What are the common signs and symptoms of systemic lupus erythematosus (SLE)?

Systemic Lupus Erythematosus: Common Signs and Symptoms

Systemic lupus erythematosus presents most commonly with constitutional symptoms (fatigue, fever), mucocutaneous manifestations (lupus-specific rash, mouth ulcers, alopecia), and musculoskeletal complaints (joint pain, myalgia) as the earliest disease features. 1

Constitutional Symptoms

• Fatigue is among the most frequently reported symptoms and represents a major determinant of quality of life in SLE patients 1
• Fever may occur during initial disease activity and must be carefully distinguished from infection 2
• These constitutional symptoms often appear before more specific organ manifestations become evident 1

Mucocutaneous Manifestations

• Lupus-specific rash is a hallmark early complaint, with cutaneous manifestations including acute cutaneous lupus, subacute cutaneous lupus, chronic cutaneous lupus (including discoid lesions), and intermittent cutaneous lupus 3, 1
• Mouth ulcers (oral ulcers) are common presenting features 1
• Alopecia (hair loss) frequently occurs and can be non-scarring or scarring depending on the type of cutaneous involvement 1
• Cutaneous lupus may require evaluation by an experienced dermatologist and skin biopsy for definitive diagnosis, as many conditions can mimic lupus 3

Musculoskeletal Symptoms

• Arthralgia (joint pain) is one of the most common initial symptoms reported by patients 1, 4
• Arthritis can occur and is included in SLE classification criteria 4
• Myalgia (muscle pain) is frequently reported as an early manifestation 1, 4
• Pain in SLE can be multifactorial and may be out of proportion to visible inflammation in some patients, reflecting both nociceptive and nociplastic mechanisms 5

Renal Involvement

• Proteinuria or hematuria may present early in disease, often before patients are symptomatic 2
• Renal manifestations occur commonly and warrant close monitoring with serum creatinine, urinalysis, and urine protein/creatinine ratio 3
• Renal involvement carries significant prognostic implications and requires aggressive management 3

Neuropsychiatric Manifestations

• Neuropsychiatric symptoms occur in approximately 50-60% of patients, most commonly at disease onset or within the first year 3, 2
• Headache is the most frequent neuropsychiatric symptom, though it does not usually reflect overt CNS lupus activity 3
• Mood disorders (including depression and anxiety) are common but often do not represent active CNS disease 3
• Seizures can occur and may reflect inflammatory CNS involvement requiring immunosuppressive therapy 3
• Cognitive impairment (affecting memory, attention, concentration, and word-finding) may be present and should be assessed by clinical history 3
• More severe manifestations include psychosis, transverse myelitis, optic neuritis, and peripheral neuropathy, which typically indicate inflammatory processes requiring glucocorticoids and immunosuppressive therapy 3

Hematologic Abnormalities

• Thrombocytopenia, leukopenia, or lymphopenia may be detected on routine laboratory testing 2
• Severe anemia has been associated with organ involvement and disease progression 3
• Severe leucopenia and lymphopenia increase the risk of infections 3

Serositis

• Pleuritis and pericarditis can cause chest pain and represent inflammatory manifestations that may require anti-inflammatory therapy 1, 6

Critical Diagnostic Considerations

• Over 90% of SLE patients have positive anti-nuclear antibodies (ANA), with significant titers accepted as 1:80 or greater 6
• Additional autoantibodies include anti-double-stranded DNA, anti-Sm, and antiphospholipid antibodies, which help establish diagnosis and predict specific organ involvement 1
• Hypocomplementemia (low C3, C4) is often associated with active disease, particularly renal involvement 3

Important Clinical Pitfalls

• Fever in SLE patients must always prompt evaluation for infection before attributing it to disease activity alone, as infections are a major cause of morbidity and mortality 2
• Headache, mood disorders, and mild cognitive dysfunction are common but do not usually reflect overt CNS lupus activity; excluding these manifestations increases the specificity of neuropsychiatric lupus diagnosis from 46% to 93% 3
• Pain that seems out of proportion to inflammation may reflect nociplastic mechanisms (central sensitization) rather than active inflammatory disease, requiring different management approaches 5
• C-reactive protein (CRP) is often not elevated in SLE despite active disease; significantly elevated CRP (>50 mg/L) should raise suspicion for superimposed infection 3