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Flashcards in Connective tissue diseases Deck (46):
1

What is systemic lupus erythamatous?

Systemic autoimmune disease where the immune system attacks the bodies own cells and tissues resulting in inflammation.
The antibody-immune complexes precipitate and cause a further immune response.

2

Epidemiology of SLE

Occurs in females more than males.
Afro-caribbeans more than europeans etc.

3

What causes SLE?

Combination of genetic factors- increased incident among relatives
Hormonal factors-incidence increased with those with higher oestrogen
Environmental factors-virus's, UV light, silica dust
Immunological factors

4

Pathogenesis of SLE

Primarily due to loss of immune regulation. Increased (and defective) apoptosis is caused. The necrotic cells then release nuclear material that can act as auto-antigens.
Autoimmunity probably results from extended exposure to these.
B and T cells are stimulated
Autoantibodies are produced.

5

Renal disease associated with SLE pathogenesis.

Immune complexes deposit in the mesangium (structure associated with capillaries in the glomerulus). Complexes consist of nuclear antigens and anti-nuclear antibodies. Complexes then form in the circulation then they are deposited. This activates complement which attracts leukocytes (WBC) and they release cytokines.
Cytokine release perpetuates inflammation and eventually can cause necrosis and scarring.

6

Mucocutaneous features of SLE (region of the body where mucus transitions to skin)

Photosensitivity
Malar rash (that may or may not be associated with sun exposure)- however spares the nasolabial folds.
Discoid lupus erythamatous (may scar)- disc like plaques on scalp
Subacute cutaneous lupus (skin plaques
Painless mouth ulcers
Alopecia (non scarring)

7

Musculoskeletal features of SLE

Non-deforming polyarthritis/polyarthralgia_ has a rheumatoid arthritis distribution but no radiological changes.
Deforming arthropathy (deforming disease of the joint)
Erosive arthritis- rare
Myopathy- weakness, myalgia, myositis

8

Serositis (inflammation of the serous membrane) features of SLE

Pericarditis
Pleurisy
Pleural and pericardial effusions

9

Renal features of SLE

Proteinurea of greater than 500mg in 24 hours.
Red cell cast

10

Neurological features of SLE

Depression/ psychosis
Migrainous headache
Siezures
Cranial or peripheral neuropathy
Mononeuritis multiplex- form of damage to one or more peripheral nerves

11

Haematological features of SLE

Lymphadenopathy
Leucopenia- reduction in number of white cells
Lymphopenia- reduction in number of lymphocytes
Haemolytic anaemia- reduction in RBC
Thrombocytopenia

12

Antiphospholipid syndrome

Disorder of the immune system that causes blood clots.
Venous and arterial thrombosis
Livido reticularis- lace like purplish discolouration of the skin
Associated with other autoimmune conditions especially SLE
Thrombocytopenia- deficiency of platelets in the blood.

13

Susceptibility to infection in relation to SLE

Intrinsic factors- low complements
-Impaired cell mediated immunity
-defective phagocytosis
-poor antibody response to certain antigens

Extrinsic factors-
steroids
Other immunosuppresive drugs

14

Investigations into SLE

Antinuclear antibodies
Anti-double stranded DNA
Anti- ENA
Antiphospholipid antibodies

15

Antinuclear antibodies (ANA)

95% positive in SLE patients
Also found in conditions such as RA, HIV and hep B

16

When should a positive ANA test be taken seriously?

When other antinuclear antibodies are also positive such as Anti-dsDNA, Anti-Sm, Anti-Ro, Anti-RNP

When the patient presents with CTD features

17

Anti-double stranded DNA

Occurs in approximately 60% of patients with SLE
Highly specific to SLA
Titre correlates with overall disease activity
May be associated with lupus nephritis

18

Anti- ENA

Anti- extractable nuclear antigens- group of over 100 types of which
-Anti-Ro makes up- 60%
-Usually associated with anti- La
Associated with cutaneous manifestations
Secondary sjogens features
Congenital heart block and neonatal LE

Anti-Sm (10-20%) is highly specific-probably association with neurological involvement
Anti-RNP (30%)- overlap features- raynauds phenomonom, sclerodermatous skin lesions, low grade myositis

19

Antiphospholipid antibodies

Anti-cardiolipin antibodies
Lupus anticoagulant
Anti- beta 2 cytokine
Must be positive on two occasions 12 weeks apart.

20

Once a diagnosis of SLE is established, what should you do?

Screen for organ involvement

21

Investigations of SLE for organ involvement

CXR
Pulmonary function tests
CT chest
Urine protein quantification
Renal biopsy
Echocardiogram
Nerve conduction studies
MRI brain

22

How do you monitor SLE activity?

Thorough clinical examination and BP
Anti-dsDNA correlates with disease intensity
C3/C4 levels negatively correlate
Urine examination including protein cells and casts
FBC and blood biochemistry

23

General management of SLE

Counselling family, patient etc.
Regular monitoring
Avoiding excessive sunlight exposure
Pregnancy issues

24

Drug treatment for SLE

NSAIDS and simple analgesia
Steroids
Antimalarials
Immunosupressive therapy
Biologics (in severe disease)

25

Anti-malarials in the treatment of SLE

Useful for arthritis, cutaneous manifestations and constitutional symptoms
May reduce systemic complications

26

Steroids in the treatment of SLE

Useful but may cause unwanted side-effects
Various doses are needed for different manifestations.
Low dose e.g. prednisolone (<15mg/day) for skin rashes, arthritis and serositis
Medium dose e.g. (0.5mg per kg/d) for resistant serositis, haemotological abnormalities etc.
High dose (1mg per kg/d) for severe haematological changes, major organ damage.

27

Immunosupressive therapy for treatment of SLE

Azathioprine
Cyclophosphamide
Methotrexate
Mycophenolate mofetil

28

Side effects of immunosupressive therapy for treatment of SLE

Can cause bone marrow suppression
Can cause increased susceptibility to infection
Potentially teratogenic (disturb the development of the embryo)

29

Biologics in the treatment of SLE

Anti-CD20 (Rituximab)
Anti-Blys (Belimumab)

30

Treatment of mild SLE

Topical steroids, NSAIDs and HQC

31

Treatment of moderate SLE

Oral steroids
Azathioprine
Methotrexate

32

Treatment of severe SLE

IV steroids
Cyclophosphamide
Rituximab

33

Define a connective tissue disease

Characterised by the presence of spontaneous overactivity of the immune system.
Often associated with specific auto-antibodies which can help define the condition.

34

How do connective tissue diseases related to systemic lupus erythamatous

They can all be features of SLE. E.g. antiphospholipid syndrome could manifest on its own or could be part of SLE.

35

Antiphospholipid syndrome diagnosis

Positive anticardiolipin antibodies
AND/OR
Lupus anticoagulant activity
AND/OR
Anti- beta2 glycoprotein

36

Affects of antiphospholipid syndrome on pregnant women?

Responsible for 15% of recurrent foetal loss
Or eclampsia
Or placental insufficiency

37

Other features of antiphospholipid syndrome

Superficial thrombophlebitis and livedo reticularis
Mild/moderate thrombocytopenia (deficiency of platelets)
Neurological features – migraine, transverse myelitis
Libman-Sacks endocarditis
Catastrophic anti-phospholipid syndrome

38

Treatment of antiphospholipid syndrome

For the thrombosis- life long anticoagulation
Pregnancy loss- aspirin and heparin during pregnancy to prevent eclampsia.
Attention to vascular risk factors.

39

Sjogrens syndrome

Autoimmune condition
Lymphocyte infiltration of exocrine glands causing xerostomia (stress in the mouth caused by change in composition of saliva) and keratoconjunctivitis sicca (dryness of the conjunctiva)
May be primary or secondary to other autoimmune conditions

40

Classification of primary sjogrens syndrome

Subjective ocular symptoms(daily for > 3 months)
Subjective oral symptoms (daily for > 3 months)
Objective evidence of ocular dryness
Objective evidence of salivary gland involvement
Immunology – either Ro, La or both
Biopsy evidence of lymphocytic infiltrate

Need 4 of 6 and must include either immunology or biopsy evidence

41

Other manifestations of sjogrens syndrome

Fatigue
Arthralgia
Raynauds
Salivary swelling
Lymphadenopathy
Skin and vaginal dryness
Interstitial lung disease
Neuropathy
Lymphoma (x40 risk)
Renal tubular acidosis
Neonatal complete heart block (anti-Ro)

42

Primary sjogrens disease

Prevalence of 1-3%
Most people remain undiagnosed
Serious complications are very rare.

43

Treatment of sjogrens disease

Eye drops, punctal plugs
Saliva replacement
Pilocarpine
Hydroxychloroquine
Steroids and immunosuppression
Attention to cardiovascular risk factors

44

Systemic sclerosis

Autoimmune
Vasculopathy (Raynaud’s Syndrome)
Inflammation
Fibrosis – excess deposition of collagen in skin and internal organs

CREST-Calconosis, Raynaud’s, Esophageal dysmotilty, Sclerodactyly, Telangiectasia. Can also feature pulmonary hypertension in ~30%

45

Organ manifestations of systemic sclerosis

GI- Oesophageal hypomobility
Small bowel hypomobility, bacterial overgrowth
Pancreatic insufficiency
Rectal hypomobility

Respiratory-
Interstitial lung disease
Pulmonary hypertension
Chest wall restriction

Renal
Hypertensive renal crisis
Ischaemic

Cardiovascular
Raynaud’s with digital ulceration
Atherosclerotic disease
Hypertensive cardiomyopathy

46

Treatments of systemic sclerosis

Calcium channel blockers
Prostacyclin (Iloprost)
ACE inhibitors
Prednisolone
Immunosuppression
Bosentan, Sildenafil