LncRNA microarray profiling identifies novel circulating lncRNAs in hidradenitis suppurativa.

Long noncoding RNAs (lncRNAs) have been demonstrated to be involved in biological processes, both physiological and pathological, including cancer, cardiovascular diseases, multiple sclerosis, autoimmune hepatitis and types I and II diabetes. LncRNAs are also known to have a critical role in the physiology of skin, and in the pathology of cutaneous diseases. LncRNAs are involved in a wide range of biological activities, including transcriptional post­transcriptional processes, epigenetics, RNA splicing, gene activation and or silencing, modifications and/or editing; therefore, lncRNAs may be useful as potential targets for disease treatment. Hidradenitis suppurativa (HS), also termed acne inversa, is a major skin disease, being an inflammatory disorder that affects ~1% of global population in a chronic manner. Its pathogenesis, however, is only partly understood, although immune dysregulation is known to have an important role. To investigate the biological relevance of lncRNAs with HS, the most differentially expressed lncRNAs and mRNAs were first compared. Furthermore, the lncRNA­microRNA regulatory network was also defined via reverse transcription­quantitative PCR analysis, whereby a trio of lncRNA expression signatures, lncRNA­TINCR, lncRNA­RBM5­ASI1 and lncRNA­MRPL23­AS1, were found to be significantly overexpressed in patients with HS compared with healthy controls. In conclusion, the three lncRNAs isolated in the present study may be useful for improving the prognostic prediction of HS, as well as contributing towards an improved understanding of the underlying pathogenic mechanisms, thereby potentially providing new therapeutic targets.

Italian National Registry of Alopecia Areata: an epidemiological study of 699 Italian patients.

BACKGROUND: Alopecia areata (AA) is an organ-specific autoimmune disease that affects the hair follicles of the scalp and the rest of the body causing hair loss. Due to the unpredictable course of AA and the different degrees of severity of hair loss, only a few well-designed clinical studies with a low number of patients are available. Also, there is no specific cure, but topical and systemic anti-inflammatory and immune system suppressant drugs are used for treatment. The need to create a global registry of AA, comparable and reproducible in all countries, has recently emerged. An Italian multicentric electronic registry is proposed as a model to facilitate and guide the recording of epidemiological and clinical data and to monitor the introduction of new therapies in patients with AA. METHODS: The aim of this study was to evaluate the epidemiological data of patients with AA by collecting detailed information on the course of the disease, associated diseases, concomitant and previous events, and the clinical response to traditional treatments. Estimate the impact on the quality of life of patients. RESULTS: The creation of the National Register of AA has proven to be a valid tool for recording, with a standardized approach, epidemiological data, the trend of AA, response to therapies and quality of life. CONCLUSIONS: AA is confirmed as a difficult hair disease to manage due to its unpredictable course and, in most cases, its chronic-relapsing course, capable of having a significant impact on the quality of life of patients.

Long-term Effectiveness and Safety of Upadacitinib for Atopic Dermatitis in a Real-world Setting: An Interim Analysis Through 48 Weeks of Observation.

BACKGROUND: Janus kinase (JAK) inhibitors, including upadacitinib, have been recently approved for the treatment of moderate-severe atopic dermatitis (AD) and real-world data on upadacitinib effectiveness and safety are limited. This interim analysis aimed to assess effectiveness and safety of upadacitinib throughout 48 weeks of observation in a real-world adult AD population. METHODS: This prospective study collected data on adult patients affected by moderate-to-severe AD and treated with upadacitinib at the dosage of either 15 mg or 30 mg daily based on the physician decision. Upadacitinib was prescribed in the context of a national compassionate use programme. In this interim analysis, within patient comparisons of continuous scores of different scales (namely Eczema Area and Severity Index [EASI], body surface area [BSA], Dermatology Life Quality Index [DLQI], Patient Oriented Eczema Measure [POEM], Numeric Rating Scale [NRS] subtests) were performed. The percentage of patients achieving EASI 75, EASI 90 and EASI 100 at Week 16, 32 and 48 was also evaluated. RESULTS: One hundred and forty-six patients were included in the analysis. Upadacitinib 15 mg or 30 mg daily was prescribed as monotherapy in most cases (127/146, 87.0%). Upadacitinib was initially prescribed at the dosage of 30 mg daily in 118 of 146 (80.8%) patients and 15 mg daily in 28/146 (19.2%) patients. A significant improvement in the clinical signs and symptoms of AD was detected by Week 16 and throughout the study period. EASI 75, EASI 90 and EASI 100 responses were achieved by 87.6%, 69.1% and 44.3% at Week 48, associated with a sustained reduction in the mean values of all physician-reported (EASI and BSA) and patient-reported (Itch- Sleep- and Pain-NRS, DLQI, and POEM) disease severity outcomes, up to 48 weeks of treatment. Treatment response observed in 15 mg upadacitinib-treated patients was comparable with that detected in 30 mg upadacitinib-treated patients, revealing no statistical difference between the two patient sub-cohorts. Through the observation period, dose reduction or escalation was observed in 38/146 (26%) of treated cases. Overall, 26 of 146 (17.8%) patients experienced at least one adverse event (AE) during the treatment period. In total, 29 AEs were recorded and most of them were evaluated as mild to moderate, while in 4 cases the occurrence of AE led to drug discontinuation, for a total of 7/146 (4.8%) dropouts. CONCLUSION: This study provides strong evidence of a sustained response obtained by upadacitinib in AD patients, who had failed to respond to conventional or biological systemic agents, through 48 weeks of observation. Upadacitinib was also demonstrated to be advantageous in terms of flexibility in dose reduction or escalation as upadacitinib dose was shaped on clinical needs that, in a real-world setting, might frequently change.

Hidradenitis Suppurativa Burdens on Mental Health: A Literature Review of Associated Psychiatric Disorders and Their Pathogenesis.

Skin, mental health and the central nervous system (CNS) are connected by a deep link. It is not only the aesthetic and sometimes the disfiguring aspects of dermatological conditions that can cause a severe psychological burden; also, different studies have shown how chronic skin-inflammatory diseases may influence the activity of the CNS and vice versa. Moreover, the skin and brain share a common embryogenic origin. Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease affecting the hair follicles of the apocrine regions. The main clinical features are nodules, abscesses, cysts, fistulae and disfiguring scars. Pain and stinking discharge from fistulae are often present. It is not surprising that the psychological burden associated with HS is frequently a challenge in dermatologists' daily routines. Patients often suffer from depression and anxiety, but also from substance abuse, psychotic and bipolar disorders and an increased suicide risk. The aim of this article is to review the main psychiatric disorders associated with HS and their pathophysiology. Research on Pubmed was conducted with the key words Hidradenitis suppurativa, psychiatric, depression, anxiety, bipolar, schizophrenia, abuse, suicidal. A high incidence of psychiatric disorders has been described in HS compared to controls. Hidradenitis suppurativa is not a rare disease, and acknowledging the HS psychological burden, psychiatric-associated diseases and associated biomolecular pathways will help dermatologists to better care for their patients.

Adiponectin Contributes to the Inflammatory Milieu in Hidradenitis Suppurativa.

Introduction: Hidradenitis suppurativa (HS) is a severe chronic skin disease. Although the pathogenesis remains unclear, at the basis of HS there is an enhancement of the immune and inflammatory response together with a susceptibility to environmental factors. Cytokine dysregulation is crucial in HS severity and progression. Objectives: The aim of this study was to analyze serum levels of different cytokines focusing on adiponectin concentration and its oligomers in HS patients compared to both obese and healthy subjects. Methods: The concentrations of adiponectin and cytokines were measured using enzyme-linked immunosorbent assay (ELISA); the oligomeric distribution of adiponectin (low molecular weight (LMW), medium molecular weight (MMW) and high molecular weight (HMW) oligomers)was evaluated through Western Blotting analysis. Results: Total adiponectin is statistically higher in HS patients compared to matched controls and obese subjects. Interestingly, Adiponectin oligomerization state is altered in HS, with an increase of HMW oligomers. Serum levels of PDGF-BB, IL-1ß, IL-5, Il-6, IL12, IL13, IL15, IL-17, GMCSF, INFγ, VEGF and MCP-1 are statistically higher while IL-1ra and RANTES levels are statistically lower in HS patients compared to healthy controls. Interestingly, adiponectin positively correlates with PDGF-BB, and IL-13. Conclusions: Our data confirmed that the complex network that links metabolism to immune homeostasis is dysregulated in HS and that adiponectin and its HMW oligomers are actively involved in this disease. In addition, the correlation between adiponectin and PDGF-BB, and IL-13 extends the role of this adipokine in modulation of the immune response, in particular regulating the innate immune system rather that the adaptive one. Further researches are needed to clarify the complex inflammatory milieu that characterizes HS syndrome.

The Impact of Psoriasis and Atopic Dermatitis on Quality of Life: A Literature Research on Biomarkers.

Psoriasis (PSO) and Atopic dermatitis (AD) are common inflammatory skin diseases that affect people of all ages globally. They negatively impact the quality of life (QoL) of patients in health-related aspects such as physical, psychological and mental functioning. Here, we conducted a review of studies relating to candidate biomarkers and indicators associated with QoL impairment in PSO and AD. Data research was performed using PUBMED and SCOPUS databases from inception to September 2022. Most of the included studies reported genomic or proteomic biomarkers associated with disease activity and QoL outcomes. Sociodemographic, clinical and therapeutic factors have also been implicated in deterioration of life quality in these patients. The inclusion of clinical characteristics, QoL impairment and co-diagnosis should be considered in drug development programs, since processing biomarkers based on an increased number of features in addition to drug class and disease will intensify the value of the biomarker itself, thereby maximizing the future clinical utility as a stratification tool.

Evaluation of the Role of Faecal Calprotectin in the Management of Psoriatic Patients under Treatment with Biologic Drugs.

Background: Fecal calprotectin has emerged as a significant, validated, and non-invasive biomarker allowing for the evaluation of inflammatory bowel disease. Our study assessed the reliability of the use of faecal calprotectin as a valuable tool in the management of psoriatic patients on biological therapy. Methods: This was a single-centre prospective study including adult patients affected by moderate-to-severe psoriasis starting biological therapy. Faecal calprotectin levels were evaluated at baseline and at week 24 (W24) of treatment in all enrolled patients. Results: Overall, 129 patients were enrolled. The mean baseline faecal calprotectin levels were 74.7 µg/g and a significant reduction was detected at W24 of biological therapy (57.5 µg/g). An analysis of faecal CP values stratified by therapy type was performed. No significant reduction was assessed at W24 for any of the anti-IL17 drugs, whereas a significant reduction was detected for all IL23 inhibitors. Conclusions: Our study showed the potential use of faecal CP levels as a valuable tool for exploring intestinal inflammation in the management of psoriatic patients undergoing treatment with biologic drugs.

Circulating microRNAs in Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a pathology characterized by chronic inflammation and skin lesions. The molecular basis of the inflammatory network remains unclear; however, since microRNAs (miRNAs) are involved in the modulation of inflammation, the composition of a micro-transcriptome RNA library using the blood of HS patients was analysed here. The total miRNA expression profiles of miRNAs from HS patients was assayed by real-time qPCR. Here, compared to healthy controls, miR-24-1-5p, miR-146a-5p, miR26a-5p, miR-206, miR338-3p, and miR-338-5p expression was found significantly different in HS. Knowing the significance of the miRNA mechanism in inflammatory and immune progression, we suggest that miRNA profiles found in HS patients can be significant in understanding the pathogenesis modality and establishing efficient biomarkers for HS early diagnosis. In particular, miR-338-5p was closely related to HS invasiveness and production of cytokines and was atypically overexpressed. miR-338-5p may represent a good promise as a non-invasive clinical biomarker for HS.

Impact in Contact Dermatitis during and after SARS-CoV2 Pandemic.

Purpose of the review: Due to the recent COVID-19 pandemic, several skin conditions have emerged due to the preventive measures adopted by both health care workers and the general population against SARS-CoV-2. Above all, wearing of personal protective equipment, frequent hand-washing and disinfecting of surfaces have resulted in an increased risk of irritant or allergic contact dermatitis. The aim of this review is to investigate contact dermatitis associated with COVID-19 pandemic period. Recent findings: There is a real evidence of the rising prevalence of irritant and allergic contact dermatitis in response to the COVID-19 pandemic. The most commonly recorded symptoms are dryness, itch and redness of the skin. Nasal bridge, cheeks, forehead and hands represent the mainly affected skin sites. Summary: Contact dermatitis lesions may appear as a result of various recommendations to prevent transmission of COVID-19. Procedures to alleviate pressure and friction, gentle skin care and adequate moisturizing, have been identified as important preventive strategies for contact dermatitis related to personal protective equipment and personal hygiene measures.