Joint station Flashcards

1
Q

What is the pathophysiology of SLE?

A

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

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2
Q

What are the triggers for flare ups?

A

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.

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3
Q

How can SLE present?

A

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.

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4
Q

What can cause SLE?

A

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.

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5
Q

What drugs can cause drug induced lupus?

A

Drugs that are definitely known to cause drug induced lupus (DIL) include:

Sulfadiazine.

Hydralazine.

Procainamide.

Isoniazid.

Methyldopa.

Quinidine.

Minocycline.

Chlorpromazine.

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6
Q

How can drug induced lupus present?

A

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.

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7
Q

How can drug induced lupus be investigated and managed?

A

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.

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8
Q

How can SLE be investigated?

A

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.

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9
Q

What can be used to diagnose SLE?

A

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.

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10
Q

What is the diagnostic criteria for SLE?

A

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.

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11
Q

How can SLE be monitored?

A

anti Ds DNA,c3,c4,ESR

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12
Q

What is Antiphosholipid syndrome?How does it present?

A

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
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13
Q

What antibodies are positive in antiphosholipid syndrome?

A

anticardiolipin,anti beta 2 glycoprotein 1,lupus anticoagulant

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14
Q

How can antiphosholipid syndrome be treated?

A

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

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15
Q

What are the side effects of Hydroxychloroquine and how can it be monitored?

A

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’

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16
Q

How can disease severity be classified in SLE?

A

Principles of management

The management of SLE is enormously complex and can involve a number of immunosuppressants. The treatment regimens often follow a pattern of induction and maintenance:

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.
Here we give a basic overview of the management options. For those interested in more detail and a description of mild, moderate and severe see The British Society for Rheumatology guideline for the management of systemic lupus erythematosus in adults. The management of lupus nephritis is considered separately and is not covered here.

Mild SLE

Typical manifestations of mild SLE include ‘fatigue, malar rash, diffuse alopecia, mouth ulcers, arthralgia, myalgia, platelets 50–149 × 109/L’.

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).

Moderate SLE

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’.

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 refractory cases the monoclonal antibodies rituximab and belimumab may be used.

Severe SLE

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’.

Patients with severe SLE - those with organ or life-threatening manifestations require immediate and intensive treatment. Investigations must be ordered to exclude other causes or to understand the nature of the underlying manifestation.

The management of severe SLE depends on the nature of the complication. Immunosuppressive regimens for severe active SLE includes prednisolone, hydroxychloroquine, methotrexate, azathioprine, mycophenolate and ciclosporin. With time medications are reduced and stopped, typically continuing hydroxychloroquine.

IV immunoglobulin and plasmapheresis may be used certain circumstances:

Refractory cytopaenias
Thrombotic thrombocytopaenic purpura
Rapidly deteriorating acute confusional state
Catastrophic variant of APS

17
Q

How can SLE be treated?

A

Preventative treatment

Avoiding triggers:

Oestrogen-containing contraception.
Overexposure to sunlight.
Infections.
Stress.
Pharmacological management

Management will be consultant lead and depends on the severity of the disease:

NSAIDs and hydroxychloroquine are the mainstay of SLE treatment and may be sufficient for mild disease alone ± short courses of corticosteroids for flares.
More prominent organ involvement may require long-term corticosteroids, usually in combination with a DMARD as a ‘steroid sparing agent’ to reduce the steroid dose.
Severe flares causing serious renal, neurological or haematological effects may require high dose corticosteroids in combination with immunosuppressants. Cyclophosphamide is effective and is the usual choice.

Thrombocytopenia or leucopoenia:

IV immunoglobulin infusions may be beneficial.
Antiphospholipid syndrome:

Antiplatelets or anticoagulation.
Seizures:

Anti-epileptic medication may be needed.

18
Q

How can lupus nephritis be treated?

A

Renal disease:

Monitoring blood pressure and urinalysis (proteinuria or haematuria) to detect lupus nephritis early is essential. Hypertension should be treated aggressively, usually with ACE-inhibitors. Full renal failure will require corticosteroids and cyclophosphamide

19
Q

What are the emergencies in SLE?

A

Lupus Glomerulonephritis

Many patients have chronic symptoms and the symptoms of an emergency (like Lupus Glomerulonephritis) may be subtle to spot.
If Lupus Glomerulonephritis is untreated, patients will develop renal damage. This is the reason why all patients with SLE have a urine dipstick test to assess for proteinuria.
If it is frankly nephrotic (proteinuria, hypoalbuminemia and oedema), an urgent admission is required.
The mainstay of treatment is high dose steroids plus immunosuppression.
Cerebral Lupus

Cerebral Lupus can have many different presentations. Patients can present with fits, psychosis, severe unremitting headaches or impairment of consciousness. Patients will often have other signs of active SLE disease.
It is often difficult to distinguish the mild cases of Cerebral Lupus from depression or infection.
The ESR and anti ds-DNA antibody titres will be raised whereas the complement C3 and C4 levels will be low. The C-Reactive Protein (CRP) levels will often not be markedly raised. Sometimes, the blood markers of active SLE disease and the MRI scan can be normal.
The management of Cerebral Lupus consists of high dose steroids and immunosuppression (Cyclophosphamide/Azathioprine). The response may be very slow but eventually these patients often do very well with no long term damage.

20
Q

What is the prognosis of SLE?

A

80% survival at 15 years.Increased long term risk of CVD and osteoporosis

Causes of premature death include active disease, thrombotic complications, infections, cardiovascular disease and treatment complications.

Factors associated with a poorer prognosis include black ethnicity, male sex, lupus nephritis, hypertension and antiphospholipid antibodies / antiphospholipid syndrome.

21
Q

What are the renal complications of SLE and how are they treated?

A

Lupus nephritis is a severe manifestation of systemic lupus erythematosus (SLE) that can result in end-stage renal disease. SLE patients should be monitored by performing urinalysis at regular check-up appointments to rule out proteinuria.

WHO classification
class I: normal kidney
class II: mesangial glomerulonephritis
class III: focal (and segmental) proliferative glomerulonephritis
class IV: diffuse proliferative glomerulonephritis
class V: diffuse membranous glomerulonephritis
class VI: sclerosing glomerulonephritis

Class IV (diffuse proliferative glomerulonephritis) is the most common and severe form. Renal biopsy characteristically shows the following findings:
glomeruli shows endothelial and mesangial proliferation, ‘wire-loop’ appearance
if severe, the capillary wall may be thickened secondary to immune complex deposition
electron microscopy shows subendothelial immune complex deposits
granular appearance on immunofluorescence

Management
treat hypertension
corticosteroids if clinical evidence of disease
immunosuppressants e.g. azathioprine/cyclophosphamide

22
Q

What drugs worsen SLE?

A

Cocp and sulphonamides

23
Q

What medication should be avoided in renal disease?

A

NSAID

24
Q

When would a temporal arterial biopsy be done in GCA?

A

14 days of starting steriods

25
Q

How can polymyalgia rheumatic present?

A

Bilateral aching,tenderness and stiffness in shoulders,hips and proximal limbs,fatigue,fever,weightloss,depression,carpal tunnel syndrome,tenosynovitis
Raised Alp

26
Q

How to differentiate polymyalgia rheumatica from polymyositis

A

No weakness and ck normal

27
Q

How can polymyalgia rheumatica be treated?

A

Prednisolone 15mg.Expect dramatic response within one week.Mose need steroids for more than 2 years so give bone protection