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Flashcards in Connective tissue diseases Deck (63):

What connective tissue diseases exist?

¬ Anti-phospholipid syndrome
¬ Sjogrens syndrome
¬ Systemic sclerosis
¬ Dermatomyositis
¬ Polymyositis
¬ Mixed Connective Tissue Disease


SLE - what is this?

¬ Systemic autoimmune disease that can affect any part of the body.
Skin/joints/internal organs commonly affected
¬ As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage.
¬ Antibody-immune complexes precipitate and cause a further immune response.


What is the epidemiology of SLE:
-racial preponderance?

¬ Prevalence 20-150/100 000
¬ It affects females more than males 9:1
¬ Commoner in urban areas
¬ Prevalence is higher in Asians, Afro-Americans, Afro-Caribbeans and Hispanic americans compared with americans of european descent
¬ Commoner in Asian Indians than Caucasians in UK
Uncommon in African blacks


What is the aetiology of SLE

A mixture of:


Describe the genetic factors involved in SLE?

¬ high concordance in monozygotic twins, increased incidence amongst relatives, identification of gene abnormalities predisposing to lupus


Describe the hormonal factors in SLE?

¬ incidence increased in those with higher oestrogen exposure - early menarche, on oestrogen containing contraceptives and HRT


Describe the environmental factors in SLE?

¬ Viruses eg Epstein-Barr Virus
¬ UV light may stimulate skin cells to secrete cytokines stimulating B-cells
¬ Silica dust (found in cleaning powders, cigarette smoke and cement) may increase risk of developing SLE


Describe the pathogenesis of SLE?

Often cells that have been killed break down and these broken down pieces and insides of the cells ‘float about’.
In lupus antibodies are created against this material = autoantibodies

¬ Primarily due to loss of immune regulation
¬ Increased and defective apoptosis (programmed cell death)
¬ Necrotic cells release nuclear material which act as potential autoantigens
¬ Autoimmunity possibly results by the extended exposure to nuclear and intracellular autoantigens – cell material ‘floats’ about for longer than it should.
¬ B and T cells are stimulated
¬ Autoantibodies are produced

These autoimmune complexes sit in basement membranes of blood vessels
=inflammatory response
= damage to the membranes


What classification criteria is used for SLE?

SLICC classification criteria for SLE
-clinical critera
-immunologic (ANA/Anti-DNA/Anti-Sm/Antiphospholipid/low complement (C3/C4/CH50)/direct coomb's test)

have to have 4 or more criteria, at least one clinical and one immunologic


What consitutional symptoms are seen in SLE?

¬ Fever
¬ Malaise
¬ Poor appetite
¬ Weight loss
¬ Fatigue


What mucocutaneous features are seen in SLE?

¬ Photosensitivity – rash that appears and lasts for days/weeks
¬ Malar rash
λ may or may not be associated with sun exposure
¬ Discoid lupus erythematosus – solely skin lupus
Scaly,well defined rash
¬ Subacute cutaneous lupus
This rash needs to be biopsied to confirm it is lupus


What MSK features are seen in SLE?

¬ Non-deforming polyarthritis/polyarthralgia
λ RA distribution but no radiological erosion
¬ Deforming arthropathy - Jaccoud’s arthritis
¬ Erosive arthritis - rare
¬ Myopathy - weakness, myalgia & myositis (muscle inflammation)


What pulmonary features are seen in SLE?

¬ Pleurisy
¬ Infections
¬ Diffuse lung infiltration and fibrosis
¬ Pulmonary hypertension
¬ Pulmonary infarct


What cardiac features are seen in SLE?

¬ Pericarditis
¬ Cardiomyopathy
¬ Pulmonary hypertension
¬ Libman Sach endocarditis – sterile endocarditis (rare!)


What renal complication exists for SLE? What is done for SLE pts?

-Have to do urinalysis on SLE patients for blood and protein in urine as kidney symptoms are litte/non-existant until it is too late!


What can be the presentation of glomerulonephritis in SLE?

λ Proteinuria
λ Urine sediments
λ Urine RBC and casts
λ Hypertension
λ Acute renal failure
λ Chronic renal failure


What neurologic features are seen in SLE?

¬ Depression/psychosis
λ Not always related to disease activity

¬ Migranous headache

¬ Cerebral ischaemia
λ TIAs or stroke

¬ Cranial or peripheral neuropathy

¬ Cerebellar ataxia


What haematological features are seen in SLE?

¬ Lymphadenopathy
λ ~25% of all patients during their course of illness

¬ Leucopenia (low white cells)

¬ Anaemia
λ haemolytic
λ normochromic normocytic

¬ Thrombocytopenia (low platelets)


What intrinsic factors increase susceptability to infection in SLE patients?

-low complement
-impaired cell mediated immunity
-defective phagocytosis
-poor abody response to certain antigens


What extrinsic factors increase susceptability to infection in SLE patients?

-immunosuppressive drugs
-nephrotic syndrome


What screening tests are done for SLE?

¬ Full blood count
¬ Renal function tests including
urine examination
¬ Anti-nuclear antibody (not everyone who has this has SLE)
¬ Anti-double stranded DNA antibodies
¬ Complement levels

Anti-nuclear antibody - positive in >95% of patients, not specific
Anti-dsDNA antibody - specific and varies with disease activity
Anti-Sm - specific but low sensitivity
Anti Ro, anti-La and anti-RNP - may be seen in SLE but may also be seen in other conditions
C3/4 levels - low when disease active, especially renal disease


When should a +ve ANA test be taken seriously?

-this is positive in 95% SLE but also in 20% of normal population and other autoimmune conditions

-only take seriously if other antinuclear abodies of +ve:
When the patient presents with CTD features


Which autoantibody is highly specific for SLE? What does the titre correlate with?

-occurs in 60% of pts with SLE
-titre correlates with overall disease activity


anti-ENA antibodies:
-which is usually assoc. with cutaneous manifestations?
-what else is this assoc. with?

-usually assoc. with anti-La
-secondary sjogrens
-congenital heart block and neonatal LE


anti-ENA antibodies - which is highly specific?

anti-Sm (10-20%)
-neurological involvement assoc.


Which anti-ENA antibody is assoc. with overlap features of sclerodermatous skin lesions, Raynaud’s phenomenon, low grade myositis

-Anti-RNP (30%)


How is SLE activity monitored?

¬ Thorough clinical assessment including BP
¬ Anti-dsDNA level positively correlates with activity
¬ C3/C4 levels negatively correlate with activity
¬ Urine examination including protein, cells and casts
¬ Full blood count
¬ Blood biochemistry


What is the drug treatment for SLE?

-NSAID and simple analgesia


What are anti-malarials used for?

¬ chloroquine and hydroxychloroquine
λ Useful for arthritis, cutaneous manifestations and constitutional symptoms
λ May reduce systemic complications
(everyone is put on hydroxycholoroquine)


What is steroid treatment used for?

λ Very useful but long term use is associated with numerous side-effects
λ Variable doses for different manifestations
¥ small doses (prednisolone <15 mg/d) for skin rashes, arthritis and serositis
¥ moderate doses (0.5 mg/kg/d) for resistant serositis, haematologic abnormalities and class V GN
¥ high doses (1mg/kg/d or IV) for severe/resistant haematologic changes, diffuse GN and major organ involvement


What immunosuppression is used? what are the complications of this?

¥ Azathioprine
¥ Cyclophosphamide
¥ Methotrexate
¥ Mycophenolate mofetil

¬ All can cause bone marrow suppression
¬ All can cause increased susceptibility to infection
¬ Potentially teratogenic


What biologics are used for SLE?

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


What is the treatment in general for SLE:
-mild disease
-moderate disease
-severe disease

Mild - skin disease:
-topical steroids

Moderate - arthritis/some types organ involvement:
-Oral steroid

Severe organ disease:
-IV steroids


Antiphospholipid syndrome:
-what is this characterised by?

¥ Positive anti-cardiolipin (anti-phospholipid) antibodies and / or lupus anticoagulant activity and / or anti-beta2-glycoprotein on 2 occasions at least 12 weeks apart.

¥ Arterial / venous thrombosis

¥ Pregnancy loss of with no other explanation 10-34/40 or 3 pregnancy losses with no other explanation <10/40 or 1 pre-term <34/40 because of eclampsia, severe pre-eclampsia or with signs of placental insufficiency
(one of these laboratory and one of these clinical features must be present to make diagnosis – must be interpreted in context)

There may be thrombocytopenia and prolongation of APTT.


Who is affected by antiphospholipid syndrome?

¥ Responsible for 15% of cases of recurrent foetal loss and 20% of recurrent thrombosis in young people

¥ Occurs in young women M:F 1:3.5


Who else can have anti-cardiolipin antibodies?

¥ ~30% people with SLE have anti-cardiolipin antibodies (may occur in other CTDs)

¥ 1-5% healthy population have anti-cardiolipin antibodies


What other manifestations of antiphospholipid syndrome exist?

¥ Superficial thrombophlebitis and livedo reticularis
¥ Mild/moderate thrombocytopenia
¥ Neurological features – migraine , transverse myelitis
¥ Libman-Sacks endocarditis
¥ Catastrophic anti-phospholipid syndrome
⇒ Patient presents with severe cns involvement
⇒ Usually a patient has been on warfarin and then have been taken off it for some reason


What is the treatment for antiphospholipid syndrome?

¥ Thrombosis – lifelong anti-coagulation
¥ Warfarin for anticoagulation
¥ These patients need a higher target INR
¥ In future yrs other newer anticoag. Drugs will take over (rivaroxiban)
¥ Pregnancy loss – aspirin + heparin during pregnancy
¥ Attention to vascular risk factors


what is sjogrens syndrome?

¥ Autoimmune condition
¥ Lymphocyte infiltration of exocrine glands causing xerostomia and keratoconjunctivitis sicca
¥ May be primary or secondary to other autoimmune conditions


What is the classification of 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


What clinical test can be done for sjogrens syndrome?

schirmers test


What are other manifestations of sjogrens?

¥ 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)


What is the peak age and gender preponderance of sjogrens?

¥ Peak age 40-60, M:F 1:9
¥ Serious complications very rare compared with other CTDs

¥ Prevalence ~1-3%
¥ Most undiagnosed


What is the treatment of sjogrens?

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


What is systemic sclerosis?

Systemic sclerosis (SSc) is a multisystem autoimmune disease in which there is increased fibroblast activity resulting in abnormal growth of connective tissue. This causes vascular damage (vasculopathy – raynaud’s syndrome) and fibrosis. Fibrosis (excess deposition of collagen in skin and internal organs) occurs in skin, the gastrointestinal (GI) tract and other internal organs.


What are the two types of systemic sclerosis?

(previously known as CREST – Calconosis, Raynaud’s, Esophageal dysmotilty, Sclerodactyly, Telangiectasia)
¥ Features as above BUT pulmonary hypertension in ~30%
¥ Other systemic features may rarely occur
¥ Associated with anti-centromere antibodies

¥ Skin changes within 1 year of Raynaud’s
¥ Truncal and acral skin involvement
¥ Early significant organ involvement (kidneys, lungs, gut, muscle, joints, heart)
¥ Anti-Scl-70 antibodies

Raynauds phenomenon is a common early finding and it is unusual to have the condition without Raynauds.

Cutaneous involvement has 3 phases: (1) oedematous, (2) indurative, and (3) atrophic. Skin becomes thickened and tight.

Features are divided into major and minor:

Major: includes centrally located skin sclerosis that affects the arms, face, and/or neck

Minor: includes sclerodactyly and atrophy of the fingertips and bilateral lung fibrosis.

A diagnosis is made when a patient has 1 major and 2 minor features.


What signs are seen in the hand with systemic sclerosis?

o Swelling (non-pitting oedema) of fingers and toes - a common early sign; digits may look sausage-like; hand movement may be limited.
o Skin becomes hard and thickened - this may limit joint movement or cause joint contractures; in the fingers, this is known as sclerodactyly.
o Swelling and sclerosis reduce hand movements, so patients may be unable to make a fist, or to place the palmar surfaces together - the 'prayer sign'.
o Fingertips may have pitting, ulcers or loss of bulk from finger pads.
o Raynaud's phenomenon. This is the most common symptom and is present at some point in 90% of cases. Raynaud's phenomenon with puffy fingers is thought to be a cardinal sign of likely SSc.[5] 


What is calcinosis?

nodules or lumps of chalky material which may break through the skin.


What signs are seen in the face and mouth in systemic sclerosis?

o Tightening of facial skin.
o Tight lips (microstomia) - can make dental hygiene difficult.


What general skin signs are seen in systemic sclerosis?


Salt and pepper' appearance of skin, due to areas of hypopigmentation and hyperpigmentation.

Dry or itchy skin; reduced hair over affected skin areas.


What GI manifestations are seen in systemic sclerosis?

¥ Oesophageal hypomobility
¥ Small bowel hypomobility, bacterial overgrowth
¥ Pancreatic insufficiency
¥ Rectal hypomobility


What respiratory manifestations are seen in systemic sclerosis?

¥ Interstitial lung disease
¥ Pulmonary hypertension
¥ Chest wall restriction


What renal manifestations are seen in systemic sclerosis?

¥ Hypertensive renal crisis
¥ Ischaemic


What cardiovascular manifestations are seen in systemic sclerosis?

¥ Raynaud’s with digital ulceration
¥ Atherosclerotic disease
¥ Hypertensive cardiomyopathy


What is the peak age and M:F preponderance of systemic sclerosis?

¥ Peak age 25-55
¥ Prevalence 1:10,000
¥ M:F 1:4


What treatments exist for systemic sclerosis?

¥ Calcium channel blockers - raynauds
¥ Prostacyclin (Iloprost) - raynauds
¥ ACE inhibitors - renal involvement
¥ Prednisolone
¥ Immunosuppression - interstitial lung disease
¥ Bosentan, Sildenafil - raynauds
¥ PPI for reflux


What is mixed connective tissue disease?

defined by various combinations and minor and major criteria:

Major Criteria

¥ Severe myositis.
¥ Pulmonary involvement.
¥ Raynaud's phenomenon.
¥ Swollen hands observed.
¥ Sclerodactyly.
¥ Anti-U1-RNP >1:10,000.

Minor Criteria

¥ Alopecia
¥ Leukopenia
¥ Anaemia
¥ Pleuritis
¥ Pericarditis
¥ Arthritis
¥ Trigeminal neuralgia
¥ Malar rash
¥ Thrombocytopenia
¥ Mild myositis
¥ History of swollen hands


What autoantibodies are found in SLE?

ANA, Anti-DNA binding, Anti-Sm, Anti-Ro and La


What autoantibodies are found in sjogrens syndrome?

Anti-Ro and La


What autoantibodies are found in systemic sclerosis?

Anti- centromere, Anti-scl-70


What auto-antibodies are found in mixed connective tissue disease



What auto-antibodies are found in polymyositis?



What auto-antibodies are found in anti-phospholipid syndrome?

Anti-cardiolipin antibodies, lupus anti coagulant