This document discusses systemic lupus erythematosus (SLE), an autoimmune disease where organs and cells are damaged by autoantibodies and immune complexes. It covers the etiology, pathogenesis, clinical manifestations, diagnosis, and management of SLE. Key points include that SLE affects multiple organ systems and has varied clinical presentations. Diagnosis is based on meeting 4 out of 11 American College of Rheumatology criteria including positive antinuclear antibodies and anti-dsDNA antibodies. Treatment involves managing symptoms across organ systems with medications like steroids, hydroxychloroquine, immunosuppressants, and targeting specific organ involvement. The goal is to control disease activity, prevent organ damage, and improve quality of life.

1. SYSTEMIC LUPUS ERYTHEMATOSIS
ETIOPATHOGENESIS,CLINICAL
FEATURES AND DIAGNOSIS AND
RECENT ADVANCES IN
MANAGEMENT OF SLE
CHAIR PERSON- DR KALINGA. B. E
STUDENT- DR ASHWINI NAIK

2. OVERVIEW
1. DEFINITION
2. ETIOLOGY
3. PATHOGENESIS
4. CLINICAL MAIFESTATIONS
5. DIAGNOSIS
6. MANAGEMENT

3. DEFINITION
Systemic lupus erythematosus (SLE) is an
autoimmune disease in which organs and
cells undergo damage initially mediated by
tissue-binding autoantibodies and immune
complexes.

4. • Autoantibodies are present for a few
years before the first clinical symptom
appears.
• Ninety percent of patients are women
of child-bearing years
• People of all genders, ages, and ethnic
groups are susceptible.

5. • The prevalence reported in India is 3 – 15 per
100000 population
• 124/100000 in western data
• Highest prevalence is in African-American
and Afro-Caribbean women
• Lowest prevalence is in white men.

6. PATHOGENESIS AND
ETIOLOGY

7. The exact etiology of SLE is not known.
1. Autoantibodies against nuclear and
cytoplasmic components
2. Genetic Predisposition/ Factors
3. Immunological factors
4. Environmental factors

12. LE cell Phenomenon

13. CLINICAL MANIFESTATIONS

18. Clinical features may be quite variable
ranging from mild joint involvement to severe
life threatening disease.
Diagnostic criteria developed by ACR in 1971
revised in 1982 and then in 1997

19. Diagnosis
• ACR criteria 4out of 11
• Constellation of signs , symptoms and
serological tests
• Most common manifestations
• Constitutional
• Cutaneous
• Articular manifestations

20. Fatigue
42% of patients have fever .
SLE is cause of PUO in less than 5% of
patients.
Fever can also be because of medications,
malignancies and infections.

21. ACLE – a c u t e c u t a n e o u s l u p u s
Classical malar
rash

22. SCLE-non scarring, photosensitive lesions that
can be papulosquamous resembling psoriasis or
annular polycyclic with central clearing.
Predilection for back, neck, shoulders and spares
face. Heal without scarring
Annular type associated with anti-SSA/Ro
antibody.(seen in Sjogren,RA)
Drugs- ACEIs,CCBs ,Hydrochlorthiazide

25. CCLE- skin atrophy and scarring
Discoid LEis most common.
Follicular plugging is characterstic finding
Permanent alopecia, SCCcan occur if untreated

27. Photosensitivity
Alopecia
Mucosal ulcers
Lobar panniculitis - subcutaneous nodule (lupus
profundus)

28.  Arthritis and arthralgia-present in 90%
 Hand deformity similar to Jaccoud’s arthropathy
because of ligament and joint capsule laxity.
 Avascular necrosis- 10%
 Deforming arthritis
 Salmonella septic arthritis
 Myositis

30.  Significant cause of morbidity and mortality
 Upto 90% have pathological evidence
 50% have clinical evidence
 Typically develops within first 36 months of disease
 Frequency decreases after 5 yrs.
 Features -
1. Proteinuria,
2. Hematuria,
3. Hypertension,
4. Pyuria,
5. Urinary casts,
6. Deranged RFT.
.
LUPUS NEPHRITIS

31. Class I Minimal mesangial lupus nephritis (Light microscopy : Normal glomeruli)
Class II Mesangial proliferative LN (few isolated subepithelial/endothelial deposits visible by
IF or electron microscopy)
Class III Focal lupus nephritis (<50% glomerulli, sub endothelialdeposits)
III A Active lesions
III A/C Active and Chronic Lesions
III C Chronic Lesions
Class IV Diffuse lupus nephritis( >50% glomeruli involved, Segmental and Global lesions)
IV – S(A) Active lesions - Diffuse segmental proliferative lupus nephritis
IV – G(A) Active lesions - Diffuse global proliferative lupus nephritis
IV – S
(A/C)
Active & chronic lesions - Diffuse segmental proliferative & sclerosing lupus
nephritis
IV – G
(A/C)
Active & chronic lesions - Diffuse global proliferative & sclerosing lupus nephritis
IV – S(C) Chronic inactive lesions with scars - Diffuse segmental sclerosing lupus nephritis
IV – G(C) Chronic inactive lesions with scars - Diffuse segmental global lupus nephritis
Class V Membranous lupus nephritis
Class VI Advanced sclerosing lupus nephritis

32.  Immune complex mediated GN-most common
 Tubulointerstitial disease- predictor of poor long
term renal outcome
 Vascular disease - Lupus vasculopathy
TMA,
Vasculitis
Arteriosclerosis
Non specific vascular sclerosis
 Biopsy is diagnostic
 Finding of TMA should suggest APLA nephropathy

33. • Mesangial nephritis is most common
• Class IV patients tend to relapse most frequently
• Class V-anti C1q Ab has best negative predictive
value for predicting flares
• Despite treatment, 10% patient will progress to
ESRD
• Type I and Type IV RTA also is reported.

34. Pleuritis- upto 50%
Lupus pneumonitis
Chronic Interstitial Lung disease
NSIP(non specific interstitial pneumonia)
UIP (usual interstitial pneumonia)
Diffuse alveolar haemorrhage
PAH-0.5 to 14% of patients
Shrinking lung syndrome
PLEUROPULMONARY INVOLVEMENT

35.  Myocarditis-in 10%
 Pericarditis – 50%
 Valvular Abnormalities- 60% of patients
 Valvular thickening with mitral and aortic valve
involvement
 Libman Sacks endocarditis – 43%
 Valvular regurgitation 25%
 Valvular stenosis in 4%

36. CAD-Atherosclerosis, coronary
vasculitis, coronary artery thrombosis
Young women with SLE have 50 fold higher
risk of MI.
Rule out APLA because thrombosis can be the
initial presentation
Additional risk factors- Steroids use,
Hypertension

37. Neuropsychiatric manifestations
of SLE
Central nervous
system
Acute confusional state
Cognitive dysfunction
Psychosis
Mood disorder
Anxiety disorder
Headache
Cerebrovascular accident
Myelopathy
Movement disorder
Aseptic meningitis
Seizure disorder
Demyelinating syndrome
Peripheral nervous
system
Cranial neuropathy
Polyneuropathy
Plexopathy
Mononeuropathy single/multiplex
Guillein- Barre syndrome
Myesthenia gravis
Autonomic disorders

38. G I involvement
• Pain abdomen
• Nausea, vomiting,diarrhea
• Vasculitis of intestine- perforations
,ischemia,bleeding sepsis
• Liver involvement
Hematological manifestations
• Anaemia
• Leukopenia
• Lymphopenia
• Thrombocytopenia

39. Eye involvement
• Sicca syndrome
• Non specific conjunctivis
• Retinal vasculitis
• Optic neuritis

40. Viral infections-Parvo B19,Hep Band Hep C,CMV
and EBV, HIV
Malignancy-particularly NHL
Autoimmune disorders- RA, Dermatomyositis ,
Still’s disease
MCTD
Drug induced lupus-Antihistone Ab are present
in >95% of cases except those by minocycline (ds
DNA and p ANCA)

41. DIAGNOSIS

42.  SLE is diagnosed based on constellation of
symptoms
 Positive antinuclear antibodies(ANA)
 Anti ds DNA is highly specific for SLE(60%)
 Anti Sm is also highly specific for SLE(30%)
 Complement consumption leads to
hypocomplementemia

43. Homogenous- anti dsDNA, speckled- anti RNP, nucleolar- anti
RNA polymerase I/III,cytoplasmic-anti Jo-1

44. • Hematuria (usually microscopic)
• Urine sediment - cells and casts.
• Granular and fatty casts - proteinuric Nephritis
• Erythrocyte, leukocyte, and mixed cellular casts -
nephritic disease.
• Broad and waxy casts - chronic renal failure.
• Significant proteinuria (more than 0.5 g of protein
per 24 hours)

45.  Any sign of renal involvement
 significant proteinuria
 glomerular hematuria
 Unexplained renal insufficiency with normal
urinary findings.
 Spot urine protein-creatinine ratio (UPCR)

46. Management

47. Recommendations for the management of patients with systemic
lupus erythematosus (EULAR)
SLE is a multisystem disease—occasionally limited to one or few organ
SLE care is multidisciplinary
Treatment of organ-threatening/life-threatening SLE includes an initial
period of high-intensity immunosuppressive therapy
- control disease activity
- consolidate response & prevent relapses
Treatment goals include long-term patient survival, prevention of organ
damage and optimisation of health-related quality of life

48. • Education
• Physical and lifestyle measures
• Emotional support.
• Adjunctive measures

51. Local Therapy
For cutaneous manifestations
 Steroid creams - Desonide (mild potency),
Triamcinolone (moderate potency), or Clobetasol
(high potency)
 Topical calcineurins - Pimecrolimus creams and
Tacrolimus ointments

52. Plasmapheresis - TTP
Cryoglobulinemia
NMO
Pulmonary hemorrhage
Hyperviscosity syndrome
Laser therapy - Telangiectasias
Refractory discoid lesions.
Photopheresis – Refractory skin lesions

53. Rituximab
Epratuzumab
Ocrelizumab
Belimumab(approved by FDA)
Atacicept
Abatacept
Other therapies-IVIg,DHEA,Clofazimine

54.  Constitutional symptoms-moderate dose steroids
 Cutaneous disorders-steroids,topical, HCQ/CQ. Oral ulcers
by cyclosporine and triamcinolone dental gels.
 Cutaneovascular- CCBs, PDEIs, PGs, cold preventive
measures
 Musculoskeletal Lupus-NSAIDs, Steroids, HCQ, AZA, MTX,
Leflunomide(no MMF)
 Cardiopulmonary-NSAIDs, Steroids, HCQ
 Pulmonary HTN by vasodilators, anticoagulation
 Hematological-Steroids, IVIg and Rituximab ( for
ITP),apheresis

56. Demographic
• Black race
• Males
• children
Clinical:
• Hypertension
• Failure to achieve or marked delay (>2 years) in achieving renal
remission
• Multiple flares of lupus nephritis
• Pregnancy

57. Laboratory:
 Nephritic urinary sediment
 Azotemia
 Anemia
 Thrombocytopenia
 Antiphospholipid antibodies
 Thrombotic microangiopathy
 Hypocomplementemia (especially falling levels)
 High anti-DNA titer (especially rising titers)
 Persistent severe nephrotic syndrome

58. Histologic
 Proliferative glomerulonephritis
 Mixed membranous (class V)
 Proliferative (class III-IV) glomerulonephritis
 Cellular crescents & Fibrinoid necrosis
 Very high activity index (>12)
 moderate to high chronicity index (>3)
 Combinations of active (cellular crescents) and chronic
(interstitial fibrosis) histologic features
 Extensive subendothelial deposits

60.  The ultimate goal of treatment should be complete renal response,
UPCR of less than 0.5 and normal or near-normal (within 10% if
initially abnormal) GFR
 Partial renal response as at least 50% reduction in UPCR and normal
or near-normal (within 10% if initially abnormal) GFR achieved 6-12
months of initiation of therapy
 Refractory disease
(1) any reproducible reduction in UPCR during the first 3 to 4 months
(2) partial renal response after 6 to 12 months
(3) complete renal response after 1 to 2 years of immunosuppressive
treatment.

63. Establishment of NPSLE
diagnosis
Cerebrospinal fluid examination
primarily to exclude infection
Autoantibody profile
(antiphospholipid, antiribosomal
P)
Neuroimaging to assess brain
structure and function
Neuropsychological assessment
■Identification of aggravating
factors
Hypertension, infection,
metabolic abnormalities
Symptomatic therapy Anticonvulsants, psychotropics,
anxiolytics
Cognitive rehabilitation
■ Immunosuppression Corticosteroids, azathioprine,
cyclophosphamide,
mycophenolate mofetil, B-
lymphocyte depletion
Anticoagulation Heparin, warfarin

68. • Lupus disproportionately affects women
• Manifestations can affect both maternal &fetal
outcome
• Pretem labour
• IUGR
• Hypertensive disorders
• Maternal death
• Fetal death

69. DRUGS RECOMMENDATIONS
NSAID S With caution in 1st trimester
Avoid in last trimester
Corticosteroid s Pednisolone & Methylprednisolone
are safe in all trimester and breast
feeding
Hydroxychloroquine Safe throughout pregnancy
Azathioprine Safe throughout pregnancy – limit
dose 2mg/kg/day
Calcineurin inhibitors Safe throughout pregnancy

70.  Rituximab and belimumab are not recommended in
pregnancy
 Cyclophosphamide, methotrexate, mycophenolate,
leflunomide, and warfarin, is contraindicated in
pregnancy, because of their teratogenicity
 These medications should be discontinued at least 3
months before conception.

71.  Asymptomatic carriers of antiphospholipid antibodies with no history
of pregnancy loss or thrombosis - treatment is generally not
needed.
 In women with a history of recurrent pregnancy loss or
thrombosis - low-dose aspirin combined with either unfractionated
heparin or enoxaparin
 For women in whom combination therapy has been ineffective – Ivig
, corticosteroids, and plasmapheresis

72.  Treatment of high-risk patients is continued for at least 6 to 8
weeks after delivery because of a continuing thrombosis risk in
the postpartum period.
 Women with a history of recurrent thrombosis may need
lifelong treatment.