HFMD is an acute infectious disease caused by enteroviruses (CoxA16 and EV71), mostly occurring in preschool children, with the highest incidence in the under-3 age group. The disease is mainly transmitted through the gastrointestinal tract, respiratory tract and close contact, with both patients and latent infections as the source of infection. The main symptoms are papular rash and herpes on the hands, feet and mouth. Meningitis, encephalitis, encephalomyelitis, pulmonary edema and circulatory disorders may occur in a few cases, mostly caused by EV71 infection, and the main cause of death is brainstem encephalitis and neurogenic pulmonary edema.
I. Clinical manifestations
Incubation period: mostly 2-10 days, average 3-5 days.
(A) Common case performance
Acute onset, fever, scattered herpes on the oral mucosa, maculopapular rash and herpes on the hands, feet and buttocks, which may be surrounded by an inflammatory redness and less fluid in the herpes. It may be accompanied by cough, runny nose, and loss of appetite. Some cases present only with a rash or herpetic pharyngitis. Most cases heal within a week and the prognosis is good. In some cases, the rash is atypical, e.g., a single site or only a maculopapular rash.
(B) Severe cases
In a few cases (especially those younger than 3 years old), the disease progresses rapidly, with meningitis, encephalitis (brainstem encephalitis is the most dangerous), encephalomyelitis, pulmonary edema, circulatory disorders, etc. In a very few cases, the disease is critical and can lead to death, and surviving cases can have sequelae.
1, neurological manifestations: poor mental health, drowsiness, easily startled, headache, vomiting, delirium or even coma; limb tremors, myoclonus, nystagmus, ataxia, oculomotor disorders; weakness or acute flaccid paralysis; convulsions. On examination, meningeal stimulation signs, diminished or absent tendon reflexes, and positive pathological signs such as Bartholomew’s sign were seen.
2, respiratory manifestations: shallow breathing, dyspnea or rhythm changes, lip cyanosis, cough, coughing white.
3, circulatory system manifestations: pale gray face, skin pattern, cold extremities, cyanosis of fingers (toes); cold sweating; prolonged capillary refill time. Heart rate increases or decreases, pulse is shallow or weak or even disappears; blood pressure increases or decreases.
II. Laboratory tests
(A) Blood count
Leukocyte count is normal or decreased, and in critical cases, it may be significantly increased.
(B) Blood biochemical examination
Some cases may have mildly elevated ALT, AST, CK-MB, and in critical cases, elevated cTnI and blood glucose, but C-reactive protein (CRP) is generally not elevated. Lactate levels are elevated.
(iii) Blood gas analysis
Respiratory system involvement may include decreased partial pressure of arterial blood oxygen, decreased oxygen saturation, increased partial pressure of carbon dioxide, and acidosis.
(iv) Cerebrospinal fluid examination
Neurological involvement may be characterized by clear appearance, increased pressure, increased white blood cell count, mostly mononuclear cells, normal or mildly increased protein, and normal sugar and chloride.
(V) Pathogenic examination
CoxA16, EV71 and other enterovirus-specific nucleic acid positive or isolated to enterovirus. The rate of positive pharyngeal and airway secretions, herpes fluid, and stool is high.
(vi) Serological examination
There is more than 4-fold increase in serum CoxA16, EV71 and other enterovirus neutralizing antibodies during the acute and recovery periods.
III. Physical examination
(i) Chest X-ray examination
It may show increased texture of both lungs, grid-like and patchy shadows, and some cases are unilateral.
(B) Magnetic resonance imaging
There may be abnormal changes in neurological involvement, with brainstem and spinal cord gray matter damage predominant.
(C) Electroencephalogram
The EEG may show diffuse slow waves, and a few cases may show spiky (sharp) slow waves.
(iv) Electrocardiogram
No specific changes. Sinus tachycardia or bradycardia, prolonged Q-T interval, and ST-T changes are seen in a few cases.
IV. Diagnostic criteria
(A) Clinical diagnosis of cases
1.Onset in the epidemic season, commonly seen in preschool children, infants and young children.
2. Fever with rash on hands, feet, mouth and buttocks, some cases may be feverless.
Very few severe cases have an atypical rash, which makes clinical diagnosis difficult and needs to be combined with etiological or serological examination to make a diagnosis.
In cases without rash, the clinical diagnosis of HFMD is not appropriate.
(II) Confirmed cases
Clinical diagnosis can be confirmed if the case has one of the following.
1. Positive specific nucleic acid test for enterovirus (CoxA16, EV71, etc.).
2.Enterovirus was isolated and identified as CoxA16, EV71 or other enterovirus that can cause HFMD.
3.Serum CoxA16, EV716 or other enteroviruses that can cause HFMD have more than 4-fold elevation of neutralizing antibodies during the acute and recovery periods.
(C) Clinical classification
1.Ordinary cases: hand, foot, mouth and buttock rash with or without fever.
2.Severe cases.
(1) Heavy: manifestations of neurological involvement. For example: poor mental health, drowsiness, easy to startle, delirium; headache, vomiting; limb tremors, myoclonus, nystagmus, ataxia, oculomotor disorders; weakness or acute flaccid paralysis; convulsions. Signs can be seen as meningeal irritation signs and diminished or absent tendon reflexes.
(2) Critical type: those with one of the following conditions.
(i) Frequent convulsions, coma, brain herniation.
(②Respiratory distress, cyanosis, bloody foamy sputum, pulmonary rales, etc.
(③) Shock and other circulatory insufficiency manifestations.
V. Differential diagnosis
(A) Other childhood rash diseases
Common cases of HFMD need to be differentiated from papular urticaria, chickenpox, atypical measles, early childhood emergency rash, herpes zoster and rubella. The differentiation can be based on epidemiological features, rash pattern, location, time of rash onset, presence of swollen lymph nodes, and accompanying symptoms, with the rash pattern and location being the most important. Ultimately, the differentiation can be based on pathogenesis and serological tests.
(B) Encephalitis or meningitis caused by other viruses
The clinical manifestations of encephalitis or meningitis caused by other viruses, such as herpes simplex virus, cytomegalovirus (CMV), EBV, respiratory viruses, etc., are similar to those of severe cases of HFMD combined with CNS damage, and for those with an atypical rash, specimens should be taken as soon as possible for virological examination of enteroviruses, especially EV71, based on the epidemiological history, and combined with pathogenic or serological tests to make a (ii) Diagnosis.
(C) Poliomyelitis
Severe HFMD combined with acute flaccid paralysis (AFP) needs to be differentiated from poliomyelitis. The latter mainly presents as bimodal fever, with flaccid paralysis occurring before or during the fever remission in the second week of the disease, and the disease mostly reaches its peak after the fever recedes without a rash.
(iv) Pneumonia
Neurogenic pulmonary edema can occur in severe HFMD and should be differentiated from pneumonia. Pneumonia mainly manifests as fever, cough, shortness of breath and other respiratory symptoms, usually without rash, without pink or bloody foamy sputum; chest X-ray aggravation or reduction are in gradual evolution, visible solid lung lesions, pulmonary atelectasis and pleural effusion, etc.
(E) Fulminant myocarditis
Severe cases of HFMD with circulatory disorders as the main manifestation need to be differentiated from fulminant myocarditis. Fulminant myocarditis without rash, with severe arrhythmias, cardiogenic shock, As syndrome episodes manifested; myocardial enzyme profile is mostly significantly elevated; chest X-ray or cardiac ultrasound suggests an enlarged heart and slower recovery from abnormal cardiac function. Eventually, the identification can be based on pathogenic and serological tests.
VI. Early identification of severe cases
Patients with the following characteristics, especially those under 3 years of age, may develop into critical cases within a short period of time, and should be closely observed for changes in condition, necessary ancillary examinations, and targeted rescue and treatment.
(A) Persistent high fever that does not subside.
(B) Poor mental health, vomiting, easy to be frightened, shaking limbs and weakness.
(C) Increased respiration and heart rate.
(iv) Cold sweats, poor peripheral circulation.
(v) Hypertension.
(vi) Significant increase in peripheral blood leukocyte count.
(vii) Hyperglycemia.