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 [disease name] include [complication 1], [complication 2], and [complication 3]. Prognosis is generally poor, and the 10-year mortality rate of patients with systemic lupus erythematosus is approximately 40%.
- OR
- Depending on the extent of the tumor at the time of diagnosis, the prognosis may vary. However, the prognosis is generally regarded as poor/good/excellent
- [Disease/malignancy] is associated with a 5 year survival rate of [#]%.
- The presence of metastasis is associated with a particularly poor prognosis among patients with [disease/malignancy]. The 5 year event free survival rate is less than [#]%.
Natural History
- Systemic lupus erythematosus (SLE) is an autoimmune disease. SLE is a disease of waxing and waning, with a lot of flare up episodes. SLE usually develop in the second and third decade of life, although it can develop in 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
- Mostly associated with auto-immune antibody production
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)
- The phase due to damages of the auto-antibodies to the body tissues (mostly related to disease itself)
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
- The phase of damages due to complications of longstanding disease, immunosuppressive therapy, and end organ damages (irreversible damages and complications)
Complications
Complications that can develop as a result of prolonged activation of systemic lupus erythematosus or the SLE therapy are:
Gastrointestinal involvement
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 peritonitis: an infection that develops in the peritoneum mainly due to lupus vasculitis
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
- Alveolar hemorrhage (AH) is a rare complication that is considered as one of the most important lethal complications of SLE.
Thromboembolic disease
- Chronic inflammation during the disease flare ups is an important characteristic in SLE patients that increase the risk of thromboembolic events.
Pulmonary hypertension
- An increase in blood pressure in the pulmonary artery or lung vasculature, leading to shortness of breath, dizziness, fainting, and other symptoms, all of which are exacerbated by exertion
Shrinking lung syndrome
- A rare complication of SLE, that can cause dyspnea and shortness of with a reported prevalence of 0.5% of this overall population
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Cardiac involvement
Valvular disease
- Valvular involvement in systemic lupus erythematosus (SLE) is the most prevalent form of heart 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. Involvement of the mitral valve is most frequently encountered.
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Nonbacterial thrombotic endocarditis
- a spectrum of noninfectious lesions of the heart valves that is most commonly seen in advanced malignancy.
Pericardial disease
Acute pericarditis
Myocarditis
Coronary heart disease
Neurological involvement
Cognitive dysfunction
Stroke
Seizures
Psychosis
Headache
Neuropathies
- Pulmonary:
- Shrinking lung ===== Pleuropulmonary manifestations =====
- pleuritis: considered one of the commons of thoracic manifestations 2
- acute lupus pneumonitis
- diaphragmatic dysfunction and shrinking lung syndrome
- cavitating pulmonary nodules
- pulmonary hypertension
- pulmonary vasculitis
- pulmonary embolism (often due to circulating anticardiolipin antibodies)
- pulmonary haemorrhage / alveolar haemorrhage (reflecting diffuse endothelial injury)
- chronic interstitial pneumonitis: may complicate 3-13% of patients
- interlobular septal thickening 6
- pulmonary fibrosis associated with this can occur but is rare 1
- parenchymal bands
- subpleural bands
- bronchiectasis
- bronchial wall thickening
- pleural thickening
- bronchiolitis obliterans (with or without organising pneumonia)
- opportunistic pulmonary infection or drug toxicity from immunosuppressive therapy ===== Cardiac complications =====
- pancarditis
- Libman-Sacks endocarditis: sterile vegetations on the mitral and aortic valves (rare) Hepatic disease may be more common in SLE than initially thought.
Prognosis
The prognosis of systemic lupus erythematosis is ranging from a benign illness to an extremely rapid progressive disease that can lead to a fulminant organ failure and death poor/good with treatment. Without treatment, (disease name) will result in ___. SLE is associated with a 1/5/10 year mortality of __ among patient with ______ (for example high grade lesions). The presence of nephritis is associated with a particularly poor prognosis among patients with SLE.
- 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
- Lower incidence of:
- For an example of a prognosis section within a natural history, complications and prognosis page, click here.
OGNOSIS — Systemic lupus erythematosus (SLE) can run a varied clinical course, ranging from a relatively benign illness to a rapidly progressive disease with fulminant organ failure and death. The five-year survival rate in SLE has dramatically increased since the mid-20th century, from approximately 40 percent in the 1950s to greater than 90 percent since 1980s [121-125]. The improvement in patient survival is probably due to multiple factors including increased disease recognition with more sensitive diagnostic tests [126], earlier diagnosis or treatment, the inclusion of milder cases, increasingly judicious therapy, and prompt treatment of complications [127]. Despite these improvements, patients with SLE still have mortality rates ranging from two to five times higher than that of the general population [128].
Prognostic factors — Poor prognostic factors for survival in SLE include [122,123,129-137]:
●Renal disease (especially diffuse proliferative glomerulonephritis)
●Hypertension
●Male sex
●Young age
●Older age at presentation
●Low socioeconomic status
●Black race, which may primarily reflect low socioeconomic status
●Presence of antiphospholipid antibodies
●Antiphospholipid antibody syndrome
●High overall disease activity
Causes of death — The major causes of death in the first few years of illness are active disease (eg, central nervous system [CNS] and renal disease) or infection due to immunosuppression, while causes of late death include complications of SLE (eg, endstage renal disease), treatment complications, and cardiovascular disease [127,130,138-143]. The frequency of the different causes of death is best illustrated by a 2014 meta-analysis of 12 studies which included 27,123 patients with SLE (4993 observed deaths) [144]. This analysis reported an overall threefold increased risk of death in patients with SLE (standardized mortality rate [SMR] 2.98, 95% CI 2.32-3.83) when compared with the general population. The risks of death due to cardiovascular disease, infection, and renal disease were significantly increased. Mortality due to malignancy was not found to be increased, while patients with renal disease were found to have the highest mortality risk (SMR 7.90, 95% CI 5.5-11.0).
African Americans and Mexican Hispanics in the United States have a poorer renal prognosis than Caucasians, a finding not entirely independent of socioeconomic status [24]. African Americans are more likely to have anti-Sm, anti-RNP, discoid skin lesions, proteinuria, psychosis, and serositis [24-26]. African Americans and Latin Americans with lupus nephritis are also less likely to respond to cyclophosphamide treatment than Caucasians [27].
●The clinical status is poorer in those with less education [24,28]; this effect may reflect poor compliance [29]. Clinical status is also poorer in those with lower socioeconomic status and with inadequate access to medical care [30].
●The extent and degree of activity of SLE varies in different countries and in different ethnic groups [30-32].
●Men with lupus tend to have higher frequencies of renal disease, skin manifestations, cytopenias, serositis, neurologic involvement, thrombosis, cardiovascular disease, hypertension, and vasculitis than women [33]. By contrast, Raynaud phenomenon, photosensitivity, and mucosal ulceration are less frequent manifestations in men than women. Most, but not all studies suggest that men have a higher one-year mortality rate [33-38].
●SLE in children tends to be symptomatically more severe than in adults, with a high incidence of malar rashes, nephritis, pericarditis, hepatosplenomegaly, and hematologic abnormalities [22,34].
Lupus tends to be milder in older adults, who often have a presentation more similar to that of drug-induced lupus. Clinical features of lupus in older patients include the following [34,39-41]:
●A lower ratio of affected women to men than for younger patients
●Lower incidence of malar rash, photosensitivity, purpura, alopecia, Raynaud phenomenon, renal, central nervous system, and hematologic involvement
●Lower prevalence of anti-La, anti-Sm, and anti-RNP antibodies and of hypocomplementemia
●Greater prevalence of sicca symptoms, serositis, pulmonary involvement, and musculoskeletal manifestations
●Greater prevalence of rheumatoid factor
Prognosis markers:
- Serum anti-dsDNA titres is correlated with LN, progression to end-stage renal disease, and increased disease severity, damage or poor survival.
- Antiphospholipid antibodies are strongly associated with features of the antiphospholipid syndrome (APS) (arterial/ venous thrombosis, fetal loss, thrombocytopenia), CNS involvement (especially cerebrovascular disease), severe LN, damage accrual, and death.
- Anti-Ro (SS-A) and anti-La (SS-B) antibodies have been associated with neonatal lupus, and congenital heart block in the children of seropositive mothers.
- Antibodies to other extractable nuclear antigens (anti-Ro/La/Sm/RNP) have been associated with mucocutaneous involvement and less severe nephropathy in most studies