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Cytomegalovirus Mononucleosis

Cytomegalovirus mononucleosis is a viral infection caused by a virus from the Herpesviridae family. It primarily affects immunocompetent patients and is similar in presentation to mononucleosis caused by the Epstein-Barr virus.


Cytomegalovirus mononucleosis presentation is indistinguishable from mononucleosis caused by Epstein-Barr virus (EBV) apart from several details discussed later. Mononucleosis manifests chiefly in young children and adolescents who had no prior immunocompromising diseases [2].

Presentation in this disease roughly consists of a triad of fatigue, fever, and lymphadenopathy. Fatigue, although a subjective symptom, is very well documented in the literature [1] [2]. Fever up to 40.9°C can last for more than a week. Lymphadenopathy in CMV mononucleosis does not only affect cervical lymph nodes, but also involves mesenteric nodes. Patients present with abdominal pain due to these enlarged nodes along with hepatomegaly and splenomegaly. Swelling of the eyelids follows cervical lymphadenopathy with a disturbance of blood flow in the facial area [2].

To differentiate the mononucleosis caused by CMV from that caused by EBV, physicians must primarily seek immunologic evidence. Although, some features of presentation can help to distinguish the two conditions. CMV is thought to provoke larger mesenteric lymphadenopathy and swelling of the eyelids. Likewise, a skin rash commonly develops due to a reaction of complement fixing antibodies (for which CMV is responsible) to antibiotics [3]. The rash can be macular, papular, maculopapular or similar to the rubella rash [4]. To confirm a rash caused by CMV, a use of antibiotics has to be documented and possible prior causative agents excluded from history [2].

Additionally, sore throat, inflamed and hypertrophied tonsils with possible purulent plaques, and hyperemic pharynx is often documented on examination [2] [5].

Cervical Lymphadenopathy
  • Cervical lymphadenopathy, hepatomegaly and lymphocytosis (greater than 5000/microliter) were more common in children and protracted fever more common in adults.[ncbi.nlm.nih.gov]
  • Swelling of the eyelids follows cervical lymphadenopathy with a disturbance of blood flow in the facial area. To differentiate the mononucleosis caused by CMV from that caused by EBV, physicians must primarily seek immunologic evidence.[symptoma.com]
  • Discussion: Infectious Mononucleosis is a syndrome typically seen in teenagers and young adults, which is characterized by fever, cervical lymphadenopathy, pharyngitis and fatigue.[shmabstracts.com]
  • Cervical lymphadenopathy is less commonly seen in heterophile-negative mononucleosis.The results of liver function tests are abnormal.[atsu.edu]
  • Patients with CMV mononucleosis may be older, have a longer duration of fever, and have less cervical lymphadenopathy. However, such clinical findings are inadequate to differentiate between the two viruses.[emedicine.medscape.com]
Infectious Mononucleosis
  • Exudative tonsillitis indistinguishable from infectious mononucleosis was sometimes seen in children but never in adults.[ncbi.nlm.nih.gov]
  • Abstract The mononucleosis-like syndrome due to cytomegalovirus (CMV) has many clinical features in common with classic Epstein-Barr virus (EBV) induced infectious mononucleosis (IM).[ncbi.nlm.nih.gov]
  • Infectious mononucleosis. mononucleosis (mono) [mon′ōno̅o̅′klē·ō′sis] Etymology: Gk, monos, single; L, nucleus, nut kernel; Gk, osis, condition mononucleosis See Infectious mononucleosis . mon·o·nu·cle·o·sis ( mon'ō-nū-klē-ō'sis ) Presence of abnormally[medical-dictionary.thefreedictionary.com]
  • Hectic fever was a characteristic feature in these otherwise remarkably asymptomatic individuals, without the classic features of heterophile-positive infectious mononucleosis.[ncbi.nlm.nih.gov]
  • Abstract Infectious mononucleosis (IM) is a clinical syndrome that is common in adolescents and young adults and is characterized by fever, lymphadenopathy, pharyngitis, and fatigue.[ncbi.nlm.nih.gov]
  • Abstract A 61-year-old man was admitted to our hospital because of fever and general malaise. We diagnosed his condition as cytomegalovirus (CMV) mononucleosis by hematological testing.[ncbi.nlm.nih.gov]
  • […] monocytes) in the blood. cytomegalovirus mononucleosis an infectious disease caused by a cytomegalovirus and resembling infectious mononucleosis. infectious mononucleosis an acute infectious disease caused by the Epstein-Barr virus; symptoms include fever, malaise[medical-dictionary.thefreedictionary.com]
  • The characteristic set of symptoms for mono is the clinical triad of sore throat, fever and lymphadenopathy together with significant malaise.[quidel.com]
  • Malaise and difficulty concentrating may last for months longer. EBV is not, however, a cause of chronic fatigue syndrome. The following are the most common symptoms of mononucleosis. However, each adolescent may experience symptoms differently.[vidanthealth.com]
Fever of Unknown Origin
  • Prompt diagnosis of CMV infection may exclude CMV-MN from the list of fevers of unknown origin, thus avoiding laborious patient workups.[ncbi.nlm.nih.gov]
  • False-positive reactions have resulted from the presence of rheumatoid factors. [27] CMV infection should be suspected in patients with clinical mononucleosis or fever of unknown origin. Most cases have a paucity of physical examination findings.[emedicine.medscape.com]
Epigastric Pain
  • Abstract A 44-year-old man with epigastric pain, fever, and atypical lymphocytosis was found to have severe antral gastritis with radiologic and endoscopic features suggestive of malignancy.[ncbi.nlm.nih.gov]
  • These results suggest that different mechanisms are operative in immunoregulation of lymphocyte recognition responses to the polyclonal activator Con A and immune-specific viral antigens during human CMV infection.[ncbi.nlm.nih.gov]
  • Abstract A 44-year-old man with epigastric pain, fever, and atypical lymphocytosis was found to have severe antral gastritis with radiologic and endoscopic features suggestive of malignancy.[ncbi.nlm.nih.gov]
  • This small outbreak suggests that CMV may be acquired as a venereal infection that sometimes progresses to the mononucleosis syndrome.[ncbi.nlm.nih.gov]
  • We studied the kinetic of release of sCD8 and sIL-2R during the convalescent phase in 8 patients and the data we have obtained suggest that sCD8 and sIL-2R may be of value in monitoring T cells activation during CMV mononucleosis.[ncbi.nlm.nih.gov]
  • This data suggests that, as with hepatitis B, viral antigen is not identifiable in acute CMV hepatitis in the immunocompetent host, perhaps due to active destruction of infected cells.[ncbi.nlm.nih.gov]
Guillain-Barré Syndrome
  • Rare complications include: Colitis Guillain-Barré syndrome Nervous system (neurologic) complications Pericarditis or myocarditis Pneumonia Rupture of the spleen Inflammation of liver (hepatitis) When to Contact a Medical Professional Call for an appointment[mountsinai.org]
  • Complications of infection are uncommon in immunocompetent hosts but include: Guillain-Barré syndrome. Meningoencephalitis. Pericarditis. Myocarditis. Thrombocytopenia. Haemolytic anaemia.[patient.info]
  • […] in immunocompetent hosts, even severe cases, is usually good, rarely requires a full course of antiviral treatment, and usually resolves during CMV induction therapy. [8] Rarer manifestations of CMV infections in immunocompetent individuals include Guillain-Barré[emedicine.medscape.com]


Cytomegalovirus mononucleosis can be diagnosed by detecting IgM or IgG antibodies to CMV. Reagents for immunoglobulin precipitation tend to be expensive and an algorithm of immunological testing was proposed by Tsaparas et al [6]. It is based on exclusion and suggests that:

  1. Firstly, an assessment of heterophile antibodies (monospot test) must be made. Heterophile antibodies are present in EBV infection and mostly negative in CMV and other causative agents. Hence positive results exclude CMV.
  2. Lymphocytosis or more than 10% of atypical lymphocytes are pathognomic for either EBV or CMV, and exclude HIV as the causative agent.
  3. Negative serology for EBV-specific IgM antibodies excludes EBV.
  4. If EBV IgM is negative, then specific IgM for CMV will either confirm CMV or exclude it.
  5. If CMV IgM serology is negative, there should be a suspicion of toxoplasmosis, hepatitis A, B, C or herpesvirus 6 mononucleosis.

Other tests for providing evidence is pp65 phosphoprotein antigen detection and polymerase chain reaction (PCR) in qualitative or quantitative modality. Pp65 method is proposed to be very accurate, efficient, and overall a cost-effective test [7].

Blood analyses comprises of a complete blood count with findings of leukopenia (that is more common in CMV infection) or lymphocytosis. Also, atypical lymphocytes or virocytes are sought as they are pathognomic for mononucleosis [2] [8]. Thrombocytopenia is not a common finding in a mononucleosis patient but is seen more frequently in CMV rather than EBV infection [2] [9].

Ultrasonography is useful in monitoring abdominal organ enlargement, specifically spleen, liver, and mesenteric lymph nodes [2].

In CMV mononucleosis aspartate and alanine transaminases are elevated and should be monitored for a possible liver damage [10].

Complement Fixing Antibody
  • Likewise, a skin rash commonly develops due to a reaction of complement fixing antibodies (for which CMV is responsible) to antibiotics. The rash can be macular, papular, maculopapular or similar to the rubella rash.[symptoma.com]
  • A significant rise of complement-fixing antibodies to CMV was found during the disease. Cytomegalovirus was isolated from the urine of four patients.[annals.org]
  • In a large study of 494 patients with infectious mononucleosis, 79% of cases were due to EBV, and, in the 73 heterophile antibody–negative patients, approximately half of these were CMV positive (rising complement-fixing antibodies). [25] In about a third[emedicine.medscape.com]
Viral Inclusion Body
  • Cytomegalic cells and viral inclusion bodies are usually absent. The picture is similar to that of infectious mononucleosis and can be confused with acute viral hepatitis. Diagnosis ( By Dr.[meddean.luc.edu]
Liver Biopsy
  • Abstract Six liver biopsies from previously healthy adult patients with cytomegalovirus (CMV) mononucleosis were studied by routine light microscopy and by the immunoperoxidase technique for CMV antigen.[ncbi.nlm.nih.gov]


  • Treatment with a proton pump inhibitor to suppress gastric acid secretion was useful to mitigate the epigastralgia and to hasten the ulcer healing.[ncbi.nlm.nih.gov]
  • Treatment . Treatment is chiefly symptomatic. Rest is especially important in the early stages of the disease, or later if the liver is involved. There is as yet no specific treatment for mononucleosis, and no immunization is available.[medical-dictionary.thefreedictionary.com]
  • Management of patients with immunodeficiency [ 12 ] The drug of choice for treatment of CMV disease is intravenous ganciclovir, although valganciclovir may be used for CMV treatment in selected cases.[patient.info]
  • Treatment In most children, there is no need for specific treatment for CMV infections.[healthychildren.org]
  • This illness requires no treatment as it goes away by itself. What is the treatment for CMV? There is no treatment for CMV mononucleosis, as it goes away by itself.[irishhealth.com]


  • However, screening for congenital CMV infection is not currently recommended in the UK. [ 13 ] Prognosis The prognosis of patients with CMV hepatitis is generally good. Most patients recover completely.[patient.info]
  • Outlook (Prognosis) Fever usually goes away in 10 days, and swollen lymph glands and spleen return to normal in 4 weeks. Fatigue may linger for 2 to 3 months. Possible Complications Throat infection is the most common complication.[nicklauschildrens.org]
  • What Is the Prognosis? Most children with CMV infections remain symptom free and lead completely normal lives, even though the virus remains inactive in the body.[healthychildren.org]
  • (Outcomes/Resolutions) A healthy immune system recovers faster, with little or no treatment, from Acute Cytomegalovirus Infection If the health condition of the patient is adversely affected, or if there are other complications, then the prognosis of[dovemed.com]
  • What Is the Prognosis for an Epstein-Barr Virus Infection? The prognosis for Epstein-Barr virus infection is good. Almost all people infected with EBV recover completely in about one to three months.[emedicinehealth.com]


  • Etiology CMV, or HHV-5, is a herpes virus . As is seen with all herpes viruses, infection is lifelong.[atsu.edu]
  • (Etiology) Acute Cytomegalovirus Infection is a contagious disease spreading by physical contact, such as through: Saliva Nasal fluids Vaginal fluids Semen Placenta Blood Organ transplantation It affects those who have weak immune systems, or those rendered[dovemed.com]
  • In rare cases, CMV can cause community-acquired pneumonia in immunocompetent hosts [8] and should be considered a possible etiology (along with influenza [human, swine, avian] and adenovirus) in cases of severe viral community-acquired pneumonia. [8][emedicine.medscape.com]
  • Etiology CMV, or human herpes virus 5, is a DNA virus that belongs to the family Herpesviridae and the subfamily Betaherpesvirinae.[dermatologyadvisor.com]


  • Abstract Seventy consecutive cases of cytomegalovirus mononucleosis (CMV-MN) were examined retrospectively from their clinical, epidemiological and serological aspects.[ncbi.nlm.nih.gov]
  • "Congenital cytomegalovirus (CMV) epidemiology and awareness". J Clin Virol. vol. 46. 2009; Dec. pp. S6-S10.[dermatologyadvisor.com]
  • Newborn screening of saliva or dried blood spots may provide better insights into the current epidemiology of congenital infection.[clinicaladvisor.com]
  • Epidemiology Infection rates are highest in children younger than age 6 and are increased for young adults.[atsu.edu]
  • Epidemiology Worlwide estimates of CMV infection prevalance vary from 50% to over 70% of all adults. [ 2 ] Infection may be passed via body fluids - eg, kissing, sexual intercourse and blood transfusion, or by tissue donation.[patient.info]
Sex distribution
Age distribution


  • The pathophysiology of splenic infarct in our patient was not determined and he was not tested for a hypercoagulable state.[shmabstracts.com]
  • Useful For Suggests clinical disorders or settings where the test may be helpful Aiding in the diagnosis of acute or past infection with cytomegalovirus (CMV) Determination of prior exposure to CMV Clinical Information Discusses physiology, pathophysiology[mayomedicallaboratories.com]
  • The role viremia plays in the pathophysiology of CMV disease is unknown. Life-threatening CMV pneumonia may develop in immunocompromised patients, with the incidence varying based on the type of transplant received.[emedicine.medscape.com]
  • Pathophysiology Upon infection of cells, CMV causes cytomegaly and condensation of the nuclear mass, while infection of organs results in inflammation and resultant organ dysfunction.[dermatologyadvisor.com]


  • This prevents documentation of the time of fetal infection. In the instance described, a 17-year-old pregnant female developed cytomegalovirus mononucleosis during her first trimester.[pediatrics.aappublications.org]
  • Although the more obvious symptoms may disappear after a period of rest, sufficient rest and curtailed activities must be maintained in order to improve the patient's severely weakened condition and prevent recurrence.[medical-dictionary.thefreedictionary.com]
  • Can CMV Infection Be Prevented? Currently, there's no vaccine to prevent CMV infection. Washing hands well and often can help reduce the risk of infection.[kidshealth.org]
  • How can CMV be prevented? CMV is common and usually not preventable. There is no licensed available vaccine against CMV.[texaschildrens.org]
  • An effective vaccine for the prevention of maternal CMV infection is requried.[patient.info]



  1. Cengiz AB, Cultu-Kantaroğlu O, Seçmeer G, Ceyhan M, Kara A, Gürgey A. Infectious mononucleosis in Turkish children. Turk J Pediatr. 2010; 52(3):245-54.
  2. Medović R, Igrutinović Z, Radojević-Marjanović R. Clinical and laboratory differences between Epstein–Barr and cytomegalovirus infectious mononucleosis in children. Srp Arh Celok Lek. 2016 Jan-Feb; 144(1-2):56-62.
  3. Klemola E, Von Essen R, Henle G, Henle W. Infectious-mononucleosis-like disease with negative heterophil agglutination test. Clinical features in relation to Epstein-Barr virus and cytomegalovirus antibodies. J Infect Dis. 1970 Jun; 121(6):608-14.
  4. Cohen JI, Corey GR. Cytomegalovirus infection in the normal host. Medicine (Baltimore). 1985 Mar; 64(2):100-14.
  5. Balasubramanian S, Ganesh R, Kumar JR. Profile of EBV associated infectious mononucleosis. Indian Pediatr. 2012; 49(10):837-8.
  6. Tsaparas YF, Brigden ML, Mathias R, Thomas E, Raboud J, Doyle P. Proportion positive for Epstein-Barr virus, cytomegalovirus, human herpesvirus 6, Toxoplasma, and human immunodeficiency virus types 1 and 2 in heterophile-negative patients with an absolute lymphocytosis or an instrument-generated atypical lymphocyte flag. Arch Pathol Lab Med. 2000;124:1324–30.
  7. Franco RF, Montenegro RM, Machado AB, Paris F, Menezes DS, Manfro RC. Evaluation of diagnostic tests for cytomegalovirus active infection in renal transplant recipients. J Bras Nefrol. 2017 Mar; 39(1):46-54.
  8. Balasubramanian S, Ganesh R, Kumar JR. Profile of EBV associated infectious mononucleosis. Indian Pediatr. 2012; 49(10):837-8.
  9. Son KH, Shin MY. Clinical features of Epstein–Barr virus-associated infectious mononucleosis in hospitalized Korean children. Korean J Pediatr. 2011; 54(10):409-13.
  10. Van den Bruel A, Thompson MJ, Haj-Hassan T, et al. Diagnostic value of laboratory tests in identifying serious infections in febrile children: systematic review. BMJ. 2011; 342:d3082.

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Last updated: 2018-06-21 19:17