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Dermoscopic Features of Subcorneal Hematoma on the Palms and Soles: Differences from Acral Melanoma. 手掌和足底角膜下血肿的皮肤镜特征:与角黑色素瘤的区别。
Sang-Hyeon Won, Kyung-Nam Bae, Kihyuk Shin, Hoon-Soo Kim, Hyun-Chang Ko, Byung-Soo Kim, Moon-Bum Kim

Background: The diagnosis of subcorneal hematoma (SH) can be challenging because the clinical presentation of SH can resemble melanocytic lesions. Few studies have examined the characteristic dermoscopic features of SH, but a more detailed large-scale study is needed to overcome the diagnostic challenge of differentiating it from acral melanoma.

Objectives: To describe the dermoscopic features of SH.

Methods: We evaluated the clinical and dermoscopic features of 50 SH lesions from 43 patients at the Pusan National University Hospitals (Busan and Yangsan).

Results: In the color analysis, 86% of cases showed the bruise color sign; 7 cases had a single color (red to purple: 2; black: 1; brown: 4). Typical dermoscopic features of SH, acral nevi, and acral melanoma-associated patterns were observed in 60%, 0%, and 72% of lesions, respectively. Hematoma-associated patterns were homogenously red-to-black with or without satellite globules (32%) and pebbles on the ridges (28%). Acral melanoma-associated patterns showed a parallel ridge pattern (PRP) (52%), irregular dots and globules (50%), polychromia (34%), asymmetry (24%), irregular blotches (10%), and ulcers (10%). No case showed blue-white veils, regression structures, atypical vascular patterns, or irregular fibrillar patterns. The bruise color sign was positive in most cases, with acral melanoma-associated patterns (88.9%).

背景:角膜下血肿(SH)的诊断具有挑战性,因为其临床表现可能与黑色素细胞病变相似。很少有研究探讨了角膜下血肿的皮肤镜特征,但需要进行更详细的大规模研究,以克服将角膜下血肿与口角黑色素瘤相鉴别的诊断难题:描述SH的皮肤镜特征:方法:我们评估了釜山大学医院(釜山和梁山)43名患者的50个SH皮损的临床和皮肤镜特征:在颜色分析中,86%的病例表现为瘀斑色征;7 例病例为单一颜色(红色至紫色:2 例;黑色:1 例;棕色:4 例)。在 60%、0% 和 72% 的病变中分别观察到 SH、尖锐痣和尖锐黑色素瘤相关模式的典型皮肤镜特征。与血瘤相关的图案为均匀的红黑色,伴有或不伴有卫星球(32%),以及脊上的卵石(28%)。口腔黑色素瘤相关形态表现为平行脊形态(PRP)(52%)、不规则点状和球状(50%)、多色(34%)、不对称(24%)、不规则斑点(10%)和溃疡(10%)。没有病例出现蓝白色纱幔、回归结构、非典型血管形态或不规则纤维形态。大多数病例的瘀斑颜色征呈阳性,并伴有尖锐黑色素瘤相关形态(88.9%)。
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引用次数: 0
Hypersensitivity Reactions to Homemade Topical Preparations. 自制外用制剂的过敏反应。
Mislav Rončević, Katarina Radas, Suzana Ljubojević Hadžavdić

Homemade topical preparations are becoming increasingly popular due to the widespread belief that herbal and natural products are a safer and better option in the treatment of various conditions. However, homemade topical preparations can precipitate allergic and irritant reactions, depending on the herbal composition of the preparation. Hypersensitivity reactions to such preparations range from contact allergic dermatitis, contact irritant dermatitis, contact urticaria, toxic reaction, photosensitivity, and phototoxic reaction. In Europe, and especially in the Mediterranean area, medicinal herbs from the Compositae family and aromatic Mediterranean herbs are most frequently used in the formulation of topical preparations. Although plants are regarded as strong sensitizers, the number of reported cases of hypersensitivity reactions is relatively small. The problems are limitations in diagnostics due to the lack of necessary patch test substances and the danger of active sensitization during testing. Caution is required in patients prone to allergies and those with existing dermatoses, who should be advised to use registered preparations. The first step in management is cessation of exposure, followed by implementation of topical corticosteroids. Systemic corticosteroid therapy is reserved for more severe cases.

由于人们普遍认为草药和天然产品是治疗各种疾病的更安全、更好的选择,自制外用制剂越来越受欢迎。然而,自制外用制剂可能会引发过敏和刺激反应,这取决于制剂中的草药成分。对这类制剂的过敏反应包括接触性过敏性皮炎、接触性刺激性皮炎、接触性荨麻疹、毒性反应、光敏性反应和光毒性反应。在欧洲,尤其是在地中海地区,菊科药用植物和地中海芳香植物最常用于配制外用制剂。虽然植物被认为是强致敏剂,但报告的超敏反应病例数量相对较少。问题在于,由于缺乏必要的斑贴试验物质,诊断受到限制,而且在试验过程中存在主动致敏的危险。对于易过敏的患者和已有皮肤病的患者应谨慎使用,建议他们使用注册制剂。治疗的第一步是停止接触,然后使用局部皮质类固醇。全身性皮质类固醇治疗适用于较严重的病例。
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引用次数: 0
Switching between JAK Inhibitors in Patients with Atopic Dermatitis: Unanswered Questions in Daily Clinical Practice. 特应性皮炎患者更换 JAK 抑制剂:日常临床实践中的未解之谜。
Styliani Mastraftsi, Michail Bakakis, Aikaterini Tsiogka, Ileana Afroditi Kleidona, Stamatios Gregoriou

Data on switching between agents in patients with atopic dermatitis (AD) are scarce (1-3). We report the case of a patient with severe AD and inadequate response to upadacitinib who showed a complete response after switching to abrocitinib. A 23-year-old male patient with severe AD was enrolled in the Measure Up double-blind, placebo-controlled, phase 3 randomized clinical trial. At baseline, the Eczema Area Severity Index (EASI) was 50.6, the Investigator's Global Assessment (IGA) was 4, the affected Body Surface Area (BSA) was 80%, and the Worst Pruritus-Numeric Rating Scale (WP-NRS) was 10/10 (Figure 1). At week 124, the patient discontinued participation in the trial, while EASI was 9.2, IGA 3, BSA 20%, and WP-NRS 5/10 at the time. After one month off treatment, and while expecting unblinding, the patient again presented with exacerbation of AD, since EASI was 45.6, IGA 4, BSA 80%, and WP-NRS 10/10. At that point of time, access to both dupilumab and tralokinumab was not available in Greece, while upadacitinib was avoided due to inadequate patient satisfaction, partly due to recurrent ocular herpes simplex infections during the previous upadacitinib treatment. The patient was prescribed abrocitinib 200 mg daily. One month after initiation of therapy, the patient achieved complete control of the disease (EASI 0.0, IGA 0, BSA 0%, and WP-NRS 0/10) (Figure 2). This has been maintained with no reported adverse events after 12 months of continuous treatment. After unblinding, the patient was confirmed to have received 15 mg of upadacitinib daily during his participation in the clinical trial. When to switch agents in the treatment of patients with severe AD if the response is not adequate, and what agent to switch to, is an issue that is not clearly defined. Data available from the JADE EXTEND study concluded that patients failing to achieve efficacy outcomes with dupilumab can benefit from switching to both doses of abrocitinib (1). However, a number of patients in this study did not achieve efficacy outcomes even after treatment with 200 mg of abrocitinib. Furthermore, sub-population analysis of the JADE EXTEND study, evaluating difficult-to-achieve patient-oriented outcomes such as Patient Oriented Eczema Measure (POEM) ≤2 and Dermatology Life Quality Index (DLQI) ≤1, further emphasized that switching might be beneficial for a significant number of patients, but unmet need was still evident for some of them (4). The literature lacks data on switching between Janus kinase (JAK) inhibitors in AD. Treat-to-target might be different for early control of the disease, as baricitinib and upadacitinib were assessed at 16 weeks, while abrocitinib was assessed at 12 weeks in the pivotal studies. Regarding the present case, the different clinical response obtained cannot be clearly defined since abrocitinib and upadacitinib are both selective JAK1 inhibitors. Consequently, the targeted inflammatory pathways and the expected regulation of immune funct

特应性皮炎(AD)患者换药的数据很少(1-3)。我们报告了一例严重特应性皮炎患者的病例,该患者对达帕替尼反应不足,但在换用阿罗西替尼后出现了完全反应。一名23岁的男性重症AD患者参加了Measure Up双盲、安慰剂对照3期随机临床试验。基线时,湿疹面积严重性指数(EASI)为50.6,研究者总体评估(IGA)为4,受影响体表面积(BSA)为80%,最严重瘙痒-数字评分量表(WP-NRS)为10/10(图1)。第 124 周时,患者停止了试验,当时的 EASI 为 9.2,IGA 为 3,BSA 为 20%,WP-NRS 为 5/10。停药一个月后,在期待解除绑定的同时,患者再次出现 AD 病情加重,EASI 为 45.6,IGA 为 4,BSA 为 80%,WP-NRS 为 10/10。当时,希腊还不能同时使用杜必鲁单抗和曲妥珠单抗,而达达替尼因患者满意度不高(部分原因是在之前的达达替尼治疗期间复发了眼部单纯疱疹感染)而未被使用。患者接受了阿罗西替尼治疗,每天 200 毫克。开始治疗一个月后,患者的病情得到了完全控制(EASI 0.0,IGA 0,BSA 0%,WP-NRS 0/10)(图 2)。连续治疗 12 个月后,患者的病情得到了控制,且未出现任何不良反应。解除盲法后,确认患者在参与临床试验期间每天服用了 15 毫克的达帕西替尼。在治疗重症AD患者时,如果反应不充分,何时换药以及换用哪种药物是一个尚未明确界定的问题。JADE EXTEND 研究的数据表明,使用杜必鲁单抗疗效不佳的患者可以从换用两种剂量的阿罗西替尼中获益(1)。然而,在这项研究中,一些患者在接受了 200 毫克阿罗西替尼治疗后仍未取得疗效。此外,JADE EXTEND 研究的亚人群分析评估了患者导向湿疹测量(POEM)≤2 和皮肤科生活质量指数(DLQI)≤1 等难以达到的患者导向结果,进一步强调了换药可能对大量患者有益,但其中一些患者的需求仍未得到满足(4)。文献中缺乏有关AD患者切换Janus激酶(JAK)抑制剂的数据。在关键研究中,巴利昔尼和达帕替尼在16周时进行了评估,而阿罗西替尼在12周时进行了评估,因此早期疾病控制的目标治疗可能有所不同。就本病例而言,由于阿罗西替尼和达达替尼均为选择性 JAK1 抑制剂,因此无法明确界定所获得的不同临床反应。因此,所针对的炎症通路和预期的免疫功能调节可能是相似的。我们可以认为,阿罗西替尼的高剂量与奥达替尼的低剂量相比,可能是反应改善的原因。然而,我们无法评估临床结果是否与每天服用30毫克全剂量的奥帕他替尼具有可比性,也无法评估每天服用100毫克半剂量的阿罗西替尼是否也会导致同一患者的反应不充分。多年来,在同一类治疗药物之间进行转换也一直是银屑病治疗中争议颇多的问题;然而,最近的数据表明,在白细胞介素(IL)-17A 拮抗剂之间进行转换可能对某些患者有益,尽管其潜在的作用机制仍在研究之中(5,6)。在应答不足的情况下,治疗方法的调整可包括:增加剂量、在 JAK 抑制剂的基础上增加甲氨蝶呤等传统治疗方法、改用单克隆类药物或改用另一种 JAK 抑制剂,同时考虑到已发表的对新型药物疗效的荟萃分析。因此,在目前的 AD 治疗中,确定从治疗到靶点、转换或增加治疗的逐步算法的需求尚未得到满足。不同国家的报销政策不同,再加上缺乏比较研究,可能会使在现有治疗指南中增加此类建议变得更加复杂。
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引用次数: 0
Aquatic/aquagenic Dermatoses: The Thin Line Between Pool Palms and Aquagenic Syringeal Acrokeratoderma. 水生/水源性皮肤病:泳池手掌与水生注射性角化病之间的一线之隔。
Deniz Demircioğlu, Emel Öztürk Durmaz

Pool palms and pool toes are friction or pressure-induced aquatic dermatoses resulting from extensive and repetitive rubbing of fingers, palms, soles, and toes against the rough anti-slippery surfaces or edges of pools. Aquagenic syringeal acrokeratoderma is a sporadic, episodic, and acquired disorder of palmar skin linked to water exposure. Herein we describe a case of aquatic/aquagenic dermatosis that presented clinical and diagnostic difficulties. Differentiating between pool palms and aquagenic syringeal acrokeratoderma is a challenge, and we believe that both disorders lie on a spectrum of watersport dermatoses.

泳池手掌和脚趾是由于手指、手掌、脚底和脚趾与泳池粗糙的防滑表面或边缘广泛、反复摩擦而引起的摩擦性或压力性水生皮肤病。水生鞘状角化性皮炎是一种偶发性、发作性和获得性的掌跖皮肤疾病,与接触水有关。在此,我们描述了一例水生/水生皮肤病病例,该病例给临床和诊断带来了困难。我们认为,这两种疾病都属于水上运动皮肤病。
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引用次数: 0
Flat Warts (Verrucae Planae) Confined to the Pigment of a Tattoo: A Rare Tattoo-associated Complication. 扁平疣(扁平疣)局限于纹身色素:一种罕见的纹身相关并发症。
Nika Filipović, Davor Tomas, Marija Buljan

Tattoos are a form of decorative body art in which pigment dyes of different colors are inoculated into the skin. It is estimated that 15-25% of general population has one or more tattoos (1), and the reasons for the popularity of this procedure may include greater social acceptance, aesthetic appeal, or perhaps the option of using laser removal techniques to eliminate unwanted tattoos. Even though modern professional tattoos are usually performed in sterile conditions, complications still occur, and with increasing numbers of people getting tattoos, the incidence of tattoo-associated side-effects presenting to dermatologists, which may be as high as 2%, is likely to increase (2). Herein we present a case of a 43-year-old male patient with multiple HPV-associated flat warts (verrucae planae) confined to the black pigment of a tattoo done 15 years ago. A 43-year-old patient presented to our clinic due to eczema on the trunk. However, during skin examination, we observed asymptomatic verrucous papules confined to the black ink of a tattoo done 15 years ago on the lateral side of his right lower leg (Figure 1a). Clinical examination showed multiple, discrete, skin-colored, verrucous papules disseminated exclusively within the lines of the black-colored tattoo. Full skin examination did not reveal any similar lesions anywhere else on the body. Dermoscopically, papules showed a discretely papillomatous surface and sharp borders (Figure 1b). The patient had another black tattoo on his trunk, in which no similar lesions were found. All his tattoos had been done more than 15 years ago in a professional tattoo salon and with no previous history of cutaneous lesions within tattoos. The patient had no other medical conditions and was not taking any medications. Additionally, no history of warts or other HPV-related lesions of the skin or mucosal membranes could be established. A biopsy of an individual papule was taken and sent for a histopathological analysis, which subsequently showed hyperkeratotic, orthokeratotic, and parakeratotic acanthotic epidermis with hypergranulosis and rare cells with perinuclear halo indicative of koilocytes (Figure 3b). Immunohistochemical analysis showed negative reaction for p16 and p53, while Ki67 was positive only in rare basal and suprabasal cells. These findings were indicative of low-risk HPV, and the diagnosis of HPV-induced verruca plana was ultimately established. The patient was then successfully treated with cautious curettage of the lesions, leaving no scars. Due to the growing popularity of tattoos, especially among younger populations, it is necessary to emphasize the possibility of various tattoo-related side-effects that can still occur due to improper preparation of the tattoo location, contamination of ink products, improperly sterilized instruments, or due to insufficient personal hygiene following tattooing (3). In the past, tattoo-associated infections were significantly more frequent, with the high

起初,人们认为这是由于HPV通过受污染的仪器、墨水或患者自身疣的自体接种而接种所致,但一些证据表明,HPV不太可能在墨水中存活,如果接种了疣,它们将在所有墨水颜色中平等地发生。Ruocco等人(7)的另一种理论通过“免疫功能受损区”机制解释了这一现象,其中在黑色墨水中发现的多环芳烃产生活性氧(ROS),可以破坏细胞结构,从而增加包括HPV在内的各种感染的风险。此外,黑色墨水含有几乎纯的纳米颗粒,与彩色墨水中发现的大颗粒相比,它们与更多的活性氧产生有关(7,8)。扁平疣有几种治疗方案,如液氮冷冻疗法、5%氟尿嘧啶外用、5%咪喹莫德外用、0.025-0.050%维甲酸、10%水杨酸或10-30%乙醇酸。这些治疗方法有不同的成功率。破坏性的方式,如手术切除、刮除或激光消融可能会严重损害纹身并造成疤痕,因此不定期进行。有必要强调的是,尽管今天的纹身方法是无菌的,但仍然可能出现并发症,医学专业人士,即皮肤科医生应该注意这些问题。想要纹身的人应该被建议只去有执照的纹身店找有执照的纹身师。既往患有以同构现象为特征的皮肤病的患者,如牛皮癣或扁平苔藓,特别容易出现与纹身相关的不良反应,应建议患有严重皮肤病的患者避免纹身。此外,有过疣史的人应该意识到疣发生的可能性,甚至在纹身后几年或几十年。虽然大部分纹身副作用只是不方便,但也有可能出现严重的并发症,因此要慎重对待。
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引用次数: 0
Insulin Growth Factor-1 Status in Hidradenitis Suppurativa: A French Institutional Pilot Study. 胰岛素生长因子-1在化脓性汗腺炎中的地位:一项法国机构试点研究。
Perrine Rousseau, Alexandra Poinas, Damien Masson, Kalyane Bach-Ngohou, Michel Nguyen, Marie Le Moigne, Barbara Bregeon, Florence Vrignaud, Amir Khammari, Brigitte Dréno

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease of the follicles in the apocrine glands and is associated with a deficiency in the innate immunity of the skin. It is characterized by the occurrence of nodules, abscesses, fistulas, scars.

Objective: Although a relationship has already been demonstrated between HS and innate immunity, IGF-1 status in patients with HS is still unknown. The objective of this pilot study was to determine IGF-1 status in patients with HS as well as its potential relationship with the clinical profile of the disease.

Methods: This monocentric and cross-sectional study involved 39 patients hospitalized at the Dermatology Department of CHU Nantes between November 2014 and January 2018. Clinical data and IGF1 status were collected during the follow-up consultation.

Results: Forty-nine percent of the patients had very low levels of IGF-1. At the clinical level, these patients were young and with a short duration of disease. The major difference was that IGF1-deficient patients had a higher BMI than others. The others factors differing between the two patient groups did not reach statistical significance.

Conclusion: This exploratory pilot study indicates that HS with a low level of IGF-1 could represent a specific phenotype of patients with HS. These preliminary results have to be confirmed with a larger cohort, as they could have practical consequences in the therapeutic care of these patients.

背景:化脓性汗腺炎(HS)是大汗腺中卵泡的慢性炎症性皮肤病,与皮肤先天免疫缺陷有关。它的特点是出现结节、脓肿、瘘管、疤痕。目的:虽然HS与先天免疫之间的关系已经被证实,但HS患者的IGF-1状态仍然未知。本初步研究的目的是确定HS患者的IGF-1状态及其与该疾病临床特征的潜在关系。方法:本研究为单中心横断面研究,纳入2014年11月至2018年1月在南特医学院皮肤科住院的39例患者。随访时收集临床资料和IGF1状态。结果:49%的患者IGF-1水平很低。在临床水平上,这些患者年轻,病程短。主要的区别是igf1缺陷患者的BMI高于其他人。两组患者其他因素差异无统计学意义。结论:本探索性前期研究提示,低水平IGF-1可能代表HS患者的一种特定表型。这些初步结果必须在更大的队列中得到证实,因为它们可能对这些患者的治疗护理产生实际影响。
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引用次数: 0
PAPA Syndrome: Challenges in Achieving Long-Term Remission. PAPA综合征:实现长期缓解的挑战。
Hana Smajlović, Asja Prohić

For over two decades, the acronym PAPA syndrome has been used to describe an autoinflammatory condition caused by missense mutations in the PSTPIP1 (proline-serine-threonine phosphatase interacting protein 1) gene and clinically characterized by the presence of pyogenic arthritis, pyoderma gangrenosum (PG), and acne (1,2). Due to the involvement of the PSTPIP1 gene in the regulation of innate immunity, mutations of this gene cause abnormal activation of inflammasomes, complexes of NLRP3/ASC/caspase-1 proteins. As a result, production of interleukin-1β, a key molecule that triggers synthesis of cytokines necessary for the recruitment of neutrophils, is significantly increased (2,3). Additionally, the levels of other pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ) and interleukin 17 (IL-7) are also elevated, which further disrupts inflammatory mechanisms in the microenvironment (4). Since hyperproduction of IL-1 and other involved cytokines is the predominant event in the pathogenesis, these molecules are promising targets in the treatment of PAPA syndrome. Corticosteroids and biologics are currently the most commonly used agents for inducing and hastening remission of symptoms (5). A substantial step forward in the treatment of PAPA syndrome has been the introduction of medications blocking the cytokines crucial in the pathogenesis of this disorder, with TNF-α and IL-1 inhibitors being the most frequent choice of such biological therapy (6). We report the case of a 22-year-old male patient with PAPA syndrome who was referred to our department 18 months ago due to exacerbation of skin changes. Initial presentation and subsequent evolution of disease in this patient matched the typical clinical pattern of PAPA syndrome. The first symptoms occurred at the age of two in the form of unspecific joint disease that was diagnosed as juvenile idiopathic arthritis. Subsequently, in the early adolescence the patient presented with new skin changes manifesting as severe acne and persistent pyoderma gangrenosum-like ulcers. At the same time, severity of joint involvement gradually decreased. After the characteristic phenotype of the disease had fully developed, suspicion of possible syndromic origin of symptoms arose. For this reason, genetic analysis was performed as requested by attending pediatricians at the University Clinical Center in Sarajevo, and E250Q mutation of the PSTPIP1 gene was detected. Thus, the diagnosis of PAPA syndrome was confirmed. Throughout the duration of the disease, several types of medication had been introduced in the treatment with varying success. Earliest joint symptoms were alleviated with non-steroidal anti-inflammatory drugs, while repeated courses of corticosteroids were the mainstay of the therapy during a decade-long period. As a consequence of prolonged steroid therapy, growth disorder, among various other side-effects, had been especially pronounced. Acting as a classic ster

20多年来,首字母缩略词PAPA综合征一直被用来描述由PSTPIP1(脯氨酸-丝氨酸-苏氨酸磷酸酶相互作用蛋白1)基因错义突变引起的自身炎症,临床特征为存在化脓性关节炎、坏疽性脓皮病(PG)和痤疮(1,2)。由于PSTPIP1基因参与先天免疫的调控,该基因的突变会导致炎性小体NLRP3/ASC/caspase-1蛋白复合物的异常激活。因此,白细胞介素-1β的产生显著增加(2,3),白细胞介素-1β是触发中性粒细胞募集所需细胞因子合成的关键分子。此外,其他促炎细胞因子,如肿瘤坏死因子-α (TNF-α)、干扰素-γ (INF-γ)和白细胞介素17 (IL-7)的水平也升高,这进一步破坏了微环境中的炎症机制(4)。由于IL-1和其他相关细胞因子的过量产生是发病机制的主要事件,这些分子是治疗PAPA综合征的有希望的靶点。皮质类固醇和生物制剂是目前最常用的诱导和加速症状缓解的药物(5)。在PAPA综合征的治疗中,一个实质性的进步是引入了阻断在该疾病发病机制中至关重要的细胞因子的药物。TNF-α和IL-1抑制剂是此类生物治疗的最常见选择(6)。我们报告一例22岁的PAPA综合征男性患者,18个月前因皮肤变化加剧而转介至我科。该患者的最初表现和随后的疾病演变符合典型的PAPA综合征的临床模式。最初的症状出现在两岁时,以非特异性关节疾病的形式被诊断为幼年特发性关节炎。随后,在青少年早期,患者出现了新的皮肤变化,表现为严重的痤疮和持续的脓皮坏疽样溃疡。同时,关节受累的严重程度逐渐降低。在疾病的特征性表型完全发展后,怀疑症状可能是综合征起源。因此,根据萨拉热窝大学临床中心主治儿科医生的要求进行了遗传分析,检测到PSTPIP1基因的E250Q突变。因此,PAPA综合征的诊断得到证实。在整个疾病期间,在治疗中引入了几种类型的药物,取得了不同程度的成功。最早的关节症状通过非甾体类抗炎药物得到缓解,而在长达十年的治疗期间,皮质类固醇的反复疗程是主要的治疗方法。由于长期使用类固醇治疗,生长障碍和其他各种副作用尤为明显。作为一种经典的类固醇免疫抑制剂,甲氨蝶呤也是患者治疗方案的一部分。最后,生物制剂,包括TNF-α和IL-a抑制剂,作为剩余的治疗选择分别给予。然而,阿达木单抗表现出对关节症状的主要作用,而在随后的阿那真纳治疗期间,先前未检测到的乙型肝炎感染再次激活。由于这种不良反应,阿那白停止了治疗。初步检查时,患者表现为多发红斑、部分去皮丘疹和结节,并在整个背部、胸部、肩部和上臂的皮肤上残留炎症后色素沉着的斑块和疤痕(图1、图2)。肘部存在术后疤痕,这是由于先前为缓解疼痛和改善功能而对持续受影响的关节进行手术所致。也观察到。下肢可见几个边缘受损的较小溃疡(图3),以及残留的色素沉着和瘢痕(图4)。此外,患者报告轻微创伤后出现脓疱和未愈合的溃疡,这与PAPA综合征的共同特征疼痛现象相对应。与严重的皮肤变化相比,关节症状较轻。在对患者的病史和现状进行全面评估后,开始采用多药治疗方案,包括阿达木单抗、异维甲酸和强的松。在12个月的治疗期间定期检查表明,所施药物稳定了患者的病情,减轻了更严重和急性的皮肤变化,减缓了症状的进一步恶化。由于PAPA综合征的罕见性,有关其治疗的数据很少。
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引用次数: 0
The Role of T Follicular Helper Cells in Clinical Remission and Relapse in Patients with Pemphigus Treated with Rituximab. T滤泡辅助细胞在利妥昔单抗治疗的天疱疮患者的临床缓解和复发中的作用。
Ayşe Akman Karakaş, Erkan Ergün, Nurten Sayın Ekinci, Aslı Toylu, Soner Uzun, Erkan Alpsoy

Background: Pemphigus is a rare chronic autoimmune disease. Recent studies have found that T follicular helper (Tfh) cells may play a role in autoimmune diseases. In this study, Tfh cells frequency, BCL6 gene expression, IL-21, and IL-6 cytokines levels were examined, with the aim of understanding the effect of RTX on these cells in the onset of clinical remission or relapse in patients with pemphigus.

Methods: 20 patients with pemphigus vulgaris and 20 healthy controls without any autoimmune diseases that were admitted to the Dermatology and Venereology Clinic of the Akdeniz University Hospital were included. Peripheral blood sample was taken from all individuals and studied to analyze Tfh cell distribution, IL-21 and IL-6 distribution in CD3+CD4+CXCR5+ lymphocytes with flow cytometry, plasma IL-21 levels with ELISA, and mRNA levels that refer to BCL6 expression with PCR.

Results: Circulating Tfh cell distribution and IL-21 and IL-6 distribution in CD3+CD4+CXCR5+ lymphocytes and mRNA levels that refer to BCL6 expression showed no difference between patient and control groups. However, in patients who had received rituximab treatment there was a significant reduction in Tfh cells compared with other groups. Plasma IL-21 levels were significantly higher in the patient group.

Conclusions: We found that plasma concentrations of the cytokine IL-21 were greatly increased in the pemphigus compared with the control group. There were no significant differences in Tfh cell percentages between the patient and control groups. Tfh cells were decreased in patients who received rituximab treatment. Our findings show that the response to RTX in pemphigus causes a reduction in circulating T follicular helper cells, but not in the plasma IL-21 level. Further studies are required to clarify the role of Tfh cells in pemphigus vulgaris.

背景:天疱疮是一种罕见的慢性自身免疫性疾病。最近的研究发现,T滤泡辅助细胞(Tfh)可能在自身免疫性疾病中发挥作用。本研究通过检测Tfh细胞频率、BCL6基因表达、IL-21和IL-6细胞因子水平,旨在了解RTX在天疱疮患者临床缓解或复发时对这些细胞的影响。方法:选取在Akdeniz大学医院皮肤性病科门诊就诊的20例寻常型天疱疮患者和20例无自身免疫性疾病的健康对照。采集所有个体外周血,流式细胞术分析Tfh细胞分布、CD3+CD4+CXCR5+淋巴细胞中IL-21和IL-6的分布,ELISA法分析血浆IL-21水平,PCR法分析BCL6表达相关mRNA水平。结果:患者与对照组循环Tfh细胞分布、CD3+CD4+CXCR5+淋巴细胞中IL-21、IL-6分布及BCL6表达相关mRNA水平均无差异。然而,在接受利妥昔单抗治疗的患者中,与其他组相比,Tfh细胞显著减少。患者组血浆IL-21水平明显升高。结论:我们发现,与对照组相比,天疱疮患者血浆细胞因子IL-21浓度显著升高。患者与对照组间Tfh细胞百分比无显著差异。接受利妥昔单抗治疗的患者Tfh细胞减少。我们的研究结果表明,天疱疮患者对RTX的反应导致循环T滤泡辅助细胞减少,但不影响血浆IL-21水平。需要进一步的研究来阐明Tfh细胞在寻常型天疱疮中的作用。
{"title":"The Role of T Follicular Helper Cells in Clinical Remission and Relapse in Patients with Pemphigus Treated with Rituximab.","authors":"Ayşe Akman Karakaş, Erkan Ergün, Nurten Sayın Ekinci, Aslı Toylu, Soner Uzun, Erkan Alpsoy","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Pemphigus is a rare chronic autoimmune disease. Recent studies have found that T follicular helper (Tfh) cells may play a role in autoimmune diseases. In this study, Tfh cells frequency, BCL6 gene expression, IL-21, and IL-6 cytokines levels were examined, with the aim of understanding the effect of RTX on these cells in the onset of clinical remission or relapse in patients with pemphigus.</p><p><strong>Methods: </strong>20 patients with pemphigus vulgaris and 20 healthy controls without any autoimmune diseases that were admitted to the Dermatology and Venereology Clinic of the Akdeniz University Hospital were included. Peripheral blood sample was taken from all individuals and studied to analyze Tfh cell distribution, IL-21 and IL-6 distribution in CD3+CD4+CXCR5+ lymphocytes with flow cytometry, plasma IL-21 levels with ELISA, and mRNA levels that refer to BCL6 expression with PCR.</p><p><strong>Results: </strong>Circulating Tfh cell distribution and IL-21 and IL-6 distribution in CD3+CD4+CXCR5+ lymphocytes and mRNA levels that refer to BCL6 expression showed no difference between patient and control groups. However, in patients who had received rituximab treatment there was a significant reduction in Tfh cells compared with other groups. Plasma IL-21 levels were significantly higher in the patient group.</p><p><strong>Conclusions: </strong>We found that plasma concentrations of the cytokine IL-21 were greatly increased in the pemphigus compared with the control group. There were no significant differences in Tfh cell percentages between the patient and control groups. Tfh cells were decreased in patients who received rituximab treatment. Our findings show that the response to RTX in pemphigus causes a reduction in circulating T follicular helper cells, but not in the plasma IL-21 level. Further studies are required to clarify the role of Tfh cells in pemphigus vulgaris.</p>","PeriodicalId":94367,"journal":{"name":"Acta dermatovenerologica Croatica : ADC","volume":"31 2","pages":"72-79"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138441954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prognostic Value of Lactate Dehydrogenase in Patients with Melanoma Treated with Pembrolizumab. 乳酸脱氢酶在派姆单抗治疗黑色素瘤患者中的预后价值。
Aleksandar Popović, Ivan Petković, Aleksandra Dimitrijevic, Andrija Jović

Introduction: Elevated LDH levels have been extensively reported as a biomarker of poorer outcome in patients with melanoma during the chemotherapeutic era. The role of LDH level as a prognostic factor for treatment outcomes in patients with metastatic melanoma treated with immunooncological therapy has also been reported but requires further analysis.

Objectives: In this study, we aimed to evaluate the prognostic value of lactate dehydrogenase (LDH) among patients with metastatic and unresectable melanoma treated with pembrolizumab in terms of progression-free survival (PFS).

Methods: The study included 59 patients with unresectable and metastatic melanoma treated with pembrolizumab. A comparison was performed between patients with normal and elevated levels of LDH in terms of PFS, with subgroup analysis.

Results: There was a significant reduction in PFS among patients with elevated levels of LDH compared with patients with normal levels of LDH (NR vs. 5 months; P=0.02). Patients with elevated LDH levels were older (P=0.01), with liver metastasis (P=0.004), and with less frequent CNS deposits (P=0.028).

Conclusion: Although novel agents improved outcomes in patients with melanoma, high levels of LDH persist as an independent prognostic biomarker of poor prognosis.

导读:在化疗时代,LDH水平升高被广泛报道为黑色素瘤患者预后较差的生物标志物。在接受免疫肿瘤治疗的转移性黑色素瘤患者中,LDH水平作为预后因素的作用也有报道,但需要进一步分析。目的:在这项研究中,我们旨在评估乳酸脱氢酶(LDH)在接受派姆单抗治疗的转移性和不可切除黑色素瘤患者的无进展生存期(PFS)方面的预后价值。方法:该研究纳入了59例使用派姆单抗治疗的不可切除和转移性黑色素瘤患者。比较LDH水平正常和升高患者在PFS方面的差异,并进行亚组分析。结果:与LDH水平正常的患者相比,LDH水平升高的患者PFS显著降低(NR vs. 5个月;P = 0.02)。LDH水平升高的患者年龄较大(P=0.01),伴有肝转移(P=0.004),中枢神经系统沉积较少(P=0.028)。结论:尽管新型药物改善了黑色素瘤患者的预后,但高水平的LDH仍然是预后不良的独立预后生物标志物。
{"title":"Prognostic Value of Lactate Dehydrogenase in Patients with Melanoma Treated with Pembrolizumab.","authors":"Aleksandar Popović, Ivan Petković, Aleksandra Dimitrijevic, Andrija Jović","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Introduction: </strong>Elevated LDH levels have been extensively reported as a biomarker of poorer outcome in patients with melanoma during the chemotherapeutic era. The role of LDH level as a prognostic factor for treatment outcomes in patients with metastatic melanoma treated with immunooncological therapy has also been reported but requires further analysis.</p><p><strong>Objectives: </strong>In this study, we aimed to evaluate the prognostic value of lactate dehydrogenase (LDH) among patients with metastatic and unresectable melanoma treated with pembrolizumab in terms of progression-free survival (PFS).</p><p><strong>Methods: </strong>The study included 59 patients with unresectable and metastatic melanoma treated with pembrolizumab. A comparison was performed between patients with normal and elevated levels of LDH in terms of PFS, with subgroup analysis.</p><p><strong>Results: </strong>There was a significant reduction in PFS among patients with elevated levels of LDH compared with patients with normal levels of LDH (NR vs. 5 months; P=0.02). Patients with elevated LDH levels were older (P=0.01), with liver metastasis (P=0.004), and with less frequent CNS deposits (P=0.028).</p><p><strong>Conclusion: </strong>Although novel agents improved outcomes in patients with melanoma, high levels of LDH persist as an independent prognostic biomarker of poor prognosis.</p>","PeriodicalId":94367,"journal":{"name":"Acta dermatovenerologica Croatica : ADC","volume":"31 2","pages":"86-91"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138441952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Impact of Blue Light Irradiation on Keratinocytes in Vitro. 蓝光照射对体外角质形成细胞的影响。
Markus Denzinger, Andreas K Nüssler, Fabian Medved, Sabrina Krauß, Adrien Daigeler, Manuel Held, Claudius Illg

Background: This study examined the effects of irradiation with blue light on HaCaT keratinocytes. As irradiation with blue light is known to be antimicrobial, it offers a promising alternative therapy for contaminated wounds. There is evidence that red light promotes wound healing, but the potential benefits of irradiation with blue light have not yet been adequately investigated.

Methods: The rate of wound closure in sterile and contaminated cells was measured using an in vitro scratch assay wound-healing model. Additionally, cell viability after treatment was determined using a Sulforhodamine B (SRB) assay.

Results: In both the sterile and contaminated groups, treated cells showed delayed wound closure when compared with cells not irradiated with blue light. Additionally, treatment with blue light resulted in poorer viability in the treatment groups.

Conclusion: Although irradiation with blue light may offer a promising alternative therapy for reducing bacterial colonization, our data indicate that re-epithelization may be negatively influenced by blue light. Further research is needed to clarify possible wound healing applications.

背景:本研究考察了蓝光照射对HaCaT角质形成细胞的影响。由于已知蓝光照射具有抗菌作用,它为污染伤口提供了一种很有前途的替代疗法。有证据表明红光能促进伤口愈合,但蓝光照射的潜在益处尚未得到充分研究。方法:采用体外划伤实验创面愈合模型,测定无菌和污染细胞创面愈合率。此外,使用Sulforhodamine B (SRB)测定处理后的细胞活力。结果:在无菌组和污染组中,与未照射蓝光的细胞相比,处理过的细胞伤口愈合延迟。此外,蓝光治疗导致治疗组的生存能力较差。结论:虽然蓝光照射可能是减少细菌定植的一种有希望的替代疗法,但我们的数据表明蓝光可能会对再上皮产生负面影响。需要进一步的研究来阐明可能的伤口愈合应用。
{"title":"The Impact of Blue Light Irradiation on Keratinocytes in Vitro.","authors":"Markus Denzinger, Andreas K Nüssler, Fabian Medved, Sabrina Krauß, Adrien Daigeler, Manuel Held, Claudius Illg","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>This study examined the effects of irradiation with blue light on HaCaT keratinocytes. As irradiation with blue light is known to be antimicrobial, it offers a promising alternative therapy for contaminated wounds. There is evidence that red light promotes wound healing, but the potential benefits of irradiation with blue light have not yet been adequately investigated.</p><p><strong>Methods: </strong>The rate of wound closure in sterile and contaminated cells was measured using an in vitro scratch assay wound-healing model. Additionally, cell viability after treatment was determined using a Sulforhodamine B (SRB) assay.</p><p><strong>Results: </strong>In both the sterile and contaminated groups, treated cells showed delayed wound closure when compared with cells not irradiated with blue light. Additionally, treatment with blue light resulted in poorer viability in the treatment groups.</p><p><strong>Conclusion: </strong>Although irradiation with blue light may offer a promising alternative therapy for reducing bacterial colonization, our data indicate that re-epithelization may be negatively influenced by blue light. Further research is needed to clarify possible wound healing applications.</p>","PeriodicalId":94367,"journal":{"name":"Acta dermatovenerologica Croatica : ADC","volume":"31 2","pages":"64-71"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138441953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Acta dermatovenerologica Croatica : ADC
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