Identifying Key Drivers in the Pathogenesis of Martorell Hypertensive Ischaemic Leg Ulcer: A Comparative Analysis with Chronic Venous Leg Ulcer.

Martorell hypertensive ischaemic leg ulcer (Martorell HYTILU) is a rare but significant cause of distal leg ulcers. Although hypertension and diabetes are known factors in its development, the precise pathogenesis of Martorell HYTILU remains elusive. To reach a better understanding of Martorell HYTILU, transcriptomic analysis was conducted through RNA sequencing and immunohistochemical comparison of Martorell HYTILU (n = 17) with chronic venous ulcers (n = 4) and healthy skin (n = 4). Gene expression analysis showed a marked activation of immune-related pathways in both Martorell HYTILU and chronic venous ulcers compared with healthy skin. Notably, neutrophil activity was substantially higher in Martorell HYTILU. While pathway analysis revealed a mild downregulation of several immune pathways in Martorell HYTILU compared with chronic venous ulcers, keratinization, cornification, and epidermis development were significantly upregulated in Martorell HYTILU. Additionally, STAC2, a gene encoding for a protein promoting the expression of the calcium channel Cav1.1, was significantly upregulated in Martorell HYTILU and was detected perivascularly in situ (Martorell HYTILU n = 24; chronic venous ulcers n = 9, healthy skin n = 11). The high expression of STAC2 in Martorell HYTILU suggests that increased calcium influx plays an important role in the pathogenesis of the disease. Consequently, calcium channel antagonists could be a promising treatment avenue for Martorell HYTILU.

Management and treatment outcome of DRESS patients in Europe: An international multicentre retrospective study of 141 cases.

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but potentially fatal drug hypersensitivity reaction. OBJECTIVE: To explore treatment approaches across Europe and their impact on the disease course, as well as prognostic factors and culprit drugs. METHODS: In this retrospective European multicentric study, we included patients with probable or certain DRESS (RegiSCAR score ≥ 4) between January 2016 and December 2020. Independent associations between clinical parameters and the risk of intensive care unit admission and mortality at three months were assessed using a multivariable-adjusted logistic regression model. RESULTS: A total of 141 patients from 8 tertiary centres were included. Morbilliform exanthem was the most frequent cutaneous manifestation (78.0%). The mean affected body surface area (BSA) was 67%, 42% of the patients presented with erythroderma, and 24.8% had mucosal involvement. Based on systemic involvement, 31.9% of the patients had a severe DRESS. Anticonvulsants (24.1%) and sulphonamides (22.0%) were the most frequent causative agents. In all, 73% of the patients were treated with systemic glucocorticoids, and 25.5% received topical corticosteroids as monotherapy. Few patients received antiviral drugs or anti-IL5. No patients received intravenous immunoglobulins. The overall mortality was 7.1%. Independent predictors of mortality were older age (≥57.0 years; fully adjusted OR, 9.80; 95% CI, 1.20-79.93; p = 0.033), kidney involvement (fully adjusted OR, 4.70; 95% CI, 1.00-24.12; p = 0.049), and admission in intensive care unit (fully adjusted OR, 8.12; 95% CI, 1.90-34.67; p = 0.005). Relapse of DRESS and delayed autoimmune sequelae occurred in 8.5% and 12.1% of patients, respectively. CONCLUSIONS: This study underlines the need for diagnostic and prognostic scores/markers as well as for prospective clinical trials of drugs with the potential to reduce mortality and complications of DRESS.

Compression Stocking With 100% Donning and Doffing Success: An Open Label Randomised Controlled Trial.

OBJECTIVE: The aim of this study was to test whether an investigational two layer stocking exerting 27-29 mmHg pressure at the medial supramalleolar level, but without compression in the foot and heel, is easier to put on and take off than a standard stocking of the same compression class (23-32 mmHg), and also to assess the prevention of diurnal oedema with both types of stocking. METHODS: This was an open label randomised controlled trial, which included 47 patients. All participants were at least 65 years of age and suffered from chronic venous disease class C3 - C6 in one leg. The primary end point was donning success; secondary endpoints were doffing success, prevention of diurnal oedema over one day, and the comfort of wearing the stocking. Patients were randomly allocated to one of two groups. Both types of compression stocking were compared in each group for ease of donning and doffing in the manner of a crossover study. Subsequently, patients wore the stocking type assigned to their group for a whole day to evaluate comfort and the effect on diurnal leg volume. RESULTS: All participants were able to don the investigational stocking unaided, compared with 75% for the standard stocking (p < .001). Unaided removal success was 100% with the investigational stocking vs. 66% for the standard stocking (p < .001). There was no significant difference in leg volume reduction between the study groups after a day of wear. The investigational stocking was also rated as being more comfortable than the standard stocking (p < .001). CONCLUSION: The investigational stocking, which has no compression in the foot or heel area, is significantly easier to don and doff, with no inferiority in oedema prevention, compared with a standard stocking of the same compression class.

The impact of gender and sex in psoriasis: What to be aware of when treating women with psoriasis.

Psoriasis is a common chronic inflammatory skin disease with an exceptionally high burden for women. Objective: Sex-dependent differences in disease manifestation, severity, treatment choices, subjective disease perception, and the impact on quality of life and risk factors are described and comprehensively discussed. Methods: A literature search was conducted using MEDLINE (PubMed) and the Cochrane Library for systematic reviews to investigate the challenges in treating women with psoriasis. Results and conclusions: The incidence, prevalence, and manifestation of psoriasis of the skin are similar between different sexes. Genetic and environmental factors such as obesity and metabolic syndrome are risk factors and are not equally relevant or pronounced in women and men. Overall, women have a lower disease severity measured by the Psoriasis Area Severity Index, which is associated with a higher impairment of their life quality measured by the Dermatology Life Quality Index compared with men. In addition, women with psoriasis are more likely to have depression than men. Hormonal factors affect psoriasis, with a correlation of high estrogen levels and improvement of psoriasis. Data regarding differences in prescribing patterns of systemic treatments and the severity of psoriasis are not entirely consistent. Registry studies show that men tend to have more severe psoriasis and, in some cases, are prescribed systemic therapies more frequently. Women tend to respond better to systemic treatments and to experience more adverse events. Treatment options are the same for both sexes, except during pregnancy and lactation. Various treatment options are contraindicated due to fear of fetal or neonate harm and lack of data. Topical steroids can be prescribed with a high degree of safety during pregnancy. For other topical therapies (calcineurin inhibitors and vitamin D analogs), no studies of adverse effects in pregnancy are available, and safety data mainly stem from studies examining effects after systemic administration. Antitumor necrosis factor monoclonal antibodies (except for certolizumab pegol) have been associated with a possible increased risk of preterm birth, low gestational age, and cesarean deliveries. Prospective data on the safety of biologics other than antitumor necrosis factor-alpha antibodies to accurately assess whether novel biologics (eg, anti-interleukin 17, 12/23, 23) can be used for systemic therapy in pregnancy are lacking or currently being conducted.