Rheumatoid arthritis and SLE/systemic manifestations

Question 1

CONNECTIVE TISSUE DISORDERS

Key conditions

Answer 1

Question 2

RHEUMATOID ARTHRITIS

Answer 2

• Chronic joint inflammation that can result in joint damage
• Site of inflammation is the synovium
• Associated with autoantibodies:
• Rheumatoid factor
• Anti-cyclic citrullinated peptide (CCP) antibodies

Synovitis is main pathology here

Question 3

Ankylosing spondylitis

Answer 3

• Chronic spinal inflammation that can result in spinal fusion and deformity
• Site of inflammation includes the enthesis
• No autoantibodies (‘seronegative’)

Key pathology is attacking the anthesis where the ligmanet tendons insert into bone

Question 4

SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

Answer 4

• Chronic tissue inflammation in the presence of antibodies directed against self antigens
• Multi-site inflammation but particularly the joints, skin and kidney
• Associated with autoantibodies:
• Antinuclear antibodies
• Anti-double stranded DNA antibodies
• Anti-phospholipid antibodies

Production of immune complexes due to antibodies being formed against self antigens. Multisystem disease as the immune complexes formed can affect anywhere in body.

Question 5

CONNECTIVE TISSUE DISORDERS-there are similarities between the connective tissue disorders

Key points:

Answer 5

Arthralgia-pain but no obvious inflammation ie no heat, redness or swelling

Arthalgia is very common in CT disorders

Question 6

Raynaud’s phenomenon

Answer 6

Trigger-cold, but can occur in normal temp

Ischaemic changes affecting fingers-white, blue then red and painful

CT disorders often have this so ask about it!

Question 7

SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

Answer 7

Condition of young people, typically women (9:1)

• Raynaulds phenomenon, athralgia, mouth ulcers found in lupus and other connective tissue disorders
• Malar rash is specific to lupus, spares nasolabial folds

Question 8

SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) pathogenesis:

Note: square brackets on slides mean we don’t need to know ie this one!

Answer 8

Immune complexes bind to antibody or Fc rceeptors mediating inflammation

Question 9

Autoantibodies in rheumatology-need to learn

Answer 9

Seronegative-no antibodies

SLE-anti-phospholipid antibodies are associated with arterial and venous thrombosis, so if detected in treatment need to give anti-thrombotic agents. This can lead to miscarriages as can cause thrombosis of the placenta.

Question 10

ANTINUCLEAR ANTIBODIES:

Answer 10

Just be aware

Question 11

Autoantibodies in SLE:

Answer 11

Question 12

SYSTEMIC LUPUS ERYTHEMATOSUS investigations:

Answer 12

Break down into daignosis, so we have antibody screens and then we break into organ systems. Very important to investigate kidney function so look at protein in urine as causes glomerular damage causing inappropriate protein leaking into urine.

ESR is high like in Rheumatoid arthritis

But in absence of infection CRP is normal UNLIKE rheumatoid which has both high

Only if infection or inflammation ie serosistis which will cause CRP to be high in lupus.

In SLE: ESR high (often driven by high immunoglobulin levels), CRP typically normal *except* if there is significant joint inflammation or serositis (inflammation of pleural or pericardial membranes). I think exact reason unclear but must be due to nature of the inflammation. If the CRP is up in SLE, you first suspicion should be an infection rather than the SLE. Remember these patients are often immunosuppressed due to medications and so are vulnerable to infection.

Question 13

Disease activity in SLE

Measure component of immune complexes, so as immune complexes rise, the amount of Anti double stranded DNA rises.

Took many immune complexes, trigger this pathway so it uses up C3 and C4 so these levels decrease. We measure C3 and C4. Complement drops and DNA rises

Answer 13

Question 14

Disease activity in SLE

Complement drifts down as DNA goes up. The patient’s lupus is active so we need to meet this patient, have they got symptoms, is there evidence of kidney involvement etc.

Answer 14

On right, circled in albumin to creatinine ratio, measuring protein in urine. These are high ie abnormal.

This is lupus glomerular nephritis

Look how insensitive measuring renal function is in these patients eg creatine etc. Must do urine protein measurement, not just basic kidney screen.

Question 15

Disease activity in SLE

Answer 15

Can get autoimmune haemolytic anaemia driven by lupus.

Question 16

SLE Management:

Answer 16

RA-aim is to prevent joint damage

In lupus, we aim to get disease remission. Can’t get rid of autoantibodies but we can switch inflammatory process off and evoke remission via reducing complement activation and Fc receptor induced inflammation and use immunosuppressive agents (can use glucocorticoids, but not for a long time)

Rituximab is also used to treat RA

Antiphosopholipid status is important as increases susceptibility to arterial and venous thromboses (increases risk of miscarriage because of this)

Need to protect them from infections

This is a disorder of young women and lost of the therapies are contraindicated for pregnancy so this needs to be planned ahead of time.

Question 17

SJÖGREN’S SYNDROME

Answer 17

Autoimmune mediated inflammation of exocrine glands

Can happen in association with RA and SLE so secondary S

But can happen on its own ie primary S

Question 18

INFLAMMATORY MUSCLE DISEASE

Answer 18

Can occur on its own ie primary disorder but also with lupus so secondary disorder

Question 19

SYSTEMIC SCLEROSIS

Answer 19

Rarest of connective tissue disorders

Diffuse fibrous changes in skin so causes skin thickening

Extent of skin involvement can vary-diffuse or limited

Raynauds is always present in this and can occur without cold trigger and can lead to digital ischaemia. So is vasculopathy.

Question 20

OVERLAP SYNDROME

Answer 20

Question 21

Autoantibodies in rheumatology

Answer 21

Don’t need to know yet!

But this is useful in diagnosis of the above conditions

Question 22

Case discussion:

Answer 22

1)

• Ask if she has a family history of autoimmune conditions particularly lupus
• See if arthalgia is symmetrical
• Ask if she has been having headaches
• Ask if the changes in finger colour was accompanied by tingling and whether it is triggered by the cold or whether it occurs frequently with no cause
• Ask about muscle weakness (for inflammatory muscle disease)
• Ask if she has had hair loss
• Ask if they have previously had DVT, or miscarriages, this indicates propensity of venous and artreial thrombosis common with anti-phospholipid antibodies as with this can get thrombosis of developing placenta leading to miscarriage.
• Antiphospholipid antibodies -> can lead to clots (DVT/PE) AND recurrent miscarriage

2)

• Malar rash with nasolabial sparing
• Fever-high temperature
• Check for mouth sores
• Test joint function
• Look for reynald’s
• Pain on inspiration, so think of possible pleurisy-inflammation of lining of lung. Listen for pleural rub-as lupus can cause problems in multiple areas. Pleurisy is a condition in which the pleura — two large, thin layers of tissue that separate your lungs from your chest wall — becomes inflamed. Also called pleuritis, pleurisy causes sharp chest pain (pleuritic pain) that worsens during breathing.
• Dull lung bases ie air not getting to bases of lung may be caused by fluid in the lung ie pleural effusion-so breath sounds may be absent. Here dull lung bases so would think effusion causing reduced air entry
• Quiet heart sounds could be due to pericarditis-rare but check for heart rub
• peripheral oedema-nephrotic syndrome (as immune complexes are landing in the glomeruli and causing damage so protein will be found in urine) or heart failure

3)

• Complete blood count. This test measures the number of red blood cells, white blood cells and platelets as well as the amount of hemoglobin, a protein in red blood cells. Results may indicate you have anemia, which commonly occurs in lupus. A low white blood cell or platelet count may occur in lupus as well.
• Erythrocyte sedimentation rate. This blood test determines the rate at which red blood cells settle to the bottom of a tube in an hour. A faster than normal rate may indicate a systemic disease, such as lupus. The sedimentation rate isn’t specific for any one disease. It may be elevated if you have lupus, an infection, another inflammatory condition or cancer.
• Kidney and liver assessment. Blood tests can assess how well your kidneys and liver are functioning. Lupus can affect these organs.
• Urinalysis. An examination of a sample of your urine may show an increased protein level or red blood cells in the urine, which may occur if lupus has affected your kidneys.
• Antinuclear antibody (ANA) test. A positive test for the presence of these antibodies — produced by your immune system — indicates a stimulated immune system. While most people with lupus have a positive ANA test, most people with a positive ANA do not have lupus. If you test positive for ANA, your doctor may advise more-specific antibody testing
• Test for anti-phospholipid antibodies as if present these give indication of arterial and venous thrombosis.
• Chest X-ray as shortness of breath and chest pain to rule out pneumonia or PE
• Measure C3 and C4 levels in relation to double stranded DNA
• Kidney biopsy would be done in lupus patients with kidney involvement as this helps in management of lupus. We would expect renal pathologist to say he sees glomeruli showing signs of inflammation, the tubal interstitium looks normal. It’s a glomerulonephritis. We could expect to see immune complexes deposited in glomerli, they stain for immunoglobulin as this is part of the complexes and complement which would be found in high amounts in the glomeruli
• In this setting if ANA is up then it is Lupus

4)

• SLE-as photosensitive rash, ESR up, CRP low (very leading for SLE), lymphopenia
• Less likely to be scleroderma due to lung involvement, but possible as finger changes etc.
• Would do other autoantibodies shown on last slide incase dealing with an overlap syndrome

5)

• Treat with glucocorticoids often given by IV for rapid action-short term
• Treat with immunosuppressive agents
• Treat with immune modulators
• If any presence of anti-phospholipid antibodies-need to give anti-thrombotic therapy
• Biologics eg Rutixumab