What are the typical clinical manifestations of systemic lupus erythematosus?

Clinical Signs of Systemic Lupus Erythematosus

Systemic lupus erythematosus 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

• Fever is a critical red flag that mandates immediate exclusion of infection before attributing it to lupus activity alone, particularly when C-reactive protein exceeds 50 mg/L. 1
• Fatigue and malaise are common but non-specific presenting symptoms. 2

Mucocutaneous Manifestations

• Both lupus-specific lesions (acute cutaneous lupus, subacute cutaneous lupus, chronic discoid lupus, and intermittent cutaneous lupus) and non-specific skin findings characterize SLE. 3
• Accurate diagnosis often requires assessment by an experienced dermatologist and skin biopsy to differentiate from mimicking dermatologic conditions. 3
• The malar ("butterfly") rash and photosensitivity are classic acute cutaneous manifestations. 1
• Discoid lesions present as raised, scaly, erythematous plaques that can cause scarring and permanent alopecia. 4
• Oral and nasal ulcers occur frequently, often painless. 2

Musculoskeletal Involvement

• Arthritis and arthralgias are among the most common presenting features, typically involving small joints of the hands, wrists, and knees in a symmetric pattern. 1
• Joint involvement is usually non-erosive, distinguishing it from rheumatoid arthritis. 2

Renal Manifestations

• Lupus nephritis occurs in up to 45% of patients, with renal flares occurring at an incidence of approximately 0.1–0.2 flares per patient per year. 3
• Hypertension is a common clinical indicator of active renal disease. 3
• Proteinuria, abnormal urine sediment (cellular casts, hematuria), and elevated serum creatinine signal kidney involvement. 3
• Five-year renal survival is influenced by age, ethnicity, baseline serum creatinine, presence of hypertension, complement C3 levels, and histologic activity/chronicity indices on kidney biopsy. 3

Hematologic Abnormalities

• Severe cytopenias—including marked anemia, thrombocytopenia, leukopenia, and lymphopenia—signal active disease and are associated with poorer prognosis and increased infection risk. 3
• Autoimmune hemolytic anemia and immune thrombocytopenia can occur. 2
• Lymphopenia is particularly common and correlates with disease activity. 3

Neuropsychiatric Involvement

• Neurological involvement is frequent in SLE and encompasses both central and peripheral nervous system manifestations. 3
• The most common neuropsychiatric syndromes include:
  • Headache (most frequent) 3
  • Mood disorders including depression and psychosis 3
  • Cognitive impairment affecting memory, attention, concentration, and word-finding 3
  • Seizures 3
  • Cerebrovascular disease including stroke 3
  • Acute confusional state or coma 3
  • Transverse myelitis/myelopathy 3
  • Cranial or peripheral neuropathy 3
  • Optic neuritis 3
• No specific validated instrument exists for routine neuropsychiatric assessment; clinical monitoring relies primarily on detailed history taking. 3

Cardiopulmonary Manifestations

• Serositis including pleuritis and pericarditis are classic features. 2
• Myocarditis and endocarditis (Libman-Sacks) can occur but are less common. 5
• Patients with SLE have markedly increased risk of premature atherosclerosis and cardiovascular disease that cannot be fully explained by traditional risk factors alone. 1
• Pulmonary manifestations include pleural effusions, acute lupus pneumonitis, pulmonary hemorrhage, and interstitial lung disease. 5

Cardiovascular Risk Factors

• Hypertension prevalence in SLE ranges from 11.5% to 75%. 1
• Dyslipidemia prevalence in SLE also ranges from 11.5% to 75%. 1

Gastrointestinal Involvement

• Gastrointestinal manifestations are less common but may include mesenteric vasculitis, pancreatitis, hepatitis, and protein-losing enteropathy. 1

Serologic and Immunologic Indicators

• Low complement levels (C3, C4) are associated with active disease but do not predict future flares. 3
• Anti-dsDNA antibodies correlate with disease activity, particularly renal involvement. 3
• Antiphospholipid antibodies, when present, significantly increase the risk of thrombosis and pregnancy complications. 3

Associated Complications and Comorbidities

• Infections represent a major cause of morbidity and mortality due to both disease-related immune dysregulation and immunosuppressive therapy. 3
• Osteoporosis affects 4%–24% of SLE patients, with vertebral fracture rates between 7.6% and 37%. 1
• Cancer incidence is elevated in SLE, notably non-Hodgkin's lymphoma, cervical, breast, and lung cancers. 3, 1
• Avascular necrosis, particularly of the femoral head, occurs with increased frequency. 3
• Diabetes mellitus risk is increased, often related to chronic glucocorticoid use. 3

Critical Clinical Pitfalls

• The clinical picture of SLE 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
• Fever should never be presumed to stem solely from lupus activity; systematic infection work-up is mandatory, especially when CRP exceeds 50 mg/L. 1
• Numerous non-lupus conditions can mimic SLE manifestations, often requiring thorough evaluation and, when indicated, tissue diagnosis such as biopsy. 1
• Multisystem involvement is the rule rather than the exception—subclinical abnormalities are common even in patients appearing to be in clinical remission. 6