Effectiveness and tolerability of chlormethine gel for the management of mycosis fungoides: a multicenter real-life evaluation.

Background: Topical chlormethine (CL) is recommended as a first-line treatment for early-stage mycosis fungoides (MF) and in 2017, the European Medicines Agency approved the CL gel formulation to treat adult patients. More recently, to increase patient compliance and adherence, clinicians have developed flexible protocols that allow the concomitant use of CL gel with topical corticosteroids in daily practice regimens. Therefore, sharing real-life data on CL gel use and side effects management may help improve the use of this agent. Objectives: To expand knowledge about the actual use of CL gel in patients with MF, the present study assessed the improvement of MF skin lesions after CL gel treatment and provided information on the management of cutaneous adverse events (AEs) in a real-life setting. Methods: This was an Italian retrospective study conducted among six dermatology referral centers. Patients ≥18 years affected by MF and in treatment with CL gel (160 µ/g), alone or in combination according to routine clinical practice, between December 2019 and December 2021 were considered. The study's primary aim was to evaluate the effectiveness of CL gel in terms of overall response rate (ORR) after 3 months of treatment. Results: A total of 79 patients (61% male) with different stages of MF (84% early stage) were included. CL gel was prescribed mainly in association with topical corticosteroids (66% of patients). ORR after 3 months of treatment was 42%, with no differences between early- and advanced-stage MF. Response rates improved over time up to 97% after 18 months of treatment. Overall, 66 AEs were reported in 67% of patients; most were hyperpigmentation (45%) and irritant contact dermatitis (37%). Six AEs led to treatment discontinuation, and five out of six (83%) patients who reported these events resumed treatment after interruption. No AEs were classified as severe. Conclusions: Our observations support the use of CL gel in patients with early- and advanced-stage MF, making it a valuable treatment option.

Primary cutaneous non-Hodgkin lymphoma: results of a retrospective analysis in the light of the recent ILROG guidelines.

PURPOSE:: To analyze clinical outcome, local response, survival and toxicity in patients with primary cutaneous lymphoma (PCL) treated with radiotherapy. METHODS:: From 1995 to 2014, 112 patients were treated. B-cell lymphomas (CBCLs; n = 86) and T-cell lymphomas (CTCLs; n = 23) were analyzed separately. Clinical and therapeutic characteristics (age, sex, histology, primary treatment and radiotherapy modality) were related to response to treatment, survival and toxicity. RESULTS:: CBCLs were divided into 4 subgroups: marginal-zone lymphoma (n = 20), follicle center lymphoma (n = 32), diffuse large-cell lymphoma (DLBCL; n = 22) and DLBCL-leg type (n = 12). No significant correlation was found between doses and systemic treatments, extent of biopsy and number of lesions. DLBCL-leg type patients were older (p = 0.05), had disseminated disease (p = 0.034), and more frequently had local (p = 0.01) or systemic recurrence (p = 0.05). CTCLs were divided into 4 subgroups: α/ß CTCL (n = 3), nasal type CTCL (n = 0), γ/δ CTCL (n = 10) and mycosis fungoides (n = 10). Longer disease-free survival was observed in patients obtaining complete remission (p<0.001). CONCLUSIONS:: Radiotherapy is feasible, safe and effective for localized PCLs. The choice of dose is related to histological subgroups and the related prognoses. Survival results are very good also in relapsing disease. In advanced cutaneous lymphoma radiotherapy alone has mainly a role in symptom palliation.

A retrospective analysis of real-life practice of off-label photodynamic therapy using methyl aminolevulinate (MAL-PDT) in 20 Italian dermatology departments. Part 1: inflammatory and aesthetic indications.

Experimental investigations have demonstrated that photodynamic therapy (PDT) with methyl aminolevulinate (MAL) may be a useful treatment in several inflammatory skin disorders and aesthetic indications. To assess the effectiveness, tolerability and safety of off-label MAL-PDT in daily clinical practice in 20 Italian hospital centers, a retrospective observational study of medical records of patients treated for off-label inflammatory and aesthetic indications was carried out. In all patients standard treatment options had been either ineffective, unacceptably toxic, or medically contraindicated. Clinical data regarding 221 patients affected by 22 different diseases were collected. The most common off-label indication was acne vulgaris, with >75% improvement in 72.8% of patients. Other disorders of the sebaceous gland, i.e. acne rosacea, hidradenitis suppurativa and sebaceous hyperplasia, were less responsive. Alopecia areata did not show any improvement. Granuloma annulare and necrobiosis lipoidica showed marked or moderate response in the majority of treated patients. The rate of patients with complete remission was lower for inflammatory skin disorders with hyperkeratosis, i.e. psoriasis (6/17) and porokeratosis (3/16). The efficacy for lichenoid dermatoses was dependent on the clinical variant (erosive and scleroatrophic were more responsive than hypertrophic). Only 1 of 6 patients with Zoon balanitis had a marked improvement. MAL-PDT of venous leg ulcers, photo-aging and hypertrophic scars led to a marked remission in 3/5, 3/6 and 5/8 patients, respectively. The treatment had to be interrupted because of strong pain and burning in 24 patients. Long term adverse events were not registered. Most patients with marked improvement had lasting remission with overall excellent cosmetic outcomes. The present findings demonstrate a high interest in off-label uses of MAL-PDT for inflammatory skin disorders. According to the observed clinical responses, safety, and favorable cosmetic results, MAL-PDT seems to have a potential therapeutic role for the treatment of granulomatous dermal disorders and follicular inflammatory diseases whereas results in other conditions are less encouraging.

A retrospective analysis of real-life practice of off-label photodynamic therapy using methyl aminolevulinate (MAL-PDT) in 20 Italian dermatology departments. Part 2: oncologic and infectious indications.

Photodynamic therapy (PDT) with methyl aminolevulinate (MAL) has been suggested as a useful treatment option in a number of skin tumors, other than approved indications, and infections. However, evidence is poor because it is mainly supported by isolated case reports or small case series, often with conflicting results. To assess the effectiveness, tolerability and safety of off-label MAL-PDT in daily clinical practice in 20 Italian hospitals, a retrospective observational study of medical records of patients treated for off-label oncologic and infectious skin conditions was carried out. In all patients standard treatment options had been either ineffective, unacceptably toxic, or medically contraindicated. Clinical data from 145 patients were analyzed. Actinic cheilitis showed a complete remission (CR) in 27 out of 43 treated patients and CR was maintained at follow-up. CR was registered in 3 of 8, 5 of 8 and 10 of 17 treated patients who were affected by extra-mammary Paget's disease (EMPD), erythroplasia of Queyrat (QD), and invasive squamous cell carcinoma (SCC), respectively. Five out of 19 patients with cutaneous T cell lymphoma had a complete remission. Cutaneous B-cell lymphoma, malignant fibrous histiocytoma, mastocytosis and nevus sebaceous were not responsive. Warts were treated in 30 patients and 15 had a complete remission. However, periungueal and plantar lesions were much more responsive than flat and common lesions. Condylomata showed a CR in 2 out of 5 male patients but treatment was painful. Bowenoid papulosis showed only a partial improvement. Atypical mycobacteriosis and chronic cutaneous leishmaniasis were successfully treated. Submammary candidal intertrigo and interdigital intertrigo with Pseudomonas aeruginosa did not improve. Among off-label oncological uses of MAL-PDT, the therapy of actinic cheilitis was the most investigated and showed the best results. In addition, MAL-PDT was used successfully in the majority of patients with QD, EMPD and invasive SCC. Treatment of specific cutaneous infections was well tolerated and gave a good therapeutic result in a few patients, but it does not seem to give substantial advantages over conventional treatment options.

Narrowband ultraviolet B phototherapy is a suitable treatment option for solar urticaria.

BACKGROUND: Narrowband (NB) ultraviolet (UV) B lamps are widely used for treatment and prophylaxis of several skin diseases. OBJECTIVE: We sought to assess the efficacy of two protocols of NB-UVB therapy for the prophylaxis of UVB-sensitive and UVB-insensitive solar urticaria (SU). METHODS: Subjects affected by SU underwent phototesting for assessment of the minimal erythemal dose and minimal urticarial dose. Patients without urticarial response to UVB underwent a single daily exposure every other day for 4 weeks (group A). Patients with a urticarial test response to broadband UVB or NB-UVB (group B) received 3 daily exposures (on working days) for the first week. Afterward, they were treated as the patients of group A for 3 weeks. Follow-up visits took place after 1 and 3 months. RESULTS: A total of 39 patients completed the study. In groups A (29 patients) and B (10 patients), the median total number of exposures was 12 (interquartile range [IQR]: 12; 15) and 25.5 (IQR 24; 27), respectively. The median total NB-UVB dose was 10.3 J/cm(2) (IQR 9.9; 11) for group A and 9.1 J/cm(2) (IQR 8.5; 10.6) for group B. At follow-up visits, patients reported good tolerance to the sun. LIMITATIONS: A direct comparison of NB-UVB with UVA or psoralen plus UVA for the photoprophylaxis of SU is still lacking. CONCLUSION: NB-UVB phototherapy was well-tolerated and effectively prevented SU relapses.

Dermoscopic, histological and immunohistochemical evaluation of cancerous features in acquired melanocytic nevi that have been repeatedly exposed to UVA or UVB.

Previous studies have reported that repeated solar and artificial UVB (280-320 nm) and UVA (320-400 nm) exposures can modify acquired melanocytic nevi (AMN). We therefore investigated the clinical, dermoscopic, histological and immunohistochemical changes in AMN exposed to UVB and UVA radiation. Twenty healthy volunteers with at least three AMN on the trunk were enrolled in the present study and randomized into two groups to receive equally effective doses of narrow-band (NB)-UVB or UVA1. Three exposures per week were delivered for a total of 4 weeks. During exposures, one AMN was left unprotected, a second one was shielded with an opaque adhesive tape and the third nevus was covered with a commercial sunscreen. After the irradiation cycle, the AMN were surgically removed and underwent histological and immunohistochemical assessment of melanocyte/melanogenesis-related proteins (MART-1, tyrosinase, HMB-45), cell cycle activation markers (Ki-67, topoisomerase IIalpha, p53, Cdk2) and transcription factors (microphthalmia-associated transcription factor, STAT3). Nevi that were exposed to NB-UVB or UVA1 also showed statistically significant increase in size and changes in their dermoscopic features, including overall darkening, increased pigment network expression, formation of branched streaks, and increased number and size of brown globules and dots. AMN that had been covered with opaque tape or sunscreen did not show changes in size or dermoscopic features following UVA1 or NB-UVB exposure. Histological and immunohistochemical analysis did not show any significant change in exposed AMN in comparison with AMN shielded with an opaque adhesive tape or covered with the sunscreen.

Merkel cell carcinoma arising in immunosuppressed patients treated with high-dose ultraviolet A1 (320-400 nm) phototherapy: a report of two cases.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumour of the skin. Though immunodeficiency is the most relevant risk factor, ultraviolet (UV) radiation is also involved, but as of yet we do not know the action spectrum, pattern or dose which would produce a dangerous exposure. A retrospective study of two immunosuppressed patients who developed MCC during, or soon after a treatment cycle with high dose UVA1 exposures was conducted, in order to understand wether repeated exposures to suberythemogenic UVA1 radiation may have a cancerogenic activity provoking MCC in immunosuppressed patients.

Cutaneous distribution of plasmacytoid dendritic cells in lupus erythematosus. Selective tropism at the site of epithelial apoptotic damage.

Recent evidences suggest a significant role of Plasmacytoid dendritic cells (PDC) role in the pathogenesis of lupus erythematosus (LE) via production of type I IFN. Taking advantage on the availability of multiple reagents (CD123, BDCA2, and CD2ap) specifically recognizing PDC on fixed tissues, we investigated the occurrence of PDC in a cohort of 74 LE patients. The large majority of LE biopsies (67/74; 90.5%) showed cutaneous infiltration of PDC. PDC were more frequently observed (96.4 vs 72.2) and numerous in cutaneous LE compared to systemic LE (SLE) and correlated with the density of the inflammatory infiltrate (r=0.40; p<0.001). PDC reduction in SLE might be related to a broader tissue distribution of this cellular population, as indicated by their occurrence in kidneys in 11 out of 24 (45.8%) cases studied. The distribution of cutaneous PDC showed two distinct patterns. More commonly, PDC were observed within perivascular inflammatory nodules in the dermis, associated with CD208+ mature DC and T-bet+ cells [D-PDC]. A second component was observed along the dermal-epithelial junction [J-PDC], in association with cytotoxic T-cells in areas of severe epithelial damage. Notably, chemerin reactivity was observed in 64% of LE biopsies on endothelial cells and in the granular layer keratinocytes. Cutaneous PDC in LE strongly produced type I IFN, as indicated by the diffuse MxA expression, and the cytotoxic molecule granzyme B. This study confirms cutaneous PDC infiltration as hallmark of LE. The topographical segregation in D-PDC and J-PDC suggests a novel view of the role of these cells in skin autoimmunity.

Reflectance confocal microscopy for the in vivo detection of Treponema pallidum in skin lesions of secondary syphilis.

BACKGROUND: Secondary syphilis is a diagnostic challenge that relies on microscopic and laboratory tests. OBJECTIVE: We sought to assess the usefulness of in vivo reflectance confocal microscopy (RCM) to detect Treponema pallidum in lesions suggestive of secondary syphilis. METHODS: Macular and papular skin lesions from 3 patients clinically suggestive of secondary syphilis were imaged by RCM and confirmed by skin punch biopsy. RESULTS: In all lesions RCM demonstrated elongated small bright particles with a spiral shape intermingled with the keratinocytes. These features corresponded with immunohistochemical findings that revealed several spirochetes infiltrating the epidermis. LIMITATIONS: Unlike immunohistochemistry, RCM did not visualize T pallidum in the dermis and vascular walls because of limited imaging depth. The specificity and sensitivity of this technique need to be assessed. CONCLUSION: RCM may be an effective diagnostic tool for in vivo real-time imaging of T pallidum in skin lesions of secondary syphilis, and seems to correlate well with immunohistochemistry.

A short cycle of narrow-band UVB phototherapy in the early phase of long-term efalizumab can provide a quicker remission of moderate and severe psoriasis: a pilot study.

BACKGROUND: Efalizumab, albeit highly efficient in psoriasis treatment, displays a slower rate of clearance when compared to anti-tumor-necrosis-factor-alpha drugs. It has been suggested that a combination of treatments might accelerate efalizumab response. OBJECTIVE: To determine whether the combination of narrow-band ultraviolet B (NB-UVB) phototherapy and efalizumab could improve the therapeutic efficacy of efalizumab alone in moderate to severe psoriasis. methods: Ten patients underwent a treatment cycle with a whole-body NB-UVB phototherapy (3 sessions a week) during the first 4 weeks of a 6-month treatment with efalizumab at 1 mg/kg body weight/week. In addition, one of two similar plaques, selected for each patient, was shielded during phototherapy. RESULTS: A statistically significant reduction of the psoriasis severity index score was observed at 4 weeks in the irradiated plaque. A Psoriasis Area and Severity Index 75 was achieved by 70% of patients by week 12 as compared to 22-39% reported in the literature. CONCLUSION: This pilot study indicates that the combination with NB-UVB improves the efficacy of efalizumab monotherapy in the treatment of moderate to severe psoriasis.

Reflectance confocal microscopy for in vivo skin imaging.

Reflectance confocal microscopy (RCM) is a novel noninvasive technique for "in vivo" examination of the skin. In a confocal microscope, near- infrared light from a diode laser is focused on a microscopic skin target. As this light passes between cellular structures having different refraction indexes, it is naturally reflected, and this reflected light is then captured and recomposed into a two-dimensional gray scale image by computer software. Focusing the microscope (adjusting the focal point on the z-axis) allows images to be obtained of different levels within the skin. Commercially available microscope systems of this type can create images with enough detail for use in histological analysis. The first investigations using these microscopes served to identify the appearance of the various cell populations living in the different layers of normal skin. Today, the main interest has become focused on the use of these microscopes as a diagnostic tool: a means of investigating benign and malignant tumors of melanocytes and keratinocytes, and, more importantly, the findings of this field of study can be used to develop a diagnostic algorithm which would be not only highly sensitive but specific as well. The aim of the paper is to provide an updated literature review and an in-depth critique of the state-of-the-art of RCM for skin cancer imaging with a critical discussion of the possibilities and limitations for clinical use.

Clinical and echographic analysis of photodynamic therapy using methylaminolevulinate as sensitizer in the treatment of photodamaged facial skin.

BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) using aminolevulinic acid (ALA) has been previously investigated in the treatment of photodamaged skin. The aim was to assess efficacy and tolerability of methylaminolevulinate (MAL) as a substitute for ALA in PDT treatment of actinic keratosis (AK) and photoaging. STUDY DESIGN/MATERIALS AND METHODS: Twenty patients with multiple (n = 137) AKs and severe photodamage of the face were treated. Metvix (Galderma, France) was applied under occlusion for 3 hours before exposure to 37 J/cm(2) of red light (Aklilite CL 128, Photocure, Norway). Two treatments were given at monthly intervals. RESULTS: The clearance rate of AKs was 88.3%, and global score which we use to rate photoaging, mottled hyperpigmentation, fine lines, roughness, and sallowness of the skin showed improvement, but deep wrinkles, teleangiectasia, facial erythema, and sebaceous gland hypertrophy did not change. The treatments were well tolerated. High-resolution echography showed an increase in skin thickness, pixels count and area, as well as a reduction of the subepidermal low-echogenic band (SLEB) thickness. CONCLUSION: MAL-PDT is an effective treatment for multiple AKs. In addition, it improves clinical signs of photodamage of the surrounding skin.

Photodynamic therapy with methylaminolevulinate as a valuable treatment option for unilesional cutaneous T-cell lymphoma.

BACKGROUND: Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma (CTCL). Unilesional MF is characterized by a limited involvement of the skin and a chronical, though indolent course. If lesions are refractory to topical steroids, therapies such as localized chemotherapy, photochemotherapy and radiotherapy are available. However, they have several acute and chronic side-effects and toxicity may accumulate if repeated and protracted treatment cycles are delivered to refractory or relapsing lesions. The present study aims to assess the efficacy of photodynamic therapy (PDT) with topical methylaminolevulinate (MAL) in the treatment of unilesional MF. METHODS: Five patients were enrolled who had unilesional MF that did not respond to treatment with topical steroids, localized psoralen and UVA therapy or UVA1 phototherapies. A 20% MAL (Metvix cream) cream was applied under occlusive dressing for 3 h. Soon afterwards, skin was irradiated with 37.5 J/cm(2) of red light (635+/-18 nm) delivered by an Aktilite CL128 lamp (PhotoCure ASA) with an irradiance of 86 W/cm(2) at skin level. PDT was repeated once weekly until complete clearing of the lesions was obtained, or, in the case of partial clearing, the therapy was interupted when three successive treatments provided no further improvement. All patients underwent a skin biopsy before and after PDT. RESULTS: A complete remission was observed in four patients and a partial improvement in one. The median number of treatments was six (range 1-9). In no cases was recurrence seen at follow-up (ranging from 12 to 34 months). Treatments were well tolerated and local anesthesia was never requested. CONCLUSION: In conclusion, here, PDT was seen to be an effective and well-tolerated treatment option for unilesional MF.

Wegener's granulomatosis of the penis: genital presentation of systemic disease.

Wegener's granulomatosis (WG) is a systemic vasculitis of small and medium-size vessels, mostly affecting the respiratory tract and the kidneys, although any organ may be involved. This case concerns a 50-year-old man in whom WG caused an asymptomatic erosion on the glans penis and prepuce. Histological examination showed an unspecific inflammatory infiltrate. Four months later, a sudden and simultaneous onset of lesions of the upper respiratory tract and kidneys occurred, as well as peripheral neuropathy, polyarthritis, positivity of antineutrophilic cytoplasmic antibodies and its proteinase 3 subset. Histological examination of a nodular lesion on the left leg showed leukocytoclastic vasculitis of small and medium-size vessels, suggesting the diagnosis of WG. Cases in which isolated unspecific erosive lesions of the penis are the only symptoms of WG have been seen in only 4 other patients so far, and a correct diagnosis was only possible due to a careful follow-up study.