Systemic Lupus Erythematosus

Contributor: Laura Tarter, MD

CASE 1

A 25 year old female presents with fatigue, arthralgias, and a rash. She reports that she has been having joint pain with worsened stiffness and swelling in the mornings for the past three months. She has also noted rashes, particularly on her face and neck, over this same time period. On exam, several MCPs are tender to palpation with trace synovitis, and she has multiple well-demarcated erythematous plaques on her face and neck with fine overlying scale. Basic labs are notable for a total lymphocyte count of 500, a creatinine of 1.6, and red blood cell casts and 3+ proteinuria on urinalysis. A 24-hour urine protein returns at 4.2 grams/day. Autoantibody testing is notable for a positive ANA at a titer of 1:640 with a diffuse homogeneous staining pattern, the presence of high titer double stranded DNA antibodies, the presence of anti-Smith antibodies, and hypocomplementemia.

What is the significance of the tests ordered in making the diagnosis of SLE?

  • SLE is diagnosed based on both clinical and laboratory features. The American College of Rheumatology has developed classification criteria for lupus, used as a aid in the diagnosis of this complex multi-organ system disease, but primarily intended for use in studies. More recently, the Systemic Lupus International Collaborating Clinics Classification Criteria for SLE have also been developed.
  • Immunologic criteria play a significant role in the diagnosis of SLE. ANA positivitiy is found in almost all patients with SLE; while the ANA is very sensitive for the diagnosis of SLE (>99%), it is not specific. Other autoantibodies frequently seen in patients with SLE are the following: anti-dsDNA (40%), anti-Smith (30%), anti-RNP (30%), anti-SSA/Ro (35%), anti-SSB/La (15%), antiphospholipid antibodies (30%).

What are the typical features seen in this patient that are helpful in making the diagnosis of SLE?

  • Fatigue is very common in SLE (80-100%) but non-specific; other tiologies should also be considered.
  • Mucocutaneous lesions occur in 80% of patients, including acute utaneous lupus (particularly malar rash), chronic cutaneous lupus most commonly discoid lupus erythematosus, as evident in this patient), oral ulcers, and non-scarring alopecia.
  • Cytopenias are common, particularly lymphopenia.
  • Renal involvement occurs in > 50% of patients. Diagnostic clues include proteinuria, hematuria, and RBC casts, as evident in this patient.

What are the typical features seen in this patient that are helpful in making the diagnosis of SLE?

  • Fatigue is very common in SLE (80-100%) but non-specific; other tiologies should also be considered.
  • Mucocutaneous lesions occur in 80% of patients, including acute utaneous lupus (particularly malar rash), chronic cutaneous lupus most commonly discoid lupus erythematosus, as evident in this patient), oral ulcers, and non-scarring alopecia.
  • Cytopenias are common, particularly lymphopenia.
  • Renal involvement occurs in > 50% of patients. Diagnostic clues include proteinuria, hematuria, and RBC casts, as evident in this patient.

What are the next steps in management of this patient? 

CASE 2

A 32 year old female with a 7 year history of SLE (manifestations: +ANA, +Smith, +SSA, malar rash, pleuritis, arthritis) comes to your primary care clinic for a routine visit. She has been doing well. Her medications include Hydroxychloroquine 400mg daily and a multivitamin.

From a primary care perspective, what health care maintenance should be addressed with this patient?

  • Cardiovascular risk factor assessment: given the increased risk of early atherosclerosis in SLE, patients with SLE should have annual evaluation of modifiable cardiovascular risk factors and appropriate intervention when indicated. Appropriate testing includes the following: blood pressure assessment, fasting lipid panel, blood sugar and/or hemoglobin A1C, BMI calculation, and query about tobacco use.
  • Vaccinations: it is recommended that SLE patients have annual influenza vaccines and a pneumococcal vaccination.
  • Sun protection: all SLE patients should be counseled on the importance of sun protection (including protective clothing and broad spectrum sunscreen with anti-UVA and UVB).
  • Age-appropriate cancer screening: growing evidence suggests that SLE patients have an increased risk of malignancy and should at the very least undergo routine cancer screening.
  • Contraceptive choice: all patients on immunosuppressive therapy should be counseled on the safety of becoming pregnant while on medications. If medications are being used that are contraindicated during pregnancy, appropriate contraceptive choices should be offered to the patient or a referral to an OB/GYN made.
  • Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that may affect the skin, joints, kidneys, and other organs. While SLE can occur in people of all ages, it disproportionately affects women of childbearing age and minority populations in the US.

Patient Care

  1. Understand the ACR Endorsed Criteria and SLICC diagnostic criteria for systemic lupus erythematosus.
  2. Recognize the clinical manifestations of systemic lupus erythematosus.
  3. Obtain an appropriate history to determine if a patient might have SLE.
  4. Recognize when ANA testing should be utilized.
  5. Determine who should be referred to a rheumatologist for evaluation of a positive ANA.
  6. Determine the appropriate serologic testing used to support the diagnosis of SLE.
  7. Identify the tests used to screen for anti-phospholipid antibodies.
  8. Identify the most common serious complications of systemic lupus.
  9. Identify the most common causes of early mortality in patients with systemic lupus.
  10. Recognize serious infection in a patient with systemic lupus on immunosuppressant therapy.
  11. Recognize the high incidence of cardiovascular disease in patients with SLE and the appropriate steps for screening for modifiable cardiovascular risk factors.

Medical Knowledge

  1. Determine which population subgroups are at greatest risk for development of SLE.
  2. Interpret the results of ANA and ENA testing.
  3. Interpret the results of anti-phospholipid antibody testing.
  4. Describe the different types of lupus nephritis and the implications of pathologic features on treatment strategies.
  5. Recognize the pulmonary, cardiac, renal, gastrointestinal, hematologic, neurologic, musculoskeletal, and mucocutaneous manifestations of lupus.
  6. Identify the similarities and differences between drug-induced lupus and SLE.
  7. Understand the limitations of SLE diagnostic criteria.
  8. Identify the drugs most often used to treat SLE and the potential toxicities of these agents.
  9. Understand the role of prevention in the primary care of patients with SLE (including careful attention to the following: modifiable cardiovascular risk factor screening, bone health, reproductive health and contraception, and vaccinations).

Practice Based Learning and Improvement

  1. Set goals for learning about SLE pathophysiology, clinical manifestations, and treatment options.
  2. Demonstrate the ability to review and interpret literature relevant to the care of patients with SLE.  

Interpersonal and Communication Skills

  1. Discuss the results of ANA testing with a patient.
  2. Discuss the results of anti-phospholipid antibody testing with a patient.
  3. Discuss the diagnosis of SLE with a patient.
  4. Discuss the need for appropriate follow up and monitoring with a patient.
  5. Comprehensively explain different treatment options based on disease manifestations.
  6. Discuss pregnancy risks associated with active SLE.
  7. Discuss the risk of early atherosclerosis in SLE and appropriate preventive steps with a patient.

Professionalism

  1. Recognize the importance of patient confidentiality and privacy.
  2. Understand the need to provide supportive care.
  3. Encourage patients to ask questions regarding their disease and empower them to be active participants in their care.
  4. Provide adequate time and accessibility to address patient concerns.
  5. Demonstrate an understanding of informed consent with regard to therapeutic options in the treatment of SLE.

Systems Based Practice

  1. Create a team approach to manage patients with SLE, engaging physicians from multiple disciplines.
  2. Identify barriers to access and delivery of care for patients with complex, multi-system diseases.
  3. Understand the resources available to improve delivery of care and patient support.
  4. Identify the ways in which one can be a patient advocate, including obtaining prior authorization for medications, treatments, and diagnostic tests.
  5. Demonstrate an awareness of the economic implications of a diagnosis of SLE for the patient, as well as the potential implications for the healthcare system of caring for patients with chronic diseases.

References

  • Doria A, Gatto M, Zen M, et al. Optimizing outcome in SLE: treating-to-target and definition of treatment goals. Autoimmunity Reviews 2014;13:770-777.
  • Hahn BH, McMahon M, Wilkinson A, et al. American College of Rheumatology guidelines for screening, case definition, treatment and management of lupus nephritis. Arthritis Care Res 2012;64:797-808. 
  • Knight JS and Kaplan MJ. Cardiovascular disease in lupus: insights and updates. Curr Opin Rheumatol 2013;25:597-605.
  • Okon LG and Werth VP. Cutaneous lupus erythematosus: diagnosis and treatment. Best Pract Res Clin Rheumatol 2013;27:391-404.
  • Petri M, Orbai A, Alarcon GS, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arth Rheum 2012;64: 2677-2686.
  • Yazdany J, Panopalis P, Gillis JZ, et al. A quality indicator set for systemic lupus erythematosus. Arth Rheum 2009;61:370-377.

Questions

(Answer questions 1 – 5 on a piece a paper. Find Answer Key at the bottom on the page.)

CASE 1

A 28 year-old woman presents with fatigue, arthralgias, intermittent headaches, and easy bruising. Basic laboratory testing is notable for a white blood cell count of 3.2, absolute lymphocyte count of 0.8, and platelets of 15. On chart review, a complete blood count 2 years prior was notable for a white blood cell count of 3.0, and an absolute lymphocyte count of 0.6. Creatinine, liver function tests, albumin, urinalysis, and coagulation testing are all normal. Autoantibody testing is notable for a positive ANA at a titer of 1:1280 with a diffuse homogeneous staining pattern, the presence of double stranded DNA antibodies at a titer of 1:640, and hypocomplementemia. Exam is notable for malar erythema, multiple painless oral ulcers, and ecchymoses predominantly over the extensor surfaces of her lower extremities. No splenomegaly was noted on exam.

1) Does this patient meet classification criteria for SLE?

  1. Yes
  2. She has features of SLE but does not meet classification criteria
  3. No

2) Which of the following etiologies should be considered in the differential diagnosis of her thrombocytopenia?

  1. Idiopathic thrombocytopenic purpura (ITP)
  2. Thrombotic thrombocytopenic purpura (TTP)
  3. Autoimmune hepatitis (AIH)

CASE 2

A 32 year-old male with known SLE (+ANA, +Smith, hypocomplementemia, discoid lupus erythematosus (DLE), prior class III/V lupus nephritis, prior neuropsychiatric SLE) is admitted with chest pain. He describes the pain as pleuritic in nature, worse with lying down, and improved with leaning forward. He has had mild upper respiratory symptoms for 1 week, low-grade fevers at home, and does note a non-productive cough. He has been on a stable dose of Plaquenil 400mg daily, Mycophenolate mofetil 1000mg daily, and Prednisone 5mg daily. No recent travel.

Vital signs in the emergency room are notable for a temperature of 100 F and heart rate of 109.  His lung exam is clear to auscultation bilaterally. The remainder of his exam is notable for hypopigmented peri-auricular lesions consistent with inactive DLE.

3) Which of the following is the least likely explanation of his symptoms?

  1. Pleuropericarditis
  2. Bacterial pneumonia
  3. Pulmonary embolism
  4. Myocardial infarction
  5. All of the above need to be addressed with further evaluation

The patient has classic symptoms for pleuropericarditis (pleuritic chest pain worsened with lying flat and relieved with leaning forward). However, particularly in patients with SLE, the differential for cardiopulmonary processes is broad, and it is critical that multiple potential etiologies be considered. There is a markedly increased risk of cardiovascular disease (4-fold increased risk). Pulmonary embolism is also more common in patients with SLE (often in the presence of antiphospholipid antibodies), as are infections, particularly in patients on immunosuppressive therapy.

Basic labs are notable for a white blood cell count of 3.2 and otherwise normal CBC, normal liver function tests, normal creatinine, and urinalysis without blood or protein. A chest x-ray is done and shows a normal cardiac silhouette and very slight blunting of the costophrenic angles. Apart from HR of 110, ECG is unremarkable. Initial troponin is negative.

4) What further workup is indicated?

  1. CT angiogram of the chest
  2. Echocardiogram
  3. Sputum culture

5) At this point, what medications changes should be made to treat his symptoms?

  1. Increase Prednisone to 60mg daily
  2. Start Colchicine 0.6mg twice daily
  3. Start Rituximab 375 mg/m2 weekly x 4 doses

Answer Key

Case 1

1) The correct answer is A.

The patient meets both the ACR classification criteria for SLE (1997 update of 1982 criteria) and the 2012 SLICC classification criteria for SLE.

She fulfills 4 of 11 ACR classification criteria for SLE (> 4 needed to meet criteria): +ANA, immunologic disorder (+dsDNA, hypocomplementemia), hematologic disorder (thrombocytopenia, leukopenia on > 2 occasions, lymphopenia on > 2 occasions), malar rash, and oral ulcers.

She also fulfills 6 of 17 SLICC classification criteria for SLE  (> 4 needed with at least 1 immunologic and 1 clinical criteria met): +ANA, +dsDNA, hypocomplementemia, leukopenia/lymphopenia, thrombocytopenia, acute cutaneous lupus (malar rash), oral ulcers.

2) The correct answers are: A and B.

Thrombocytopenia in SLE has multiple possible etiologies, including ITP, TTP, the antiphospholipid antibody syndrome, as well as medication toxicity, viral infection, and malignancy. Liver disease, including AIH, can lead to hypersplenism, splenic sequestration of platelets, and consequently thrombocytopenia. However, she has normal liver function tests and normal synthetic function on laboratory analysis, no splenomegaly on exam, and no stigmata of chronic liver disease, making AIH extremely unlikely.

Case 2

3) The correct answer is A.

All of the above need to be addressed with further evaluation.

The patient has classic symptoms for pleuropericarditis (pleuritic chest pain worsened with lying flat and relieved with leaning forward). However, particularly in patients with SLE, the differential for cardiopulmonary processes is broad, and it is critical that multiple potential etiologies be considered. There is a markedly increased risk of cardiovascular disease (4-fold increased risk). Pulmonary embolism is also more common in patients

4) The correct answers are A and B.

Given the lack of pulmonary infiltrates on chest x-ray, bacterial pneumonia is less likely. Despite the normal cardiac silhouette and lack of ECG changes, pericarditis remains possible and an echocardiogram is indicated. A pulmonary embolism also still needs to be considered.

CT angiogram of the chest is negative for pulmonary embolism. Echocardiogram shows a small pericardial effusion and is otherwise unremarkable

5) The correct answers are A and B.

The patient has classic symptoms for pericarditis and a small effusion on echocardiogram supporting this diagnosis. Therapeutic approaches include: increasing corticosteroid dose (PO or IV if necessary), colchicine, and consideration of NSAID therapy (to be employed with caution in this patient with a history of lupus nephritis). In the outpatient setting, depending on his response, a change to his baseline immunosuppressive regimen may be indicated. However, there is not an indication for use of rituximab in this setting.

Last updated February 2015