What are the clinical manifestations of systemic lupus erythematosus?

Clinical Manifestations of Systemic Lupus Erythematosus

SLE presents with an extremely variable clinical picture affecting multiple organ systems, with mucocutaneous manifestations, arthritis, and renal involvement being the most common features, though the disease can affect virtually any organ. 1, 2

Constitutional and General Symptoms

• Fatigue, fever, and malaise are frequent presenting symptoms that significantly impact quality of life, though these are non-specific and must be distinguished from infection or other complications. 2, 3
• Fever in SLE patients requires immediate exclusion of infection before attributing it to disease activity alone, particularly when CRP exceeds 50 mg/L. 4, 5

Mucocutaneous Manifestations

• Skin involvement occurs in the vast majority of patients (up to 98.75% in recent cohorts), making it one of the most common presenting features. 6
• Cutaneous manifestations include:
  • LE-specific lesions: acute cutaneous LE (including malar rash), subacute cutaneous LE, chronic cutaneous LE (discoid lupus), and intermittent CLE. 1
  • LE-non-specific lesions: various other dermatologic findings that can occur in SLE. 1
• Oral ulcers are extremely common (98.75% prevalence) and represent one of the classification criteria. 6
• Alopecia affects up to 95% of patients and can be diffuse or patchy. 6
• Diagnosis of cutaneous lupus may require evaluation by an experienced dermatologist and skin biopsy, as many conditions can mimic LE. 1

Musculoskeletal Manifestations

• Arthritis and arthralgia are among the most frequent manifestations, occurring in approximately 83.75% of patients. 6
• Joint involvement is typically non-erosive and symmetric, affecting small joints of the hands, wrists, and knees. 3, 7

Renal Manifestations

• Lupus nephritis occurs in approximately 50% of SLE patients and represents one of the most serious organ manifestations. 6
• Renal involvement shows significant gender differences, with notable variations in SLE nephritis prevalence (p=0.048). 6
• Renal flares are common, occurring in up to 45% of patients with established nephritis at a rate of 0.1-0.2 flares per patient per year. 1, 4
• Clinical indicators include:
  • Elevated serum creatinine
  • Proteinuria (assessed via urine protein/creatinine ratio)
  • Active urine sediment with cellular casts
  • Hypertension 1, 4
• Variables associated with 5-year renal survival include age, ethnicity, serum creatinine, hypertension, C3 complement levels, and kidney biopsy findings (activity and chronicity indices). 1, 4

Hematologic Manifestations

• Anemia is the most prevalent hematologic abnormality (66.25%), followed by other cytopenias. 6
• Severe cytopenias indicate active disease and worse prognosis:
  • Severe anemia
  • Thrombocytopenia
  • Leukopenia
  • Lymphopenia (which specifically increases infection risk) 4
• Autoimmune hemolytic anemia shows significant gender-specific differences (p=0.046). 6

Neuropsychiatric Manifestations

• Neurological involvement affects both central and peripheral nervous systems and occurs frequently in SLE. 1
• The most common neuropsychiatric syndromes include:
  • Headache
  • Mood disorders (including depression and psychosis)
  • Seizures
  • Cognitive impairment (affecting memory, attention, concentration, and word-finding)
  • Cerebrovascular disease
  • Acute confusional state
  • Cranial or peripheral neuropathy
  • Transverse myelitis 1, 2
• Assessment is challenging as no specific validated instrument exists for routine clinical practice; monitoring relies primarily on clinical history. 1

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. 2
• Hypertension prevalence ranges from 11.5% to 75% in SLE patients. 2
• Dyslipidemia prevalence ranges from 11.5% to 75% in SLE patients. 2
• Pericarditis and myocarditis can occur as direct manifestations of lupus activity. 8, 7

Pulmonary Manifestations

• Pleuritis and pleural effusions are common thoracic manifestations. 8
• Interstitial lung disease, pulmonary hypertension, and acute lupus pneumonitis can occur but are less frequent. 8, 7

Gastrointestinal Manifestations

• Gastrointestinal involvement occurs but is less common than other organ systems. 2
• Can include mesenteric vasculitis, pancreatitis, and hepatitis. 7

Serological and Immunological Features

• Anti-nuclear antibodies (ANA) are positive in 98.8% of patients, making this the most sensitive serological marker. 6
• Anti-dsDNA antibodies are present in 61.3% and correlate with disease activity, particularly renal involvement. 6
• Low complement levels (C3, C4) are associated with active disease but have no predictive value for future flares. 4

Associated Conditions and Complications

• Antiphospholipid antibodies are present in a subset of patients and significantly increase risk of thrombosis and pregnancy complications. 2
• Osteoporosis prevalence ranges from 4% to 24%, with vertebral fracture prevalence between 7.6% and 37%. 2
• Cancer incidence is increased, particularly:
  • Hematological malignancies
  • Cervical cancer
  • Breast cancer
  • Lung cancer 2
• Infection risk is substantially elevated due to both disease-related immune dysregulation and immunosuppressive therapy. 2

Critical Clinical Pitfalls

• The clinical picture is extremely variable between patients and can change over time within the same patient, requiring ongoing vigilance. 1, 2
• Disease activity must be carefully distinguished from:
  • Organ damage (irreversible structural changes)
  • Drug toxicity effects
  • Intercurrent infections 1, 2
• Never assume fever is solely due to lupus activity—infection must be systematically excluded, especially when CRP exceeds 50 mg/L. 4, 5
• Many conditions can mimic lupus manifestations, necessitating thorough evaluation and sometimes tissue diagnosis. 1