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.

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(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,