|
<Case
Presentation:>
This 20-year-old young lady had been diagnosed as a patient
of systemic lupus erythematosus (SLE) for two years. Her
initial presentations included malar rash and nephrotic
syndrome. During the past two years, she was regularly
followed up in outpatient clinic at National Taiwan University
Hospital and received cyclophosphamide and prednisolone to
control the disease activity of SLE. Meanwhile, her hemogram
usually revealed leukocytosis (9000 ~ 14000 /μL) with anemia
and thrombocytopenia and her kidney and liver function were
within normal limits.
On
April 6, 2004, she developed general discomfort without fever. Two
days later, she began to suffer from persistent dull
epigastralgia. At the same time, multiple itching and painful skin lesions
over her trunk and back were noted. They began as discrete,
erythematous, maculopapular and rapidly became vesicular and
then pustular on an erythematous base. She took some herb
drugs by herself at that time. However, the skin lesions
progressed to involve face, scalp, and upper extremities and
the epigastralgia persisted. Therefore, she visited a local
hospital on April 9, 2004, where leukocytosis up to 15620 /μL
with neutrophilia, abnormal liver function [aspartate
aminotransferase (AST), 322 U/L; alanine aminotransferase
(ALT), 303 U/L], and jaundice (total bilirubine, 2.1 mg/dL)
were noted. She was then referred to NTUH and admitted for
further management.
At admission, her vital signs were
stable without fever. Multiple different-staged skin pustules
over her back and trunk were found. However, marked
leukocytosis (white blood cell count, 23620 /μL),
thrombocytopenia (147 K/μL), and abnormal liver function tests
(AST, 1067 U/L; ALT, 670 U/L) were found. Renal function test
and coagulation tests were normal. Her chest radiology was
normal. Under the impression of varicella, SLE related
hepatitis, and suspected secondary infection, she was put on
parenteral acyclovir. On the second day of hospitalization,
the patient remained afebrile. However, cold sweating, back
pain, and pain over right upper quadrant of abdomen were
noted. The follow-up laboratory data revealed progressively
abnormal liver function test (AST, 4975 U/L; ALT, 2570 U/L),
leukocytosis (white blood cell count, 26700 /μL),
thrombocytopenia (68 K/μl), and prolonged PT and PTT (INR
2.3). Ecchymosis and blood oozing from puncture sites were
also noted later. The abdominal computed tomography (CT) scan
did not reveal specific finding. For the existence of frank
disseminated intravascular coagulopathy (DIC), the patient was
then put on empirical antibiotics with ciprofloxacin and
penicillin G. The disease activity of SLE, based on the titers
of C3, C4, anti-nuclear antibody, and anti-double-strand DNA
antibody, did not exacerbate compared to previous data. Blood
samples were also submitted to the special laboratory of
Center for Diseases Control (CDC) for any possible pathogen by
PCR and serologic methods. However, on the third day of
hospitalization, her liver function deteriorated further (AST
up to 19884 U/L, ALT up to 9661 U/L). Sudden onset dyspnea
followed by shock and loss of consciousness developed in the
morning. The arterial blood gas examination revealed severe
acidosis (pH = 7.034, PaCO2 =
26.7 mmHg,
PaO2 = 69.4 mmHg,
HCO< SUB > 3
< /SUB
> = 7.1 mEq/L). Resuscitation was
started immediately. However, intractable metabolic acidosis
and DIC resulting in massive as well as multifocal bleeding
persisted and progressed. She finally passed away despite
intensive and prolonged resuscitation at noon on the third
hospitalization day.
Her blood samples submitted to CDC for special examinations
revealed high copies of varicella-zoster virus (VZV) in serum
(24530 copies/mL). Other examinations, including IgM and IgG
for VZV, and blood culture for bacteriae, were all
negative.
<案例分析>
這是一個患有紅斑性狼瘡（SLE）之成年女性，在罹患原發性（primary）水痘病毒（VZV）感染後，併發猛爆性水痘肝炎
（varicella hepatitis）致死的案例。
一般而言，原發的VZV感染，即俗稱的水痘，一般常見於兒童，通常為一自限性（self-limited）的疾病。然而在公共衛生大幅進步、生活水準提高之後，臨床可見愈來愈多的成人病患。VZV感染後，潛伏期約為10至21天；發病時的症狀主要包括發燒（可高燒至39.4o
）、肌肉酸痛、倦怠、及皮疹。水痘的皮疹，最初出現在軀幹及臉上，隨後很快的擴散至全身；而皮疹最初為紅色斑塊或丘疹（maculopapules），在數小時至數天內演變微小水泡（vesicles），之後再演變為膿泡（pustules），
最後再結痂痊癒。典型的水痘水泡具有一直徑0.5到1公分的erythematous
base，有人稱為「玫瑰花瓣上的露珠（dew
drop）」；並且在同一時間點上，病患身上同時會有進展到不同時期的皮膚變化。嚴重時，病患的喉嚨、陰道也可出現水泡。
在免疫力不全患者的身上，水痘病毒較容易有內臟侵犯（visceral
involvement）的現象（高達30%）；一旦有內臟侵犯的情況，死亡率可高達15%。成年人感染水痘，其臨床症狀通常較兒童來的嚴重，發生併發症的比率也較高。在兒童身上，中樞神經系統是除了皮膚黏膜系統外，VZV最常侵犯的地方；可以引起encephalitis，transverse myelitis，Guillain-Barre
syndrome等。而水痘性肺炎（varicella
pneumonitis）是水痘嚴重的併發症之一；成年人比兒童患者容易產生（可高達20%），臨床症狀包含呼吸急促、咳嗽、呼吸困難、肋膜性胸痛（pleuritic
pain）、以及咳血等；胸部X光上的變化主要為nodular lesion以及interstitial
pneumonitis；肺炎症狀通常會隨者皮膚病灶的好轉而緩解。其它較少見的併發症包含myocarditis、corneal
lesions、nephritis、arthritis、bleeding diatheses、acute
glomerulonephritis、以及hepatitis。
水痘所引起的hepatitis，絕大部分以無臨床症狀的肝功能異常來表現。然而，在極少數的情況下，會如同本病例般的以猛爆性肝炎、
迅速致死的狀況來表現。查詢世界文獻，目前可考之案例共有八例（含本病患）；而八名病患均為迅速死亡，死亡前均可見AST及ALT之檢測值快速攀升、無法控制的代謝性酸血症、以及無法控制的DIC。八位病患之中，有七名為免疫不全的病患，暗示此種病例較容易發生在免疫不全的患者身上。特別的是，此類病患均無水痘性肺炎的表徵，卻有明顯的右上腹及背部疼痛的現象，此或許是臨床診斷的重要線索。
至於VZV感染的治療，主要是acyclovir；當水痘患者本身為免疫不全宿主時，可考慮投予acyclovir治療。另外，當有varicella
pneumonitis時，也應使用acyclovir治療。至於encephalitis和猛爆性肝炎的患者，目前並無足夠證據支持使用acyclovir治療對其臨床症狀有所幫助。
水痘是屬於空氣傳染的一種傳染病，病患在皮疹出現前的48小時至膿泡結痂後的4~5天均具有傳染力。當水痘患者住院時，應住在負壓隔離病房，以保障醫護人員及其它病患的安全。
|
Case Discussion
繼續教育考題