Clinical manifestations and diagnosis of Raynaud's phenomenon
雷诺现象的临床表现和诊断
著者：Fredrick M Wigley, MD 译者：刘湘源
Raynaud's phenomenon (RP) is an exaggerated vascular response to cold temperature or emotional stress. The phenomenon is manifested clinically by sharply demarcated color changes of the skin of the digits. Abnormal vasoconstriction of digital arteries and cutaneous arterioles due to a local defect in normal vascular responses is thought to underlie the disorder .
雷诺现象是对遇冷或情绪应急的一种过度的血管反应。该现象临床上表现为指（趾）皮肤明显的颜色改变。本病的基础是因正常血管反应的局部缺陷而导致的指（趾）动脉和皮肤小动脉的异常血管收缩。
RP is considered primary if these symptoms occur alone without evidence of any associated disorder. By comparison, secondary RP refers to the presence of the disorder in association with a related illness, such as systemic lupus erythematosus and scleroderma.
如果这些症状单独出现而无任何合并的疾病，则认为是原发雷诺现象。相比而言，继发雷诺现象指存在合并某相关疾病如SLE和硬皮病的病症。
This card will review the clinical manifestations and diagnosis of Raynaud's phenomenon. The pathogenesis and treatment of this disorder are presented separately.
本章节将综述雷诺现象的临床表现和诊断。其发病机制和治疗分别叙述。
PREVALENCE – Community-based surveys have only recently been performed to estimate the prevalence of RP in the general population. In these surveys, prevalences of RP have ranged from 5 to 20 percent in women and 4 to 14 percent in men. These relatively wide ranges reflect in part the populations that are studied. As an example, RP is more common inFrance(17 percent) than in theUnited States(5 percent). Most data support a prevalence of 3 to 4 percent in various ethnic groups; a recent survey performed by the author in an African-American community also found a prevalence of 3 percent (unpublished observation). RP is more common among young women, younger age groups, and family members of patients with RP.
发生率—最近进行的社区调查评估了一般人群的雷诺现象的发生率。在这些调查中发现，在妇女中的雷诺现象的发生率为5%-20%，在男性中为4%-14%，结果范围相对宽部分反映出所研究的人群。例如，法国比美国更普遍（分别为17%和5%）。大多数的资料支持在不同种族人群中的发生率为3%-4%。最近有作者对非洲-美国人社区进行的调查也发现其发生率为3%（结果未报告）。雷诺现象在年轻妇女、较年轻组和家族中有雷诺现象的成员更常见。
CLINICAL MANIFESTATIONS – Raynaud's phenomenon most often affects the hand; attacks also frequently occur in the toes, but patients are less likely to complain of lower extremity symptoms. A typical episode is characterized by the sudden onset of cold fingers (or toes) in association with sharply demarcated color changes of skin pallor (white attack) and/or cyanotic skin (blue attack). With rewarming, the ischemic phase (white or blue attack) usually lasts for 15 to 20 minutes. The skin subsequently blushes upon recovery, thereby resulting in the erythema of reperfusion.
临床表现—雷诺现象最常累及手，也可出现足趾的发作，但患者较少抱怨下肢的症状。典型发作的特征是遇冷手指（或足趾）突然发病，有明显的皮肤颜色变白（白色发作）或青紫（蓝色发作）改变，复温后，缺血阶段通常持续15-20分钟，然后皮肤恢复性变红，因此导致再灌注性红斑。
A Raynaud's attack typically begins in a single finger and then spreads to other digits symmetrically in both hands. The index, middle, and ring finger are the most frequently involved digits, while the thumb is often spared entirely. Cutaneous vasospasm is also common at other sites, including the skin of the ears, nose, face, knees and nipples. A common pathophysiologic feature of affected areas is the presence of thermoregulatory vessels.
典型的雷诺现象发作以单个手指开始，然后对称性累及双手的其他手指。示指、中指和环指是最常累及的手指，而拇指常完全不受累。在其他部位的皮肤血管痉挛也常见，包括耳、鼻、膝关节和乳头的皮肤。这些受累部位的共同病理生理特征是存在温度调节性血管。
Livedo reticularis – The patient with RP may also have mottling of the skin of the arms and legs during a cold response, a sign called livedo reticularis. This finding is benign and completely reversible with rewarming. Livedo reticularis may also be found in patients with vasculitis or occlusive vascular disease (eg, due to atheroemboli or thrombosis).
网状青斑—有雷诺现象的患者在对冷反应期间也可有手臂和腿皮肤的青斑，称为网状青斑征。这种现象是良性的，复温后可彻底逆转。网状青斑也可发生在血管炎或闭塞性血管疾病患者（如由于动脉粥样硬化性栓塞或血栓形成
Symptoms of low blood flow and ischemia – The symptoms of RP may include complaints resulting from low blood flow or ischemia. As an example, mild RP may be associated with sensations of pins and needles, numbness and/or clumsiness of the hand, and finger aching. The signs of uncomplicated RP should be completely reversible on rewarming or reduction of stress. In severe secondary RP, pain or ulceration of the skin (typically the tips of the fingers and toes) may result from critical tissue ischemia.
低血流量和缺血的症状—雷诺现象的症状可包括因低血流量或缺血所致的主诉。例如，轻度雷诺现象可合并针刺样、麻木和（或）手笨拙感，及手指疼痛。不复杂的雷诺现象的体征应在复温或精神紧张度下降后可逆性完全恢复，在严重继发性雷诺现象，极度的组织缺血可导致皮肤疼痛或溃疡（典型性地出现在手指和足趾尖）。
Provoking factors – Patients note that exposure to cold temperature triggers RP. More importantly, the provocation occurs during relative shifts from warmer to cooler temperatures. As a result, mild cold exposures such as air-conditioning or the cold of the refrigerated food section of the grocery store may cause an attack. Although attacks occur locally in the fingers, a general body chill will also trigger an episode, even if the hands or feet areas are kept warm. To avoid RP, therefore, patients must maintain whole body warmth.
诱发因素—患者注意到暴露在冷温下可触发雷诺现象。更为重要的是，触发可出现在从较温暖的环境中变换到较冷的环境期间，结果，如在空调或食品杂货店食物冷冻区这样的轻度冷环境中也可诱发发作。虽然发作仅局限在手指局部，但全身性的寒冷（即使手或足保温）也将触发发作。因此，为避免雷诺现象，患者必须保持整个身体的温暖。
An attack of RP may also occur after stimulation of the sympathetic nervous system (such as emotional stress, sudden startling). It is not uncommon for the physician to witness a typical attack during the first encounter with a frightened or nervous patient.
雷诺现象的发作也可出现在交感神经系统刺激之后（如情绪紧张，突然惊吓）。对于内科医生来说，当第一次遇到受到惊吓或神经质的患者时，目击典型的发作并不少见。
DIAGNOSIS – A diagnosis of RP may be made if the patient provides a history of the sudden onset of symptoms characteristic of a Raynaud's attack. Such a history alone must be accepted as diagnostic, since no simple office test consistently triggers an attack. In fact, attempts to induce an attack, such as a cold water challenge, are not recommended since the responses are inconsistent even in those with definite RP. However, digital vascular responses to cooling, using complex instrumentation to measure digital blood pressure, digital blood flow, and skin temperature, may distinguish patients with primary RP from normal individuals and those with scleroderma .
诊断—如果患者提供以雷诺现象突然发作为特征的症状的病史时，则可诊断雷诺现象。这种的单独的病史必需接受具有诊断性，因为没有简单的诊室试验可一致性地触发发作。其实，并不推荐诱发发作试验（如冷水试验），因为即使在有肯定的雷诺现象患者，反应也是不一致的。然而，冷却下的手指血管反应可通过复杂的仪器测定手指血压、血流和皮肤温度来获得，可用来鉴别原发雷诺现象和正常人及硬皮病患者。
Finger systolic pressure and response to cold challenge (digital artery closing temperature) can be measured by using the Neilson technique . A digital blood pressure cuff is placed around the proximal phalanx. The cuff is inflated to a suprasystolic pressure, and the opening pressure is determined as the cuff is deflated. The temperature can be changed around the finger by placing a second cuff containing water at various temperatures on the proximal part of the finger. The water temperature is slowly lowered until digital artery closure (Raynaud's attack) is detected by a drop of the systolic digital pressure to zero by a transducer, Doppler flowmeter or strain gauge placed on the distal finger. The temperature at which closure occurs is the "closing temperature." Skin temperature can also be monitored by a small thermometer attached to the skin.
可用Neilson技术测得手指收缩压及对冷刺激反应（指动脉闭合温度）。用指测血压布袖带缠绕近节指骨，袖带充气超过收缩压，当袖带放气时测得收缩压。用装有不同温度水的第2个袖带缠绕手指近节来改变手指周围的温度，水的温度缓慢降低直到放置在指远节的传感器（多普勒流量计或应力计）显示手指收缩压降低到零，即指动脉关闭（雷诺现象发作），动脉关闭时的温度就是“闭合温度”，用紧贴在皮肤上的小温度计可监测出皮肤的温度。
The complaint of cold hands or feet is very common in the general population and must be distinguished from RP, which involves both cool skin and cutaneous color changes. Normal individuals will cool the skin and may experience some skin mottling on cold exposure. However, unlike RP, the recovery phase of vascular flow is not delayed and there is no prolonged sharp demarcation of color changes in skin.
手或足发冷在一般人群中是很普遍的，必须与雷诺现象相鉴别，雷诺现象是既有皮肤发冷，也有皮肤颜色的改变。正常人遇冷后，皮肤将发凉，可有一些皮肤呈斑点状。然而，不象雷诺现象，其血流恢复期并不延迟，也无长时间的明显皮肤颜色改变。
To aid in making a diagnosis, one investigator has introduced the use of a standard questionnaire and actual color photos of witnessed attacks that the patient must identity. This method has been used in epidemiologic studies investigating the prevalence of RP in the community .
为有助于诊断，一个研究人员推荐用一份标准问卷及让患者鉴认出发作时的实际颜色像片，该方法已应用于调查社区雷诺现象发生率的流行病学研究。
Clinical criteria – Clinical criteria describing relative degrees of certainty in the diagnosis of RP have recently been proposed:
• Definite RP – Repeated episodes of biphasic color changes upon exposure to cold
• Possible RP – Uniphasic color changes plus numbness or paresthesia upon exposure to cold
• No RP – No color changes upon exposure to cold
We presently use these criteria as a practical guide to the diagnosis of RP.
临床标准—最近有人提出了诊断雷诺现象的相对把握度的临床标准：
• 肯定的雷诺现象—遇冷后反复发作的双项颜色改变；
• 可能雷诺现象—遇冷后出现单项颜色改变加上麻木或感觉异常；
• 无雷诺现象—遇冷后无颜色的改变。
我们目前就是应用这项标准来指导诊断雷诺现象。
Prior to discussing the evaluation of the patient with RP, it is helpful to first briefly review the definition and clinical characteristics of the primary and secondary forms of the disorder. The presence or absence of these findings help direct patient assessment.
在讨论雷诺现象患者的鉴定之前，先简单复述一下原发和继发雷诺现象的定义和临床特征。有或无这些特征有助于指导病人评价。
PRIMARY AND SECONDARY RAYNAUD'S PHENOMENON – Patients with RP are considered to have either a primary or secondary process:
• Primary RP – Primary RP or idiopathic Raynaud's disease have become popular terms to describe those patients without a definable cause for their vascular events. In this setting, RP is considered to be an exaggeration of normal vasoconstriction to cold exposure. Most investigators feel the term "disease" is inappropriate, and prefer using the term primary RP for otherwise healthy individuals.
原发和继发雷诺现象——有以下原发或继发性病变则考虑为雷诺现象患者：
• 原发雷诺现象—原发或特发雷诺病已成为一种普及术语，来描述那些不存在可解释的血管疾病的患者，从这个角度来说，雷诺现象被认为是遇冷后正常血管的一种过度收缩。大多数研究人员人员对健康个体采用“雷诺病”术语是不合适的，而愿意使用“原发雷诺现象”术语。
• Secondary RP – Secondary RP refers to those patients with RP in whom an associated disease or cause may underlie the attacks [8]. Other investigators prefer the term Raynaud's syndrome [10].
• 继发雷诺现象——继发雷诺现象指的是那些所合并的疾病或病因作为发作基础的雷诺现象患者。其他一些研究人员愿意用“雷诺综合征”术语。
Primary RP – Primary RP has an age of onset between 15 and 40 years of age (with a mean of 30 years), is more common in women, and may occur in multiple family members . Specific criteria for the diagnosis were first proposed by Allen and Brown in 1932 . These criteria have been revised to include modern laboratory measurements and nailfold capillary microscopy, and to provide a diagnosis of primary RP without the previous requirement of two years of follow-up.
原发雷诺现象—原发雷诺现象的发病年龄在15-40岁（平均年龄30岁），在女性多见，可出现在多个家族成员。其诊断特殊标准最早由Allen和Brown于1932年提出。这些标准已得到修订的包括现代实验室检查和甲襞毛细血管显微术，以及随访2年未出现前面提到的要求才能诊断原发雷诺现象。
Current criteria for the diagnosis of primary Raynaud's phenomenon include the following:
• Symmetric episodic attacks
• No evidence of peripheral vascular disease
• No tissue gangrene, digital pitting, or tissue injury
• Negative nailfold capillary examination
• Negative antinuclear antibody test and normal erythrocyte sedimentation rate
目前诊断原发雷诺现象的标准包括以下：
• 对称性发作
• 无外周血管疾病的证据
• 无组织坏疽、指（趾）凹陷或组织损伤
• 甲襞毛细血管检查阴性
• 抗核抗体阴性和血沉正常
Although patients with primary RP are generally otherwise healthy, comorbid conditions can occur that may aggravate attacks. These include hypertension, atherosclerosis, cardiovascular disease, and diabetes mellitus.
虽然原发性雷诺现象患者一般是健康的，但合并出现的某些不健康情况可使发作加重，这些情况包括高血压、动脉粥样硬化、心血管疾病和糖尿病。
Secondary RP – Since a variety of possible insults can disrupt the normal complex regulation of regional blood flow to the digits and skin, the number of disorders associated with RP is extensive. The most common associated disorders are scleroderma, systemic lupus erythematosus, other connective tissue diseases, and occlusive vascular disease.
继发性雷诺现象—因为多种可能的刺激可打破指（趾）和皮肤的局部血流的正常复杂调节，但是与雷诺现象相关的疾病数量是广泛的。最常见相关的疾病是硬皮病、SLE、其他结缔组织病和闭塞性血管病变，
However, since primary RP is common in the general population, some reported associations of RP have not been proven. As an example, the prevalence of RP in rheumatoid arthritis is controversial. Some surveys suggest no increase in risk , but a recent study found that 54 of 322 (17.2 percent) patients with rheumatoid arthritis had RP. The patients with RP in the last study had a slightly higher incidence of vasculitis.
然而，因原发雷诺现象在一般人群中普遍，故雷诺现象的某些所报告的相关因素还未得到证实，如在类风湿关节炎中雷诺现象的发生率是有争论的，某些调查提示其危险性无增高，但最近对322例RA患者的研究发现，有54例（占17.2%）的患者有雷诺现象，这项最新研究中有雷诺现象的患者发生血管炎的几率有轻度升高。
EVALUATION – Although extensive special testing is not always necessary, every patient with a diagnosis of RP should be carefully evaluated, beginning with an attempt to identify a secondary cause. Clinical clues to suggest secondary RP include [15]:
评估—虽然不需总是进行广泛的特殊试验，但每个诊断雷诺现象的患者应仔细做评估，以努力鉴定继发性因素开始，提示继发性雷诺现象的临床线索包括：
• Later age of onset (greater than 40 years)
• Male sex
• Painful severe events with tissue sign of ischemia (ulceration)
• Asymmetric attacks
• RP associated with signs or symptoms of another disease
• Abnormal laboratory parameters suggesting vascular disease or an autoimmune disorder
• RP associated with ischemic signs or symptoms proximal to the fingers (such as the hand or arm) or toes (foot or limb).
• 发病年龄较晚（大于40岁）
• 男性患者
• 有组织缺血征（溃疡）的疼痛性严重事件
• 非对称性发作
• 与其他疾病的症状与体征相关的雷诺现象
• 提示血管疾病或自身免疫性疾病的异常实验室指标
• 在手指近端（如手或臂）或足趾近端（如足或下肢）的缺血性体征或症状相关的雷诺现象。
Beyond a good history and physical examination, the basic evaluation of the patient with RP should therefore include a sedimentation rate, antinuclear antibody (ANA) titer, and nailfold capillaroscopy. These findings will direct any further specific testing needed to diagnosis a secondary cause. An evaluation for specific autoantibodies should be initiated if a positive ANA is found (see below).
除好的病史和体格检查外，雷诺现象患者的基础评估应包括血沉、ANA和甲襞毛细管显微镜检查，其结果所见可指导进行为诊断继发因素所需的进一步特殊试验，如果ANA阳性，则应开始进行特殊自身抗体的检测。
Patients whose clinical characteristics satisfy the criteria for primary RP (as mentioned above) may require only a basic evaluation that includes a microscopic assessment of nailfold capillaries. This examination is performed by dropping oil on the periungual area and examining with an ophthalmoscope set at diopter 40, or with a dissecting microscope. Enlarged or distorted capillary loops suggest an underlying or an increased likelihood of eventually developing a connective tissue disease . If the enlargement is associated with loss of capillaries, then the patient is more likely to have or develop scleroderma.
临床特点满足上面提到的原发雷诺现象的诊断标准的患者，也许仅需要进行一项基础检查，包括甲襞毛细管的显微镜检查。进行这项检查需在甲周点滴油，用屈光度为40的眼底镜，或用解剖显微镜进行检查。扭转或扩张的毛细血管环提示最终发展为结缔组织病的潜在可能性或可能性增高。如果扩张合并毛细血管丧失，则患者更可能有或发展为硬皮病
