RA

- RF
- Anti-CCP
- Prevalence, female, middle age
- Smoking, HLA-DR4
- CVD mortality
- Patterns (mostly insidious, but other possible)
Dx
- Undifferentiated inflammatory arthritis (UIA)
- ACR criteria 1988 (4 of; >6wks; clinical/serology/radi)
- Predictive testing
- ACR/EULAR 2011 mx if ≥6 (joint no/ serology/duration/acute phase reactive)
MSS
- MCP, PIP, wrist joint synovitis, cervical spine
- Ulnar deviation, Bboutonniere, Swan neck, Z deformity of thumbs
- Tenosynovitis (CTS, extensor tendon rupture), ligament laxity (Atlanto-axial sublax)
Extra-articular (30% true extra articular)
- True extra-articular
o Rheumatoid nodules (subcut/visceral; accelerated by methotrexate)
o Eye: keratoconjunctivitis sicca, episcleritis, scleritis, scleromalacia (blue
sclera), scleromalacia perforans
o Vasculitis: nail fold infarcts, sensory neuropathy, ulceration, mononeuritis
multiplex, arteries
o Cardiopulmonary: pleural/pericardial/intertstitial lung/Caplan syndrome
o Felty syndrome (splenomegaly, neutropenia, RA) a/w leg ulcers, LN, anaemia
- Systemic effects of inflammation
o Malaise, fever, weight loss, myalgia
o Anameia of chronic disease
o Coronary heart disease
o Osteoporosis (also due to immobility)
o Lymphadenopathy
o Amyloidosis
- Non articular manifestations of joint/tendon
o Entrapment neuropathy (CTS)
o Cervical myelopathy (due to atlanto axial sublaxation)
o Hoarseness and stridor (cricoarytenoid arthritis)
- Adverse drug effects
o Skin rashes (NSAI, DMARD)
o Renal impairment (NSAID)
o GI (Peptic/intestinal ulcer, diarrhea with leflunomide)
o HT (NSAID, cyclosporine A, leflunomide)
o Respi (acute pneumonitis with methotrexate or leflunomide)
o Infection
- Others
o Palmar erythema (common)
o Pyoderma gangrenosum (non infective ulcer – deep, usu on legs)
o Recurrent respiratory infection
 o Depression
Ix
- X rays (ST swelling, osteoporosis, joint space narrowing, destruction, subluxation)
- Lab (RF, anti-CCP, ESR/CRP/ALP, anaemia Ig, complement (normal), ferritin (raised –
acute phase)
- Synovial fluid (exclude sepsis, gout)
Disease activity
- DAS28 (disease activity score using 28 joints) – no. of swollen joint, tender joint, ESR
Drugs
- Symptom modifying
- (reduce pain/stiffness/swelling)
o NSAIDs
- Disease modifying (DMARD)
- (Above + reduce ESR/CRP, correct anaemia, slow progression)
o Methotrexate (DMARD of choice)
 Takes week to be effective (bridge with corticosteroids)
Others
 Sulfasalazine, Leflunomide, Hydroxychloroquine
 Others: gold, azathioprine, ciclosporin, D-penicillamine
o Biological DMARD
 Enhanced when combined with methotrexate
 Infliximab, Entanercept, Adalimumab, Certulizumab pegol,
Golimumab (all TNF-alpha)
 Rituximab (CD20)
 Tocilizumab (IL6)
 Abatacept (CTLA4)
 Anakinra (IL1)
 S/E injection rxn, immunosuppression, ca, multiple sclerosis, ANA
 For severe RA (DAS28 >5.1) when standard DMARD failed
Spondyloarthropathies (HLA-B27 associated disorders)
- Seronegative (RA –ve) inflammatory arthritis / spondylitis
- Asym, larger joints
- MSS: Enthesitis, sacroiliitis, dactylitis
- Extra-articular: Uveitis, Psoriasis, IBD, aortitis/endocartitis
- Genetic: Fam Hx, HLA-B27
HLA-B27
- AS (90%), Reiter (70%), Enteropathic spondylitis (50%), Psoriatic arthritis (20%)
AS
- Inflammatory back pain, stiffness +/- anterior chest pain, young men (15-40)
- Articular: Scaroiliitis, spondylitis, peripheral arthritis, intervertebral discitis (rare)
- Extra-articular: Uveitis, Aortic incompetence, (apical lung fibrosis, aortitis,
amyloidosis, heart block)
Dx
- Requires RADI evidence (of Sacroiliitis, inflammatory spinal pain) – X ray/MRI
- ESR/CRP/ALP, normochromic anaemia, radiology
Radi
- Sacroiliac: blurred joint margin, erosion, sclerosis, fusion
- Spine: loss of lumbar lordosis, squaring of vertebrae, Romanus lesion (erosion of
corner of vertebral bodies), Bamboo spine (calci in spinal lig, enthesitis (calci)
Assessment
- BAS-DAI (Bath AS disease activity index)
o Find pt suitable for anti-TNFa tx + assess tx response)
o Fatigue, spinal pain, joint pain, localized tenderness, morning stiffness
Tx
- Physio
- NSAID, DMARD (methotrexate, sulfasalazine –peripheral arthritis), Anti-TNFa (good)
- Surgery
Reactive arthritis
- 1-3 weeks after infection
- Reiter (Triad: arthritis, conjunctivitis, urethritis)
- Rare: Heart, lung ,CNS
- Others: Circinate balanitis, Buccal/lingual ulcers, keratoderma blenorrhagica, Iritis
- Fever, weight loss
- Tx: NSAIDs, DMARD, Corticosteroids
Psoriatic arthritis
Classification Criteria for Psoriatic Arthritis (CASPAR)
- ≥3 points with inflammatory arthritis / spondylitis = psoriatic arthritis
o Psoriasis / Fhx (2points)
o Typical psoriatic nail dystrophy (1point)
o Negative RF (1point)
o Dactylitis (1point)
o Radiographic evidence of new bone formation (1point)
- Pattern (Polyar, DIP, sacroiliitis/spondylitis, asym oligoarthritis, arthritis mutiloans)
- Features (nail pitting/oncholysis, DIP arthritis, telescoping fingers in arthritis
mutilans, paravertebral calcification, Dactylitis)
- Tx: like RA
Inflammatory connective tissue disorders
Markers
- ANA IF pattern
o Homogenous = lupus
o Speckled = mixed CTD
o Nucleolar = scleroderma
o Centromere = CREST (calcinosis, Raynauds, Eso, Sclerodactyly, telangiectasia)
- ANA: drug induced lupus, SLE, Scleroderma, Sjogren, mixed CTD, (Polymyositis, 5%
normal), (ANA in RA  Felty or Sjogren)
- Anti-dsDNA  SLE
- ENA
o Anti-Ro – Sjogren/congenital heart block/neonatal lupus/ANA-ve SLE
o Anti-La – primary Sjogren
o Anti-Sm – SLE (20%, very specific, high risk of renal lupus)
o Anti-RNP – Mixed CTD (100%), SLE
o Anti-Jo1 – polymyositis
o Anti-Scl70 – Progressive systemic sclerosis
o Anti-centromere – CREST syndrome
- APLA
o Thrombosis, transient neuro deficits, fetal loss, livido reticularis,
thrombocytopenia (Hughes syndrome)
o Lupus anticoagulant, Anti-Cardiolipin (Beta2glycoprotein-1)
o Reflected in: false +ve VDRL, prolonged APTT
SLE
- Inflammatory CTD + small vessel vasculitis + non-organ specific autoantibodies
Features
- Anti-dsDNA
- Common: Skin rashes (malar, discoid, photosensitive), arthralgia, fever
- Other: Neuropsychiatric (pyschosis, seizures), Alopecia, Serositis (pericarditis,
pleurisy), oral/nasal ulcers, Renal (proteinuria, GN), Resp (pneumonitis), Cardiac
(myocarditis, endocarditis/Libman sacks), Haematological (pancytopenia), Raynaud’s
CBC
- Anaemia (of chronic disease), hemolytic anaemia
- Neutropenia
- Thrombocytopenia
- Lymphopenia
Lab
- ESR (disease activity), CRP (if active joint/serositis/flare)
- C3,C4 (low  lupus nephritis)
Variants
- Drug induced
o ANA +ve dsDNA –ve
o Resolve on stopping drugs – procainamide, isoniazid, hydralazine)
- APLS (Hughs syndrome)
o Recurrent thromboses, fetal loss, thrombocytopenia
o Libman sacks endocarditis, focal neuro lesion (CVA/TIA)
Tx
 - Sunscreens (sunburn  flare)
- NSAID (arthritis
- Hydroxychloroquine
- Corticosteroids, immunosuppressive drugs
- Plasma exchange, biological agents
- RF reduction (CVS – BP, smoking, lipid, obesity, exercise)
DM and PM
Features
- Mus: Proximal weakness, swelling/tenderness
- Other: ILD, Eso dysfunction, arthralgia, weight loss/fever
- Skin rash: Heliotrope, Gottrons (scaly papules over MCP/PIP), Periungual
telangiectasia, Erythematous macules
- a/w malignancy
Juvenile DM
- Common: Vasculitis, ectopic calcification, lipodystrophy
Lab
- Mus: CK, AST, LDH
- EMG, Biopsy (inflammation, necrosis, regeneration)
Autoantibodies
- ANA, Anti-Jo1 (acute onset myositis, ILD etc)
Tx
- Corticosteroids, immunosuppressive
Systemic sclerosis
- Thickening + fibrosis of skin (scleroderma)
Features
- Raynauds a/w digital ulcers and calcinosis (unusu in primary)
- MSS – arthralgia, erosive arthritis, myositis, flexion deformities
- Pulmonary – ILD, pul HTN
- Renal – Scleroderma renal crisis
- Scleroderma – early edematous, later indurated, pigmented and los hair
- GI – motility
Ix
- ESR/CRP
- RF (30%), ANA (90%)
- Anti-Scl70 (diffuse scleroderma + limited involvement)
- Anti-centromere (limited scleroderma + systemic involvement)
Pattern
- Limited (CREST) – better prognosis
o Face/neck/limbs distal to elbow and knee
o Raynauds, Pul HTN common
- Diffuse
o Trunk/proximal limbs + above
o Swelling of fingers, arthritis, Renal crisis more
- Scleroderma without internal organ disease
o Plaques
Mx
- Screen Pul HTN/Pul fibrosis
 - Monitor renal involvement (BP, Cr)
- Supportive: PPI (reflux), antibiotics, vasodilators (Raynauds), infuse iloprost (severe)
- Specific: immunosuppressant, corticosteroids (pul fibrosis), ACEI (renal),
sildenafil/bbiloprost/bosentan for pul HTN
Sjogren syndrome
- Lymphocytic infiltration of exocrine glands (lacrimal, salivary)
- 30% of RA have secondary Sjogren
Features
- Dryness (eyes, mouth, resp with hoarseness, vaginal)
- Arthralgia/arthritis
- Raynauds, Vasculitic purpura
- Lymphadenopathy, Gland swelling (parotid)
- RTA
- (Neuropathies, Pancreatitis)
Lab
- Anameia, leukopenia
- ANA (frequent), Anti-Ro, Anti-La (both in primary Sjogren), RF (+ve in most)
- ESR/CRP
- Polycloncal hypergammaglobulinaemia
Tx
- Artificial tears, lacrimal punctae plugging, mouth spray
- NSAID (arthritis)
Mixed CTD/overlap syndromes
- One specific overlap syndrome, mixed CTD, is a/w anti-RNP
- Raynaud’s, swollen hands + features from at least ≥ 2 CTD (SLE, scleroderma, PM)
Vasculitis
- Systemic  malaise, fever, weight loss + specific organs sx
- Dx: clinical + lab + biopsy/angiography
- Etiology: infections, malignancy, drugs
o Immune complex  hep B associated polyarterits nodosa
o Direct endothelial cell infection  HIV
o Anti-endothelial cell antibodies  Kawasaki, Bechet
o ANCA-mediated neutrophil activation: Wegener’s granulomatosis,
microscopic polyangiitis
o T cell dependent injury  giant cell arteritis
- Features
o General
 Constitutional (fever, weight loss, fatigue, anorexia)
 MSS (arthralgia, arthritis, myalgia)
o Specific organ
 Kidney  GN
 Respi  alveolitis, hemorrhage, infiltrate
 Neuropathy  mononeuritis multiplex, sensory neuropathy
 (GI  Diarrhea, abd pain, perforation, hemorrhage)
 CVS  claudication, angina, MI
 CNS  headache, visual loss, stroke, seizures
 Skin  livedo reticularis, vasculitic lesions (purpura, erythema
multiforme), urticarial
- Chapel Hill Classification (2012)
o Large vessel
 Takayasu’s arteritis
 Giant cell arteritis
o Medium vessel
 Kawasaki’s disease
 Polyarteritis nodosa (PAN)
o Small vessel
 ANCA-associated vasculitis
 Granulomatosis polyangiitis (Wegener’s granulomatosis)
 Eosinophilic granulomatosis polyangiitis (Churg-Strauss)
 Microscopic polyangiitis
 Immune complex vasculitis
 Anti-GBM disease (Goodpasture’s)
 IgA vasculitis (Henoch-Schonlein purpura)
 Cryoglobulinaemic vasculitis
 Hypocomplementaemic urticarial vasculitis
o Variable vessel
 Behcet’s disease
 Cogan syndrome
o Single organ
 Primary CNS vasculitis
 Isolated aortitis
 Cutaneous arteritis
  Cutaneous leukocytoclastic angiitis
o Vasculitis associated with systemic disease
 Lupus vasculitis
 Rheumatoid vasculitis
 Sarcoid vasculitis
- Others
o Vasculitis a/w probable aetiology
 Hep C associated cryoglobulinaemic vasculitis
 Hep B associated vasculitis (PAN)
 Drug associated immune complex vasculitis
 Drug associated ANCA associated vasculitis
 Cancer associated vasculitis
- ANCA
o In vasculitis, UC, autoimmune hepatitis, CTD, drug reactions
o Two IF staining patterns
 Cytoplasmic (cANCA) a/w anti-PR3
 Perinuclear (pANCA) a/w anti-MPO
o Non vasculitic ANCA +ve  no antiPR3 or antiMPO
 Granulomatosis polyangiitis  usu antiPR3
 Esosinophilic granulomatosis polyangiitis  antiPR3, antiMPO (75%)
 Microscopic polyangiitis  antiMPO
Giant cell arteritis
- 70yo, unilat headache, scalp pain, jaw claudication, visual sx
- Constitutional (fever, weight loss, anorexia)
- Polymyalgia rhuematica (50% of GCA have)
Exam
- Tenderness, eye (reduced VA, VF, RAPD, pale/swollen disc, CRAO), upper CN palsies
- Large vessel giant cell arteritis (GCA)  asymmetrical pulses and bruits
Dx
- ACR: three of
o Onset >50yo
o New headache
o Temporal artery abnormality: tenderness / decreased pulsation
o Positive temporal artery biopsy
o Elevated ESR
- Cx: Early (visual loss/stroke), late (aortic aneurysm, dissection), tx (steroid s/e)
- Tx: early high dose corticosteroid (then taper), methotrexate (adjunct), aspirin
Polymyalgia rheumatic (PMR)
(Syndrome of pain and stiffness, not vasculitis) (15% develop GCA)
o >50yo, >2weks
o Bilateral (shoulder/pelvic girdle) aching, morning stiffness >45min
o Acute phase response
- DDX: RA, crystal arthropathy (need to rule out: infection/malignancy/other rheumat)
- Tx: Corticosteroid tapered according to sx
Takayasu’s arteritis (pulseless disease)
- Aortic + its main branches  arm claudication, no pulses, bruits
- Systemic sx (malaise, weight loss, fever), Visual disturbances (30%)
 o Dx: angiography
o Tx: steroids, arterial reconstruction / bypass
Kawasaki’s disease
- Acute febrile + systemic vasculitis
- Children <5yo, Rickettsia
o Fever  then trhombocytosis
o Mucocutaneous  rashes, red cracked lips, strawberry tongue, conjunctivitis
o Vasculitis  coronary aneurysm, MI
o LN (esp cervical)
- Corticosteroids are contraindicated ( more coronary aneurysms)
- Aspirin (acute febrile phase), antiplatelet (resovled phase), IV Ig
Polyarteritis nodosa (PAN)
- Hep B associated
- Lung, kidney, skin, peripheral nerves, gut, joint
Granulomatosis with polyangiitis (Wegener’s)
- Respiratory tracts, GN
- ANCA +ve (90%), usu Anti-PR3
Eosinophilic granulomatosis with polyangiitis (Churg-Strauss Syndrome)
- Respiratory tracts, GN, + (skin, peripheral nerves)
- A/w asthma, eosinophilia
- ANCA +ve (50%), both antiMPO (75%) & antiPR3 (25%)
Microscopic polyangiitis
- Pulmonary capillaries (infiltrates, hemorrhage), GN (v common)
- + (skin, peripheral nerves) + (gut, eye)
- ANCA _ve (70%), usu antiMPO
Behcet syndrome
- Rare, Turkey, Eastern Mediterranean
- HLA-B5, immune-mediated occlusive vasculitis and venulitis
Main features
- Recurrent oral ulcer (100%), recurrent painful genital ulcer (80%)
- Recurrent iritis (60-70%), Skin lesions (60-80%)
- Others features etc
Crystal arthropathies & OA
Gout
- Acute crystal arthritis (first MTP)
- Gouty nephropathy (tubulointerstitial/crystal, acute precipitate/AKI, urate stone)
- Chronic tophaceous arthritis (aggregates in articular, periarticular, nonarticular/ear)
Associations
- HT, HL, obesity, DM
Aetiology
- Purine breakdown  uric acid
o Synthesis/Diet/released at cell death
- Causes
o Primary hyperuricaemia
 Idiopathic (mostly under-excretion)
 Enzyme deficiencies
 HGPRT (hypoxanthine-guanine-phospho-ribosyl-transferase)
def = Lesch Nyhan syndrome
o Secondary
 Increased production/intake/release
 Hemat: MPD, LPD
 High purine diet (beer)
 Cytolytic therapy/Acidosis/Extreme exercise/Psoriasis
 Decreased excretion
 Renal failure, Drugs (diuretics), Alcohol
 Lead intoxication, Down syndrome
Dx
- -ve birefringent needle shaped crystals in joint fluid
- Chronic tophaceous: X ray  large punched out erosions distant from joint
Tx
- Acute: NSAID, colchicine, prednisolone, Canakinmumab (IL1beta – not general)
- Prophylaxis: avoid dehydration, stop diuretics, reduce alcohol, weight
- Urate lowering (Xanthine oxidase inhibitor): Allopurinol, Febuxostat
o (Uricosuric agents): probenecid
o Losartan, fenofibrate
o (Uricase agents): pegloticase, raspuricase – mainly for tumour lysis syndrome
- Urate lowering tx indication
o Recurrent/visible tophi/renal/urate stone/cannot stop diuretics
o Aim: reduce serum urate to <0.3 mmol/L
Calcium pyrophosphate deposition disease (CPDD)
- Idiopathic, age-related, metabolic (hyperCa, hypoMg)
- +ve birefringent brick shaped crystals
Variants
- Asym (radiological chondrocalcinosis)
- Acute monoarthritis (pseudogout – knee, elbow, shoulder)
- Inflammatory polyarthritis (mimicking RA)
- OA (hips, knees, index and middle MCP)
Causes
- HyperPTH (hyperCa), HypoMg etc.
 Tx
- Asym  no tx
- Treat underlying metabolic dx
- Acute attack: NSAID/colchicine/corticosteroids
- Prophylaxis: colchicine/NSAID
- Chronic: methotrexate/hydroxychloroquine
OA
- Softening & degradation of articular cartilage + secondary changes in adjacent bone
- RF: Obesity
Joints
- DIP (Heberden’s nodes), PIP (Bouchard’s nodes)
- Base of thumb (first CMC joint)
- Hips, knees, spine
o MCP joints suggest a secondary cause (CPDD)
OA subsets
- Primary
o Localized
o Generalized
- Secondary ???
o Inherited dysplastic disorders
o Mechanical damage (osteonecrosis, post-meniscectomy)
o Metabolic (ochronosis, acromegaly)
o Previous inflammation (sepsis, gout, RA)
Dx
- Clinical (>45, activity related joint pain, morning stiffness <30min or no stiffness)
Tx
- Education, exercise, weight loss
- Analgesics (NSAID), TENS pain relief, surgery (joint replacement)

Arthritis in children
JIA
- Persistent arthritis >6wks, onset <16yo
Subtypes (at least 7)
- Systemic onset JIA (Still’s disease)
- Oligoarthritis (≤4 joints, uveitis risk)
- Extended Oligoarthritis (>4 joints)
- RF –ve polyarthritis
- RF +ve polyarthritis
- Psoriatic arthritis (uveitis common)
- Enthesitis related arthritis