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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.


Presentation

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].

Fever
  • 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. Fever up to 40.9 C can last for more than a week.[symptoma.com]
  • 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]
  • See also GLANDULAR FEVER (infectious mononucleosis). Mononucleosis An infectious disease with symptoms that include severe fatigue, fever, sore throat, and swollen lymph nodes in the neck and armpits.[medical-dictionary.thefreedictionary.com]
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]
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]
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]
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]
Purpura
  • Acute cytomegalovirus mononucleosis has been associated with maculopapular rashes, petechiae, purpura, urticaria, ulcerative lesions, and vesicular eruptions.[ncbi.nlm.nih.gov]
  • Manifestations of Congenital Cytomegalovirus Inclusion Disease Microcephaly Thrombocytopenia with petechiae or purpura Intracerebral calcification Hepatosplenomegaly Chorioretinitis Rash Seizure disorders Jaundice Mental retardation and hearing loss ([atsu.edu]
  • The infection acquired in the may present a serious illness which begins shortly after birth with jaundice, purpura, hemolytic anemia, thrmobocytopenia, brain damage, microcephaly and paravetricular calcifications.[meddean.luc.edu]
  • Other cutaneous manifestations that have been reported include purpura, petechiae, morbilliform eruption, maculopapular rash, vesicles, and indurated plaques and nodules (Figure 3, Figure 4, Figure 5). Figure 2.[dermatologyadvisor.com]
Maculopapular Rash
  • Acute cytomegalovirus mononucleosis has been associated with maculopapular rashes, petechiae, purpura, urticaria, ulcerative lesions, and vesicular eruptions.[ncbi.nlm.nih.gov]
  • Maculopapular rash Maculopapular rash may be caused by a large variety of infectious and noninfectious agents. Maculopapular rashes associated with pruritus are not caused by infectious agents.[emedicine.medscape.com]
  • Other cutaneous manifestations that have been reported include purpura, petechiae, morbilliform eruption, maculopapular rash, vesicles, and indurated plaques and nodules (Figure 3, Figure 4, Figure 5). Figure 2.[dermatologyadvisor.com]
Urticaria
  • Acute cytomegalovirus mononucleosis has been associated with maculopapular rashes, petechiae, purpura, urticaria, ulcerative lesions, and vesicular eruptions.[ncbi.nlm.nih.gov]
Arthralgia
  • Abstract A 35 year old previously healthy physician had clinical manifestations of a mononucleosis illness complicated by arthralgia, vesicular pharyngitis and hepatitis.[ncbi.nlm.nih.gov]
  • In immunocompetent patients 90%: asymptomatic course 10% : CMV mononucleosis Fever, malaise, myalgia / arthralgia, fatigue, headache Less common: sore throat, cervical lymphadenopathy, hepatomegaly, splenomegaly Differential diagnosis: infectious mononucleosis[amboss.com]
  • The presentation of “CMV syndrome” (consisting of fever, leukopenia, atypical lymphocytes, hepatomegaly, myalgia, and arthralgia) is the most common manifestation of primary CMV in kidney transplant patients. 26 The Author show all author info GREGORY[aafp.org]
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]

Workup

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]

Treatment

  • 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]

Prognosis

  • 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

  • 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]

Epidemiology

  • 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]
Sex distribution
Age distribution

Pathophysiology

  • ., bone marrow, lungs, kidneys) References: [1] [2] [3] Pathophysiology Clinical features CMV infection is usually asymptomatic. Severe manifestations occur in immunocompromised states (e.g., following organ transplantation, AIDS ).[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]

Prevention

  • 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]

References

Article

  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: 2019-07-11 20:14