Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by autoantibodies against nuclear antigens. It can affect multiple organ systems. The presentation, pathogenesis, clinical features, investigations, management, and prognosis of SLE are discussed in detail in this document. Key points include that SLE predominantly affects women and certain races disproportionately. Genetic and environmental factors contribute to its pathogenesis. A variety of clinical manifestations are described affecting the skin, joints, kidneys, lungs, and other organs. Management involves controlling symptoms, preventing organ damage, and maintaining remission, often through medications like hydroxychloroquine and corticosteroids. Prognosis has improved over time but risks of infection and accelerated

1. SYSTEMIC LUPUS
ERYTHEMATOSUS
PRESENTED BY:
DR.TAHIRA AGHANI

2. OBJECTIVES
 Introduction
 Epidemiology
 Pathogenesis
 Clinical features
 Investigations
 Management
 Prognosis

3. Introduction
 SLE is an autoimmune disorder characterised by
autoantibodies to nuclear antigens .It can affect
multiple organ systems .
 Many of its clinical manifestation are secondary to
the trapping of the antigene antibody complexes in
cappilaries of visceral structures or to autoantibody
mediated destruction of host cells
(eg.thrombocytopenia).
 Clinical course is marked by spontaneous remission
and relapses.

4. Epidemiology
 Incidence : SLE is influenced by many factors
including sex , race and genetic inheretance.
 Sex: About 85% patients are women.
 In older individuals sex distribution is more equal.
 Race: SLE occurs in 1:1000 white women but in
1:250 in black women.
 & 25-70% in identical twins.

5. Pathogenesis
The cause of SLE is incompletetly understood but
genetic factors play an important role.
 SLE is emphasized by the high frequency of certain
HLA haplotypes especially DR2 and DR3 .And null
complement alleles.
 SLE is associated with inherited mutations
compliment components (C1Q , C2 and C4)

6.  From an immunological standpoint , the characteristic
feature of SLE is autoantibody production.These
autoantibodies have specificity for a wide range of
targets but many are directed against antigens present
within the cells or within the nucleus.
 SLE may occur because of defects in apoptosis or in the
clearance of apoptotic cells which cause inappropriate
exposure of intracellular antigens on cell surface
leading to polyclonal B andT cell production.

7.  Environmental factors causes flares of lupus,
such as UV light and infection ,increase
oxidative stess and cause cell damage.

8. ClinicalFeatures
 Systemic features:
 Fever, malaise,wt loss, mild lymphadenopathy
 Arthritis
 Arthalgia is a common symptom occurring in 90%
of patients .Joint deformities may occur( jaccoud
arthropathy) as a result of tendon damage but also
can lead to reversible swan neck deformities but
joint erosions do not occur.

9.  Raynoudphenomenon is common.
 Skin:
 Rash is common in SLE .
 The classic butterfly facial rash (upto 20%)
 Subacute cutaneous lupus erythematosus
 Discoid lupus rash.

10. Butterflyrash
Most common acute SLE rash
▶ Fixed erythema, flat or
raised, over the malar
eminences.
▶Tending to spare the
nasolabial folds

11. Discoidlupusrash
Erythematous raised patches
with adherent keratotic
scaling and follicular
plugging
Atrophic scarring may occur
in older lesions

12. Subacutecutaneouslupuserythematosis
SCLE rash consists of scaly red
patches similar to psoriasis or
circular flat red-rimmed lesions

13. Ocularmanifestations
 Sjogren’s syndrome and non-specific
conjunctivitis are common in SLE and rarely
threaten vision.
 In contrast retinal vasculitis and optic neuritis
are serious manifestations that can lead to
transient or permanent monocular blindness.

14.  Kidney:
 Renal envolvement is one of the main
determinant s of prognosis.
 The typical renal lesion is proliferative
glomerulonephritis characterised by hematuria
,proteinuria , and casts on urine microscopy.
 CVS : The most common manifestation is
pericarditis.Myocarditis and Libman Sack
endocarditis.

15. Lupusnephritis
 Class 1 : Minimal Mesangial Lupus nephritis.
 Class 2: Mesangial Proliferative lupus
nephritis.
 Class 3 : Focal Lupus nephritis
 Class 4: Diffuse Lupus nephritis
 Class 5 : Membraneous Lupus nephritis
 Class 6 : Advanced Lupus nephritis

16.  Lung:
 pleurisy and pleural effusion are common but
atelectasis , pnemonitis and pulmonary fibrosis
can also occur.
Neurological:
 Its complications include phycosis , seizures ,
cognitive impairment , peripheral and cranial
neuropathy , transverse myelitis and stroke.
 .

17.  Haematogical :
Neutropenia , thrombocytopenia , hemolytic
anemia , lymphopenia may occur.
 GIT :
Oral ulcers may occur and mesentric vasculitis is
a serious complication.

18. Investigations

21.  Antibodies to ds.DNA and to Sm are specific
for SLE but not sensitive since they are
present in only 6o% ang 30% of patient
respectively.
 Depressed serum complement level
suggestive of disease activity often return
towards normal in remission.

22. Management
 Therapeutic goals are to educate the patient
about the nature of the illness , to control
symptoms and to prevent organ damage.

23.  Mildto ModerateDisease :
 Patients with mild disease restricted to skin
and joints can sometimes be managed with
analgesics.
 NSAID’s and Hydroxychloroquiune (2oo to
400mg daily) are required .Dose of
hydroxychloroquine should not be exceded
5mg/kg/day.
 However corticosteriods are also necessary
Dose: predinisolone 0.07 to 0.3mg/kg/day qod (5
to 20mg / day ) in milder disease.

24.  For severe SLE prednisolone dose is 0.5 to 1
mg/kg (40 to 60mg/day)
 Increased doses of steriods are required for
flares inactivity or complication such as
pleurisy or pericarditis.

25.  Life threatening disease
 High dose corticosteroids or
immunsupressant are required for treatment
of CNS ,renal and cardiac involment.
 Commonly used regimen is pulse
methylprednisolone (10mg/kg/iv) coupled
with cyclophosphamide (15mg/kg/iv)
repeated at 2 t0 3 intervals for 6 cycles.

26. However immunosuppressant are also necessary
often in combination with corticosteriods.
Azathioprine (2 to 2.5 mg/kg/day)
Methotrexate (10 to 25mg/week)
Mycophenolate mofetil (2 to 3 g/day)
Monoclonal antibody belimumab which target
the B cells growth factor BLyS has recently has
been shown to be effective ,in patient with active
SLE who don’t respond adequetly to standard
therapy.

27.  Maintenance therapy
 Long term aim is to continue the lowest dose
of corticosteriods and immunosupressants
that will maintain remission .
 A typical regime is to start to oral
predinisolone in a dose of 40 to 60mg daily
on cessation of pulse therapy , gradually
reducing to reach a target of 10 to 15 mg /day
or less by 3 months

28. Prognosis
 In most patients the illness persues a relapsing
and remmiting course .
 10 years survival rates exceeding 85% are
routine.
 Mortility in SLE shows a bimodal pattern in
early years after diagnosis, infection especially
with opportunist are the leading cause of
death, followed by active SLE due to CNS or
kidney disease.

29.  In later years accelerated atherosclerosis link
to chronic inflammation becomes a major
cause of death.
 Patients with SLE should receive influenza
vaccination every year and pneumococcal
vaccination every 5 years.
 SLE patients have a higher risk of developing
malignancy especially lymphoma , lung
cancer , cervical cancer , so preventing cancer
screening should be followed .

30. DrugInducedlupus
 Drug induced lupus shares several clinical
and serological features with SLE but is due
ongoing exposure to a drug and resolves
when offending drug is discontinued.
 As a general rule ,It presents with arthralgia ,
myalgia and serositis but but not renal or
neurologic involvement or other features of
SLE.

31.  Serological testing reveals elevated titers of
antinuclear antibodies in all patients, but
antibodies to DNA ,Sm, Rnp, SS-A and SS-B
are rare.
 Antibodies to histone are common.
 Complements levels are usually normal.

32.  List of drugs causing lupus
 Antiarrhythmic: procainamide ,
disopyramide,proprafenone , quinidine
 Antihypertensive:hydralazine , beta blockers and severa
angiotensin converting enzyme inhibitors ,methyldopa .
 Antipsycotics : chlorpromazine and lithium
 Antithyroid : propylthiouracil
 Anticonvulsants : carbamazepine and phenytoin
 Diuretics : hydrochlorothiazide
 Antirheumatic : sulphasalazine
 Antibiotics : isoniazid , minocycline
 Antihyperlipidmics : lovastatin and simvaststatin
 Others :TNF inhibitors and interferons

33.  Special conditions in SLE that may require additional or
different therapies.
 Cresentic lupus nephritis: Most authorities
recommend that cyclophosphamide in high
dose or high doses of mycophenolate are the
induction therapy of choice, in addition to
glucocorticoids.
 Membranous lupus nephritis: Recent
prospective control trails suggest that
alternate day glucocorticoid plus
cyclophosphamide or mycophenolate or
cyclosporins are all effective in majority of
patients in reducing proteinuria.

34.  Pregnancy and Lupus: Fertility rates for women
and men with SLE are probably normal.
 Rate of fetal loss is increased approximately 2
to 3 fold in women with SLE.
 Supression of disease activity can be achieved
by administration of systemic glucocorticoids.
 Glucocorticoid are approved by FDA as
pregnancy category A ( no evidence of
teratogenicity in human studies.)

35.  Cyclosporins , tacrolumus , rituximab listed as
category C (may be teratogenic in animals
but no good evidence in humans.)
 Azathioprine ,hydroxychloroquine ,
mycophenoline and cyclophosphamide are
catogery D ( there is evidence of
teratogenicity in humans but benefits might
out way risks in certain situations .)
 Methotrexate is catogery X ( Risk out way
benefits )

36.  Additional potential problems for the fetus is
presence of antibodies to Ro , associated with
neonatal lupus consisting of rash and
congenital heart block. So the presence of
antiR0 , required monitoring of fetal heart
rates with prompt inteventions.

37.  Lupus and antiphospholipid antibody syndrome:
 patients with SLE who have venous or
arterial clotting or repeated fetal losses and
atleast 2 positive results for Apl have APS
should be managed with long term
anticoagulation.
 Target INR of 2 t0 2.5 is recommended.

38.  Microvascular thrombotic crises ( TTP and HUS) :
 It most commonly occurs in young
individuals with lupus nephritis.
 Plasma exchange or extensive
plasmapheresis with concomitant
glucocorticoid therapy.

39.  Lupus dermatitis:
 Patients with any form of lupus dermatitis should
minimize exposures to UV light with appropriate
clothing and sun screens.
 Topical glucocorticoids and antimalarials such as
hydroxychloroquine are effective in reducing
lesions.
 Systemic treatment with retinoid acid is a useful in
patients with inadequate improvement on
glucocorticoids or antimalarials.