SYSTEMIC LUPUS ERYTHEMATOSUS
sle is a multisystemic autoimmune disease.
Autoantibodies are made against a variety of autoantigens (eg ana) which form immune complexes.
Inadequate clearance of immune complexes results in a host of immune responses which cause tissue inflammation and damage.
Environmental triggers play a part (eg ebv)
PREVALENCE
~0.2%. ♀:♂≈9:1, typically women of child-bearing age
Commoner in African-Caribbeans, Asians, and if hla b8, dr2, or dr3 +ve
~10% of patients have a 1st- or 2nd-degree relative with sle
CLINICAL FEATURES
or organ-specific and caused by active inflammation or damage
Other features include
Features often non-specific (malaise, fatigue, myalgia, and fever)
Remitting and relapsing illness of variable presentation and course
weight loss
alopecia
nail-fold infarcts
non-infective endocarditis
lymphadenopathy
Raynaud’s (30%)
stroke
retinal exudates
TO DIAGNOSE >/= 4 (at least 1 clinical and 1 lab) or biopsy-proven lupus nephritis with positive ana or anti-dna.
CLINICAL CRITERIA
5 Synovitis:
6 Serositis:
4 Oral/nasal ulcers:
8 Neurological features:
10 Leucopenia:
3 Non scarring alopecia:
9 Haemolytic anaemia.
2 Chronic cutaneous lupus:
7 Urinanalysis:
1 Acute cutaneous lupus:
LAB CRITERIA
Fixed erythema, flat or raised, over the malar eminences, tending to spare the nasolabial folds
Occurs in up to 50%
Malar rash/butterfly
Bullous lupus,
toxic epidermal necrolysis variant of sle,
maculopapular lupus rash,
photosensitive lupus rash, or subacute cutaneous lupus (non-indurated psoriasiform and/or annular polycyclic lesions that resolve without scarring).
Discoid rash, erythematous raised patches with adherent keratotic scales and follicular plugging ± atrophic scarring. Think of it as a three-stage rash affecting ears, cheeks, scalp, forehead, and chest: erythema→pigmented hyperkeratotic oedematous papules→atrophic depressed lesions.
(In the absence of other causes.)
(In the absence of other causes.)
(Involving two or more joints or two or more tender joints with >30 minutes of morning stiffness.)
Presence of proteinuria (>0.5g/d) or red cell casts.
a) Lung (pleurisy for >1 day, or pleural effusions, or pleural rub;
b) pericardial pain for >1 day, or pericardial effusion, or pericardial rub, or pericarditis on ecg.
psychosis;
Seizures;
mononeuritis multiplex;
myelitis;
peripheral or cranial neuropathy;
cerebritis/acute confusional state in absence of other causes.
(wcc <4.) At least once, or lymphopenia (lymphocytes <1) at least once.
11 Thrombocytopenia:
(Platelets <100.) At least once.
1 +ve ana (+ve in >95%).
2 Anti-dsdna. (High in ~60% of cases.)
3 Anti-Smith antibodies present.
4 Antiphospholipid Abs present.
5 Low complement (c3, c4, or c50).
6 +ve Direct Coombs test.
IMMUNOLOGY
40% are rhf +ve;
antiphospholipid antibodies (anticardiolipin or lupus anticoagulant) may also be +ve.
ena may be +ve in 20–30% (anti-Ro, anti-La, anti-Sm, anti-rnp);
sle may be associated with other autoimmune conditions: Sjögren’s (15–20%), autoimmune thyroid disease (5–10%).
A high anti-double-stranded dna (dsdna) antibody titre is highly specific, but only +ve in ~60% of cases.
95% are ana +ve.
MONITORING ACTIVITY
2 Complement: ↓c3, ↓c4 (denotes consumption of complement, hence ↓c3 and ↓c4, and ↑c3d and ↑c4d, their degradation products).
3 esr.
1 Anti-dsdna antibody titres.
Also: bp, urine for casts or protein (lupus nephritis, below), fbc, u&e, lfts, crp (usually normal)
think of sle whenever someone has a multisystem disorder and ↑esr but crp normal. If ↑crp, think instead of infection, serositis, or arthritis. Skin or renal biopsies may be diagnostic.
DRUG INDUCED LUPUS
Causes (>80 drugs) include
isoniazid, hydralazine (if >50mg/24h in slow acetylators), procainamide, quinidine, chlorpromazine, minocycline, phenytoin, anti-tnf agents.
It is associated with antihistone antibodies in >95% of cases. Skin and lung signs prevail (renal and cns are rarely affected).
The disease remits if the drug is stopped. Sulfonamides or the oral contraceptive pill may worsen idiopathic sle.
MANAGEMENT
• General measures:
Maintenance:
Refer: complex cases should involve specialist sle/nephritis clinics.
Hydroxychloroquine, unless contraindicated, reduces disease activity and improves survival.
Screen for co-morbidities and medication toxicity.
High-factor sunblock.
For skin flares, first trial topical steroids.
Azathioprine, methotrexate, and mycophenolate as steroid-sparing agents.
Belimumab (monoclonal antibody) used as an add-on therapy for auto-antibody positive disease where disease activity is high
nsaids (unless renal disease) and hydroxychloroquine for joint and skin symptoms.
Mild flares:
(No serious organ damage.)
Hydroxychloroquine or low-dose steroids.
Moderate flares:
(Organ involvement.)
May require dmards or mycophenolate.
Severe flares:
urgent high-dose steroids, mycophenolate, rituximab, cyclophosphamide.
mdt working vital for neuropsychiatric lupus (psychometric testing, lumbar puncture may be indicated).
If life- or organ-threatening, eg haemolytic anaemia, nephritis, severe pericarditis or cns disease;
LUPUS NEPHRITIS
May require more intensive immunosuppression with steroids and cyclophosphamide or mycophenolate.
bp control vital (e.g. ace-i).
Renal replacement therapy may be needed if disease progresses; nephritis recurs in ~50% post-transplant, but is a rare cause of graft failure
PROGNOSIS
~80% survival at 15 years
There is an increased long-term risk of cvd and osteoporosis.
ANTIPHOSPHOLIPID SYNDROME
Can be associated with sle (20–30%)
Often occurs as a primary disease.
Antiphospholipid antibodies (anticardiolipin & lupus anticoagulant, anti-β 2 glycoprotein 1)
RX
DX
Persistent antiphosphlolipid antibodies with clinical features.
Anticoagulation; seek advice in pregnancy
Antiphospholipid antibodies cause clots:
Thrombocytopenia. Thrombotic tendency affects cerebral, renal, and other vessels.
Coagulation defect (arterial/venous),
Obstetric (recurrent miscarriage),
Livedo reticularis,