systemic lupus erythematosus
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Systemic Lupus Erythematosus
Systemic Lupus ErythematosusAutoimmune diseaseOrgans and cells undergo damage mediated
by tissue-binding autoantibodies and immune complexes
90% are women of child-bearing yearsIn the US: 15-50 per 100,000
highest prevalence in African Americans
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
The Case
E.G., 21 FemaleCame in with a chief complaint
of SEIZURES
The Case to manage
A diagnosed case of systemic lupus
erythematosus since December 2008
Initially presented withmalar 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-diabeticnon-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
Review of Systems
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 HISTORYPt 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 HISTORYG1P0 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 RR 40 Temp 38C
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
Physical Examination
Neuro Pt is awake, with regard, responds to name calling, inconsistently follows commands, with no verbal output, uncooperative. CN: I – not assessedII – pupils 2/2 EBRTL, primary gaze midline, (-) preferential gazeIII, IV, VI – (+) slight LR palsy, R; (+) visual threat, BV – brisk cornealsVII – (-) facial assymetryVIII – gross hearing intactIX, X – good gag and swallow XII – refuses to protrude tongue With spontaneous, purposeful movement of the extremities.Withdraws to pain, B ext. (-) Babinski (-) clonuspatient resists neck flexion.(-)dysmetria/dysdiadochokinesia(-) nystagmusMOTOR Strength: 3/5 on all extremities Sensory: WTP on all extremities
Physical Examination
Date 02/28 InterpGlucose 5.83 NBUN --Creatinine 72 NSodium 134 Sl lowPotassium 3.5 HypokalemiaChloride 100 Normal
Date 02/28 Protime Ctrl 12.4 Patient 9 Activity >1 INR 1
Date 02/28 Control 36.1 Patient 43.1 Px:Ctrl Ratio 1.19
Date Normal 2/28 WBC 4-11x109/L 14.1 LeucocytosisRBC 4-6x109/L 3.55 Low Hgb 120-180g/L 103 LowHct 0.370-0.540% 0.291 LowMCV 80-100fL 81.8 normalMCH 27-31pg 29.1 NormalMCHC 320-360g/L 356 NormalRDW-CV 11-16 L 15.2 LowPlatelets 2-4x1011/L CLUMPING then
94 Neut% 0.5-0.7 0.764 elevatedLymph% 0.2-0.5 0.197 nMono% 0.02-0.09 0.036 nEo% 0.0-0.06 0.002 nBaso% 0.0-0.02 0.001 N
Date Normal 02/28 FiO2 60 Temp Hb pH 7.35-7.45 7.429 PCO2 35-45mmHg 26.4 PO2 90-100mmHg 63.5 HCO3 22-28mEq/L 17.9 TCO2 Beb O2 sat’n 92.9
Date Normal 02/28 Color Yellow dark yellow Transparency Clear/hazy sl turbid SG 1.016-1.022 1.02 PH 4.6-6.5 6 Sugar (-) (-) Albumin (-) +++ RBC 0/0-2/hpf 1-2 WBC 0-2/0-5/hpf 15-25 Casts hyaline, coarse,
fine, granular, RBC, WBC, waxy
8-25 hyaline casts 0-2 waxy casts 2-4 coarse granular casts
Crystals Small amounts Epith cells Small amounts occasional Bacteria (-) 2+ Mucus thr Small amounts rare RBC morph
ECG2/28: sinus tachycardia, normal axis, low voltage complexes3/11: sinus tachycardia, normal axis, low voltage complexes3/12: sinus tachycardia, normal axis, low voltage complexes
Plasma K7.6
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 activityt/c SLE cerebritis, myocarditist/c sec APASCommunity Acquired Pneumoniar/o SOL vs electrolyte imbalance vs CNS infection as cause of seizureAnemia of chronic diseaseComplicated UTI
Present Working Impression
Diagnosis
?
Systemic ManifestationsSeverity varies from mild and intermittent to
severe and fulminantExacerbations interspersed with periods of
relative quiescencePermanent complete remissions (absence of
symptoms with no treatment) – rareSystemic symptoms, particularly fatigue and
myalgias/arthralgias – present most of the timeSevere systemic illness requiring
glucocorticoid therapy can occur with fever, prostration, weight loss, and anemia with or without other organ-targeted manifestations.
Musculoskeletal
Cutaneousdiscoid lupus erythematosus (DLE), systemic
rash, subacute cutaneous lupus erythematosus (SCLE), or "other"
Hematologic
Normochromic, normocytic anemiaLymphopenia, not granulocytopenia
RenalDangerous proliferative forms of glomerular
damage (ISN III, IV)microscopic hematuria and proteinuria
(>500mg/24h)One half develop nephrotic syndromeMost develop hypertension
Vascular OcclusionsIncreased prevalence of TIA, CVD, MI
Increased in patients with antibodies to phospholipids (aPL)
Associated with hypercoagulability and acute thrombotic events
Accelerated atherosclerosisCharacteristics 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
SLE or not?Diffuse process of vascular occlusive disease?
Cardiopulmonary
GastrointestinalAutoimmune peritonitis and/or intestinal
vasculitisInc in AST and ALT
OcularSicca syndromeNonspecific conjunctivitisRetinal vasculitis and optic neuritis – threaten
vision
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 AntibodiesANA – positive in >95% usually at the onset of
symptomsAnti-dsDNA – specific
Increases in titers herald a flare, particularly nephritis or vasculitis
Anti-Sm – specificUsually does not correlate with disease activity
aPL – not specific for SLEClassification criterionIdentify patients with increased risk for
venous/arterial clotting, thrombocytopenia, and fetal loss
ELISA for anticardiolipinInternationally standardized
Phospholipid-based activated prothrombin time (dilute Russell venom viper test)sensitive
Anti-RoNot used for diagnosticsIncreased risk for neonatal lupus, sicca
syndrome, and SCLE
Standard Tests for DiagnosisCBCPlatelet countUrinalysis
Tests for Disease CourseHb levelsPlatelet countU/ASerum crea/albuminAnti-DNAC3Activated complement productsIFN-inducible genesSoluble IL-2Urinary adiponectin or monocyte chemotactic
protein 1
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 DiseaseNSAIDs – analgesic/anti-inflammatory
For arthritis and arthralgiasIncreased risk for NSAID-induced aseptic
meningitis, elevated serum transaminases, HPN, renal dysfunction
May increase MIAntimalarials (hydroxychloroquine, chloroquine,
quinacrine) – reduce dermatitis, arthritis, fatigueReduces the number of disease flaresReduce accrual of tissue damage over timeRetinal toxicity
Low-dose systemic glucocorticoids
Life-threatening Diseasesystemic 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
CyclophosphamideAlkylating agentFor patients with ISN gr III or IV, reduced
progression and improves survival500-750 mg/m2 IV, monthly for 3-6 monthsOvarian failure – GnRH agonist prior to each doseDuration 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 mofetilrelatively 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 responsea purine analogue and cycle-specific
antimetaboliteSlower to influence responseContraindicated in patients with homozygous
deficiency of TMPT enzyme
ChlorambucilAlkylating agentHigher risk of irreversible bone marrow
suppressionMethotrexate
Folinic acid antagonistFor arthritis and dermatitis but not in life-
threateningLeflunomide
Relatively lymphocyte-specific pyrimidine antagonist
CyclosporineInhibits production of IL-2 and T-lymphocyte
fxns
Pregnancy and LupusRate of fetal loss is increased
Higher in mothers with high disease activityAntiphospholipid antibodiesnephritisShould be controlled with
prednisone/prednisolone11-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 treatedmost 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.
SLE in Pregnancy
+ aPL x 2 and prior fetal lossesHeparin plus low-dose aspirin
Anti-RoAssoc with neonatal lupus (rash and congenital
heart block)
Poor maternal outcomes – active nephritis or irreversible organ damage
Lupus and Antiphospholipid Antibody Syndromevenous 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 CrisisThrombotic Thrombocytopenic PurpuraHemolytic Uremic Syndrome
High mortality rateYoung, with lupus nephritis
Labs: identification of schistocytes on PBS, elevated LDH
Tx: plasma exchange or extensive plasmapheresis
Lupus Dermatitisminimize exposure to ultraviolet lightsunscreens with a sun protection factor of at
least 15Topical glucocorticoids and antimalarialsSystemic retinoic acidIn therapy resistant: topical tacrolimus,
systemic dapsone, or thalidomide
Preventive TherapiesVaccinationsSuppressing recurrent UTIPrevention of osteoporosisControl of hypertensionManagement of hyperglycemia, dyslipidemia,
and obesity
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)
PrognosisDisability is common25% may experience remissionsLeading cause of death in 1st decade –
systemic disease activity, renal failure, infections, thromboembolic
THANK YOU!
END…
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 PODS> 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 PODA> SLE in activity
t/c SLE cerebritist/c pneumonia in the ICH, PU 15 1/7 weeks AOG by LUTZ.
P> IVF: D5NR1L x 10Piperacillin 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 regardBP 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
02/28/201010 :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 cannulaMedications:
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.
03/02/2010dyspneic 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.
03/03/04Patient 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,
03/04/2010S> (-) seizures, vomiting, headache, LOC (+) mild DOB
O> BP 100-120/70-80, HR 130-140, RR 24-40 38.2CHBS, 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.
03/04/2010OB-GYN cleared pt for CT scan. Fetal biometry and viability recommended
03/04/2010OPHTHA: 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.
03/05/2010O> 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.
03/09/10Patient 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.
03/10/10Patient’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
03/11/10Patient 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.
03/11/10Post-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.
03/11/10She 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:
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