0006) and an EASI-75 response (ARCADIA 1: 270 [44%] vs 93 [29%], adjusted difference 14·9% [7·8-22·0], p<0·0001; ARCADIA 2: 220 [42%] vs 80 [30%], adjusted difference 12·5% [4·6-20·3], p=0·0006). Significant benefits were observed with nemolizumab for all key secondary endpoints including improvement in itch, as early as week 1, and sleep improvement by week 16. The safety profile was similar between nemolizumab plus TCS-TCI and placebo plus TCS-TCI. In the safety sets, 306 (50%) of 616 participants (ARCADIA 1) and 215 (41%) of 519 participants (ARCADIA 2) who received nemolizumab plus TCS-TCI had at least one treatment-emergent adverse event (serious treatment-emergent adverse events in six [1%] and 13 [3%], respectively); and 146 (45%) of 321 (ARCADIA 1) and 117 (44%) of 263 (ARCADIA 2) who received placebo plus TCS-TCI had at least one treatment-emergent adverse event (serious treatment-emergent adverse events in four [1%] and three [1%], respectively). Ten serious treatment-emergent adverse events possibly related to nemolizumab were reported in five (1%) participants in ARCADIA 2. No deaths occurred. INTERPRETATION: Nemolizumab plus TCS-TCI was efficacious and showed statistically and clinically significant improvements in inflammation and itch in adults and adolescents with moderate-to-severe atopic dermatitis. Nemolizumab might offer a valuable extension of current therapies if approved. FUNDING: Galderma.

Rapid and sustained improvements in itch and quality of life with upadacitinib plus topical corticosteroids in adults and adolescents with atopic dermatitis: 52-week outcomes from the phase 3 AD Up study.

Purpose: Atopic dermatitis (AD) adversely impacts quality of life (QoL). We evaluated the effect of upadacitinib, an oral selective Janus kinase inhibitor approved for moderate-to-severe AD, plus topical corticosteroids (+TCS) on patient-reported outcomes (PROs) over 52 weeks.Materials and methods: In the phase 3 AD Up study (NCT03568318), adults and adolescents with moderate-to-severe AD were randomized 1:1:1 to once-daily upadacitinib 15 mg, 30 mg, or placebo + TCS. Itch, skin pain/symptoms, sleep, QoL, daily activities, emotional state, mental health, and patient impressions of disease severity/improvement/treatment satisfaction were assessed.Results: This analysis included 901 patients. Within 1-2 weeks, PRO improvements were greater with both upadacitinib doses than with placebo (p <.05). Improvements increased through weeks 4-8; rates were generally maintained through week 52. At week 52, the proportion of patients with clinically meaningful improvements in itch (Worst Pruritus Numerical Rating Scale improvement ≥4), skin pain (AD Symptom Scale Skin Pain improvement ≥4), sleep (AD Impact Scale [ADerm-IS] Sleep improvement ≥12), daily activities (ADerm-IS Daily Activities improvement ≥14), and emotional state (ADerm-IS Emotional State improvement ≥11) ranged from 62.1%-77.7% with upadacitinib 15 mg + TCS and 71.3%-83.6% with upadacitinib 30 mg + TCS.Conclusions: Upadacitinib + TCS results in rapid, sustained improvements in burdensome AD symptoms and QoL.

[Treatment of psoriasis vulgaris : Therapy strategies for optimal patient-centered care]. / Therapie der Psoriasis vulgaris : Therapiestrategien für eine optimale patientenzentrierte Versorgung.

Psoriasis is a chronic inflammatory systemic disease that requires optimal long-term management due to its high prevalence in the population and the numerous comorbidities that severely impair quality of life. A variety of treatment options are now available. In addition to objective skin findings and a specific location such as nails or genital area, the presence of psoriatic arthritis and other comorbidities as well as the disease burden of the affected person play a decisive role in individualized treatment decision-making. Good communication with the patient is fundamental to understand the individual needs and expectations of the patient. Shared decision-making can positively influence adherence and thus also the clinical outcome and patient satisfaction. In addition, interdisciplinary collaboration is crucial and often necessary for a comprehensive therapy strategy.

[Inflammatory dermatoses in children and adolescents : Diagnosis and treatment of atopic dermatitis and psoriasis]. / Entzündliche Dermatosen im Kindes- und Jugendalter : Diagnostische und therapeutische Besonderheiten anhand der atopischen Dermatitis und der Psoriasis.

Atopic dermatitis (AD) and psoriasis belong to the most common inflammatory dermatoses that we treat in everyday clinical practice. AD manifests in more than 70% of cases before the age of 5 years. Approximately one-third of psoriasis patients report on onset of disease in the first two decades of life. Here, we are going to review both disorders in the light of pediatric dermatology. We are going to discuss selected subtypes and present clues for further examination with respect to the differential diagnoses and comorbidities. The article provides insight into current therapeutic developments that are relevant for the treatment of children and adolescents.

Gender perspective in psoriasis: a scoping review and proposal of strategies for improved clinical practice by European dermatologists.

Background: The prevalence of psoriasis is similar between men and women; however, evidence exists of sex- and gender-related differences in disease expression, impact, coping, and needs of patients with psoriasis. These differences are essential and should be considered in clinical practice and research. Objective: To compile available evidence on sex- and gender-related differences in psoriasis, identify the most critical gaps in clinical practice and research, and use it to propose strategies for improved clinical practice. Methods: Six European dermatologists selected the topics to consider according to their relevance in the dermatology setting with the support of methodologists. Evidence on sex- and gender-related differences was obtained by a scoping review based on search strategies in Medline and Cochrane Library from inception to October 2021 using the following terms: arthritis, psoriatic, psoriasis, gender, and sex. The panel discussed the results and proposed strategies by consensus. Results: The scoping review identified broad themes: (1) clinical expression, (2) severity and patient-reported outcomes, (3) psychosocial impact, (4) access to treatments and propensity to treat, (5) comorbidities, and (6) treatment effect. The strategies are based on these broad themes. Limitations: No risk of bias assessment was done due to the scoping nature of the review. Conclusion: This review offers insights into gender differences in psoriasis, providing a foundation for improving clinical practice and patient outcomes.

Comparison of different skin care regimens in patients with moderate to severe atopic dermatitis receiving systemic treatment: A randomized controlled trial.

BACKGROUND: Moderate to severe AD can be successfully managed by systemic treatments. Current guidelines also recommend emollients or emollients 'plus' and eudermic cleansers for all AD patients to improve the skin barrier and provide anti-irritant and anti-pruritic effects. OBJECTIVES: To investigate the efficacy of skin care (in addition to systemic treatment) with an Emollient 'plus' balm designed to improve the skin barrier and skin microbiome plus a corresponding syndet compared to usual commercial emollients and cleansers. METHODS: In a randomized controlled multicenter study, patients with moderate to severe AD (Severity scoring of atopic dermatitis [SCORAD] score ≥ 40) receiving systemic treatment (cyclosporin A, dupilumab or a Janus kinase inhibitor) were randomized 1:1 to apply twice daily for 10 weeks Emollient 'plus' after pre-cleaning with the syndet (Emollient 'plus' group) or to continue with their usual emollient and cleanser (Control group). Assessments included SCORAD, pruritus on a Visual Analog Scale, Dermatology quality of life questionnaire (DLQI), efficacy and tolerance questionnaires. RESULTS: Included were 57 patients with mean age of 38 years (range 19-70 years). The mean amount of emollient used after 10 weeks was 447.3 g (range 29-1099 g) and 613.2 g (range 97-2565 g) for the Emollient 'plus' versus the Control, respectively (p = 0.0277). After 10 weeks, subjects in the Emollient 'plus' had a significantly greater reduction in current pruritus (p = 0.0277) and a greater reduction in some DLQI items compared to the Control group. CONCLUSIONS: In patients with moderate to severe AD receiving systemic treatment, the Emollient 'plus' regimen significantly improved pruritus and quality of life items compared to the control, while using 23% less product over a 10-week period. These results stress the importance of daily use of emollients, especially emollients 'plus' to improve signs, symptoms and quality of life in patients with AD.

Trial of Intravenous Immune Globulin in Dermatomyositis.

BACKGROUND: Intravenous immune globulin (IVIG) for the treatment of dermatomyositis has not been extensively evaluated. METHODS: We conducted a randomized, placebo-controlled trial involving patients with active dermatomyositis. The patients were assigned in a 1:1 ratio to receive IVIG at a dose of 2.0 g per kilogram of body weight or placebo every 4 weeks for 16 weeks. The patients who received placebo and those without confirmed clinical deterioration while receiving IVIG could enter an open-label extension phase for another 24 weeks. The primary end point was a response, defined as a Total Improvement Score (TIS) of at least 20 (indicating at least minimal improvement) at week 16 and no confirmed deterioration up to week 16. The TIS is a weighted composite score reflecting the change in a core set of six measures of myositis activity over time; scores range from 0 to 100, with higher scores indicating greater improvement. Key secondary end points included at least moderate improvement (TIS ≥40) and major improvement (TIS ≥60), and change in score on the Cutaneous Dermatomyositis Disease Area and Severity Index. RESULTS: A total of 95 patients underwent randomization: 47 patients were assigned to the IVIG group, and 48 to the placebo group. At 16 weeks, 79% of the patients in the IVIG group (37 of 47) and 44% of those in the placebo group (21 of 48) had a TIS of at least 20 (difference, 35 percentage points; 95% confidence interval, 17 to 53; P<0.001). The results with respect to the secondary end points, including at least moderate improvement and major improvement, were generally in the same direction as the results of the primary end-point analysis, except for the change in creatine kinase level (an individual core measure of the TIS), which did not differ meaningfully between the two groups. Over 40 weeks, 282 treatment-related adverse events occurred in the IVIG group, including headache (in 42% of patients), pyrexia (in 19%), and nausea (in 16%). A total of 9 serious adverse events that were considered to be related to IVIG occurred, including 6 thromboembolic events. CONCLUSIONS: In this 16-week trial involving adults with dermatomyositis, the percentage of patients with a response of at least minimal improvement based on a composite score of disease activity was significantly greater among those who received IVIG than among those who received placebo. IVIG was associated with adverse events, including thromboembolism. (Funded by Octapharma Pharmazeutika; ProDERM ClinicalTrials.gov number, NCT02728752.).

Efficacy of Secukinumab Across Subgroups and Overall Safety in Pediatric Patients with Moderate to Severe Plaque Psoriasis: Week 52 Results from a Phase III Randomized Study.

BACKGROUND: The efficacy and safety of biologic treatments for children and adolescents with moderate to severe psoriasis should be examined over a considerable time period and in different subgroups. OBJECTIVE: We report the efficacy and safety of secukinumab low dose (LD) and high dose (HD) regimens in pediatric patients with moderate to severe psoriasis for up to Week 52. METHODS: This was a randomized, open-label, parallel-group, multicenter study in patients aged  6 to < 18 years. Patients were randomized in a 1:1 ratio to receive LD (75/75/150 mg; N = 42) or HD (75/150/300 mg; N = 42) subcutaneous secukinumab. At randomization, patients were stratified by weight (< 25, 25 to < 50, ≥ 50 kg) and disease severity (moderate/severe). The study is ongoing; the present analysis included data up to Week 52 collected from August 29, 2018 (first patient first visit) to May 28, 2020 (last patient last visit for Week 52). Efficacy was measured using Investigator's Global Assessment modified 2011 0/1 (IGA 0/1) and Psoriasis Area Severity Index (PASI) 75/90/100 response. Safety outcomes included assessment of adverse events. RESULTS: Of the 84 enrolled patients, 78 (92.9%) completed 52 weeks of treatment. Overall, response rates for PASI 75 and IGA 0/1 were similar between the LD (92.8/88.9%) and HD (93.3/84.7%) groups at Week 52. In the LD and HD groups, PASI 90/100 responses at Week 52 were 78.7/53.5% and 84.7/70.0%, respectively. The proportions of IGA 0/1 and PASI 75/90 responders were comparable for the age, body weight, and disease severity subgroups in the secukinumab LD and HD groups. Mean absolute PASI change from baseline at week 52 was - 17.3 ± standard deviation 5.0 and - 18.2 ± 7.0, a percentage change of - 94.3 and - 94.5% for the LD and HD groups, respectively. More than 70% of evaluable patients achieved Children's Dermatology Life Quality Index 0/1 at Week 52 (LD 70.7%; HD 70.3%). The safety profile was consistent with that in adults, with no new safety signals for either secukinumab dosing regimen. CONCLUSION: A high proportion of pediatric patients with psoriasis responded to both dosing regimens of secukinumab and maintained clinical responses through 52 weeks of treatment. No clinical difference was observed in the efficacy of secukinumab across the pediatric subgroups. Safety events were consistent with the established safety profile of secukinumab. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03668613.

A phase 3 open-label, randomized multicenter study to evaluate efficacy and safety of secukinumab in pediatric patients with moderate to severe plaque psoriasis: 24-week results.

BACKGROUND: Psoriasis affects 0.13%-2.1% of children and adolescents. Despite a high unmet need, the current treatment options approved for pediatric psoriasis are limited. OBJECTIVE: To evaluate the efficacy and safety of 2 secukinumab dosage regimens (low dose: 75/75/150 mg; high dose: 75/150/300 mg) stratified and randomized by weight (<25 kg, 25 to <50 kg, ≥50 kg) and disease severity (moderate, severe) in pediatric patients aged 6-<18 years with moderate to severe plaque psoriasis. METHODS: This is a phase 3, open-label, randomized, multicenter study (NCT03668613). RESULTS: Both secukinumab doses were superior to historical placebo with respect to psoriasis area and severity index (PASI)-75/90 and investigator global assessment 0/1 responses at week 12. The estimated probability of a positive treatment effect (ie, log odds ratio > 0) for low- or high-dose secukinumab compared to historical placebo is 1 (ie, 100%). For the low and high doses at week 12, the investigator global assessment 0/1 response rates were 78.6% and 83.3%, respectively, and the PASI-90 response rates were 69% and 76.2%, respectively. The PASI-75 response rate was 92.9% for both the doses. LIMITATIONS: This is an open-label study design without a control arm. CONCLUSION: Secukinumab dosing regimens were efficacious and well tolerated in pediatric patients with moderate to severe plaque psoriasis.

Quality-of-Life Outcomes, Effectiveness and Tolerability of Apremilast in Patients with Plaque Psoriasis and Routine German Dermatology Care: Results from LAPIS-PSO.

INTRODUCTION: Psoriasis is a systemic inflammatory disease characterised by pruritic skin lesions that impair quality of life (QOL). Long-Term Documentation of the Utilization of Apremilast in Patients with Plaque Psoriasis under Routine Conditions (LAPIS-PSO; ClinicalTrials.gov: NCT02626793) was a 52-week, prospective, multicentre, observational cohort study conducted in real-world dermatology clinical settings in Germany. We evaluated physician- and patient-reported outcomes for QOL, effectiveness and tolerability in patients with moderate to severe psoriasis vulgaris in LAPIS-PSO. METHODS: The primary endpoint was the percentage of patients achieving Dermatology Life Quality Index (DLQI) score ≤ 5 or ≥ 5-point improvement from baseline in DLQI score at visit 2 (~ 4 months after baseline). Secondary endpoints included assessments of symptoms and disease severity. Tolerability was evaluated based on adverse events (AEs). A pre-defined subgroup analysis based on baseline Physician's Global Assessment (PGA) score (2 or 3 versus 4) was performed. Data were examined descriptively through visit 5 (~ 13 months) using the last-observation-carried-forward (LOCF) approach and data as observed. RESULTS: In total, 257 patients were included for efficacy assessment. On LOCF analysis, most patients achieved the primary endpoint at visit 2 (66.5%); DLQI response was maintained at visit 5 (72.4%). Earlier treatment response was observed in patients with a PGA score of 2 or 3 versus 4 (visit 1 PASI ≤ 3: 20.5% versus 10.8%). Adverse events were consistent with the known safety profile of apremilast. CONCLUSIONS: In routine clinical care in Germany, patients with moderate to severe plaque psoriasis benefited from apremilast treatment up to ~ 13 months, consistent with findings from clinical trials, with a good safety profile.

[Successful treatment of generalized pustular psoriasis with certolizumab]. / Erfolgreiche Behandlung einer generalisierten pustulösen Psoriasis mit Certolizumab.

Generalized pustular psoriasis is a rare, often relapsing and usually severe inflammatory skin disease with concomitant systemic symptoms in many cases. The disease is in part due to mutations in the gene of the interleukin-36 receptor antagonist (IL36RN) explaining the autoinflammatory nature of this condition. Here, we report on a 39-year-old pregnant woman who stopped her medication with secukinumab due to her pregnancy. Subsequently, she suffered from severe exacerbation of her disease and was admitted to our hospital. The patient had a known mutation in the IL36RN (Ser113Leu) gene. At the 33rd week of her pregnancy therapy with certolizumab was initiated and resulted in a rapid remission within a few weeks. After the patient gave birth, remission could be maintained under the given therapy with this biologic.

Efficacy and safety of abrocitinib in adults and adolescents with moderate-to-severe atopic dermatitis (JADE MONO-1): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial.

BACKGROUND: Abrocitinib, an oral selective Janus kinase 1 inhibitor, was effective and well tolerated in adults with moderate-to-severe atopic dermatitis in a phase 2b trial. We aimed to assess the efficacy and safety of abrocitinib monotherapy in adolescents and adults with moderate-to-severe atopic dermatitis. METHODS: In this multicentre, double-blind, randomised phase 3 trial (JADE MONO-1), patients (aged ≥12 years) with moderate-to-severe atopic dermatitis (Investigator Global Assessment score ≥3, Eczema Area and Severity Index [EASI] score ≥16, percentage of body surface area affected ≥10%, and Peak Pruritus Numerical Rating Scale score ≥4) with a bodyweight of 40 kg or more, were enrolled at 69 sites in Australia, Canada, Europe, and the USA. Patients were randomly assigned (2:2:1) to oral abrocitinib 100 mg, abrocitinib 200 mg, or placebo once daily for 12 weeks. Randomisation was done using an interactive response technology system, stratified by baseline disease severity and age. Patients, investigators, and the funder of the study were masked to study treatment. The coprimary endpoints were the proportion of patients who had achieved an Investigator Global Assessment response (score of 0 [clear] or 1 [almost clear] with a ≥2-grade improvement from baseline), and the proportion of patients who achieved at least a 75% improvement in EASI score from baseline (EASI-75) score, both assessed at week 12. Efficacy was assessed in the full analysis set, which included all randomised patients who received at least one dose of study medication. Safety was assessed in all randomised patients. This study is registered with ClinicalTrials.gov, NCT03349060. FINDINGS: Between Dec 7, 2017, and March 26, 2019, 387 patients were enrolled: 156 were assigned to abrocitinib 100 mg, 154 to abrocitinib 200 mg, and 77 to placebo. All enrolled patients received at least one dose of study treatment and thus were evaluable for 12-week efficacy. Of the patients with available data for the coprimary endpoints at week 12, the proportion of patients who had achieved an Investigator Global Assessment response was significantly higher in the abrocitinib 100 mg group than in the placebo group (37 [24%] of 156 patients vs six [8%] of 76 patients; p=0·0037) and in the abrocitinib 200 mg group compared with the placebo group (67 [44%] of 153 patients vs six [8%] of 76 patients; p<0·0001). Of the patients with available data for the coprimary endpoints at week 12, compared with the placebo group, the proportion of patients who had achieved an EASI-75 response was significantly higher in the abrocitinib 100 mg group (62 [40%] of 156 patients vs nine [12%] of 76 patients; p<0·0001) and abrocitinib 200 mg group (96 [63%] of 153 patients vs nine [12%] of 76 patients; p<0·0001). Adverse events were reported in 108 (69%) of 156 patients in the abrocitinib 100 mg group, 120 (78%) of 154 patients in the abrocitinib 200 mg group, and 44 (57%) of 77 patients in the placebo group. Serious adverse events were reported in five (3%) of 156 patients in the abrocitinib 100 mg group, five (3%) of 154 patients in the abrocitinib 200 mg group, and three (4%) of 77 patients in the placebo group. No treatment-related deaths were reported. INTERPRETATION: Monotherapy with oral abrocitinib once daily was effective and well tolerated in adolescents and adults with moderate-to-severe atopic dermatitis. FUNDING: Pfizer.

Genetic variants in FBLIM1 gene do not contribute to SAPHO syndrome and chronic recurrent multifocal osteomyelitis in typical patient groups.

BACKGROUND: Syndrome of synovitis acne pustulosis hyperostosis osteitis (SAPHO) and chronic recurrent multifocal osteomyelitis (CRMO) present two diseases of a dermatologic and rheumatologic spectrum that are variable in manifestation und therapeutic response. Genetic risk factors have long been assumed in both diseases, but no single reliable factor has been identified yet. Therefore, we aimed to clinically characterize a patient group with syndrome of synovitis acne pustulosis hyperostosis osteitis (SAPHO) (n = 47) and chronic recurrent multifocal osteomyelitis (CRMO)/ chronic non-bacterial osteomyelitis (CNO) (n = 9) and analyze a CRMO candidate gene. METHODS: Clinical data of all patients were collected and assessed for different combinations of clinical symptoms. SAPHO patients were grouped into categories according to the acronym; disease-contribution by pathogens was evaluated. We sequenced coding exons of FBLIM1. RESULTS: Palmoplantar pustular psoriasis (PPP) was the most common skin manifestation in CRMO/CNO and SAPHO patients; most SAPHO patients had sterno-costo-clavicular hyperostosis. The most common clinical category of the acronym was S_PHO (n = 26). Lack of pathogen detection from bone biopsies was more common than microbial isolation. We did not identify autosomal-recessive FBLIM1 variants. CONCLUSIONS: S_PHO is the most common combination of symptoms of its acronym. Genetic analyses of FBLIM1 did not provide evidence that this gene is relevant in our patient group. Our study indicates the need to elucidate SAPHO's and CRMO/CNO's pathogenesis.

Clinical management of pruritus.

The care of patients with chronic pruritus as a symptom of a wide variety of underlying diseases continues to confront dermatologists with diagnostic and therapeutic challenges. However, a structured history and a physical examination may already substantially help in narrowing down the number of potential differential diagnoses. Apart form reducing the intensity of pruritus, identification and appropriate treatment of the underlying disease are important needs of patients. If these goals doesn't lead to improvement of itch, current guidelines provide a number of topical and systemic therapies for symptomatic treatment. Various skin lesions (for example, xerosis caused by irritant substances, secondary scratch lesions) prompt patients to consult a dermatologist, but most cases require an interdisciplinary therapeutic approach to identify potential internal medicine, neurologic, or psychosomatic aspects. Although great strides have been made in basic research, specific therapies are still rare, and a precise knowledge of the legal framework for the implementation of guidelines (for example, off-label use) is essential. This CME article gives an overview of the causes of and treatment options for chronic pruritus and discusses both advances in basic research as well as progress in clinical knowledge.

Melanoma-derived IL-1 converts vascular endothelium to a proinflammatory and procoagulatory phenotype via NFκB activation.

Spreading of melanoma is associated with efficient extravasation of circulating tumor cells from the vascular system into distant target organs. This process is accompanied and supported by proinflammatory and procoagulatory conditions. In this study, we analysed the ability of human melanoma cell lines to activate endothelial cells (ECs) in vitro. Some melanoma cells, that is, MV3, were shown to trigger an prompt calcium-flux-dependent, procoagulatory endothelial response that was accompanied by luminal release of ultra-large von Willebrand factor (ULVWF) fibres that were immobilized to the endothelial surface layer. In contrast to MV3-derived supernatant, prolonged treatment of ECs with WM9-derived supernatant mediated a pronounced activation of nuclear factor kappa B (NFκB). NFκB activation in ECs was dependent on both IL-1α and IL-1ß secreted from melanoma cells. Melanoma-derived IL-1 mediated an upregulation of proinflammatory cytokines IL-6 and IL-8, the intercellular adhesion molecule-1 (ICAM-1), the vascular cell adhesion molecule-1 (VCAM-1) and the procoagulatory tissue factor (TF) in ECs. Our data show that melanoma cells activate ECs either directly and within seconds or by an IL-1-mediated NFκB activation. Both pathways of EC activation convert the regular repressive function of ECs on inflammation and coagulation to a proinflammatory and procoagulatory surface that supports tumor progression.