Presentation of Case
A 19-year-old male patient presented to our hospital because of fevers for 3 weeks. The patient had been well until 3 weeks before this presentation, when fever, chills, productive cough, sore throat, and diarrhea developed. He was first seen at an outside clinic, where bilateral tonsil enlargement was noted, and a diagnosis of acute exudative tonsillitis was made, for which an oral antibiotic (Augmentin) and antipyretics were given. The sore throat improved with medications, but the intermittent fevers persisted. Newly developed skin rashes developed two weeks after the first fever episodes. The rashes, measured about 5 mm, were well-circumscribed, oval, pink macules, which distributed over the abdomen, back, arms, and palms. It was non-itchy, and resolved spontaneously after one week. Ten days before presentation, he was admitted to another hospital because of prolonged fever and tea-color urine. Liver-function tests revealed elevated aminotransferases (AST, 2894 U/L; AST, 843 U/L) and total bilirubin (5.31 mg/dL) upon admission. Yellowish skin and sclera were noted. Abdominal sonography reportedly showed hepatomegaly and mild splenomegaly. Tests of serologies for viral hepatitis A, B, and C were reportedly negative. Other serological tests for CMV IgM, EBV-CA IgM, and HIV using ELISA were all negative. He was then referred to our hospital.
On examination, he was in mild distress. The temperature was 36.9 ℃, the pulse rate 102 per minute, the respiratory rate 17 breaths per minute, and the blood pressure 124/66 mm Hg, and the oxygen saturation 96% while he was breathing ambient air. The skin was yellowish with faint brownish rash over thr abdomen, back, arms and palms (Figure 1). Several lymph nodes, 0.5 to 1 cm in diameter, were palpable at the bilateral neck. The breath sounds were clear to auscultation, and the abdomen was mildly distended, with increasing dullness at the right upper quadrant on percussion. Laboratory-test results are shown in Table 1. A chest radiograph showed a small pleural effusion in the right lung, and the computed tomography of the abdomen showed hepatomegaly and a small amount of ascites.
He was a college student and had travled to Tokyo with his family 2 weeks before the onset of fever. He reported no recent sick contacts, or wading in the water. He didn’t smoke, drink alcohol, or used illicit drugs. He also denied any unprotected sexual exposure.
After admission, a diagnosis of infectious-mononucleosis-like disease was made. A test for HIV using a fourth-generation HIV Ag/Ab combo testing kit reported positive and an plasma HIV RNA load was 11,500,000 copies/ml and the CD4 count 161 cells/μL. Combination antiretroviral therapy with tenofovir, lamivudine, and raltegravir was started. His liver function gradually improved with antiretroviral therapy.
Table 1. The results of laboratory studies
1.CBC and differential count:
WBC
/μl |
RBC
M/μl |
Hb
g/dl |
Plt
K/μl |
Hct
% |
MCV
fL |
Band
% |
Seg
% |
Baso
% |
Eos
% |
Mono
% |
Lymph
% |
3390 |
4.69 |
12.6 |
96 |
37.1 |
79.1 |
0 |
56.0 |
0.1 |
0 |
17.0 |
27.0 |
2. Biochemistry:
ALT
U/L |
AST
U/L |
T-bil
mg/dL |
D-bil
mg/dL |
GGT
U/L |
ALP
U/L |
Cre
mg/dL |
Na mmol/L |
K mmol/L |
Albumin
g/dL |
CRP
mg/dL |
924 |
2777 |
12.59 |
8.35 |
942 |
304 |
0.5 |
133 |
4.5 |
2.9 |
0.65 |
3.Other studies:
Ceruloplasmin
mg/dL |
VDRL/RPR Test |
19.9 |
Non-Reactive |
Figure 1. The skin appeared yellowish, with faint brownish macular rash over the abdomen.
討論
本病例為急性愛滋病毒感染 (acute HIV infection) 個案。在愛滋病毒感染者當中，急性感染 (acute infection) 一般定義為初感染時，表現出症狀的時期，而早期感染 (early infection) 則一般定義為初感染的 6 個月內。在 愛滋病毒感染者中，約有 10-60% 感染者不會表現出急性症狀。[1]平均來說，從獲得感染到表現急性症狀的時間是二至四周，大多數症狀都可以自行緩解，然而其嚴重度的表現與症狀持續的時間長短，在不同的病人身上，有很大的歧異。症狀上，最常見的有：發燒、淋巴結腫大 (頸部、腋下、枕部等部位)、喉嚨痛、皮疹、肌肉酸痛、關節酸痛、頭痛 (Table 2) 。 具有這些症狀的病人，即符合『急性反轉錄病毒症候群』(acute retroviral syndrome)。常見病人在症狀出現時，因喉嚨痛就診，檢查發現有咽喉水腫、扁桃腺腫大，甚至表面有膿滲出，而被診斷為急性扁桃腺炎。皮疹多見出現於發燒後 48-72 小時，並可能持續 5-8 天後自行緩解，典型皮疹為分布在臉部、脖子、軀幹， 5-10 mm 的粉紅至深紅色、不凸起、邊緣清楚的紅疹。頭皮、四肢、手掌、腳掌雖較不常見，亦可能出現皮疹。雖然這些症狀單獨出現並不具高特異性，但某些表現強烈暗示此急性愛滋病毒感染之診斷，如以上症狀表現大於兩至三週，或有粘膜潰瘍。其潰瘍典型為粘膜上的淺潰瘍，具白底及紅色邊緣，可出現在口腔、肛門、陰莖、食道上。這些臨床症狀的越嚴重、時間越長，預後則越差。[2] 腸胃道症狀中，較常見的有嘔吐、腹瀉、食慾變差，甚至體重減輕 (平均減輕 5 公斤)。頭痛可能伴隨後眼窩痛，其可能是因為愛滋病毒造成無菌性腦膜炎 (aseptic meningitis) 所造成的症狀。肺部表現除了乾咳之外，較少其他症狀。另外，伺機性感染雖然一般較常見於晚期愛滋病患者，亦可見於急性愛滋病毒感染患者，其中最常見的是口腔、食道的念珠菌感染。在實驗室檢查方面，急性感染期間，病毒快速複製，因此可以看到血漿中愛滋病毒量非常高，如大於 100,000 copies/mL ，且 CD4 也會暫時減少。其餘較不具特異性的實驗室數據，包括：白血球降低、肝功能升高、貧血、血小板低下......等等。與急性愛滋病毒感染需鑑別的診斷，包括引起感染性單核球增多症 (infectious mononucleosis) 的 Epstein-Barr病毒 (EBV) 感染、巨細胞病毒 (cytomegalovirus, CMV) 感染、弓蟲症 (toxoplasmosis)、德國麻疹 (rubella)、梅毒 (syphilis)、病毒性肝炎 (viral hepatitis)、瀰漫性淋病雙球菌感染 (disseminated gonococcal infection) 等。
此病例病人之急性愛滋病毒感染併嚴重肝炎，為此急性感染症候群其中較罕見之表現。台灣亦有高雄榮總之本土資料流行病學統計[3]，從 1990 至 2009，二十年間收集了 23 個急性愛滋病毒感染病例，其中肝功能異常者有 15位 (佔 65.2%)。其中肝功能指數，AST 中位數為 112 U/L (62-969 U/L)，ALT 為 146 U/L (42-1110 U/L)。另外，台大醫院從 1997 至 2010 亦累積 160 位急性愛滋病毒感染，在其中 103 位有肝功能資料的病患中，肝功能異常的有 62 位，而AST 或 ALT 上升至正常值五倍以上的也有 14 位。
在診斷與治療方面，早期感染時，病毒抗體的血清檢查，如 ELISA test，因血中抗體尚未生成足夠量，檢驗常為陰性。此病例後來所用的第四代 HIV Ag/Ab combo test，作為愛滋病毒感染的篩檢，比傳統的 ELISA 多檢驗了愛滋病毒的 p24 抗原，可更早期檢驗是否有 愛滋病毒感染，於感染過後二至三週，即可有陽性反應。 Table3 列出常見的愛滋病毒檢驗，從感染到檢驗陽性所需的時間，可以看到抗體檢測皆有二週到八週不等的『空窗期』(window period)。若臨床上高度懷疑病人為急性愛滋病毒感染，但檢驗愛滋病毒抗體 ELISA 為陰性時，可以選擇直接檢驗血中愛滋病毒量，或者相隔一至二周後，再次檢驗愛滋病毒抗體。急性感染若無症狀或症狀輕微，病人可能不會就醫，但若症狀嚴重，通常也預示著此病人的預後較差。[2] 另外，急性愛滋病毒感染時的症狀，推測跟此時病人體內高量的病毒血症相關，不論是直接引起症狀，或是引起免疫相關的反應。因此，雖然缺乏這群病人用抗反轉錄病毒藥物的臨床研究，但從早期感染、及慢性感染者的資料推估，美國愛滋病毒治療指引仍然建議應在急性愛滋病毒感染時投予抗反轉錄病毒藥物的雞尾酒療法 (combined antiretroviral therapy)。[1] 在一個回顧型研究，對於 12 個月內感染 愛滋病毒的患者，給予抗病毒藥物，可以達到很好的抑制病毒的效果。[4]
總結來說，急性愛滋病毒感染，是在臨床上常被忽略的診斷，而此群患者亦有可能發生嚴重的症狀，甚至走上器官衰竭的路。因此，戰勝此疾病，端賴臨床醫師能夠適時地給予患者正確的診斷，並給予抗病毒藥物治療，才不會錯失黃金治療時機。
Table 2. 急性愛滋病毒感染 (acute HIV infection) 常見的臨床表現。[2] *
Homosexual or heterosexual route of transmission.#IVDU, intravenous drug use
Features (%) |
Overall
(n = 378) |
Male
(n = 355) |
Female
(n = 23) |
Sexual*
(n = 324) |
IVDU#
(n = 34) |
Fever |
75 |
74 |
83 |
77 |
50 |
Fatigue |
68 |
67 |
78 |
71 |
50 |
Myalgia |
49 |
50 |
26 |
52 |
29 |
Skin rash |
48 |
48 |
48 |
51 |
21 |
Headache |
45 |
45 |
44 |
47 |
30 |
Pharyngitis |
40 |
40 |
48 |
43 |
18 |
Cervical adenopathy |
39 |
39 |
39 |
41 |
27 |
Arthralgia |
30 |
30 |
26 |
28 |
26 |
Night sweats |
28 |
28 |
22 |
30 |
27 |
Diarrhea |
27 |
27 |
21 |
28 |
23 |
Table 3. 愛滋病毒感染相關檢測，暴露至檢驗陽性所需時間[5]。
Test |
Target of detection |
Approximate time to positivity (days) |
Enzyme-linked immunoassay |
First generation |
IgG antibody |
35 to 45 |
Second generation |
IgG antibody |
25 to 35 |
Third generation |
IgM and IgG antibody |
20 to 30 |
Fourth generation |
IgM and IgG antibody and p24 antigen |
15 to 20 |
Western blot |
|
IgM and IgG antibody |
35 to 50 (indeterminate) |
45 to 60 (positive) |
HIV viral load test |
Sensitivity cut-off,50 copies/mL |
RNA |
10 to 15 |
Ultrasensitive cut-off, 1 to 5 copies/mL |
RNA |
5 |
參考文獻
- Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf (Accessed on May 01, 2014).
- Daar ES, Pilcher CD, Hecht FM. Clinical presentation and diagnosis of primary HIV-1 infection. Curr Opin HIV AIDS 2008; 3:10-5
- Chen Y-J, Tsai H-C, Cheng M-F, Lee SS-J, Chen Y-S. Primary Human Immunodeficiency Virus Infection Presenting as Elevated Aminotransferases. J Microbiol Immunol Infect 2010; 43:175-79
- Kassutto S, Maghsoudi K, Johnston MN. Longitudinal analysis of clinical markers following antiretroviral therapy initiated during acute or early HIV type 1 infection. Clin Infect Dis. 2006;42(7):1024-31
- UpToDate: Acute and early HIV infection: Clinical manifestations and diagnosis
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Case Discussion
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