Systemic Lupus Erythematosus Flashcards
Systemic lupus erythematosus: diagnostic symptoms - SOAP BRAIN MD
Serositis
Oral ulcers
Arthritis
Photosensitivity, pulmonary fibrosis
Blood cells
Renal, Raynaud’s
ANA
Immunologic (anti-Sm, anti-dsDNA)
Neuropsych
Malar rash
Discoid rash however, not in order of diagnostic importance
Systemic lupus erythematosus (SLE) is a multi-system, inflammatory, autoimmune disorder.
Systemic lupus erythematosus (SLE) is a multi-system, inflammatory, … disorder.
SLE is thought to affect almost 1 in … individuals in the UK.
SLE is thought to affect almost 1 in 1000 individuals in the UK.
SLE - It often presents in women of reproductive age, with an average age at diagnosis of …, but can manifest at any age. The condition is more common in … and those of Afro-Caribbean or South Asian descent.
SLE - The gender imbalance depends on age, but is greatest during reproductive years when SLE is 7-15 times more common in … than ….
The gender imbalance depends on age, but is greatest during reproductive years when SLE is 7-15 times more common in women than men.
SLE is an autoimmune condition characterised by loss of tolerance to …
SLE is an autoimmune condition characterised by loss of tolerance to self-antigens.
Clinical manifestations of SLE
SLE is a multi-system disorder that may present with non-specific constitutional symptoms, arthritis, skin rashes or evidence of organ dysfunction.
non-specific constitutional symptoms, arthritis, skin rashes or evidence of organ dysfunction - what is this describing?
SLE
General features of SLE include…
Non-specific symptoms like fatigue and malaise are common as is weight loss prior to diagnosis. Fever may be seen and myalgia is frequently experienced.
… is the most common clinical manifestation of SLE affecting up to 90% of patients
Arthritis is the most common clinical manifestation of SLE affecting up to 90% of patients
Arthritis is the most common clinical manifestation of SLE affecting up to 90% of patients. There are a number of patterns:
… small joint … arthritis (most common form) Jaccoud arthropathy (rare) Avascular necrosis (rare)
Symmetrical small joint polyarticular arthritis (most common form) Jaccoud arthropathy (rare) Avascular necrosis (rare)
Skin manifestations in SLE:
Involvement of the skin is seen in around 85% of cases. Numerous different manifestations may be seen. The butterfly (malar) rash is characteristic rash of SLE - an erythematous rash that lies on the cheeks and across the bridge of the nose. Photosensitivity is common and alopecia may occur.
NOTE: … lupus refers to a benign version of SLE confined to the skin.
NOTE: Discoid lupus refers to a benign version of SLE confined to the skin.
Kidney involvement in SLE:
… is seen in 25-50% of patients. Various forms of … may be seen and all patients with SLE should have regular screening for haematuria, proteinuria and evidence of renal impairment.
Nephritis is seen in 25-50% of patients. Various forms of glomerulonephritis may be seen and all patients with SLE should have regular screening for haematuria, proteinuria and evidence of renal impairment.
There are many pulmonary manifestations of SLE, which affect up to 50% of patients, including: (4)
Pleurisy
Pneumonitis
Pleural effusions
Pulmonary fibrosis
The most common cardiac manifestation of SLE is …. Disease may also effect the myocardium, valves, coronary vessels and conduction system.
The most common cardiac manifestation of SLE is pericarditis. Disease may also effect the myocardium, valves, coronary vessels and conduction system.
Less common cardiac manifestations of SLE include:
Libman-Sacks endocarditis
Myocarditis
Heart block
Libman-Sacks endocarditis
Myocarditis
Heart block
Vasculitis may be seen in … and can affect vessels of all sizes.
Vasculitis may be seen in … and can affect vessels of all sizes.
Neuropsychiatric manifestations: SLE
Fluctuating cognitive dysfunction is relatively common in patients with SLE. Some are affected by seizures, ataxia and psychosis. Polyneuropathy and cranial nerve lesions may be seen.
Fluctuating …. dysfunction is relatively common in patients with SLE. Some are affected by seizures, ataxia and psychosis. Polyneuropathy and cranial nerve lesions may be seen.
Fluctuating cognitive dysfunction is relatively common in patients with SLE. Some are affected by seizures, ataxia and psychosis. Polyneuropathy and cranial nerve lesions may be seen.
Eyes: … syndrome is seen in around 15% of patients with SLE
Eyes: Sjogren’s syndrome is seen in around 15% of patients with SLE
… - Gastrointestinal manifestations from mouth ulcers to mesenteric vasculitis. Lupus hepatitis and acute pancreatitis may also occur.
SLE - Gastrointestinal manifestations from mouth ulcers to mesenteric vasculitis. Lupus hepatitis and acute pancreatitis may also occur.
Haematology manifestations in SLE : … of chronic disease is common, …penia and …penia may also be seen.
Haematology manifestations in SLE : Anaemia of chronic disease is common, leucopenia and thrombocytopenia may also be seen.
Though not technically a manifestation patients with SLE have been noted to have an increased risk of …
Though not technically a manifestation patients with SLE have been noted to have an increased risk of non-Hodgkin lymphoma.
The diagnosis of … relies on suggestive clinical features or organ involvement and the presence of characteristic immunological findings.
The diagnosis of SLE relies on suggestive clinical features or organ involvement and the presence of characteristic immunological findings.
The diagnosis of SLE can at times be challenging. This is reflected by the multiple diagnostic criteria that have been developed. These include:
EULAR/ACR (2019): Positive ANA is required, then there are ten criteria (clinical and immunological) with patient said to have SLE if they score 10 or more points.
SLICC (2012): Patients meet 4 of 17 criteria with a requirement that one comes from the clinical criteria and one from the immunological criteria.
Diagnosis is not mandated by these criteria but they can be useful definitions to enable comparative research.
EULAR/ACR (2019): Positive ANA is required, then there are ten criteria (clinical and immunological) with patient said to have SLE if they score 10 or more points.
SLICC (2012): Patients meet 4 of 17 criteria with a requirement that one comes from the clinical criteria and one from the immunological criteria.
Diagnosis is not mandated by these criteria but they can be useful definitions to enable comparative research.
Bedside investigations for SLE
Bedside
Blood tests for SLE (8)
FBC Renal function Clotting screen LFT ESR/CRP Creatine kinase Vitamin D3 Thyroid profile
Immunology - SLE
Antinuclear antibody (ANA): Positive in about 95% of patients with SLE, however it is non-specific and may be seen in other conditions or entirely well patients.
C3/C4 level: Low levels are seen in SLE.
Anti-dsDNA and anti-Smith antibodies: The presence of these antibodies is specific for SLE and highly predictive.
Antiphospholipid antibodies (lupus anticoagulant, anti-cardiolipin antibodies, anti-beta2-glycoptrotein-1): It is advised antiphospholipid antibodies are ordered in all patients at time of diagnosis particularly if past history of miscarriages or venous thromboembolism.
Anti-Ro/La and anti-RNP antibodies: Relatively poor sensitivity and non-specific with Anti-Ro/La seen in Sjogren’s.
Direct Coombs test: Assess for evidence of haemolytic anaemia.
Immunoglobulins
…: Positive in about 95% of patients with SLE, however it is non-specific and may be seen in other conditions or entirely well patients.
Antinuclear antibody (ANA): Positive in about 95% of patients with SLE, however it is non-specific and may be seen in other conditions or entirely well patients.
Antinuclear antibody (ANA): Positive in about 95% of patients with …, however it is non-specific and may be seen in other conditions or entirely well patients.
Antinuclear antibody (ANA): Positive in about 95% of patients with SLE, however it is non-specific and may be seen in other conditions or entirely well patients.
C3/C4 level: … levels are seen in SLE.
C3/C4 level: Low levels are seen in SLE.
Anti-dsDNA and anti-Smith antibodies: The presence of these antibodies is specific for … and highly predictive.
Anti-dsDNA and anti-Smith antibodies: The presence of these antibodies is specific for SLE and highly predictive.
Antiphospholipid antibodies (lupus anticoagulant, anti-cardiolipin antibodies, anti-beta2-glycoptrotein-1): It is advised antiphospholipid antibodies are ordered in all patients with … at time of diagnosis particularly if past history of miscarriages or venous thromboembolism.
Antiphospholipid antibodies (lupus anticoagulant, anti-cardiolipin antibodies, anti-beta2-glycoptrotein-1): It is advised antiphospholipid antibodies are ordered in all patients at time of diagnosis particularly if past history of miscarriages or venous thromboembolism.
SLE - Anti-Ro/La and anti-RNP antibodies: Relatively poor sensitivity and non-specific with Anti-Ro/La seen in …..
Anti-Ro/La and anti-RNP antibodies: Relatively poor sensitivity and non-specific with Anti-Ro/La seen in Sjogren’s.
SLE - Direct … test: Assess for evidence of haemolytic anaemia.
Direct Coombs test: Assess for evidence of haemolytic anaemia.
Urine tests SLE:
Urinalysis
Random protein:creatinine ratio / 24-hr urine collection for protein
Imaging - SLE
Chest X-ray: Helps to identify cardiac/respiratory complications.
MSK X-rays: May be ordered of the relevant joint in patients presenting with arthropathy.
Renal USS: In patients with suspected lupus nephritis or as part of an AKI screen to exclude other causes.
CT chest: To evaluate the lungs in patients presenting with features suggesting involvement.
CT/MRI brain: May be ordered in patients presenting with neurological signs.
Echocardiogram: May be used in patients with suspected pericardial or valvular involvement.
Biopsy - SLE
Skin: … shows immune deposits at the dermal-epidermal boundary. Of use in patients with skin lesions and diagnostic uncertainty.
Kidney: An invasive investigation that is not without complication (e.g. infection, bleeding). Highly sensitive and specific for lupus … though it use as an investigation should be at the discretion of a nephrologist.
Skin: Immunofluorescence shows immune deposits at the dermal-epidermal boundary. Of use in patients with skin lesions and diagnostic uncertainty.
Kidney: An invasive investigation that is not without complication (e.g. infection, bleeding). Highly sensitive and specific for lupus nephritis though it use as an investigation should be at the discretion of a nephrologist.
Certain medications may trigger an autoimmune response that leads to a clinical syndrome similar to ….
Certain medications may trigger an autoimmune response that leads to a clinical syndrome similar to SLE.
…-induced lupus refers to a specific clinical syndrome whereby a medication causes an SLE-like illness. It has very similar clinical manifestations to idiopathic SLE, but there are some clinical and immunological features that differ between the two conditions.
Drug-induced lupus refers to a specific clinical syndrome whereby a medication causes an SLE-like illness. It has very similar clinical manifestations to idiopathic SLE, but there are some clinical and immunological features that differ between the two conditions.
Common drugs implicated in drug-induced lupus
High (> 5%): Procainamide, hydralazine
Moderate (1-5%): Quinidine
Low (0.1-1%): Penicillamine, carbamazepine, methyldopa, minocycline
Very low (< 0.1%): multiple agents
High (> 5%): Procainamide, hydralazine
Moderate (1-5%): Quinidine
Low (0.1-1%): Penicillamine, carbamazepine, methyldopa, minocycline
Very low (< 0.1%): multiple agents
These drugs can lead to …
Drug-induced lupus High (> 5%): Procainamide, hydralazine Moderate (1-5%): Quinidine Low (0.1-1%): Penicillamine, carbamazepine, methyldopa, minocycline Very low (< 0.1%): multiple agents
The clinical spectrum of drug-induced lupus is highly variable. Patients will usually have features of fever, arthralgia/arthritis, myalgia, rash, and/or serositis. Severe … … involvement is uncommon. Additionally, … involvement is far less common in drug-induced lupus compared to idiopathic SLE. Symptoms most commonly start months to years after exposure to the culprit medication, but can be more abrupt.
The clinical spectrum of drug-induced lupus is highly variable. Patients will usually have features of fever, arthralgia/arthritis, myalgia, rash, and/or serositis. Severe internal organ involvement is uncommon. Additionally, cutaneous involvement is far less common in drug-induced lupus compared to idiopathic SLE. Symptoms most commonly start months to years after exposure to the culprit medication, but can be more abrupt.
One of the hallmarks of drug-induced lupus is the presence of anti-…. autoantibodies, which are found in >95% of cases (formation is drug-specific). Anti-dsDNA, which is highly specific for idiopathic SLE, is uncommon in the drug-induced form.
One of the hallmarks of drug-induced lupus is the presence of anti-histone autoantibodies, which are found in >95% of cases (formation is drug-specific). Anti-dsDNA, which is highly specific for idiopathic SLE, is uncommon in the drug-induced form
Lifestyle and modifiable risk factors - SLE
An active and healthy lifestyle based upon a balanced diet. In patients with existing (or whom develop) co-morbidities such as hypertension or diabetes arrange regular reviews and optimisation of their management.
Smoking is of course an independent risk factor for cardiovascular disease and numerous malignancies (amongst other conditions). Additional smoking is known to exacerbate aspects of SLE (renal and skin disease), and adds to the existing increased risk of cardiovascular disease.
Excessive sun exposure should be avoided and use of SPF advised.
The management of SLE is enormously complex and can involve a number of immunosuppressants. The treatment regimens often follow a pattern of … and …
Induction therapy: Aggressive therapy aimed at halting disease progression and inducing remission. Prednisolone and hydroxychloroquine commonly used with a combination of other immunosuppressants depending on severity.
Maintenance therapy: Less intensive therapy aimed at preventing relapse, again may be made up of a combination of immunosuppressants. Once stable remission is achieved these can be reduced and stopped, typically with hydroxychloroquine continuing.
Induction therapy for SLE:
Aggressive therapy aimed at halting disease progression and inducing …. P… and hydroxychloroquine commonly used with a combination of other immunosuppressants depending on severity.
Induction therapy: Aggressive therapy aimed at halting disease progression and inducing remission. Prednisolone and hydroxychloroquine commonly used with a combination of other immunosuppressants depending on severity.
Maintenance therapy for SLE: Less intensive therapy aimed at preventing …, again may be made up of a combination of …. Once stable remission is achieved these can be reduced and stopped, typically with hydroxychloroquine continuing.
Maintenance therapy: Less intensive therapy aimed at preventing relapse, again may be made up of a combination of immunosuppressants. Once stable remission is achieved these can be reduced and stopped, typically with hydroxychloroquine continuing.
Once stable remission is achieved in SLE immunosuppressants can be reduced and stopped, typically with … continuing.
Once stable remission is achieved in SLE immunosuppressants can be reduced and stopped, typically with hydroxychloroquine continuing.
Typical manifestations of … SLE include ‘fatigue, malar rash, diffuse alopecia, mouth ulcers, arthralgia, myalgia, platelets 50–149 × 109/L’.
Typical manifestations of mild SLE include ‘fatigue, malar rash, diffuse alopecia, mouth ulcers, arthralgia, myalgia, platelets 50–149 × 109/L’.
Typical manifestations of … SLE include ‘fever, lupus-related rash up to 2/9 body surface area, cutaneous vasculitis, alopecia with scalp inflammation, arthritis, pleurisy, pericarditis, hepatitis, platelets 25–49 × 109/L’.
Typical manifestations of moderate SLE include ‘fever, lupus-related rash up to 2/9 body surface area, cutaneous vasculitis, alopecia with scalp inflammation, arthritis, pleurisy, pericarditis, hepatitis, platelets 25–49 × 109/L’.
Typical manifestations of … SLE include ‘rash involving >2/9 body surface area, myositis, severe pleurisy and/or pericarditis with effusion, ascites, enteritis, myelopathy, psychosis, acute confusion, optic neuritis, platelets <25 × 109/L’.
Typical manifestations of severe SLE include ‘rash involving >2/9 body surface area, myositis, severe pleurisy and/or pericarditis with effusion, ascites, enteritis, myelopathy, psychosis, acute confusion, optic neuritis, platelets <25 × 109/L’.
Historically SLE has had a very poor prognosis with a 5-year survival of just 40% in the 1950’s. With earlier diagnosis and better treatment regimens this has dramatically improved with more recent studies quoting 10-year survival of …%.
Historically SLE has had a very poor prognosis with a 5-year survival of just 40% in the 1950’s. With earlier diagnosis and better treatment regimens this has dramatically improved with more recent studies quoting 10-year survival of 92%.
Causes of premature death of … include active disease, thrombotic complications, infections, cardiovascular disease and treatment complications.
Causes of premature death of SLE include active disease, thrombotic complications, infections, cardiovascular disease and treatment complications.
Factors associated with a poorer prognosis with SLE include …
black ethnicity, male sex, lupus nephritis, hypertension and antiphospholipid antibodies / antiphospholipid syndrome.
Those with … SLE are more likely to require higher doses of steroids such as prednisolone, hydroxychloroquine is normally used. Additional agents may include methotrexate, azathioprine, mycophenolate and ciclosporin.
Those with moderate SLE are more likely to require higher doses of steroids such as prednisolone, hydroxychloroquine is normally used. Additional agents may include methotrexate, azathioprine, mycophenolate and ciclosporin.
In patients with mild SLE treatments include … and prednisolone (oral/topical). … may be used as are short courses of NSAIDs (in the absence of contraindications).
In patients with mild SLE treatments include hydroxychloroquine and prednisolone (oral/topical). Methotrexate may be used as are short courses of NSAIDs (in the absence of contraindications).
What is this representing?
SLE
SLE is associated with … antibodies
SLE is associated with anti-nuclear antibodies (ANA).
…. is specific to SLE, meaning patients without the condition are very unlikely to have these antibodies.
Anti-double stranded DNA (anti-dsDNA) is specific to SLE, meaning patients without the condition are very unlikely to have these antibodies.
Antiphospholipid antibodies and antiphospholipid syndrome can occur secondary to SLE. They can occur in up to 40% of patients with SLE and are associated with an increased risk of …
Antiphospholipid antibodies and antiphospholipid syndrome can occur secondary to SLE. They can occur in up to 40% of patients with SLE and are associated with an increased risk of venous thromboembolism.
Recurrent … is common in systemic lupus erythematosus.
Recurrent miscarriage is common in systemic lupus erythematosus. It is associated with other pregnancy complications such as intrauterine growth restriction, pre-eclampsia and pre-term labour.
Venous thromboembolism is particularly associated with … syndrome occurring secondary to SLE.
Venous thromboembolism is particularly associated with antiphospholipid syndrome occurring secondary to SLE.
Neuropsychiatric SLE is caused by inflammation in the central nervous system. It can present with optic … (inflammation of the optic nerve), … … (inflammation of the spinal cord) or p…
Neuropsychiatric SLE is caused by inflammation in the central nervous system. It can present with optic neuritis (inflammation of the optic nerve), transverse myelitis (inflammation of the spinal cord) or psychosis.
Lupus nephritis occurs due to inflammation in the kidney. It can progress to end-stage renal failure. It is assessed using …-… ratio and renal biopsy. The renal biopsy is often repeated to assess response to treatment.
Lupus nephritis occurs due to inflammation in the kidney. It can progress to end-stage renal failure. It is assessed urine protein:creatinine ratio and renal biopsy. The renal biopsy is often repeated to assess response to treatment.
SLE - Interstitial lung disease can be caused by inflammation in the lung tissue. This leads to pulmonary …
SLE - Interstitial lung disease can be caused by inflammation in the lung tissue. This leads to pulmonary fibrosis.
Biological therapies are considered for patients with severe disease or where patients have not responded to other treatments. The main options in SLE are:
Rituximab is a monoclonal antibody that targets the CD20 protein on the surface of B cells
Belimumab is a monoclonal antibody that targets B-cell activating factor
