Chief Resident

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Chief Residents Conference

• Carrie Morgan MD
• April 17, 2008

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The Clue
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Chief Complaint

• 12 yo female with hypertension and seizures

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Presentation

• Life-flight to VCH with new onset of tonic-clonic
  seizures x4 (ceased with ativan) and elevated
  BPs 131-197 systolic/ 90-125 diastolic
• Neurologically intact and sleepy though
  arousable, some complaints of headache

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History

• Initially presented to ENT 1 mo prior with
  complaint of lymphadenopathy on and off for
  several years
• Previous FNA 2 months prior showed reactive
  lymphadenopathy

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History

• Also during this time, she was seen in Cardiology
  clinic for hypertension and functional heart
  murmur
• First noted few months ago when taken at Wal-Mart
• BP systolics 115-130s at home, but noted to be
  140 on PCP office visit

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History

• At that time she had no change in activity or
  ability to keep up with peers, no weight loss, no
  fevers

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History

• ECHO and EKG in Cardiology clinic are normal --
  no cause for HTN found
• Started on amlodipine
• Excisional biopsy scheduled per ENT for
  lymphadenopathy

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Further Course

• 2 weeks after initial Cardiology visit, patient
  returned to PCP with malaise and myalgias but no
  fever
• Diagnosed with pneumonia on CXR and started on
  Azithromycin (Z-pack)

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Further Course

• Follow-up in Cardiology clinic 5 days later and
  still feels unwell with significant malaise and
  myalgias, still no fever
• Completed 5d of Azithromycin, no difficulty
  breathing, nasal flaring, or retractions per mom
• Nausea and dizziness with amlodipine

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Medical History

• PMH
• Term delivery
• Premenarchal
• Recurrent, diffuse LAD
• HTN

• Meds
• Zyrtec 10mg daily

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Social History

• Lives in Ft. Campbell with mother, father, and
  sibling.
• Father is in the military and was deployed at the
  time of presentation
• In 6th grade, doing well.

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Family History

• Father had a stroke at age lt55yo
• Mother has hypothyroidism and a history of breast
  cancer
• GM deceased at age 58 from CV disease
• Healthy sibling

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Physical Exam

• VITALS P96 RR 24-28 Tc AF
• Wt 67.4 Kg (96thtile) Ht 164.5 cm
• 4 ext BP
• RU 154/99
• LU 142/100
• RL 181/100
• LL 185/100

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Physical Exam

• General NAD
• HEENT diffuse, nontender, mobile LAD measuring
  1-2cm at most throughout anterior and posterior
  triangles of neck
• CV RRR, II/VI blowing SEM best heard at LLSB, no
  carotid bruits
• PULM decreased air movement and crackles at the
  left lung base

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Physical Exam

• Abd NT, ND, no hepatomegaly
• Ext Warm, well perfused, 2 pulses
• Neuro CNs grossly intact, strength intact
• Skin No rash

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Labs

• WBC 10.8 Hgb 9.6 PCV 29 plt 191
• Diff 89N, 5L, 1 AtyL, 4M
• ALC 540, ANC 9610
• CRP 3.1
• Na 142 K 3.6 Cl 110 CO2 27
• BUN 11 Cr 0.79 Glc 91
• TSH 5.26 fT4 9.8
• Renin Activity lt0.2

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Plan

• Started on 10d of Cefuroxime
• Changed to HCTZ
• Nephrology referral made for HTN
• F/U with PCP in 1-2 days

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Case Summary

• 12yo female patient with a history of diffuse
  lymphadenopathy, anemia, lymphopenia, acute
  pneumonia with effusion and hypertension who
  presents to ED with seizures and hypertension
• Thoughts?

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Fast Forward to ED

• Admitted to PICU for Nicardipine gtt
• ECHO now with small pericardial effusion and
  mild-mod depressed wall motion
• Keppra for seizure control
• Neurology, Cardiology, and Renal Consults

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Labs at this time

• UA 4 albumin, 5-10 RBC
• Spot urine protein 17.5
• Na 137 K 4.3 BUN 52 Cr 1.7 alb 1.6
• Nl LFTs
• CRP 2.2
• ASO 29
• UDS positive for opiates, acetaminophen

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More lab results

• C3 39 C4 7
• ANA positive, smooth gt1160
• antiDNA gt200 (neg lt25)
• Coombs positive

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What about the seizures?

• MRI/MRA next day

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Diagnosis

• SLE with Lupus Nephritis
• presenting as
• Hypertensive Encephalopathy, specifically
  Posterior Reversible Encephalopathy Syndrome
  (PRES)

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The Clue
prez or press!
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Posterior Reversible Encephalopathy Syndrome

• Clinical syndrome of headache, decreased
  consciousness, visual changes, and seizures
• Associated with characteristic imaging findings
  of posterior cerebral white matter edema
• Syndrome is not always reversible
• Not always confined to posterior regions of brain

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Pathogenesis

• Related to disordered cerebral autoregulation and
  endothelial dysfunction
• Anatomic distribution not well understood
• Fewer adrenergic nerves around intracerebral
  vessels in posterior circulation than anterior

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Upper limit of cerebral autoregulation exceeded
Arterioles dilate
Cerebral blood flow increases
Brain hyperperfusion, esp at arterial border zones
Extravasation of fluid and blood products in
brain parenchyma
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Associated Diseases

• Vasculitis
• SLE
• Cryoglobulinemia
• Polyarteritis nodosa
• Acute Renal Diseases
• HUS
• Immunosuppressive Drugs
• Eclampsia

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Differential Diagnosis

• Stroke
• Venous thrombosis
• Toxic or metabolic encephalopathy
• Demyelinating disorders
• Vasculitis
• Encephalitis

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Imaging

• Neuroimaging is often necessary with previous
  differential and essential to the diagnosis
• Typically see white matter edema in posterior
  cerebral hemispheres
• Distribution is NOT confined to single vascular
  territory
• Findings resolve in days to weeks

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Treatment

• Treat hypertension!
• Treat seizures!
• No longterm risk for seizure recurrence, AEDs
  can be weaned
• If eclampsia, deliver the baby!

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Prognosis

• Usually fully reversible after removal of
  inciting factor and blood pressure brought under
  control
• Rarely death with progressive cerebral edema or
  intracranial hemorrhage

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SLE in Children

• Fundamentally similar to adults except therapy
  has much greater impact on physical growth and
  development
• Same diagnostic criteria used in pediatrics and
  adults

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SLE in Children

• Childhood SLE tend to be more severe than
  adult-onset
• Renal involvement more common in children than
  adults

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SLE in Children

• Affects 5,000-10,000 children in US
• Five times more common in girls
• Usually gt10yo at presentation, rare lt5yo
• Differences in ethnicity are important
• Most common in Asian females, African Americans

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Diagnostic Criteria

• Hematologic disorder
• Immunologic disorders
• Antinuclear antibody
• Serositis
• Neurologic disorder 

• Malar rash
• Discoid rash 
• Photosensitivity 
• Oral ulcers 
• Arthritis 
• Renal disorder

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Diagnostic Criteria

• Classical SLE many criteria
• Definite SLE 4 or gt criteria
• Probable SLE 3 criteria
• Possible SLE 2 criteria
• Children with few criteria should be followed
  closely for further progression

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Lupus Nephritis

• 82 of children with SLE have renal involvement
• In 90 of those, renal disease onset is within
  the first 2 yrs of diagnosis
• Can range from asymptomatic urinary findings to
  renal failure

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Lupus Nephritis

• Most often seen with following clinical findings
• Low serum albumin
• HTN
• Proteinuria
• Abnormal serum markers for SLE

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Pathogenesis

• Immune-Complex mediated glomerular disease
• Pattern of disease relates to site of formation
  of immune deposits
• In SLE, deposits are primarily DNA-anti-DNA

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Pathogenesis

• I- no BM projections but deposits subepithelial
• II BM projections around deposits
• III deposits incorporated into BM
• IV deposits fade, thickened BM remains
• V deposits subendothelial

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Pathogenesis

• Mesangial and subendothelial deposits have access
  to vascular space and can activate complement

Complement activation results in chemoattractants
and influx of neutrophils and mononuclear cells

• Damage causes hematuria, proteinuria, and decline
  in renal function

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Pathogenesis

• Deposits in subepithelial space can also activate
  complement but inflammatory cells are halted by
  the GBM
• This results in proteinuria primarily

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Lupus Nephritis

• Classfication system based on histology
• Minimal mesangial (class I) mesangial deposits,
  but normal glomeruli on light microscopy
• Mesangial proliferative (class II) mesangial
  hypercellularity or mesangial matrix expansion
• Focal nephritis (class III) lt50 of glomeruli on
  light microscopy affected
• Subdivided into Active and/or Chronic (scarring)
• Associated with subendothelial deposits

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Lupus Nephritis

• Classification system based on histology
• Diffuse segmental or global (class IV) gt50
  glomeruli on light microscopy affected
• Associated with subendothelial deposits
• Also subdivided into Active /or Chronic
• Membranous (class V) Subepithelial immune
  deposits (global or segmental) on
  immunofluorescence EM
• Advanced sclerosing (class VI) Greater than 90
  of glomeruli sclerosed globally

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Lupus Nephritis

• Tubuloreticular structures in the endothelial
  cells are relatively specific for lupus nephritis
• Production induced by alpha-interferon

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Therapy

• Immunosuppression is mainstay
• Steroids PLUS
• Cytotoxic agents
• Mycophenolate mofetil (Cellcept)
• Cyclophosphamide (Cytoxan)
• Less commonly tacrolimus (Prograf) and
  cyclosporine

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Therapy

• Other therapeutic considerations
• ACE inhibitor or ARB for blood pressure control
  (renally mediated hypertension)
• PCP prophylaxis
• GI prophylaxis
• Calcium for chronic steroid side effects
• Statin for hyperlipidemia (mostly only in adults)

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Therapy

• Cytotoxic agents are related to occurrence of
  malignancies and sterility
• Gonadal toxicity related to total dosage
  (gt200mg/kg) age
• Steroids and their effects on growth, especially
  if started prepubertal

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Response

• Criteria for treatment response
• Improving GFR
• Resolving proteinuria
• /- Cr level

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Thanks

• Up-to-Date
• Perfumo F and Martini A. Lupus nephritis in
  children. Lupus (2005) 14 83-88.
• Dr. Jabs
• Dr. Wushensky