Autoimmune Disorders and MHC

Autoimmune Disorders

• Four examples of autoimmune disorders:
  • Rheumatoid Arthritis (RA)
  • Sjogren's Syndrome (SS)
  • Systemic Lupus Erythematosus (SLE)
  • Scleroderma

Rheumatoid Arthritis (RA)

• Associated with MHC, specifically HLA-DR4 (70%)
• Auto-antibodies: Rheumatoid Factor (RF) and Anti-Citrullinated Protein Antibodies (Anti-CCP)
• RF binds to Fc receptors on IgG
• 80% of RA patients have RF
• 1% of the population has RA, with a female to male ratio of 2.5:1
• Three clinical features:
  • Symmetrical inflammatory polyarthritis
  • Progressive joint damage and deformity
  • Systemic disease
• Seven criteria for RA diagnosis:
  • Morning stiffness
  • Symmetrical arthritis
  • >3 joints affected
  • Hands arthritis
  • Subcutaneous nodules
  • Rheumatoid Factor (RF)
  • Radiographic changes (Must have at least 3 out of 7 criteria)
• Three symptoms:
  • Pain, swelling, and morning stiffness
  • Malaise
  • Non-articular symptoms
• Five signs:
  • Swelling
  • Warmth
  • Tenderness
  • Limited movement
  • Deformity
• Five occurrences with the hands of an RA patient:
  • Boutonnière deformity (thumb)
  • Ulnar drift (fingers point away from thumb)
  • Z-shaped thumb
  • Swan neck deformity of hands
  • Subluxed MCP joints
• Two pathologies:
  • Chronic inflammatory reaction of the synovium resulting in 'pannus' (granulation tissue)
  • Subcutaneous nodes in skin, pleura, pericardium, and lung
• Seven complications:
  • Rheumatoid nodules
  • Tendon rupture
  • Anemia
  • Vasculitis of blood vessels in skin
  • Nerve entrapment due to damage of wrist (e.g., median nerve)
  • Atlanto-axial subluxation of the neck or TMJ
  • Eye complications due to Sjogren's and episcleritis
• Four treatments:
  • Analgesia (e.g., NSAIDs)
  • DMARDs (immunosuppressive therapy)
  • TNF monoclonal antibodies (e.g., infliximab, etanercept)
  • Anti-B cell monoclonal antibodies (e.g., rituximab)
• Dental relevance:
  • Hand deformity affects oral hygiene
  • Carpal tunnel syndrome (tingling and numbness in hands)
  • Atlanto-axial subluxation during GA (difficulty moving neck)
  • TMJ dysfunction (hard to open mouth)
  • Sjogren's syndrome (elevated levels of caries due to alteration of protein profile and change in composition of saliva)
  • Anemia (lack of red blood cells due to lack of B12; tongue may hurt and ulcers are common)
  • Complications of systemic treatment (e.g., glucocorticoids used on immunocompromised patients may not work, so healing time is increased as immunosuppressed patients have an increased risk of infection and bruising)

Sjogren's Syndrome (SS)

• Chronic immune system disorder
• Two types:
  • Primary: dryness of eyes, mouth, and vagina
  • Secondary: secondary to RA, PSS, and SLE
• Male to female ratio: 1:9
• Two peaks of onset: mid-30s and postmenopausal (45-60)
• Pathology: autoimmune sialadenitis (inflammation of lacrimal and salivary glands)
• Four symptoms:
  • Sicca symptoms (dryness of mouth, eyes, skin, and vagina)
  • Excessive fatigue, arthralgia (joint pain), and myalgia (muscle pain)
  • Swollen salivary glands and lachrymal glands
  • Increased risk of lymphoma or maltoma (B cell lymphoma Mucosal Associated Lymphoid Tissue)
• Three investigations:
  • Schirmer test
  • Ultrasound of salivary glands
  • Labial gland biopsy
• Dental relevance:
  • Dry mouth (dental caries, loss of teeth, candida infections)
  • Salivary gland enlargement
  • Complications of systemic treatment
• Treatment: keep mouth hydrated (Xylitol Chewing Gum for stimulation of Salivary Glands & Flow)

Systemic Lupus Erythematosus (SLE)

• Male to female ratio: 1:9
• Peak onset: 20-40 years
• Autoimmune multi-system disease
• Characterized by arthralgia and skin rashes
• Pathology: widespread vasculitis of capillaries, arterioles, and venules
• Aetiology:
  • Genetic
  • Complement deficiency
• Triggers:
  • UV light
  • Infection
  • Drugs (e.g., slow acetylators and hydralazine)
• Four immunological mechanisms:
  • Polyclonal B cell activation
  • Production of anti-nuclear antibodies (ANA)
  • Impaired T cell function
  • Failure to remove immune complexes
• Five clinical features:
  • Photosensitivity rash
  • Vasculitis with gangrene (loss of blood flow at the tips of fingers)
  • Cerebral micro-infarcts (memory problems and headaches)
  • Lupus nephritis (affects kidney, causing blood in urine, elevated blood pressure, and edema of the feet)
  • Anti-phospholipid syndrome (increased tendency to clotting with venous thrombosis, arterial thrombosis, recurrent fetal loss, thrombocytopenia, and livedo reticularis)
• Five variants:
  • Discoid lupus (DLE)
  • Subacute cutaneous (SCLE)
  • Systemic lupus erythematosus
  • Anti-phospholipid syndrome
  • Drug-induced lupus
• Seven investigations:
  • ESR raised
  • Normal CRP
  • RF increased
  • ANA increased
  • Anemia (normochromic normocytic, haemolytic)
  • Neutropenia, thrombocytopenia
  • Reduced complement
• Three treatments:
  • Antimalarials
  • Prednisolone
  • Immunosuppressive agents
• Prognosis: 95% survive for a maximum of 5 years
• Dental relevance:
  • Oral ulceration
  • Immunosuppression and candidiasis
  • Dry mouth
  • Often mistaken for lichen planus in the oral cavity

Scleroderma (Systemic Sclerosis)

• Three types:
  • Systemic fibrosis (diffuse systemic sclerosis)
  • CREST syndrome (Calinosis, Raynaud's, oesophageal involvement, sclerodactyly, telangiectasia)
  • Morphoea (localized to skin)
• Male to female ratio: 1:3
• Peak onset: unknown

Autoimmune Disorders

• Four examples of autoimmune disorders:
  • Rheumatoid Arthritis (RA)
  • Sjogren's Syndrome (SS)
  • Systemic Lupus Erythematosus (SLE)
  • Scleroderma

Rheumatoid Arthritis (RA)

• Associated with MHC, specifically HLA-DR4 (70%)
• Auto-antibodies: Rheumatoid Factor (RF) and Anti-Citrullinated Protein Antibodies (Anti-CCP)
• RF binds to Fc receptors on IgG
• 80% of RA patients have RF
• 1% of the population has RA, with a female to male ratio of 2.5:1
• Three clinical features:
  • Symmetrical inflammatory polyarthritis
  • Progressive joint damage and deformity
  • Systemic disease
• Seven criteria for RA diagnosis:
  • Morning stiffness
  • Symmetrical arthritis
  • >3 joints affected
  • Hands arthritis
  • Subcutaneous nodules
  • Rheumatoid Factor (RF)
  • Radiographic changes (Must have at least 3 out of 7 criteria)
• Three symptoms:
  • Pain, swelling, and morning stiffness
  • Malaise
  • Non-articular symptoms
• Five signs:
  • Swelling
  • Warmth
  • Tenderness
  • Limited movement
  • Deformity
• Five occurrences with the hands of an RA patient:
  • Boutonnière deformity (thumb)
  • Ulnar drift (fingers point away from thumb)
  • Z-shaped thumb
  • Swan neck deformity of hands
  • Subluxed MCP joints
• Two pathologies:
  • Chronic inflammatory reaction of the synovium resulting in 'pannus' (granulation tissue)
  • Subcutaneous nodes in skin, pleura, pericardium, and lung
• Seven complications:
  • Rheumatoid nodules
  • Tendon rupture
  • Anemia
  • Vasculitis of blood vessels in skin
  • Nerve entrapment due to damage of wrist (e.g., median nerve)
  • Atlanto-axial subluxation of the neck or TMJ
  • Eye complications due to Sjogren's and episcleritis
• Four treatments:
  • Analgesia (e.g., NSAIDs)
  • DMARDs (immunosuppressive therapy)
  • TNF monoclonal antibodies (e.g., infliximab, etanercept)
  • Anti-B cell monoclonal antibodies (e.g., rituximab)
• Dental relevance:
  • Hand deformity affects oral hygiene
  • Carpal tunnel syndrome (tingling and numbness in hands)
  • Atlanto-axial subluxation during GA (difficulty moving neck)
  • TMJ dysfunction (hard to open mouth)
  • Sjogren's syndrome (elevated levels of caries due to alteration of protein profile and change in composition of saliva)
  • Anemia (lack of red blood cells due to lack of B12; tongue may hurt and ulcers are common)
  • Complications of systemic treatment (e.g., glucocorticoids used on immunocompromised patients may not work, so healing time is increased as immunosuppressed patients have an increased risk of infection and bruising)

Sjogren's Syndrome (SS)

• Chronic immune system disorder
• Two types:
  • Primary: dryness of eyes, mouth, and vagina
  • Secondary: secondary to RA, PSS, and SLE
• Male to female ratio: 1:9
• Two peaks of onset: mid-30s and postmenopausal (45-60)
• Pathology: autoimmune sialadenitis (inflammation of lacrimal and salivary glands)
• Four symptoms:
  • Sicca symptoms (dryness of mouth, eyes, skin, and vagina)
  • Excessive fatigue, arthralgia (joint pain), and myalgia (muscle pain)
  • Swollen salivary glands and lachrymal glands
  • Increased risk of lymphoma or maltoma (B cell lymphoma Mucosal Associated Lymphoid Tissue)
• Three investigations:
  • Schirmer test
  • Ultrasound of salivary glands
  • Labial gland biopsy
• Dental relevance:
  • Dry mouth (dental caries, loss of teeth, candida infections)
  • Salivary gland enlargement
  • Complications of systemic treatment
• Treatment: keep mouth hydrated (Xylitol Chewing Gum for stimulation of Salivary Glands & Flow)

Systemic Lupus Erythematosus (SLE)

• Male to female ratio: 1:9
• Peak onset: 20-40 years
• Autoimmune multi-system disease
• Characterized by arthralgia and skin rashes
• Pathology: widespread vasculitis of capillaries, arterioles, and venules
• Aetiology:
  • Genetic
  • Complement deficiency
• Triggers:
  • UV light
  • Infection
  • Drugs (e.g., slow acetylators and hydralazine)
• Four immunological mechanisms:
  • Polyclonal B cell activation
  • Production of anti-nuclear antibodies (ANA)
  • Impaired T cell function
  • Failure to remove immune complexes
• Five clinical features:
  • Photosensitivity rash
  • Vasculitis with gangrene (loss of blood flow at the tips of fingers)
  • Cerebral micro-infarcts (memory problems and headaches)
  • Lupus nephritis (affects kidney, causing blood in urine, elevated blood pressure, and edema of the feet)
  • Anti-phospholipid syndrome (increased tendency to clotting with venous thrombosis, arterial thrombosis, recurrent fetal loss, thrombocytopenia, and livedo reticularis)
• Five variants:
  • Discoid lupus (DLE)
  • Subacute cutaneous (SCLE)
  • Systemic lupus erythematosus
  • Anti-phospholipid syndrome
  • Drug-induced lupus
• Seven investigations:
  • ESR raised
  • Normal CRP
  • RF increased
  • ANA increased
  • Anemia (normochromic normocytic, haemolytic)
  • Neutropenia, thrombocytopenia
  • Reduced complement
• Three treatments:
  • Antimalarials
  • Prednisolone
  • Immunosuppressive agents
• Prognosis: 95% survive for a maximum of 5 years
• Dental relevance:
  • Oral ulceration
  • Immunosuppression and candidiasis
  • Dry mouth
  • Often mistaken for lichen planus in the oral cavity

Scleroderma (Systemic Sclerosis)

• Three types:
  • Systemic fibrosis (diffuse systemic sclerosis)
  • CREST syndrome (Calinosis, Raynaud's, oesophageal involvement, sclerodactyly, telangiectasia)
  • Morphoea (localized to skin)
• Male to female ratio: 1:3
• Peak onset: unknown