JC84 (Medicine) - SLE Flashcards
SLE
Definition
Chronic multisystem autoimmune disorder
Characterized by immunological disturbances resulting in excessive production of autoantibodies
Causing direct tissue damage and immune complex-mediated tissue or organ inflammation
SLE
Typical demographics
Genetic risk factors
Female: Male = 9:1
Most common in blacks, 50-70/100k in Orientals
Genetic predisposition
→ HLA-B8, DR2, DR3 or other genes that influence sex hormone status
→ complement deficiency (impaired phagocytosis)
High concordance rate in monozygotic twins
Increased risk of SLE in 1st degree relatives
Triggering events of SLE
→ Infections: EBV, parvovirus B19, rhabdovirus, HIV-1, adenovirus, salmonella
→ Drugs: Proxainamide, Hydralazine
→ Chemical agents: hydrazine, tartrazine, dyes, eosin, heavy metals (mercury, gold, cadmium)
→ Food: L-canavanine, e.g. alfalfa seeds and sprouts
→ UV light
List drugs that induce SLE and exacerbate SLE
Trigger:
Procainamide
Hydralazine
Others (rare): B-blocker, quinidine, penicillamine, isoniazid, phenytoin, chlorpromazine
Exacerbate:
Lovastatin
Sulphonamide
Estrogens
Pathogenesis of SLE
What is the role of B and T cells?
loss of self-tolerance in immune system secondary to predisposing genetic factors and environmental triggers
B-cell:
→ AutoAb production due to
- Reaction to self-antigens (eg. dsDNA, RNPs)
- Activation by helper T cells
→ Auto-antibodies form immune complex (consists of nuclear antigens, IgG and antinuclear antibodies)
→ deposit in tissues and organ, esp kidney, and activate complement system to cause inflammation and tissue damage
T lymphocyte changes:
→ ↓cytotoxic and suppressor T cells
→ ↑helper T cell pop’n → ↑production of autoAb
Defective phagocytosis
→ Defective phagocytosis of immune complexes or apoptotic cells
Name 2 classification criteria for SLE
Why are classifications useful?
SLICC: Consists of clinical features and immunological features
EULAR/ ACR guideline: Consists of clinical features and immunologic features
Use of classification:
- Distinguish SLE from spectrum of autoimmune rheumatic diseases
- No overlaping score/ double count of clinical or immunological features
- Clearly defined cut-off for SLE
Precipitating factors for SLE relapse *
Precipitating factors for relapse:
Drug non-compliance (most common)
Infection
Stress
• Physical stress including surgery
• Psychological stress
Pregnancy
Drug-induced
UV light exposure
Constitutional symptoms of SLE *
→ Fever: only during flares, readily remits with NSAIDs, paracetamol or steroids (no remission = think infection)
→ Weight loss: usually only during flares
→ Poor appetite, malaise: continuous even when no flares
Musculoskeletal features of SLE *
- *Arthritis**: early onset, symmetrical, migratory non-erosive polyarthritis
- Morning stiffness: in minutes (cf >1h in RA)
- Joint involvement: similar to RA, i.e. knees, carpal joints, PIPJ, NO DEFORMITIES
- Deforming variant (Jaccoud arthritis)
Avascular necrosis of femoral head
Osteoporosis
Myopathy: myalgia, tenderness and weakness
Myasthenia gravis
Cutaneous features of SLE *
Photosensitivity
Cutaneous lupus erythematosus: 3 forms
- Malar/ Butterfly rash (spares nasolabial folds)
- Subacute (annular / psoriaform): non-scarring, sparing of face
- Discoid lupus erythematosus: hyperkeratosis, follicular plugging lesions, scarring alopecia if on scalp
Cutaneous vasculitis
- Telangiectasia
- Raynaud phenomenon
- Periungual erythema
- Livedo reticularis
Oral ulcers: multiple, affect different sites
Erythema nodosum
Purpuric skin rash
Pulmonary features of SLE *
→ Chest infection
→ Pleuritis: always bilateral
→ Interstitial lung disease (3-9%): usually non-specific interstitial pneumonia (NSIP)
→ Pulmonary embolism and infarct
→ Rare: recurrent atelectasis, acute pneumonitis, pHTN, pulmonary haemorrhage
Cardiac features of SLE *
Pericarditis ± effusion: pleuritic substernal chest pain, audible rub
Coronary artery disease
Valvular disease, e.g. Libman-Sacks endocarditis (non-bacterial endocarditis, vegetation of fibrin and immune cells)
Myocarditis, Cardiomyopathy
Vascular features of SLE *
Raynaud phenomenon: intermittent acral pallor followed by cyanosis and erythroderma
Vasculitis (11-36%): most commonly small vessels but can also involve medium/large vessels
Thromboembolic disease: both arterial and venous circulations
Gastrointestinal features of SLE *
→ Esophagus: motility disorder (40%), infective esophagitis (e.g. Candida, CMV, HSV), pill-related oesophagitis
→ Liver: asymptomatic dLFT, AI hepatitis
→ Pancreas: acute pancreatitis
→ Intestine (rare): pseudo-obstruction, protein losing enteropathy, mesenteric vasculitis
Ocular features of SLE *
→ Keratoconjunctivitis sicca due to 2o Sjogren
→ Scleritis: deep boring eye pain, acute redness and photophobia
→ Acute visual loss
→ Chronic changes: corneal deposit, maculopathy, retinal vasculopathy (cytoid bodies)
Renal features of SLE *
→ Lupus nephritis**: isolated proteinuria/haematuria, nephrotic or nephritic syndrome due to Glomerulonephritis
→ Tubulointerstitial nephritis: presenting with tubular dysfunction, eg. ↓concentration ability
→ Renal vascular disease due to immune complex deposits or microvascular thrombosis
Define Class I to VI of Glomerulonephritis
I = normal
II = Mesangial prolfieration
III = Focal proliferative
IV = Diffuse proliferative
V = membranous
VI = Sclerotic
Neurological features of SLE *
Neuropsychiatric: Depression, Psychosis, Migrainous headache
Neurological:
1) Ischemia/ clot:
Cerebral ischemia
Retinopathy
Cranial/ peripheral neuropathy
Myelitis
2) Movement disorder:
Chorea
Cerebellar ataxia
3) Infection:
Meningitis and cerebral abscesses
Haematological features of SLE *
Thrombo-embolism: due to Anti-phospholipid syndrome, Vasculitis, steroid use
NcNc anaemia: anaemia of chronic disease, AIHA, GI loss
Leukopenia: Neutropenia due to viral infection, immunosuppression, Anti-leukocyte antibodies
Thrombocytopenia: due to anti-platelet antibody/ ITP, APLS, medication, thrombotic microangiopathy
Pancytopenia: Sepsis, myelosuppression, thrombotic microangiopathy, hematological malignancy
Splenomegaly
The most common causes of death in SLE **
Infection - most important cause in early - mid stage
Cardiovascular thrombosis - most important in late stage
Explain why SLE patients are highly susceptible to infection
Intrinsic to immune system:
- Low complement concentration
- Anti-leukocyte antibodies
- Poor cell-mediated immunity and defective phagocytosis
- Poor spleen function
Extrinsic/ iatrogenic:
- Steroid use and immunosuppression therapy
- Uremia and nephrotic syndrome
Antiphospholipid syndrome *
Key clinical features
Clinical diagnostic criteria
→ Non-superficial vascular thrombosis **Must have feature/ Definitive**
→ Adverse pregnancy outcome/ pregnancy loss
→ Persistent presence of antiphospholipid antibodies 12 weeks apart, i.e. lupus anticoagulant, anti-cardiolipin Ab, anti-β2 glycoprotein I Ab
Criteria:
Sapporo criteria: consists of Vascular thrombosis, Pregnancy loss and antiphospholipid antibodies for Dx
Advantages of SLICC criteria over ACR criteria for classification of SLE
→ Allow dx solely based on biopsy-proven lupus nephritis
→ Avoid the possible duplication of highly correlated cutaneous features (e.g. malar rash and photosensitivity)
→ Include more cutaneous manifestations (e.g. SCLE), neurologic manifestations of SLE and more immunologic criteria (e.g. low complement)
→ Greater sensitivity (97% vs 83%) but lower specificity (84 vs 96%)
Mnemonic for ACR criteria for SLE
Mnemonic for ACR criteria = SOAP BRAIN MD
SOAP = serositis, oral ulcer, arthritis, photosensitivity
BRAIN = blood count low, renal, ANA, immunological, neurological
MD = malar rash, discoid rash
First line investigations for SLE **
□ Blood: CBC, L/RFT, ESR+/-CRP
□ Urine: urinalysis, microscopy, protein/creatinine ratio
□ Immune markers:
→ Antinuclear antibodies (ANA) for screening
→ Anti-ds DNA, anti-ENA, antiphospholipid Ab, C3/4 if ANA +ve or SLE highly suspected
→ Rheumatoid factor for r/o other AI diseases (e.g. RA, Sjogren syndrome)
Specific organ involvement e.g. CXR, ECG, renal Bx
Anti-nuclear antibodies
Clinical use
Limitations
Accuracy
When should a positive ANA result be taken for Dx?
Use: Diagnosis ONLY when taken with other factors
Limitations: Titre NOT correlate with severity, False negative if severe proteinuria, Non-specific to SLE (confounding RA, Sjogren, normal population)
Accuracy: Highly sensitive, non-specific
Diagnostic when:
- Clinical picture suggests connective tissue disease
- Other autoantibodies are present
- Evidence of immune complex disease
Anti-dsDNA
Use
Accuracy
□ Clinical use: Diagnosis and monitoring of disease progression (esp. for lupus nephritis), Titer correlated with disease activity
□ Accuracy: high specificity to SLE, occurs in ~60% SLE patients
Anti-ENA
- Clinical use
- List subtypes of Anti-ENA and their clinical use
Clinical use:
- Prognosis value, Anti-Sm is diagnostic of SLE (other Anti-ENAs are not diagnostic)
- Predict clinical manifestations
Anti-Sm - highly specific to SLE, Neurological involvement
Anti-Ro - Secondary Sjogren’s, Congenital heart block, neonatal lupus, cutanous conditions. Not specific or sensitive to SLE
Anti-RNP - Overlap features: eg. sclerodermatous skin lesions, Raynaud phenomenon, low-grade myositis. Not specific or sensitive to SLE
Anti-P - neurological diseases
Monitoring methods for SLE **
Monitoring of disease activity: NO role for ANA and anti-ENA
□ Thorough clinical assessment including BP
□ Anti-dsDNA: +ve correlation with activity
□ C3/4 levels: inversely correlate with activity
□ Urinalysis: including protein, cells, casts
□ CBC and blood biochemistry
General management of SLE
Genetic Counselling with patients, spouse, relatives
- Explain disease, drug compliance, pregnancy issues and fertility issue
Regular monitoring:
- Check BP and urine dipstick every visit with thorough PE
- Check disease activity: anti-dsDNA, C3/4, ESR, CBC, L/RFT
- Eye exam and ophthalmoscope exam
Modify risk factors:
- Smoking cessation (smoking a/w poor response to HCQ)
→ Avoid excessive sun exposure
→ Avoid potential antigenic stimuli: triggering drugs/ chemicals/ dyes…
→ Infection control
Supportive treatment, eg. Dialysis, RRT
Aims of SLE treatment
Course of Tx
- Target remission
- Prevent flares
- Prevent end-organ damage (e.g. renal disease)
- Prevent APS
- Limit treatment in clinically asymptomatic pt, Use lowest glucocorticoid dosage
- Improve QoL
Course:
- Induction therapy + 3 years immunosuppressive maintenance therapy
- Anti-malarial drugs as mainstay Tx
Define the target glucocorticoid use in SLE
Long term: Prednisolone <7.5mg/day
Use pulses of IV methylprednisolone for a lower starting dose and faster tapering
Early initiation of immunosuppressive drugs is better
Define steroid dosages for different manifestations of SLE
Low dose (<15mg/d) for skin rashes, arthritis, serositis
Moderate dose (0.5mg/kg/d) for resistant serositis, hematologic S/S and lupus nephritis
High dose (≥1-2mg/kg/d) for severe hematologic S/S and major organ involvement
Mainstay/ empirical medical treatment options for SLE **
Hydroxychloroquine (HCQ) or chloroquine (CQ)** Mainstay
Other Immunosuppressants
- Steroids
- Non-steroid: azathioprine, methotrexate, MMF
- Biologics: anti-CD20 (rituximab), anti-BAFF (belimumab)
Hydroxychloroquine (HCQ) or chloroquine (CQ) for SLE
- Indication
- Dosage
- Benefits
- S/E
- Indication: all SLE pts unless C/I
- Dosage: <7mg/kg to avoid toxicity
- Benefits:
Reduce systemic complication, improve pregnancy outcome, reduce secondary infectious disease complication - S/E: bluish skin discoloration (esp. UV exposure), corneal deposits (reversible), bull’s eye maculopathy, RETINAL TOXICITIES
Hydroxychloroquine (HCQ) for SLE
Major risk factors for retinal toxicities
Long duration of treatment
Dosage >5mg/kg/day
Chronic kidney disease
Pre-existing retinal or macular diseases
Treatment of fever in SLE
→ NSAIDs, paracetamol ± low to moderate dose steroids
→ MUST r/o underlying infective or drug-related causes if unresponsive
Treatment of Raynaud’s phenomenon
→ General measures
- Avoid sudden cold exposure
- *- Keep hands warm,** warm hands to alleviate attacks
- *- Smoking cessation** (vasoconstricting effect of cigarettes)
- *- Avoid sympathomimetic drugs,** e.g. decongestants, diet pills
- *- Avoid repeated trauma** to fingertips
→ Pharmacological therapy if ineffective control
- 1st line: slow release / long-acting CCB, e.g. nifedipine, amlodipine
- 2nd line: sildenafil, topical nitrates, losartan or fluoxetine, Botox A injection (sympathectomy)
Treatment for joint pain in SLE
→ Symptomatic relief e.g. NSAIDs, acetaminophen
→ Empirical Tx +/- immunosuppressants for refractory cases»_space; Steroid, MMF, Azathioprine, Methotrexate
Treatment of pleuritis and pericarditis in SLE
Pleuritis
→ NSAIDs, eg. naproxen
→ Systemic steroids: prednisolone
Pericarditis
→ Asymptomatic: conservative tx
→ Symptomatic:
- HCQ, short course NSAIDs or low to medium dose steroids
- Colchicine
- Percutaneous drainage
Treatment of neuropsychiatric features of SLE
Neuropsychiatric lupus
→ Symptomatic relief: anti-convulsant, anti-psychotics, antidepressants, sedative
→ Prophylaxis for CVD: aspirin / warfarin
