Joint station Flashcards
What is the pathophysiology of SLE?
SLE is an autoimmune condition characterised by loss of tolerance to self-antigens.
It has been proposed that SLE may arise from exposure of the immune system to blebs, cellular remnants, from apoptotic cells. These blebs which feature self-antigens are not efficiently removed and are carried to lymphoid tissue.
An immune response is raised when these are taken up by antigen-presenting cells and presented to T-lymphocytes resulting in B-lymphocyte activation and autoantibody production.
The failure to inactivate lymphocytes responding to self-antigens leads to circulating autoantibodies and immune mediated damage to ones own cells.
Pathophysiology
autoimmune disease: SLE a type 3 hypersensitivity reaction
associated with HLA B8, DR2, DR3
thought to be caused by immune system dysregulation leading to immune complex formation
immune complex deposition can affect any organ including the skin, joints, kidneys and brain
What are the triggers for flare ups?
Triggers for flares
It follows a relapsing-remitting course and organ involvement tends to become prominent in flares. Flares can be triggered by:
Oestrogen-containing contraception.
Overexposure to sunlight.
Infections.
Stress.
How can SLE present?
Dermatological presentations
Photosensitivity, which is the most common dermatological feature of SLE. This especially occurs in the form of a malar rash (symmetrical, butterfly shaped rash across both cheeks).
Discoid rash (round, raised plaques).
Mouth / nose / genital ulcers.
Hair loss.
Cutaneous vasculitis, which manifests as splinter haemorrhages / purpura.
Note that a variant of lupus called discoid lupus exists which causes a discoid rash alone with no other features of SLE.
Presentations involving joints
Arthritis (non-erosive) or arthralgia. The usual presentation is a polyarthritis which may be symmetrical or asymmetrical.
Cardiovascular presentations
Raynaud’s phenomenon.
Pericarditis, which is the most common cardiac feature of SLE.
Myocarditis, which can present as arrhythmias and heart failure.
Increased cardiovascular disease risk.
Respiratory presentations
Pleurisy and pleural effusions.
Pneumonitis, which in the acute form can mimic pneumonia, chronic pneumonitis causes pulmonary fibrosis.
Renal presentations
Lupus nephritis, which is the most common cause of lupus-related death.
It can be asymptomatic for a time before it presents as either nephritic or nephrotic syndrome.
Patients should be monitored regularly for renal disease. This monitoring includes checking blood pressure (in case of sudden hypertension) and urinalysis (for proteinuria or haematuria).
Neurological presentations
Seizures. Migraines. Peripheral neuropathies. Psychiatric symptoms including psychosis or depression or anxiety. Haematological presentations
Anaemia of chronic disease (common). Lymphopenia (common). Autoimmune haemolytic anaemia. Thrombocytopenia. Leucopoenia. Gastrointestinal presentations
Peritonitis (aseptic).
Hepatosplenomegaly.
Overlap of SLE with other diseases
SLE patients can frequently develop the following conditions:
Secondary Sjogren’s syndrome
Secondary anti-phospholipid syndrome
Mixed connective tissue disease (features of SLE, systemic sclerosis and poly/dermatomyositis)
Though not technically a manifestation patients with SLE have been noted to have an increased risk of non-Hodgkin lymphoma.
What can cause SLE?
Aetiology
The aetiology of SLE appears to be an interplay of genetic, hormonal and environmental factors.
SLE is a complex condition with an aetiology that is not completely understood. Here we discuss some of the most important and well characterised aetiological factors.
Genetics
Genetics play a major role in the development of SLE. Monozygotic twins have high concordance, estimated to be around 25% whilst dizygotic twins have concordance of just 3%. Genome studies have identified numerous genes that may influence the chance of developing SLE. As may be expected, affected sites include the HLA region on chromosome 6 and genes encoding for immune cells.
Hormones
Premenopausal women are most commonly affected and it is thought the sex hormones play an important aetiological role. There has been some evidence indicating those with early menarche or on oestrogen containing therapies have an increased risk of developing SLE.
Drugs
A numbers of medications including hydralazine, isoniazid and penicillamine have been shown to trigger a form of SLE.
Viral factors
Viruses have been implicated as triggers for SLE. In particular there is suspicion infection with Epstein-Barr virus may be involved.
What drugs can cause drug induced lupus?
Drugs that are definitely known to cause drug induced lupus (DIL) include:
Sulfadiazine.
Hydralazine.
Procainamide.
Isoniazid.
Methyldopa.
Quinidine.
Minocycline.
Chlorpromazine.
How can drug induced lupus present?
DIL presents as a milder form of SLE and is triggered by chronic use of certain drugs for over one month. Crucially symptoms should not be present before starting the drug, and should stop after discontinuing the drug. Although DIL can present with any feature of SLE, the most common features are:
Systemic upset (fever / fatigue / myalgia).
Arthritis (non-erosive) or arthralgia.
Serositis in the form of pleurisy or pericarditis.
Dermatological features of SLE such as the characteristic malar rash are less common in DIL, and SLE renal disease (the most common cause of death in SLE) and neurological involvement are rare.
While SLE usually occurs in females, DIL occurs in males and females equally.
How can drug induced lupus be investigated and managed?
Blood tests:
DIL patients may be positive for ANA, but they should not be positive for the SLE specific autoantibodies Anti-dsDNA and Anti-sm.
They may be positive for Anti-histone however, which is considered specific for DIL.
Inflammatory markers may be raised.
How can SLE be investigated?
Bedside
Vital signs
Blood sugar
ECG
Bloods
FBC Renal function Clotting screen LFT ESR/CRP Creatine kinase Vitamin D3 Thyroid profile Immunology
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
Urine
Urinalysis
Random protein:creatinine ratio / 24-hr urine collection for protein
Imaging
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
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.
What can be used to diagnose SLE?
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.
What is the diagnostic criteria for SLE?
The large number of potential symptoms can be difficult to remember, but the mnemonic A RASH POINts MD can help to remember the American College of Rheumatology Diagnostic Criteria and thus the important symptoms and investigations - presence of ≥4 supports the diagnosis:
Arthritis / arthralgia.
Renal disease.
ANA positive.
Serositis (pericarditis / pleurisy / pleural effusion).
Haematological (haemolysis / low WCC / platelets / lymphocytes).
Photosensitivity rash.
Oral ulcers.
Immunological tests positive (anti-dsDNA, anti-Sm, anti-phospholipid).
Neuropsychiatric (seizures, psychosis).
Malar rash.
Discoid rash.
Note: There is now a move towards using the SLICC Classification Criteria for SLE. Although similar to the above criteria it requires ≥4 findings with at least one clinical feature and one laboratory test (e.g. ANA, anti-DNA, anti-Sm, anti-phospholipid, low complement, direct Coomb’s test) present.
How can SLE be monitored?
anti Ds DNA,c3,c4,ESR
What is Antiphosholipid syndrome?How does it present?
Antiphospholipid syndrome is an acquired disorder characterised by a predisposition to both venous and arterial thromboses, recurrent fetal loss and thrombocytopenia. It may occur as a primary disorder or secondary to other conditions, most commonly systemic lupus erythematosus (SLE)
In pregnancy the following complications may occur: recurrent miscarriage IUGR pre-eclampsia placental abruption pre-term delivery venous thromboembolism
What antibodies are positive in antiphosholipid syndrome?
anticardiolipin,anti beta 2 glycoprotein 1,lupus anticoagulant
How can antiphosholipid syndrome be treated?
Management
low-dose aspirin should be commenced once the pregnancy is confirmed on urine testing
low molecular weight heparin once a fetal heart is seen on ultrasound. This is usually discontinued at 34 weeks gestation
these interventions increase the live birth rate seven-fold
What are the side effects of Hydroxychloroquine and how can it be monitored?
Hydroxychloroquine is used in the management of rheumatoid arthritis and systemic/discoid lupus erythematosus. It is pharmacologically very similar to chloroquine which is used to treat certain types of malaria.
Adverse effects
bull’s eye retinopathy - may result in severe and permanent visual loss
recent data suggest that retinopathy caused by hydroxychloroquine is more common than previously thought and the most recent RCOphth guidelines (March 2018) suggest colour retinal photography and spectral domain optical coherence tomography scanning of the macula
baseline ophthalmological examination and annual screening is generally recommened
A contrast to many drugs used in rheumatology, hydroxychloroquine may be used if needed in pregnant women.
Monitoring
the BNF advises: ‘Ask patient about visual symptoms and monitor visual acuity annually using the standard reading chart’