SLE By Kisembo Ivan

1. SYSTEMIC LUPUS ERYTHEMATUS
Kisembo Ivan
22/U/20696

2. INTRODUCTION
Systemic lupus Erythematosus
(SLE) is a multisystem
autoimmune disorder with a
number of clinical
manifestations.
EPIDEMIOLOGY
The prevalence ranges from
about 0.03% in Caucasian to
0.2% in Afro –Caribbean. Some
90% of affected patients are
female and the peak age at
onset is
between 20 and 30 years .

3. Pathophysiology
• The cause of SLE is incompletely understood but
genetic
• factors play an important role. There is a higher
concordance in monozygotic twins and the disease is
strongly associated with polymorphic variants at the
HLA locus.
• In a few instances, SLE is associated with inherited
• mutations in complement components C1q, C2 and
C4, in the immunoglobulin receptor FcγRIIIb or in the
DNA exonuclease TREX1.

4. Pathophysiology continue..
• 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
cell or within the nucleus. This has led to the
hypothesis that SLE may occur because of
defects in apoptosis or in the clearance of
apoptotic cells,

5. Pathophysiology cont…
• which causes inappropriate exposure of
intracellular antigens on the cell surface,
leading to polyclonal B and T cell activation
and autoantibody production.
• This is supported by the fact that
environmental factors that cause flares of
lupus, such as UV light and infections, increase
oxidative stress and cause cell damage.

6. Clinical features
• Symptoms such as fever, weight loss and mild lymph
adenopathy may occur during flares of disease activity,
whereas others such as fatigue, malaise and fibromyalgia
like symptoms can be constant and not particularly
associated with active inflammatory disease.

7. Clinical features
• Arthritis occurs in 90% of patients(early morning stiffness).
• Raynaud’s phenomenon and presents in combinatination
with arthragia or arthritis
Mouth ulcer, mesenteric vasculitis with abdo
• Pain Arthritis occurs in 90% of patients(early morning
stiffness).
• Raynaud’s phenomenon and presents in combinatination
with arthragia or arthritis
Mouth ulcer, mesenteric vasculitis with abdo
pain

8. Clinical Features
• Skin Rash is common in SLE precipitated by
exposure to UV light.
• Kidney involvement is determinant of prognosis
with renal lesion in proliferative
glomerulonephritis.
• Cardiovascular manifestation with pericarditis.
• Pleural effusion leads to breathlessness.
• Headache, Fatigue and poor concentration.
• Neutopenia, Lymphopenia, thrombocytopenia or
haemolytic anaemia may occur.

9. Investigation
• Screen for ANA and antibodies to extractable
nuclear antigens. Patients with active SLE
almost always test positive for ANA, but ANA
negative SLE can very rarely occur.
• ESR Increased , leucopenia and lymphopenia.
• CRP normal in active SLE.

10. Management
• PREVENTION
• The therapeutic goals are to educate the
patient about the nature of the illness, to
control symptoms and prevent organ damage.
Patients should be advised to avoid sun and
UV light exposure and to employ sun blocks.

11. Mild to Moderate.
• Patients with mild disease restricted to skin and
joints
can sometimes be managed with analgesics, NSAID
and hydroxychloroquine (200–400 mg daily).
Frequently, however, corticosteroids are also
necessary
• (prednisolone 5–20 mg/day), often in combination
with immunosuppressant such as methotrexate,
azathioprine or mycophenolate mofetil.

12. Life-threatening disease
• High dose corticosteroids and
immunosuppressant are required for the
treatment of renal, CNS and cardiac
involvement. A commonly used regimen is
pulse methylprednisolone (10 mg/kg IV),
coupled with cyclophosphamide (15 mg/kg
IV), repeated at 2–3 weekly intervals for six
cycles.

13. RHEUMATOID ARTHRITIS
• Definition:
Rheumatoid arthritis (RA) is the most common
persistent inflammatory arthritis, occurring
throughout the world and in all ethnic groups.
Attacks tend to be bilateral with symmetrical
involvement that cause joint destruction.

14. Epidemiology :
The prevalence is lowest in black Africans and
Chinese, and highest in Pima
Indians. In Caucasians, approximately 0.8–1.0%
are affected,
with a female to male ratio of 3 : 1

15. Causes
• Genetic, epigenetic and environmental factors
are implicated in the pathogenesis of RA. The
concordance rate of RA is higher in
monozygotic (12–15%) than in dizygotic twins
(3%), and there is an increased frequency of
disease in first degree relatives of patients.

16. Pathophysiology
• The clinical onset of RA is characterised by
infiltration of the synovial membrane with
lymphocytes, plasma cells, dendritic cells and
macrophages. CD4+ T lymphocytes, including
Th1 cells (interferon gamma (IFN γ) producers)
and Th17 cells (IL 17A, IL 17F and IL 22
producers), play a central role by interacting
with other cells in the synovium.

17. Pathophysiology
• Synovial macrophages are activated by immune
complexes and local damage associated
molecules. These act on synovial fibroblasts, to
promote swelling of the synovial membrane and
damage to soft tissues and cartilage.
• Similarly, activation of osteoclasts by RANKL and
chondrocytes by
• cytokines such as IL 1 and TNF drives
destruction of bone and cartilage respectively.

18. Pathophysiology cont…..
• The RA joint is hypoxic and this promotes new
blood vessel formation
• (neoangiogenesis). Thus the inflamed
synovium becomes vascularised, with highly
activated endothelial cells supporting the
recruitment of yet more leucocytes to
perpetuate the inflammatory process.

19. Clinical presentation
• Stiffness and pain in the joints (usually >3,
symmetrical, worse in the morning)
• Joints are swollen, warm, inflamed, and
sensitive to touch Fingers are most affected
(metacarpophalangeal, or proximal
interpahalangeal), but all small and medium
size joints can be affected (rarely hips and
spine)

20. Clinical manifestation continue.
• Extra articular manifestations: mild fever,
weakness, lethargy, anorexia, weight loss,
rheumatoid nodules (20%) at extensor surface
like forearm below joint
• It is a CHRONIC disease with flare-up,
remission, and exacerbations
• In advanced cases, joint deformities may
occur

21. Clinical presentation cont…
• Ulna deviation in Rheumatoid arthritis hand

22. Diagnosis
• Criterion Score
• Joints affected
• 1 large joint 0
• 2–10 large joints 1
• 1–3 small joints 2
• 4–10 small joints 5
• Serology
• Negative RF and ACPA 0
• Low positive RF or ACPA 2
• High positive RF or ACPA 3
• Duration of symptoms
• < 6 wks 0
• > 6 wks 1
• Acute phase reactants
• Normal CRP and ESR 0
• Abnormal CRP or ESR 1
• Patients with a ascore of > 6 are considered to have definite RA

23. Investigation
CRP
• ESR
• Ultrasound or MRI
• Rheumatoid factor and anti-citrullinated
peptide antibodies. To establish diagnosis.
• X-rays
• Functional assessment to reveal level of
damage.

24. Clinical features cont,
• Urinalysis
• Full blood count
• Other tests include Urea, creatinine.
• liver function tests to monitor drug safety.

25. Management
• Relief of symptoms
• Preservation of joint function
• Suppression of active disease, and slowing
progression of disease (prevention of structure
damage and deformity)
• Maintenance of patient’s normal lifestyle
• Symptomatic treatment can be started at lower
level but appropriate management requires
referral for specialist care.

26. Management

27. Management cont….
• For pain and inflammation in acute flare
• Rest the affected joints
‰
• Any NSAIDS e.g. ibuprofen 400 mg every 8hours
‰
• Or diclofenac 50 mg every 8 hours
‰
• Or indomethacin 50 mg every 8 hours
‰
• Long term treatment is not advised because
• of toxicity, and because NSAIDS do not
modify the progression of disease

28. Management cont..
• DMARD= disease modified antirheumatic drugs.
• Methotrexate 5-25mg per week intially mothly,
then every 3 months
• Sulfasalazine 2-4g/day monthly for 3 months
then 3 monthly.
• Hydroxychloroquine 200-400mg/day 12 monthly.
• Leflunomide 10-20mg/day 2-4 weekly.
• Gold I.M injection 50mg monthly
• 0thers include D-penicillamine 250-750mg/day,
ciclosporin 150-300mg/day.

29. Management continued.
• Corticosteriods :
• One strategy is to give high dose of oral
prednisolone intially 60mg daily as its gradually
reduced over 3 months or low dose
prednisolone(5-10mg daily for 6-24 months).
• Intramuscular injection of methylprednisolone or
triamcinolone every 6-8weeks. To treat flares for
those on NSAIDs.
• Other treatment we have surgery where
synovectomy is done.

30. Ankylosing spondylitis
• Ankylosing spondylitis (AS) is characterised by
a chronic inflammatory arthritis
predominantly affecting the sacroiliac joints
and spine, which can progress to bony
fusion of the spine.

31. Prevalance
• The onset is typically between the
• ages of 20 and 30, with a male preponderance of
about
• 3 : 1. In Europe, more than 90% of those affected
are HLA B27 positive. The overall prevalence is
less than
• 0.5% in most populations. Over 75% of patients
are able to remain in employment and enjoy a
good quality of life

32. Pathophysiology
• Ankylosing spondylitis is thought to arise from
an as yet ill defined interaction between
environmental pathogens and the host
immune system in genetically susceptible
individuals. Increased faecal carriage of
Klebsiella aerogenes occurs in patients with
established AS and may
relate to exacerbation of both joint and eye
disease.

33. Pathophysiology cont…
• The HLA B27 molecule itself is implicated
through its antigen presenting function (it is a
class I MHC molecule) or because of its
propensity to form homodimers that activate
leucocytes. HLA B27 molecules may also
misfold, causing increased endoplasmic
reticulum stress. This could lead to inflammatory
cytokine release by macrophages and dendritic
cells, thus triggering inflammatory disease.

34. Clinical features
• Cardinal feature is ;
• low back pain and early morning stiffness with
radiation to the uttocks or posterior thighs. Symptoms
usually excerbatd by inactivity relieved by movement.
• Rigid spine
• Reduced range of lumbar spine movement.
• Restricted chest expansion.
• Chet pain
• Marked kyphosis, fatigue and peripheral arthritis
(40%)

35. Investigations
• X-rays of the spine(lateral thoracolumbar). .
Erosive changes may be seen in the symphysis
pubis, the ischial tuberosities and
peripheral joints.
MRI sacrolitis
HLA-B27-Positive
CRP-elevated

36. Diagnosis
• Ankylosing spondylitis can be diagnosed when
X-ray evidence of sacroiliitis occurs with one
other feature on history or
clinical examination

37. Fine symmetrical marginal typical of
ankylosing spondylitis(arrow)

38. Management
• The aims of management are to relieve pain
and stiffness, maintain a maximal range of
skeletal mobility and avoid the development
of deformities.
• Education
• Appropriate Physical activity, with daily back
extension exercises at early stage.

39. Management cont.
• NSAIDS and analgesics are often effective in
relieving symptoms and may alter the
underlying course of disease.

40. .
• for every resource on earth has been aligned
to fit the provision of men who are in
accordance with the will of God