Connective Tissue Disease

Question 1

What is the epidemiology of systemic lupus erythematous and what are the risk factors?

Answer 1

Female to male 9:1

Commoner in Afro-Caribbean, Hispanic American, Asian and Chinese patients
Common in people below 50y/o

Genetic, environmental, hormonal and immunological factors

Question 2

What is systemic lupus erythematous?

Answer 2

Systemic autoimmune condition that can affect almost any part of the body

Immune complexes form and precipitate causing further immune response

Question 3

Describe the pathogenesis of systemic lupus erythematous

Answer 3

Loss of immune regulation
Increased and defective apoptosis
Necrotic cells release nuclear materials which act as auto-antigens
Auto-immunity results from exposure to nuclear and cellular auto-antigens
B and T cells are stimulated
Autoantibodies are produced
Complexes of antigens and auto-antibodies form and circulate
Deposition of immune complexes in basement membrane
Activation of complement which attracts leucocytes which release cytokines
Cytokine release perpetuates inflammation which causes necrosis and scarring

Question 4

What are the clinical presentations of SLE?

Answer 4

EULAR/ACR 2019 SLE classification criteria
ANA must be positive (anti-nuclear antibody)
Score >10

Special Notes:
*Rash spares nasal fold (butterfly/coin/ring)
*Acute pericarditis has an ECG presentation - Diffuse concave upward ST segment elevation in most leads, PR depression in most leads (may be subtle) and sometimes notching at the end of the QRS complex
*Renal (Proteinuria high in 24 hrs, biopsy proven nephritis, red cell casts in biopsy)

Question 5

What is the difference between acute cutaneous lupus erythematous and subacute cutaneous lupus erythematous?

Answer 5

Presentation for acute: butterfly rash sparing nasolabial fold
Presentation for subacute: ring-shaped rash with scaly border and lighter centre

Question 6

What is the importance and limitations of serologic testing in SLE?

Answer 6

Anti-nuclear antibody (ANA) is positive in low level in a portion of healthy population, but high conc. does indicate disease

Anti-dsDNA antibody is present in 60% of lupus patients (MOST SPECIFIC for SLE - titre rises with disease severity) –> related to kidney functions

Antiphospholipid antibodies - one of the criteria for SLE diagnosis, associated with vascular thrombosis and recurrent miscarriages

Complement - clinically useful test, high in earlier stages (eg. during clinical flare)

Anti Ro antibody - Neonatal lupus

Anti Smith - highly specific for lupus, but only present in a portion of lupus patient

Question 7

How is SLE managed? (and therapeutic options)

Answer 7

• sun protection measures
• hydroxychloroquine (can help with symptoms, some protective effect against systemic involvement)
• minimise steroid use (only short courses)
• monitor disease activity using SLEDAI score

Question 8

Why might complement be low in serological testing of lupus?

Answer 8

Complement proteins get used up in deposition of immune complexes in liver

Question 9

How would compromised kidneys present serologically?

Answer 9

In early stages, proteins are abnormal but U&C would be normal (when U&C are affected, kidney is quite severely affected)

Question 10

Is antimicrobial prophylaxis required when taking potent immunosuppression drugs for SLE?

Answer 10

MMF does not require prophylaxis, whereas CYC would require some regular prophylaxis

Question 11

What are connective tissue diseases?

Answer 11

Conditions associated with spontaneous overactivity of the immune system

Specific auto-antibodies are present

They evolve over months to years sometimes leading to organ failure and death

Question 12

What are the core clinical presentations involved in autoimmune diseases of connective tissues?

Answer 12

White fingers
Joint pain and swelling
Muscle pain/weakness
Rash
Red/painful eye
SOB
Abnormal blood results
Painful/uncomfortable mouth

Question 13

Is fibromyalgia common in autoimmune disease?

Answer 13

yes

Question 14

Are autoimmune diseases more common in women or men?

Answer 14

women

Question 15

What are some signs of autoimmune diseases of joints?

Answer 15

Arthralgia (muscle stiffness)/arthritis
Muscle pain/weakness
Photosensitivity

Raynaud’s phenomenon - fingers turn white in cold weather (vasoconstriction)
*Primary (w/o underlying autoimmune disease, young) and secondary (w/ autoimmune disease - structural change in endothelium, older) Raynaud’s

Sicca symptoms (dryness) in absence of other causes
Dysphagia
SOB
Neurological symptoms
Recurrent miscarriage/pregnancy complications
Unprovoked thrombosis in youngsters

Question 16

Which antibody is the general screeninig test for all autoimmune diseases?

Answer 16

ANA antibody
Only +ve test of this would result in test for other antibodies

Question 17

What is systemic sclerosis?

Answer 17

Condition characterised by skin thickening
90% of patients present with Raynaud’s

2 types:
Diffuse cutaneous vs. Limited cutaneous (skin involvement only below elbows/knees of extremities)
- Both types can have involvement of other organs

Question 18

What is pathogenesis of SSc?

Answer 18

Vascular/Endothelial alterations due to genetic predisposition –> Chronic inflammation –> persistent myofibroblast existence –> vasculopathy and tissue fibrosis in lung/skin/heart

Myofibroblast contributes to ECM formation and produces vasoconstrictors under normal conditions, this function can lead to unwanted thickening of tissues under pathology

Question 19

What are symptoms of limited cutaneous SSc? (CREST abbrev.)

Answer 19

Calcinosis
Raynaud’s - spasm of blood vessels in response to cold/stress
Esophageal dysfunction - acid reflux/decreased motility
Sclerodactyly - thickening and tightening of the skin on fingers and hands
Telangiectasias - dilation of capillaries causing red marks on surface of skin

Question 20

What are other associated symptoms in systemic sclerosis?

Answer 20

Pulmonary fibrosis
Pulmonary hypertension (would be rather late-stage, especially associated with limited cutaneous)
Renal crisis

Question 21

What are antibodies relevant in systemic sclerosis?

Answer 21

Antinuclear antibodies (ANA) are positive in most patients with systemic sclerosis. They are non-specific.

Anti-centromere antibodies –> limited cutaneous systemic sclerosis.

Anti-Scl-70 antibodies –> diffuse cutaneous systemic sclerosis and more severe disease

Question 22

How to manage systemic sclerosis and its symptoms (eg. Raynaud’s, upper GI reflux, anorectal disease, lung fibrosis, renal crisis)?

Answer 22

For limited, start with vascular therapy
For diffuse, start with both vascular and immunosuppression
For both, manage organ comorbidities

*Scleroderma renal crisis - control blood pressure

Question 23

What is Sjogren’s syndrome?

Answer 23

B cell disease
Lymphocytic infiltration of exocrine glands

Dry eyes/eye lids(keratoconjunctivitis sicca) for over 12 weeks
Dry mouth at night
Hard to swallow dryer foods
Vaginal dryness for pre-menopausal women

Most common in 45-55 age group

Question 24

How does Sjogren’s syndrome present?

Answer 24

Blepharitis
Salivary gland inflammation –> dry mouth (lack of saliva)
Tooth decay (due to lack of saliva)
Lymphoma (bc this is B cell disease)
Dry cough
Multisystem involvement - eg. Renal tubular acidosis (protons reabsorbed in distal tubule; metabolic acidosis)

Although is sicca is very common in Sjogren’s patients, not all patients with sicca have Sjogren’s syndrome

Question 25

How to diagnose Sjogren’s?

Answer 25

ANA usually +ve
Anti-Ro and Anti-La are very specific to Sjogren’s, but not so sensitive
*Negative antibody –> salivary gland ultrasound + biopsy

Usually high ESR, plasma viscosity, IgG
Cytopaenias

Question 26

How to treat Sjogren’s?

Answer 26

Tackle symptoms:
Artificial tears and salivary supplements; vaginal lubricant
Strong fluoride toothpaste
HCQ for fatigue and arthralgia
Immunosuppression for major organ involvement

Question 27

What is mixed connective tissue disease?

Answer 27

a rare autoimmune disease diagnosed when a specific antibody known as anti-U1-ribonucleoprotein is present (and dsDNA -ve), and there are features of at least two connective tissue diseases, including systemic lupus erythematosus, systemic sclerosis, polymyositis, dermatomyositis, and rheumatoid arthritis

Question 28

What is antiphospholipid antibody syndrome?

Answer 28

Presence of antiphospholipid antibodies on 2 occasions 12 weeks apart
*anti-cardiolipin antibody (IgG/IgM), lupus anticoagulant, beta-2 glycoprotein

“sticky blood syndrome” - more prone to blood clot

Question 29

What are primary and secondary antiphospholipid antibody syndromes?

Answer 29

Primary - no other underlying autoimmune disease
Secondary - usually seen in 20% of patients with lupus

Question 30

How to treat antiphospholipid antibody syndromes?

Answer 30

lifelong anticoagulation with warfarin if thrombosis

Pre-pregnancy (warfarin is teratogenic, so) - LMWH and aspirin continue right into the post-partum period

If presence of antibodies but no manifestations, management unclear

Question 31

How does livedo reticularis present?

Answer 31

a cutaneous physical sign characterized by transient or persistent, blotchy, reddish-blue to purple, net-like cyanotic pattern