David H. Darrow
The tonsils and adenoid are anatomic structures that are highly predisposed to infectious and inflammatory processes. These areas are exposed to external influences during speech, mastication, deglutition, and respiration. Additionally, children use the oral and nasal cavities as areas of exploration. The immaturity of the immune system in children also places them at even greater risk for local infection and inflammation. This chapter reviews the diagnosis and management of the infectious and inflammatory disorders in children that are of the greatest importance to the otolaryngologist.
Functions of the Tonsils and Adenoid
The palatine tonsils and adenoid are tissues of “Waldeyer ring,” a group of lymphoepithelial tissues that also includes the tubal tonsils in the nasopharynx and the lingual tonsil. Collectively, these tissues participate in the mucosal immune system of the pharynx. Positioned strategically at the entrance of both the gastrointestinal and the respiratory tracts, the tonsils and adenoid serve as secondary lymphoid organs, initiating immune responses against antigens entering the body through the mouth or nose. The size of the tonsils appears to correlate with their level of immunological activity, peaking between the ages of 3 and 10 years, and demonstrating age-dependent involution. There is also some evidence that their size increases with the bacterial load.
The tonsils are covered by a nonkeratinizing stratified squamous epithelium featuring some 10 to 30 deep crypts that effectively increase the surface area exposed to incoming antigens. The crypts occasionally harbor degenerated cells and debris that give rise to so-called “tonsilloliths,” in which the presence of biofilms has also been implicated. Although the tonsils lack afferent lymphatics, the epithelium contains a system of specialized channels lined by “M” cells that take up antigens into vesicles and transport them to the intraepithelial and subepithelial spaces where they are presented to lymphoid cells. The transport function of M cells also serves as a portal for mucosal infections and immunizations, and M cells also can initiate immunologic responses within the epithelium, introducing foreign antigens to lymphocytes and antigen-presenting cells (APCs).
After passing through the crypt epithelium, inhaled or ingested antigens reach the extrafollicular region or the lymphoid follicles. In the extrafollicular region, APCs process the antigens and present them to helper T lymphocytes that stimulate proliferation of follicular B lymphocytes. The B lymphocytes ultimately develop into one of two types of cell: antibody-expressing B memory cells capable of migration to the nasopharynx and other sites, or plasma cells that produce antibodies and release them into the crypt lumen. Tonsillar plasma cells can produce all five immunoglobulin (Ig) classes that help combat and prevent infection. In addition, the contact of memory B-cells in the lymphoid follicles with antigen is an essential part of the generation of a secondary immune response.1,2
Among the Ig isotypes, IgA may be considered the most important product of the adenotonsillar immune system. In its dimeric form, IgA can attach to the transmembrane secretory component (SC) to form secretory IgA, a critical component of the mucosal immune system of the upper airway. This component is necessary for binding of IgA monomers to each other and to the SC, and is an important product of B-cell activity in the tonsil follicles. While the tonsils produce immunocytes bearing the joining (J) chain carbohydrate, SC is produced only in the adenoid and extratonsillar epithelium, and therefore only the adenoid possesses a local secretory immune system.3
Overview of Infectious and Inflammatory Diseases of the Tonsils and Adenoid
Pharyngotonsillitis is a general term used to describe diffuse inflammation of the structures of the oropharynx, including the tonsils. The disorder presents with symptoms of sore throat; however, objective signs of inflammation must be present to make the diagnosis. Pharyngotonsillitis may be classified based on duration of symptoms as acute, subacute, or chronic, with most patients presenting acutely. Alternatively, inflammatory disease of the nasopharynx may be considered nasopharyngitis, in which common symptoms include rhinorrhea, nasal congestion, sneezing, and cough. Inflammation limited to the adenoid pad (adenoiditis) is difficult to diagnose in the primary care setting due to the inaccessibility of this tissue to direct visualization.
Common Viral Infection of the Tonsils and Adenoid
Nasopharyngitis typically occurs during the cold weather months among young children during their early exposures to respiratory viruses. Adenoviruses, influenza viruses, parainfluenza viruses, and enteroviruses are the most common etiologic agents. Rhinovirus and respiratory syncytial virus occur almost exclusively in preschool children and are rarely associated with overt signs of pharyngeal inflammation. Adenoviruses are more common among older children and adolescents. Nasopharyngitis of viral etiology may also cause a concomitant pharyngotonsillitis. The infection is most commonly acute and self-limited, with symptoms resolving within 10 days. Nonviral agents are less frequently associated with nasopharyngitis, but may include Corynebacterium diphtheriae, Neisseria meningitidis, Haemophilus influenzae, and Coxiella burnetii.
The viruses responsible for pharyngotonsillitis are more diverse than those in nasopharyngitis; adenoviruses, influenza viruses, parainfluenza viruses, enteroviruses, Epstein-Barr virus (EBV), and Mycoplasmaaccount for some 70% of these infections. As in nasopharyngitis, most viral pharyngotonsillitis requires no specific therapy.
Group A β-Hemolytic and Other Streptococci
The group A β-hemolytic Streptococcus (GABHS) is the most common bacterium associated with pharyngotonsillitis in children. In the 70 years since the advent of antibiotics, most pharyngeal infections by GABHS have been benign, self-limited, and uncomplicated processes. In fact, most patients improve symptomatically without any medical intervention whatsoever. However, a small number of affected children continue to develop renal and cardiac complications following GABHS infection, and some authors have implicated GABHS in the development of common childhood neuropsychiatric disorders. In addition, there is evidence that early antibiotic therapy may be useful in treating the symptoms of GABHS. As a result, appropriate diagnosis and treatment is imperative.
The incidence of GABHS pharyngitis has not been estimated on the basis of population-based data. Nevertheless, “strep throat” is well recognized as a common disease among children and adolescents. The incidence peaks during the winter and spring seasons, and is more common in cooler, temperate climates. Close interpersonal contact in schools, military quarters, dormitories, and families with several children appears to be a risk factor for the disease.
Transmission of GABHS is believed to occur through droplet spread. Individuals are most infectious early in the course of the disease, and the risk of contagion depends on the inoculum size and the virulence of the infecting strain. The incubation period is usually between 1 and 4 days. After starting antimicrobial therapy, most physicians will allow affected children to return to school within 36 to 48 hours. The role of individuals colonized with GABHS in the spread of the disease is uncertain, although data suggest that carriers rarely spread the disease to close contacts.4
The streptococci are gram-positive, catalase-negative cocci, characterized by their growth in long chains or pairs in culture. These organisms are traditionally classified into 18 groups with letter designations (Lancefield groups) on the basis of the antigenic carbohydrate component of their cell walls. While the GABHS is isolated from most patients with streptococcal pharyngitis, groups C, G, and B streptococci may also occasionally cause this disorder. Further subclassification of streptococci is made based on their ability to lyse sheep red blood cells in culture; the β-hemolytic strains cause hemolysis associated with a clear zone surrounding their colonies, while α-hemolytic strains cause partial hemolysis and gamma-hemolytic strains cause no hemolysis. The α-hemolytic strains are normal flora of the oral cavity and pharynx and should not be confused with the more pathogenic β-hemolytic strains.
The primary determinant of streptococcal pathogenicity is an antigenically distinct protein known as the M protein. This molecule is found within the fimbriae, which are finger-like projections from the cell wall of the organism that facilitate adherence to pharyngeal and tonsillar epithelium. Over 120 M serotypes are known. The M protein allows Streptococcus to resist phagocytosis in the absence of type-specific antibody. In the immunocompetent host, the synthesis of type-specific anti-M and other antibodies confers long-term serotype specific immunity to the particular strain in question. In laboratory-produced penicillin-resistant strains of GABHS, the M protein is absent, thereby rendering these strains more vulnerable to phagocytosis. This finding may help explain why no naturally occurring penicillin-resistant GABHS have yet been isolated.
GABHS are capable of elaborating at least 20 extracellular substances that affect host tissue; the interested reader may find a complete discussion of these substances elsewhere. Among the most important are streptolysin O, an oxygen-labile hemolysin, and streptolysin S, an oxygen-stable hemolysin, which lyse erythrocytes and damage other cells such as myocardial cells. Streptolysin O is antigenic, while streptolysin S is not. GABHS also produce three erythrogenic or pyrogenic toxins (A, B, and C) whose activity is similar to that of bacterial endotoxin. Other agents of significance include exotoxin A, which may be associated with toxic shock syndrome, and bacteriocins, which destroy other gram-positive organisms. Spread of infection may be facilitated by a variety of enzymes elaborated by GABHS, which attack fibrin and hyaluronic acid.
Signs and symptoms of GABHS pharyngotonsillitis are acute in onset, usually characterized by high fever, odynophagia, headache, and abdominal pain. However, the presentation may vary from mild sore throat and malaise (30 to 50% of cases) to high fever, nausea and vomiting, and dehydration (10%).4 The pharyngeal and tonsillar mucosa are typically erythematous and occasionally edematous, with exudate present in 50 to 90% of cases. Cervical adenopathy is seen in 30 to 60% of cases. Most patients improve spontaneously in 3 to 5 days, unless otitis media, sinusitis, or peritonsillar abscess (PTA) occur secondarily.
The risk of rheumatic fever following GABHS infection of the pharynx is approximately 0.3% in endemic situations, and 3% under epidemic circumstances.4 A single episode of rheumatic fever places an individual at high risk for recurrence following additional episodes of GABHS pharyngitis. Acute glomerulonephritis occurs as a sequelae in 10 to 15% of those infected with nephritogenic strains.4 In patients who develop these sequelae, there is usually a latent period of 1 to 3 weeks.
Pediatric autoimmune neuropsychiatric disorder associated with group A streptococcal infection (PANDAS) has been described as a selective immunopathy similar to Sydenham chorea in which the response to streptococcal infection leads to dysfunction in the basal ganglia, resulting in tic, obsessive-compulsive, and affective disorders.5 Classically, the behaviors are abrupt in onset and must have some temporal relationship to infection by GABHS. Clinical improvement has been reported among some patients treated with antibiotics, particularly as prophylaxis against recurrence. However, a cause-and-effect association of PANDAS with GABHS infection has yet to be established. Many experts believe that, as has been observed with other stressors, infection of any kind may provoke the neuropsychiatric phenomena.6
Early diagnosis of streptococcal pharyngitis has been a priority in management of the disease, primarily due to the risk of renal and cardiac sequelae. Several studies of the predictive value of various combinations of signs and symptoms to distinguish streptococcal from nonstreptococcal pharyngitis have found no clinically reliable predictors. Taken together, these studies demonstrate a false-negative rate of approximately 50% and a false-positive rate of 75%.7 Adenopathy, fever, and pharyngeal exudate have the highest predictive value for a positive culture and rise in antistreptolysin O (ASO) titer, and absence of these findings in the presence of cough, rhinorrhea, hoarseness, or conjunctivitis most reliably predicts a negative culture, or positive culture without rise in ASO.7
Most clinicians advocate throat culture as the gold standard for diagnosis and treatment of GABHS. However, the tonsils, tonsillar crypts, or posterior pharyngeal wall must be swabbed for greatest accuracy. Tests for rapid detection of the group-specific carbohydrate simplify the decision to treat at the time of the office visit, and often eliminate the need for additional postvisit communication. However, while these tests have demonstrated a specificity of greater than 95%, their sensitivity is generally in the 70 to 90% range. As a result, many clinicians advocate throat culture for children with suspected streptococcal disease and negative rapid strep tests. Rapid antigen detection is usually more expensive than throat culture, and this technique must still be interpreted with care given the high incidence of posttreatment carriers. Studies also suggest possible clinician bias in interpretation of this test.
Carriage of GABHS may be defined as a positive culture for the organism in the absence of a rise in ASO convalescent titer, or in the absence of symptoms. The prevalence of GABHS carriers has been estimated at anywhere from 5 to 50% depending on the time of year and location, but this may be an overestimate as some antibiotics may occasionally interfere with the rise in ASO titer. Carriers are at low risk to transmit GABHS or to develop symptoms or sequelae of the disease. The importance of this condition is in the distinction of true acute streptococcal pharyngitis from nonstreptococcal sore throat in a carrier. When this distinction is important, a baseline convalescent ASO titer should be drawn. A subsequent positive test may be defined as a twofold dilution increase in titer between acute and convalescent serum, or any single value above 333 Todd units in children.7 However, a low titer does not rule out acute infection, and a high titer may represent infection in the distant past. As a result, the American Academy of Pediatrics and the Infectious Disease Society of America recommend that testing for GABHS should not be performed in children with conjunctivitis, cough, hoarseness, coryza, diarrhea, oral ulcerations, or other clinical manifestations highly suggestive of viral infection. Furthermore, it is critical that patients referred to for potential tonsillectomy for “recurrent strep” be ruled out as carriers before they are considered candidates for surgery.
Although most upper respiratory infections by GABHS resolve without treatment, antimicrobial therapy likely prevents suppurative and nonsuppurative sequelae, including rheumatic fever, and may also hasten clinical improvement.8,9 Treatment is therefore indicated for most patients with positive rapid tests for the group A antigen. When the test is negative or not available, one may be treated for a few days while formal throat cultures are incubating.
GABHS is sensitive to several antibiotics, including penicillins, cephalosporins, macrolides, and clindamycin. Expert panels have designated penicillin the drug of choice in managing GABHS owing to its track record of safety, efficacy, and narrow spectrum.10,11 To date, no strains of GABHS acquired in vivo have demonstrated penicillin resistance or increased minimum inhibitory concentrations in vitro.12Beginning in the 1980s, several studies reporting a decrease in bacteriologic control rates, attributed primarily to inoculum effects and to increased tolerance to penicillin.13,14 Whether cephalosporins may achieve greater eradication of GABHS than penicillin remains controversial.15,16
Depot benzathine penicillin G is still advocated by the American Heart Association for primary treatment of GABHS pharyngitis; however, a 10-day course of penicillin given orally is the most widely prescribed regimen. Twice-daily dosage by the enteral route yields results similar to those obtained with four-times-a-day dosage. Courses of shorter duration are associated with bacteriologic relapse and are less efficacious in the prevention of rheumatic fever. Amoxicillin appears to have efficacy equal to that of penicillin.14 In poorly compliant or penicillin-allergic patients, azithromycin given once daily for 5 days may be a reasonable alternative. Erythromycin is now used less commonly than in the past due to its gastrointestinal side effects.
Most patients with positive cultures following treatment are GABHS carriers; these individuals need not be retreated if their symptoms have resolved. For patients in whom complete bacteriologic clearance is desirable, such as those with a family member with a history of rheumatic fever, a course of clindamycin or a second course of penicillin combined with rifampin may yield increased success. In patients with recurrent symptoms, serotyping may aid in distinguishing bacterial persistence from recurrence. There are no data available regarding the use of antibiotic prophylaxis in these patients, and in such cases tonsillectomy may sometimes be advantageous. During antimicrobial therapy, patients must be monitored carefully for fluid intake, pain control, and impending suppurative complications such as PTA.
Pharyngitis is one of the hallmarks of infectious mononucleosis (IM), a disorder associated with primary infection by the EBV. Worldwide, some 80 to 95% of adults exhibit serologic reactivity to EBV antigens. However, while primary infection by EBV occurs during the second and third decade in developed nations and regions of high socioeconomic status, young children may still be exposed, especially in developing countries and regions of low socioeconomic status. When the virus is acquired at a younger age, symptoms are generally less severe.
The incidence of IM in the United States is approximately 1 per 50 to 100,000 per year, but increases to approximately 100 per 100,000 among adolescents and young adults. Infected individuals transmit EBV by way of saliva exchanged during kissing or other close contact.
EBV is a member of the herpes virus family that preferentially infects and transforms human B lymphocytes. The virus enters the cell by attaching to a receptor designed for proteins of the complement chain, and its genetic material is transported by vesicles to the nucleus, where it dwells as a plasmid and maintains a “latent” state of replication. An incubation period of 2 to 7 weeks follows initial exposure, during which EBV induces a proliferation of infected B cells. This process is subsequently countered by a potent cellular immune response, characterized by the appearance of atypical lymphocytes (most likely T lymphocytes responding to the B-cell infection) in the blood. The number of infected circulating B cells is reduced during this 4- to 6-week period.
IM is characterized by a prodrome of malaise and fatigue, followed by the acute onset of fever and sore throat. Physical examination typically reveals enlarged, erythematous palatine tonsils, in most cases with yellow–white exudate on the surface and within the crypts. Cervical adenopathy is present in nearly all patients, and involvement of the posterior cervical nodes often helps distinguish EBV infection from that by streptococcus or other organisms. Between the second and fourth weeks of illness, about 50% of patients develop splenomegaly, and 30 to 50% develop hepatomegaly. Rash, palatal petechiae, and abdominal pain may also be present in some cases. The fever and pharyngitis generally subside within 2 weeks, while adenopathy, organomegaly, and malaise may last as long as 6 weeks.
Diagnosis of IM can usually be made on the basis of clinical presentation, absolute lymphocytosis, the presence of atypical lymphocytes in the peripheral smear, and detection of Paul-Bunnell heterophile antibodies. The latter is the basis of the Mono-Spot, Mono-Diff, and Mono-Test assays, which test for agglutination of horse erythrocytes. Children under 5 years of age may not develop a detectable heterophile antibody titer; in these patients, it is possible to determine titers of IgG antibodies to the viral capsid antigen, as well as antibodies to the “early antigen” complex. Antibodies to EBV nuclear antigen appear late in the course of the disease (Table 6.1).
In most cases of IM, treatment is supportive. In severe cases, particularly those with respiratory compromise due to severe tonsillar enlargement and those with hematologic or neurologic complications, a course of systemic steroids may hasten resolution of the acute symptoms. Placement of a nasopharyngeal trumpet or endotracheal intubation may be necessary on rare occasions when severe airway compromise occurs. Antibiotics may be useful in cases of concomitant group A β-hemolytic pharyngotonsillitis; however, ampicillin can cause a rash in this setting.
The use of antiviral agents in IM has yielded disappointing results. In clinical trials, acyclovir reduced viral shedding in the pharynx but demonstrated little efficacy in the treatment of symptoms. Other agents have exhibited greater in vitro effect than acyclovir but have yet to be tested clinically.
Exposure to EBV has been implicated in the development of posttransplantation lymphoproliferative disorder (PTLD). Children who have received bone marrow and solid organ transplants may develop abnormal proliferation of lymphoid cells in the setting of immunosuppression; approximately 80% of affected individuals have a history of EBV infection.17 EBV seronegative transplant recipients may develop acute EBV infection from environmental exposure or from the EBV seropositive donor once they become immunosuppressed.17 The clinical presentation is variable and can mimic graft-versus-host disease, graft rejection, or more conventional infections. Signs and symptoms may resemble an IM-like illness or an extranodal tumor, commonly involving the gut, brain, or the transplanted organ. Mononucleosis-like presentations typically occur in children within the first year after transplant, and are often associated with primary EBV infection after transfer of donor virus from the grafted organ. Extranodal tumors are more common among EBV-seropositive recipients several years after the transplant.18 Studies have shown that young age at the time of transplant and EBV seronegativity conferred increased risk of adenotonsillar hyperplasia, which may be a precursor to PTLD.17 A higher incidence of PTLD has also been demonstrated with use of more potent immunosuppressive agents.
Initial management involves reduction of immunosuppression with care to preserve the transplanted organ. Patients who do not tolerate or respond to reduction of immunosuppression require more aggressive therapy and often have a poorer prognosis. Additional treatments include antivirals, such as acyclovir and ganciclovir, antibody therapy, interferon, chemotherapy, and radiation therapy with varying results. Prognosis is poor with mortality rates as high as 50 to 90%.18 Novel forms of immunotherapy have been tested in PTLD, including both antibody and cell-mediated approaches.
Peritonsillar infection may present as either cellulitis or abscess. Most cases are thought to represent a suppurative complication of tonsil infection. Peritonsillar infection occurs more commonly in adolescents and young adults than in young children. Affected patients present with symptoms of sore throat, odynophagia, fever, voice change, and otalgia. Common physical findings include fever, drooling, trismus, muffled “hot potato” voice, and pharyngeal asymmetry with inferior and medial displacement of the tonsil. Radiographic evaluation is usually not necessary, but may be useful in young or uncooperative children or in equivocal cases. Although some authors have found intraoral ultrasound to be useful in adults, computed tomography with contrast remains the imaging modality of choice in children.
While patients with peritonsillar cellulitis may be treated with antibiotics alone, most abscesses require removal of the pus as definitive therapy. Evacuation of PTA can be managed by needle aspiration, incision and drainage, or immediate (“quinsy”) tonsillectomy with nearly equivalent efficacy.19 In very young or poorly cooperative patients, or in those in whom an abscess has been inadequately drained, tonsillectomy is curative and essentially eliminates any chance of recurrence.
Abscess cultures usually reveal a polymicrobial infection, often containing gram-positive organisms and anaerobes. Appropriate antimicrobial therapy in the emergency room or office setting would include initial parenteral administration of penicillin with or without metronidazole, clindamycin, or ampicillin-sulbactam. Options for oral therapy include amoxicillin-clavulanate, penicillin, and clindamycin, although children may resist taking the latter due to its taste. Intravenous hydration should also be considered for those individuals who have not been able to take liquids orally.
The efficacy of tonsillectomy in the prevention of recurrent PTA has now been compared with that of watchful waiting in a prospective, controlled trial. Studies demonstrate an increased rate of recurrent PTA among those who also had recurrent tonsillitis. A case series suggests that recurrence may be predicted based on a history of two to three episodes of acute tonsillitis in the year before the initial episode20; such a history has been elicited in 15 to 30% of patients with PTA.19–21 Based on the available evidence, it has been suggested that routine elective tonsillectomy or quinsy tonsillectomy is not indicated for patients who present with their first PTA. However, if a patient is a candidate for elective tonsillectomy for other reasons (i.e., two to three tonsillitis events in the previous 12 months), then it seems rational to perform a quinsy tonsillectomy for treatment, or to proceed with planned elective tonsillectomy after successful abscess drainage.19–21
Chronic tonsillitis is poorly defined in the literature but may be the appropriate terminology for sore throat for at least 3 months accompanied by tonsillar inflammation. Affected individuals may report symptoms of chronic sore throat, halitosis, or debris or concretions in the tonsil crypts known as “tonsilloliths.” Affected patients may also have persisting cervical adenopathy. Throat culture in such cases is usually negative. Although no clinical trials exist to help guide medical management of such patients, tonsillectomy seems reasonable for those patients who do not respond to improved oropharyngeal hygiene and aggressive antibiotic therapy.
Recurrent Tonsillitis and Tonsillectomy
When tonsils have been recurrently or chronically infected, the controlled process of antigen transport and presentation is altered due to shedding of the transporting M cells from the tonsil epithelium.1 As a result, tonsillar lymphocytes can theoretically become overwhelmed with persistent antigenic stimulation, rendering them unable to respond to antigens or to function adequately in local protection or reinforcement of the upper respiratory secretory immune system. Furthermore, the direct influx of antigens disproportionately expands the population of mature B-cell clones and, as a result, fewer early memory B cells go on to become J-chain-positive IgA immunocytes.1 There would therefore appear to be a therapeutic advantage to removing recurrently or chronically diseased tonsils. The surgeon should bear in mind, however, that tonsillectomy and adenoidectomy procedures remove a source of immunocompetent cells, and some studies demonstrate minor alterations of Ig concentrations in the adjacent tissues following tonsillectomy.2,22
Cultures from the deeper tissues of recurrently infected tonsils frequently reveal unusual pathogens including Staphylococcus aureus, H. influenzae, Actinomycetes, Chlamydia, Mycoplasma, and anaerobes; however, it remains unclear whether such cultures truly represent the offending organisms. Several studies suggest that bacteria in biofilms may be more important in recurrent tonsillitis than their planktonic counterparts.
Recurrent sore throat of a noninfectious nature is a hallmark of Marshall syndrome. This disorder is characterized by periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA), occurring primarily in children less than 5 years of age. The illness usually lasts more than 5 days and recurs at regular intervals of 3 to 6 weeks.23 Systemic steroids and cimetidine have demonstrated efficacy in controlling the events.23 Two small randomized controlled trials demonstrated that tonsillectomy was effective in treating PFAPA syndrome, but children in the control groups also showed improvement.24 Tonsillectomy may be considered based on the frequency of illness, severity of infection, and the child's response to medical management.
Appropriate medical and surgical management of children with recurrent infectious pharyngotonsillitis depends on accurate documentation of the cause and severity of the individual episodes as well as the frequency of the events. The clinician should record for each event a subjective assessment of the patient's severity of illness; physical findings including body temperature, pharyngeal and/or tonsillar erythema, tonsil size, tonsillar exudate, cervical adenopathy (presence, size, and tenderness); and the results of microbiologic testing for GABHS. A summary of the documentation should be made available to the consultant to aid in the medical decision-making regarding potential surgical intervention. In children with recurrent sore throat whose tests for GABHS are repeatedly positive, it may be desirable to rule out streptococcal carriage concurrent with viral infection as carriers are unlikely to transmit GABHS or to develop suppurative complications or nonsuppurative sequelae of the disease such as acute rheumatic fever. Supportive documentation in children who meet criteria for tonsillectomy may include absence from school, spread of infection within the family, and a family history of rheumatic heart disease or glomerulonephritis.
In all randomized controlled trials of tonsillectomy for infection, sore throat with each event was a necessary entrance criterion, and in most of these trials sore throat was the primary outcome studied. As a result, no claim can be made that tonsillectomy is indicated for children whose constellation of symptoms does not include sore throat, even when GABHS can be cultured from the throat. These studies also suggest that patients whose events are less severe or well documented do not gain sufficient benefit from tonsillectomy to justify the risk and morbidity of the procedure; in such patients, tonsillectomy should be considered only after a period of observation during which documentation of additional events may be made.
Children with frequent recurrences of throat infection over a period of several months demonstrate high rates of spontaneous resolution.25 As a result, an observation period of at least 12 months is generally recommended before consideration of tonsillectomy. In rare cases, early surgery may reasonably be considered for severely affected patients, such as those with histories of hospitalization for recurrent severe infections, rheumatic heart disease in the family, or numerous repeat infections in a single household (“ping-pong spread”), or those with complications of infection such as PTA or Lemierre syndrome (thrombophlebitis of the internal jugular vein).
Observation of patients is also a reasonable management strategy in children who have had frequent recurrences of pharyngotonsillitis for more than 1 year. In several studies, children demonstrated spontaneous improvement without surgery during the follow-up period, often with patients no longer meeting the original criteria for study entry. The natural history of recurrent pharyngotonsillitis is also found to be favorable in case series that describes patients on “wait lists” for tonsillectomy; many children who were reevaluated after months on such lists later no longer met the criteria for surgery.
Tonsillectomy has been suggested for centuries as a means of controlling recurrent infection of the throat. However, clinical trials investigating the efficacy of tonsillectomy have had a high risk of bias because of poorly defined entrance criteria, nonrandom selection of operated subjects, exclusion of severely affected patients, or reliance on caregivers for postoperative data collection. In the most frequently cited trial, Paradise and colleagues25 included patients only if their episodes of throat infection met strict criteria as outlined in Table 6.2. The key findings of the study were as follows:
1. A mean rate reduction of 1.9 episodes of sore throat per year among tonsillectomized children during the first year of follow-up compared with controls. However, the sore throat associated with performance of the surgery (which would otherwise count as one episode) was excluded from the data. In the control group, patients also improved compared with their preenrollment frequency of infection, experiencing a mean of only 3.1 annual events. Differences between groups were reduced in the second year and were not significant by the third year of follow-up.
2. For episodes of moderate or severe throat infection, the control group experienced 1.2 episodes compared with 0.1 in the surgical group. The rate reductions diminished over the subsequent 2 years of follow-up and were not significant in the third year.
3. Mean days with sore throat in the first 12 months were not statistically different between the two groups, but included a predictable period of sore throat postoperatively.
Table 6.2 The “Paradise Criteria” for Tonsillectomy in Recurrent Tonsillitis
Frequency of sore throat events
• Seven or more episodes in the preceding year, or
• Five or more episodes in each of the preceding 2 years, or
• Three or more episodes in each of the preceding 3 years
• Temperature >38.3°C, or
• Cervical lymphadenopathy (tender lymph nodes or >2 cm), or
• Tonsillar exudate, or
• Positive culture for GABHS
Antibiotics are administered at appropriate dose for proven or suspected episodes of GABHS
• Each episode and its qualifying characteristics are synchronously documented in the medical record, or
• In cases of insufficient documentation, two subsequent episodes of throat infection are observed by the clinician with frequency and clinical features consistent with the initial history
Adapted from: Paradise JL, Bluestone CD, Bachman RZ, et al. History of recurrent sore throat as an indication for tonsillectomy. Predictive limitations of histories that are undocumented. N Engl J Med 1978;298(8):409–413.
GABHS: group A β-hemolytic Streptococcus.
The Paradise group reported a second study26 with less rigorous criteria for the number of episodes, clinical features required for diagnosis of pharyngitis, and documentation (i.e., four to six episodes in the last year or three or four episodes per year in the past 2 years). In the two arms of the study (tonsillectomy or adenotonsillectomy vs. control, and adenotonsillectomy vs. control), patients undergoing surgery experienced rate reductions of 0.8 and 1.7 episodes/year, respectively, in the first year. For episodes of moderate or severe sore throat, control subjects in the two arms of the study combined experienced 0.3 episodes/year overall compared with 0.1/year in subjects undergoing surgery. Mean days with sore throat in the first 12 months were not statistically different in either arm of the study. The investigators concluded that the modest benefit conferred by tonsillectomy in children moderately affected with recurrent throat infection did not justify the inherent risks, morbidity, and cost of the surgery.
A randomized controlled trial comparing tonsillectomy with watchful waiting in children aged 2 to 8 years, examined fever >38°C for at least 1 day as the primary outcome measure. During a mean follow-up period of 22 months, children in the tonsillectomy group had 0.2 fewer episodes of fever per person year, and from 6 to 24 months there was no difference between the groups. The surgical group also demonstrated, per person year, mild reductions in throat infections (0.2), sore throats (0.6), days with sore throat (5.9), and upper respiratory tract infections (0.5). Pooled data from these studies were also analyzed in a Cochrane systematic review.27 Patients undergoing tonsillectomy experienced 1.4 fewer episodes of sore throat in the first year compared with the control group; however, the “cost” of this reduction was one episode of sore throat in the immediate postoperative period.
Despite the modest advantages conferred by tonsillectomy for sore throat, studies of quality of life universally suggest a significant improvement in patients undergoing the procedure. Only two of these studies enrolled children exclusively and both reported improved scores in nearly all subscales. However, both also had numerous methodological flaws including enrollment of patients with “chronic tonsillitis” without definition based on signs and symptoms, absence of a control group, low response rates with potential selection bias, poor follow-up, and caregiver collection of data.
A 2011 guideline on tonsillectomy suggests that tonsillectomy for severely affected children with recurrent throat infection should be considered an “option.”28 Families of patients who meet the appropriate criteria for tonsillectomy as described above must weigh the modest anticipated benefits of tonsillectomy for this indication against the natural history of resolution and the risk of surgical morbidity and complications.
Recurrent and Chronic Adenoiditis
The disorders characterized in children as adenoiditis, rhinosinusitis, and nasopharyngitis are not easily distinguished from one another on the basis of symptoms. Most individuals in whom the diagnosis is made present with nasal stuffiness, mucopurulent rhinorrhea, chronic cough, halitosis, and “snorting” or “gagging” on mucus throughout the day. However, there are no established criteria for making this diagnosis, or for differentiating it from viral upper respiratory illness or acute sinusitis.
In chronic or recurrent nasopharyngitis, the persistence of disease may be due to colonization by pathogenic bacteria. H. influenzae, S. pneumoniae, S. pyogenes, and S. aureus are commonly found in adenoid cultures and tissue samples among children so affected. Rates of drug-resistant bacteria may be higher among patients with chronic or recurrent infection. Furthermore, molecular typing of paired bacterial isolates from the adenoid and lateral nasal wall in children undergoing adenoidectomy demonstrates a high degree of correlation, and sinonasal symptom scores appear to correlate with quantitative bacteriology of the adenoid “core” and not with adenoid size. Several studies have demonstrated bacterial biofilm formation in the adenoid; however, it is not clear if this is more common in persistent and recurrent nasopharyngitis than in obstructive adenoid hyperplasia. In some patients, sinonasal infection is more likely due to stasis of secretions secondary to obstructive adenoid tissue rather than bacterial factors, although the two may certainly be related. Gastroesophageal reflux has not been established as a cause of chronic adenoid inflammation.
Data suggest that adenoidectomy may be useful in the management of children with persistent and recurrent sinonasal complaints, although a systematic review indicates the evidence is currently inadequate to firmly establish efficacy.29 Most clinicians favor adenoidectomy before consideration of endoscopic sinus surgery, especially for those children with recurrent acute symptoms rather than those with more chronic sinonasal disease.
Other Inflammatory Tonsil and Adenoid Disorders
Halitosis may result from food debris and bacteria retained within the crypts of the tonsils and adenoid. However, although bad breath is considered an indication for tonsillectomy by some, the evidence for this practice is lacking. A wide variety of other causes should be investigated including periodontal disease, debris of the tongue or lingual tonsils, sinonasal infection or foreign body, and gastroesophageal reflux.
Infection by Neisseria gonorrhea is a rare cause of pharyngotonsillitis resulting from orogenital contact. In young children gonococcal infection occurs due to sexual abuse, and adolescent girls may contract this infection from consensual orogenital sex.
Gonococcal infection of the throat most commonly presents as an exudative pharyngitis accompanied by fever and adenopathy, but this infection is symptomatic less than 70% of the time. Urethritis in males, and vulvovaginitis in females, and the presence of concomitant sexually transmitted diseases may be more consistent clinical indicators. The pharyngeal infection usually resolves spontaneously within 10 to 12 weeks but should be treated when diagnosed. In most cases, gonococcal pharyngitis may be adequately treated with a single parenteral administration of ceftriaxone or cefotaxime, although some physicians prefer to continue the injections daily for 7 to 10 days. Treatment should also be offered to the offending individual, and the infections must be reported to the appropriate local and national authorities.
Diphtheria pharyngitis, caused by the gram-positive bacillus C. diphtheriae, is a rare but serious cause of airway obstruction in children acquired via the respiratory passages. With aggressive immunization programs, diphtheria infection has become all but extinct in developed countries; no cases have been reported in the United States since 2003. Nevertheless, scattered cases over earlier decades have been observed among unimmunized or underimmunized individuals in lower socioeconomic groups. In fact, a large proportion of adults in the western world lack protective serum levels of diphtheria immunity.
Following an incubation period of 2 to 4 days, diphtheria exotoxin is released by the organism, initiating local tissue necrosis and exudate. The exudate within the airway turns fibrinous, and develops into an adherent gray membrane containing inflammatory cells, epithelial cells, and red blood cells. Enlargement of the membrane and progressive edema cause airway compromise and stridor, and dislodgement of the membrane may cause frank obstruction. Systemic effects of the toxin include myocarditis, peripheral neuritis, and acute tubular necrosis of the kidneys.
Definitive diagnosis is made on the basis of a culture of the membrane and/or demonstration of toxin production by immunoprecipitation, polymerase chain reaction, or immunochromatography; however, management should not be delayed for culture results. Pharyngeal membranes due to diphtheria are tenacious and difficult to remove; patients with airway compromise may urgently require a more secure airway. Once the airway is established, antitoxin and antibiotic therapy with penicillin or erythromycin are subsequently administered, and nonimmune personal contacts are treated as well. Prognosis depends on the immunization status of the host, the promptness of medical therapy, and the virulence of the infecting organism. Prevention of diphtheria is achieved through immunization during infancy.
Kawasaki Disease (Mucocutaneous Lymph Node Syndrome)
Kawasaki disease (KD) is a multisystem vasculitis characterized by fever, rash, pharyngitis, conjunctival inflammation, edema of the extremities, and cervical adenopathy. Initially reported in the Japanese literature in 1967 as a benign disorder of childhood, KD has been linked over the past three decades to serious cardiac complications, arthritis, and several other manifestations. The etiology of KD remains unknown; epidemiologic and clinical data occurrence of KD support an infectious etiology, but a mode of transmission has not been determined. About 80% of KD cases occur in children below 5 years of age.30 The disease is slightly more common in males and among individuals of Asian extraction. Between 3000 and 5000 cases occur annually in the United States.30
KD occurs in three distinct clinical phases. The acute phase lasts 1 to 2 weeks, and is characterized by prolonged high spiking fever, rash, erythema of the bulbar conjunctiva, swelling and erythema of the extremities, and adenopathy. Oral and oropharyngeal manifestations are also common, including swollen, fissured, and bleeding lips; “strawberry tongue” (resulting from diffuse erythema and prominent papillae); and erythema of the oropharyngeal mucosa. Each of these findings is observed in over 90% of patients, except for adenopathy >1.5 cm, which is seen in 50 to 75%. In the subacute phase, days 10 to 25, most of these signs and symptoms resolve, but irritability and conjunctival changes usually persist. The toes and fingers begin to desquamate and joint pain is present in approximately 30% of patients. Cardiac dysfunction, including coronary arteritis, vascular dilatation and aneurysm formation, myocarditis, arrhythmia, and coronary insufficiency, occurs in about 20% of children during this period. The third, or convalescent, stage begins when clinical signs of KD have completely resolved and ends when the sedimentation rate returns to normal. KD may also be associated with sterile pyuria, aseptic meningitis, hepatic dysfunction, distension of the gallbladder, diarrhea, uveitis, otitis media, and pneumonitis.
Therapy for KD in the acute phase is directed at prevention of cardiac complications. High-dose aspirin is usually administered (with a watchful eye for signs of Reye syndrome) to decrease myocardial inflammation and prevent thrombosis. Anesthetic and antacid mouthwashes may alleviate odynophagia. Lubrication of the lips may reduce fissuring and bleeding. Intravenous immunoglobulin (IVIG) results in a more rapid anti-inflammatory effect than that seen with aspirin alone. IVIG also appears to lessen the risk of long-term coronary artery abnormalities. Once the convalescent phase is reached, patients are generally monitored at regular intervals for evidence of cardiac complications.
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