Systemic Lupus

Erythematosus
Aditi Gaikwad, 007
Chirag Agrawal, 042
Rheumatology Elective Posting Aman Desai, 050
AKS Unit, Department of Medicine, Seth GSMC & Jay Damle, 088
KEMH Karan Khot, 101
 Let's Define first

Chronic Multisystem autoimmune connective tissue disease

Epidemiology

● Prevalence - 3.2 per 1,00,000

● Female : Male - 9:1
● Age group - 17-55 years
 PATHOGENESIS
Interplay of genetic, immunological and environmental factors

1. Genetic factors - early complement deficiency C1q, C2 and C4, HLA DRB1 03 and
HLA DR3 associations
2. Environmental factors - UV B rays, Smoking, OCP and HRT, Epstein Barr virus
infection
3. Immunological factors - Immune dysregulation, Failure of self tolerance in B
cells, defective clearance of apoptotic debris, defective phagocytosis, defective
NETosis

Type 3 Hypersensitivity reaction

Central key cytokine in the pathogenesis - IFN alpha/ Type 1 IFN

CLINICAL FEATURES
CONSTITUTIONAL SYMPTOMS (90-95%)
Most common symptoms encountered in new, recurrent as well as flares of SLE

● Fatigue
● Fever
● Weight changes
MUCOCUTANEOUS INVOLVEMENT (80%)

SKIN MUCOSAL
MANIFESTATIONS MANIFESTATIONS
Eg. rash, alopecia Eg. oral,
nasopharyngeal ulcers
 SKIN
MANIFESTATIONS

LE - Specific LE - Non Specific

ACLE SCLE CCLE VASCULAR OTHER

Acute Cutaneous Subacute Cutaneous Chronic Cutaneous

Lupus Erythematosus Lupus Erythematosus Lupus Erythematosus Vasculitis Alopecia
Palpable purpura Sclerodactyly
Nodules, ulcers Calcinosis cutis
Rheumatoid
Vasculopathy nodules
LOCALISED ANNULAR Discoid LE Livedo reticularis Urticaria
(Malar rash) Periungual telangiectasia Acanthosis
Lupus Profundus
PSORIASIFORM Raynaud’s nigricans
GENERALIZED Chilblain LE Lichen planus
(Lupus Dermatitis, TEN)
 MALAR RASH
Photosensitive

Bilaterally symmetrical

Non scarring

Spares nasolabial fold

d/d : Dermatomyositis

Acne rosacea
 Subacute Cutaneous Lupus Erythematosus

ANNULAR PSORIASIFORM

Scaly, annular, erythematous plaques Resembles psoriasis or eczema

Fuse to form polycyclic morphology
 Chronic Cutaneous Lupus Erythematosus

DISCOID LUPUS ERYTHEMATOSUS LUPUS PROFUNDUS CHILBLAIN LUPUS

Erythematous scaly plaques DLE with scarring alopecia

that lead to dyspigmentation Affects cold exposed areas
Indurated subcutaneous nodules
and scarring Biopsy shows lobular panniculitis Painful plaques, progress to
ulceration
MUSCULOSKELETAL INVOLVEMENT (95%)

Joint Muscle
● Polyarthralgia/polyarthritis ● Myalgia(m/c)
● Inflammatory
● Myositis with muscle
● B/L symmetrical
● Peripheral small joints (no weakness
axial involvement)
● Non erosive
● Deformities
● D/D
D/D

● Rheumatoid Arthritis
● Psoriatic Arthritis
● Other CTDs (Systemic Sclerosis, Sjögren’s syndrome, Polymyositis,
Dermatomyositis)
● CPPD disease
HEMATOLOGICAL MANIFESTATIONS (85%)

Anemia Thrombocytopenia Leukopenia

● Anemia of Chronic ● Secondary ITP ● Lymphopenia

Disease
- Manifests as
petechiae, purpura or ● No granulocytopenia
● Autoimmune bleeding from other
Hemolytic Anemia sites
(AIHA) - PLC>40,000 with no
- Anti-erythrocyte bleeding
antibodies (Warm Ab) manifestations doesn't
- Rapidly progressive require treatment
NERVOUS SYSTEM MANIFESTATIONS (60%)
● Cognitive dysfunction - memory and reasoning
● Headaches - can indicate flare
○ d/d tension headaches, migraine
● Seizure
● Psychosis
○ d/d functional psychosis, glucocorticoid induced psychosis
● Myelopathy
● Cerebrovascular events
○ Stroke, TIA
● Peripheral nervous system
○ Mononeuritis multiplex complex, polyneuropathy
CARDIAC MANIFESTATIONS (60%)
Pericardium
● Pericarditis
● Rarely,Tamponade
Myocardium
● Lupus myocarditis ( Anti-Ro 52)
Endocardium
● Libmann-Sachs Endocarditis
● Valvular involvement (m/c: MR)
PULMONARY MANIFESTATIONS (50%)
Pleural
● M/C: Pleuritis with B/L small pleural effusion
● Exudative (rule out other causes)
Parenchymal
● Lupus Pneumonitis
● Shrinking lung syndrome (Anti-Ro 52)
● ILD (rare)
● Emergency: Diffuse Alveolar Hemorrhage
LUPUS NEPHRITIS (30-50%)
● Nephritis is the most serious manifestation of SLE
● Nephrotic syndrome
● End stage renal disease
● Histologic classification based on biopsy
● Indications for biopsy:
- Proteinuria >1g/24h
- Proteinuria >500mg with microscopic hematuria
Classification of Lupus Nephritis (ISNRPS)

Class I: Minimal mesangial Lupus Nephritis

Class II: Mesangial Proliferative Lupus Nephritis
Class III: Focal Lupus Nephritis
Class IV: Diffuse Lupus Nephritis
Class V: Membranous Nephropathy
Class VI: Advanced Sclerotic Lupus Nephritis
Management of Lupus Nephritis

Class I and II: Do not require treatment

Class III and IV:
Class V:
1. Urine protein <1g : Steroids + ACEI
2. Urine protein >1g : Steroids + MMF
VASCULAR INVOLVEMENT (30-50%)
Vasculitis; small or medium vessel vasculitis

● Cutaneous vasculitis
○ Small vessel vasculitis- palpable purpura, urticaria, bullous lesions etc
○ Medium vessel vasculitis- nodules, ischemic ulcers
● CNS vasculitis
○ Peripheral - mononeuritis multiplex complex causing weakness, sensory loss
○ Central - cognitive dysfunction, seizures, demyelinating syndrome
● Gastrointestinal vasculitis (Lupus enteritis)
○ Mortality - 50%
○ Mesenteric vasculitis - Bowel ischemia, perforation, heamorrhage
● Renal vasculitis
○ Uncomplicated vascular immune deposits
○ Arteriosclerosis
○ Non Inflammatory necrotizing vasculopathy
○ Thrombotic microangiopathy
○ True renal vasculitis
● Pulmonary vasculitis
○ Diffuse alveolar haemorrhage
● Coronary vasculitis
● Retinal vasculitis

** Association with APS (Antiphospholipid syndrome)

Ocular
● Sicca syndrome
● Conjunctivitis
● Episcleritis
● Vasculitis

Gastrointestinal
● Non specific (nausea, vomiting, diarrhea, GERD)
● Abnormal liver enzymes (autoimmune hepatitis, pancreatitis)
● Vasculitis
 EMERGENT COMPLICATIONS IN
SYSTEMIC LUPUS ERYTHEMATOSUS
Cerebrovascular complications
Seizures:

● Usually GTCS
● Management: Immunosuppression + Antiepileptics

Cerebrovascular accidents:

● Can be due to 2° vasculitis or APS/LSE related thromboembolism

● Presents as acute onset focal neurological deficit
● Management: Thrombolysis; however, can cause complications if stroke was
due to vasculitis
Cerebrovascular complications
Due to prothrombotic state resulting from 2° APS:

1. Dural venous sinus thrombosis:

○ Presentation varies from new onset headache to syncope/coma
○ Imaging by CT may be falsely negative

1. Spinal artery thrombosis

○ Presents as acute sensory/motor functional loss
Respiratory system complications
Pulmonary thromboembolism:

● Presents as acute onset severe

dyspnea, chest pain and
productive cough
● Management: Anticoagulation
Respiratory system complications
Diffuse alveolar hemorrhage:
● High mortality
● Presents with fever, cough
(usually hemoptysis), dyspnea
and hypoxia
● BAL shows hemosiderin laden
macrophages
● Management: Supportive care,
high dose corticosteroids,
plasmapheresis
Cardiovascular complications
Acute coronary syndrome:

● Increased incidence in SLE patients than general population at all ages

● Management same as regular population

Libman Sachs endocarditis:

● Consists of sterile valvular vegetation

● Can lead to acute onset thromboembolism, valvular insufficiency
Gastrointestinal complications
Mesenteric vasculitis:

● Presents as acute, diffuse abdominal pain

● In early stages can be managed by supportive care and corticosteroids
● If bowel necrosis is present, surgical resection necessary
ANTI PHOSPHOLIPID ANTIBODY
SYNDROME (APS)
Pathogenesis
The following antibodies are seen in APS:
● Anti β2 glycoprotein antibody: Causes thrombosis
● Anti cardiolipin antibody
● Lupus anticoagulant antibody: Causes thrombocytopenia
Classical presentation: Thrombosis + Thrombocytopenia

Exacerbation occurs due to additional prothrombotic state eg smoking, obesity

Clinical features
● Deep venous thrombosis
● Fetal loss
● CNS manifestations
○ Cerebrovascular stroke
○ Migraine
○ Epilepsy
○ Chorea
● Autoimmune hemolytic anemia
Diagnostic criteria
Laboratory criteria:

● Any one of three autoantibodies being positive twice in a period of ≤ 12 weeks

Clinical criteria:

● Bad obstetric history: Any one of the following

○ ≥3 abortions occurring within 10 weeks of intrauterine life
○ ≥1 abortions occurring after 10 weeks of intrauterine life
○ Premature delivery (<34 weeks) due to obstetric complications
● Evidence of thrombosis

For definitive APS, one laboratory criterion and one clinical criterion are required
Management
Drugs used for management:

● LMWHs
● Warfarin (not to be used in pregnancy)
● Low dose aspirin
● Corticosteroids + IVIg/Plasmapheresis (Catastrophic APS)
 INVESTIGATIONS
AND
DIAGNOSTIC CRITERIA
 INVESTIGATIONS
BASE LINE INVESTIGATION
● CBC
● ESR and CRP
● C3 C4 levels
● 24 hour urine protein levels
INVESTIGATIONS SPECIFIC TO CTD
● ANA - Indirect Immunofluorescence method, significant titre >1:80, Intensity and
Pattern
● Anti-dsDNA
● ANA immunoblot
 ANTIBODY CLINICAL UTILITY

Antinuclear antibodies Best screening test

Anti-dsDNA SLE specific and correlates with disease

activity

Anti-Sm Highly specific for SLE

Anti-C1q Associated with active lupus nephritis

Anti-U1RNP Mixed Connective Tissue Disease

Anti-Ro(SS-A) and Anti-La(SS-B) Sjogren’s syndrome

Antihistone Drug induced Lupus

Antineuronal antibody Correlates with active CNS Lupus

Anti Ribosomal-P antibody Correlates with depression/psychosis due

to CNS Lupus
 SLE- Treatment

1.Aim of the treatment

2.General considerations
3.Treatment algorithm
4.Commonly used drugs
General Considerations

SPF
Treatment Algorithm
 Commonly used drugs
Drugs used commonly are :
Conservative management:NSAIDS + HCQ(Low dose
corticosteroids may be added) Topical sunscreens
Moderate to severe SLE: Azathioprene,
Methotrexate,Cyclophosphamide,MMF
Resistant lupus: Rituximab , Calcineurin inhibitors
1. MOA
2. Dose/regimen
3. Side effects
Thank you