What are the typical clinical manifestations of systemic lupus erythematosus (SLE)?

Clinical Manifestations of Systemic Lupus Erythematosus

SLE presents with an extremely variable clinical picture involving virtually any organ system, with mucocutaneous manifestations, arthritis, and renal disease being the most frequently observed features. 1

Constitutional Symptoms

• Fatigue is among the earliest and most common complaints in SLE patients, often preceding other manifestations 2
• Fever must prompt immediate exclusion of infection, particularly when C-reactive protein exceeds 50 mg/L, because fever alone cannot be reliably attributed to lupus activity 1
• Weight loss and malaise frequently accompany active disease 2

Mucocutaneous Manifestations

• Lupus-specific skin lesions occur in three forms: acute cutaneous lupus (including the classic malar "butterfly" rash), subacute cutaneous lupus (photosensitive, annular or papulosquamous lesions), and chronic cutaneous (discoid) lupus 1, 3
• Mouth ulcers (typically painless oral or nasal ulcerations) are characteristic 2
• Alopecia (non-scarring hair loss) is a common early complaint 2
• Photosensitivity is particularly associated with anti-Ro antibodies and subacute lupus 3
• Accurate diagnosis often requires assessment by an experienced dermatologist with skin biopsy to differentiate from mimicking conditions 1

Musculoskeletal Manifestations

• Arthralgia and joint pain are among the most common initial symptoms, frequently reported at disease onset 4, 2
• Arthritis in SLE is typically non-erosive, affecting small and large joints without warmth, presenting mainly with pain and swelling 3
• Myalgia (muscle pain) is a frequent early complaint 2
• Deforming arthropathy can occur in three patterns: non-erosive Jaccoud's arthropathy (most frequent), erosive symmetrical polyarthritis resembling rheumatoid arthritis ("rhupus"), and mild deforming arthropathy 5
• Joint manifestations respond rapidly to small or moderate doses of corticosteroids 3

Renal Manifestations

• Lupus nephritis affects up to 45% of patients, with renal flares occurring at approximately 0.1–0.2 flares per patient-year 1
• Hypertension commonly signals active renal disease 1
• Proteinuria, abnormal urinary sediment (cellular casts, hematuria), and elevated serum creatinine indicate kidney involvement 1
• Lupus nephritis leads to end-stage renal disease in 10% of cases at 10 years 6

Hematologic Abnormalities

• Severe cytopenias—including marked anemia, thrombocytopenia, leukopenia, and lymphopenia—indicate active disease and are linked to poorer prognosis 1
• Lymphopenia is especially common and correlates with disease activity 1
• These hematologic abnormalities increase infection risk substantially 1

Neuropsychiatric Manifestations

Common neuropsychiatric manifestations (cumulative incidence >5%) include cerebrovascular disease and seizures 7

Relatively uncommon manifestations (1–5% incidence) include:

• Severe cognitive dysfunction (affecting memory, attention, concentration, and word-finding) 7, 1
• Major depression 7
• Acute confusional state 7
• Peripheral nervous disorders 7
• Psychosis 7

Additional neuropsychiatric syndromes include:

• Headache (most frequent neuropsychiatric symptom) 1
• Transverse myelitis/myelopathy 1
• Cranial or peripheral neuropathy 1
• Optic neuritis 1
• Movement disorders including chorea 7

Most (50–60%) neuropsychiatric events occur at disease onset or within the first year after SLE onset, commonly (40–50%) in the presence of generalized disease activity 7

Cardiovascular Manifestations

• Patients with SLE have markedly increased risk of premature atherosclerosis and cardiovascular disease that cannot be fully explained by traditional risk factors alone 1
• Hypertension prevalence ranges from 11.5% to 75% 1
• Dyslipidemia prevalence ranges from 11.5% to 75% 1
• Pericarditis and myocarditis can occur during active disease 2

Gastrointestinal Involvement

• Gastrointestinal manifestations are less common but may include mesenteric vasculitis, pancreatitis, and hepatitis 1

Serologic and Immunologic Features

• Antinuclear antibodies (ANA) are positive in virtually all SLE patients and serve as the mandatory entry criterion for classification 6
• Low complement levels (C3, C4) are associated with active disease but do not predict future flares 1
• Anti-dsDNA antibodies correlate with disease activity, particularly renal involvement 1
• Antiphospholipid antibodies markedly increase the risk of thrombosis and pregnancy complications 1

Associated Complications

Infections represent a major cause of morbidity and mortality due to both disease-related immune dysregulation and immunosuppressive therapy 1

Other significant complications include:

• Osteoporosis (affects 4%–24% of patients, with vertebral fracture rates between 7.6% and 37%) 1
• Avascular necrosis, particularly of the femoral head 1
• Diabetes mellitus (often related to chronic glucocorticoid use) 1
• Elevated cancer incidence, especially non-Hodgkin lymphoma, cervical, breast, and lung cancers 1

Critical Clinical Pitfalls

• The clinical picture is highly heterogeneous and can evolve over time within the same individual, necessitating continuous vigilance 1
• Distinguishing active disease from irreversible organ damage, drug toxicity, and intercurrent infections is essential for appropriate management 1
• Manifestations such as headache, mood disorders, anxiety, and mild cognitive dysfunction are common but do not usually reflect overt CNS lupus activity 7
• Chronic widespread pain typical of fibromyalgia is frequently associated with SLE and may interfere with daily activities, requiring identification and prompt treatment to avoid dangerous over-treatment 4