Systemic lupus erythematosus: Clinical sciences

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. 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. 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. 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. 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. On the other hand, if your patient does meet criteria, diagnose systemic lupus erythematosus.