Upper Respiratory Tract Infections

Foundations

Tonsillopharyngitis (pharyngitis) is generally a benign, self-limited inflammatory syndrome of the oropharynx. Although most cases are mild, severe cases may lead to airway swelling, dehydration from decreased oral intake, and suppurative complications, including peritonsillar abscess, deep space infection, and hematogenous spread. A majority of cases are viral and caused by common cold viruses. Bacterial infection is responsible for approximately 5% to 10% of adult and 20% to 30% of pediatric cases. Common bacterial causes of pharyngitis include group A beta-hemolytic Streptococcus (GAS), non–group A Streptococcus , Fusobacterium, and mixed aerobes and anaerobes ( Table 61.1 ). Transmission occurs through direct person-to-person contact or via aerosolized respiratory secretions. Although fomite transmission is rare, crowded conditions such as in schools, daycare, and military training facilities increase transmission rates.

Tonsils are lymphoid tissue covered with respiratory epithelial tissue. Waldeyer ring refers to the lymphoid tissue in the pharynx consisting of the palatine tonsils (commonly referred to as tonsils), pharyngeal tonsils (adenoids), tubal tonsils (surrounding eustachian tubes), and lingual tonsils at the base of the tongue. Tonsillar infection, inflammation, and hypertrophy may occur in any of these locations ( Fig. 61.1 ). Although rare, lingual tonsillitis predominantly occurs in patients who had their palatine tonsils removed.

Clinical Features

Symptom chronicity, associated complaints, patient comorbidities, and patient risk factors are important considerations. Acute presentations are more likely to be infectious, whereas more chronic presentations raise concern for noninfectious or neoplastic etiologies. Sore throat, odynophagia, fever, malaise, and tender anterior cervical adenopathy are the most common symptoms. Although presentation differs by the disease process, erythema, edema, and petechiae of the oropharynx ( Fig. 61.2 ), as well as palatine tonsillar plaques ( Fig. 61.3 ), are common findings.

Viruses that cause the common cold are responsible for 30% to 60% of pharyngitis cases (see Table 61.1 ). Symptoms may overlap with GAS but are unlikely to be as severe and are associated with rhinorrhea, cough, conjunctivitis, congestion, and headache. Viral symptoms usually precede symptoms of a sore throat. Inflammation and hypertrophy of tissue in the Waldeyer ring without exudate is common.

Infectious mononucleosis, caused by the Epstein-Barr virus (EBV), classically presents with the triad of fever, tonsillar pharyngitis, and posterior cervical lymphadenopathy. The incubation period is 3 to 7 weeks, and patients experience a prodrome of fever, chills, and malaise. Most patients have exudative pharyngitis with tonsillar hypertrophy (see Fig. 61.3 ). Petechiae are intermittently present at the junction of the hard and soft palate (see Fig. 61.2 ). In severe cases, upper airway swelling may lead to difficulty managing secretions, stridor, and dyspnea. Splenomegaly is present in approximately half the cases. A pruritic morbilliform rash may occur regardless of contact with beta-lactam antibiotics. Jaundice is rare.

Influenza may present with nonexudative pharyngitis and sore throat along with generalized fever, chills, myalgia, and headaches. Human immunodeficiency virus (HIV) and cytomegalovirus can present as a mononucleosis-like illness. Pharyngitis and hypertrophy of tissue in the Waldeyer ring may also occur. The acute retroviral syndrome of primary HIV infection includes fever, sore throat, nontender lymphadenopathy, diffuse maculopapular rash, arthralgias, mucocutaneous ulcerations, and diarrhea. Spread by sexual contact, herpes simplex pharyngitis presents with painful vesicles or ulcerations on an erythematous base on the lips, tongue, palate, or mucosa ( Fig. 61.4 ). Patients with oropharyngeal herpes have palatal hyperemia with sore throat, odynophagia, stomatitis, and tender cervical adenopathy. Immunosuppressed patients with oropharyngeal herpes may present with large ulcerations, and bacterial superinfection is possible. Coxsackie virus may also cause herpangina with oral and pharyngeal erythematous papulo-vascular ulcerations. Coxsackie virus also causes small tender, nonpruritic, cutaneous lesions on the palms, soles, and buttocks.

Group A beta-hemolytic Streptococcus is a gram-positive coccus that grows in chains and is the most frequent cause of bacterial pharyngitis, most commonly in children ages 5 to 15 years. Humans are the only carrier of GAS, and asymptomatic carrier status is uncommon. The incubation period is typically 2 to 5 days. Virulence factors of GAS include host inflammatory mediators, bacterial cell wall, and secreted enzymes and exotoxins. Infection is most common in the fall and winter. Untreated, symptoms last 3 to 7 days, and patients are contagious up to one week after symptom resolution. Treated, symptoms resolve approximately 16 hours sooner than in untreated patients, and the contagious period decreases to 24 hours after the start of antibiotics. Rapid onset of sore throat, odynophagia, cervical adenopathy, fevers, chills, and neck stiffness are characteristic. Headache, abdominal pain, nausea, and vomiting may be present. GAS does not present with trismus, cough, conjunctivitis, diarrhea, rhinorrhea, or oral ulcerations.

Exam findings include symmetric erythema and edema of the oropharynx, gray/white tonsillar exudates (see Fig. 61.3 ), palatal petechiae (see Fig. 61.2 ), and tender cervical adenopathy. GAS pharyngitis associated with a desquamating, fine, sandpaper-like rash is called scarlet fever and is related to an exotoxin-producing strain of GAS. Suppurative complications of GAS include acute otitis media, mastoiditis, meningitis, peritonsillar and retropharyngeal abscess, and rarely, necrotizing fasciitis or hematogenous spread to distant sites. Acute rheumatic fever and post-streptococcal glomerulonephritis are rare in the general population. The decrease in the frequency of acute rheumatic fever is likely due to a shift in the streptococcal M protein types leading to decreased rheumatogenicity rather than due to the increased use of antibiotics.

Non–group A Streptococcus also causes acute pharyngitis with a similar presentation to GAS, but acute infection is difficult to distinguish from normal upper respiratory flora on respiratory culture. Fusobacterium necrophorum is an anaerobic gram-negative rod that is part of the normal oral flora and causes pharyngitis in patients 15 to 45 years old with a similar presentation to GAS. Fusobacterium is the primary causative agent in septic jugular vein thrombophlebitis (Lemierre syndrome). The early identification and treatment ( Table 61.2 ) of Fusobacterium in pharyngitis remains unclear; Fusobacterium should be considered in young adults with ongoing severe symptoms.

Arcanobacterium haemolyticum is a nonmotile beta-hemolytic gram-positive bacillus that is not part of the upper respiratory flora and is associated with a minority of pharyngitis cases with peak prevalence in the late teens. It is associated with deep space infections such as retropharyngeal abscesses. Along with pharyngitis, patients may also experience an urticarial, maculopapular rash that spares the face, palms, and soles. Francisella tularensis is a zoonotic gram-negative bacillus that may cause a false-positive monospot test and has atypical lymphocytes on peripheral smear. It can present as pharyngitis and a flu-like illness in patients with a contaminated food or water source. ^, Mycoplasma pneumoniae and Chlamydia pneumoniae pharyngitis may occur as part of an outbreak in crowded conditions. Lower respiratory tract infection and rhinosinusitis may occur.

Neisseria gonorrhoeae is an intracellular gram-negative diplococcus that is transmitted through sexual contact. Patients are usually symptomatic with tonsillitis and found to have enlarged tonsils with a white-yellow exudate in the tonsillar crypts. Chlamydia trachomatis pharyngitis has a similar presentation to gonococcal pharyngitis and is transmitted through sexual contact. Treponema pallidum is the spirochete that causes syphilis. Primary infection can present with painless oral ulceration. Secondary syphilis may have associated pharyngitis with localized adenopathy that can be mistaken for carcinoma. Patients with atypical presentations, risk factors for sexually transmitted infections, or no other apparent cause should have a focused sexual history and appropriate testing based on their response.

Diphtheria is caused by the gram-positive bacillus Corynebacterium diphtheriae . Although the incidence has decreased because of vaccination, diphtheria should be considered in patients who traveled to endemic areas or who are not vaccinated. The incubation period is 2 to 5 days. Early symptoms are typical of generalized pharyngitis with sore throat, cervical adenopathy, and fever. Toxin-producing strains may create a pseudomembrane that is grayish-green to black (if bleeding occurs) that tightly adheres to mucosal tissue and is friable. Severe forms may obstruct the airway and may be associated with extensive swelling of the tonsils, uvula, and anterior neck. Toxins produced can affect distant sites causing myocarditis, neuritis, and acute tubular necrosis. Non–toxin producing strains cause moderate to severe pharyngitis without pseudomembrane formation.

Oral candidiasis presents with a white pseudomembrane over the tongue, buccal mucosa, palate, and oropharynx that can be scraped off with a tongue depressor. It occurs most commonly in immunocompromised patients, the elderly, patients with recent antibiotic exposure, and those on chronic steroids. Chronic hyperplastic candidiasis may present as elevated white plaques that cannot be scraped off of the buccal mucosa.

Differential Diagnosis for Emergency Presentation

A focused differential for pharyngitis is largely guided by the history and physical exam with attention to systemic signs and symptoms. Table 61.1 lists the infectious and noninfectious causes of pharyngitis.

Diagnostic Testing

Diagnostic testing is not required if features strongly suggest a viral etiology: associated with rhinorrhea, cough, conjunctivitis, congestion, and headache which usually precede symptoms of a sore throat. Testing for Epstein-Barr virus (EBV) can be considered in patients with splenomegaly, posterior cervical adenopathy, palatal petechiae, and those patients with persistent symptoms despite adequate treatment for GAS pharyngitis. The initial testing for infectious mononucleosis is a heterophile antibody test (Monospot). The Monospot has high specificity but variable sensitivity, with false-negative results in children and early in the infection. If the antibody test is negative and the patient remains symptomatic, we recommend follow-up with their primary care physician and retesting in 7 to 10 days or checking an EBV viral capsid antigen IgM. Viral load is not validated for infectious mononucleosis. Mononucleosis causes an absolute lymphocytosis with greater than 10% atypical lymphocyte count due to EBV’s effect on B lymphocytes and the cytotoxic T-cell response. Influenza is tested with a PCR nasal or oral pharyngeal swab. Influenza testing should occur in patients with fevers, myalgia, headache, and sore throat occurring when influenza viruses are circulating in the community, when the patient is being admitted to the hospital, or when testing will influence management. HIV testing is performed with a fourth-generation combination assay. It should be performed in patients with risk factors and persistent pharyngitis symptoms without any other etiology. Herpes is diagnosed with PCR testing of a viral swab from an ulcer or unroofed vesicle or HSV IgG and IgM serology.

Rapid antigen testing is recommended as a first-line diagnostic test for GAS pharyngitis. These patients present with sore throat, fever, exudative pharyngitis, and cervical lymphadenopathy without associated cough or rhinorrhea. Scoring systems such as the Centor criteria ( Box 61.1 ) should be used to identify adults who do not require further testing or treatment. The score should not be used in patients who are immunocompromised, have complicated comorbid conditions, or have symptoms for greater than 5 days. Patients with zero or one Centor criterion should not be tested or treated. Empiric treatment is not recommended for any patient. ^, Rapid antigen tests are highly sensitive and specific when performed correctly (swabbing the bilateral tonsils and the posterior pharynx, avoiding the buccal mucosa and tongue). A positive test indicates the presence of GAS and does not require follow-up testing. If the antigen testing is negative, a confirmatory culture on sheep blood agar is recommended in children, can be considered in adolescents, and is not necessary in adults. There is no role for antistreptolysin O titers.

Patients with persistent symptoms and unknown etiology should undergo throat culture. Arcanobacterium haemolyticum is performed on human blood agar. Diphtheria requires culture on Loeffler medium. The laboratory should be notified if there is concern for Arcanobacterium or diphtheria, which would be indicated in patients with severe pharyngitis or the appearance of gray pseudomembrane in the posterior oropharynx. Candida is diagnosed when budding yeast with or without pseudohyphae is seen on the Gram stain or potassium hydroxide stain. A throat swab with a nucleic acid amplification test is recommended for Chlamydia trachomatis and Neisseria gonorrhoeae.

Management

For a majority of cases, supportive care alone with nonsteroidal antiinflammatory medications or acetaminophen will be sufficient. There is no direct evidence of benefit from warm salt gargles, lozenges, soft or cold foods, or humidified topical analgesics. Viscous lidocaine should be avoided due to the potential for suppression of cough and gag and risk for aspiration. Treatment for infectious mononucleosis is supportive. Corticosteroids are not recommended for infectious mononucleosis, except in the cases of significant oropharyngeal edema with stridor or change in phonation. Treatment of influenza should be started as soon as possible on documented or suspected influenza cases in hospitalized patients, children less than 2 years old, adults 65 years and older, pregnant women and within 2 weeks postpartum, patients with immunosuppression, and patients with chronic cardiac, pulmonary, hepatic, renal or hematologic disorders. Clinicians can consider antiviral treatment in patients not at high risk for complications and outpatients with symptom onset less than 2 days before presentation, and in those symptomatic with household contact with those at high risk for compilations of influenza, or health care workers with contact with those at high risk for complications. Treatment consists of antiviral medication (oral oseltamivir, inhaled zanamivir, or intravenous peramivir.) HIV requires referral to appropriate providers for the initiation of antiretroviral medications.

The rationale for the treatment of GAS is to decrease the length of symptoms, suppurative complications, and the infectious period. Prophylactic antibiotics to close contacts of infected patients is not recommended. Retesting after treatment is not required unless there are recurrent symptoms. Treatment failures may be related to carrier status, lack of compliance, recurrent exposure, resistant bacteria, or eradication of protective flora. Treatments of pharyngitis are listed on Table 61.2 . We recommend steroid administration for GAS. A single dose of corticosteroids such as dexamethasone appears to be safe and leads to a decrease in symptom duration. Patients with recurrent episodes of GAS should be referred to an otolaryngologist for consideration of tonsillectomy. Diphtheria is treated with diphtheria antitoxin (DAT) and penicillin or erythromycin. Mild candidal pharyngitis treatment is topical with clotrimazole troches or nystatin swish and swallow, whereas moderate to severe forms require systemic therapy with fluconazole.

Disposition

Patients with uncomplicated pharyngitis may be discharged and treated as outpatients. Patients with evidence of upper airway obstruction including stridor, difficulty managing secretions, and changes in phonation or severe systemic symptoms such as hypotension or altered mental status require consultation with an otolaryngologist and admission to the hospital.

Foundations

Acute laryngitis is an inflammation of the larynx which is predominantly caused by viral infections. Chronic laryngitis is diagnosed after three weeks of continuous symptoms and may be due to gastroesophageal reflux, overuse of the voice, trauma, thermal and chemical burns, irritants, and allergic reactions.

Diffuse inflammation of the larynx caused predominantly by viral infection results in mucosal edema and laryngeal obstruction. It occurs most commonly in children ages 1 to 5 years and is more frequently seen in the winter and spring. Immunocompromised patients can develop laryngitis caused by opportunistic fungal and viral infections. Patients with frequent use of inhaled corticosteroids are also at increased risk for fungal laryngitis.

Clinical Features

Laryngeal inflammation and edema cause sore throat, hoarse voice, inspiratory stridor, fever, and barking cough. Chronic laryngitis may additionally present with globus sensation and excessive throat clearing. Laryngitis may exist on its own or be part of a constellation of symptoms of upper airway infection including epiglottitis. Epiglottitis generally includes inflammation of the arytenoids and aryepiglottic folds and is sometimes referred to as supraglottitis. Inflammation of the glottis, arytenoids, and aryepiglottic folds increases the potential for acute upper airway obstruction, though the majority of cases of laryngitis are self-limited.

Differential Diagnosis for Emergency Presentation

The etiologies of laryngitis are similar to pharyngitis displayed in Table 61.1 , with the majority being caused by the viruses that cause the common cold. The differential diagnosis includes infectious etiologies such as retropharyngeal abscess and noninfectious etiologies such as anaphylaxis, angioedema, tumor, thyroiditis, chemical or thermal injury, and foreign body.

Diagnostic Testing

There is no specific diagnostic testing for laryngitis, and the majority of cases will resolve within two weeks. Routine viral testing or bacterial cultures are not recommended.

Management

The majority of patients with laryngitis will improve without intervention. Systemic steroids have been shown to decrease symptom severity in pediatric patients; we recommend dexamethasone 0.6 mg/kg given via intramuscular, intravenous, or oral route depending on patient ability to tolerate oral intake and intravenous access availability with a maximum dose of 10 mg. Immunocompromised patients and patients with symptoms persisting for greater than two weeks should be referred to otolaryngology.

Disposition

Laryngitis can be treated on an outpatient basis. Exceptions occur when symptoms of laryngitis are occurring concomitantly with symptoms of supraglottitis/epiglottitis.

Foundations

Acute epiglottitis is an inflammation of the epiglottis and commonly the supraglottic region, including the arytenoids, base of the tongue, and vallecula. It is sometimes referred to as supraglottitis, but we will use the term epiglottitis. It is a rare but potentially life-threatening disease because of rapidly occurring airway obstruction and asphyxiation. Since the widespread adoption of the Haemophilus influenzae type B conjugate vaccine, epiglottitis is more common in adults than children. Patients with diabetes, immunosuppression, and substance abuse issues, including tobacco and alcohol, are at increased risk for its development. ^, The majority of cases are caused by bacterial infection, including Haemophilus influenzae (type B and non-typeable), Streptococcus pneumoniae, and Staphylococcus subspecies. Noninfectious causes of epiglottitis include burns, trauma, and inhalational injury.

Clinical Features

Symptoms are on a spectrum from sore throat, dysphagia, odynophagia, fever, hoarseness, and foreign body sensation in early stages to stridor, inability to manage secretions, and breathlessness with signs of airway compromise. Patients may sit forward in a sniffing position to maintain airway patency if there is sufficient swelling.

Differential Diagnosis

The differential diagnosis for epiglottitis includes infectious etiologies such as retropharyngeal abscess and noninfectious etiologies such as anaphylaxis, angioedema, tumor, thyroiditis, chemical or thermal injury, and foreign body.

Diagnostic Testing

Flexible laryngoscopy is the gold standard for diagnosis of epiglottitis and should be performed in patients presenting with symptoms of epiglottitis including sore throat, voice changes, and stridor. Lateral neck radiographs with an epiglottis width greater than 5.5 mm (“thumb sign” Fig. 61.5 ) have moderate sensitivity but cannot be used to rule out epiglottitis. We recommend against an initial diagnostic CT scan of the neck because of the need for supine positioning and potential for airway obstruction. Do not swab the posterior throat or use a tongue depressor because this may exacerbate the edema.