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]

  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. [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]

  Significant differences were found only for the presence of cervical lymphadenopathy, which was more frequent in the Epstein-Barr group (83.2%) compared with the cytomegalovirus group (75%). Fever was the most frequent symptom in both groups. [journals.lww.com]

  Cervical lymphadenopathy is less commonly seen in heterophile-negative mononucleosis.The results of liver function tests are abnormal. [atsu.edu]

• Infectious Mononucleosis

  /mono·nu·cle·o·sis/ ( -noo″kle-o´sis ) excess of mononuclear leukocytes (monocytes) in the blood. cytomegalovirus mononucleosis an infectious disease caused by a cytomegalovirus and resembling infectious mononucleosis. infectious mononucleosis an acute [medical-dictionary.thefreedictionary.com]

  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]

  CMV mononucleosis is the heterophile-negative cause of infectious mononucleosis that is most likely to be confused with EBV infectious mononucleosis. [emedicine.medscape.com]

• Malaise

  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]

  The characteristic set of symptoms for mono is the clinical triad of sore throat, fever and lymphadenopathy together with significant malaise. [quidel.com]

  […] 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]

  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]

• Lymphadenopathy

  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. [symptoma.com]

  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]

  The characteristic set of symptoms for mono is the clinical triad of sore throat, fever and lymphadenopathy together with significant malaise. [quidel.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]

• Splenectomy

  We describe a case of severe CMV mononucleosis that was acquired naturally decades after splenectomy. [ncbi.nlm.nih.gov]

• Epigastric Pain

  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]

  He presented with 3 weeks history of diarrhea associated with epigastric pain. Endoscopy was done and duodenal biopsies were taken to rule out gluten-enteropathy. [Figure 1] shows the microscopic image of duodenal biopsy with CMV inclusion bodies. [caijournal.com]

• 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]

  Cytomegalovirus Infection in a Normal Person Common Less common Rare Asymptomatic* Exudative pharyngitis Icteric hepatitis Mononucleosis syndrome Splenomegaly Guillain-Barré syndrome Fever Cervical adenopathy Encephalitis Malaise Nonspecific rash Myocarditis [aafp.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]

  However, the mononucleosis syndrome associated with CMV typically lacks signs of enlarged cervical lymph nodes and splenomegaly. [27] [12] CMV has also been associated with Guillain–Barré syndrome, [28] type 1 diabetes, [29] and type 2 diabetes. [30] [en.wikipedia.org]

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].

• Erythrocytes Increased

  Complement-fixation antibody titers against cytomegalovirus and levels of activity against cord erythrocytes increased as the anemia worsened and remained at high levels when recovery from the anemia occurred. [ncbi.nlm.nih.gov]

• 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

  Groups of hepatocytes surrounding these areas contain intranuclear eosinophilic viral bodies (Cowdry type A inclusions). Inflammatory response is minimal. Enlargement and multinucleation may precede the appearance of inclusion bodies. [meddean.luc.edu]

  PCR and in-situ hybridization positivity does not necessarily mean active infection as these may be positive in latent infection. [39], [40] Light microscopy for a demonstration of CMV inclusion bodies is an easy technique, but viral inclusion bodies [caijournal.com]

  Two cells (centre-left) have the characteristic (cytoplasmic) viral inclusion bodies (small pink globules ). H&E stain. CMV infection can be demonstrated microscopically by the detection of intranuclear inclusion bodies. [en.wikipedia.org]

• 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. 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]

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]

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]

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]

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]

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]

(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 Pathogen : cytomegalovirus ( CMV, human herpes virus 5, HHV-5 ) Transmission Blood transfusions Sexual transmission Droplet transmission Transplant-transmitted infection (e.g., bone marrow, lungs, kidneys) References: [1] [2] [3] Pathophysiology [amboss.com]

Etiology CMV, or HHV-5, is a herpes virus. As is seen with all herpes viruses, infection is lifelong. [atsu.edu]

Elevated white blood cell count will be noted during lab work and may remain this way for up to 4 months. [8] Etiology/Causes Mono is caused by the Epstein-Barr virus, a form of herpesvirus. [physio-pedia.com]

(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]

Abstract Seventy consecutive cases of cytomegalovirus mononucleosis (CMV-MN) were examined retrospectively from their clinical, epidemiological and serological aspects. [ncbi.nlm.nih.gov]

Epidemiology Epidemiological data refers to the US, unless otherwise specified. [amboss.com]

“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]

Etiology Pathogen : cytomegalovirus ( CMV, human herpes virus 5, HHV-5 ) Transmission Blood transfusions Sexual transmission Droplet transmission Transplant-transmitted infection (e.g., bone marrow, lungs, kidneys) References: [1] [2] [3] Pathophysiology [amboss.com]

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]

Welcome to PT 635 Pathophysiology of Complex Patient Problems This is a wiki created by and for the students in the School of Physical Therapy at Bellarmine University in Louisville KY. [physio-pedia.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]

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]

An effective vaccine for the prevention of maternal CMV infection is requried. [patient.info]

How can CMV be prevented? CMV is common and usually not preventable. There is no licensed available vaccine against CMV. [texaschildrens.org]

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]

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.