Lupus Today: Advances in Diagnosis and Treatment

这里是梅奥诊所访谈，一档为医生和其他医疗专业人员精心策划的每周播客。

This is Mayo Clinic talks, a curated weekly podcast for physicians and other health care providers.

我是您的主持人达里尔·丘特卡，来自明尼苏达州罗切斯特的梅奥诊所，是一名内科医生。

I'm your host, Darryl Chutka, a general internist at Mayo Clinic in Rochester, Minnesota.

系统性红斑狼疮是一种慢性自身免疫性疾病，常伴随多种免疫学和实验室检查异常。

Systemic lupus is a chronic autoimmune disease with a variety of immunologic and laboratory abnormalities.

它的临床表现多样，可能影响多个器官系统。

It has numerous clinical manifestations potentially involving multiple organs.

它被称为‘模仿大师’，因为症状常与其他疾病相似，很多患者在确诊为狼疮之前，已经饱受症状困扰多年。

It's known as the great imitator because it can mimic a variety of other diseases, and it's not uncommon for patients to have symptoms for a number of years before a diagnosis of lupus is actually established.

那么，哪些症状应该让我们警惕可能是狼疮呢？

So what symptoms should alert us to the possibility of lupus?

如果抗核抗体滴度偏低但呈阳性，我们该怎么处理？

What do we do with a low titer positive ANA?

如何确诊？全科医生在狼疮患者的管理中扮演什么角色？

How is a firm diagnosis established, and what role does the primary care play in the management of those with lupus?

今天我们将围绕狼疮的诊断与治疗进展展开讨论，我将向我的嘉宾——来自明尼苏达州罗切斯特梅奥诊所的乌玛·塔纳拉辛汉医生请教这些问题。

I'll be asking these questions in more of my guest, doctor Uma Thanarajasingham from the Mayo Clinic at Rochester, Minnesota, as we discuss lupus today, advances in diagnosis and treatment.

您正在收听的是梅奥诊所谈话节目。

You're listening to Mayo Clinic talks.

乌玛，欢迎你，感谢你今天抽出时间来参加。

Uma, welcome, and thank you for joining me today.

谢谢你的邀请。

Thank you for having me.

能来到这里我很高兴，也很期待能深入聊聊这个我每天都会接触到的疾病。

It's it's a pleasure to be here, and I'm excited to talk more about this, disease that I see day in and day out.

我猜你确实见得不少。

I'll bet you do.

我这里也有不少这样的患者，所以我也希望能从这次对话中学到一些新东西。

I have a fair number of patients with it as well, so I'm hoping to learn something from this also.

那我先问一个题，这个问题其实能聊上一整小时，但我们今天简要带过。

So I'm gonna start well, we could spend a whole hour on this next question, but we'll make it brief.

你能描述一下系统性红斑狼疮患者体内通常发生的病理机制吗？

I want you to describe some of the typical pathophysiology that incurs in those with lupus.

是的。

Yeah.

正如你刚才提到的，红斑狼疮是一种非常复杂的自身免疫病，几乎可以影响九个不同器官系统，而且表现形式多种多样。

So as you very well highlighted, lupus is a very complex autoimmune disease, and it can affect up to nine different organ systems in almost any permutation.

这种复杂的临床表现背后，是极其复杂的免疫病理过程。

And so underlying that very complex clinical phenotype is a very complex immunopathologic process.

在红斑狼疮中，免疫系统在适应性免疫和先天免疫多个层面都出现失调，最终导致身体失去对自身的耐受性。

And so there's really a degree of immune dysregulation in lupus that occurs at multiple levels of the adaptive immune response, the innate immune response that can culminate in a loss of self tolerance.

从免疫学角度看，患者通常会产生大量自身抗体，这些抗体专门攻击自身的细胞核成分。

So immunologically speaking in lupus, you tend to see excess autoantibody production, and these are autoantibodies that are directed against self nuclear antigens.

这会引发免疫复合物形成和沉积，造成组织损伤，同时还会干扰多种信号通路，尤其是导致I型干扰素过度产生，加剧炎症反应。

And the result of that can be immune mediated damage, mediated by immune complex formation and deposition in addition to dysregulation at the level of different pathways, cytokine mediated processes of inflammation, in particular excess type one interferon production.

正是这些免疫失调通路的复杂互动，加上环境和遗传因素，共同促成了红斑狼疮的临床表现。

So it's this kind of complex interplay of different pathways of immune dysregulation that can culminate in a presentation of lupus together, of course, with environmental and genetic factors.

狼疮确实会累及很多患者的多个器官。

Well, lupus does involve multiple organs on many on in many patients.

最常见的受累器官是哪些？

Which ones are most typically involved?

这还是要看具体患者和他们的临床表现。

So, again, it really depends on the patient and the phenotype.

总的来说，狼疮常影响肌肉骨骼系统，比如引发炎症性关节炎。

So broadly speaking, we can see lupus affect the musculoskeletal system, you know, in terms of presentation of an inflammatory type of arthritis.

皮肤方面也很常见，有各种黏膜皮肤表现，比如蝶形红斑、口腔黏膜炎，还有不同类型的皮疹。

We see many different versions of lupus affecting the skin, various mucocutaneous manifestations, that malar rash, mucositis, different types of rashes.

狼疮还可能影响肾脏，导致免疫介导的肾功能损伤，也会累及心肺系统，常见的是浆膜炎，比如胸腔积液、心包积液之类的。

Lupus can also affect the kidneys and cause different types of immune mediated renal failure and also the cardiopulmonary system typically in the form of serositis, like pleural effusions, pericardial effusions, and the like.

这些是主要的受累系统，但也会波及血液系统和神经系统，比如血细胞减少或神经病变，不过这些情况比肌肉骨骼、黏膜皮肤和肾脏问题要少见一些。

So those are kind of the big subgroups, but it can also, of course, affect the hematologic system, the neurologic system in different ways such as cytopenias and neuropathies as well, but those tend to be a little less common than than the musculoskeletal, mucocutaneous, and nephrology domains.

对。

Mhmm.

谁最容易得红斑狼疮？

Who's at greatest risk for getting lupus?

有哪些具体的危险因素吗？

Are there specific risk factors?

是的。

Yes.

简单来说，女性患红斑狼疮的风险最高。

So I I mean, simply put, females are at greatest risk for developing lupus.

女性患病人数是男性的九倍左右，尤其是育龄期女性更容易发病。

So females lupus affects females more than males in nine to one ratio, and it, in particular, affects women of childbearing ages.

15到44岁之间是红斑狼疮发病率最高的年龄段。

So between the ages of 15 to 44 is kind of the peak incidence of lupus.

在某些种族和族裔群体中，疾病负担更重，比如非裔、拉丁裔和原住民。

We tend to see the greatest burden of disease in certain racial and ethnic minorities such as specifically blacks, Hispanics, and Native Americans.

非裔女性的发病率和患病率最高，具体原因还不完全清楚，但显然存在遗传倾向，让这个群体整体风险更高。

And it's black females who actually carry the highest incidence and prevalence of lupus, and we don't particularly or exactly understand why, but there's certainly a genetic predisposition there that puts this group, I think, at a at a much higher risk overall.

是的

Mhmm.

明白了

Okay.

我手头有几个慢性狼疮患者，回想起来，其中有好几位花了好几年才最终确诊。

I have several patients with chronic lupus, and as I think about them, I can think of several where it took literally several years for a firm diagnosis to be established.

这种情况常见吗？

Is that common?

是的

Yes.

狼疮的诊断延迟非常普遍。

A delay in diagnosis is very common in lupus.

一方面，因为这种病本身比较少见。

One, because overall, the disease is rare.

作为梅奥诊所的医生，加上我们接诊的患者群体大多是转诊来的，我们可能接触到的病例相对更多一些。

You know, I think maybe as Mayo Clinic providers and and in terms of the referral basis in our patient population, we may tend to see these diseases more commonly.

但在普通人群中，全科医生可能在成千上万的患者里，才遇到一两个狼疮患者。

But in the general population, family practice provider may, in caseload of thousands of patients, may only carry one or two patients with lupus.

所以诊断这种病可能很困难，因为医生对它的了解有限，这自然会导致诊断延迟。

So the recognition of the disease can be difficult because knowledge about the disease may be limited, and that can certainly lead to delays in diagnosis.

而且，由于狼疮的表现形式多种多样，常常会模仿其他疾病，有时患者会被误诊为别的病。

And, of course, because of the varied phenotype, which can be a mimicker of so many other diseases, sometimes patients can be treated as something else altogether.

我还觉得，因为狼疮主要影响年轻女性，有时候症状会被忽视，甚至被归因于其他原因，直到排除了狼疮的可能性。

I also think that because this does affect young women disproportionately that sometimes, symptoms might be overlooked or even dismissed as other causes prior to lupus diagnosis being considered.

明白了。

Okay.

我猜大多数患者都是在成年早期确诊的，但我也知道，年纪大了也可能得这个病。

I would imagine most patients are diagnosed in early adulthood, but I understand it's also possible to get this in older ages.

晚发的狼疮和常见的早发类型有什么不同吗？

Does the late onset lupus differ from the more typical early onset?

是的。

Yeah.

我们通常把晚发性红斑狼疮定义为50岁及以上人群，而早发性则是50岁之前确诊。

I mean, we tend to think of late onset lupus as maybe affecting people age ages 50 and older and early onset lupus as being, yeah, less than a diagnosis at age less than 50.

晚发性红斑狼疮和早发性在临床表现上确实存在一些差异。

There have been some differences in the clinical phenotype of late onset lupus than early onset.

一般来说，发病越早，病情往往越重，更容易出现器官损伤，免疫活动性也更强，比如血液检查异常多、血清学指标活跃；而晚发性的病程可能相对温和，更多表现为肌肉骨骼症状，同时心肺受累也更常见，比如浆膜炎、胸膜积液、心包积液等。

In general, we tend to observe that the earlier the disease shows up, the more severe it is, the the more propensity it has for end organ damage and being very immunologically active, meaning a lot of abnormal blood tests and serologic disease activity, whereas late onset lupus may have potentially less severe course, maybe more musculoskeletal involvement is a clinical phenotype as well as we see more cardiopulmonary involvement, meaning serositis, so pleurisy, pleural effusions, pericardial effusion.

所以老年患者的表现确实略有不同，病情可能没那么严重，但预后并不一定更好。

So there is a slightly distinct phenotype with maybe a less severe phenotype seen in the older age group, but outcomes aren't necessarily better in this older age group.

年纪大了才得红斑狼疮，并不意味着结果会更乐观。

So getting lupus as an old as an older adult doesn't necessarily portend better outcomes.

我觉得部分原因在于，这个年龄段的人往往合并症更多，医生有时会倾向保守治疗，用的药物没那么激进，反而可能导致临床效果更差。

And part of that, I think, is because that age group carries more comorbidities, and there might be a tendency to undertreat or use less aggressive medications in an older age group, which could then lead to poorer clinical outcomes.

这就是我们观察到的这种差异。

So so that's kind of the the dichotomy we see there.

明白了。

Okay.

狼疮患者常常表现为肌肉骨骼症状，而且往往比较模糊，我们在基层医疗中经常遇到这类症状。

Well, patients with lupus often present with musculoskeletal symptoms, often somewhat vague, and we see a lot of musculoskeletal symptoms in primary care.

那什么样的表现应该让我们怀疑这些症状可能是狼疮，而不是其他更常见的疾病呢？

What should make us think that these may represent lupus rather than other more common things?

是的。

Yeah.

说实话，这确实挺难的，因为狼疮最常见的初发症状就是疲劳、全身不适、关节痛，有时候还伴有低烧。

That I mean, it's a tough one because, in general, the most common presenting symptoms of lupus are fatigue, malaise, arthralgias, and maybe, you know, sense of low grade fever.

这些症状都太泛泛了，没什么特异性。

So these are highly nonspecific symptoms.

对。

Mhmm.

所以，从病史入手，尽量把症状问得具体一点，会很有帮助。

So, historically, if you can drill a patient down to potentially more specific, get as specific as possible would be helpful.

比如这个关节痛，有没有炎症的特征？

So that arthralgia, does that have an inflammatory component?

也就是说，病人描述的关节疼痛和晨僵，持续超过三十分钟，还可能累及对称的小关节，比如手腕、脚踝、脚部和手指的小关节？

Meaning, is a patient describing joint pain and stiffness in the morning that lasts more than thirty minutes and might be involving symmetric small joints like wrists and ankles, feet, small joints of the hands?

有没有伴随肿胀？如果服用非甾体抗炎药后症状明显缓解，这算不算一个关键线索？

Is there some degree of associated swelling, and is there a dramatic response, for example, if they can take them to NSAIDs?

这样就勾勒出一个典型的炎性关节炎的临床图像。

So this builds this clinical picture of inflammatory arthritis, broadly speaking.

这就能帮我们把普通的关节痛和炎性关节炎区分开来。

So that can raise a red flag and help sort out arthralgias from inflammatory arthritis.

如果病人提到对光敏感或者有皮疹，能拿出照片的话，看到脸颊和前额出现蝶形红斑，鼻唇沟区域却没受累，这种表现对系统性红斑狼疮来说就很有提示性。

And if patients are describing kind of photosensitivity or rashes, if they can bring in a picture of a rash and you see something that looks like this malar rash, this erythema across the cheeks, forehead that seems to spare the nasolabial folds, this can be, again, a very specific potential symptom for lupus.

尤其是当这些症状出现在年轻女性身上时，我们就得提高警惕，考虑系统性红斑狼疮的可能性，并进一步做相关检查。

And especially if all of this is occurring in a young female patient, then I would start to kind of pull up some alarm bells for lupus and maybe taking next steps towards looking for that.

假设有一位患者来就诊，我们怀疑他可能患有系统性红斑狼疮，

Well, let's say we have a patient who shows up in our office and we suspect they may have lupus.

那初步评估应该包括哪些内容？

What should an initial evaluation consist of?

是的。

Yes.

我觉得，对于这类患者，做一套基础检查是非常合理的，比如血常规，看看有没有异常的血细胞减少、贫血、血小板减少或淋巴细胞减少；还有生化面板，评估肾功能，加上尿常规和炎症指标。

I think, you know, it is more than reasonable in these patients to obtain some basic labs like CBC, looking for any unusual cytopenias, anemia, thrombocytopenia, a lymphopenia, a chem panel, of course, to assess renal function along with the urinalysis and inflammatory markers.

这始终是个不错的起点，而且相对经济实惠，我觉得。

So that's always a good starting point, relatively cost effective starting point, I would say.

如果你遇到一些更具体的症状，比如提示红斑狼疮的警示信号，可以先查抗核抗体，也就是ANA。

And I would say that if you have these specific maybe more specific symptoms that are raising red flags for lupus, you could start by ordering the antinuclear antibody test first, just just the ANA.

如果检查结果出来是ANA阳性，再加上这些临床表现，甚至其他异常，那即使是全科医生，也可以考虑进一步做更具体的狼疮自身抗体检测。

And then I think if the lab is coming back with an abnormal or a positive ANA with those clinical symptoms and maybe even other abnormalities, then more specific autoantibody testing for lupus could be considered even by the primary care physician.

这些更具体的检测包括双链DNA抗体、补体C3和C4，还有抗Sm抗体。

And those more specific tests could be tests such as the double stranded DNA and the complement c three, c four, and anti Smith antibodies.

如果你在合适的临床背景下发现ANA阳性，这些抗体就可以作为进一步评估的选项。

So those are antibodies that could be considered if you are seeing a positive ANA in the appropriate clinical context.

好的。

K.

那要怎样才能做出明确的诊断呢？

So what's needed to establish a definitive diagnosis?

是需要临床表现和实验室检查两者结合，还是单靠实验室检查就够了？

It both clinical and laboratory or just laboratory?

你需要哪些依据？

What do you need?

对。

Yeah.

系统性红斑狼疮有几套分类标准，但我们要强调的是，这些标准本质上是用于分类的，不是诊断用的。

So we have we have sets of classification criteria in lupus, and the caveat that we always provide here is that their classification diagnostic criteria.

它们的主要用途是在研究中筛选患者，确保你研究的群体是明确可界定的。

So it's strictly meant to be applied when you're trying to put patients into a research study so that you have, you know, a population that you can define that you are studying.

其中一套叫SLICC的分类标准，也可以用来做临床诊断。

In the one set of classification criteria called the SLIC classification criteria can also be used diagnostically.

没错，你说得对。

And, yes, you're right.

诊断系统性红斑狼疮需要结合临床标准和实验室标准，两者必须同时满足。

There is a component of clinical based criteria as well as laboratory based criteria, and both have to be met in order to classify as having lupus.

临床标准主要涵盖血液系统、神经系统、肌肉骨骼、黏膜皮肤、肾脏以及全身性表现，此外还有具体的实验室指标。

And so the clinical criteria kind of look at the hematologic realm, neurologic, musculoskeletal, mucocutaneous, renal, and constitutional spectrum, and then there's specific laboratory based criteria.

比如抗核抗体、双链DNA抗体和抗Sm抗体，这些对系统性红斑狼疮特异性很高，所以被纳入诊断标准。

So the ANA, double stranded DNA, and Smith antibodies in particular are very specific for lupus, so that's why they are in these classification criteria.

我们还把抗磷脂抗体和补体蛋白的检测结果也包含在诊断标准里。

We also include ant the presence of antiphospholipid antibodies in this classification criteria and complement proteins as well.

具体要看你用的是哪一套诊断标准，只要临床和实验室指标综合起来达到要求，就可以确诊为系统性红斑狼疮。

So depending on what class classification criteria you are looking at, if the presence are met across clinical and laboratory spectrum to together combined, you can classify as having lupus.

有没有患者临床症状很明显，但实验室检查却正常？反过来，有没有实验室异常但没症状的？

Are there patients who present with clinical symptoms but have normal laboratory tests and vice versa?

有没有人实验室指标异常，但还没出现任何临床症状？

Are there patients who have abnormal lab tests but have no symptoms yet?

有的。

Yes.

这两种情况都存在。

To both of those.

但总的来说，对于ANA阴性的狼疮，我们应该保持高度谨慎的态度。

But I would say that in general, the entity of ANA negative lupus should be approached with a great degree of skepticism.

作为狼疮专科医生，我可以说，几乎所有的狼疮患者，接近百分之百都会呈现ANA阳性。

You know, as a lupus provider, in general, almost all, close to a hundred percent of lupus patients should have a positive ANA.

作为全科医生，如果你临床上高度怀疑是狼疮，但检查结果对不上，我建议你尽早请风湿免疫科的同事会诊，弄清楚下一步该怎么诊断，而不是轻易就说出‘狼疮’这个词。

And I think as a primary care provider, if you have a high degree of suspicion for lupus clinically but the tests aren't adding up, I would certainly try to involve colleagues from rheumatology to try to understand what the next best steps are to proceed diagnostically before maybe even evoking the phrase lupus.

因为患者很可能确实有自身免疫病，但未必是狼疮。

Because they may certainly have an autoimmune disease, but maybe it's not lupus.

比如可能是干燥综合征，它的ANA阳性率就没有狼疮那么高。

Maybe it's Sjogren's where the association with an ANA is not as strong as lupus, for example.

所以，在ANA阴性的情况下，我会对诊断为狼疮持保留态度。

So I would have skepticism about bringing up lupus in the setting of a negative ANA.

同样，像类风湿关节炎这样的病，也可能没有阳性ANA或其他相关的实验室指标。

Again, you can also have things like rheumatoid arthritis without necessarily the presence of a positive ANA or the other accompanying laboratory tests.

另一部分就是，那这个病人我该怎么处理？

And then the other part of the spectrum is, yeah, what do I do with this patient?

不知怎么的，所有这些检查都做了，结果发现了ANA和双链DNA抗体。

For some reason, all these labs were checked and we're seeing an ANA and we're seeing a double stranded DNA.

但他们没有任何症状。

They don't have any symptoms.

那这种情况我该怎么办？

What do I do about that?

很多自身抗体其实会在临床确诊前几年就出现在患者血液里。

And some of these a lot of autoantibodies appear in a patient's blood many years before a clinical diagnosis is made.

通常我们认为，免疫系统的异常活动可能在症状出现前就持续了多年，甚至长达十年。

So in general, we think that immunologically stuff is happening in someone's immune system for years before the tip of the iceberg is actually visualized, and that can be up to a decade.

当你在无症状患者身上发现这些抗体时，往往很难决定该如何处理。

And then when you start to see those antibodies in an asymptomatic patient, it can be difficult to know what to do with those patients.

如果患者ANA和双链DNA抗体都强阳性，即使还没有症状，也建议他们去看风湿科医生，确保我们问全了所有关键问题，做了全面检查，别漏掉早期狼疮，或者至少确认是否需要长期随访。

I would say that if you have a patient with strong positive ANA and was found to have a strong positive double stranded DNA, even if the symptoms aren't present, it's reasonable to have them go see a rheumatologist to make sure that we've asked all the right questions, assessed a thorough exam, and and make sure we're not missing early lupus, or maybe there's someone who just needs to be monitored over time.

有些患者血液中出现这些阳性抗体，但一辈子都不会发展成自身免疫病，而我们却无法预知谁会属于哪种情况。

There are some patients that have these positive serologies that never manifest an autoimmune disease either in their lifetime, and we don't know who's gonna fall into what category.

我想问你一件事，这真的让我很头疼。

I wanna ask you about something that really frustrates me.

有些患者症状特别模糊，可能就是疲劳，或者有点关节痛，结果却做了ANA检测，发现是低滴度阳性。

A patient who presents with very vague symptoms, maybe fatigue, maybe a little bit of joint pains, but somehow that patient ends up getting an ANA checked and it's positive but low titer.

那这类患者你该怎么处理？

What do you do with those patients?

是的。

Yes.

说实话，我专门做过讲座，就是讲ANA阳性这个问题，原因就在这儿。

I mean, I I give whole talks on the positive ANA for this exact reason.

我遇到的最大误解，或者说误区，导致了太多不必要的转诊，就是以为ANA阳性就等于狼疮，或者等于自身免疫病。

So the biggest misconception or fallacy, I guess, that I come across and leads to a lot of unnecessary referrals, I think, is that a positive ANA equals lupus or positive ANA equals autoimmune disease.

尤其是低滴度的情况下，这完全不对。

And in low titers, in particular, that's simply not true.

在没有自身免疫病的人群中，也能看到一部分人ANA检测呈阳性。

You can see a positive ANA in a subset of the otherwise normal population that does not have autoimmune diseases.

随着年龄增长，人群中阳性率可高达百分之五，甚至接近百分之十五到二十。

Up to five percent of the population, as we get a bit older, that can approach fifteen to twenty percent.

ANA阳性还有其他多种原因。

And there are other reasons to have a positive ANA.

在基层医疗中，解释ANA阳性的最佳思路之一，是看看患者正在服用哪些药物，比如是否在服用甲状腺激素。

And I think in primary care, one of the big the best explanations for a positive ANA is if you look at the patient's medication list and see, are they taking thyroid hormone supplementation?

他们有没有自身免疫性甲状腺疾病，比如桥本甲状腺炎？

Do they have autoimmune thyroid disease like Hashimoto's?

大约百分之四十五到五十的桥本甲状腺炎患者，会因为交叉反应出现ANA阳性，这是针对某些共同的核抗原产生的反应。

Well, about forty five to fifty percent of patients with Hashimoto's can have a positive ANA due to cross reactivity against these nuclear kind of shared sort of nuclear antigen pattern.

ANA阳性的原因有很多，其他自身免疫病、家族中有自身免疫病史，也都可能是诱因。

So there are many other explanations for a positive ANA, and other autoimmune diseases can be amongst them a family history of autoimmune diseases.

某些药物也可能引发ANA阳性。

Certain drugs can induce an ANA.

对于那些不符合狼疮典型表现的患者，低滴度的ANA常常有其他解释。

There's often an alternative explanation for a low titer ANA in a patient who just doesn't fit the right phenotype for lupus.

所以我尽量建议基层医生们，要谨慎安排ANA检测。

So judicious ordering of that ANA is what I try to counsel my colleagues in primary care on if possible.

这正是我平时对住院医师和学生们说的话。

And that's exactly what I tell residents and students.

如果你决定做一项检查，就要准备好应对异常结果，至少得想清楚接下来怎么办。

If you're gonna order a test, be prepared to do something if that test is abnormal or at least figure out what you're gonna do.

没错。

Right.

基层医生其实是检测的把关人，乱开检查很容易打开潘多拉的盒子，给患者带来巨大压力。

I mean, primary care are the gatekeepers of testing, and and so it can really open a Pandora's box and can really induce a lot of stress for that patient.

现在有了ChatGPT这类工具，再加上互联网早就普及了，很容易让人钻进各种信息死胡同。

I mean, now with things like chat GPT and we've had the Internet for a long time, it it it can lead to a lot of rabbit holes.

对。

Yeah.

我们来聊聊狼疮的治疗吧。

Let's talk about the management of lupus.

过去几十年里，标准治疗方式有哪些变化？

What's been the standard treatment and what's evolved over the past couple decades?

对。

Yeah.

标准的治疗方案里，非药物干预主要有几项关键内容。

So standard approach to treatment, you know, non pharmacological is a couple of key things.

就像很多初级保健中的问题一样，如果患者吸烟或接触烟草，一定要帮他们戒掉，因为这会让病情全面恶化，尤其是皮肤症状，还会降低药物在狼疮治疗中的效果。

Like so many things in primary care, if a patient is smoking or has exposure to tobacco to try to eliminate that as that makes everything worse and makes skin disease and lupus worse, and it smoking actually is a roadblock to the effectiveness of drugs in lupus management.

一旦移除了这个障碍，那些对治疗反应不佳的患者，有时反而会对非常轻微的治疗产生很好的反应。

And if we can take that roadblock away, those who are recalcitrant to treatment sometimes turn around and become very sensitive to even minimal treatment for lupus.

所以除了戒烟，还要强调防晒，因为紫外线是狼疮最重要的环境诱因之一，容易引发病情复发。

So that counseling and also photo protection, so sun protection, because we know that UV light is one of the big environmental triggers for lupus and can actually trigger flares of disease.

防晒措施包括使用SPF50以上的防晒衣物，关注紫外线指数，尽量避免日晒。

So sun protection, s using high SPF 50 or higher SPF impregnated clothing, watching the sun UV index and avoidance of sun.

我丈夫是皮肤科医生，经常接诊皮肤型红斑狼疮患者，他总是建议：只要能避开日照高峰时段，具体时间要看你离赤道有多远，这就是最好的防护。

My husband is a dermatologist and sees a lot of cutaneous lupus, and he would just tell people, if you can avoid the sun between certain hours depending on how far you are from the Equator, that's the best protection.

这些就是非药物治疗的核心要点。

So those are the cornerstones of nonpharmacologic therapy.

至于药物治疗，我们希望所有红斑狼疮患者都能长期服用羟氯喹，也就是Plaquenil。

And then pharmacologic therapy, essentially, we would like patients with our patients with lupus to have hydroxychloroquine or Plaquenil to be in the water.

这是一种非常温和的药。

So it's a very mild medication.

它原本是抗疟药，已经用了很久了。

It is an antimalarial, so it's been around for a long time.

但聪明的免疫学家发现，它能有效调节免疫系统，又不会造成深度免疫抑制。

But very smart immunologists have found that it has incredible immune modulating effects without being deeply immunosuppressive.

在治疗红斑狼疮方面，它的效果非常好。

And it is a very efficacious medication in in lupus.

它能防止长期器官损伤，延长寿命，对心血管系统也有显著益处，研究已证实它能降低红斑狼疮患者因心血管疾病死亡的风险。

It prevents long term organ damage, and it can extend longevity, and it actually has a very strong benefit in terms of from the cardiovascular system and and has been shown to prevent mortality from cardiovascular disease in patients with lupus.

所以，这是治疗狼疮的核心药物。

So that is kind of the cornerstone medication for lupus management.

有什么新进展吗？

Anything new?

最近有不少新东西。

There are a lot of new things.

其余的治疗主要依靠强效的免疫抑制药物。

So in general, the rest of the treatment is is based on strong immunosuppressive medications.

这些药都比羟氯喹强得多，具体用哪种，要看哪些器官受累以及病情如何。

They're all, know, much stronger than Plaquenil, and that's based on what organs are involved and and and what's going on.

过去十五年里，狼疮的治疗取得了很大进展。

There have been a lot of advances in lupus management in the last decade and a half.

以前，我们只能从其他自身免疫病那里借药来用，这些药并不是专门针对狼疮的发病机制。

You know, before, we would have to borrow a lot of medications from other autoimmune diseases that were not necessarily targeted to lupus specific pathways.

但过去十五年，已经有两种新型生物制剂被批准用于治疗狼疮。

But in the last fifteen years, we've had, you know, two new biologic medications approved for lupus.

一种叫贝利木单抗，商品名是Benlysta，它能抑制一种叫BLIS的B淋巴细胞刺激因子。

One is a medication called belimumab or Benlysta, which inhibits a b lymphocyte stimulating factor called BLIS.

它专门针对狼疮中过度活跃的通路，已获批用于系统性狼疮，最近还新增了狼疮性肾炎的适应症。

So it's a it specifically targets an overactive pathway in lupus and has been approved for systemic lupus and more recently picked up indications for lupus nephritis.

这对很多狼疮患者来说简直是重大突破。

So that's been a game changer for a lot of lupus patients.

另一款更近期获批的药物是2021年上市的阿尼鲁单抗，商品名Saphnelo，是一种针对I型干扰素的单克隆抗体。

And another more even more recent medication approved in 2021 was called anifrolimab or safnello, which is a monoclonal antibody against type one interferon.

它作用于干扰素通路，已获批用于中重度狼疮患者，在治疗严重皮肤狼疮和部分肌肉骨骼表现方面效果非常显著。

So it targets the interferon pathway, and that's been approved for patients with moderate to severe lupus and has been quite remarkable in the management of severe cutaneous lupus and some of the musculoskeletal manifestations of lupus.

这两款新药都针对狼疮中失调的特定通路，因此成为我们治疗狼疮的重要补充。

So these are two big new medications that target specific pathways dysregulated in lupus, and so they've been welcome additions to our armamentarium for lupus management.

那我们来聊聊全科医生在其中的角色。

Well, let's talk a little bit about the role of the primary care clinician.

大多数患者在刚出现狼疮症状时，并不会直接去看风湿科医生。

Most patients, when they develop lupus, probably don't present to a rheumatologist.

你们的人手实在太少了。

There just aren't enough of you.

所以他们通常先去看全科医生。

So they're often seen in primary care.

除了怀疑和初步确诊之外，全科医生在狼疮患者的管理中还承担哪些职责？

So in addition to suspecting the disease and maybe establishing a diagnosis, what other roles do the primary clinician play in the management of patients with lupus?

我觉得，除了在诊断过程中负责把关常规化验外，全科医生在维护这类患者的整体健康、调整危险因素方面也至关重要，哪怕是对年轻患者。要知道，狼疮、类风湿关节炎这类自身免疫病患者，尤其是类风湿和狼疮，患心血管疾病、心梗和中风的风险比普通人群高出两到三倍。

I think, in addition to being the gatekeepers of general lab ordering in the diagnostic process, primary care has a crucial role in the general health maintenance and risk factor modification of this patient population even in younger patients because it's important to know that patients with lupus and rheumatoid arthritis, autoimmune diseases overall, but especially well studied in RA and lupus, are at two to threefold higher risk for cardiovascular disease, MI, and stroke compared to the general population.

这主要是因为慢性炎症加速了动脉粥样硬化的进程。

And that's thought to be due to, you know, accelerated atherosclerosis in the setting of chronic inflammation.

所以，即使是30岁的狼疮女性患者，控制心血管风险、管理危险因素也很关键，这方面我特别依赖全科医生帮忙，因为我们往往更关注狼疮本身的并发症和免疫抑制治疗。

So even in a 30 year old female patient with lupus, risk factor modification, cardiovascular risk management is important, and that is a crucial role that I rely on our primary care doctors to try to help us manage because we tend to try to focus on the complications of lupus and the immunosuppressive management and all of that.

另一个我看到全科医生能发挥的作用，是帮我们控制激素的使用量。

The other role I see for primary care is to try to be stewards like we are of steroid exposure.

对吧？

Right?

有时候，我们这边号很难挂，风湿科医生也联系不上，甚至根本约不上。

So sometimes, you know, we are hard to get into and, you know, can't can't reach your rheumatologist or we can't even get you in.

那我们能做点什么？

What can we do?

至少我们可以先给你用点激素缓解一下，有些情况确实需要这么做。

Well, we can at least try to get you on some steroids to help, and I think in some cases, that's necessary.

但也要注意剂量、使用时间，以及激素的累积用量。

But being mindful of the dose, the duration, and the cumulative exposure to steroids is important too.

年轻患者尤其要注意，长期用激素会增加骨质疏松、感染这些风险。

Young patients, you know, there's the risk for osteoporosis, infection, all of those things that come with chronic steroid use.

所以，控制好激素的使用，也是全科医生的重要职责。

So being a steward of that is also an important role for our primary care providers.

这两大块，就是我看到的主要作用。

So those are the two big categories that I see.

那对于那些住在偏远农村、很难接触到风湿科医生的患者呢？

What about the patient who may live in maybe one of the more rural areas of our country and doesn't have easy access to a rheumatologist.

全科医生该怎么监测患者使用羟氯喹或免疫抑制剂的情况呢？

How should primary care clinicians clinicians monitor patients' things such as hydroxychloroquine or the immunosuppressants?

是的。

Yeah.

我们通常会和风湿科医生合作，支持社区里的全科医生，如果他们能放心开一些我们常用的药，对提升患者的就医可及性很有帮助。

I mean, I think we often will partner with rheumatology with with our primary care providers in the community because to the extent that a primary care provider might be comfortable, even prescribing some of our more common medications would be helpful to improve access to care for patients.

比如羟氯喹，这是治疗狼疮的核心药物，全科医生完全可以开处方。它的主要毒性是视网膜毒性，虽然罕见，但会随时间累积。

So hydroxychloroquine, for example, that that cornerstone medication for lupus can be prescribed by a primary care doctor, and the main toxicity for hydroxychloroquine is a retinal toxicity that is rare and is cumulative over time.

所以我们建议患者在开始用药前做一次全面的眼科检查，包括眼底检查、视野检查和OCT检查。

And so basically, we ask that a patient have a eye exam that includes a fundoscopic exam, a visual field, and an OCT at baseline.

如果用药超过五年，之后每年都要复查一次，监测是否有毒性反应。

And then if they've been on the medication for more than five years, an annual exam to monitor for that toxicity.

对于羟氯喹来说，这就是主要的监测要求。

That's the main monitoring that needs to occur, for example, with hydroxychloroquine.

另外，系统通常也会提醒注意QTc间期延长的问题。

There will always be alerts that come up with QTc prolongation.

它和很多心脏药物合用不太安全，所以有时需要监测这些患者的QT间期。

It doesn't play well with a lot of cardiac medications, so sometimes you need to monitor the QT interval in some of these patients.

除了羟氯喹，我们每种免疫抑制剂的监测指标都略有不同，比如甲氨蝶呤，通常每几个月要查一次血常规、肝功能和肌酐。

And then beyond hydroxychloroquine, each of our immunosuppressive medications have slightly different monitoring parameters, checking CBC, LFT's creatinine every few months, for example, in methotrexate.

举个例子，如果一个患者每年只能看一次风湿科，但你每六个月就见他一次，处理其他问题，想知道还能做点什么来帮着监测狼疮情况，我建议每次见面时，查个血常规、生化全套、尿常规，再加上炎症指标，这些都能帮助早期发现狼疮的其他并发症，比如血细胞减少或无症状的肾脏问题。

But in general, say you have a patient who is can only see their rheumatologist once a year, but you are seeing them, you know, every six months for other issues and wondering what else can I do to help kinda monitor from the lupus perspective, I would say in general, a CBC, a chem panel, and a urinalysis, as well as inflammatory markers, when you see them every six months, can also be helpful screening for other complications of lupus, the cytopenias, the kidney complications of lupus that could come up where patients are otherwise asymptomatic?

对吧？

Right?

这些检查在你接诊时顺手做一下，也会很有帮助。

So that could be helpful for you to grab when you see them as well.

明白了。

Okay.

疫苗接种方面有什么需要注意的吗？

Any issues with immunizations?

没有。

No.

其实没有，只是如果要给患者使用更强的免疫抑制剂，比如甲氨蝶呤或生物制剂，而且患者年龄在50岁以下，我们通常会建议提前完成一套加强疫苗接种，帮助提升免疫力，再开始用药。

Not really, other than to know that if you're we're gonna be starting a patient on a stronger immunosuppressive medication such as methotrexate or one of the biologics, and they may be under the age of 50, there might be an accelerated vaccination schedule that we recommend to kind of boost their immunity before we we put them on immunosuppressive medications.

比如，对于还没到推荐接种肺炎球菌疫苗年龄的患者，我们仍建议尽早接种，同时也要提前安排带状疱疹疫苗接种——不是减毒活疫苗，而是灭活的带状疱疹疫苗。

So this is where we would say it would be important for a patient, you know, under the age of the recommended age for a pneumococcal vaccinate vaccine to receive that vaccine, also to accelerate the vaccination schedule for shingles, not the live vaccine, but the attenuated vaccine for shingles.

所以，对于即将接受强效免疫抑制治疗的患者，提前安排加速接种疫苗是有必要的。

So there may be an accelerated vaccination schedule in a patient who's about to receive stronger immunosuppression.

明白了。

Okay.

那对于狼疮患者来说，什么是缓解状态？

So what does it mean for a patient with lupus to be in remission?

我们说的缓解，就是患者临床感觉良好，没有狼疮症状——比如关节炎不发作了，皮肤也恢复正常，整体状态不错。

So our goal for remission is for a patient to clinically feel well, right, to not have their lupus symptoms, meaning their, say, inflammatory arthritis is a nonfactor, and their skin is clear, and they are feeling well.

精力充沛，自我感觉几乎没有不适。

Their energy level is good, and they are reporting minimal symptoms.

也就是说，患者自己觉得好，医生观察也觉得好，再加上实验室指标也显示处于缓解状态。

So patient provided report feeling well, clinician observing that they're feeling well, and then laboratory parameters that indicate that they are in also a state of remission.

炎症指标正常，有些患者在缓解期时，双链DNA水平也会恢复正常，补体水平也会回升。

So flat inflammatory markers, and if they have had elevation in double stranded DNA, some patients will actually normalize their double stranded DNA, normalize their complements when they're in a state of remission.

这并不是每个患者都会发生，但确实有一部分患者会这样。

That doesn't happen all the time, but in some patients.

我们会综合患者的自我感受、临床表现以及实验室检查结果，来判断是否达到了缓解状态。

So we take into account patient reported outcomes, how they look in the clinic, and what their lab looked like to to create and hopefully see a picture of remission.

您认为在未来几年，系统性红斑狼疮的治疗上会有哪些新的突破吗？

Do you see anything new and exciting regarding the advances of management of lupus in the near future?

我觉得系统性红斑狼疮的治疗前景非常广阔。

I think there is a lot on the horizon for lupus management.

目前至少有90种药物正在研发或临床试验中，专门针对狼疮的不同通路。

More and more, there are about at least 90 drugs in and under clinical development specifically for lupus at this point in time targeting different pathways.

是的。

Mhmm.

所以我认为，未来不久我们可能会有新的口服靶向药，通过作用于全新的通路来治疗狼疮。

So I think in the near future, we may have new targeted therapies that are oral medications that explore novel pathways in lupus.

所以我觉得治疗模式会持续不断地发展。

So I think the treatment paradigm is going to be ever evolving.

我觉得前景非常令人期待，虽然还不到全面应用的时候，但CAR-T细胞疗法这类长期耗竭B细胞的手段，未来五年左右可能会成为主流，长远来看或许会彻底改变我们治疗狼疮的方式。

There is, I think, a very exciting potential, not quite ready for prime time, but in CAR T cell therapy, so kind of prolonged B cell depleting approaches in lupus that might come to the forefront in the next maybe five or so years that may change how we treat lupus in in the long term.

我对未来五到十年狼疮治疗会如何发展，真的非常期待。

So I'm very excited about, you know, what the next five to ten years are going to look like in terms of lupus treatment for our patients.

对。

Mhmm.

我们刚才和梅奥诊所风湿免疫科的乌玛·塔纳拉辛汉医生讨论了系统性红斑狼疮。

We've been discussing systemic lupus with doctor Uma Thanarajasingham from the Division of Rheumatology at the Mayo Clinic.

乌玛，非常感谢您今天与我们分享您的专业见解。

Uma, thank you so much for sharing your expertise with us today.

能来这儿非常荣幸。

It was a pleasure to be here.

谢谢你们的邀请。

Thanks for having me.

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非常感谢您一直以来的收听。

We're honored to have you as a listener.

下周再会，祝您健康。

Tune in again next week, and stay well.