1. Rheumatology: Back to Basics: 2016
James Gillray
“The Gout”
1799

3. Immune Mechanisms of Disease
Type I: Anaphylactic IgE eg. asthma
Type II: Cytotoxic eg. AIHA
Type III: Immune Complex eg. SLE
Type IV: Cell-mediated/Delayed Hypersensitivity: T-cells
eg. Contact dermatitis

4. GENETICS
ENVIRONMENT
Infections...
AUTOIMMUNITY

5. HLA: Disease Associations
HLA B27 (MHC Class I)
- Ankylosing Spondylitis Reiter’s/reactive arthritis
- Psoriatic arthritis
- IBD arthropathy
HLA DR4, DR1 (MHC Class II) - RA
HLA DR3 (MHC Class II)
- SLE, Sjogren’s, Type I DM…

6. We love our antibodies...

7. Rheumatoid Factor Rheumatoid Arthritis: - sensitivity = 70%
Anti-antibodies (Fc domain of IgG)
Rheumatoid Arthritis:
- sensitivity = 70%
- poor prognosis
- extra-articular features
Non-specific:
- other rheumatic diseases eg. Sjogren’s
- chronic inflammatory diseases
- chronic infections – SBE, Hep C
% over age 65

8. Anti-Citrullinated Peptide Antibodies (CCP or ACPA)
More specific for RA
More sensitive than RF in early RA
Associated with worse prognosis

9. Antinuclear Antibodies
Sensitivity for SLE 90%+
Specificity low
- other autoimmune diseases
- family members
- drugs
- ...

10. Raynaud’s phenomenon Cold, stress 3 phases: white blue  red
5 % of normals
90% - scleroderma
Consider ANA when screening (SLE, CREST)

11. ANA: Anti-centromere pattern: Limited Systemic Sclerosis (CREST)

12. Other Autoantibodies Anti-DNA (native, double-stranded)
- SLE- sensitivity 60-70%
- specificity ~ 100%
- correlate with disease activity
Anti-SSA, SSB (Ro, La)
- Sjogren’s, SLE
- congenital complete heart block

13. Antibodies to Ro/SSA 30-35% of patients with Lupus Associated with:
- Sjogren’s syndrome
- photosensitive rashes “subacute cutaneous lupus”
- Neonatal lupus
- transient rashes
- congenital complete heart block

14. Adult: Subacute Newborn: Cutaneous Lupus Neonatal Lupus
Antibodies to Ro/SSA
Adult: Subacute Newborn:
Cutaneous Lupus Neonatal Lupus

15. Antiphospholipid Antibodies
Anticardiolipin antibodies
Lupus anticoagulant
Anti -2 GPI
Associations:
- thrombosis
- recurrent pregnancy losses
SLE, other CTD’s, primary

16. Anti-Neutrophil Cytoplasmic Antibodies (ANCA)
Patients with suspected vasculitis:
- Granulomatosus with polyangiitis (GPA) Wegener’s
- pulmonary/renal
- RPGN
- cocaine
Cytoplasmic
Perinuclear

17. Anti-Neutrophil Cytoplasmic Antibodies (ANCA)
Patients with suspected vasculitis
- pulmonary/renal syndromes
cANCA: Granulomatosus with polyangiitis (GPA) Wegener’s:
- 80% sensitive and specific
- specificity is for PR-3
pANCA: less specific

18. Specific Diseases…

19. Osteoarthritis (OA) The most common type of arthritis
Disease of cartilage (cf. RA)
Characterized by:
- Cartilage degradation, loss
- hypertrophic bone formation
(osteophytes...

20. Primary (idiopathic) OA
Peripheral Joints:
- hands - DIP, PIP (cf. RA)
- 1st C-MC
- feet - 1st MTP
- large weight-bearing joints - hips, knees
Spine - apophyseal joints
- intervertebral discs

21. OA: Heberden’s (DIP) Bouchard’s (PIP) Nodes

22. Osteoarthritis: X-ray 1st C-MC Joint
Joint space narrowing
Subchondral sclerosis
Osteophytes

23. Rheumatoid Arthritis Prevalence 1:100
small joint, symmetric polyarthritis
+ AM stiffness
chronic (>6weeks)
Path = synovial inflammation
Extra-articular features

24. DIPs 
(spared)
PIPs 
MCPs 

25. Rheumatoid Arthritis Deformities Nodules Periarticular osteopenia
Marginal erosions

26. RA: Extra-articular Features
Skin - sc nodules, vasculitis...
Eyes - sicca, scleritis, episcleritis
Lungs - pleurisy/effusion
- interstitial fibrosis
- nodules
Cardiac - pericarditis, nodules
Hematologic - anemia, Felty’s (neutropenia…)
Neurologic - peripheral neuropathy...

27. Scleritis

28. RA: Nodules

29. RA: Factors Associated with Poor Prognosis
RF, CRP, anti-CCP (ACPA) positivity
HLA-DR4 haplotype
Degree of disease activity at onset …
 Early aggressive therapy

30. RA: Treatment Symptomatic - rest, education - splints, orthotics
- ASA, NSAID’s, Coxibs
Disease Modifying Anti-Rheumatic Drugs (DMARDs)

31. RA: Common DMARD’s Methotrexate Hydroxychloroquine Sulfasalazine
New Biologics...

32. RA: New Therapies - Biologics
anti-TNF
soluble TNF receptor
other mechanisms: CTLA4-Ig, IL-6, B-cells…
Concerns: - cost
- parenteral (most)
- risk of infections, TB

34. Systemic Lupus Erythematosus
Affects 1: individuals
African American blacks > Asian, hispanics, native NA > Caucasian
Females : Males = 9:1
Any age - usually young females in their reproductive years

35. Lupus: Criteria Malar rash Hematology: Photosensitivity anti-WBC
Discoid rash
Mucosal ulcers
Arthritis
Serositis “Pleurisy”
Renal
CNS
Hematology:
anti-WBC
anti-platelet
anti-rbc
Immunologic:
anti-DNA
anti-phospholipid
anti-Sm
Antinuclear antibodies

36. SLE: Organs Affected Joints: 80-90% Skin: 70%, often photosensitive
Serositis: 50%
Kidneys: 25-50%
CNS: 15%

37. Discoid Lupus Plaques Photosensitive Often head & neck Scarring
10% develop SLE

38. Lupus: Treatment Sunscreens, sunprotection Anti-inflammatory drugs
Anti-malarial drugs
Steroids
Immunosuppressants
Mycophenolate mofetil

39. Systemic Sclerosis (Scleroderma): Skin thickening, tightening

40. Scleroderma - small blood vessels = SPASM, ischemia +
Disorder of:
- small blood vessels = SPASM, ischemia +
- overproduction of connective tissue
(collagen) = FIBROSIS

41. Scleroderma: Types Systemic - Diffuse
- Limited (CREST) anti-centromere
Localized - morphea
- linear scleroderma

42. Scleroderma Lungs - fibrosis - Pulmonary hypertension GI - GERD...
Renal - malignant hypertension
- microangiopathic anemia - renal failure
- ACE Inhibitors!!!!!!!!!!!!!!!

43. Limited Scleroderma (CREST)
Calcinosis
Telangiectasias

44. Acute Monoarthritis (in absence of trauma)
Infection
Crystal (gout, pseudogout)
Spondyloarthropathy

45. Synovial Fluid Testing
Cell count, differential
WBC: = non-inflammatory
,000 = inflammatory
>75,000 = septic
Gram stain, C&S
Crystals

46. Spondyloarthropathies
Axial and/or peripheral joints
HLA-B27
Path = enthesopathy
Inflammatory back pain
Extra-articular:
- uveitis etc.
RF negative
Ankylosing Spondylitis
Reiter’s/reactive arthritis
Psoriatic arthritis
Inflammatory Bowel Disease

47. Enthesitis Erosion Calcaneal Spur
Reiter’s - erosion at Achilles insertion into calcaneus and extra bone at site of plantar fasciitis
Calcaneal Spur

48. Achilles tendinitis

49. Inflammatory low back pain?
Insidious onset
Worse with rest
Better with activity
Morning stiffness
Family history
Bilateral Sacroiliitis

50. Ankylosing Spondylitis

51. HLA-B27: Disease Associations
Ankylosing Spondylitis >90%
Reiter’s syndrome/ reactive 80%
Inflammatory bowel disease 50%
Psoriatic Arthritis
- with spondylitis 50%
- with peripheral arthritis 15%
Caucasians %
Inuit %

52. Reactive Arthritis: Concept
A sterile inflammatory arthritis
- triggered by an infection
- at a distant site (GI or GU)
- in a genetically susceptible host

53. Bacteria that Trigger Reactive Arthritis
Post-venereal: Chlamydia trachomatis
Post-dysenteric:
Salmonella
Shigella flexneri
Yersinia enterocolitica
Campylobacter
Clostridium difficile

54. HLA-B27: Reactive Arthritis
Campylobacter

55. Spondyloarthropathies: Extra-articular features
Skin: Psoriasis, E. nodosum, pyoderma gangrenosum...
Eyes: iritis, conjunctivitis
Lungs: apical pulmonary fibrosis
Cardiac: aortic insufficiency, conduction abnormalities
Neurologic: cauda equina...

57. Reiter’s Syndrome

58. Gout
Acute monoarthritis
- lasts days
- recurrent attacks
Uncontrolled hyperuricemia
 tophi
 polyarthritis

59. Gout: uric acid crystals
Needle-shaped
Strong negative bireringence
Phagocytosed by PMN’s

60. Gout: Treatment Asymptomatic hyperuricemia  none
Acute attack - NSAID’s
- colchicine
- steroid’s
Indications to lower uric acid – allopurinol, febuxistat
- renal stones
- frequent attacks
- tophi

61. Pseudogout - CPPD Acute monoarthritis Knees, wrists Chondrocalcinosis
Pyrophosphate crystals:
- rhomboid
- weak positive birefringence

62. Vasculitis: Classification NB! can have overlap...
1. Large Vessel Vasculitis
2. Medium Vessel Vasculitis
3. Small Vessel Vasculitis

63. Large Vessel Vasculitis
- Giant Cell Arteritis
- Takayasu’s (Aortic Arch Syndrome)

64. Medium Vessel Vasculitis
- Polyarteritis nodosa (PAN)
- Kawasaki Disease
- Primary CNS Vasculitis

65. Small Vessel Vasculitis
Palpable purpura
Most common vasculitis
Leukocytoclastic vasculitis
Ag (eg. Infection, drug)
+ Ab  immune complex
Rule out other organ involvement (kidney, lung…)

66. Small Vessel Vasculitis
- ANCA Associated: - Wegener Granulomatosis
- Churg-Strauss Syndrome
- Microscopic Polyangiitis (MPA)
- Henoch-Schönlein Purpura (HSP)
- Vasculitis with connective tissue diseases
- Vasculitis/essential mixed cryoglobulinemia (Hep C)
- Hypersensitivity vasculitis (leukocytoclastic)
- Vasculitis with viral infections (Hep B, C, HIV, CMV, parvo-B19)

67. Small Vessel Vasculitis: ANCA associated: e.g. GPA Wegener’s
Small + medium vessels
Granulomatous
Upper +/- lower respiratory (ulcers, sinuses...)
Renal

68. Anti-Neutrophil Cytoplasmic Antibodies (ANCA)
Patients with suspected vasculitis:
Pulmonary - renal:
- GPA/Wegeners
- ...
Cytoplasmic
Perinuclear

69. ANCA Immunofluorescence cytoplasmic - cANCA perinuclear - pANCA
Solid Phase Assays (ELISA…) :
pANCA = anti-MPO (myeloperoxidase)
cANCA = anti-PR3 (proteinase 3)

70. cANCA (anti-PR3)
Highly sensitive, specific for Wegener’s granulomatosis
Specificity: 95%

71. Large Vessel Vasculitis Giant Cell (Temporal) Arteritis

72. Large Vessel Vasculitis Giant Cell Arteritis (GCA)
Age >50 years - mean = 70 years
Symptoms related to arteries:
- headache, scalp tenderness
- visual loss
- jaw claudication

73. Giant Cell (Temporal) Arteritis
Diagnosis:
- CBC - anemia of chronic disease
- ESR - markedly elevated, often >100
- Biopsy temporal artery
Treatment: URGENT! (prevent visual loss)
- steroids - prednisone 60mg daily...

74. Fibromyalgia Prevalence 3% widespread pain, tender points
sleep disturbance
Absence of inflammatory markers…
Exclusion of other systemic disorders
Treatment: - education
- exercise
- low dose tricyclic
- New = pregabalin, duloxetine
Canadian Guidelines

76. NSAIDs, Coxibs

77. Toxicity: ASA and NSAIDs
GI: ulcers, bleeding
CVS: hypertension, increased risk MI, stroke
Renal: Na retention, edema, renal failure
CNS
anti platelet effects
contraindicated ASA hypersensitivity
avoid if possible - pregnancy and lactation

78. Cox-2 “specific” Inhibitors (coxibs)
improved GI safety
no effect on platelets
efficacious in RA, OA, pain
CVS, renal effects like other NSAID’s
 caution! - elderly hypertension
- cardiac disease
- renal disease

79. The diaper is full so this must be…