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Approach to Rheum Labs: Anti-nuclear Antibody Speciation

by Carlo Raj, MD
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    00:01 In Rheumatology come under a classification known as connective tissue diseases.

    00:07 Let’s take a look at these important differentials, shall we? The classification overall-I brought a picture- Systemic Lupus Erythematosus (SLE).

    00:19 What I’ve done here for you is giving you a large circle and then you have other differentials which we’ll take a look at which will share the signs and symptoms of SLE but there’ll be subtle differences which then separate them from the diagnosis of SLE.

    00:37 You’ll see what I’m referring to next.

    00:39 There you have it.

    00:41 Now PM/DM stands for polymyositis or dermatomyositis and we’ll talk about that in great detail.

    00:50 Please do not get caught up on the abbreviations right now.

    00:53 I’ll play around with those as we move forward.

    00:55 Scleroderma, Raynaud’s, RA stands for rheumatoid arthritis, Sj?gren, all these are on this ring of spectrum, as you see here, of SLE and so for the most part you can imagine that some of the lab markers that you will be interpreting are going to be shared with all these differentials, aren't they? For example, antinuclear antibodies or ANA.

    01:19 Now, ultimately, as I told you you’ll see here the shared boxes and this for the most part represents the overlap that takes place with signs and symptoms of the patient along with the lab markers that we shall be discussing.

    01:32 So what are these approach or what is the approach to the rheum labs? One interpretation of autoimmune in general of or by rheumatologists is usually done as a consult, isn’t it? And many of you will go on to become a rheumatologist.

    01:49 It’s a beautiful specialty.

    01:51 Now labs, however, do not make or break the diagnosis of autoimmune disease so what you will be paying attention to what have to be the signs and symptoms that the patient is presenting with when they’re coming in or the symptoms that he or she might be coming in with.

    02:09 So let’s talk about each one of these markers.

    02:12 One of the markers that’s universal of connective tissue disease, as I showed you spectrum from the previous discussion, is antinuclear antibody (ANA).

    02:23 Multiple antibodies that demonstrates specificity for nuclear acids and nucleoproteins, so literally it’s attacking what’s in your nucleus, but as I told you it’s not specific.

    02:37 Measured by immunofluorescence microscopy; reported as a titer.

    02:42 As what? A screening test for connective tissue disease, an exception rheumatoid arthritis- I’ll talk to you about that in great detail when the time is right- and possesses high sensitivity with very low specificity as I told you.

    02:59 So in other words, that ring that I showed you, our connective tissue diseases, will be positive for ANA.

    03:05 But whenever you find ANA to not be present or negative, then you pretty much have ruled out the connective tissue disease but there’s an exception.

    03:15 It’s a positive ANA seen with aging, can be seen with HIV, maybe viral hepatitis, interstitial lung disease, TB, malignancy, especially lymphomas B-cell type.

    03:25 And if negative, as I said, that connective tissue disease can be effectively ruled out, except for rheumatoid arthritis.

    03:33 I want you to be a little careful, I've been obviously we’ll go through a lot more markers for RA.

    03:39 Well, if the ANA is positive then you need to further specify.

    03:46 For example, we talked about SLE and a very dangerous type of presentation, an SLE patient who may present with both nephritic, in other words maybe hypertension, hematuria, RBC cast or nephrotic where then 3½ grams of protein loss, maybe hypoalbuminemia, lots of edema so on and so forth; well that’s a combination of both nephrotic and nephritic.

    04:15 Continuing our discussion, if ANA is positive, then order test to then while speciate the type of ANA.

    04:25 For example you find, in addition to ANA, it is double-stranded DNA and at this point you know there’s connective tissue disease.

    04:33 Now the patient’s presenting-wait now, listen here- we have hypertension, your hematuria, you have RBC casts that you find obvious in the urine.

    04:40 In addition, you find greater than 3½ grams of protein that’s being lost, there’s hypoalbuminemia, therefore resulting in edema formation.

    04:48 Why am I bringing that up here? I gave you combination of both nephritic and nephrotic in a patient who then presents with double-stranded DNA.

    04:55 No doubt, this would be a severe form of SLE-induced kidney damage which I’m giving you as being DPGM, Diffused Proliferative Glomerulonephritis.

    05:05 That’s the most dangerous one; combination of nephritic and nephrotic.

    05:08 That is what double-stranded DNA means to you.

    05:11 How many kidneys do you have? One, two-yes, double-stranded DNA, if that helps you.

    05:17 Specific for SLE, especially the lupus type of nephritis that I just talked to you about.

    05:22 Titers can be used for monitoring the disease, so hopefully you’d be able to manage a patient effectively where kidney damage is not permanent.

    05:32 If you find SS-A or SS-you’ve heard of SS-A and SS-B, that’s where we’re headed.

    05:38 SS-A, you must know, is also called Ro and if you’re thinking about Ro or SS-A it could be seen with Sj?gren’s syndrome.

    05:48 Now, since we’re talking about connective tissue disease let me give you a preface for each one of this real quick.

    05:53 If it’s one description that you have to give Sj?gren’s, the name would be dryness.

    05:57 We talk about dry eyes, xerostomia and no saliva, so we talk about xerostomia.

    06:05 SLE associated with photosensitivity, SLE neonatal lupus, what’s my topic? SS-A/Ro.

    06:13 SLE fetal congenital heart block in mothers with SLE.

    06:20 Whereas if it’s SS-B, and you must memorize it, SS-B is also called La and it’s seen in Sj?gren’s syndrome specifically.

    06:30 The combination of the two, a La and Ro, SS-B, SS-A, respectively, will be more specific to Sj?gren.

    06:39 We have ribonucleoprotein, that’s what RNP stands for.

    06:44 RNP are actually what SS-A and SS-B are, okay? However, if you then find a specific type of ribonucleic protein (RNP) called U1, then you might be thinking about a condition known as mixed connective tissue disease; the combination of lupus scleroderma and myositis.

    07:04 Keep that in mind.

    07:06 But please know that RNP is generic for the above elements, however, the one that I gave you more specific was called U1 RNP.

    07:17 If ANA is positive and you continue our discussion speciating our ANA.

    07:23 Patient now comes back to be positive for antiscleroderma-70 or other words Scl-70.

    07:31 Please know the other name.

    07:33 Can you tell me the other name for Scl-70? Topoisomerase 1, right? Anti-topoisomerase 1, Scl-70.

    07:43 Now you ask yourself this question.

    07:45 This type of scleroderma that the patient’s suffering from, is it a scleroderma in which the face looks glassy, perfect, no wrinkles, the patient is older? It ain’t botox, but if this cutaneous scleroderma, hence, I give you shiny, taut, tight skin, no wrinkles; but then the patient also is suffering from lung disease, interstitial type, because of fibrosis.

    08:16 The combination of visceral organ plus cutaneous no longer puts you in the camp of limited, now I put you in the camp of what’s known as your systemic scleroderma, is that clear? What’s systemic mean? Systemic is much more dangerous it’ll kill you.

    08:34 The patient may die of fibrosis, in other words the diaphragm becomes fibrosed and the patient will then die of respiratory lung disease or maybe there is fibrosis taking place in the kidney; two major organs that are targets, possibly, of anti-Scl-70 type of scleroderma.

    08:50 Systemic is what you need to memorize, please.

    08:53 So if this is systemic, what is meant by the definition of limited? Limited type of scleroderma- I’m gonna tell you how to approach this in a second.

    09:03 First, the skin is going to appear taut, no wrinkles.

    09:06 That’s it.

    09:08 No organ involvement, alright? That’s gonna be skin, in other words, cutaneous type of scleroderma.

    09:14 So if two types of scleroderma based on the markers that we’re finding here, connective tissue disease, ANA positive, Scl-70, systemic.

    09:22 If it’s anti-centromere it’s limited to what? The skin, cutaneous.

    09:27 You’re gonna find limited type of scleroderma as part of a constellation of conditions or presentation known as CREST.

    09:35 C stands for calcinosis, so look for calcium.

    09:40 You also take the C please and then make it or have you put it together with centromere.

    09:50 So C as in CREST, C as in centromere.

    09:53 So that C is gonna help you then identify two things in CREST, calcinosis and centromere.

    10:00 But the centromere is for what kind of scleroderma? Limited.

    10:04 What does limited mean? You’re limited to the skin.

    10:07 What about R? R stands for Raynaud.

    10:11 We’ll talk about that in greater detail.

    10:12 What’s Raynaud mean? Raynaud means that you’re going to have vasospasms taking place in the fingers, aren’t they? Especially with exposure to what type of environment? Cold.

    10:23 Then you have E which is esophageal dysmotility.

    10:26 S, the fingers look like that of a witch, in other words long and tapered like a witch.

    10:32 Hopefully my fingers aren’t, are they? I could be a witch-I don’t know-I don’t have sclerodactyly.

    10:39 That’s what S stands for.

    10:40 And then T stands for telangiectasia.

    10:43 What’s that mean? Little capillaries that are undergoing dilation.

    10:46 Welcome to CREST, welcome to centromere.

    10:48 Anti-histone, what does that mean? You’ve heard a drug such as procainamide, hydralazine, isoniazid? These are drugs in which in a slow acetylator, in a slow acetylator- and from pharmacology remember- in slow acetylator that might be taking such drugs may then cause drug-induced SLE.

    11:06 How would you know? When I have anti-histone as your marker.

    11:10 A type of ribonucleoprotein known as anti-Jo-1 Ab.

    11:16 That’s something that you wanna keep in mind seeing an anti-synthetase syndrome which is a combination of polymyositis which I’ll walk you through in greater detail, and interstitial lung disease.

    11:28 In fact, what’s gonna happen in a little bit-let me warn you- is the fact that we’re gonna go through some connective tissue disease, especially rheumatoid arthritis, in which there are going to be some interesting, interesting extra articular manifestations.

    11:41 So here, an extra connective tissue disease manifestation is a polymyositis plus interstitial lung disease issue called anti-synthetase syndrome.


    About the Lecture

    The lecture Approach to Rheum Labs: Anti-nuclear Antibody Speciation by Carlo Raj, MD is from the course Connective Tissue Diseases. It contains the following chapters:

    • Anti-nuclear Antibody Speciation
    • Positive ANA and Anti-Scl-70

    Included Quiz Questions

    1. Rheumatoid arthritis
    2. Polymyositis
    3. Scleroderma
    4. Sjogren’s disease
    5. Systemic lupus erythematosus
    1. Anti-dsDNA
    2. SS-A/Ro
    3. SS-B/La
    4. RNP.
    5. ANA
    1. Anti-SSB/La
    2. ANA
    3. Scl-70
    4. dsDNA
    5. RNP
    1. Anti-topoisomerase 1
    2. dsDNA
    3. RNP
    4. SS-A/Ro
    5. Anti-histone antibodies
    1. Anti-centromere antibodies
    2. ANA
    3. Anti-dsDNA antibodies
    4. RNP
    5. SS-A/Ro
    1. Anti-Jo-1 antibodies
    2. Anti-Scl-70 antibodies
    3. Anti-histone antibodies
    4. RNP
    5. dsDNA
    1. SS-A/Ro
    2. Anti-Scl-70
    3. dsDNA
    4. RNP
    5. Anti-histone

    Author of lecture Approach to Rheum Labs: Anti-nuclear Antibody Speciation

     Carlo Raj, MD

    Carlo Raj, MD


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