Which Factors Are Associated with Persistence of Depressive and Anxiety Symptoms in Patients Affected by Atopic Dermatitis despite 2-Year Treatment with Dupilumab?

Background: Atopic Dermatitis (AD) is a prevalent inflammatory skin disease whose course is often complicated by the presence of concomitant anxiety and depressive disorders. Dupilumab has been demonstrated to be largely effective in AD. The aims of the present study were to (1) to verify the effectiveness of 2-year dupilumab treatment on the depressive and anxiety symptoms of patients affected by AD and (2) to identify predictors of the persistence of psychiatric symptoms despite maintenance treatment with dupilumab. Methods: A total of 331 patients with severe AD were assessed at baseline and at different times over 2 years by a large set of rating scales, including the Eczema Area and Severity Index (EASI), the Hospital Anxiety and Depression Scale (HADS), and the Dermatology Life Quality Index (DLQI). Paired sample t-tests were performed to verify the effectiveness of dupilumab on the severity of AD and mental health items. Two binary logistic regression models were then used to identify the predictors of the persistence of clinically significant depression and anxiety, defined by a score ≥ 8 on each sub-scale of the HADS. Results: After 2 years of treatment with dupilumab, the patients benefited, showing a significant improvement in both the dermatological disease and comorbid depression/anxiety (p < 0.001 for all scales). Overall, 17.5% and 13% of patients, respectively, reported residual depressive and anxiety symptoms after the 2-year treatment with dupilumab. The baseline predictors of the persistence of clinically significant depressive symptoms after the 2-year treatment with dupilumab were found to be a higher body mass index (BMI) (p = 0.012), a lower impact of dermatological disease on quality of life (p = 0.015), and more severe depressive symptoms (p < 0.01), while for anxiety, the only predictor was found to be female gender (p = 0.03). Conclusions: Using a multidisciplinary approach, at baseline, dermatologists should more closely monitor patients who are at a greater risk of maintaining residual psychiatric symptoms despite therapy, such as those with more severe depressive symptoms and those who are overweight.

Biosensing circulating MicroRNAs in autoinflammatory skin diseases: Focus on Hidradenitis suppurativa.

MicroRNAs (miRNAs) play a crucial role in the early diagnosis of autoinflammatory diseases, with Hidradenitis Suppurativa (HS) being a notable example. HS, an autoinflammatory skin disease affecting the pilosebaceous unit, profoundly impacts patients' quality of life. Its hidden nature, with insidious initial symptoms and patient reluctance to seek medical consultation, often leads to a diagnostic delay of up to 7 years. Recognizing the urgency for early diagnostic tools, recent research identified significant differences in circulating miRNA expression, including miR-24-1-5p, miR-146a-5p, miR26a-5p, miR-206, miR338-3p, and miR-338-5p, between HS patients and healthy controls. These miRNAs serve as potential biomarkers for earlier disease detection. Traditional molecular biology techniques, like reverse transcription quantitative-polymerase chain reaction (RT-qPCR), are employed for their detection using specific primers and probes. Alternatively, short peptides offer a versatile and effective means for capturing miRNAs, providing specificity, ease of synthesis, stability, and multiplexing potential. In this context, we present a computational simulation pipeline designed for crafting peptide sequences that can capture circulating miRNAs in the blood of patients with autoinflammatory skin diseases, including HS. This innovative approach aims to expedite early diagnosis and enhance therapeutic follow-up, addressing the critical need for timely intervention in HS and similar conditions.

Immunotherapy in cutaneous melanoma and biologics in psoriatic disease: similarities and differences from a clinical multidisciplinary perspective.

INTRODUCTION: Immunomodulating therapies harness the power of the immune system to combat disease. In advanced melanoma, immune checkpoint inhibitors have significantly improved survival outcomes by activating the immune system to recognize and eliminate cancer cells. In psoriasis, interleukin inhibitors effectively suppress inflammation and improve disease symptoms. AREAS COVERED: We provide a meta-opinion-based consensus paper on the analogies and differences in treatment mechanisms, duration, frequency between immunotherapy for advanced melanoma and biologics for psoriasis. Combining the current scientific evidence with expert insights, we provide valuable guidance for future research and decision-making processes. EXPERT OPINION: The development of immunological treatments in melanoma and psoriasis has revolutionized dermatology, but the quest for tailored therapies that maximize efficacy continues. Managing cutaneous exacerbations during melanoma immunotherapy in psoriatic patients remains challenging. Similarly, treating oncologic psoriasis patients resistant to traditional therapies requires individualized approaches. Research is needed to identify response predictors in both conditions and address the sustainability of healthcare systems due to the high cost of biologics. Drug delay studies for psoriasis and longer follow-up evaluations after immunotherapy discontinuation in melanoma are essential for optimizing treatment outcomes and resource allocation.

S2k guidelines on diagnosis and treatment of linear IgA dermatosis initiated by the European Academy of Dermatology and Venereology.

INTRODUCTION: Linear IgA dermatosis (LAD) is a rare subepidermal autoimmune bullous disease (AIBD) defined by predominant or exclusive immune deposits of immunoglobulin A at the basement membrane zone of skin or mucous membranes. This disorder is a rare, clinically and immunologically heterogeneous disease occurring both in children and in adults. The aim of this project is to present the main clinical features of LAD, to propose a diagnostic algorithm and provide management guidelines based primarily on experts' opinion because of the lack of large methodologically sound clinical studies. METHODS: These guidelines were initiated by the European Academy of Dermatology and Venereology (EADV) Task Force Autoimmune Bullous Diseases (AIBD). To achieve a broad consensus for these S2k consensus-based guidelines, a total of 29 experts from different countries, both European and non-European, including dermatologists, paediatric dermatologists and paediatricians were invited. All members of the guidelines committee agreed to develop consensus-based (S2k) guidelines. Prior to a first virtual consensus meeting, each of the invited authors elaborated a section of the present guidelines focusing on a selected topic, based on the relevant literature. All drafts were circulated among members of the writing group, and recommendations were discussed and voted during two hybrid consensus meetings. RESULTS: The guidelines summarizes evidence-based and expert opinion-based recommendations (S2 level) on the diagnosis and treatment of LAD. CONCLUSION: These guidelines will support dermatologists to improve their knowledge on the diagnosis and management of LAD.

Hidradenitis Suppurativa-Related Autoinflammatory Syndromes: An Updated Review on the Clinics, Genetics, and Treatment of Pyoderma gangrenosum, Acne and Suppurative Hidradenitis (PASH), Pyogenic Arthritis, Pyoderma gangrenosum, Acne and Suppurative Hidradenitis (PAPASH), Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis (SAPHO), and Rarer Forms.

Hidradenitis suppurativa (HS) is an autoinflammatory skin disorder of the terminal hair follicle, which can present in sporadic, familial, or syndromic form. A classification has been proposed for the latter, distinguishing cases associated with a known genetic condition, with follicular keratinization disorders or with autoinflammatory diseases. This review focuses on the clinical and genetic features of those entities (ie, pyoderma gangrenosum [PG], acne and HS; PG, acne, pyogenic arthritis and HS; psoriatic arthritis, PG, acne and HS; synovitis, acne, pustulosis, hyperostosis, osteitis; and so forth) for which the collective term HS-related autoinflammatory syndromes is proposed.

Effectiveness, Tolerability, and Drug Survival of Risankizumab in a Real-World Setting: A Three-Year Retrospective Multicenter Study-IL PSO (ITALIAN LANDSCAPE PSORIASIS).

BACKGROUND: Risankizumab is a humanized monoclonal antibody that selectively inhibits interleukin-23. It has been approved for moderate-to-severe plaque psoriasis and has shown efficacy and safety in clinical trials and real-world experiences. This study aimed to evaluate the long-term effectiveness, safety, and drug survival of risankizumab in a real-life setting. MATERIALS AND METHODS: We included patients treated with risankizumab from January 2019 to February 2023. A Psoriasis Area and Severity Index score (PASI) was collected at weeks 0, 16, 28, 52, 104, and 156, when available. The occurrence of any adverse events was recorded at each visit. RESULTS: We enrolled 1047 patients. At week 52, a ≥90% improvement in PASI was observed in 81.44% of patients, with a continuous improvement throughout the study (88.99% and 99.07% at weeks 104 and 156, respectively). After three years of treatment, all patients involving the scalp, palms/soles, and genitalia and 95% of patients with nail psoriasis achieved a complete or almost complete skin clearance. No significant safety findings were observed, and 90.73% of the patients were still on treatment after 36 months. CONCLUSIONS: This study supports the long-term effectiveness and safety of risankizumab in a real-world setting, even in patients involving difficult-to-treat areas.

Treatment of Psoriasis Patients with Latent Tuberculosis Using IL-17 and IL-23 Inhibitors: A Retrospective, Multinational, Multicentre Study.

BACKGROUND: Tuberculosis has a major global impact. Immunocompetent hosts usually control this disease, resulting in an asymptomatic latent tuberculosis infection (LTBI). Because TNF inhibitors increase the risk of tuberculosis reactivation, current guidelines recommend tuberculosis screening before starting any biologic drug, and chemoprophylaxis if LTBI is diagnosed. Available evidence from clinical trials and real-world studies suggests that IL-17 and IL-23 inhibitors do not increase the risk of tuberculosis reactivation. OBJECTIVE: To evaluate psoriasis patients with treated or untreated newly diagnosed LTBI who received IL-17 and IL-23 inhibitors and the tolerability/safety of tuberculosis chemoprophylaxis. METHODS: This is a retrospective, observational, multinational study from a series of 14 dermatology centres based in Portugal, Spain, Italy, Greece and Brazil, which included adult patients with moderate-to-severe chronic plaque psoriasis and newly diagnosed LTBI who were treated with IL-23 or IL-17 inhibitors between January 2015 and March 2022. LTBI was diagnosed in the case of tuberculin skin test and/or interferon gamma release assay positivity, according to local guideline, prior to initiating IL-23 or IL-17 inhibitor. Patients with prior diagnosis of LTBI (treated or untreated) or treated active infection were excluded. RESULTS: A total of 405 patients were included; complete/incomplete/no chemoprophylaxis was administered in 62.2, 10.1 and 27.7% of patients, respectively. The main reason for not receiving or interrupting chemoprophylaxis was perceived heightened risk of liver toxicity and hepatotoxicity, respectively. The mean duration of biological treatment was 32.87 ± 20.95 months, and only one case of active tuberculosis infection (ATBI) was observed, after 14 months of treatment with ixekizumab. The proportion of ATBI associated with ixekizumab was 1.64% [95% confidence interval (CI): 0-5.43%] and 0% for all other agents and 0.46% (95% CI 0-1.06%) and 0% for IL-17 and IL-23 inhibitors, respectively (not statistically significant). CONCLUSIONS: The risk of tuberculosis reactivation in patients with psoriasis and LTBI does not seem to increase with IL-17 or IL-23 inhibitors. IL-17 or IL-23 inhibitors should be preferred over TNF antagonists when concerns regarding tuberculosis reactivation exists. In patients with LTBI considered at high risk for developing complications related to chemoprophylaxis, this preventive strategy may be waived before initiating treatment with IL-17 inhibitors and especially IL-23 inhibitors.

Biologics for Hidradenitis suppurativa: evolution of the treatment paradigm.

INTRODUCTION: Hidradenitis suppurativa (HS) is an autoinflammatory skin disease with a high unmet need for effective medical management. Clinically, it is characterized by inflammatory nodules that may progress into abscesses, draining tunnels and extensive scarring, mainly affecting apocrine gland-bearing areas. AREAS COVERED: Treatment options include topical and systemic medications and a variety of surgical procedures. The anti-TNF-α antibody adalimumab and the anti-IL-17 secukinumab are the only two approved biologics for HS, showing moderate efficacy. HS research is a rapidly growing field, with a wide range of agents leveraging distinct mechanisms of action currently under development. Drugs targeting the IL-17 and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways are the most advanced in both ongoing and completed Phase 3 studies, promising deeper levels of response. Use of other, off-label biologics is also discussed. EXPERT OPINION: A therapeutic algorithm is proposed based on comorbidities and existing evidence. Patient-tailored combinations between biologics and other biologics or small molecules will hopefully allow clinicians to target most events in HS pathophysiology in a complementary way while obtaining a meaningful effect on their devastating manifestations.

Extensive and Persistent Dermal Melanocytosis in a Male Carrier of Mucopolysaccharidosis Type IIIC (Sanfilippo Syndrome): A Case Report.

Congenital dermal melanocytosis (DM) represents a common birthmark mainly found in children of Asian and darker skin phototype descent, clinically characterized by an oval blue-grey macule or macules, commonly located on the lumbosacral area. In rare DM cases, when presenting with diffuse macules persisting during the first years of life, it could represent a cutaneous feature of mucopolysaccharidoses (MPS). Extensive congenital DM is actually associated with Hurler syndrome (MPS type I) and Hunter syndrome (MPS type II), although several reports also described this association with MPS type VI and other lysosomal storage disorders (LySD), including GM1 gangliosidosis, mucolipidosis, Sandhoff disease, and Niemann-Pick disease. Here, we present the case of a two-year-old boy presenting with extensive dermal melanocytosis, generalized hypertrichosis, and chronic itch, harboring a heterozygous variant of uncertain significance, NM_152419.3: c.493C>T (p.Pro165Ser), in the exon 4 of HGSNAT gene, whose mutations are classically associated with MPS IIIC, also known as Sanfilippo syndrome. This is the first report that highlights the association between extensive congenital DM and MPS type IIIC, as well as a pathogenetic link between heterozygous LySD carrier status and congenital DM. We speculate that some cases of extensive congenital DM could be related to heterozygous LySD carriers, as a manifestation of a mild clinical phenotype.

Clinical Features and Response to Treatment in Elderly Subjects Affected by Hidradenitis Suppurativa: A Cohort Study.

Hidradenitis suppurativa (HS) is a chronic-relapsing inflammatory skin disease. It usually appears in the second and third decades, but a smaller proportion of patients develop late-onset HS. Geriatric HS, defined as the persistence or the development of HS after the age of 65 years, has been poorly explored. This study aimed to investigate the clinical features, treatment management and response to therapies of HS elderly subjects (≥65 years old). We designed a multicentric observational study, gathering data from seven Italian university hospitals. Demographic and clinical data of HS patients aged over 65 years were collected at baseline, week 12 and week 24. Overall, 57 elderly subjects suffering from HS were enrolled. At baseline, disease severity was predominantly moderate-to-severe, with 45.6% of patients classified as Hurley III. The gluteal phenotype was the most frequently observed; it also appeared to affect patients' quality of life more than other phenotypes. Gluteal involvement was detected in about half (49.1%) of cases and associated with severe stages of the disease. In terms of therapeutic response, Hurley III patients showed the persistency of higher values of mean IHS4, DLQI, itch- and pain-NRS scores compared to Hurley I/II. In conclusion, disease severity in this subpopulation appears high and treatment is often challenging.

A Multidisciplinary Approach to Patients with Psoriasis and a History of Malignancies or On-Treatment for Solid Tumors: A Narrative Literature Review.

Psoriasis is a chronic immune-mediated disease that is linked to an increased risk of cancer. Although numerous studies have explored whether neoplasms are concurrent conditions or are induced by psoriasis, a definitive definition remains elusive. In this study, we conducted a comprehensive narrative literature review to offer practical guidance to oncologists and dermatologists regarding the initiation and discontinuation of biologics for psoriasis. The findings indicate that a customized approach is recommended for each patient, and that a history of malignancies does not constitute an absolute contraindication for biologics. Growing evidence supports the treatment of selected patients, emphasizing a nuanced assessment of benefits and risks. There is a lack of data specifying a safe timeframe to initiate biologics following a neoplasm diagnosis due to influences from cancer-related and patient-specific characteristics impacting prognosis. Some patients may continue anti-psoriasis therapy during cancer treatments. Enhanced comprehension of the biological mechanisms in cancer progression and the immune microenvironment of psoriasis holds promise for refining therapeutic strategies. In conclusion, a personalized treatment approach necessitates collaboration between oncologists and dermatologists, considering factors such as cancer prognosis, psoriasis clinical manifestations, patient characteristics, and preferences when making treatment decisions.