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Systemic Lupus Erythematosus. Systemic Lupus Erythematosus. Autoimmune disease Organs and cells undergo damage mediated by tissue-binding autoantibodies and immune complexes 90% are women of child-bearing years In the US: 15-50 per 100,000 highest prevalence in African Americans.

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systemic lupus erythematosus1
Systemic Lupus Erythematosus
  • Autoimmune disease
  • Organs and cells undergo damage mediated by tissue-binding autoantibodies and immune complexes
  • 90% are women of child-bearing years
  • In the US: 15-50 per 100,000
    • highest prevalence in African Americans
pathogenesis
Pathogenesis

(1) activation of innate immunity (dendritic cells) by CpG DNA, DNA in immune complexes, and RNA in RNA/protein self-antigens;

(2) lowered activation thresholds of adaptive immunity cells (antigen-specific T and B lymphocytes);

(3) ineffective regulatory and inhibitory CD4+ and CD8+ T cells;

(4) reduced clearance of apoptotic cells and of immune complexes

slide6

The Case

E.G., 21 Female

Came in with a chief complaint of SEIZURES

slide7

The Case to manage

A diagnosed case of systemic lupus erythematosus since December 2008

Initially presented with

malar rash, photosensitivity, arthralgia, hair loss and oral ulcers, edema of both lower and upper extremities, weakness

-> was ANA (+)

slide8

The Case to manage

Maintained on

prednisone 10 mg once a day

hydrochloroquine 200 mg once a day

slide9

The Case to manage

Regular follow up in the OPD (Fammed and Rheuma)

non-hypertensive

non-diabetic

non-asthmatic

slide10

The Case to manage

Currently pregnant

(PU 14 1/7 weeks AOG, G1P0)

on follow-up at the PGH OB HRC, last seen February 17, 2010

slide11

The Case to manage

2 WEEKS PTA

(+) decreased appetite

(+) gradually increasing generalized body weakness

(-) interventions or consults

slide12

The Case to manage

4 DAYS PTA

generalized weakness now more prominent on both right upper and lower extremities

(+) behavioral change

(+) general decrease in activity

(+) episodes of staring blankly into space

(+) cough productive of whitish phlegm

(+) febrile episodes (qualitative)

(-) nasal congestion

slide13

The Case to manage

2 HOURS PTA

(-) rousability

(+) seizure - upward rolling of the eyeballs, grinding of teeth and clenched fists (duration ~5 minutes)

-> Promptly rushed to PGH, hence this admission

review of systems
Review of Systems
  • General (+) fever, (-) nausea and vomiting, (+) weakness, (+) weight loss
  • Integumentary(+) malar rash, (-) discoid rash,(-) hairloss
  • Eyes (–) blurring of vision
  • Ears(–) loss of hearing, tinnitus
  • Nervous (–) dysphagia, dysphonia, seizures, dizziness, (+) headache prior
  • Respiratory (+) cough, (+) exertionaldyspnea, (-) colds
  • Circulatory (–) chest pain, (-) bleeding
  • Digestive (-) melena, (-) constipation, (-) diarrhea, (-) abdominal pain
  • Urinary/ Reproductive System

(-) urinary incontinence, (-) polyuria/nocturia, dysuria (-) dribbling, (-) tea colored urine,

(+) vaginal spotting (Feb 14, 2010)

  • Endocrine System(–) heat intolerance, (-) polyphagia, polydipsia, polyuria
  • Joints (–) tremors, (+) joint pain
slide15

PAST MEDICAL HISTORY

(+) SLE, 2008

(-) HPN, DM, goiter, BA, PTB, Ca,

(-) heart problems

(-) allergy

FAMILY MEDICAL HISTORY

(-) SLE, HPN, DM, goiter, BA, Ca, heart problems

slide16

PERSONAL/SOCIAL HISTORY

Pt lives with live-in partner, a college graduate (BA HRM), currently unemployed.

Non-smoker, occasional alcoholic beverage drinker.

(-) known exposure to chemicals, and radiation

OBSTETRIC HISTORY

G1P0

LMP: October 9, 2009 , PU 14 1/7 weeks AOG by LUTZ

slide23

ECG

2/28: sinus tachycardia, normal axis, low voltage complexes

3/11: sinus tachycardia, normal axis, low voltage complexes

3/12: sinus tachycardia, normal axis, low voltage complexes

Plasma K

7.6

2D ECHO: concentric LVH with good wall motion and contractility, EF=73% minimal pericardial effusion, mild pulmo HPN, incidental finding of pleural effusion, mild TR, PR.

CRANIAL CT – enhanced: unremarkable

slide24

Present Working Impression

Systemic lupus erythematosus in activity

t/c SLE cerebritis, myocarditis

t/c sec APAS

Community Acquired Pneumonia

r/o SOL vs electrolyte imbalance vs CNS infection as cause of seizure

Anemia of chronic disease

Complicated UTI

systemic manifestations
Systemic Manifestations

Severity varies from mild and intermittent to severe and fulminant

Exacerbations interspersed with periods of relative quiescence

Permanent complete remissions (absence of symptoms with no treatment) – rare

Systemic symptoms, particularly fatigue and myalgias/arthralgias – present most of the time

Severe systemic illness requiring glucocorticoid therapy can occur with fever, prostration, weight loss, and anemia with or without other organ-targeted manifestations.

cutaneous
Cutaneous

discoid lupus erythematosus (DLE), systemic rash, subacutecutaneous lupus erythematosus (SCLE), or "other"

hematologic
Hematologic

Normochromic, normocytic anemia

Lymphopenia, not granulocytopenia

renal
Renal
  • Dangerous proliferative forms of glomerular damage (ISN III, IV)
    • microscopic hematuria and proteinuria (>500mg/24h)
    • One half develop nephrotic syndrome
    • Most develop hypertension
vascular occlusions
Vascular Occlusions
  • Increased prevalence of TIA, CVD, MI
    • Increased in patients with antibodies to phospholipids (aPL)
    • Associated with hypercoagulability and acute thrombotic events
    • Accelerated atherosclerosis
  • Characteristics associated with increased risk for atherosclerosis include older age, hypertension, dyslipidemia, dysfunctional proinflammatory high-density lipoproteins, repeated high scores for disease activity, high cumulative or daily doses of glucocorticoids, and high levels of homocysteine.
neurologic
Neurologic

SLE or not?

Diffuse process of vascular occlusive disease?

gastrointestinal
Gastrointestinal

Autoimmune peritonitis and/or intestinal vasculitis

Inc in AST and ALT

ocular
Ocular

Sicca syndrome

Nonspecific conjunctivitis

Retinal vasculitis and optic neuritis – threaten vision

lab tests
Lab Tests

(1) to establish or rule out the diagnosis;

(2) to follow the course of disease, particularly to suggest that a flare is occurring or organ damage is developing; and

(3) to identify adverse effects of therapies

tests for antibodies
Tests for Antibodies
  • ANA – positive in >95% usually at the onset of symptoms
  • Anti-dsDNA – specific
    • Increases in titers herald a flare, particularly nephritis or vasculitis
  • Anti-Sm – specific
    • Usually does not correlate with disease activity
  • aPL – not specific for SLE
    • Classification criterion
    • Identify patients with increased risk for venous/arterial clotting, thrombocytopenia, and fetal loss
slide40

ELISA for anticardiolipin

    • Internationally standardized
  • Phospholipid-based activated prothrombin time (dilute Russell venom viper test)
    • sensitive
  • Anti-Ro
    • Not used for diagnostics
    • Increased risk for neonatal lupus, sicca syndrome, and SCLE
standard tests for diagnosis
Standard Tests for Diagnosis

CBC

Platelet count

Urinalysis

tests for disease course
Tests for Disease Course

Hb levels

Platelet count

U/A

Serum crea/albumin

Anti-DNA

C3

Activated complement products

IFN-inducible genes

Soluble IL-2

Urinary adiponectin or monocytechemotactic protein 1

treatment
Treatment

(1) whether disease manifestations are life-threatening or likely to cause organ damage, justifying aggressive therapies;

(2) whether manifestations are potentially reversible;

(3) the best approaches to preventing complications of disease and its treatments

non life threatening disease
Non-life Threatening Disease
  • NSAIDs – analgesic/anti-inflammatory
    • For arthritis and arthralgias
    • Increased risk for NSAID-induced aseptic meningitis, elevated serum transaminases, HPN, renal dysfunction
    • May increase MI
  • Antimalarials (hydroxychloroquine, chloroquine, quinacrine) – reduce dermatitis, arthritis, fatigue
    • Reduces the number of disease flares
    • Reduce accrual of tissue damage over time
    • Retinal toxicity
  • Low-dose systemic glucocorticoids
life threatening disease
Life-threatening Disease
  • systemic glucocorticoids
    • (0.5–2 mg/kg per day PO or 1000 mg of methylprednisolone sodium succinate IV daily for 3 days followed by 0.5–1 mg/kg of daily prednisone or equivalent
    • 4–6 weeks of these doses.
    • Maintenance dose: 5 -10 mg of prednisone or equivalent per day or 10-20 mg every other day.
  • May add cytotoxic/immunosuppressive drugs
slide49

Cyclophosphamide

    • Alkylating agent
    • For patients with ISN gr III or IV, reduced progression and improves survival
    • 500-750 mg/m2 IV, monthly for 3-6 months
    • Ovarian failure – GnRH agonist prior to each dose
    • Duration of therapy
    • once monthly IV for 6 months followed by 2 more years of quarterly doses,
    • for 12 weeks followed by azathioprine
    • for 6 months followed by azathioprine or mycophenolate.
slide50

Mycophenolatemofetil

    • relatively lymphocyte-specific inhibitor of inosinemonophosphatase and therefore of purine synthesis
    • Safer in maintaining improvement after a 6-month induction phase
  • Azathioprine – slower to influence response
    • a purine analogue and cycle-specific antimetabolite
    • Slower to influence response
    • Contraindicated in patients with homozygous deficiency of TMPT enzyme
slide51

Chlorambucil

    • Alkylating agent
    • Higher risk of irreversible bone marrow suppression
  • Methotrexate
    • Folinic acid antagonist
    • For arthritis and dermatitis but not in life-threatening
  • Leflunomide
    • Relatively lymphocyte-specific pyrimidine antagonist
  • Cyclosporine
    • Inhibits production of IL-2 and T-lymphocyte fxns
pregnancy and lupus
Pregnancy and Lupus
  • Rate of fetal loss is increased
    • Higher in mothers with high disease activity
    • Antiphospholipid antibodies
    • nephritis
    • Should be controlled with prednisone/prednisolone
      • 11-dehydrogenase 2 in placenta
  • Adverse effects on offspring: low birth weight, CNS developmental abnormalities, predilection toward metabolic syndrome
sle in pregnancy
SLE in Pregnancy
  • Flares of SLE
    • uncommon during pregnancy
    • often easily treated
    • most common symptoms of these flares include arthritis, rashes, and fatigue.
  • increases the risk of
    • spontaneous abortion
    • intrauterine fetal death, 
    • Preeclampsia
    • intrauterine growth retardation,
    • preterm birth.
  • Prognoses best when SLE is quiescent for at least 6 months before the pregnancy and when the mother's underlying renal function is stable and normal or near normal.
slide54

+ aPL x 2 and prior fetal losses

    • Heparin plus low-dose aspirin
  • Anti-Ro
    • Assoc with neonatal lupus (rash and congenital heart block)
  • Poor maternal outcomes – active nephritis or irreversible organ damage
lupus and antiphospholipid antibody syndrome
Lupus and Antiphospholipid Antibody Syndrome

venous or arterial clotting, and/or repeated fetal losses, and at least two positive tests for aPL have APS

Target INR of 2-2.5 (1 epi of venous clotting)

INR 3-3.5 (recurring clots or arterial clotting)

microvascular thrombotic crisis
Microvascular Thrombotic Crisis

Thrombotic Thrombocytopenic Purpura

Hemolytic Uremic Syndrome

High mortality rate

Young, with lupus nephritis

Labs: identification of schistocytes on PBS, elevated LDH

Tx: plasma exchange or extensive plasmapheresis

lupus dermatitis
Lupus Dermatitis

minimize exposure to ultraviolet light

sunscreens with a sun protection factor of at least 15

Topical glucocorticoids and antimalarials

Systemic retinoic acid

In therapy resistant: topical tacrolimus, systemic dapsone, or thalidomide

preventive therapies
Preventive Therapies

Vaccinations

Suppressing recurrent UTI

Prevention of osteoporosis

Control of hypertension

Management of hyperglycemia, dyslipidemia, and obesity

prognosis
Prognosis
  • Survival
    • 95% at 5 years
    • 90% at 10 years
    • 78 at 20 years
  • In poor countries – glucocorticoid is the sole therapy, worse prognosis
  • Poor prognosis
    • High serum crea[>124 mol/L (>1.4 mg/dL)]
    • Hypertension
    • nephrotic syndrome (24-h urine protein excretion >2.6 g)
    • anemia [hemoglobin <124 g/L (<12.4 g/dL)]
    • Hypoalbuminemia
    • Hypocomplementemia
    • aPL
    • male sex
    • ethnicity (African American, Hispanic, and mestizo heritage)
prognosis1
Prognosis

Disability is common

25% may experience remissions

Leading cause of death in 1st decade – systemic disease activity, renal failure, infections, thromboembolic

slide62
END…
  • THANK YOU!
slide63

02/28/2010 DEM

received GCS 5 E2V1M2

BP 100/70, HR 88, RR 18; CBG 163

given Diazepam 5 mg IV

intubated with note of yellowish secretions per ET tube

GCS 10, E4V1M5 bilateral rhonchi, (+) Babinski, left and decorticate posturing, right.

A> PU 14 1/7 weeks AOG, G1P0; SLE not in activity, t/c SLE cerebritis. Referred to POD.

slide64

02/28/2010 POD

  • S> received stuporous, E2V1M5, intubated
  • vitals: BP 120/80, HR 110, RR 24, T 38.4C.
  • (-) malar rash, no oral ulcers,
  • (+) rhonchi BLF,
  • tachycardic,
  • regular rate and rhythm,
  • (-) murmurs,
  • pupils sluggishly reactive to light,
  • (+) babinski bilateral,
  • (+) doll’s eye
slide65

02/28/2010 POD

  • A> SLE in activity
  • t/c SLE cerebritis
  • t/c pneumonia in the ICH,
  • PU 15 1/7 weeks AOG by LUTZ.
  • P> IVF: D5NR1L x 10
  • PiperacillinTazobactam 4.5 g IVq8,
  • Hydrocortisone 200 mg IV after Pip-tazo load Diazepam 5 mg IV for frank seizures,
  • Paracetamol 300mg IV q4 for T>38C.
  • hooked to a mechanical ventilator.
  • Referred to OB.
slide66

02/28/2010 OB

Examined

benefits of MPPT treatment was deemed to supercede risks

MPPT treatment allowed to start

slide67

02/28/2010 RHEUMA

S> awake but with (-) verbal output and regard

BP 120/80, HR 118, RR 20,

(+) crackles BLF,

tachycardic with S3 gallop,

no lateralizing signs.

A> SLE in activity, (cerebritis, myocarditis),

t/c APAS,

CAP,

r/o SOL,

electrolyte imbalance,

CNS infection

slide68

02/28/2010 RHEUMA

P> Recommended MPPT regimen:

500mg methylprednisolone + 250cc D5W x 6 D1 500mg methylprednisolone + 250cc D5W x 4 D2 500mg methylprednisolone + 250cc D5W x 4, D3

  • 02/28/2010
  • 10 :30 AM – patient was extubated by MICU senior prior to admission to MICU.
  • 11: 00 AM – admitted at MICU, bed 5
slide69

02/28/2010 (1st MICU day, 1st hospital day)

received awake with no verbal output

BP 100/70, HR 132, RR 24

rhonchi on bilateral lung fields.

put on O2 support via nasal cannula

Medications:

1. Pip-tazo 4.5 gm IV q8

2. Hydrocortisone 100 mg IV q8

3. Omeprazole 40 mg tab 1 tab OD

4. CaCO3 1 tab OD

5. NAC 200 mg sachet, 1 sachet + 50 cc water TID 6. Salbutamol neb Q6.

Feeding started via NGT.

slide70

03/01/2010

2D echo results: concentric LVH with good wall motion and contractility, EF=73% minimal pericardial effusion, mild pulmo HPN, incidental finding of pleural effusion, mild TR, PR.

Cardio service no longer highly considering myocarditis.

Neuro: diazepam 5mg IV for frank seizures, leviteracetam 500mg tab 1 tab BID.

Rheuma: SLE activity in the patient are cerebritis, nephritis and serositis (due to pericardial and pleural effusion seen on 2D echo). Plan for MPPT therapy, to hold hydroscortisone while on MPPT.

slide71

03/02/2010

dyspneic episodes not relieved by nebulization but not associated with desaturation.

Breath sounds were noted to be harsher.

She was given Furosemide 40mg and there was noted improvement in dyspnea.

slide72

03/03/04

Patient awake, conversant, comfortable in bed, still with dyspneic episodes and harsh breath sounds on chest PE.

new labs: Urine CS – No growth after 2 days;

ET CS – moderately heavy growth of S. aureus (sensitive to Clindamycin, Erythromycin, Gentamicin, Ofloxacin resistant to penicillin.

slide73

03/03/04

NEURO:

S> blurring of vision, OS>OD.

Still with no recurrence of seizure,

(-) headache, vomiting, LOC.

O> Oriented to time and place, neurologic PE: normal.

Motor strength: from 4/5 to 5/5 on all extremities.

P> Patient referred to Ophtha for the BOV.

Clindamycin discontinued on the basis of sufficient coverage by Pip-tazo as recommended by IDS,

slide74

03/04/2010

S> (-) seizures, vomiting, headache, LOC (+) mild DOB

O> BP 100-120/70-80, HR 130-140, RR 24-40 38.2C

HBS, and occasional crackles and rhonchi on bilateral lung fields. fever

Tachycardic, normal rhythm, no murmurs.

A> SLE in activity (nephritis, serositis, hematologic, t/c cerebritis, NPSLE); pneumonia in the ICH, r/o APAS, UTI, PU 15 4/7 wks AOG by EUTZ, NIL.

slide75

03/04/2010

OB-GYN cleared pt for CT scan.

Fetal biometry and viability recommended

slide76

03/04/2010

OPHTHA:

VA 20/25 (near vision chart), eoms full and equal, tonometry soft OU. ; Slit beam: AC formed, cornea looks clear, lens look clear, (-) dye uptake. ; On indirect fundoscopy, clear media, distinct disc borders, CD ratio 0.3, AV 2:3, (+) exudates on vessels, (-) hemorrhages, retina attached.

t/c SLE retinopathy, OU.

good VA

Patient’s serum K found to be 2.9, correction started for a K deficit of 222. Oral KCl 30cc q8 x 5.

slide77

03/05/2010

O> dyspneic, tachycardic, tachypneic. (+) harsh breath sounds, crackles and rhonchi all over both lung fields. Hemoglobin decreased from 81 to 78. Crea 100 Mg 0.89 Na 144 K 2.9. P> for BT with 2 units pRBC.

3:00 PM, the pt was referred for DOB -> nebulized with 1 neb salbutaol, given 40 mg furosemide IV.

slide78

03/05/2010

3:35 PM, the pt was persistently dyspneic with 02 saturation decreasing from 95 -> 87 -> 84%. Pt was intubated ET size 7.5, level 21. Subsequently hooked to mech vent with the following settings: AC mode, FiO2 100%, BUR 16, IFR 60, PEEP 5, TV 450cc. (+) copious whitish to yellowish secretion per ET. : BP 100-120/70-80, HR 160s, RR 20 CAB, O2 sat 100%.

Pt was also sent to radio for CT scan after intubation. Cranial CT scan results: Unremarkable.

slide79

03/09/10

Patient was referred for desaturation, noted to be dyspneic. Suction was done, found to have mucus plug, and ET out. Patient was reintubated with ET size 7.5, level 20, tolerated very well, hooked to MV with settings: AC mode FiO2 40%, BUR 16, IFR 60 PEEP 5, TV 450 cc (+) copious whitish secretions per ET.

Patient became persistently tachypneic (30s): MV settings were adjusted as follows: SIMV, FiO2 35%, TV 400, BUR 12, PEEP 5, I:E 1:2.

slide80

03/10/10

Patient’s K was low at 2.7. This was corrected with 60 mEqs K x 1L pNSS x 10H x 3 cycles.

There was also note of harsh breath sounds despite regular suctioning, along with a spike in temperature, on ave 39C, which remained constant throughout the day, sepsis was a strong consideration so a shift of antibiotic medication from Pip-Tazo to Meropenem was ordered to provide wider and stronger coverage of nosocomial pathogens

slide81

03/11/10

Patient arrested and was revived after 7 minutes, 2 epinephrine ampoules were given. Post ACLS: BP 110/70, HR 136, O2 sat 100%, ECE, CBS. Suctioning was done with no resistance and minimal brownish secretions per ET.

Possible cause of code: NFA secondary to Hypokalemia, r/o PE. MICU ROD then changed MV settings to: AC mode FIO2 100%, BUR 16, IFR 60, PEEP 5, TV 400cc. She was also given Heparin 3600 ‘u’ as IV bolus then started on Heparin drip: 10000 ‘u’ heparin + enough pNSS to make 100cc in a soluset to run for 7cc/hr.

slide82

03/11/10

Post-code, she was E1V1M1. Also on PE, there was note of an S3 gallop.

Post-code ECG showed ST, NA, low voltage complexes.

Her ECG at 9am had similar findings: ST, NA, low voltage complexes.

Electrolytes were obtained revealing high K at 7.7 so KCl drip was discontinued.

slide83

03/11/10

She had a complete abortion at 1pm and was immediately seen by the OB service, there was no uterine atony. Stat Hgb and Hct were 61 and 0.148 respectively, and she had hypotensive episodes (lowest 70/50) and was immediately given 500cc fast drip of pNSS and so 2’u’ pRBC were processed as quickly as possible. She also had Dopamine on standby, 400mg in 250cc D5W, to run at 38cc/hr max, to be down titrated by 2cc/hr until it reaches 10cc/hr if BP remains above 90/60.

Her PWI was revised to: