What are the signs and symptoms of Systemic Lupus Erythematosus (SLE)?

Systemic Lupus Erythematosus: Signs and Symptoms

Systemic lupus erythematosus is a multisystem autoimmune disease that most commonly presents with constitutional symptoms, mucocutaneous manifestations (including lupus-specific rashes and mouth ulcers), musculoskeletal complaints (arthritis, joint pain, myalgia), and can progress to involve renal, neurologic, hematologic, cardiovascular, and pulmonary systems, predominantly affecting women of reproductive age. 1, 2, 3

Constitutional and Early Manifestations

The earliest complaints in most patients include:

• Fatigue is a prominent early symptom 3
• Fever occurs during disease flares and must be distinguished from infection 2
• Weight loss may accompany active disease 3

Mucocutaneous Manifestations

Skin involvement is classified into distinct categories:

• Lupus-specific skin lesions include acute cutaneous lupus, subacute cutaneous lupus, chronic cutaneous lupus, and intermittent cutaneous lupus 2
• Malar rash (butterfly rash) is characteristic 3, 4
• Discoid lesions correlate with long-term prognosis 1
• Mouth ulcers are common early manifestations 3
• Alopecia (hair loss) frequently occurs 3
• Photosensitivity is present in many patients 1

Musculoskeletal Symptoms

• Arthritis is a frequent presenting symptom and provides prognostic information 1, 2, 3
• Joint pain (arthralgia) without frank arthritis 3
• Myalgia (muscle pain) 3

Renal Manifestations

Kidney involvement is a major determinant of morbidity and mortality:

• Proteinuria indicates kidney involvement 2, 4
• Hematuria may be present 2
• Impaired renal function develops in approximately 40% of SLE patients as lupus nephritis 4
• Renal disease relapses occur in up to 45% of patients 2
• Hypertension is common, especially with renal involvement 2

Neuropsychiatric Manifestations

Neurological involvement is frequent and diverse:

• Headache is among the most common neuropsychiatric syndromes 2
• Mood disorders including depression 2
• Seizures are significant manifestations that correlate with outcome 1, 2
• Psychosis is a serious neuropsychiatric manifestation 1, 2
• Cognitive impairment affects many patients 2

Hematologic Abnormalities

Blood count abnormalities provide both diagnostic and prognostic information:

• Anemia is associated with organ involvement and disease progression 2
• Thrombocytopenia (low platelet count) indicates renal disease and worse prognosis 1, 2
• Leukopenia and lymphopenia increase infection risk 2
• Cytopenia is included in classification criteria 4

Cardiovascular Manifestations

• Pericarditis and other cardiac manifestations occur 2
• Serositis (inflammation of serous membranes) correlates with outcome 1
• Increased risk of atherosclerosis and cardiovascular disease is a major concern 2

Pulmonary Manifestations

Respiratory involvement affects 20% to 90% of patients during disease course:

• Pleural involvement is the most common pulmonary manifestation 1
• Dyspnea (shortness of breath) should prompt evaluation for lung disease 1
• Chest pain may indicate pleuritis or other pulmonary involvement 1
• Reduced exercise tolerance 1
• Cough 1
• Hemoptysis (coughing blood) 1
• Interstitial lung disease occurs in 1% to 15% of patients, though less severe than in other connective tissue diseases 1
• Tachypnea is a risk factor for ILD development 1

Laboratory and Immunologic Findings

These findings support diagnosis and monitoring:

• Anti-double-stranded DNA antibodies are relatively specific for SLE 1, 4
• Low complement levels (C3/C4) often correlate with disease activity 1, 2, 4
• Antiphospholipid antibodies indicate increased risk for thrombosis and pregnancy complications 2
• Anti-Sm antibodies are highly specific 4
• Anti-Ro/SSA and anti-La/SSB antibodies provide prognostic information 1
• Anti-U1-RNP antibodies are associated with ILD risk 1
• C-reactive protein is typically not elevated unless infection or serositis is present 2
• Elevated CRP is a risk factor for ILD 1

Additional Clinical Features

• Raynaud phenomenon is associated with ILD development 1
• Abnormal nail-fold capillaries are risk factors for ILD 1
• Gastroesophageal reflux disease increases ILD risk 1

Important Clinical Pitfalls

Symptoms may worsen during pregnancy, particularly in patients with lupus nephritis and antiphospholipid antibodies, requiring heightened vigilance 2. The disease course is highly variable, and approximately 10% of patients with lupus nephritis progress to end-stage renal disease within 10 years 4. Pulmonary manifestations follow a chronic course associated with significantly worse prognosis and higher mortality 1.