Herpes simplex

Introduction to herpes simplex Herpes simplex is an infectious skin disease caused by herpes simplex virus (HSV) infection. The clinical feature of herpes simplex is the appearance of a single atrial blisters in the skin mucosa, which occurs mainly in the face or genital area and is prone to recurrence; the systemic symptoms are generally mild; but if herpetic encephalitis or systemic disseminated herpes occurs, then The condition can be quite serious and even life-threatening. HSV can cause intrauterine infection, and the fetus can be born with various forms of congenital malformation or developmental disorders, which is one of the common causes of the so-called "TORCH" syndrome. basic knowledge The proportion of illness: 0.025% Susceptible people: people with poor health habits Mode of infection: contact spread Complications: premature birth

Herpes simplex cause

(1) Causes of the disease

Herpes is a common and historically infectious skin disease; the relevant records are even seen in ancient Greece. In the 18th century, the existence of genital herpes was clinically noticed. After the 19th century, due to the industrial revolution, the population was densely populated and the population Large-scale mobility, increased chances of spreading herpes through general contact and sexual contact, led to an increase in the incidence of herpes-like diseases; physicians gradually recognized its infectivity and sexual transmission, and later discovered that herpes virus is characterized by latent infection.

The herpesvirus family is divided into three subfamilies, , , and , including 114 members, which have certain host specificity and infect human or other animals respectively. Currently, human herpesvirus includes at least 8 members.

The pathogen of herpes simplex is human herpes simplex virus. It is classified into the human herpesvirus family A subfamily, herpes simplex virus genus, and is divided into two subtypes: HSV-1 and HSV-2. The HSV-1 subtype mainly invades the waist. The above parts, especially the face, brain tissue, etc.; and HSV-2 mainly invade the lower part of the waist, especially the genitals, so it is called genital herpes; but this distinction is not strict.

Herpes simplex virus is spherical, consisting of a nucleocapsid and a viral envelope. The nucleocapsid is in the shape of an icosahedron and consists of 162 shell particles. The core contains a viral genome and is a linear double-stranded DNA molecule with a length of 15226 kb. The homology between the two subtypes of HSV-1 and HSV-2 is only 47% to 50%, the herpes simplex virus genome encodes at least 70 different proteins, and the mature viral nucleocapsid contains at least seven proteins. The inner surface of the nucleocapsid has a layer of inner membrane with a physical structure that is not completely defined. It contains four protein components and is involved in the transcriptional replication of viral genes. The outer membrane of herpes simplex virus is a bilayer containing lipoprotein with complex glycoprotein components. There are at least six species; wherein the antigen specificity of glycoprotein gG is a serological basis for identifying HSV-1 or type 2, and after the herpes simplex virus invades the host cell, the viral DNA enters the nucleus and replicates, and at the same time, the viral DNA The transcript enters the cytoplasm and directs the synthesis of the viral structural protein in the cytoplasm; subsequently, the progeny viral DNA returns to the cytoplasm and assembles into infectious mature virus particles in herpes simplex virus. Replication, mature viral particles about a minority, and the rest is due to failure to timely processing, packaging, and is rapidly degraded or become non-infectious immature virus particles.

Herpes simplex virus is not strong against the outside world. It is heated at 56 °C for 30 min, irradiated with ultraviolet light for 5 min, and can be inactivated by a lipid solvent such as diethyl ether; however, its biological activity can be preserved for a long time at -70 °C.

In the in vitro culture environment, herpes simplex virus can infect almost all kinds of embryonic and neonatal animal-derived fibroblasts and epithelial cells, and quickly produce visible lesions; therefore, in some difficult cases, the method of in vitro culture of virus can be Used to help with clinical diagnosis.

(two) pathogenesis

After the herpes simplex virus invades, it can cause infection in the invasion; but in general, the virus goes up along the local nerve endings and is introduced into the ganglion. After a short period of 2 to 3 days of replication, the virus enters the latent infection state. The above-mentioned transient replication does not produce intact infectious virus particles. Under appropriate conditions, the herpes simplex virus can be activated and replicated in large quantities, and then spread down the nerve branches of the ganglion to the cells of the peripherally-dominated tissue. Causes herpes attacks, when the local infection is heavier, the virus can spread along the lymphatic vessels and cause lymphadenitis; when the body's immune function is low, viremia can form, and systemic disseminated infection occurs.

An important feature of herpes simplex virus infection is that the virus can be lurking in the body for a long time, and it can be recurrent due to irritation. The mechanism can be lurking in the ganglion of the innervation area of the lesion at the time of the virus invasion, such as trigeminal The ganglion, the vagus ganglion, the sacral ganglion, etc., the latent viral genome is freely present in the nerve cells, and can even be integrated into the host cell chromosome. When it is stimulated by certain factors, it can be activated, and the virus spreads along the nerve trunk. The chromophoric pyknosis of the dominant region produces a characteristic intracellular nuclear eosinophilic inclusion body (Cowdry A inclusion body); the membrane of adjacent infected cells fuses to form multinucleated giant cells; the cell necrosis disintegrates to form a single atrial Thin-walled blister can be surrounded by blush and local inflammatory reaction. In patients with primary herpes, the deep inflammatory reaction around the blister is heavier, and the recurrent herpes is lighter. After the blister collapses, the surface peels within a few hours. Superficial ulcers occur, and herpes lesions in the mucous membranes of the skin are more limited, but newborns and immunocompromised people may form viremia, even Body infections, involving vital organs, for herpes encephalitis or disseminated neonatal herpes in patients with congestive reflect its solid organ lesions of hemorrhagic necrosis and even more significant than the skin lesion, it is more serious illness.

Herpes simplex prevention

Neonates, immunocompromised persons, patients with chronic skin diseases such as eczema, as far as possible to avoid contact with patients with this disease, pregnant women with genital herpes should be cesarean section, can avoid birth canal infection, genital herpes patients should avoid sex, Avoiding magnetic therapy can reduce its spread. For repeated female genital herpes, regular cervical smears should be performed to detect cervical cancer early.

After the emergence of herpes simplex in the child care institution, it should be isolated at home, and can be returned after the treatment is cured. Pregnant women with genital herpes should be delivered by cesarean section. Pregnant women with a history of genital herpes should take amniotic fluid to test IgM type HSV. If the antibody is positive, it indicates that the fetus is suffering from intrauterine infection. Discuss with the patient whether to consider selecting 0.1% eye drops and isolate it from the affected mother to avoid feeding from the mother until the mother is cured; waiting for delivery and postpartum During the observation period, the mother and her newborn should be isolated from other maternal and newborns.

Adhere to the pre-marital medical examination system, avoid sexual intercourse and promote safe sex; if necessary, use condoms during sexual intercourse to help control or reduce the prevalence of genital herpes infection, organ transplantation (including bone marrow transplantation) immediately after surgery With acyclovir, patients with frequent recurrence of herpes should try to remove or avoid the predisposing factors. All of the above measures can help prevent the occurrence of herpes simplex infection or the original concealed infection. At present, the vaccine against herpes simplex has been used. Enter the clinical trial phase.

Herpes simplex complications Complications

Herpes infection can aggravate clinical symptoms after secondary bacterial infection. Herpetic keratitis is one of the common causes of blindness; genital herpes may cause psychogenic and organic sexual dysfunction in patients, intrauterine Infection can lead to premature birth, or congenital malformations.

Herpes simplex symptoms common symptoms herpes zoster-like appearance leucorrhea bleeding constipation nausea septic convulsions hand and foot long blisters toxemia small blisters on hand

Herpes simplex is classified into primary and recurrent.

The initial period of herpes simplex is 2 to 12 days, an average of 6 days. After treatment or self-remission of the initial herpes, the virus can still lie in the body for a long time, due to fever, ultraviolet radiation, wind, menstruation, trauma, emotional , tension, gastrointestinal dysfunction and other stimulating factors are activated, manifested as recurrent herpes, and often recurrent, many patients with recurrent herpes may have prodromal symptoms before the onset, such as local paresthesia.

Except for a few patients with systemic disseminated infection or herpetic encephalitis, herpes simplex is mostly erosive lesions of local skin mucosa. Systemic symptoms are generally mild, but relatively, systemic symptoms of patients with primary herpes It is often more obvious than recurrent herpes. The skin mucosal damage of the initial herpes often takes 2 to 3 weeks to heal, while the lesions of patients with recurrent herpes often disappear within 1 week. According to the anatomical features of the distribution of herpes lesions, Herpes can be named in different clinical categories as follows:

1. cutaneous herpes are more common in recurrent herpes or adult-onset herpes, which can occur in any part of the body, especially at the junction of the skin and mucous membranes. It is more common around the lips, mouth and around the nostrils. For "cold sore", when the skin herpes starts, itchy local, followed by burning or stinging, congestion and redness, large blisters of rice, several or dozens of clusters; blisters do not fuse with each other, but at the same time There are many clusters of blister, the blister wall is thin, the blister fluid is clear, and the blistering is broken in a short period of time. The patients with primary herpes, especially the traumatic skin herpes caused by the virus invading the obvious trauma of the skin, during the onset Often accompanied by local lymphadenitis and fever, some can reach 39 ~ 40 ° C, but most of the disease is not heavy; 2 ~ 10 days after the disease of dry skin and scarring, the entire course of disease is 2 to 3 weeks, the lesions are generally not left behind Scars may have localized pigmentation, but they will gradually subside in a short period of time.

2. Oral herpes Herpes and ulcers appear in the oral mucosa, tongue, gums, pharynx, and even lymph nodes. Oral herpes is more common in children under 5 years of age, but adults can also suffer, especially in the mouth - Genital sexual intercourse actor, in recent years, due to changes in sexual attitudes, such herpes patients with oral herpes are often seen clinically.

3. Genital herpes (genital herpes) is mainly caused by HSV-2 subtype infection, genital, perineal and genital skin around the thigh and buttocks can be affected, herpes, ulcers, and punctate or flaky erosion, male patients Most occur in the glans, foreskin, penis, etc., can also involve the scrotum, patients can feel local pain and discomfort, herpes virus infection caused by prostatitis, cystitis is rare; but the patient may still detect the virus in the semen, HSV-2 recessive Infection can lead to male infertility.

Female patients are more common in large, labia minora, clitoris, vagina, cervix, and can also affect the urethra. In general, if the lesion is confined to the cervix, the patient's symptoms may not be obvious, herpes cervicitis may only show increased vaginal discharge, or even asymptomatic However, genital herpes damage often leads to local and systemic symptoms such as local pain, paresthesia, urinary tract irritation, inguinal lymphadenopathy, and fever.

The anorectal rectum in patients with genital herpes can also be affected, especially in those with a history of anal intercourse, also known as herpetic proctitis. Because of the special site, it is easy to be mixed with suppurative secondary infection, so the symptoms of herpetic proctitis are more serious, patients have Anorectal pain, especially during defecation, often accompanied by urgency, fever, inguinal lymphadenitis, reflex urinary retention, constipation, etc.; or patients with fear of defecation due to pain, leading to constipation and dysuria, examination of perianal ulcers, some Although the patient's appearance of the anus is not abnormal, rectal microscopy can detect proximal mucosal herpes, pustular rash or diffuse erosion. Severe genital herpes can be complicated by aseptic meningitis or sacral nerve root myelitis. Causes neuralgia.

Due to the anatomical features of the genital area, genital herpes has a longer course than other areas of skin mucosal herpes. The initial onset can reach 3 to 6 weeks, and the recurrence of genital herpes is more common. Some patients may cause ulceration after healing. Plaque adhesion, urethral stricture and other sequelae, pregnant women with genital herpes may also lead to miscarriage, premature delivery or neonatal herpes infection, studies have suggested that in the mechanism of cancer such as cervical cancer, although the infection of human papillomavirus is more important However, there may still be some correlation with herpes simplex virus infection.

It should be emphasized that many male and female genital herpes patients are very mild and may have no obvious symptoms, which is one of the reasons for not being able to seek medical treatment in time, and thus further spread to their sexual partners.

4. Ocular herpes is herpes keratitis or conjunctivitis; most of them are unilateral, often accompanied by ipsilateral herpes herpes or edema and swollen lymph nodes, and damaged cornea with dendritic ulcer. Cause corneal perforation, iridocyclitis or anterior chamber empyema, severe cases can cause blindness.

5. Eczema-like herpes (eczema herpeticum) is a chronic dermatitis, dermatitis and other chronic skin diseases, combined with herpes simplex virus infection and caused by the disease, easily misdiagnosed as the original eczema aggravation, eczema-like herpes is a chickenpox Varicelliform eruption, the initial manifestation of small skin blisters, but later can be fused, bleeding or turned into pustules, some blister central can be umbilical concave; with local lymphadenopathy and fever, due to secondary bacterial infection Or due to the spread of viral blood, involving brain tissue or other important organs, the disease is further deteriorated, and the mortality rate can reach 10% to 50%.

6. herpetic whitlow (herpetic whitlow) herpes lesions occur at the terminal knuckles, and deep into the nail bed to form a hive-like necrosis; so local pain is severe, a migraine-like, may be associated with axillary lymph node enlargement, the course of 7 ~ For 10 days, medical workers who are often exposed to herpes with bare hands are at risk of developing the disease.

7. herpetic encephalitis (herpetic encephalitis) whether it is a primary or recurrent herpes infection, may cause herpetic encephalitis, herpetic encephalitis mainly involves the temporal lobe and brain stem, often forming hemorrhagic necrosis, The symptoms of temporal lobe are heavy; they can be damaged first, then spread to the opposite side, and spread to the meninges. This disease can be the result of viremia, but often herpesviruses invade the brain directly along the nascent pharynx along the olfactory nerve. Therefore, patients can be free of viremia, and it is difficult to detect the virus in cerebrospinal fluid, and only about 1/4 of patients with herpetic encephalitis are accompanied by cold sores. Clinical diagnosis is sometimes difficult.

Patients with acute onset, chills, fever, headache, nausea, vomiting, convulsions, convulsions, coma; physical examination of meningeal irritation, pyramidal tract signs, sensory loss, optic disc edema; cerebrospinal fluid examination pressure increased, clear appearance, The protein is moderately increased, the amount of sugar is normal or low, and the number of white blood cells is moderately increased, mostly below 0.4×109/L, mainly lymphocytes, and early may also be mostly neutrophils; EEG and brain scanning tips Localized lesions such as temporal lobe or diffuse lesions of brain tissue, about 2/3 of patients with herpetic encephalitis died within 2 weeks after onset, and survivors often have varying degrees of sequelae.

8. Neonatal HSV infection is generally caused by mothers with genital herpes, so neonatal herpes infection is mainly caused by HSV-2 subtype infection. Neonatal herpes infection mainly occurs in perinatal period, mostly in Infected by the mother during vaginal delivery; or after the mother's pregnancy is infected with herpes, the virus enters the uterine cavity through the cervix, resulting in intrauterine infection, intrauterine infection of the fetus can be premature, or born in various forms of congenital malformations, Or after birth, mental retardation, the so-called "TORCH" syndrome, which is named after toxoplasmosis ("T"), the initial acronym of the English name of other viruses together, that is, "TORCH" "TORCH" syndrome is one of the important topics currently facing reproductive health medicine. See "Cytomegalovirus infection" for details.

Neonatal infection with herpes virus may be asymptomatic and concealed, and may also cause clinical manifestations of different forms or degrees. Light is only oral, skin, and eye herpes. In severe cases, it is a central nervous system infection or even a whole body. A sporadic infection.

The clinical manifestations of neonatal herpes simplex infection may be fever, jaundice, difficulty breathing, hepatosplenomegaly, bleeding tendency, convulsions, coma, and one third of these children have no skin herpes damage, so it may Misdiagnosed as neonatal sepsis or other diseases, the mortality rate can be as high as 95%, and survivors often have different degrees of sequelae.

9. The systemic disseminated HSV infection is mostly neonatal, as described above; but it can also occur in primary or secondary immune suppression (eg AIDS patients or organ transplant patients), clinical The performance is severe, the mortality rate can reach 70%, or it is a chronic process.

10. HSV infection and HIV infection Epidemiological surveys in patients with genital herpes simplex indicate that such patients have a higher probability of contracting other sexually transmitted diseases, including HIV infection; in part because of HSV infection Genital skin mucosal erosion damage increases the chance of invasion of other sexually transmitted diseases pathogens. For obvious reasons, the rate of HSV infection among HIV-infected people is also higher than that of the general population. Because of the low immune function of AIDS patients, it not only causes herpes recurrence rate to be more High, and herpes is also a serious condition, often manifested as the persistence, destructive damage, and even destruction of the mucous membranes of the face and vulva.

Herpes simplex examination

The use of PCR technology for HSV gene detection can provide direct evidence of herpes simplex virus in patients; its sensitivity is high, and it can be detected within a few hours, which has become an important means for clinical diagnosis of HSV infection or poisoning; However, it must be carried out in an experimental medical laboratory that has passed the technical certification, and care should be taken to avoid contamination during the operation. In view of the fact that HSV-2 recessive infection may be a cause of male infertility, for the infertility clinic, PCR technology should be used to detect HSV as a routine for semen and cervical spleen screening.

Suspected and neonatal patients with intrauterine HSV infection, serum (can be collected cord blood or heel blood specimens) IgM-type HSV antibody test positive can be diagnosed, due to the high rate of HSV antibody detection in the adult population, most of the Self-hidden infection, and the presence of antibodies can not completely protect the body from repeated infections of herpesviruses; therefore, for adult cases, positive HSV antibody test is not helpful for clinical diagnosis; however, negative HSV antibody test can help to eliminate simple Herpes (if the subject has a defective immune response function, this is not the case).

Herpes simplex virus is easy to carry out in vitro cell culture and can produce visible cytopathic changes; therefore, cotton swabs can be used to sample cells in the lesion or to collect cerebrospinal fluid and other body fluid specimens for inoculation of cells, culture and isolation of viruses for diagnosis; and cell immunohistochemistry can be used. Immunofluorescence technique was used to detect herpes simplex virus antigen protein, or in situ hybridization technique to detect its genetic components, and further to classify HSV-1 and HSV-2. Viral cell culture identification is the gold standard for HSV diagnosis. However, its technical requirements are relatively high. High, so it is difficult to promote it in the clinic.

The early epidermis of histopathology is a multi-atrial blister with reticular degeneration, which is polymerized into a single atrial blister, with fibrin, inflammatory cells and balloon degeneration cells in the bleb, and basophilic inclusion bodies (late eosinophilic) in the nucleus. Patients with inflammatory cell infiltration of the dermis may have vasculitis changes.

Diagnosis of herpes simplex

It is not difficult to diagnose a typical herpes lesion on the surface of the body; for patients with lesions only in the depth of the tract, such as the genital tract, respiratory tract, and rectum, if it is neglected by a thorough physical examination, it may be misdiagnosed; Herpes is damaged, and the body is not exposed to herpes such as herpetic encephalitis. The clinical diagnosis is not easy. Therefore, pay attention to collecting epidemiological data: for example, the history of exposure of herpes patients, high-risk groups (such as plethora With a history of herpes, it is important to prompt a diagnosis.

Differential diagnosis

1. Herpes zoster is distributed along the peripheral nerves on one side of the body. The lesions are a large number of clustered blisters, herpes, and arranged in strips. The basal inflammation is obvious, often accompanied by significant neuralgia.

2. Impetigo is more common in children, more common in summer and autumn, contact with strong contagious, large blister, there is a purplish secretion of honey yellow suede, scattered distribution.

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