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我们将为大家提供2期连载内容，本文为第1期 摘要 脂溢性皮炎是一种慢性复发性炎症性皮肤病，以鳞屑及边界不清的红斑为特征。成人脂溢性皮炎的患病率大约为5％。尽管脂溢性皮炎的确切病因至今尚不明确，但马拉色菌、激素（雄激素）、皮脂水平和免疫反应对其发展起着重要的作用。其他因素包括药物、冬季温度以及压力也可能加剧脂溢性皮炎。可供选择的治疗方法有很多，其中包括抗真菌制剂、外用弱效类固醇和钙调磷酸酶抑制剂（免疫调节剂）。本文对目前现有的关于成人脂溢性皮炎的发病机制以及治疗方法进行了总结。 简介 脂溢性皮炎（SD）是一种常见的慢性复发性炎症性皮肤病，临床上以鳞屑及边界不清的红斑为特征。SD主要累及皮脂分泌丰富的部位，其中包括头皮、面部、上胸部和背部。成年SD的患病率大约为5％。与女性相比，该疾病更多于见男性。在成年人中，发病高峰期在30岁和40岁之间。尽管脂溢性皮炎的确切病因至今尚不明确，但马拉色菌、激素（雄激素）、皮脂水平和免疫反应在其发病机制中起着重要的作用。一些研究人员提出马拉色菌（以前称为卵状糠秕孢子菌）在脂溢性皮炎中起着关键的作用。抗真菌疗法导致马拉色菌菌属定植减少，并且随后皮损消失，这强有力的证明了马拉色菌菌属在SD发展过程中的重要作用。其他的治疗方法包括糖皮质激素、免疫调节剂和抗生素。 病因和发病机制 尽管这种疾病的发病率较高，但对其确切病因知之甚少。然而，一些因素（马拉色菌、激素、皮脂水平、免疫反应、神经源性因素、外部因素）可能参与了SD的病因和发病机制，但其确切发病机制仍然存在争议。 马拉色菌菌属 越来越多的证据表明，马拉色菌菌属是SD发病的主要致病因素。抗真菌治疗后，马拉色菌数量减少，并且皮损消失。这强有力的证明了马拉色菌菌属在SD发展过程中起着重要的作用。马拉色菌菌属是亲脂性酵母，普遍存在于患者的皮肤。它们主要位于脂质丰富的区域。然而，目前已经鉴定出11个物种，其中7种与人体皮肤菌群和SD相关。在受累皮肤中检测到Malassezia (M.) furfur, M. restricta, M. sympodialis, M. globosa, M. obobtusa和M. slooffiae的存在。然而，在SD皮损中M. globosa 和 M. restricta占主要地位，尤其是头皮处。由于马拉色菌菌属具有产生脂酶的能力，它们可将皮脂分解释放油酸和花生四烯酸而引发炎症反应。这两种不饱和脂肪酸直接刺激角质形成细胞并且产生脱屑的作用。此外，由环氧化酶代谢产生的花生四烯酸作为促炎性类花生酸类物质（特别是前列腺素）的来源，引发炎症反应，并且损害角质层。受累部位的角质形成细胞受到刺激后，产生炎性细胞因子，进一步加强和维持炎症反应。由马拉色菌脂酶释放的饱和脂肪酸，作为这些酵母菌的“增殖养料”导致马拉色菌驱动的致病“恶性循环”。 激素和皮肤脂质 SD并不总是与皮脂过度分泌相关。但是，50％的患者为油性、皮脂过多的皮肤。如上所述，皮脂脂质是马拉色菌增殖以及初始促炎症因子合成所必需，因此一定量的皮脂是必要的，其为SD的发展提供了充足的条件。因此，SD皮损主要位于皮脂腺丰富的区域。SD在青春期和青少年期最为常见，因为此时期皮脂分泌最多。同时也可能与激素相关：该疾病不仅好发于青春期，而且与女性相比，SD在男性中更为常见，这表明了雄激素对于毛囊皮脂腺单位的影响。 免疫反应 因为SD是一种炎症性疾病，主要伴有马拉色菌，因此有理由假设不适当的免疫反应可能参与了其发病机制。尽管参与SD的免疫发病机制尚不清楚，但一些研究表明SD患者免疫功能低下。与普通人群（约3％）相比，在HIV阳性和AIDS患者中，SD患病率显著增高（34％-83％），这一证据强有力的证实了免疫缺陷是其致病因素。此外，在HIV阳性患者中，SD的临床表现更加严重（通常累及到四肢）；因此，一些学者认为，在这些免疫功能缺陷的患者中，SD被认为是一种独特的疾病（“获得性免疫缺陷综合征脂溢样皮炎”）。由Bergbrant等人的研究直接表明与对照组相比，SD患者T细胞功能受损，且外周血液中NK细胞的数目显著增加。同一项研究也表明了SD患者血清总IgA和IgG抗体水平增加，并且其他的几项研究也证实这一结果。有趣的是，虽然在SD患者中存在高球蛋白血症，但是对马拉色菌抗原具有特异性的抗体的滴度并未升高，这表明免疫球蛋白产生的增加，是对酵母毒素和脂酶活性的反应。Faergemann等人发现在SD皮肤受累部位伴有NK细胞和巨噬细胞浸润，同时伴有局部补体激活以及诱发促炎细胞因子，共同导致表皮细胞的破坏。考虑到马拉色菌可存在于皮肤共生体，但并不引起任何免疫反应或炎症反应，因此可以得出， 在SD患者中，对该酵母的异常免疫反应，可能会通过其他致病因素的相互作用产生影响，并且可能会支配和调节个体的免疫应答。 神经源性因素 在长期的临床观察中发现，帕金森病的患者经常出现SD，尤其是那些伴有长期的、严重的皮脂溢出的患者，因为他们为马拉色菌的增殖提供了适当的条件。由于在单侧帕金森综合征患者中出现了双侧皮脂溢出，因此这些皮脂水平的变化可能是由内分泌而非神经因素导致。在帕金森氏症患者中发现血浆α-黑素细胞刺激激素（α-MSH）的水平增加，这可能是由于缺乏MSH抑制因子，导致巴胺神经元活动降低。 因此，在帕金森患者中，应用左旋多巴成功修复MSH-抑制因子的合成并且减少了皮脂分泌。左旋多巴对于皮质的作用仅限于治疗帕金森氏病的患者，而其他皮脂溢出性疾病如痤疮，左旋多巴对皮脂分泌没有影响。此外，帕金森患者面部僵硬（假面具样面容）可以继发导致皮脂累积增加，从而进一步促进SD的发展。对于应用精神病药物治疗的患者，以及迟发性运动障碍、中枢神经系统创伤和面神经麻痹的患者，经常出现SD可能也是由于相似的机制。在抑郁症患者中也观察到SD频繁出现，但这可能是由于抑郁症患者倾向呆在室内，以及卫生习惯改变有关。 其他因素 SD是一种季节性的疾病；该疾病在秋冬天更易复发。情绪压力也能够引发该疾病;据报道在战争时期，作战部队中脂溢性皮炎发病率较高。传统上，饮食可以影响SD的发展。伴有严重锌缺乏症的肠病性肢端皮炎和肢端皮炎样疾病的患者可能会产生脂溢性皮炎样的皮疹。普通的SD对于补锌治疗无效。 临床表现 典型的SD皮损为红色斑片，表面覆油腻性鳞屑。该疾病好发于皮脂腺丰富区域，如头皮、发际线、眉毛、眉间、鼻唇沟、耳后、上胸部、背部、腋窝、脐部和腹股沟。通常伴有瘙痒，尤其是头皮和外耳道。头皮皮损可延伸至前额皮肤并且形成鳞屑性红色边界，称为“额皮脂溢疹”。胸部可能出现两种类型的SD，一种是常见的花瓣样型，一种是非常罕见的糠疹样型。花瓣样类型起初表现为红色到褐色的毛囊和毛囊周围丘疹，随后发展为类似花瓣或徽章样的斑片。糠疹样型可能是花瓣样SD严重的急性型。这种类型沿皮纹泛发性分布斑疹和斑片，与玫瑰糠疹相似。在某些个体中，耳道的慢性皮炎可以是SD的唯一临床表现。SD另外一种常见的症状为沿着眼睑边缘分布的，伴有蜂蜜色痂皮的眼睑炎。当仅出现这种临床症状时，不能简单的对其诊断。该病的严重类型是泛发性剥脱性红皮病（脂溢性红皮病）。 SUMMARY Seborrheic dermatitis is a chronic relapsing inflammatory skin disorder clinically characterized by scaling and poorly defined erythematous patches. The prevalence of adult seborrheic dermatitis is estimated at 5%. Although the exact cause of seborrheic dermatitis has yet to be understood, Malassezia yeasts, hormones (androgens), sebum levels and immune response are known to play important roles in its development. Additional factors including drugs, winter temperatures and stress may exacerbate seborrheic dermatitis. A variety of treatment modalities are available, including antifungal agents, topical low-potency steroids and calcineurin inhibitors (immunomodulators). This review summarizes current knowledge on the etiopathogenesis and therapy of adult seborrheic dermatitis. INTRODUCTION Seborrheic dermatitis (SD) is a common chronic relapsing inflammatory skin disorder clinically characterized by poorly defined erythematous patches and scaling. SD primarily affects sebum rich areas, including scalp, face, upper chest and back. The prevalence of adult SD is estimated at 5%. This condition is more common in males than in females. Among adults, the peak incidence is in the third and fourth decades of life. Although the exact cause of SD has yet to be understood, Malassezia yeasts, hormones (androgens), sebum levels and immune response are known to play important roles in its etiopathogenesis. Some researchers propose a pivotal role for Malassezia yeasts (formerly called Pityrosporum ovale) in seborrheic dermatitis. Antifungal therapy leads to decreased colonization with Malassezia spp. and concomitant disappearance of skin lesions, which is probably the strongest evidence that Malassezia spp. have momentous role in the development of SD. Other therapeutic options include corticosteroids, immunomodulators and antibiotics. ETIOLOGY AND PATHOGENESIS Despite quite a high prevalence of this disorder, the exact cause is poorly understood. However, several factors (Malassezia yeasts, hormones, sebum levels, immune response, neurogenic factors, external factors) seem to be involved in SD etiopathogenesis, but the exact pathogenetic mechanism still remains controversial. Malassezia species Growing evidence indicates that Malassezia spp. are a major etiologic factor in SD development. The number of Malassezia spp. decreases after antifungal therapy with disappearance of skin lesions. This is probably the strongest evidence that Malassezia spp. have an important role in the development of SD. Malassezia spp. are lipophilic yeasts that are ubiquitous residents of the skin. They are predominantly situated on lipid-rich anatomic areas. Whereas eleven species have been identified, seven of them are associated with human skin flora and SD. Malassezia (M.) furfur, M. restricta, M. sympodialis, M. globosa, M. obobtusa and M. slooffiae have been detected on affected skin. However, M. globosa and M. restricta predominate in SD lesions, particularly on the scalp. Since Malassezia spp. have the ability to produce lipases, they can initiate inflammatory response by releasing oleic and arachidonic acid from the sebum lipids. Both of these unsaturated fatty acids have direct irritative and desquamative effects on keratinocytes. Furthermore, arachidonic acid metabolized by cyclooxygenase serves as a source of proinflammatory eicosanoids (particularly prostaglandins), leading to inflammation and consequent damage of stratum corneum. Keratinocytes at affected areas are stimulated to produce proinflammatory cytokines that further enhance and maintain the inflammatory response. Malassezia-driven pathogenetic “vicious circle” closes owing to the fact that saturated fatty acids, released by Malassezia lipases, are used as a “proliferative fuel” for these yeasts. Hormones and skin lipids SD is not always associated with excessive secretion of sebum. However, 50% of patients have oily, sebum rich skin. As mentioned above, sebum lipids are essential for Malassezia proliferation and synthesis of initial proinflammatory factors, so a certain amount of sebum is always required in order to provide permissive conditions for SD development. Therefore, SD lesions are predominantly located on skin areas rich in sebaceous glands. SD is most common in puberty and adolescence, during periods of highest sebum production. There is also a possible hormonal link: not only does the disease occur in puberty, but SD is more common in males than in females, suggesting an influence of androgens on the pilosebaceous unit. Immune response Since SD is an inflammatory condition, largely accompanied by the presence of Malassezia yeast, it is reasonable to assume that inappropriate immune response may contribute to the pathogenesis. Although the immune pathogenetic mechanism involved in the development of SD is not clearly understood, several studies indicate immune dysfunction in SD patients. The strongest evidence for immunodeficiency as an etiologic factor comes from findings that SD prevalence is significantly higher (34%-83%) among HIV positive and AIDS patients compared to general population (approximately 3%). Furthermore, in HIV positive patients, a more severe clinical presentation of SD (often affecting even extremities) has been observed; hence, SD in these patients is considered by some authors as a distinctive entity (“seborrheic-like dermatitis of acquired immunodeficiency syndrome”). Studies conducted by Bergbrant et al. have directly shown impaired function of T cells and increased number of NK cells in peripheral blood of SD patients compared to control group. The same study showed increased levels of total serum IgA and IgG antibodies in patients with SD, which was also confirmed by several other studies. Interestingly, despite the presence of hypergammaglobulinemia in SD patients, there were no elevated titers of antibodies specific to Malassezia antigens, suggesting that increased immunoglobulin production occurs as a response to yeast toxins and lipase activity. Faergemann et al. found infiltration of NK cells and macrophages in SD affected skin areas, with concomitant local activation of complement and proinflammatory cytokine induction, which all together can result in epidermal devastation. Considering the fact that Malassezia may be present on the skin commensally, without provoking any immune reaction or inflammation, it could be concluded that in SD patients an abnormal immune reaction to the yeasts occurs, which is influenced by the interplay of other pathogenetic factors that may govern and modulate an individual immune response. Neurogenic factors The frequent occurrence of SD in patients with Parkinson’s disease has long been clinically observed, particularly in those with prolonged and severe seborrhea, which provides permissive conditions for Malassezia proliferation. Since bilateral seborrhea occurs in patients with unilateral parkinsonism, it seems that these changes in sebum level are provoked endocrinologically rather than neurologically. This is supported by the findings of increased plasma α- melanocyte stimulating hormone (α-MSH) levels in patients with Parkinson’s disease, probably due to the lack of MSH-inhibiting factor as a consequence of insufficient dopaminergic neuronal activity. Namely, treatment with L-dopa successfully restores MSH-inhibiting factor synthesis and reduces sebum secretion in parkinsonian patients. This sebostatic effect of L-dopa is limited exclusively to patients with Parkinson’s disease, whereas in other seborrheic conditions such as acne, L-dopa has no effect on sebum production. Furthermore, facial immobility of Parkinson’s disease patients (mask-like face) can secondarily lead to the increased sebum accumulation, thus additionally contributing to the tendency of SD development. Similar mechanisms may be, at least partially, responsible for the frequent occurrence of SD in patients treated with neuroleptic drugs, as well as in patients with tardive dyskinesia, central nervous system trauma and facial nerve palsy. Frequent occurrence of SD is also observed in depressive disorders, but this could be attributed to the tendency of depressed patients to remain indoors, as well as to altered hygiene habits. Other factors SD has a seasonal aspect; relapse of the disease is more common in low fall and winter. The condition can be triggered by emotional stress; a high rate of seborrhea is reported among combat troops in war times. Traditionally, diet is blamed for the development of SD. A severe zinc deficiency in patients with acrodermatitis enteropathica and acrodermatitis- like conditions can produce a seborrheic dermatitis- like rash. Common SD does not respond to supplementary zinc therapy. CLINICAL FEATURES Typical SD lesions are erythematous patches, with greasy large scales. The disorder has a predilection for areas with numerous sebaceous glands, such as scalp, hairline, eyebrow, glabella, nasolabial folds, ears, upper chest, back, axillae, umbilicus and groins. Patients often report pruritus, especially on the scalp and in the ear canal. Scalp lesions may extend into the forehead skin and form scaly erythematous border called “corona seborrheica“. Two forms of SD may occur on the chest, a common petaloid type and quite rare pityriasiform type. The petaloid type starts with red to brown follicular and perifollicular papules, which develop to patches that resemble the shape of flower petals or medallion. The pityriasiform type is probably an acute severe form of petaloid SD. This type has generalized maculae and patches that follow the skin lines mimicking pityriasis rosea. In some individuals, chronic dermatitis of the ear canal may be the only manifestation of SD. Another common symptom of SD is blepharitis with honey-colored crusts along the rim of the eyelid. When only this manifestation is present, the diagnosis is not simple. A serious variant of this skin disorder is generalized exfoliative erythroderma (seborrheic erythroderma). 由MediCool医库软件 冯飞飞编译 本文出自：Acta Dermatovenerol Croat 2012;20(2):98-104 |
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