Systemic Lupus Erythematosis

1
Systemic Lupus Erythematosis
2
Patient

• 14 year old girl
• Presented 2 mths previously with dyspnoea and
  chest pain at a regional hospital
• Initially treated as pneumonia
• Progressed to ICU admission
• 5 seizures in ward (started on phenytoin)
• TB as a child
• No history of medicines, allergies, family risk
• Development Grade 6 doing well

3
History continued

• Transferred to tertiary hospital
• Blood tests done, started on prednisone
• Referred to Renal Clinic for renal biopsy

4
Results from clinic

• ANA, ANF, Anti-Sm, Anti dsDNA, Ro, La Positive
• Low C3, C4

5
On Examination

• Weight 44,7 kg (25th)
• Height 170 cm (75th)
• Apyrexial, RR 18, HR 119, BP 96/70
• Marfanoid habitus, rash on face and body
• Not anaemic, no oedema, shotty cervical glands
• CVS tachycardic
• Resp, Abdo, neuro, ENT normal
• Musculo-skeletal Marfanoid. No arthritis
• Tanner stage 4

6
Urine

• 4 haemoglobin, no protein
• Spun scanty red cells and casts
• Lab 18 000 leukocytes lt 1000 RBCs
• Epithelial cells
• Gram negative bacilli

7
Laboratory investigations

• Hb 11 (MCV 90.6), Plt 369 000
• WCC 5.6 (N61, M4, L35)
• UE, CMP normal
• ESR 36, CRP 2.7
• INR, PTT, CK, Cholesterol, WR normal

8
Special investigations

• CXR - residual opacification (RUL
  RML) with fluid in fissure - ?some
  scoliosis - Heart size aortic
  knuckle normal
• ECG normal
• Echo pending
• Ophthalmology, dermatology consultations pending

9
Introduction to SLE

• Auto-immune disorder
• Multisystem microvascular inflammation
• Formation of autoantibodies
• Chronic with relapsing and remitting course

10
Pathophysiology

• Proposed mechanism for autoantibodies
• Defect in apoptosis
• ?cell death ? disturbance in immune tolerance
• Plasma nuclear antigens displayed on cell
  surface
• Dysregulated lymphocytes target Ag (normally
  intracellular)
• Immune complexes form in microvasculature ?
  complement activation inflammation
• Ag-Ab complexes deposit in basement membranes of
  skin and kidneys

11
Etiology

• Unknown
• At least 10 gene loci known to ? risk
• Genetic predisposition (10x more in monozygotic
  twins)
• Human leukocyte Ag ? HLA-DR2, HLA-DR3
  HLA-B8
• Null complement alleles congenital ?complement
  (esp C4, C2 etc)

12
Epidemiology

• Prevalence 4 250/100 000
• Incidence US 1/10 000
• Onset before 8 yrs unusual
• Female predominance (prepubertal 41,
  postpubertal 81)
• Rare in black African population

13
History

• Constitutional fatigue, fever, weight loss
• Skin malar rash, photosensitive, discoid lupus,
  alopecia, Raynaud phenomenon, livido reticularis
• Musculoskeletal arthralgia, myalgia, arthritis
• Renal
• Neuropsychiatric headache, mood disorders,
  cognitive disorders, psychosis, seizures, TIA/
  stroke, movement disorders, mononeuritis
• Pulmonary chest pain, dyspnoea
• Gastrointestinal Abdominal pain, jaundice
• Cardiac heart failure/chest pain
• Haematological multiple cytopenias
• Other miscarriages, family history of
  autoimmune disease

14
On examination

• Constitutional lymphadenopathy,
  hepatosplenomegaly
• Musculoskeletal Jaccoud arthropathy
• Dermatologic - capillaroscopy
• Renal
• Neuropsychiatric
• Cardiopulmonary friction rubs, pulmonary
  embolism, Libman-Sacks endocarditis
• GIT peritonitis, pancreatitis, mesenteric
  vasculitis

15
Diagnostic criteria

• American College of Rheumatology
• 4/11 criteria (sens 85, specif 95)
• SOAP BRAIN MD
• Serositis heart, lung, peritoneum
• Oral ulcers painless esp palate
• Arthritis non-erosive
• Photosensitivity

16
Diagnostic criteria continued

• Blood disorders - ?RBC (Coombs ), PLT, WCC,
  Lymphocytes
• Renal involvement proteinuria / casts
• ANA titer gt 1160
• Immunologic phenomena LE cells, anti-dsDNA Ab,
  anti-Sm Ab, antiphospholipid Ab, false WR
• Neurological disorders seizures/ psychosis
• Malar rash cheeks nasal bridge
• Discoid rash rimmed with scaling, follicular
  plugging

17
Laboratory studies

• High clinical suspicion/ high ANA titres
• SLE Screen
• FBC and diff
• S-creatinine
• Urinalysis with microscopy
• Basic inflammatory markers
• Antibodies to dsDNA
• Complement
• ANA subtypes (anti-Sm, Ro, La, RNP Abs)

18
Autoantibody tests used in SLE

• ANA screening test (95 sensitivity)
• Anti-dsDNA (high specifcity, sens 70)
• Anti-Sm (most specific Ab for SLE, 30 sens)
• Anti-Ro/anti-La (15 in SLE patients, neonatal
  disease)
• Anti-ribosomal P (uncommon, assoc lupus
  cerebritis)
• Anti-RNP (overlap)
• Anticardiolipin (antiphospholipid Ab syndrome)
• Lupus Anticoagulant (antiphospholipid Ab
  syndrome)
• Coombs test (Ab on RBCs)
• Anti-histone (drug-induced lupus)

19
Radiological studies

• Joint x-rays no erosions, periarticular
  osteopenia soft tissue swelling
• CXR/CT chest interstitial lung disease,
  pneumonitis, pulmonary emboli, alveolar
  hemorrhage
• CTBrain or Brain MRI angiography lupus white
  matter changes, vasculitis or stroke
• Echo pericardial effusion, pulmonary
  hypertension or Libman-Sacks endocarditis

20
Invasive procedures

• LP nonspecific ?cells protein, ? glucose
• Renal biopsy prognosis and Rx
• Skin biopsy

21
Lupus nephritis
Class I Minimal mesangial Normal light microscopy abnormal electron microscopy
Class II Mesangial proliferative Hypercellular on light microscopy
Class III Focal proliferative lt50 glomeruli involved
Class IV Diffuse proliferative gt50 glomeruli involved segmental/global
Class V Membranous Predominantly nephrotic disease
Class VI Advanced sclerosing Chronic lesions and sclerosis

22
Differential diagnosis

• Drug induced lupus erythematosis
• Vasculitis
• Leukemia
• HIV
• Multiple sclerosis
• Parvovirus or other viral infections

23
Treatment principles

• Depends on disease severity
• Fever, skin, musculoskeletal and serositis
  milder disease
• CNS and renal involvement aggressive Rx
• Emergencies - severe CNS involvement
  - systemic vasculitis
  - profound thrombocytopenia
  (TTP-like syndrome)
  - rapidly progressive nephritis
  - diffuse alveolar hemorrhage

24
Medications used

• NSAIDS
• Chloroquine
• Steroids
• Cyclophosphamide
• Azathioprine
• Mycophenolate
• (Rituximab)
• Plasma exchange/ IVIG

25
Preventive care

• Medication-related (steroid) complications (Ca,
  vit D, bisphosphonates)
• Aggressive BP and lipid control
• Immunization (complement deficient)
• Stress-dose steroid protocols for patients on
  maintenance corticosteroids (surgery/ infection)
• Avoid UV exposure
• Avoid estrogen therapies
• Avoid sulfa-containing medications
• Pregnancy planning

26
Prognosis

• Benign to rapidly progressive
• Better for isolated skin musculoskeletal
  disease vs renal and CNS
• Death rate 3X age-comparable general
  populationMortality
• Nephritis (most within 5 yrs of symptoms)
• Infectious (active SLE Rx most common)
• CVS disease (50X more MI than other woman)
• Malignancy (chronic inflammation Rx)

27
Summary

• Autoimmune disorder
• Multiple manifestations
• Aggressive investigation and treatment
• Continued surveillance