Real-Time Confocal Imaging for Hidradenitis Suppurativa: Description of Morphological Aspects and Focus on the Role of Follicular Ostia.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory skin disease involving the follicular unit. Growing evidence suggests a crucial role of hyperkeratosis, infundibular plugging and perifolliculitis in its pathogenesis. OBJECTIVES: To characterize the microscopic morphology of open comedos using in vivo reflectance confocal microscopy (RCM) and define alterations occurring in HS normal-appearing perilesional skin compared to healthy skin of a control group, discussing therefore microscopic differences. MATERIALS AND METHODS: Twenty patients (11 males, 9 females; aged 19-51 years) affected by HS were recruited. RCM was performed on open comedos of axillary/inguinal regions and on normal-appearing skin areas distant at least 1.5 cm from HS lesions. Ten healthy individuals (6 males, 4 females) were included as control group. RESULTS: RCM aspects of 78 open comedos were explored, observing circular/ovoidal structures disclosing a hyperrefractive amorphous material (72/78, 92.3%) within the infundibular cavity surrounded with a bright (51/78, 65.4%) and regular (52/78, 66.2%) border. Follicular ostia of HS perilesional skin (n = 541) compared to follicular ostia of a control group (n = 321) were characterized by a larger infundibular diameter (183.4 vs. 85.8 µm) and diverged in terms of material collected inside infundibula (44.5 vs. 21%) and keratinization of the border (47.6 vs. 25.5%). CONCLUSION: In vivo characterization of open comedos and the recognition of microscopic subclinical alterations of HS normal-appearing skin, compared to healthy skin, could add further insights into the definition of biological events leading to HS manifestations, including the dysregulated process of keratinization.

Microblotches on Dermoscopy of Melanocytic Lesions are Associated with Melanoma: A Cross-sectional Study.

Numerous dermoscopic structures for the early detection of melanoma have been described. The aim of this study was to illustrate the characteristics of dermoscopic structures that are similar to blotches, but smaller (termed microblotches), and to evaluate their association with other well-known dermoscopic structures. A cross-sectional study design, including 165 dermoscopic images of melanoma was used to define microblotches, and 241 consecutive images of naevi from the HAM10000 database, were studied to evaluate the prevalence of this criterion in both groups. Microblotches were defined as sharply demarcated structures ≤1 mm, with geographical borders visible only with dermoscopy. Microblotches were present in 38.7% of the melanomas and 6.7% of the naevi. Moreover, microblotches were associated with an odds ratio (OR) of malignancy of 5.79, and were more frequent in invasive melanoma than in the in-situ subtype (OR 2.92). Histologically, they correspond to hyperpigmented parakeratosis or epidermal consumption. In conclusion, microblotches are related to melanomas. This finding could help dermatologists to differentiate between naevi and melanomas.

Confocal Assessment of Pigmented-Mucosal Lesions: A Monocentric, Retrospective Evaluation of Lip and Genital Area.

INTRODUCTION: Pigmentation of lip and/or genitalia is mainly due to the development of benign melanotic macules, with a less occurrence of melanocytic and other non-melanocytic lesions. Mucosal melanoma has worse prognosis compared with cutaneous counterpart, hence identification of atypical features for an early diagnosis is crucial. OBJECTIVES: The aim of this study was to report further data of confocal features characterizing pigmented mucosal lesions of genital area and of the lips and test the diagnostic role of the reflectance confocal microscopy (RCM)lip score. METHODS: Clinical, dermoscopic and RCM images of histologically proven pigmented lesions, involving the genital area (vulva or glans penis) and lip, were retrospectively reviewed. RCM images were evaluated for malignant criteria, and statistical analysis was conducted for categorical variables. RESULTS: Seventy pigmented lesions were included in the study and divided into two groups based on the body area location: lip (17) and genital area (53). Architectural disarray (P = 0.002), dendritic (P = 0.031) and roundish cells in epidermis (P < 0.0001), interpapillary dendritic cells (P = 0.039) and junctional atypical cells (P = 0.002) were associated to genital melanoma. Melanoma involving the lip was characterized by roundish cells in epidermis, a criterion found in one labial benign lesion, only (P = 0.005). Main limitations of the study are the inclusion of low melanomas and the presence of epidermal dendritic cells in melanosis and melanoma, as a confusing factor in imaging. CONCLUSIONS: Dermatologists should consider confocal microscopy as an adjunctive tool to dermoscopy in the differential diagnosis of pigmented mucosal lesions, especially in presence of clinical and dermoscopic findings suspicious for malignancy.

Enteric-coated mycophenolate sodium as a steroid-sparing agent in pemphigus treatment: a retrospective study.

Several immunosuppressive drugs are used as steroid-sparing agents in pemphigus vulgaris (PV) treatment, with the aim of reducing the cumulative dose of steroids and minimizing the side effects of long-term steroid treatment. The objective of this study is to evaluate the efficacy and safety of enteric-coated mycophenolate sodium (EC-MPS) as a steroid-sparing agent in PV patients. We performed a retrospective study on PV patients who had attended our dermatology department between October 2004 and December 2010 and who had been treated with a combined therapy of systemic corticosteroids and EC-MPS. In the 16 enrolled patients, the introduction of EC-MPS allowed the tapering of systemic corticosteroids, and in 12 of these patients, complete remission was achieved in the time of observation, on average in 4.3 months. Corticosteroid withdrawal was possible in two patients, and EC-MPS was very well tolerated. No serious adverse events were recorded. EC-MPS is a valid therapeutic opportunity as a steroid-sparing agent in PV patients.

Melanoma on tattoos: a case study and review of the literature

Background: Decorative tattooing is a very widespread and constantly increasing practice, especially among young people. Objectives: Here, we report a case study of melanoma occurring on a tattoo on the left arm and provide an overview of all cases reported so far. Materials & Methods: A systematic literature search of publications was conducted from inception to September 2021 via Medline (PubMed), Scopus and Google Scholar, in order to identify all cases of primitive melanomas arising on tattoos. Results: In total, 35 cases (32 males, three females) of melanoma arising on tattoos on skin were identified. Interestingly, most melanomas occurred on dark blue (10/35), black (12/35) or blue tattoos (3/35). Conclusion: Due to the low number of melanoma cases arising on tattoos, it is not possible to confirm whether tattoos play a cancerogenic role. However, tattooing may make it more difficult to detect and monitor pigmented lesions, potentially delaying the diagnosis of cutaneous malignancies. Patients at high risk of melanoma should be warned about the risks associated with such procedures.

Treatment adherence with diclofenac 3% gel among patients with multiple actinic keratoses: an integrated low-intensity intervention program versus standard-of-care.

BACKGROUND: Diclofenac 3% gel is a widely used topical treatment with proven efficacy in reducing the burden of actinic keratosis (AK); however, clinical benefit might not fully translate in clinical practice as nonadherence is substantial for prolonged treatment regimens. We evaluated the efficacy of an integrated low-intensity intervention program versus standard-of-care on treatment adherence among patients with multiple AK receiving diclofenac in hyaluronic acid gel 3%. METHODS: We designed an open label, randomized, parallel group, interventional, multicenter, longitudinal cohort study including patients with multiple, grade I/II AKs. Visits were scheduled for end of treatment (T4), follow-up 1 (T5) and follow-up 2 (T6) at 90, 180 and 365 days from baseline, respectively. Patients in the intervention group received additional visits at 30 and 60 days from baseline, a brief health education intervention, an enhanced patient-physician communication, a weekly SMS reminder to medication prescriptions. RESULTS: Patients were equally allocated between intervention (intervention group [IG], N.=86) and control group ([CG] N.=86); at baseline, both groups had similar socio-demographic and clinical characteristics. Change scores from baseline showed a slight increment in quality of life related to AK in both groups (CG: ΔT4-T1=-0.079; IG: ΔT4-T1=-0.006; P=0.39) and in quality of physician-patient interaction reported by IG (ΔT3-T2=0.18; P<0.0001). Adherence rate was not statistically different between IG and CG (28.4% vs. 40.7%; P=0.11). Patients reported similar satisfaction for effectiveness, convenience and side effects of treatment. Clinical conditions improved over time and results did not differ between groups; complete clearance rate at 1 year was 18% and 29% for CG and IG, respectively. CONCLUSIONS: Our findings showed no difference in adherence rate between the two groups, suggesting that enhanced follow-up interventions and health care education may not be sufficient drivers to promote adherence among this clinical population. Further studies are needed to explore barriers to adherence with treatments for AKs.

Reflectance confocal microscopy and its role in the follow-up of a topical treatment for lentigo maligna.

BACKGROUND: In recent years, there has been an ongoing interest in topical treatment for lentigo maligna (LM) as imiquimod 5% cream owing to the localization of this tumor and the advanced age of patients; however, the efficacy of imiquimod 5% cream is controversial, and the rate of local relapses is about 25-53%. Reflectance confocal microscopy (RCM) is a noninvasive diagnostic tool useful not only for diagnostic purpose but also for monitoring the response to the local treatment of LM. Our aim was to demonstrate the role of RCM in the follow-up of a topical treatment with imiquimod 5% cream in clinical practice. METHODS: We report three patients with histopathologically confirmed LM who were not candidates for surgery and were successfully treated with imiquimod 5% cream. In such patients, dermatoscopic images and reflectance confocal microscopy were useful to evaluate treatment response and to verify long-term clinical benefits during the follow-up visits. RESULTS: No relapses were observed in our patients 18 months after the end of treatment; although, continuous follow-up visits are needed in these patients. CONCLUSIONS: In the case series presented herein, we highlight the importance of RCM as a noninvasive tool to monitor the efficacy of imiquimod to treat LM during and after treatment. Detailed confocal images of two of our patients allowed us to establish the persistence of atypical cells and to continue treatment, although clinical and dermatoscopic examinations showed "apparent complete remission" after the first cycle of therapy.

Lentigo maligna: diagnosis and treatment.

Lentigo maligna (LM) is an in situ subtype of melanoma, clinically presenting as a pigmented, asymmetric macule that originates mostly on the head and neck and spreads slowly. The diagnosis may be challenging both for clinicians and pathologists. Dermatoscopy and reflectance confocal microscopy represent a useful tool in the differentiation of LM from other pigmented lesions, such as pigmented actinic keratosis, solar lentigines, seborrheic keratosis and lichen planus-like keratosis. Moreover, those non-invasive diagnostic technique may be crucial in the selection of optimal biopsy sites in equivocal lesions, in pre-surgical mapping and in evaluating and monitoring response to non-surgical treatments. Histologic examination remains the gold standard for the diagnosis of LM, showing a lentiginous proliferation of basal atypical melanocytes on a severe sun-damaged skin. The management of LM is constantly evolving. Treatments include surgery (the first choice, when available), radiotherapy and imiquimod cream (in patients not candidates to surgery). Many other possible treatments for LM have been tested, but they are not yet supported by strong evidences. We collected current guidelines and PubMed available reviews, studies and case-reports in order to make an overview on diagnosis and treatment of LM.

Behavioral and demographic factors associated with occurrence of non-melanoma skin cancer in organ transplant recipients.

BACKGROUND: Non-melanoma skin cancers (NMSC) are the most common epithelial malignancies in organ transplantation recipients (OTRs). In Italy, incidence rates of post-transplantation NMSC are approximately 5% after 5 years and 10% after 10 years since organ transplantation. The objective was to describe risk factors associated with NMSC in a cohort of renal and liver transplant recipients, in a single-center longitudinal study. METHODS: Renal and liver transplant patients, who underwent transplantation between June 1985 and December 2015, were visited for the first time or followed-up in a dedicated outpatient clinic every six months until July 2016. RESULTS: We included 356 renal and 76 liver transplant patients. 108 OTRs (25.6%) presented 299 NMSC. 74 patients developed actinic keratosis (17.1%), 36 patients squamous cell carcinoma (8.5%), and 52 patients basal cell carcinoma (12.3%). Time from transplantation and kidney transplant were the main risk factors for NMSC. Higher incidences of all NMSC were observed in patients >60 years, males and smokers, while decreased incidences were detected in individuals with higher educational levels. Multiple logistic regression models confirmed that male gender (RR 3.3, P=0.001), cigarette smoking (RR 2.0, P=0.026), light eye color (RR 2.9, P=0.001) and family history of cancer (RR 1.8, P=0.042) were independently associated with NMSC. CONCLUSIONS: Dermatological follow-up is important in OTRs, due to the higher risk of tumors and mainly NMSC. Clinical and environmental factors, including cigarette smoking, are useful in characterizing OTR with higher risk of NMSC.

Melanoma and non-melanoma skin cancer in psoriatic patients treated with high-dose phototherapy.

OBJECTIVES: The carcinogenic effect of plus ultraviolet A (PUVA)-therapy in psoriatic patients has been widely demonstrated, while data on the safety of narrow band (311 nm) ultraviolet B (nb-UVB) are scarce. We investigated the occurrence of melanoma and non-melanoma skin cancer (NMSC) in psoriatic patients treated with nb-UVB or PUVA-therapy. METHODS: This retrospective study included patients affected by psoriasis, who had been treated with nb-UVB or PUVA-therapy. Clinical data and phenotypic risk factors were collected and a total body examination was performed at a routine appointment during the study period. RESULTS: We examined 92 patients (60 males and 32 females; mean age: 53.5 years, range: 20-83 years) treated with PUVA-therapy (42/92, 45%) or with nb-UVB (50/92, 55%) for 1-28 years (mean: 7.1 years). Among patients treated with PUVA, nine skin tumors (one melanoma, seven basal cell carcinoma (BCCs) and one squamous cell carcinoma (SCC)) were detected in 2/42 (4.7%) patients, while in the nb-UVB group, 14 skin tumors including two melanomas, four BCCs, and eight SCCs were diagnosed in 6/50 (12%) patients. CONCLUSIONS: A noteworthy number of NMSC were diagnosed in this Mediterranean population of patients exposed to high-dose UV treatment. A thorough risk-benefit evaluation should always be done before UV treatment and patients should be carefully monitored for skin cancer during and after treatment discontinuation.

Treatment of psoriasis with etanercept in immunocompromised patients: Two case reports.

Tumour necrosis factor (TNF)-α blocking agents have revolutionized the treatment of psoriasis and psoriatic arthritis. Concerns remain about increased susceptibility to infection and onset of malignancies, and the use of TNF-α agents in patients with HIV infection or undergoing immunosuppressant treatment is debated. We report cases of severe plaque psoriasis in a patient with HIV infection and in a liver transplant recipient who were successfully treated with etanercept, an anti-TNF-α agent, without notable side-effects.

Clinical, histopathological, and immunological evaluation of a series of patients with erythema nodosum.

BACKGROUND: The pathogenesis of erythema nodosum (EN) is still poorly understood, and studies evaluating the involvement of a cytokine network are very scarce. OBJECTIVES: To investigate clinical and pathological features, the cytokine profiles, and the balance of T-regulatory (Treg) and T-helper (Th)17 cells in serum and lesional skin of patients with EN. METHODS: Patients with a diagnosis of EN were consecutively enrolled, and their clinical and histopathological features were recorded. A panel of cytokines was evaluated in both serum and lesional skin using enzyme-linked immunosorbent assay. Real-time polymerase chain reaction was performed to evaluate the Treg/Th17 cell balance. RESULTS: Histopathological examination of skin biopsy specimens from all patients (four women and one man) showed classical features of EN. The most widely expressed cytokines were innate immunity cytokines (mainly tumor necrosis factor alpha, interleukin-8 and -6) and growth factors (mainly granulocyte colony-stimulating factor and monocyte chemoattractant protein-1). The Treg/Th17 balance was highly different between patients. CONCLUSIONS: The present study emphasizes the crucial role of neutrophils in the pathogenesis of EN, as high levels of cytokines and growth factors mainly involved in neutrophil recruitment and activation were detected.