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Associated complications are......
Written by | Dr. Lau
As a pediatrician, I often encounter children with recurrent fever, pharyngitis, tonsillitis, and some children even have recurrent fever several times within 1 month.
Recently admitted to a 11-year-old girl, intermittent fever for half a year, each fever for 3~5 days, interval of 1 week to half a month, recurrent fever, physical examination except for pharyngeal congestion, the rest of the physical examination is negative, the laboratory inflammatory indicators are normal or slightly higher, has been hospitalized in the local hospital for 3 times, each anti-infective treatment effect is significant, but the fever is easy to recur.
After admission to our hospital, the relevant etiological examination was improved, except for anti-streptococcal hemolysin O higher than normal, the rest of the etiological examinations were negative, preliminary consideration: streptococcal infection, why streptococcal infection can cause recurrent pharyngitis and fever in children, the following is a detailed introduction to the relevant knowledge of streptococcal infection.
Epidemiology of streptococcal infections
Epidemiological characteristics and pathogenic mechanism of group A streptococcus (GAS):
01
GAS epidemiology:
It often colonizes the human pharynx and can also cause superficial, invasive, toxin-mediated, and postinfectious immune diseases on the surface of unclean skin.
Humans are the only host of GAS, which is mainly transmitted through air droplets, skin and mucosal contact, poor sanitation and crowded living are conducive to the transmission of GAS and cause infection.
In addition, GAS can also be transmitted through contaminated food.
The population is generally susceptible to GAS, and most of the patients are children aged 5~15 years, the elderly and those with weakened immunity.
02
Pathogenesis of GAS infection:
The pathogenicity of GAS is related to the multiple virulence factors it produces, which invade deep tissues and lead to disease by promoting the adhesion of bacteria to host cells. The toxicity factors that have been discovered so far can be divided into two categories: bacterial components and secretory components.
1. Bacterial components are the structural virulence factors of the bacteria, mainly including bacterial surface proteins, capsule, fimria, etc., which are related to enhancing the adhesion ability of pathogens to host cells and promoting bacteria to evade the host immune defense mechanism. The surface protein is mainly M protein, which is the most important bacterial protein component, and is also one of the most important virulence factors and serotyping basis of GAS, and some specific regions of M protein may also be used as common antigens to cross-react with some antigenic components of the human body, causing autoimmune diseases, such as rheumatic fever.
2. Secretory components refer to a variety of secretory virulence factors produced by GAS, such as streptococcal thermogenic exotoxin, wall protease, secreted lipase, streptococcal hemolysin, hyaluronidase, etc., which are mostly related to the destruction of host cells and interference with the immune system. Superantigen is one of the most powerful known T cell activators, which plays an important role in the pathogenic process of streptococcal infection and can promote the colonization, proliferation and spread of streptococcus. Streptococcal superantigens have been implicated in a range of GAS diseases, including invasive infections such as necrotizing fasciitis, streptococcal toxic shock syndrome (STSS), Kawasaki disease, psoriasis, and acute rheumatic fever (ARF).
Complications in children with GAS infection
According to the epidemiological characteristics of GAS and the pathogenic mechanism of infection, children infected with GAS are more susceptible to the following diseases:
GAS has a broad pathogenic spectrum, ranging from asymptomatic carriers, superficial infections (e.g., acute pharyngeal/tonsillitis, impetigo, erysipelas, vaginitis, postpartum infections, etc.), deep infections (e.g., cellulitis, acute necrotizing fasciitis (ANF), acute myositis, bacteremia, sepsis, pericarditis, meningitis, pneumonia, septic arthritis, osteomyelitis, etc.), to toxin-mediated diseases (e.g., scarlet fever, STSS, purpura fulminans, etc.), postinfectious immune diseases (e.g., rheumatic fever, Post-acute streptococcal glomerulonephritis (APSGN), autoimmune neuropsychiatric diseases in children associated with streptococcal infection (PANDAS), etc.].
01
Acute pharyn/amygdala:
It is the most common disease after GAS infection and is one of the leading causes of sore throat in children and adolescents in outpatient and emergency departments. The incubation period of acute GAS pharyngeal/tonsillitis is 2~4 days, and the typical symptoms are sudden high fever, severe pharyngeal pain, swollen and painful lymph nodes in the anterior neck, and there may be a history of exposure to GAS infection.
02
Skin and soft tissue infections:
GAS is one of the most important bacterial causes of skin and soft tissue infections.
03
Scarlet fever:
It is an acute respiratory infectious disease caused by GAS, with nursery children and school-age children as the most common age group, and winter and spring as the high incidence season, and boys are relatively common. The main clinical features are fever, pharyngeal symptoms, and rash. Among them, acute pharyngeal/tonsillitis can be manifested as sore throat, pharyngeal congestion, large tonsils, some children can see yellow-white exudate on the surface of the tonsils, children can see red and swollen tongue papilla, and later manifestations are obvious taste buds, granular, like bayberry, called "bayberry tongue".
The rash is a characteristic change of scarlet fever, which is mainly manifested as a congestive (white when pressed), scarlet small maculopapular rash that looks like goosebump and is sandpaper-like to the touch on the first day of onset. The rash begins behind the ears, on the neck, and on the upper chest, and spreads rapidly to the trunk and extremities. Linear petechiae called "Patrick lines" often appear in skin folds, particularly in the cubital fossa and axillary folds. The rash on the face is subtle and congested, but the area around the mouth and nose is characterized by a "perioral pallor circle" due to the absence of hyperemia. The rash resolves in about 1 week and is accompanied by desquamation. Some children have membranous peeling of the palms and feet in the later stages.
04
WEAPON:
It is an autoimmune disease caused by GAS infection, which usually occurs 2~3 weeks after pharyngeal infection. The clinical manifestations of ARF vary in severity and mainly depend on the location and degree of disease invasion, and there is often a history of GAS pharyngeal infection 1~5 weeks before the onset of the disease. It is often acute and can occur repeatedly if not prevented.
The lesions mainly affect the heart and joints, and other organs, such as the skin, serous membranes, central nervous system, lungs, and kidneys, can also be affected, but the most serious and common damage is cardiac damage. Clinical symptoms may also include general malaise, lack of energy, fatigue, paleness, abdominal pain and other manifestations.
50%~60% of children have arthritis or arthralgia, characterized by migratory and polyarthritis, mainly involving large joints, and local manifestations such as redness, swelling, heat, and pain may appear, with limited activities, sometimes exudation, but no suppuration. Joint pain usually resolves completely within 2 weeks with treatment, leaving no joint deformity, but often recurring.
Carditis accounts for 40%~50% of children with ARF and is the main cause of death of ARF.
In addition, ARF can also be manifested as chorea, which often appears 1~6 months after GAS infection, mostly in 4~7-year-old girls, mainly unilateral, manifested as aimless, involuntary, unconscious and atypical trunk or limb movements, facial can have eyebrows and eyes, crooked mouth and other manifestations, but also shrug, dysgraphy, micro-motor uncoordination, decreased writing ability, restlessness, clumsiness, unsteady gait and language impairment, etc., aggravated when excited and concentrated, and the symptoms can disappear after falling asleep. The course of the disease is about 3 months.
ARF can also appear annular erythema and subcutaneous nodules, the former is seen in 2%~5% of children with ARF, mainly located on the trunk and proximal flexor side of the limbs, showing annular or semi-annular pale red erythema, more obvious when fever, the skin in the ring is normal, sometimes faint, transient, can last for several weeks; the latter can be seen in 5%~10% of children with ARF, is round, slightly hard, painless, movable small nodules, no adhesion with the surface skin, no inflammation such as redness and swelling, mainly located in the subcutaneous tissue of the extensor side of the elbow, wrist, knee, ankle and other joints.
05
Acute poststreptococcal glomerulonephritis (APSGN):
It is a disease that is mostly secondary to pharyngeal or skin GAS infection, and is clinically characterized by hematuria, proteinuria, hypertension, edema, oliguria, and decreased complement. APSGN is more common in boys aged 5~12 years old, and it is more common in spring and autumn, and it can be distributed or popular. Children with this disease often have a history of prodromal GAS infection, and the length of the prodromal period is related to the location of GAS infection, which is mostly 1~3 weeks after pharyngeal infection, and 2~4 weeks or even 3~6 weeks after skin infection.
GAS treatment
01
Treatment goals for acute GAS pharyngeal/tonsillitis include:
Reduce the severity and duration of symptoms, prevent the occurrence of ARF, reduce purulent complications, and reduce the chance of transmission to close contacts. Once GAS pharyngeal/tonsillitis is confirmed, anti-infective therapy is recommended.
02
Skin management is emphasized for GAS skin infections, and children can be bathed normally and showered preferably.
Clothes and towels used by infected people should be washed daily and not shared with others. At the same time, we actively remove the triggers and maintain good hand hygiene to prevent the recurrence of the disease. Localized treatment of mild and moderate infections is sufficient, but when skin lesions are extensive, especially when there is fever and lymphadenitis, combined systemic anti-infection therapy is required. Topical drugs are based on the principles of sterilization, astringency, and prevention of further spread of infection, and commonly used are mupirocin ointment, fusidic acid ointment or compound polymyxin B ointment. Erysipelas or cellulitis lesions that are soft and fluctuating in the middle require prompt surgical incision and drainage.
03
The main points of treatment of scarlet fever are the same as those of acute pharyngeal/tonsillitis.
04
Principles of ARF treatment include:
(1) Application of antimicrobial drugs: the purpose is to eliminate pharyngeal GAS infection and avoid recurrence of ARF, which can be a single intramuscular injection of benzathine penicillin, or oral penicillin or amoxicillin (course of treatment 10d). Once the diagnosis of ARF or RHD (rheumatic heart disease) is confirmed, secondary prevention should be implemented as soon as possible to prevent recurrence of ARF, including regular use of antimicrobial drugs, to prevent recurrence of ARF and exacerbation of RHD due to future GAS infection.
The main points are as follows:
(a) ARF with carditis and cardiac sequelae (persistent valvular disease) should be proactive for 10 years or until the age of 40 (whichever is longer);
(b) ARF with carditis but no cardiac sequelae should be proactive for 10 years or until the age of 21 years (whichever is longer);
(c) Patients without carditis with ARF should be proactive for 5 years or until the age of 21 years (whichever is longer). Benthathine penicillin G (≤ 27kg: 600,000 U; >27kg: 1.2 million U), intramuscular injection once every 3~4 weeks, or penicillin V orally (0.25g, 2 times/d), but oral prophylaxis is less effective than intramuscular injection.
(2) Anti-rheumatic therapy: simple joint involvement, non-steroidal anti-inflammatory drugs are preferred, aspirin is commonly used, the starting dose is 3~4g/d for adults, 80~100mg/(kg·d) for children, the maximum amount can not exceed 3g/d, divided into 3~4 oral doses. Other nonsteroidal anti-inflammatory drugs may also be used. Patients with carditis are generally treated with glucocorticoids, commonly used prednisone, the initial dose is 30~40mg/d for adults and 1.0~1.5mg/(kg·d) for children, divided into 3~4 oral doses, and the dose is reduced to 10~15mg/d after remission.
Patients with pericarditis, carditis and acute heart failure can be treated with intravenous dexamethasone 5~10mg/d or intravenous hydrocortisone 200mg/d, and changed to oral glucocorticoid therapy after the condition improves. Arthritis alone is treated for 6~8 weeks, and carditis is treated for at least 12 weeks. In patients with cardiac insufficiency, selective use of vasodilators, diuretics, and inotropes should be considered to improve cardiac function. Heart valve surgery may be considered in rheumatic carditis, especially if there is stenosis or severe insufficiency.
(3) Chorea: valproic acid is preferred, the drug is ineffective or severe chorea, such as paralyzed patients, carbamazepine can be used. Other dopamine receptor antagonists, such as haloperidol, may also be effective.
05
APSGN Treatment:
Rest, low-salt diet and water restriction, infection control, diuresis, antihypertensive treatment.
summary
If streptococci is positive, anti-infection treatment should be carried out, anti-streptolysin value, electrocardiogram, urine routine should be monitored regularly, and the child should be alerted to rheumatic fever involving the heart after infection, and glomerulonephritis affecting the kidneys.
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References:[1]Yu Dingle, Lu Qinghua, You Yuanhai, et al.Expert consensus on the diagnosis, treatment and prevention of diseases related to group A streptococcal infection in Chinese children[J].Chinese Journal of Practical Pediatrics,2022,37(21):1604-1618.DOI:10.3760/cma.j.cn101070-20220815-00974.
Editor in charge: Xiang Yu
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