Interleukin-1 family cytokines and soluble receptors in hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic skin disease, characterized by clinical inflammation of the hair follicle with the recurrence of abscesses, nodules, and tunnels. Recently, several studies suggested a role of IL-1 family (IL-1F) cytokines in eliciting and sustaining the disease. The aim of this work is to perform a comprehensive analysis of IL-1F cytokines, soluble inhibitors and receptors in a cohort of HS patients not treated with biological agents. Sixteen patients affected by HS and 16 healthy controls were recruited; clinical data were collected and disease severity evaluated by means of the International HS Severity Score System (IHS4). Serum levels of IL-1F cytokines, inhibitors and receptors were measured using a Multiplex Assays. IL-18 and free IL-18 levels were significantly higher in patients vs controls. Among soluble inhibitors, IL-1Ra, IL-1R2 and ST2/IL-1R4 were significantly increased. IL-18, free IL-18 and IL-33 levels are strongly correlated with IHS4. Also the inhibitors IL-1Ra and IL-18BP show a correlation with IHS4. The data obtained in this study confirm the involvement of IL-1F cytokines in mediating the disease and determining its severity and suggest a possible role for IL-18 as novel serum biomarker of active disease.

Wound area severity index (WASI): A novel tool for assessing and predicting healing times in hidradenitis suppurativa postsurgical wounds.

Hidradenitis suppurativa (HS) presents challenges in management due to its chronic nature and high risk of recurrence. Post-surgical wound care plays a crucial role in treatment, even if standardized methods for assessing and predicting healing times are lacking. The aim of the study is to introduce the Wound Area Severity Index (WASI) as a novel tool to guide clinicians in assessing postsurgical wound progression and predicting potential healing times. A team of wound healing experts assessed 93 post-surgical HS wounds resulting from wide excision and secondary intention healing. For each wound healing time, wound area, wound bed score (WBS), and WASI were evaluated. WASI includes four parameters: area, temperature, depth and wound Bed, each with four severity levels. The total WASI score ranges from 4 to 16. Spearman correlation and Kruskal-Wallis tests were employed for statistical analysis. WASI strongly correlated with wound healing time (rho: 0.813, p < 0.001). Higher WASI scores were associated with prolonged healing, while lower scores indicated almost healed wounds. The WASI score has proven to be more highly predictive of healing times when compared to the individual parameter of the Area (moderate positive correlation, r: 0.77) and the WBS (negative correlation, r: -0.72). A total WASI score of 4 corresponded to a median healing time of 7 days, while a score exceeding 9 suggested a median healing time of 56 days. WASI has proven to be a valuable tool for assessing and predicting healing times in post-surgical HS wounds. Its simplicity, cost-effectiveness, and ability to integrate multiple parameters make it a promising addition to wound care practice.

Presurgical Mapping With Ultra-high Frequency Ultrasound of Hidradenitis Suppurativa Lesions Treated With Wide Local Excision and Secondary Intention Healing.

BACKGROUND: Hidradenitis suppurativa (HS) is a challenging chronic inflammatory condition often requiring surgical intervention, such as wide local excision. Preoperative mapping with ultra-high frequency ultrasound (UHFUS) enables detailed assessment of lesion extension, particularly identifying tunnels and fistulas, facilitating surgical planning. OBJECTIVE: This study aimed to analyze recurrence rates of HS lesions previously mapped with UHFUS and treated with wide excision and secondary intention healing. MATERIALS AND METHODS: A retrospective single-center study enrolled 40 patients with HS undergoing wide excision surgery after UHFUS mapping. Patients were assessed weekly until complete healing and then every 3 months, evaluating clinical and sonographic signs of relapse and pain using the visual analogue scale. RESULTS: Results showed a population predominantly composed of women (65%) with a mean age of 39 years and a medium HS-Hurley score of 2.5. Over a 22-month follow-up, only 10% experienced clinical relapse, achieving an 90% total remission rate. Pain scores decreased significantly from Week 0 to Week 4. CONCLUSION: The study highlights the clinical challenge of HS management, particularly regarding surgical planning and lesion margin definition. The remission rate observed in this study suggests the effectiveness of UHFUS-guided surgical approaches. Future studies should extend observation periods to further validate these findings.

Risankizumab as a Therapeutic Approach for Recalcitrant Pyoderma Gangrenosum.

ABSTRACT: Pyoderma gangrenosum (PG) is a neutrophilic dermatosis that is challenging to diagnose and treat. Clinicians frequently use fast-acting corticosteroids, which are subsequently combined with slower-acting immunosuppressants to progressively taper the corticosteroid dosage. Current research is focused on the use of monoclonal antibodies (mAbs) directed against target molecules involved in the pathogenesis of PG. However, available data on their efficacy are based on sporadic case reports and clinical experiences, so the authors aimed to evaluate the efficacy of risankizumab, an anti-interleukin-23 mAb, in the management of two complex PG cases. The authors enrolled two patients with PG who were already treated with immunosuppressive therapies. Their management was based on the off-label use of an mAb directed against the p19 subunit of interleukin-23: risankizumab. Patients received subcutaneous injections of 150 mg at the start of treatment, at week 4, and then every 10 weeks thereafter. Systemic therapy was combined with local management of ulcers, based on the principles of TIME (tissue, infection, moisture balance, and epithelialization) applied to the inflammatory and noninflammatory phases of PG. Clinical resolution was obtained at week 24 for patient 1 and week 16 for patient 2 and was maintained until week 40, without adverse effects or disease recurrence. These clinical cases demonstrate that risankizumab is a valid tool in terms of efficacy and safety for complicated cases of multirefractory PG when provided in parallel with local personalized wound management.

A real-life experience as a proof of Guselkumab effectiveness and safety in patients with moderate to severe psoriasis.

Psoriasis is a skin disorder characterized by chronic inflammation driven by different immunologic pathways, among which the IL-23/Th17 axis plays a pivotal role. For this reason, the use of IL23p19 inhibitors in psoriasis treatment has been evaluated over the years. Guselkumab, a totally human IgG1 lambda monoclonal antibody, that selectively blocks the p 19 subunit of IL- 23 has demonstrated high efficacy and safety throughout several, randomized, double-blind phase III trials (VOYAGE 1 and 2, NAVIGATE and ECLIPSE). We designed a single-center retrospective cohort study in a population consisting of 46 patients followed from December 2018 to April 2021. After a diagnosis of moderate to severe psoriasis, all the patients were considered suitable to receive treatment with Guselkumab. In our population, among those who achieved clinical improvement in terms of Psoriasis Area Severity Index (PASI), PASI 75, 90, and 100 were achieved on average on weeks 14, 19, 21 respectively. We then analyzed a subgroup of our population, consisting of 35 patients, who had an identical follow-up time of 28 weeks, thus observing the trend in mean PASI at subsequent assessments and the number of patients who had reached PASI 75, PASI 90, and PASI 100 at week 4 (10; 3; 1), week 12 (12; 13; 11), week 20 (7; 6; 2), and week 28 (1; 4; 6), respectively. The results obtained are in line with those obtained from previous studies, thus confirming that Guselkumab is an excellent choice in terms of security, long-term efficacy, and overall tolerance.

Monoclonal Antibodies in the Management of Inflammation in Wound Healing: An Updated Literature Review.

Chronic wounds pose a significant clinical challenge due to their complex pathophysiology and the burden of long-term management. Monoclonal antibodies (mAbs) are emerging as a novel therapeutic option in managing difficult wounds, although comprehensive data on their use in wound care are lacking. This study aimed to explore existing scientific knowledge of mAbs in treating chronic wounds based on a rationale of direct inhibition of the main molecules involved in the underlying inflammatory pathophysiology. We performed a literature review excluding primary inflammatory conditions with potential ulcerative outcomes (e.g., hidradenitis suppurativa). mAbs were effective in treating wounds from 16 different etiologies. The most commonly treated conditions were pyoderma gangrenosum (treated with 12 different mAbs), lipoid necrobiosis, and cutaneous vasculitis (each treated with 3 different mAbs). Fourteen mAbs were analyzed in total. Rituximab was effective in 43.75% of cases (7/16 diseases), followed by tocilizumab (25%, 4/16 diseases), and both etanercept and adalimumab (18.75%, 3/16 conditions each). mAbs offer therapeutic potential for chronic wounds unresponsive to standard treatments. However, due to the complex molecular nature of wound healing, no single target molecule can be identified. Therefore, the use of mAbs should be considered as a translational approach for limited cases of multi-resistant conditions.

The Role of Ultra-High-Frequency Ultrasound in Pyoderma Gangrenosum: New Insights in Pathophysiology and Diagnosis.

Pyoderma gangrenosum (PG) is a neutrophilic dermatological disease, whose pathogenesis is still poorly clarified. Because of the lack of validated criteria for diagnosis and response, PG treatment is still challenging and should be differentiated in the inflammatory and non-inflammatory phases. Our study aimed to provide a new semi-quantitative approach for PG diagnosis and monitoring, identifying ultra-high-frequency ultrasound (UHFUS) early biomarkers associated with the transition between the two phases. We enrolled 13 patients affected by painful PG lesions evaluated during the inflammatory phase (T0) and during the non-inflammatory phase (T1): pain was measured by the Visual Analogue Scale (VAS); clinical features were recorded through digital photography; epidermis and dermis ultrasound (US) characteristics were evaluated by UHFUS examination with a 70 MHz probe (Vevo MD® FUJIFILM VisualSonics). In T1 UHFUS examination, the presence of hyperechoic oval structures was lower compared to T0 (p value < 0.05). An hyperechogenic structure within the oval structure, suggestive of a hair tract, was evident in T0 and absent in T1 (p value < 0.05). In T0, blood vessels appear as U-shaped and V-shaped anechoic structures with a predominance of U-shaped vessels (p value < 0.05) compared to the more regular distribution found in T1. Finding early biomarkers of the transition from the inflammatory to the non-inflammatory phase could provide new insight in terms of therapeutic decision making and response monitoring. The differences found by this study suggest a potential use of UHFUS for the development of an objective standardized staging method. Further investigations will be necessary to confirm our preliminary results, thus providing a turning point in PG early detection, differential diagnosis and treatment monitoring.

Ultra-High Frequency UltraSound (UHFUS) Assessment of Barrier Function in Moderate-to-Severe Atopic Dermatitis during Dupilumab Treatment.

Atopic dermatitis (AD) is a chronic multifactorial inflammatory disease characterized by intense itching and inflammatory eczematous lesions. Biological disease-modifying drugs, such as dupilumab are recommended for patients with moderate-to-severe AD, refractory to systemic immunosuppressive therapies. Disease monitoring is performed by clinical scores. Since 1970, however, the use of ultrasound and particularly high-frequency ultrasound (HFUS), has identified alterations in dermal echogenicity, called the subepidermal low-echogenic band (SLEB), that correlates with disease severity and response to treatment. We enrolled 18 patients with moderate-to-severe AD, divided into two groups: twelve patients in the dupilumab treatment (Group A) and six patients in standard treatment, from February 2019 to November 2019. We performed ultra-high frequency ultrasound (UHFUS) evaluation of lesional and non-lesional skin, focusing on SLEB average thicknesses measurement, epidermal thickness, and vascular signal in correlation with objective disease scores (EASI, IGA), patient's reported scores (Sleep Quality NRS and Itch NRS), and TEWL and corneometry at baseline (T0), after 1 month (T1) and 2 months (T2). The SLEB average thickness measurement, vascular signal, and epidermal thickness showed a statistically significant reduction in lesional skin of the biological treatment group and no significant reduction in non-lesional skin in both groups. In the lesional skin of the standard treatment group, only epidermal thickness showed a statistically significant reduction. Our study demonstrates that SLEB measurement, vascular signals, and epidermal thickness could be used as objective parameters in monitoring the AD treatment response, while the presence of SLEB in non-lesional skin could be used as a marker of subclinical inflammation and could predict development of clinical lesions, suggesting a pro-active therapy. Further follow-up and research are needed to clarify the association of SLEB decrease/disappearance with a reduction of flares/prolongment of the disease remission time.

Ultra-High-Frequency Ultrasound as an Innovative Imaging Evaluation of Hyaluronic Acid Filler in Nasolabial Folds.

Dermal hyaluronic acid (HA) fillers are used for nasolabial fold correction, but no study is still available on the use of ultra-high-frequency ultrasound (UHFUS) with 70 MHz probes for the evaluation of HA distribution and wrinkle amelioration. We selected 13 patients who received HA filler, evaluated before (Time (T) 0) and after injection (T1), and after 24 weeks (T2). The dermal thickness and distribution of HA were registered, as well as the Wrinkle Severity Rating Scale (WSRS), Global Aesthetic Improvement Scale (GAIS), and wrinkle 3D fullness. The UHFUS dermal thickness was increased by 11% for both sides at T1 and by 7.4% and 6.8% for the right and left side, respectively, at T2 (p < 0.01). The 3D wrinkle fullness showed a T1 increase (+0.59 cc and +0.79 cc for the right and left side, respectively) with a T2 maintenance of 45% of the T1 fullness (p-value < 0.001). The only clinical score significantly modified was WSRS, with a reduction of 56% at T1 and of 47.1% at T2 (p-value < 0.001). Our study then demonstrated the efficacy of UHFUS in the assessment of nasolabial fold correction, representing also the first multi-modal evaluation of HA persistence and its visual subsequent aesthetic results.

An Integrated Systemic and Local Wound Management in Recalcitrant Pyoderma Gangrenosum.

Pyoderma gangrenosum (PG) is a neutrophilic inflammatory dermatosis, whose management still represents a clinical challenge due to frequent unresponsive cases. The aim of our study was to evaluate the efficacy of a novel, combined approach including local wound management, based on the principle of PG-TIME and a systemic therapy with an anti interleukin (IL)-17A monoclonal antibody (mAb). We presented a case of a 37-year-old female patient, affected by multi-refractory PG. The patient was treated with a combined approach of both local and systemic therapy. Wound clinical improvement was assessed by Wound Bed Score (WBS), wound size was evaluated through 3D camera laser scanner, and pain was evaluated with visual analog scale (VAS). After 52 weeks of therapy, the association of local wound management with ixekizumab 80 mg [160 mg at time (T) 0; 80 mg every 2 weeks until week 12; 80 mg every 4 weeks] allowed us to perform skin grafting and obtain complete wound healing. Our clinical case demonstrated the efficacy of a novel combination therapy for the treatment of recalcitrant PG based on IL-17 mAbs and local wound management built on the main features of PG-TIME.

Assessment and Monitoring of Nail Psoriasis with Ultra-High Frequency Ultrasound: Preliminary Results.

Psoriatic onychopathy is one of the clinical presentations of psoriasis and a well-known risk factor for the development of psoriatic arthritis. High-frequency ultrasounds (HFUS > 20 MHz) have recently been used to evaluate the nail apparatus of healthy and psoriatic subjects. The aim of our study was to detect by means of ultra-high-frequency ultrasound (UHFUS 70-100 MHz) alterations of the nail bed and matrix in patients with psoriatic onychopathy and to monitor these parameters during the treatment with monoclonal antibody (mAb). We enrolled 10 patients with psoriatic onychopathy and naive to previous biologic therapies. Patients were evaluated at baseline, after 1 month and after 3 months from the beginning of mAb therapy by a complete clinical assessment and US evaluation. A UHFUS examination with a 70 MHz probe was performed on the thumbnail (I), the index fingernail (II) and the nail with greater clinical impairment (W). The following measurements were analyzed: nail plate thickness (A), nail bed thickness (B), nail insertion length (C), nail matrix length (D) and nail matrix thickness (E). Among the various parameters analyzed, some measures showed a statistically significant decrease with p-value < 0.05 (t0 WA = 0.52 mm vs. t2 WA = 0.42 mm; t0 WB = 2.8 mm vs. t2 WB = 2.4 mm; t0 WE = 0.76 mm vs. t2 WE = 0.64 mm; t0 IIA = 0.49 mm vs. t2 IIA = 0.39 mm). In conclusion, UHFUS could represent a viable imaging technique for the real-time evaluation and monitoring of psoriatic onychopathy, thus supporting the clinical parameters and revealing any subclinical signs of early drug response.

Mitotic rate as a predictive factor for positive sentinel lymph nodes in pT1 and pT2 melanomas.

Sentinel lymph node biopsy is a crucial step in the management of patients affected by melanoma. The decision whether to perform it or not is based on different histological parameters, but the mitotic rate is no longer considered a prognostic variable after the release of the 8th edition of the American Joint Committee on Cancer (AJCC) guidelines. Our objective was to investigate the risk factors that increase the chance for sentinel lymph node positivity in melanomas with a Breslow thickness of less than 2.00 mm, including the mitotic count. A retrospective single-center study was performed on a homogenous cohort of 408 patients treated for cutaneous melanoma. Histological and clinical features were gathered and correlated with the increased risk for sentinel lymph node positivity by means of univariate and multivariate analyses. A statistically significant correlation between a high mitotic index and a positive sentinel lymph node was found in pT1 and pT2 patients, suggesting that in the case of pT1a melanoma with a high number of mitoses, a discussion about whether a sentinel lymph node biopsy is required should be done.

Pso-Reg: a web registry for psoriasis in real life.

BACKGROUND: Psoriasis (PsO) is a common immune mediated inflammatory disease, affecting about 60 million people worldwide. Although current therapies have dramatically changed the therapeutic approach to the disease, the heterogeneity of responses often results in an essential unmet clinical need. This study describes the design and development of the Psoriasis Registry (Pso-Reg), an Italian electronic-based-registry, aimed to collect real life data of patients with psoriasis. METHODS: Pso-Reg is a multicenter, retrospective and observational cohort study based on the Research Electronic Data Capture (REDcap) tool. Five Italian medical centres were part of the network and all patients affected by PsO were included in the study. Socio-demographic, clinical characteristics, laboratory findings and therapies were collected, and descriptive analysis was carried out. RESULTS: Among the 768 patients analyzed, 446 were men (58.1%), with a mean age of 55.5 years. The first more frequent comorbidity was psoriatic arthritis (26.8%), followed by hypertension (25.3%), diabetes (10%) and dyslipidemia (11.7%). Of the entire cohort, 240 patients (38.2%) had a positive family history for PsO. Vulgar type was the most common phenotype (85.5%), with a major involvement of the scalp (13.8%). The mean PASI (Psoriasis Area Severity Index) score at the baseline was 7.5 (7.8). At the enrolment, 107 patients were treated with topic treatments (13.9%), 5 with phototherapy (0.7%), 92 with cDMARDs (conventional disease-modifying anti-rheumatic drugs) (12.0%) and 471 with biologic therapies (61.3%). CONCLUSIONS: Real-life data from Pso-Reg could contribute providing the rationale for an individual-based strategy and a more tailored approach for the management of psoriasis.

Whole transcriptome-based skin virome profiling in typical epidermodysplasia verruciformis reveals α-, ß-, and γ-HPV infections.

HPVs are DNA viruses include approximately 450 types that are classified into 5 genera (α-, ß-, γ-, µ-, and ν-HPV). The γ- and ß-HPVs are present in low copy numbers in healthy individuals; however, in patients with an inborn error of immunity, certain species of ß-HPVs can cause epidermodysplasia verruciformis (EV), manifesting as recalcitrant cutaneous warts and skin cancer. EV presents as either typical or atypical. Manifestations of typical EV are limited to the skin and are caused by abnormal keratinocyte-intrinsic immunity to ß-HPVs due to pathogenic sequence variants in TMC6, TMC8, or CIB1. We applied a transcriptome-based computational pipeline, VirPy, to RNA extracted from normal-appearing skin and wart samples of patients with typical EV to explore the viral and human genetic determinants. In 26 patients, 9 distinct biallelic mutations were detected in TMC6, TMC8, and CIB1, 7 of which are previously unreported to our knowledge. Additionally, 20 different HPV species, including 3 α-HPVs, 16 ß-HPVs, and 1 γ-HPV, were detected, 8 of which are reported here for the first time to our knowledge in patients with EV (ß-HPV-37, -47, -80, -151, and -159; α-HPV-2 and -57; and γ-HPV-128). This study expands the TMC6, TMC8, and CIB1 sequence variant spectrum and implicates new HPV subtypes in the pathogenesis of typical EV.

Epidemiology of melanoma: the importance of correctly reporting to the cancer registries.

In Italy, few epidemiologic studies have been conducted by tracing melanoma reports directly in the electronic registers of the operating units of pathologic anatomy. The Cancer Registers of the Italian regions receive only partial and incomplete data on the diagnoses of melanoma, for this reason, the incidences are usually underestimated. Our work offers a precise picture of the epidemiologic situation of melanoma in a homogenous sample of patients residing in a geographic area traditionally considered to have a high incidence of melanoma.

Risk factors in pediatric melanoma: a retrospective study of 39 cases.

Pediatric melanoma is a rare form of the tumor whose epidemiology is widely increasing thanks to the improvement of dermoscopic and anatomopathologic diagnostic techniques. Although it is a tumor of considerable interest in adults, little has been described about the pediatric field. The objective of our study was then to identify the possible risk factors for the development of melanoma in the pediatric population. We performed a retrospective study conducted in the Melanoma and Skin Cancer Unit and Unit of Dermatology (Livorno, Italy). We analyzed a population of 38 children under 21 years with a diagnosis of melanoma. This population was compared with a control population of 114 children followed up in our dermatologic clinic. From our combined univariate-multivariate statistics analysis, the number of nevi [regression coefficient (RC) of 1.04 and odds ratio (OR) of 2.8 confidence interval (Cl, 1.2-6.6)], and family history of melanoma [RC of 1.99 and OR of 7.3 (Cl, 2.3-22.7)] emerged as possible risk factors for the development of melanoma. The identification of these elements would allow the physician to carry out a more targeted preliminary assessment of the patient, potentially decisive in cases of diagnostic doubt of the lesion. Our study also lays the foundations for identifying those children who, despite not having received a diagnosis of melanoma on histologic examination, should be considered as patients susceptible to a focused follow-up, because of the presence of the risk factors that emerged from our research.