What is the recommended workup for a patient suspected of having Systemic Lupus Erythematosus (SLE)?

Recommended Workup for Systemic Lupus Erythematosus (SLE)

The comprehensive workup for a patient suspected of having Systemic Lupus Erythematosus (SLE) should include laboratory tests, clinical assessment, and screening for comorbidities to establish diagnosis and assess disease activity.

Initial Diagnostic Evaluation

• Antinuclear antibody (ANA) testing should be the first laboratory test when SLE is clinically suspected (involvement of two or more organ systems). A negative ANA or positive at less than 1:40 strongly argues against SLE, while results positive at greater than 1:40 merit further evaluation 1.

• Complete autoantibody panel should include:

  • Anti-dsDNA antibodies
  • Anti-Ro/SSA antibodies
  • Anti-La/SSB antibodies
  • Anti-RNP antibodies
  • Anti-Sm antibodies
  • Antiphospholipid antibodies
  • Complement levels (C3, C4) 2

• Complete blood count (CBC) to assess for cytopenias 2

• Inflammatory markers:

  • Erythrocyte sedimentation rate (ESR)
  • C-reactive protein (CRP)
  • Serum albumin 2

• Renal function assessment:

  • Serum creatinine (or eGFR)
  • Urinalysis
  • Urine protein/creatinine ratio 2

Organ-Specific Assessment

• Renal assessment: Patients with abnormal urinalysis or raised serum creatinine should undergo:

  • Urine protein/creatinine ratio (or 24-hour proteinuria)
  • Urine microscopy
  • Renal ultrasound
  • Consider renal biopsy 2

• Neuropsychiatric assessment: Monitor for neuropsychological symptoms through focused history:

  • Seizures, paresthesias, numbness, weakness
  • Headache, epilepsy, depression
  • Cognitive impairment (attention, concentration, word finding, memory difficulties) 2

• Mucocutaneous assessment: Characterize lesions according to classification systems:

  • LE-specific lesions
  • LE-nonspecific lesions
  • LE mimickers
  • Drug-related lesions
  • Use validated indices (e.g., CLASI) to assess activity and damage 2

• Ophthalmologic assessment: Baseline eye examination is recommended, especially for patients who will be treated with glucocorticoids or antimalarials 2

Comorbidity Screening

• Cardiovascular risk assessment:

  • Smoking status
  • History of vascular events (cerebral/cardiovascular)
  • Physical activity level
  • Use of oral contraceptives/hormonal therapies
  • Family history of cardiovascular disease
  • Blood cholesterol and glucose
  • Blood pressure
  • Body mass index and/or waist circumference 2

• Infection risk screening:

  • HIV based on patient's risk factors
  • HCV, HBV based on risk factors (particularly before immunosuppressive therapy)
  • Tuberculosis according to local guidelines
  • Consider CMV testing during treatment in selected patients 2

• Osteoporosis assessment:

  • Calcium and vitamin D intake
  • Exercise habits
  • Smoking status
  • Follow osteoporosis screening guidelines for postmenopausal women and patients on steroids 2

• Cancer screening according to general population guidelines, including cervical smear tests 2

Disease Activity and Quality of Life Assessment

• Disease activity should be evaluated using a validated index at each visit 2

• Organ damage should be assessed annually 2

• Quality of life should be evaluated by patient history and/or by a 0-10 visual analog scale (patient global score) at each visit 2

• Drug toxicity monitoring based on specific medications 2

Clinical Approach

• Apply the 2019 European Alliance of Associations for Rheumatology/American College of Rheumatology classification criteria which are 96.1% sensitive and 93.4% specific for SLE 3

• Recognize that SLE diagnosis remains clinical, with classification criteria often used for diagnosis with significant caveats 4

• Be aware that approximately 40% of people with SLE develop lupus nephritis, and an estimated 10% of those develop end-stage kidney disease after 10 years 3

Important Considerations and Pitfalls

• Diagnostic pitfall: SLE is a great imitator of other diseases, making diagnosis difficult. Consider alternative diagnoses if ANA is negative 1

• Treatment planning: The primary goal of treatment is to achieve disease remission or quiescence, defined by minimal symptoms, low levels of autoimmune inflammatory markers, and minimal systemic glucocorticoid requirement 3

• Referral indications: Patients with increased disease activity, complications, or adverse effects from treatment should be referred to a rheumatologist 5

• Long-term monitoring: Patients with established nephropathy require more frequent monitoring (every 3 months for the first 2-3 years) of proteinuria, immunological tests, urine microscopy, and blood pressure 2