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].

• Infectious Mononucleosis

  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]

• 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]

  […] 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]

• 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]

  […] 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, sore throat, lymphadenopathy [medical-dictionary.thefreedictionary.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]

• Splenectomy

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

• 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]

  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]

• 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]

• Severe Abdominal Pain

  abdominal pain, due to CMV affecting the intestines CMV mononucleosis - a disease presenting signs and symptoms similar to infectious mononucleosis, which include fatigue, nausea, tonsillitis, and sore throat Complications due to congenital CMV infection [dovemed.com]

• Suggestibility

  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]

• 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]

  […] 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 Sore throat Anemia [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]

  Other clinical abnormalities have been associated with CMV infection in normal hosts, including Guillain-Barré syndrome, meningoencephalitis, hemolytic anemia, and thrombocytopenia [ 1 ]. [herpesviridae.biomedcentral.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].

• Lymphocytes Increased

  During convalescence, helper T lymphocytes increase, suppressor T lymphocytes decrease, and Con A responses return to normal. [ncbi.nlm.nih.gov]

• 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]

• Intranuclear Inclusion Bodies

  The demonstration of intranuclear inclusion bodies in a few gastric glandular epithelial cells contributed to the diagnosis of CMV gastritis. [ncbi.nlm.nih.gov]

  inclusion bodies that have an owl-eye appearance Monospot (heterophile antibody ) test : negative Serological tests Direct evidence of viremia : especially useful in immunosuppressed patients PCR to detect CMV DNA in bodily fluids Indirect immunofluorescence [amboss.com]

  The biopsy showed stratified squamous epithelium with plenty of inflammatory cells with large cells showing typical intranuclear inclusion bodies suggestive of CMV esophagitis [Figure 3]. [caijournal.com]

  Morphologically, it is characterized by the presence of intranuclear inclusion bodies. Definition (MSH) Infection with CYTOMEGALOVIRUS, characterized by enlarged cells bearing intranuclear inclusions. [fpnotebook.com]

  Morphologically, it is characterized by the presence of intranuclear inclusion bodies. Cytomegalovirus (cmv) is a virus found around the world. It is related to the viruses that cause chickenpox and infectious mononucleosis (mono). [icd10data.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]

  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]

• 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]

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