Infectious mononucleosis

Introduction to infectious mononucleosis Infectious mononucleosis is an acute mononuclear-macrophage system proliferative disease caused by EB virus infection, and the course of disease is often self-limiting. Clinical manifestations of irregular fever, lymphadenopathy, sore throat; laboratory tests can be found in peripheral blood mononuclear cells significantly increased, abnormal lymphocytes, heterophilic agglutination test and anti-EBV antibody positive. basic knowledge The proportion of illness: 0.03%--0.07% Susceptible people: no specific people Mode of infection: non-infectious Complications: myocarditis, acute nephritis, pleural effusion

Causes of infectious mononucleosis

(1) Causes of the disease

In 1920, pathologists Sprunt and Evans first described the clinical features of IM. In 1932, Paul and Bunnell found a heterophilic antibody in the serum of IM patients that agglutinates sheep red blood cells. In 1964, Epstein, Achong and Barr DNA virus is found in the original lymphocytes cultured in Burkitt's lymphoma patients in Africa. It is also found that the virus can also be present in other diseases, so it is called Epstein barr virus (EBV), Epstein-Barr virus is herpesvirus, also known as human herpesvirus. Type 4 (HHV-4), a double-stranded DNA virus, consists of a nucleoid, a capsid, a capsomere, an envelope containing a viral DNA. The membrane shell is an icosahedral stereo-symmetric shape composed of tubular protein subunits; the envelope is derived from the host cell membrane and is divided into three layers with radial spinous processes on the surface.

Epstein-Barr virus has very special growth requirements, and it only breeds in African lymphoma cells, blood of infectious mononucleosis patients, leukemia cells and healthy human brain cells, so virus isolation is difficult, but Epstein-Barr virus can make antibodies negative. Lymphocytes in lymphocytes or fetal lymphoid organs are transformed into mother cell lines containing viral particles, so cord blood lymphocyte transformation tests can be used to examine Epstein-Barr virus, in addition, using cellular DNA and 3H-labeled viral DNA hybridization assays or cells DNA and Epstein-Barr virus RNA hybridization experiments, it can be found that the Epstein-Barr virus gene can be integrated into the genome of the host cell, and the expression of the viral gene can be increased when the bromine deoxyuridine is added to the culture medium or the culture medium lacking arginine. Amplitude.

Epstein-Barr virus has six antigenic components, such as viral capsid antigen (VCA), membrane antigen (MA), early antigen (EA, which can be subdivided into diffuse component D and localized component R). , complement-binding antigen (ie soluble antigen S), EB virus nuclear antigen (NA), lymphocyte detected membrane antigen (LYDMA), the first five can produce their respective antibodies; LYDMA The corresponding antibody has not been detected.

(two) pathogenesis

The pathogenesis of the disease has not yet been fully elucidated. The virus enters the oral cavity and replicates in the epithelial cells of the pharynx and parotid gland, which in turn invades the blood circulation and causes viremia, and further involves the tissues and organs of the lymphatic system. The receptor for EB virus (CD21) is involved first. In the acute phase, there is one virus per 100 B lymphocytes. When the recovery period is reduced, the number is reduced to 1/100 million. There are data showing memory B lymphocytes. It can still carry the virus for a long time, which may be related to the latent infection of the virus. The virus invades the B cell and causes its antigenic change, which in turn causes a strong reaction of the T cell. The latter can directly fight the B cell infected by the Epstein-Barr virus, in the peripheral blood. Abnormal lymphocytes are mainly T cells, CD4 T cells decrease, and CD8 T cells increase.

In the control of infection, cell-mediated immunity may play a more important role than humoral immunity. In the early stage of disease, NK cells, non-specific cytotoxic T cells (CTL) are very dense for the proliferation of B lymphocytes that control EB virus infection. Important; late stage disease, HLA-restricted CTL can specifically destroy virus-infected cells.

Infectious mononucleosis prevention

There is no effective preventive measure for this disease. It is recommended that the respiratory tract should be isolated in the acute phase. The respiratory secretions should be chlorinated, chloramine or boiled. However, it is considered that it is not necessary to isolate the patient. The viremia may be long after the patient recovers. For several months, if you are a blood donor, the blood donation period must be extended to at least 6 months after the onset of illness.

Infectious mononucleosis complications Complications Myocarditis Acute nephritis pleural effusion

1. Nervous system neurological complications are the primary factors for the death of early infectious mononucleosis. The timely manifestations of acute wave meningitis, radiculitis, brainstem encephalitis, etc., the incidence rate is about 1%, usually Occurred 1 to 3 weeks after onset; clinical manifestations of headache, dizziness, insomnia, convulsions, coma, hemiplegia, meningeal irritation, etc., occasionally acute cerebellar syndrome, transverse myelitis, manifested as unclear, eyeball Tremors, gait paralysis, ataxia, paraplegia, etc., although the condition of the nervous system complications is heavier, but most patients can fully recover, and rarely leave sequelae.

Infectious mononucleosis can activate a potential measles virus by suppressing immunity, leading to subacute sclerosing panencephalitis (SSPE).

2. Respiratory system accounts for about 5%, mainly for hilar lymphadenopathy and spotted shadows in the lungs, a few with pleural effusion, patients may have dry cough, antibacterial therapy is ineffective, pathological changes are similar to other viral pneumonia, generally Within 1 to 4 weeks, it will subside.

3. In the cardiovascular system complicated with myocarditis, the electrocardiogram showed T inverted, the low level and the PR interval were prolonged, and it could cause sudden death. At the autopsy, the myocardial fibers showed severe necrotizing inflammatory changes.

4. The kidney may involve the renal parenchyma and interstitial. The incidence of acute nephritis can be as high as 13%. The clinical manifestation is general nephritis, which is mainly characterized by rapid edema, protein in the urine, granular casts and cell casts. Causes transient urea nitrogen, elevated creatinine, but acute renal failure is rare, renal lesions are generally reversible, and the prognosis is good.

5. The glandular gland is mostly seen in the course of about 1 week. It is bilateral, with moderate tenderness, no suppuration, about 1 week subsided. Other complications include gastrointestinal bleeding, pericarditis, hemolytic anemia, and agranulocytosis. , thrombocytopenia, secondary infection, rupture of the spleen, etc.

6. About 30% of other patients may have hemolytic streptococcal infection, the incidence of spleen rupture is about 0.2%, usually more than 10 to 21 days after the disease, about 6% of patients with myocarditis.

Symptoms of Infectious Mononucleosis Symptoms Common symptoms Nausea, nasal congestion, liver function, abnormal spleen hyperactivity, multiple needle tip-like sputum, visible small bleeding, spotted papules

The incubation period ranges from 5 to 15 days, most of which are 10 days. The onset is urgent and slow, and nearly half have general malaise, headache, dizziness, chills, stuffy nose, nausea, vomiting, loss of appetite and other prodromal symptoms. The clinical manifestations are diverse, and each epidemic is very different from its main symptoms. The typical and common symptoms are:

1. Fever except for extremely light cases, all have fever, body temperature varies from 38.5 to 40 °C, can be relaxation, irregular or missed type, heat range from several days to several weeks, but also up to 2 ~ 4 For months, fever may be accompanied by chills, chills, heat may gradually recede or retreat, and the disease may have a relatively slow pulse in the early stage.

2. More than 90% of patients with lymphadenopathy have lymph node lesions, 60% of them have superficial lymphadenopathy, systemic lymph nodes can be involved, neck lymph nodes are the most common, underarm, inguinal, second, thoracic, mediastinal, mesenteric Lymph node can also be involved, ranging from 1 to 4 cm in diameter, showing moderate hardness, dispersing without adhesion, no obvious tenderness, no suppuration, bilateral asymmetry, swollen lymph nodes subsiding, usually within 3 weeks, even sustainable Longer time.

3. About half of patients with angina have pharynx, sacral (hanging sag), tonsil and other congestion, edema or swelling, a few ulcers or pseudomembrane formation, every patient has sore throat, small bleeding points in the ankle, gums It can also swell and has ulcers, and throat and tracheal edema are rare.

4. Liver, splenomegaly about 10% of cases have hepatomegaly, liver function abnormalities up to 2 / 3, 5% ~ 15% of jaundice, more than 50% of cases have splenomegaly, mostly only under the costal margin 2cm ~ 3cm, even spleen rupture can occur.

5. About 10% of rashes have rashes, pleomorphic, rash, scarlet fever-like rash, nodular erythema, urticaria, etc., occasionally hemorrhagic, more common in the trunk, less affected limbs, often 1 to 2 weeks after onset, 3 to 7 days subsided, leaving no traces, no desquamation, more typical mucosal rash, manifested as multiple needle-like defects, seen at the junction of soft, hard palate.

6. Nervous system symptoms The nervous system is rarely involved, manifested as acute aseptic meningitis, meningoencephalitis, brainstem encephalitis, peripheral neuritis, etc., clinical symptoms may appear, cerebrospinal fluid may have moderate protein And lymphocytes, and abnormal lymphocytes, the prognosis is mostly good, and those who are seriously ill will not leave sequelae after recovery.

Examination of infectious mononucleosis

1. The total number of white blood cells in blood is different. It can be normal at the beginning of the disease. The total number of white blood cells is often increased from 10 to 12 days after onset. The highest is 60×109/L, and it returns to normal in the third week.

Abnormal lymphocytes can occur on the 1st to 21st day of onset, and the proportion of peripheral blood nucleated cells can reach 10% to 30%, which is important when more than 10% or absolute value is greater than 1×l09/L.

Abnormal lymphocytes can be divided into three types according to their cell morphology: foam type, irregular type, and naive type (Fig. 2). This is especially common in the past. This abnormal cell may originate from T cells and may also be found in other viruses. Diseases, such as viral hepatitis, epidemic hemorrhagic fever, chickenpox, mumps, etc., but the percentage is generally less than 10%.

Recent studies have shown that peripheral blood smears in patients with acute infectious mononucleosis can show apoptotic lymphocytes, and the peripheral blood of a group of 27 patients with infectious mononucleosis is detected by flow cytometry. Lymphocyte apoptosis (88.9%) was found in 24 of the patients, compared with 3.75% in the control group. Therefore, apoptotic lymphocytes in peripheral blood may be a strong evidence for the diagnosis of infectious mononucleosis.

Platelet count can be reduced, about half of the patients have a platelet count below 140 × 109 / L, but rarely cause purpura, very few patients still have neutropenia or lymphopenia, mostly in the first month of the disease, may be Aberrant immune response, eosinophils do not disappear throughout the course of the disease, and are often increased during the recovery phase.

2. Bone marrow is lack of diagnostic significance, but other diseases such as blood diseases may be excluded. The neutrophil nucleus may be left-shifted in the bone marrow, the reticular cells may proliferate, and abnormal lymphocytes may appear, but this phenomenon may also be peripheral Due to hemodilution, granulomatous lesions can be found in the bone marrow.

3. The heterophilic agglutination test is 80% to 90% positive by the Paul-Bunnell heterophilic agglutination test. The principle is that the patient's serum often contains a heterophile antibody belonging to IgM, which can be agglutinated with sheep red blood cells or horse red blood cells. The duration of antibody in the body lasts for an average of 2 to 5 months. Those with late-onset heterophilic antibodies often recover slowly. About 10% of cases have negative heterophilic agglutination test, mostly light, especially in children, but Epstein-Barr virus antibody assays were all positive.

Normal people, patients with serum disease, and a small number of patients with lymphoblastoma, monocytic leukemia, tuberculosis, etc., may also have positive results in heterophilic agglutination tests (except for serum diseases, antibody titers are low), but available Guinea pig kidney and bovine erythrocyte absorption test to identify, normal people and the above-mentioned various patients (except for serum disease patients), blood heterophilic antibodies can be completely absorbed by the guinea pig kidney or partially absorbed by bovine red blood cells, and the patient's blood heterophilic antibody It can be partially absorbed by the kidneys of guinea pigs and fully absorbed by bovine red blood cells, while antibodies in the blood of patients with serum diseases can be completely absorbed by both.

The heterophilic agglutination test method is simple and suitable for routine clinical examination. Its titer has clinical value from 1:50 to 1:224. It is generally considered that its titer is diagnostic value above 1:80. If the heterophilic antibody is measured weekly. If its potency increases by more than 4 times, it is more meaningful. The use of horse red blood cells instead of sheep red blood cells, or papain-treated sheep red blood cells instead of guinea pig kidneys to absorb serum can improve the sensitivity and specificity of this test. The slide agglutination method was used to replace the sheep red blood cells with horse red blood cells, and the results were faster and more sensitive than the test tube method.

4. Epstein-Barr virus antibody determination After the human body is infected with Epstein-Barr virus, it can produce shell antibody, anti-membrane antibody, early antibody, neutralizing antibody, complement-binding antibody, virus-related nuclear antibody, etc., and the time and significance of various antibodies.

IgG-type VCA is elevated in the early stage of the disease, and it exists for a long time, and the titer does not change significantly. Therefore, although this index is conducive to epidemiological investigation, the clinical diagnosis value is not large. Generally, the titer is 1:160. The above suggestion may have a recent infection. There is no parallel relationship between this antibody and the heterophilic antibody. There is no clear relationship between the titer and the condition and the blood. If the specific IgM VCA can be determined, it is more conducive to diagnosis. It is only 4 to 8 weeks old and is valuable for the diagnosis of patients with current infections and negative for heterophile antibodies.

5. Epstein-Barr virus isolation Epstein-Barr virus can be cultured from the oropharyngeal lavage fluid and blood lymphocytes of patients, but the diagnosis can be isolated because the virus can be isolated from normal people and other diseases.

6. Other application of bovine erythrocyte hemolysis test to determine the serum hemolysin titer, such as titer above 1:400 is quite valuable for the diagnosis of this disease, in the acute phase of the disease can still detect a variety of autoantibodies, about 70% The patient has anti-I cold agglutinin, which lasts for about 6 weeks, and most patients may also have rheumatoid factor and anti-nuclear antibody positive.

In addition, more than half of patients may have alanine aminotransferase (ALT) abnormalities, generally elevated in the first week of the disease, peaked in the second week, can be reduced to normal within 5 weeks, and neurological symptoms may still appear Cerebrospinal fluid changes, mainly in the increase of the number of cells (tens to hundreds per microliter), mainly lymphocytes, abnormal lymphocytes can be found, sugar and chloride changes little, protein can be slightly elevated.

According to the condition, clinical manifestations, symptoms, signs, choose to do ECG, B-ultrasound, X-ray, CT and other examinations.

Diagnosis and diagnosis of infectious mononucleosis

Diagnostic criteria

The course of the disease varies from a few days to 6 months, but most of them are 1 to 3 weeks, occasionally recurrence, the course of recurrence is shorter, and the condition is mild. The disease course of a few cases can be delayed for several months or even years. It is called chronic active EB virus infection.

Because the clinical manifestations of this disease are sometimes varied, it is necessary to increase the vigilance against this disease to prevent missed diagnosis or misdiagnosis.

The disease is generally based on acute onset, fever, angina, lymphadenopathy, peripheral blood atypical lymphocytosis (>10%), positive heterophilic agglutination test can be diagnosed, EBV-specific serological examination, such as: EBV Positive IgM antibodies, or a dynamic increase in IgG antibody titers can be diagnosed as IM caused by EBV.

Fever with lymphadenopathy, and hepatosplenomegaly is very common, but at the same time there are obvious angina, especially exudative tonsillitis is rare, therefore, pay attention to clinical physical examination, carefully observe the pharynx, find angina Obviously, it should be highly suspected that IM, IM with multiple organ damage, its clinical manifestations are more complicated, and the diagnosis is more difficult. At this time, if the angina is prominent, it can provide important diagnostic clues for IM.

Peripheral blood cells appear in peripheral blood, which is helpful for the diagnosis of IM, but it is not specific. It must take into account other related viral infections and the possibility of protozoal infection; the detection of serum HA, especially in the short-term increase in titer, The relative specificity of IM is one of the important means of diagnosis; the detection of various EBV antibodies has a discriminating value for difficult cases, among which VCAIgM has the highest detection value, and VCAIgG titer is also valuable in the short term, such as Simultaneous detection of antibodies or antigens of other viruses that cause changes in IM blood is more conducive to pathogenic diagnosis.

Differential diagnosis

1. Nervous system neurological complications are the primary factors for the death of early infectious mononucleosis. The timely manifestations of acute wave meningitis, radiculitis, brainstem encephalitis, etc., the incidence rate is about 1%, usually Occurred 1 to 3 weeks after onset; clinical manifestations of headache, dizziness, insomnia, convulsions, coma, hemiplegia, meningeal irritation, etc., occasionally acute cerebellar syndrome, transverse myelitis, manifested as unclear, eyeball Tremors, gait paralysis, ataxia, paraplegia, etc., although the condition of the nervous system complications is heavier, but most patients can fully recover, and rarely leave sequelae.

Infectious mononucleosis can activate a potential measles virus by suppressing immunity, leading to subacute sclerosing panencephalitis (SSPE).

2. Respiratory system accounts for about 5%, mainly for hilar lymphadenopathy and spotted shadows in the lungs, a few with pleural effusion, patients may have dry cough, antibacterial therapy is ineffective, pathological changes are similar to other viral pneumonia, generally Within 1 to 4 weeks, it will subside.

3. In the cardiovascular system complicated with myocarditis, the electrocardiogram showed T inverted, the low level and the PR interval were prolonged, and it could cause sudden death. At the autopsy, the myocardial fibers showed severe necrotizing inflammatory changes.

4. The kidney may involve the renal parenchyma and interstitial. The incidence of acute nephritis can be as high as 13%. The clinical manifestation is general nephritis, which is mainly characterized by rapid edema, protein in the urine, granular casts and cell casts. Causes transient urea nitrogen, elevated creatinine, but acute renal failure is rare, renal lesions are generally reversible, and the prognosis is good.

5. The glandular gland is mostly seen in the course of about 1 week. It is bilateral, with moderate tenderness, no suppuration, about 1 week subsided. Other complications include gastrointestinal bleeding, pericarditis, hemolytic anemia, and agranulocytosis. , thrombocytopenia, secondary infection, rupture of the spleen, etc.

6. About 30% of other patients may have hemolytic streptococcal infection, the incidence of spleen rupture is about 0.2%, usually more than 10 to 21 days after the disease, about 6% of patients with myocarditis.

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