Treatment of extramammary Paget's disease with imiquimod in a real-life setting: a multicenter retrospective analysis in Spain.

BACKGROUND: Topical imiquimod has shown to be an effective treatment for EMPD, although available evidence supporting its use is based on case reports and small series of patients. OBJECTIVES: To investigate the therapeutic outcomes and analyze potential clinico-pathological factors associated with imiquimod response in a large cohort of EMPD patients. METHODS: Retrospective chart review of 125 EMPD patients treated with imiquimod at 20 Spanish tertiary-care hospitals. RESULTS: During the study period, patients received 134 treatment regimens with imiquimod, with 70 (52.2%) cases achieving complete response (CR), 41 (30.6%) partial response and 23 (17.2%) no response. The cumulative CR rates at 24 and 48 weeks of treatment were 46.3% and 71.8%, respectively, without significant differences between first-time and previously treated EMPD. Larger lesions (≥6 cm; p = 0.038) and EMPD affecting >1 anatomical site (p = 0.002) were significantly associated with a worse treatment response. However, the CR rate did not differ significantly by the number of treatment applications (≤4 vs. > 4 times/week; p = 0.112). Among patients who achieved CR, 30 (42.9%) developed local recurrences during a mean follow-up period of 36 months, with an estimated 3 and 5-year recurrence free-survival of 55.7% and 36.4%, respectively. CONCLUSIONS: Imiquimod appears as an effective therapeutic alternative for both first-line and previously treated EMPD lesions. However, a less favorable therapeutic response could be expected in larger lesions and those affecting >1 anatomical site. Based on our results, a 3-4 times weekly regimen of imiquimod with a treatment duration of at least 6 months could be considered an appropriate therapeutic strategy for EMPD patients.

Polysensitization in the Spanish Contact Dermatitis Registry (REIDAC): A 2019-2022 prospective study with cluster and network analysis.

BACKGROUND: There is still limited clinical-practice data on specific clinical and patch test features, as well as on allergen clusters in polysensitization (PS). OBJECTIVES: To determine the frequency, relevance, symptoms duration and risk factors in polysensitized patients and to assess possible allergen aggregation. METHODS: Prospective multicentric study (January 2019-December 2022) conducted in setting of the Spanish Contact Dermatitis Register (REIDAC). Clinical and patch test data of polysensitized and oligosensitized patients were compared, and risk factors of PS were investigated with logistic multivariate regression. Unsupervised hierarchical clustering and network analysis were used to study allergen aggregation in PS. RESULTS: A total of 10,176 patients were analysed. PS was found in 844 (8.3%). Current relevance was significantly higher in polysensitized patients (p < 0.01). Risk factors for PS were atopic dermatitis (OR: 1.58, 95% CI: 1.24-2.02), age (≥60 years vs. ≤24 years, OR: 1.75, 95% CI: 1.25-2.44) and some special locations (legs vs. face OR: 1.54, 95% CI: 1.05-2.25, hands vs. face OR: 1.46, 95% CI:1.15-1.85, arms vs. face OR: 1.49, 95% CI:1.01-2.20, trunk vs. face OR: 1.40, 95% CI:1.06-1.85). Cluster and network analyses revealed specific-allergen clusters and significant associations, including allergens belonging to metals group, fragrances and botanicals group, topical drugs group, rubber allergens and biocides. CONCLUSIONS: This study confirms that PS is structured by discernible patterns of specific-allergen clusters and reinforces significant allergen associations in PS. Cross-reactivity and/or concomitant sensitization could explain the formation of allergen clusters in PS.

Macrocheilia as an Atypical Clinical Presentation of Capillary Malformation-Arteriovenous Malformation Type 2.

This case report describes a 53-year-old man with multiple erythematous macules and papules diffusely distributed on the frontal area, cheeks, eyelids, nose, and supralabial skin.

Eruptive syringomas associated with milia-like idiopathic calcinosis cutis.

An 11-year-old boy presented generalized eruptive syringomas (ESs) associated with multiple milia-like whitish palmar papules corresponding to dermal calcium deposits. A relationship between calcium deposits distribution to an underlying eccrine duct was noted on pathology. The observation of dermal calcium deposits and its association with generalized ESs may support a possible sweat duct origin of this uncommon and peculiar form of superficial calcinosis cutis.

Solar Urticaria: An Ambispective Study in a Long-term Follow-up Cohort with Emphasis on Therapeutic Predictors and Outcomes.

Solar urticaria is a rare photodermatosis with several unknown pathogenic, clinical and therapeutic aspects. This study analysed the clinical and therapeutic features of a long-term follow-up solar urticaria cohort, with a focus on omalizumab management and outcomes, and characterized omalizumab response with the use of the high-affinity immunoglobulin E (IgE) receptor (FcεRI) and the Urticaria Control Test. An observational, unicentric, ambispective study was conducted from 2007 to 2023. Solar urticaria was diagnosed in 41 patients with a median follow-up of 60 months. Thirteen patients were prescribed omalizumab, with a median treatment time of 48 months. A significant decrease in FcεRI baseline levels and subsequent median increase in Urticaria Control Test was evidenced after omalizumab prescription in all patients. Drug survival at 48 months was at 88.9%. Omalizumab stepping-down protocol led to sustained omalizumab discontinuation in only 1 patient. Median basal Urticaria Control Test was lower (p < 0.01) in patients who were prescribed omalizumab and in patients without remission. This study contributes to our knowledge of omalizumab outcomes in real-life clinical practice and highlights the pathogenic importance of IgE-mediated pathways in solar urticaria, where FcεRI emerges as a possible biomarker of omalizumab response.

CLA+ memory T cells in atopic dermatitis: CLA+ T cells and atopic dermatitis.

Circulating skin-homing cutaneous lymphocyte-associated antigen (CLA)+ T cells constitute a small subset of human memory T cells involved in several aspects of atopic dermatitis: Staphylococcus aureus related mechanisms, the abnormal Th2 immune response, biomarkers, clinical aspects of the patients, pruritus, and the mechanism of action of targeted therapies. Superantigens, IL-13, IL-31, pruritus, CCL17 and early effects on dupilumab-treated patients have in common that they are associated with the CLA+ T cell mechanisms in atopic dermatitis patients. The function of CLA+ T cells corresponds with the role of T cells belonging to the skin-associated lymphoid tissue and could be a reason why they reflect different mechanisms of atopic dermatitis and many other T cell mediated skin diseases. The goal of this review is to gather all this translational information of atopic dermatitis pathology.

Therapeutic outcomes and survival analysis of Extramammary Paget's disease: A multicentre retrospective study of 249 patients.

BACKGROUND: Evidence regarding long-term therapeutic outcomes and disease-specific survival (DSS) in Extramammary Paget's disease (EMPD) is limited. OBJECTIVES: To assess the DSS and outcomes of surgical and nonsurgical therapeutic modalities in a large cohort of EMPD patients. METHODS: Retrospective chart review of EMPD patients from 20 Spanish tertiary care hospitals. RESULTS: Data on 249 patients with a median follow-up of 60 months were analyzed. The estimated 5-, 10-, and 15-year DSS was 95.9%, 92.9%, and 88.5%, respectively. A significantly lower DSS was observed in patients showing deep dermal invasion (≥1 mm) or metastatic disease (P < .05). A ≥50% reduction in EMPD lesion size was achieved in 100% and 75.3% of patients treated with surgery and topical therapies, respectively. Tumor-free resection margins were obtained in 42.4% of the patients after wide local excision (WLE). The 5-year recurrence-free survival after Mohs micrographic surgery (MMS), WLE with tumor-free margins, WLE with positive margins, radiotherapy, and topical treatments was 63.0%, 51.4%, 20.4%, 30.1%, and 20.8%, respectively. LIMITATIONS: Retrospective design. CONCLUSIONS: EMPD is usually a chronic condition with favorable prognosis. MMS represents the therapeutic alternative with the greatest efficacy for the disease. Recurrence rates in patients with positive margins after WLE are similar to the ones observed in patients treated with topical agents.

High-throughput RNA sequencing of the T cell receptor alpha and beta chains for simultaneous clonality and biological analyses in Sezary syndrome.

BACKGROUND: Previous investigations pointed out a role for antigen stimulation in Sezary syndrome (SS). High-throughput sequencing of the T cell receptor (TR) offers several applications beyond diagnostic purposes, including the study of T cell pathogenesis. METHODS: We performed high-throughput RNA sequencing of the TR alpha (TRA) and beta (TRB) genes focusing on the complementarity-determining region 3 (CDR3) in 11 SS and one erythrodermic mycosis fungoides (MF) patients. Five psoriasis patients were employed as controls. Peripheral blood CD4+ cells were isolated and RNA sequenced (HiSeq2500). High-resolution HLA typing was performed in neoplastic patients. RESULTS: Highly expanded predominant TRA and TRB CDR3 were only found in SS patients (median frequency: 94.4% and 93.7%). No remarkable CDR3 expansions were observed in psoriasis patients (median frequency of predominant TRA and TRB CDR3: 0.87% and 0.69%, p < 0.001 compared to SS). CDR3 almost identical to the predominant were identified within each SS patient and were exponentially correlated with frequencies of the predominant CDR3 (R2 = 0.918, p < 0.001). Forty-six different CDR3 were shared between SS patients displaying HLA similarities, including predominant TRA and TRB CDR3 in one patient that were found in other three patients. Additionally, 351 antigen matches were detected (Cytomegalovirus, Epstein-Barr, Influenza virus, and self-antigens), and the predominant CDR3 of two different SS patients matched CDR3 with specificity for Influenza and Epstein-Barr viruses. CONCLUSIONS: Besides detecting clonality, these findings shed light on the nature of SS-related antigens, pointing to RNA sequencing as a useful tool for simultaneous clonality and biological analysis in SS.

Are multi-detector computed tomography and cone-beam computed tomography exams and software accurate to measure the upper airway? A systematic review.

BACKGROUND: Cone-beam computed tomography (CBCT) has several applications in various fields of dental medicine such as diagnosis and treatment planning. When compared to computed tomography (CT), CBCT's radiation exposure dose is decreased by 3%-20%. However, CBCT produces more scattered signals and may present poorer image quality when compared to medical CT. OBJECTIVES: To review the findings regarding the accuracy of multi-detector computed tomography (MDCT) and CBCT and to compare the different software programs that segment the upper airway. SEARCH METHODS: Three databases (PubMed, Medline, and Web of Science) were searched for articles and a manual search was performed. SELECTION CRITERIA: The inclusion criteria were defined following the PICO framework: P-any patient with a CBCT or CT; I-dimensional evaluation of the upper airway using MDCT or CBCT; C-phantoms; O-the primary outcome was MDCT and CBCT accuracy, the secondary outcome was the evaluation and comparison of software programs used to segment the upper airway. DATA COLLECTION AND ANALYSIS: Articles that met eligibility criteria were assessed using the Critical Appraisal Skills Program Checklist. RESULTS: Among the 16 eligible studies, 6 articles referred to the accuracy of MDCTs or CBCTs and 10 to the accuracy of the software. Most articles were qualified as high quality. CONCLUSIONS: MDCT and CBCT scans' accuracy in upper airway dimensional measurements depends on machine brand, parameters, and segmentation technique. Regarding the segmentation technique, 12 programs were studied. Most either underestimated or overestimated upper airway measurements. In particular, OnDemand3D and INVIVO showed poor accuracy. On the contrary, Invesalius, and MIMICS were accurate in assessing nasal cavities when using an interactive threshold. However, results varied due to methodological differences among the studies. Finally, fully automatic segmentation based on artificial intelligence may represent the future of airway segmentation because it is faster and seems to be accurate. However, further studies are necessary. REGISTRATION: This study was registered in Prospero (International Prospective Register of Systematic Reviews) with the ID number CRD42022373998.

Autoimmune Diseases and Low Baseline IgE in Chronic Spontaneous Urticaria: A Clinical and Therapeutic Prospective Analysis in Real-Life Clinical Practice.

BACKGROUND: Autoimmunity contributes to the pathogenesis of chronic spontaneous urticaria (CSU). The subtyping of CSU has revealed an autoimmune form of CSU. Despite autoimmune diseases having been associated with CSU, there are few prospective studies that have evaluated the characteristics and biomarkers of patients with CSU and autoimmune disease in a real-life practice setting. OBJECTIVE: To evaluate the presence of specific biomarkers for the presence of autoimmune disease in CSU and to analyze the clinical and therapeutic features of patients with CSU and autoimmune disease. METHODS: The clinical, laboratory, and therapeutic features of patients with CSU at a tertiary-level center were prospectively collected. Data obtained were compared in function of the presence/absence of autoimmune disease and typified according to IgE levels. RESULTS: Patients with CSU who had associated autoimmune disease corresponded to middle-aged women with a common pattern of blood test findings: both low baseline IgE and high-affinity receptor of IgE expression, basopenia, eosinopenia, higher baseline erythrocyte sedimentation rate and D-dimer, increased presence of antinuclear antibodies, IgG against thyroid peroxidase, and positive autologous serum skin test result. Total baseline IgE less than or equal to 43.8 IU/mL was both the optimal cutoff to predict autoimmune disease in the CSU cohort and a significant risk factor for the presence of autoimmune disease in the regression analysis. CONCLUSIONS: In real-life clinical practice, characteristics of patients with CSU and autoimmune disease share common features with type IIb autoimmune CSU. Total baseline IgE less than or equal to 43.8 IU/mL has been detected as a possible biomarker of autoimmune disease in patients with CSU.

Melanoma-specific survival is worse in the elderly: a multicentric cohort study.

We aimed to characterise cutaneous melanoma in the elderly and determine its association with poorer prognosis. We studied a prospective cohort of the melanoma population in Catalonia between 2012 and 2016. We compared young patient group (<75 years old) with elderly patient group (≥75 years old). We included 3009 patients (52.5% women) from 14 centres, with a mean age at diagnosis of 61.1 years. In the ≥75-year-old group there was a predominance of men (53.9% vs. 45.5%, P  < 0.001), melanoma was more frequently located in the head and neck area (37.7% vs. 15.5%, P  < 0.001) and lentigo maligna melanoma subtype was significantly more frequent (31.4% vs. 11.6%, P  < 0.001), as were nodular melanoma and acral lentiginous melanoma ( P  < 0.001). In older people, Breslow index, the presence of ulceration and mitotic rate were higher than in younger people. Kaplan-Meier survival curves showed longer melanoma-specific survival (MSS) and melanoma-free survival (MFS) in <75-year-old group compared to the elderly group. Cox regression models demonstrated reduced MSS in patients ≥75 years regardless of gender, location, IB, ulceration and lymph node status at diagnosis (HR 1.54, P  = 0.013) whereas MFS was not independently associated with elderly when head and neck location was considered. Age appears to be an independent risk factor for MSS but not for MFS. Worse melanoma prognosis in elderly could be explained by factors unrelated to the tumour, such as age-related frailty and comorbidities that limit the access to systemic treatments and, eventually, age-related immune dysfunction.

Hemosiderotic Xanthelasmas. A New Clinicopathological Variant of Xanthelasma Palpebrarum or a Localized Variant of Xanthosiderohistiocytosis of the Eyelids?

ABSTRACT: Xanthelasma palpebrarum represent the most common subtype of cutaneous plane xanthomas. Xanthosiderohistiocytosis is considered a rare variant of xanthoma disseminatum, with only 4 cases reported to date. We report the case of a man with progressive pigmented lesions on the 4 eyelids that could correspond to hemosiderotic xanthelasmas or a localized variant of xanthosiderohistiocytosis.