Pediatric Infectious Diseases – Hand, Foot, and Mouth Disease
Hand, foot, and mouth disease (HFMD) is a common infectious disease caused by a variety of enteroviruses, mainly in infants and children. Most patients have mild symptoms and are characterized by fever and rash or herpes on the hands, feet and mouth. A small number of patients can be complicated by aseptic meningitis, encephalitis, acute flaccid paralysis, respiratory tract infection and myocarditis, etc. Individual children with severe disease progress rapidly and are prone to death. Adolescent children and adults do not develop disease after infection, but are able to transmit the virus. The enteroviruses that cause HFMD include enterovirus 71 (EV71) and some serotypes of group A coxsackieviruses (CoxA) and echoviruses (Echo). Enteroviruses are highly infectious and can easily cause epidemics or outbreaks.
I. Pathogenesis
The viruses that cause HFMD are mainly coxsackieviruses of the family Small RNA Viruses, enteroviruses of the genus Coxsackievirus A group 16, 4, 5, 7, 9, 10, B group 2, 5, 13; Echovirus and enterovirus 71, of which EV71 and CoxAl6 are the most common.
Enterovirus 71 is the latest novel enterovirus discovered, a heat- and acid-resistant small RNA virus that causes lesions in mammary rats. The disease virus was first isolated in 1969 from the cerebrospinal fluid of a child with meningoencephalitis in California, USA, and its serotype was identified in 1992. Since then, similar cases have been found in New York and Melbourne at the same time and have appeared in clusters, and several strains of different types have been isolated so far.
Enterovirus is suitable for survival and transmission in wet and hot environments, and is insensitive to ether, dechlorinated bile salts, etc. 75% alcohol and 5% cresol soap solution (Lysol) cannot inactivate it, but is sensitive to ultraviolet light and drying. Various oxidizing agents (potassium permanganate, bleach, etc.), formaldehyde, iodine can inactivate the virus. The virus can be inactivated rapidly at 50 ℃, but 1 mol concentration of divalent cation environment can improve the resistance of the virus to heat inactivation, the virus can survive for 1 year at 4 ℃, at -20 ℃ can be stored for a long time, the virus can survive for a long time in the external environment.
II. Epidemiology
1. Epidemiological profile.
(1) Hand, foot and mouth disease is a global infectious disease, most regions of the world have reported the epidemic. 1957 New Zealand first reported the disease. 1958 isolated coxsackie virus, 1959 proposed hand, foot and mouth disease named. The causative agent of HFMD identified early on was mainly CoxAl6, and EV71 was first identified in the United States in 1969. Since then EV71 infection has alternated with CoxAl6 infection and become the main pathogen of HFMD.
(2) There is no obvious regional prevalence of HFMD. The disease can occur throughout the year, with summer and autumn being the most common and the onset of winter being less common. During the epidemic, collective infections in kindergartens and child care centers and family clusters can occur. Enterovirus is highly contagious, with a large proportion of hidden infections, complex transmission routes, and rapid transmission, which can cause a wide range of epidemics in a short period of time, making it difficult to control the epidemic.
2.Infectious source: human is the only host of enterovirus, patients and hidden infected people are the infectious source of the disease.
3, the transmission route: enterovirus is mainly through the fecal – oral and (or) respiratory droplet transmission, but also by contact with the patient’s skin, mucosal herpes fluid and infection. It is not clear whether it can be transmitted by water or food. The virus can be detected in the pharynx and feces of infected patients several days before the onset of the disease, and is usually most contagious within 1 week after the onset of the disease.
Patient feces, herpes fluid and respiratory secretions and their contaminated hands, towels, handkerchiefs, tooth cups, toys, eating utensils, milk utensils, bedding, underwear and medical instruments can cause the spread of the disease.
4, susceptibility: people are generally susceptible to enteroviruses, and specific immunity can be obtained after both dominant and recessive infections, the duration of which is not yet clear. There is no cross-immunity between the various types of the virus. All age groups can be infected with the disease, but the incidence is highest in the age group ≤3 years.
Third, the pathogenesis and pathology
One theory is that the virus invades from the pharynx or intestine, multiplies in the local mucosa or lymphatic tissues, and is discharged locally, which can cause local symptoms. Subsequently, the virus invades the local lymph nodes and thus enters the blood circulation leading to the first viraemia. The virus invades the reticuloendothelial tissue, deep lymph nodes, liver, spleen and bone marrow through the blood circulation and multiplies and enters the blood circulation as a result, causing the second viremia. The virus may enter various organs of the body, such as the central nervous system, skin mucosa, heart, etc., with the blood flow to further multiply and cause lesions.
2. Vascular metaplasia and tissue inflammatory lesions occur in susceptible individuals after infection with EV71. When the virus involves the central nervous system, tissue inflammation is more intense than neurotoxic effects, and the endothelium of small vessels in the central nervous system is most vulnerable to damage. Cell fusion, vascular inflammatory changes, and thrombosis can lead to ischemia and infarction. In the local tissues of the spinal cord, brainstem, mesencephalon, brain, and cerebellum, there is extensive perivascular and parenchymal cell inflammation in addition to neurotropic effects.
IV. Clinical manifestations
The incubation period is 2-5 days.
1. General manifestations: At the early stage of infection, patients show low fever, runny nose, decreased appetite, mouth pain, vomiting, diarrhea, etc. Small herpes appear in the oral mucosa, often distributed in the tongue, buccal mucosa, hard palate, but also in the tonsils, gums and pharynx, etc., and ulcers are formed after the herpes breaks down. The oral lesions can be accompanied by maculopapular rash on the skin, maculopapular rash and herpes on the hands, feet and buttocks. The maculopapular rash quickly turns into a small herpetic rash with an inflammatory red halo around the herpes, less fluid in the herpes, eccentric distribution, 3-7 mm in diameter, slightly hard texture, ranging from a few to dozens, self-absorbing in 2-3 days, without leaving a scab. Most of them are benign processes, mostly self-healing, but can recur, sometimes accompanied by aseptic meningitis, myocarditis, etc. Some cases present only as a rash or herpetic pharyngitis. No sequelae.
2, severe patient performance: a few patients (especially those younger than 3 years old) may develop encephalitis, encephalomyelitis, meningitis, pulmonary edema, circulatory failure, etc.
(1) Neurological system: clinical manifestations are varied and the severity of the disease varies, generally manifesting as clonus, vomiting, ataxia, intentional tremor, nystagmus and emotional indifference, etc.; physical examination shows meningeal irritation signs and diminished or absent tendon reflexes; critical cases may manifest as frequent convulsions, coma, cerebral edema and brain herniation; cranial MRI and electroencephalography help to clarify the severity of the disease.
(2) Respiratory system: shallow and difficult breathing, altered respiratory rhythm, cyanosis of lips and mouth, white, pink or bloody foamy fluid (sputum), sputum sound or wet woven wool can be heard in the lungs
(3) Circulatory system: pale face, increased or slow heart rate, shallow, weakened or even absent pulse, cold extremities, cyanosis of fingers (toes), increased or decreased blood pressure.
V. Laboratory tests
1. Routine examination: routine blood tests show an increase in lymphocytes and monocytes, normal or increased leukocytes, and in severe cases, the leukocyte count may be significantly increased.
2.Blood biochemical examination: some cases may have mildly elevated ALT, AST, CK-MB, and blood glucose may be elevated in severe cases.
3.Ethiological examination: EV71 virus can be isolated from pharyngeal swab or throat wash, stool or anal swab, cerebrospinal fluid or herpes fluid, and specific EV71 nucleic acid is positive or isolated.
4, serum antibody examination: enterovirus type-specific identification mainly relies on serum neutralization experiments, LMB combination serum can greatly simplify the identification process, but the neutralization of some strains is unstable, still need to be identified by monovalent serum, another thing to note is that the agglomeration of virus particles will affect the neutralization effect, such as EV71 neutralization experiments need to use a single dispersed virus. Patients with positive serum specific IgM antibodies, or with more than 4-fold elevation of serum IgG antibodies in the acute and recovery phases, have diagnostic significance.
5.Chest X-ray: It may show increased texture of both lungs, grid-like, dot-like and large shadows, and some cases are unilateral, and rapidly progress to large bilateral shadows.
6.Magnetic resonance imaging: brainstem and spinal cord gray matter damage is the main focus.
7.Electroencephalogram: some cases may show diffuse slow waves, and a few cases may show spike (sharp) slow waves.
8.Electrocardiogram: no specific changes. Sinus tachycardia or bradycardia, ST-T changes may be seen.
VI. Diagnosis
It develops in the epidemic season, commonly in preschool children, and is more common in infants and young children.
1.Diagnosis based on.
(1) The main manifestation is fever, maculopapular rash and herpes on hands, feet, mouth and buttocks, which may be accompanied by symptoms of upper respiratory tract infection.
(2) In some cases, the rash on the hands, feet and buttocks or herpetic pharyngitis is the only manifestation.
(3) Severe cases may show neurological involvement, respiratory and circulatory failure, etc. Laboratory tests may include increased peripheral blood leukocytes, increased blood glucose and cerebrospinal fluid changes, and abnormalities in electroencephalography, magnetic resonance imaging and chest x-ray.
2. Confirmation basis: Based on the clinical diagnosis, positive EV71 nucleic acid test, isolated EV71 virus or positive EV71 IgM antibody test, more than 4 times increase of EV71 IgG antibody or change from negative to positive.
VII. Differential diagnosis
1. Foot-and-mouth disease is caused by foot-and-mouth disease virus, and there are currently 7 serotypes and 65 subtypes. It mainly affects domestic animals such as pigs, cattle and horses. Although it is pathogenic to humans, it is not sensitive. It generally occurs in livestock areas, and is common in adult herders, and is present in all seasons. Oral mucosal rash easily fused into larger ulcers, rash on the back of the hands and between the fingers and toes, with itching and pain.
2, herpetic stomatitis can develop in all seasons, mainly scattered. There is usually no rash, and occasionally a herpes rash can appear on the lower abdomen.
3. Herpes cheilitis, which can be caused by Cox group A virus, has lesions in the posterior part of the oral cavity; e.g., tonsils, soft palate, palatal lobe, rarely involving the buccal mucosa, tongue, and gingiva. Atypical, scattered HFMD is difficult to differentiate from rash febrile disease, and pathogenic and serologic tests must be done.
VIII. Treatment
In terms of treatment, the prognosis of this disease is generally good if there are no complications, and it is mostly cured within 1 week. The treatment principle is mainly symptomatic treatment.
1. Hand, foot and mouth disease / herpes pharyngitis stage.
(1) General treatment Pay attention to isolation, avoid cross-infection, proper rest, light diet, good oral and skin care.
(2) Symptomatic treatment Treat fever, vomiting, diarrhea, etc. accordingly.
2. Neurological involvement stage: Patients in this stage show neurological symptoms and signs, such as headache, vomiting, poor mental health, irritability, drowsiness, limb weakness, muscle spasm, convulsions or acute flaccid paralysis, etc.
(1) Control intracranial hypertension Limit fluid intake, give mannitol 0.5-1.0 g/kg every 4-8 h, 20-30 min intravenously, and adjust the interval and dose of medication according to the condition. If necessary, add furosemide.
(2) Intravenous immunoglobulin The total amount is 2g/kg, given in 2-5 d.
(3) Apply glucocorticoids as appropriate. Reference dose: methylprednisolone 1-2 mg.