登革熱病例報告和致病機轉
李健明 MD, PhD
Outline
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Case presentation
Diagnosis
Pathophysiology
Treatment
Conclusion
Basic information of the patient
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Name: 王OO
Chart number: 31191845
Gender: male
Age: 48 years old
Marriage: married
Occupation: laborer
Past history: none
Chief Complaint
Vomiting for one day
Presented to the ER at 8:32 a.m. of 28 July
How to tackle vomiting
1. Axioms: HT, PE s/s, labTx, op, H.
2. DxD: CNS v. GI, ID, chemicals/Rx,
metabolic, psychologic flowchart
3. HTDx: abrupt, timing, vomitus, abd.
pain, diarrhea, wt. loss…
4. LT
5. Imaging studies
6. Antiemetics
Present illness
28 Jul.
29 Jul
1. Fever
2. Vomiting: coffee-ground vomitus
3. Diarrhea: watery bloody stool
4. Decreased urine output
ED: Dengue NS1 (nonstructural protein 1)
rapid test: positive
Central venous catheter at 11:57 a.m.
Rx: ceftriaxone
•ELISA DENV IgM negative, IgG negative
•PCR positive
•CVP = 10 mm Hg
•Furosemide 40mg stat
Physical examination at the ED
• BW: 80kg at presentation
• The vitals: 36.5 degrees Celsius/97 beats per
min/18 breaths per min; 134/100 mm Hg
• Mentality, alert and oriented
• Lung: clear breathing sounds
• Skin: ???
• Dark greenish loose stool
Laboratory tests at the ED
Hematology
• WBC
Band form
Segmented form
Lymphocytes
Monocytes
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Hemoglobin
Hematocrit
Platelet
PT
aPTT
CRP
5,800/mm3
15%
71%
8%
6%
18.9 g/dL
51.6%
14,000/mm3
14.4 sec
48 sec
88 mg/dL
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Biochemistry
Glucose (rand) 363 mg/dL
BUN
50 mg/dL
Creatinine
4.1 mg/dL
AST
4,319 IU/L
ALT
1,257 IU/L
LDH
7,881 IU/L
Bilirubin
3.6 mg/dL
Na
129 mEq/L
K
3.9 mEq/L
CK
3,639 IU/L
Myoglobin
595 ng/mL
The 48M presented to the ED
• CC: Vomiting for 1 day
• PI: fever, vomiting > 5 times, watery diarrhea, blood
tinged, intermittent periumbilical abdominal pain
• LT: WBC 5800, Hct 52, plt 14k. glucose (random) 330,
BUN 50, Cr 4.1, AST 4319, ALT 1257, Bilirubin 3.7,
CT 3639, CKMB 3.5, PT 14 (11), aPTT 48 (25), CRP
89, stool OB 3+; fibrinogen 231, FDP 27.7 (ref< 5), D
dimer 7463.4 (ref< 500).
• Urinalysis: cloudy, pH 5.5, protein +, glucose 2+, blood
3+, sediment RBC 25.
D1
Arterial blood gas: breathing
ambient room air
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pH
PCO2
PO2
Bicarbonate
Base excess
7.36
19.9
79.8
11.2
-11.4
Diagnosis
1. Severe dengue fever
2. Multi-organ dysfunction Sx: kidney, liver
3. Probable coexisting bacterial infection
and severe sepsis
4. Suspected type 2 diabetes mellitus
D1
80kg
Hydration
DENV NS1 +
FFP and platelet transfusion
Flomoxef (Flumarin) for probable bacterial
infection and severe sepsis
D6
DENV IgM +, IgG +
D8
90kg
Unstable
hemodynamics
dyspnea,
hypoxemia
MODS
Active GI
bleeding
IV fluid
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Platelet
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Day
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Hct
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Day1
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D35
Blood component transfusion
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Platelet
PRBC
FFP
day 1
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I/O
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day 1
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Daily urine output
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mL
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1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39
Day
Creatinine
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Day1 2
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Flomoxef
D1-4
Cefpirom
(cefrom)
D5-11
Ciprofloxacin
D11-19
Imipenem
D19-29
All of bacterial cultures: sterile
Ceftazidime
(fortum)
D36-40
Ciprofloxacin
D40-51
TMP-SMZ
(baktar)
D51-62
D35: Cultures of blood (2/2) and urine grew Elizabethkingia
meningoseptica; urine culture grew Candida albicans.
Hospitalization
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CXR
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CVVH
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HD
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Day 1
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BW: 80
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90
Platelet
WBC
Hct
Creatinine
15
81kg
AST
Heart rate
I/O
D1:7/28
JSH
D3
JSH
D8
JSH
Final diagnosis
• Severe dengue fever
• Septic shock; acute hepatitis, rhabdomyolysis
• Acute kidney injury s/p continuous venovenous
hemofiltration and intermittent hemodialysis
• Acute respiratory failure s/p mechanical ventilation
• Disseminated intravascular coagulation?
– Gastrointestinal bleeding?
• Probable acute pancreatitis?
• Bacteremia on D35: Elizabethkingia meningoseptica
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JSH
Causes of rhabdomyolysis
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Infection
Chemicals: drugs, O2, CO, K, Ca, P, H+
Trauma
Exercise/immobalization
Temperature
Endocrinopathy
Genetics
Connective tissue diseases
JSH
Complications of rhabdomyolysis
1. Acute renal failure: ?acetazolamide,
?mannitol, ?NaHCO3
2. Coagulation defect
3. Arrhythmias
4. Acidosis
5. Hypovolemia
6. Hepatic dysfunction
7. Compartment syndrome
Reservoir of dengue
Sylvatic cycle Rural areas  Human cycle
Natural reservoir: monkeys
Since Japanese era: 斷骨熱
1981: Liou Chou township of Ping Dong
county
• Endemic: annual cases.
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Diagnosis of
dengue
Confirmed
1. IgM seroconversion
in paired sera
2. IgG seroconversion
3. Four fold IgG titer
increase
4. PCR +
5. Virus culture +
Highly suggestive
1. NS1 Ag screening test
2. IgM + in a single serum sample
3. IgG + in a single serum sample
with a high titer >1280
Pathogenesis of dengue fever
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Target cells: mononulear cells
Antibody: enhanced Ab
Bystanders: dndothelial cells and platelets
Organs: liver, brain, skin
Complications: plasm leakage, bleeding
Antibody-dependent enhancement
• Intrinsic ADE: ↑intracellular infection
↑Attachment or internalization: 100- 1,000X
mononuclear phagocytes
• Immune complex suppression of innate cellular immunity
• Extrinsic ADE
↑infectivity, infection rate, no. of infected cells
• Infant’s maternal Ab < protective level: 1st dengue fever,
more severe
• Those who received blood transfusion from an infected
donor, JEV vaccination, 2nd and 3rd infection
• Heterotypic Ab is protective: < 2 years
Treatment of dengue: Q3D
1. Stop NSAIDs, coumadin, heparin, statins,
phosphodiesterase inhibitors, factor Xa inhibitors,
acetaminophen
2. Antipyretics: antihistamine, iv fluid, bath, shower
3. Antipruritics: antihistamine
4. Antiemetics: metoclopramide, prochlorperazine
5. Analgesic: opioids;
6. Hydration: saline, D5W; Nutrition: nephrosteril
7. Prophylactic platelet transfusion useless for
stopping bleeding
Primary afferent transducers
1. Mechanical
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ASIC1, 2, 3: visceral
Cav 3.2
TRPV1, 4
TRPA1, TRPAK
TREK ½
P2X3
2. Thermal
• TRAAK/TREK-1
• NaV1.8
• TRPA1: cold sensitivity
• TRPM8
• TRPV1, 2, 3, 4
3. Chemical
Conclusion: 2 ADEs
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Virology: DENV 1-4 (5); RNA, prone to infidelity
Immunology: platelet, antibody-dependent enhancement
Hematology: platelet, coagulation, endothelium
Pharmacology: adverse drug effects-drug induced liver
injury, thrombocytopenia, and coagulopathy
5. Pathophysiology: water/plasma leak, pain, fever, itch,
vomiting, bleeding; 血、水
6. General medicine: water vs over-hydration, antipyretics,
analgesics, anti-inflammatics, anti-emetics, anti-pruritics,
No more platelet transfusion, antibiotics?!
7. Knee-jerk medicine: x  [a, b]