TOPIC 44: Systemic Lupus Erythematosus – Understand the clinical presentation and evaluation of a patient with systemic lupus erythematosus
OFFICIAL ABP TOPIC:
Understand the clinical presentation and evaluation of a patient with systemic lupus erythematosus
BACKGROUND
Childhood-onset systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect multiple organ systems. While childhood-onset SLE can occur at any age, it is most common in adolescents and rare before age 5. Early recognition and treatment are essential to reducing organ damage and mortality in children with SLE.
CLINICAL MANIFESTATIONS OF SLE
SLE has significant variability and can affect any organ system. Most patients have a gradual onset of constitutional symptoms over weeks to months.
KEY MANIFESTATIONS BY SYSTEM
|
ORGAN SYSTEM |
KEY MANIFESTATIONS |
|
Mucocutaneous |
Malar butterfly rash sparing the nasolabial folds, discoid lesions, photosensitivity, oral/nasal ulcers, alopecia, Raynaud phenomenon, livedo reticularis IMAGE: www.pbrlinks.com/RAYNAUDS1 |
|
Musculoskeletal |
Arthritis (nonerosive, polyarticular), arthralgia, myositis |
|
Renal |
Proteinuria, hematuria, hypertension, nephrotic syndrome, lupus nephritis |
|
Hematologic |
Autoimmune hemolytic anemia, leukopenia, lymphopenia, thrombocytopenia, antiphospholipid syndrome (causes thrombosis) |
|
Neuropsychiatric |
Headaches, mood disorders, cognitive dysfunction, psychosis, seizures, transverse myelitis, neuropathies |
|
Cardiopulmonary |
Pericarditis, pleuritis, pulmonary hemorrhage, interstitial lung disease |
|
Constitutional |
Fever, weight loss, fatigue, lymphadenopathy |
EVALUATION OF SLE
HISTORY AND PHYSICAL
- Detailed history of constitutional symptoms and multisystem involvement (including fever, weight loss, fatigue, rashes, joint pain).
- Family history of autoimmune diseases.
- Complete exam with focus on skin, joints, and neurologic system.
DIAGNOSIS
SLE is most common in adolescents aged 12-14 years, with a strong female predominance (4.5-7.2:1) and higher incidence in non-White populations, including Black, Hispanic, Asian, and Native American individuals. It is also important to note that definitive diagnosis may not be possible at initial presentation. Symptoms accumulate over time.
DIFFERENTIAL DIAGNOSIS
SLE can be difficult to diagnose because of the variety of potential signs and symptoms, which may take years to develop. Symptoms may also mimic other autoimmune, infectious, or neoplastic conditions.
- ANA-negative SLE is very rare. Consider alternative diagnoses if ANA negative.
- SLE can occasionally present with isolated cytopenias or nephritis years before other symptoms appear.
|
CONDITION |
DISTINGUISHING FEATURES |
|
Leukemia |
Night pain, pancytopenia, hepatosplenomegaly, blasts on peripheral smear. |
|
Juvenile Idiopathic Arthritis |
Erosive arthritis, lack of systemic involvement, normal complement levels. |
|
Parvovirus B19 |
Positive parvovirus IgM, transient cytopenias, no nephritis or ANA positivity. |
|
Dermatomyositis |
Heliotrope rash (www.pbrlinks.com/DERMATOMYOSITIS1), Gottron papules (www.pbrlinks.com/DERMATOMYOSITIS2), muscle weakness, elevated CK. |
|
Post-streptococcal GN |
Recent strep infection, low C3 but normal C4, no autoantibodies. |
DIAGNOSTIC CRITERIA
Classification criteria are not required for diagnosis in a patient with clear multisystem clinical findings. There are no unanimously agreed-upon diagnostic criteria for SLE, but the criteria below, which are used for research studies, commonly aid in the clinical diagnosis.
|
CRITERIA |
REQUIRED FEATURES |
KEY POINTS |
|
2019 EULAR/ ACR Criteria |
ANA ≥ 1:80, total score ≥10 |
Emphasizes both clinical and immunologic domains. |
|
ACR Criteria |
≥4 of 11 clinical/immunologic criteria (malar rash, photosensitivity, discoid rash, oral ulcers, arthritis, serositis, renal disease, neurologic disorder, hematologic disorder, +ANA, +anti-dsDNA/anti-Smith) |
Commonly used but less sensitive for early disease. |
|
SLICC Criteria |
≥4 criteria (≥1 clinical, ≥1 immunologic) OR biopsy-proven nephritis with ANA/anti-dsDNA |
Most sensitive for early SLE. Allows single organ involvement if supported by biopsy findings. |
DIAGNOSTIC TESTING
- Initial Tests: CBC (cytopenias), CMP (elevated creatinine, hypoalbuminemia), U/A (hematuria, proteinuria, WBCs), C3/C4 (low in active disease), ANA (positive in nearly 100%).
- Confirmatory Tests: Anti-dsDNA, anti-Smith, antiphospholipid antibodies (anticardiolipin, lupus anticoagulant, anti-β2 glycoprotein 1).
- Additional Tests:
- Brain MRI and lumbar puncture for neuropsychiatric symptoms such as seizures or psychosis.
- Echo and CXR for cardiopulmonary symptoms such as chest pain or dyspnea.
- Kidney biopsy for renal disease.
AUTOANTIBODY TESTS, THEIR PREVALENCE IN SLE, AND THEIR CLINICAL RELEVANCE
|
AUTOANTIBODY |
PREVALENCE |
CLINICAL RELEVANCE |
|
ANA |
Nearly 100% |
Sensitive but not specific for SLE. Entry criterion for diagnosis. |
|
Anti-dsDNA |
>75% |
Highly specific for SLE. Associated with active nephritis. |
|
Anti-Smith |
30–40% |
Specific for SLE but not predictive of severity. |
|
Anti-Ro/SSA, Anti-La/SSB |
16–32% |
Associated with subacute cutaneous lupus and neonatal lupus. |
|
Antiphospholipid (aCL, LA, anti-β2GPI) |
38–87% |
Associated with thrombosis risk and antiphospholipid syndrome. |