RHEUMATOLOGY

DISEASES
Vigneswari A/P Thirunavukkarasu (180714)
Lim Li Jun (182421)
Ng Yiet Fai (183844)
Outline
◦ Rheumatoid Arthritis (RA)
◦ Systemic Lupus Erythematous (SLE)
◦ Systemic Sclerosis
◦ Gout
RHEUMATOID ARTHRITIS
(RA)
Epidemiology
• Rheumatoid arthritis (RA) is a chronic inflammatory disease,
characterised by a symmetrical, deforming, peripheral polyarthritis.
• Worldwide, the annual incidence of RA is approximately 3 cases per
10,000 population.
• The prevalence rate is approximately 1%, increasing with age and
peaking between the ages of 35 and 50 years.
• RA affects all populations.
• First-degree relatives of individuals with RA are at 2- to 3-fold higher
risk for the disease. 
• Women are affected by RA approximately 3 times more often than
men are but sex differences diminish in older age groups.
• HLA DR4/DR1 linked (associated with increase in severity)
• Increase prevalence in smokers
Pathophysiology of RA
Clinical Presentation
Intra-articular Extra-articular
• Symmetrical swollen, painful • Systemic
and stiff small joints of hands • Musculoskeletal
and feet • Haematological
• Can fluctuate and larger joints • Lymphatic
may become involved • Ocular
• Characteristic deformities: • Vasculitis
• Swan neck • Cardiac
• Boutonniere (button hole • Pulmonary
deformity) • Neurological
• Z deformity of thumb
2010 Rheumatoid Arthritis Classification Criteria
An American College of Rheumatology/European League Against Rheumatism Collaborative Initiative
Investigations
• Full blood count
• Inflammatory marker: ESR, CRP
• Rheumatoid factor (RhF)
• Anti-citrullinated peptide antibody (ACPA/anti-CCP)
• Liver function test
• Renal profile
• X-ray of joints & chest
• Ultrasound/ MRI
Monitoring disease activity
Principles of management
• Refer early to rheumatologist to prevent irreversible destruction
• Early use of DMARDs and biological agents
• Steroids rapidly reduce symptoms and inflammation
• NSAIDs are good for symptoms relief but have no effect on disease
progression
• Physio- and occupational therapy
• Surgery may relieve pain, improve function and prevent deformity
• Manage risk factors
• The mainstay treatment of RA comprises the early use of small-
molecule disease-modifying antirheumatic drugs (DMARDs) , and
corticosteroids for induction of remission
 Disease modifying antirheumatic drugs
(DMARDs)
Drug Usual maintenance Principal side effects Monitoring requirement
dose and frequency

Methotrexate 5-25mg/wk GI upset, stomatitis, rash, alopecia, FBC, LFT

hepatotoxicity, acute pneumonitis Initially monthly, then
every 3 months

Sulfasalazine 2-4g/day Nausea, GI upset, rash, hepatitis, FBC, LFT

neutropaenia, pancytopaenia Monthly for 3 months,
(rare) then 3-monthly
Hydroxychloroquine 200-400mg/day Rash, nausea, diarrhoea, Visual aquity, fundoscopy
headache, corneal deposits, 12-monthly
retinopathy (rare)
Leflunomide 10-20 mg/day Nausea, GI upset, rash, alopecia, FBC, LFT, BP
hepatitis, hypertension 2-4 weekly
Steroids
• Useful for treating acute exacerbation: IM depot methylprednisoone
80-120mg
• Intra-articular steroids have a rapid but short term effect
• Oral steroids: prednisolone 7.5mg/day
• May control difficult symptoms but side effects preclude routine
long-term use
Biological therapies
• Anti-TNF-alpha
• Etanercept, Infliximab, Adalimumab, Certolizumab, Golimumab
• Anti-B-cell therapy
• Rituximab
• Inhibitor of T-cell activation
• Abatacept
• Anti-IL-6
• Tocilizumab
• Anti-IL-1
• Anakinra
 Tofacitinib
JAK -
Biologics

TNFi Non TNFi

Rituximab – CD 20 -
Certolizumab
Etarnecept Abatacept – fusion
– hu
Infliximab - ch protein ( MHC -)
- lack Fc seg
Adalimumab - hu Tocilizumab – IL 6 -
Golimumab - hu
Non-pharmacological treatments
• Occupational therapy
• Podiatry
• Footwear advice
• Psychological advice
• Surgery
 SYSTEMIC LUPUS
ERYTHEMATOSUS (SLE)
 Outline
• Definition
• Prevalence
• Pathophysiology
• Aetiology
• Diagnosis – SLICC Criteria
• Management
 Definition
• SLE is a multisystemic autoimmune disease in which autoantibodies are
made against a variety of antigens.

Source: Oxford Handbook of Medicine, 10th Edition

 Prevalence
• Around 0.2% worldwide
• Female > Male (Ratio 9:1)
• Typically women of child-bearing age
• Common in African-carribeans and Asian
 Pathophysiology
• Immunopathology results in
polyclonal B-cell secretion of
pathogenic autoantibodies
causing tissue damage via
multiple mechanisms:
• Immune complex formation and
deposition
• Complement activation
• Other direct effects
 Aetiology
• Exact aetiology is unknown
• Multiple factors are associated with predisposition of developing SLE
• Genetic: HLA B8, DR2, DR3
• Immunological
• Hormonal
• Environmental – EBV, smoking
 Diagnosis
• Systemic Lupus International Collaborating Clinics (SLICC) Criteria

1.) Fulfillment of at least 4 criterias, with at least 1 clinical criterion AND

1 immunologic criterion
OR
2.) Biopsy-proven Lupus nephritis with positive ANA or anti-dsDNA
antibodies.
 SLICC - Clinical Criteria
1. Acute cutaneous lupus
2. Chronic cutaneous lupus
3. Oral or nasal ulcers
4. Non-scarring alopecia
5. Synovitis/arthritis
6. Serositis (pleuritis or pericarditis)
7. Renal (proteinuria >0.5g/dL or more than 3+, or cellular casts)
8. Neurologic (seizure or psychosis, no other cause)
9. Haemolytic anaemia
10. Leukopenia (< 4000/mm3 on 2 or more occasions)
11. Thrombocytopenia (<100 x 10^9/L) in the absence of drug effect
 SLICC – Immunologic Criteria
1. ANA
2. Anti-dsDNA
3. Anti-Sm
4. Antiphospholipid antibody
5. Low complement(C3, C4)
6. Direct Coombs test in the absence of haemolytic anaemia
 Acute cutaneous lupus
• Photosensitive rash, slightly raised erythema
• Occasionally scaly rash
• Butterfly/ malar rash

Chronic cutaneous lupus

• Discoid Lupus Erythematosus (DLE) – 20% SLE pts have discoid rash
• Roughly circular, slightly raised, scaly hyperpigmented erythematous
rims and depigmented
Oral ulcers
• Usually painless

Non-scarring alopecia
• Diffuse thinning or hair fragility with visible broken hairs
 Synovitis/arthritis
• Non-erosive arthritis involving 2 or more joints,
• Characterized by:
-Swelling or effusion
OR
-Tenderness in 2 or more joints and 30 minutes or more of morning
stiffness.
 Serositis
1.) Pleuritis
• Pleuritic pain/ pleuritic rub
• +/- Evidence of pleural effusion

2.) Pericarditis
• Documented by ECG
• Pericardic rub
• Evidence of pericardial effusion
 Renal disorder
1.) Persistent proteinuria >0.5 g/day or more than 3+
OR
2.) Cellular casts: RBC, Hb, granular, tubular or mixed
 CNS/ Neurological disorder
1.) Seizures
• With no other causes: electrolyte imbalance, head trauma etc

2.) Psychosis
• With no other causes: drug induced, uremia, ketoacidosis, electrolyte
imbalance etc
 Haematological disorder
1.) Haemolytic anaemia: with reticulocytosis
2.) Leukopenia: <400/mm3 on 2 or more occasions
3.) Lymphopenia: <1500/mm3 on 2 or more occasions
4.) Thrombocytopenia: <100 x 10^9/L in the absence of drug effect
 Immunological disorder
1.) Anti-dsDNA antibody
2.) Anti-Sm antibody
3.) Antiphospholipid antibody
Positive (+ve) based on:
-an abnormal serum level of IgG or IgM anticardiolipin Ab
-positive result for lupus anticoagulant using a standard method
-false +ve syphilis serology: if +ve for >6 months & confirmed by –ve
Treponema pallidum immobilization and fluorescent treponemal Ab
absorption tests (The phospholipid reagents used for syphilis can cause
false +ve in pts with antiphospholipid Ab)
 Antinuclear antibody (ANA)
• +ve in >95% pts
• ANA above laboratory reference range
• In the absence of drugs known to be associated with drug-induced
lupus syndrome
 Management
• Individualised therapy according to clinical manifestations and
severity.
• Aim: Good quality of life, control clinical manifestations and prevent
serious end organ damage.
• Pharmacological vs Non-pharmacological
 Non-pharmacological treatment
• Avoid excessive exposure to sunlight
• Use sunscreen
• Patient education – complications of disease, contraception during
active phase/flare etc
• Support group
• Healthy diet and lifestyle modification to prevent cardiovascular
disease
 Pharmacological treatment
• NSAIDs and painkiller: Arthralgia, arthritis, serositis
• Topical corticosteroid: Cutaneous lupus
• Antimalarial drugs (hydroxychloroquine 200-400mg daily): Mild skin
disease, fatigue, arthralgia that cannot be controlled with NSAIDs but
patient need regular eye checks because of rare retinal toxicity
• Control CVS risk such as HTN and hyperlipidemia
 Pharmacological treatment (cont.)
Life-threatening disease (renal, CNS and cardiac involvement)
• High dose corticosteroids + immunosuppressant
• Eg: Methyprednisolone (10mg/kg) + Cyclophosphamide (15mg/kg)
repeat at 2 – 3 weekly interval for 6 cycles

Maintance therapy
• Oral prednisolone (40 – 60 mg/ daily) gradually reducing to targeted
dose 10 – 15 mg/ daily less by 3 months
• +Azathioprine (2 – 2.5mg/kg/day), methotrexate (10 -25 mg/ week)
 Treatment side effects
Occur with prolonged use of high dose steroids:
• Cushing’s disease/ appearance
• Hypertension
• Diabetes mellitus
• Osteoporosis
• Immunosuppression: recurrent infection
• Cataract
• Narrow-angle glaucoma
• Psychosis
 Treatment side effects
Cyclophosphamide side effects:
• Haemorrhagic cystitis
• Cannot get pregnant 6 months before and after treatment
• Hair loss
 References
1.) SLE, Oxford Handbook of Clinical Medicine, 10th Edition.
2.) SLE clinical examinations, textbook: Talley & Connor, 7th Edition.
3.) SLICC criteria – RheumTutor.com
SYSTEMIC SCLEROSIS
(SCLERODERMA)
Epidemiology
• Incidence and prevalence vary across studies
• Incidence: 8 to 56 new cases per million yearly
• Prevalence: 38 to 341 cases per million yearly
• Female > male
Clinical Presentation
• Cutaneous manifestation
• Digital vasculopathy
• Musculoskeletal manifestation
• Gastrointestinal involvement
• Pulmonary involvement
• Cardiac involvement
• Renal involvement
• Neuromuscular involvement
• Genitourinary involvement
Skin Manifestation
• Variable extent and severity of skin thickening and hardening
• Earliest area of involvement:
• Fingers
• Hands
• Face
• Edematous swelling and erythema precede skin induration
 Skin Manifestation
Shiny skins suggests impending skin
Diffusely puffy fingers thickening

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Other Prominent Skin Manifestation
• Early stages: pruritus and oedema
• Skin hyperpigmentation/ depigmentation
• Loss of appendicular hair
• Dry skin
• Capillary changes at the nail beds
• Lipoatrophy (diffuse loss of subcutaneous adipose tissue that most apparent in the face,
buttocks, legs, and arms)
• Ulceration at DIP and PIP joints (due to repetitive microtrauma over tightened skin)
• Digital tips ulcer with/without pitting at finger tips
• Telangiectasia (visibly dilated blood vessel on the skin or mucosal surface)
• Calcinosis cutis (calcium deposits form in the skin)
Other Prominent Skin Manifestation

Telangiectasia Calcinosis Cutis on radiograph

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s-disorders/idiopathic-telangiectasias HEUM%2F7539&search=systemic%20sclerosis&rank=1~150&source=see_link
Digital Vasculopathy
• Reynaud’s Phenomenon
• Classically reversible vasospasm due to functional changes in the digital
arteries of hand and foot
• Chronic leads to progressive structural changes in small blood vessels
• Finally permanently impaired flow
• Prolonged RP lasting more than 30 minutes
• With ischemic pain, digital ulceration and trophic changes
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Mnemonics: SCLERODERMA
• Skin: Hyperpigmentation, telangiectasia, subcutaneous calcification, fingertips ulcer
• Cardiac: Myocardial fibrosis, cardiac failure
• Lung: Interstitial lung disease, aspiration pneumonia, pulmonary hypertension
• Esophageal dysfunction
• Raynaud’s phenomenon
• Obstruction (pseudo) of intestine
• Dry eyes/mouth (Sjogren’s syndrome)
• Endocrine (hypothyroidism)
• Renal failure: malignant hypertension
• Myopathy
• Arthritis
Diagnosis: ACR/EULAR 2013 Criteria for Classification of Systemic
Sclerosis
Disease Subset of Systemic Sclerosis
• Limited cutaneous systemic sclerosis
• More commonly present as skin sclerosis distal to elbow and knees
• And most have CREST syndrome
• Calcinosis cutis
• Raynaud phenomenon
• Esophageal dysmotility
• Sclerodactyly
• Telangiectasia
• Diffuse cutaneous systemic sclerosis
• More rapid progression
• Early development of lung fibrosis and higher risk of renal and cardiac involvement
• Systemic sclerosis sine scleroderma
• Positive ANA
• Systemic sclerosis with overlap syndrome
• Presence of SLE, inflammatory arthritis and inflammatory muscle disease
Management
• Organ based symptomatic therapy
• Systemic immunosuppressive therapy
• Reduce progression/severity of complication
• Severe progressive diffuse skin involvement
• Interstitial lung disease
• Myocarditis
• Severe inflammatory myopathy with or without arthritis
• Systemic Sclerosis with overlap syndrome might need different
therapeutic approach following predominant features of the overlap
syndrome (SLE, polymyositis)
Organ Based treatment
• Skin
• Morphea: Topical with tacrolismus and corticosteroid, intralesional
corticosteroid
• Diffuse skin sclerosis: immunosuppressive therapy with methotrexate,
mycophenolate mofetil. If refractory, consider cyclophosphamide.
• Pruritus: antihistamines
• Telangiectasia: cosmetic problem may be treated with laser therapy if large
lesion
• Calcinosis cutis: oral minocycline 50-100mg daily 6-12 weeks to prevent pain
and ulceration. If refractory, consider surgical removal
Organ Based treatment
• Raynaud Phenomenon
• Non pharmacological
• Avoidance of cold exposure
• Maintain whole body and digital warmth
• Avoidance of repeated trauma to fingertips and vibration
• Pharmacological
• Calcium channel blocker
• Amlodipine 5-20mg daily
• Nifedipine 30-120mg daily
• Phosphodiesterase type 5 inhibitor
• Sildenafil 20mg OD/BD/TDS
GOUT
Epidemiology

Protective Factor
• Women in reproductive age
• due to protective effect of
oestrogen enhancing renal uric
acid clearance
Clinical Presentation

Gout flares Tophaceous gout

• Severe pain, redness, warmth,
swelling and disability
• Onset: at night
• Signs of inflammation extending
beyond joint
• Normally involves ankle, wrist,
finger, olecranon bursa
Tophus
Copyrights apply
Copyrights apply
Copyrights apply
Management
• Treatment of Gout Flares
• Systemic and intraarticular glucorticoids:
• oral prednisolone 30-40mg once daily until flare resolution and taper over 7-10 days
• Arthrocentesis with joint fluid aspiration and intraarticular glucocorticoid for patient with
1 or 2 inflamed joints/unable to take oral medication
• NSAIDs
• Naproxen 500mg BD
• Ibuprofen 800mg TDS
• Diclofenac 50mg BD
• Celecoxib 200mg BD
Management
• Treatment of Gout Flares
• Colchicine
• Used when
• Glucocorticoid and NSAIDs contraindicated or intolerance
• In patients initiating anti-inflammatory gout flare therapy within 24 hours of symptoms onset
• Initial oral dose 1.2mg, followed by 0.6mg after 1 hour OR oral 0.6mg TDS on first day of
therapy
• Followed by oral 0.6mg BD or OD until 3 days after complete resolution of gout flare
• Contraindicated in renal and hepatic impairment
• Biologic agents
Management
• Urate lowering therapy
• Indication: frequent/disabling gout flares, tophi and structural joint damage, gout with renal
insufficiency
• Target urate level: serum urate <6mg/dL for patient without tophi and <5mg/dL for patient with tophi
• First line: Xanthine oxidase inhibitor Allopurinol 100mg OD with weight adjusted creatinine clearance
>60mL/minute, dose titration by 100mg every 2 to 4 weeks
• Dosing varies for reduced renal function
• Stop therapy if presence of signs of hypersensitivity and rash
• Combination with uricosuric if inadequate
• Prophylaxis during initiation of urate lowering therapy
• Colchicine 0.6mg OD or NSAIDs such as naproxen 250mg BD to prevent recurrent episode of gout
flares
• Prophylaxis duration
• 3-6 months after normal level is achieved if no tophi
• 6 to 12 months if tophi present
References
◦ M. Longmore, I. B. Wilkinson, A. Baldwin, E. Wallin, Oxford Handbook of Clinical Medicine, 9 th
Edition, 2014, Oxford University Press.
◦ B. R. Walker, N. R. Colledge, S. H. Ralston, I. D. Penman, Davidson’s Principles & Practice of
Medicine, 22nd Edition, 2014, Elsevier Limited.
◦ Rheumatoid Arthritis (RA): Practice Essentials, Background, Pathophysiology. (2020). Retrieved from
https://emedicine.medscape.com/article/331715-overview
◦ 2010 Rheumatoid Arthritis Classification Criteria; An American College of Rheumatology/European
League Against Rheumatism Collaborative Initiative