Case Discussion < Presentation of a case >      A 28-year-old man sought medical attention because of prolonged fever for 2 weeks. He had been in good state of health until 2 weeks ago, when he began to have high fevers; his temperature could be as high as 39.5℃ which was sometimes accompanied by chills, profound fatigue, and malaise. The fevers could be relieved temporarily by acetaminophen. There was no diurnal or nocturnal pattern. There was no sore throat, rhinorrhea, cough, dyspnea, nausea, vomiting, dizziness, photophobia, diarrhea, constipation, abdominal pain, joint pain, night sweats or weight loss. Because of prolonged fever, he visited our clinic for help.      He was a pharmaceutical representative and denied any other disease. There was no history of smoking, alcohol drinking, allergy, animal contact, recent travel, transfusion, tattoo, illicit drug use, commercial sex or homosexuality.      On physical examination, he had clear consciousness but was ill-looking. His height was 175 cm and weight was 75 kg. The temperature was 38.3°C, the pulse rate was 113 beats per minute and the respiratory rate was 16 breaths per minute. His blood pressure while in supine position was 136/77 mmHg. His conjunctivae were pink, and the sclerae were anicteric. The pupils were isocoric with prompt light reflexes. There was no oral thrush or oral ulcers in the oral cavity. The neck was supple without lymphadenopathy, engorged jugular veins, palpable thyroid gland or carotid bruits. The chest wall expansion was symmetric, and breath sounds were bilaterally clear. The heart beats were regular without audible murmur. The abdomen was soft. Bowel sounds were normoactive and liver and spleen were impalpable. His extremities were freely movable without edema. There was no cyanosis, petechiae, purpura or pigmentation. The genitalia were free of ulcers and discharge. < Laboratory data > 1. CBC/DC WBC HB PLT Seg Mono Lym Aty. lym K/μL g/dL K/μL % % % % 3.4 13.4 172 46 8 36 10  2. BCS+e- ALB TP T-Bil AST ALT ALP γ-GT g/dL g/dL mg/dL U/L U/L U/L U/L 4.0 7.0 0.6 268 526 190 53 UN CRE Na+ K+ CRP Glucose LDH mg/dL mg/dL mmol/L mmol/L mg/dL mg/dL U/L 10.1 0.7 138 4.2 0.9 110 1268 3. Urine analysis   Appearance Sp. Gr pH Protein Glucose Ketone OB       g/dL mg/dL     Y;C 1.02 6.5 - - - -   Urobilirubin Bilirubin Nitrate WBC RBC Epi Cast           HPF   1.0 - - 0-1 0-1 0-1 -    4. Other tests EBV- VCA-IgG EBV- VCA-IgM CMV IgM CMV IgG Anti-HIV 1 :80(+) 1 :10(-) + 1 :4 (-) -   IgM anti-HAV IgG anti-HAV IgM anti-HBc Anti-HBs HBs Ag - - - + - Anti-HBc Anti-HCV Toxoplasma IgM Toxoplasma IgG + - - <6.5 EBV = Epstein-Barr virus; VCA = viral capsid antigen; Ig G = immunoglobulin G; IgM = immunoglobulin M; CMV = cytomegalovirus; HIV = human immunodeficiency virus; HAV=hepatitis A virus ; HBc= hepatitis B core antigen ; HBs Ag =hepatitis B surface antigen ; HBV hepatitis B virus ; HCV = hepatitis C virus. < Course and treatment >      Relative lymphocytosis in peripheral blood sample with more than 10% atypical lymphocytosis was reported and infectious mononucleosis was diagnosed. Because IgM for EBV-VCA was negative and IgM for CMV was positive, infectious mononucleosis due to CMV infection was diagnosed. Supportive management with regular acetaminophen and hydration was given. Follow-up IgG for CMV turned positive four weeks later. The levels of aminotransferases decreased gradually. He was discharged in a stable condition. < Discussion >       臨床上病患出現持續發燒的時間延長，周邊血液檢查有相對較高數量(超過50％)的單核細胞(mononuclear cells，包括淋巴球及單核球)，且不典型淋巴球(atypical lymphocyte)超過10％，即可診斷為傳染性單核球過多症(infectious mononucleosis)。79％的傳染性單核球過多症是由Epstein-Barr virus (EBV)所引起，而剩下的多為急性巨細胞病毒感染(acute cytomegalovirus infection)所致，稱為CMV mononucleosis。其他更少見原因包括愛滋病毒(human immunodeficiency virus)、肝炎病毒、及弓漿蟲(Toxoplasma gondii)感染。       CMV mononucleosis可以發生於任何年紀，尤其好發於性行為頻繁的年輕成人，為接觸性傳染；潛伏期約20至60天，病程可持續2至6週，會有較長時間的高燒，有時會伴隨著寒顫、極度無力。常常出現肌肉酸痛、頭痛及脾臟腫大。相對於EB病毒常會造成的喉嚨痛、滲出性咽炎、及頸部淋巴腺腫大，在CMV mononucleosis病患反而少見。少數病人會出現德國麻疹樣疹(rubelliform rash)、肺炎、肋膜炎、心肌炎、關節炎及腦炎。      實驗室檢查可以發現相對多的淋巴球，而總白血球數可能是低、正常或偏高；雖然黃疸不常見，但是肝功能指數(serum aminotransferase & alkaline phosphatase)常常是上升的。異質性抗體(heterophil antibody)呈陰性、EBV的IgM呈陰性，且CMV的IgM呈陽性，即可診斷為CMV mononucleosis。亦可能短暫地出現冷凝球蛋白(cryglobulins)、類風濕性因子(rheumatoid factors)、冷凝集素(cold agglutinins)，及抗核抗體(antinuclear antibody)。非常少數的情況下會出現溶血性貧血、血小板過低及白血球過低。       CMV mononucleosis是一種自限性疾病，只需要支持性治療，一般不會留下後遺症。但是在非常少數情況也可能致死。可以持續數個月至數年在病患的尿液、生殖器分泌物及唾液中發現CMV。 < Reference > Cytomegalovirus. Am Fam Physician 2003;67:519. Mandell GL, Douglas RG, Bennett JE. Mandell, Douglas, and Bennett's Principles and practice of infectious diseases. 5th ed. Philadelphia: Churchill Livingstone, 2000. > 繼續教育考題 1. (B) 造成急性單核球過多症(acute mononucleosis syndrome)最常見的病毒？ A Human herpesvirus 6 B Epstein-Barr virus C Cytomegalovirus D Human immunodeficiency virus E Hepatitis B virus 2. (B) 下列哪一個檢查結果可以排除Epstein-Barr virus感染？ A 抗核抗體(ANA)陽性 B 異質性抗體(antiheterophil)陰性 C 類風濕性因子(rheumatoid factor)陽性 D 冷凝球蛋白(cryglobulins)陰性  E 冷凝集素(cold agglutinins)陽性 3. (C) 有關CMV mononucleosis的敘述何者有誤？ A 接觸性感染 B 支持性療法即可 C 主要以低體溫表現 D 潛伏期可達60天之久 E 少見頸部淋巴結腫大 4. (A) 有關CMV mononucleosis的敘述何者有誤？ A 常出現黃疸  B 肝功能指數(AST & ALT)常上升 C 脾臟腫大 D 白血球數增加 E 白血球數減少 5. (B) 對於診斷CMV mononucleosis下列哪一個檢查最適合？ A Heterophil antibody test B CMV IgM antibodies C CMV IgG antibodies D CMV polymerase chain reaction E CMV culture 6. (E) 有關CMV的傳染途徑下列何者最少見？ A 唾液 　 B 精液 C 陰道分泌物 D 尿液 E 血液 答案解說 【B 】Any febrile illness in which more than 10 percent of the patient's lymphocytes are atypical should raise the suspicion of mononucleosis. Though EBV will be the causative agent in the majority of cases, the differential diagnosis includes infection due to CMV, T. gondii, human herpesvirus 6, drug reactions, acute viral hepatitis, and acute HIV infection. 【B】The possibility of acute CMV infection should be explored if a negative heterophil antibody test rules out EBV mononucleosis. CMV infection, serum sickness, or another viral illness rarely causes a false-positive heterophil antibody test. 【C】A typical mononucleosis syndrome consists of an acute febrile illness with an increase of 50 percent or more in the number of lymphocytes or monocytes, with at least 10 percent of the lymphocytes being atypical. 【A】The characteristic laboratory abnormality of CMV mononucleosis is relative lymphocytosis in peripheral blood, with more than 10% atypical lymphocytes. Total leukocyte counts may be low, normal, or markedly elevated. Although significant jaundice is uncommon, serum aminotransferase and alkaline phosphatase levels are often moderately elevated. 【B】The best diagnostic test for establishing CMV mononucleosis is serology for CMV IgM antibodies, which should be positive in the majority of patients during the symptomatic phase of the illness. CMV polymerase chain reaction (PCR) or culture is not useful in the diagnosis of primary CMV infection, because a positive test may only reflect viral shedding via a transient reactivation from the latent state. 【E】CMV infection requires close, intimate contact with a person excreting the virus in their saliva, urine or other bodily fluids. CMV can be sexually transmitted and can also be transmitted via breast milk, transplanted organs, and rarely from blood transfusions.