登革熱病例報告和致病機轉

李健明 MD, PhD

Outline

1. Case presentation

2. Diagnosis

3. Pathophysiology

4. Treatment

5. Conclusion

Basic information of the patient

• 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, labTx, op, H.

2. DxD: CNS v. GI, ID, chemicals/Rx, metabolic, psychologic flowchart

3. HTDx: abrupt, timing, vomitus, abd. pain, diarrhea, wt. loss…

4. LT

5. Imaging studies

6. Antiemetics

29 Jul

1. Fever2. Vomiting: coffee-ground vomitus3. Diarrhea: watery bloody stool 4. Decreased urine output ED: Dengue NS1 (nonstructural protein 1)

rapid test: positiveCentral venous catheter at 11:57 a.m.Rx: ceftriaxone

28 Jul.

• ELISA DENV IgM negative, IgG negative• PCR positive• CVP = 10 mm Hg• Furosemide 40mg stat

Present illness

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 Biochemistry

• WBC 5,800/mm3

Band form 15%

Segmented form 71%

Lymphocytes 8%

Monocytes 6%

• Hemoglobin 18.9 g/dL• Hematocrit 51.6%• Platelet

14,000/mm3

• PT 14.4 sec• aPTT 48 sec• CRP 88 mg/dL

• 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

• pH 7.36• PCO2 19.9

• PO2 79.8

• Bicarbonate 11.2• Base excess -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

HydrationDENV NS1 +

D1

FFP and platelet transfusion

Flomoxef (Flumarin) for probable bacterial infection and severe sepsis

Unstable hemodynamics

dyspnea, hypoxemia

MODSActive GI

bleeding

D8 90kg

D6

DENV IgM +, IgG +

80kg

day 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 CE/ 通用格式

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IV fluid

Day 1

2 3 4 5 6 7 8 9 10 11 12 13 14 15CE/ 通用格式

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CE/ 通用格式Platelet

Day1 2 3 4 5 6 7 D35CE/ 通用格式

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Hct

day 1 2 3 4 5 6 7 8 9CE/ 通用格式

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PlateletPRBCFFP

Blood component transfusion

day 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

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I/O

Daily urine output

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Day

mL

Day1

2 3 4 5 6 7 8 9 10 11 12 13 14 15CE/ 通用格式

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Creatinine

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.

Day 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

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Hospitalization

Platelet WBC Hct CreatinineAST Heart rate I/O

CVVH HD

1 2 3 4 5 6 7 8CXR

BW: 80 90 81kg

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

JSH

Causes of rhabdomyolysis

1. Infection

2. Chemicals: drugs, O2, CO, K, Ca, P, H+

3. Trauma

4. Exercise/immobalization

5. Temperature

6. Endocrinopathy

7. Genetics

8. Connective tissue diseasesJSH

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.

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

• 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: Q3D1. 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

• 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 ADEs1. Virology: DENV 1-4 (5); RNA, prone to infidelity

2. Immunology: platelet, antibody-dependent enhancement

3. Hematology: platelet, coagulation, endothelium

4. 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]