When IL-17 inhibitors fail : real-life evidence to switch from secukinumab to adalimumab or ustekinumab

Psoriasis is a chronic, systemic inflammatory disease that in the moderate to severe forms may benefit of biologics, namely TNF and IL-12/23 and IL-17 inhibitors. Loss of response, lack of response or discontinuation due to adverse events represent a concrete therapeutic challenge for dermatologists that have to switch patients to other treatments. Although some evidences already exist toward the switch from IL-12/23 and TNF inhibitors to IL-17 inhibitors, conversely nothing is present toward the switch from IL-17 inhibitors to IL-12/23 and TNF inhibitors. We performed a real-life study enrolling 50 patients randomly switched to adalimuamb, a TNF inhibitor, or ustekinumab, an IL-12/23 inhibitor. Our observational study suggests that switching from IL-17i to TNFi and IL-12/23i is a safe and effective therapeutic strategy

Fasting and Its Impact on Skin Anatomy, Physiology, and Physiopathology: A Comprehensive Review of the Literature

Skin serves as the first protective line and barrier of the body. Like many other organs, skin can be affected by several disorders in response to external factors such as pathogens, ultraviolet light, and pollution, as well as endogenous alterations related to aging and/or oxidative stress disturbance. Researchers have reported new insights into how skin cells are altered in response to caloric restriction diets in mammals. One of the most well-known caloric restriction diets is the Ramadan intermittent fasting, which is a radical change in the diet plan of practitioners for the period of one lunar month. Ramadan fasting represents the fourth of the five pillars of the Islamic creed. Even though infirm individuals are waived to take part in this religious duty, patients with various health problems, including those with different skin disorders, might choose to share this event with peers and family members. No standardized protocols or guidelines exist, however, to advise their physicians on the proper management of their patients' condition during fasting. With an increasing Muslim population living in Western countries, this topic has started to draw substantial attention, not only of Middle-Eastern physicians, but also of clinicians in the West. For this purpose, we carried out a comprehensive overview on the topic. Our main findings are that: (1) there is a strong need for evidence-based suggestions and guidance. Literature on the impact of the Ramadan fasting, as well as of other kinds of fasting, on skin diseases is scarce and of poor quality, as well as the information available from the Internet; (2) patients willing to fast should be advised about the importance of taking proper treatments or consider alternative options including administration of trans-dermal/topical drugs, as they are permitted during daylight hours. Further, non-compliance has important, clinical and economic implications for an effective patient management

Nonalcoholic fatty liver disease prevalence in an Italian cohort of patients with hidradenitis suppurativa: A multi-center retrospective analysis

BACKGROUND Nonalcoholic fatty liver disease (NAFLD) includes two distinct conditions, with different histologic features and prognosis: non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). Furthermore, NASH is the more aggressive necro-inflammatory form, which may accumulate fibrosis and result in End stage liver disease (ESLD). NAFLD is also linked to systemic inflammatory conditions such as psoriasis. NAFLD is currently the most common cause of ESLD in Western countries, becoming a serious public health concern. Hidradenitis suppurativa (HS) is a systemic inflammatory/autoinflammatory disease of the terminal follicular epithelium of the apocrine gland with a prevalence of 0.05% to 4.10%. Due to its systemic inflammatory behavior several comorbidities were recently associated, however liver ones were scarcely assessed. AIM To evaluate the prevalence and characteristics of NASH/NAFL in HS patients. METHODS This retrospective study is a sub-analysis of a larger study carried out in 4 Italian dermatological centers. In this cohort, there were 83 patients: 51 patients with HS only, 20 patients with HS/NAFL and 12 with HS/NASH. RESULTS Inflammatory comorbidities were present in 3.9% of HS only patients, 25% of HS/NAFL patients and 58.3% of HS/NASH patients (P < 0.001). Similarly, mean Autoinflammatory Disease Damage Index (ADDI) was significantly higher among patients with HS/NASH (5.3 ± 2.2, P < 0.001) compared to patients with HS/NAFL or HS only (2.8 ± 1.6 and 2.6 ± 1.4 respectively). Furthermore, ADDI correlates with IHS4 in HS, HS/NAFL and HS/NASH. Diabetic patients have higher Hurley score than not diabetic ones. Ultrasound examination was significantly different in the three groups. CONCLUSION HS patients displayed a high prevalence of NASH/NAFLD and ultrasound examination should be particularly addressed to patients that display high ADDI scores

Neutrophilic Dermatoses and Their Implication in Pathophysiology of Asthma and Other Respiratory Comorbidities: A Narrative Review

Neutrophilic dermatoses (ND) are a polymorphous group of noncontagious dermatological disorders that share the common histological feature of a sterile cutaneous infiltration of mature neutrophils. Clinical manifestations can vary from nodules, pustules, and bulla to erosions and ulcerations. The etiopathogenesis of neutrophilic dermatoses has continuously evolved. Accumulating genetic, clinical, and histological evidence point to NDs being classified in the spectrum of autoinflammatory conditions. However, unlike the monogenic autoinflammatory syndromes where a clear multiple change in the inflammasome structure/function is demonstrated, NDs display several proinflammatory abnormalities, mainly driven by IL-1, IL-17, and tumor necrosis factor-alpha (TNF-a). Additionally, because of the frequent association with extracutaneous manifestations where neutrophils seem to play a crucial role, it was plausible also to consider NDs as a cutaneous presentation of a systemic neutrophilic condition. Neutrophilic dermatoses are more frequently recognized in association with respiratory disorders than by chance alone. The combination of the two, particularly in the context of their overlapping immune responses mediated primarily by neutrophils, raises the likelihood of a common neutrophilic systemic disease or an aberrant innate immunity disorder. Associated respiratory conditions can serve as a trigger or may develop or be exacerbated secondary to the uncontrolled skin disorder. Physicians should be aware of the possible pulmonary comorbidities and apply this knowledge in the three steps of patients' management, work-up, diagnosis, and treatment. In this review, we attempt to unravel the pathophysiological mechanisms of this association and also present some evidence for the role of targeted therapy in the treatment of both conditions

Psoriasis and Respiratory Comorbidities : the Added Value of Fraction of Exhaled Nitric Oxide as a New Method to Detect, Evaluate, and Monitor Psoriatic Systemic Involvement and Therapeutic Efficacy

Psoriasis is a chronic inflammatory systemic disease characterized by a wide range of comorbidities. Respiratory comorbidities are currently poorly characterized and with discordant results. The systemic state of inflammation caused by psoriasis acts de novo on respiratory tissues and amplifies preexisting inflammation from asthma or chronic obstructive pulmonary disease. Because the lungs act as a gas exchanger between the internal and external environment, the impact of chronic psoriasis inflammation may be easily assessed through the analysis of exhaled breath. The fraction of exhaled nitric oxide test (FeNO) is a potential noninvasive solution that can provide quantitative and qualitative indices of respiratory airway inflammation. FeNO is routinely used to screen and manage asthmatic patients. Recent pilot studies contain encouraging data that underscore its possible use with systemic inflammatory nonpulmonary diseases, such as psoriasis. FeNO may therefore be a useful tool to evaluate underestimated airway inflammation and at the same time globally evaluate the impact of systemically antipsoriatic therapies

Evaluation of the glycemic effect of methotrexate in psoriatic arthritis patients with metabolic syndrome: A pilot study

Methotrexate (MTX) is a systemic immunosuppressant drug used for the treatment of psoriasis and psoriatic arthritis. Previous studies demonstrated a potential association between psoriasis and diabetes mellitus, obesity, atherosclerosis, hypertension, eventuating into metabolic syndrome. This study aimed at exploring the glycemic effects of MTX in psoriatic arthritis (PsA) patients. In this prospective cross-sectional study, 27 patients with PsA were evaluated. The status of PsA and presence of accompanying metabolic syndrome was determined by standard criteria and indices. Blood indicators including HbA1c, erythrocyte sedimentation rate, fasting blood sugar, total cholesterol, high-density lipoprotein, triglycerides, and C-reactive protein were examined before and 12 weeks after MTX therapy. There were no significant changes between HbA1c levels before and after MTX therapy in both genders (men: P=0.131, women: P=0.803). In addition, HbA1c levels in PsA patients with metabolic syndrome were not different before and after treatment (P=0.250). Finally, HbA1c levels did not change in PsA patients without metabolic syndrome before and after therapy (P=0.506). MTX in PsA patients does not appear to have hyperglycaemic effects in the short-term and can be safely used in patients with metabolic syndrome and diabetes

CoNIC Challenge: Pushing the Frontiers of Nuclear Detection, Segmentation, Classification and Counting

Nuclear detection, segmentation and morphometric profiling are essential in helping us further understand the relationship between histology and patient outcome. To drive innovation in this area, we setup a community-wide challenge using the largest available dataset of its kind to assess nuclear segmentation and cellular composition. Our challenge, named CoNIC, stimulated the development of reproducible algorithms for cellular recognition with real-time result inspection on public leaderboards. We conducted an extensive post-challenge analysis based on the top-performing models using 1,658 whole-slide images of colon tissue. With around 700 million detected nuclei per model, associated features were used for dysplasia grading and survival analysis, where we demonstrated that the challenge's improvement over the previous state-of-the-art led to significant boosts in downstream performance. Our findings also suggest that eosinophils and neutrophils play an important role in the tumour microevironment. We release challenge models and WSI-level results to foster the development of further methods for biomarker discovery

Vitamin Din trichology: A comprehensive review of the role of vitamin Dand its receptor in hair and scalp disorders

Vitamin Dplays an important role in maintaining the homeostasis of various biological systems. Beside its well-known function in calcium and phosphate metabolism, it plays a major role in pathophysiology of skin and adnexa. Indeed, Vitamin D, through its receptor (VDR), decreases keratinocyte proliferation, improves their differentiation and modulates both cutaneous innate (antimicrobial activity and antigen presentation) and adaptative immunity (Tand B lymphocyte function). The maintenance of normal hair is dependant on the integrity of the dermis, epidermis and hair cycles. Beside its effect on epidermal differentiation, VDRplays a vital role in preserving the hair follicle integrity. While the relevance of VDRhas been fully elucidated, the real value of Vitamin Din the hair follicle cycle still remains uncertain. To date, results in literature remain contradicting and far from definitive; still, the role of Vitamin D in the various forms of human alopecia is likely to be significant. The aim of this article is to review evidence about the role of Vitamin Dand its receptor in trichology, with a focus on scarring and non-scarring alopecia and in particular on the potential therapeutic use of Vitamin Dfor hair and scalp disorders

Nanodermatology-based solutions for psoriasis : State-of-the art and future prospects

Nanodermatology is an emerging, multidisciplinary science, arising from the convergence of nanotechnology, pharmacology, physics/biophysics, chemistry/biochemistry, chemical engineering, material science, and clinical medicine. Nanodermatology deals with (a) skin biology, anatomy, and physiology at the nanoscale (\u201cskin nanobiology\u201d), (b) diagnosis performed by means of novel diagnostic devices, assisted by nanobiotechnologies (\u201cnanodiagnosis\u201d), and (c) treatment through innovative therapeutic agents, including phototherapy (\u201cphotonanotherapy\u201d/\u201cphotonanodermatology\u201d) and systemic/topical drug administration (\u201cnanotherapy\u201d) at the nanoscale, and drug delivery\u2014such as transdermal or dermal drug delivery (TDDD/DDD)\u2014enhanced and improved by nanostructures and nanodrugs (\u201cnanodrug delivery\u201d). Nanodermatology, as a super-specialized branch of dermatology, is a quite recent specialty: the \u201cNanodermatology Society\u201d founded by the eminent dermatologist Dr. Adnan Nasir, was established in 2010, with the aim of bringing together different stakeholders, including dermatologists, nanotechnology scientists, policy-makers and regulators, as well as students and medical residents. Psoriasis has a prevalence of 2\u20133% worldwide and imposes a severe clinical and societal burden. Nanodermatology-based solutions appear promising for the proper treatment and management of psoriasis, assisting and enhancing different steps of the process of health-care delivery: from the diagnosis to the therapeutics, paving the way for a personalized approach, based on the specific dysregulated biomarkers