Prevalence of subungual melanoma in patients with cutaneous malignant melanoma: A systematic review and meta-analysis.

BACKGROUND: Subungual melanoma (SUM) is a rare type of cutaneous malignant melanoma (CMM) associated with poor prognosis, while data regarding its prevalence are scarce. OBJECTIVES: We sought to provide a comprehensive systematic review and meta-analysis of the prevalence rates of SUM among all types of CMM, considering certain demographic and clinical characteristics. METHODS: The MEDLINE electronic database was searched systematically to identify eligible studies providing prevalence rate estimates of SUM in patients with CMM. Included studies were further analysed to estimate the relative prevalences of SUM according to study design, study years, geographical region and sex distribution. RESULTS: Twenty-eight studies met the inclusion criteria. The overall SUM prevalence was 1.9% (95% CI [1.5%-2.3%]). The prevalence of SUM did not differ significantly between population- and hospital-based studies and remained stable over time. However, it was found to be significantly higher in Asians compared to patients of other geographical regions as well as in studies with more men than women compared to those with female preponderance (p < 0.001). CONCLUSIONS: In all, the overall SUM prevalence among all subtypes of CMM was estimated at 1.9%, without significant changes over time, and was found to exhibit significant variability between subgroups of different geographical regions.

Management of primary plantar hyperhidrosis with botulinum toxin type A: A retrospective case series of 129 patients.

BACKGROUND/OBJECTIVES: To date, scientific data on the efficacy of botulinum toxin type A (BoNT-A) for primary plantar hyperhidrosis (PPH) are mainly derived from case reports and small case series. Herein, we sought to assess the efficacy and safety of BoNT-A for PPH on a large series of patients. METHODS: Medical records of patients who were referred to the outpatient department for hyperhidrosis of a tertiary care hospital and received BoNT-A for PPH from March 2003 until December 2022 were reviewed. RESULTS: A total of 129 patients [12 males, 117 females; median age 32 years (range, 16-72)] were included in the study, after excluding 24 patients with insufficient documented follow-up data. Most patients [115 (89.1%)] received onabotulinumtoxin-A, nine (7.0%) abobotulinumtoxin-A and five (3.9%) both in subsequent sessions. The mean number of sessions was 2.02 [standard deviation (SD), 2.29] and the mean duration of response 6.16 months (SD, 4.01). The percentage of response, as evaluated by Minor's test, was 71.67%, 63.44%, 47.78% and 34.13% after 1, 3, 6 and 9 months, respectively. Most patients were satisfied (21.7%) or very satisfied (58.9%) with the treatment. No serious side effects were reported. CONCLUSIONS: The results of this retrospective study suggest that BoNT-A is an effective and safe treatment option for PPH.

Adalimumab-Induced Paradoxical Psoriasis Treated with Biologics Targeting the IL-17/IL-23 Axis in Patients with Hidradenitis Suppurativa.

BACKGROUND: Paradoxical psoriasis (PP) has been mainly described in patients receiving tumor necrosis factor-α (TNFα) inhibitors for inflammatory bowel disease or psoriasis vulgaris, while such data in the context of hidradenitis suppurativa (HS) are scarce. The purpose of this study was to demonstrate the course of PP and the underlying HS upon switching from adalimumab to a biologic agent targeting the interleukin (IL)-17/IL-23 axis. METHODS: The electronic medical database of the outpatient department for HS of a tertiary hospital for skin diseases was searched to identify patients with moderate-to-severe HS under treatment with adalimumab, who developed PP and were switched to biological therapy with an IL-17 or IL-23 inhibitor between February 2016 and January 2022. Disease assessment scores were evaluated at baseline, at time of PP development, as well as six and 12 months thereafter. RESULTS: Among the 83 patients who received adalimumab for the treatment of HS between February 2016 and January 2022, 10 patients (12%) developed paradoxical psoriasiform skin reactions after a median time of seven (range, 2-48) months. There were four females (40%) and six males (60%) with a median age of 42.5 (range, 33-56) years. Five patients presented with plaque psoriasis and five with palmoplantar pustulosis, while four had intertriginous and three nail involvement. In most of the patients, HS responded well to adalimumab at onset of PP. Eight patients were changed to secukinumab, one to ustekinumab, and one to risankizumab. HS further improved in all but 2 patients, one receiving secukinumab and one receiving risankizumab. In addition, all patients achieved improvement of PP. CONCLUSION: Despite the small number of patients, this study provides support that patients with adalimumab-induced PP may benefit from biologics targeting the IL-17/IL-23 axis. Further studies are needed to establish the optimal therapeutic strategy of the anti-TNFα-induced PP in the context of HS.

Bullous Pemphigoid Associated with Anti-programmed Cell Death Protein 1 and Anti-programmed Cell Death Ligand 1 Therapy: A Review of the Literature.

Bullous pemphigoid constitutes a rare dermatological immune-related adverse event of programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors. Herein, we review all published cases of anti-PD-1/PD-L1 related bullous pemphigoid and discuss current knowledge on this condition. Clinical and diagnostic findings were found to resemble those of classic bullous pemphigoid. A delayed onset of bullous pemphigoid after commencement of immunotherapy as well as a frequent precendence of a refractory pruritic eruption prior to blister development was oberved, both posing diagnostic challenges. In addition to topical and systemic treatment, most patients required either discontinuation or permanent interruption of immunotherapy. Assessment of tumour outcome did not reveal improved survival in patients developing bullous pemphigoid during immunotherapy, as suggested for other types of skin toxicity, including vitiligo. Better understanding of the pathogenetic mechanism and prognostic implications of this increasingly-reported adverse event is essential in order to establish optimal diagnostic and therapeutic management of these patients.

Efficacy of long-term intralesional triamcinolone in Morbihan's disease and its possible association with mast cell infiltration.

Morbihan's disease is characterized by chronic persistent facial edema of the upper half of the face, absence of typical diagnostic findings, and refractoriness to treatment. A 44-year-old man was diagnosed with Morbihan's disease based on clinical signs and histopathology, which showed dermal edema in upper dermis, discrete lymphocytic infiltrate without granulomatous reaction, and mast cell infiltration. After long-term therapy with intralesional triamcinolone a remarkable objective and subjective clinical response was observed. Reported cases of Morbihan's disease are reviewed, with respect to their treatment and histopathological findings. Mast cell infiltration has been observed on histopathology in most patients who responded to intralesional triamcinolone, suggesting a possible marker of response. The long-lasting response seen in our case indicates the efficacy of intralesional triamcinolone in this rare condition.

Tinea Incognito: Challenges in Diagnosis and Management.

Tinea incognito is a dermatophyte infection with atypical features, due to the use of topical or systemic steroids or other immunosuppressive medications. Delayed diagnosis, spread of the infection to critical body surfaces, resistance to antifungal drugs, and increased costs due to prolonged hospitalization and multiple treatment regimens often complicate tinea incognito. It can affect individuals of all ages and genders, but it is more common in children. Atypical clinical appearance often necessitates differentiation from other diseases such as eczema, seborrheic dermatitis, lupus erythematosus, psoriasis, or other non-fungal skin conditions. The treatment of tinea incognito usually involves discontinuation of topical steroids or other immunosuppressive medications. Preventive measures and management of the underlying fungal infection are necessary and can be achieved with antifungal drugs. Patients should wear loose cotton clothes, use boiling water for laundry, and iron their clothing before wearing them. Additionally, they should avoid sharing bed linens, towels, clothes, and shoes. This review aims to raise awareness of tinea incognito among health practitioners, provide tips for detecting the disorder, include it in the differentials, and evaluate the available diagnostic procedures.

Interleukin antagonists for atopic dermatitis: a new era of therapy.

INTRODUCTION: Over the last decade, increasing understanding of the immunopathogenesis of atopic dermatitis (AD) enabled the recognition of multiple therapeutic targets and subsequently the development of novel, highly effective systemic treatments, including interleukin (IL)-antagonists. To date, the IL-4Ra-inhibitor dupilumab and the IL-13 inhibitor tralokinumab have gained regulatory approval in Europe for the treatment of moderate-to-severe AD, while more than 70 new therapeutics are currently in development. AREAS COVERED: In this review, we address the role of ILs in the pathogenesis of AD and provide an overview of the novel and investigational IL-antagonists, as regards their efficacy and safety on moderate-to-severe AD. EXPERT OPINION: Current data have established IL-4 and IL-13 inhibitors as effective and safe for the treatment of moderate-to-severe AD, as regards the rapid control of flares as well as the long-term remission of the disease. Data regarding the efficacy and safety of other IL-inhibitors, including those targeting IL-31, IL-22, IL-33, IL-36 and IL-18, are accumulating. There is still an unmet need for real-world-evidence studies and head-to-head studies for both currently available and future agents in AD treatment. Establishing predictive biomarkers of treatment response in a disorder of such considerable heterogenicity might help physicians pursue a patient-tailored therapeutic response.

Insights into Early Systemic Treatment in Atopic Dermatitis: Scientific Facts and Practical Considerations.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized clinically by pruritus, and pathophysiologically by immune dysregulation, and compromised skin barrier function. While topical therapies are currently the cornerstone of AD management, especially in mild disease, recent advancements in systemic treatments and a deeper understanding of similar skin diseases, such as psoriasis, have highlighted the importance of early intervention. In this commentary, we explore the potential benefits of early systemic intervention in AD, with pruritus determining such a decision. Building on this concept, we assume that, through the timely systemic treatment that targets the immune dysregulation present in AD, the progression of the disease could be modified, improving overall patient outcomes. Early systemic intervention may minimize systemic inflammation, halting the "atopic march" and disrupting the "itch-scratch" cycle. Managing pruritus at its root could prevent secondary complications and reduce the psychosocial burden of the disease. This paradigm shift fosters a collaborative healthcare approach that empowers patients with long-term disease control strategies. In conclusion, the safety and efficacy of novel systemic treatments offer a compelling scenario for early intervention in atopic dermatitis care.

Eccrine Porocarcinoma: A Review of the Literature.

Eccrine porocarcinoma (EPC) constitutes a rare malignant adnexal tumor, which accounts for about 0.005-0.01% of all cutaneous malignancies. It may develop de novo or arise from an eccrine poroma, after a latency period of years or even decades. Accumulating data suggest that specific oncogenic drivers and signaling pathways may be implicated in its tumorigenesis, while recent data have demonstrated a high overall mutation rate attributed to UV exposure. Diagnosis may be challenging and should rely on the combination of clinical, dermoscopical, histopathological and immunohistochemical findings. The literature is controversial regarding tumor behavior and prognosis and, therefore, there is no consensus on its surgical management, utility of lymph-node biopsy and further adjuvant or systemic treatment. However, recent advances in tumorigenesis of EPC may aid in the development of novel treatment strategies, which could improve survival of advanced or metastatic disease, such as immunotherapy. This review presents an update of the epidemiology, pathogenesis and clinical presentation of EPC and summarizes current data on diagnostic evaluation and management of this rare cutaneous malignancy.

Switching between JAK Inhibitors in Patients with Atopic Dermatitis: Unanswered Questions in Daily Clinical Practice.

Data on switching between agents in patients with atopic dermatitis (AD) are scarce (1-3). We report the case of a patient with severe AD and inadequate response to upadacitinib who showed a complete response after switching to abrocitinib. A 23-year-old male patient with severe AD was enrolled in the Measure Up double-blind, placebo-controlled, phase 3 randomized clinical trial. At baseline, the Eczema Area Severity Index (EASI) was 50.6, the Investigator's Global Assessment (IGA) was 4, the affected Body Surface Area (BSA) was 80%, and the Worst Pruritus-Numeric Rating Scale (WP-NRS) was 10/10 (Figure 1). At week 124, the patient discontinued participation in the trial, while EASI was 9.2, IGA 3, BSA 20%, and WP-NRS 5/10 at the time. After one month off treatment, and while expecting unblinding, the patient again presented with exacerbation of AD, since EASI was 45.6, IGA 4, BSA 80%, and WP-NRS 10/10. At that point of time, access to both dupilumab and tralokinumab was not available in Greece, while upadacitinib was avoided due to inadequate patient satisfaction, partly due to recurrent ocular herpes simplex infections during the previous upadacitinib treatment. The patient was prescribed abrocitinib 200 mg daily. One month after initiation of therapy, the patient achieved complete control of the disease (EASI 0.0, IGA 0, BSA 0%, and WP-NRS 0/10) (Figure 2). This has been maintained with no reported adverse events after 12 months of continuous treatment. After unblinding, the patient was confirmed to have received 15 mg of upadacitinib daily during his participation in the clinical trial. When to switch agents in the treatment of patients with severe AD if the response is not adequate, and what agent to switch to, is an issue that is not clearly defined. Data available from the JADE EXTEND study concluded that patients failing to achieve efficacy outcomes with dupilumab can benefit from switching to both doses of abrocitinib (1). However, a number of patients in this study did not achieve efficacy outcomes even after treatment with 200 mg of abrocitinib. Furthermore, sub-population analysis of the JADE EXTEND study, evaluating difficult-to-achieve patient-oriented outcomes such as Patient Oriented Eczema Measure (POEM) ≤2 and Dermatology Life Quality Index (DLQI) ≤1, further emphasized that switching might be beneficial for a significant number of patients, but unmet need was still evident for some of them (4). The literature lacks data on switching between Janus kinase (JAK) inhibitors in AD. Treat-to-target might be different for early control of the disease, as baricitinib and upadacitinib were assessed at 16 weeks, while abrocitinib was assessed at 12 weeks in the pivotal studies. Regarding the present case, the different clinical response obtained cannot be clearly defined since abrocitinib and upadacitinib are both selective JAK1 inhibitors. Consequently, the targeted inflammatory pathways and the expected regulation of immune functionality could be similar. We may assume that the high dose of abrocitinib vs. the low dose of upadacitinib could have accounted for the improved response. However, it is impossible to assess whether clinical outcomes would have been comparable with the administration of the full dose of upadacitinib 30 mg daily or whether usage of a half-dose of abrocitinib 100 mg daily would have also resulted in inadequate response in the same patient. Switching within the same class of treatment agents has also been a heavily-debated issue for psoriasis for many years; however, recent data suggest that switching between interleukin (IL)-17A antagonists may be of benefit to some patients, although the underlying mechanism of action is still under investigation (5,6). Treatment modification in inadequate response could include: up-dosing, adding classical treatments like methotrexate to the JAK inhibitor, switching to monoclonals, or switching to another JAK inhibitor, taking into account published metanalyses of the efficacy of novel agents. Consequently, there is an unmet need to determine an algorithmic step-by-step approach of treat-to-target and switching or adding treatment in the current landscape of AD therapy. Different policies of reimbursement in different countries, along with a lack of comparative studies, may complicate adding such recommendations to existing treatment guidelines.

The Impact of Treatment with IL-17/IL-23 Inhibitors on Subclinical Atherosclerosis in Patients with Plaque Psoriasis and/or Psoriatic Arthritis: A Systematic Review.

Accumulating evidence considers psoriasis a systemic inflammatory disorder that is associated with comorbidities such as psoriatic arthritis, cardiovascular disease, and metabolic syndrome. Although the precise pathogenetic links between psoriasis and atherosclerosis warrants further investigation, it is believed that chronic systemic inflammation along with the T helper (Th)-1 and Th17 polarization are associated with endothelial dysfunction and subsequent acceleration of atherosclerosis. Considering the above, several studies have evaluated if optimal control of the inflammation in psoriasis by inhibiting interleukins targeting the Interleukin (IL)-23/Th17 axis could subsequently reduce the atherosclerotic process during anti-psoriatic treatment by using a variety of surrogate markers of subclinical atherosclerosis. This systematic review summarizes current knowledge on the pathogenetic mechanisms and diagnostic evaluation of atherosclerosis in the context of psoriasis and provides a systematic review of the literature on the impact of treatment with biologics targeting the IL-23/Th17 axis on subclinical atherosclerosis in patients with plaque psoriasis and/or psoriatic arthritis.