Features of tattoo-associated cutaneous lymphoid hyperplasia on reflectance confocal microscopy and line-field confocal optical coherence tomography.

The popularity of tattoos has led to an increase in associated skin reactions, including complications such as infection, allergic reactions and rare conditions such as tattoo-induced cutaneous lymphoid hyperplasia (CLH). CLH is a benign lymphoproliferative reaction with clinical features resembling malignant cutaneous lymphomas. Non-invasive diagnostic tools like reflectance confocal microscopy (RCM) and the new line-field confocal optical coherence tomography (LC-OCT) are being studied in dermatology better to understand the morphological patterns of many dermatological diseases. Between September 2021 and May 2023, patients with suspicious lesions for tattoo-related CLH were analysed using RCM and LC-OCT before confirming the diagnosis of CLH through skin biopsy and histopathological examination. The study included five cases of CLH. It focused on the analysis of high-quality LC-OCT images/videos and RCM images to investigate the features of CLH in tattooed individuals. Most (80%) cases exhibited a mixed T and B lymphocyte infiltration subtype, while 20% showed a predominant T infiltration subtype. RCM and LC-OCT revealed characteristic features, including architectural disarray, fibrosis, lymphoid infiltrates, and pigment deposits in the epidermis and dermis. Non-invasive tools such as RCM and LC-OCT are valuable in diagnosing tattoo-related CLH. While skin biopsy remains the current standard for diagnosis, RCM and LC-OCT can serve as helpful adjuncts in identifying the most representative area for biopsy. They may potentially become alternative diagnostic options in the future, offering benefits in terms of cost, diagnostic efficiency, aesthetics and patient satisfaction as the prevalence of tattoo-related adverse reactions continues to rise.

A randomized split-face clinical trial of conventional vs indoor-daylight photodynamic therapy for the treatment of multiple actinic keratosis of the face and scalp and photoaging.

BACKGROUND: Recently, indoor daylight photodynamic therapy (idl-PDT) has been developed; however, its efficacy and tolerability remain to be assessed. OBJECTIVE: This is a not-inferiority study to compare treatment outcomes of cPDT with a red LED lamp and idlPDT with a polychromatic white LED lamp in adult patients affected by symmetrical AKs of face and/or scalp. METHODS: In this comparative, intra-patient, split-face, randomized clinical trial forty-three adult patients were enrolled. Two contralateral and symmetrical target areas of the face and/or scalp harboring at least 5 AKs were selected and randomized 1:1 to treatment with cPDT and idlPDT. The AKs number and cumulative area were assessed at baseline (T0). Efficacy and cosmetic outcome were assessed 3 months after treatment (T1). RESULTS: Total AKs number and area reduced significantly with both idlPDT (p < .0001) and cPDT (p < .0001) in comparison to baseline. cPDT was more painful (p < .0001) and induced a more severe inflammation (p < .0001). Twenty-nine patients (70.7%) gave their overall preference to idlPDT (p < .001). CONCLUSION: idlPDT may represent an alternative treatment protocol to cPDT for in-office treatment of AKs patients with better tolerability and a not inferior efficacy.

Clinical and dermoscopic changes of acquired melanocytic nevi of patients treated with afamelanotide.

BACKGROUND: Afamelanotide (AFA) is a synthetic analogue of α-melanocyte-stimulating hormone that is approved for the treatment of patients affected by erythropoietic protoporphyria (EPP). AFA induces a "sun free" tanning and changes of acquired melanocytic nevi (AMN) that are generically described as "darkening". OBJECTIVES: To assess clinical and dermoscopic AMN changes during AFA treatment. METHODS: Adult EPP patients treated with two AFA implants 50 days apart were enrolled. They underwent a clinical and dermoscopic examination of all AMN at baseline (T0), and after 5 (T1) and 12 (T2) months from the first AFA implant. The general pattern, symmetry, number, and size of pigmented globules, morphology of the pigment network, and dermoscopic melanoma features were assessed. RESULTS: Fifteen patients were enrolled with 103 AMN. At T1 all reticular and 2-component AMN showed a focal network thickening that returned to baseline by T2. The increase of globules' number was observed at T1 but not at T2. The difference in number was not influenced by patients' age or phototype. Dermoscopic changes suggestive of malignancy were never seen. The development of new AMN was never registered. CONCLUSIONS: AFA treatment induces reversible changes of AMN dermoscopic morphology without findings suggestive of malignant transformation and it does not stimulate the development of new AMN.

European Dermatology Forum guidelines on topical photodynamic therapy 2019 Part 2: emerging indications - field cancerization, photorejuvenation and inflammatory/infective dermatoses.

In addition to approved indications in non-melanoma skin cancer in immunocompetent patients, topical photodynamic therapy (PDT) has also been studied for its place in the treatment of, as well as its potential to prevent, superficial skin cancers in immune-suppressed patients, although sustained clearance rates are lower than for immune-competent individuals. PDT using a nanoemulsion of ALA in a daylight or conventional PDT protocol has been approved for use in field cancerization, although evidence of the potential of the treatment to prevent new SCC remained limited. High-quality evidence supports a strong recommendation for the use of topical PDT in photorejuvenation as well as for acne, refractory warts, cutaneous leishmaniasis and in onychomycosis, although these indications currently lack approvals for use and protocols remain to be optimized, with more comparative evidence with established therapies required to establish its place in practice. Adverse events across all indications for PDT can be minimized through the use of modified and low-irradiance regimens, with a low risk of contact allergy to photosensitizer prodrugs, and no other significant documented longer-term risks with no current evidence of cumulative toxicity or photocarcinogenic risk. The literature on the pharmacoeconomics for using PDT is also reviewed, although accurate comparisons are difficult to establish in different healthcare settings, comparing hospital/office-based therapies of PDT and surgery with topical ointments, requiring inclusion of number of visits, real-world efficacy as well as considering the value to be placed on cosmetic outcome and patient preference. This guideline, published over two parts, considers all current approved and emerging indications for the use of topical photodynamic therapy in Dermatology prepared by the PDT subgroup of the European Dermatology Forum guidelines committee. It presents consensual expert recommendations reflecting current published evidence.

Effects of MAL-PDT, ingenol mebutate and diclofenac plus hyaluronate gel monitored by high-frequency ultrasound and digital dermoscopy in actinic keratosis - a randomized trial.

BACKGROUND: The efficacy for actinic keratosis (AK) clearance of field-directed treatments has been investigated in randomized studies against placebo, but the comparison of results is difficult for several methodological reasons. OBJECTIVES: The present study aims to compare efficacy of MAL-photodynamic therapy (MAL-PDT), ingenol mebutate gel (IMB) and diclofenac plus hyaluronate gel (DHA) on multiple AKs assessing a new performance index of efficacy, the cumulative AK area and evaluating dermoscopical and high-frequency ultrasound (HFUS) changes. METHODS: Patients with ≥5 Olsen II AKs in a 25 cm2 area of the scalp and face were enrolled and randomized to one of the treatment choices. Number of AKs and cumulative area were assessed before and after treatment. Dermoscopy and HFUS were performed on a single AK and surrounding photo-damaged skin in the treatment area. RESULTS: Cumulative AKs area reduced significantly more with PDT compared to other treatment options and with IMB in comparison to DHA. PDT was also the only treatment option that increased at a significant level the dermal density in both target AK and the surrounding skin and decreased significantly the SLEB thickness in the perilesional skin at HFUS. CONCLUSIONS: MAL-PDT is more effective than IMB and DHA for reducing the cumulative AK area which is calculated digitally from 3D pictures and should be the preferred performance index for the evaluation of the efficacy of treatments for AKs, rolling out clinical and dermoscopy evaluation. MAL-PDT improves all HFUS features of chronic photodamages of the dermis of the skin underlying and surrounding the AK spots.

Sunbeds and carcinogenesis: the need for new regulations and restrictions in Europe from the Euromelanoma perspective.

Experimental investigations have definitely assessed that ultraviolet A (UVA) as well as ultraviolet B (UVB) radiation induce mutagenic DNA photoproducts and other cell damages with a carcinogenic potential. Artificial tanning increases significantly the lifetime risk for basal cell carcinoma, squamous cell carcinoma and melanoma particularly in subjects with fair skin type, subjects with a history of skin cancer or frequent childhood sunburn or if exposures took place at an age younger than 18 years. In addition, experimental and clinical evidence indicate that UVA exposure promotes skin photoageing. Therefore we are dealing with a recreational activity (for customers) and a profitable business (for the tanning industry) with human costs, i.e. an increase in morbidity and mortality by skin cancer, and health and social costs leading to an increased expenditure by the European national health systems. In a few European countries, legislation has recently prohibited the use of sunbeds for minors, pregnant women, people with skin cancer or a history of skin cancer and individuals who do not tan or who burn easily from sun exposure. However, this legislation seems to be insufficient from a photobiological perspective, and importantly, it is largely disregarded by consumers and tanning industry. Therefore the Euromelanoma group proposes a new, more stringent regulation for the tanning industry and restrictions for customers, particularly for those individuals with constitutional and anamnestic risk factors. Finally, we ask for an enhanced commitment to increase the awareness of the general population on the risk of artificial tanning.

Clinical, histological and high-frequency ultrasonographic evaluation (50 MHz) of morphoea treated with ultraviolet A1 phototherapy.

BACKGROUND: There are few studies in the literature correlating the ultrasonographic findings, clinical scoring systems or histological findings in morphoea after ultraviolet (UV)A1 phototherapy. AIMS: To evaluate the quantitative and morphological aspects of high-frequency ultrasonography in the treatment of plaque morphoea in response to UVA1 phototherapy, and to correlate these with clinical and histological scores. METHODS: In total, 17 patients with morphoea were studied. Initially and at study end, high-frequency ultrasonography (50 MHz) was performed on the edge of a morphoea lesion treated with UVA1 phototherapy. A quantitative and qualitative analysis of dermal features was performed and compared with the features of healthy skin. Skin biopsy specimens were obtained from lesions analysed at the beginning and end of the study, assessing dermal sclerosis and dermal inflammatory infiltrate and their distribution. RESULTS: All affected skin showed a statistically significant increase in dermal thickness and hypoechogenicity, corresponding to a reduction in dermal density by ultrasonography compared with healthy skin. Morphological evaluation identified undulations of the dermis in 11 of 17 lesions (64.7%) and in 5 healthy skin areas (29.4%) (P = 0.08), while 'yoyo' figures were identified in 8 lesions (47%) but only 1 healthy skin area (5.9%) (P = 0.02). Ultrasonographic morphological analysis highlighted an improvement in dermal hyperechogenic bands and disappearance of yoyo figures after UVA1 treatment. Histology revealed a reduction in dermal sclerosis and inflammation, although this was not statistically significant. CONCLUSIONS: Ultrasonographic pattern analysis of morphoea is a suitable technique for monitoring UVA1 phototherapy response.

Cutaneous infiltration of plasmacytoid dendritic cells and T regulatory cells in skin lesions of polymorphic light eruption.

BACKGROUND: Polymorphic light eruption (PLE) is the most common autoimmune photodermatosis. Plasmacytoid dendritic cells (PDCs) are important mediators of innate antimicrobial immunity involved in the pathogenesis of many inflammatory skin diseases. In addition to PDCs, regulatory T cells (Tregs) are involved in controlling inflammation and adaptive immunity in skin by their immunosuppressive capacity. OBJECTIVE: The aim of this study was to investigate the presence of PDCs and Tregs in photoexposed skin from PLE compared to healthy skin. METHODS: Patients with PLE diagnosis and healthy controls were recruited and underwent a photoprovocative test. A 4-mm punch biopsy was taken from the site of positive photoprovocation test reaction, and immunohistochemistry for BDCA2 as marker for PDCs, CD4 and FOXP3 as markers for Tregs was performed. Double immunostain for FOXP3 and CD4 was performed as well. Absolute counts for CD4, BDCA2 and FOXP3 were performed in at least 5 High Power Fields (HPF). Percentage of CD4-, BDCA2- and CD4FOXP3-positive cells over the total inflammatory infiltrate was assessed for each case. RESULTS: We enrolled 23 patients and controls. BDCA2+ cells were present in 91.3% of PLE skin samples and 100% of healthy volunteer. Both in PLE patients and healthy controls, PDCs distribution was mainly dermic (P < 0.05). Compared to healthy controls, both epidermic and dermic BDCA2+ cells count were significantly higher in PLE patients (P < 0.05). Both in PLE patients and healthy controls, Tregs distribution was mainly dermic (P < 0.05). The presence of both CD4+ cells and FOXP3+ cells was significantly higher in the dermis of PLE patients compared to controls (P < 0.05). Relative percentages of cellular infiltrations confirmed these results. CONCLUSIONS: D-PDCS and Tregs may play a significant role in the development of PLE, and dermal distribution of PDCs in PLE skin biopsies seems to confirm a possible overlap with cutaneous lupus erythematosus (CLE).

Italian expert consensus for the management of actinic keratosis in immunocompetent patients.

Actinic keratosis (AK) is a common skin disease which can potentially progress to invasive squamous cell carcinoma (iSCC). Given that mortality rates and health-care cost associated with iSCC are substantial, the management of AK represents an important public health issue. Several effective lesion-directed and field-directed treatments are available. Ablative procedures (e.g. cryosurgery, excision, laser ablation, curettage alone or with electrodessication) are considered cost-effective options for solitary lesions. Field-directed therapies (e.g. Ingenol Mebutate, imiquimod, PDT, 5-Fluorouracile, diclofenac 3%, 5-FU + Salicylic acid) can be used over large epidermal surfaces and are directed to treat both individual visible lesions and cancerization fields. In order to provide guidance for management choice in clinical practice, several guidelines concerning the diagnosis and treatment of AK have been published in the past decade. However, the introduction of novel therapeutic options requires continuous updates of recommendations and adaptation to national contexts. The present review summarizes the existing evidence and reports the results of a consensus workshop on the management of AK.

A new approach for presurgical margin assessment by reflectance confocal microscopy of basal cell carcinoma.

BACKGROUND: Surgical excision represents the most common elective treatment for basal cell carcinoma (BCC). Several noninvasive approaches have been proposed for in vivo determination of tumour margin, in order to achieve radical removal. OBJECTIVES: To propose a new approach through the combination of dermoscopy and reflectance confocal microscopy (RCM) for lateral margin detection in BCC. METHODS: Ten patients with lesions clinically suggestive of nonpigmented BCCs with ill-defined margins were enrolled. All BCCs were dermoscopically evaluated first and the ill-defined margins were marked with a superficial cut and then inspected using RCM. RESULTS: RCM evaluation showed BCC foci beyond the presurgical marker in three out of 10 lesions. Histology confirmed the RCM results: the presence of BCC features across the cut, corresponding to two superficial BCCs and a morpheaform BCC. CONCLUSIONS: This new procedure helped to improve the identification of proper margins for surgical excision in nonpigmented BCC with clinically and dermoscopically ill-defined margins.

Scleredema. A multicentre study of characteristics, comorbidities, course and therapy in 44 patients.

BACKGROUND: The prognostic and therapeutic features of scleredema are poorly documented. OBJECTIVES: To describe the characteristics of patients with scleredema regarding demographics, clinical characteristics, comorbidities, therapeutic interventions and course. METHODS: We conducted a retrospective multicentre study. RESULTS: We identified 44 patients (26 men).The mean age at diagnosis was 53.8 years. The most common associated disorders were endocrine/metabolic diseases including 30 patients suffering from diabetes, mostly type 2 diabetes. Monoclonal gammopathies were confirmed in five cases. A preceding respiratory tract infection was not a feature. Treatments with different combination or sequential modalities were used with variable results. Phototherapy (UVA1 or PUVA) was the treatment associated with higher, although partial response. Systemic corticosteroids and immunosuppressive drugs were reserved to patients with severe disease in whom phototherapy had failed or for patients with multiple myeloma. Forty-one patients were followed up (mean period: 32.2 months).Thirty-nine patients are alive, 30 with and 9 without skin disease. Two patients died of cardiovascular complications due to myeloma and severe diabetes. CONCLUSIONS: Scleredema is a chronic debilitating disease associated with diabetes and metabolic syndrome, unresponsive to various treatments but not necessarily a life-threatening condition. Although there is no definitive treatment, phototherapy should be attempted first. Treatment of primary disease including strict glycaemic control combined with physical therapy should be also employed.