sle

1. SYSTEMIC LUPUS ERYTHEMATOSUS
Presenters: Dr Maureen Kashem (Paediatrics)
Dr Esther Wangui (Int.Medicine)
Facilitator: Dr Eugene Genga

2. OBJECTIVES
1. What is SLE?
2. What is the epidemiology of SLE?
3. How to diagnose SLE?
4. What is the pathophysiology of SLE?
5. How to treat SLE?
6. What are the complications of SLE?
7. What is the prognosis of SLE?

3. Case Study: Diagnosing SLE
• Kelsey, a 23-year-old woman
– Unremarkable history until 3 months ago
– Currently feels tired and achy, flu-like symptoms, heavier than usual
periods
• Physical exam
– Some fullness at MCP joint
– Dull discomfort on taking deep breaths
– Mild erythematous rash on cheeks
– Mild erythema on forearms
• Social
– Under stress at work, poor sleep, lack of exercise

4. Case Study: Laboratory Findings
• Normal UEC panel
• Mild anemia (Hb = 11.0 g/dL)
• Ferritin = 8 ng/mL
• Urine: trace proteinuria, no casts or red cells
• ANA screen: notable for a 1:160 speckled pattern
• ESR rate = 30 mm/hr
• CRP 15 mg/L (normal < 5 mg/L)

5. Case Study: Work-Up
• Serology
– Rheumatoid factor: 25 (normal <20)
– Anti-CCP: negative
– C3 complement: 68 (normal ≥ 70)
– C4 complement: 13 (normal ≥ 14)
– Anti-Sm +ve, RNP -ve, SSA -ve, SSB -ve, and anti-dsDNA +ve
• Chest X-ray: small right pleural effusion
• Urine protein/creatinine ratio: essentially negative

6. DEFINITION
Definition
 chronic, multisystem inflammatory disease characterized
by autoantibodies directed against self-antigens, immune
complex formation, and immune dysregulation resulting
in damage to essentially any organ.
Background:
 First written description in13th century( Rogerius) named
it lupus( Latin for wolf) as cutaneous similar to a wolf
bite.
 Osler recognized systemic features without skin .
 Diagnosis with (LE) cells in 1948.
 In 1959, anti-DNA.

7. EPIDEMIOLOGY
• The epidemiology of systemic lupus erythematosus (SLE) in Africa is largely
undetermined,
• Perception persists that the incidence of SLE on the continent is very low.
• Recent studies as well as our own experience, however, suggest that this is not
the case.
• The apparent low incidence rate in Africa may be the result of underdiagnosis low
disease recognition within primary health care settings, limited access to
diagnostic tools and inadequate numbers of specialist physicians.

8. Global and regional prevalence and incidence of systemic lupus
erythematosus in low-and-middle income countries: a systematic
review and meta-analysis- July 2022
The highest estimates of incidence and prevalence of SLE were in
Brazil [8.7(95% CI 6.3–11.7)/100 000 persons and in Kenya 3000
[95% 1800–5600]/100 000 persons, respectively. The lowest
incidences of SLE were reported in Ukraine (0.3 (95% CI 0.0–1.8)/100
000 people, and the lowest prevalence was in India 3.2 (95% CI 0–
6.86)/100,000 persons.

10. EPIDEMIOLOGY
♀ ♂
85% are women
DECADE
1st 2nd 3rd 4th 5th 6th 7th 8th 9th 10th
PREVALENCE
Ratio peaks in reproductive years
4
64
91
138
211
271
0 50 100 150 200 250 300
White Men
White
Asian
Hispanic
African American
Native American
Prevalence (per 100,000)
Half develop organ-threatening disease
Nonorgan-
threatening
Organ-
threatening
Sex, Race, and Ethnicity

11. EPIDEMIOLOGY CONT....
• 85% - 90% of patients with SLE are women.
• Black women have a higher incidence compared to the white
population, 164 (white) to 406 (Black)/ 100,000
• Age at onset 65% of patients with SLE is 16-55 years

12. EPIDEMIOLOGY IN CHILDREN
• Account for 15-20% of SLE patients
• Incidences ranges 0.36-2.5 per 100,000 children
• Prevalence of 1.89-34.1 per 100,000
• Peak age of onset is 12.6 years
• Prevalence seems higher in blacks, with more severe
disease and renal involvement

13. KNH DATA IN THE LAST 5 YEARS
2018 <1YR 1-4 5-9 10-12 TOTAL
SLE WITH
ORGAN
INVOLVEME
NT
0 0 2 1 3
2019 SLE WITH
ORGAN
INVOLVEME
NT
3 1 5 6 15
2020 ‘’ 0 2 0 8 10
2021 “ 0 0 2 13 15
2022 “ 0 0 0 12 12
2023 “ 0 0 10 14 24

14. DIAGNOSTIC CRITERIA OF SLE
• ACR revised criteria classification of SLE (1997)
• SLICC Revision of the ACR Classification of SLE
• 2019 EULAR/ACR criteria- active in use currently

15. ACR (1997) Revised Criteria for Classification of SLE
Skin Criteria
• Butterfly rash
• Discoid rash
• Sun sensitivity
• Oral ulcerations
Systemic Criteria
• Arthritis
• Serositis
• Kidney disorder
• Neurological disorder
Laboratory Criteria
• Blood abnormalities • Positive ANA blood test
• Immunologic disorder
o Antiphospholipid antibodies, lupus anticoagulant, anti-DNA, false-positive syphilis test,
positive anti-Sm
4 of 11 needed for a diagnosis
Hochberg MC. Arthritis Rheum. 1997;40:1725. Tan EM, et al. Arthritis
Rheum. 1982;25(11):1271-1277.

16. Petri M, et al. Arthritis Rheum
2009;60:S338.
SLICC Revision of the ACR Classification of SLE
Renal biopsy OR
Clinical criteria (at least 1)
• Cutaneous: acute or subacute cutaneous lupus, chronic cutaneous lupus, nasal/oral ulcers, nonscarring alopecia
• Inflammatory synovitis in ≥2 joints or ≥2 tender joints with morning stiffness that are observed
• Organs: renal (U Pr/Cr >0.5G or RBC casts), neurologic (seizures, psychosis, mononeuritis multiplex, myelitis, peripheral or
cranial neuropathy, cerebritis), hematologic (hemolytic anemia, WBC<4000 x 1 or lymphs <1000 x 1, platelets <100K
once)
Laboratory (at least 1)
ANA, anti ds DNA (2x reference range if ELISA), anti Sm, anticardiolipin Ab 2X normal, lupus anticoagulant, biologic false
positive, anti beta-2 glycoprotein, low C3, C4 or CH50, direct Coombs without hemolytic anemia
Total of 4 clinical/lab criteria need to be present
94% sensitive, 92% specific, fewer misclassifications (P=0.0082). 716 scenarios.

17. 2019 EULAR/ACR criteria2
Domain Criteria Points
Constitutional Fever 2
Hematologic
Leukopenia
Thrombocytopenia
Autoimmune hemolysis
3
4
4
Neuropsychiatric
Delirium
Psychosis
Seizure
2
3
5
Mucocutaneous
Non-scarring alopecia
Oral ulcers
Subacute cutaneous or discoid
lupus
Acute cutaneous lupus
2
2
4
6
Serosal
Pleural or pericardial effusion
Acute pericarditis
5
6
Musculoskeletal Joint involvement 6
Renal
Proteinuria > 0.5 g/24 h
Renal biopsy class II or V lupus
nephritis
Renal biopsy class III or IV lupus
nephritis
4
8
10
The European League Against
Rheumatism
(EULAR)/American College of
Rheumatology (ACR)
classification criteria for SLE
were developed to improve
detection of early or new-onset
SLE as well as improve the
sensitivity and
specificity compared
with previous criteria [1].
Patients with a score of 10 or
more points are classified as
having SLE. With a positive
ANA as an entry level

18. Immunological criteria
Domain Criteria Points
Antiphospholipid antibodies
Anti-cardiolipin antibodies or
Anti-β2GP1 antibodies or
Lupus anticoagulant
2
Complement proteins
Low C3 or low C4
Low C3 and low C4
3
4
SLE-specific antibodies
Anti-dsDNA antibody or
Anti-Smith antibody
6

19. Incidence of Clinical and Laboratory Manifestations of SLE

20. KELSEY’S SLE DIAGNOSIS
Positive ANA
Positive AntiSM, Anti DsDNA- 6
Joint involvement - 6
Sunsensitive- erythema on sun exposed area
Malar rash - 6
Serositis- Pleural effusion - 5
Low C3 and C4 - 4
TOTAL SCORE-27

21. Etiology
• Multifactorial
• Interplay between:
1. Genetic factors,
2. hormonal factors,
3. environmental factors
4. Immune system dysregulation

22. 1)Genetic and epigenetic risk factors
• High heritability (44%)
• Polygenic inheritance/Monogenic inheritance
• Monogenic lupus, a rare variant is characterized by :
early onset, severe symptoms,
strong family history,
Consanguinity.

23. • Epigenetic alterations that have been reported in SLE
include:
changes in DNA methylation (e.g., hypo methylation in
CD4+ T cell and B cells of loci encoding inflammatory
cytokines),
histone deacetylation and
altered micro RNA (miRNA) expression.

25. 2)Environmental Factors
• Environmental triggers interact with genetic factors.
• Includes:
Biologic –EBV, Mycoplasma pneumoniae
Physical(UV radiation)- DNA damage
Chemical factors.
• Chemical risk factors for SLE include smoking,
environmental toxins and certain medications eg
procainamide, hydralazine,Isoniazid.

26. 3)Hormonal Risk Factors
• F>M with a ratio of 9:1(Menarche to Menopause)
• Estrogen is known to modulate lymphocyte function,
altering the thresholds for B-cell apoptosis and activation
and promoting T-cell activation.
• Affects the expression of immunomodulatory cytokines,
including IL-1 and IL-17.
• Progesterone and testosterone are protective.

27. 4)Immune System Dysregulation
• Both innate and adaptive systems involved.
• IFN, Pro-inflammatory cytokines, T and B cells, Immune
complex deposition.
• Loss of self tolerance to self antigens leading to
exaggerated autoimmune response.
• Abnormal apoptosis and impaired clearance of apoptotic
cells or their debris.
• Impaired phagocytosis.
• Mediators are auto-antibodies and immune complexes
formed.

28. A model of SLE Pathogenesis

30. SLE associated Auto-Antibodies
• ANA: 1:80
• Anti-dsDNA, Anti-histone Ab
• Anti-ENA: Anti-Sm, Anti-RNP, Anti-Ro/SSA, Anti-
La/SSB
• Antibodies against non nuclear Ag: Anti-c1q, Anti-
lipoprotein, Anti-endothelial Ab
• Anti-Ribosomal P Ab
• Antiphospholipid Ab(thrombosis)

31. Manifestations and Complications

32. • Constitutional symptoms are the most common group
of symptoms in SLE; they include fatigue, fever, anorexia,
lymphadenopathy and splenomegaly
• Musculoskeletal complications-arthritis/arthralgia,
myositis/myalgia, osteonecrosis and osteoporosis – have
a collective prevalence of >90% in patients with SLE

33. Figure 6-1: Jaccoud’s Arthropathy in a Patient with SLE. (A) Flexion deformities, ulnar deviation, and
mild swan neck deformities. (B) The deformities are reduced with minimal pressure against the
underlying table. Source: Adapted from: Barilla-LaBarca ML, Horowitz D, Marder G, Furie R.
Musculoskeletal system: articular disease, myositis, and bone metabolism. In: Lahita RG. Systemic
Lupus Erythematosus. Sixth ed. Amsterdam: Academic Press; 2021:541-559.

34. • Cutaneous Complications-occur in up to 80% of
patients and representing the first sign of disease in ~25%
of cases.

35. • Lupus-specific cutaneous manifestations
acute CLE, most often manifesting as a non-discoid malar
rash
subacute CLE, commonly presenting with nonindurated
psoriasiform and/or annular polycyclic rash and
chronic CLE (CCLE), in which discoid lesions are most
common

36. The first-line treatment options for cutaneous
manifestations include topical agents (including GCs and
calcineurin inhibitors) and/or systemic agents (GCs and
antimalarials).
Second-line options include MTX, retinoids, dapsone and
MMF.

37. • Hematologic Complications-Cytopenias commonly
occur in patients with SLE, affecting either single blood
cell lineages (e.g., leukopenia, thrombocytopenia,
anemia) or a combination of two or more lineages.
• Anemia-Chronic dx, AIHA
• Lymphopenia
• Thrombocytopenia-TTP

38. • Lupus Nephritis- Significant contributor to the morbidity
and mortality of SLE. Lupus nephritis occurs in
approximately 50% of all patients with SLE and typically
manifests in the first 3 years following diagnosis.
• Urinalysis (proteinuria),serum creatinine, urine
protein:creatinine ratio
• Nephrotic Syndrome/HTN
• Renal Biopsy- Gold standard

40. Lupus Nephritis

41. • Cardiovascular Manifestations and Complications-
atherosclerotic and non atherosclerotic CVD
• SLE inflammatory disease/prevalence of CVD risk factors
• Pericarditis, myocarditis, pericardial effusion, heartfailure,
Valvular heart disease, Fibrinous endocarditis(Libman-
Sacks)

42. • Gastrointestinal manifestations:
TYPICAL
• Esophageal dysmotility
• Hepatomegaly
• Splenomegaly
• Elevated liver function tests
UNUSUAL
• Mesenteric vasculitis (with or without infarcts)
• Colitis
• Protein-losing enteropathy
• Primary biliary cirrhosis
• Budd-Chiari syndrome
• Ascites

43. • Neuropsychiatric
• Direct immune attack or pharmacotherapy related.
• These mechanisms can act in both (PNS) and (CNS) to
cause neuropsychiatric (NP) SLE.
• Cognitive impairment, mood disorder, anxiety disorder,
headache or migraine, seizure disorders, stroke,
psychosis, acute confusional state , mononeuropathy ,
polyneuropathy , myelopathy , demyelinating syndrome ,
cranial neuropathy , autonomic disorder ,Guillain–Barré
syndrome (AIDP), myasthenia gravis (rare).

45. • Pulmonary Complications-
Pleuritis, Pleural effusions
Airway disease (obliterative bronchiolitis)
Parenchymal manifestations include diffuse alveolar
hemorrhage , acute lupus pneumonitis, interstitial lung
disease and cryptogenic organizing pneumonia (rare).
Vascular pulmonary manifestations include pulmonary
hypertension and pulmonary embolism

46. • Others:
Chronic infections,
Associations with other autoimmune diseases eg
Sjogren’s syndrome, antiphospholipid syndrome.
Variable risk for malignancy-increased risk of
hematological, lung, thyroid, liver, cervical and
vulvovaginal cancer and a reduced risk of breast,
endometrial and possibly ovarian cancer

47. ANTIPHOSPHOLIPID SYNDROME
• Autoimmune disease associated with increased risk of
thrombosis due to procoagulatory antibodies.
• Antibodies form complexes with anticoagulant proteins
thus inactivating them e.g. protein C , S and antithrombin
3.
• Antibodies activate platelets and vascular endothelium
leading to increased platelet binding.
• This induces a hypercoagulable state (Increase risk of
thrombosis and embolism)

48. • Primary(Idiopathic, associated with HLA-DR7) or
secondary(associated with other autoimmune diseases e.g.
SLE, RA,Neoplasms, HIV, Hep B/C, bacterial infections e.g.
Lyme dx, T.B)
• MC in individuals< 50yrs.
• Recurring venous, arterial or microcirculation thrombotic
events and obstetric complications
I. Venous: DVT,PE, Livedo reticularis, Ulceration
II. Arterial:Stroke, MI, ischemia or gangrene
III. Capillaries: splinter hemorrhages
IV. Obstetric: recurrent miscarriages and premature births
V. Nonthrombotic manifestaions e.g. VHD,neurocognitive
disorders

49. • Confirmed by detection of serum antiphospholipid
antibodies: lupus anticoagulant., anticardiolipin
antibodies(IgG/M), anti-b2-glycoprotein antibodies(IgG/M)
in addition to presence of clinical typical symptoms.
• Other tests e.g. CBC, Coagulation Profile-prolonged
aPTT.
• In symptomatic patients>1 aPL antibody present supports
diagnosis.
• Long-term APS management e.g. systemic
anticoagulation is determined by patients risk of future
thrombotic complications.

52. Management Principles SLE

54. Special Consideration: Lupus in pregnancy
• Rate of fetal loss is increased (approximately 2-3 fold) in
women with SLE.
• Fetal demise is higher in mothers with high disease activity,
antiphospholipid antibodies, and/or nephritis
• Suppression of disease activity can be achieved by
administration of systemic glucocorticoids.
• A placental enzyme, 11--dehydrogenase 2, deactivates
glucocorticoids; it is more effective in deactivating prednisone
and prednisolone than dexamethasone and betamethasone.
• Therefore, maternal SLE should be controlled with
prednisone/prednisolone at the lowest effective doses for the
shortest time required.

55. • In SLE patients with aPL (on at least 2 occasions) and prior
fetal losses, treatment with heparin (standard or low-
molecular-weight) plus low-dose aspirin has been shown in
prospective controlled trials to increase significantly the
proportion of live births.
• An additional potential problem for the fetus is the presence
of antibodies to Ro, sometimes associated with neonatal
lupus consisting of rash and congenital heart block.
• It can be life-threatening. Therefore the presence of anti-Ro
requires vigilant monitoring of fetal heart rates with prompt
intervention (delivery if possible) if distress occurs,

56. PROGNOSIS OF SLE
• Depends on organ involvement
• Access to therapy
• Social/ family support
• Types of SLE:
Monogenic/polygenic

58. References
• UptoDate
• (2016) Lupus: Systemic and cutaneous, Basicmedical
Key. Available at: https://basicmedicalkey.com/lupus-
systemic-and-cutaneous
• Systemic lupus erythematosus. clinical immunology
• 2019 European League Against Rheumatism/American
College of Rheumatology Classification Criteria for
Systemic Lupus Erythematosus