Transcript 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
 (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
The Case
E.G., 21 Female
Came in with a chief complaint of
SEIZURES
The Case to manage
systemic
lupus erythematosus
A diagnosed case of
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 (+)
The Case to manage
Maintained on
prednisone 10 mg once a day
hydrochloroquine 200 mg once a day
The Case to manage
Regular follow up in the OPD (Fammed and Rheuma)
non-hypertensive
non-diabetic
non-asthmatic
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
The Case to manage
2 WEEKS PTA
(+)
decreased appetite
gradually increasing generalized
body weakness
(+)
(-)
interventions or consults
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
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
 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, (+) exertional dyspnea, (-) 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
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
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
General
Survey:
Pt is awake, with regard, responds to name calling,
inconsistently follows commands, with no verbal output.
Vital Signs:
BP 100-110/60-70 HR 142
HEENT:
(+) slight exophthalmos, anicteric sclerae, pink palpebral
conjunctivae, (-) TPC, ANM, (-) NVE, (-) CLAD
Chest/Lungs:
ECE, (+) bibasal and mid-field rhonchi, both lung fields
CVS:
AP, DHS, tachycardic, regular rhythm, (-) murmurs
Abdomen:
flat, normoactive bowel sounds, soft, (-) masses, (-) tenderness,
liver edge not palpable
GU/IE:
Deferred
Skin/
Extremities:
FEP, PNB, (-) edema/cyanosis, (+) blanching erythematous rash
over extremities
RR 40
Temp 38C
Neuro
Pt is awake, with regard, responds to name calling, inconsistently follows
commands, with no verbal output, uncooperative.
CN:
I – not assessed
II – pupils 2/2 EBRTL, primary gaze midline, (-) preferential gaze
III, IV, VI – (+) slight LR palsy, R; (+) visual threat, B
V – brisk corneals
VII – (-) facial assymetry
VIII – gross hearing intact
IX, X – good gag and swallow
XII – refuses to protrude tongue
With spontaneous, purposeful movement of the extremities.
Withdraws to pain, B ext.
(-) Babinski
(-) clonus
patient resists neck flexion.
(-)dysmetria/dysdiadochokinesia
(-) nystagmus
MOTOR Strength: 3/5 on all extremities
Sensory: WTP on all extremities
Date
Protime Ctrl
Patient
Activity
INR
02/28
12.4
9
>1
1
Date
Glucose
BUN
Creatinine
Sodium
Potassium
Chloride
Date
Control
Patient
Px:Ctrl Ratio
02/28
5.83
72
134
3.5
100
02/28
36.1
43.1
1.19
Interp
N
-N
Sl low
Hypokalemia
Normal
Date
WBC
RBC
Hgb
Hct
MCV
MCH
MCHC
RDW-CV
Platelets
Normal
4-11x109/L
4-6x109/L
120-180g/L
0.370-0.540%
80-100fL
27-31pg
320-360g/L
11-16 L
2-4x1011/L
Neut%
Lymph%
Mono%
Eo%
Baso%
0.5-0.7
0.2-0.5
0.02-0.09
0.0-0.06
0.0-0.02
2/28
14.1
3.55
103
0.291
81.8
29.1
356
15.2
CLUMPING then
94
0.764
0.197
0.036
0.002
0.001
Leucocytosis
Low
Low
Low
normal
Normal
Normal
Low
elevated
n
n
n
N
Date
FiO2
Temp
Hb
pH
PCO2
PO2
HCO3
TCO2
Beb
O2 sat’n
Normal
02/28
60
7.35-7.45
35-45mmHg
90-100mmHg
22-28mEq/L
7.429
26.4
63.5
17.9
92.9
Date
Color
Transparency
SG
PH
Sugar
Albumin
RBC
WBC
Casts
Crystals
Epith cells
Bacteria
Mucus thr
RBC morph
Normal
Yellow
Clear/hazy
1.016-1.022
4.6-6.5
(-)
(-)
0/0-2/hpf
0-2/0-5/hpf
hyaline, coarse,
fine, granular,
RBC, WBC, waxy
Small amounts
Small amounts
(-)
Small amounts
02/28
dark yellow
sl turbid
1.02
6
(-)
+++
1-2
15-25
8-25 hyaline casts
0-2 waxy casts
2-4 coarse granular casts
occasional
2+
rare
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
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
 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.
 discoid lupus erythematosus (DLE), systemic rash,
subacute cutaneous lupus erythematosus (SCLE), or
"other"
 Normochromic, normocytic anemia
 Lymphopenia, not granulocytopenia
 Dangerous proliferative forms of glomerular damage
(ISN III, IV)
 microscopic hematuria and proteinuria (>500mg/24h)
 One half develop nephrotic syndrome
 Most develop hypertension
 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 highdensity lipoproteins, repeated high scores for disease
activity, high cumulative or daily doses of
glucocorticoids, and high levels of homocysteine.
 SLE or not?
 Diffuse process of vascular occlusive disease?
 Autoimmune peritonitis and/or intestinal vasculitis
 Inc in AST and ALT
 Sicca syndrome
 Nonspecific conjunctivitis
 Retinal vasculitis and optic neuritis – threaten vision
 (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
 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
 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
 CBC
 Platelet count
 Urinalysis
 Hb levels
 Platelet count
 U/A
 Serum crea/albumin
 Anti-DNA
 C3
 Activated complement products
 IFN-inducible genes
 Soluble IL-2
 Urinary adiponectin or monocyte chemotactic protein 1
 (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
 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
 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
 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
(1) once monthly IV for 6 months followed by 2 more years
of quarterly doses,
(2) for 12 weeks followed by azathioprine
(3) for 6 months followed by azathioprine or
mycophenolate.
 Mycophenolate mofetil
 relatively lymphocyte-specific inhibitor of inosine
monophosphatase 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
 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
 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
 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.
 + 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
 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)
 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
 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
 Vaccinations
 Suppressing recurrent UTI
 Prevention of osteoporosis
 Control of hypertension
 Management of hyperglycemia, dyslipidemia, and
obesity
 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)
 Disability is common
 25% may experience remissions
 Leading cause of death in 1st decade – systemic disease
activity, renal failure, infections, thromboembolic
 THANK YOU!
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.
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
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
Piperacillin Tazobactam 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.
02/28/2010 OB
Examined
benefits of MPPT treatment was deemed to
supercede risks
MPPT treatment allowed to start
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
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
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.
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.
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.
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.
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,
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.
03/04/2010
OB-GYN cleared pt for CT scan.
Fetal biometry and viability recommended
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.
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.
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.
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.
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
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.
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.
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: