11. Rheumatology: rheumatoid arthritis & systemic lupus Flashcards
LOs
autoimmune or not auto-immune disorder?
- Rheumatoid arthritis (RA)
- Sjogren’s Syndrome (SS)
- Systemic lupus erythematosus (SLE)
- Scleroderma
- osteoarthritis
AUTOIMMUNE
- Rheumatoid arthritis (RA)
- Sjogren’s Syndrome (SS)
- Systemic lupus erythematosus (SLE)
- Scleroderma
NOT-AUTOIMMUNE
5. osteoarthritis
- Rheumatoid arthritis (RA)
- Sjogren’s Syndrome (SS)
- Systemic lupus erythematosus (SLE)
- Scleroderma
- aetiopathogenesis of these disorders
- Associated with MHC:
- Immunological associations
1
* Unknown cause
* Combination of genetic and environmental factors leading to breakdown of immune tolerance
2
- strong HLA association
- Rheumatoid Arthritis (RA): HLA-DR4 (more frequent in smokers, 20-40x more risk)
- Systemic Lupus Erythematosus (SLE): HLA-DR3, complement components
- Progressive systemic sclerosis (PSS): HLA-DR3
3
* serology often positive for a variety of autoantibodies
- Histology shows evidence of immune involvement
autoantibodies to know for each autoimmune disease
RA: :
- RF (Rheumatoid factor) non-specific (one of the
most common in RA, but not exclusive to RA,
found in other inflamm + infectious diseases)
- Anti CCP (anti-citrullinated protein antibodies)
95% specific o RA)
SLE: ANA + dsDNA (antinuclear antibodies)
PSS: Scl 70
Sjogren’s: ENA (Ro, La) RF
NOTE
- PSS = progressive systemic sclerosis
- ENA = extractable nuclear antibodies
RHEUMATOID FACTORS
- what are rheumatoid factors?
- what autoimmune disorders is RF found in?
1
- autoantibodies directed to IgG antibodies
- can be IgG or IgM
- May be any isotype but is directed to Fc IgG
2
* RA 80%
* Sjogren’s 70%
* Cryoglobulinaemia >90%
RHEUMATOID ARTHRITIS clinical features
- % of pop
- F:M
- what is it?
- symptoms
- signs
1
1% population
2
F:M 2.5:1
3
- Symmetrical polyarthritis often starts in hands and wrists
- Systemic disease which may have extra-articular involvement
4
Symptoms
~ pain
~ swelling
~ morning stiffness
~ malaise
~ non-articular symptoms
5
Signs
~ Swelling
~ warmth (erythema)
~ tenderness
~ limited movement
~ deformity
IMAGE 1
- early stage of RA
- erythema over knuckles
- swelling - 2nd and 3rd joints
- otherwise they look relatively normal
IMAGE 2
- advanced rheumatoid changes
- fingers pointing outwards (ulnar drift)
- MCP swelling
- z shapes thumb
IMAGE 1
- dislocation on sole of feet
IMAGE 2
- toes are no longer able to touch ground
ANATOMY OF RA JOINT VS HEALTHY JOINT
HEALTHY JOINT
- normal synovial membrane
- lined by synoviocytes
- wide joint space
RA JOINT
- thickening of synovial membrane
- overgrowth of synoviocytes
- influx of inflamm cells
- each of these prod cytokines - stimulating inflam
- forming planus
- panus activates osteoclast to eat away at bone
- this removes + damages’ cartilage overlying the bone
- causes inflam of overlying soft tissues
- damages ligaments and structures supporting itself
- damages joint itself
SUMMARY
*Granulation tissue forms at the edges of the synovial lining (pannus)
* The synovium thickens (pannus)
* Then Complement activation and release of destructive enzymes occurs
*Cytokines and chemokines attract and accumulate immune cells, i.e. activated Tand B cells, monocytes and macrophages in the joint space
* Cytokines stimulate inflammation
* Panus activates osteoclasts to eat away at bone
*Osteoclast production results in:
~ degradation of bone tissue
~ remove + damages’ cartilage
overlying the bone
~ ligaments and structures
supporting itself being damaged
~ joint itself being damaged
- loss of cartilage
- loss of bone
Complications of RA
§ Rheumatoid nodules
= inflamm in subcutaneous tissues = same type of
inflamm that occurs in plannus
- can occur, hands forearm, lungs, etc
§ Tendon rupture
- leads to subluxation
§ Normochromic, normocytic anaemia
§ Nerve entrapment e.g. median nerve
- (damage at writs causes this)
§ Vasculitis
- inflamed blood vessels
- can lead to gangrene occur
§ Atlanto-axial subluxation
- important for anaesthetists to assess patients
as mishandling of neck can lead to this + spinal
cord entrapment in patients with RA
§ TMJ can be affected
§ Eye complications
SPLIT PREVIOUS PIC IN 2???
Treatments specific for RA
- Analgesia (e.g. NSAIDs reduce pain and swelling)
- meds can cause comp - bad for kidney, can
cause GI bleeding, iron deficiency) - DMARDs (disease modifying anti rheumatic drugs) especially methotrexate, hydroxychloroquine for mild
to moderate
- can cause infection - TNFa blockade e.g. Infliximab, Etanercept
- Anti-B cell monoclonal ab e.g. rituximab
(patients given aggressive treatment early on to prevent RA comp so patients at higher risk of comp from medicines than RA
Relevance to dentistry
§ Hand deformity – oral hygiene, blister packs
§ Carpal tunnel syndrome
§ Atlanto-axial subluxation during GA
§ TMJ dysfunction
§ Sjogren’s syndrome
- dryness in mouth, eyes, genital tract
§ Anaemia
- relevance = healing capacity, anesthesia
capacity
- type??
§ Complications of systemic treatment
- infection
RA KEY POINTS
- Common autoimmune disease
- The joint complications are not usually seen nowadays due to improved therapy
- Multisystem disease – remember the extra-articular complications
- Remember the DMARD /immunosuppressive treatment may impact your dental care
SJOGREN’S SYNDROME
primary or secondary disease?
can be both
- PRIMARY
~ dry eyes
~ dry mouth
~ dry vagina - SECONDARY (to other autoimmune diseases)
~ rheumatoid arthritis
~ PSS
~ SLE - patients may have over lying autoimmune disorders so it’s harder to distinguish/ may have mix of symptoms
SJOGREN’S SYNDROME
- what is it?
- F:M
- age
- symptoms
- increases risk of what
1
* Autoimmune sialadenitis
2
* F > M (9:1)
3
* 2 Peaks of onset
* mid 30s & postmenopausal 45-60
4
* Sicca symptoms (95%) - Dryness of mouth, eyes, skin, vagina
Dental carries; loss of teeth, candida
* Excessive fatigue (75%), arthralgia & myalgia
* Swollen salivary glands/lachrymal glands
5
* Increased risk of lymphoma/Maltoma
~ B cell lymphoma Mucosal Associated
Lymphoid Tissue
IMAGE 2
- tongue would be sticky if place mirror
- packed with candida - needs to be regularly treated
- lobulated fissured tongue
SJOGREN’S SYNDROME
What Investigations are required?
MEASURE SALIVARY FLOW
- Unstimulated whole salivary flow
(Normal > 0.2 ml/min)
- Stimulated parotid flow
(Normal > 0.4ml/min)
SCHIRMER TEST (measure tear flow)
- Anaesthetise eye first then apply filter paper to lower lid - measure how far moistness travels
- Sjogren’s - moistens less than 5 mm in 5 minutes.
- Normal is ≥15 mm wetting of the paper after 5 minutes
BLOODS
- FBC, inflammatory markers
- Auto antibodies, Ro & La
- Others as indicated
- Ultrasound of salivary glands
(has largely replaced Sialography & Scintigraphy) - Labial gland biopsy – dense focal lymphocytic
infiltrate
SJOGREN’S SYNDROME
Relevance to dentistry
§ Dry mouth - Dental carries, loss of teeth,
candida, periodontal disease
§ risk of lymphomas
§ Salivary gland enlargement
§ Complications of systemic treatment
LUPUS ERYTHEMATOSUS
variants
- Discoid lupus (DLE) – scarring skin lesions /oral (affect just mouth)
- Subacute cutaneous (SCLE) (rash, systemic disease)
- SLE
- Anti-phospholipid syndrome
- Drug-induced lupus (uncommon)
LUPUS ERYTHEMATOSUS
- what is it?
- SLE is a multi-system disease
- patients may be genetically predisposed
- race or families with autoimmune history may be at higher risk
LUPUS ERYTHEMATOSUS
pathology?
– widespread vasculitis of capillaries, arterioles
and venules
LUPUS ERYTHEMATOSUS
aetiology
– genetic, complement deficiency
LUPUS ERYTHEMATOSUS
triggers
– UV light
- infection
- drug induced
LUPUS ERYTHEMATOSUS
investigations
BLOOD
- inflamm markers
* ESR raised
* CRP (normal)
- ANA +
- Double stranded DNA ab+ (specific for systemic lupus)
- RF+
- Complement – reduced
- Skin biopsy
how might the brain be affected
- small vessel vasculitis may occur
- cerebral microinfarcts
lead to:
headaches, dizziness,
behaviour changes,
hallucinations, and even
strokes or seizures
Many people with lupus
experience memory
problems and may have
difficulty expressing their
thoughts
how might the kidneys be affected
lupus nephritis
5% patients with SLE will develop
some degree of renal involvement
This may manifest as:
Foamy urine due to increased
protein in the urine
Brownish urine due to blood in the
urine
Elevated creatinine in the blood
High blood pressure
Swelling (oedema) of the feet,
lower legs and occasionally the
eyelids
5% patients with SLE will develop
some degree of renal involvement
This may manifest as:
Foamy urine due to increased
protein in the urine
Brownish urine due to blood in the
urine
Elevated creatinine in the blood
High blood pressure
Swelling (oedema) of the feet,
lower legs and occasionally the
eyelids
may have renal failure
- one of the causes of fatality in lupus patients
variant = antiphospholipid syndrome
what is it?
(can be part of systemic lupus or just have antiphospholipid syndrome)
- Increased tendency to clotting:
*Venous thrombosis
*Arterial thrombosis
*Recurrent foetal loss
(miscarriage cause)
*Thrombocytopenia
*Livedo Reticularis
Relevance of lupus erythematosus to
dentistry
- Oral ulceration
- Complications of systemic treatment
- Candida (as a result of systemic treatment) (also other systemic treatment effects - hypertension etc)
- +/-Dry mouth
- have something that looks like lichen planus BUT it is really a oral manifestation of lupus
SCLERODERMA
subtypes?
- rare group of diseases (need to be aware of them)
- Systemic fibrosis (Diffuse systemic sclerosis)
~ Lungs
~ Kidneys
~ Gastrointestinal tract: malabsorption
~ Thickening of skin starts distally
+ Endothelial damage ultimately leading
to vasoconstriction
+ Fibroblast activation - Limited systemic/ CREST syndrome
- Localised to skin - morphoea
DIFFUSE SYSTEMIC SCLEROSIS
- antibody?
- what happens
- signs + symptoms?
- how can it affect diff parts of body (eg lungs, kidneys, etc)
1
- Scl 70 antibody
2
- progressive thickening of skin
- becomes injurated with flexion of fingers
- starts distally (tips of fingers/ toes), works it way proximally)
- can cover whole body (usu just limbs)
3
- shiny waxy look to skin
- digital gangrene occuring (loss of blood supply to tips)
- bone loss (due to loss of blood supply)
4
- tightening around mouth
~ can lead to perioral firing + microstomia
- thickening of bowel wall + loss of villi hence malabsorption
- thickening of arterioles in kidney
- thickening in lungs - can lead to pulmonary fibrosis (morbidity?)
hand arteriogram of hand with scleroderma
what can we see?
- loss of blood supply to fingers
skin biopsy, normal vs scleroderma
NORMAL
- loose connective tissue in upper dermis + subcutis
- structures visible:
~ fat
~ inflamm cells
~ sweat glands
~ hair follicles
~ etc
PSS SKIN
- loss of cellularity
- loss of structures
- reduction of blood vessels
- thickened collagen throughout dermis into subcutis
LIMITED SYSTEMIC (CREST SYNDROME)
what does C.R.E.S.T stand for?
(features that would be affected)
- Calcinosis
- Raynaud’s phenomenon
- Oesophagus
- Sclerodactyly
- Telangiectasia
- Calcinosis
~ deposition of Ca in finger tips or soft tissues - Raynaud’s phenomenon
~ reflex spasm of blood vessels to hands + feet - Oesophagus
~ dysmotility
~ loss of peristalsis - Sclerodactyly
~ claw like deformity - Telangiectasia
~ visible on face
CREST: Raynaud’s phenomenon
- reflex spasm of blood vessels to hands + feet
- Reversible skin colour change
~ White to blue to red - Due to Vasospasm
- Induced by cold or emotion
- reflex vasodilatations resulting in erythema + burning hot hands so can go back to normal
- no reflex vasodilatation
- can progress to gangrene
CREST: oesophageal involvement
- dysmotility
- pooling of liquid + solids
CREST: calcinosis
- extrusion of Ca deposits through skin
Treatments (lupus, system sclerosis, Sjogren’s (sometimes))
- Analgesics
- Glucocorticoids
- Immunosuppressive:
~ cyclophosphamide
~ azathioprine
~ mycophenolate mofetil - Biologics
- all of these treatments side effects that you need to be aware of
Treatment of Raynaud’s:
- Physical (gloves)
- Nifedipine (calcium channel antagonist)
- Losartan (angiotensin II antagonist)
(antagonists act as vascular dilators to maintain blood flow)
Relevance to dentistry
- Microstomia
- Widened periodontal membrane
- Severe sclerodactyly – difficulty with OH
- Immunosuppression
OSTEOARTHRITIS
- age
- % genetic predisposition
- pathogenesis
- stimuli
- Primary + secondary
1
* population over 60 yrs
2
* 10% genetic predisposition
3
* degenerative disease of cartilage
4
* mechanical insults
* biochemical abnormalities of cartilage
5
PRIMARY OA:
Majority of cases
Strong family history
Onset around 50
SECONDARY:
Congenital abnormality of joints, structural disorders in children, trauma,
OSTEOARTHRITIS
clinical features
signs
- Pain – worse with use
- Morning stiffness <30 mins
- Disability
Signs
* Swelling – hard and bony
* Crepitus
* Muscle wasting (as painful so less use - important to build muscle)
* Limited movement
* Joint deformity
* Monoarticular occasionally
* Bilat and symmetrical e.g. knees, hands, hips
s
Relevance to dentistry
- Reduced mobility
- Reduced manual dexterity
- TMJ dysfunction
