最新国际纤维肌痛指南表明焦点转移

圣迭戈——以色列特拉维夫Sourasky医学中心的Jacob N. Ablin博士在美国风湿病学会(ACR)年会上指出，近来分别由加拿大、以色列和德国的多学科专家组独立编撰的纤维肌痛指南之间具有很高的一致性，提示这种常见且令人烦恼的综合征的概念化和治疗正在发生重大变化。

“这三部指南均强调应根据关键症状和严重程度量身定制治疗方案，并且将非药物治疗作为所有患者的首要选择。”三者均强调了自我管理策略的必要性，包括有氧运动、认知行为治疗、多成分锻炼和心理治疗。


Jacob Ablin博士

“这三个组织对药物治疗的推荐都相对不太积极。与流行的观点相反，药物治疗实际上只能产生相对轻微的效果。而且这三个组织均提醒注意药物副作用，后者可能与纤维肌痛症状相似。”

目前美国食品药品管理局(FDA)批准了三种药物用于治疗纤维肌痛：普瑞巴林(Lyrica)、度洛西汀(Cymbalta)和米那普仑(Savella)。但在德国指南中，这三种药物只获得了较弱的C级推荐(Schmerz 2012;26:287-90)，原因是三者均未能在关键的欧洲临床试验中达到主要终点。

“尽管药物治疗必然会在纤维肌痛的管理中继续占有一席之地，非药物治疗的长期安全性和效果应该得到认可和重视。纤维肌痛不是类风湿关节炎：我们还没有针对纤维肌痛的真正的缓解疾病抗风湿药物。”

药物治疗是非常有用的辅助手段，而非必要手段。对于很可能将接受长期治疗的患者而言，这是新指南带来的一个重要信息。

德国和以色列的指南包含了针对多种补充和替代医学(CAM)治疗方法的具体建议，包括太极、引导想象、针灸、瑜伽和水疗等。相反，加拿大指南(CMAJ 2013;185:E645-51)认为，现有证据不足以支持在纤维肌痛中应用CAM治疗方法。

德国指南建议采取分级治疗：轻度纤维肌痛患者由初级保健医生管理，鼓励其参加体育活动和社会活动，而不推荐给予额外治疗和特殊照顾。对于中度纤维肌痛患者，治疗计划包括有氧运动、限定时间的心理治疗和转诊至专家，并可选择药物治疗。对于有重度纤维肌痛症状的患者和早期干预手段不奏效的中度纤维肌痛患者，最好在专科门诊或住院部接受治疗，强调对精神合并症的治疗。在德国，由于这些治疗已被证明可减少丧失工作能力的情况，所以保险公司会报销这些治疗的费用。

以色列指南的不同之处在于，它不以纤维肌痛的初始严重程度为依据。首先，患者会接受关于其疾病和治疗原则的教育。他们还会获得一份个体化有氧运动计划，并被推荐参加水中练习。医生会开具阿米替林10~25 mg睡前服用的处方，并推荐其接受认知行为治疗。

第二步是在12周后再次评估。如果患者的病情没有明显好转，可考虑用一种5羟色胺去甲肾上腺素再摄取抑制剂代替阿米替林，或在阿米替林的基础上添加一种选择性5-羟色胺再摄取抑制剂，同时使用普瑞巴林改善睡眠和减轻疼痛。推荐接受水疗和瑜伽或另一种冥想性运动。

与德国指南一样，加拿大指南也推荐将纤维肌痛的诊断和护理集中到初级保健机构，而只是有选择地转诊到专科医疗机构。加拿大指南的主要作者、麦克吉尔大学的Mary-Ann Fitzcharles博士指出，这三部独立编撰的指南对纤维肌痛的广义临床概念有相同的看法。“我们都认为纤维肌痛既不是一种独特的风湿性疾病，也不是一种精神障碍，而是跨度很大的多种医学症状的集合体。如果只关注疼痛的话，就会忽视患者所遭受的痛苦中的相当大一部分。”

加拿大和德国的指南建议将压痛点检查从患者评价中剔除，取而代之的是广泛软组织压痛检查。以色列指南则建议保留压痛点检查。

一名与会者明确反对取消压痛点检查。“激痛点检查一直是临床医生评估患者可信度的手段。假如不做激痛点检查，我怎么知道患者究竟是真的罹患了纤维肌痛还是假装疼痛以骗取残疾证明？”

Fitzcharles博士答道：“我们都知道激痛点检查结果取决于由谁来做激痛点检查，以及施压的程度，它的确是一项非常不准确的临床评估。不过我承认，假如放弃激痛点检查，我们就必须努力思考拿什么来替代它，以供基层医生使用。”

他指出，目前之所以对纤维肌痛充满疑问，是因为还没有找到具有决定性的生物标志物。

Fitzcharles博士报告称担任Purdue制药、礼来、辉瑞和Valeant的顾问和/或接受其提供的研究资助。Ablin博士是辉瑞的顾问。

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By: BRUCE JANCIN, Internal Medicine News Digital Network

SAN DIEGO – The high degree of consistency among recent national fibromyalgia guidelines developed independently by multispecialty panels in Canada, Israel, and Germany suggests big changes are afoot in how this common and vexing syndrome is conceptualized and treated, according to Dr. Jacob N. Ablin.

"I hope to convey the feeling that there is somewhat of a paradigm change in the recommendations regarding treatment of fibromyalgia as expressed by these three guidelines. All three emphasize an individually tailored approach based upon the key symptoms and severity, with nonpharmacologic therapies as the major positive first choice for all.

The emphasis is on the necessity of self-management strategies, which include aerobic exercise, cognitive-behavioral therapy, and multicomponent exercise and psychologic therapies," he said at the annual meeting of the American College of Rheumatology.

"Pharmacologic therapies were less enthusiastically recommended by all three groups. Contrary to popular perception, the drugs actually achieve only relatively modest effects. And all three groups caution about the side effects of drugs, which may mimic fibromyalgia symptoms," added Dr. Ablin of the Tel Aviv Sourasky Medical Center.

The three medications approved by the Food and Drug Administration for the treatment of fibromyalgia – pregabalin (Lyrica), duloxetine (Cymbalta), and milnacipran (Savella) – received only a weak grade C recommendation in the German guidelines (Schmerz 2012;26:287-90) because all three failed to achieve their primary endpoints in pivotal European clinical trials.

"While drug treatments absolutely continue to play a role in the management of fibromyalgia, the long-term safety and efficacy of nonpharmacologic treatments should be appreciated and stressed. Fibromyalgia is not rheumatoid arthritis: We don’t have true disease-modifying antirheumatic drugs for fibromyalgia.

And until we do, pharmacologic treatment is a very useful adjunct, not an imperative. This is an important message for patients, who will probably need treatment for many years to come," Dr. Ablin explained.

The German and Israeli guidelines contain detailed recommendations for a variety of complementary and alternative medicine (CAM) practices, including Tai Chi, guided imagery, acupuncture, yoga, and spa therapy. In contrast, the Canadian guidelines (CMAJ 2013;185:E645-51) deem current evidence insufficient to support the use of CAM practices in fibromyalgia.

The German guidelines recommend a graded approach to treatment. Patients with mild fibromyalgia are to be managed by primary care physicians, with advice given to engage in physical exercise and social activities, with no additional treatment recommended and no specialist care.

In moderate fibromyalgia, the treatment plan involves aerobic exercise, time-limited psychological therapy, and referral to a specialist, with drug therapy optional. Patients with severe fibromyalgia symptoms, as well as those with moderate fibromyalgia unresponsive to the earlier-stage interventions, are best managed in a specialized day clinic or inpatient service that emphasizes psychiatric treatment of mental comorbidities, according to the German guidelines. In Germany, insurance companies cover these more intensive services because of their proven track record in reducing occupational disability.

The Israeli approach is different in that it is not based upon the initial severity of fibromyalgia. In step 1, patients receive education about their disorder and the principles involved in its treatment. They also get an individualized aerobic exercise program and are referred for aquatic exercise. Amitriptyline at 10-25 mg at bedtime is prescribed, and a referral is to be made for cognitive-behavioral therapy.

Step 2 is based upon a reassessment 12 weeks after starting step 1. If the patient isn’t doing significantly better, consideration is given to substituting a serotonin-norepinephrine reuptake inhibitor for the amitriptyline, or adding a selective serotonin reuptake inhibitor to amitriptyline, along with prescribing pregabalin to improve sleep and reduce pain. Referral is made for spa therapy and yoga or another meditative movement practice.

As in the German guidelines, the Canadian guidelines also recommend that fibromyalgia diagnosis and care be centered in the primary care setting, with only selective referrals for specialist care.

Dr. Mary-Ann Fitzcharles, lead author of the new Canadian guidelines, said all three guidelines, developed independently on three continents, share in common the same broad clinical concept of fibromyalgia.

"We are all speaking with one voice with the same message: We accept that fibromyalgia is neither a distinct rheumatic nor mental disorder, but rather a cluster of symptoms spanning a broad range of medical disciplines. We’re saying that just focusing on pain is taking away from a large component of the suffering of many of these patients," according to Dr. Fitzcharles of McGill University, Montreal.

The Canadian and German guidelines advise dropping the tender point examination from the patient evaluation, replacing it with an examination for generalized soft tissue tenderness. The Israeli guidelines retain the tender point exam.

One audience member vigorously objected to eliminating the tender point examination.

"The trigger point exam has always been a way for physicians to assess whether the patient is believable. Without using a trigger point exam, I might as well just sign a blank check. How am I going to weed out those who have fibromyalgia from those who are faking and seeking disability status?" he asked.

Dr. Fitzcharles responded: "I think we all know that depending upon who is doing the trigger point exam and how hard you’re pressing, you can make positive trigger points or you can cool them down. So it really is a very inaccurate clinical assessment.

However, I will concede that in taking away the security blanket of trigger points from this condition, we now have to think very hard about putting something back in its place for the average primary practitioner to use in the office," the rheumatologist said.

Just what that might be remains unclear, he said. "The conundrum of fibromyalgia is that we have no defining biomarker as yet," Dr. Fitzcharles noted.

She reported serving as a consultant to and/or receiving research funding from Purdue Pharma, Eli Lilly, Pfizer, and Valeant. Dr. Ablin is a consultant to Pfizer.