Vascular skin manifestations in patients with severe COVID-19 in intensive care units: a monocentric prospective study.

Various skin manifestations have been reported during the coronavirus disease 2019 (COVID-19) pandemic. Among these are acral vascular skin lesions in non-severe patients, but few studies have focused specifically on patients with severe COVID-19 admitted to the intensive care unit (ICU) We aimed to assess the frequency of acral vascular skin manifestations (AVSM) in patients admitted to the ICU based on systematic dermatological examination We conducted a clinical, observational and prospective study in the ICU of Lille University Hospital (France). All adult patients with RT-PCR-confirmed severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) infection were included on May 5th and 6th, 2020 A total of 39 patients with severe COVID-19 were examined (34 males and five females; median age: 61 [55-59]). We observed AVSM in 11/39 patients (28%) including five with acral necrotic lesions, three with haemorrhagic blisters, one with acral livedoid rash, and one with erosive distal lesions. Chilblain or chilblain-like lesions were not seen, unlike ambulatory or non-severe patients described in the literature. There was no difference regarding the median length of stay in the ICU, initial symptoms of COVID-19 or baseline characteristics, except for a lower BMI in patients with AVSM. All patients had biological coagulation abnormalities (e.g. higher levels of fibrinogen or D-dimers), but there was no difference between patients with and without AVSM AVSM are infrequent and heterogenous and seem to be non-specific to patients with severe SARS-CoV-2, and possibly unrelated to COVID-19. The pathophysiology of AVSM described during the COVID-19 pandemic is not fully elucidated.

Impact of Extra-Intestinal Manifestations at Diagnosis on Disease Outcome in Pediatric- and Elderly-Onset Crohn's Disease: A French Population-Based Study.

Background: Extraintestinal manifestations (EIM) have been associated with more severe course of inflammatory bowel disease. The aim was to study the frequency of EIM in pediatric- and elderly-onset Crohn's disease (CD) and the factors associated with EIM and their impact on long-term disease outcome. Methods: Pediatric- (age at diagnosis younger than 17 years) and elderly-onset CD patients (age at diagnosis 60 years or older) from a prospective population-based registry (EPIMAD) were recruited. Data on EIM and clinical factors at diagnosis and at maximal follow-up were collected. Results: We included 535 pediatric- and 370 elderly-onset patients (median age 14.5 and 69.9 years; median follow-up 11.1 and 5.9 years). Extraintestinal manifestations presented in 23.5% of childhood-onset and 4.9% of elderly-onset individuals at diagnosis, while in 29.8% and 5.9% of patients, EIM developed newly during the follow-up (hazard ration [HR] 4.4, 95% CI, 2.7-7.0, P < 0.001). The most frequently involved organ in both age cohorts, either at diagnosis or during disease course, were joints (pediatric: 11.2% and 22.6%; elderly: 3.2% and 3.5%, respectively) followed by skin (pediatric: 15.9% and 13.6%; elderly: 2.7% and 2.7%, respectively). Extraintestinal manifestations at diagnosis were associated with increased risk for corticosteroids (HR 1.42, 95% CI, 1.14-1.78 and HR 3.38, 95% CI, 1.88-6.08) and immunosuppressive therapy (HR 1.30, 95% CI, 1.02-1.65 and HR 4.24, 95% CI, 1.91-9.42), in both age populations. Conclusions: Extraintestinal manifestations occurred at lower frequency in elderly-onset compared with pediatric-onset patients. In both age populations, presence of EIM at diagnosis independently increased the need for corticosteroid and immunosuppressive treatment.

Features of Patients With Crohn's Disease and Hidradenitis Suppurativa.

BACKGROUND & AIMS: There have been reports of an association between Crohn's disease and hidradenitis suppurativa, a chronic, relapsing, inflammatory condition of the skin. We investigated features of hidradenitis suppurativa in patients with Crohn's disease by analyzing clinical data and performing a literature review. METHODS: We performed a retrospective study by using information from the Mount Sinai Medical Center database from 2003 through 2013; International Classification of Diseases, 9th Revision codes were used to identify patients who had both Crohn's disease and hidradenitis suppurativa. We identified a total of 18 patients with inflammatory bowel disease (15 with Crohn's disease, 3 with ulcerative colitis) and hidradenitis suppurativa. We also performed a systematic search for publications listed in PubMed through December 2013. RESULTS: We identified 15 patients with Crohn's disease and hidradenitis suppurativa who met the inclusion criteria (11 women, 4 men). Nine patients were black, 5 were white, and 1 was Asian. Regions most affected by hidradenitis suppurativa included the axilla (53%), inguinal region (47%), and perianal region (73%). Seven patients had colonic Crohn's disease, and 8 had ileocolonic Crohn's disease; 10 patients had perianal disease. Fourteen patients received medical treatment for hidradenitis suppurativa and for Crohn's disease. Twelve patients were treated with tumor necrosis factor inhibitors for Crohn's disease (11 received infliximab and 4 received adalimumab). Nine patients required dose escalation; 11 responded to tumor necrosis factor inhibitors, and 8 required surgery. Four patients were treated with tumor necrosis factor inhibitors for hidradenitis suppurativa (all with infliximab). Three required a dose escalation; 4 responded to tumor necrosis factor inhibitors, and 3 required surgery. CONCLUSIONS: Crohn's disease and hidradenitis suppurativa are severe inflammatory conditions that can develop in the same patient. They frequently require increased medical and surgical therapy.

Another facet to the anticancer response to lamellarin D: induction of cellular senescence through inhibition of topoisomerase I and intracellular Ros production.

Lamellarin D (LamD) is a marine alkaloid with broad spectrum antitumor activities. Multiple intracellular targets of LamD, which affect cancer cell growth and induce apoptosis, have been identified. These include nuclear topoisomerase I, relevant kinases (such as cyclin-dependent kinase 2) and the mitochondrial electron transport chain. While we have previously demonstrated that LamD at micromolar range deploys strong cytotoxicity by inducing mitochondrial apoptosis, mechanisms of its cytostatic effect have not yet been characterized. Here, we demonstrated that induction of cellular senescence (depicted by cell cycle arrest in G2 associated with ß-galactosidase activity) is a common response to subtoxic concentrations of LamD. Cellular senescence is observed in a large panel of cancer cells following in vitro or in vivo exposure to LamD. The onset of cellular senescence is dependent on the presence of intact topoisomerase I since topoisomerase I-mutated cells are resistant to senescence induced by LamD. LamD-induced senescence occurs without important loss of telomere integrity. Instead, incubation with LamD results in the production of intracellular reactive oxygen species (ROS), which are critical for senescence as demonstrated by the inhibitory effect of antioxidants. In addition, cancer cells lacking mitochondrial DNA also exhibit cellular senescence upon LamD exposure indicating that LamD can trigger senescence, unlike apoptosis, in the absence of functional mitochondria. Overall, our results identify senescence-associated growth arrest as a powerful effect of LamD and add compelling evidence for the pharmacological interest of lamellarins as potential anticancer agents.

Skin side effects of inflammatory bowel disease therapy.

Skin manifestations are common in patients suffering from inflammatory bowel disease (IBD) and can be associated with the disease itself, with nutritional deficiencies, or with therapy. All drugs currently used for treating IBD have the potential to cause dermatologic manifestations that can have a wide range of clinical presentations, from mild drug eruptions to potentially life-threatening immune-mediated reactions. The wider use of thiopurines and anti-tumor necrosis factor in the past years has led to the recognition of 2 more skin complications of IBD therapy: the potentially disfiguring non-melanoma skin cancer associated with the current or past use of thiopurines and the paradoxical new onset or exacerbation of anti-tumor necrosis factor-associated psoriasis. Despite being rare, these complications can be severe and lead to therapy discontinuation, and therefore, gastroenterologists need to become familiar with their epidemiology, diagnosis, and management. Herein, we reviewed the skin side effects of IBD therapy, specially focusing in thiopurines and anti-tumor necrosis factor therapy and in the recently described skin cancer and psoriasis, and we tried to advance some practical algorithms that can provide some help to the clinicians dealing with these complications in their day-by-day practice.

Successful treatment with adalimumab in a familial case of gastrointestinal Behcet's disease.

We present here two siblings with a history of recurrent oral and genital ulcers, neurological and gastrointestinal manifestations. The diagnosis of Behçet's disease in a context of familial aggregation was assumed. Facing repeated steroid-dependent flares and failure of maintenance therapies with colchicine and intolerance to pentoxifilline and disulone, adalimumab was started. Rapid response was observed in both patients, with clinical remission after induction therapy, which currently sustains under maintenance schedule. This case report suggests the effectiveness of adalimumab as first anti-TNFα in case of steroid-dependent/resistant gastrointestinal BD.

[Cutaneous infections]. / Les infections cutanées.

The epidermis, the human being's primary protection against infection and aggression, can crack or split, and result in microbial bacteria penetrating it. Infections may, however, stem from other sources, such as viruses which enter the body via the respiratory tract, and then appear on the skin.

Severe skin lesions cause patients with inflammatory bowel disease to discontinue anti-tumor necrosis factor therapy.

BACKGROUND & AIMS: Psoriasiform and eczematiform lesions are associated with anti-tumor necrosis factor (TNF)-α therapies. We assessed clinical characteristics, risk factors, and outcomes of skin disease in patients with inflammatory bowel diseases that presented with psoriasiform and eczematiform lesions induced by anti-TNF-α agents. METHODS: We studied 85 patients (69 with Crohn's disease, 15 with ulcerative colitis, and 1 with indeterminate colitis; 62 women) with inflammatory skin lesions (62 psoriasiform and 23 eczematiform lesions). RESULTS: Twenty-four patients had a history of inflammatory skin lesions and 15 had a familial history of inflammatory skin disease. Locations of eczematiform lesions varied whereas scalp and flexural varieties were mostly psoriasiform. Skin lesions emerged but inflammatory bowel disease was quiescent in 69 patients following treatment with any type of anti-TNF-α agent (60 with infliximab, 20 with adalimumab, and 5 with certolizumab). Topical therapy resulted in partial or total remission in 41 patients. Patients with psoriasiform lesions that were resistant to topical therapy and that changed anti-TNF-α therapies once or twice developed recurring lesions. Overall, uncontrolled skin lesions caused 29 patients to stop taking TNF-α inhibitors. CONCLUSIONS: Inflammatory skin lesions following therapy with TNF-α inhibitors occurred most frequently among women and patients with a personal or familial history of inflammatory skin disease; lesions did not correlate with intestinal disease activity. Recurring and intense skin lesions caused 34% of patients in this study to discontinue use of anti-TNF-α agents.