Internal Case Discussion

Systemic Lupus Erythematosus

(SLE) and Susp. Sepsis dt UTI with
Normal Procalcitonin

Esther Mayrita
Moderator
dr. Anik Widijanti, SpPK(K)
 DATA BASE
Female 37 yo/ Heteroanamnesis
Chief Complain
Incoherent Speech
History of present illness
• She had incoherent speech accompany with general weakness
and loss of appetite since 1 week ago.
• She also had productive cough with yellowish sputum since 5
days ago and sometimes accompanied with fever.
• She also complaint about redness in her face when exposure to
the sun, oral ulcer, leg swelling and hairfall in this 1 month
• She was hospitalized in public health for 1 week and referred to
RSSA with diagnosis SLE
 DATA BASE
Past medical History
She was diagnosis with hypertension (BP 180/100mmHg), DM
(Blood sugar 400mg/dl), lupus and renal disturbance since 3
month ago and routine controlled in Rheumatology Clinic in
RSSA with treatment furosemide 40mg-40mg-0, letonal 1x25mg,
irbesartan 1x300mg, metil prednisolon 32mg-32mg-0, vip
albumin 3x1 capsule, and atorvastatin 0-0-20mg.
Family History:
She had been married, have 2 children, and working as a teacher
 PHYSICAL EXAMINATION
General Look severly ill, GCS 446, Height 155cm, weight 72 kg,
appearance BMI 30 (Obesity)
Vital sign BP 172/98 mmHg, Pulse 94 x/minutes, RR 24 x/minutes,
Tax : 35,70C
Head & Pale conjunctiva (+), moon face, alopecia, Icteric (-),
Neck lymphonode enlargement (-/-), JVP R+4 cmH2O
Thorax Cor : ictus invisible, palpable at ICS V MCL sinistra, S1:S2
reguler, murmur (-)
Pulmo : Breath sound vesicular, Rh (+/-), Wh (-/-)
Abdomen Ptechiae (+), Rounded, soefl, bowel sound normal, Liver
span 10 cm, lien unpalpable
Extremity Edema (+/+), vasculitis (+), ptechiae (+)
 Hematology 25/10 31/1 1/11 2/11 Reference range
Prev.Lab
Hb 8,8 7,3 8 7,7 11.4 – 15,1 g/dL
RBC 3,05 2,61 2,57 2,72 4.0 – 5.0 x 106/µL
WBC 8,98 4,23 5,81 6,22 4.7 – 11.3 x 106 /µL
Ht 24,7 21,2 21,6 23,4 38- 42 %
PLT 12 12 15 21 142– 424 x 103/µL
MCV 81 81,2 84 86 80 – 93 fL
MCH 28,9 28 31,1 28,3 27 – 31 pg
MCHC 35,6 34,4 37 32,9 32 – 36 g/dL
RDW 14,8 16,7 18,1 19 11.5 – 14.5 %
Diff :- Eos 0 0 0 0 0-4
− Baso 0 0 0 0 0-1
− Stab 0 0 0 0 3-5
− Seg 91 95 90 92 51-67
− Limf 5 2 5 4 25-33
− Mono 4 3 3 4 2-5
IPF 15 1,1-6,1 %
 Hematology 4/11 5/11 6/11 Reference range
Hb Melena 5,90 5,90 5.90 11.4 – 15,1 g/dL
RBC 2,15 2,15 2,15 4.0 – 5.0 x 106/µL
WBC 7,85 4,02 4,02 4.7 – 11.3 x 106 /µL
Ht 18,80 18,50 18,50 38- 42 %
PLT 24 25 25 142– 424 x 103/µL
MCV 90,80 86 86 80 – 93 fL
MCH 28,50 27,4 27,40 27 – 31 pg
MCHC 31,40 31,9 31,90 32 – 36 g/dL
RDW 20,60 20 20 11.5 – 14.5 %
Diff :- Eos 0 0 0 0-4 %
− Baso 0 0 0 0-1 %
−Stab 0 0 0 3-5 %
−Seg 86 86 86 51-67 %
−Limf 9 10 10 25-33 %
−Mono 4 4 4 2-5 %
 Blood 25/10 31/10 3/11 6/11 Reference
Chemistry Prev.
Lab
AST 23 22 0-32 U/L
ALT 37 28 0-33 U/L
Albumin 2,40 2,43 2,25 3,5 – 5,5 g/dL
Ureum/ 170,2/ 115/ 137,1/ 164,9/ 16,6 – 48,5 mg/dL
Bun 79,53 53,7 64,06 77,05
Creatinine 1,28 0,92 1,19 1,64 < 1,2 mg/dL
eGFR MDRD 49,87 73,01 54.25 37,5 79-131 mL/min
Bilirubin
Total 0,67 <1,0 mg/dL
Direct 0,43 <0,25 mg/dL
Indirect 0,24 <0,75 mg/dL

7
 Blood 31/10 1/11 2/11 3/11 4/11 5/11 Reference
Chemistry
FBG 329 129 60-100 mg/dL
RBS 457 131 250 <200 mg/dL
POCT 411- 200- 282- 404- 152- 246
400 - 227- 385- 389- 115-
373 290- 242 367- 122-
259- 355- 166-
289- 389- 111-
335- 334 176-
310 129-
185-
2HPP 462 277 <130 mg/dl
Calcium 7,8 7,6-11 mg/dL
Lactate 1,8 Vein 0,5-2,2 mmol/L
(Vein?) Artery 0,5-1,6 mmol/L
 Immunoserology 31/10 Reference
ANA test 1,20 Ratio <1
Procalcitonin 0,31 <0,5 low risk to septic shock
>2 high risk to septic shock
Anti dsDNA IgG 6,30 Negative <20IU/mL
Positive >20 IU/mL
Anti dsDNA IgM 2,80 Negative <20IU/mL
Positive >20 IU/mL

Blood Coagulation 31/10 Reference

PPT 11,7 9,3 - 11,4 second
INR 1,13 0.8 – 1.30
APTT 31 24,5 - 32,8 second
Electrolyte 25/10 28/10 31/10 Reference
Prev Lab Prev Lab
Na 128 135 139 136-145 mmol/L
Corrected? Corrected? (Corrected)
K 6,43 3,36 2,46 3,5-5,0 mmol/L
Cl 103 107 111 98-106 mmol/L

Electrolyte 1/11 3/11 5/11 6/11 Reference

Na 136 137 141 142 136-145 mmol/L
K 3,10 5,24 6,06 5,31 3,5-5,0 mmol/L
Cl 115 122 128 127 98-106 mmol/L
Serum 328 317 285-295 mOsm/kg
Osmolality
 Urinalysis
Parameter 31/10 3/11 Reference
Turbidity Clear Cloud
Colour Yellow Yellow
pH 6,0 6,0 4,5 – 8,0
Spesific Grafity 1,020 1,020 1,005 – 1,030
Glucose 3+ 1+ Negative
Protein 2+ 3+ Negative
Keton Negative Negative Negative
Bilirubin Negative Negative Negative
Urobilinogen Negative 1+ Negative
Nitrit Negative Positive Negative
Leukocyte 1+ 1+ Negative
Blood 3+ 3+ Negative
 Urinalysis
Parameter 31/10 3/11 Reference Value
10x: Epithel 1,3 20,6 ≤1
Cast : Negative Negative
- Hyaline (LPF) - - ≤2
- Granule (LPF) - - Negative
40x: Erytrocyte 216,6 71,9 ≤3
- Eumorphic 96 -
- Dysmorphic 4 -
Leukocyte (HPF) 29,7 11,8 ≤5
Crystal (HPF) - -
Bacterial 3736,7 25186,3 <93 x 103/ml
 Blood Gas
31/10 1/11 3/11 Reference
Analysis
pH 7,48 7,44 7,43 7.35-7.45
PCO2 31,4 29,1 24,1 35 – 45 mmHg
PO2 67,1 139,5 104,3 80 – 100 mmHg
HCO3 23,5 20 16,2 21 – 28 m mol/L
O2 sat Art 93,6 98,9 97,8 > 95 %
BE -0,3 -4,3 -8,3 (-3) - (+3) m mol/L
Hb 7,3 7,3 5,7 g/dL

• 31/10 - Alkalosis Respiratory uncompensated

• 1/11 - Alkalosis Respiratory compensated
 Other Examination
ECG CXR

Conclusion :
Sinus Rythm 78 bpm + Right
ventricle hyperthrophy
Conclusion : Pneumonia ,
Cardiomegally
 Interpretation Data
• This is a case of 37 year old woman with laboratory
results showed :
• Anemia normochromic anisocytosis, mild
leukopenia, thrombocytopenia, elevated IPF
hypoalbuminemia, azotemia renal, hyperglycemia,
positive ANA test, hyponatremia, hypokalemia,
glucosuria, proteinuria, leukocyturia, hematuria,
bacteriuria, Alkalosis Respiratory uncompensated
• ECG : Right ventricle hyperthrophy
• CXR : Cardiomegally
 Interpretation Data
• From history, physical examination and other examinations she
was diagnosis with :
1. SLE with organ involvement and imbalance electrolyte
2. HHD
3. DM type 2 uncontrolled
4. Susp. Sepsis dt UTI, pneumonia
• Suggestion : Blood smear evaluation, reticulocyte, coombs test,
blood and urine culture, ALP, GGT, total protein, Globulin,
echocardiography, NT Pro BNP, Head MRI
• Monitoring : CBC, urinalysis, creatinine, ureum, albumin, serum
electrolyte, bilirubin T/D/I, FBG, 2HPP, procalcitonin
Systemic Lupus Erythematosus (SLE)
• Systemic Lupus Erythematosus (SLE) is an autoimmune disease
in which organs and cells undergo damage initially mediated by
tissue-binding autoantibodies and immune complexes.
• Pathogenesis : 1. Activation of innate immunity; 2. Lowered
activation thresholds and abnormal activation pathways in
adaptive immunity cells (T and B lymphocytes); 3. Ineffective
regulatory CD4+ and CD8+ T cells
• Manifestations of SLE can involve the skin, joints, kidney, central
nervous system, cardiovascular system, serosal membranes, and
the hematologic and immune systems

Goldman: Cecil Medicine, 23rd ed

SLE Pathophysiology
SLICC Classification Criteria for Systemic Lupus
Erythematosus
Clinical Criteria Immunologic Criteria
1. Acute cutaneous lupus 1. ANA
2. Chronic cutaneos lupus 2. Anti-DNA
3. Oral nasal ulcers 3. Anti-Sm
4. Non Scarring alopecia 4. Antiphospholipid Ab
5. Arthritis 5. Low Complement
6. Serositis (C3,C4,CH50)
7. Renal 6. Direct Coomb’s test
8. Neurologic (do not count in the
9. Hemolytic anemia presence of
10. Leukopenia hemolytic anemia)
11. Trombocytopenia (<100.000/mm3)
Requirement >4 criteria (at least 1 clinical and 1 laboratory criteria) OR
Biopsy proven lupus nephritis with positive ANA or Anti-DNA
 Neuropsychiatric Systemic Lupus
Erythematosus (NPSLE)
• Neuropsychiatric systemic lupus erythematosus (NPSLE) is a
generic definition referring to a series of neurological and
psychiatric symptoms directly related to SLE
• The prevalence of NPSLE was 44.5 % in prospective studies versus
17.6 % in retrospective studies
• In the acute setting, management of these patients does not
differ from other non-SLE subjects presenting with the same NP
manifestation
• NPSLE is a severe complication of SLE that contributes
considerably to quality of life, morbidity and mortality.
 Neuropsychiatric Syndromes According to
The American College of Rheumatology
Central nervous system Peripheral nervous system
Neurological Focal 1. Aseptic meningitis 13. Guillain-Barré
syndromes 2. Cerebrovascular disease 14. Autonomic disorder
3. Demyelinating syndrome 15. Mononeuropathy
4. Headache 16. Myasthenia gravis
5. Movement disorder 17. Cranial neuropathy
6. Myelopathy 18. Plexopathy
7. Seizure disorders 19. Polyneuropathy
Psychiatric Diffuse 8. Acute confusional state
syndromes 9. Anxiety disorder
10. Cognitive dysfunction
11. Mood disorder
12. Psychosis
 Nephritis Lupus

• SLE is a chronic inflammatory disease that affects the kidneys in

about 50%of patients.
• Lupus nephritis is a major risk factor for overall morbidity and
mortality in SLE,
• Laboratory diagnosis for nephritis lupus :
• Blood tests : BUN, serum creatinine, laboratory for lupus disease
activity like complement level, antibodies to DNA, ESR, CRP, etc
• Urine tests: urinalysis-presence of blood of proteine in urine as
well as presence of RBC casts, spot urine for UPCR, 24 hr urine for
creatinine clearance and protein
• Kidney biopsy

Amani et al. Update on Lupus Nephritis . Clin J Am Soc Nephrol , 2016.

1. SLE In This Patient
This Patient
• Female 37 years old SLE with organ
• Incoherent speech involvement and
• History of SLE imbalance electrolyte
• SLICC Score 8
• Treatment with
furosemide

Suggestion : Blood smear evaluation, reticulocyte,

coombs test, NT Pro BNP, urine electrolyte, head MRI
Monitoring : CBC, urinalysis, creatinine, ureum, albumin,
serum electrolyte
 SLE and Diabetes
• Systemic lupus erythematosus (SLE) is a chronic
autoimmune disease and glucocorticoid is the mainstay
of treatment in SLE.
• The reported incidence of steroid-induced diabetes
mellitus (SDM) ranged between 1–53%the and
development of SDM may further exacerbate the CVD
risk in SLE patients.
• Higher numbers of system involvement, abdominal
obesity, hypertriglyceridemia and the use of oral
prednisolone of ≥ 1 mg/kg/day were associated with
SDM
Shaharir et al. Steroid-induced diabetes mellitus in SLE patients: analysis from a Malaysian multi-
ethnic lupus cohort. International Journal of Rheumatic Diseases 2015; 18: 541–547
2. Diagnosis DM In this Patient
Theory
American Diabetes Association
(ADA) Criteria
• FPG ≥126 mg/dL (7.0
mmol/L).
• 2-h PG ≥200 mg/dL (11.1
mmol/L) during an OGTT.
• A1C ≥6.5% (48 mmol/mol).
• Classic symptoms of
hyperglycemia or
hyperglycemic crisis, a RPG
≥200 mg/dL (11.1 mmol/L).
Suggestion : Profil Lipid, monitoring FBG, and 2HPP
This Patient
• Female 37 years old
• Overweight
• Hyperglycemia (random, fasting,
2HPP)
• History of corticosteroid
medication
• Treatment with insulin
intravenous 5U/hour until blood
glucose<200 mg/dL
DM Type 2 dt Steroid Induced
3. Cardiovascular Disease in SLE

• Cardiovascular disease (CVD) has emerged as one of

the most important causes of morbidity and mortality
in SLE
• A significant percentage of patients with SLE have
evidence of subclinical vascular disease, such as
increased carotid intima-media thickness (CIMT) and
myocardial perfusion abnormalities
• The clinical manifestations of CAD in SLE can result
from several pathophysiologic mechanisms, including
atherosclerosis, arteritis, thrombosis, embolization,
spasm, and abnormal coronary flow
Knight et al. Cardiovascular disease in lupus: insights and updates . Curr Opin Rheumatol. 2013
Heart Disease in This Patient
3. Cardiovascular Disease in This Patient
This Patient Diagnosis
• Female 37 years old Hypertensive heart
• History of HT, DM, SLE disease (HHD)
• Overweight, hypertension
• ECG : Right ventricle
hyperthrophy
• CXR : Cardiomegally
Suggestion
• Diagnosis with SLE and
Echocardiography,
DM type 2 dt steroid
NT Pro Bnp
induced
 Sepsis

• Sepsis is defined as life-threatening organ dysfunction caused

by a dysregulated host response to infection
• Patients with SLE are highly susceptible to infections due to
the combined effects of their immunosuppressive therapy and
the abnormalities of the immune system that the disease
itself causes, which can increase mortality in these patients.
• PCT has a higher diagnostic value than CRP in the detection of
bacterial sepsis in patients with autoimmune diseases, with a
sensitivity of 75% and a specificity of 90%

1. JAMA. 2016;315(8):801-810; 2. Ospina FE,et al. Distinguishing infections vs flares in patients

with systemic lupus erythematosus. www.rheumatology.oxfordjournals.org
Sepsis

Score 6
4. Sepsis in this Patient
This Patient
• Female 37 year old
• Fever and cough 5 days
• GCS 14, tachycardia, tachypneu
• Mild Leukopenia, normal procalcitonin
• Urinalysis : Glucosuria, proteinuria, leukocyturia,
hematuria, bacteriuria
• CXR : Pneumonia
• SOFA Score 6
4. Sepsis in This Patient

Diagnosis
Sepsis dt UTI and Pneumonia (on treatment)

Suggestion
CBC, urinalysis, creatinine, ureum, bilirubin T/D/I,
culture (blood, urine and sputum), ALP, GGT, total
protein, globulin, monitoring procalcitonin
Normal Procalcitonin
in Sepsis
 Procalcitonin
• Procalcitonin (PCT) is used as a biomarker for the diagnosis
of sepsis, severe sepsis and septic shock.
• Peak levels of PCT occur at 24 to 48 hr after sepsis
• The classic indications for PCT measurement are:
(i) Confirmation or exclusion of diagnosis of sepsis, severe
sepsis, or septic shock,
(ii) Severity assessment and follow up of systemic
inflammation mainly induced by microbial infection, and
(iii) Individual, patient adapted guide of antibiotic therapy and
focus treatment.

Meisner M. Update on Procalcitonin Measurements.Ann Lab Med 2014;34:263-273

 PCT Production
Elevated calcium level,
LPS, Microbial Toxin,
inflammatory mediators
CALC-1 Glucocorticoid CGRP,
Glucagon, Gastrin or β-
like IL-6, TNF-α, etc
adrenergik stimulations

Endocrine
Adipocytes cells Thyroid
Inflammatory PCT
PCT
CT-mRNA
CT-mRNA
ProCT

ProCT
CT

Blood Circulation
Procalcitonin in this patient
0,31 ng/mL
False Positive and Negative Procalcitonin
False-positive in the absence of a bacterial infection
• Newborns physiologically • Chemical pneumonitis,
during first days of life, • Severe burns and heat strokes,
• ARDS, • Medullary thyroid cancer,
• Malaria, • Small cell cancer of the lung,
• Systemic fungal infections • Carcinoid tumours with
• Severe mechanical trauma, paraneoplastic hormone
• Administration of monoclonal production, inflammation
or polyclonal anti-thymocyte associated with “cytokine
globulin storms
False-negative in the presence of a bacterial infection
• Early course of infections, localised infections subacute
endocarditis

Crain MC, Muller B. Procalcitonin in bacterial infections – hype, hope, more or less?. SWISS MED WKLY 2005;135:451–460
 Normal Procalcitonin InThis Patient
This Patient Normal procacitonin
• Female 37 year old because :
• Non Septic condition
• Cough, and fever 5 days (Post therapy infections)
• History of hospitalized 1 • Localised infections (UTI,
week in private hospital pneumonia)
• Normal procalcitonin
• Diagnosis with
1. SLE
2. HHD Suggestion :
3. DM type 2 Monitoring Procalcitonin
5. Susp. Sepsis dt UTI and
pneumonia
 Conclusion
• This is a case of 37 year old woman with diagnosis :
1. SLE with organ involvement and Imbalance
electrolyte
2. HHD
3. DM type 2 uncontrolled
4. Sepsis dt UTI, pneumonia (on treatment)
• Normal procalcitonin in sepsis can caused non septic
condition (post therapy infections) or localised
infections (UTI and pneumonia)
 Conclusion
• Suggestion : Blood smear evaluation, reticulocyte,
coombs test, ALP, GGT, total protein, globulin, blood and
urine culture, echocardiography, NT Pro BNP, Kidney
biopsy, Head MRI
• Monitoring : CBC, urinalysis, creatinine, ureum,
albumin, serum electrolyte, bilirubin T/D/I, FBG, 2HPP,
procalcitonin
1. PCCL Problem List Idx Pdx

Laboratory SLE SLE with • Blood smear

• Anemia normochromic complication evaluation,
anisocytosis, mild Imbalance reticulocyte,
leukopenia, electrolyte coombs test,
thrombocytopenia, urine
elevated IPF electrolyte
• Hypoalbuminemia, • Monitoring :
azotemia, positive ANA test, CBC, urinalysis,
• hyponatremia, creatinine,
hypokalemia, ureum,
• proteinuria, leukocyturia, albumin, serum
hematuria, bacteriuria electrolyte
Clinical finding
• Female 37 yo
• Incoherent speech
• History of SLE
• SLICC Score 8
• Treatment with furosemide
2. PCCL Problem Idx Pdx
List
Laboratory result Hyper- DM Type 2 dt • Profil Lipid,
• Hyperglycemia glycemia Steroid Induced HbA1c
(random, fasting, 2HPP) • monitoring FBG,
• Glucosuria, proteinuria, and 2HPP
leukocyturia,
hematuria, bacteriuria
Clinical finding
• Female 37 years old
• Overweight
• History of DM and
corticosteroid
medication
• Treatment with insulin
intravenous 5U/hour
until blood
glucose<200 mg/dL
3. PCCL Problem List Idx Pdx
Clinical Finding • Cardiac Hypertensive • Echocardiography
• Female 37 years failure heart disease • NT Pro Bnp
old (HHD)
• History of HT, DM,
SLE
• Overweight,
hypertension
• ECG : Right
ventricle
hyperthrophy
• CXR :
Cardiomegally
• Diagnosis with SLE
and DM type 2 dt
steroid induced
4. PCCL Problem Idx Pdx
List
Laboratory Results SIRS Susp. Sepsis dt UTI • CBC, urinalysis,
• Mild Leukopenia, and Pneumonia creatinine,
normal procalcitonin ureum, bilirubin
• Urinalysis : glucosuria, T/D/I, culture
proteinuria, (blood, urine and
leukocyturia, hematuria, sputum),
bacteriuria • Monitoring
• SOFA Score 6 procalcitonin
Clinical Finding
• Female 37 year old
• Fever and cough 5 days
• GCS 14, tachycardia,
tachypneu
• CXR : Pneumonia
 STAGE LUPUS NEPHRITIS
Lupus nephritis is staged according to the classification
revised by the International Society of Nephrology (ISN)
and the Renal Pathology Society (RPS) in 2003, as follows:
• Class I – Minimal mesangial lupus nephritis
• Class II – Mesangial proliferative lupus nephritis
• Class III – Focal lupus nephritis (active and chronic;
proliferative and sclerosing)
• Class IV – Diffuse lupus nephritis (active and chronic;
proliferative and sclerosing; segmental and global)
• Class V – Membranous lupus nephritis
• Class VI – Advanced sclerosis lupus nephritis
 Magnetic Resonance Imaging
• Magnetic resonance imaging (MRI) plays an important role in
the diagnostic work-up of SLE patients with NP symptoms.
• The MRI may help differentiating secondary NPSLE from primary
NPSLE by detecting abnormalities that are not directly caused by
SLE involvement of the CNS such as brain abscesses, progressive
multifocal leukoencephalopathy, and mycotic aneurysms
(Sibbitt et al. 1999).
• Furthermore, MRI may reveal abnormalities in primary NPSLE.
• The most common MRI findings in NPSLE are small punctate
focal hyperintensities [on T2-weighted or fl uid-attenuated
inversion recovery (FLAIR) images] in the subcortical white
matter (WM; 15–60%; Fig. 21.1) and cerebral atrophy (Fig. 21.2).
 Computed Tomography in NPSLE
• Computed tomography (CT) of the brain has been found to be abnormal in 29–
59% of patients with NPSLE (Sibbitt et al. 1999).
• In a study by Gonzalez-Scarano, the most common CT finding in a series of 29
NPSLE patients was sulcal enlargement, either with or without ventricular
enlargement, which was most prominent in patients with either psychosis or
dementia.
• In addition, infarcts and intracranial hemorrhages were observed in this study
(Gonzalez-Scarano et al. 1979). Jacobs and co-workers found no abnormalities
on CT in a group of 13 NPSLE patients (Jacobs et al. 1988).
• Computed tomography is particularly insensitive for pathology underlying non-
focal presentations such as seizures, confusional states, major depression, and
cognitive disorders (Sibbitt et al. 1989); therefore, CT should only be considered
as a primary approach when MRI is not tolerated, unavailable, or
contraindicated (Sibbitt et al. 1999).
SLEDAI SCORE INTERPRETATION