SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

DEFINITION Systemic lupus erythematosus is a multi-system autoimmune disease which is characterized by production of antinuclear antibodies. SLE is a prototype of human immune complex disease.

INCIDENCE AND PREVALENCE Incidence – 4 to 7 new cases per 100,000 per year Prevalence – 1:2,000 population Age – Peak onset 15 to 45 years old Female:Male ratio – 4 to 10 :1 Black:White ratio – 3:1 Prevalence in all women ages 15 to 64 is 1/700 Prevalence in black women of same age is 1/245 Other populations commonly affected: Hispanics Chinese

Pathogenesis and pathophysiology

Familial/Genetics/HLA

Common Clinical Manifestations Of SLE Manifestation Approximate Frequency Arthralgia/Myalgia 95 Fatigue 90 Fever 80 Central Nervous System 75 Skin Changes 71 Anemia 60 Adenopathy 50 Gastrointestinal 50 Renal Changes 50 Pericarditis 48 Leukopenia 42 Pleural Effusion 30 Arthritis

1982 CLASSIFICATION CRITERIA SLE Serositis Oral ulcers Arthritis Photosensitive rash Blood dyscrasias Renal disorder ANA Immunologic disorder Neurologic disorder Malar rash Discoid rash ** SLE if 4 of 11 present serially or simultaneously

SKIN INVOLVEMENT ACUTE SUBACUTE CHRONIC

MALAR RASH Fixed erythema Flat or raised Spares the nasolabial folds

MALAR RASH

Lupus band test

DLE Plugging atrophy scar telangiectasia erythematous raised rim above trans-nipple line

DISCOID RASH Raised Patches Adherent Keratotic Scaling Follicular Plugging Older Lesions May Cause Scarring

Balloon degeneration of epidermal cells

LE-nonspecific Skin Lesions Panniculitis Urticarial lesions (5-10%) Vasculitic lesions Raynaud’s phenomenon (50%)

Lupus Paniculitis

OTHER SLE RASHES Palmar Erythema and Rash Subacute Cutaneous Lupus Erythematosus (SCLE) Bullous Lupus Dermatitis Neonatal Lupus Raynaud’s Phenomenon

Subacute Cutaneous Lupus Erythematosus (SCLE)

Bullous Lupus Dermatitis

Neonatal Lupus

ORAL ULCERS Can affect all mucosal surfaces Painless (which distinguishes them from aphthous ulcers)

ORAL ULCER

ALOPECIA

SEROSITIS Pleuritis, Pericarditis or Peritonitis.

ARTHRITIS Clinically indistinguishable from RA Nonerosive Symmetric Inflammatory > 2 peripheral joints

Arthritis (Non-erosive, usually symmetric) Bone & Joints in SLE Arthralgia Arthritis (Non-erosive, usually symmetric) Nodules (10%) Tenosynovitis Jaccoud’s joint Osteonecrosis Osteoporosis

Jaccoud’s Arthropathy

PHOTOSENSITIVITY Skin Rash From UV irradiation

BLOOD DYSCRASIAS Hemolytic anemia with reticulocytosis or Leukopenia- <4,000 WBC on > 2 occasions or Lymphopenia- <1,500 on 2 occasions or Thrombocytopenia- <100,000

RENAL DISORDER Persistent proteinuria > 0.5 grams/day or Cellular casts or > 10 RBC/HPF

LUPUS RENAL HISTOLOGY WHO designation: I: Normal light microscopy, but immuo- globulin and /or complement deposits II: Mesangial Lupus Nephritis III: Focal Proliferative Glomerulonephritis IV: Diffuse Proliferative Glomerulonephritis V: Membranous Nephritis

RENAL INVOLVEMENT 1.Msangial Glumerolonefritis(2) 2.Focal Proliferative Glumerolonephritis(3) 3.Diffuse Proliferative Glumerolonephritis(4) 4.Memberanous Nephritis(5) 5. Glumerolosclerosis(6) 7.Tubulointerstitial Nephritis 8.Infection 9.Drug-Induced Nephritis

Lupus Nephritis: Manifestations Proteinuria: ~100% Nephrotic syndrome: 50% Granular casts: 30% Red cell casts: 10% Microscopic hematuria: 80% Macroscopic hematuria: 1-2% Reduced renal function: 40-80% Hypertension: 15-50%

Class II: Pure Mesangial Mild to moderate proteinuria and hematuria.No HTN Little or no evidence of renal insufficiency.

Class III: Focal Proliferative GN Less than 50% of glomeruli and less than 50% of each glomeruli are involved. Subendothelial deposits clinically:

Focal Proliferative Glomerulonephritis

Class IV: Diffuse Proliferative GN The most severe form of lupus nephritis. Along with class III, makes >50% of cases subendothelial deposits clinically:

Diffuse Proliferative Glomerulonephritis

Class V: Diffuse Membranous GN Subepithelial deposits 5 - 10 % of all • lupus nephritides. Presents • mainly with massive proteinuria. Subepithelial deposits

Membranous Glomerulonephritis

Subepithelial deposit in Membraneous GN

SLE & Respiratory System Pulmonary Disease Acute lupus pneumonitis Alveolar hemorrhage Chronic ILD Lymphocytic pneumonia Bronchiolitis obliterans Respiratory Muscle Disease Shrinking lung syndrome Pleural disease Pleuritis Upper Airway disease Epiglotitis Subglotic stenosis Laryngeal edema Laryngeal ulceration Cricoarythenoid arthritis Necrotizing vasculitis Vascular Disease Pulmonary hypertension Pulmonary embolism Acute reversible hypoxemia

GI INVOLVEMENT Peritonitis Vasculitis Pancreatitis IBD( collagenous colitis)

NEUROLOGIC DISORDER Seizures Psychosis

NEUROPSYCHIATRIC MANIFESTATIONS 9.Aseptic Meningitis 10.MS-like Disorder 11.Guillan-Barre Syn. 12.SAH 13.Ataxia 14.Dementia 15.Psychiatric Disorders 1.Headache 2.Seizure 3.Stroke 4.Chorea 5.Neuropathy 6.Vertigo 7.Tinnitus 8.Transverse Myelitis

CNS LUPUS

Antinuclear antibodies

ANTINUCLEAR ANTIBODY Significant titer is > 1:80 Found in 95% SLE patients but also- Interstitial pulmonary fibrosis MCTD PSS Polymyositis Procainamide/Hydralazine/Dilantin RA Sjogrens syndrome Normal population

ANA - RIM PATTERN

ANA - HOMOGENOUS

ANA - SPECKLED

ANA - NUCLEOLAR

LE-cell LE-cell is an in-vitro phenomenon where a PMN phagocytoses the antibody-coated nucleus of a cell. The technique is an insensitive way to detect anti-nuclear antibody in a serum specimen.

Hematoxyllin Body Hematoxyllin body is the in-vivo counterpart of LE cell. It is considered pathognomonic for SLE lesions.

IMMUNOLOGIC DISORDER anti-ds DNA antibody (anti-native DNA ab) or anti-SM antibody or antiphospholipid antibody based on either: abnormal serum IgG or IgM anticardiolipin ab or lupus anticoagulant or false positive RPR or VDRL for > 6 months and confirmed by t. Pallidum immobilization or fluorescent treponemal antibody (FTA) absorption test.

APS IgG ,IgM APL LA assay VDRL hypercoagulable state

LEIBMAN-SACHS ENDOCARDITIS

Prognosis Creatinin > 1.4 HTN NS(> 2.6 g/24h) anemia low C and albomin low socioeconomic state major organ involvement APS+ thrombocytopenia

Mortality Infection & renal involvement in 1st decade Thromboembolic phenomena in the 2th.

Treatment NSAIDs antimalarials sunscreens(SPF >15) androgens (DHEA) immuno-suppression anti-thrombotics & anti-platelets IvIG BMT

THERAPY Serositis NSAID Arthritis NSAIDs Blood dyscrasias Corticosteroids Immunosuppressive Arthritis NSAIDs Hydroxychloroquine Immunosuppressive Drugs Blood dyscrasias

THERAPY cont. Renal Corticosteroids Neurologic Symptomatic Immunosuppressive Neurologic Symptomatic Corticosteroids Rash Topical Corticosteroids Systemic Steroids Hydroxychloroquine Immunosuppressive Drugs