Rheumatology Flashcards
Joint pain
DDx
- Monoarthritis
Septic shock
Gout, pseudogout
Haemarthrosis: trauma, Coagulopathy
OA
Monoarthritis onset of RA/SpA/SLE
Bursitis, tendonitis - Oligoarthritis (2-4 joints)
- Sondyloarthropathies (SpA)
• AS
• PsA
• Reactive arthritis
• IBD-associated arthritis - Polyarthritis (≥5 joints)
Acute
• infective: Gonococcal, Streptococci, IE, Lyme, viral, rheumatic fever
• inflammatory
Chronic ≥ 6 weeks
• inflammatory: RA, SpA, CTD (e.g. SLE, SSc, vasculitis)
• Non-inflammatory: multiple OA, gout/CPPD, malignancy
Important questions
• Onset: acute (septic, gout), chronic (i.e. ≥ 6 weeks)
• Severity: pain score, night pain, impact on ADL, impact on mood & social
• Differentiate inflammatory vs degenerative
Inflammatory
- variable joint involvement
- exacerbate by rest and relive by motion
- early morning stiffness >1h
- erythema, swelling, warmth
- systemic complaints
Dengerative
- weight-bearing joint
- exacerbate by motion, relieve by rest
- early morning stiffness <30min
- joint locking
• Differentiate seropositive vs seronegative arthritis (SpA)
Seropoitive
- F>M
- arthritis: symmetrical, peripheral smal joints: PIPJ, MCPJ
- Raynaud’s phenomenon
- +ve RF
- -ve HLA-B27
Seronegative
- M>F
- Asymmetrical arthritis, peripheral and axial joint
- Acute anterior uveitis, IBD, reactive arthritis, psoriasis (PsA)
- -ve RF
- +ve HLA-B27
Investigations
• Bloods: CBC, LRFT, CaPO4, urate, ESR/ CRP, ANA/ RF/ anti-CCP
• Urinalysis
• Imaging: X-ray of affected joints; musculoskeletal USG (MSUS) & MRI if indicated
• ± Joint fluid: microscopy, cell count, gram stain, C/ST, AFB smear & culture
• ± Synovial biopsy (if undetermined)
Cervical C1/2 subluxation
Clinical features
• Suspect in RA patients with long-standing and severe disease
• S/S: Neck pain radiating towards occiput, clumsiness, abnormal gait, spastic quadriparesis, sensory & sphincter disturbances
• 4 forms: anterior > posterior > lateral > vertical
Investigations
• Plain AP & Lateral XR C-spine with flexion and extension views
o Atlanto-dental interval (ADI): C1 anterior arch to C2 dens
(normal < 3mm, clinically significant >5mm, need surgery if >8mm)
• Dynamic (flexion-extension) MRI C-spine: bone marrow oedema, needed if surgery
Management
• Conservative (if no signs of cord compression): stiff neck collar, avoid high-impact exercise, neuropathic pain relief
• Surgical (if signs of cord compression): craniocervical decompression, cervical
Scleroderma renal crisis
• Found in 10-15% of scleroderma patients, life-threatening (can progress to ESRD within 1-2 months)
• Pathology: vasculopathy —> intra-renal arterial stenosis —> activate RAAS
• Risk factor: steroid use (esp. in diffuse SSc)
Clinical features
• Sudden onset, no significant prodromal symptoms, rapid progressive
• Presentations: Malignant HT, AKI, ± microangiopathic haemolytic anaemia
Management
• BP control: ACEI (± CCB)
• ESRD: dialysis, renal transplant
Temporal arteritis / Giant cell arteritis
Pathology: granulomatous inflammation of large vessels (e.g. H&N, aortic branches)
ACR classification criteria (≥3/5) – “BATHE”
• Biopsy evidence: necrotizing arteritis, predominant mononuclear cells / multinucleated giant cells (granuloma)
• Age ≥ 50y
• Tenderness/ decreased pulsation of temporal artery
• New onset localised Headache
• ESR > 50
Clinical features
• S/S: throbbing headache, scalp tenderness, tender temporal a., constitutional symptoms (fever, weight loss)
• Jaw claudication: pain on prolonged chewing 越咬越痛 (occluded mandibular branch of ECA)
• Polymyalgia rheumatica (PMR) in 40-50%: aching & morning stiffness in bilateral shoulder and hip girdles
• Complications:
o Anterior ischaemic optic retinopathy (AION): sudden painless blindness (vasculitis of post. ciliary arteries)
– may be preceded by amaurosis fugax, 15-20% permanent visual loss
o Aortic arch syndrome: aneurysm, dissection, stenosis of aorta and its major branches (DDx Takayasu’s arteritis) – both arm BP!
Management
• Investigations: ESR (often >100), temporal artery ultrasound (halo sign), consult NS for biopsy (1 side, 1cm long)
• High-dose prednisolone 1mg/kg/day: save vision of other eye & prevent brainstem stroke
o Acute visual changes: consider IV pulse methylprednisolone (250-1000mg) daily x 3 days
o Taper steroid according to clinical S/S and ESR, mean duration 18-24 months
• Refractory case: anti-IL6 (tocilizumab)
Monitoring
• Frequent FU: at least monthly for first 6 months, then 3-monthly
• Investigations on FU: CBC, RFT, ESR, CRP, glucose; CXR for aortic aneurysm (Q2y)
Pulmonary renal syndrome
Clinical entities characterised by rapidly progressive GN and diffuse alveolar haemorrhage - causes include
• Goodpasture syndrome
• ANCA-associated vasculitis e.g. GPA, eGPA, MPA
• SLE, drug-induced (PTU)
Clinical features
Suspect if unexplained pulmonary & renal symptoms, even if they do not occur at the same time
• AKI & signs of GN: haematuria, peripheral oedema
• Acute pulmonary haemorrhage: SOB, cough, haemoptysis, fever
Investigations
• ESR/CRP increase
• Renal involvement: RFT, urinalysis, renal biopsy (pauci-immune GN)
• Lung involvement: CXR, HRCT, bronchoscopy
• Underlying cause: anti-dsDNA/ C3/ C4, anti-GBM (Goodpasture), c-ANCA & p-ANCA, anti-histone Ab (drug)
Management
• Remove offending drug
• Organ support: dialysis, ventilator (+/- consult ICU)
• High-dose steroid / IV pulse steroid
• Cyclophosphamide / rituximab if refractory
• Plasma exchange possibly useful in: AKI requiring dialysis / pulmonary haemorrhage / anti-GBM +ve patients
Rheumatic arthritis
• Most common chronic inflammatory arthritis (~0.35% in HK, M:F = 1:3), a/w HLA-DR4
• Definition: chronic, symmetric, erosive synovitis of multiple peripheral joints
• Pathogenesis: type III immune response against synovium —> pannus formation (granulation tissue) and inflammatory infiltrates —> erode into cartilage & juxta-articular bone —> irreversible deformity
Clinical features
Bilateral symmetric involvement of joints
• Duration > 6 weeks
• Joints: small joints of hand and feet, then “spread” to any peripheral joints
o Most common joints: MCPJ, PIPJ, wrist
o DIPJ & axial joints usually spared (little synovial lining) except C1/2)
• Early joint swelling: morning stiffness > 1h, exacerbated with rest, relieved with use
• Late joint damage & deformities:
o Boutonniere deformity (buttonhole): flexed PIPJ, hyperextended DIPJ
o Z deformity of thumb: flexed MCPJ, hyperextended IPJ
o Swan neck deformity: hyperextended PIPJ, flexed DIPJ
o Ulnar deviation & volar subluxation of MCPJ
o Radial deviation at wrist joint, piano key movement of ulnar styloid
o Foot: hallux valgus, hammer toe, claw toe, “cock up” deformity
Extra-articular manifestations
Skin:
- Rheumatoid nodules: RF +ve —> poorer prognosis
- Raynaud’s phenomenon: usually RF +ve
- 2° Sjögren’s syndrome
MSK:
- Osteoporosis: due to chronic inflammation & steroid use
- Muscle weakness: due to synovitis, myositis, drug- induced (steroid, hydroxychloroquine, statin)
Eye:
- Episcleritis/ scleritis
Lung:
- Interstitial lung disease (RA-related, MTX-induced)
- Rheumatoid nodules (specific), Caplan syndrome (RA + pneumoconiosis), pleuritis, pleural effusion
Heart :
- Pericarditis, myocarditis
- Independent CV risk factor: due to chronic inflammation
Neuro:
- Carpel tunnel syndrome (∵tenosynovitis)
- Myelopathy due to atlantoaxial instability
Haemat:
- Anaemia:
• Disease-related: anemia of chronic disease, RA-associated pernicious anaemia, Felty’s syndrome (RA
+ splenomegaly + neutropenia), AIHA
• Tx-related: NSAID (GIB), MTX (myelosuppression, folate deficiency), SSZ (haemolytic anaemia), Increased risk of lymphoma, 2° amyloidosis
Investigations (SAQ!)
• Bloods:
o Baseline: CBC, LRFT, HBsAg, anti-HCV, G6PD
o Acute phase reactants: CRP, ESR
o Serology:
- RF (70%): IgM autoAb against Fc fragment of IgG
—> False +ve: normal population (~4%, up to 25% in elderly), other CTD (e.g. SLE, Sjogren, cryoglobulinemia), SBE, TB
- Anti-CCP (50-75%): similar sensitivity, more specific (96%)
Serology only for diagnostic and prognostic but not disease monitoring
2010 ACR/EULAR classification criteria
≥6 points = classified as RA
Must exclude DDx (e.g. PsA, SSc)
In case of erosiveness (chronic RA
deformity), no other points needed
• XR joint: (early RA can be normal —> soft tissue swelling —> periarticular bony erosion —> periarticular osteopenia —> narrowed joint space —> marginal erosions —> subluxation —> ankylosis
• USG: if clinical examination is inconclusive, to detect early signs of synovitis
• ± Joint aspirate: exclude septic arthritis and crystal arthropathies
• MRI: bone marrow edema (40-60%, a/w poor prognosis)
Assessment of disease activity
• DAS28: # of tender joints (TJ) and swollen joints (SJ), ESR, General Health status (GH)
• Others: ACR 20/50/70 response criteria, Simplified Disease Activity Index
(SDAI), Clinical Disease Activity Index (CDAI)
Management (SAQ!)
Principles:
• Early diagnosis: best outcome within 2 years of onset
• Early aggressive treatment (initiate within window of opportunity: ≤3-6 months of symptom onset)
• Maintain lowest possible disease activity (DAS28 < 2.6) – FU every 3 months
• Treat-to-target (target low disease activity / clinical remission within 6 months)
Management: multidisciplinary approach (PT, OT, podiatrist, dietitian)
• Non-pharmacological: exercise, smoking cessation, CV risk optimization, immunisation, occupation modification
• Pharmacological:
o Symptomatic relief: analgesics / NSAIDs
o Low-dose + short-term (<3-6 months) steroids: bridging when switching DMARDs
o Disease-modifying antirheumatic drugs (DMARDs): proven to alter disease course, start asap
o Algorithm: Switch therapy if <50% activity improvement at 3 months, or target not reached at 6 months
1. Conventional synthetic (csDMARD) - All take time to act (~6 weeks):
• Methotrexate*: 1st line unless C/I, oral 7.5-16mg weekly, taken with folic acid 2d after
- Efficacy: 25-40% improve with MTX monotherapy, ~50% if MTX + steroids
- S/E: GI upset, myelosuppression, hepatotoxicity, nephrotoxicity, teratogenicity
• Sulfasalazine: C/I in G6PD, S/E: yellowish secretions, GI upset, leucopenia, liver
• Leflunomide: S/E GI upset, leucopenia, liver, teratogenicity
• Hydroxychloroquine: S/E GI upset, bluish skin pigmentation, maculopathy
2. Biological DMARDs (SC/IV only)
• TNF inhibitors: infliximab, adalimumab, etanercept, golimumab, certolizumab
T cell costimulation (CD80 & CD86) inhibitor: abatacept
IL-6R inhibitor: tocilizumab, sarilumab
Anti-CD20: rituximab
3. Targeted synthetic (tsDMARD)
• Janus kinase inhibitors (PO): tofacitinib, baricitinib, upadacitinib
- S/E: herpes zoster infection (check VZV Ab before initiation)
Poor prognostic factors:
consider biologics
- Moderate-to-high disease
activity (DAS28)
- High ESR / CRP
- High swollen joint counts
- High RF / anti-CCP titres
- Early joint damage (bony
erosions on XR)
- Failure of ≥ 2 csDMARDs
- Family Hx of RA
Allowed in pregnancy
- Steroids
- Sulfasalazine
- Hydroxychloroquine
Systemic lupus erythematosus
Overview
• A chronic, multisystem, autoimmune disease
characterised by exacerbation and remission
• Predominant in female (9:1)
• Drug-induced lupus (e.g. hydralazine,
procainamide, isoniazid)
Pathophysiology
Multifactorial
• Genetic predisposition: HLA-DR2/DR3/A1/B8
• Hormonal factors: estrogen, progesterone
• Environmental factors: infection (EBV), stress, UV
• Type III HSR: immune complex —> deposition causes inflammation in skin, glomeruli, etc
• Type II HSR: autoantibodies —> cytopenia
Classification criteria: EULAR/ ACR criteria 2019
• 7 Clinical domains + 3 immunological domains
• SLE if ANA positive + total score of ≥10
S/S:
Constitutional Sx
- Fever, weight loss, poor appetite
Cutaneous lupus
- Malar rash (butterfly rash): usually no scarring
• Erythematous maculopapular rash in butterfly distribution over the cheeks and bridge of nose, sparing nasolabial fold
- Photosensitivity
- Non-scarring alopecia
- Discoid lupus: raised erythema with
scaling, follicular plugging and scarring
Other skin Sx
- Oral / Nasal ulcers (usually painless), nail change (periungal infarct, splinter haemorrhage)
- Palmar erythema, vasculitis rash (purpura), livedo reticularis, subcutaneous nodules (5%)
- Raynaud’s phenomenon (20%)
Joint involvement
- Symmetrical non-erosive small joint polyarthritis resembling RA (90%)
—> If deformed: Jaccoud arthropathy (involve ligament & peri-articular soft tissue)
- Myalgia: inflammatory myositis (less common) vs drug-induced (steroid, statin, HCQ)
- AVN hip: active disease, steroid-induced
- Osteoporosis:
• Disease-related: lack of sun exposure, renal osteodystrophy (lupus nephritis)
• Treatment-related: steroid, cyclophosphamide (premature menopause
Respiratory
- Interstitial lung disease (basal), pleural effusion
Cardiovascular
- Increased CVS risk (accelerated coronary atherosclerosis)
• Disease-related: chronic inflammation, HT due to lupus nephritis, APS
• Treatment-related: steroid
- Non-bacterial endocarditis (Libman-Sacks endocarditis*)
- Pericardial effusion / pericarditis
Renal (50%)
- Lupus nephritis: refer below
Neuropsychiatric
- All kinds of manifestations possible; lupus headache (tight band), stroke (suspect APS), seizure, mononeuritis multiplex, psychosis (DDx: steroid-induced)
Eye
- Fundoscopy: optic neuritis, cytoid bodies (retinal infarcts), papilledema
- Sjogren’s syndrome
Haematological
- Anemia: micro (GI bleed due to steroid use) vs normo (ACD) vs macro (AIHA)
- Neutropenia, thrombocytopenia, LN, splenomegaly
*Libman-Sacks endocarditis (pathognomonic): atypical sterile valvular vegetations, diffuse leaflet thickening, etc.
^DDx of Jaccoud’s arthropathy: rheumatic fever, Parkinson’s disease
Investigations (as in EULAR criteria)
• Bloods: CBC d/c, LFT (decrease albumin), RFT, ESR/CRP, clotting, DAT, FBG/lipids (CV risk)
• Urine: urine dipstick, microscopy, uPCR
• Autoimmune markers:
- ANA (100%) —> Most sensitive, entry criteria for Dx
- Anti-dsDNA (60%) —> Highly specific, for Dx and monitoring (only if it fluctuates with severity)
- Anti-Sm (10-30%) —> Most specific, a/w neurological involvement
- Anti-ENA (anti-Ro & anti-La) —> Associated with subacute cutaneous lupus; - Anti-Ro: a/w photosensitivity, congenital heart block
- Antiphospholipid Ab (40%) —> Refer below for clinical features of APLS
- C3/C4 —> Low in active disease (esp. C3): consumption of C’ for opsonization of IC
Management (SAQ!)
Non-pharm Mx
• Sun protection: avoid UV light, use umbrella, long-sleeve clothes, SPF15+ sun lotion
• Exercise & smoking cessation (affect response to HCQ)
• Vaccination
• Screen and control CVS risk factors
• Avoid offending drugs and OCP
Pharm Mx
Acute flare-up: steroid, immunosuppressant (MMF, cyclophosphamide)
Maintenance therapy
• Mild disease (skin, joint, mucosal involvement)
o Hydroxychloroquine: overall stabilising SLE, decrease infection, decrease lipid, anti-thrombotic
o ±NSAID: symptomatic relief for arthralgia, fever, headache
o ± short-term low-dose steroid (pred ≤7.5mg/day)
o ± topical steroids: skin rash
o ± azathioprine: mild hemat / renal involvement
o ± methotrexate: refractory skin/joint disease
• Severe disease (life-threatening major organ involvement, e.g. kidney, CNS, CVS)
o Hydroxychloroquine +
o Induction: high dose steroid (1-2mg/kg/day) / IV pulse steroids 0.5-1g/day x 3 days
o Maintenance: steroid-sparing agents (AZA/MTX, MMF, cyclophosphamide (IV/PO)) ± low-dose steroids
• Other adjuncts if refractory:
o Biologics: belimumab (BLyS inhibitor), anifrolumab (anti-IFN1 receptor)
o Plasma exchange / IVIG / rituximab (not FDA approved)
o Vasodilators (for PAH), anticoagulation
o Under Ix: obinutuzumab (CD20), daratumumab (CD38), litifilimab
Hydroxychloroquine:
• Take ≥12 weeks to see effect
• Withdrawal may trigger flare
• S/E: GI upset (MC), corneal
deposition (reversible), Bull’s eye maculopathy (irreversible), bluish skin pigmentation
Disease monitoring
• Clinical assessment: 甩頭髮、⽣痱滋、⼼⼝痛、氣促、腳腫、關
節痛、肌⾁痛、頭痛、發燒、出疹
• Bloods: BP, CBC, LFT, RFT
• Urine: urine dipstick, urinalysis and uPCR (lupus nephritis)
• Serology: C3/4, anti-dsDNA, CRP (not ESR)
o ANA not useful: not correlate with activity
o ESR not useful: always high, not correlate with activity
o CRP: moderate in serositis/arthritis, must r/o infection before adding immunosuppressants
• Eye check: annually after 5 years of HCQ use
• Disease activity: SLE disease activity index (SLEDAI) >4 = flare
• Damage: SLICC/ACR-DI score (see note)
Poor prognostic factors
• Young male
• Lupus nephritis
• APLS
• High overall disease activity
Active disease vs damage
• Active disease: manifestations of the underlying inflammatory process in
terms of magnitude and intensity
• Damage: degree of irreversible organ dysfunction
• Manifestation that indicates active disease (but not damage)
o Malar rash
o Non-scarring alopecia
o Oral ulcers
o Joint pain
• Manifestations that indicates damage (but not active disease)
o Raynaud’s phenomenon
Special considerations in SLE
1. Fever in SLE:
Fever in SLE = sepsis until proven otherwise
Ix: septic work up, CRP
Mx: Withhold immunosuppressants, stress-dose steroids, empirical broad-spectrum ABx
2. Hip pain in SLE
DDx: active disease, septic arthritis, steroid-induced AVN
Ix: USG hip, MRI hip
3. Pregnancy in SLE
Before conception: achieve remission for ≥6 months
Use barrier contraceptives: OCP exacerbates lupus activity
Check bloods (anti-Ro/ La, LAC, aCL) before pregnancy
Continue HCQ: stabilize SLE, improve fetal outcome, stopping may precipitate flare
SLE increases risk of pregnancy complications:
• Recurrent miscarriage (APLS): consider aspirin ± LMWH
• Neonatal lupus: congenital complete heart block (anti-Ro/ La)
• Pre-eclampsia, IUGR: add aspirin
Pregnancy increases risk of SLE flare-up
Lupus nephritis
• Risk factors: juvenile SLE, male
• Clinical features: variable, e.g. microscopic haematuria, proteinuria, AKI
o Depend on pathophysiology (anti-DNA IC deposition): mesangial deposits —> activate C’ —> nephritic-like;
subepithelial deposit —> nephrotic-like
Renal biopsy
• Indications of renal biopsy (important because Mx is guided by histology)
o Proteinuria > 0.5g/day
o Persistent hematuria
o Raised Cr not attributed to another mechanism
• Renal biopsy report:
o Histology
o Activity index: proliferation & inflammation —> determine intensity of treatment
o Chronicity index: degree of sclerosis, fibrosis —> prevent further worsening by CV risk control (ACEI, statins)
• Repeat biopsy if disease progresses
WHO classification
Class I —> Minimal mesangial —> Conservative Tx (BP control, RAAS inhibitor, HCQ)
Class II —> Mesangial proliferative —> Conservative Tx (BP control, RAAS inhibitor, HCQ), Consider low-dose steroids if proteinuria >1g/day, anti-dsDNA or decrease C3
Class III —> Focal
Class IV —> Diffuse
Class V —> Membranous
—> Indication of immunosuppressants (EULAR):
• Active Class III / IV
• Class III + V / Class IV + V
• Pure Class V + proteinuria >1g/day despite anti-proteinurics (e.g. ACEI)
V Membranous
Regimen
• Induction (6 months): high-dose steroid + IV MMF / cyclophosphamide^
• Maintenance (≥ 2 years): low-dose steroid + MMF / azathioprine
Class VI —> Advanced sclerosing —> ESRD planning
MMF vs cyclophosphamide:
• MMF is first-line due to less S/E (Cyc:
premature ovarian failure, haemorrhagic
cystitis),
• Cyclophosphamide is faster onset: reserved for rapidly progressive GN / poor RFT
• Cyclophosphamide cannot be used for
maintenance Tx
• If pure class V, cyclophosphamide is not
indicated —> use MMF
Antiphospholipid syndrome
APLS occurs in ~30% of SLE. 2% of population is Ab +ve.
Diagnostic criteria
• Clinical criteria: any one of
o Recurrent thrombosis: venous (DVT/ PE) or arterial (stroke/ ACS/ PVD)
o Recurrent miscarriage
• Antiphospholipid antibody: lupus anticoagulant (↑APTT, most thrombogenic) > anti-cardiolipin > anti-β2
glycoprotein (most specific for APLS, but limited sensitivity —> only check if another two -ve)
o Require TWO measurements 12 weeks apart
Other associations
• Thrombocytopenia: usually mild, no treatment required
• Livedo reticularis (presence of small clots in capillaries) (fig.)
• Valvular heart lesions
Management
• 2° prevention: lifelong warfarin (INR 2-3) ± aspirin (if arterial thrombosis)
o DOAC should not be used: thrombotic risk
• Recurrent thrombosis despite anticoagulation: higher target INR (3-4) / add aspirin or HCQ / switch to LMWH
• Catastrophic APS (CAPS: widespread thrombosis with multiple organ damage that develops within a week):
anticoagulation + high-dose steroid + IVIG / plasma exchange
• Pregnancy: aspirin +/- LMWH
Scleroderma / systemic sclerosis
Pathophysiology: all S/S linked to these 3 independent processes (must know!)
• Immunological activation1
• Occlusive vasculopathy2
• Tissue fibrosis3
Signs
• CREST syndrome for limited SSc:
o Calcinosis
o Raynaud’s phenomenon2
o Esophageal dysmotility3: GERD
o Sclerodactyly3: thickened tight skin, digital ulcers/gangrene, atrophic nails, shortening of fingers, non-pitting edema decrease ROM
o Telangiectasia2: usually at nail fold capillaries
• Acro-osteolysis: bone resorption of distal phalanges (refer to diagram)
• Facial features: pinched beak-like nose, thin lips, radial furrows around mouth, microstomia
Types
1. Limited SSc
- anti-centromere
- Slow development of skin ; Distal to elbow and knee
- Raynaud’s: Long preceding history
- Organ involvement
Late
• GI: GERD3 common, a/w PBC
• Lung: Type 1 PAH2 +/- ILD
• Renal: uncommon
• Cardiac: less severe
- Diffuse SSc
- Anti-Scl70, anti-RNA polymerase III
- Rapid and progressive skin development, extending to proximal extremities
- sudden onset of Raynaud’s phenomenen
- Organ involvement
Early
• GI: GERD3, malabsorption
• Lung: ILD1,3 +/- 2° PAH
• Renal: scleroderma renal crisis2
• Cardiac: more severe (pericarditis, arrhythmia)
EULAR/ACR classification criteria for SSc (2017)
• For reference only: Sclerodactyly extending proximal to MCPJ alone as a sufficient criterion
Investigations
• Bloods: CBC, RFT, ESR
• Autoimmune markers:
o ANA: highly sensitive (95%), reconsider diagnosis if negative
o Scleroderma-related Ab: anti-centromere, anti-Scl70, anti-RNA polymerase III
• Imaging: X-ray hands, nailfold capillaroscopy
• Investigations for organ involvement:
o CXR, HRCT, PFT (ILD), Doppler echocardiogram (pulmonary HT)
o OGD / manometry (GERD
Management
Organ-based symptomatic treatment
1. Skin
- Good skin hygiene, low-dose steroids (avoid high dose), ?methotrexate, D-penicillamine
2. Raynaud’s
Keep warm, avoid stress & smoking, stop beta-blockers (exacerbate), avoid trauma (H’stix),
Vasodilators: CCB (amlodipine), ARB, PDE inhibitors (sildenafil)
3. GI
- GERD – PPI / H2 blockers
- Dysmotility – prokinetics (e.g. metoclopramide)
4. Renal
- ACEI for renal crisis, avoid high dose steroid (prednisolone > 10mg/day)
5. Lung
- ILD: immunosuppressants1 (MMF/ cyclophosphamide / rituximab / tocilizumab), nintedanib3
- Pul HT: vasoactive agents e.g. bosentan/ sildenafil / riociguat (sGC sensitizer)
6. MSK
- Arthritis: NSAIDs
Newer treatment: Autologous HSCT if severe / refractory
Raynaud’s phenomenon
Peripheral digital ischaemia due to vasospasm, causing painful cold fingers with triphasic colour changes
• Pallor (vasospasm) —> Cyanosis (vasodilation with deoxygenated blood) —> Rubor (reactive hyperemia)
Causes:
• Primary: Raynaud’s disease (usually ANA -ve)
• Secondary:
o Autoimmune: SLE, RA, SSc, MCTD
o Blood: polycythaemia, leukaemia
o Cryoglobulinaemia
o Drugs: beta blocker
o Endocrine: DM, hypothyroidism, phaeochromocytoma
Mixed connective tissue disease
Definition: connective tissue disease, combination of SLE, scleroderma, polymyositis
• Favourable prognosis
• “Diagnostic shift”: could later evolve into another CTD (e.g. SLE)
Clinical features
• Skin (MC): Puffy hands (2/3), Raynaud’s phenomenon (90%), sclerodactyly (1/3)
• MSK: myositis (2/3), RA-like synovitis (75-95%)
• Other organs: esophageal involvement (50%), pulmonary hypertension (25%), ILD (50%)
Serology
• ANA: high titre of speckled pattern
• RF: +ve in 30-100%
• Anti-RNP +ve
• Anti-dsDNA: low titre, infrequent
• Anti-Sm: -ve
• Complements: normal or increase
SLE and MCTD often overlap – features
supporting MCTD:
• Early Raynaud phenomenon
• Pulmonary hypertension
• Absence of renal and neurological S/So
Treatment
• Systemic steroid
o Excellent response for inflammatory process (myositis, synovitis) but not vascular process (Raynaud, PAH)
o Rarely induce SSc-like renal crisis
• Choice of additional agents: depend on organ and extent of involvement
Idiopathic inflammatory myopathies
Definition: autoimmune disease characterised by proximal muscle weakness ± skin rash
Classification
Traditionally 5 major disease entities
• Polymyositis 多發性肌炎
• Dermatomyositis ⽪肌炎
• Inclusion body myositis (IBM): very rare in HK, proximal + distal muscle weakness, failed response to treatment;
Dx inclusion bodies in muscle biopsy
• Cancer-associated myositis (CAM)
• Myositis associated with other CTD
Newer disease entities
• Clinically amyopathic dermatomyositis (CADM): cutaneous manifestations, but no muscle weakness for ≥6 mo
• Immune-mediated necrotizing myopathy (IMNM)
Aetiology/ association
• 1/3 malignancy (lung, breast, gastric, NPC) – usually diagnosed within
1 year of DM/PM
• 1/3 autoimmune (connective tissue disease)
• 1/3 idiopathic
Clinical features
• Proximal myopathy: symmetrical weakness in shoulder girdle + hip
girdle, bulbar muscle involvement (dysphagia, dysphonia, HOV)
• Cutaneous manifestations - usually appear before myopathy
o Heliotrope rash: periorbital edema with violaceous colour
o Gottron’s papules: pink papules on dorsal surface of IP joints –
pathognomonic
o Shawl sign and V sign: poikilodermatous erythematous rash over neck and upper shoulders
- Poikiloderma: hypo/hyperpigmentation + telangiectasias + skin atrophy
o Mechanic’s hands: hyperkeratosis and scaling with fissures on digits
o Holster’s sign: poikiloderma in lateral aspects of thigh
o Calcinosis cutis
o Dilated nailfold capillaries
- ILD
Anti-synthetase syndrome: constellation of clinical findings in 30% of IIM
• Diagnostic criteria: Presence of anti-synthetase antibodies (Jo-1, PL7, PL12, EJ, OJ) + 2 major / 1 major 1
minor
o Major criteria: ILD, DM, PM
o Minor criteria (“ARM”): Arthritis, Raynaud’s phenomenon, Mechanic’s hands
• Typically not associated with malignancy and less muscle involvement
Diagnostic criteria
Bohan and Peter criteria (1975): PM require all of 1-4, DM require any 3 in 1-4 + 5
1. Symmetrical weakness of limb-girdle muscles and anterior neck flexors
2. Muscle biopsy: typical of myositis
3. Muscle enzyme elevation (esp. CK)
4. EMG: typical of myositis (spontaneous fibrillation; polyphasic low-amplitude motor unit potential)
5. Cutaneous manifestations of DM: e.g. heliotrope rash, Gottron’s papules
2017 EULAR/ACR classification criteria for IIM: include age of onset, antibodies (only anti-Jo1 now), different scoring
with / without muscle biopsy
Investigations
• Bloods: ESR/CRP (increase), muscle enzymes (CK, LDH, AST), TFT (rule out thyroid myopathy)
• Autoantibodies panel:
Myositis-specific autoAb:
- Anti-Jo-1 —> Anti-synthetase syndrome
- Anti-Mi-2 —> DM, good response to treatment
- Anti-MDA5 —> CADM with rapidly progressive ILD, skin rash, poor prognosis
manifestations
- Anti-Tif1 —> DM, strongly associated with malignancy (50%), severe skin rash,
less ILD, poor prognosis
Myositis-associated autoAb: found in IIM patients with features of other CTD
• Definitive: EMG, muscle biopsy, ± skin biopsy
• Investigations to rule out malignancy:
o Refer ENT (NPC), Gynae (CA cervix), GI (upper and lower endoscopy)
Management
Non-pharmacological: bed rest in acute attacks, sun protection, physiotherapy to prevent contracture, IV fluids
(rhabdomyolysis prophylaxis), stop statins
Pharmacological:
• High-dose steroid (PO prednisolone 1mg/kg/day): prolonged therapy until active disease controlled for 1 year
• Steroid-sparing agents: initiated with steroids to decrease steroid dose and S/E
o Azathioprine
o Methotrexate
o Hydroxychloroquine (topical): only effective for skin disease
• IVIG for severe or refractory disease
Sjogren’s syndrome
Definition: systemic autoimmune disease with lymphocytic infiltration of exocrine glands
• M:F = 1:9
• Primary vs secondary to other connective tissue diseases, e.g. RA, scleroderma, SLE, polymyositis
• Increased risk of lymphoma (5%), esp. B cell NHL
Clinical features
• Keratoconjunctivitis sicca (dry eyes): Cx - corneal ulceration, eyelid infection
• Xerostomia (dry mouth): Cx – dental caries, oral candidiasis
• Salivary and lacrimal gland enlargement: r/o NHL
• Systemic complications
o Cutaneous: vasculitis rash
o MSK: arthritis, myositis
o Lung: ILD
o Neuro: peripheral neuropathy
o Renal: Type 1 RTA, GN
o Liver: PBC
o Hemat: cytopenia, hypergammaglobulinemia, lymphoproliferative diseases
Diagnosis: ACR/EULAR 2016
Entry criteria: dry eyes OR dry mouth
Classified as SS if score ≥ 4
Investigations
• Serology: ANA (≥1:320 supports Dx), RF (often +ve), anti-Ro (SS-A), anti-La (SS-B)
• Dry eye: consult ophthalmology
o Schirmer’s test: filter paper at lower eyelid, hyposecretion if wet < 5mm at 5min (normal 15mm)
o Tear film break-up time (TBUT): ≤ 10 seconds
• Dry mouth
o Sialometry: saliva production < 1.5ml in 15min
o Salivary gland scintigraphy
o USG / CT / MRI parotid gland
• Demonstration of lymphocytic infiltration
o Lip biopsy for histology of labial salivary glands if uncertain diagnosis
Management
• Non-pharmacological
o Punctum plug
o Chewing gum, maintain oral hygiene
• Drugs for symptomatic relief
o Dry eyes: artificial tears (e.g. hypromellose), lubricant (e.g. Duratears), topical cyclosporin, topical steroids
o Dry mouth: artificial saliva, muscarinic agents (e.g. pilocarpine) – poorly tolerated due to S/S
o Dry skin: topical cream
• Immunosuppressants: for systemic involvement
o Methotrexate: for MSK / skin involvement (no large RCT)
o Cyclosporine A: promising effects for MSK involvement
o Rituximab / Belimumab / Abatacept
• Lifelong surveillance for non-Hodgkin lymphoma (esp. MALToma and DLBCL)
Spondyloarthritides
Overview
Definition: a family of inflammatory joint diseases, characterised by
• Enthesitis (inflammation of tendon/ligament/capsule that is attached to bone) and secondary synovitis
• Seronegative (RF -ve), but association with HLA-B27
- Axial SpA
AS
- 3:1 M:F
- 20s age onset
- 100% back pain
- Peripheral less common; LL>UL
- EAM (6A): acute anterior uveitis, apical fibrosis, AR, autoimmune (IBD), amyloidosis, atlanto-axial subluxation
- X-RAY:
SIJ: sclerosis, fusion
Spine: syndesmophytes,
Romanus lesion, bamboo
spine - Peripheral SpA
• PsA
- 3:1
- 35-45 age onset
- 20-40% axial
- Common peripheral , UL>LL
- Skin lesions: psoriasis, dactylitis, nail dystrophy
- X-RAY:
DIPJ: pencil-in-cup deformity
Small joint (MCPJ/ PIPJ) erosion & fusion
• ReA
- 15:1
- 20s age onset
- 40-60% axial
- LL>UL
- Urethritis /Uveitis/ conjunctivitis
Circinate balanitis Keratoderma
blenorrhagica
- X-RAY :
- asymmetric syndesmophytes
• IBD-SpA
- 15:1
- and age
- 5-20% axial
- LL>UL
- Erythema nodosum; Pyoderma gangrenosum
- X-RAY : rarely erosive
Investigations
• Bloods: CBC, CRP/ ESR, HLA-B27, RF (-ve)
• Imaging: XR, MRI
Diagnostic criteria
SpA features x 11
ASAS classification for AxSpA:
- Back pain for >/= 3 months and age onset <45y
- radiological sacrolitis plus at least 1 SpA feature / HLA-b27+2 other SpA feature
ASAS classification for peripheral SpA:
- peripheral nam infestation only / arthritis or enthesitis or dactylitis plus
>1 SpA feature
Ankylosis spondylitis
Clinical features
Axial involvement
• Inflammatory back pain / buttock pain:
o Characteristics: age onset < 45y, duration > 3mo, insidious onset, nocturnal pain, morning stiffness > 30min, improved with movement but not with rest
o Start at SI joint and ascends upwards
• Neck pain: C-spine involvement
• Reduced spinal ROM:
o Cauda equina syndrome
o Reduced chest expansion (costosternal and manubriosternal joint)
o Question mark deformity: loss of lumbar lordosis, fixed thoracic kyphosis, cervical flexion
o Prone to spine fractures and whiplash injury
Peripheral involvement
• Arthritis: typically asymmetrical oligoarthritis, e.g. hip (poor prognostic factors)
• Enthesitis: e.g. Achilles tendinitis, plantar fasciitis
• Dactylitis uncommon (poor prognostic factors)
Extra-articular manifestations (6A): eye (acute anterior uveitis – ciliary flush, miotic pupils), lung (apical fibrosis),
CVS (AR), GI (Autoimmune IBD), renal (Amyloidosis, IgA nephropathy), neurologic (Atlantoaxial subluxation)
Axial SpA classified into:
• Ankylosing spondylitis (AS):
sacroiliitis or spondylitis on XR -
more advanced disease
• Non-radiographic axial
spondyloarthritis (nr-axSpA):
sacroillitis or no changes on MRI -
earlier disease
Physical examination
• Lumbar spine: forward flexion - modified Schober test (normal: by 5cm); lateral flexion - middle finger-to-floor distance (normal < 10cm)
• Thoracic spine: Chest expansion (>4cm at nipple line)
• Cervical spine: occiput-to-wall distance (normal: 0cm), tragus-to-wall distance (normal: <14cm)
• Sacroiliitis: FABER test (flexion + abduction + ER), Gaenslen’s test
• LL: palpate for plantar fasciitis & Achilles’ tendonitis, intermalleolar distance
• CVS: AR murmur
• Lung: apical fibrosis
• Eye: uveitis
Investigations (SAQ!)
• Bloods: CBC, LRFT, ESR/CRP, RF, HLA-B27 (useful if no radiological evidence)
• Imaging:
o XR SI joint: sclerosis + no narrowed joint space (Grade 2), narrowed joint space (Grade 3), ankylosis (Grade 4)
o XR spine:
- Romanus lesion (squaring of vertebral body with shiny corners - reactive sclerosis 2° to inflammatory erosions at endplates)
- Syndesmophytes
- Bamboo spine (late stage)
- Anderson lesion: erosion at discovertebral junction
o MRI SI joint: subchondral bone marrow oedema (increased MRI signal)
o DEXA scan: baseline for osteopenia
Assessment of disease activity
• BASDAI (Bath Ankylosing Spondylitis Disease Activity Index): active disease ≥4 out of 10
o ASAS 50 response criteria: BASDAI ¯ 50%
• Others: BASFI (Functional), BASMI (Metrology), BAS-G (Global score)
• Acute phase reactants (ESR/CRP)
Management
Non-pharmacological: smoking cessation (reduce burden to restrictive lungs), stretching exercise (esp. swimming),
posture education, physiotherapy
Pharmacological:
• NSAIDs / COX-2 inhibitors (± GI protection if high GI risk) – continuous Tx slows radiographic progression
• NO proven effective DMARD for axial disease
o Local steroid, methotrexate, sulphasalazine: only for peripheral joints
- Avoid IA steroid use in Achilles tendon: risk of tendon rupture
• Biologics (if persistent high disease activity despite 2 NSAIDs for ≥1 month each): anti-TNFa (e.g. etanercept),
anti-IL17 (SC secukinumab) ± JAK inhibitors
o Anti-IL1 / anti-IL6: not useful for SpA (c.f. RA)
Surgical (rarely required now): corrective spinal surgery, joint replacement
Poor prognostic factors
• Young onset
• Clinical: hip arthritis, dactylitis
• Biochemical: high ESR
• Treatment: poor response to NSAID
Psoriatic arthritis
Overview
30% psoriasis population has arthritis, among them:
• 60% psoriasis precedes arthritis
• 20% arthritis precedes psoriasis: differentiate
from RA – see below
• 20% concurrent
Differences between RA and PsA
RA
- 1:3
- Arthritis: Symmetrical polyarthritis
Spare DIPJ
Tenderness precedes deformity
Erosive cervical disease (C1/2)
- skin: rheumatoid nodules
- radiology: Joint erosions, periarticular
osteopenia, joint space narrowing
- serology: RF, anti-CCP
- genetics: weak association with HLA-DR4
PsA
- 1:1
- arthritis: Asymmetrical (5 patterns)
DIPJ involvement
Less tender, may present with deformity
Enthesitis, dactylitis, spondylitis / sacroiliitis
- skin: Psoriasis: extensor surfaces ± hidden areas
Nail dystrophy: onycholysis, pitting, ridging
- radiology: Early deformity: “pencil-in-cup” deformity, telescoping of digits, periosteal new bone formation
- serology: RF (10%), antiCCP (15%)
- genetics: HLA-b27+ve
Clinical features
• Psoriasis:
o Well-demarcated erythematous plaques with silvery scale
o Common in extensor surface of elbows & knees
o Hidden lesions are common: e.g. scalp / hairline, behind ear /inside ear canal,
back, under breasts, around umbilicus, around perineum
• Arthritis: 5 subtypes (Moll and Wright) (“DRAMA”)
o DIPJ predominant (DDx: OA): a/w nail changes, more in males
o RA-like symmetric polyarthritis: more in females, no rheumatoid nodules
o AS-like predominant spondyloarthritis
o Arthritis mutilans: complete destruction of small joints with telescoping of digits
o Asymmetric oligoarthritis, i.e. ≤ 4 large/ small joints (MC): a/w dactylitis
• Periarticular involvement:
o Dactylitis (uniform swelling of soft tissues of fingers): usually 3rd / 4th toe
o Enthesitis: e.g. Achilles tendon
o Nail dystrophy: pitting, subungual hyperkeratosis, onycholysis, oil drop sign, etc (fig.)
• Extra-articular: anterior uveitis, apical fibrosis
• Associated with metabolic syndrome
Classification of Psoriatic Arthritis (CASPAR) criteria
Entry criteria: Inflammatory articular disease (joint, spine, enthesitis)
PLUS 3 points:
• Evidence of psoriasis: current (+2) —> if not, personal history (+1) —> if not, family history (+1)
• Psoriatic nail dystrophy: onycholysis / pitting / hyperkeratosis (+1)
• Evidence of dactylitis: current (+1) —> if not, personal history (+1)
• RF -ve (+1)
• Imaging evidence of juxta-articular new bone formation (+1)
Investigations
• Bloods: CBC, LRFT, ESR/CRP, HLA-B27, RF (-ve)
• XR joints: pencil-in-cup deformity at IP joints (simultaneous erosion at head of middle phalanx + new bone formation at base of distal phalanx), small joint erosion & fusion, syndesmophytes
Assessment of disease activity
PsA Disease Activity Score (PASDAS): tender & swollen joints, dactylitis, enthesitis
Disease Activity Index for PsA (DAPSA): tender & swollen joints, CRP, global VAS, pain VAS
Management
Non-pharmacological: education, stretching exercise, physiotherapy, smoking cessation
Pharmacological:
• Symptom-based treatments
1. Arthritis
- NSAIDs / local steroid injection if mild arthritis
- Early use of DMARDs if active arthritis (≥3 tender / swollen joints, dactylitis count 1)
• Methotrexate: preferred in psoriatic arthritis (also active against skin psoriasis)
• Sulfasalazine: preferred in non-psoriatic SpA
• Leflunomide
• Cyclosporin: also active against skin psoriasis
• Avoid HCQ: may exacerbate psoriasis
- Psoriasis
• Topical steroids: fluocinolone < betamethasone < clobetasol, lotion < cream < ointment < occlusive dressing
o Commonly prescribed: 0.1% betamethasone
• Topical tar products e.g. shampoo, bathing soap
• Vit D analogues, e.g. calcipotriol
• Phototherapy: UVA/ UVB - Enthesitis
- NSAIDs if mild, ± local steroid injection (except Achilles’ tendon: rupture risk!)
- All csDMARD are not useful —> Step up to biologics (e.g. anti-TNFα, anti-IL-17) - Dactylitis
- NSAIDs if mild, anti-TNFα if refractory
• AVOID systemic steroid: flare-up of pustular / erythrodermic psoriasis upon tapering
• Biologics (anti-TNFα, anti-IL17, anti-IL23, JAK inhibitors): for all kinds of severe presentations
Reactive arthritis (Reiter’s syndrome)
Definition: onset of peripheral arthritis with extra-articular manifestations that appears shortly after GI/ GU infections,
M:F = 15:1
Pathogens
• GI (dysentery): Shigella, Salmonella, Campylobacter, Yersinia
• GU: Chlamydia trachomatis, Gonococcal,
Mycoplasma
Clinical features
• Classical triad: can’t see, can’t pee, can’t climb a tree (conjunctivitis + urethritis/
cervicitis + asymmetrical LL large joint arthritis)
• Extra-articular manifestations
o Skin:
- Circinate balanitis (painless vesicles on prepuce & glans
penis, later forming ulcers) (fig.)
- Keratoderma blennorrhagica (hyperkeratotic skin lesions
on palms & soles) (fig.)
- Subungual hyperkeratosis (same as PsA)
o GI: oral ulcers
o Eye: conjunctivitis, anterior uveitis
Diagnosis: clinical (Ix mainly to rule out DDx)
• ESR/CRP increase
• Joint aspiration: rule out septic arthritis
• RF/ anti-CCP/ ANA -ve: rule out RA/SLE
• Workup for preceding infection e.g. urethral swab
Management
• Arthritis: NSAID/ IA steroid
• Urethritis (Chlamydia): doxycycline
• Anterior uveitis: topical steroid
IBD-associated arthritis
Musculoskeletal manifestations of IBD
• Enteropathic arthritis (20% in CD, 10% in UC): follow onset of bowel disease
• Sacroiliitis (16%) & AS (6%): predate or follow onset of bowel disease
Enteropathic arthritis
• Clinical features
o Arthritis: large LL joints > small joints
o Type 1 coincides with exacerbation of underlying bowel disease
• Management: treat IBD
Gout
Aetiology
• Primary: HGPRT deficiency/ Lesch-Nyhan syndrome, PRPP synthetase overactivity
• Secondary:
o Underexcretion (90%), e.g. CKD, dehydration, drugs
o Overproduction (10%), e.g. leukaemia, tumour lysis syndrome, polycythaemia, psoriasis
Risk factors
• Non-modifiable: genetics, male (M:F = 9:1), elderly
• Modifiable:
o Diet: purine-rich food (e.g. seafood, viscera, beans), alcohol, fructose; (dairy products / coffee are protective)
o Drugs: diuretics, pyrazinamide, cyclosporine/tacrolimus, ACEI, low-dose aspirin, levodopa
o Other common triggers: infection, dehydration, surgery (usually post-op D3-5)
Clinical features
• Acute gouty arthritis (MC 1st MTPJ): severe intense pain, swelling, erythema, reduced ROM
• Chronic tophaceous gout: bone erosion, reduced joint space due to extensive tophi
o Common sites: fingers, toes, ear helix, olecranon bursa, Achilles tendon
• Urolithiasis (urate stone)
• Urate nephropathy: renal insufficiency
Investigations
Gout is a clinical diagnosis!
• Screen comorbidities: RFT (+ eGFR), fasting glucose, lipids, BP, BMI
• Urate level: NOT useful in acute setting (~50% normal), only as monitoring
o Best time to measure: ≥2 weeks post-flare
• HLA-B*5801: before prescribing allopurinol
• XR: joint effusion, “punched out” erosion with overhanging sclerotic margin, preserved joint space
• Joint aspirate (gold standard, not routine): needle-shaped, negatively birefringent crystals under polarised light
microscopy; culture -ve (r/o septic arthritis)
Management (SAQ!)
Acute gouty attack
• Non-pharmacological: RICE, rehydration
• NSAID vs colchicine vs corticosteroid
- NSAID/COX2 + PPI
- high dose, tapering 5 days (e.g. indomethacin )
- renal impairment: decrease dose
- C/I in severe renal impairment, GI bleed, heart failure
- S/E: PUD, worst HF, AKI, fluid retention - Colchicine
- Acute gout: 1mg —> 0.5mg 1hr later
- prophylaxis: 0.5mg BD
- must stop in nausea / diarrhoea
- renal impairment: decrease frequency
- C/I:
Severe renal/hepatic impairment
Co-use of strong CYP3A4 inhibitor (e.g. calthromycin, statin, cyclosporine, verapamil)
- S/E: diarrhoea, nausea, peripheral neuropathy, liver failure, pancytopenia - Steroid (PO, IM, IA)
- acute gout: PO prenisolone 30-35mg/day x 5 days / IA steroids
- Prophylaxis: PO pared <10mg/day
- C/I: Septic arthritis, DM, PUD
- for renal failure man and old man
Long-term management
Lifestyle modification: avoid triggers
• Avoid alcohol and drugs that exacerbate gout (e.g. diuretics, low-dose aspirin)
• Diet: Fluid intake, low purine diet, limit high fructose corn syrup (e.g. CocaCola), weight reduction
• Adjust medications: switch thiazide diuretics to losartan (decrease urate levels), switch statins to atorvastatin
Urate lowering agents:
• Indications:
o Recurrent attacks ≥ 2/ year
o Complications: chronic tophaceous gout, urate stone, CKD / gout nephropathy
• Treatment target: serum urate < 0.36 mmol/L (<0.30 mmol/L if tophaceous gout)
- Xanthine oxidase inhibitor
• Allopurinol: purine, non-selective XOI
o Investigations before initiation: HLA-B*5801 (AHS), RFT (increase rash —> half dose)
o Timing:
- Avoid if not yet started, start 1-2 weeks after acute attack resolves: fluctuation of serum UA precipitates crystals and causes gout
- Continue if already started
o Dose: start at 100mg daily, titrate up weekly to 300-800mg daily
- Cover with colchicine 0.5mg BD (or NSAID) for 1-2 weeks before starting allopurinol (↓risk of paradoxical exacerbation due to sudden drop in urate level)
- Continue colchicine/NSAID for 6 months (or 3 months if urate target is achieved)
o Side effects (usually appear around 3 weeks)
- Skin rash (5%): stop stat
- Allopurinol hypersensitivity syndrome (AHS - 0.1%)
—> Risk factors: Han Chinese, elderly, poor RFT; not dose-dependent
—> S/S: rash, eosinophilia, fever, hepatitis, progressive renal failure (mortality: 27%)
- Interstitial nephritis
- Diarrhea (3-5%)
- DDI: azathioprine (XO metabolises azathioprine to inactive metabolite) —> decrease 50% dose of azathioprine to prevent severe myelosuppression
• Febuxostat: non-purine, selective XOI
o Alternative for patient with allopurinol skin reaction / HLA*B-5801 +ve/ severe renal impairment
o Avoid if Hx of IHD / CHF
o S/E: liver impairment (stop if LFT > 3x ULN)
o Dose: 40-80mg daily
o DDI: azathioprine
- Uricosuric agents
- Rarely used now (XOI effective), MoA: inhibit PCT urate anion exchangers
• Probenecid: caution if renal impairment (GFR < 60), urate stone, high 24h urine UA excretion
• Benzbromarone: hepatotoxicity
• Sulfinpyrazone: bone marrow suppression, not licensed in HK - Uricase
- Rasburicase (used for TLS prophylaxis), pegloticase (N/A in HK)
• Consider if failed other treatment and prefer faster resolution of tophus
• Avoid in G6PD deficiency
Surgery: only for complications associated with tophaceous gout, e.g. active infection, nerve compression
Treatment of asymptomatic hyperuricemia
Occur in 2-13% of general population ( with age), most never develop gout / stones
• Not recommended: most never develop gout / uric acid stones
• Exception: prophylactic treatment for patients on cytotoxic therapy to prevent acute uric acid nephropathy
Pseudogout
• Definition: deposition of calcium pyrophosphate dihydrate (CPPD) crystals within joint space
• Mimic gout except
o Affect older age (>60)
o More proximal joints (e.g. knee, shoulders)
o Positively birefringent crystal
Risk factors
• Hyperparathyroidism, hypoPO4, hypoMg
• Hypothyroidism
Clinical features
• Asymptomatic: seen on XR only
• Acute arthritis: similar to acute gouty attack, but MC knee & shoulders
• Pseudo-OA
• Pseudo-RA
Investigations
• Joint aspiration:
o To r/o gout & septic arthritis
o Calcium pyrophosphate crystal: positive birefringence, rhomboid shaped
• XR: chondrocalcinosis (opacities in fibrocartilage, e.g. knee menisci) (fig.)
Septic arthritis
Pathogens
• Native joint: Staphylococcus aureus; TB (immunocompromised), Neisseria gonorrhoea (STD)
• Prosthetic joint: Staphylococcus epidermidis
Clinical features
• Hot, swollen & tender joint is septic arthritis until proven otherwise (even in the absence of fever, leukocytosis,
elevated ESR/CRP)
• Joints involved: monoarthritis (90%), oligoarthritis or polyarthritis
Investigations
• Bloods: CBC d/c, RFT/LFT, blood culture
• Joint fluid: WBC D/C (usually >50-100k WBC, neutrophil predominant), polarising microscopy (may co-exist with crystal arthropathy), urgent gram stain, C/ST
• Imaging: XR joint
• If gonococcal infection suspected: swabs of pharynx, urethra, cervix, anorectum
Management
• Therapeutic joint aspiration to dryness
• Analgesia (NSAIDs)
• Empirical IV antibiotics according to clinical suspicion and urgent gram stain, then adjust according to C/ST
• Consult orthopaedics for drainage (esp. infected prosthesis) – usually require OT for hip infection
• Start physiotherapy early
G+ cocci in cluster —> S aureus: Vancomycin
G+ cocci in chain -> Streptococcus —> penicillin
G- bacilli —> Enterobacteriae —> Cetixone
G- diplococci —> Neiserria gonorrhea —> ceftrixone + doxycycline
Vasculitis
Overview
Definition: inflammation and subsequent necrosis of blood vessels causing tissue ischaemia or infarct
Chapel Hill Classification (by vessel size): large, medium, small (ANCA vs IC), variable
Signs and symptoms
• Common to all vasculitides: unexplained systemic illness with constitutional symptoms, with no evidence of
malignancy / infection / drug-induced / other CTD
• Large vessel disease: limb / jaw claudication, asymmetric BP, absent pulses, bruits, aortic disease
• Medium vessel disease: livedo reticularis, subcutaneous nodules, digital infarct, Raynaud’s phenomenon
• Small vessel disease: leucocytoclastic vasculitis (non-blanchable palpable purpura, blisters/ ulcers), GN,
pulmonary haemorrhage, mononeuritis multiplex
Investigations: biopsy if tissue accessible, angiography if tissue inaccessible
Management: steroid ± other immunosuppressants
Takayasu arteritis (large vessel vasculitis)
Definition: granulomatous inflammation affecting aortic arch & abdominal aorta, a.k.a. “pulseless disease”
• Usually affect females <50 years old (c.f. GCA)
Specific clinical features
• Bruits (80%)
• Asymmetrical (absent/weak) peripheral pulses
• Aortic disease: aneurysm / AR
• Ischemia: Limb claudication, angina, mesenteric ischemia, stroke/TIA
• increase BP: renal artery stenosis
• Subclavian steal syndrome
Investigations: increase ESR/CRP, angiogram (CTA/MRA)
Management: high dose steroids + steroid-sparing agents (MTX/AZA)
Polyarteritis nodosa (medium vessel vasculitis)
Definition: necrotizing vasculitis of medium/small arteries, not associated with ANCA
• Can be idiopathic / secondary e.g. HBV (HBsAg included in ACR criteria)
Specific clinical features:
• Skin: livedo reticularis, digital ulcers / gangrene, subcutaneous nodules
• CNS: mononeuritis multiplex, polyneuropathy
• CVS: MI
• GU: orchitis (testicular pain)
• Renal: HT, increase urea/Cr
Management:
• Induction: steroids + steroid-sparing agents: CYC (severe) vs MTX/AZA (non-severe)
• Maintenance: non-GC non-CYC immunosuppressant x 18months, taper GC
ANCA-associated vasculitis (smal-vessel disease)
ANCA-associated vasculitis
ANCA: anti-neutrophil cytoplasmic antibodies
• p-ANCA (perinuclear) = anti-myeloperoxidase (anti-MPO)
• c-ANCA (cytoplasmic) = anti-proteinase-3 (anti-PR3)
- Microscopic polyangiitis (MPA)
- Nexrotizing non-granulomatous vasculitis
- P-ANCA +ve
- S/S:
Common vasculitic manifestations:
• Skin: Cutaneous vasculitis - palpable purpura
• Renal: Pauci-immune glomerulonephritis
• Lung: Diffuse alveolar haemorrhage
• Neuro: Mononeuritis multiplex - peripheral neuropathy
• No ENT/upper airway involvement
- Ix:
CBC D/C, ESR/CRP, ANCA, RFT & urinalysis
Skin biopsy: histology & direct IF (for deposition of Ig around blood vessels)
Biopsy of involved organs: kidney, vessels
- Mx:
Induction: glucocorticoid + CYC/RTX (if severe) or MTX/MMF (if non-severe)
Maintenance: AZA/MTX or continue RTX (if severe), taper GC
Rescue: plasma exchange
- Monitoring: Birmingham Vasculitis Activity Score (severe: BVAS > 3) - Granulomatous with polyangiitis (GPA / Wegener’s granulomatosis)
- Necrotizing granulomatous vasculitis
- C-ANCA +ve (80%), P-ANCA +ve (20%)
- S/S:
Common vasculitic manifestations:
• Skin: Cutaneous vasculitis - palpable purpura
• Renal: Pauci-immune glomerulonephritis
• Lung: Diffuse alveolar haemorrhage
• Neuro: Mononeuritis multiplex - peripheral neuropathy
• Upper airway: rhinosinusitis, recurrent epistaxis, nasal crusting/ulcers, saddle nose deformity
• Lower airway: pulmonary infiltrates / nodules / cavities
• Ear: otitis media, otorrhoea
• Eye: scleritis, retro-orbital mass
- Ix:
CBC D/C, ESR/CRP, ANCA, RFT & urinalysis
Skin biopsy: histology & direct IF (for deposition of Ig around blood vessels)
Biopsy of involved organs: kidney, vessels
• CXR/CT sinus
- Mx:
Induction: glucocorticoid + CYC/RTX (if severe) or MTX/MMF (if non-severe)
Maintenance: AZA/MTX or continue RTX (if severe), taper GC
Rescue: plasma exchange
- Monitoring: Birmingham Vasculitis Activity Score (severe: BVAS > 3) - Eosinophilia granulomatosis with polyangiitis (eGPA / Churg-Strauss syndrome)
- Eosinophil-fish necrotizing vasculitis
- P-ANCA +ve
- S/S:
Common vasculitic manifestations:
• Skin: Cutaneous vasculitis - palpable purpura
• Renal: Pauci-immune glomerulonephritis
• Lung: Diffuse alveolar haemorrhage
• Neuro: Mononeuritis multiplex - peripheral neuropathy
Three phases: - Asthma and atopic allergies e.g. allergic rhinitis
- Eosinophilic infiltrative disease: pneumonia, esophagitis, GE
- Vasculitis e..g myocarditis
- Ix:
CBC D/C, ESR/CRP, ANCA, RFT & urinalysis
Skin biopsy: histology & direct IF (for deposition of Ig around blood vessels)
Biopsy of involved organs: kidney, vessels
• Blood: eosinophilia
- Mx:
Induction: glucocorticoid + CYC/RTX (if severe) or MTX/MMF (if non-severe)
Maintenance: AZA/MTX or continue RTX (if severe), taper GC
Rescue: plasma exchange
- Monitoring: Birmingham Vasculitis Activity Score (severe: BVAS > 3)
Immune-complex mediated vasculitis
- IgA vasculitis/ Henoch- Schonlein purpura (HSP)
- Systemic vasculitis with deposition of IgA-containing IC
S/S: fever, arthralgia, GN, colicky abdominal pain (intussusception —> Mx: steroids), symmetrical purpura over
buttocks and extensors of LL) - Cryoglobulinemia vasculitis
- Cryoglobulins: Ig that precipitate at temperature <37°C and redissolve upon warming
- Brouet classification criteria: 3 types
Type 1
• Ig: Monoclonal IgG / IgM
• Causes: Monoclonal gammopathy e.g. MGUS, MM, WM
S/S: Vascular occlusion: digital ischemia, livedo reticularis, Raynaud’s phenomenon
• Lab: Etiology: HBsAg, anti-HCV, anti-HIV, ANA, anti-dsDNA, anti-Sm, anti-Ro/La,
anti-RNP, ANCA ± biopsies (skin, renal, BM, etc.) - Mixed types (Type 2 / Type 3)
• Type 2: mixture of monoclonal & polyclonal
• Type 3: mixture of polyclonal
• Causes: HCV / HIV / HBV infection, Autoimmune e.g. SLE, RA, SS
• S/S: Meltzer’s triad: palpable purpura, arthralgia, weakness / myalgia
• Lab: Etiology: HBsAg, anti-HCV, anti-HIV, ANA, anti-dsDNA, anti-Sm, anti-Ro/La,
anti-RNP, ANCA ± biopsies (skin, renal, BM, etc.)
Buerger’s disease
- Also known as thromboangiitis obliterans – highly cellular, inflammatory thrombus
- Usually occur in <50yo, smoking
S/S: distal extremity ischemia, digital ulcers/gangrene
Mx: smoking cessation, vasodilators (e.g. CCB)
Behçet’s disease
• Pathology: systemic vasculitis of unknown etiology that affect al size of vessels
• “Silk road disease”
Clinical features
• Triple symptom complex:
o Oral aphthous ulcers
o Genital ulcers
o Uveitis
• Other S/S:
o Positive pathergy test: skin prick with 20G needle —> positive if pustule-like lesion afte 48h
- DDx: pyoderma gangrenosum, Sweet syndrome
o Arthritis
o Neuro-Behçet’s: parenchymal vs non-parenchymal, precipitated by cyclosporin A
o Vascular Behçet’s: venous thrombosis (MC), pulmonary aneurysm can be life-threatening
o Intestinal-Behçet’s: IBD-like symptoms, ulcers may perforate
Management:
- Oral / genital ulcer
—> Mild: topical steroid
—> Severe: colchicine, systemic steroid, immunosuppressants
- Uveitis
—> Systemic steroids + azathioprine; cyclosporin A if refractory
- Arthritis
—> Colchicine
- Vascular / Neuro / Intestinal
—> Systemic steroids + immunosuppressants
• Other agents: apremilast (PDE4 inhibitors), anti-TNF
IgG4-related disease
Pathology
• Hallmark: lymphoplasmacytic tissue infiltrate of mainly IgG4 +ve plasma cells
• “Storiform” pattern of fibrosis – cartwheeling appearance of fibroblasts and inflammatory cells
Clinical presentation
Many previously recognized entities now fall within the spectrum of IgG4-RD
• Type 1 (IgG4-related) autoimmune pancreatitis (AIP) – prototype of IgG4-RD
• IgG4-related sclerosing cholangitis
• Mikulicz syndrome: dacryoadenitis & sialadenitis
• Kuttner tumor: submandibular gland
• Riedel’s thyroiditis (S/S: wood-like hard goitre, DDx: lymphoma)
• Retroperitoneal fibrosis
• Inflammatory pseudotumors: orbits, lungs, kidneys, other organs
• Sclerosing aortitis and periaortitis
• IgG4-related kidney disease:
tubulointerstitial nephritis (TIN)
Phenotypes
• Group 1: pancreato-hepato-biliary disease
• Group 2: Retroperitoneal fibrosis ± aortitis
• Group 3: head-and-neck limited disease
• Group 4: Classic Mikulicz syndrome with systemic involvement
Diagnosis
Tests: serum IgG4, tissue biopsy with immunostaining (>10 IgG4 +ve plasma cells per HPF, IgG4:IgG ratio)
Management
• Glucocorticoids as first-line treatment e.g. prednisolone 0.6mg/kg/day
• ± other immunosuppressants: rituximab preferred over AZA/MTX/MMF
