Rheumatology - SLE Flashcards by Max Kam

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

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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

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Triggering events of SLE

→ Infections: EBV, parvovirus B19, rhabdovirus, HIV-1, adenovirus, salmonella

→ Drugs: Procainamide, Hydralazine

→ Chemical agents: hydrazine, tartrazine, dyes, eosin, heavy metals (mercury, gold, cadmium)

→ Food: L-canavanine, e.g. alfalfa seeds and sprouts

→ UV light

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List drugs that induce SLE and exacerbate SLE

Trigger:
 Procainamide
 Hydralazine
 Others (rare): B-blocker, quinidine, penicillamine, isoniazid, phenytoin, chlorpromazine

Exacerbate:
 Lovastatin
 Sulphonamide
 Estrogens

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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

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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

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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

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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

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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

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Cutaneous features of SLE *

Photosensitivity

Cutaneous lupus erythematosus: 3 forms
- Malar/ Butterfly rash (spares nasolabial folds)
- Subacute (annular / psoriaform): non-scarring, sparing of face, very photosensitive
- Discoid lupus erythematosus: hyperkeratosis, follicular plugging lesions, scarring alopecia if on scalp

Cutaneous vasculitis
- Telangiectasia
- Raynaud phenomenon
- Periungual erythema
- Livedo reticularis (screen anti-phospholipid antibody)

Oral ulcers: multiple, affect different sites

Erythema Marginatum
Erythema nodosum/ lupus panniculitis

Purpuric skin rash

Bullous lesions (ddx herpes zoster, bullous pemphigoid)

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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

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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

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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

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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

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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)

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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

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Define Class I to VI of Glomerulonephritis

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I = normal

II = Mesangial prolfieration

III = Focal proliferative

IV = Diffuse proliferative

V = membranous

VI = Sclerotic

Neurological features of SLE *

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Neuropsychiatric: Depression, Psychosis, Migrainous headache

Neurological:
1) Ischemia/ clot:
Cerebral ischemia
Retinopathy
Cranial/ peripheral neuropathy
Myelitis

MG, GBS, Mono-polyneuropathy

2) Movement disorder:
Chorea
Cerebellar ataxia

3) Inflammation:
Aseptic Meningitis and cerebral abscesses

4) Eye
Cytoid bodies (decrease VA, similar to Roth’s spot in subacute bacterial IE)

Haematological features of SLE *

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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

Secondary HLH

TTP

The most common causes of death in SLE **

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Infection - most important cause in early - mid stage

Cardiovascular thrombosis - most important in late stage

Explain why SLE patients are highly susceptible to infection

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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

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→ 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

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→ 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

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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: i**nversely 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 >> **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**

Rheumatology - SLE Flashcards

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