Part I. Introduction, categorization, histology, pathogenesis, and risk factors
第一部分绪论、分类、组织学、发病机制和危险因素
英文原文
Rosacea is a chronic inflammatory skin condition that affects approximately 16 million Americans. Four distinct subtypes of rosacea have been recognized, with transient and nontransient facial flushing, telangiectasia, and inflammatory papules and pustules being among the more commonly recognized features. Although the exact pathogenesis of rosacea is unknown, dysregulation of the innate immune system, overgrowth of commensal skin organisms, and aberrant neurovascular signaling may all have a role in promoting the clinical features of rosacea.
对应中文
玫瑰痤疮是一种慢性炎症性皮肤病，影响着大约1600万美国人。玫瑰痤疮有四种不同的亚型，其中一过性和非一过性面部潮红、毛细血管扩张、炎性丘疹和脓疱是最常见的特征。虽然玫瑰痤疮的确切发病机制尚不清楚，但天然免疫系统的失调、皮肤共生生物的过度生长以及神经血管信号的异常都可能在玫瑰痤疮的临床特征中起到促进作用。
Erythematotelangiectatic rosacea (subtype I)
红斑毛细血管扩张型玫瑰痤疮(Ⅰ型)
英文原文
ETR is characterized by nontransient episodes of flushing and persistent central facial erythema. Redness may also involve the peripheral face, ears, neck, and upper aspect of the chest, but periocular skin is typically spared.Telangiectases are also common in ETR, but they are not required for diagnosis.
对应中文
ETR的特点是非一过性潮红和持续性中央面部红斑。发红也可累及周边面部、耳朵、颈部和胸部上部，但眼周皮肤除外。毛细血管扩张在ETR中也很常见，但不是诊断的必需条件。
Papulopustular rosacea (subtype II)
丘疹脓疱型玫瑰痤疮(II型)
英文原文
In addition to the characteristics seen in ETR, patients with PPR experience transient papules or pustules in a central facial distribution. In severe cases, these episodes of inflammation can lead to chronic facial edema.
对应中文
除了在ETR中看到的特征外，PPR患者还会出现面部中央分布的一过性丘疹或脓疱。在严重的情况下，这些炎症发作可能会导致慢性面部水肿。
Phymatous rosacea (subtype III)
肥大增生型玫瑰痤疮（III型）
英文原文
Phymatous rosacea is characterized by thickened, enlarged skin with irregular surface nodularities. These changes can occur in any sebaceous facial region, but the nose is the most commonly affected site. Unlike the other subtypes of rosacea—in which females are predominantly affected—males are more commonly affected by phymatous rosacea.
对应中文
肥大增生型玫瑰痤疮的特征是皮肤增厚、增大、皮肤表面有不规则结节。这些变化可能发生在面部任何皮脂腺区域，但鼻子是最常见的受影响部位。与女性占优势的其他类型玫瑰痤疮不同的是，男性更容易受到肥大增生型玫瑰痤疮的影响。
Ocular rosacea (subtype IV)
眼型(IV型)
英文原文
Ocular rosacea was defined by the National Rosacea Expert Committee as having $1 of the following signs or symptoms: watery or bloodshot appearance, foreign body sensation, burning or stinging, dryness, itching, light sensitivity, blurred vision, telangiectases of the conjunctiva and lid margin, or lid and periocular erythema. Other signs include blepharitis, conjunctivitis, and irreg- ularity of the eyelid margins. Chalazia and styes are also common signs of ocular rosacea.Because there is no diagnostic test for ocular rosacea, the diagnosis relies on the physician’s clinical judgment. Ocular involvement is estimated to occur in 6% to 50% of patients with cutaneous rosacea and can occur with or without a diagnosis of cutaneous rosacea. The severity of ocular symptoms may not correlate with the severity of cutaneous findings.According to a study of 99 subjects with both ocular and cutaneous rosacea, just more than half of these subjects had cutaneous disease before being diagnosed with ocular rosacea, while 20% of subjects were diagnosed with ocular disease first.In rare cases, decreased visual acuity may result from scarring and surface irregularities of the cornea.Therefore, it may be beneficial to screen patients with cutaneous rosacea for ocular symptoms and to consider referring anyone with ocular discomfort or hyperemia of the conjunctiva or lid margin for ophthalmologic evaluation.
对应中文
国家玫瑰痤疮专家委员会将眼型玫瑰痤疮定义为具有1个以上下面（眼部）症状或体征：水样或血丝样外观、异物感、灼热或刺痛、干燥、瘙痒、光敏感、视力模糊、结膜和眼睑边缘毛细血管扩张，或眼睑和眼周红斑。其他体征包括睑缘炎、结膜炎和眼睑边缘异常。睑板腺囊肿和睑腺炎也是眼部玫瑰痤疮的常见体征。由于眼部玫瑰痤疮没有诊断试验，诊断依赖于医生的临床判断。据估计，6%至50%的皮肤玫瑰痤疮患者发生眼部受累，可在诊断为或未诊断为皮肤玫瑰痤疮的情况下发生。眼部症状的严重程度可能与皮肤发现的严重程度无关。根据对99名患有眼部和皮肤玫瑰痤疮的受试者的研究，这些受试者中只有一半以上在被诊断为眼部玫瑰痤疮之前患有皮肤病，而20%的受试者首先被诊断为患有眼部疾病。在极少数情况下，角膜瘢痕化和表面不规则可能导致视力下降。因此，对有眼部症状的皮肤玫瑰痤疮患者应该进行眼型玫瑰痤疮筛查，并考虑对任何有眼部不适或结膜充血或睑缘充血的患者进行眼科评价可能是有益的。
HISTOLOGY
组织学
英文原文
It is not necessary to obtain a skin biopsy specimen in order to reach a diagnosis of rosacea. Many of the histopathologic findings in the different rosacea subtypes are nonspecific, and therefore obtaining a biopsy specimen should be reserved for cases in which the diagnosis is uncertain or when other diagnoses must be ruled out. In ETR, typical histologic findings include dilation of superficial blood vessels and low-grade perivascular lymphohistiocytic inflammation with occasional plasma cells. In PPR, papules usually contain a prominent perivascular and perifollicular inflammatory infiltrate in the superficial and mid-dermis consisting of lymphocytes, neutrophils, and plasma cells. Pustular lesions usually have a superficial accumulation of neutrophils that, unlike acne vulgaris, extends beyond the follicle.The histopathologic examination of phymatous rosacea reveals sebaceous gland hyperplasia, follicular plugging, telangiectases, pronounced thickening and fibrosis of the dermis, and large deposits of dermal mucin.
对应中文
要得到玫瑰痤疮的诊断，不需要获得皮肤活检标本。在不同的玫瑰痤疮亚型中，许多组织病理学发现是非特异性的，因此，在诊断不确定或必须排除其他诊断的情况下，应保留获得的活检标本。在ETR中，典型的组织学表现包括浅表血管扩张和血管周围低级别淋巴组织细胞炎症，偶见浆细胞。在PPR中，丘疹通常在由淋巴细胞、中性粒细胞和浆细胞组成的真皮表层和中层有明显的血管周围和滤泡状炎性浸润。脓疱型皮损表面有中性粒细胞积聚，与寻常痤疮不同，它延伸到毛囊之外。玫瑰痤疮的组织病理学检查显示皮脂腺增生、毛囊堵塞、毛细血管扩张、真皮明显增厚和纤维化、真皮粘液大量沉积。
PATH****OPHYSIOLOGY
病理生理学
英文原文
The exact pathogenesis of rosacea remains unclear. Although the higher incidence of rosacea in individuals of Celtic and Northern European descent suggests that there may be a genetic component to the disorder, genomic association studies have failed to identify a causative gene. Instead, rosacea patients have an increased expression of a variety of genes with roles in both the innate and adaptive immune systems. These results are consistent with findings in the laboratory, where significant research has been dedicated to studying the dysregulation of the innate immune system in rosacea. Microorganisms, such as Demodex folliculorum, Staphylococcus epidermidis, and others may also contribute to the pathogenesis of rosacea by stimulating the innate immune system. Based on the common triggers for rosacea exacerbations, ultraviolet (UV) light radiation and the transient receptor potential (TRP) family of receptors may also play a role in the pathogenesis of rosacea.
对应中文
玫瑰痤疮的确切发病机制尚不清楚。虽然Celtic人和北欧后裔中玫瑰痤疮的发病率较高，表明该疾病可能有遗传因素，但基因组关联研究未能确定致病基因。相反，玫瑰痤疮患者的多种基因表达增加，这些基因在先天免疫系统和适应性免疫系统中都起作用。这些结果与实验室的发现一致，实验室的重要研究致力于研究玫瑰痤疮天然免疫系统的失调。毛囊蠕形螨、表皮葡萄球菌等微生物也可能通过刺激天然免疫系统而导致玫瑰痤疮的发病。基于玫瑰痤疮恶化的共同诱因，紫外线(UV)光辐射和TRP家族也可能在玫瑰痤疮的发病机制中发挥作用。
DYSREGULATION OF THE INNATE IMMUNE SYSTEM
先天性神经失调
英文原文
Key points
1.Rosacea patients have an increased baseline expression of cathelicidin and kallikrein 5, the predominant serine protease responsible for cleaving cathelicidin into its active form
2.Increased levels of Toll-like receptor 2, which activates kallikrein 5, are seen in patients with rosacea
3.Matrix metalloproteinases that activate kallikrein 5 are also increased in patients with rosacea
对应中文
要点
1.玫瑰痤疮患者组织抗菌肽和激肽酶5的基线表达增加，主要的丝氨酸蛋白酶，负责将抗菌肽切割成活性形式
2.玫瑰痤疮患者可见激活激肽酶5的Toll样受体2水平升高
3.玫瑰痤疮患者激活激肽酶5的基质金属蛋白酶也增加
MICROORGANISMS
微生物
英文原文
Key points
1.Demodex folliculorum and Staphylococcus epidermidis may contribute to rosacea’s pathophysiology by stimulating Toll-like receptor 2
2.Helicobacter pylori’s contribution to rosacea symptoms are unclear, but are suggested by the high prevalence of H pylori seropositivity in the rosacea population, including a high prevalence of virulent strains of this bacterium
3.Bacillus oleronius exposure may contribute to rosacea’s pathophysiology by causing production of matrix metalloproteinase-9, tumor necrosis factor, and interleukin-8
对应中文
要点
1.毛囊蠕形螨和表皮葡萄球菌可能通过刺激Toll样受体2而参与玫瑰痤疮的病理生理
2.幽门螺杆菌对玫瑰痤疮症状的贡献尚不清楚，但玫瑰痤疮人群中幽门螺杆菌血清学阳性率高流行，包括提示该菌强毒株的高流行
3.油状芽胞杆菌暴露可能通过引起基质金属蛋白酶9、肿瘤坏死因子和白细胞介素8的产生，参与玫瑰痤疮的病理生理过程
英文原文
Microorganisms have been hypothesized to play a role in the pathogenesis of rosacea, but their exact role is unclear. Several studies have reported differences in the microbial burden of common skin commensals, such as D folliculorum and S epidermidis, on the skin of healthy subjects and subjects with rosacea, and in bacteria not typically present on the skin, including Helicobacter pylori and Bacillus oleronius.It remains controversial whether this dysbiosis triggers rosacea, or whether the dysbiosis is a response to changes in the skin microenvironment resulting from rosacea’s underlying pathophysiology.
对应中文
目前均假设微生物在玫瑰痤疮的发病机制中起作用，但其确切作用尚不清楚。一些研究报告了健康受试者和玫瑰痤疮受试者皮肤上常见皮肤共生菌（如毛囊蠕形螨和表皮葡萄球菌）的微生物负荷差异，以及皮肤上通常不存在的细菌（包括幽门螺杆菌和油性芽孢杆菌）的微生物负荷差异。这种失调是否会引发玫瑰痤疮，或者这种失调是否是对玫瑰痤疮潜在病理生理学引起的皮肤微环境变化的反应，目前仍存在争议。
英文原文
The saprophytic mite D folliculorum commonly resides in the sebaceous glands of healthy skin. Individuals with rosacea have been shown to have a higher density of Demodex mites on their facial skin compared to individuals without rosacea,suggesting that these mites may play a role in the pathogenesis of rosacea. In 1 study, patients with ETR and PPR had a 5.7-fold increase in D folliculorum density compared to healthy controls. Other studies measuring Demodex infestation rates (typically defined as $5 Demodex mites/cm2) have shown significantly higher infestation rates in rosacea patients, with rates ranging from 35% to 50%.A study comparing permethrin 5% cream, metronidazole 0.75% gel, and placebo in the treatment of PPR found that permethrin treatment was more effective than metronidazole in terms of decreasing D folliculorum colonization, but did not lead to improved clinical efficacy over metronidazole.These findings suggest that D folliculorum alone is not responsible for rosacea; however, they do not rule out a role for D folliculorum in rosacea’s pathogenesis.
对应中文
腐生毛囊蠕形螨通常存在于健康皮肤的皮脂腺中，有玫瑰痤疮的个体面部皮肤上蠕形螨密度比无玫瑰痤疮的高30-32个，提示这些螨类可能在玫瑰痤疮的发病中起作用。在1项研究中，与健康对照组相比，ETR和PPR患者的毛囊蠕形螨密度增加了5.7倍。其他测量蠕形螨感染率 (通常定义为≥5蠕形螨/㎝²) 的研究显示，玫瑰痤疮患者的感染率明显更高，感染率从35%到50%不等。一项研究比较了5%氯菊酯乳膏、0.75%甲硝唑凝胶，在PPR治疗中的对照剂发现，在减少毛囊蠕形螨定植方面氯菊酯治疗比甲硝唑更有效，但与甲硝唑相比并没有导致临床疗效的提高。这些发现表明，玫瑰痤疮并非由毛囊蠕形螨引起；然而，他们并不排除毛囊蠕形螨在玫瑰痤疮发病中的作用。
英文原文
Several studies have proposed mechanisms through which D folliculorum may contribute to the pathogenesis of rosacea. Because these mites release chitin, which can activate TLR2,the high prevalence of these mites may lead to increased protease activity. In addition, these mites have been shown to harbor the bacterium B olenorium, which may also play a role in rosacea’s pathogenesis.
对应中文
一些研究提出了毛囊蠕形螨可能参与玫瑰痤疮的发病机制。因为这些螨虫释放几丁质，几丁质可以激活TLR2，所以这些螨虫的高流行率可能导致蛋白酶活性增加。除此之外，这些螨虫被证明携带油状芽孢杆菌，这也可能在玫瑰痤疮的发病中起作用。
英文原文
S epidermidis is the most prevalent commensal bacteria on healthy human skin, where it plays a crucial role in the skin’s defense against pathogens. Certain strains of these bacteria produce AMPs shown to selectively inhibit the growth of pathogens, including Staphylococcus aureus.Cultures of the pustules from PPR patients have shown S epidermidis to be the singular bacterium present in these lesions.Further investigation of cultured Sepidermidis isolates suggests that the strains present on rosacea-affected skin may differ from those present on healthy skin. S epidermidis isolates from pustules of PPR patients incubated at 37℃ produced different proteins compared to control skin, and these isolates were beta-hemolytic compared to the nonhemolytic properties of S epidermidis cultured from control skin.These findings suggest that the S epidermidis strains present in the skin of patients with rosacea may secrete virulence factors not seen on control skin. These factors may stimulate the innate immune system, leading to the onset or propagation of rosacea symptoms. In addition, S epidermidis antigens are recognized by TLR2, and, together with elevated TLR2 levels, increased S epidermidis expression in lesional rosacea skin may result in increased expression of AMPs.
对应中文
表皮葡萄球菌是健康人皮肤上最常见的共生细菌，在皮肤抵御病原体方面起着至关重要的作用。这些细菌的某些菌株产生AMPs，显示其选择性地抑制病原体的生长，包括金黄色葡萄球菌。PPR患者脓疱的培养表明表皮葡萄球菌是这些皮损病变中存在的唯一细菌。进一步研究培养的表皮葡萄球菌分离物表明，玫瑰痤疮皮肤上存在的菌株可能与健康皮肤上存在的菌株不同。与对照组皮肤相比，从37℃培养的PPR患者脓疱中分离的表皮葡萄球菌产生不同的蛋白质，并且与从对照皮肤培养的表皮葡萄球菌的非溶血特性相比，这些分离物具有溶血性。这些发现表明，玫瑰痤疮患者皮肤中存在的表皮葡萄球菌菌株可能分泌出在对照皮肤上看不到的毒性因子。这些因素可能刺激先天免疫系统，导致玫瑰痤疮的发生或传播。此外，表皮葡萄球菌抗原被TLR2识别，并且，随着TLR2水平的升高，玫瑰痤疮病变皮肤中表皮葡萄球菌表达的增加可能导致AMPs表达的增加。
英文原文
The role of H pylori and other intestinal bacteria in the pathogenesis of rosacea remains controversial. While some studies report an increased prevalence of H pylori seropositivity in patients with rosacea, others have failed to confirm this association.In addition, findings have varied with respect to whether eradication of these gastrointestinal bacteria improves rosacea.The fact that oral antibiotics are standard treatment options for both conditions further complicates the interpretation of these findings. Two separate studies separating out patients with previous antibiotic use show a strong correlation between rosacea and H pylori infection.Further evidence of the role of H pylori in rosacea is supported by the increased number of H pylori strains testing positive for the cytotoxinassociated gene A (CagA) protein in patients with rosacea. CagA is an H pylori virulence factor. Sixty-seven percent of patients with rosacea tested positive for CagA-positive H pylori strains, and 75% were positive for antibodies against CagA.The underlying pathogenesis of how H pylori infection triggers rosacea is unknown, though, reinforcing the need for additional studies investigating the relationship between this bacterium and rosacea.
对应中文
幽门螺杆菌和其他肠道细菌在玫瑰痤疮发病机制中的作用仍然存在争议。虽然一些研究报告了玫瑰痤疮患者中幽门螺杆菌阳性率的增加，但其他研究未能证实这种联系。此外，关于根除这些胃肠道细菌是否改善玫瑰痤疮，研究结果各不相同。口服抗生素是这两种疾病的标准治疗选择，这使得对这些发现的解释更加复杂。分开使用抗生素的门诊患者的两项独立研究显示，玫瑰痤疮与幽门螺杆菌感染之间有很强的相关性。在玫瑰痤疮患者中，细胞毒素相关基因A (CagA)蛋白检测呈阳性的幽门螺杆菌菌株数量增加，进一步证明了幽门螺杆菌在玫瑰痤疮中的作用。CagA是一种幽门螺杆菌毒力因子：67%的玫瑰痤疮患者检测出CagA阳性的幽门螺杆菌株，75%的患者检测出CagA抗体阳性。幽门螺杆菌感染引发玫瑰痤疮的潜在发病机制尚不清楚，因此需要进一步研究这种细菌和玫瑰痤疮之间的关系。
英文原文
B oleronius is a nonmotile, Gram-negative, endospore-forming bacteria whose role in rosacea was suggested after it was cultured from a D folliculorum mite in a patient with rosacea.Neutrophils from healthy subjects that have been exposed to B oleronius have increased production of MMP-9, tumor necrosis factor, and interleukin-8,similar to the inflammatory mediators of PPR.In rosacea patients, B oleronius triggers a proliferative response from a significantly higher number of peripheral blood mononuclear cells than in control subjects again suggesting a role of this bacteria in triggering the symptoms of rosacea.
对应中文
油状芽孢杆菌是一种不可移动的革兰阴性内孢子形成细菌，最早发现是在一例玫瑰痤疮患者的毛囊蠕形螨培养物中，提示了其在玫瑰痤疮中的作用。感染油状芽孢杆菌的健康受试者的中性粒细胞增加产生了MMP-9、肿瘤坏死因子和白细胞介素-8，类似于PPR的炎症介质。与对照组相比，在玫瑰痤疮患者中，油状芽孢杆菌引发的外周血单核细胞数量显著增加，再次表明这种细菌在引发玫瑰痤疮反应中发挥了作用。
ULTRAVIOLET LIGHT RADIATION
紫外线辐射
英文原文
UV radiation is a known trigger of flushing and can worsen the symptoms of rosacea. The presence of solar elastosis on skin biopsy specimens obtained from patients with rosacea and the high prevalence of rosacea among individuals with fair skin also suggest a role for UV radiation in the pathogenesis of rosacea; however, a recent study examining lifetime UV exposure and prevalence of rosacea failed to confirm this correlation.UVA light in particular causes overexpression of MMPs and collagen denaturation,both of which have been shown to contribute either directly or indirectly to the clinical manifestations of rosacea. UVB light increases production and secretion of fibroblast growth factor 2 and vascular endothelial growth factor 2 from human and mouse epidermal keratinocytes,again contributing to the hypervascularity seen in the skin of patients with rosacea. UV radiation also contributes to the majority of ROS present in the skin. Individuals with rosacea have increased levels of ROS in their skin compared to healthy controls.ROS have a proinflammatory effect on the skin, and can signal through TLR2 receptors, further propagating the KLK5ecathelicidin inflammatory cascade present in the skin of patients with rosacea.In addition, a recent study suggested that ROS may signal through neurogenic receptors to cause the vasodilator response seen in rosacea.
对应中文
紫外线辐射是引起潮红的一个已知诱因，它会加重玫瑰痤疮的症状。从玫瑰痤疮患者获得的皮肤活检标本上存在太阳弹力组织增生症以及皮肤白皙的个体中玫瑰痤疮的高患病率也表明紫外线辐射在玫瑰痤疮的发病机制中起作用；然而，最近一项调查终生紫外线照射和玫瑰痤疮患病率的研究未能证实这种相关性。紫外线尤其会导致基质金属蛋白酶的过度表达和胶原蛋白的变性，这两种因素都被证明可以直接或间接导致玫瑰痤疮的临床表现。UVB光促进人和小鼠表皮角质形成细胞产生和分泌成纤维细胞生长因子和血管内皮生长因子，再次导致玫瑰痤疮患者皮肤血管增多。紫外线辐射也是皮肤中存在的大部分活性氧的来源。与健康对照组相比，玫瑰痤疮患者皮肤中的ROS水平升高。ROS对皮肤具有促炎作用，并可通过TLR2受体发出信号、进一步传播玫瑰痤疮患者皮肤中存在的KLK5抗菌肽炎症级联反应。此外，最近的一项研究表明，ROS可能通过神经源性受体发出信号，导致玫瑰痤疮出现的血管舒张反应。
NEUROGENIC DYSREGULATION
神经源性失调
英文原文
The fact that many of rosacea’s triggers, including temperature changes and spicy food, activate sensory nerves prompted further investigation into the role of the skin’s nervous system in rosacea. Two subfamilies within the transient receptor potential (TRP) family of cation channels have emerged as possible contributors to rosacea’s pathogenesis based on their functions and their ability to mediate sensory and inflammatory signaling. The first group is the vanilloid (TRPV) receptors, consisting of 6 distinct channels (TRPV1-6), the first 4 of which have been shown to be active in rosacea. The first of these receptors, TRPV1, is expressed by sensory nerves and other nonneural cells, such as keratinocytes, where it is activated by capsaicin, heat, and inflammatory states,and ultimately plays a role in vasoregulation and nociception. TRPV2, -3, and -4 have also been identified on both neuronal and nonneuronal cells, such as keratinocytes, endothelial cells, and immune cells. TRPV2 has a role in innate immunity, inflammation, nociception, heat sensing, and vascular regulation. TRPV3 and TRPV4 are both activated by increased temperatures; however, TRPV3 is involved in thermosensation and keratinocyte differentiation, while TRPV4 is thought to function as an osmoreceptor and to cause vasodilation and mechanical and inflammation- evoked hyperalgesia. mRNA for TRPV1, -2, and -3 is upregulated in the skin of patients with rosacea compared to healthy control skin, and dermal immunostaining for TRPV2, -3, and -4 was increased in certain rosacea subtypes compared to dermal sections from patients with healthy skin,further supporting the role of these receptors in rosacea.
对应中文
事实上，玫瑰痤疮的许多诱因，包括温度变化和辛辣食物，都会激活感觉神经，这一事实促使人们进一步研究皮肤神经系统在玫瑰痤疮中的作用。根据玫瑰痤疮的功能和介导感觉和炎症信号的能力，瞬时感受器电位(TRP)家族阳离子通道中的两个亚家族可能参与玫瑰痤疮的发病。第一类是香草酸(TRPV)受体，由6个不同的通道(TRPV1-6)组成，前4个通道在玫瑰痤疮中被证明是活跃的。第一种受体TRPV1由感觉神经和其他非神经细胞(如角质形成细胞)表达，在角质形成细胞中被辣椒素、热和炎症状态激活，并最终在血管调节和伤害性感受中发挥作用。TRPV2、-3、-4在角质形成细胞、内皮细胞和免疫细胞等神经性和非神经性细胞上也被检测到。TRPV2在先天免疫、炎症、伤害性感受、热敏和血管调节等方面发挥作用。TRPV3和TRPV4都被温度升高激活，但TRPV3参与体温感觉和角质形成细胞分化，而TRPV4被认为是一种渗透压感受器，可以引起血管扩张、机械性和炎症诱发的痛觉过敏。与健康对照皮肤相比，玫瑰痤疮患者皮肤中TRPV1、-2和-3的mRNA表达上调，某些玫瑰痤疮亚型的真皮中TRPV2、-3和-4的免疫染色比健康皮肤的真皮切片增强，进一步支持了这些受体在玫瑰痤疮中的作用。
ABNORMAL BARRIER FUNCTION
屏障功能异常
英文原文
As a result of the pathophysiologic changes in rosacea, the skin of these patients has been shown to have a decreased barrier function. Compared to control subjects, subjects with both ETR and PPR have increased transepidermal water loss and heightened reactivity to the lactic acid stinging test, a skin irritation test taken to measure skin barrier function.In another study of subjects with PPR, these patients were found to have reduced epidermal hydration and a more alkaline centrofacial region compared to controls. Treating these patients with a 6-week course of systemic minocycline resulted in decreased erythema and increased epidermal hydration.One explanation for these changes stems from a study showing that PAR2 activation impedes barrier homeostasis in a serine proteaseedependent fashion. In addition, use of a topical serine protease inhibitor in this study accelerated barrier recovery after an acute exacerbation.These findings suggest that increased serine protease levels in rosacea subjects may contribute to the decreased barrier function and that treating rosacea may help restore the skin barrier.
对应中文
由于玫瑰痤疮的病理生理改变，这些患者的皮肤显示屏障功能降低。与对照组相比，ETR和PPR的受试者经皮失水增加，对乳酸刺痛试验(一种用来测量皮肤屏障功能的皮肤刺激性试验)的反应性增强。在另一项对PPR受试者的研究中，发现这些患者与对照组相比，真皮水合减少，面部中心区更偏碱性。对这些患者进行为期6周的全身性米诺环素治疗，可减少红斑并增加非正常水合作用。这些变化的一种解释来自一项研究，该研究表明以丝氨酸蛋白酶依赖的方式激活PAR2可以阻碍屏障内稳态。此外，在本研究中使用特异性丝氨酸蛋白酶抑制剂可加速急性发作后的屏障恢复。这些发现表明，玫瑰痤疮受试者皮肤蛋白酶水平升高可能导致屏障功能降低，治疗玫瑰痤疮可能有助于恢复皮肤屏障。
RISK FACTORS
危险因素
英文原文
To date, no specific risk factors have been associated with rosacea. Given that vascular dysregulation has been recognized in the pathophysiology of rosacea, several studies have investigated a potential relationship between rosacea and other conditions in which vascular dysregulation is known to occur. For example, a recent case control study of subjects who suffer from migraines found that women ＞50 years of age who had migraines had a slightly increased risk of developing rosacea. Similarly, a case control study of rosacea patients found that these patients had a slightly higher risk of developing cardiovascular disease.Although it is difficult to draw conclusions from such a limited number of studies, these findings suggest the need for additional investigation into whether the vascular dysfunction seen in rosacea could be signaling a systemic issue.
对应中文
到目前为止，还没有特定的危险因素与玫瑰痤疮有关。鉴于在玫瑰痤疮的病理生理学中已经认识到血管调节障碍，一些研究已经调查了玫瑰痤疮和已知发生血管调节障碍的其他疾病之间的潜在关系。例如最近一项针对偏头痛患者的病例对照研究发现，超过50岁患有偏头痛的人患玫瑰痤疮的风险略有增加。同样，对60例玫瑰痤疮患者进行的病例对照研究发现，这些患者患心血管疾病的风险也稍高。尽管很难从如此有限的研究中得出结论，但这些发现表明有必要进一步调查玫瑰痤疮是否存在血管功能障碍。
英文原文
In conclusion, rosacea is a chronic inflammatory condition affecting skin mainly of the central face. Four main subtypes of rosacea are recognized, all of which are usually diagnosed clinically. Although the cause of rosacea remains unclear, dysregulation of the innate and adaptive immune systems and the nervous system seem to contribute to its pathogenesis, ultimately leading to hypersensitive skin in response to common environmental triggers. Through additional research, advances in the understanding of rosacea can hopefully shed light on the remaining questions regarding rosacea.
对应中文
总而言之，玫瑰痤疮是一种慢性炎症性疾病，主要影响皮肤的中央面部。常见的玫瑰痤疮有四种主要亚型，临床上通常都诊断为玫瑰痤疮。虽然玫瑰痤疮的病因尚不清楚，但先天性和获得性免疫系统以及神经系统的失调似乎是其致病原因之一，最终导致皮肤对常见环境刺激反应过敏。通过进一步的研究，对玫瑰痤疮的理解进展有望阐明关于玫瑰痤疮的其余问题。
REFERENCES
1.Two AM, Wu W, Gallo RL, Hata TR. Rosacea: part I. Introduction, categorization, histology, pathogenesis, and risk factors. J Am Acad Dermatol. 2015 May;72(5):749-58; quiz 759-60.