Assessment of Patient-Reported Outcomes at 48 Months of Treatment with Dupilumab for Severe Atopic Dermatitis: A Single-Center Real-Life Experience with 126 Patients.

BACKGROUND: The main objective was to analyze patient-reported outcomes (PRO) trends over a four-year period in severe atopic dermatitis (AD) patients treated with dupilumab. METHODS: data from 126 severe patients receiving dupilumab for at least 48 months were collected. The clinical scores assessed included the Eczema Area and Severity Index (EASI), Pruritus Numerical Rating Scale (NRS), Sleep NRS, Patient-Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI), and Atopic Dermatitis Control Tool (ADCT). RESULTS: the study compellingly demonstrates dupilumab's effectiveness in reducing EASI and improving PROs, with sustained enhancements observed beyond the initial twelve months of treatment. Univariate and multivariate regression analyses show that baseline factors do not significantly increase the risk of adverse outcomes related to Pruritus NRS, POEM, or ADCT at T48. The robust correlation between ADCT and other PROs suggests closely aligned changes. CONCLUSION: Dupilumab's benefits endure beyond the first year, emphasizing its long-term efficacy, and consistently improves AD outcomes regardless of individual characteristics or clinical variables. ADCT appears to be a practical and versatile tool for the streamlined assessment of AD treatment outcomes.

Topical Treatment of Melanoma In Situ, Lentigo Maligna, and Lentigo Maligna Melanoma with Imiquimod Cream: A Systematic Review of the Literature.

INTRODUCTION: The classical management of melanoma is surgery, but this can be challenging because of several factors, such as age, body area, lesion size, among others. Topical imiquimod may be a therapeutic option for the treatment of melanoma in situ and lentigo maligna melanoma due to its efficacy, tolerability, and non-invasiveness. The purpose of this systematic review is to assemble current evidence on the treatment of non-metastatic melanoma with topical imiquimod. METHODS: The PubMed/MEDLINE and Cochrane Library databases were searched as the primary sources using the main search terms "imiquimod" combined with "lentigo maligna" and "melanoma" with the command "AND." Articles were identified, screened, and extracted for relevant data, following the PRISMA guidelines. RESULTS: A total of 87 studies covering 1803 lesions treated with imiquimod cream were identified and included in this sytematic review. Forty-nine studies were case reports, 16 were retrospective analyses, 3 were open label trials, six were case series; one study was a controlled randomized trial, one was a randomized trial, and one was a single-arm phase III trial. Because of the high number of low-evidence studies, the overall risk of bias resulted high. In 55 studies, imiquimod 5% was used in monotherapy as the primary treatment; only in one study was imiquimod 3.75% introduced. In most cases, the topical treatment was applied once daily, with the exception of nine cases where an increased daily dosage was prescribed. The total duration of the treatment regimen was extremely variable and depended on body area and tolerability, with differences among patients of the same study. In six studies, imiquimod was used as neoadjuvant therapy before the surgical excision, and in 11 studies it was used after surgery as complementary or adjuvant therapy. In total, 1133 of the 1803 (62.8%) lesions were reported to be cleared after the treatment, taking into account that not all of the patients completed the treatment. Of these 1133 lesions, histological clearance was achieved in 645 (56.9%) lesions and clinical clearance only was achieved in 490 (43.2%) lesions; relapse occurred in 107 lesions. CONCLUSIONS: The heterogeneity of the studies included in this systematic review precludes the drawing of any relevant conclusions regarding the application of imiquimod. Its efficacy in melanoma in situ and lentigo maligna melanoma has been demonstrated, but further evidence from controlled studies concerning the modalities is missing.

The role of imaging technologies in the diagnosis of hidradenitis suppurativa.

Hidradenitis suppurativa is a chronic, inflammatory, recurrent, and debilitating disease of the hair follicle. It presents with painful, deep-seated, inflamed lesions, such as nodules, abscesses, sinus tracts, and fistulas, generally located in the main folds. Clinical severity assessment alone can be reductive; noninvasive skin imaging technologies, such as ultrasound, magnetic resonance imaging, medical infrared thermography, computed tomography, and positron emission tomography, provide subclinical anatomical and functional details. These instrumental techniques confirm the clinical suspect, thus allowing an earlier diagnosis and improving patients' clinical evaluation, staging, and management. Finally, they might be helpful for preoperative mapping. In this contribution, we provide an overview of the current knowledge about noninvasive skin imaging techniques with a particular focus on ultrasonography, which is widely used thanks to its precision, versatility, and availability.

Thyroid Autoimmunity in CSU: A Potential Marker of Omalizumab Response?

The response of severe chronic spontaneous urticaria (CSU) to omalizumab largely depends on the autoimmune or autoallergic endotype of the disease. Whether thyroid autoimmunity may predict omalizumab response along with total IgE in CSU is still unclear. Three hundred and eighty-five patients (M/F 123/262; mean age 49.5 years; range 12-87 years) with severe CSU were studied. Total IgE levels and thyroid autoimmunity (levels of anti-thyroid peroxidase [TPO] IgG) were measured before omalizumab treatment. Based on the clinical response, patients were divided into early (ER), late (LR), partial (PR) and non (NR) responders to omalizumab. Thyroid autoimmunity was detected in 92/385 (24%) patients. Altogether, 52%, 22%, 16% and 10% of patients were ER, LR, PR and NR to omalizumab, respectively. Response to omalizumab was not associated with thyroid autoimmunity (p = 0.77). Conversely, we found a strongly positive association between IgE levels and omalizumab response (p < 0.0001); this association was largely driven by early response (OR = 5.46; 95% CI: 2.23-13.3). Moreover, the predicted probabilities of early response strongly increased with increasing IgE levels. Thyroid autoimmunity alone cannot be used as a clinical predictor of omalizumab response. Total IgE levels remain the only and most reliable prognostic marker for omalizumab response in patients with severe CSU.

Uses of Polypodium leucotomos Extract in Oncodermatology.

The effects of UV radiation on the skin and its damage mechanisms are well known. New modalities of exogenous photoprotection have been studied. It was demonstrated that Polypodium leucotomos extract acts as an antioxidant, photoprotectant, antimutagenic, anti-inflammatory, and immunoregulator. It is effective when taken orally and/or applied topically to support the prevention of skin cancers. It also has an important role in preventing photoaging. This review aims to report the mechanisms through which Polypodium leucotomos acts and to analyze its uses in oncodermatology with references to in vitro and in vivo studies. Additionally, alternative uses in non-neoplastic diseases, such as pigmentary disorders, photosensitivity, and atopic dermatitis, have been considered.

Lymph Node Involvement in Axillary Hidradenitis Suppurativa: A Clinical, Ultrasonographic and Bacteriological Study Conducted during Radical Surgery.

BACKGROUND: Hidradenitis suppurativa (HS) is an inflammatory and chronic-recurrent disease of the hair follicle. Its aetiopathogenesis is not completely known. Although bacterial colonization and superinfection are clinically relevant, lymph node involvement has rarely been studied. OBJECTIVES: In this pilot retrospective study, we evaluated the clinical and microbiological nodal involvement in patients with axillary hidradenitis suppurativa. MATERIALS AND METHODS: We retrospectively analyzed patients suffering from axillary hidradenitis suppurativa and referred to the Dermatology Unit of the Foundation Ca' Granda Ospedale Maggiore Policlinico in Milan between October 2018 and November 2019. The sampling procedure took place during the surgical excision of lesions at the Operative Unit of Plastic and Reconstructive Surgery of Policlinico San Donato Hospital. Three types of sample were sent to microbiological analysis: exudate swab, axillary lymph node, fistula. RESULT: In total, we recruited 10 patients. Two of them underwent bilateral axillary surgery. Nine lymph nodes were analyzed. In one patient, bacterial culture in lymph nodes, skin lesions and fistulae matched. CONCLUSIONS: Unequivocable conclusions cannot be drawn due to the low number of patients. Further studies are necessary to confirm the preliminary results of our retrospective pilot study.

Vascularization and fibrosis are important ultrasonographic tools for assessing response to adalimumab in hidradenitis suppurativa: Prospective study of 32 patients.

Hidradenitis suppurativa (HS) is a debilitating skin disease presenting with nodules, abscesses, and fistulae preferentially in the main folds. Adalimumab is the only licensed biologic for moderate-to-severe HS. Ultrasound demonstrated good sensitivity to provide anatomic and functional information in HS; in particular assessing vascularization, related to inflammation, and fibrosis in HS lesions before and after adalimumab treatment with ultrasound and Color Doppler may integrate clinical evaluation with imaging. Patients with moderate-to-severe HS were enrolled in this observational prospective study. Clinical evaluation (according to Hurley classification and International Hidradenitis Suppurativa Severity Score System score) and ultrasound (according to US HS-PGA)/Color Doppler were performed at baseline and after 12 weeks of adalimumab. Ultrasound was used for assessing fibrosis and Color Doppler for vascularization. For each patient, the three most severe lesions among abscesses and fistulae were chosen for total 96 lesions. Thirty-two patients were included, 18 men (56%) and 14 women (44%) with mean age 41.2. Mean IHS4 was 22.4 at baseline and dropped to 14.7 at week 12. Based on US HS-PGA, 14 out of 32 patients fell down by one or more classes of severity. Interestingly, adalimumab led to overall decrease in vascularization, particularly in lesions with intense vascular flow, which were 78 (81.3%) at baseline and became only 25 (26.04%). Finally, marked increase in fibrosis was seen after adalimumab, notably in lesions without fibrosis, which were 81 (84.4%) at baseline and became 15 (15.6%). This study confirms the efficacy of adalimumab in HS and provides value for vascularization and fibrosis as important ultrasonographic tools integrating clinical scores.

Color Doppler as a tool for correlating vascularization and pain in hidradenitis suppurativa lesions.

BACKGROUND: Hidradenitis suppurativa (HS) is a debilitating, chronic-relapsing, inflammatory skin disease of apocrine gland-bearing skin, presenting with nodules, abscesses, and fistulae. Ultrasound is used to classify HS lesions but evaluation of vascularization, related to tissue inflammation, needs Color Doppler. The aim was to correlate vascularization of HS lesions with patients' reported pain. METHODS: Vascularization was assessed with Hitachi Arietta V-70 sonographer according to a four-category system ranging from absent (0), minimal (1), moderate (2) vascularization, and detectable vascular flow (3). Pain was scored with Numeric Rating Scale (NRS) from 0 to 10. RESULTS: Twenty-four patients were included, 13 men (54.2%) and 11 women with mean age of 37.2 (range: 19-61 years). Sixty-nine HS lesions were studied: none of the lesions with absence of vascularization was painful. Lesions with minimal vascularization had a mean NRS value of 3.1 (range: 0 to 7; standard deviation [SD]: 1.6). Lesions with moderate vascularization had a mean NRS value of 6.4 (range: 4-8; SD: 1.4). Lesions with intense vascular flow had a mean NRS value of 7.8 (range: 5-9; SD: 1.7). Correlation Spearman's rank coefficient calculated between the class of vascularization and the mean NRS value was 0.98, supporting high correlation between intensity of vascularization and local pain. CONCLUSION: The present study is the first one demonstrating correlation between vascularization of HS lesions assessed with Color Doppler and local pain. Color Doppler may be a dynamic diagnostic tool that can address the therapeutic approach and assess response to treatment in HS.