< Presentation of case >
The 54-year-old male, a storekeeper, was admitted to the Emergency Department (ER) of this hospital because of intermittent fevers and respiratory failure. He had been diagnosed as having diabetes mellitus and hypertension for 10 years, for which who received regular medications. He denied a history of recent travel or animal contact, or similar cases in the work place or family. He had been otherwise well until 6 days earlier, when he developed fevers with chills, myalgias and headache. The symptoms persisted despite taking medications prescribed at local clinics. He sought medical attention at another hospital, where abnormal liver function test results were found and computed tomography (CT) of the abdomen showed gall bladder stones and wall thickening with triple layer sign, which suggested acute cholecystitis. Blood transfusion was given before operation and laparoscopic cholecystectomy was performed. After operation, progressive respiratory distress and shock developed and he was intubated and was transferred to this hospital.
On arrival at ER, the blood pressure was 80/40 mmHg, heart rate 155 beats per minute, respiratory rate 25 breaths per minute, and temperature 40 ℃ and oxygen saturation by pulse oximetry was 90% when he was placed on mechanical ventilator support with 100% oxygen. His conjunctiva was pink and sclera was mildly icteric. The neck was supple without lymphadenopathy, goiter or jugular venous distension. The heart beats were regular without murmurs. Bilateral diffuse crackles were noted on chest auscultation. The abdominal examination showed normoactive bowel sounds and there was no tenderness or muscle guarding. The extremities were freely movable without skin rashes or eschar. No petechiae or ecchymosis was noted.
< Laboratory and Image Study >
1. CBC/DC
|
WBC |
Seg/Band |
Hb |
PLT |
CRP |
Lactate |
|
/μL |
% |
g/dL |
K/μL |
mg/dL |
mmol/L |
On admission |
17180 |
71/16 |
13.4 |
74 |
18.79 |
3.68 |
2. Biochemistry
|
Alb |
AST |
ALT |
T-BIL |
D-BIL |
ALP |
r-GT |
BUN |
Cre |
Na |
K |
|
g/dL |
U/L |
U/L |
mg/dl |
mg/dl |
U/l |
U/l |
mg/dL |
mg/dL |
mM |
mM |
On admission |
3.39 |
295 |
152 |
3.52 |
2.49 |
380 |
206 |
20.3 |
1.6 |
140 |
4.4 |
3. Urinalysis
|
Sp. Gr. |
pH |
Protein |
Glucose |
Ketones |
O.B. |
Bilirubin |
On admission |
1.010 |
6.5 |
+ |
+ |
+/- |
+ |
+ |
|
Nitrite |
RBC |
WBC |
Epith Cell |
Cast |
Crystal |
Bact. |
On admission |
- |
15-20 |
2-5 |
0-2 |
- |
- |
- |
4. Arterial blood gas
|
PH |
PCO2(mmHg) |
PaO2 (mmHg) |
HCO3 (mmol/L) |
On admission |
7.35 |
33.3 |
82.8 |
18.6 |
Ventilator setting: PCV mode, FiO2: 100%, PEEP: 12cm H2O, Pi: 15cm H2O |
5. CXR on arrival at the ER (Figure 1) : Bilateral diffuse infiltration, consistent with acute respiratory distress syndrome
6. Influenza A+B rapid test: negative
7. HBsAg: negative, Anti-HCV: negative
8. Sputum Gram stain: few PMNs, few epithelial cells, no bacteria
< Course and Treatment >
After admission, tests for legionellosis, leptospirosis, scrub typhus, Q fever and influenza were performed at Taiwan Centers for Disease Control (CDC). Levofloxacin (750 mg QD iv), doxycyline (100 mg bid po) and oseltamivir (150 mg bid po) were prescribed. Oseltamivir was discontinued on the 3rd day of hospitalization, when a negative RT-PCR for influenza was reported by CDC. His oxygenation and shock status improved since the 3rd hospital day onward and he was extubated on the 6th day smoothly. Doxycycline was discontinued after completion of the 7-day course. He was discharged with oral levofloxacin on the 13th hospital day. Tests for Legionellosis, leptospirosis, scrub typhus, Q fever and influenza were all reported negative by CDC. Polymerase chain reaction (PCR) for endemic typhus (Richettsia typhi) was positive and seroconversion of serum antibody IgM, IgG was documented, with indirect fluorescent antibody (IFA) IgM > 1:160 and IFA IgG > 1: 640.
< 病例分析 >
地方性斑疹傷寒(Endemic typhus)，又名鼠斑疹傷寒(murine typhus)，是由Richettsia typhi引起的人畜共通傳染病。此病在熱帶及亞熱帶地區較常見，通常是由受感染的鼠蚤所傳播。Richettsia typhi 在鼠蚤的腸道上皮複製後便排到鼠蚤的糞便中，而Richettsia typhi在鼠蚤的糞便接觸到鼠蚤咬出的傷口後進入人體。Richettsia typhi進入人體內之後會造成全身性的血管炎(vasculitis)進而產生臨床上的症狀。臨床上的表現通常無特異性，其中發燒(93-100%)、頭痛(10-91%)、肌肉痠痛(8-10%)和噁心(14-59%)是較常發生的早期表現；隨著疾病的進展，約有14-44%的病人會有呼吸道的症狀(cough)，而約有3.75%的病人進展到呼吸衰竭而需要插管。通常地方性斑疹傷寒的病程並不嚴重, 但仍有約10%的病人需要進入加護病房照顧，而有4%住院病人死亡。
在疾病前七天內，約有1/4到1/2的病人會有白血球低下(合併血小板低下)的表現。而最常發現的實驗室異常是aspartate aminotransferase(AST)輕微到中等程度的升高(67-92%)，而alanine aminotransferase (ALT)、alkaline phosphotase數值也會上升。約有90%的病人會發現有hypoalbuminemia. 地方性斑疹傷寒大部分都是根據臨床上的表現而懷疑感染，在懷疑有感染時便應開始治療而不應該等待實驗室的確診。主要的實驗室診斷方法是血清學的檢驗(indirect fluorescent antibody, IFA)。近來有新的檢驗方法，如周邊血液立克次體核酸的PCR檢測法(polymerase reaction amplification of richettsial nucleic acid in peripheral blood)，但目前仍缺乏足夠敏感度和特異性的研究報告。
治療地方性斑疹傷寒的藥物為四環黴素類的抗生素，如doxycycline。其他替代性的藥物有：chloramphenicol 及 fluoroquinolones類的藥物。給予適當的治療後，平均大約在三天後會退燒，但治療應該持續到退燒後2-3天。
地方性斑疹傷寒臨床表現與其他非典型的感染一樣，均不具有特異性，臨床醫師在疾病初期很可能將病人當成一般的感冒治療，因此臨床醫師必須具有高度的警覺性，對於不明原因發燒，合併其他類似病毒感染的症狀及不明原因肝功能異常的病人，一定要將非典型感染(包括leptospirosis, Q fever, richettsial infections)列入鑑別診斷，確定的診斷則必須仰賴實驗室的檢查.
地方性斑疹傷寒於台灣的個案數量並不多，而地方性斑疹傷寒造成肺炎及急性呼吸窘迫症候群及休克的個案在文獻上更只有少數零星的病例報導。此病例到院時向疾病管制局通報[恙蟲病](Scrub typhus, Richettsial tsutsugamushi) 而疾病管制局額外檢驗了[地方性斑疹傷寒](Endemic typhus, Richetssial typhi) 才獲得了解答。此兩種疾病在臨床表現方面相當難以區分。
在地域的區分方面, 2009義大醫院賴醫師等人在台灣醫誌發表針對南台灣的Q fever、scrub typhus 及 endemic typhus的流行病學調查指出，Q fever 的個案數最多，其次為scrub typhus，而enedemic typhus個案數最少。其中endemic typhus 的病例為隨機式的分布，而scrub typhus 的病例都較集中於山區。
而在理學檢查方面，若在病人身上發現有eschar，則病人有相當大的可能為恙蟲病感染；而在實驗室檢查方面，有研究指出在恙蟲病的病人會有較多的腎功能異常、血小板低下及敗血症的表現。雖說如此，在臨床上仍會時常面臨無法區分兩者的狀況。
< 參考文獻 >
- Principles and Practice of Infectious Diseases. 7th edition
- Dumler JS, et al. JAMA 1991;266:1365-70
- Suputtamongkol Y. et al. Ann. N.Y. Acad. Sci 2009;1166:172-9.
- Lai CH. et al. J Formos Med Assoc 2009;108:367-76.
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Case Discussion
繼續教育考題