Rheumatology: Rheumatoid Arthritis & Systemic Lupus

• What is the aetiopathogenesis of rheumatoid arthritis (RA)?

  -Unknown.

  
  

  -Probably results from a combination of genetic and environmental factors leading to breakdown of immune tolerance
• What are the other autoimmune diseases as well as RA associated with in terms of aetiopathogenesis?

  
• What are auto-antibodies?

  Antibodies produced by the immune system that mistakenly target and attack the body's own tissues.
• What are the auto-antibodies present in RA?

  -RF (rheumatoid factor) present in RA, but non-specific

  -95% specific to RA is the anti-CCP(anti-citrullinated protein antibodies)
• What are the auto-antibodies present in systemic lupus erythematosus (SLE)?

  ANA (antinuclear antibodies), specifically dsDNA antibodies
• What is the auto-antibody present in progressive systemic sclerosis (PSS)?

  Scl 70
• What are the auto-antibodies present in Sjogren's syndrome?

  ENA (extractable nuclear antigen) antibodies (Ro, La) as well as RF
• What are rheumatoid factors?

  Auto-antibodies which target and attack IgG antibodies or IgM produced by the body itself.

  
  

  This leads to inflammation, joint damage etc.
• How prevalent is RA?

  1% of population is affected with a female predisposition in the ratio F:M being 2.5:1
• What is RA?

  -Symmetrical polyarthritis which often starts in hands and wrists.

  
  

  -It's a systemic disease which may have extra-articular movement.

  
  

  -This means RA doesn't only affect joints but also other organs and systems in the body.
• What are the symptoms and signs of RA?

  Symptoms:

  Pain

  Swelling

  Morning stiffness

  Malaise (fatigued)

  Non-articular symptoms

  Signs:

  Swelling

  Warmth

  Tenderness

  Limited movement

  Deformity
• What can advanced RA look like?

  -Boutonniere deformity of thumb (z-shaped)

  
  

  -Ulnar deviation of metacarpophalangeal joints

  
  

  -Swan neck deformity of fingers

  
• What does the anatomy of a RA joint look like compared to a healthy joint?

  In the RA joint:

  1.The synovial membrane is thickened

  2.There's an overgrowth of the synovia sites (pannus)

  3.Marked influx of inflammatory cells; each of those producing cytokines which stimulates inflammation

  4.Osteoclasts get activated to eat away at the bone

  5.Cartilage overlying the bone is getting damaged and removed

  6.Swelling of the overlying soft tissues is caused; there's damage to the ligaments and structures supporting the joints

  7.The joint itself also gets damaged

  
• What does the pannus look like histologically?

  
• What are some of the complications of RA?

  Rheumatoid nodules

  
  

  Tendon rupture

  
  

  Normochromic, normocytic anaemia

  
  

  Nerve entrapment e.g. median nerve

  
  

  Vasculitis

  
  

  Atlanto-axial subluxation

  
  

  Eye complications

  
• How are patients with RA treated?

  Analgesia (e.g. NSAIDs (non-steroidal anti-inflammatory drugs) reduce pain and swelling)

  DMARDs (disease-modifying antirheumatic drugs) especially methotrexate; hydroxychloroquine for mild to moderate

  TNFa (tumour necrosis factor-alpha) blocker e.g. Infliximab, Etanercept

  Anti-B cell monoclonal ab e.g. rituximab
• What is the relevance of RA to dentistry?

  Hand deformity - oral hygiene, blister packs

  
  

  Carpal tunnel syndrome

  
  

  Atlanto-axial subluxation during GA

  
  

  TMJ dysfunction

  
  

  Sjogren's syndrome

  
  

  Anaemia

  
  

  Complications of systemic treatment
• What is Sjogren's syndrome?

  An autoimmune disease which can cause oral and ocular dryness.

  
  

  It can either be a primary disease (dry eyes, mouth, vagina, etc.) or it can be secondary to other autoimmune diseases (e.g. RA, PSS, SLE)
• What is the incidence of Sjogren's syndrome and who is most likely to get it?

  It's quite rare but it's much more common in females (F>M 9:1) with 2 peaks of onset: mid 30s and then postmenopausal 45-60 due to reduction is oestrogen
• What are the symptoms of Sjogren's syndrome?

  Sicca symptoms (95%): dryness of mouth, eyes, skin, vagina

  Excessive fatigue (75%)

  Arthralgia - pain in joints without joint inflammation.

  Myalgia - muscle pain/aching

  Dental caries

  Loss of teeth

  Candida

  Swollen salivary glands

  Lacrimal glands

  
• If you have Sjogren's syndrome, what is there also an increased risk of?

  Lymphoma/MALToma (mucosa-associated lymphoid tissue)

  
  

  Have to look out for B cell lymphoma, mucosa-associated lymphoid tissue
• What investigations are required in order to diagnose Sjogren's syndrome?

  -Measure salivary flow, whether it's stimulated or unstimulated.For stimulated parotid flow, normal is >0.4ml/minFor unstimulated whole salivary flow, normal is >0.2ml/min

  -Schirmer test

  -Do bloods:FBC, inflammatory markers, auto-antibodies Ro and La, others as indicated

  Ultrasound(has largely replaced sialography & scintigraphy)

  Labial gland biopsy

  
• What is the relevance of Sjogren's syndrome to dentistry?

  Xerostomia

  Dental caries

  Loss of teeth

  Candida

  Salivary gland enlargement

  Complications of systemic treatment
• What are the variants of lupus erythematosus?

  Discoid lupus (DLE)–scarring skin lesions/oral (affects either just skin or just mouth)

  Subacute cutaneous (SCLE)-rash, systemic disease (predominantly affects skin but has some features of systemic disease)

  SLE(predominantly systemic but might include skin rash/oral lesion)

  Anti-phospholipid syndrome(sticky blood, prone to clots)

  Drug-induced lupus

  
• What is the aetiology of SLE?

  SLE is a multi-system disease

  
  

  Pathology- widespread vasculitis (immune system mistakenly attacks blood vessels) of capillaries, arterioles and venules

  
  

  Aetiology- genetic, complement deficiency

  
  

  Triggers- UV light, infection, or even drugs
• What are cerebral micro-infarcts?

  Blood vessels in the brain affected.

  
  

  White spots in the brain present

  
• What investigations would we undertake in diagnosing lupus?

  In the bloods, you're looking for raised ESR, ANA, positive RF etc.

  
• What is lupus nephritis?

  Connective tissue disorder resulting from an abnormal immune system

  
  

  Foamy urine = increased protein in urine

  
  

  Brownish urine due to blood present

  
  

  Elevated creatine in the blood

  
  

  High bp

  
  

  Oedema of feet, lower legs and eyelids.

  
  

  5% of patients with SLE will develop some degree of renal involvement

  
• What can anti-phospholipid syndrome lead to?

  Increased tendency to clotting

  
  

  Venous thrombosis

  
  

  Arterial thrombosis

  
  

  Recurrent foetal loss

  
  

  Thrombocytopenia - low platelet count

  
  

  Livedo Reticularis - net-like pattern on skin due to change in blood flow affected small blood vessels in the skin.
• What is the relevance of lupus erythematosus to dentistry?

  Oral ulceration

  
  

  Complications of systemic treatment

  
  

  Candida

  
  

  +/-Dry mouth (xerostomia)

  
  

  Main differential is lichen planus (you might think the patient has lichen planus, but it's actually an oral manifestation of their lupus)
• What are the subtypes of scleroderma?

  - Systemic fibrosis

  
  

  - Limited systemic / CREST syndrome

  
  

  - Localised to skin - morphoea

  
• What can patients with diffuse systemic sclerosis have?

  Scleroderma - thickening of skin

  
  

  Skin induration - hardening/thickening of skin

  
  

  Flexion Fingers: start to bend in and become claw-like and this starts distally & gradually works its way proximally

  
  

  Digital gangrene may occur

  
  

  Skin may look shiny

  
  

  In terms of facial changes, the patient could develop microstomia and struggle to open their mouth wide

  
  

  Can also have pulmonary fibrosis, diverticula (malabsorption), intimal arterial proliferation (kidney)

  
• What is affected in the more limited systemic disease variations of lupus?

  CREST:

  Calcinosis- calcium deposit in fingertips/soft tissues

  Raynaud's phenomenon- episodes of reduced blood flow to fingers and toes = turn white or blue

  Esophagus (oesophagus)- difficulty swallowing

  Sclerodactyly- thickening and tightening of the skin on the fingers and hands.

  Telangiectasia- dilated blood vessels that appear as red spots on skin, particularly on face and hands

  
• What treatments are there for these patients with lupus, systemic sclerosis, etc.?

  Analgesics

  Glucocorticoids

  Immunosuppressive: cyclophosphamide, azathioprine, mycophenolate mofetil

  Biologics
• How is Raynaud's treated?

  Physical: gloves (heated)

  
  

  Nifedipine: Ca channel antagonist

  
  

  Losartan: angiotensin II antagonist
• What is the relevance of scleroderma to dentistry?

  Microstomia - abnormally Small mouth

  
  

  Widened periodontal membrane

  
  

  Severe sclerodactyly- difficulty with OH

  
  

  Immunosuppression
• What is osteoarthritis (OA)?

  Non-autoimmune degenerative joint disease
• Who is most commonly affected by OA?

  The general population >60yrs old

  There is a 10% genetic predisposition though
• What is the pathogenesis of OA?


  Degenerative disease of cartilage

  
  

  (may be genetic or mechanical insults, or biochemical abnormalities of cartilage)
• Compare and contrast primary OA with secondary OA.

  Primary OA:

  Majority of casesStrong family historyOnset around 50

  Secondary OA:

  Congenital abnormality of jointsStructural disorders in children which can lead to trauma causing OA