SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

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SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)
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TYPES OF LUPUS ERYTHEMATOSUS

• Systemic lupus erythematosus (SLE)
• Discoid lupus erythematosus (DLE)
• Drug-induced lupus erythematosus (DILE)
• Neonatal lupus erythematosus (NLE)

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CASE STUDY 16 YEAR OLD FEMALE

• Presented to family physician c/o
• Fatigue and malaise
• Severe sunburn rash on hands and arms following
  day at beach
• Followed by strange rash on cheeks and bridge
  of nose
• History and physical
• ? of mononucleosis at 15 years
• Pain (mild) and stiffness in fingers of both
  hands and both hips in am beginning at 15 years
• Fever (99 F)
• No present medications

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CASE STUDY 16 YEAR OLD FEMALE

• Laboratory testing
• CBC with differential
• Mild anemia, leukopenia and lymphopenia
• Monospot test
• Negative
• Antinuclear antibody (ANA)
• IFA using Hep-2 cells
• Positive with homogeneous pattern and titer of
  11280
• Double-stranded DNA antibodies
• IFA using Crithidia luciliae
• Positive at a titer of 11280

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CASE STUDY 16 YEAR OLD FEMALE

• Laboratory Testing
• C3 level was 70 mg/dL (85 200 mg/dL)
• Urinalysis was normal
• IgG level was 1820 mg/dL (600 1600 mg/dL)
• Treatment with
• Hydroxychloroquine (Plaquenil)
• Avoid direct sunlight
• 2 months later
• Pain in joints worsened and diffuse swelling
• Nightly fever (101 F) and chills
• Enlarged lymph nodes behind ears and back of neck

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CASE STUDY 16 YEAR OLD FEMALE

• Laboratory Testing
• C3 level of 45 mg/dL (85 200 mg/dL)
• Double-stranded DNA antibodies
• Positive at titer of 12560
• Treated with
• Prednisone (20 mg bid)
• Naproxen (Naprosyn) (250 mg bid)
• Two months later
• Asymptomatic with C3 level of 120 mg/dL

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CASE STUDY 6 WEEK INFANT GIRL

• Referred to dermatologist by pediatrician for
  skin rash which began 8 days prior
• Physical Exam
• Irritable but consolable infant in no acute
  distress
• Skin Rash
• Initial presentation of erythematous scaling
  plaque on left cheek
• Evolution into numerous plaques on face and scalp
  with fewer lesions on trunk and extremities

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CASE STUDY 6 WEEK INFANT GIRL

• Mother
• No problems with pregnancy or delivery
• Diagnosed with SLE 2 years prior
• Asymptomatic with no current therapy
• No family history of lupus
• Laboratory (infant)
• CBC (normal)
• Liver function test (normal)
• ANA by IFA (positive)
• Fine speckled pattern with titer of 11280

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CASE STUDY 6 WEEK INFANT GIRL

• Cardiology Consultation
• Electrocardiogram
• Normal sinus rhythm
• Echocardiogram
• No cardiac malformations or cardiomyopathy
• Treatment
• Mild topical steroid
• Lesion resolution at 4 months of age
• Consultation with mother
• Present and future concerns

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SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

• Autoimmune disease affecting multiple organ
  systems
• Relapsing (flares) and remitting course
• Protean clinical manifestations
• Etiology is unknown
• Female to male ratio is 91
• Age of onset
• 16 to 55 years (65)
• lt 16 years (20)
• gt 55 years (15)

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SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

• Prevalence of 40 to 50 cases / 100,000
• Major causes of mortality
• Infections and nephritis (early)
• Athrosclerosis (late)
• Risk factors
• Genetics (HLA-A1, HLA-B8 and HLA-DR3)
• Race (AA, Hispanic, Asia gt Caucasian)
• Hormones
• Chemicals
• Microorganisms

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SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) - PATHOGENESIS

• Defective regulation of apoptosis
• Accelerated rate of apoptosis in macrophages
  mediated (in part) by T cells
• T-cell mediated APC apoptosis
• Defective clearance of apoptotic cells
• Increased cell death with nuclear antigens
  exposed
• Nuclear antigens
• DS-DNA, Smith, Sjogrens syndrome A (SSA) and B
  (SSB)
• Deposition of autoantibody-nuclear antigen
  complexes

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CLINICAL MANIFESTATIONS OF SLE

• General (Constitutional)
• Fever, chills, headache, fatigue, malaise and
  weight loss
• Renal
• Hematuria, proteinuria
• Skin
• Malar Butterfly rash
• Photosensitivity rash
• Cardiac
• Myocarditis, pericarditis, endocarditis
• Athrosclerosis

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CLINICAL MANIFESTATIONS OF SLE

• Central nervous system
• Cognitive dysfunction
• Pulmonary
• Pleurisy
• Musculoskeletal
• Myalgias, arthralgias and arthritis
• Hematologic
• Anemia, leukemia, thrombocytopenia
• Lymphatic system
• Lymphadenopathy

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AMERICAN COLLEGE OF RHEUMATOLOGY (ACR) CRITERIA
FOR DIAGNOSIS OF SLE

• Serositis (Pleurisy, pericarditis)
• Oral ulcers
• Arthritis
• Photosensitivity
• Blood disorders (Leukopenia, thrombocytopenia)
• Renal involvement
• Antinuclear antibodies (ANA)
• Immunologic phenomena false-positive Rapid
  Plasma Reagin (RPR)
• Neurologic disorder
• Malar rash
• Discoid rash

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ANTINUCLEAR ANTIBODY (ANA) TEST

• Diagnostic test for autoimmune diseases
• Detects autoantibodies against nuclear and
  cytoplasmic antigens
• Nuclear and cytoplasmic antigens
• DS-DNA, SS-A, SS-B, Smith, RNP, Scl-70, M2
• Laboratory methods
• Enzyme immunoassay (EIA)
• Immunofluorescence assay (IFA)
• Indirect or direct

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ANTINUCLEAR ANTIBODY (ANA) BY IFA (PROCEDURE)

• Dilute patient serum 140
• Add patient serum specimens and controls
  (positive and negative) to wells of Teflon coated
  slide
• Monolayer of HEp-2 cells (Human carcinoma of
  larynx)
• Interphase and mitotic phase cells
• Incubate at RT for 20 minutes, then gently wash
  with PBS
• Add fluorescent conjugate sheep anti-human IgG
  with fluorescein isothiocyanate (FITC)

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ANTINUCLEAR ANTIBODY (ANA) BY IFA (PROCEDURE)

• Incubate at RT for 10 minutes in dark
• Gently wash with PBS
• Add 1 drop of mounting medium to each well and
  coverslip
• Examination with fluorescent microscopy at 200x
• Apple-green fluorescence
• Nuclear and /or cytoplasmic patterns
• Screen positive (1 to 2 fluorescence at 140)

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INTERPRETATION OF ANTINUCLEAR ANTIBODY (ANA) BY
IFA IN SLE

• Positive specimens
• Apple-green fluorescence of nuclear region
• Patterns of nuclear fluorescence
• Homogeneous or speckled (fine or coarse)
• Antigens associated with patterns
• Homogeneous (ds-DNA)
• Coarse Speckled (SSA and Sm)
• Fine Speckled (SSB and SSA)
• Specimens are quantified by dilution (2-fold
  serial)
• Interpretation
• Negative (lt 140)
• Indeterminate (180)
• Positive (gt 1160)

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DISCOID LUPUS ERYTHEMATOSUS

• Limited to skin (Face, scalp and ears)
• 5 of total lupus cases
• 5 develop systemic lupus
• Pathophysiology
• Genetic predisposition (?)
• Heat shock protein
• Induced in keratinocytes by UV light
• Target for cytotoxic Gamma/Delta T cells
• Laboratory diagnosis
• Histopathology
• ANA (20 positive)

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DRUG-INDUCED LUPUS ERYTHEMATOSUS (DILE)

• Autoimmune disease associated with
• Long term use wide spectrum of drugs
• 5 of all lupus cases
• High risk drugs
• Procainamide (Pronestyl)
• Hydralazine (Apresoline)
• Quinidine (Quinaglute)
• Isoniazid (INH)
• Minocycline (Minocin)

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DRUG-INDUCED LUPUS ERYTHEMATOSUS (DILE)

• Pathophysiology
• Genetic predisposition
• HLA DR4 with hydralazine
• Rate of acetylation
• Fast
• Slow
• Higher rate of DILE
• Oxidative metabolism of metabolites by
  neutrophils
• Creates reactive metabolites which disrupt T cell
  tolerance

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DRUG-INDUCED LUPUS ERYTHEMATOSUS (DILE)

• Epidemiology DILE
  SLE
• Age of onset 50 to 70 years
  20 to 30 years
• Race White gt Black
  Black gt White
• Female/male ratio 11
  91
• Laboratory Diagnosis
• ANA 98
  98
• Anti-dsDNA lt 0.1
  85
• C3 level Normal
  Decreased
• Clinical Diagnosis
• Resolution of symptoms after stopping drug (1 to
  2 weeks)

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NEONATAL LUPUS ERYTHEMATOSUS

• Etiology
• Passive transfer across placenta of maternal IgG
  autoantibodies
• Anti-SSA/Ro, Anti-SSB/La
• Diagnosis in pregnant females
• SLE or Sjogrens syndrome
• 1 of newborns with maternal autoantibodies
  develop NLE
• Incidence in US of 120,000 live births
• Clinical manifestations
• Cardiac (conduction defects, rhythm
  abnormalities)
• Dermatologic (erythematous papules and annular
  plaques)
• Hematologic (thrombocytopenia, leukopenia,
  anemia)
• Hepatic (hepatitis)

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NEONATAL LUPUS ERYTHEMATOSUS

• Dermatology Manifestations
• 90 of cases with skin lesions
• 70 present at birth
• Cardiac Pathophysiology
• Deposition of autoantibodies (anti-SSA) at
  arterioventricular node
• Dermatologic Pathophysiology
• Deposition of autoantibody (anti-SSB) at
  dermal-epidermal junction

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NEONATAL LUPUS ERYTHEMATOSUS

• Congenital complete heart block
• 15 to 30 of cardiac manifestations
• Develops 18 to 20 weeks gestation
• 20 to 30 mortality
• Laboratory diagnosis in newborn
• ANA
• Anti-SSA/Ro and Anti-SSB/La
• Complete blood count (CBC)
• Liver function tests (LFT)

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