Laryngitis

Background
Laryngitis is one of the most common conditions identified in the
larynx. Laryngitis, an inflammation of the larynx, manifests in both
acute and chronic forms.
Acute laryngitis has an abrupt onset and is usually self-limited. If a
patient has symptoms of laryngitis for more than 3 weeks, the
condition is classified as chronic laryngitis. The etiology of acute
laryngitis includes vocal misuse, exposure to noxious agents, or
infectious agents leading to upper respiratory tract infections. The
infectious agents are most often viral but sometimes bacterial.
See the image below.

This view
depicts the larynx of a 62-year-old woman with an intermittent history
of exudative acute laryngitis that was treated conservatively.
Courtesy of Ann Kearney, Palo Alto, Calif.
View Media Gallery
Rarely, laryngeal inflammation results from an autoimmune condition
such as rheumatoid arthritis, relapsing polychondritis, Wegener
granulomatosis, or sarcoidosis. A case report showed a 2-year-old
intubated patient who was given activated charcoal for poisoning,
resulting in obstructive laryngitis. This unusual case demonstrates
the myriad potential etiologies of acute laryngitis.
Chronic laryngitis, as the name implies, involves a longer duration of
symptoms; it also takes longer to develop. Chronic laryngitis may be
caused by environmental factors such as inhalation of cigarette
smoke or polluted air (eg, gaseous chemicals), irritation
from asthma inhalers, vocal misuse (eg, prolonged vocal use at
abnormal loudness or pitch), or gastrointestinal esophageal reflux.
Vocal misuse results in an increased adducting force of the vocal
folds with subsequent increased contact and friction between the
contacting folds. The area of contact between the folds becomes
swollen. Vocal therapy has the greatest benefit in the patient with
chronic laryngitis.
Although acute laryngitis is usually not a result of vocal abuse, vocal
abuse is often a result of acute laryngitis. The underlying infection or
inflammation results in a hoarse voice. Typically, the patient
exacerbates the dysphonia by misuse of the voice in an attempt to
maintain premorbid phonating ability.
Pathophysiology
Acute laryngitis is an inflammation of the vocal fold mucosa and
larynx that lasts less than 3 weeks. When the etiology of acute
laryngitis is infectious, white blood cells remove microorganisms
during the healing process. The vocal folds then become more
edematous, and vibration is adversely affected. The phonation
threshold pressure may increase to a degree that generating
adequate phonation pressures in a normal fashion becomes difficult,
thus eliciting hoarseness. Frank aphonia results when a patient
cannot overcome the phonation threshold pressure required to set
the vocal folds in motion.
The membranous covering of the vocal folds is usually red and
swollen. The lowered pitch in laryngitic patients is a result of this
irregular thickening along the entire length of the vocal fold. Some
authors believe that the vocal fold stiffens rather than thickens.
Conservative treatment measures, as outlined below, are usually
enough to overcome the laryngeal inflammation and to restore the
vocal folds to their normal vibratory activity.
Epidemiology
Frequency
United States
The exact prevalence of acute laryngitis is not reported because
many patients often use conservative measures to treat their
inflammation rather than seek medical consultation. Symptoms of an
upper respiratory tract infection often accompany the disease; thus,
patients are accustomed to managing their own treatment.
Nevertheless, laryngitis is one of the most common laryngeal
pathologies.
A study by Bhattacharyya suggested that annually about 1% of
children in the United States are effected by voice or swallowing
problems, with laryngitis being a common diagnosis in these cases.
Using the 2012 National Health Interview Survey, the study found
that an estimated 839,000 children in the United States (1.4%)
reported a voice problem in the 12 months preceding the survey, with
53.5% of these youngsters having been given a diagnosis for it, the
most prevalent being laryngitis (16.6%) and allergies (10.4%). [1]
A retrospective study by Roy et al indicated that among elderly
members of the US population (those over age 65 years) who saw a
primary care physician or otolaryngologist, acute and chronic
laryngitis were among the most frequent laryngeal/voice disorder
diagnoses, along with nonspecific dysphonia and benign vocal fold
lesions. The study, which was based on information from a national
administrative database, also found that among the elderly, women
had greater odds of developing acute laryngitis than did men. [2]
Mortality/Morbidity
Because acute laryngitis is usually self-limited and treated with
conservative measures, significant morbidity and mortality are not
encountered. Patients who develop acute laryngitis from an infectious
etiology rather than vocal trauma may ultimately injure their vocal
folds. The deficient voice production in patients with acute laryngitis
may result in application of a greater adduction force or tension to
compensate for the incomplete glottic closure during an acute
laryngitic episode. This tension further strains the vocal folds and
decreases voice production, ultimately delaying return of normal
phonation.
In 1997, Ng conducted a study of the aerodynamic and acoustic
characteristics of acute laryngitis. [3] His study demonstrated that
across the 5 vowels, the fundamental frequency values were lower in
patients with acute laryngitis than in patients with a normal voice. The
authors concluded that acute laryngitis changes the vocal fold mass,
resulting in a reduction of the fundamental frequency; other authors
have anecdotally corroborated this finding. [4]
Patients with acute laryngitis have an increased open quotient value.
This indicates that the patient's vocal folds are open longer, and less
time is spent in the closed position, which contributes to the
hoarseness and breathiness of the voice.
Laryngitis has a significant economic impact. Over the economic
burden, pharmaceutical costs were approximately 30% of such
costs. [5]
Age
Studies have demonstrated that, usually, acute laryngitis affects
individuals aged 18-40 years. Children, a category not included in the
above study, are clinically observed with acute laryngitis when aged 3
years and older

URI
Practice Essentials

Upper respiratory tract infection (URI) represents the most common

acute illness evaluated in the outpatient setting. URIs range from the
common coldtypically a mild, self-limited, catarrhal syndrome of the
nasopharynxto life-threatening illnesses such as epiglottitis (see
the image below).

Lateral neck radiograph demonstrates epiglottitis. Courtesy of

Marilyn Goske, MD, Cleveland Clinic Foundation.

View Media Gallery

Signs and symptoms

Details of the patient's history aid in differentiating a common cold

from conditions that require targeted therapy, such as group A
streptococcal pharyngitis, bacterial sinusitis, and lower respiratory
tract infections. Clinical manifestations of these conditions, as well as
allergy, show significant overlap.

Viral nasopharyngitis
Patients with the common cold may have a paucity of clinical findings
despite notable subjective discomfort. Findings may include the
following:

Nasal mucosal erythema and edema are common

Nasal discharge: Profuse discharge is more characteristic of
viral infections than bacterial infections; initially clear secretions
typically become cloudy white, yellow, or green over several days,
even in viral infections
Foul breath
Fever: Less common in adults but may be present in children
with rhinoviral infections

Group A streptococcal pharyngitis The following physical findings

suggest a high risk for group A streptococcal disease [1] :

Erythema, swelling, or exudates of the tonsils or pharynx

Temperature of 38.3C (100.9F) or higher
Tender anterior cervical nodes (1 cm)
Absence of conjunctivitis, cough, and rhinorrhea, which are
symptoms that may suggest viral illness [2]

Acute bacterial rhinosinusitis In children, acute bacterial sinusitis is

defined as a URI with any of the following [3] :

Persistent nasal discharge (any type) or cough lasting 10 days

or more without improvement
Worsening course (new or worse nasal discharge, cough,
fever) after initial improvement
Severe onset (fever of 102 or greater with nasal discharge) for
at least 3 consecutive days

In older children and adults, symptoms (eg, pain, pressure) tend to

localize to the affected sinus.

Epiglottitis

This condition is more often found in children aged 1-5 years, who
present with a sudden onset of the following symptoms:

Sore throat
Drooling, difficulty or pain during swallowing, globus sensation
of a lump in the throat
 Muffled dysphonia or loss of voice
Dry cough or no cough, dyspnea
Fever, fatigue or malaise (may be seen with any URI)
Tripod or sniffing posture

Laryngotracheitis and laryngotracheobronchitis

Nasopharyngitis often precedes laryngitis and tracheitis by

several days
Swallowing may be difficult or painful
Patients may experience a globus sensation of a lump in the
throat
Hoarseness or loss of voice is a key manifestation of laryngeal
involvement

Features of whooping cough (pertussis) are as follows:

The classic whoop sound [4] is an inspiratory gasping squeak

that rises in pitch, typically interspersed between hacking coughs
The whoop is more common in children
Coughing often comes in paroxysms of a dozen coughs or
more at a time and is often worst at night

The 3 classic phases of whooping cough are as follows:

Catarrhal (7-10 days) with predominantly URI symptoms

Paroxysmal (1-6 weeks) with episodic cough
Convalescent (7-10 days) of gradual recovery[5]

See Clinical Presentation for more detail.

Diagnosis

Tests of nasopharyngeal specimens for specific pathogens are

helpful when targeted therapy depends on the results (eg, group A
streptococcal infection, gonococcus, pertussis). Specific bacterial or
viral testing is also warranted in other selected situations, such as
when patients are immunocompromised, during certain outbreaks, or
to provide specific therapy to contacts.

Diagnosis of specific disorders is based on the following:

Group A streptococcal infection: Clinical findings or a history of

exposure to a case, supported by results of rapid-detection assays
 and cultures (positive rapid antigen detection tests do not
necessitate a backup culture)
Acute bacterial rhinosinusitis: Laboratory studies are generally
not indicated; Computed tomography (CT) scanning or other sinus
imaging may be appropriate if symptoms persist despite therapy or
if complications (eg, extension of disease into surrounding tissue)
are suspected
Influenza: Rapid tests have over 70% sensitivity and more than
90% specificity
Mononucleosis: Heterophile antibody testing (eg, Monospot)
Herpes simplex virus infection: Cell culture or polymerase
chain reaction (PCR) assay
Pertussis: Rapid tests; culture of a nasopharyngeal aspirate
(criterion standard)
Epiglottitis: Direct visualization by laryngoscopy, performed by
an otorhinolaryngologist
Gonococcal pharyngitis: Throat culture forNeisseria
gonorrhoeae

Blood cultures are typically appropriate only in hospitalized patients

with suspected systemic illness. Imaging studies are warranted in
patients with suspected mass lesions (eg, peritonsillar abscess,
intracranial suppurative lesions).

See Workup for more detail.

Management

Symptom-basedtherapy represents the mainstay of URI treatment in

immunocompetent adults. Antimicrobial or antiviral therapy is
appropriate in selected patients.

Epiglottitis

Immediately admit the patient to the nearest hospital

Avoid instrumentation; insertion of tongue depressors or other
instruments may provoke airway spasm and precipitate respiratory
compromise
Monitor for respiratory fatigue, visually and with continuous
pulse oximetry
Administer oxygen according to pulse oximetry results
Have equipment and personnel available for immediate
intubation if necessary
 Start intravenous (IV) antibiotics after collecting culture
specimens
Empiric coverage for Haemophilus influenzaeis appropriate;
common choices include ceftriaxone or other third-generation
cephalosporins, cefuroxime, and cefamandole
Correct volume deficits with IV fluids; avoid sedatives

Laryngotracheitis

Hospitalization may be necessary, especially in infants and

young children who have hypoxemia, volume depletion, a risk of
airway compromise, or respiratory fatigue
Mild cases of croup (ie, laryngotracheobronchitis) may be
managed at home with moist air inhalation
Hospitalized patients require monitoring for respiratory fatigue,
visually and with continuous pulse oximetry
Expertise for immediate intubation and access to the necessary
equipment are required if respiratory failure is a possibility
Administer humidified oxygen to all hypoxemic patients. In
patients who do not require oxygen therapy, a cool-mist humidifier
may be used
IV or oral glucocorticoids are commonly used to reduce
symptoms and shorten hospitalization in patients with moderate to
severe croup
Inhaled racemic epinephrine may temporarily dilate the airways

Rhinosinusitis

Most cases of acute rhinosinusitis, including mild and moderate

bacterial sinusitis, resolve without antibiotics [6]
Consider antibiotic treatment if symptoms persist without
improving for 10 or more days, or if symptoms are severe or
worsening during a period of 3-4 days or longer [7]
Give first-line antibiotics for 5-7 days in most adults; for 10-14
days in children
Begin treatment with an agent that most narrowly covers likely
pathogens, includingStreptococcus pneumoniae, nontypeable H
influenzae, and Moraxella catarrhalis
Initial first-line options include amoxicillin/clavulanate
Alternatives in penicillin-allergic patients are doxycycline and
respiratory fluoroquinolones (eg, levofloxacin, moxifloxacin)
 In patients who worsen or do not improve after 3-5 days of
empirical therapy, consider resistant pathogens, structural
abnormality, or noninfectious etiology
Adjunctive therapy for adults includes nasal saline irrigation
and intranasal steroids

Group A streptococcal disease

Oral penicillin or amoxicillin for 10 days for patients without an

allergy to penicillin
If compliance is a concern, consider a single IM injection of
benzathine penicillin G
A first-generation cephalosporin may be used in patients with
non-anaphylactic penicillin allergy
Options for penicillin-allergic patients include clindamycin or
clarithromycin for 10 days or azithromycin for 5 days [2]

See Treatment and Medication for more detail.

Background

Upper respiratory tract infection (URI) represents the most common

acute illness evaluated in the outpatient setting. URIs range from the
common coldtypically a mild, self-limited, catarrhal syndrome of the
nasopharynxto life-threatening illnesses such as epiglottitis.

Viruses account for most URIs (see Etiology). Appropriate

management in these cases may consist of reassurance, education,
and instructions for symptomatic home treatment. Diagnostic tests for
specific agents are helpful when targeted URI therapy depends on
the results (see Workup). Bacterial primary infection or superinfection
may require targeted therapy (see Treatment).

The upper respiratory tract includes the sinuses, nasal passages,

pharynx, and larynx, which serve as gateways to the trachea,
bronchi, and pulmonary alveolar spaces. Rhinitis, pharyngitis,
sinusitis, epiglottitis, laryngitis, and tracheitis are specific
manifestations of URIs. Further information can be found in the
Medscape Reference articles Acute Laryngitis, Acute Sinusitis,
Allergic Rhinitis, Bacterial Tracheitis, Croup, Epiglottitis, Pharyngitis,
and Viral Pharyngitis.

Common URI terms are defined as follows:

 Rhinitis: Inflammation of the nasal mucosa
Rhinosinusitis or sinusitis: Inflammation of the nares and
paranasal sinuses, including frontal, ethmoid, maxillary, and
sphenoid
Nasopharyngitis (rhinopharyngitis or the common cold):
Inflammation of the nares, pharynx, hypopharynx, uvula, and
tonsils
Pharyngitis: Inflammation of the pharynx, hypopharynx, uvula,
and tonsils
Epiglottitis (supraglottitis): Inflammation of the superior portion
of the larynx and supraglottic area
Laryngitis: Inflammation of the larynx
Laryngotracheitis: Inflammation of the larynx, trachea, and
subglottic area
Tracheitis: Inflammation of the trachea and subglottic area

Pathophysiology

URIs involve direct invasion of the mucosa lining the upper airway.
Inoculation of bacteria or viruses occurs when a persons hand
comes in contact with pathogens and the person then touches the
nose or mouth or when a person directly inhales respiratory droplets
from an infected person who is coughing or sneezing.

After inoculation, viruses and bacteria encounter several barriers,

including physical, mechanical, humoral, and cellular immune
defenses. Physical and mechanical barriers include the following:

Hair lining the nose filters and traps some pathogens

Mucus coats much of the upper respiratory tract, trapping
potential invaders
The angle resulting from the junction of the posterior nose to
the pharynx causes large particles to impinge on the back of the
throat
Ciliated cells lower in the respiratory tract trap and transport
pathogens up to the pharynx; from there they are swallowed into
the stomach

Adenoids and tonsils contain immune cells that respond to

pathogens. Humoral immunity (immunoglobulin A) and cellular
immunity act to reduce infections throughout the entire respiratory
tract. Resident and recruited macrophages, monocytes, neutrophils,
and eosinophils coordinate to engulf and destroy invaders.
A host of inflammatory cytokines mediates the immune response to
invading pathogens. Normal nasopharyngeal flora, including various
staphylococcal and streptococcal species, help to defend against
potential pathogens. Patients with suboptimal humoral and
phagocytic immune function are at increased risk for contracting a
URI, and they are at increased risk for a severe or prolonged course
of disease.

Inflammation (chronic or acute) from allergy predisposes to URI.

Children with allergy are particularly subject to frequent URIs.

Infection

Person-to-person spread of viruses accounts for most URIs.

Household and child care settings can serve as reservoirs for
infection. Bacterial infections may develop de novo or as a
superinfection of a viral URI.

Viral agents occurring in URIs include a vast number of serotypes,

which undergo frequent changes in antigenicity, posing challenges to
immune defense. Pathogens resist destruction by a variety of
mechanisms, including the production of toxins, proteases, and
bacterial adherence factors, as well as the formation of capsules that
resist phagocytosis.

Incubation times before the appearance of symptoms vary among

pathogens. Rhinoviruses and group A streptococci may incubate for
1-5 days, influenza and parainfluenza may incubate for 1-4 days, and
respiratory syncytial virus (RSV) may incubate for a week. Pertussis
typically incubates for 7-10 days, or even as long as 21 days, before
causing symptoms. Diphtheria incubates for 1-10 days. The
incubation period of Epstein-Barr virus (EBV) is 4-6 weeks.

Most symptoms of URIsincluding local swelling, erythema, edema,

secretions, and feverresult from the inflammatory response of the
immune system to invading pathogens and from toxins produced by
pathogens.

An initial nasopharyngeal infection may spread to adjacent

structures, resulting in the following:

Sinusitis
Otitis media
Epiglottitis
Laryngitis
 Tracheobronchitis
Pneumonia

Inflammatory narrowing at the level of the epiglottis and larynx may

result in a dangerous compromise of airflow, especially in children, in
whom a small reduction in the luminal diameter of the subglottic
larynx and trachea may be critical. Beyond childhood,
laryngotracheal inflammation may also pose serious threats to
individuals with congenital or acquired subglottic stenosis.

Susceptibility

Genetic susceptibility is involved in determining which patients have

more severe disease courses than others. There are some
recognized candidate gene polymorphisms with known functional
changes in genes that may lead to immunosuppression. [8] It has also
been shown that host immunogenetic variation plays a role in the
immune response to H1N1 and H5N1 viruses, thereby influencing
disease severity and outcome in influenza caused by these
viruses. [9, 10]

Etiology

Most URIs are viral in origin. Typical viral agents that cause URIs
include the following:

Rhinoviruses
Coronaviruses
Adenoviruses
Coxsackieviruses

For the most part, similar agents cause URI in adults and children;
however, Moraxella catarrhalis and bocavirus cause URIs more
commonly in children than in adults.

Nasopharyngitis

Of the more than 200 viruses known to cause the symptoms of the
common cold, the principal ones are as follows:

Rhinoviruses: These cause approximately 30-50% of colds in

adults; they grow optimally at temperatures near 32.8C (91F),
which is the temperature inside the human nares
 Coronaviruses: While they are a significant cause of colds,
exact case numbers are difficult to determine because, unlike
rhinoviruses, coronaviruses are difficult to culture in the laboratory
Enteroviruses, including coxsackieviruses, echoviruses, and
others

Other viruses that account for many URIs include the following:

Adenoviruses
Orthomyxoviruses (including influenza A and B viruses)
Paramyxoviruses (eg, parainfluenza virus [PIV])
RSV
EBV
Human metapneumovirus (hMPV)
Bocavirus: Commonly associated with nasopharyngeal
symptoms in children [11]

Unidentified, but presumably viral, pathogens account for more than

30% of common colds in adults. In addition, varicella, rubella, and
rubeola infections may manifest as nasopharyngitis before other
classic signs and symptoms develop.

Pharyngitis

This is most often viral in origin. Recognition of group A streptococcal

pharyngitis is vital because serious complications may follow
untreated disease.

Viral causes of pharyngitis include the following:

Adenovirus: May also cause laryngitis and conjunctivitis

Influenza viruses
Coxsackievirus
Herpes simplex virus (HSV)
EBV (infectious mononucleosis)
Cytomegalovirus (CMV)

Bacterial causes of pharyngitis include the following:

Group A streptococci (approximately 5-15% of all cases of

pharyngitis in adults; 20-30% in children) [2]
Group C and G streptococci
Neisseria gonorrhoeae
 Arcanobacterium ( Corynebacterium)hemolyticum
Corynebacterium diphtheriae
Atypical bacteria (eg, Mycoplasma pneumoniae and Chlamydia
pneumoniae; absent lower respiratory tract disease, the clinical
significance of these pathogens is uncertain)
Anaerobic bacteria

Rhinosinusitis

Rhinosinusitis in an immunocompetent person is typically related to

an uncomplicated viral URI. Viral causes are similar to those of viral
nasopharyngitis and include the following:

Rhinovirus
Enterovirus
Coronavirus
Influenza A and B virus
PIV
RSV
Adenovirus

Bacterial causes are similar to those seen in otitis media. Bacterial

pathogens isolated from maxillary sinus aspirates of patients with
acute bacterial rhinosinusitis include the following [7] :

Streptococcus pneumoniae: 38% in adults, 21-33% in children

Haemophilus influenzae: 36% in adults, 31-32% in children
Moraxella catarrhalis: 16% in adults; 8-11% in children
Staphylococcus aureus: 13% in adults, 1% in children

Other pathogens include group A streptococci and other

streptococcal species. Uncommon causes include C pneumoniae,
Neisseriaspecies, anaerobes, and gram-negative rods.

Nosocomial sinusitis often involves pathogens that colonize the

upper respiratory tract and migrate into the sinuses. Prolonged
endotracheal intubation places patients at increased risk for
nosocomial sinusitis. Methicillin-resistant S aureus(MRSA) is less
common than sensitive staphylococci. [7] Gram-negative bacilli
(eg, Escherichia coli,Pseudomonas aeruginosa) are other causes.

Aspergillus species are the leading causes of noninvasive fungal

sinusitis. Although fungi are part of the normal flora of the upper
airways, they may cause acute sinusitis in patients with
immunocompromise or diabetes mellitus.

Epiglottitis

This is a bacterial infection. In the vast majority of children, H

influenzae type b (Hib) is isolated from blood or epiglottal cultures.
Since the routine use of the Hib conjugate vaccine began in 1990,
case rates in children younger than 5 years have declined by more
than 95%. The prevalence of invasive Hib disease is approximately
1.3 cases per 100,000 children. [12] Rates in adults have remained low
and stable; Alaskan Natives have the highest rates of disease.

Other bacteria, found more commonly in adults than in children,

include group A streptococci, S pneumoniae, and M catarrhalis. In
adults, cultures are most likely to be negative.

Laryngotracheitis

Croup, or laryngotracheobronchitis, is typically caused by PIV type 1,

2, or 3. PIVs account for up to 80% of croup cases. PIV type 1 is the
leading cause of croup in children. [13] Other viruses include influenza
viruses and RSV. Uncommon causes include hMPV, adenovirus,
rhinovirus, enterovirus (including coxsackievirus and enteric
cytopathic human orphan [ECHO] viruses), and measles virus.

Approximately 95% of all cases of whooping cough are caused by

the gram-negative rod Bordetella pertussis. The remaining cases
result from B parapertussis.

Other forms of laryngitis and laryngotracheitis are typically caused by

viruses similar to those that cause nasopharyngitis, including
rhinovirus, coronavirus, adenovirus, influenza virus, parainfluenza
virus, and RSV. Candida species may cause laryngitis in
immunocompromised hosts.

Bacterial laryngitis is far less common than viral laryngitis. [14] Bacterial
causes include the following:Group A streptococci

Corynebacterium diphtheriae, an aerobic gram-positive rod that

may infect only the larynx or may represent an extension of
nasopharyngeal infection
Chlamydia pneumoniae
Mycoplasma pneumoniae
Moraxella catarrhalis
 H influenzae
S aureus
Mycobacterium tuberculosis: Tuberculosis has been reported in
renal transplant recipients and human immunodeficiency virus
(HIV) infected patients

Risk factors for URIs

Risk factors for contracting a URI include the following:

Contact: Close contact with small children who frequent group

settings, such as school or daycare, increases the risk of URI, as
does the presence of URI in the household or family
Inflammation: Inflammation and obstruction from allergic rhinitis
or asthma can predispose to infections
Travel: The incidence of contracting a URI is increased
because of exposure to large numbers of individuals in closed
settings
Smoking and exposure to second-hand smoke: These may
alter mucosal resistance to URI
Immunocompromise that affects cellular or humoral immunity:
Weakened immune function may result from splenectomy, HIV
infection, use of corticosteroids, immunosuppressive treatment
after stem cell or organ transplantation, multiple medical problems,
or common stress; cilia dyskinesia syndrome and cystic fibrosis
also predispose individuals to URIs
Anatomic changes due to facial dysmorphisms, previous upper
airway trauma, and nasal polyposis
Carrier state: Although some people are chronic carriers of
group A streptococci, repeated URIs in such patients may be viral
in origin [2]

Epidemiology

URIs are the most common infectious illness in the general

population and are the leading cause of missed days at work or
school. They represent the most frequent acute diagnosis in the
office setting. [15]

Nasopharyngitis

The incidence of the common cold varies by age. Rates are highest
in children younger than 5 years. Children who attend school or day
care are a large reservoir for URIs, and they transfer infection to the
adults who care for them. In the first year after starting at a new
school or day care, children experience more infections, as do their
family members. Children have about 3-8 viral respiratory illnesses
per year, adolescents and adults have approximately 2-4 colds
annually, and people older than 60 years have fewer than 1 cold per
year.

Pharyngitis

Acute pharyngitis accounts for 1% of all ambulatory office

visits. [15] The incidence of viral and bacterial pharyngitis peaks in
children aged 4-7 years.

Rhinosinusitis

Sinusitis is common in persons with viral URIs. Transient changes in

the paranasal sinuses are noted on computed tomography (CT)
scans in more than 80% of patients with uncomplicated viral
URIs. [16] However, bacterial rhinosinusitis occurs as a complication in
only about 2% of persons with viral URIs. [17]

Epiglottitis

The occurrence of epiglottitis has decreased dramatically in the

United States and other developed nations since the introduction of
Hib vaccine. A Swedish study documented that the Hib vaccination
program was associated with a decrease in the overall annual
incidence of acute epiglottitis from 4.5 cases to 0.98 cases per
100,000 population; the incidence decreased in children and adults.
However, the annual incidence of pneumococcal epiglottitis in adults
increased from 0.1 to 0.28 cases per 100,000 population over the
same period. [18]

Laryngitis and laryngotracheitis

Croup, or laryngotracheobronchitis, may affect people of any age but

usually occurs in children aged 6 months to 6 years. The peak
incidence is in the second year of life. Thereafter, the enlarging
caliber of the airway reduces the severity of the manifestations of
subglottic inflammation.

Vaccination has dramatically reduced rates of pertussis. However,

the incidence of whooping cough in the United States has increased
steadily since 2007, reaching approximately 9 cases per 100,000
population in 2010. Rates of pertussis are highest in infants below
age 1 year; adolescents and adults accounted for approximately 44%
of the 27,550 cases of pertussis reported in the United States in
2010. [19]

Worldwide, pertussis has an estimated incidence of 48.5 million

cases and causes nearly 295,000 deaths per year. In low-income
countries, the case-fatality rate among infants may be as high as
4%. [20]

Although pertussis is a nationally notifiable disease in the United

States, many cases likely go undiagnosed and unreported. On the
other hand, challenges in laboratory diagnosis and overreliance on
polymerase chain reaction (PCR) assays have resulted in reports of
respiratory illness outbreaks mistakenly attributed to pertussis. [21]

Occurrence rate of selected pathogens

Group A streptococcal bacteria cause approximately 5-15% of all

pharyngitis infections,[2] accounting for several million cases of
streptococcal pharyngitis each year. This infection is rarely diagnosed
in children younger than 2 years.

Influenza affects approximately 5-20% of the US population during

each flu season. [22] Early presentations include symptoms of URI.

EBV infection affects as many as 95% of American adults by age 35-

40 years. Childhood EBV infection is indistinguishable from other
transient childhood infections. Approximately 35-50% of adolescents
and young adults who contract EBV infection have mononucleosis. [23]

Diphtheria rates fell dramatically in the United States after the advent
of diphtheria vaccine. Since 1980, the prevalence of diphtheria has
been approximately 0.001 case per 100,000 population. A confirmed
case of the disease has not been reported in the United States since
2003. [24] However, diphtheria remains endemic in developing
countries.

Seasonality

Although URIs may occur year round, in the United States most colds
occur during fall and winter. Beginning in late August or early
September, rates of colds increase over several weeks and remain
elevated until March or April.[25] Epidemics and mini-epidemics are
most common during cold months, with a peak incidence from late
winter to early spring.
Cold weather results in more time spent indoors (eg, at work, home,
school) and close exposure to others who may be infected. Humidity
may also affect the prevalence of colds, because most viral URI
agents thrive in the low humidity that is characteristic of winter
months. Low indoor air moisture may increase friability of the nasal
mucosa, increasing a person's susceptibility to infection.

Laryngotracheobronchitis, or croup, occurs in fall and winter.

Seasonality does not affect rates of epiglottitis.

The figure below illustrates the peak incidences of various agents by

season. Rhinoviruses, which account for a substantial percentage of
URIs, are most active in spring, summer, and early autumn.
Coronaviral URIs manifest primarily in the winter and early spring.
Enteroviral URIs are most noticeable in summer and early fall, when
other URI pathogens are at a nadir. Adenoviral respiratory infections
can occur throughout the year but are most common in the late
winter, spring, and early summer.

Seasonal variation of selected upper respiratory tract infection

pathogens. PIV is parainfluenza virus, RSV is respiratory syncytial

virus, MPV is metapneumovirus, and Group A Strept is group A
streptococcal disease.
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Seasonal influenza typically lasts from November until March. Some

PIVs have a biennial pattern. The patterns for human PIV types 1-3
are as follows:

Human PIV type 1: Currently produces autumnal outbreaks in

the United States during odd-numbered years; the leading cause
of croup in children
Human PIV type 2: May cause annual or biennial fall outbreaks
Human PIV type 3: Peak activity is during the spring and early
summer months; however, the virus may be isolated throughout
the year. [13]

Human metapneumovirus (hMPV) infection may also occur year

round, although the infection rates peak between December and
February.

Race- and sex-related demographics

No notable racial difference is observed with URIs. However, Alaskan
Natives have rates of Hib disease higher than those of other
groups. [12]

Sexual disparities among URIs are as follows:

Rhinitis: Hormonal changes during the middle of the menstrual

cycle and during pregnancy may produce hyperemia of the nasal
and sinus mucosa and increase nasal secretions; URI may be
superimposed over these baseline changes and may increase the
intensity of symptoms in some women
Nasopharyngitis: The common cold occurs frequently in
women, especially those aged 20-30 years [25] ; this frequency may
represent increased exposure to small children, who represent a
large reservoir for URIs, but hormonal effects on the nasal mucosa
may also play a role
Epiglottitis: A male predominance is reported, with a male-to-
female ratio of approximately 3:2
Laryngotracheobronchitis, or croup: More common in boys than
in girls, with a male-to-female ratio of approximately 3:2

Age-related demographics

The incidence of the common cold varies by age. Rates are highest
in children younger than 5 years. Children have approximately 3-8
viral respiratory illnesses per year, while adolescents and adults have
approximately 2-4 colds a year, and people older than 60 years have
fewer than 1 cold per year.

The age-related occurrence of other infections is as follows:

Viral and bacterial pharyngitis: Peaks in children aged 4-7

years.
Epiglottitis: Typically occurs in children aged 2-7 years and has
a peak incidence in those aged 3 years
Laryngotracheobronchitis (croup): As previously stated, it may
affect people of any age but usually occurs in children aged 6
months to 6 years; the peak incidence is in the second year of life

Prognosis

URIs cause people to spend time away from their usual daily
activities, but alone, these infections rarely cause permanent
sequelae or death. URIs may, however, serve as a gateway to
infection of adjacent structures, resulting in the following infections
(and others, as well):

Otitis media
Bronchitis
Bronchiolitis
Pneumonia
Sepsis
Meningitis
Intracranial abscess

Serious complications may result in clinically significant morbidity and

rare deaths.

Nasopharyngitis

A common cold may last up to 14 days, with symptoms averaging 7-

11 days in duration. [17]

Fever, sneezing, and sore throat typically resolve early, whereas

cough and nasal discharge are among the symptoms that last
longest.

Attendance at day care may affect the duration of symptoms in young

children. In one study, the duration of viral URIs ranged from 6.6 days
for children aged 1-2 years in home care to 8.9 days for children
younger than 1 year who were in day care. Young children in day
care were also more likely to have protracted respiratory symptoms
lasting more than 15 days. [26]

Most patients with influenza recover within a week, although cough,

fatigue, and malaise may persist for up to 2 weeks. For newborns,
elderly persons, and patients with chronic medical conditions, the flu
may be life threatening. More than 200,000 people per year are
hospitalized because of complications of the flu, with 0.36 deaths per
100,000 patients occurring annually.[27] Influenza may be followed by
bacterial superinfection.

Pharyngitis

Viral pharyngitis typically resolves in 1-2 weeks, but

immunocompromised persons may have a more severe course.

Untreated group A streptococcal pharyngitis can result in the

following:
 Acute rheumatic fever
Acute glomerulonephritis
Peritonsillar abscess
Toxic shock syndrome
Impetigo
Cellulitis or abscess
Otitis
Sinusitis
Conjunctivitis
Bronchitis

Mortality from group A streptococcal pharyngitis is rare, but serious

morbidity or death may result from one of its complications.

Streptococcal pharyngitis without complications rarely poses

significant risk for morbidity. However, retropharyngeal, intraorbital, or
intracranial abscesses may cause serious sequelae. The risk of
mortality is significant in patients who progress to streptococcal toxic
shock syndrome, which is characterized by multiorgan failure and
hypotension.

In patients with penicillin-sensitive streptococcal pharyngitis,

symptomatic improvement is expected within 24-72 hours if antibiotic
treatment is started in the first 24 hours after onset. Treatment
failures are common and are mainly attributed to poor adherence,
antibiotic resistance, and untreated close contacts, usually within the
household or family.

A chronic carrier state may develop with group A streptococcal

infection. Eradicating the pathogen is difficult in these cases;
however, carriers without active symptoms are unlikely to spread
group A streptococci, and they are at low risk for developing
rheumatic fever.

Mononucleosis

With infectious mononucleosis from EBV, complete resolution of

symptoms may take up to 2 months. Acute symptoms rarely last
more than 4 months. EBV typically remains dormant throughout the
patient's life. Reactivation of the virus is not usually symptomatic.

Rhinosinusitis
The prognosis is generally favorable for acute rhinosinusitis, and
many cases appear to resolve even without antibiotic therapy. As
many as 70% of immunocompetent adults with rhinosinusitis begin to
improve within 2 weeks of presentation without antibiotics. With
antibiotics, up to 85% have improvement at 2 weeks. Complete
resolution may take weeks to months.

Sinusitis itself is rarely life threatening, but it can lead to serious

complications if the infection extends into surrounding deep tissue,
including the following:

Orbital cellulitis
Subperiosteal abscess
Orbital abscess
Frontal and maxillary osteomyelitis
Subdural abscess
Meningitis
Brain abscess

Epiglottitis

Epiglottitis poses a risk of death due to sudden airway obstruction

and other complications, including septic arthritis, meningitis,
empyema, and mediastinitis. In adults, epiglottitis has a fatality rate of
approximately 1%.

The prognosis is favorable with appropriate airway management, and

most patients noticeably improve within 24-48 hours after antibiotics
are started. Rarely, cases of epiglottitis may recur. Recurrent
symptoms raise concern about potential underlying disorders, such
as rheumatic conditions, sarcoidosis, and occult malignancy.

Laryngitis and laryngotracheitis

With croup, laryngotracheobronchitis typically begins to improve

within 3-4 days. Recovery is usually complete. However, patients
may have a recurrence, including during the same season.

Pertussis (whooping cough) leads to hospitalization in more than half

of infants younger than 12 months and particularly in infants younger
than 6 months. Infants and young children are most susceptible to
severe courses that include respiratory compromise.

Of infants who are hospitalized with pertussis, approximately 50%

have apnea, 20% develop pneumonia, 1% have seizures, 1% die,
and 0.3% have encephalopathy. [28] Recovery from whooping cough is
typically complete. However, paroxysms of coughing may last for
several weeks.

Complications

Most URIs are self-limited and resolve completely. However, a variety

of conditions may complicate a URI. Fluid loss may occur in patients
unable to tolerate adequate oral intake because of upper airway
inflammation or may result from fever. Otitis media may complicate
5% of colds in children and up to 2% of colds in adults [29]

Airway hyperreactivity may increase after a URI, resulting in new or

exacerbated asthma. Cough asthma, wherein a cough is the
predominant manifestation of reactive airways disease, may mimic
ongoing infection. This may be diagnosed with pulmonary function
testing.

A postinfectious cough is defined as coughing that persists 3-8 weeks

after the onset of a URI in the absence of other clearly defined
causes. Exacerbations of chronic obstructive pulmonary disease,
including emphysema and chronic bronchitis, may occur during and
after a URI. Upper airways cough syndrome (post-nasal drip) may
result from upper airway secretions dripping onto the pharynx.
Epistaxis may also occur.

Lower respiratory tract disease and sepsis represent serious

complications, especially in patients with immunocompromise. Lower
respiratory tract disease should be considered when symptoms such
as fever, cough, sputum, and malaise worsen progressively or after
initial transient improvement. Tachypnea and dyspnea are also signs
of lower respiratory involvement.

Viral infection and resulting inflammation may make an individual

susceptible to concomitant or sequential infection with a bacterial
agent. Streptococcus pneumoniae, Staphylococcus aureus, H
influenzae, and Streptococcus pyogenes are common superinfecting
agents. Meningococci may cause superinfection with influenzal
infections.

Inflammation of the larynx and trachea area may lead to airway

compromise, especially in children and in patients with narrowed
airways due to congenital or acquired subglottic stenosis. The work
of breathing during epiglottitis or laryngotracheitis may lead to
respiratory failure. Sleep apnea may occur from hypertrophied
tonsils.

Deep tissue infection may occur by extension of the infection into the
orbit, middle ear, cranium, or other areas. Peritonsillar abscess
(quinsy) may complicate bacterial pharyngitis, leading to difficulty
swallowing and pain radiating to the ear. Retropharyngeal abscess
may also complicate pharyngitis. Lemierre syndrome is an extension
of pharyngitis that leads to a suppurative thrombophlebitis of the
internal jugular vein; septic thromboemboli may then spread
throughout the body.

Complications of sinusitis include the following:

Orbital cellulitis
Subperiosteal abscess
Orbital abscess
Mastoiditis
Frontal or maxillary osteomyelitis
Subdural abscess
Cavernous sinus thrombosis
Brain abscess

Suspect a deep tissue infection when a patient has orbital or

periorbital swelling, proptosis, impaired extraocular movements, or
impaired vision. Signs of increased intracranial pressure (eg,
papilledema, altered mental status, neurologic findings) may suggest
intracranial involvement.

Encephalitis, meningitis, or subarachnoid hemorrhage may follow a

URI. Osteomyelitis may complicate persistent or recurrent sinusitis.
Osteomyelitis may affect the orbital plate, frontal bone, or sphenoid
bone. Mucoceles are expanding cystic defects of the paranasal
sinuses that may result from prolonged sinusitis. Epiglottic abscess
may result from epiglottitis.

Lymphadenitis may follow or accompany URI. Guillain-Barr

syndrome may manifest as an ascending polyneuropathy a few days
or weeks after a URI. In children or adolescents, the use of aspirin
during a viral infection may rarely cause Reye syndrome. Aspirin is
contraindicated for the management of fevers in children or
adolescents.
URI, especially with fever, may increase the work of the heart, adding
strain to persons with suboptimal cardiovascular status, and can lead
to cardiovascular decompensation. Myositis or pericarditis may result
from viral infection.

Hyperglycemia may occur during a URI in patients with diabetes. Rib

fracture may be seen following an episode of severe coughing, such
as that associated with whooping cough. Hernia may develop
following an episode of severe coughing.

Cutaneous complications such as rash, cellulitis, and toxic shock

syndrome may occur with group A streptococcus. This pathogen can
also be associated with glomerulonephritis, acute rheumatic fever,
and PANDAS syndrome (Pediatric Autoimmune Neuropsychiatric
Disorders Associated with Streptococcal infections).

Hemoptysis suggests the possibility of tuberculosis. A tuberculin skin

test, chest radiography, or both are appropriate in these patients.

Complications of specific conditions

Complications of group A streptococcal disease

Group A streptococcal pharyngitis is of special concern because its

complications include streptococcal toxic shock syndrome, acute
rheumatic fever (ARF), acute glomerulonephritis, and scarlet fever,
as well as cutaneous infections. In addition, this pathogen is readily
transmissible, especially in households, families, and other intimate
groups.

ARF affects approximately 3% of patients with strep throat, primarily

occurring in persons aged 6-20 years. The condition develops
approximately 2-4 weeks after streptococcal pharyngitis occurs, and
it may last several months. Signs of rheumatic fever include arthritis,
fever, and valvular disease. Uncommon features include an
expanding truncal exanthem (erythema marginata), subcutaneous
nodules, and chorea.

Poststreptococcal glomerulonephritis can affect persons of any age

group, but it is most common in children aged 3-7 years. Boys are
affected slightly more often than girls. Patients with
glomerulonephritis may have loss of appetite, lethargy, dull back
pain, and dark urine. Blood pressure may be elevated, and edema
may occur.
Scarlet fever is a self-limited exanthem that spreads from the chest
and abdomen to the entire body. Tiny red papules create a rough skin
texture similar to that of sandpaper. The rash is typically blanching.
Although it commonly affects the face, circumoral pallor is present.
During recovery, the skin on the fingers and toes peels. Streptococcal
toxic shock syndrome may also occur, affecting skin and mucosa.

PANDAS is a rare syndrome in children and adolescents, who

experience sudden onset or worsening of obsessive-compulsive
disorder following streptococcal infection. Associated manifestations
include tics and a variety of neuropsychiatric symptoms. [30]

Complications of mononucleosis

Complications can include the following:

Splenic rupture
Hepatitis
Guillain-Barr syndrome
Encephalitis
Hemolytic anemia
Agranulocytosis
Myocarditis
Burkitt lymphoma
Nasopharyngeal carcinoma
Rash (with concomitant use of ampicillin)

Complications of diphtheria

Complications may include airway obstruction, myocarditis,

polyneuritis, thrombocytopenia, and proteinuria. Among patients who
survive diphtheria, as many as 20% have permanent hearing loss or
other long-term sequelae. [13]

Complications from pertussis

More than half of infants younger than 12 months who contract

pertussis require hospitalization, especially those who are younger
than 6 months. Complications of pertussis in hospitalized infants
include the following [28] :

Apnea (50%)
Pneumonia (20%)
Seizures (1%)
 Encephalopathy (0.3%)
Death (1%)

In addition, severe cough may result in rib fractures, hernia,

incontinence, or subconjunctival hemorrhages.

Complications of influenza

These include the following:

Bacterial superinfection
Pneumonia
Volume depletion
Myositis
Pericarditis
Rhabdomyolysis
Encephalitis
Meningitis
Myelitis
Renal failure
Disseminated intravascular coagulation

As with any systemic infection, the flu poses a risk of worsening

underlying medical conditions, such as heart failure, asthma, or
diabetes. After influenzal infection, children may experience sinus
problems or otitis media.

Patient Education

Address the patient's expectations about antibiotic therapy. Validate

the patient's symptoms and their severity, listen to the concerns
expressed, and educate the patient about possible consequences of
inappropriate antibiotic use, including consequences affecting
him/her and the community.

Many people hold misperceptions about the duration and intensity of

symptoms associated with URI and about the benefits and risks of
antibiotic therapy. Some are unaware that cold symptoms may last as
long as 14 days. Some believe that antibiotics will help them to avoid
serious disease and recover more quickly than without treatment.

Patients may expect to receive antibiotics solely based on the

severity of their symptoms, and they may not appreciate the negative
consequences of using antibiotics in viral disease. Negative results
on a rapid strep test may provide reassurance about the
appropriateness of supportive care.

Actively promote self-care, and outline a realistic time course for the
resolution of symptoms. Reassure the patient about access to clinical
care and follow-up in the event that symptoms progress. Briefly
explore factors that may have contributed to the current infection, and
address prevention for the future.

Patient satisfaction is less linked to antibiotic prescriptions and more

linked to the quality of the physician-patient interaction. Reflecting
understanding of the details of the patient's situation, expressing
concern for the patient's well-being, explaining how
recommendations are appropriately tailored to the individual's current
condition, and providing reassurance are important to patient
satisfaction.

Patients should be counseled on handwashing and proper methods

of covering coughs and sneezes. Patients who smoke should receive
smoking cessation encouragement and materials. When antibiotics
are prescribed, patients should be instructed to complete the full
course of antibiotic therapy.

Patients should be instructed to follow up when indicated or if

symptoms worsen. Finally, patients with infectious mononucleosis
should be instructed to avoid contact sports for 6 weeks because of
the possibility of splenic rupture.

For patient education information, see the Headache and Migraine

Center, as well as Sinus Infection and Sore Throat.