Rheumatology JC084: Facial Rash And Painful Fingers: SLE Flashcards
***Salient features of SLE
- Young female
- Multi-system disease
- **Constitutional symptoms (malaise, fever, facial rash)
- **Inflammatory polyarthritis
- **Cutaneous manifestation (rash, purpuric petechiae)
- **Haemic involvement (pancytopenia, high ESR)
- ***Renal involvement (high creatinine, urine protein) - Possible triggering factor
- Autoimmunity
- **Positive AutoAb screen (ANA, Anti-dsDNA, Anti-ENA, ACA)
- **Coomb’s test (AIHA) - Immune complex disease (***Primary Pathology of SLE)
- ↓ complement levels
Spectrum of Autoimmune rheumatic diseases
SLE: part of spectrum of autoimmune rheumatic disease
1. SLE (overlapping features with all below diseases)
2. Sjögren’s syndrome
3. Rheumatoid arthritis (RA)
4. Systemic sclerosis (SSc)
5. Dermatomyositis (Dm)
6. Polymyositis (Pm)
7. Undifferentiated connective tissue disorder (uCTD)
8. Anti-phospholipid Ab syndrome (APS)
9. Primary biliary cirrhosis (PBC)
***Systemic Lupus Erythematosus (SLE)
**Chronic **Multisystem ***Autoimmune disorder
Loss of tolerance to nuclear self Ag —> AutoAb production —> IC deposition (SpC Revision)
Characterised by:
Profound immunological disturbances
—> excessive production of **AutoAb
—> some cause **direct tissue damage / others take part in immune complex (IC) formation
—> failure to remove ICs / accumulation of ICs (most important pathological mechanism of tissue damage in SLE)
—> **secondary inflammation
—> **Inflammatory + ***Thrombotic pathology (often Ab mediated)
(Self notes:
- IC formation —> Complement activation to clear IC —> Complement consumed during flare
- If born with Complement deficiency —> fail to clear IC —> more IC deposition —> prone to SLE flare)
(Web:
The complement system involves both the innate and the adaptive immune systems and has important roles in the pathogenesis of SLE. Complement deficiencies within the classical pathway (C1q, C4 and C2) of activation predispose for development of the autoimmune disease SLE. The association between complement deficiencies and SLE could be explained by several mechanisms, including impaired clearance of immune complexes and impaired handling of apoptotic cells, aberrant tolerance induction or changes in cytokine regulation. Also during SLE disease flares, the complement system is activated giving rise to partial deficiency or dysfunction due to consumption. On the other hand, complement also takes part in the inflammatory reaction in the disease that gives rise to the tissue and organ damage.)
Genome wide association studies (GWAS) in SLE
Genetic components play a large role:
1. T cell activation
- PTPN22
- TNFSF4
- HLA class 2
- B cell signaling
- BANK1
- BLK
- PRDMI - Immune complex + Ag clearance
- ITGAM
- TREX1
- FcRγ genes
- Complement genes - TLR-IFN pathways
- IRF5
- STAT4
- IRAK1
Epidemiology of SLE
- Wide racial differences in incidence, prevalence, clinical presentation, course of disease
—> ***Caribbean blacks (most prevalent, 1 in 250 + worst disease outcomes)
—> Orientals (~50-70 / 100,000)
—> Caucasians (~10-20 / 100,000 + best disease outcomes) - F:M = 9:1
- Affect women of child-bearing age (SpC Revision) - Genetic predisposition
- High concordance rate in identical twins (24-70%)
- 10% of 1st degree relatives have abnormal serology (not necessarily develop SLE)
- **Association with HLA B8, DR2, DR3 + Other HLA 3 + Non-HLA genes
- Genes that influence sex hormone status
- **Complement deficiency e.g. C4 deficiency occurs in ~5% of SLE patients - Some infections may be protective (e.g. ***malaria)
- SLE common in Afro-Americans but rare in Afro-Africans
***Trigger agent in SLE
- Infections
- e.g. EBV, parvovirus B19, rhabdovirus, HIV-1, adenovirus, salmonella - Chemical agents
- e.g. hydrazine, tartrazine, hair dyes, eosin, heavy metals (mercuric chloride, gold, cadmium) - Certain foods
- e.g. L-canavanine (alfafa seeds and sprouts) - ***UV lights (UVA,UVB)
-
**Drugs that may induce SLE
- Common: **Procainamide (anti-arrhythmic), ***Hydralazine
- Rare: β-blockers, D-penicillamine, Isoniazid, Phenytoin, Chlorpromazine, Quinidin, Reserpine -
**Drugs that may exacerbate SLE
- **Lovastatin
- ***Sulphonamide-containing drugs
- Estrogen OC pills (probably ok if disease is quiescent)
***Pathophysiology of SLE
Genetic background
—> ↑ Apoptosis rate
—> ***AutoAg (i.e. self Ag)
—> Recognised by T / B cells
—> T / B cell activation
Environmental Triggering factors
—> Activation of T cells
—> Activation of B cells
—> **AutoAb (Detectable but not pathogenic / Ab that cause Direct tissue damage / Ab that contribute to IC formation)
—> **IC trapped in microcirculation
—> ***Secondary inflammation
—> ↑ Adhesion molecule expression / endothelial damage
—> Failure to remove AutoAb / IC
—> Inflammatory-induced Tissue damage
***Classification criteria for SLE
NOT diagnostic criteria!
Allow comparison between cohort
- ACR 1982
- SLE: 4 out of 11 criteria
- Malar rash
- Discoid lupus erythematosus
- Photosensitivity
- Oral ulcers
- Arthritis
- Serositis
- Renal disorder
- Neurological disorder
- Haematological disorder
- Immunological disorders e.g. Anti-Sm, Anti-DNA, ACA
- ANA - SLICC 2012
- more features included
—> **Clinically related (e.g. cutaneous manifestation)
—> **Immunological features (e.g. ANA, Anti-dsDNA)
—> ***Evidence of IC formation (e.g. low complement, direct coombs test) - EULAR / ACR 2019
- **Scoring system based on
—> 1. **Clinical domains (Constitutional, Cutaneous, Arthritis, Neurologic, Serositis, Haematologic, Renal)
—> 2. **Immunologic domains (Antiphospholipid Ab, Complement proteins, Highly specific Ab)
- SLE:
—> **>=10 points
—> **ANA >=1/80
—> **At least 1 clinical domain
—> exclude other more likely disease
—> no double count within each domain, domain with highest point only
—> criteria can be serial / in parallel
—> higher the point, more specific the symptom is
***Clinical features of SLE
記: CRANCHS (Constitutional, Renal, Arthritis, Neurological, Cutaneous, Haematological, Serositis)
- Constitutional symptoms
- Fever
- Malaise
- Poor appetite
- Weight loss - Mucocutaneous
- Photosensitivity
- **Malar (butterfly) rash (may / may not associate with sun exposure, **nasolabial folds often spared)
- **Discoid lupus erythematosus (advancing inflammatory elevated edge, necrosis in centre with scarring even after treatment —> early treatment needed)
- **Subacute cutaneous lupus
- **Cutaneous vasculitis (nail edge / fold, splinter haemorrhages, palm, elbow, lower limb) (can lead to gangrene)
- **Livedo reticularis (non-specific rash)
- Hair loss (scarring / non-scarring)
- **Purpuric skin rash
—> thrombocytopenia
—> leukocytoclastic vasculitis (raised (∵ edema), papule, tender (∵ inflammation))
- Erythema nodosum
- Oral ulcers
- **Raynaud’s phenomenon - Musculoskeletal
- **Non-deforming polyarthritis / polyarthralgia —> RA distribution but **NO radiological erosions
- Avascular necrosis (secondary to vasculitic process / steroid use)
- Deforming arthropathy - **Jaccoud’s arthritis (uncommon, deforming but non-erosive)
- Erosive arthritis (rare)
- **Myopathy —> weakness, myalgia, myositis (low grade) (may be drug induced / SLE complications)
- Myasthenia gravis - Pulmonary
- **Pleurisy (∵ serositis)
- Infections
- Recurrent atelectasis (shrunken lungs)
- **Diffuse lung infiltration + fibrosis
- Pulmonary hypertension
- Pulmonary infarct - Cardiac
- **Pericarditis —> Pericardial effusion
- Cardiomyopathy
- Pulmonary hypertension
- **Libman-Sacks endocarditis (aseptic endocarditis) - Glomerulonephritis (often asymptomatic) (need renal biopsy to diagnose)
- **Proteinuria (must check urine dipstick for protein + RBC)
- Urine sediments
- Urine RBC + casts
- HT
- Acute / Chronic renal failure
- **WHO class 1-6
—> Normal
—> Mesangial
—> **Focal proliferative (of inflammatory cells within glomeruli) (most severe) —> need immunosuppressant
—> **Diffuse proliferative (most severe) —> need immunosuppressant
—> Membranous (Secondary membranous GN) (BM thickened —> proteinuria but less likely to develop renal failure —> better prognosis than class 3, 4)
—> Sclerotic (dead glomeruli, not salvageable) - Neurological
Unknown patho-etiology
- Depression / Psychosis
—> not always related to disease activity
—> considerable variability
—> usually reversible
—> somatic treatment may help
- Migranous headache
—> peri-menstrual
—> may be associated with disease activity
—> poor response to treatment
Known patho-etiology: Vasculitis, Thrombosis, AutoAb mediated, Infection related, Unknown
- **Cerebral ischaemia (microinfarct / TIA / stroke)
- Retinopathy (cotton wool spot)
- Cranial / **Peripheral neuropathy
- Myelitis
- Chorea
- Cerebellar ataxia
- Meningitis + Cerebral abscesses
- Haematological features
- Lymphadenopathy (25% patient)
- Pancytopenia
- Leukopenia (Anti-leukocyte Ab)
- Anaemia (Haemolytic anaemia, Normochromic normocytic)
- Thrombocytopenia (Anti-platelet Ab, Anti-phospholipid syndrome)
- **Thrombosis
—> **Secondary Anti-phospholipid syndrome
—> Vasculitis
—> Use of corticosteroid
- Splenomegaly (onion-skin lesions) - Susceptibility to infection (**most important cause of death in SLE!!!)
Intrinsic factors
- **Low complements
- ***Anti-WBC Ab (Low WBC)
- Impaired cell mediated immunity
- Defective phagocytosis
- Poor Ab response to certain Ag
- Hyposplenism
Extrinsic factors
- **Steroid
- Other immunosuppressive drugs
- **Nephrotic syndrome
- Uraemia
Lupus band test for Cutaneous lupus
Lupus band:
- Deposition of immune complexes (shown by Immunofluorescence stain in dermal-epidermal junction)
***Screening tests for suspected SLE
-
**ANA (Anti-nuclear Ab”s”)
- usually suffices
- **very high sensitivity but very low specificity (non-specific) + non-diagnostic
—> negative ANA to **rule out SLE except when typical features are present (SpC Revision)
—> higher titre —> more specific
—> pattern of ANA —> determine target of AutoAb
- a group of AutoAb against nuclear component of cell (e.g. DNA, ribosome)
- collectively detected by a single assay
—> Anti-ssDNA
—> Anti-histone
—> **Anti-dsDNA
—> **Anti-ENA (Anti-Sm, Anti-Ro, Anti-RNP, Anti-La, Anti-P)
- Anti-dsDNA, Anti-ENA, **APA only if ANA +ve / SLE strongly suspected
- staining pattern has no prognostic values (e.g. homogeneous, speckled, nucleolar etc.)
- serum titre does ***NOT correlate with disease severity / activity (∵ non-specific)
- may become negative if there is severe proteinuria - ***Complement levels
- depressed during active disease —> indicate IC formation - Rheumatoid factor
- exclude possible RA / Sjogren’s - Ig pattern (only if strong degree of suspicion)
- CBC + D/C
- RFT including **urine examination including protein, cells, **casts
- Albumin + Globulin level in serum
(8. Dense fine speckle pattern (DFS) (SpC Medicine)
- IF stain
- 越低越positive)
When should a positive ANA test be taken seriously?
- When presents with ***Connective tissue disease features
- When other AutoAb e.g. **APA (Anti-phospholipid Ab), **Positive direct coombs test (Haemolytic anaemia) are present
- Where there is evidence of IC disease
***Common AutoAb in SLE
- Anti-dsDNA Ab (60-70%)
- Anti-ENA Ab
- Anti-Ro (40-50%) +/- Anti-La (30-40%)
- Anti-Sm (10-20%)
- Anti-RNP (30-40%) - Antiphospholipid Ab (not part of ANA family)
- Anti-cardiolipin Ab (IgG + IgM)
- Anti-β2 glycoprotein 1 Ab
- Lupus anticoagulant (coagulation assay)
Anti-dsDNA
- ~60% of SLE patients
- ***Highly specific for SLE —> One of classification criteria for SLE
- Titre ***correlate with disease activity
- may be associated with ***Lupus nephritis
Anti-ENA
- A group of different AutoAb
—> Anti-Ro (40-50%) +/- Anti-La (30-40%)
—> Anti-Sm (10-20%)
—> Anti-RNP (30-40%) - Most, except ***Anti-Sm, are not diagnostic of SLE
- Probably ***no correlation with disease activity
- Found in many ***connective tissue disorders
- May **predict clinical manifestations —> may have **prognostic value
- Anti-Sm:
- **highly specific (~10-20%)
- 1 of classification criteria
- **neurological involvement - Anti-Ro
- not sensitive / specific (~60%)
- usually associated with Anti-La
- **cutaneous manifestations (e.g. photosensitivity)
- **Secondary Sjogren’s features
- ***congenital heart block + neonatal LE - Anti-RNP
- not sensitive / specific (~30%)
- ***sclerodermatous skin lesions, Raynaud’s phenomenon, low grade myositis - Anti-P (Anti-ribosomal P Ab) (~40%)
- ***neurological disease
Antiphospholipid syndrome (APLS)
Anti-phospholipid Ab:
3 members
1. Anti-cardiolipin Ab (IgG + IgM)
2. Anti-β2 glycoprotein 1 Ab
3. Lupus anticoagulant (coagulation assay)
Anti-phospholipid syndrome:
- +ve **Anti-cardiolipin Ab or **Lupus anticoagulant
Clinical presentation:
1. Arterial / Venous **thrombosis
2. Superficial thrombophlebitis and **Livedo reticularis (wiki: caused by reduction in blood flow through arterioles, resulting in deoxygenated blood showing as blue discolouration)
3. Transverse myelitis
4. **Recurrent abortions
5. Mild / Moderate **thrombocytopenia
Primary vs Secondary APLS:
Primary APLS:
- Anti-PL Ab
- All above clinical presentations
- but NO underlying conditions
Secondary APLS
- Anti-PL Ab
- All above clinical presentations
- ***HAVE underlying conditions
—> SLE
—> Other connective tissue disorders (RA, Sjogren’s)
NB: patients with other conditions may have Anti-PL but not clinical presentations —> do NOT have APLS
Antibodies in SLE (SpC Revision)
ANA:
- Very good sensitivity for SLE (>90%)
- Low specificity
- Good for excluding SLE (but if typical features present still cannot rule out diagnosis)
Anti-dsDNA:
- Renal involvement
- CNS involvement
- Titre correlate with SLE disease activity
Anti-Sm:
- Renal involvement
- CNS involvement
- Specific for SLE
Anti-RNP:
- Raynaud’s phenomenon
- mCTD associated
Anti-Ro:
- Photosensitivity
- Subacute cutaneous lupus
- Neonatal lupus
- Sjogren syndrome
Anti-La:
- Neonatal lupus
- Sjogren syndrome
Anti-phospholipid Ab:
- Thrombotic complications
- Pregnancy complications
Anti-globulin test (Coomb’s test):
- AIHA
Monitoring SLE activity
- Thorough clinical assessment (including BP)
—> e.g. skin rash, arthritis, alopecia, oral ulcers, pleuritic chest pain - ANA, Anti-ENA have NO role
- **Anti-dsDNA level **positively correlates with activity (often ↑ before clinical manifestations —> window of preclinical flare)
- **C3 / C4 levels **negatively correlate with activity (often ↓ before clinical manifestations —> window of preclinical flare)
- Urine examination including protein, cells, ***casts
- CBC
- Blood biochem
CRP and SLE
- Active SLE disease does ***NOT evoke a CRP response (most cases)
- High CRP level in SLE —> suspect ***infection
- Active **arthritis, **serositis, ***vasculitis may have moderately elevated CRP
General management of SLE
- Counselling (patients, spouse, relatives)
- ***poor compliance a major risk factor of poor prognosis - Regular monitoring
- ***Avoid triggers: excessive sun-exposure, ?oral contraceptives
- Avoid potential antigenic stimuli
- ***Infection control
- ***Pregnancy issues
- Supportive treatment e.g. dialysis
4 overarching principles:
1. SLE a multisystem disease, diagnosis based on clinical grounds + serologic abnormalities
2. SLE care is multidisciplinary, based on a shared patient-physician decision
3. Organ / Life-threatening complications require initial high-intensity + subsequent maintenance immunosuppressive therapy
4. Treatment goals include disease activity, long-term patient survival, prevent organ damage, optimisation of health-related QOL
Treat to target in SLE: Recommendations
- Target should be ***remission / lowest possible disease activity where remission cannot be reached
- Prevention of ***flares (organ damage, poor prognosis): a realistic target, should be therapeutic goal
- Treatment in clinically asymptomatic patients should NOT be escalated based solely on stable / persistent serological activity
- i.e. ***NOT treat asymptomatic patients - Prevention of ***damage accumulation should be a major therapeutic goal
- Factors negatively influencing HRQoL
- e.g. chronic fatigue, pain, depression should be addressed in addition to disease control / damage prevention - Early recognition + Treatment of ***renal involvement strongly recommended
- Lupus nephritis, following **induction therapy, **>=3 years of immunosuppressive ***maintenance treatment is recommended
- Maintenance therapy: aim for ***lowest GC dosage needed to control disease
- if possible, withdraw completely - Prevention + treatment of ***APS should be a therapeutic goal
- Irrespective of use of other treatments, serious consideration should be given to use of ***anti-malarials
- Relevant therapies adjunctive to any immunomodulation should be considered to control comorbidity in SLE patients
Drug treatment for SLE
4 recommendations:
1. Goals of treatment
- aim at remission / **low disease activity + prevention of flares in all organs
- **lowest possible dose of GC
- flares are to be treated according to the severity of organs by adjusting ongoing therapies
- General treatment of SLE
- **HCQ recommended for ALL
- **GC
- **Immunosuppressive therapies (e.g. MTX)
- **Biologics (Belimumab / Rituximab / Anifrolumab (Type 1 IFN (SpC Revision))) - Treatment of Specific manifestations
- Skin (protection from sunlight, early diagnosis of discoid lupus (prevent scarring))
- Neuropsychiatric disease (e.g. anticoagulant to prevent stroke)
- Haematological disease (do not treat low WBC (2.5) / platelet (50-75) unless significantly diminished)
- ***Renal disease (proliferative disease require active treatment, sclerotic disease require supportive treatment) - Treatment of Comorbidities
Glucocorticoids
- GC provide rapid symptom relief
- Manage acute SLE flare (SpC Revision)
- Long term aim: **Prednisolone <=7.5 mg/day / **Discontinue
2 approaches:
1. Use of ***pulses of IV methylprednisolone
- may allow for a lower starting dose + faster tapering
- ***Early initiation of immunosuppressive drugs
- to minimise long term SE of steroid (i.e. steroid-sparing)
Variable doses for different manifestations
- Small doses (prednisolone <15 mg/day): skin rash, arthritis, serositis
- Moderate doses (0.5 mg/kg/day): resistant serositis, haematologic abnormalities (e.g. thrombocytopenia, leukopenia, active haemolytic anaemia), class 5 GN
- High doses (***1-2 mg/kg/day): severe / resistant haematologic changes, diffuse GN, major organ involvement
***General treatment of SLE
Drugs:
1. **Hydroxychloroquine HCQ (for all severity)
2. **GC PO/IM (for mild), GC PO/IV (for >= moderate)
3. ***Methotrexate / Azathioprine (for mild / moderate)
4. Calcineurin inhibitor (for moderate)
5. Mycophenolate mofetil (MMF) (for >= moderate)
6. Cyclophosphamide (for severe)
7. Belimumab (for moderate refractory)
8. Rituximab (for severe refractory)
9. Anifrolumab (Type 1 IFN) (SpC Revision)
Adjunct:
- Sun protection
- Vaccination
- Exercise
- Smoking cessation
- BW control
- BP control
- Lipid
- Glucose
- ***Antiplatelet / Anticoagulant (in APL positive patients)
Target:
- **Remission (SLEDAI (disease activity index): 0 + HCQ + No GC)
- **Low disease activity (SLEDAI <=4 + HCQ + Pred <=7.5 mg/day)
Hydroxychloroquine (金雞納)
- Indicated for almost all patients (unless CI)
- Useful for **arthritis, **cutaneous manifestations, constitutional symptoms
- Prevents flare, reduce damage accrual, lipid improvement, lower thrombotic risks etc. (SpC Revision)
Effect:
- ↓ Systemic complications, flares
- Improve prognosis of major organ disease e.g. Lupus nephritis
- Improve pregnancy outcomes (e.g. lower pre-eclampsia risk)
- ↓ Secondary infectious disease complications
SE (SpC Revision):
- Diarrhoea
- **Maculopathy
- **Skin hyperpigmentation
Monitoring:
- Drug blood levels (to assess compliance)
- >10% **retinal toxicities after 20 years of use (e.g. Bull’s eye maculopathy)
- major risk factors
1. **Duration of treatment
2. Dose (risk is very low for dose <5 mg/kg/day) (Dose dependent)
3. CKD
4. Pre-existing retinal / macular disease
Will still get worse for a while since drug is trapped in retina
Immunosuppressive agents
- Azathioprine (***hepatotoxicity)
- Cyclophosphamide (infertility, ***haemorrhagic cystitis (IV Mesna))
- Cyclosporin A (***nephrotoxicity)
- Methotrexate (***hepatotoxicity)
- Leflunomide (hepatotoxicity)
- Mycophenolate mofetil
- Tacrolimus (***nephrotoxicity)
All of above:
1. **BM suppression
2. **↑ Susceptibility to infection
3. Potentially carcinogenic
4. Potentially ***teratogenic
Belimumab / Rituximab
Target B cells:
Rituximab: Anti-CD20
Belimumab: Anti-BAFF (B cell activating factor: cytokine that differentiation / proliferation of B cell)
Long term survival of SLE
Significantly improved 5 / 10-year survival (although still not reach 100%)
- 5% 5-year mortality (95% survive beyond 5 years)
- 12% 10-year mortality (88% survive beyond 10 years)
What do patients with SLE die of?
Complications of SLE in first few years
- Risk factors
- Late disease onset
- Male SLE
- Lower socioeconomic class (lack of understanding / compliance to monitoring + drug treatment) -
**Infection
- most important cause of death in **early / medium stage of disease -
**Cardiovascular thrombosis
- major cause of death in **late stage - Disease involvement of major organs
Cutaneous manifestations of LE (SpC Teaching Clinic)
Specific:
1. Malar rash
2. Subacute cutaneous lupus
- Papulosquamous
- Annular / Polycyclic
3. Discoid lupus
Non-specific:
1. Photosensitivity
2. Alopecia
3. Raynaud’s phenomenon
4. Livedo reticularis
5. Bullous
6. Lupus panniculitis
7. Vasculitis
8. Urticaria-like vasculitis (last >24 hours vs Hives)
9. Oral ulcerations
10. Nail changes
Malar rash
- A type of ***Acute cutaneous LE (self notes)
- Occur acutely in SLE patients
- ***NOT necessarily indicate active systemic disease
- ***Spare nasolabial fold (vs Heliotrope rash)
DDx:
- Rosacea
- Heliotrope rash from Dermatomyositis
- Malar flush (from mitral stenosis)
NB:
- **Photosensitive dermatitis + **Discoid lesions may occur in a ***malar distribution in patients with both SCLE and DLE
Subacute Cutaneous LE (SCLE)
**Photosensitivity is a hallmark for SCLE (Anti-Ro related)
- 75% female
- 30-50% of these patients may demonstrate systemic features
- Systemic disease tends to be **mild
- ***Nephritis rarely occurs
2 types:
1. Papulosquamous
2. Annular (環狀) / Polycyclic (六角形)
vs Discoid lesions:
- Non-indurated (non-palpable)
- Little / No telangiectasia or follicular plugging
Discoid LE
- A type of ***Chronic cutaneous LE (self notes)
- **Well demarcated, erythematous, infiltrated plaque with associated epidermal **atrophy, **telangiectasia, **scaling
- results in **hypo / **hyperpigmentation + ***scarring
- more common in ***female patients (75%)
- most frequently limited to ***photosensitive areas (head and neck) but can occur also in non-photosensitive areas
2 types:
1. **Cutaneous lupus
- Discoid is sole manifestation of lupus in the **absence of systemic disease
- 5% will develop systemic features
-
**Cutaneous manifestation of SLE
- Can also occur as a **cutaneous manifestation of SLE
- 15-20% of SLE patients
Treatment of Cutaneous LE
Conventional treatment:
1. Photoprotection
- Both UVA + UVB may induce lesions in photosensitive individuals
- Avoid sun exposure esp. 10am-3pm
- Wear photo-resistant clothing + broad rimmed hat
- Apply sunscreen with >=SPF15 (>=20-30 minutes before sun exposure)
- Broad spectrum sunscreens may offer better protection
- Take protective measures during prolonged car travel
- Topical steroids
- Risk of **atrophy
—> Potency tailored to **location of lesions
—> Low potency: face (∵ thin skin)
—> Medium potency: trunk + extremities
—> High potency: palms + soles
- ***Limited value in widespread DLE + most SCLE
- Application over large body surface —> Significant specific absorption with toxicity - Intralesional steroids
- Useful in **localised disease / individual **DLE lesions, particularly over face, scalp, palms, soles
- When lesions too numerous, injection of intralesional steroids is NOT safe / practical approach - Antimalarial Drugs
- Response rates >80% for DLE + SCLE
- Most commonly used:
—> **HCQ sulphate
——> **200-400 mg/day (i.e. 5 mg/kg/day)
——> Therapeutic benefit not observed till
***>=6 weeks (Full effect seen)
—> Quinacrine hydrochloride
(—> Chloroquine phosphate (very toxic))
SE of Antimalarials
- Generally well tolerated
-
**Retinal toxicity
- Rarely occurs when total daily dose of HCQ **<6 mg/kg/day, Chloroquine <4 mg/kg/day
- Baseline + Periodic ophthalmology at ***6 months interval —> detect early + reversible retinopathy - ***Hyperpigmentation
- Blue black skin discolouration in sun exposed areas
- Light coloured hair may also turn white
- Yellow discolouration of skin, sclera and bodily secretion with Quinacrine - Bone marrow toxicity (rarely occur)
- Haemolytic anaemia (rarely occur)
- Neuropathy (rarely occur)
Poor response to HCQ
Temporarily switch to:
One of induction strategies
1. Chloroquine induction
- 500 mg/day for 1 month
—> 250 mg/day for 1 month
—> 250 mg every other day
- Quinacrine induction
- 100 mg/day for 4-6 weeks
—> Dose tailed down gradually - High dose HCQ induction
- 600-800 mg/day for 4-6 weeks
OR
Combination strategies:
1. HCQ 200-400 mg/day + Quinacrine 100 mg/day
2. Chloroquine 250 mg/day + Quinacrine 100 mg/day
Treatment of Refractory cutaneous LE
- Various classes of therapeutic agents have been used (from case reports, case series or open trials of small numbers of patients)
- Retinoids
- Dapsone
- Vitamin E
- Clofazimine
- Thalidomide
- Oral gold
- Cytotoxic drugs
- IFN Alfa
- Pulsed methylprednisolone
- Extracorporeal photochemotherapy
- Sex hormone modulation
Thalidomide
Treatment for Erythema nodosum
Rheumatological indications:
1. Cutaneous lupus
2. RA
3. Ankylosing spondylitis
4. Behcet’s syndrome
SE:
1. Peripheral neuropathy
- Symmetrical painful paresthesia of hands and feet
- Accompanied by sensory loss in lower limbs
- No connection with either duration / dose
- PE for signs of neuropathy should be performed monthly for first 3 months and periodically thereafter
- ***6 monthly NCV
- Teratogenicity
- Amelia / phocomelia
- Duodenal stenosis
- Esophageal fistulae
- Neural tube abnormalities
- Micro-ophthalmia
- Deformities of ears - Others
- Amenorrhoea
- Drowsiness
- Constipation
- Weight gain
- Vertigo
- Skin dryness
- Insomnia
Monitoring:
NCV study every 6 months to monitor irreversible polyneuropathy
Renal manifestations in SLE
- 50-70% patients
Clinical features:
1. Asymptomatic
2. Abnormal urinalysis
- Haematuria
- Cast (Hyaline / Granular)
- Pyuria
- Proteinuria
3. HT
4. Nephrotic syndrome
5. Renal failure
WHO classification 1982:
1: Normal glomeruli
2: Pure mesangial nephritis
3: Focal segmental GN
4: Diffuse proliferative GN
5: Membranous GN (may occur in combination with 3/4)
6: Advanced sclerosing GN (seldom seen since relative CI to renal biopsy)
Visual loss in SLE
Acute visual loss:
1. Retinal / Choroidal ischaemia
- Immune complex-mediated vasculitis
- Occlusion associated with Antiphospholipid Ab
- Retinal tears
- Choroidal disease can lead to multifocal serous elevations of RPE and adjacent retinal sensory tissue with resulting macular pathology and retinal detachment - Glaucoma
- Known complication of steroid (occasionally in non-steroid treated lupus - Optic / Retrobulbar neuritis
- Cortical infarcts of the brain
- SE of drugs
Cytoid bodies:
- 5-24 % of SLE patients
- Small white spots in SLE patients’ fundi
- Equivalent to Roth’s spot in IE
- Infarction from vasculitis / thromboemboli
- Characterised histologically by hypertrophy / ganglioform degeneration of nerve fibre
Neuropsychiatric manifestations in SLE
Causes:
1. SLE itself
2. SE of drugs (e.g. steroid psychosis)
3. Electrolyte abnormalities (e.g. Sjogren causing RTA)
4. Inherent behavioural / cognitive defects
5. Infection
6. Complication (e.g. Uraemic encephalopathy)
- Central nervous system
- Aseptic meningitis
- Cerebrovascular disease
- Demyelinating syndrome
- Headache
- Movement disorder
- Myelopathy (Longitudinal rather than Transverse)
- Seizure disorder
- Acute confusional state
- Anxiety disorder
- Cognitive dysfunction
- Mood disorders
- Psychosis - Peripheral nervous system
- **Guillain-Barre syndrome
- **Myasthenia gravis
- Autonomic neuropathy
- Mononeuropathy (single / multiplex)
- Cranial neuropathy
- Plexopathy
- Polyneuropathy
Haematological manifestations of SLE
- Anaemia
- Chronic inflammation
- Deficiency states: Fe, Vit B12
- Autoimmune haemolysis
- Medications related (e.g. MMF; NSAID / steroid causing GI bleed)
- Thrombotic microangiopathy - Leukopenia
- Common + Correlates with disease activity
- Neutropenia: Viral infection, Immunosuppressive medication, Splenomegaly
- ***Lymphopenia - Thrombocytopenia
- Could be the presenting problem
- Autoimmune
- Medications related
- Splenomegaly
- Thrombotic microangiopathy - Pancytopenia
- Sepsis
- Bone marrow toxicity from drugs
- Thrombotic microangiopathy
- Splenomegaly
- Haematological malignancies
- Macrophage activation syndrome (Secondary haemophagocytic lymphohistiocytosis) - APLS
- Lymphadenopathy (may need to exclude Lymphoma)
- Splenomegaly
- Thrombotic microangiopathy
Cardiac manifestations of SLE
- Pericardial disease
- Myocarditis
- Valvular disease (Libman-Sacks endocarditis)
- Mitral valve most common
- Vegetations and thickening
- Associated with Antiphospholipid Ab - Conduction abnormalities
- Sinus tachycardia common
- 1st degree heart block (often transient)
- Complete heart block (rare) - Coronary artery disease (∵ vasculitis)
Pulmonary manifestations of SLE
- Pleural involvement
- ILD
- Lupus pneumonitis (Aseptic pneumonitis, diagnosis of exclusion)
- Pulmonary hypertension (may need RH catheterisation to diagnose)
- Shrinking lung syndrome (∵ Affect phrenic nerve —> diaphragmatic breathing)
