Case Discussion    <Case History>      This 60 year-old woman,a case of hypertension and asthma for years, suffered from myocardial infarction 10 years ago. She had a fall into a pool 2 weeks before admission and began to have dry cough, general malaise, muscle pain and poor appetite since then. The symptoms persisted under medication from a local doctor. She suffered from headache, nausea and weakness on April 26 and was admitted to local hospital under the impression of pneumonia on April 27. She became sickner and even was too weak to walk. On April 28, she was noted be have tonic seizure with loss of consciousness. Similar episodes were noted about six times within 8 hours. Her consciousness became drowsy and she was intubated. She was transferred to our hospital for further care on April 29.      She denied other systemic disease, smoking, alcohol drinking or allergy history. She did not travel recently. The family history is unremarkable.      On arrival at our ER, her blood pressure was 146 / 94 mmHg, temperature was 39 ℃, and pulse rate was 134 /min. She was intubated and consciousness was drowsy. The pupils were isocoric with prompt light reflex. The conjunctiva was not pale and the sclera was anicteric. The neck was supple and there was neither goiter nor lymphadenopathy. The jugular vein was not engorged. The breath sounds were coarse without wheezes and the heartbeats were regular without audible murmur. The abdomen was soft without tenderness or rebounding pain. Liver and spleen were impalpable. The extremities were not edematous and there was no skin lesion.       Hemogram revealed markedly leukocytosis with left shift (WBC=18,730 /uL, neutrophil 80.6%) and thrombocytopenia (platelet=37,000/uL). PT was 13.8s/12.6s and PTT was 74.5s/37.5s. Peripheral blood smear showed marked thrombocytopenia, no giant platelets, no fragmented RBC, no RBC anisocytosis. Blood chemistry studies showed hyperglycemia, abnormal renal function, abnormal liver function, rhabdomyolysis, slight hyponatremia, and elevated C-reactive protein (shown in the data list). Arterial blood gas disclosed metabolic acidosis (PH 7.31, PCO2 24.1 mmHg, HCO3- 11.8 mEq/L) and lactic acid was 5.2 mM. Chest X ray was clear. Under the impression of severe sepsis probably due to meningoencephalitis, intravenous ceftriaxone and acyclovir were given. Brain CT was arranged and she was admitted to ICU immediately.        Brain CT did not reveal significant finding. CSF study disclosed high opening pressure (open pressure=270 mmH2O, close pressure=120 mmH2O) and high protein level (160 mg/dL), no pleocytosis (WBC=2; lymphocyte=1 and neutrophil =1), no hypoglycorrhachia (sugar=164 md/dL) but RBC= 230/uL. Seizure did not recurred after the use of dilantin. EEG revealed mild diffuse cortical dysfunction. Brain MRI disclosed bilateral temporal lobe swelling compatible with encephalitis. Infection specialist suggested further work-up of atypical pathogen due to multiple organ involvement. Doxycycline and penicillin-G were added. Thrombocytopenia, coagulopathy, renal function, liver function, metabolic acidosis and consciousness improved gradually and she was extubated on the third day of admission. She was transferred to general ward. Fever subsided gradually. She was discharged on 5/10 with stable condition.      Blood cultures of bacteria and fungus were negative. The CSF cultures of bacteria, fungus, virus and TB were negative. Cryptococcal antigen of CSF and blood were negative. Autoimmune profiles were negative. HSV PCR of CSF was negative. Serologies for mycoplasma pneumoniae, leptospirosis, Japanese encephalitis virus were negative. Paired serum of rickettsia was positive for Orientia tsutsugamushi. <Laboratory Data>   GLU UN CRE Na K Cl T-BIL AST CK CK-MB   mg/dl mg/dl mg/dl mM mM mM mg/dl U/l U/l U/l 910427   24  1.3         132     910429  261 53 2.79 128.8 4.14 100.0 0.65 84 571 31 910508   13 0.6 145.0 3.5     30       Albumin globulin LDH ALP lactic acid CRP   g/dL g/dL U/L U/L mM mg/dL 910429 1.97 2.55 995 179 5.32 9.62     WBC RBC HB HCT MCV MCH MCHC PLT   K/μL M/μL g/dL % fL pg g/dL K/μL 910427     14.2         118 910429 18.73 6.8 14.6 43.7 64.3 21.5 33.4 37 910429 17.14 5.32 11.4 33.4 62.8 21.4 34.1 12 910508 6.33 4.13 9.4 29.5 71.4 22.8 31.9 239                   Seg Eos. Baso. Mono Lym. 910429 80.6 0.1 0.2 6.9 12.2       PT PT Cont PTT  PTT Cont   sec  sec sec sec 910429 13.8 12.6 74.5 37.5 910501 11.2 12.5  38.2 35.8   PH PCO2 PO2 HCO3 BaseExcess   * mmHg mmHg mEq/l mEq/l 910429 7.31 24.1 119.1 11.8 -12.7 910504 7.44 40.3 77.3 27.0 3.1 項 目 檢驗值 參考值 (單位) Fibrinogen 215 214 ~ 474 (mg/dl) 3P 1+ Negative FDP 5-10 <10 (μg/ml) D-Dimer 2.96 <0.5 (μg/ml) SPINAL FLUID   Pandy's Test None-Apelt Cell Count L/N India Ink 910429 Negative Negative WBC2; (RBC:230/uL) L:N=1:1 Negative    病例分析       此60歲女士一開始以非特異性(non-specific)症狀表現，疲倦，全身沒力，肌肉酸痛，胃口變差，然後才出現頭痛、噁心、發燒、白血球增高、最後發生痙攣及神智不清，整個過程會讓人想到encephalitis。但是病患並無明顯的neck stiffness，且出現許多器官機能受損(肝臟GOT GPT升高，腎功能急速惡化，rhabdomyolysis)，所以可能的診斷是encephalitis with multiple organs involvement，非典型的致病菌(例如：leptospirosis, rickettesia等)必須列入考慮，在empirical antibiotis的使用下，病情改善，而能很快的出院。最後在疾病管制局配對血清學(paired serum)檢驗下，才能確定是scrub typhus。      此病患在高度懷疑有encephalitis with multiple organs involvement的情況下，仍有其他systemic diseases需要考慮，例如autoimmune diseases(如SLE等全身性vasculitis)，thrombotic thrombocytopenic purpura(TTP)等。而血液抹片並沒有破碎的RBC，RBC形狀正常可排除TTP的可能。在抗生素治療下，病情改善迅速，而autoimmune profile皆negative，比較不像autoimmune diseases。       在懷疑encephalitis的情況下，不管是細菌或病毒培養，或血清免疫學的檢查，皆須有幾日或幾星期的檢查。必須根據臨床的判斷儘速給予適當的抗生素治療，第三代cephalosporin對blood-brain barrier通透性佳，且對大部份革蘭性陰性菌有效，penicillin-G對listeriosis, leptospirosis有效，minocycline對rickettsia及chlamydia有效，acyclovior可治療herpes simplex encephalitis。        恙蟲病又稱斑疹傷寒(scrub typhus)，台灣地區是屬於恙蟲病的分佈區域，人遭蟲叮咬而感染，叮咬處會結痂形成eschar，且可能會有淋巴腫大及皮膚紅疹，但並不是所有的病患皆有這些表現。Orientia tsutsugamushi是obligate intracellular bacterium，進入人體後侵犯endothelial cells，而造成廣泛的vasculitis (可包括capillaries, arterioles，及small arteries，而產生各個器官的症狀，嚴重的病患可產生pneumonitis, meningitis, encephalitis以及DIC，沒有適當的治療可能造成死亡。      繼續教育考題 1. (A) The most common symptoms or signs of encephalitis include: (1) altered consciousness (2) headache (3) seizures (4) personality changes A (1)+(2)+(3)+(4) B (1)+(2)+(3) C (2)+(3)+(4) D (2) E (3)+(4) 2. (A) A 50-year-old Taiwanese presents with intermittent fever to 39.5℃, malaise and general myalgia for 10 days. On physical examination, an eschar was found on his left foot, with left tender inguinal lymphadenopathy. Maculopapular rashes were noted on trunks and extremities. Which of the following is the most likely pathogen of this disease? A Orientia tsutsugamushi B Rickettsia rickettsii C Coxiella burnetii D Chlamydia pneumoniae E Listeria monocytogenes 3. (A) Scrub typhus is caused by A Orientia tsutsugamushi B Rickettsia typhi C Rickettsia rickettsii D Rickettsia prowazekii E Salmonella typhi 4. (A) Orientia tsutsugamushi: A may cause an eschar B can be cultured on artificial media C is spread by mosquito D all known to be sensitive to tetracyclines E causes typhoid fever 5. (A) Which of the following statements about scrub typhus is true? A The disease is limited to eastern and southeastern Asia, India, and northern Australia and the adjacent islands. B Urticaria is the skin finding frequently associated with scrub typhus. C It is caused by a tiny extracellular parasite D The parasite lives primarily in louse E Diagnosis is usually confirmed by culture of the pathogen 6. (C) Which is the first-line treatment for scrub typhus? A Ampicillin B Fluconazole C Doxycycline D Ceftriaxone E Acyclovior 7. (E) Which of the following is the arthropod vector of Orientia tsutsugamushi? A mosquito B louse C tick D flea E mite 8. (E) Which of the following statements about scrub typhus is true? A Laboratory studies of choice are serological tests for antibodies because actual isolation and culture of rickettsiae is difficult, expensive, and dangerous B The Weil-Felix agglutination test (looking for antibodies to Proteus OX-K for scrub typhus) may not be as sensitive or specific. C The Weil-Felix agglutination test is usually not positive until the second week of illness, so it often will not pick up early cases of disease. D The fluorescent antibody test is used most often because it can identify antibodies to Rickettsia tsutsugamushi and is a specific test. E All of the above. 9. (E) Which of the following statements about scrub typhus is true? A The incubation period from the mite bite is 6-18 weeks following inoculation. B In untreated patients, the mortality rate for scrub typhus varies from 80-100%. C Untreated patients never die. D Even with the proper antibiotic treatment, mortality rate are still high (around 50%) E Serodiagnosis usually takes time and late treatment may bring serious clinical outcome. When scrub typhus disease is suspected, empiric treatment with tetracycline should be considered. Effective treatment can reduces mortality to essentially nil. 10. (E) Untreated scrub typhus patients can develop A encephalitis B pneumonitis C circulatory failure D die E all of the above   答案解說 腦炎可有頭痛、神智不清、人格異常、抽搐等症狀。 病患有eschar併有局部淋巴腺腫痛以及紅疹，在台灣地區應考慮Orientia tsutsugamushi感染之恙蟲病。 Scrub typhus(斑疹傷寒)是由Orientia tsutsugamushi所引起。 Orientia tsutsugamushi B) 是intracellular pathogen，不能用一般media培養。 C) 是由mite叮咬人類，而將此病菌傳給人類。 D) 已有報告指出對tetracycline resistant之Orientia tsutsugamushi菌種 E) 會造成斑疹傷寒(scrub typhus)，而不是傷寒(typhoid fever)。 B) 常見皮膚症狀是eschar以及maculopapular rash。 C) 是由intracellular pathogen-Orientia tsutsugamushi所引起。 D) 是由mite傳染。 E) 診斷通常是由血清學檢查。 治療斑疹傷寒的首選藥是tetracycline類的藥物。 是由mite叮咬人類由引起傳染。 A-D)敘述皆是正確的。 (A) 潛伏期約6-18天(通常是10-12天)。 (B) (C) 未治療的病患死亡率約30％。 (D)即早給予適當的治療死亡率幾乎可降至0％。 未治療的病患會發生許多併發症，如encephalitis、pneumonitis、shock、甚至死亡。 Top of Page