Connective Tissue Disorders

Question 1

What is SLE?

Answer 1

Multi-systemic autoimmune inflammatory disease.
Antibodies are made against a variety of autoantigens (ANA) which form immune complexes. Inadequate clearance of these immune complexes results in a host of immune responses which cause tissue inflammation and damage.

Question 2

Prevalence of SLE? Average age of diagnosis?

Answer 2

90% are women of child bearing age
49 average age
Affects 1 in 1000
10x more common in African Caribbean’s

Question 3

What factors play a role in the development of SLE?

Answer 3

Genetic, hormonal and environmental.

Environmental trigger = damages cells (Epstein-Barr virus) or UV light

Hormones = premenopausal women are most commonly affects (oestrogen link)

Genetics = Monozygotix twins have high concordance (25%)
Genome studies: HLADR2, DR3, C4 null allele involvement.

Question 4

What is the pathophysiology of SLE?

Answer 4

SLE is an autoimmune condition characterised by loss of self tolerance to self-antigens.
Exposure of immune system to cellular remnants from apoptotic cells - remnants feature self antigens and are not effectively removed and carried to the lymphoid tissues.

Remnants taken up by APCs and presented to T cells leading to B lymphocyte activation and antibody production.

Lymphocytes respond to self-antigens and leads to circulating autoantibodies and immune mediated damage to our own cells.

Question 5

Examples of clinical features of SLE?

Answer 5

1. Dermatological - rashes such as malar rash, generalised erythema, discoid rash, scarring alopecia
2. Rheumatological - inflammatory arthritis
3. Nephrology - nephritis, nephrosis and renal failure
4. Cardiological - pericarditis, acute MI
5. Respiratory medicine - pleural effusion, pulmonary embolism
6. Neurological - numerous including seizures, psychosis
7. Oral - ulcerations
8. Obstetrics - recurrent abortions and abnormal clotting
9. Gastro symptoms

Question 6

What are the 11 clinical criteria for SLE? How many of these need to be present for a diagnosis of SLE to be made?

Answer 6

> 4 criteria needed and 1 lab and 1 clinical criteria needed or biopsy showing positive ANA or anti-DNA antibodies.

1. Malar/rash - butterfly rash occurs in up to 50%, photosensitive rash
2. Discoid rash: erythematous raised patches with adherent keratotic scales and follicular plugging (with or without scarring)
3. Non scarring alopecia
4. Oral or nasal ulcers - as mucosa is affected
5. Arthritis: involving 2 or more joints with >30mins morning stiffness - symmetrical arthritis, can be deforming. Non-erosive.
6. Serositis: lung (pleuritis as membrane around lungs inflames), pericarditis (inflammation around the heart)
7. Urinalysis: proteinuria due to renal disorders
8. Neurological features: seizures, psychosis, myelitis, acute confused state
9. Haemolytic disorders
   → anaemia if RBC targeted - coombs positive
   → leucopenia if WBC targeted
   → thrombocytopenia if platelets targeted
10. Antinuclear antibodies
    → Sensitive but not specific as other diseases cause ANA too
11. Other autoantibodies
    → Anti smith - specific for SLE
    → Anti-dsDNA - specific more SLE
    → Anti-phospholipid antibody - can also occur in other diseases

Question 7

What are the 6 lab criteria which can help diagnose SLE?

Answer 7

1. Positive ANA (+ in 95%) - positive in 5% normal pop too and positive in other diseases so it is not diagnostic for lupus.
2. Anti-dsDNA - highly specific for SLE but only positive in 60% cases
3. Anti-smith antibodies present - specific for SLE
4. Anti-phospholipid Abs present
5. Low complement
6. Positive direct Coombs test

Question 8

What other autoimmune conditions can SLE be associated with?

Answer 8

Sjorgens (15-20%)

Autoimmune thyroid disease (5-10%)

Question 9

What are some drugs which can induce lupus?

Answer 9

• isoniazid
• hydralazine
• procainamide
• chloropromazine
• phenytoin
• quinidine

Question 10

Management of SLE?

Answer 10

• Education and support to patients
• UV protection sunscreen
• Hydrocholoroquine
• Topical steroids for skin flares
  Smoking cessation

Question 11

What drugs are used to induce remission in SLE?

What is used for maintenance therapy in SLE?

Answer 11

Induce remission: prednisolone and hydroxychloroquine

Maintenance:

• NSAIDS & hydroxychloroquine for joint and skin problems
• Mexotrexate, mycophenate and azathioprine as steroid sparing agents
• Hydroxychloroquine for mild flares
• DMARDs and mycophenate for moderate flares
• High dose steroids, mycophenate, rituximab & cyclophosphamide for severe flares

Question 12

What is Raynaud’s phenomenom? What are the 3 changes which occur?

Answer 12

Peripheral digit ischaemia due to paroxysmal vasospasm precipitated by cold or emotion - typically ears, nose, fingers and toes.

• Pale: ischaemia - vasoconstriction where there is lack of blood supply to fingers, toes, nose
• Blue: deoxygenated/hypoxia
• Red: reactive hyperaemia - vasodilation and burning sensation

Question 13

What is the difference between primary and secondary raynauds?

Answer 13

Primary affects fingers and toes symmetrically and usually no underlying damage to arteries. It is common in pregnancy and occupations such as drilling.
Can be caused by stress, cold, nicotine, caffeine, or medication which affect the SNS
Secondary: affects fingers and toes asymmetrically and progressive severity due to underlying damage to arteries. Is associated with connective tissue disorders.

Question 14

Which is the most common form of EDS?

Answer 14

Hypermobile (hEDS)

Question 15

What is EDS type 4?

Answer 15

EDS type 4 is mainly a vascular problem with spontaneous rupture and aneurysm formation in early adulthood - characteristically affects large arteries within the abdomen and aorta

Question 16

What is marfans?

What are the characteristic changes?

Answer 16

Marfan syndrome is one of the most common connective tissue disorders of the body where there is faulty collagen leading to skeletal changes.

• being tall
• abnormally long and slender limbs, fingers and toes (arachnodactyly)
• heart defects
• lens dislocation– wherethe lensof the eye falls into an abnormal position

Question 17

Name 4 auto immune connective tissue diseases

Answer 17

1. Systemic lupud erythematous (SLE)
2. Systemic sclerosis
3. Primary Sjorgen’s syndrome
4. Dermatomyositis / Polymyositis

Question 18

What is systemic sclerosis?

What antibody do 90% of patients have?

Answer 18

Systemic sclerosis is a rare, chronic autoimmune rheumatic disorder characterised by degenerative changes and scarring in the skin, joints, and internal organs and by blood vessel abnormalities. The cause of systemic sclerosis is unknown.

90% are ANA positive, 30-40% have anticentromere antibodies.

Question 19

What are the features of limited systemic sclerosis? (CRESTP)

Answer 19

Calcium deposits under skin
Raynauds
Oesophageal reflux, strictures and dysphagia due to dilated oesophagus
Sclerodactyly - tight skin around fingers
Telangectasia due to dialted capillaries
Pulmonary arterial hypertension - can be life threatening

Question 20

Treatment for raynauds

Answer 20

Physical protection and warmth

Vasodilators - nifedipine, ilioprost, sildenafil

Question 21

How do we treat the features of systemic sclerosis?

Answer 21

- Raynauds
→ physical protection
→ Vasodilators (nifedipine, iloprost, sildenafil)
→ Fluxetin
→ Sympathectomy
- Gastro-oesophageal reflux
→ PPIs for life
- Prevention of renal crisis
→ ACE inhibs
- **Early detection of pulmonary HTN**
→ Annual echocardiogram & pulmonary function tests
- Treatment of skin oedema
→ No treatment
→ Cytotoxic drugs
→ Autologous stem cell transplant

Question 22

What is sjorgens syndrome?

Answer 22

A chronic inflammatory autoimmune disorder which can be primary (disease in it’s own right) or secondary (associated with CTD, eg. RA, SLE, systemic sclerosis)

Question 23

Does sjorgens commonly affect men or women

Answer 23

More women

Question 24

What is the pathophysiology of sjorgens

Answer 24

There is lymphocytic infiltration and fibrosis of exocrine glands, leading to a loss of secretory cells especially in lacrimal and salivary glands.

Question 25

Clinical features of sjorgens

Answer 25

Decreased production of tears (dry eyes)
Decreased salivation
Difficulty swallowing and cracking of tongue
Parotid swelling
Vaginal dryness, dry bough, dysphagia
Rash
Arthritis
Vasculitis
Strong association with gluten sensitivity
Renal tubular acidosis

Question 26

Lab features of sjorgens?

Answer 26

• Positive ANA
• Positive RF
• Positive Ro and La
• Negative DS DNA
• Raised immunoglobulins
• Abnormal salivary glands on ultrasound
• Sialadenitis on lip biopsy

Question 27

Management for sjorgens

Answer 27

Tear and saliva replacement
Hydroxychloroquine for fatigue, myalgia, arthralgia, rashes
Corticosteroids and immunosuppressants for extra-glandular disease

Question 28

What is dermatomyositis / polymyositis?

Answer 28

Autoimmune disease where the body is attacking it’s own skin and muscle.

Question 29

Pathophysiology of dermatomyositis?

Answer 29

• Immune cells confuse normal muscle and skin proteins with foreign antigens (molecular mimicry)
• Immune cells activate complement cascade leading to formation of MAC and accumulation in the capillaries → destruction of capillary walls and microinfarctions
• Damage to blood vessels leads to less oxygen supply to the muscles and skin causing ischaemia.
• Exact triggers are unknown but genetic and environmental factors (HLADR3 and HLADR5 are associated with someone developing dermatomyositis after exposure to coxsackie virus or specific tumour antigens (breast, lung, ovarian))
• Myositis may be present as paraneoplastic phenomenom, commonly from lung, pancreatic, ovarian or bowel malignancy = Screen for cancers.
• Muscle weakness may also cause dysphagia, dysphonia or respiratory weakness.

Question 30

Symptoms / signs of dermatomyositis?

Answer 30

Macular rash (over shoulders and back)
Lilac purple (heliotrope) rash on eyelids and oedema
Gottron papules on elbows and knees
Photosensitive rashes

Question 31

Management of dermatomyositis?

Answer 31

Prednisolone
Immunosuppressives and cytotoxics in resistant cases
Hydroxychloroquine for skin disease
Sun avoidance and protective clothing