Could this be systemic lupus erythematosus (SLE)?

Could This Be Systemic Lupus Erythematosus?

Yes, it could be lupus if the patient presents with a combination of constitutional symptoms, mucocutaneous manifestations, musculoskeletal complaints, and specific laboratory findings—particularly in young women, with even higher suspicion in patients of Asian, African/Caribbean, or Hispanic descent. 1, 2

Key Clinical Presentations to Assess

Early and Common Manifestations

The earliest complaints typically include:

• Constitutional symptoms: Fever during disease flares (must distinguish from infection) 1
• Mucocutaneous findings: Lupus-specific rash (acute, subacute, chronic, or intermittent cutaneous lupus), mouth ulcers, and alopecia 1, 3
• Musculoskeletal symptoms: Joint pain and myalgia 3
• Fatigue: A prominent early feature 3

Critical Organ Involvement Indicators

Look specifically for:

• Renal involvement: Proteinuria (dipstick ≥2+), hematuria with acanthocytes (≥5%), red blood cell casts, white blood cell casts, or declining eGFR without other attributable cause 4, 1
• Hematologic abnormalities: Anemia, thrombocytopenia (indicates worse prognosis and potential renal disease), leukopenia, or lymphopenia (increases infection risk) 1
• Cardiovascular signs: Hypertension (especially with renal involvement), pericarditis 1
• Neuropsychiatric symptoms: Headache, mood disorders, seizures, cognitive impairment 1

Diagnostic Approach Algorithm

Step 1: Screen with Laboratory Testing

• Autoantibodies: Anti-double-stranded DNA, anti-Sm antibodies, antiphospholipid antibodies 3
• Complement levels: Low C3/C4 often correlates with disease activity 1
• Complete blood count: Assess for cytopenia 2
• Urinalysis: Check for proteinuria and abnormal sediment 4
• C-reactive protein: Typically NOT elevated unless infection or serositis is present (important distinguishing feature) 1

Step 2: Apply Classification Criteria

The 2019 EULAR/ACR classification criteria are 96.1% sensitive and 93.4% specific for SLE, incorporating weighted clinical factors (fever, cytopenia, rash, arthritis, proteinuria) and immunologic measures (SLE-specific autoantibodies, low complement) 2, 5

Step 3: Quantify Proteinuria if Present

If dipstick shows ≥2+ protein or abnormal sediment is detected, quantify proteinuria to assess for lupus nephritis 4

Step 4: Consider Kidney Biopsy

A kidney biopsy is essential when renal involvement is suspected because clinical findings do not always correlate with severity, and biopsy results inform treatment decisions and prognosis by distinguishing active (reversible) from chronic (irreversible) lesions 4

High-Risk Populations Requiring Heightened Suspicion

• Demographics: Approximately 90% of SLE patients are female 2
• Race/ethnicity: Asian, African/Caribbean, and Hispanic descent populations have higher incidence 4
• Age: Childhood-onset SLE is associated with higher incidence of lupus nephritis and more severe disease 4

Critical Pitfalls to Avoid

Infection Mimicry

• Fever in SLE must be distinguished from infection, as infections account for 25-50% of overall mortality 4
• CMV infection may mimic active SLE, particularly in patients on high-dose corticosteroids; test for CMV antigenaemia in this context 4
• Screen for HIV, HBV, and HCV before starting immunosuppressive therapy in patients with risk factors 4

Delayed Renal Assessment

• Kidney involvement can remain asymptomatic for significant periods 4
• Proteinuria severity varies considerably in active nephritis and can appear "insignificant" initially 4
• Repeated investigations over time are essential to note progression 4

Drug-Induced Lupus Consideration

• Exclude drug-induced lupus by reviewing medication history, particularly psychiatric medications 6
• Drug-induced lupus resolves after discontinuation of the offending agent 6

Prognosis and Mortality Considerations

• Overall mortality: SLE patients have an almost 5-fold increased risk of death compared to the general population 4
• Lupus nephritis: Approximately 40% of SLE patients develop lupus nephritis, and 10% of those progress to end-stage kidney disease after 10 years 2
• Major causes of death: Infections, hypertension, coronary heart disease, diabetes mellitus, atherosclerosis, and certain cancers (non-Hodgkin's lymphoma, lung cancer, hepatobiliary cancer) 4
• Predictors of worse outcomes: Time from onset to diagnosis >1 year, renal involvement, high disease activity, severe organ involvement 7