Systemic lupus erythematosus (SLE): Clinical practice

Systemic Lupus Erythematosus, or lupus, is an autoimmune disease, where essentially any tissue or organ can be the target of inflammation.

Often there are periods of illness, called flares, and periods of remission during which there are few symptoms.

The diagnosis of lupus is made when 4 or more out of 11 criteria are met.

The first three have to do with the skin.

The first is a malar rash, sometimes just called a “butterfly rash”, which is a rash over the cheeks that spares the nasolabial folds and appears after sun exposure.

Second is a discoid rash, which is chronic erythematous rash in sun-exposed areas like the arms and legs that are plaque-like or patchy redness and can scar.

Third, is a general photosensitivity of the skin — essentially a catch-all category for other rashes that happen to sun-exposed areas — typically only lasting a couple of days.

Lupus can also damage the inner membrane or mucosa of various tissues, so the fourth criteria is ulcers in the mouth or nose.

The fifth criteria is serositis which is inflammation of the serosa, which is like the outer membrane of an organ or tissue.

It can manifest as pleuritis, which is inflammation of the lining around the lungs and chest cavity; as pericarditis, which is inflammation of the lining of the heart; or as peritonitis, which is inflammation of the lining of the abdomen.

Now, in addition to pericarditis, it’s worth noting that lupus can also cause inflammation of the myocardium, leading to myocarditis, or the endocardium, leading to Libman-Sacks endocarditis, where clumps of fibrin and immune cells form vegetations on the mitral valve.

The sixth criteria is arthritis, and two or more joints have to get inflammed to meet the criteria.

The seventh criteria is evidence of kidney damage based on protein or cells in the urine.

It’s generally caused by lupus nephritis, which is a type of glomerulonephritis due to immune complex deposition along the glomerular basement membrane.

Lupus nephritis can ultimately lead to end-stage kidney failure, which is the leading cause of morbidity and mortality among individuals with lupus.

The eighth criteria is neuropsychiatric conditions like headaches, seizures, psychosis, and mood disorders like depression.

The ninth criteria is having autoantibodies against blood components causing cell destruction, and leading to conditions like anemia, thrombocytopenia, or leukopenia.

The final two criteria have to do with having specific antibodies in the blood.

The tenth criteria is having antinuclear antibody or ANA, which targets nuclear antigens.

Now a large proportion of patients with lupus have these, meaning this test is very sensitive, but it isn’t very specific, because it can be found in other autoimmune diseases.

The eleventh criteria is having one of three other autoantibodies.

The first is anti-Smith, which is an antibody against small ribonucleoproteins.

The second is anti-dsDNA, which is against double stranded DNA and is often seen more during flares, especially in individuals with kidney involvement.

These two are relatively specific for lupus.

The third type of antibody is antiphospholipid, which is actually an antibody that’s made against proteins that are bound to phospholipids, and is less specific for lupus, meaning that it can pop up in other situations.

There are three types of antiphospholipid antibodies.

The first is anticardiolipin, which can cause a false-positive test for syphilis since anticardiolipin antibodies are sometimes involved in syphilis.

The other two antiphospholipid antibodies arelupus anticoagulant also called lupus antibody, and anti-beta2 glycoprotein I.

Sometimes, because of these, patients with lupus develop an antiphospholipid syndrome, where the antiphospholipid antibodies cause a hypercoagulable state, meaning they’re more prone to developing clots and having complications like deep vein thrombosis, hepatic vein thrombosis, and stroke.

Now, lupus can also cause additional symptoms that aren’t part of the diagnostic criteria.

Systemic symptoms include fever, fatigue, myalgia, unintentional weight loss, and lymphadenopathy.

There can also be vasculitis, which can manifest as palpable purpura, petechiae, panniculitis, skin ulcers, splinter hemorrhages, and livedo reticularis - which is where there’s a lace-like purplish discoloration of the skin.

Another vascular condition that can occur in lupus is Raynaud’s phenomenon, which is where arterial spasm causes reduced blood flow to the fingers.

It typically lasts for minutes, and the fingers turn white and then blue, often with numbness or pain, and then as blood flow returns, the fingers turn red and burn.

Finally, lupus increases the likelihood of thromboembolic disease, specifically a blood clot can form in a blood vessel and then breakaway to plug up a smaller vessel in another organ like the lungs, brain, or kidneys.

Finally, lupus can cause activation of the complement system and during a flare it can cause consumption of complement factors like C3 and C4. So in summation, if an individual meets the diagnostic criteria, they may have many of these additional findings as well.

Next up, is laboratory testing.

That includes getting a complete blood count and differential, to look for leukopenia, anemia, and thrombocytopenia; as well as a creatinine level which might reveal renal dysfunction.

In addition, it’s important to get antinuclear antibodies, anti-double-stranded DNA, anti-Smith, and antiphospholipid antibodies, as well as an ESR and CRP to look for evidence of systemic inflammation.

In addition, C3 and C4 levels, and a CH50, can be obtained to see if there’s an effect on the complement system.

Now, because lupus nephritis is such a serious problem, a urinalysis should be done to check for it and distinguish nephritic syndrome, which has faster evolution towards end-stage renal failure, from nephrotic syndrome.

In nephritic syndrome, there’s a triad of hematuria, hypertension and azotemia with subsequent renal failure.

Whereas in nephrotic syndrome there’s the pentad of edema, proteinuria, dyslipidemia, lipiduria, and hypoalbuminemia.

More specific organ involvement may require additional studies.

For inflamed joints, plain radiographs can show joint deformities, and an ultrasound might detect synovitis or joint effusions.

Chest X rays may be done for a suspected pleural effusion, interstitial lung disease, or cardiac abnormalities, while echocardiography and an EKG can be done to look for evidence of cardiac involvement - like pericarditis, myocarditis, and endocarditis.

An MRI may be needed to evaluate any neurologic deficits or cognitive dysfunction.

Finally, a biopsy of an involved organ, mainly the skin or kidneys, is often helpful in confirming the disease or tracking its progression.

The key goals of therapy are to minimize both damage from the disease and toxicity from medications.

So treatment is mainly aimed at preventing or limiting the severity of flares of the disease.

To help prevent flares means being careful to avoid triggers like sunlight, certain foods and medications, and tobacco.

So individuals can avoid sunlight exposure with hats and long-sleeved clothes, avoid certain foods, exercise regularly, quit smoking, use immunizations to prevent serious infections, avoid medications like isoniazid, hydralazine, and procainamide, and carefully navigate pregnancy.

Treatment is based upon the severity of disease.

Individuals with mild lupus manifestations, which generally means only having skin, joint, and mucosal involvement, are given hydroxychloroquine or chloroquine.

They sometimes also use nonsteroidal antiinflammatory drugs or NSAIDs and short courses of low-dose glucocorticoids, meaning less than 7.5 mg of prednisone per day.

Individuals with moderate lupus involvement are defined as having significant but non-organ-threatening disease, along with constitutional, cutaneous, musculoskeletal, or hematologic manifestations.

These individuals usually respond to hydroxychloroquine or chloroquine plus short courses of up to 15 mg of prednisone per day.

Finally, individuals with severe or life-threatening lupus manifestations with major organ involvement, such as the kidneys and central nervous system, are usually treated in the hospital with a short course of high doses of systemic glucocorticoids, meaning 1 to 2 mg per kilogram per day of prednisone.

This can be supplemented with other immunosuppressive medications like cyclophosphamide, azathioprine, or mycophenolate mofetil.

This initial therapy is followed by less intensive maintenance therapy with a lower dose of glucocorticoids to keep them in remission.

Unfortunately, some individuals don’t respond to glucocorticoids or other immunosuppressive agents.

In those cases, biologic medications can be tried like belimumab, a human monoclonal antibody that inhibits the activation of B cells, or rituximab, a chimeric monoclonal antibody against CD20, which is found on the surface of B cells, and triggers B cell death.

Summary

Alright, as a quick recap… Systemic lupus erythematosus is diagnosed when 4 out of 11 criteria are met.

These are a malar rash; discoid rash; photosensitivity; oral or nasal ulcers; serositis; arthritis in two joints; renal involvement; neuropsychiatric conditions; hematologic conditions like anemia, leukopenia, and thrombocytopenia; antinuclear antibodies; or another type of autoantibody like anti-double-stranded DNA, anti-Smith, or antiphospholipid antibodies.

To help prevent flares, individuals should avoid triggers.

Mild lupus is treated with hydroxychloroquine or chloroquine, with or without NSAIDs and short-term low-dose glucocorticoids.

Moderate lupus is treated with hydroxychloroquine or chloroquine and short-term glucocorticoids.

Finally, severe or life-threatening lupus is treated with short-term high-dose glucocorticoids with or without other immunosuppressive medications like cyclophosphamide, azathioprine, or mycophenolate mofetil.

Unresponsive cases may be treated with biologic medications like belimumab or rituximab.