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.

Serum Amyloid A: A Potential New Marker of Severity in Hidradenitis Suppurativa.

Introduction: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with systemic inflammation and high impact on quality of life. Treatment strategies are still inadequate with a lack of inflammation biomarkers. We conducted a prospective study to assess the correlation between serum amyloid A (SAA) levels and active lesion count; disease severity; Dermatology Life Quality Index (DLQI); smoking; BMI; and lesion sites. Methods: Forty-one patients (M/F: 22/19) were enrolled. Demographic, clinical, laboratory, and therapeutic data were assessed at baseline on patients not under treatment or in wash-out from systemic treatment for at least 2 weeks. Associations were investigated by univariate and multivariate analyses. Results: SAA levels were significantly associated with number of nodules (p = 0.005), abscesses (p < 0.001), fistulas (p = 0.016), and severe IHS4 (p = 0.088 and r = 0.514). Gluteal localization was correlated with high values of mSartorius and severe IHS4. Conclusions: We recommend assessment of SAA levels to monitor therapeutic response in patient with HS in order to prevent disease's flare and potential complications.

Fractional Epidermal Skin Grafts in Hard-to-Heal Wounds: Case Series.

Cellutome™ is a minimally invasive, automated system for harvesting fractional epidermal micrografts. This therapy is indicated for granulating, small size, poor exuding acute wounds. We enrolled 15 patients with 9 venous leg ulcers and 6 atypical ulcers. The micrografts were applied with a nonadherent dressing and covered with a polyurethane foam and multilayer bandage. We scheduled 3 weekly visits for the change of the secondary dressings and multilayer bandage and clinical assessment (Wound Bed Score [WBS], pain assessment, and healing rate). The lesions were measured with the Silhouette Star™ system, a software that allows measurement of perimeter and area from a digital image. The only symptom during the procedure was a sensation of warmth. The donor area healed in 2 weeks in all patients (n = 15). We reported an area reduction of 24.30% in typical ulcers and 38.82% in atypical ulcers after 3 weeks. The average WBS improved in all ulcers from 13.06 to 14.93. The average healing rate was 0.19 mm/day both in typical and atypical ulcers. Consequently, in our small case series fractionated epidermal graft treatment significantly promoted the healing rate in all chronic ulcers regardless of etiology. Future studies with larger case series will be needed.

Non-invasive imaging techniques in presurgical margin assessment of basal cell carcinoma: Current evidence.

BACKGROUND: The diagnosis of basal cell carcinoma (BCC) is based on clinical and dermoscopical features. In uncertain cases, innovative imaging techniques, such as reflectance confocal microscopy (RCM) and optical coherence tomography (OCT), have been used. The main limitation of these techniques is the inability to study deep margins. HFUS (high-frequency ultrasound) and the most recent UHFUS (ultra-high-frequency ultrasound) have been used in various applications in dermatology, but they are not yet routinely used in the diagnosis of BCC. A key point in clinical practice is to find an imaging technique that can help to reduce post-surgical recurrences with a careful presurgical assessment of the lesional margins. This technique should show high sensitivity, specificity, reproducibility and simplicity of execution. This concept is very important for the optimal management of patients who are often elderly and have many comorbidities. The aim of the paper is to analyse the characteristics of current imaging techniques and the studies in the literature on this topic. MATERIALS AND METHODS: The authors independently searched the MEDLINE, PubMed, Embase, Scopus, ScienceDirect and Cochrane Library databases for studies looking for non-invasive imaging techniques for the presurgical margin assessment of BCC. RESULTS: Preoperative study of the BCC subtype can help to obtain a complete excision with free margins. Different non-invasive imaging techniques have been studied for in vivo evaluation of tumour margins, comparing the histologic evaluation with a radical surgery. The possibility to study the lateral and deep margins would allow a reduction of recurrences and sparing of healthy tissue. CONCLUSION: HFUS and UHFUS represent the most promising, non-invasive techniques for the pre-operative study of BCC facilitating the characterization of vascularization, deep lateral margins and high-risk subtypes, although they are limited by insufficient literature unlike RCM and OCT.

The Association Between pH and Fluorescence as Noninvasive Diagnostic Tools in Chronic Wounds.

MolecuLight i:X is a noninvasive, portable device that captures images, measures wound areas, and allows the evaluation of the bacterial environment in real time. The aim of the study was to correlate the different fluorescence (light green, red, cyan) and dark red-purple-black color areas with average pH values in these areas and with average wound bed score (WBS). During a 4-week period, we enrolled 43 adult patients (23 females and 20 males) with clinically infected and uninfected chronic ulcers. In our study, the mean age was 68 years old. The etiologies were 21 venous ulcers, 3 arterial ulcers, 4 vasculitis, 7 pyoderma gangrenosum, 7 traumatic ulcers, and 1 neoplastic ulcer. The average area was 16.92 cm2 and the average WBS was 9.17. A total of 16 ulcers (37%) were positive for clinical signs and symptoms of infection and 27 ulcers were negative (63%). Thirty-six ulcers emitted a single fluorescence: cyan (n = 13), red (n = 1), light green (n = 14), and dark red-purple-black (n = 8). Six wounds showed a double fluorescence area: red and cyan (n = 1) and cyan and light green (n = 5). One ulcer emitted a triple fluorescence area: red, cyan, and light green. Overall in 43 ulcers, we found 43 fluorescence and 8 dark red-purple-black color. We found significant data between pH and fluorescence. pH values on wound bed confirm in a noninvasive way the correlation between fluorescence and bacterial burden. Moreover, MolecuLight i:X is able to detect objectively the bacterial proliferation, in contrast with pH which cannot distinguish different types of bacteria.

The Genetic Basis of Dormancy and Awakening in Cutaneous Metastatic Melanoma.

Immune dysregulation, in combination with genetic and epigenetic alterations, induces an excessive proliferation of uncontrolled melanoma cells followed by dissemination of the tumor cells to distant sites, invading organs and creating metastasis. Although immunotherapy, checkpoint inhibitors and molecular targeted therapies have been developed as treatment options for advanced melanoma, there are specific mechanisms by which cancer cells can escape treatment. One of the main factors associated with reduced response to therapy is the ability of residual tumor cells to persist in a dormant state, without proliferation. This comprehensive review aimed at understanding the genetic basis of dormancy/awakening phenomenon in metastatic melanoma will help identify the possible therapeutical strategies that might eliminate melanoma circulating tumor cells (CTCs) or keep them in the dormant state forever, thereby repressing tumor relapse and metastatic spread.

The Role of Autoflorescence Imaging Device in the Evaluation of Bacteria Burden Control.

MolecuLight i:X is a autofluorescence, portable device that allows an assessment of wound area, perimeter, width and length and an evaluation in real time of wound surface bacteria (>104 CFU/g). Primary objective of our study was to evaluate the reduction of bacterial load associated to 3 different therapeutic approaches: dressings and multicomponent bandages (Group1), sharp debridement, dressings and multicomponent bandages (Group 2), and 10 patients treated with zinc oxide bandage (Group 3). Secondary objective was NRS pain scale, Wound Bed Score (WBS) and Quality of Life (QoL) assessment. Despite the improvement of bacterial load, WBS, Qol and NRS was evident in all 3 groups, the analysis of our results demonstrates that the application of zinc oxide bandage, directly in contact with the wound bed and/or the perilesional skin, resulted in a higher improvement and a significant reduction of WBS and bacterial load. Fluorescence imaging can help the specialist in a more targeted assessment and management of infection. Sharp debridement and antiseptic dressings are classically used to reduced bacteria burden. Zinc oxide directly on the wound is an interesting cost-effective option to control different types of bacteria.

Impact of psychiatric comorbidities in psoriasis, hidradenitis suppurativa and atopic dermatitis: The importance of a psychodermatological approach.

BACKGROUND: There is a strong interaction between the immunological and nervous system in the skin. Lesions that are physically disfiguring and chronically relapsing have a high impact on quality of life (QoL) and can result in the emergence of psychiatric disorders. The literature data confirm a higher prevalence of psychiatric disorders in patients with psoriasis, hidradenitis suppurativa (HS) and atopic dermatitis (AD), but such data are compromised by low-quality evidence due to methodological heterogeneity. OBJECTIVES: The primary aim was to analyse the prevalence of psychiatric comorbidities in a group of psoriasis, AD and HS patients compared with a control group. The secondary aims were to evaluate the impact of psychiatric comorbidities on the disease development, severity, flare-ups and QoL. METHODS: A total of 59 cases and 64 controls were included. RESULTS: Generalized anxiety disorder and depressive disorder with anxious distress were found to be risk factors for AD. Age, smoking and substance-related disorder showed a specific association with HS. Major depressive disorder showed a specific association with dermatology life quality index (DLQI) and all the above disease flare-ups. CONCLUSIONS: Atopic dermatitis, psoriasis and HS are associated with psychiatric disorders. A psychodermatological approach improves outcomes in terms of QoL, disease flare-ups and long-term management.

Prognostic Indicators of Wound Healing in Atypical Wounds: A Case Series.

Healing rate is the most accurate method to predict healing; however, there are no data in atypical ulcers. We retrospectively analyzed clinical features, associated comorbidities, and therapies of 159 patients with atypical ulcers. In a subgroup of 59 patients, we analyzed the areas, perimeters, and the healing rate (mm/d) as prognostic indicators of wound healing. Atypical ulcers were more frequent among women (n = 98) with an average age of 76 years. Confirmed by biopsy, the etiologies were as follows: inflammatory diseases (38%), neoplastic ulcers (29%), vasculitis (21%), drug-induced ulcers (7%), and infectious ulcers (4%). Systemic therapies were applied based on the different etiologies. Wound bed preparation principles guided the local treatment. The average reduction of the area during the observation interval was 36%, while the average reduction in the perimeter was 41%. Overall, 51 ulcers showed a reduction in wound size and 8 ulcers showed an increase. Neoplastic ulcers were the group with the fastest healing rate, with an average speed of 0.24 mm/d. The slowest healing occurred in the inflammatory group with an average healing rate of 0.032 mm/d. The initial area and perimeters influenced wound healing; however, ulcer etiology and comorbidities significantly altered the healing rate.

Local Management of Malignant and Unresectable Fungating Wounds: PEBO Assessment.

Malignant fungating wounds (MFWs) represent a major problem for public health. The most common symptoms associated with MFWs are pain, exudate, bleeding and odor. The aim of the study was to optimize the local management and dressing of MFWs. We developed a standardized 4- step approach to MFWs based on Pain, Exudate, Bleeding and Odor management in a case series of 24 patients: we call this the PEBO approach. We analyzed etiologies, localization, Quality of Life (QoL), pain and clinical signs and symptoms. We assessed the ulcers at baseline, after two weeks and after one month. In our study, most patients showed an improvement in the QoL using PEBO approach, although some experienced a deterioration in their general clinical conditions. Non-cytolesive cleansing, atraumatic dressings were applied to allow pain relief. Non-adherent dressings were combined with a secondary dressing in the case of exudate. Achieving hemostasis with dressing or medication is a priority in MFW management. Antibacterial dressings and odor absorbent dressings were used for odor absorption. Surgical debridement, adherent dressing and occlusive dressings were avoided. Dressing changes were programmed twice a week for four weeks. PEBO simplified the complex aspects of this type of ulcer, and could help physicians, nurses, and also the rest of the team, including the patients themselves and their family, in the multidisciplinary palliative care of MFWs.

Ultra-high-frequency ultrasound monitoring of melanomas arising in congenital melanocytic nevi: a case series.

The aims of our study were to evaluate with ultra-high-frequency ultrasound (UHFUS) the ultrasound features of congenital melanocytic nevi (CMNs) and malignant melanomas (MMs) arising in CMNs and the correlation between ultrasonographic thickness and histological thickness in MMs. We evaluated 10 patients with small-medium CMNs and 10 patients with MMs arising in small-medium CMNs. We collected patient's data, clinical and dermoscopic features. The UHFUS was performed using a 70 MHz frequency probe to study the ecostructure, shape and vascularization. Breslow thickness was compared with ultrasonographic thickness. In the MMs group the following dermoscopic features were described: hyperpigmentation (n = 9), regression area (n = 6), whitish-blue veil (n = 5), thickened network (n = 5), irregular globules (n = 3), inverse network (n = 2) and striae (n = 1). Hyperpigmentation (n = n = 9), thickened network (n = 7), irregular globules (n = 5), regression area (n = 5), striae (n = 1) and whitish-blue veil (n = 1) were found in the CMNs group. The multicomponent pattern was present in both MMs (n = 4) and in CMNs (n = 5). Moreover, the parameters indicative of suspected malignancy were variously combined in the two groups, without showing significant differences in the statistical analysis; with the exception of the blue veil that correlated with the diagnosis of MM. Ultrasonoghaphic vascularization was an ever-present parameter in MMs (100%), with high intensity of intratumoral signal, as opposed to CMNs. We also found a statistically significant correlation between ultrasound thickness and Breslow thickness. In the future, this technique could implement the diagnostic preoperative phase of MMs arising in CMNs in combination with standard clinical-dermatoscopic evaluation.

Ultrasound-guided injection of intralesional steroids in acute hidradenitis suppurativa lesions: A prospective study.

The management of hidradenitis suppurativa (HS) flares with intralesional steroids lacks strong scientific evidence but limited data suggest that it may be useful. The objective of this study is to assess the clinical and ultrasound responses of HS flares to ultrasound-guided injections of intralesional triamcinolone (40 mg/ml) with a dilution 1:4 versus 1:2 at 30-day (t1), 60-day (t2), and 90-day (t3) follow-up. We recruited patients with ≤3 acute lesions, unresponsive to topical therapy. At baseline we assessed lesions clinically and by ultra-high frequency ultrasound (48 or 70 MHz) and randomly performed an ultrasound-guided injection of triamcinolone. Assessments were repeated at t1, t2, and t3 follow-up, re-injecting the lesion in the case of no or partial response. We treated 49 lesions: 38.8% showed improvements at t1; 46.9% at t2; 6% at t3; and 8.3% showed no clinical and ultrasound improvements. Long-term follow-up data confirmed a statistically significant reduction in Visual Analogue Scale (VAS)-pain, Dermatology Life Quality Index (DLQI), and HS-Physician Global Assessment (HS-PGA), as well as edema and vascular signals. No adverse effects were reported. Our study suggests that ultrasound-injections with a 1:2 dilution are beneficial for HS flares that do not respond to topical treatment and should be included in the therapeutic algorithm.

Seborrheic keratosis-like melanoma: a diagnostic challenge.

This article summarizes the main epidemiologic and diagnostic features of seborrheic keratosis-like (SK-like) melanoma. We performed a review of the current literature. The real and current incidence and prevalence of SK-like melanoma are unknown. Many lesions are misdiagnosed and not excised with histopathologic confirmation, or excised without an appropriate surgical approach due to a benign clinical and dermoscopic appearance. SK-like melanoma presents both melanoma and SK features. SK-like melanoma and SK are often clinically indistinguishable even for experienced dermatologists. Clinically, it develops as a black-dark brown or light slightly elevated, papule, nodule or plaque with rapid growth and a regular or irregular shape. SK-like melanoma presents melanocytic and nonmelanocytic dermoscopic features. Irregular dark-brown dots/globules, a blue-grayish veil, streaks, irregular pigmentation or network and brown lines point to a melanoma diagnosis. Among the nonmelanocytic features, milia-like cysts and comedo-like openings have been highlighted. The association of polarized and nonpolarized dermoscopic techniques is more accurate for studying the dermoscopic features of SK-like melanoma. If the dermoscopic features are unclear, further investigations with reflectance confocal microscopy (RCM) or biopsy with histologic examination are essential. SK-like melanoma is a dermatologic challenge. Careful clinical and dermoscopic evaluation favor a correct diagnosis. In unclear cases, it is important to perform a biopsy with histologic examination to confirm the correct diagnosis.

Definition of treatment goals in terms of clinician-reported disease severity and patient-reported outcomes in moderate-to-severe adult atopic dermatitis: a systematic review.

BACKGROUND: Atopic dermatitis (AD) is a chronically relapsing skin disease. Although a definitive cure is not available, appropriate treatment can control the disease. The advent of biologic drugs has led to the need for a clear definition of the disease severity and treatment response. A standardized list of outcomes that defines clinician-reported disease severity and patients' reported severity are therefore essential. Solid criteria to define the response to treatment and treatment failure are lacking to date. OBJECTIVE: This systematic review defines treatment goals in terms of clinician-reported disease severity and patient-reported outcomes, referring to the published moderate-to-severe AD clinical trials. The application of these goals in daily clinical practice will ensure a better selection of available treatment options, thus increasing patient quality of care. MATERIALS AND METHODS: A systematic literature search was performed to identify the treatments goals of randomized controlled clinical trials (RCTs) on moderate-to-severe adult AD published between January 2000 and October 2020. RESULTS: In total, 14 studies met the eligibility criteria. The most widely used tools in terms of clinician-reported disease severity were the Scoring of Atopic Dermatitis (SCORAD) followed by the Eczema Area Severity Score (EASI) and Investigator Global Assessment (IGA). For disease severity scales as efficacy outcome in RCTs, the greatest standardization and reproducibility was for improvement of at least 50% in EASI score and IGA score reduction of ≥2 grades from baseline. The most widely used tools from the patients' perspective were the Dermatology Life Quality Index (DLQI), Numeric Rate Scale (NRS)-itch and Patient Oriented Eczema Measure Score (POEM). In terms of patients' reported efficacy outcomes in RCTs, a numerical DLQI, NRS-itch and POEM score improvement of at least 4 points from baseline was reported. CONCLUSIONS: This systematic review highlights the need for collaboration between experts in order to define and optimize treatment outcomes. Despite considerable progress in harmonizing outcome measures, promoted by the foundation of the Harmonizing Outcome Measures for Eczema (HOME) initiative in 2008, our results demonstrate that this endpoint is still an unmet need. Based on the literature data we propose a minimum treatment goal algorithm for use in daily clinical practice aimed at stimulating a discussion on how the care of AD patients could be further improved.