Systemic lupus erythematosus: Clinical sciences

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Introduction0:00–0:35

Systemic lupus erythematosus or SLE for short, or simply lupus, is a chronic autoimmune condition that can affect pretty much any organ system!
Affected individuals produce autoantibodies and immune complexes that mediate tissue damage, which commonly results in dermatologic, hematologic, renal, joint, and nervous system manifestations.
Now, if a patient presents with a chief concern suggesting systemic lupus erythematosus, you should first perform a focused history and physical examination.

History and physical 0:35–1:59

Your patient will likely describe nonspecific systemic symptoms like fatigue, fever, malaise, or weight loss. They may also report photosensitivity of the skin, joint pain, pleuritic chest pain, as well as neurologic or psychiatric symptoms, such as cognitive dysfunction or even seizures.
On the flip side, the physical exam usually reveals a classic malar rash, also known as a butterfly rash, since erythema specifically affects the nose and cheeks, sparing the nasolabial folds.
Another skin finding is a discoid rash, which is a chronic erythematous rash in sun-exposed areas like the arms and legs that are plaque-like or patchy redness and can scar.
Other important findings include painless oral and nasal ulcers, as well as symmetric tenderness and swelling of the small joints, most commonly in the hands and wrists.
Finally, auscultation may reveal decreased breath sounds or a pericardial friction rub.Based on these findings, you should suspect SLE.Now that we suspect SLE, based on our history and physical findings, your next step is to order labs.

Suspect SLE1:59–2:35

These include CBC and CMP, an antinuclear antibody; anti-double-stranded DNA and anti-Smith antibodies; as well as antiphospholipid antibodies.
Also, don’t forget to check complement C3 and C4 levels. Finally, you should send urine for a urinalysis, and order the urine spot protein-to-creatinine ratio to assess for proteinuria.
Now let’s take a look at our lab results. The CBC could reveal low hemoglobin, WBCs, and platelets, while the CMP could show elevated creatinine.

Lab results2:35–3:16

Antibody testing will reveal a positive ANA, with or without anti-double-stranded DNA, anti-Smith, and antiphospholipid antibodies.
Similarly, C3 and C4 levels might be low, but that’s not always the case. Finally, urinalysis findings could reveal the presence of blood, protein, and cellular casts on microscopy; while the urine spot protein-to-creatinine ratio might be elevated.
Once you get the results, your next step is to use Classification Criteria for SLE. These criteria were designed to select patients to enroll in research trials and not for diagnostic purposes.

SLE Diagnosis3:16–7:15

However, since no single finding or test can diagnose lupus, these criteria are helpful when evaluating patients. To diagnose SLE, this requires that the ANA titer be greater than or equal to 1 to 80.
If the patient meets this criterion, you should consider additional criteria that includes specific signs, symptoms, and lab findings seen in individuals with SLE.
Each of these is given a weighted score, and a total score of 10 or more is consistent with a diagnosis of lupus. Okay, to make the diagnosis, you need to consider clinical domains, of which there are seven, and immunologic domains, of which there are three.For clinical domains, you should consider Constitutional symptoms, which include fever; or there may be Neuropsychiatric symptoms, like delirium, psychosis, or seizure; or Mucocutaneous manifestations, such as non-scarring alopecia, oral ulcers, discoid lupus, or cutaneous lupus.
Your patient may also have Musculoskeletal manifestations, like arthritis. There could also be Serosal manifestations, including pleural or pericardial effusions, or pericarditis; or even Renal involvement, like proteinuria or lupus nephritis.
Finally, you should consider Hematologic abnormalities, like leukopenia, thrombocytopenia, or autoimmune hemolysis. In terms of immunologic domains, there will likely be SLE-specific antibodies, like anti-double stranded DNA antibodies or anti-Smith antibodies.
You may also see abnormal Complement proteins, like low C3 or C4; and finally, the patient may have antiphospholipid antibodies, such as lupus anticoagulant, anti-cardiolipin, and anti-Beta 2 glycoprotein 1 antibodies.
Keep in mind that positive antiphospholipid antibodies can be found in patients without lupus, and are consistent with a diagnosis of antiphospholipid antibody syndrome.
Antiphospholipid antibody syndrome is an autoimmune condition that’s associated with arterial, venous, and microvascular thrombosis, as well as pregnancy complications, such as fetal loss and preeclampsia.Here’s a high-yield fact!
Some of the main findings of patients with lupus can be remembered with the mnemonic SOAP BRAIN MD. S stands for serositis, which can include pericarditis, pleuritis, or peritonitis.
O is for oral or nasal ulcers, while A is for arthritis in 2 or more joints. Then there’s Photosensitivity; and Blood disorders including anemia, leukopenia, thrombocytopenia, leukemia, or lymphoma.
R stands for renal involvement, which refers to lupus nephritis caused by immune complex deposition along the glomerular basement membrane.
A is for ANA, while I is for other immunologic phenomena, meaning other autoantibodies. N stands for Neurologic and psychiatric conditions, such as headaches, seizures, and mood disorders like depression.
Finally, we have our skin conditions, namely Malar rash and Discoid rash.Now, if your patient doesn’t meet the criteria, consider alternative diagnoses.

SLE7:15–7:30

On the other hand, if your patient does meet criteria, diagnose systemic lupus erythematosus. Once you diagnose SLE, your next step is to assess for renal involvement.

Renal involvement7:30–9:19

This can be identified by the presence of proteinuria or cellular casts on urinalysis, as well as elevated serum creatinine or a reduced estimated glomerular filtration rate.
If any signs of renal involvement are present, you should suspect lupus nephritis and order a renal biopsy. If the biopsy reveals immune complex-mediated glomerulonephritis, diagnose lupus nephritis.There are six different classes of lupus nephritis that can be distinguished by analysis of a renal biopsy.
The class of lupus nephritis has important prognostic implications and guides treatment. The management primarily relies on hydroxychloroquine.
However, if your patient has more severe nephritis, such as class III, IV, or V lupus nephritis, begin glucocorticoids with mycophenolate mofetil or cyclophosphamide.
Additionally, if the urinalysis demonstrates proteinuria, start an ACE inhibitor or angiotensin receptor blocker to protect the glomeruli from further damage.
If hypertension persists despite these medications, your patient may need to start additional antihypertensive medication or implement lifestyle changes to achieve adequate blood pressure control.
Here’s a clinical pearl! Patients who don’t have renal involvement at the time of diagnosis can still develop lupus nephritis later, so continue to monitor urine studies and serum creatinine regularly.
Ok, let’s go back and discuss individuals with lupus who have no sign of renal involvement. In this case, your next step is to assess the disease severity.

Disease severity9:19–9:41

Based on clinical manifestations, the severity of this condition can be subdivided into mild, moderate, or severe.Let’s start by discussing mild disease.

Mild disease9:41–10:29

If your patient presents with mild skin and joint involvement, in combination with possible mild cytopenia, such as a platelet count between 50,000 and 100,000, then they have mild disease severity.
In this case, begin treatment with hydroxychloroquine. If they have an adequate response, which means that symptoms improve or resolve, continue the current management.
On the other hand, if they have an inadequate response, add to the current management an NSAID or low-dose glucocorticoid.
Glucocorticoids should be used for the shortest duration and at the lowest dose possible to achieve remission, and then taper and discontinue, if possible.Okay, let’s switch gears and talk about patients with moderate disease.

Moderate disease10:29–11:33

These patients have more extensive skin or joint involvement, or moderate cytopenias, such as a platelet count between 20,000 and 50,000.
There also might be additional organ involvement, such as serositis, which can present with small pleural or pericardial effusions; or gastrointestinal manifestations, like hepatitis or enteritis.
However, there’s no organ-threatening disease. In these patients, begin treatment with hydroxychloroquine, as well as a glucocorticoid, and then assess your patient’s response.
If they have an adequate response, taper the glucocorticoid dose, with the goal of discontinuing it. On the other hand, if your patient has an inadequate response, consider adding an additional immunosuppressive medication, such as azathioprine, mycophenolate mofetil, or a calcineurin inhibitor like cyclosporine or tacrolimus.Finally, let’s talk about individuals with severe disease.

Severe disease11:33–13:04

If your patient has organ-threatening disease, including neurologic or renal manifestations, severe cytopenias, such as a platelet count below 20,000, or large pericardial or pleural effusions, then they have severe disease.
Start your patient on hydroxychloroquine, a high-dose glucocorticoid, and either mycophenolate mofetil or cyclophosphamide.
Next, assess their response to treatment. If adequate, taper the glucocorticoid dose, with the goal of discontinuing it.
On the other hand, if they have an inadequate response, you can switch to an alternative immunosuppressive agent; for example, if they were taking mycophenolate mofetil, switch to cyclophosphamide, or vice versa.
Finally, some patients may benefit from an alternative immunomodulator like rituximab. One last clinical pearl!
Hydroxychloroquine is the first-line treatment for all individuals with lupus, as it reduces the risk of flares, prevents end-organ damage, and increases long-term survival.
Thus, it should be continued during periods of remission, even during pregnancy. Keep in mind that hydroxychloroquine may cause retinal toxicity, so make sure your patient sees an ophthalmologist annually.Alright, as a quick recap… If you suspect lupus, assess for the classification criteria for SLE to confirm the diagnosis.

Review13:04–14:03

Then, determine the degree of renal involvement. If renal involvement is present, order a renal biopsy to evaluate for lupus nephritis.
If renal biopsy confirms lupus nephritis, begin treatment with hydroxychloroquine and consider additional immunosuppressive medications.
Next, determine the disease severity. All individuals with lupus, including those with mild disease, should be started on hydroxychloroquine; while those with moderate disease also require glucocorticoids, and those with inadequate response may also need an additional immunosuppressive medication like azathioprine, mycophenolate mofetil, or calcineurin inhibitors.
Lastly, patients with severe disease need hydroxychloroquine,