Systemic Lupus Erythematosus

- Systemic lupus erythematosus (SLE) is a multisystem autoimmune connective tissue

disorder with various clinical presentations.
Pathophysiology
- The cause is incompletely understood
- Genetic factors (HLA-DR and HLA-DQ regions)
- Inherited mutation of complement components C1q, C2 and C4
- The characteristic feature is autoantibody production (against antigen present within the
cell or within the nucleus)
- Hypothesis: defect in apoptosis or in the clearance of apoptotic cells, which causes
inappropriate exposure of intracellular antigens on the cell surface, leading to polyclonal
B cell and T cell activation and autoantibody production
- Environmental factors: ultraviolent light, infections, oxidative stress
Clinical features of SLE
- Peak age of onse – 20-30 years
- Female to male ratio – 9:1
- More common African or Asians
General features
- Fever in up to 50% of patients
- Marked malaise and tiredness
Musculoskeletal features
- Joint involvement is the most common clinical feature ≥ 90%
▪ Migratory arthralgia with mild morning stiffness
▪ Tenosynovitis and small joint synovitis (that may mimic RA)
▪ Joint deformities are rare (in contrast to RA)
▪ Deformities may result from tendon inflammation and damage rather than from
born erosion (Jaccoud’s arthropathy)
- Myalgia –in up to 50% but myositis only in <5%
Mucocutaneous features
- Occurs in 75% of patients
 - Classic butterfly facial rash (20% of patients) – raised and painful or pruritic sparing the
nasolabial folds with photosensitivity
- Discoid lupus- hyperkeratosis and follicular plugging with scarring alopecia
- Diffuse non-scarring, alopecia
- Other skin manifestations
▪ Periungual erythema, vasculitis and livedo reticularis
Renal features
- Occurs in 30% of patients
- One of the main determinants of prognosis and regular monitoring of urinalysis and blood
is essential
- Typical renal lesion →proliferative glomerulonephritis with hematuria, proteinuria and
casts on urine microscopy
- Classification of lupus nephritis
▪ Class I – Minimal mesangial lupus nephritis
▪ Class II – Mesangial proliferative lupus nephritis
▪ Class III – Focal lupus nephritis
▪ Class IV – Diffuse lupus nephritis
▪ Class V – Membranous lupus nephritis
▪ Class VI – Advanced sclerotic lupus nephritis
CNS features (Neuropsychiatric SLE)
- Occurs in up to 60% of patients
- Fatigue, headache, poor concentration are common, even in the absence of laboratory
evidence of active disease
- Specific features of cerebral lupus include visual hallucinations, chorea, organic psychosis,
transverse myelitis and lymphocytic meningitis
- Epilepsy, cerebrovascular disease, cerebellar ataxia, cranial nerve lesions and
polyneuropathy may be seen.
Pulmonary features
- Occurs on 50% of Patients
- Recurrent pleurisy and pleural effusions are the most common manifestations
- Lupus pneumonitis
 - Pulmonary fibrosis
- Risk of thromboembolism is increased, especially in patients with antiphospholipid
antibodies
Cardiovascular features
- Occurs in 25% of patients
Cardiac
- Pericarditis with small pericardial effusion is common.
- Myocarditis with arrhythmias
- Non- infective endocarditis (Libman-Sacks endocarditis)
Vascular
- Raynaud’s phenomenon
- Vasculitis
- Antiphospholipid syndrome – arterial and venous thromboses
- Increased risk of atherosclerosis (stroke and myocardial infarction)
Haematological features
- Occurs in up to 75% of patients
- Antibody-mediated destruction of blood cells →pancytopenia
- Neutropenia, lymphopenia, thrombocytopenia and hemolytic anemia
- The degree of lymphopenia can be a guide to disease activity
- Although ESR is usually elevated, CRP is often normal unless there is serositis or infection.
Ocular features
- Retinal infarcts (cytoid bodies)
- Retinal haemorrhages
- Secondary Sjogren’s syndrome
- Episcleritis, conjunctivitis or optic neuritis may occur but blindness is uncommon.
Gastrointestinal features
- Oral ulcers are common and may be a presenting feature.
- Mesenteric vasculitis causing bowel infarction or perforation
- Liver involvment and pancreatitis – uncommon
Drug-induced SLE
- Hydralazine, isoniazid, procainamide and penicillamine
- Arthralgia and mild systemic features
- Kidneys and CNS are not affected
- Usually disappears when the offending drug is stopped.
Investigations
Blood tests
Full blood count
- Pancytopenia
- Anemia of chronic disease or autoimmune hemolytic anemia
- Leucopenia, lymphopenia
- Thrombocytopenia
ESR
- Raised in proportion to the disease activity
CRP
- Usually normal but may be high in serositis or infection
Urea and creatinine
- Raised in lupus nephritis
Autoantibodies
- ANA – high sensitivity (100%), low specificity (10-40%)
- Anti-dsDNA – high specificity (95%), moderate sensitivity (70%)
- Anti-Sm- specific for SLE
- Anti-Ro (anti-SSA) and anti-La (anti-SSB) – Associated with Sjogren’s syndrome,
neonatal lupus with congenital heart block
- Antiphospholipid antibodies - ↑ risk of arterial thrombosis and recurrent abortion
- Anti-histone antibodies – drug-induced SLE
Serum complement C3 and C4 levels
- Reduced during active disease
Coombs test (if hemolytic anemia is suspected)
Urine tests
Urine REME
- Proteinuria
- Cellular casts (red cell, granular or tubular)
24 hour urinary protein or urinary protein creatinine ration
Biopsy
- Deposition of IgG and complement are seen in renal and skin biopsies
Management
The therapeutic goals are to educate the patient about the nature of the illness, to control
symptoms and to prevent organ damage and maintain normal function

Treatment of non-organ threatening lupus

Mild disease activity (SLEDAI < 6)
- Mild disease restricted to skin and joints
- Hydroxychloroquine
- Prednisolone 5-20mg/day, often in combination with immunosuppressants such as
methotrexate, azathioprine or mycophenolate mofetil(MMF)
- NSAID should be given as necessary

Moderate disease activity (SLEDAI 6-12)

- Prednisolone 0.5mg/day for 2-4 weeks and taper gradually (if necessary pulse ivi
methylprednisolone 250 mg for 1-2 days can be given)
- Hydroxychloroquine 200 mg/day
- Azathioprine or methotrexate or MMF or leflunomide or ciclosporin or tacrolimus

Severe disease activity (SLEDAI > 12)

Indications of intensive therapy
1. Renal indication
- Confirmed proteinuria of  1g/day
- Combination of the followings (at least 2 tests done within a short period of time and
in the absence of alternative causes)
o Proteinuria  0.5 g/day plus hematuria ( 5RBCs/hpf or cellular casts or initial
rising creatinine)
o Proteinuria  0.5 g/day plus extra-renal manifestation
2. Extra-renal indications
- Neuropsychiatric SLE
- Organ-threatening vasculitis (retinal, mesenteric, coronary, severe digital vasculitis
impending gangrene)
 - Myocarditis, severe pericarditis impending cardiac tamponade
- Severe interstitial lung disease
- Severe symptomatic myositis
- Lupus gut enteropathy
- Hematological involvement (severe AIHA)
Phases
1. Induction therapy (month 1-6)
2 options
- Monthly CYC regimen
o Month 1 (IVI methylprednisolone 500 mg OD for 3 days , IVI CYC 400 to 600
mg OD for 1 day + IVI equivalent dose of mesna)
o Month 2-6 (IVI CYC OD for 1 day + equivalent dose of mesna)
o Throughout 6 month period, tapering dose of prednisolone or equivalent dose
of methylprednisolone (start with 1mg/kg/day for one month and tapered
gradually monthly)
- Daily MMF regimen
o Month 1 (initial pulse IVI methylprednisolone 500 mg OD for 3 months)
o PO MMF 1.5 to 2 g/day
o Throughout 6 month period, tapering dose of prednisolone
2. Maintenance therapy (for those who response to induction therapy)
- MMF 1-1.5 g/day
- Azathioprine
- Leflunomide
- Three monthly ivi CYC regimen
- Maintenance therapy should be at least 3- 5 years
- Lowest possible dose of steroid that can control the disease activity should be used
Treat to target
- It is suggested to attain mild disease activity or remission and to prevent the disease
flare
Adjunct treatment
- Hydroxychloroquine to reduce renal flares, limit the accrual of renal and cardiovascular
damage
- Avoid sun and ultraviolet light exposure and to employ sun blocks (sun protection
factor 25–50).
- Calcium and vitamin D supplementation
- Cholesterol lowering with statins (for persistent dyslipidemia)
- ACEI or ARB (for patients with proteinuria or hypertension)
- Immunization of non-live vaccine (Hepatitis B vaccine, yearly influenza vaccine, 5
yearly pneumococcal vaccine)
- Regular aerobic exercise
- Sleep hygiene

Follow up
- Every 4 weeks for the first 6 months after diagnosis or flare and then according to the
response to treatment
- Monitoring of disease activity should be lifelong at least every 3-6 months interval