Rapid Efficacy of riSankizumab in pretibial psoriasis invOLVEment: RESOLVE.

Background: Despite extraordinary improvements in the management of psoriasis in recent times, some areas of the body, such as the pretibial area, still show an unsatisfactory response and a more significant impact on patient quality of life. This multicentre study focuses on psoriasis affecting sensitive areas (particularly the pretibial area), its impact on quality of life and the therapeutic response to risankizumab. Methods: This multicentre prospective observational study recruited patients with moderate-to-severe psoriasis with pretibial area involvement. All patients underwent treatment with risankizumab (150 mg every 3 weeks), and efficacy was assessed after 24 weeks. Results: The study included 128 patients with a mean age of 51 years, suffering from moderate-to-severe psoriasis with involvement of the pretibial area with median total Psoriasis Area Severity Index score of 17.05 and Dermatology Life Quality Index of 16.27. The group was further divided into two sub-groups: the 'mother patch' group, in whom the very first psoriatic plaque appeared in the pretibial region (45 patients), and the 'non-mother patch' group, in whom the psoriatic lesion in the pretibial region was present but not as the first manifestation (83 patients). In order to better assess the involvement of psoriasis in the pretibial area, the pretibial plaque lesion severity index was also calculated at baseline in all patients: extent 2.75, erythema 2.64, infiltration 2.45 and desquamation 2.38. All participants in this study showed a good therapeutic response, with a reduction in all scores. Conclusions: The pretibial area is becoming an object of therapeutic interest due to some resistance to clearance and the consequent impairment of patient quality of life. This study showed that risankizumab can give favourable therapeutic results not only in patients with moderate-to-severe psoriasis with involvement of the difficult-to-treat areas but particularly in patients with recalcitrant plaques in the pretibial area.

Interleukin-13 Inhibitors in the Treatment of Atopic Dermatitis: The Role of Tralokinumab.

INTRODUCTION: The advent of biotechnological drugs has significantly changed the management of atopic dermatitis (AD) and the approach to the moderate-to-severe form of this chronic relapsing disease. OBJECTIVES: The aim of our review is to summarize the current literature on anti-interleukin (IL)-13 in atopic dermatitis. METHODS: A literature search was organized and a systematic review was performed to summarize the most recent evidence supporting the efficacy and safety of tralokinumab. RESULTS: Tralokinumab (anti-IL-13) 300 mg every 2 weeks subcutaneously has proven effective in several clinical trials in adults and adolescents with moderate to severe atopic dermatitis inadequately controlled with other topical or systemic therapies. Tralokinumab was found to be significantly superior in terms of efficacy in reducing Investigator's Global Assessment (IGA), Eczema Area and Severity Index (EASI) -75, Numeric Pain Rating Scale (NRS) pruritus, and Dermatology Life Quality Index (DLQI) scale numbers. During follow-up, tralokinumab was well tolerated with limited severity of adverse events. CONCLUSIONS: Tralokinumab leads to statistically significant improvements in disease severity and outcome scores. It represents an effective treatment option for adults with moderate to severe AD, but further large-scale studies are needed to verify long-term superiority over other treatments.

Extracellular vescicles in psoriasis: from pathogenesis to possible roles in therapy.

Psoriasis is a chronic inflammatory disease affecting skin and joints characterized by a chronically altered immune and inflammatory response. Several factors occur from the onset to the development of this disease due to different types of cells spatially and temporally localized in the affected area, such as, keratinocytes, macrophages, neutrophils and T helper lymphocytes. This scenario leads to the chronic release of high levels of inflammatory mediators (i.e., IL-17, IL-23, IL-22, TNF-α, S100 proteins, Defensins) and lastly parakeratosis and thickening of the stratum spinosum. Extracellular vesicles (EVs) are small double membraned biological nanoparticles that are secreted by all cell types and classified, based on dimension and biogenesis, into exosomes, microvesicles and apoptotic bodies. Their role as vessels for long range molecular signals renders them key elements in the pathogenesis of psoriasis, as well as innovative platforms for potential biomarker discovery and delivery of fine-tuned anti-inflammatory therapies. In this review, the role of EVs in the pathogenesis of psoriasis and the modulation of cellular microenvironment has been summarized. The biotechnological implementation of EVs for therapy and research for new biomarkers has been also discussed.

OPT-In; Optimized Patient Treatment Outcomes in Plaque Psoriasis: A 3-Year State-Transition Treatment-Sequencing Model in the Italian Setting.

INTRODUCTION: There are several treatment options for plaque psoriasis (PsO), but uncertainty remains around the optimal sequencing of treatments. The aims of this study were to investigate how adopting a best-treatment-first treatment sequence impacts patient outcomes and healthcare systems and to quantify the cost of treatment failure to the healthcare system. METHODS: A 3-year state-transition treatment-sequencing model which identifies all possible treatment sequences in PsO was adapted to the Italian healthcare setting. Treatments considered in the model are those with European Medicines Agency marketing authorization and reimbursement in Italy as of December 2022. Italian market share data (2019-2021) and list prices (2022) informed the current prescribed sequences; these sequences were compared against all possible sequences to determine opportunities for improvement. Both the national perspective in Italy as well as the local perspective from seven regions were considered. The cost of treatment failure was informed through a questionnaire circulated to Italian dermatologists. RESULTS: Overall, 1284 possible treatment sequences are possible when four lines of treatment are considered for patients with moderate-to-severe PsO in Italy. Within the estimated range of treatment failures across those sequences (0.97-2.56 per patient over 3 years), current prescribing behavior from the national perspective suggests patients will face 1.44 failures on average; this highlights the potential for improvement. For every treatment failure, the cost borne by the Italian National Healthcare Service (NHS) is €676.80. Overall, prescribing more optimized treatment sequences results in a 22.95% reduction in failures with a 2.27% increase in costs. The regional analyses found similar trends. CONCLUSIONS: Results suggest that selecting the most effective treatment sequences for incident patients provides the greatest opportunity to reduce treatment failures and maximize patient outcomes with a modest impact on costs. While regional variations exist, there is room for improvement across the board, which could translate to more efficient local healthcare systems.

Rapid response on facial psoriasis to bimekizumab: case series.

Psoriasis is a chronic inflammatory disease that can affect any part of the body but, when it appears in certain areas, like the face, it can have a very significant psychological impact. Biologics, in particular IL-17 and IL-23 drug inhibitors, have shown relevant clinical efficacy in the management of psoriatic lesions in difficult-to-treat areas. In post hoc analysis of phase III trials in plaque psoriasis, bimekizumab has shown safety and complete clearance of high-impact areas. However, these studies did not focus on the effect of bimekizumab on facial lesions. Therefore, this case series represents the first clinical real-life experience of rapid and successful management of facial psoriasis with bimekizumab in six patients.

18F-FDG PET-CT Scans in Oncology Patients Treated with Hyaluronic Acid Filler: Not Always a Pitfall.

The use of hyaluronic acid (HA) fillers in oncology patients undergoing PET-CT scans is a topic of debate due to potential interference with imaging accuracy. A 54-year-old female, postmelanoma metastasectomy in the parotid region with subsequent facial nerve palsy (FNP), received HA filler injections for facial symmetry and functional restoration. Follow-up PET-CT scans showed no interference or artifacts attributable to HA injection, allowing for accurate imaging results. This case suggests that HA fillers administered in oncology patients may not universally pose challenges or disrupt PET-CT imaging interpretation. Due to the possible false positives induced by fillers, the inclusion of aesthetic treatments in patients' anamnesis is a crucial step to accurately interpret PET-CT images. Although maintaining high level of caution in interpreting PET-CT results after filler injection is essential, our case emphasizes the safety of this procedure in oncology patients undergoing follow-up PET-CT scans.

Successful Treatment with Bimekizumab of a Psoriatic Patient Undergoing Hemodialysis: A Case Report and Review of the Literature.

Background/Objectives: Treating psoriasis patients requires the consideration of potential underlying complications like latent viral infections and chronic kidney disease, which may influence therapy selection. Case presentation: A patient with end-stage kidney disease (ESKD) undergoing hemodialysis (HD) was successfully treated with bimekizumab, an IgG1 humanized monoclonal antibody inhibiting interleukin (IL)-17A and IL-17F. This case appears to be the first documented instance of effective anti-IL-17A/IL-17F antibody treatment in a psoriasis patient undergoing HD, with a sustained positive response for eight months. Discussion: Studies indicate the comparable pharmacokinetics, efficacy, and safety of certain psoriasis drugs in patients with chronic kidney disease (CKD) and those with normal renal function. The positive clinical outcome observed following treatment with bimekizumab aligns with the existing literature on this topic. However, further studies are needed to objectively evaluate the pharmacokinetics, efficacy, and safety of this drug in this specific setting. Conclusions: This documented case represents the first known use of bimekizumab to treat psoriasis in patients undergoing dialysis, suggesting its potential effectiveness and safety in this population.

Efficacy and safety of tildrakizumab in elderly patients: real-world multicenter study (ESTER - study).

Purpose of the article: Interleukin-23 inhibitors, such as tildrakizumab, have emerged as safe and effective options for the management of psoriasis. Yet their efficacy in elderly patients (aged 65 years or more), particularly in those with difficult-to-treat areas involvement, remains insufficiently explored. We conducted this real-life retrospective multicentric observational study to assess the effectiveness of tildrakizumab in elderly patients with moderate-to-severe psoriasis, with involvement of difficult-to-treat areas.Materials and methods: We enrolled forty-nine patients aged 65 years old or more (mean age 73.1 ± 6.0), all treated with tildrakizumab for at least 28 weeks. The effectiveness of tildrakizumab was assessed by Static Physician's Global Assessment of Genitalia (sPGA-G), fingernail-PGA (f-PGA), palmoplantar PGA (pp-PGA), scalp-specific PGA (sc-PGA), and Psoriasis Area and Severity Index (PASI) scores.Results: Significant improvements in PASI scores were observed within 28 weeks of treatment, with 77.5%, 60%, and 45.2% of patients achieving PASI75, PASI90, and PASI100, respectively. The mean PASI decreased significantly from baseline (13.6 ± 9.9) to 1.3 ± 1.7 at week 28. More than 90% of patients had clear sPGA-G and pp-PGA scores and over 70% had clear f-PGA and sc-PGA scores after 28 weeks.Conclusions: Our findings suggest that tildrakizumab could be a valuable option for the treatment of elderly patients, including those with difficult-to-treat areas involvement.

On the potential role of naturally occurring carboxylic organic acids as anti-infective agents: opportunities and challenges.

Carboxylic organic acids are intermediates of central carbon metabolic pathways (e.g. acetic, propionic, citric, and lactic acid) long known to have potent antimicrobial potential, mainly at acidic pHs. The food industry has been leveraging those properties for years, using many of these acids as preservatives to inhibit the growth of pathogenic and/or spoilage fungal and bacterial species. A few of these molecules (the most prominent being acetic acid) have been used as antiseptics since Hippocratic medicine, mainly to treat infected wounds in patients with burns. With the growth of antibiotic therapy, the use of carboxylic acids (and other chemical antiseptics) in clinical settings lost relevance; however, with the continuous emergence of multi-antibiotic/antifungal resistant strains, the search for alternatives has intensified. This prospective article raises awareness of the potential of carboxylic acids to control infections in clinical settings, considering not only their previous exploitation in this context (which we overview) but also the positive experience of their safe use in food preservation. At a time of great concern with antimicrobial resistance and the slow arrival of new antimicrobial therapeutics to the market, further exploration of organic acids as anti-infective molecules may pave the way to more sustainable prophylactic and therapeutic approaches.

Supraorbital Basosquamous Carcinoma Treated with Cemiplimab Followed by Sonidegib: A Case Report and Review of the Literature.

Basal cell carcinoma (BCC) is a skin cancer with low local aggressiveness and a low tendency to metastasize. Basosquamous Carcinoma (BSC) represents an aggressive histological subtype of BCC with intermediate features between Squamous Cell Carcinoma (SCC) and BCC. Cemiplimab is currently approved as first-line therapy in SCC and second-line therapy in BCC patients who have progressed on or are intolerant of a Hedgehog pathway Inhibitor (HHI). Our study describes the case of a 59-year-old man with BSC who was successfully treated with 5 cycles of Cemiplimab as first-line therapy and Sonidegib as second-line therapy. Currently, the efficacy of Cemiplimab against BSC and other histopathological subtypes of BCC has not been fully elucidated, as has the role of sequential or combination therapy with Cemiplimab and HHI in the management of BSC. The aim of this case report is to highlight the need to outline the use of checkpoint inhibitors in BCCs and focus attention on the synergistic role of Cemiplimab and HHIs in such a controversial entity as BSC.

A Case of Psoriatic Disease and Hidradenitis Suppurativa in a Child with Chromosome 17q21.31 Microduplication Syndrome.

Psoriatic disease is a chronic, relapsing inflammatory disorder, characterized mostly by cutaneous erythematous scaly plaques sometimes associated with arthritis. Hidradenitis suppurativa (HS) is a chronic relapsing inflammatory disease of the apocrine glands, characterized clinically by painful abscesses, sinus tracts and scars. It typically occurs after puberty, affecting mainly intertriginous areas of the body. There is a strong association between HS and psoriasis since they share the same pathogenic inflammatory pathway. The patient presented: low birthweight, microcephaly, facial dysmorphisms, lumbar hyperlordosis, walking difficulties, global psychomotor developmental delay and learning disabilities. A genetic evaluation revealed a 2.5 Mb de novo microduplication in the 17q21.31 chromosomal region. Dermatological examination revealed HS (Hurley stage II-HS) distributed in the genital area and inguinal folds, psoriatic plaques on the retroauricolar folds, on the elbows bilaterally and on the lateral aspect of the right ankle and psoriatic arthritis. The patient was treated with adalimumab, with a marked improvement of both conditions. To our best knowledge, we report the first case of coexisting Psoriatic Arthritis Disease and Hidradenitis Suppurativa in a child with chromosome 17q21.31 microduplication syndrome. We hypothesize that gene CRHR1 duplication included in the 17q21.31 chromosomal region might be involved in the pathogenesis of both diseases.

Brodalumab for the Treatment of Moderate-to-Severe Psoriasis: An Expert Delphi Consensus Statement.

Brodalumab is a recombinant, fully human immunoglobulin IgG2 monoclonal antibody specifically targeted against interleukin-17RA that has been approved for the treatment of moderate-to-severe psoriasis in Europe. We developed a Delphi consensus document focused on brodalumab for the treatment of moderate-to-severe psoriasis. Based on published literature and their clinical experience a steering committee drafted 17 statements covering 7 domains specific to the treatment of moderate-to-severe psoriasis with brodalumab. A panel of 32 Italian dermatologists indicated their level of agreement using a 5-point Likert scale (from 1 = "strongly disagree" to 5 = "strongly agree") using an online modified Delphi method. After the first round of voting (32 participants), positive consensus was reached for 15/17 (88.2%) of the proposed statements. Following a face-to-face virtual meeting, the steering committee decided that 5 statements would form "main principles" and 10 statements formed the final list. After a second round of voting, consensus was reached in 4/5 (80%) of the main principles and 8/10 (80%) for consensus statements. The final list of 5 main principles and 10 consensus statements identify key indications specific to the use of brodalumab in the treatment of moderate-to-severe psoriasis in Italy. These statements aid dermatologists in the management of patients with moderate-to-severe psoriasis.

External Validation of the IHS4-55 in a European Antibiotic-Treated Hidradenitis Suppurativa Cohort.

BACKGROUND: Previously, a new dichotomous outcome was developed, calculated as 55% reduction in the International Hidradenitis Suppurativa 4 (IHS4-55) score. It was validated in datasets of adalimumab and placebo-treated HS patients. External validation is an important aspect of clinical outcomes. OBJECTIVES: We aimed to externally validate the novel dichotomous IHS4-55 in a non-biologic treated dataset of HS patients. METHODS: Data from a previously published European-wide prospective clinical study of antibiotic treatment of HS patients were used to assess the association of IHS4-55 achievement with individual reduction in inflammatory nodules, abscesses, and draining tunnels. Moreover, the associations between IHS4-55 positivity and achievement of the minimal clinically important differences (MCIDs) for Dermatology Life Quality Index (DLQI), Numerical Rating Scale (NRS) Pain, and NRS Pruritus were analyzed. RESULTS: Data were obtained from 283 individual patients, of which 36.4% (103/283) were treated with clindamycin and rifampicin and 63.6% (180/283) with tetracyclines for 12 weeks. Achievers of the IHS4-55 demonstrated a significant reduction the counts of inflammatory nodules, abscesses, and draining tunnels (all p < 0.001). Additionally, IHS4-55 achievers had an odds ratio for achieving the MCID of DLQI, NRS Pain, and NRS Pruritus of 2.16 (95% CI 1.28-3.65, p < 0.01), 1.79 (95% CI 1.10-2.91, p < 0.05), and 1.95 (95% CI 1.18-3.22, p < 0.01), respectively. CONCLUSIONS: This study shows the external validity of the novel IHS4-55 by demonstrating a significant association between IHS4-55 achievement and a reduction in inflammatory lesion counts as well as achievement of MCIDs for DLQI, NRS Pain, and NRS Pruritus in an antibiotic-treated cohort. These findings support the use of the IHS4-55 as a novel primary outcome measure in clinical trials.

Guselkumab for the treatment of severe plaque psoriasis in a schizophrenia patient.

A wide range of comorbid conditions are associated with psoriasis, many studies have drawn attention to a higher prevalence of psychiatric comorbidities in psoriatic population. Herein, we present a case of a Caucasian 44-years-old man suffering from a severe schizophrenia, who received guselkumab (a human monoclonal antibody targeting the p40 subunit of IL-23) for the treatment of a moderate-to-severe plaque type psoriasis. After 3 months, the patient reached complete resolution of psoriasis without any side effects, maintained at 6 months follow up visit. Some studies have highlighted the hypothesis that an hyperactivation of immune response appears to be one of the main mechanisms underlying the increased risk of this association. In particular, the axis il-17/il-23 plays a central role in the pathogenesis of this disease. Further research will be needed to assess whether anti-IL23 drugs could be a more suitable therapeutic option in psoriatic patients with schizophrenia.

Long term efficacy, safety, and tolerability of tildrakizumab in epileptic patient with psoriasis and eczema.

Psoriasis is a chronic inflammatory disease which mostly affects skin. Tildrakizumab is a specific anti-interleukin -23p19 monoclonal antibody approved for the treatment of plaque psoriasis in adults. Herein, we report about a patient who came to our attention for a moderate-to-severe plaque psoriasis, involving primarily upper limbs, elbow, abdomen and knees (PASI 18 - DLQI 22). His medical history was relevant for epilepsy controlled pharmacologically. In addition, an eczematous and edematous appearance of the tibial area was detected; the histologic findings did not contradict the diagnostic hypothesis of subacute spongiotic dermatitis. The patient was treated with Tildrakizumab. After 12 weeks the clinical lesions improved significantly, and the eczematous component disappeared in the tibial area bilaterally. The clinical improvement was maintained even after one year of therapy. Tildrakizumab showed excellent results in the control of psoriasis, with an excellent safety profile. The promising results of clinical trials have been confirmed in a real-life setting. There are no reports about its safety in epileptic patients. In our case, neurological adverse events did not verify and tildrakizumab managed to control both the psoriatic and eczematous components.