complete presentation on systemic lupus erythematosus and its mangament

1. LUPUS ERYTHEMATOSUS
MODERATOR-DR VIJAY PALIWAL SIR
PRESENTOR – Dr. JOLLY MERTIA

2. HISTORY
• Lupus – latin term – meaning wolf
• Erythematosus – red rash
• 1851, Dr. Cazenave , looked like wolf bites , named it DLE
• 1885 , Sir William Osler , named it SLE

3. INTRODUCTION
• Wide array of illness
• linked to autoimmunity to self nucleic acid and associated
proteins
• TYPES –
A. CUTANEOUS LE
• Acute LE
• Subacute LE
• Chronic LE
B. SYSTEMIC LE

4. Classification criteria
• American rheumatology association criteria (ARA) 1971
• The criteria of the American College of Rheumatology(ACR),
first published in 1982 and revised in 1997
• Systemic Lupus International Collaborating Clinics (SLICC)
2012.
• New ACR/ EULAR criteria 2019

6. NEW ACR/EULAR CRITERIA

7. Epidemiology
• SLE – 15-44years – F:M = 13:1 ; 2:1 in children and elderly
• All ethnicities, more prevalent in non caucasians
• DLE – 2:1 ; F:M ,peak age 4th decade
• Out of all the SLE patients
• ACLE 35 – 60%
• SCLE 7-27%
• CCLE 15-30%

8. Natural history and course
• SLE is a chronic disease of variable severity with a waxing and
waning course
• significant morbidity , can be fatal if not treated early
patients .
• .

9. Aetiology and pathogenesis
1.Genetic factors
• Reported concordance rate in identical twins is 65%
• Most consistent association are between HLADR2
and HLADR3 in white people.

10. Important immunological pathways identified
through susceptibility gene analysis

11. 3.Environmental factors
• Ultraviolet light
• Medications
• smoking
• silica
• Infections like Epstein–Barr virus (EBV)
• Stress, trauma
• Drugs

12. 4.Hormonal factors
• estrogen or prolactin or testosterone
• can lead to an autoimmune phenotype
• increase mature high-affinity auto-reactive B cells.
• OCPs ,
• early menarche
• post menopausal estrogen

13. Pathogenesis and pathophysiology
Immune responses against endogenous nuclear antigens

14. Mechanism of organ damage
• Vascular damage in SLE -
• Homocysteine and proinflammatory cytokines, such as IFNα,
impair endothelial function and decrease the availability of
endothelial precursor cells to repair endothelial injury.
• Impaired DNA repair as a result of mutations of the 3’ repair
exonuclease 1 (TREX1), and increased accumulation of single
stranded DNA may activate the IFN-stimulatory DNA
response and direct immune-mediated injury to the
vasculature.

15. Clinical features
1.Mucocutaneous features
• almost universal in SLE with both lupus-specific and non-
specific lesions.
• Chances of developing SLE-
SCLE-50%
Localised DLE - 5%
Disseminated DLE -20%

16. Galliams Classification of skin lesions associated
with lupus erythematosus
LE – SPECIFIC SKIN DISEASE
A.Acute cutaneous LE (ACLE)-
1. Localised (malar rash or butterfly rash)
2. Generalised (maculo-papular rash, Photosensitive lupus
dermatitis , TEN variant )
B. Subacute cutaneous LE (SCLE)-
1.Annular SCLE
2. Papulosquamous or psoriasisform lesion: Photosensitive, spares
face
C. Chronic cutaneous LE (CCLE)
1. Classic discoid LE (DLE)-localised and disseminated
2. Hypertrophic/verrucous DLE

17. LE – SPECIFIC SKIN DISEASE contd….
3. Lupus profundus/lupus panniculitis
4. Mucosal DLE
5. Oral DLE
6.Conjunctival DLE
7. Lupus tumidus
8. Chilblain LE/ perniotic
9. Lichenoid DLE (LE/ lichen planus overlap )

18. LE-Non specific lesion
A. Cutaneous vascular disease-
1.Vasculitis-
a. leukocytoclastic
- Palpable purpura
- Urticarial vasculitis
b. Polyarteritis nodosa-like cutaneous lesions
2.Vasculopathy
a.Degos disease-like lesions
b.Secondary atrophie blanche (syn. livedoid vasculitis)

19. LE-Non specific lesion contd..
3. Periungual telangiectasia
4. Livedo reticularis
5. Thrombophlebitis
6. Raynaud phenomenon
7. Erythromelalgia

20. B. Nonscarring alopecia
1.Lupus hair
2.Telogen effluvium
3.Alopecia areata
C. Sclerodactyly
D. Rheumatoid nodules
E. Calcinosis cutis

21. F. LE-nonspecific bullous lesions
G. Urticaria
H. Papulonodular mucinosis
I. Acanthosis nigricans
J. Erythema multiforme
K.Leg ulcers
L. Lichen planus
M. Cutis laxa / anetoderma

25. DLE

26. Lupus profundus
Lupus affecting the fat
underlying skin aka ‘lupus
panniculitis’.
Dented
scar and
Nodule.

27. lupus erythematosus tumidus
• Tumidus dermal form of lupus.
• Characteristically photosensitive
• Red, swollen, urticaria-like
plaques
• Ring-shaped (Annular) or
arciform

28. mucosa
• association with systemic disease activity
• SLE – 25 – 45%
• SLE -Painless ,shallow ,occurring in crops mainly over hard
palate
• DLE- buccal mucosa most commonly affected; hard palate
,vermilion border of lips are others.
• Lesions are of 3 types- erythematous lesions, discoid lesions
and ulcers.
.

29. • Discoid lesions – white papule, central erythema, border zone
of irradiating white striae , and telegiectasia (20%)
• Ulcers – painful superficial erosions with irregular serrated
margins

30. Musculoskeletal features
• 53–95%
• arthralgias/ arthritis
• Rarely tendinitis , tenosinovitis.
• Subcutaneous nodules along the flexor tendons of hand.
• Rhupus

31. Jaccoud arthropathy,
severe deformity of the
hands with ulnar
deviation and
swan‐neck confi-
guration, often with
little pain and good
function,
occurred in 13% of pts

32. • Generalised myalgia and muscle tenderness are common
during disease exacerbations.
• Inflammatory myositis
• Avascular necrosis (AVN) of bone; Symptomatic 5–12%.
• Osteoporosis

33. 3. Renal features-
• 40–70%
• major cause of morbidity and hospital admissions.
• MPGN type 2-4 - Proteinuria , haematuria, red cell cast
• Membranous GN (type 5)- severe proteinuria, nephrotic
syndrome
• Urinalysis to detect and monitor disease renal activity.
• Most common – type 4

35. 4. Nervous system features
• 19 syndromes observed , collectively are referred to as
neuropsychiatric SLE (NPSLE) syndromes.
• in decreasing order of frequency –
• cognitive dysfunction>Headache>Mood disturbances >
cerebrovascular disease> seizures > polyneuropathy> anxiety>
psychiosis
• Anti ribosomal P ab associated with lupus psychosis

36. 5. Cardiovascular features
• Pericarditis (common) 25%
• Libman–Sacks endocarditis -1–2% of patients.
• left side of the heart commonly involved.
• myocarditis
• one of the main prognostic predictors in SLE
• Coronary artery disease is the most common cause of death
in patients with longstanding SLE.

37. 6. Respiratory system
• The most common - pleuritis .
• pneumonitis – acute and chronic
• interstitial lung disease (ILD) 3–13%
• Pulmonary hypertension and pulmonary hemorraghe
• Shrinking lung syndrome

38. . Lymph node
• Lymphadenopathy characterised by typically soft , non-
tender, discrete lymph nodes usually detected in the cervical,
axillary, and inguinal area.
.Spleen
• 10–45% of patients, particularly during active disease
• Splenic atrophy and functional hyposplenism have also been
reported.

39. 8. Haematologic features
• Anemia - most common and correlates with disease
activity.
• Leukopenia
• Pancytopenia
• Cause= haemolysis, bone marrow suppression ,
myelofibrosis, aplastic anaemia

40. • thrombocytopenia .
• M.C cause- immune-mediated platelet destruction
• increased platelet consumption may also occur due to micro-
angiopathic haemolytic anaemia or hypersplenism.

41. GIT
• 50% of patients
• Common- anorexia, nausea and vomiting
• Abdominal pain may be due to mesenteric vasculitis,
hepatobiliary disease, pancreatitis
• late complications – cirrhosis

42. 10.Thyroid disease .
• hyperthyroidism
• hypothyroidism
• thyroid autoantibodies in patients without diagnosed thyroid
disease
11.Involvement of the ears .
• Sudden sensorineural hearing loss
• may be associated with the antiphospholipid syndrome.

43. 12. Ophthalmic features
• Most common – keratoconjunctivitis sicca
• infarction of the retinal vasculature secondary to
antiphospholipid antibodies
• ‘cotton wool’ spots in the retina
• Cataract
• Uveitis, scleritis, optic neuritis extremely rare

44. SLE and pregnancy
Mothers.
• There is no significant difference in fertility if renal functions
are normal.
• Flares- increases from 40 to 60%
• Lupus Nephritis and antiphospholipid antibodies – risk factor
pre-eclampsia .

45. Fetus
• susceptibility - mother has a history of Lupus Nephritis,
antiphospholipid, anti-Ro and/or anti-La antibodies
• increased risk of miscarriage, stillbirth, premature delivery,
intrauterine growth restriction, and fetal heart block.
• Cutaneous manifestation- 50% ; erythematous , slightly scaly
eruptions on face and periorbital skin
• Cardiac manifestation- conduction defect (1-2%)

46. Drug-induced lupus
• DIL should be suspected in patients with
• no diagnosis or history of SLE,
• who develop a positive ANA and at least one clinical feature
of lupus after
• an appropriate duration of drug exposure( 3- 6 months)
• and whose symptoms resolve after discontinuation of the
drug.

47. • commonly in older age group.
• Haematological abnormalities, kidney disease, and CNS lupus
are uncommon.
• Antihistone antibodies >95% of cases
• hypocomplementaemia and anti-DNA antibodies absent
• Arthralgia- 1st and common , constitutional symptoms
• Cutaneous – malar rash, vasculitic, bullous , EM like
• SCLE – common
• Less- scarring alopecia ,discoid lesion , oral ulcer

48. Drugs causing lupus

49. Morbidity, comorbidities, and
mortality
• early mortality - lupus activity and infection,
• late mortality - atherosclerotic complications.
Infections-
• 20–55% of all deaths
• due to underlying immune dysregulation and therapeutic
factors

50. Prognostic indicators
• poor prognosis (50%mortality in 10 years) at time of diagnosis
associated with –
• High serum creatinine (>1.4 mg/dl)
• Hypertension
• Nephrotic syndrome( 24 h urine protein >2.6g)
• Anaemia(Hb < 12.4 gm/dl)
• Hypoalbuminemia
• Hypocomplementemia
• Antiphospholipid antibodies
• Male
• Blacks
• Low socioeconomic status

51. How to approach a case of lupus
• History
• Examination
• Investigations – routine : hematological
• CBC with DLC , ESR , CRP, LFT, RFT , Urinalysis
• Specific:
• 24 hour urine protein ,
• ANA , DsDNA, Coombs , VDRL, C3 and C4 levels
• Antiphospholipid antibodies
• Anti smith , SSA, SSB, U1RNP
• Radiological : chest x ray , USG abdomen

52. • HISTOLOGICAL-
• skin biopsy
• Lupus band test
• LE cell test /Phenomenon

53. Histopathology
• Epidermal atrophy , hyperkeratosis
• Apoptotic keratinocytes
• Basement membrane thickening
• Lymphocytic interface dermatitis with basal layer
degeneration(hydropic), civatte bodies
• Perivascular and periadnexal lymphohistiocytic infilterate –
dense
• Follicular plugging
• Dermal mucinosis

54. • SCLE-
• More prominent interface changes – hydropic deg.
• Civatte bodies- numerous.
• Lymphocytic infilterate – band like, upper dermis
• ACUTE-
• focal vacoular degeneration
• Infilteration- more neutrophils

55. AUTOANTIBODIES ASSOCIATED WITH SLE

56. ANA TESTING IN SLE
• Immunofluorescence-ANA:
• Inexpensive and easy to perform, with high sensitivity and
specificity
• Majority of the laboratories around the world are now using
HEp-2 cell substrates(cultured cells of laryngeal squamous cell
carcinoma )
• IF-ANA test is widely used and considered to be gold standard

57.  ANA titer :
• It is directly proportional to antibody concentration
• low titer - less significant than a high titer
• may be seen even in healthy individuals.
• Acc. To EULAR criteria , ANA titre of >1:80 - considered
significant

58. MANAGEMENT OF SLE
• General measures
• counseling – outcome, complication , precautions
• Sun protection
• Regular exercise , stretching , diet
• Vitamin D supplementation
• Stop smoking
• Prevention of co-morbidities

59. Monitoring
• Assess disease activity and damage
• CBC, DLC
• ESR,CRP
• LFT, RFT
• URM – serial test if abnormal
• 24hour urine protein , ACR ratio, creat cl, usg renal
• If renal disease- annual GFR
• Renal biopsy

60. • Serology-
• DsDNA
• Complement
• Cardiovascular risk – ECG, ECHO ,lipid profile
• Blood sugar
• Risk of osteoporosis- DEXA

61. LOCAL THERAPY
• TOPICAL STEROIDS
•Topical Pimecrolimus 1% cream and tacrolimus 0.1% ointment
• calcipotriol
•Topical methotrexate
•Intralesional steroids

62. • ANTIMALARIAL -
• Hydroxychloroquine sulfate
• MOA-(1) light filtration (2) immunosuppressive actions
• (3) antiinflammatory actions, (4) antiproliferative effects through
an inhibition of DNA/RNA biosynthesis
• Slow response , may take 2 or 3 months for efficacy to be
appreciated
SYSTEMIC THERAPY

63. HYDROXYCHLOROQUINE
DOSE-usually 200 mg once or twice per day.
 efficacy of HCQ established in studies with a prescribed dose
of 6.5 mg/kg/day
 At this dose, eye toxicity is quite unlikely

64. • Provide rapid symptom relief.
• Low dose oral prednisolone (0.1-0.2 mg/kg)- mild SLE and
musculoskeletal manifestations resistant to other thaerpy
• High dose oral prednisolone(1-1.5 mg/kg)
• intravenous Methyprednisolone(1g /day for 3 days) – CNS, renal
manifestation or systemic vasculitis.
• Once controlled ,dose can be reduced to <7.5mg / day.
GLUCOCORTICOIDS

65. • more rapid GC tapering
• prevent disease flares.
• The choice depends on prevailing disease manifestation(s),
patient age and childbearing potential, safety concerns and cost.
• Methotrexate (MTX) (7.5 -25mg/week)
• Azathioprin(1.5-2.5mg/kg)
• MMF(1- 3gm/day)
IMMUNOSUPPRESSIVE AGENTS

66. • Cyclophosphamide (1-5mg/kg)
• Calcineurin inhibitors
tacrolimus (0.15 – 0.2 mg/kg)
cyclosporin

67. NON IMMUNOSUPPRESSIVE OPTIONS FOR
ANTIMALARIAL REFRACTIVE DISEASE
•DAPSONE (1-1.5mg/kg)
•ACITRETINE (10-50mg/day)
•THALIDOMIDE (50-200 mg/day)
• IVIG
• LEFLUNOMIDE
• PLASMAPHERESIS

68. BIOLOGICS
• Belimumab(BAFF inhibitor)
• Rituximab(anti CD 20)
• Currently studied :
• Anifrolumab
• Ustekinumab
• Baricitinib

70. SLE IN PREGNANCY
• For a successful pregnancy –
• disease should be quiescent for at least 6 months before the
conception.
• Oral corticosteroids - relatively safe.
• May need to temporarily increase at the time of delivery and
post partum.
• If the patient is on azathioprin , it can be continued .
• Hydroxychloroquine may be continued- reduced disease
activity, risk of CHB and neonatal lupus activity.

71. LACTATION
• Safe with low dose steroids and hydroxychloroquine
• For azathioprin, feeding should be done 4 hours post maternal
dose.
• With other immunosuppresives, breast feeding should be
better avoided.

72. THANK YOU