Topical and Systemic Retinoids in the Management of Hidradenitis Suppurativa: A Comprehensive Literature Review.

Hidradenitis suppurativa (HS) is a debilitating chronic skin disorder characterized by painful inflammatory nodules, abscesses and sinus tracts involving intertriginous areas and has an adverse impact on patient quality of life. Over the past decade, the therapeutic options of HS have increased significantly to comprise multiple modalities, including topical medication, systemic therapies (mainly antibiotics, retinoids, and biologics), surgical approaches, and lifestyle modifications. Biologics alone or in combination with surgery remain the treatment of choice for moderate to severe disease. However, non-biologic therapies (including retinoids) may be used as monotherapy for mild disease and in combination with biologics and surgical treatment in moderate to severe disease. Retinoids, specifically isotretinoin, acitretin, and alitretinoin, are historically used in the management of HS, supported by anecdotal evidence and with variable treatment response. Although the current American and European guidelines offer different recommendations on the use of retinoids in HS, retinoids remain a valuable ally in HS management. This review provides a comprehensive analysis of the current scientific literature on retinoid therapy (topical and systemic) in HS, highlighting disparities in mechanisms of action, efficacy, and safety to clarify their role in HS treatment.

The sources of antimicrobial peptides against Gram-positives and Gramnegatives: our research experience.

Antibiotic resistance of Gram-positive and Gramnegative bacteria is becoming increasingly prevalent. For this reason, the search for new molecules that can overcome current resistance and also recover antibiotics that are no longer effective is becoming increasingly urgent. Our research group at the 'Polytechnic University of Marche' managed to study the effectiveness of certain antimicrobial peptides (AMPs). We decided to review our experience with AMPs by classifying them according to their origin and evaluating their effect on Gram-negative and Gram-positive bacteria. AMPs can derive from mammals, amphibians, microorganisms, and insects. In conclusion, our research experience shows that the richest source of AMPs are amphibians. However, the studies done are mainly in vitro or in animal models, requiring further human studies to assess the efficacy and safety of these molecules. AMPs may be a new therapeutic option for infections sustained by multi-resistant micro-organisms and for overcoming the mechanisms of resistance to antibiotics currently used. In particular, combining AMPs with antibiotics, including those with limited antimicrobial activity due to antimicrobial resistance, has often shown a synergistic effect, increasing or restoring their efficacy. The possibility of using manageable and relatively safe antibiotics again is crucial, considering the widespread increase in bacterial resistance in hospitals and the community. Despite a plethora of research on AMPs and their application as potential treatment on infectious diseases, this area needs further exploration. There is evidence that the characteristics of AMPs can seriously improve through structural chemical modifications and different delivery systems to become alternatives drugs to conventional antibiotics. The aim is to provide an overview of the possible sources from which AMPs are extracted, evaluating their action exclusively on Gram-positive and negative bacteria. This is to determine, based on our experience, which might be the most promising sources of AMPs for future research as well.

CT Patterns of Interstitial Lung Disease in Patients with Plaque Psoriasis: A Retrospective Case Series Study.

Background and Objectives: Recently published articles reported an association between psoriasis and interstitial lung diseases (ILDs). The aim of this study is to evaluate the differences in ILD computed tomography (CT) patterns between smoker and never smoker plaque psoriasis (PP) patients under topical treatment without psoriatic arthritis (PA), inflammatory bowel disease (IBD) or connective tissue diseases (CTDs). Matherials and Methods: Two radiologists evaluated chest CT examinations of 65 patients (33 smokers, 32 never smokers) with PP. Results: Usual interstitial pneumonia (UIP) pattern was diagnosed in 36 patients, nonspecific interstitial pneumonia pattern in 19, hypersensitivity pneumonitis in 7 and pleuropulmonary fibroelastosis (PPFE) in 3 patients. UIP pattern showed a statistically significant higher frequency in smoker patients (p = 0.0351). Respiratory symptoms were reported in 80% of patients. Conclusions: ILDs seems to represent a new comorbidity associated with psoriasis. Moreover, a statistically significant association between smokers and UIP pattern in PP patients is found. Respiratory symptoms should be evaluated in PP patients, in collaboration with a radiologist and a pneumologist. However, further studies are required to better understand the epidemiology of ILDs in PP patients.

Efficacy of Pembrolizumab in Advanced Melanoma: A Narrative Review.

Pembrolizumab has been shown to increase survival in patients with metastatic melanoma. Considering the numerous oncoming studies, we decided to conduct a narrative review of the latest efficacy evidence regarding the use of pembrolizumab, alone or in combination, in patients with metastatic melanoma. A search was conducted in PubMed using "pembrolizumab," and "metastatic melanoma" as keywords, considering studies from 2022 onward. We reviewed pembrolizumab and associations, cost-effectiveness, virus, advanced acral melanoma, long-term outcomes, real-life data, biomarkers, obesity, and vaccines. In conclusion, pembrolizumab is a fundamental option in the therapy of metastatic melanoma. However, a certain group of patients do not respond and, therefore, new combination options need to be evaluated. In particular, the use of vaccines tailored to tumor epitopes could represent a breakthrough in the treatment of resistant forms. Further studies with larger sample numbers are needed to confirm the preliminary results.

Melanoma and subcutaneous adipose tissue: Role of peritumoral adipokines in disease characterization and prognosis.

In the last decades, the concept of adipose organ has emerged, giving adipose tissue an active endocrine and immunologic function through the secretion of multiple cytokines and chemokines that seem to be implicated in the development and progression of several cancer, including cutaneous melanoma. In this pilot experimental study, we analyzed the expression in the peritumor subcutaneous adipose tissue of the most significant adipokines involved in the processes of carcinogenesis and metastasis in a population of melanoma patients and in two control groups composed of melanocytic nevi and epidermoid cysts, respectively. We correlated the results obtained with the main disease prognostic factors observing a statistically significant increase in the expression of PAI1, LEP, CXCL1, NAMPT, and TNF-α at the level of the peritumor tissue of the melanoma samples compared to the control groups and a correlation of the same with the histopathological prognostic factor of melanoma. Our preliminary study shows that the overexpression of PAI1, LEP, CXCL1, NAMPT, and TNF-α may contribute to the growth and to the local aggressiveness of cutaneous melanoma. It opens the hypothesis of a direct oncogenic role of subcutaneous adipose tissue and adipokines in the tumorigenesis of melanoma.

Systemic Antibiotic Therapy in Hidradenitis Suppurativa: A Review on Treatment Landscape and Current Issues.

Hidradenitis suppurativa (HS) is a chronic, recurrent, and inflammatory skin disease characterized by painful, deep-seated, nodules, abscesses, and sinus tracts in sensitive areas of the body, including axillary, inguinal, and anogenital regions. Antibiotics represent the first-line pharmacological treatment of HS because of their anti-inflammatory properties and antimicrobial effects. This narrative review summarizes the most significant current issues on the role of systemic antibiotics in the management of HS, critically analyzing the main limits of their use (antibiotic resistance and toxicity). Although, in the last decades, several cytokines have been implicated in the pathomechanism of HS and the research on the use of novel biologic agents in HS has been intensified, antibiotics remain a valid therapeutic approach. Future challenges regarding antibiotic therapy in HS comprise their use in association with biologics in the management of acute flare or as a bridge therapy to surgery.

New Insight into the Molecular Pathomechanism and Immunomodulatory Treatments of Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is an immune-mediated inflammatory disorder characterized by deep-seated nodules, abscesses, sinus tracts and scars localized in the intertriginous areas. It is accompanied by pain, malodourous secretion and a dramatically decreased quality of life. Although the pathogenesis has not been entirely elucidated, the primary event is follicular hyperkeratosis of the pilosebaceous apocrine unit. Since the registration of the tumor necrosis factor-alpha inhibitor Adalimumab in 2015, several cytokines have been implicated in the pathomechanism of HS and the research of novel therapeutic targets has been intensified. We provide an update on the inflammatory cytokines with a central role in HS pathogenesis and the most promising target molecules of future HS management.

The Role of Diet in Children with Psoriasis: Emerging Evidence and Current Issues.

Psoriasis is an immune-mediated inflammatory systemic disease with skin tropism and chronic relapsing course; it is associated with an increased cardiovascular risk and with many metabolic comorbidities, emerging during childhood in 22-33% of cases. Diet influences the presentation and the clinical course of inflammatory diseases, including psoriasis; in particular, it was shown that a Mediterranean, gluten-free, or low-calorie diet may positively affect disease control in adult patients with psoriasis and adequate pharmacological therapy. These three dietary regimens may play a role also in children with psoriasis. It has been demonstrated that pediatric psoriasis is associated with psychological stress, celiac disease, and obesity, which may be positively influenced by these dietary regimens, respectively. Therefore, the expertise of multiple health figures (gastroenterologists, nutritionists, pediatricians, dermatologists) is required to plan a tailor-made dietary strategy, ensuring good growth, through an adequate intake of essential micro- and macronutrients and, at the same time, impacting the pro-inflammatory biochemical profile and on the associated cardiovascular risk of psoriasis disease.

MRSA and Skin Infections in Psoriatic Patients: Therapeutic Options and New Perspectives.

Psoriatic patients present various infectious risk factors, but there are few studies in the literature evaluating the actual impact of psoriasis in severe staphylococcal skin infections. Our narrative review of the literature suggests that psoriatic patients are at increased risk of both colonization and severe infection, during hospitalization, by S. aureus. The latter also appears to play a role in the pathogenesis of psoriasis through the production of exotoxins. Hospitalized psoriatic patients are also at increased risk of MRSA skin infections. For this reason, new molecules are needed that could both overcome bacterial resistance and inhibit exotoxin production. In our opinion, in the near future, topical quorum sensing inhibitors in combination with current anti-MRSA therapies will be able to overcome the increasing resistance and block exotoxin production. Supplementation with Vitamin E (VE) or derivatives could also enhance the effect of anti-MRSA antibiotics, considering that psoriatic patients with metabolic comorbidities show a low intake of VE and low serum levels, making VE supplementation an interesting new perspective.

The Effect of Dalbavancin in Moderate to Severe Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by painful nodules, abscesses, and fistulas, localized to the areas of the folds where apocrine glands are present: the armpits, groin, inframammary region, and genital or perineal region. The management is still challenging, and it includes mainly systemic antibiotics, immunosuppressors, and biologic agents. Antibiotics are frequently used in the management of HS for their anti-inflammatory, immunomodulatory, and antimicrobial properties, but no data have been reported regarding the use of dalbavancin in HS. The aim of our practice was to evaluate efficacy, flare, and disease-free survival after dalbavancin therapy in a selected population with HS. We report the experience of the Ancona Dermatology Clinic in treating HS flare-ups with dalbavancin and its rationale for use. Our observation shows that the use of dalbavancin is an effective and well-tolerated treatment for the management of Hurley stage II-III HS; currently, dalbavancin should be considered as a supportive therapy for selected patients.

Bullous Pemphygoid and Novel Therapeutic Approaches.

Bullous pemphigoid is a subepidermal blistering disease associated with autoantibodies (auto-ab) to BP180 and BP230 which affects elderly patients, predominately. Although it is a rare disease, bullous pemphigoid is the most common among the autoimmune bullous skin diseases. Systemic corticosteroids and immunosuppressants represent milestones in the treatment of patients suffering from bullous pemphigoid; however, therapeutic management of patients still represents a clinical challenge, owing to the chronic nature of the disease and to potential adverse effects related to the long-term use of systemic treatments. Recent discoveries on the pathogenesis of bullous pemphigoid have allowed investigation of new target therapies against selective pro-inflammatory mediators. These therapies appear to yield satisfactory results with fewer side effects in cases of refractory disease. The review discusses current evidence on these new therapeutic targets and specific drugs under investigation.

Biological Treatments for Pediatric Psoriasis: State of the Art and Future Perspectives.

Psoriasis is a chronic systemic inflammatory disease that primarily affects the skin and is associated with multiple comorbidities with a considerable reduction in quality of life of affected patients. One-third of psoriasis cases begin in childhood and are associated with significant medical comorbidities such as obesity, metabolic syndrome, arthritis, and psychiatric disorders. In addition, because of its chronic nature and frequent relapses, psoriasis tends to require long-term treatment. Treatment of pediatric psoriasis usually involves the same methods used for adults. However, most treatments for pediatric psoriasis are used off-label, and research in this regard is still lacking. Targeted therapies involving the use of newly developed biologic drugs are also increasingly being applied to childhood psoriasis. This review summarizes the clinical features of pediatric psoriasis and focuses mainly on the updated concepts of pathogenesis and biological treatments of pediatric psoriasis.

Atypical Scleroderma-like Chronic GVHD in a Liver Transplant Patient, Clinical and MRI Correlations.

Dear Editor, cutaneous chronic graft versus host disease (cGVHD) is a pathological process consisting of donor-derived T-cells aimed at the antigens of the recipient. It exhibits a large range of clinical presentations resembling morphea and deep sclerosis/fasciitis, all characterized by both inflammation and progressive dermal and hypodermic fibrosis (1). Although classic scleroderma-like lesions in cGVHD are nummular or irregular plaques and linear bundles associated with hypo- or hyperpigmentation (2), we report an atypical case with ulcerative presentation. No other case-reports of morphea-like or scleroderma-like cGVHD with an ulcerated appearance after liver transplantation (LT) and magnetic resonance imaging (MRI) correlation have been found in the literature. CASE REPORT Ten months after LT due to an end-stage cirrhosis associated with multifocal hepatocarcinoma (HCC), a 61-year-old man on immunosuppressive therapy with Tacrolimus (1 mg) and Everolimus (10 mg) presented to our clinic for a skin lesion in the right scapular region. We observed a flat ulcerated plaque with areas of sclerosis, minimal necrosis, and well-defined slightly erythematous margins (Figure 1, a). On palpation, the plaque had a hard consistency and was slightly painful. The skin lesion had been preceded by subjective discomfort with stinging sensation for seven months before its onset. Gradually lesion developed starting from a small, flat, oval purplish plaque associated with a progressive increase in pain. Patient denied dysphagia, retrosternal heartburn, Raynaud's phenomenon, arthralgia, and dyspnea. A previous MRI (Figure 2, a,b) showed subcutaneous and muscle edema. Blood tests showed abnormal liver function indexes due to extrahepatic cholestasis, while C-reactive protein, erythrocyte sedimentation rate, and leukocytes were within normal ranges. Self-reactive antibodies were negative. Histological examination (Figure 1, b) identified rare dyskeratotic keratinocytes and basal lymphocyte infiltrate, a dermal dense fibrosis with the disappearance of the skin appendages, and large fibrous septa in the adipose panniculus. It led to the diagnosis of scleroderma/morphea, based on the patient's clinical history. The diagnosis of graft versus host disease scleroderma-like post liver transplant was established. The lesion was treated by topical application of 0.05% clobetasol once a day. We did not use systemic immunosuppressive therapy in order to prevent HCC recurrence. The patient is currently in clinical follow-up to identify worsening or neoplastic degeneration. CASE DISCUSSION Cutaneous cGVHD often presents clinically as an ulcerative evolution in the context of fibrosis and diffuse skin atrophy (2), but very rarely initially appears as a well-delimited ulcerated plaque. Only few cases of ulcer have been found in literature, all in patients undergoing hematopoietic stem cell transplantation (HSCT), which is associated with the highest risk of developing GVHD, 20-50% (3,4), while LT has quite low incidence, at 0.5-2% (5). To our knowledge, this is the first case report of a scleroderma-like cGVHD lesion with ulcer appearance in LT. Our patient underwent two MRIs during post-transplant follow-up, which allowed us to evaluate the deep disease evolution. The T2-weighted MRI (Figure 2, c,d) performed approximately 1 year after transplantation, demonstrated fibrous septa in the subcutaneous fat and fascial thickening, with associated muscle hypotrophy and edema. The previous MRI, performed seven months after transplantation, already showed subcutaneous tissues and fascial edema, highlighting active inflammation. This evidence suggests that MRI could identify the lesion location before clinical manifestations, providing an opportunity to intervene promptly. To the best of our knowledge, this is the first reported case of cGVHD with atypical scleroderma-like presentation in a liver transplant patient whose clinical and MRI correlations have been traced. Our suggestions are supported by the results of other previous studies (6,7) evaluating MRI performance for assessing disease extent and activity, as well as therapeutic response in HSCT.

Methicillin-resistant Staphylococcus aureus as a cause of chronic wound infections: Alternative strategies for management.

Biofilm formation at the level of a wound plays an important role in its chronicization. The difficulty of its eradication has driven research toward the discovery and synthesis of new molecules that can act on biofilm to promote wound healing. This narrative review focuses on alternative molecules that can act and promote the eradication of methicillin-resistant Staphylococcus aureus, taking into consideration its antibiotic resistance, virulence, tendency toward the tenacious colonization of wounds by biofilms, and its increased prevalence in both community and hospital settings. A selection of promising studies were reported, analyzing the in vitro and/or in vivo efficacy of bacteriophages, metal nanoparticles, RNAIII inhibiting peptide (RIP), synthetized RIP derivatives, proteinase K and hamamelitannin.

Role of Daptomycin in Cutaneous Wound Healing: A Narrative Review.

Daptomycin is active against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and the on-label indications for its use include complicated skin and skin structure infections (cSSSI). We performed a narrative review of the literature with the aim to evaluate the role of daptomycin in the skin wound healing process, proposing our point of view on the possible association with other molecules that could improve the skin healing process. Daptomycin may improve wound healing in MRSA-infected burns, surgical wounds, and diabetic feet, but further studies in humans with histological examination are needed. In the future, the combination of daptomycin with other molecules with synergistic action, such as vitamin E and derivates, IB-367, RNA III-inhibiting peptide (RIP), and palladium nanoflowers, may help to improve wound healing and overcome forms of antibiotic resistance.