Overview
A series of diseases caused by EBV infection.
Fever, swollen lymph nodes, pharyngeal swelling, sore throat, liver and spleen enlargement may be present.
This disease is mainly caused by EBV infection.
Treatment varies depending on the disease caused by EBV infection.
Definition
EBV infection refers to a series of related diseases caused by EBV infection.
Acute EBV infection is characterized by infectious mononucleosis (IM).
Some infected patients may have persistent or recurrent acute EBV-related symptoms, leading to the development of many chronic EBV infection-associated diseases, such as lymphoma in hematologic diseases, chronic active EBV infection (CAEBV), post-transplantation lymphoproliferative disorders, etc., and may even be complicated by hemophagocytic lymphohistiocytosis.
This article focuses on infectious mononucleosis as well as chronic active EBV infection.
Pathogenesis
The population is universally susceptible and occurs in all parts of the world, with more than 95% of adults worldwide having been infected with EBV, with an annual incidence of about 50-100/100,000 people, mostly in a sporadic manner [1].
It is most common in children and adolescents, and there is no gender difference in the incidence of the disease [2].
Causes
Causes
The disease is caused by EBV infection, and the basic conditions leading to the epidemic are threefold.
Source of infection
EBV carriers and patients are the main source of infection of this disease.
Route of transmission
The disease is mainly transmitted through close oral contact, such as kissing, sharing tableware, chewing food and feeding infants, etc. It can also be transmitted through droplet transmission and blood transfusion.
Susceptible people
The population is generally susceptible, but mostly in children and adolescents.
Symptoms
Main Symptoms
Infectious mononucleosis
The incubation period of the disease is 5-15 days, mostly 10 days.
The onset of the disease varies in urgency and clinical manifestations. Nearly half of the cases have prodromal symptoms, such as malaise, headache, chills, nasal congestion, nausea, loss of appetite, mild diarrhea, etc. Typical symptoms are described below.
Fever
Most patients have moderate fever, sometimes with high fever.
Most of them last for 5 to 10 days, and sometimes the low-grade fever may last for 1 month to several months.
The fever may be sudden or subside gradually.
Lymph node enlargement
Enlargement of lymph nodes can occur throughout the body, most commonly in the neck, followed by the armpits and groin (thigh roots).
Enlarged lymph nodes appear as hard, painless, pushable lumps, mostly no more than 3 centimeters in diameter.
The enlarged lymph nodes return to normal several weeks after the fever subsides.
Pharyngitis
It is mainly characterized by pharyngeal swelling, sore throat, and membranous covering of the tonsils.
In severe cases of pharyngeal swelling, breathing and swallowing difficulties may occur.
Hepatosplenomegaly
Some patients have moderate splenomegaly, with the spleen palpable under the left rib cage when lying on the right side and flexing the left lower limb, and pain and tenderness on pressure.
Some patients have enlarged liver, which can be palpated under the right rib cage, and some have mild yellowing of the skin and sclera (whites of the eyes).
Skin Rash
About 1/3 of the patients will develop a rash, which varies in shape and is often a papular or maculopapular rash that occurs on the trunk and extremities. It usually lasts about 1 week and subsides without flaking or hyperpigmentation.
Some patients may have multiple pinpoint-sized hemorrhagic dots on the palate in the mouth, which may occasionally fuse to form a large area and last for 3 to 4 days.
Chronic active EBV infection
CAEBV is characterized by persistent or recurrent episodes of infectious mononucleosis-like symptoms, including fever, abnormal liver function, splenomegaly and lymph node enlargement.
In addition, coagulation disorders, central nervous system involvement, interstitial pneumonitis, severe allergy to mosquito bites and EBV-associated cowpox-like herpes may also be present.
Complications
Splenic rupture
Initially left upper abdominal pain, pressure, rebound pain and muscle tension, gradually spreading to the whole abdomen.
Myocarditis
There may be palpitations, shortness of breath, chest tightness, and discomfort in the precordial area.
Autoimmune hemolytic anemia
There may be hemolytic symptoms such as chills, high fever, low back pain, vomiting and diarrhea.
Thrombocytopenic purpura
There may be dark purple plaques of different sizes on the skin and mucous membranes.
Neurological complications
Such as meningitis, meningoencephalitis, etc. There may be symptoms of meningeal irritation such as severe headache, vomiting, and neck stiffness.
Liver failure
There may be weakness, loss of appetite, abdominal distension, nausea, vomiting, yellow staining of the skin and sclera (whites of the eyes) that gradually deepens over a short period of time.
Consultation
Department of Medicine
Department of Infectious Diseases
If symptoms such as fever, sore throat, enlarged lymph nodes, or rash appear, it is recommended that you consult a doctor promptly.
Pediatrics
Children with the above symptoms can also consult the Department of Pediatrics.
Emergency Medicine
If there is an emergency such as high fever, convulsion, respiratory distress, etc., it is recommended to consult a doctor immediately.
Preparation for medical treatment
How to get to the doctor: registration, preparation of documents, common problems
Tips for seeking medical treatment
For those with fever, it is recommended to record the temperature change for the doctor’s reference.
It is recommended to wear loose-fitting clothes and try not to wear dresses, jumpsuits, etc. to facilitate the examination.
Preparation Checklist
Symptom Checklist
Particular attention should be paid to the time of onset of symptoms, special manifestations, etc.
Is there fever? What is the highest degree?
Is there a sore throat, redness and swelling of the throat?
Is there a rash?
Is there a palpable neck swelling? Is the swelling accompanied by pain?
Is there a palpable abdominal mass in the right upper abdomen?
How long have the above symptoms lasted?
List of medical history
Has there been any contact with patients with EBV infection?
Any history of drug or food allergy?
Any history of hypertension, diabetes, etc.?
Checklist
Test results in the last six months, which can be carried to the doctor’s office
Laboratory tests: blood test, EBV antibody test, EBV nucleic acid test, etc.
Imaging tests: abdominal ultrasound, etc.
Medication list
Medication used in the last 3 months, if available, bring along the box or package for medical consultation
Antiviral drugs: ganciclovir, acyclovir, etc.
Antipyretics and analgesics: ibuprofen, acetaminophen, etc.
Diagnosis
Diagnosis is based on
Medical history
History of close contact with EBV carriers or EBV-infected patients.
Clinical manifestations
There may be prodromal manifestations such as malaise, headache, chills, nasal congestion, nausea, loss of appetite and mild diarrhea.
There may also be fever, sore throat, pharyngeal swelling, enlarged lymph nodes, skin rash and other typical manifestations.
Some patients may have moderate splenomegaly, with the spleen palpable under the left rib cage when lying on the right side and flexing the left lower limb, and pain and tenderness on pressure.
Some patients have hepatomegaly, and the liver can be palpated under the right rib cage, and some have mild yellowing of the skin and sclera (white of the eyes).
Laboratory Tests
Blood count
A white blood cell count, the percentage of lymphocytes and monocytes, and the presence and percentage of heterogeneous lymphocytes (lymphocytes with abnormal morphology) may be used to clarify the presence of infection and aid in the diagnosis.
There may be an increased white blood cell count and an increased percentage of lymphocytes. The presence of more than 10% of heterogeneous lymphocytes is diagnostic.
Liver function tests
Some patients may have liver impairment and may have elevated aminotransferases.
Coagulation tests
Some patients may be accompanied by abnormal coagulation function, and may have decreased fibrinogen and prolonged clotting time.
EBV Antibody Measurement
IgM and IgG antibodies to viral capsid antigen (VCA) and anti-EB virus nuclear antigen antibody (anti-EBNA) IgG can be detected in serum to clarify whether or not the patient is infected with EBV.
If anti-VCA IgM is positive, anti-VCA IgG is negative and anti-EBNA IgG is negative in the antibody test, it suggests initial infection with EBV.
If anti-VCA IgG is positive and anti-EBNA IgG is negative, it suggests recent EBV infection.
Positive anti-VCA IgG and positive anti-EBNA IgG suggests previous infection with EBV.
Heterophilic Agglutination Test
To detect the presence of IgM heterophilic antibodies to EBV in the serum.
The agglutination value is above 1:64, and it is still positive after absorption by guinea pigs, which has diagnostic value.
Lacks specificity and is rarely used.
EBV nucleic acid test
Blood, urine and other body fluids are taken as specimens, and polymerase chain reaction (PCR) technology is applied to amplify viral DNA fragments for nucleic acid detection.
The presence of EBV DNA in the specimen helps to confirm the diagnosis.
Imaging
Abdominal ultrasound, abdominal CT, and chest CT can be used to clarify the presence of hepatosplenomegaly and interstitial lung disease.
Differential diagnosis
Herpes pharyngitis
Similarity: Both may have fever and symptoms of pharyngitis such as sore throat and pharyngeal swelling.
Differences: Herpes pharyngitis is mainly caused by coxsackievirus, without symptoms such as enlarged lymph nodes, liver and spleen, etc. It can be distinguished from herpes pharyngitis by combining with medical history and laboratory tests.
Exudative tonsillitis caused by streptococcus.
Similarity: both may have fever, loss of appetite, malaise, sore throat, pharyngeal swelling and other symptoms.
Differences: Exudative tonsillitis caused by streptococcus is mainly caused by hemolytic streptococcus B. It has no symptoms such as enlarged lymph nodes, liver and spleen, etc. It can be distinguished from other forms of streptococcal tonsillitis by combining with the history and laboratory examination.
Lymphocytic leukemia
Similarities: both may have malaise, fever, enlarged lymph nodes, hepatosplenomegaly, skin rash, etc.
Differences: Lymphoblastic leukemia is a blood tumor without viral infection and cannot be cured by itself; it can be differentiated by history and laboratory tests.
Cytomegalovirus infection
Similarity: Both may present with hepatosplenomegaly.
Differences: cytomegalovirus disease is less common with sore throat and enlarged cervical lymph nodes, and there is no heterophilic lectin or EBV antibody in the serum, so the diagnosis depends on virus isolation and specific antibody measurement.
Treatment
Aim of treatment: alleviate symptoms, control disease progression, prevent and reduce complications.
Treatment principle: infectious mononucleosis is self-limiting, mainly adopting general symptomatic treatment, antiviral treatment, etc.; the treatment of chronic active EBV infection is mainly to control the progression of tumors and inflammatory diseases, mainly adopting allogeneic hematopoietic stem cell transplantation and so on.
Infectious mononucleosis
General symptomatic treatment
Bed rest should be used to reduce physical exertion and promote recovery from the disease. Those with splenomegaly should even reduce their activities to prevent splenic rupture.
Drink plenty of water and eat a light, high-calorie diet.
For those with fever, physical methods or antipyretics are needed to lower the temperature, such as acetaminophen.
For sore throat, analgesics, such as indomethacin, can be used.
Those with severe liver damage need to be treated with hepatoprotective medications, such as dicyclomine.
In the presence of myocarditis, severe edema of the pharynx, autoimmune hemolytic anemia, neurological complications, etc., oral glucocorticoid therapy such as prednisone is needed.
Antiviral therapy
Mainly acyclovir and ganciclovir.
Antiviral therapy has a limited effect on the improvement of symptoms and the overall course of the disease, so it is generally not routinely used.
Chronic active EBV infection
Antiviral therapy
Currently, the efficacy of antiviral therapy such as acyclovir and interferon is not conclusive.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT)
allo-HSCT is currently recognized as a curative option for CAEBV, and it is recommended that allo-HSCT be performed as soon as possible after the diagnosis is clear.
A “three-step” transplantation program can be used, as follows.
首先联合泼尼松龙、环孢素、依托泊苷进行化学治疗抑制被激活的T淋巴细胞/NK细胞/巨噬细胞。
通过监测外周血EB病毒DNA判断化学治疗效果，若治疗无效(EB病毒DNA下降≤10%)则进入第二步多药联合化学治疗，方案首选改良CHOP(环磷酰胺+吡柔比星+长春新碱+泼尼松龙)方案，其次为ESCAP(依托泊苷+阿糖胞苷+左旋门冬酰胺酶+甲泼尼龙+泼尼松龙)方案。
第三步为allo-HSCT，即免疫功能重建，减低剂量预处理方案的3年整体生存率明显高于清髓性预处理方案。
Others
The emergence of EBV-CTL infusion, monoclonal antibodies, JAK inhibitors, histone deacetylase inhibitors, protease inhibitors, etc., has provided new ideas for treatment, but large-scale clinical trials are needed to evaluate the effects.
Prognosis
Cure
Infectious mononucleosis is self-limiting and has a favorable prognosis; most cases resolve in 2-3 weeks, with a few cases lasting 1 month or several months, and some cases may be prolonged for several years; occasional relapses occur, and the disease is less severe after relapses.
Chronic active EBV infection is easily combined with hemophagocytic lymphoproliferative syndrome, lymphoma and other diseases, and the prognosis is poor.
Harmfulness
Symptoms such as fever and sore throat may occur, affecting normal life and work.
A few may cause serious complications such as splenic rupture, myocarditis, autoimmune hemolytic anemia, thrombocytopenic purpura, meningitis, meningoencephalitis, hemophagocytic syndrome, and liver failure, which can be life-threatening.
The disease is contagious and may be transmitted to others.
Daily
Daily Management
Dietary management
It is advisable to eat nutritious, light and easily digestible food.
Drink plenty of water as appropriate, eat more fiber-rich food, such as fresh vegetables, fruits and melons, and keep bowel movement smooth.
Life management
In the acute stage, bed rest should be taken and avoid strenuous exercise.
Do not forcefully squeeze the abdomen to avoid inducing splenic rupture.
Pay attention to rest and avoid exertion.
Maintain sufficient sleep time and avoid staying up late.
Pay attention to mental health, release pressure in time, avoid anxiety, depression, excessive tension and other bad emotions.
Prevention
There is no effective means of prevention for this disease and there is no effective vaccine, but the following measures can help reduce the risk of developing the disease.
Avoid close contact with EBV-infected patients.
Exercise more, eat a healthy diet and strengthen your immunity.