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If you're looking for a shortcut to mastering one of the most uh frustrating and clinically fascinating chronic illnesses out there, you are definitely in the right place. Today we are doing a deep dive into systemic lupus arythmatosis SLE, a disease really defined by chaos.

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It is chaos, but it's it's a sort of predictable chaos. We're talking about a chronic inflammatory autoimmune disorder.

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Right.

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And it's driven by this, you know, relentless production of autoantibodies. Yeah. Especially the ones that target nuclear antigens.

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Trevor Burrus, Jr.: So it's the definition of a multi-system disease.

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Exactly. And it's characterized by these spontaneous, unpredictable cycles of remission and then relapse.

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Aaron Powell To really make this stick, let's just start with an analogy. Let's think of SLE as a wildfire.

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I like that.

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The body is this massive forest, and the auto antibodies are like these errant, self-directed sparks. They can ignite inflammation and damage literally anywhere kidneys, skin, joints, and that underlying vulnerability means a flare-up is always a risk, even in remission.

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Aaron Powell Right. So our mission today is to equip you with the essentials, diagnosis, management, and we're structuring this around those crucial clinical tasks you'll see on your boards.

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Aaron Powell Recognizing the patient, ordering the right labs.

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Aaron Powell Making the diagnosis and then setting that long-term treatment strategy.

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Aaron Powell Okay, let's unpack this. Let's start with the core engine of the disease, the pathophysiology. When those sparks hit, what are the two main ways they cause damage?

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Aaron Powell It's primarily two things. First, you get inflammation from the trapping of antigen antibody complexes. Okay. Think of these as like molecular sticky bombs. They get lodged in small blood vessels, especially in the kidneys, and they cause massive local damage.

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Aaron Powell And the second mechanism?

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Aaron Powell The second is more direct. It's autoantibody-mediated destruction of your own cells.

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Aaron Powell So that's where the cytopenias come from.

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Exactly. That direct attack can lead to things like autoimmune hemolytic anemia or thrombocytopenia.

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Trevor Burrus, and who is standing in the middle of this? This autoimmune fire risk? The epidemiology here is just it's striking.

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Aaron Powell It really is. The classic patient profile is overwhelming. We're talking young women, about 85% of cases with onset between menarch and menopause.

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But the racial disparity is something we have to highlight.

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We do. It's profound. The incidence in black women is roughly one in 400. Compared to compared to one in 1100 in white women.

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That is a huge difference. Now let's touch on the foundational science. What's the genetic link here?

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Aaron Powell Genetics play a huge role. You see a really high concordance in identical twins, sometimes up to 70%. And we often link SLE to specific HLA haplotypes, DR2 and DR3. But a key point, and this connects back to the pathophysiology, is the association with null complement alleles.

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Okay, explain that. What's the implication of having those null complement alleles?

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So low complement is a critical risk factor because the complement system is what's responsible for clearing those molecular sticky bombs.

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The immune complexes.

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Exactly. It clears them from circulation. So if that clearance mechanism is compromised, those complexes just hang around longer. They circulate and increase the chance they'll deposit in tissues, like the kidney, and start that whole destructive cycle.

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That really connects the why to the what. So now that we know who's at risk, let's talk about how they walk into the clinic. History taking, physical exam, the first step. Right. What are the three diagnostic essentials that should immediately put SLE high on your differential?

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You're looking for a triad, joint symptoms, a rash over sun exposed areas, and cytopenias.

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Anemia, leukopenia.

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Or thrombocytopenia. If you see that constellation, you have to start the workup for lupus.

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And which of those three is usually the first complaint?

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Aaron Powell Joint symptoms. They happen in over 90% of patients and are very often the earliest sign.

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And clinically, what's the key distinction for this arthritis?

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Aaron Powell It's typically non-erosive. It can be incredibly painful, but you don't generally see the kind of joint destruction you'd see in, say, rheumatoid arthritis.

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Aaron Powell But you can see some characteristic deformities.

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Aaron Powell You can. You can encounter those highly characteristic, though reducible, swan-neck deformities.

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Aaron Powell Okay, let's shift to the skin, the second key component. When we talk muca cutaneous findings, everyone just jumps to the butterfly rash. What's the reality check on that?

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Yeah. The malar or butterfly rash is highly suggestive, but it affects less than half of patients.

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Aaron Powell Less than half. Okay.

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So it's important to cast a wider net. You're looking for acute or subacute cutaneous lupus, discoid lupus, non-scarring alopecia.

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And oral ulcers.

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Yes. And the oral ulcers are typically painless. They often flare up during systemic exacerbations. And don't forget, Rhino phenomenon. That can affect about one in five patients.

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Aaron Powell Let's move to the systems that signal the fire is really out of control, the major sources of morbidity and mortality, starting with the kidneys, lupus nephritis.

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This is paramount. Kidney disease is a major driver of the long-term prognosis. You need to know the classifications, but you really have to zero in on the proliferative forms.

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Class three and four.

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Especially diffuse proliferative, which is class four. That's the most common form of severe nephritis. And it has the worst prognosis if it's not treated.

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So when you see abnormal urinary sediment, significant pro tunuria.

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You're thinking class four and you're preparing for aggressive intervention.

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And moving to the nervous system, what signs signal a life-threatening neurologic event in an SLE patient?

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Aaron Powell Well, neuropsychiatric lupus is broad. You can have psychosis, seizures, cognitive issues. But the medical emergency you have to recognize is transverse myelitis.

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Okay.

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This presents with rapidly ascending weakness, a distinct sensory level, and bowel or bladder dysfunction. This is an immediate admission high dose treatment situation.

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Aaron Powell We also see a lot of issues with the cirrhosal membranes, right?

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Pleurisy and pericarditis are very common, but often manageable.

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Mm-hmm.

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A crucial cardiovascular finding, though it's typically silent, is atypical varucous endocarditis of lib and sacs.

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That's a mouthful.

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It is. It's a non-infectious vegetating endocarditis, often leading to mitral regurgitation. And creatically, it can be a source of systemic emboli.

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That sets the stage perfectly for the next task. Using diagnostics and formulating the diagnosis. How do we filter all this information to confirm SLE?

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The clinical diagnosis requires two things: evidence of multisystem disease plus a positive antinuclear antibody, or ANA test. Right. And we rely on the 2019 ELORECER classification criteria. It gives you a structured way to combine clinical symptoms and lab results.

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Aaron Powell So walk us through those criteria just briefly. What's the absolute gateway to this diagnosis?

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Aaron Powell The Gateway is the immunological entry criterion, an ANA titer of at least one to eighty ever.

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Ever.

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If the patient has never met that threshold, they generally don't have SLE. Once that's met, you need at least one clinical criterion like arthritis, plus a cumulative score of 10 or more points from these weighted findings.

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Give us an example of how a patient quickly hits that 10-point threshold.

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Well, the highest weight is given to the most serious things. So immunologically, if you find anti-DSDNA or anti-Smith antibodies, that's six points right there. Clinically, if you do a renal biopsy and it shows class three or the YV lupus nephritis, that is a full 10 points. Diagnosis confirmed.

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Let's really dissect the serology because this is where we distinguish between screening and monitoring. ANA versus anti-DSDNA versus anti-smith.

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Okay. ANA is your screening tool. It is nearly 100% sensitive.

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Meaning if it's negative?

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If it's negative, SLE is highly unlikely. But it has poor specificity. A lot of conditions, even healthy people, can have a low positive ANA.

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Okay, so high sensitivity. What's the story with anti-DSDNA?

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Anti-DSDNA is specific for SLE, and this is the most critical factor for monitoring. Its levels often correlate directly with disease activity and lupus nephritis flares.

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So if the level spikes.

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A renal flare is likely brewing. Got it.

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And anti-SMF.

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Anti-SMF is that highly specific confirmation marker. It's present in maybe 15 to 30 percent of patients. But the key takeaway here is that anti-SMF levels do not correlate with disease activity.

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So it helps you make the diagnosis, but it's useless for tracking a flare.

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Exactly. Useless for tracking a flare or response to therapy.

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Beyond those specific antibodies, how do we monitor the general heat of the fire, the overall disease activity?

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Aaron Powell You look at complement levels, C3 and C4. Low levels suggest active disease or a current flare.

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Why?

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Because they're being consumed rapidly by those depositing immune complexes we talked about. They'll typically normalize once you get the flare under control.

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Aaron Powell And what about acute phase reactants like CRP? This is so critical when an immunosuppressed patient comes in sick.

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Right. ESR usually goes up during a flare, so it's somewhat useful. But the CRP is usually normal in a pure SLE flare.

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Unless.

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Unless the patient has active seroitis or severe arthritis. And this is a clinical must-know. If your lupus patient comes in with a fever and a very high CRP without seroitis or severe joint pain, you must suspect a concurrent infection.

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Which is a major cause of early mortality. That is extremely important. Okay, let's move into managing patients. Clinical intervention, health maintenance. We have the diagnosis. How do we treat this?

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First, education and prevention are paramount. UV light is a known trigger, so rigorous sun avoidance, broad spectrum sunscreen. That's non-negotiable.

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And emotional support, I imagine.

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Vital for managing a chronic debilitating condition.

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Aaron Powell Okay, what's the baseline first line therapy, the fire break that all SLE patients should be on?

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Hydroxychloroquine. HCQ.

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The antimalarial.

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Yes. It is recommended for all SLE patients, regardless of severity. It reduces flares, helps the skin and joints, and critically it prolongs survival.

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Aaron Powell We have to talk about the long-term risk of HCQ. What's the monitoring protocol?

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The risk is retinal toxicity, retinopathy, which can be irreversible. So monitoring is mandatory. Okay. The dose should generally be kept at or below 5 milligrams per kilogram per day. Yeah. And patients need a baseline ophthalmologic exam and then usually annual monitoring after five years of use.

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Aaron Powell When the fire just flares mildly, joint symptoms, minor rashes, what's the move?

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Short courses of low-dose corticoseroids. Prednisone, typically five to fifteen milligrams daily. NSAIDs can also help with minor joint pain.

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But when the fire hits a critical organ proliferative nephritis, CNS disease, we pull out the big guns.

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Absolutely. That calls for high-dose 5-E melphal prednisolone pulse therapy. Often 250 to 1,000 milligrams for three days combined immediately with other immunosuppressants.

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But you have to be careful with steroids long term.

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You have to be incredibly judicious. The long-term toxicities like a vascular necrosis and osteoporosis are profound.

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Focusing specifically on lupus nephritis management, what's the standard induction therapy?

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For proliferative nephritis, classes three and four, induction is typically mycophenolite mophetyl MMF plus corticozeroids.

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Okay.

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Avacyclophosphamide is an alternative. It's highly effective, but it carries higher risks like infertility and malignancy.

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What if the patient is on MMF but still has significant proteinuria, say over three grams a day?

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Then you need to augment. The guidelines recommend adding a calcineron inhibitor like Voclus burned or tachrolomus to the MMF to help get that nephritis under control.

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And what about newer biologics? Anything we should be aware of?

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Anaphrolumab is approved for active non-renal SLE that isn't responding to standard care.

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And how does it work?

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It antagonizes the type 1 interferon receptor, a key driver of inflammation in lupus. It's shown particular efficacy in patients with severe skin rashes.

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That brings us to the course and prognosis. Survival is much better now, but we need to talk about the patterns of mortality.

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Yes, 10-year survival is over 85% now. But you have to understand the striking bimodal pattern of death.

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Describe those two mortality peaks.

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So the early mortality peak in the first few years is dominated by opportunistic infections from the immunosuppression and active disease itself, especially kidney and CNS involvement.

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And the later peak.

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The second later peak, after a decade or more, is dominated almost entirely by accelerated atherosclerosis.

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That accelerated cardiovascular risk is so often overlooked. What other long-term problems demand our attention?

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A vascular necrosis or AVN, particularly in the hips and knees, is strongly linked to cumulative steroid exposure.

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And what else?

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We also need aggressive screening and management for steroid-induced osteoporosis, and there's an increased long-term risk of malignancy, specifically lymphoma and cervical cancer.

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So finally, when does this patient need to be admitted?

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Well, all SLE patients need a rheumatologist, but admission is mandatory for medical emergencies. Such as rapidly progressive glomerolonephritis, severe pulmonary hemorrhage, an active severe infection, or that transverse myelitis we mentioned. These are situations that require immediate high dose therapy to save organs and lives.

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Okay, let's bring it all back together. We defined SLE as this multi-system wildfire, stressing the impact on young women. We established the diagnostic triad is joint pain, rash, and cytopenias, needing that ANA entry criteria plus 10 points.

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And we solidify the crucial serology: ANA for sensitivity, anti-DSDNA for tracking activity, and anti-MSOMA for specificity, but no correlation with activity. And remember, high CRP in a lupus patient means infection until you prove otherwise.

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Management is universally founded on HCQ, monitored for retinal toxicity. We use low-dose steroids for mild flares and powerful combination immunosuppression like MMF for life-threatening conditions. Yes.

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And if we connect this all back to the long-term prognosis, given that 10-year survival is high, the ultimate threat to the patient is that ongoing chronic inflammatory burden that persists even during remission.

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So here's the final provocative thought for you to carry forward. Knowing that patients with SLE face a five-fold higher incidence of myocardial infarction compared to the general population, why should clinical management in all SLE patients, regardless of their current disease activity, prioritize aggressive screening and control of standard cardiovascular risk factors, things like hyperlipidemia and hypertension. It's not just about managing the autoimmune flair, it's about preventing the heart attack ten years down the line.

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That holistic view is absolutely essential for anyone managing this chronic condition. Thanks for joining us for this deep dive.

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We'll catch you next time for more must know clinical insights.