Etiology of Chronic Leg Ulcers in a Dermatologic Wound Clinic: A Retrospective Observational Study.

BACKGROUND: Chronic leg ulcers affect approximately 1% to 2% of the European population, with an increasing prevalence. The treatment of chronic wounds is a socioeconomical problem worldwide. PURPOSE: The main purpose of the current investigation was to detect the etiology of leg ulcers treated in a dermatologic wound clinic from January 1, 2010, to December 31, 2019. METHODS: This retrospective observational study was performed at the Dermatologic Clinic of Spedali Civili in Brescia, Italy. The authors enrolled 465 patients with chronic leg ulcers. RESULTS: The 3 most represented causes of ulcers were vascular (238 patients, 51.2%), inflammatory (71 patients, 15.3%) and traumatic (43 patients, 9.3%). Altogether, a total of 13 different entities were identified as a cause of leg ulcer. CONCLUSION: Vascular genesis was the most common etiology of leg ulcers in this population, even though uncommon causes were also represented. These findings are in agreement with other studies reported in the literature.

Topical Pharmacotherapy for Actinic Keratoses in Older Adults.

Actinic keratosis is caused by excessive lifetime sun exposure. It must be treated, regardless of thickness, because it is the biologic precursor of invasive squamous cell carcinoma, a potentially deadly malignancy. Physical ablative techniques such as cryotherapy, lasers, and curettage are the most used treatments for isolated lesions. Multiple lesions are treated with topical drugs, chemical peelings, and physical techniques. Drug preparations containing diclofenac plus hyaluronate, aminolevulinic acid, and methyl aminolevulinate and different concentrations of imiquimod and 5-fluorouracil are approved for this clinical indication. All treatments have a good profile of efficacy and tolerability although there are relevant differences in the clearance rate, tolerability, and type and frequency of adverse effects. In addition, they have very different mechanisms of action and treatment protocols. No differences in the efficacy and tolerability were found in older patients compared with younger patients, therefore no dose adjustments are needed. That said, older patients often need to be motivated to treat actinic keratoses and a careful attention to expectations, needs, and preferences should be used to obtain the maximal adherence and prevent treatment failure. This goal can be achieved with a careful evaluation not only of published efficacy, toxicity, and tolerability data but also of practical topics such as the frequency of daily applications, the overall duration of therapy, and the need for a caregiver. Finally, particular attention must be paid in the case of frail patients and immunosuppressed patients.

Impact of the COVID-19 pandemic and lockdown on the clinical response to dupilumab treatment and the psychological status of non-infected atopic patients.

Dupilumab is an effective treatment for atopic dermatitis and was found to improve results of clinician- and patient-oriented tests with relevant benefits across multiple domains related to the disease. To investigate the effects of significant psychological stress on clinician- and patient-oriented tests for severe AD patients treated with dupilumab. Patients were investigated before and during the COVID-19 pandemic and lockdown in a severely affected area. Forty-five adult patients suffering from severe AD were enrolled. Clinician-oriented (EASI, SCORAD and NRS scores for sleep loss and itching) and patient-oriented tests (DLQI, POEM and HADS) were administered at baseline (T0) and after 16 (T1) and 24 (T2) weeks. The T2 examination took place just before the outbreak of the COVID-19 pandemic. A further examination took place at 32 weeks (T3) during the COVID-19 pandemic and lockdown. In comparison to baseline, dupilumab treatment rapidly improved the scores of all tests. After this, the pandemic and lockdown started, and scores of clinician-oriented tests remained almost stable, while patient-oriented scores markedly deteriorated, although they remained better than at baseline. Some personal and social situations seemed to be linked to a worse result. Despite dupilumab being effective in inducing and maintaining clinical remission of AD, the COVID-19 pandemic and lockdown significantly impaired patients' perception of the disease, quality of life and anxiety and/or depression. However, this psychological status did not modify the therapeutic response to dupilumab.

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.

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.

Application of the 2017 criteria for vascular Ehlers-Danlos syndrome in 50 patients ascertained according to the Villefranche nosology.

Vascular Ehlers-Danlos syndrome (vEDS) is a rare inherited connective tissue disorder due to heterozygous pathogenic COL3A1 variants. Arterial, intestinal, and/or uterine fragility is the disease hallmark and results in reduced life expectancy. The clinical diagnosis is not always straightforward and patients' selection for molecular confirmation depends on the characteristics of applied criteria, that is, the Villefranche criteria (in use until 2017) and their revision according to the new EDS nosology. Herein, we reassessed the clinical features of 50 molecularly proven vEDS patients, diagnosed according to the Villefranche nosology between 2000 and 2016, using the 2017 classification in order to explore its clinical application. Our findings indicate that the Villefranche criteria were particularly valuable for symptomatic patients, even if with a limited specificity. Our study also suggests that the revised vEDS criteria, although expected to be more specific, might have a poorer accuracy, principally in terms of sensitivity. Both sets of criteria are less effective in presymptomatic young patients, especially in the absence of a clear-cut family history. For these patients, the careful evaluation of the cutaneous, articular, and dysmorphic features and, above all, genetic testing remain crucial to set-up proper follow-up and surveillance before catastrophic vascular and intestinal events.

Sun Exposure and Melanoma, Certainties and Weaknesses of the Present Knowledge.

Sun exposure is the main risk factor for cutaneous malignant melanoma (CMM). However, the UV-related pathogenetic mechanisms leading to CMM are far to be fully elucidated. In this paper we will focus on what we still don't fully know about the relationship between UVR and CMM. In particular, we will discuss: the action spectrum of human CMM, how different modalities of exposure (continuous/ intermittent; erythemal/ suberythemal) relate to different CMM variants, the preferential UVR induced DNA mutations observed in different CMM variants, the role of UV-related and UV-unrelated genetic damages in the same melanoma cells. Moreover, we will debate the importance of UVA induced oxidative and anaerobic damages to DNA and other cell structures and the role of melanins, of modulation of innate and acquired immunity, of vitamin D and of chronic exposure to phototoxic drugs and other xenobiotics. A better understanding of these issues will help developing more effective preventative strategies and new therapeutic approaches.