Cutaneous Disease Research Articles

P105 Adult-onset mastocytosis: a retrospective review

Abstract Mastocytosis is characterized by an abnormal proliferation of mast cells in different organs, with the skin being the most frequently affected site. Adult-onset mastocytosis often follows a chronic course and is more likely to have extracutaneous involvement. We undertook a retrospective case note review of adult patients with a diagnosis of mastocytosis in our dermatology department between 2021 and 2022. Fourteen patients were identified with a female-to-male ratio of 1.8 : 1. Median age at disease onset was 46 years (range 25–75). Lesions were described as maculopapular (n = 8), macular (n = 3), telangiectatic (n = 2) and urticated (n = 1). The torso was affected in 12 patients (86%). The most commonly reported symptom was pruritus (n = 9). Other complaints included flushing (n = 3), abdominal pain (n = 2), dizziness (n = 2), weight loss (n = 2), night sweats (n = 2), syncope (n = 1), musculoskeletal pain (n = 1) and symptoms of recurrent anaphylaxis (n = 1). Two patients were asymptomatic. Darier sign was elicited in five patients and negative in two (not documented in seven). Eight patients were assessed for lymphadenopathy and organomegaly, with no detected abnormality. Eleven patients had skin biopsies; 10 (91%) had mastocytosis in the skin confirmed on histology; one patient had a nondiagnostic histological finding, but mastocytosis was diagnosed on the basis of clinical presentation. Seven patients had elevated serum tryptase levels (> 20 ng mL−1) on at least one occasion. Bone densitometry was done in five patients with elevated serum tryptase: two had osteopenia and one had osteoporosis. Eleven patients underwent bone marrow examination. Mast cell infiltration of the bone marrow was detected in four patients; KIT mutations in bone marrow were subsequently identified in three patients. Twelve patients remain under long-term follow-up. Treatments prescribed included antihistamine (n = 10), epinephrine autoinjector (n = 6), topical steroids (n = 5), vitamin D (n = 5), calcium (n = 4), H2 blocker (n = 2), bisphosphonates (n = 2), phototherapy (n = 2), leukotriene antagonists (n = 2), cosmetic camouflage (n = 1), oral sodium cromoglicate (n = 1) and KIT–tyrosine kinase inhibitor (n = 1). Despite treatments, none of the patients had regression (partial or complete) of cutaneous disease, although no fatal outcome was observed. Four (29%) cases had a final diagnosis of indolent systemic mastocytosis (all had elevated serum tryptase levels, two had anaemia). Our findings were consistent with the literature, where serum tryptase levels rather than systemic symptoms were a reliable predictor of systemic mastocytosis. Interestingly, 10 (71%) patients had mastocytosis limited to the skin, which is in contrast to the published literature, where the majority of people with adult-onset mastocytosis have systemic forms of the disease.

Loss of epidermal glucocorticoid receptor protects against whole body metabolic dysfunction upon chronic corticosterone treatment

ObjectiveGlucocorticoid (GC) excess contributes to the development of metabolic syndrome, defined by visceral obesity, abnormal glucose tolerance, and dyslipidemia. While it is accepted that loss of metabolic control is causative of cutaneous diseases, the systemic effects of epidermal dysfunction have received limited attention. Importantly, independent of GC blood levels, skin synthesis of these hormones can provide tissue-specific variations that may affect global homeostasis. We aimed to assess whether the epidermal-specific loss of the GC receptor (GR) had an impact on the dermal white adipose tissue (dWAT), a specialized fat depot functionally different from other fat pads, as well as on whole body homeostasis. MethodsGR epidermal KO (GREKO) and control female mice were treated with oral corticosterone (CORT) for 4 weeks, a protocol inducing metabolic dysfunction. Metabolic parameters including body weight, visceral and hepatic fat accumulation, blood glucose and insulin levels, glucose tolerance tests upon fasting, and triglycerides levels, were determined. Systemic alterations of soluble factors with known roles in immunity and inflammation were also assessed by a multiplex antibody array system containing selected cytokines, chemokines, and growth factors. The levels of cutaneous GCs and the profile of skin-secreted factors were determined in tissue explants by ELISA and the multiplex array system. Morphometric studies quantitated changes in dWAT thickness and adipocyte size in both genotypes, basally and at the end of CORT treatment. The expression of adipocyte markers was assessed in purified dermal adipocytes in vehicle and CORT-treated GREKOvs controls. ResultsDespite similar circulating levels of GCs, GREKO mice were highly resistant to CORT-induced systemic metabolic anomalies including body weight gain, visceral and hepatic fat, hyperglycemia, insulinemia, and elevated levels of plasma triglycerides, leptin, FGF-21, PAI-1, and CCL11. GREKO mice featured constitutively enhanced levels of cutaneous GCs relative to controls at least partially due to keratinocyte-specific increased expression of the critical steroidogenic enzyme Cyp11b1. Also, the higher ratio of skin-secreted protective vs inflammatory adipokines in GREKOvs controls, correlated with higher capacity of adipogenic conversion in experiments using conditioned media from tissue explants. Following CORT treatment, relative to controls, GREKO mice featured reduced dWAT hyperplasia and adipocyte hypertrophy, with increased Adipoq and decreased Lipocalin 2 expression in purified dermal adipocytes. ConclusionsOverall data suggest that epidermal GR loss results in paracrine actions on dermal adipocytes as well as endocrine actions on key metabolic tissues that significantly improve the whole body metabolism in a mouse model of metabolic dysfunction.

The Impact of COVID-19 Vaccination on Inflammatory Skin Disorders and Other Cutaneous Diseases: A Review of the Published Literature

Background: Four vaccines have been authorized by the European Medicines Agency (EMA): viral vector-based vaccines (AstraZeneca; AZD1222 and Johnson & Johnson; Ad26.COV2. and 2 mRNA-based vaccines (Pfizer/BioNTech; BNT162b2 and Moderna; mRNA-1273). Adverse events (AEs) related to vaccination have been described in the literature. The main aim of the dermatological practice was to avoid the diffusion of COVID-19, allowing the continuity of care for patients. Objective: The aim of this review article is to investigate current literature regarding cutaneous reactions following COVID-19 vaccination, mainly inflammatory dermatological diseases. Materials and methods: Investigated manuscripts included metanalyses, reviews, letters to the editor, real-life studies, case series, and reports. Results: We selected a total of 234 articles involving more than 550 patients. We have divided the results section into various sub-sections to ensure greater understanding for readers. Conclusions: Clinicians should keep in mind the possibility of new onsets or the worsening of several dermatoses following vaccination in order to promptly recognize and treat these AEs. Certainly, vaccination should not be discouraged.

Blue-ringed octopus-inspired microneedle patch for robust tissue surface adhesion and active injection drug delivery.

Intratissue topical medication is important for the treatment of cutaneous, mucosal or splanchnic diseases. However, penetrating surface barriers to providing adequate and controllable drug delivery while guaranteeing adhesion in bodily fluids remains challenging. Here, the predatory behavior of the blue-ringed octopus inspired us with a strategy to improve topical medication. For effective intratissue drug delivery, the active injection microneedles were prepared in a manner inspired by the teeth and venom secretion of blue-ringed octopus. With on demand release function guided by temperature-sensitive hydrophobic and shrinkage variations, these microneedles can supply adequate drug delivery at an early stage and then achieve the long-term release stage. Meanwhile, the bionic suction cups were developed to facilitate microneedles to stay firmly in place (>10 kilopascal) when wet. With wet bonding ability and multiple delivery mode, this microneedle patch achieved satisfactory efficacy, such as accelerating the ulcers' healing speed or halting early tumor progression.

Surveillance of diphtheria in the Netherlands between 2000–2021: cutaneous diphtheria supersedes the respiratory form

BackgroundDiphtheria is a severe respiratory or cutaneous infectious disease, caused by exotoxin producing Corynebacterium diphtheriae, C. ulcerans and C. pseudotuberculosis. Diphtheria is once again prevalent due to breakdown of immunisation programmes, social disruption and unrest.AimThis study describes the notified diphtheria cases in the Netherlands between 2000–2021 and isolates that were sent to the National Institute for Public Health and the Environment (RIVM).MethodsFile investigation was performed including all notified cases and isolates of C. diphtheriae, C. ulcerans and C. pseudotuberculosis that were tested for toxin production using a toxin-PCR and Elek test. An exploratory review was performed to understand transmission in populations with a high vaccination uptake.ResultsEighteen diphtheria notifications were made with confirmed toxigenic C. diphtheriae (n = 9) or ulcerans (n = 9) between 2000 and 2021. Seventeen (94.4%) presented with a cutaneous infection. All cases with a suspected source abroad (n = 8) concerned infection with C. diphtheriae. In contrast, 9/10 cases infected in the Netherlands were caused by C. ulcerans, a zoonosis. Secondary transmission was not reported. Isolates of C. ulcerans sent to the RIVM produced more often the diphtheria exotoxin (11/31; 35%) than C. diphtheriae (7/89; 7.9%).ConclusionBoth human-to-human transmission of C. diphtheriae and animal-to-human transmission of C. ulcerans rarely occurs in the Netherlands. Cases mainly present with a cutaneous infection. Travel-related cases remain a risk for transmission to populations with low vaccination coverage, highlighting the importance of immunization and diphtheria control measures.

Diagnostic capacity for cutaneous fungal diseases in the African continent.

Cutaneous fungal infections are very common, especially in poorer communities and with intercurrent HIV infection. Determining the fungal pathogen in skin-related fungal neglected tropical diseases (NTDs) determines optimal therapy. We undertook a country survey across many African countries to determine the diagnostic capacity for skin fungal diseases. A detailed questionnaire was delivered to country contacts to collect data on availability, frequency, and location of testing for key diagnostic procedures and followed up with 2 rounds of validation by video call and by confirmation of individual country data confirmation by email. Of 47 countries with data, seven (15%) and 21 (45%) do not offer skin biopsy in the public or private sector, respectively, but 22 (46%) countries do it regularly, mostly in university hospitals. Direct microscopy is often performed in 20 of 48 (42%) countries in the public sector and not done in 10 (21%). Fungal cultures are often performed in 21 of 48 (44%) countries in the public sector but not done in nine (20%) or 21 (44%) in either public or private facilities. Histopathological examination of tissue is frequently used in 19 of 48 (40%) countries but not in nine (20%) countries in the public sector. The cost of diagnostics to patients was a major limiting factor in usage. Major improvements in the availability and use of diagnostic tests for skin, hair, and nail fungal disease are urgently needed across Africa.

Climate Change, Skin Health, and Dermatologic Disease: A Guide for the Dermatologist.

Climate change has a pervasive impact on health and is of clinical relevance to every organ system. Climate change-related factors impact the skin's capacity to maintain homeostasis, leading to a variety of cutaneous diseases. Stratospheric ozone depletion has led to increased risk of melanoma and keratinocyte carcinomas due to ultraviolet radiation exposure. Atopic dermatitis, psoriasis, pemphigus, acne vulgaris, melasma, and photoaging are all associated with rising levels of air pollution. Elevated temperatures due to global warming induce disruption of the skin microbiome, thereby impacting atopic dermatitis, acne vulgaris, and psoriasis, and high temperatures are associated with exacerbation of skin disease and increased risk of heat stroke. Extreme weather events due to climate change, including floods and wildfires, are of relevance to the dermatologist as these events are implicated in cutaneous injuries, skin infections, and acute worsening of inflammatory skin disorders. The health consequences as well as the economic and social burden of climate change fall most heavily on vulnerable and marginalized populations due to structural disparities. As dermatologists, understanding the interaction of climate change and skin health is essential to appropriately manage dermatologic disease and advocate for our patients.

Validation of Cutaneous Dermatomyositis Disease Area and Severity Index Activity Score and Other Efficacy Outcomes as Measures of Skin Disease in Dermatomyositis in the Lenabasum Phase 3 Trial

In the past decade, there have been six industry-sponsored phase 3 trials in adult patients with dermatomyositis (DM), primarily focusing on improving muscle weakness. However, skin disease is a cardinal manifestation of DM. This study evaluated the sensitivity of Cutaneous Dermatomyositis Disease Area and Severity Index Activity score, Cutaneous Dermatomyositis Activity Investigator Global Assessment, Total Improvement Score, and other outcome measures used in DM clinical trials to detect improvement in DM skin disease activity. Data analyzed from the lenabasum phase 3 trial in DM showed that improvement in Cutaneous Dermatomyositis Disease Area and Severity Index Activity score increased proportionately with the degree of patient- or physician-reported improvement in skin disease, consistently measuring improvement when clinically meaningful improvement was reported at weeks 16-52. In contrast, Cutaneous Dermatomyositis Activity Investigator Global Assessment measured little change from baseline with reported no improvement in skin disease but also a similar change from baseline with slight improvement. No Skindex-29+3 subscale performed well at reflecting increasing degrees of improvement in skin disease. Extramuscular Global Assessment and Total Improvement Score generally showed increasing levels of improvement as the degree of patient- and physician-reported improvement in skin disease increased, but these are composite measures and are not specific to improvement in DM skin disease. To measure clinically meaningful improvement in skin disease in a DM trial, Cutaneous Dermatomyositis Disease Area and Severity Index Activity score is the more sensitive outcome measure across time points.

Assessment of cutaneous disease activity in early lupus and its correlation with quality of life: a cross-sectional study.

Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease with varied dermatological manifestations that are almost universal. Overall, lupus disease has a major effect on the quality of life in these patients. We assessed the extent of cutaneous disease in early lupus and correlated it with the SLE quality-of-life (SLEQoL) index and disease activity measures. Patients diagnosed as SLE with the skin involved were recruited at the first presentation and were assessed for cutaneous and systemic disease activity using the cutaneous lupus erythematosus disease area and severity index (CLASI) and the Mexican-SLE disease activity index (Mex-SLEDAI), respectively. Quality of life was assessed with the SLEQoL tool while systemic damage was captured by the SLICC damage index. Fifty-two patients with SLE who had cutaneous involvement were enrolled (40, 76.9% females) with a median disease duration of 1month (1-3.7). The median age was 27.5years (IQR: 20-41). Median Mex-SLEDAI and SLICC damage index were 8(IQR: 4.5-11) and 0 (0-1), respectively. The median CLASI activity and damage scores were 3 (1-5) and 1 (0-1), respectively. Overall, there was no correlation between SLEQoL with CLASI or CLASI damage. Only the self-image domain of SLEQoL correlated with total CLASI (ρ = 0.32; p = 0.01) and CLASI-D (ρ = 0.35; p = 0.02). There was a weak correlation of CLASI with the Mexican-SLEDAI score (ρ = 0.30; p = 0.03) but not with the SLICC damage index. In this cohort of early lupus, cutaneous disease activity in lupus had a weak correlation with systemic disease. Cutaneous features did not appear to influence the quality of life except in the self-image domain.

Efficacy of homeopathy in association with autohemotherapy in the treatment of dogs with papillomatosis: Case report

Canine papillomatosis is an infectious-contagious pathology caused by the species-specific papillomavirus, characterized by benign neoformations, which can be manifested in the oral cavity, genital tract, lips, pharynx and esophagus. Sometimes, papillomas may occur in the plantar cushion and as a cutaneous disease. Disease transmission occurs by direct or indirect contact with secretions or blood from papillomas present in infected animals. Diagnosis is based on clinical and histopathological examinations. This study aims to report on the efficacy of homeopathic medicines in association with autohemotherapy for treating a 4-month-old American Pit Bull Terrier male dog diagnosed with oral papillomatosis. The treatment protocol was based on the exclusive use of the homeopathic drugs Kali sulphuricum, Thuya occidentalis and Acidum nitricum, associated with autohemotherapy. Complete remission of the papillomas occurred 30 days after treatment initiation, and the medication was maintained for six months to prevent recurrence. In conclusion, homeopathy and autohemotherapy can reorganize defense cells, providing the body with evident clinical improvement.

The evaluation of IgG4 and IgG expression in cutaneous Rosai-Dorfman disease

ObjectiveThe authors investigated the expression of IgG4 and IgG in cutaneous Rosai-Dorfman Disease (CRDD) to further improve the understanding of this disease. MethodsThe authors retrospectively reviewed the clinicopathological features of 23 CRDD patients. The authors diagnosed CRDD by the presence of emperipolesis and immunohistochemical (IHC) staining of histiocytes consisting of S-100(+)/CD68(+)/CD1a(-) cells. The expressions of IgG and IgG4 in cutaneous specimens were assessed by IHC (EnVision) and quantitatively calculated by a medical image analysis system. ResultsAll 23 patients, including 14 males and 9 females, were confirmed to have CRDD. Their ages ranged from 17 to 68 years (mean 47.91 ± 14.16). The most frequently affected skin regions were the face, followed by the trunk, ears, neck, limbs, and genitals. In 16 of these cases, the disease presented as a single lesion. IHC staining of sections showed that IgG was positive (≥ 10 cells/High-Power Field [HPF]) in 22 cases, while IgG4 was positive (≥ 10 cells/HPF) in 18 cases. Moreover, the IgG4/IgG proportion ranged from 1.7% to 85.7% (mean 29.50 ± 24.67%, median 18.4%) in the 18 cases. Study limitationsIn the majority of studies, as well as in the current study, the design. RDD is a rare disease, so the sample size is small. In the next studies to come, the authors will expand the sample for multi-center verification and in-depth study. ConclusionThe positive rates of IgG4 and IgG and the IgG4/IgG ratio assessed through IHC staining may be important in understanding the pathogenesis of CRDD.

Maintaining and Restoring Gradients of Ions in the Epidermis: The Role of Ion and Water Channels in Acute Cutaneous Wound Healing.

Significance: Aquaporins and ion channels establish and regulate gradients of calcium, sodium, potassium, chloride, water, and protons in the epidermis. These elements have been found to play significant roles in skin biology and wound healing. In this study, we review our understanding of these channels and ion gradients, with a special emphasis on their role in acute wound healing. Recent Advances: Specifically, we assess the temporal and spatial arrangements of ions and their respective channels in the intact skin and during wound and healing to provide a novel perspective of the role of ionic gradients through the various stages of wound healing. Critical Issues: The roles of gradients of ions and channels in wound healing are currently not well understood. A collective analysis of their traits and arrangements in the skin during wound healing may provide a new perspective and understanding of the functionality of gradients of ions and channels in skin biology and wound healing. Future Directions: It is important to elucidate how the gradients of ions and ion channels regulate and facilitate wound healing. A better understanding of the ionic environments may identify novel therapeutic targets and improved strategies to promote wound healing and possibly treat other cutaneous diseases.

Role of VivaScope 2500ex vivo confocal microscopy in skin pathology: Advantages, limitations, and future prospects.

Vivascope 2500 ex vivo confocal microscopy (EVCM) is an emerging optical imaging device that allows nuclear level resolution of freshly excised tissues. EVCM provides, rapid real-time pathological examination in many subspecialties of pathology including skin, prostate, breast, liver, etc. In contrast to traditional time-consuming frozen sectioning and histological analysis. To evaluate the current state of EVCM utilization. This study highlights the advantages, limitations, and prospects of EVCM in skin pathology. Our findings demonstrate that EVCM is a promising adjunctive tool to assess margins in Mohs surgery and to provide rapid, accurate diagnosis of cutaneous tumors, infectious and inflammatory diseases. EVCM is a revolutionary device that can be used as an adjunct to paraffin-fixed, hematoxylin and eosin-stained slides and frozen sectioning. Additional refinements are required before EVCM can be used as an alternative to frozen sectioning or traditional tissue processing.

Diseases caused by floods with a spotlight on the present situation of unprecedented floods in Pakistan: a short communication.

Few natural calamities surpass floods in their destructive capabilities. The recent floods in Pakistan were declared the world's deadliest since the South Asian floods of 2020 and were, by far, the most destructive floods in the country's history. They have resulted in significant loss of life and property and have served as the harbingers of cutaneous and noncutaneous diseases. These floods have dealt a critical blow to the country's already struggling healthcare system, which lacks resources for the prompt mobilization of medical personnel and resources to the flood-hit areas. Having lost their houses, the flood victims are wholly exposed to the elements. Lack of access to a clean water supply has predisposed them to a myriad of diseases. We believe that the consolidation of efforts by the national and international community will put an end to the plight of these flood victims. Our article highlights the significant diseases associated with floods, the challenges faced by the flood victims, and recommendations on how their situation can be improved.

Abstract 27: Demographic Factors Associated with Extracutaneous Involvement in Kaposi Sarcoma

Abstract Purpose: Kaposi sarcoma (KS) is a soft tissue tumor that typically presents with red or purple skin lesions. However, extracutaneous involvement can occur in severe disease. The National Cancer Database (NCDB) compiles data from 1,400 cancer programs across the United States; to our knowledge, there has yet to be a study in the NCDB comparing demographic features and presentation of KS with cutaneous versus extracutaneous disease. Thus, there is a need to characterize the KS cohort with regards to primary site. Methods: We conducted a retrospective analysis of the NCDB from 2004 to 2019 for Kaposi sarcoma patients (n=5,587). Analysis was completed between patients with cutaneous (n=3,963) and extracutaneous (n=1,624) involvement using Pearson Chi-square and t-tests. Survival was estimated using Kaplan-Meier curves. Results: Non-cutaneous lesions made up 29.1% of diagnoses and primarily included connective/subcutaneous tissue (12.2%), as well as digestive organs (4.1%). Median survival was lower in the extracutaneous (101.7 months) cohort compared to cutaneous (131.5 months) cohort (p<0.001). Women were more likely to present with non-cutaneous lesions compared to men (37.3% versus 27.6%, p<0.001). Spanish/Hispanic subjects were less likely to have extracutaneous involvement compared to non-Spanish/Hispanic subjects (p=0.006). Patients at academic centers were less likely to have extracutaneous lesions compared to other facilities (p<0.001). Residing in the Central United States was associated with increased incidence of extracutaneous disease (p<0.001). Patients with extracutaneous disease lived further from the reporting hospital (23.95 miles) compared to patients with cutaneous (16.24 miles) involvement (p=0.004). There was no significant difference in mean age between cutaneous (58.41 years) and non-cutaneous (57.97 years) cohorts. No clear trend existed between race, insurance status, education, or income in relation to extracutaneous disease. Conclusion: To our knowledge, our study is the first to compare demographic features and trends associated with cutaneous and extracutaneous KS in the NCDB. We revealed that extracutaneous primary site is associated with poorer survival and highlighted several significant differences between the cohorts. Citation Format: Michelle Swedek, Xinxin Wu, Peter Silberstein, Victoria Vardell. Demographic Factors Associated with Extracutaneous Involvement in Kaposi Sarcoma [abstract]. In: Proceedings of the 11th Annual Symposium on Global Cancer Research; Closing the Research-to-Implementation Gap; 2023 Apr 4-6. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(6_Suppl):Abstract nr 27.

A multicenter phase II study of cabozantinib + nivolumab for patients (pts) with advanced angiosarcoma (AS) previously treated with a taxane (Alliance A091902).

11503 Background: Collectively, sarcomas have demonstrated less benefit from immunotherapy than many other cancers. Pts with AS have limited options, particularly after taxane chemotherapy. Although AS is a vascular malignancy, anti-VEGF therapies have minimal monotherapy clinical activity. Some cutaneous AS have a high UV damage signature, but other AS often do not. Cabozantinib (C) is a multikinase inhibitor that may alter PD-1 expression in regulatory T cells, promoting an immune permissive environment when combined with nivolumab (N), a fully human anti PD-1 MAB. We hypothesize that the combination of C+N will be an effective therapy in AS, across AS subtypes. Methods: This open-label multi-arm study enrolled pts with locally advanced/metastatic AS. Arm 3, reported here, enrolled pts who had received a taxane for AS (including adjuvant) prior to study enrollment. Pts were not restricted on number of prior lines, but prior anti-VEGF and immunotherapies were not allowed. Eligible pts received C (40 mg po daily) with N (480 mg IV every 4 wks). Treatment was permitted beyond progressive disease (PD) in the 1st 12 wks (4 wk confirmatory scan), but PD response was censored at 12 wks. The Simon 2-stage design (null and alternative overall response rate (ORR) were 10% and 35%, respectively) required ≥1 confirmed response in 9 pts in the 1st stage, and >4 of 18 pts (91.4% power, alpha 0.095) for the primary endpoint. Secondary endpoints were adverse events (AEs), progression free, overall survival (PFS, OS), and pt-reported outcomes (PRO). Results: 21 eligible pts [median age 66 yrs (32-92), 10 female] received ≥1 dose of C+N. Primary disease sites: 12 cutaneous (scalp/face), 1 liver, 2 breast, 6 other. All pts received prior taxanes (11/21 = 52% as adjuvant therapy) and 5/21 (24%) had also received prior anthracycline (all relapsed AS). Primary endpoint: 13 of the first 18 evaluable patients (72%) experienced objective response (OR, 95%CI: 47%-90%). After a median follow-up of 11.2 mo, 13 of 21 pts achieved OR (11 partial response, 2 complete), for ORR 62% (95%CI: 38-82%). Responses were seen in pts with primary cutaneous disease 7/12 (58%) and noncutaneous disease 6/9 (67%). Median PFS was 9.6 mo (5.3-NR), and OS 20.5 mo (14.4-NR). Off treatment reasons include: progressive disease (14), comorbid condition unrelated to AS or study (1); 6 pts remain on study. Grade (G) 3 hypertension was the only possibly treatment related AE (TRAE) occurring in ³10%. No G 4/5 TRAE were reported. Conclusions: C + N demonstrated significant antitumor activity in taxane-pretreated AS and was well tolerated without new safety concerns. Activity of the combination was seen across AS subtypes. PRO and exploratory analyses are ongoing. Support: U10CA180821, U10CA180882, U24 CA196171; U10CA180820; https://acknowledgments.alliancefound.org . U10CA180868; U10CA180888. NCT04339738. Clinical trial information: NCT04339738 .

Light chain deposition disease: spotlight on a rare cutaneous disease.

Light chain deposition disease: spotlight on a rare cutaneous disease.

Pityriasis lichenoides presented with skin rash mimicking Urticaria: A case report.

Acute urticaria is urticaria with or without angioedema that is present for less than six weeks, while chronic urticaria is present for more than six weeks. Pityriasis lichenoides (PL) is a benign cutaneous inflammatory disease of unknown etiology. Acute PL typically resolves within a few weeks, while chronic PL lasts several months. The skin rash of PL may resemble the rash of other conditions, so the distinction is essential and depends on history and physical examination and is confirmed by skin biopsy. A 64-year-old gentleman presented with seven days history of generalized itchy skin (hives). Individual lesions last 24-48 hours and do not leave pigmentation or scarring. No systemic involvement. No specific triggers, with two previous similar episodes 30 years and 20 years ago. Levocetirizine, 5 mg tablet, was prescribed, and he was instructed to increase the dose to 4 tablets daily if needed. On reassessing the patient after ten days, he did not respond well. The rash was different from the initial one, with individual lesions lasting for five days or more, so he was referred to a dermatologist for a skin biopsy. Basic investigations were normal. Performing skin biopsy is needed to exclude other pathologies. Skin biopsy showed pathological changes of lichenoid dermatitis compatible with pityriasis lichenoides et varioliformis acuta (PLEVA). He has been treated with azithromycin 250 mg daily for three weeks with rapid and complete resolution without scaring. Urticarial rash may mimic the skin rash of other conditions. Detailed serial history and physical examination are warranted to exclude other diagnoses. Skin biopsy is needed when diagnosing conditions other than urticaria are suspected.

SIRT1 downregulation provokes immune-inflammatory responses in hair follicle outer root sheath cells and may contribute to development of alopecia areata

BackgroundSilent information regulator 1 (SIRT1), a type III histone deacetylase, is involved in various cutaneous and systemic autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, and psoriasis. However, little is known about the role of SIRT1 in the development of alopecia areata (AA). ObjectivesThis study investigated whether SIRT1 regulates the hair follicle immune system and is involved in AA pathogenesis. MethodsSIRT1 expression in human scalp tissue was analyzed using immunohistochemical staining, qPCR, and western blotting. The regulatory effect of SIRT1 was evaluated after stimulation with the double-stranded RNA mimic polyinosinic:polycytidylic acid (poly I:C) in hair follicle outer root sheath (ORS) cells and C3H/HeJ mice. ResultsSIRT1 expression was significantly reduced in the AA scalp compared to the normal scalp. SIRT1 inhibition upregulated MHC class I polypeptide-related sequence A and UL16 binding protein 3 in hair follicle ORS cells. SIRT1 inhibition also promoted the production of Th1 cytokines (IFN-γ and TNF-α), IFN-inducible chemokines (CXCL9 and CXCL10), and T cell migration in ORS cells. Conversely, SIRT1 activation suppressed the autoreactive inflammatory responses. The counteractive effect of the immune response by SIRT1 was mediated through the deacetylation of NF-κB and phosphorylation of STAT3. ConclusionSIRT1 downregulation induces immune-inflammatory responses in hair follicle ORS cells and may contribute to AA development.

Factors associated with mask-induced dermatosis and its impact on patients' quality of life.

The COVID-19 pandemic continues to have a significant impact on society, both physically and mentally. Mask use in public places has been made mandatory in many countries, as it is one of the most effective methods to prevent transmission of the virus. However, continuous mask usage has been associated with the emergence of various cutaneous diseases in the areas of contact with the mask. This study aimed to evaluate the effect of various cutaneous manifestations resulting from mask use on patients' quality of life through a questionnaire survey. This was a cross-sectional study conducted at a hospital from May to July 2022. Patients who had experienced skin symptoms related to mask use in the past or present were included in the study. Participants completed the questionnaire with informed consent. A total of 165 participants participated in the survey, with the most common complaint being itching (58.18%), followed by acne (52.73%). Itching was found to have the highest dermatology life quality index score. Patients with skin redness had a lower quality of life compared to those without it. Prolonged mask-wearing can result in skin diseases that can seriously impair patients' quality of life.