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
- First Sentences:
- If left untreated, [#]% of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3]. Common complications of [disease name] include [complication 1], [complication 2], and [complication 3]. Prognosis is generally excellent/good/poor, and the 1/5/10-year mortality/survival rate of patients with [disease name] is approximately [#]%.
- 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.
- Examples:
- Example 1: If left untreated, 20% to 30% of patients with IgA nephropathy may progress to develop ESRD. Common complications of IgA nephropathy include pro-thrombotic states, such as stroke and myocardial infarction. Prognosis is generally good, and the 5-year mortality rate of patients with IgA nephropathy is approximately 5%.
- Additional Sentences:
- [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 [#]%.
- The [Subtype of disease or malignancy] is associated with the most favorable prognosis.
- The prognosis varies with the [characteristic] of tumor: [subtype of disease/malignancy] have the most favorable prognosis.
- Examples:
- Example 1: Rhabdomyosarcoma is associated with a 5 year survival rate of 72%.
- Example 2: The presence of metastasis is associated with a particularly poor prognosis among patients with rhabdomyosarcoma. The 5 year event free survival rate is less than 30%.
- Example 3: The embryonal subtype of rhabdomyosarcoma is associated with the most favorable prognosis.
- Example 4: The prognosis varies with the location of tumor: orbital and genitourinary tract rhabdomyosarcomas have the most favorable prognosis.
Natural History
- Systemic lupus erythematosus is an autoimmune disease. There is no definite cause for the 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-specifi c 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
- Using lists can be helpful for describing this section.
- You can use these template sentences;
- "Complications that can develop as a result of (disease name) are ___ (describe in list form)".
- "Complications that can develop as a result of the treatment of (disease name) are ___ (describe in list form).
- Next to each complication, provide a brief one sentence description detailing the complication.
- For an example of the complications section in a natural history, complications and prognosis page, click here.
- 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.
Symmetric polyarthritis
Seen in 75-90% of patients with varying degrees of severity, it represents the most common presenting complaint clinically, usually worse in the morning. Areas of involvement most commonly include the small joints of the hand, knees, wrists, and shoulders.
Plain radiograph
Plain radiographs demonstrate soft tissue swelling of the involved joints, periarticular osteoporosis, and normal joint spaces. Carpal instability may be seen in 15% of patients 2.
Deforming non-erosive arthropathy
When articular abnormalities are present, approximately 5-40% will develop a deforming non-erosive arthropathy due to ligamentous laxity (not articular destruction) and muscle contracture. This is more common in those with long-standing disease. In the hands this can be classically seen on Norgaard views but absent on AP views and are termed as reducible deformities.
Due to their frequently reducible nature, deformities are seldom disabling.
Hands and feet
Symmetric involvement of interphalangeal joints is most common, showing swan neck and boutonniere deformities, subluxation with ulnar deviation at MCP joints, subluxation of the 1st metacarpophalangeal joint, a widened forefoot, and hallux valgus.
Joint space narrowing is uncommon, and when present is likely due to disuse atrophy or pressure from an adjacent subluxed bone. Altered stresses across the joint may also cause a "hook erosion" at the metacarpal heads due to capsular stress, mimicking findings of rheumatoid arthritis. This is more often observed on the radial side.
Spine
Spinal manifestations are uncommon and nonspecific, but a higher incidence of spinal findings is seen in those with deforming arthropathy. Up to 10% may have atlantoaxial subluxation/dislocation.
Myositis
Clinically observed in 30-50% of patients, true myositis occurs in approximately only 4% of patients. Elevated serum levels of muscle enzymes may or may not be observed.
Osteonecrosis
The most common location of osteonecrosis is the femoral head, but nearly any site may be affected. This is more commonly seen in younger patients and those with Raynaud phenomenon and other signs of vasculitis. This may also be seen as a complication of steroid therapy.
Spontaneous tendon weakening and rupture
Typically observed about weight bearing joints as a complication of steroid therapy.
Soft tissue calcification
Linear or nodular calcification in the subcutaneous and deep soft tissues may be seen, especially in the lower extremities. Associations with diuretic therapy and vitamin D supplementation has been documented.
Insufficiency fracture
Those with SLE are at increased risk for insufficiency fracture, possibly due to disuse demineralization or osteopenia secondary to steroid therapy, or both.
Osteomyelitis and septic arthritis
Lupus patients are at increased risk of bacterial and mycotic infections, in large part due to steroid administration and renal disease. Osteomyelitis and septic arthritis involvement are less common than infection elsewhere.
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