Retinal Microvascular Alterations in Hidradenitis Suppurativa Patients: A Pilot Study Using Optical Coherence Tomography Angiography.

Background: Hidradenitis suppurativa (HS) is a relapsing-remitting inflammatory disease characterized by the progression of asymptomatic nodules to deep-seated lesions and fistula formation that leads to suppuration and scarring. Optical coherence tomography angiography (OCTA) is a new non-invasive imaging technique that carefully analyzes retinal microvasculature networks with high-resolution imaging. Recent studies have demonstrated that retinal vessel density and retinal perfusion reflect systemic inflammatory responses. This study's aim was to analyze OCTA-derived retinal microvasculature parameters to understand if patients affected by HS and without any relevant ocular or systemic comorbidities showed impaired retinal vascular function and morphology. Method: We performed a case-control study of HS patients and age- and sex-matched control cohort. A total of 20 eyes from 10 HS patients and 30 eyes from 15 healthy controls were analyzed, and OCTA-derived microvasculature parameters were compared between groups. Results: OCTA images showed that HS patients, compared to healthy controls, were typically characterized by higher values of the foveal avascular zone (FAZ) both in the superficial capillary plexus (SCP) and in the deep capillary plexus (DCP), and by lower values of vessel density (VD)-SCP, VD-DCP, and vessel length density (VLD)-SCP in the foveal region. These findings partially reflect changes that have been demonstrated in diabetic patients that could be induced by a protracted metabolic or systemic inflammatory dysregulation. Conclusions: In conclusion, OCTA enables large-scale, non-invasive visual screening and follow-up of the retinal vasculature features, providing a new strategy for the prevention and monitoring of visual changes in HS patients.

Vitiligo Treated with Combined Piperine-Based Topical Treatment and Narrowband Ultraviolet B Therapy: Follow-Up with Reflectance Confocal Microscopy.

BACKGROUND: Reflectance confocal microscopy (RCM) has a defined in vivo morphology of vitiligo and re-pigmentation. Combination therapies seem more effective than monotherapies. OBJECTIVE: We aim to describe the clinical and RCM features of re-pigmentation with combined narrowband ultraviolet B (NB-UVB) and piperine-based topical treatment in localized vitiligo. METHODS: Eight patients enrolled at a single center received combined treatment: topical treatment was applied twice daily + NB-UVB twice weekly for 2 × 2-month periods. Clinical changes were analyzed by the Vitiligo Noticeability Scale (VNS) and percentage of re-pigmentation. The evaluator agreement was assessed. Predefined RCM features had the presence/absence of (i) blood vessels, (ii) dendritic cells, and the quantity of (i) an irregular honeycombed pattern and (ii) non-pigmented papillae. Clinical and RCM monitoring was performed at the baseline, 2, 3, 5, and 7 months. RESULTS: Macules were "slightly less noticeable" with 25-50% re-pigmentation. Irregular honeycomb patterns and non-pigmented papillae were significantly less frequently observed, and in less extended areas (T1 vs. T2, p = 0.039; T0 vs. T1, p = 0.005 and T2 vs. T4, p = 0.033). Dendritic cells and blood vessels improved, with significant changes in blood vessels (T1 vs. T2, p = 0.005 and T3 vs. T4, p = 0.008). CONCLUSIONS: RCM confirms the morphological changes induced by combined treatment for localized vitiligo.

Melanoma clinicopathological groups characterized and compared with dermoscopy and reflectance confocal microscopy.

BACKGROUND: Dermoscopic and reflectance confocal microscopy (RCM) correlations between morphologic groups of melanoma have not yet been described. OBJECTIVE: Describe and compare dermoscopic and RCM features of cutaneous melanomas with histopathological confirmation. METHODS: Single center, retrospective analysis of consecutive melanomas evaluated with RCM (2015-2019). Lesions were clinically classified as typical, nevus-like, amelanotic/nonmelanoma skin cancer (NMSC)-like, seborrheic keratosis (SK)-like and lentigo/lentigo maligna (LM)-like. Presence or absence of common facial and nonfacial melanoma dermoscopic and RCM patterns were recorded. Clusters were compared with typical lesions by multivariate logistic regression. RESULTS: Among 583 melanoma lesions, significant differences between clusters were evident (compared to typical lesions). Observation of dermoscopic features (>50% of lesions) in amelanotic/NMSC-like lesions consistently displayed 3 patterns (atypical network, atypical vascular pattern + regression structures), and nevus-like and SK-like lesions and lentigo/LM-like lesions consistently displayed 2 patterns (atypical network + regression structures, and nonevident follicles + heavy pigmentation intensity). Differences were less evident with RCM, as almost all lesions were consistent with melanoma diagnosis. LIMITATIONS: Small SK-like lesions sample, single RCM analyses (no reproduction of outcome). CONCLUSION: RCM has the potential to augment our ability to consistently and accurately diagnose melanoma independently of clinical and dermoscopic features.

Characterization of Acne-Prone Skin with Reflectance Confocal Microscopy and Optical Coherence Tomography and Modifications Induced by Topical Treatment and Probiotic Supplementation.

The evaluation of acne-prone skin and absent-to-mild acne is difficult because this condition is not associated with a clinically definable situation. Previous studies showed that apparently healthy skin in patients with previous episodes of acne shows microcomedos and infundibular hyperkeratosis upon reflectance confocal microscopy (RCM) evaluation. Our aim was to characterize the subclinical and microscopic characteristics of acne-prone skin by means of RCM and dynamic optical coherence tomography (D-OCT) and evaluate microscopic changes induced by treatment. A group of 20 patients received a daily combined treatment over a period of 3 months, consisting of probiotic supplementation with three strains of 109 colony-forming units of Lactobacillus (Lactobacillus reuteri, Lactobacillus casei subsp. rhamnosus, Lactobacillus plantarum) and a combined topical product of azelaic and hydroxypinacolone retinoate (HPR). Clinical evaluations and non-invasive imaging acquisitions using VISIA® System, RCM, and D-OCT were performed at baseline, and after 4 and 12 weeks. The total number of clinically evident non-inflammatory lesions decreased during treatment from 11.5 to 7.3 (p < 0.05). There was also an evident reduction in microscopic acne features at RCM and D-OCT, such as the number of small bright follicles, large bright follicles and vascular threshold density at 300 µm and 500 µm depths. The types and extent of microscopic alterations in acne-prone skin patients may not be evident by clinical scores. Patients with low investigator global assessment (IGA) grades are a heterogeneous population, characterized by different microscopic skin features. Acne-prone skin is susceptible to treatment, and RCM and D-OCT imaging are sensitive tools to objectively monitor subclinical skin changes.

Laser Treatment Monitoring with Reflectance Confocal Microscopy.

Laser treatments have become popular in Dermatology. In parallel to technologic development enabling the availability of different laser wavelengths, non-invasive skin imaging techniques, such as reflectance confocal microscopy (RCM), have been used to explore morphologic and qualitative skin characteristics. Specifically, RCM can be applied to cosmetically sensitive skin areas such as the face, without the need for skin biopsies. For these reasons, apart from its current use in skin cancer diagnosis, our systematic review reveals how RCM can be employed in the field of laser treatment monitoring, being particularly suitable for the evaluation of variations in epidermis and dermis, and pigmentary and vascular characteristics of the skin. This systematic review article aims to provide an overview on current applications of RCM laser treatment monitoring, while describing RCM features identified for different applications. Studies on human subjects treated with laser treatments, monitored with RCM, were included in the current systematic review. Five groups of treatments were identified and described: skin rejuvenation, scar tissue, pigmentary disorders, vascular disorders and other. Interestingly, RCM can assist treatments with lasers targeting all chromophores in the skin and exploiting laser induced optical breakdown. Treatment monitoring encompasses assessment at baseline and examination of changes after treatment, therefore revealing details in morphologic alterations underlying different skin conditions and mechanisms of actions of laser therapy, as well as objectify results after treatment.

Lentigo maligna and lentigo maligna melanoma in vivo differentiation with dermoscopy and reflectance confocal microscopy: A retrospective, multicentre study.

INTRODUCTION: Dermoscopic predictors of lentigo maligna (LM) and lentigo maligna melanoma (LMM) have been recently reported, but these have not been reported in reflectance confocal microscopy (RCM). OBJECTIVES: (i) To validate dermoscopic predictors for LM/LMM, (ii) to identify RCM patterns in LM and LMM, and (iii) correlations between dermoscopic and RCM features in LM and LMM. MATERIALS AND METHODS: A retrospective, multicentre study of consecutive lesions with histologically proven LM or LMM subtypes of the head and face, with complete sets of dermoscopic and RCM images. RESULTS: A total of 180 lesions were included (n = 40 LMM). Previously reported differential dermoscopic features for LM subtypes were confirmed. Other features significantly associated with LMM diagnosis included irregular hyperpigmented areas, shiny white streaks, atypical vessels and light brown colour at dermoscopy and medusa head-like structures, dermal nests and nucleated cells within the papillae at RCM (p < 0.05). Correlations among LM lesions between dermoscopic and RCM features included brown to-grey dots and atypical cells (epidermis), grey colour and inflammation and obliterated follicles and medusa head-like structures. Among LMM lesions, significant correlations included obliterated follicles with folliculotropism, both irregular hyperpigmented areas and irregular blotches with widespread atypical cell distribution (epidermis), dermal nests and nucleated cells within the papillae (dermis). Irregular blotches were also associated with medusa head-like structures (dermal epidermal junction [DEJ]). CONCLUSIONS: Dermoscopic and RCM features can assist in the in vivo identification of LM and LMM and many are correlated. RCM three-dimensional analysis of skin layers allows the identification of invasive components in the DEJ and dermis.

Tildrakizumab in Complex Psoriatic Patients: An Experience in Emilia-Romagna (Italy).

BACKGROUND: IL-23 inhibitors are the latest class of biologic drugs approved for moderate-to-severe psoriasis. OBJECTIVES: to investigate real-life safety and efficacy of tildrakizumab. METHODS: demographic data, medical history, psoriasis disease history, PASI, DLQI, BSA, NAPSI were recorded at weeks 0, 12, 24, 36. RESULTS: PASI, BSA, DLQI and NAPSI all decreased rapidly during the 36 week follow-up period. PASI score reduced from 12.28 to 4.65 by week 12, followed by a further decrease to 1.18 at week 36 Multiple logistic regression showed that smoking, BMI ≥30, ≥3 comorbidities, previous systemic traditional or biologic drugs, psoriatic arthritis nor difficult-to-treat areas influenced the reduction of PASI and NAPSI scores during treatment with tildrakizumab (P > .05). CONCLUSIONS: we assessed a good performance of tildrakizumab in patients with multiple comorbidities, multi-failure, elderly patients, and in subjects with psoriatic arthritis.

Skin ageing: Clinical aspects and in vivo microscopic patterns observed with reflectance confocal microscopy and optical coherence tomography.

Few studies have combined high-resolution, non-invasive imaging, such as standardized clinical images, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT), for age-related skin change characterization according to age groups. This study aimed to correlate clinical manifestations of ageing with skin cytoarchitectural background observed with high-resolution, non-invasive imaging according to age-related skin pattern distribution. A set of 140 non-pathological facial skin images were retrospectively retrieved from a research database. Subjects, aged between 20 and 89, were divided into 7 age groups. Clinical features were explored with VISIA, including hyperpigmentation, skin texture, wrinkles, pores and red areas, quantified and expressed as automated absolute scores. Previously described RCM and OCT epidermal and dermal features associated with ageing were investigated. All features were assessed for distribution and correlation among age groups. Significant direct correlations between age and clinical features were proven for cutaneous hyperpigmentation, skin texture, wrinkles and red areas. As age advances, RCM epidermal irregular honeycomb and mottled pigmentation are more frequently observed and collagen is more frequently coarse, huddled and curled, while the epidermis in OCT is thickened and the dermal density is decreased with more disrupted collagen fibres. RCM and OCT feature changes correlate directly and indirectly as well as correlating directly and indirectly with standardized clinical images. Clinical manifestations of ageing correlate with skin cytoarchitectural background observed with RCM and OCT. In conclusion, complimentary information between standardized clinical images and high-resolution, non-invasive imaging will assist in the development of future studies dedicated to skin ageing assessment and treatment effectiveness.

Combined Carbon Dioxide Laser with Photodynamic Therapy for Nodular Basal Cell Carcinoma Monitored by Reflectance Confocal Microscopy.

Introduction: Basal cell carcinoma (BCC) represents around 80% of all malignant skin cancers worldwide, constituting a substantial burden on healthcare systems. Due to excellent clearance rates (around 95%), surgery is the current gold-standard treatment. However, surgery is not always possible or preferred by patients. Numerous non-surgical therapies, sometimes combined, have been associated with promising tumor free survival rates (80-90%) in non-melanoma skin cancers (NMSCs). Most research has enrolled superficial basal cell carcinomas (sBCCs), with limited recent studies also involving low-risk nodular BCCs (nBCCs). Given lower efficacy rates compared to surgery, close monitoring during the follow-up period is essential for patients treated with non-surgical therapies. Monitoring with dermoscopy is constrained by low sensitivity rates. Reflectance confocal microscopy (RCM) is more sensitive in monitoring non-surgically treated NMSCs. Case presentation: A 41-year-old woman with a single nBCC relapse following photodynamic therapy (PDT) located on the dorsum of the nose presented to our center. Given the aesthetically sensitive location of the lesion and the patient's preference for a non-surgical approach, a combined treatment of CO2 laser and PDT was prescribed. A superpulsed CO2 laser (power: 0.5-3 W, frequency: 10 Hz, spot size 2 mm) with two PDT sessions (2 weeks apart) were conducted. At 6 weeks follow-up, monitoring performed with RCM revealed a reduction but not eradication of basaloid tumor islands. Another 2 sessions of PDT were recommended. At 3, 12 and 30 months of follow-up, the nasal dorsum area of the previous nBBC lesion was noted to be slightly hypopigmented (observed clinically), with a mild erythematous background (observed by dermoscopy). RCM evaluation confirmed the absence of RCM BCC criteria. The cosmetic outcome was very much improved. Conclusions: Combined CO2 laser and PDT for the treatment of a localized nBCC on the dorsum of the nose of a 41-year-old proved to offer tumor free survival at 30-month follow-up, as monitored with RCM. RCM is useful for the evaluation of non-surgical therapies as it has comparably higher sensitivity than dermoscopy and is especially useful in cases of suspected late recurrence. Further studies are needed to validate ongoing tumor free survival following this combined nonsurgical approach in the treatment of nBCC.

Non-Melanoma Skin Cancer Clearance after Medical Treatment Detected with Noninvasive Skin Imaging: A Systematic Review and Meta-Analysis.

BACKGROUND/OBJECTIVES: Non-melanoma skin cancer (NMSC) treated with nonsurgical therapies can be monitored with noninvasive skin imaging. The precision of dermoscopy, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) in detecting clearance is unclear. We aim to report the proportion of persisting tumors identified with noninvasive technologies available in the literature. METHODS: A systematic literature search was conducted on the PubMed and Cochrane Public Library Databases for articles published prior to November 2021. Statistical analyses were conducted with MedCalc 14.8.1 software. RESULTS: A total of eight studies (352 lesions) reporting noninvasive imaging for NMSC clearance following nonsurgical treatment were included. Most (n = 7) reported basal cell carcinoma (BCC), and one study reported squamous cell carcinoma (SCC) clearance. A meta-analysis of the BCC clearance revealed that the summary effect for RCM was higher, as compared to the other techniques. Interestingly, the sensitivity and specificity for OCT were 86.4% (95% CI: 65.1-97.1) and 100% (95% CI: 94.8-100.0), respectively, whilst, for RCM, they reached 100% (95%CI: 86.8-100) and 72.5% (95% CI: 64.4-79.7), respectively. CONCLUSIONS: Routine clinical examination and dermoscopy underperform when employed for NMSC clearance monitoring, although they represent the first approach to the patient. OCT and RCM seem to improve the detection of persistent BCC after medical treatment.

Dermoscopy, Reflectance Confocal Microscopy and Optical Coherence Tomography Features of Acne: A Systematic Review.

Noninvasive imaging techniques have recently outlined precise microscopic features of acne elementary lesions and accurate quantifications for disease severity staging and therapeutical efficacy follow-up. The aim of this review is to systematically describe current applications of dermoscopy, reflectance confocal microscopy (RCM), and optical coherence tomography (OCT) in acne vulgaris assessment and management. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. We included studies conducted on human subjects with elementary lesions of acne vulgaris, reporting assessment of the lesions with dermoscopy, RCM, and/or OCT. At present there are few large studies regarding acne and noninvasive imaging techniques, representing the main limitation of this review. Clinical examination represents the first line in acne diagnosis and treatment. However, dermoscopy, RCM, and OCT are further tools that can improve acne classification, monitoring of treatment, and pathophysiologic characterization. In the near future, dermoscopy, RCM, and OCT could become routinely used for the evaluation of acne vulgaris to provide a deeper knowledge of the disease and to guide the clinician in the prescription of tailored treatment protocols based on each patient's characteristics.

Hidradenitis suppurativa: Morphologic and vascular study of nodular inflammatory lesions by means of optical coherence tomography.

Hidradenitis suppurativa (HS) is an inflammatory disease characterized by a recurrent-remission trend and clinical lesions that range from asymptomatic to inflamed, deep-seated nodules with scarring and suppuration. The aim of our study was to identify morphologic and vascular features of HS nodules by means of dynamic optical coherence tomography (D-OCT) and to define if they are correlated to patient endotype and risk of disease progression. A set of standardized clinical pictures and D-OCT images were acquired from 57 inflammatory nodules of 40 patients affected by HS. A set of 20 clinical and D-OCT images were acquired from 20 healthy volunteers as a control group. The comparison of D-OCT features among HS and control group was analysed. The correlation between HS patient endotype and D-OCT features of the lesions was calculated. D-OCT enabled to identify vascular and morphological aspects characterizing HS nodular inflammatory lesions. In addition, several D-OCT features were significantly different among distinct disease endotypes. The characterization of HS nodular inflammatory lesions through D-OCT, corresponding to blood vessel dilation and inflammatory associated hyper-vascularization, may have important clinical consequences in the assessment of HS risk of progression, therapeutic decisions and treatment efficacy monitoring.

Unusual dermoscopic patterns of basal cell carcinoma mimicking melanoma.

BACKGROUND: Basal cell carcinoma can simulate melanoma and specific dermoscopic criteria have not yet been defined in a large cohort. OBJECTIVE: To identify dermoscopic "trump" characteristics for differential diagnosis, identify cluster groups and assess the clinical impact of this study's findings. METHODS: Retrospective, multicentric comparative study of atypical, non-facial basal cell carcinoma (≥1 seven-point checklist criteria) and melanoma (with at least one BCC criteria) at dermoscopy. Observed dermoscopic features were used to develop a proposed score. Lesion clusters were defined with hierarchical analysis. Clinical impact was assessed with a blinded reader study following this study's results. RESULTS: A total of 146 basal cell carcinoma and 76 melanoma were included. Atypical vascular pattern was common to most lesions (74.5%). Twelve trump features were included in the proposed score (sensitivity 94.1% and specificity 79.5%). Cluster analysis identified 3 basal cell carcinoma and 3 melanoma clusters. Findings improved overall diagnostic accuracy and confidence (26.8% and 13.8%, respectively; p < 0.001). CONCLUSIONS: These findings support the notion that atypical vascular pattern should be considered a shared feature of both melanoma and atypical basal cell carcinoma. Our proposed score improves diagnostic accuracy and confidence. Absence of pigmented features was associated with lower diagnostic accuracy and confidence.

Cutaneous Melanoma Systematic Diagnostic Workflows and Integrated Reflectance Confocal Microscopy Assessed with a Retrospective, Comparative Longitudinal (2009-2018) Study.

BACKGROUND: The increasing global burden of melanoma demands efficient health services. Accurate early melanoma diagnosis improves prognosis. OBJECTIVES: To assess melanoma prevention strategies and a systematic diagnostic-therapeutical workflow (improved patient access and high-performance technology integration) and estimate cost savings. METHODS: Retrospective analysis of epidemiological data of an entire province over a 10-year period of all excised lesions suspicious for melanoma (melanoma or benign), registered according to excision location: reference hospital (DP) or other (NDP). A systematic diagnostic-therapeutical workflow, including direct patient access, primary care physician education and high-performance technology (reflectance confocal microscopy (RCM)) integration, was implemented. Impact was assessed with the number of lesions needed to excise (NNE). RESULTS: From 40,832 suspicious lesions excised, 7.5% (n = 3054) were melanoma. There was a 279% increase in the number of melanomas excised (n = 203 (2009) to n = 567 (2018)). Identification precision improved more than 100% (5.1% in 2009 to 12.0% in 2018). After RCM implementation, NNE decreased almost 3-fold at DP and by half at NDP. Overall NNE for DP was significantly lower (NNE = 8) than for NDP (NNE = 20), p < 0.001. Cost savings amounted to EUR 1,476,392.00. CONCLUSIONS: Melanoma prevention strategies combined with systematic diagnostic-therapeutical workflow reduced the ratio of nevi excised to identify each melanoma. Total costs may be reduced by as much as 37%.

Dermoscopy, confocal microscopy and optical coherence tomography features of main inflammatory and autoimmune skin diseases: A systematic review.

BACKGROUND/OBJECTIVES: Non-invasive skin imaging features of main skin inflammatory and autoimmune diseases have been reported, although a comprehensive review of their correlation with histopathologic features is currently lacking. Therefore, the aim of this paper was to review the correlation of dermoscopic, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) criteria of main inflammatory and autoimmune skin diseases with their corresponding histopathologic criteria correlation. METHODS: Studies on human subjects affected by main inflammatory and autoimmune diseases, defining the correlation of dermoscopic, RCM or OCT with histopathologic criteria, were included in the review. Five groups of diseases were identified and described: psoriasiform, spongiotic and interface dermatitis, bullous diseases and scleroderma. RESULTS: Psoriasiform dermatitis was typified by white scales, corresponding to hyperkeratosis, and vessels, observed with RCM and OCT. Spongiosis, corresponding to dark areas within the epidermis with RCM and OCT, was the main feature of spongiotic dermatitis. Interface dermatitis was characterised by dermoepidermal junction obscuration. Blisters, typical of bullous diseases, were visualised as dark areas with RCM and OCT while scleroderma lesions were characterised by dermoscopic fibrotic beams, related to dermal thickness variations, with specific OCT and histopathologic correlations. CONCLUSIONS: Although the role of RCM and OCT has yet to be defined in clinical practice, non-invasive skin imaging shows promising results on inflammatory and autoimmune skin diseases, due to the correlation with histopathologic features.