Rheumatology

1. Rheumatoid Arthritis

a) What is RA
Chronic systemic inflammatory disease characterised by symmetrical, deformity and peripheral polyarthritis

b) Name the typical & atypical presentations

Typical Atypical
• Symmetrical swelling • Sudden onset
• Painful • Widespread arthritis
• Stiff small joints (hands, feet) • Palindromic RA
• Worse in morning • Persistent monoarthritis

c) Signs

Early Late
• Swollen MCP, PIP, Wrist, MTP • Ulnar deviation
• Tenosynovitis or bursitis • Subluxation of wrist & fingers
• Finger deformity
- Boutonniere
- Swan neck
- Z-deformity of thumb
• Hand extensor tendons may rupture
*Nodules are usually in seropositive RF & anti-CCP (Primarily in extensor tendon)

d) List the extra-articular manifestations

• Lungs • Eye
- Pleural disease - Episcleritis
- Interstitial fibrosis - Scleromalacia
- Bronchiolitis obliterans - Scleritis
- Organizing pneumonia - Keratoconjunctivitis

• Cardiac • Carpal Tunnel Syndrome

- IHD • Splenomegaly
- Pericarditis • Felty Syndrome (RA + Splenomegaly +
- Pericardial effusion Thrombocytopenia + Neutropenia + ↓Hb)
• Peripheral neuropathy

e) Investigations
• Serology
- Rheumatoid factor
- Anti-CCP

• Full Blood Count

- ↓ Hb, ↑ Platelets, ↑ ESR, ↑ CRP (infection)

• Imaging
Ø X-ray
- Loss of joint space
- Bony erosions
- Juxta-articular osteopenia

Ø USG, MRI
- Identify synovitis
f) Criteria of Diagnosis

Joint Involvement Serology Duration Acute Phase Reactants

1=0 (-) RF & anti-CCP = 0 < 6 weeks = 0 Normal CRP & ESR = 0
2 – 10 large = 1 (+) ↓ RF/anti-CCP = 2 > 6 weeks = 1 Abnormal CRP & ESR = 1
1 – 3 small = 2 (+) ↑ RF/anti-CCP = 2
4 – 10 small = 3
> 10 (≥1 small) = 5

g) Differential Diagnosis
• Viral arthritis
• Infection-related arthritis
• Other inflammatory arthritis
• Connective Tissue Disease
• Osteoarthritis

h) Management
• Refer to rheumatologist
• Symptom relief
Ø Simple analgesics
Ø NSAIDs
Ø COX-2 inhibitors
• Glucocorticoids(steroids) - ↓ inflammation (e.g. IM : Methylprednisolone, Po : Prednisolone)
• Disease modification
Ø DMARDs (Disease Modifying Anti-rheumatic Drugs)
o Methotrexate
o Leflunomide
o Sulfasalazine
o Hydroxycholoquine
o Other (e.g. Azathioprine, Cyclosporine A, Gold)
Ø Biologic agents
o Anti TNF- infliximab, adalimumab, golimumab, certolizumab, etanercept
o IL-6 blockade- tocilizumab
o IL-1 blockade- anakinra
o antiCD20- rituximab
o Co-stimulation blockade- abatacept
• Stop smoking
• Surgery – Synovectomy, Joint replacement, Excision

i) Synovial Fluid Health

Normal Clear, Colourless
OA Clear, Straw
Haemorrhagic Bloody, Xanthochromic
Acute Inflamed Turbid, Yellow
RA, Crystal, Septic

j) Side effects of using Glucocorticoids

• Osteoporosis
• Hypertension
• Weight gain
• Fluid retention
• Skin fragility
• Cataracts
• Hyperglycaemia
• Potential Premature cardiovascular disease
2. Osteoarthritis

a) What is OA?
Chronic degenerative joint disease which results in the progressive erosion of articular cartilage in synovial
joint

b) Classification of OA

Primary OA • Idiopathic & appear insidiously

• Oligo-articular
Secondary OA • Presence of other pre-disposing factor
- Previous trauma & mechanical problem
- Infection
- Congenital deformity (Perthe’s dz, Slipped Upper Femoral Epiphysis)
- Inflammatory
- Underlying systemic disease (e.g. DM, Obesity, Haemochromatosis)

c) Signs & Symptoms

Localised disease (Often knee/hip) Generalised disease

• Pain & crepitus on movement • Joint tenderness
• Worse with prolonged activity • Derangement
• Brief stiffness after rest (10 – 15 minutes) • Bony swelling (Heberden’s – DIP, Bouchard’s – PIP)
• Unstable joint • Reduced ROM & Mild synovitis

d) Investigation
• X-ray
- Loss of joint space
- Osteophytes
- Subarticular sclerosis
- Subchondral cysts

e) Management
• Education
- (RF : Obesity, Hereditary, Trauma)
• Lifestyle advice
- Weight loss
- Strengthening Aerobic exercise
- Shock absorbing footwear
- Pacing activities
- Use walking stick
• Acupuncture
• Transcutaneous Electrical Nerve Stimulation (TENS)
• PCM +/- NSAIDs
• Anti-neuropathic drugs
- Amitriptyline
- Gabapentin
- Pregabalin
• Intra-articular glucocorticoid injections
• Surgery – Joint replacement, Arthroscopic debridement, Arthrodesis, Knee arthroplasty
3. Ankylosing Spondylitis

a) What is AS
• Chronic inflammatory disease of the spine and sacroiliac joints of unknown etiology
• Common in males, a/w HLA-B27, 30 – 40 years

b) Signs & symptoms

• Gradual onset of low back pain
• Worsen during the night with spinal morning stiffness relieved by exercise
• Pain radiates from SI joints to hips/buttocks
• Progressive loss of spinal movement (↓thoracic expansion)

c) Extra-articular features
• Anterior uveitis
• Aortic regurgitation
• Apical lung fibrosis
• Achilles tendinitis
• Atlantoaxial subluxation
• Amyloidosis
• Autoimmune Bowel Disease - Diarrhea

d) Investigations
• Imaging
Ø MRI
- Detect active inflammation (Bone marrow edema)
- Erosions, Sclerosis, Ankylosis

Ø X-ray
- SI joint space narrowing or widening/sclerosis/erosions, ankylosis/fusion
- Vertebral syndesmophytes (often T11-L1)
- Bony proliferations (Enthesitis between ligaments & vertebrae)
- Bamboo spine appearance (Calcification of ligaments + Ankylosis)

• Full Blood Count

- Hb (Normocytic anemia), ↑ ESR, ↑ CRP, HLA – B27

e) Management
• Exercise
• NSAIDs à Relieve within 48 hours
• TNF⍺ Blockers (e.g. etanercept, aalimumab) à Severe AS
• Surgery
- Hip replacement (improve pain & mobility)
- Osteotomy (rarely done)

f) Name other Seronegative Arthritis (PEAR)

• Psoriasis
• Enteropathic
• Ankylosing Spondylitis
• Reactive/Reiter’s
4. Psoriatic Arthritis
*Psoriasis vs Eczema – Eczema has swellings while Psoriasis has skin thickening (both have rash itch & silvery scale)

a) What is Psoriatic Arthritis?

• PA is a form of arthritis that affects people who have psoriasis (red patches on skin, topped with silvery scale)

b) Clinical features
• Often asymmetric, mainly oligo-
• Pain & stiffness affecting joints, tendons, spine and entheses
• Symmetrical polyarthritis
• Inflammation of digital tendon sheaths à sausage finger (dactylitis)
• DIP joint arthritis
• Psoriatic spondylitis (inflammatory back/neck pain and prominent stiffness symptoms)
• Arthritis mutilans (fingers & toes – prominent cartilage & bone damage) – skin appears invaginated
• Enthesitis (pain & stiffness of tendons & ligaments into bone)
- Typically insertions of Achilles tendon, Plantar fascia, Patellar ligament, Hip abductor complex, Lateral
femoral condyle, Gluteus medius, Humeral epicondyle tendon, Deltoid, Intercostal muscle at ribs, Pelvic
ligament
- Nail changes : Pitting, Onycholysis, Subungual hyperkeratosis, Horizontal ridging

c) How to differentiate from RA

• Presence of skin rash
• Asymmetric
• DIP & PIP involvement (DIP is spared in RA)
• Look for psoriasis and nail changes (psoriatic nail)

d) Investigation
• Diagnosis is made on clinical grounds
• ESR & CRP are raised (active disease)
• X-rays – normal or show erosive change with joint space narrowing
- Proliferative erosions marked with new bone formation
- Absence of periarticular osteoporosis and osteosclerosis
• MRI, USG & Power Doppler
- Detect synovial inflammation and inflammation at the entheses

e) Management
• NSAIDs & Analgesics
• Intra-articular glucocorticoid injections – control isolated synovitis or enthesitis
• Avoid splint & prolonged rest because tendency to fibrous & bony ankylosis
• DMARDs – Persistent synovitis unresponsive to treatment
- If severe : Sulfasalazine, Ciclosporin, Leflunomide
5. Primary Sjogren Syndrome

a) What is Primary Sjogren Syndrome? (40 – 50 years, 9:1 female-to-male ratio, HLA-B8/DR3)
• Characterised by lymphocytic infiltration of salivary and lacrimal glands, leading to glandular fibrosis and
exocrine failure

b) Clinical features
• Keratoconjunctivitis sicca
• Conjunctivitis & Blepharitis à filamentary keratitis
• Xerostomia
• Salivary gland enlargement
• Rashes/skin irritation
• Non-erosive arthralgia
• Generalized OA
• Raynaud’s phenomenon
• Fatigue

c) Autoantibodies frequently detected

• Rheumatoid factor
• ANA
• SS-A (anti-Ro)
• SS-B (anti-La)
• Gastric parietal cell
• Thyroid

d) Associated autoimmune disorder

• SLE
• Systemic sclerosis
• Celiac disease
• Primary biliary cholangitis
• Chronic active hepatitis
• Myasthenia gravis

e) Investigation
• Schirmer tear test (measures tear flow over 5 minutes using absorbent paper strips)
• Salivary gland biopsy (demonstrate focal lymphocytic infiltrate)
• ↑ ESR, Hypergammaglobulinemia & Autoantibodies (ANA & RF)
• Chest X-ray

f) Management
• Lacrimal substitutes (e.g. Hypromellose)
• Soft contact lenses for corneal protection with filamentary keratitis
• Artificial saliva sprays, Saliva stimulating tablets, Pastilles & Oral gels à Xerostomia
• Lubricants for vaginal dryness
• Hydroxychloroquine à help fatigue
6. Gout

a) What is Gout?
Gout is a spectrum of clinical & pathological features caused by an excess burden of uric acid

b) Differential diagnosis
• Reactive arthritis
• Hemarthrosis
• Calcium Pyrophosphate Deposition
• Palindromic RA

c) Risk factors

Reduced Urate Excretion Excess Urate Production

• Impaired renal function • Impaired renal function
• Hypertension • Genetic disorders
• Metabolic syndrome • Myeloproliferative disorders
• Diuretics • Lymphoproliferative disorders
• Antihypertensives • Psoriasis
• Aspirin • Drugs

d) Diagnostic Criteria for Gout

• Definitive diagnosis : Presence of Monosodium Urate Crystals in the synovial fluid or in the tissues
• Clinical diagnosis (2 of the following criteria)
- Clear history of ≥ 2 attacks of painful join swelling with complete resolution within 2 weeks
- Clear history or Observation of Podagra (1st MTP)
- Presence of Tophus (Chalky deposits of MSU, Subcutaneous & painless, appears firm nodular/fusiform)
- Rapid response to colchicine within 48 hours of starting treatment

e) Investigation
• Serum uric acid
- Male & Post-menopausal women : 420 umol/L (7mg/dl)
- Pre-menopausal women : 360 umol/L (6mg/dl)
• Joint aspiration & Crystal identification
• Polarized light microscopy of synovial fluid
• FBC : TRO lympho/myelo proliferative disorder/ exclude Infection
• Serum Urea/Creat : TRO Renal Disease leading to hyperuricemia/ renal disease secondary to urate
nephropathy
• FSL : To detect HyperTG
• Blood Glucose: To detect presence of DM/Insulin resistance
• UFEME: Presence of blood or protein may suggest Renal Disorder
• X-ray
- Calcification in hyaline cartilage &/ fibrocartilage
- Early stages : Soft tissue swelling
- Peri-articular erosions
- Normal joint space

f) Management
• Intra-articular glucocorticoids, Colchicine (manipulates inflammatory pathways), NSAID
• Steroids
• Ice packs & bed cages
• Surgery

g) Prevention
• Lose weight, Avoid prolonged fasts, Alcohol excess, Avoid purine rich meats, Low dose aspirin
• Prophylaxis : Xanthine Oxidase Inhibitor(Allopurinol – 1st line or Febuxostat – 2nd line)
Uricosurics (Probenecid, Benzbromarone)
7. Systemic Lupus Erythematosus (SLE)

a) What is SLE?
• Multisystemic autoimmune disease
• Inadequate clearance of immune complexes results in a host of immune responses which cause tissue
inflammation and damage
Or
• Inflammatory multisystem, autoimmune disease characterized by the production of antibodies directed against
many components of cells and tissues

b) Causes
• Genes • Environment
• Behaviour - Antigen
- Smoking - Hormones (oestrogen)
- Sun exposure - Infections
- Stress - Toxins
- Toxins - Medications
- Sun exposure
- Vitamin D deficiency

c) Clinical Features

• General symptoms • Pulmonary

- Fatigue, Fever, Weight loss - Serositis
- Fibrosis
• Skin & Mucous membranes - Pulmonary emboli
- Malar rash - Pneumonitis
- Discoid lupus
- Non-scarring alopecia • Haematological
- Photosensitivity - Anaemia
- Oral/Mucosal ulceration - Leukopenia
- Raynaud’s phenomenon - Thrombocytopenia
- (Hepato) Splenomegaly
• Neuropsychiatric - Lymphadenopathy
- Headache - Antiphospholipid syndrome
- Seizures
- Stroke • Renal
- Depression - Glomerulonephritis
- Hypertension
• Cardiac
- Pericarditis
- Endocarditis

d) Clinical Criteria (SLICC Classification Criteria)

 e) Diagnose
• Fulfil ≥4 of the classification criteria
• Anti-dsDNA antibody titre (severe)
• Complement : ↓C3, ↓C4 (denotes consumption of complement, hence degradation products ↑C3d, ↑C4d)
• ESR (raised)
• Urinalysis
- Urine casts or protein
• Skin or renal biopsies

f) Management
• General measures
- High-factor sunblock
- Hydroxychloroquine
- Screen co-morbidities & medication toxicity

• Maintenance
- NSAIDs (unless renal disease)
- Hydroxychloroquine (joint & skin)
- Steroid sparing agents (e.g. Azathioprine, Methotrexate, Mycophenolate)
- Monoclonal antibody (e.g. Belimumab)

• Mild flares (no serious organ damage)

- Hydroxychloroquine
- Low-dose steroids

• Moderate flares (organ involvement)

- DMARDs
- Mycophenolate

• Severe flares
- Urgent high-dose steroids
- Mycophenolate, Rituximab, Cyclophosphamide

g) List some examples of drugs that can cause Drug-induced lupus

• Isoniazid
• Hydralazine
• Procainamide
• Quinidine
• Chlorpromazine
• Phenytoin
• Minocycline
• Anti-TNF agents

8. Anti-Phospholipid Syndrome

a) What are the causes of Anti-Phospholipid Syndrome

• Coagulation defect (arterial/venouus0
• Livedo reticularis
• Obstetric (recurrent miscarriage)
• Thrombocytopenia

b) Diagnosis
• Persistent anti-phospholipid antibodies with clinical features

c) Treatment
• Anticoagulation
• Seek advice in pregnancy
9. Systemic Sclerosis/Scleroderma

a) What is Systemic Sclerosis?

• Systemic sclerosis is an autoimmune disorder of connective tissue which results in fibrosis affecting the skin,
internal organs and vasculature

b) Clinical features
• Raynaud’s phenomenon
• Skin
- Non-pitting edema of fingers and flexor tendon sheaths
- Skin becomes shiny & taut
- Distal skin creases disappear
- Capillary loss
- Thinning of the lips & radial furrowing

• Musculoskeletal features
- Arthralgia & flexor tenosynovitis
- Restricted hand function
- Muscle weakness and wasting can result from myositis

• Gastrointestinal involvement
- Smooth muscle atrophy & fibrosis in lower 2/3 of esophagus
- Dysphagia
- Stomach à early satiety
- Outlet obstruction
- Small intestine à malabsorption
- Dilatation of bowel à pseudo-obstruction + nausea, vomiting, abdominal discomfort & distension

• Pulmonary involvement
- Pulmonary hypertension
- Exertional dyspnea
- Signs RHF

c) Investigation
• Routine haematology, Renal, Liver & Bone function test
• Urinalysis
• CXR, Transthoracic echocardiography & Lung function test à r/o interstitial lung disease, pulmonary HTN
• High-resolution lung CT if interstitial lung disease suspected
• Barium swallow à assess esophageal involvement
• Hydrogen breath test à assess bacterial overgrowth

d) Management (No current treatment available)

• Raynaud’s phenomenon & digital ulcers
- Avoid old exposure, use of thermal insulating gloves/socks & maintain high core temperature
- Persistent à Ca Channel Blockers, Losartan, Fluoxetine, Sildenafil
- IV prostacyclin, Fucidin-hydrocortisone cream à digital tip tissue, Endothelin-1 antagonist bosentan
• GI complication
- PPI à esophageal reflux
- Antibiotics à bacterial overgrowth
• Hypertension
- ACE inhibitors
• Joint involvement
- Analgesics, NSAIDs
• Progressive pulmonary hypertension
- Early : Bosentan
- Severe : Heart-lung transplant
• Interstitial lung disease
- Glucocorticoids and Cyclophosphamide