Systemic lupus erythematosus natural history, complications and prognosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mahshid Mir, M.D. [2]

Overview

Common complications of systemic lupus erythematosus include dermatitis, nephritis and arthritis. Prognosis is generally poor, and the 10-year mortality rate of patients with systemic lupus erythematosus is approximately 40%. The disease course can be divided into 4 subcategories based on the course of the disease: developmental phase, preclinical phase, clinical phase, and comorbid complication phase.

Natural History

Systemic lupus erythematosus (SLE) is an autoimmune disease. SLE is a disease of waxing and waning, with possible flare up episodes. SLE usually develops in the second and third decade of life, although it can presents any age, and start with mild symptoms such as fatigue, fever, and skin rashes. Without treatment, the patient will develop symptoms of end organ damage, which will eventually lead to death in most of the patients.

The disease course can be divided into 4 subcategories based on the course of the disease:

Developmental phase:

• Genetic mutations
• UV radiation exposure
• Smoking

Preclinical phase:

• Mostly associated with auto-immune antibody production
• Autoantibodies common to other systemic autoimmune diseases
• Proceeds with a more disease-specific clinically overt autoimmune phase

Clinical phase:

• The phase due to damages of the autoantibodies to the body tissues (mostly related to disease itself)
• Inflammation
• Involvement of first organs
• Flares
• Involvement of additional organs
• Early damages (e.g. alopecia, fixed erythema, cognitive dysfunction, valvular heart disease, avascular necrosis, tendon rupture, Jaccoud’s arthropathy, and osteoporosis)

Comorbidity-complication phase

The phase of damages due to complications of longstanding disease, immunosuppressive therapy, and end organ damages (irreversible damages and complications)

• Infections
• Atherosclerosis
• Malignancies

Factors associated with flare up:

• Stress (emotional etc.)
• Sunlight
• Ultraviolet light
• Infection
• Injuries
• Surgery
• Pregnancy
• Abrupt discontinuation of medications
• Treatment noncompliance
• Medications
• Immunizations
• Lupus nephritis
• Presence of neurologic complications
• Presence of vasculitis
• Elevated anti-dsDNA
• Low C3 level

Complications

Complications that can develop as a result of prolonged activation of systemic lupus erythematosus or the SLE therapy are:

Organ	Disease	Description	Frequency
Gastrointestinal system	Dysphagia	Usually due to an underlying esophageal motility disorder Concomitant gastroesophageal reflux disease	↑↑↑
	Peptic ulcer disease	Due to The disease itself The effect of SLE treatment	↑
	Intestinal pseudo-obstruction	May lead to mechanical obstruction of the small or large bowel in the absence of an anatomic lesion Obstructing the flow of intestinal contents	↓↓
	Protein-losing enteropathy	Occurs in patients with clinically severe SLE with multi-organ involvement Characterized by: Profound edema Hypoalbuminemia The absence of nephrotic range proteinuria	↓↓
	Hepatitis	May be due to: Drug-induced damage Steatosis Viral hepatitis (concomitant with SLE) Vascular thrombosis Overlap with autoimmune hepatitis due to SLE itself	↑
	Acute pancreatitis	Occurs usually in the setting of active SLE	↓
	Mesenteric vasculitis	Mostly involve: Medium-sized branches of the celiac artery Superior mesenteric artery Inferior mesenteric artery Features of mesenteric vasculitis include: Abdominal pain Gastrointestinal bleeding Intestinal ischemia, infarction, perforation Pancreatitis Primary spontaneous peritonitis: An infection that develops in the peritoneum mainly due to lupus vasculitis	↓↓
	Acute cholecystitis	Due to periarterial fibrosis and acute vasculitis May progress to gangrene, perforation, and sepsis	↓↓
Pulmonary involvement	Pleural disease	May lead to: Pleuritic chest pain with or without radiographic evidence of a pleural effusion Inflammation of the pleura, the lining of the pleural cavity, surrounding the lungs Pneumothorax: a collection of air within the pleural cavity	↑
	Acute pneumonitis	Fulminant form of diffuse lung injury Characterized by rapid onset with fever, cough, and shortness of breath	↓↓
	Pulmonary hemorrhage	Pulmonary alveolar hemorrhage: Acutely ill patients with hemoptysis, fever, cough, and hypoxemia Extensive blood loss Associated with high mortality rates of 70%–90%	↓↓
	Pulmonary hypertension	Increased pressure in the pulmonary artery or lung vasculature Characterized by shortness of breath, dizziness, and faint	↑
	Thromboembolic disease	Chronic inflammation that increase the risk of thromboembolic events	↑
	Shrinking lung syndrome	Characterized by dyspnea and shortness of breath (estimated prevalence approximately 0.5%)	↓↓
Cardiac involvement	Cardiomegaly	Due to: Myocarditis Libman-Sacks endocarditis Subacute bacterial endocarditis Uremia Pulmonary arterial hypertension with right-sided heart failure Corticosteroid-related cardiomyopathy	↑↑
	Valvular disease	Different valvular complications include: Libman-Sacks vegetations Valve thickening Valve regurgitation Mainly due to Immunoglobulin and complement deposition in valvular structure More frequently affect mitral valve	↑↑
	Pericardial disease	Acute pericarditis Pericardial effusion	↓
	Myocarditis	Characterized by: Chest pain ST segment elevation Elevated biomarkers of myonecrosis Heart failure Sudden death Myonecrosis may happen as a consequence of autoimmune reaction	↓
	Coronary artery disease	Mainly as a result of increased risk of atheromatous plaques due to autoimmune status of SLE	↑↑
Neurological involvement	Cognitive dysfunction	May be temporarily affected by multiple, transient metabolic and systemic processes	↑
	Stroke	Increase risk of thrombotic stroke due to small vessel vasculopathy	↓
	Seizures	May happen secondary to increased intracranial pressure: Hypercoagulability state (due to inflammation) Thrombosis within the cerebral venous	↑
	Psychosis	Can indirectly influence cognitive performance Mostly accompanied by hallucinations in SLE	↑↑
	Neuropathies	Peripheral neuropathy Mostly related to disease activity Central nervous system involvement association A predilection for asymmetric and lower extremities involvement, especially peroneal and sural nerves	↑↑
Musculoskeletal involvement	Arthritis	Mostly symmetrical and non-erosive arthritis Arthralgias Effusions Decreased range of motion of both small and large joints Morning stiffness	↑↑↑↑
	Osteonecrosis (Avascular necrosis)	Most common in the femoral head Can involve humeral head, tibial plateau, and scaphoid navicular  Usually bilateral Often asymptomatic Glucocorticoids treatment is associated with the greatest risk of developing the disease	↓
	Subcutaneous nodules	Associated with active disease and flare ups	↑
	Osteoporosis	Mostly due to glucocorticoid usage Loss of height Sudden back pain	↑
Skin disorder	Cutaneous lupus erythematosus	Erythema in a malar distribution over the cheeks and nose (but sparing the nasolabial folds), which appears after sun exposure	↑
	Photosensitivity	Common theme for skin lesions associated with SLE	↑↑↑
	Non-scarring alopecia	May occur at some point during the course of their disease	↑
	Oral and nasal ulcers	Usually painless	↑↑
	Discoid lesions	More inflammatory Have a tendency to scar	↑
Very rare disorders	Malignancy	Non-Hodgkin’s lymphoma Lung cancer Liver cancer Vulvar/vaginal cancer Thyroid cancer	↓↓↓
	Diabetes mellitus	Increase predisposition to: Lupus nephritis Peripheral neuropathy Retinal disease	↓

Prognosis

The prognosis of systemic lupus erythematosus is ranging from a benign illness to an extremely rapid progressive disease that can lead to a fulminant organ failure and death. Without treatment, systemic lupus eryhtematosus will result in a very high mortality rate, with a report of more than 60% mortality rate during the mid-20th century. SLE is associated with a 10 year mortality of more than 50% among patient with nephritis. The presence of nephritis is associated with a particularly poor prognosis among patients with SLE. The increase in survival rate of patients and better prognosis may be due to increased disease recognition with more sensitive diagnostic tests, earlier diagnosis or treatment, the inclusion of milder cases, increasingly judicious therapy, and prompt treatment of complications. Although improvement in SLE diagnosis have led to better prognosis, the mortality rate among SLE patients is still 5 times more than normal population.

Poor prognostic factors for SLE survival:

• Presence of nephritis (especially diffuse proliferative glomerulonephritis)
• Hypertension
• Male sex
• Young age
• Older age at presentation
• Low socioeconomic status
• Black race: Higher rate of nephritis
• Presence of antiphospholipid antibodies
• High overall disease activity

Prognosis markers:

Serum anti ds-DNA titres correlated with:

• • Lupus nephritis
  • Progression to end-stage renal disease
  • Increased disease severity
  • Damage or poor survival

Antiphospholipid antibodies correlated with:

• • Features of the antiphospholipid syndrome (APS)
  • CNS involvement
  • Severe lupus nephritis
  • Increase in mortality rate

SLE in men compared to women:

• Less photosensitivity
• More serositis
• Older age at diagnosis
• Higher 1 year mortality compared to women

SLE in the elderly (>65) compared to middle age prevalency:

• Lower incidence of:
  • Malar rash
  • Photosensitivity
  • Purpura
  • Alopecia
  • Raynaud’s phenomenon
  • Nephritis
  • Central nervous system involvement
• Greater prevalence of:
  • Serositis
  • Pulmonary involvement
  • Sicca syndrome
  • Musculoskeletal manifestations

References

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