Bath-PUVA still represents a valuable treatment option for the subsets of psoriatic patients who are not eligible to or rejecting systemic treatments and are not responsive to NB-UVB phototherapy.

BACKGROUND: Photochemotherapy with bathwater delivery of psoralens plus UVA exposures (bath-PUVA) is mainly used for those psoriatic patients who are not responsive to narrowband (NB)-UVB phototherapy and oral-PUVA therapy and belong to two categories (1) patients with psoriasis without systemic comorbidities who do not need long-term continuous treatment and (2) patients who have contraindications to immunosuppressive drugs and oral-PUVA or refuse systemic drugs, including oral ingestion of psoralens, for personal reasons. However, it is not known how many patients belong to the second group and how much bath-PUVA is effective and safe for them. METHODS: We have reviewed the treatment results of a cohort of 120 patients with clinical indication to bath-PUVA for the above-mentioned reasons between 2010 and 2019. These patients were selected among 2640 patients with moderate and severe psoriasis who were treated in our department in the same time interval. RESULTS: Ninety-six patients completed at least one treatment cycle with bath-PUVA. A per-protocol analysis showed that average number of treatment sessions was 21.3 ± 9.0 and the cumulative UVA dose was 80.4 ± 60.0 J/cm2 . The average PASI scores decreased from 20.8 ± 7.9 to 5.1 ± 5.4 (p < .01). Sixty-seven (69.7%) patients achieved at least a 75% improvement (PASI75 ) and, of them, 38 (39.6%) had an improvement greater than 90% (PASI90 ). Adverse effects were mild and transitory. CONCLUSION: These findings demonstrate that bath-PUVA is still a valuable treatment option for a high number of patients who reject systemic treatments or have contraindications to systemic immune-modifying drugs and have had a limited or no improvement with NB-UVB phototherapy.

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.

A Short Cycle of Narrow-Band UVB Phototherapy in the Early Phase of Dupilumab Therapy Can Provide a Quicker Improvement of Severe Atopic Dermatitis.

BACKGROUND: Since the best clinical response to dupilumab is achieved after 12-16 weeks, a combination therapy at the beginning of the treatment could be a helpful strategy to reach a faster response in patients with severe atopic dermatitis (AD). OBJECTIVES: To quantify the benefit of a combination of dupilumab treatment with a short course of narrow-band ultraviolet B (NB-UVB) phototherapy. METHODS: In the present pilot study adult patients suffering from severe AD were enrolled with a 2:1 ratio to receive treatment with dupilumab alone or dupilumab plus NB-UVB phototherapy, for 12 weeks. After the twelfth week, all patients received dupilumab only. A follow-up visit took place after 16 weeks. Both clinician-oriented and patient-oriented scores were assessed at baseline (T0) and after 4 (T1), 12 (T2) and 16 (T3) weeks. RESULTS: Forty-five adult patients were enrolled in the study. Both treatment regimens were well tolerated and very effective on all measured scores (EASI, SCORAD, BSA, NRS of itching, NRS of sleep loss, DLQI, POEM and HADS), but the combined regimen led to a more robust clinical improvement of lesions and relief of symptoms after 4 weeks. However, after 12 and 16 weeks, the additional therapeutic effect of phototherapy weakened. CONCLUSION: NB-UVB phototherapy can provide a faster remission of severe AD in the first few weeks of dupilumab therapy.

A Critical Reappraisal of Off-Label Use of Photodynamic Therapy for the Treatment of Non-Neoplastic Skin Conditions.

BACKGROUND: In the past 30 years, topical photodynamic therapy (PDT) has been investigated for the treatment of a broad spectrum of cosmetic, inflammatory, and infectious skin conditions with variable, and often contrasting, results. However, the non-expert clinician may be in difficulty evaluating these results because different sensitizers, concentrations, formulations, light sources, and irradiation protocols have been used. In addition, many of these studies have poor quality design being case reports and uncontrolled studies of few cases. SUMMARY: With the aim to clarify the potential usefulness of PDT for the treatment of infectious and inflammatory skin diseases as well as selected cosmetic indications, we searched for randomized controlled clinical trials, non-randomized comparative studies, retrospective studies, and case series studies with a number of at least 10 patients, published since 1990. Later, we reappraised the results in order to give a simple critical overview. Key Messages: Evidence from the literature seems to strongly support the use of ALA- and MAL-PDT for the treatment of common skin diseases such as acne, warts, condylomata, and Leishmania skin infection and for photorejuvenation, i.e., the correction of selected cosmetic changes of aging and photoaging. For other disorders, the level of evidence and strength of recommendation are lower, and controlled randomized studies with prolonged follow-ups are necessary in order to assess the clinical usefulness and other potential advantages over current treatment options.

Sunlight-induced Painful Skin (Sun Pain): A New Differential Diagnosis in Photodermatology.

Photodermatoses are characterized by the development of skin eruptions following exposure to ultraviolet radiation or visible light. We report here the clinical findings and results of laboratory investigations and phototesting of 6 patients who experience debilitating and excruciating pain after sun exposure ("sun pain") in the absence of any skin eruption. Phototesting with sub-erythemal doses of ultraviolet A radiation triggered localized pain in 4 patients. At follow-up, 3 female patients were found to have developed fibromyalgia, 2 male patients experienced a major depressive disorder, and another male patient had a conversion disorder. One patient also developed allodynia to tactile stimuli and one developed allodynia to thermal and tactile stimuli. Psychiatric conditions should be taken into consideration in patients presenting with excruciating and debilitating pain on exposure to ultraviolet radiation, but with absence of skin eruption. Further research is needed to evaluate whether it represents a type of allodynia triggered by exposure to ultraviolet radiation.

Clinical and Spectrophotometric Evaluation of Skin Photoadaptation in Vitiligo Patients after a Short Cycle of NB-UVB Phototherapy.

BACKGROUND: The phenomenon of photoadaptation to narrow-band ultraviolet B (NB-UVB) radiation has been previously described in vitiligo and has usually been clinically measured by the assessment of the minimal erythema dose (MED) after phototesting. OBJECTIVES: To assess the photoadaptive response in vitiligo and healthy skin after NB-UVB phototherapy not only clinically, but also by spectrophotometry. MATERIALS AND METHODS: Fourteen patients affected by generalized vitiligo underwent NB-UVB phototherapy twice weekly for 12 weeks. Before and after phototherapy, a phototesting procedure was administered on vitiligo patches and adjacent healthy skin with a solar simulated radiation (SSR). Visual assessment of the MED took place after 24 h. A spectrophotometer was used to assess the a* value and the melanin index (MI*), as signs of skin erythema and pigmentation. The photoadaptation factor (MED-PF) and the a* photoadaptation factor (a*-PF) were calculated. RESULTS: After NB-UVB phototherapy, both vitiligo and healthy skin showed an increase in MED and MI* values and a reduction of skin erythema compared to baseline (p < 0.05). MED-PF data showed a photoadaptation in 10 (71.4%) vitiligo lesions and in 12 (85.7%) healthy skin areas. The assessment of the a*-PF showed a negative mean percentage value in all affected and unaffected skin areas. CONCLUSIONS: A short cycle of NB-UVB phototherapy can induce photoadaptation in vitiligo by increasing the MED and reducing skin erythema after stimulation with SSR. This is most likely due to the physical filter function induced by ultraviolet radiation.

Prevalence of Phototherapy in the Age of Biologics.

BACKGROUND: The prevalence of narrow-band ultraviolet B (NB-UVB) use in Europe for moderate and severe psoriasis is unknown, because national registries for psoriasis do not monitor this treatment. OBJECTIVES: To quantify the use of phototherapy, biologics or conventional treatments in psoriasis, in a setting where European Medicines Agency (EMA) eligibility criteria for biologics were strictly applied, and phototherapy was included among first-line treatments. METHODS: We followed a cohort of 1,090 patients who were referred to the only centre entitled to prescribe biologics and phototherapy during a 5-year period. RESULTS: The cumulative number of treatment cycles was: 1,047 with NB-UVB phototherapy, 650 with systemic treatments and 239 with biologics; 754 patients received at least 1 course of NB-UVB phototherapy, 422 at least 1 course with a systemic treatment and 137 with a biologic; 595 patients were treated only with phototherapy. CONCLUSIONS: Regular use of NB-UVB as first-line treatment for moderate and severe psoriasis and adherence to the EMA eligibility criteria for biologics led to a relatively restricted use of biologics.

Echocardiographic evaluation of diastolic dysfunction in young and healthy patients with psoriasis: A case-control study.

Psoriasis is a systemic inflammatory disease with a great prevalence in general population. The inappropriate activation of the cellular immune system has been hypothesized to be an independent cardiovascular risk factor, given the higher incidence of cardiovascular disorders in psoriatic patients. Echocardiographic abnormalities have been demonstrated too: the aim of our study was to evaluate the presence of preclinical cardiac dysfunction in a cohort of psoriatic patients without cardiovascular risk factors. We enrolled 52 patients with the diagnosis of chronic plaque psoriasis, compared with a control group not affected by any relevant systemic diseases and inflammatory disorders. In all patients and control group, echocardiographic conventional and tissue Doppler (TDI) studies were conducted. The analysis of echocardiographic parameters revealed normal dimension, mass and systolic function of the left ventricle. Left ventricular diastolic dysfunction was found in 36.5% patients in the psoriasis group versus 0% in control group, and significant reduction of the E/A ratio was found also for the right ventricle. A significant increase of mitral regurgitation has been found in psoriatic patients (p=0.005). The early recognition of cardiovascular pre-clinic disease in psoriatic patients may guide a strict follow up and an early treatment, potentially improving cardiovascular prognosis.

Pulsed CO2 Laser Ablation of Superficial Basal Cell of Limbs and Trunk: A Comparative Randomized Clinical Trial With Cryotherapy and Surgical Ablation.

BACKGROUND: Pulsed CO2 laser is a treatment of superficial basal cell carcinoma (sBCC) although robust clinical evidence has not been reported so far. OBJECTIVE: The authors investigated efficacy, safety, time to wound healing, cosmetic outcome, patient satisfaction, and cost-effectiveness ratio of pulsed CO2 laser in comparison to cryotherapy and surgery. MATERIALS AND METHODS: BCCs of the trunk and extremities were randomized to one of the treatments. After 90 days, efficacy and cosmetic outcome were assessed. Patients recorded the time to complete healing of the wound and scored their overall satisfaction. RESULTS: Two hundred forty patients were randomized. After 3 months, complete remission (CR) rate with pulsed CO2 laser was 78.8%. This was significantly lower than surgery, whereas the CR rate with cryotherapy was not significantly different. Cosmetic result was better with surgery. High satisfaction was reported by 65.0% of patients treated with CO2 ablation. Time of wound healing was significantly shorter with CO2 laser. CONCLUSION: In comparison to cryotherapy, pulsed CO2 laser showed no statistically significant difference in efficacy, cosmetic outcome, and patient satisfaction. Time to healing was shorter; the cost and cost-effectiveness ratio were similar. Surgery had the greatest efficacy rate. The main limitation of this study was the short duration of follow-up (3 months).

A Randomized Split-Face Clinical Trial of Photodynamic Therapy with Methyl Aminolevulinate versus Ingenol Mebutate Gel for the Treatment of Multiple Actinic Keratoses of the Face and Scalp.

BACKGROUND: Photodynamic therapy with methyl aminolevulinate (MAL-PDT) and ingenol mebutate gel (IMB) are approved therapeutic options for multiple actinic keratoses (AKs). OBJECTIVE: The aim of this intraindividual, split-face, randomized clinical trial was to compare treatment outcomes of MAL-PDT and IMB. METHODS: Two symmetrical contralateral areas with a similar number of AKs were selected and randomly assigned to 3 days of an IMB treatment cycle or a single session of MAL-PDT. The next day, the local skin reaction (LSR) score was registered. The patients scored pain and time to healing of the treatment area. RESULTS: After 90 days, the complete remission rate of lesions, the number of patients with complete remission of all lesions, cosmetic outcome, and patient preference were assessed. CONCLUSION: According to our results, IMB and MAL-PDT had a similar efficacy, but the cosmetic outcome was superior with MAL-PDT. Pain was higher with PDT, but LSR was more severe and time to healing was longer with IMB. Patients preferred MAL-PDT.

Oral Polypodium leucomotos increases the anti-inflammatory and melanogenic responses of the skin to different modalities of sun exposures: a pilot study.

BACKGROUND: The effects on the inflammatory and tanning responses of sunlight/UVR of several oral antioxidants are still unknown. OBJECTIVE: Assess intensity, time course of the inflammatory, and tanning responses to increasing dosages of solar-simulated radiation (SSR) at baseline and after oral supplementation of an extract of Polypodium leucotomos (PLE). METHODS: Ten healthy subjects underwent phototesting with SSR with a visual and spectrophotometrical assessment of the responses with or without daily oral supplementation of two tablets containing 240 mg of PLE for a total of 15 days. RESULTS: Polypodium leucotomos supplementation induced a significant increase of the minimal erythema dose (MED), a faster recovery of the inflammation following the delivery of super-erythemal doses, and no significant changes of the minimal melanogenic dose (MMD). Spectrophotometric assessment of the Δa* in test areas exposed to equally doses of SSR did not show differences. CONCLUSIONS: Polypodium leucotomos supplementation increased the MED and induced a faster recovery of the inflammation and a stronger tanning response with no changes in the melanogenic threshold.

Pigmented nonmelanoma skin cancers of the genital area: a diagnostic and therapeutic challenge - monocentric experience and review of the literature.

Nonmelanoma skin cancers (NMSC), comprising basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), are typically encountered on photo-exposed skin. Nevertheless, several cases of NMSC have been described in covered areas such as the genital region; furthermore, some of these lesions may express a variable degree of pigmentation. Due to the existence of mucosal melanoma, an accurate diagnosis is paramount. In this narrative review, we focused our attention on management and - in particular- diagnosis of pigmented NMSC (pNMSC) located in the genital region, emphasizing the features assessed by dermoscopy and reflectance confocal microscopy. As an implementation, we included data on pNMSC from the Dermatology Unit of the University of Campania Vanvitelli. BCC in the genital region represents only 1% of all BCC cases. It has been supposed that the mutation of patched 1 may lead to the development of BCC even without concomitant UV exposure. Pigmented variants on genitals have seldom been described. More prominent dermoscopic features seem to be blue-gray ovoid nests and arborizing vessels associated with whitish structureless areas. SCC and Bowen's disease (BD) - a variant of in situ SCC - may be encountered in the genital area and are sometimes associated with human papillomavirus (HPV) infection. Pigmented SCC is very rare, and most of the literature is focused on pigmented BD (pBD), which is mainly characterized by gray-brown dots in a linear fashion and glomerular vessels without evident scales. In conclusion, pNMSC is rarely encountered on genitals; evaluation with dermoscopy or other ancillary devices like RCM is important both to exclude benign lesions like seborrheic keratosis and lentigo and to rule out melanoma.

Influence of regression, its extent and tumor-infiltrating lymphocytes on sentinel node status, relapse, and survival in a 10-year retrospective study of melanoma patients.

This case-control study seeks to investigate the influence of histological findings, specifically regression, its extent and tumor-infiltrating lymphocyte (TILs), on result of sentinel lymph node (SLN) biopsy, 5-year melanoma-specific survival (MSS), and relapse-free survival (RFS). We included all patients with cutaneous melanoma who underwent SLN biopsy at the Melanoma Center of the University of Brescia, following the Italian Association of Medical Oncology National guidelines from January 2008 to August 2018. Regression and its extent (<75 or ≥75%) and the presence of TILs were reevaluated by a trained dermatopathologist, adhering to the 2017 College of American Pathologists Cancer Protocol for Skin Melanoma. These patients were followed up for 5 years. Our study uncovered significant associations between regression and male sex ( P  < 0.05), melanoma location on the trunk, upper limbs, and back ( P  = 0.001), ulceration ( P  < 0.05), lower Breslow thickness ( P  = 0.001), and the presence of lymphocytic infiltration (both brisk and nonbrisk) ( P  < 0.001). Regression and its extent, however, did not appear to affect SLN positivity ( P  = 0.315). Similarly, our data did not reveal a correlation between TILs and result of SLN biopsy ( P  = 0.256). When analyzing MSS and RFS in relation to the presence or absence of regression and TILs, no statistically significant differences were observed, thus precluding the need for logistic regression and Kaplan-Meier curve analysis. This study's findings underscore that regression and TILs do not appear to exert an influence on sentinel lymph node status, MSS, or RFS in our cohort of patients.

When the diagnosis is written in the DNA: a case of erythropoietic protoporphyria in a patient with a chromosome-18 deletion.

In this case study, we describe a 21-year-old man with erythropoietic protoporphyria who sought medical attention in April 2022 for diffuse edema and erythema of the hands. These symptoms had been present since childhood and usually occurred soon after sun exposure. The patient's medical history showed that chromosome 18's long arm had partially deleted. We performed a number of tests, including measuring total erythrocyte protoporphyrin levels and utilizing a spectrofluorometer to assess the fluorometric emission peak of plasma porphyrins, based on the patient's medical history and clinical symptoms. Furthermore, a genetic analysis identified an intronic variant on one allele, c.315-48T>C (IVS3-48T>C), which is categorized as a susceptibility polymorphism, and a complete deletion of the ferrochelatase gene on the other allele. The patient's clinical condition improved following the June 2022 afamelanotide implant procedure.

Evaluation of the incidence of melanoma and non-melanoma skin cancer in patients with systemic lupus erythematosus and systemic sclerosis.

BACKGROUND: The incidence of skin cancer in patients with systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) has only been investigated with retrospective studies enrolling a low number of patients. The aims of our study were to assess the incidence of skin cancer in two large cohorts of patients, one with SLE and the other with SSc and investigating possible risk factors. METHODS: Ninety SLE, 53 SSc patients and 392 control subjects were enrolled. A questionnaire including personal and medical details was fulfilled. The severity of photoaging, photosensitivity and sun exposure habits was assessed. Skin lesions were evaluated using a video-dermatoscope. Suspicious lesions were surgically removed. RESULTS: The incidence of skin cancer was not different to those of controls. However, a decrease in the incidence of basal cell carcinoma was found in patients with SLE. This finding associated negatively with photosensitivity. SSc patients with skin malignancies did not report photosensitivity and did not adopt a careful photoprotection. A positive association was found between skin cancer and diffuse cutaneous sclerosis, pitting scars, severe photoaging and treatment with Iloprost. CONCLUSIONS: Regular avoidance of sun exposure and photoprotection are effective in reducing the development of skin cancer in patients with autoimmune diseases.

Definition of the Clinical Characteristics of Patients with Moderate and Severe Atopic Dermatitis for Whom Narrow-Band UVB (NB-UVB) and Medium-Dose UVA1 Phototherapies Are Still Valuable Treatment Options at the Age of Biologics.

Narrow-band (NB) UVB and UVA1 have been successfully used for the treatment of atopic dermatitis (AD) since the 1980s, but the clinical indications for their use "at the age of biologics" remain to be assessed. From 2013 to 2017, 145 patients underwent a first treatment cycle with phototherapy. They achieved a median final EASI score of 9.90 with UVA1 and 13.70 with NB-UVB. The rates of patients achieving an IGA score of 0/1 persistent for at least 6 months were 33% with UVA1 and 28% with NB-UVB, and the rates with an EASI90 improvement were 10.9% with UVA1 and 11.0% with NB-UVB. The cut-off baseline EASI values for a good probability to achieve a 0/1 IGA were 24.4 with UVA1 and 24.7 with NB-UVB. A 0/1 IGA persistent for at least 6 months was more likely to be achieved by patients with a history of flares interspersed with periods of mild or no disease. From 2018, we only enrolled patients with the above-mentioned characteristics. The number of treated patients was lower, but the final EASI score, the rate of patients achieving IGA 0/1 persistent for at least 6 months, and EASI90 were significantly higher. Medium-dose UVA1 and NB-UVB phototherapies remain useful for the treatment of AD patients with a baseline EASI score lower than 24.4 and 24.7, respectively, and a medical history of flares followed by prolonged periods of complete or near-complete remission.