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 arthiritis. 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 auto-antibodies 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

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	The most frequent gastrointestinal complaint and is usually due to an underlying esophageal motility disorder, concomitant gastroesophageal reflux disease.
	Peptic ulcer disease	May be due to the disease itself or the effect of SLE treatment.
	Intestinal pseudo-obstruction	A rare complication of SLE and 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	It typically occurs in patients with clinically severe SLE with multi-organ involvement and characterized with the onset of profound edema and hypoalbuminemia in the absence of nephrotic range proteinuria.
	Hepatitis	May be due to a wide range of factors including drug-induced damage, steatosis, viral hepatitis, vascular thrombosis, overlap with autoimmune hepatitis, or SLE itself.
	Acute pancreatitis	It occurs usually in the setting of active SLE.
	Mesenteric vasculitis	Most often this involves medium-sized branches of the celiac, superior mesenteric, and inferior mesenteric arteries. Features of mesenteric vasculitis include abdominal pain or gastrointestinal bleeding with intestinal ischemia, infarction, perforation, or 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 It can progress to gangrene, perforation, and sepsis.
Pulmonary involvement	Pleural disease	Pleuritis can lead to pleuritic chest pain with or without radiographic evidence of a pleural effusion. Pleuritis is a disease state in which there is inflammation of the pleura, the lining of the pleural cavity, surrounding the lungs. Pneumothorax: a collection of air within the pleural cavity.
	Acute pneumonitis	A rare and fulminant form of diffuse lung injury that generally occurs in previously healthy individuals and has a rapid onset with fever, cough, and shortness of breath.
	Pulmonary hemorrhage	Pulmonary alveolar hemorrhage: A rare complication Acutely ill patients with hemoptysis, fever, cough, and hypoxemia. Blood loss can be extensive. Associated with high mortality rates of 70%–90%
	Pulmonary hypertension	Increased pressure in the pulmonary artery or lung vasculature presents with exertional shortness of breath, dizziness, and faint.
	Thromboembolic disease	Chronic inflammation during the disease flare ups is an important characteristic in SLE patients that increase the risk of thromboembolic events.
	Shrinking lung syndrome	A rare complication of SLE, that can cause 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	Valvular involvement in systemic lupus erythematosus (SLE) is the most common form of cardiac involvement in SLE. Immunoglobulin and complement deposition in the valvular structure will lead to different valvular complications include Libman-Sacks vegetations, valve thickening, and valve regurgitation. Mitral valve is the most frequently affected valve.
	Nonbacterial thrombotic endocarditis	An spectrum of noninfectious lesions of the heart valves that is commonly seen in advanced malignancy.
	Pericardial disease	The most important way that SLE can affect the heart is through pericardium and by causing an acute pericarditis. It usually present as a positional sharp chest pain with radiation to the scapula
	Myocarditis	It may present with chest pain, ST segment elevation, elevated biomarkers of myonecrosis, heart failure, and/ or sudden death. The inflammatory response especially during disease flare ups cause myonecrosis either directly or indirectly as part of an autoimmune reaction
	Coronary artery disease	Myocardial infarction (MI) Narrowing of the small blood vessels that supply blood and oxygen to the heart as a result of accumulation of atheromatous plaques following autoimmune state of SLE	↑↑
Neurological involvement	Cognitive dysfunction	The mental status of SLE patients can be temporarily affected by multiple, transient metabolic and systemic processes
	Stroke	Small vessel vasculopathy in the brain during SLE disease is considered as one f the important factors in causing thrombosis and stroke in SLE patients
	Seizures	Increased intracranial pressure can arise from a hypercoagulability state or thrombosis within the cerebral venous and can be the reason of seizures in these patients
	Psychosis	Psychosis is fairly common in SLE and can indirectly influence cognitive performance as well. The psychosis in SLE patients is mostly accompanied by hallucinations
	Neuropathies	Peripheral neuropathy prevalence is high in SLE and it is mostly related to disease activity There is a greater chance for the patients with central nervous system involvement to show manifestation of peripheral neuropathy There is a predilection for asymmetric and lower extremities involvement, especially peroneal and sural nerves
Musculoskeletal involvement	Arthritis	Mostly symmetrical and non-erosive 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 and is often asymptomatic Glucocorticoids treatment is associated with the greatest risk of developing the disease
	Subcutaneous nodules	In association with active disease
	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/or nasal ulcers	usually painless
	discoid lesions	more inflammatory and which have a tendency to scar
Very rare disorders	Malignancy
	Diabetes mellitus
	Premature gonadal failure

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 antibodiescorrelated with
  • Features of the antiphospholipid syndrome (APS) (arterial/ venous thrombosis, fetal loss, thrombocytopenia)
  • CNS involvement (especially cerebrovascular disease)
  • Severe lupus nephritis
  • Damage accrual
  • 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
  • Renal system involvement
  • Central nervous system involvement
• Greater prevalence of:
  • Serositis
  • Pulmonary involvement
  • Sicca symptoms
  • Musculoskeletal manifestations

References

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