61
61
Acute and Chronic Laryngopharyngitis
Clint T. Allen, Brian Nussenbaum, Albert L. Merati
KEY POINTS
• Understanding the differences between the immunologic
response of the laryngopharynx to pathogenic versus
environmental stimuli will likely be critical as we better
our understanding of diseases such as allergy, reflux, and
malignancy.
• The most common causes of acute laryngopharyngitis in
the general population are infectious, as part of an upper
respiratory infection, whereas the most common causes
of chronic laryngopharyngitis in patients cared for by
otolaryngologists may be environmental insults such as
reflux and tobacco.
• Acute laryngopharyngitis is caused by a bacterial
infection in a small minority of patients—the rest are
very likely to be caused by viral infections.
• Most acute bacterial pharyngitis is caused by group A
β-hemolytic Streptococcus pyogenes (GABHS), and
rheumatic fever can be avoided with initiation of
antibiotic therapy within 10 days of the onset of
symptoms.
• Fungal laryngopharyngitis caused by Candida albicans is
common and can occur in immunocompetent as well as
immunocompromised patients.
• The impact of laryngopharyngitis includes both
short-term dysfunction during the acute phase of
infection/inflammation and longer-term, secondary
effects of the inflammatory process such as scar
formation and hypersensitivity.
WHY DOES LARYNGOPHARYNGITIS MATTER?
Functio laesa, the often overlooked “fifth sign” of inflammation—
along with rubor, tumor, dolor, and calor—describes the loss of
function in an inflamed organ, be it the liver in hepatitis or the
hoarse voice of a patient with vocal fold edema related to viral
laryngitis. The acutely or chronically inflamed laryngopharynx
does not phonate, swallow, or breathe well and is painful. These
symptoms are a direct result of host inflammatory responses to
the pathogen that lead to classic physical exam findings of erythema
and edema that are easily recognized during expert clinical examina-
tion. While clinical recognition of inflammation within the
laryngopharynx is often straightforward, diagnosing the specific
underlying infectious or inflammatory etiology to maximize effective
treatment can be challenging. Importantly, function may continue
to be impaired after the resolution of the infectious process due
to residual inflammation or inflammatory sequelae such as scar
or neural hypersensitivity. Although clinically obvious acute or
chronic laryngeal infection or inflammation leads to detectible
disturbances in laryngopharyngeal function, the degree of dysfunc-
tion caused by exposure to noninfectious, environmental antigenic
material has not been clearly described. Here, we cover common
causes of laryngopharyngitis that the practicing otolaryngologist
will certainly encounter as well as more unusual causes that must
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be considered in the differential diagnosis of patients who present
with laryngopharyngitis. While etiologies and physical manifesta-
tions of acute and chronic laryngopharyngitis overlap, this distinc-
tion serves as a practical approach for organization of this chapter.
ACUTE LARYNGOPHARYNGITIS
Viral Etiologies of Acute Laryngopharyngitis
Rhinovirus
The most common cause (30% to 60%) of acute, infectious
laryngopharyngitis in adults is a self-limited viral infection that
occurs as part of the common cold.1 The average adult gets 2 to
4 colds each year, and this accounts for close to 20% of patients
who present with an acute illness to health care providers. Rhi-
novirus is the most common etiologic agent of the common cold.
Coronavirus and parainfluenza virus are less commonly implicated.
Prior to the identification of a novel coronavirus as the cause
of severe acute respiratory syndrome (SARS), the only illness
that coronaviruses were thought to cause in humans was the
common cold.2
Rhinovirus is a single-stranded RNA virus in the Picornaviridae
family. More than 100 serotypes of rhinovirus exist. It is transmitted
through large-particle aerosols that do not directly invade the
mucosa, but rather cause an acute inflammatory reaction. Inflam-
matory mediators subsequently cause edema and hyperemia of
the laryngopharyngeal mucosa. Presenting symptoms of the
common cold may overlap with those of bacterial pharyngitis, but
the sore throat is usually not severe, and odynophagia is unusual.
Patients usually complain of nasal symptoms (rhinorrhea and nasal
stuffiness) that precede the throat symptoms. A nonproductive
cough, hoarseness, and low-grade fever may also be present. On
examination, laryngopharyngeal mucosa may be mildly erythe-
matous. Specific virologic diagnosis is unnecessary for most patients,
because it usually does not affect the management. Computed
tomography (CT) scan of the paranasal sinuses cannot reliably
distinguish patients with the common cold from those with acute
bacterial sinusitis because imaging abnormalities are frequently
found in both conditions.3 Treatment for the common cold is
symptomatic and consists of rest, oral hydration, and over-the-
counter cold medications for relief of symptoms. Most healthy
adults will recover within 1 week. Antibiotics are not routinely
used and are only indicated for secondary acute bacterial sinusitis,
which occurs in 0.5% to 5% of cases.3 The use of oral steroids
to treat routine, acute, viral-mediated laryngopharyngeal inflam-
mation in adults is anecdotal and controversial and not routinely
employed.4
Influenza Virus
In North America, influenza presents as outbreaks in the late
fall or winter. However, this disease is a worldwide problem:
each year, 500 million people globally develop influenza, and
approximately 150,000 people require hospitalization in the United
States alone.5 In nonpandemic years, 20,000 to 40,000 deaths
occur. In pandemic years, this can reach 100,000 deaths annually.
Disease varies in severity, based on several factors: influenza type
A, rather than type B, is responsible for most of the significant
897
 CHAPTER 61 Acute and Chronic Laryngopharyngitis 897.e1

Abstract Keywords
61
Inflammation of the pharynx and larynx very commonly leads to pharyngitis
symptoms that drive consultation with an otolaryngologist. Causes laryngitis
of laryngopharyngitis are diverse, ranging from self-limiting infection
infectious processes to more chronic disorders such as autoimmune inflammation
or systemic inflammatory diseases. Expert evaluation and diagnosis hypersensitivity
that ultimately directly or indirectly leads to therapeutic interven- reflux
tion is the task of the contemporary otolaryngologist. Here, we autoimmune
review the common and more rare causes of acute and chronic
pharyngitis and laryngitis that otolaryngologists must be able to
recognize. Most acute pharyngitis and laryngitis is caused by viral
or, more rarely, bacterial, infection. The differential diagnosis for
chronic inflammation in the pharynx and larynx diversifies and
requires expert physical examination to recognize infectious and
inflammatory entities that can guide the appropriate workup. How
we manage patients with symptoms arising from chronic pharyngitis
and laryngitis will likely change as we gain better insight into how
short-term infectious or inflammatory processes can lead to longer-
term laryngopharyngeal dysfunction due to scar formation and
hypersensitivity.

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898 PART V Laryngology and Bronchoesophagology
morbidity and mortality in very young patients, older patients
(>50 years old), and patients with underlying comorbidities such
as immunosuppression, cardiopulmonary disease, or diabetes.
Death is often secondary to bacterial pneumonia caused by
community-acquired pathogens such Staphylococcus aureus, and
group B Streptococcus.5
Patients present with abrupt onset of fever, headache, and
myalgias. Sore throat, malaise, chills, sweats, nonproductive cough,
and rhinorrhea shortly follow. The sore throat can be severe in
nature, and examination of the oropharynx typically reveals mild
hyperemia and edema without exudates. Lymphadenopathy is an
uncommon finding. Symptoms usually resolve after 3 to 5 days.
Supportive therapy is indicated during this time. Antiviral therapies
with M2 ion channel blockers (amantadine) or neuraminidase
inhibitors (zanamivir or oseltamivir) have been used. The neur-
aminidase inhibitors are effective against influenza types A and B
and decrease symptoms by 1 to 2.5 days when started within 2
days of developing symptoms.6 These drugs reduce complications
in high-risk populations and are recommended for patients at
high risk for complications or those with severe disease diagnosed
early.6 With the availability of new treatments that need to be
started early in the disease course to be beneficial, it is now more
desirable to make a prompt, accurate diagnosis. The FDA has
approved a few rapid diagnostic tests that give results in under
15 minutes. Compared with culture as the gold standard for labora-
tory diagnosis, the sensitivity and specificity of these tests range
from 62% to 73% and from 80% to 99%, respectively.7 Samples
should be obtained from the nose rather than from the throat.
Influenza may be prevented with the inactivated influenza
vaccine, which gets prepared yearly based on the anticipated strains
likely to appear during the flu season. Vaccination is consistently
at least 70% effective.6 The FDA has approved an intranasal vaccine
with live attenuated virus as an alternative to the traditional
inactivated injected vaccine. This vaccine more accurately mimics
natural infection and, thus, may provide a broader and more durable
immunologic response; however, because this vaccine contains
live influenza viruses, it should not be used in patients or close
contacts of patients with chronic illnesses or immunodeficiency,
children younger than 2 years, or adults older than 50 years of
age.6 The CDC recommends routine vaccination for people older
than 50 years, children between 6 and 24 months, residents and
employees of long-term care facilities, patients with chronic
cardiopulmonary disease, patients with metabolic disease or
immunosuppression, women in the second or third trimester of
pregnancy during influenza season, health care personnel, and
providers of home care to high-risk patients.5
Human Immunodeficiency Virus
Acute human immunodeficiency virus (HIV) type 1 infection causes
acute retroviral syndrome (ARS) in 40% to 90% of patients beginning
days to weeks after exposure.8 Because of the nonspecific signs
and symptoms, even patients at risk for HIV are frequently not
promptly diagnosed. Thus, ARS should be included in the dif-
ferential diagnosis in any patient with a fever of unknown origin
and risk factors for HIV exposure. Symptoms and signs include
fever, lethargy, skin rash, myalgia, headache, pharyngitis, cervical
adenopathy, and arthralgia. Pharyngitis occurs in 50% to 70% of
patients and usually appears as hypertrophy of the tissues of the
Waldeyer ring without exudates. Other laryngopharyngeal mani-
festations less commonly observed include ulcers (29%) and
candidiasis (17%).9
Diagnosis is dependent upon laboratory tests. Decreased CD4
count on a CBC, enzyme-linked immunosorbent assay (ELISA),
and western blot tests are typically negative within the first 4
weeks of infection. A quantitative plasma HIV-1 RNA level tested
by PCR is necessary to make a timely diagnosis.8,9 The high viral
titer associated with ARS is reflective of the initial burst of viremia
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with wide dissemination of virus and seeding of lymphatic organs.
The natural history of ARS is resolution of signs and symptoms,
along with the viremia, within 14 days after onset.10 Disease
progression to other HIV manifestations or acquired immune
deficiency syndrome (AIDS) ultimately occurs. Although data are
limited regarding long-term benefits of early treatment, immediate
and sustained therapy with antiretroviral medications may limit
the extent of viral dissemination, restrict damage to the immune
system, and reduce the chance of disease progression.10
In patients who develop fulminant AIDS, persistent ulcers in
the laryngopharynx can be caused by herpes simplex virus,
cytomegalovirus (CMV), Cryptococcus, histoplasmosis, mycobacterial
organisms, or lymphoma.11 In many cases, however, no identifiable
etiology is determined after exhaustive microbiologic, serologic,
and pathologic tests. The pathogenesis of these ulcers is unclear
but has been postulated to be immunogenic. These ulcers progres-
sively enlarge, have destructive behavior, and are extremely painful;
they have a propensity for the tonsillar fossa, floor of the mouth,
and epiglottis.12 The pain associated with these ulcers causes
significant odynophagia that can lead to malnutrition and wasting.
Locally injected and systemic steroids have shown success for
treating these AIDS-related ulcers11,12 and systemic thalidomide.13
Early recognition of these ulcers through expert physical examina-
tion can lead to early intervention and preservation of quality of
life for these patients.
Other Viral Etiologies of Acute Laryngopharyngitis
Adenovirus is a double-stranded DNA virus that causes pharyn-
goconjunctival fever in children and an adult febrile respiratory
illness in situations involving overcrowding and physical stress,
such as in military recruits.14 The availability of an adenoviral
vaccine in the 1970s and 1980s dramatically reduced infections
in military recruits. Interestingly, a resurgence of adenoviral
infections was observed after production of the vaccine was
halted.14 In adults, adenovirus causes pharyngitis as part of a
febrile respiratory illness, and sore throat is reported in 71% of
patients. Adenovirus directly invades the pharyngeal mucosa and
has a cytolytic effect; thus, the sore throat is typically more severe
than with the common cold. Examination reveals an exudative
pharyngitis that is difficult to distinguish from bacterial pharyngitis.
PCR is a rapid, sensitive test for detecting adenoviral DNA in
nasopharyngeal aspirates or serum.15 Adenoviral infection can be
confirmed by culture from a throat swab. The culture specimen
is grown on various cell lines in vitro, and a cytolytic effect is
observed. Immunofluorescence using an anti-adenovirus monoclonal
antibody is performed to confirm the diagnosis. Disease is usually
self-limited, and symptomatic treatment suffices for most cases. The
average duration of symptoms is 10 days. However, as with many
viral infections, complications can occur in immunocompromised
patients.
Epstein-Barr virus (EBV) is a double-stranded DNA virus that
can remain latent in B lymphocytes and intermittently replicate
in oropharyngeal epithelial cells to enable transmission through
saliva. Worldwide, 80% to 90% of adults are seropositive for EBV,
indicating prior exposure.16 Half or more of all healthy adults
exposed to EBV will develop an antibody immune response without
developing an overt illness. EBV is the causative agent of infectious
mononucleosis (IM). After an initial incubation period of 3 to 7
weeks, a prodrome of malaise, fever, and chills is followed 1 to 2
weeks later by sore throat, fever, anorexia, and lymphadenopathy
(especially cervical). Sore throat is found in 82% of patients with
IM and is the most common complaint. Examination of the
oropharynx reveals an exudative pharyngitis with erythema and
tonsillar hypertrophy (Fig. 61.1). Other findings may include diffuse
lymphoid hyperplasia of the Waldeyer ring and cervical lymph
nodes, petechiae at the hard palate–soft palate junction, and ulcers
on the pharyngeal and epiglottic mucosa.17 Immunologic studies

Fig. 61.1 Infectious mononucleosis showing the characteristic
exudative tonsillitis with tonsillar hypertrophy. (Courtesy Richard A.
Chole, MD, PhD.)
include the heterophile antibody test and EBV-specific antibody
tests.16 Treatment for most affected patients consists of supportive
care, rest, antipyretics, and analgesics. Due to increased risk of
rupture, patients should be advised to avoid contact sports until
examination and abdominal ultrasonography confirms resolution
of splenomegaly. Antivirals are not beneficial in uncomplicated
infections, and antibiotics are indicated only for secondary bacterial
infections. Ampicillin or amoxicillin should not be used because
these antibiotics cause a maculopapular rash in 95% of patients
with IM.17 Steroids are indicated for complications related to
impending upper airway obstruction, severe hemolytic anemia,
severe thrombocytopenia, or persistent severe disease.
Herpes simplex virus type 1 (HSV-1) is a double-stranded
DNA virus that has been increasingly recognized as a prevalent
cause of acute pharyngitis among college students. It accounts for
approximately 6% of cases.18 Immunosuppressed patients are also
at particular risk. Primary HSV-1 infection is characterized by
pharyngitis with or without gingivostomatitis. Recurrent herpes
labialis is a manifestation of reactivation rather than primary infec-
tion. Symptoms of primary infection include sore throat and tender
lymphadenopathy and findings include reddening and hypertrophy
of the tonsils with an overlying exudate. One third of patients
with a primary HSV infection will have at least one herpes-like
lesion—a painful, shallow ulcer—in the oral cavity or oropharynx.18
Diagnosis can be obtained by viral culture with confirmation using
immunofluorescence. Serologic tests for neutralizing antibodies
have been described but may not be reliable for diagnosing primary
infection. A paucity of data exists for treatment of primary HSV
pharyngeal infections with antivirals.
Bacterial Causes of Acute Laryngopharyngitis
Group A β Hemolytic Streptococcus pyogenes
The majority of the 10% to 20% of all adult pharyngitis cases
caused by bacterial infection are caused by group A β-hemolytic
Streptococcus pyogenes (GABHS).1 This gram-positive cocci is only
pathogenic in humans, and less than 5% of adults are asymptomatic
carriers.19 Spread occurs mostly through aerosolized microdroplets.
The pathogenesis of GABHS infections is related to virulence
factors intrinsic to the organism such as microbial enzymes and
secreted exotoxins that induce potent host inflammatory reactions.
GABHS most often induces infections and inflammatory reactions
in the pharynx, but inflammation often spreads to and involves
the larynx. Symptoms are usually rapid onset and include severe
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CHAPTER 61 Acute and Chronic Laryngopharyngitis 899
sore throat, odynophagia, cervical lymphadenopathy, fevers, chills,
malaise, headache, mild neck stiffness, and anorexia. The laryn- 61
gopharyngeal examination typically reveals erythema, edema, and
gray-white exudates that symmetrically involve the affected tissues.
Petechiae may be present on the soft palate, the tonsils are com-
monly swollen, and the breath is characteristically foul. A scarla-
tiniform rash may also be present.
If left untreated, infections are usually self-limited and consist
of localized inflammation that resolves after 3 to 7 days. Patients
are contagious during the acute illness and for approximately 1
week afterward. Prompt antibiotic treatment reduces the duration
of symptoms (if treatment begins within 24 to 48 hours of symptom
onset), reduces the period of contagiousness to 24 hours after
beginning treatment, and decreases the incidence of suppurative
complications.20 Prevention of rheumatic fever is possible if
antibiotic therapy is started up to 10 days after the onset of
symptoms. Other possible manifestations include scarlet fever,
toxic shock syndrome, necrotizing fasciitis, bacteremic spread of
infection to distant sites, and glomerulonephritis. The risk of acute
post-streptococcal glomerulonephritis is not mitigated by the use
of antibiotics.
GABHS pharyngitis is difficult to accurately diagnose solely
based on symptoms or signs because significant overlap is seen
with findings common to other causes of pharyngitis. In a popula-
tion of young adults with sore throat, clinical grounds alone
overestimated the occurrence of GABHS in 81% of the patients,
and overdiagnosis commonly led to unnecessary treatment.21 This
is problematic, because antibiotic treatment should be limited
only to patients likely to have a GABHS infection. Because of
this diagnostic difficulty, two scoring systems were developed for
predicting the likelihood of GABHS on clinical grounds alone.22,23
These clinical scoring systems, which were plagued by low specific-
ity, have largely been replaced by direct laboratory evidence of
active infection. Current recommendations by the Infectious
Diseases Society of America (IDSA) support use of contemporary
rapid antigen detection tests, which have high sensitivity (80% to
90%) and specificity (>95%) for GABHS infection. Patients with
three or more of the following symptoms, including sore throat,
fever, tender anterior cervical adenopathy, or tonsillar swelling or
exudates in the absence of cough, should undergo rapid antigen
detection. If negative and clinical suspicion is high, throat culture
is indicated.19 Adults with GABHS pharyngitis should be treated
with an antibiotic whose dose and duration is likely to eradicate
the organism from the pharynx. Penicillin or amoxicillin is the
treatment of choice because of its proven efficacy, narrow spectrum,
and low cost. No clinical isolate of GABHS has ever been docu-
mented to be resistant to penicillin.19,24 The oral course should
be for 10 days for all antibiotic choices, except when azithromycin
is used, which should be in a 5-day course. Clindamycin is an
acceptable alternative for patients with both a penicillin allergy
and a strain resistant to macrolides.
Less Common Pathogens That Can Cause
Acute Pharyngitis
• Groups B, C, and G streptococci have been cultured from
patients during episodes of acute pharyngitis.1,25 These organisms
are part of the normal upper respiratory tract flora, so dif-
ferentiating colonization from infection is difficult. Clinical
symptoms and examination findings are indistinguishable from
those of GABHS. Pharyngeal infection with groups C and G
streptococci can cause acute glomerulonephritis but has never
been shown to cause acute rheumatic fever. Whether treatment
is prescribed in all cases or just in select cases has been debated,
but penicillin and clindamycin both provide effective treatment
when necessary.
• Arcanobacterium haemolyticum is a nonmotile, β-hemolytic,
gram-positive bacillus, not part of the normal upper respiratory
900 PART V Laryngology and Bronchoesophagology
tract flora, which causes 0.5% to 2.5% of acute bacterial
pharyngitis in young adults (10 to 30 years of age) as well as
other deep-seated infections.26 The mode of transmission appears
to be airborne. The throat symptoms vary from a mild phar-
yngitis to an exudative tonsillitis to a diphtheria-like illness to
septicemia. A rash is present in 25% to 50% of patients and
may be urticarial, macular, or maculopapular. Pharyngitis caused
by A. haemolyticum is easily mistaken for GABHS or viral
pharyngitis with an exanthem because of the overlap in
symptoms. When suspected, throat culture needs to be per-
formed using 5% human blood agar. Using this culture media,
prominent hemolytic zones are formed within 24 hours by A.
haemolyticum. Sheep’s blood agar is usually used for standard
throat cultures because it is rapidly hemolyzed by GABHS,
but A. haemolyticum only forms 0.5-mm colonies with a narrow
rim of hemolysis by 48 hours using this culture media. Because
most clinical labs discard throat cultures after 48 hours, the
diagnosis is commonly missed when using this method. First-line
antibiotic therapy for A. haemolyticum pharyngitis is erythro-
mycin, but sensitivities are recommended for all positive cultures
given high rates of resistance.
• Neisseria gonorrhoeae is a sexually transmitted organism that
affects the anogenital region but can also cause gingivitis,
stomatitis, glossitis, and pharyngitis.27 Infection usually occurs
concomitantly with genital infection but rarely occurs as the
only site of involvement. Fellatio is the high-risk behavior.
Symptomatic patients usually come to medical attention with
findings suggestive of tonsillitis. The tonsils are enlarged, and
a white-yellow exudate arises from the crypts.28 Because bacteria
are usually found at the base of tonsillar crypts, it is recom-
mended to obtain Gram stain and culture specimens from deep
within the crypts. A typical Gram stain reveals intracellular
gram-negative diplococci. This finding should be confirmed
by culture on modified Thayer-Martin medium because the
pharynx can be colonized by other Neisseria species. Recom-
mended treatment is with a single dose of intramuscular cef-
triaxone. Combined treatment for Chlamydia trachomatis should
be given in all cases because this organism is not reliably
identified in throat cultures but still coexists in 45% of cases.29
Treatment for C. trachomatis consists of a single oral dose of
azithromycin as first-choice therapy or, alternatively, a 7-day
course of doxycycline.
• Treponema pallidum is the spirochete that is the causative agent
of syphilis. Primary syphilis can present with manifestations
in the oral region with the most common finding being an
ulcer on the lip, tongue, or tonsil.30 Oral involvement during
the primary stage is painless and does not present as pharyngitis.
However, if left untreated, secondary syphilis mainly presents
with systemic symptoms that may include sore throat.31 Physical
examination of the pharynx reveals oval, red maculopapules
and patches. The tonsils (unilateral or bilateral) may be enlarged
and red. Nontender lymphadenopathy can be present in the
cervical and other regions. Diagnosis during suspected cases
of secondary syphilis is made using microscopy or serologic
test; Gram stain cannot detect this bacterium. Nonspecific
(rapid plasma reagin, RPR) and specific (fluorescent treponemal
antibody absorption, FTA-ABS; treponema pallidum haemag-
glutination, TPHA) serologic tests are the tests of choice.
Treatment for primary or secondary syphilis is with a single
intramuscular dose of benzathine penicillin G.
• Diphtheria has nearly been eradicated worldwide due to the
availability of diphtheria toxoid.32 Corynebacterium diphtheriae is
a nonmotile gram-positive pleomorphic bacillus. Transmission
occurs through infected secretions from the nose, throat, eyes,
or skin lesions. Entry occurs through the mouth or nose, and the
organism initially remains localized to the mucosal surfaces of the
upper respiratory tract. Local inflammation and toxin-mediated
tissue necrosis causes formation of a fibrinous, patchy, adherent,
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gray-black pseudomembrane. The location of pseudomembranes
can be nasal, tonsillar, pharyngeal, laryngeal, or laryngotracheal.
If disease extends into or primarily involves the larynx, or if the
pseudomembrane is aspirated after sloughing, symptoms may
be severe and life threatening. Definitive diagnosis is based on
isolation of the organism with growth in Loeffler coagulated
serum, tellurite, and blood agar media. Treatment consists of
both the antitoxin (hyperimmune antiserum of equine origin)
and antibiotics (penicillin and erythromycin).
• Epiglottitis, or more properly supraglottitis, continues to be a
life-threatening infection of the upper airway in adults caused
by Haemophilus influenzae type B despite success of the vaccine
in limiting the frequency of this disorder.33 The presentation
is often quite dramatic, with an urgent call to the emergency
department for a drooling, febrile patient in respiratory distress.
Depending on the acuity of the airway embarrassment, the
adult patient may be examined fiberoptically to characterize
the nature of the obstruction; however, determination of the
severity of the obstruction and the clinical decision making
are based on a generalized assessment of the patient’s overall
appearance, in addition to nonlaryngeal airway considerations
such as body habitus, jaw and mouth opening, and neck exten-
sion. If the patient requires airway intervention, intubation in
a controlled setting (e.g., the operating room) or awake tra-
cheotomy may be appropriate. Yet, a review of 23 adult
supraglottitis cases revealed that the minority of cases (3 of
23) require airway intervention; the remainder may be managed
supportively with humidification, intravenous antibiotics, close
observation, and perhaps even steroids.34
• Laryngeal infection with Klebsiella rhinoscleromatis, part of the
disorder known as rhinoscleroma, is another infectious entity
that can affect the larynx. The disease may progress to airway
obstruction with tracheal involvement but may be limited to
rhinologic and vocal fold involvement. The disease is diagnosed
from the identification of the causative organism, a gram-
negative coccobacillus, within macrophages obtained from
mucosal biopsy specimens. These are the characteristic Mikulicz
cells of rhinoscleroma. The disease may be treated with fluo-
roquinolone antibiotics, tetracycline, and supportive airway
management.35 Patients with this disease may also need acute,
as well as long-term, surgical airway management. Amoils and
Shindo35 reported on a series of 22 patients with rhinoscleroma,
13 of whom had laryngeal involvement. Of these 13, three had
undergone tracheotomy at some point during the clinical course.
Acute Fungal Laryngopharyngitis
Nearly all cases of acute fungal infections in the pharynx and
larynx are caused by Candida albicans. Candidal laryngitis is probably
quite common.36 Patients typically come to medical attention with
hoarseness with or without accompanying throat discomfort. The
most characteristic finding is a diffuse, whitish speckling of the
vocal folds or supraglottis (Fig. 61.2), quite similar to that seen
in thrush, which affects the oral cavity and soft palate. In both
immunocompromised and immunocompetent patients, laryngeal
candidiasis should remain in the differential diagnosis when clini-
cally suspected. The causes of white lesions, or leukoplakia, on
the surface of the vocal fold epithelium are few; the differential
diagnosis includes hyperkeratosis, thick mucus, malignancy, and
candidal infection. Although formal culture is required to confirm
the diagnosis, it is neither practical nor common. It has been
theorized that patients with local risk factors, such as the recent
use of broad-spectrum antibiotics or topical (inhaled) corticosteroids,
are more prone to developing this problem. This theory is clinically
reasonable, but such an association is not exclusively the case;
Candida should be included in the differential diagnosis of a great
range of patients with epithelial abnormalities of the larynx.37

Fig. 61.2 A 60-year-old woman with several months of
hoarseness. She had been using a steroid inhaler. Examination with a
transoral rigid laryngoscope showed raised whitish plaques of the
membranous vocal folds. These responded promptly to antifungal
treatment. (Courtesy Lucian Sulica, MD, Cornell University School of
Medicine, New York.)
Disease manifestations are usually local, but rarely they can
become systemic and cause significant morbidity and mortality.
Initial therapy for uncomplicated candidiasis involving primarily
the oropharynx includes improving oral hygiene and use of topical
antifungals. Patients with a refractory or recurrent infection and
those with laryngeal disease are often treated with systemic
antifungals.36 Fluconazole is the predominant medication used to
treat laryngopharyngeal candidiasis because the predominant
organism, C. albicans, has consistently shown sensitivity to the
drug, and fluconazole is generally well-tolerated. With increased
use, however, development of resistance to fluconazole has become
a growing concern. Resistance is usually correlated to the degree
of immunosuppression and the total dose of drug. Itraconazole
is an alternative effective antifungal and should be used for
fluconazole-resistant strains.
NONINFECTIOUS CAUSES OF ACUTE LARYNGITIS
Phonotrauma
Vocal abuse, misuse, and overuse can contribute to phonotrauma.
This may result in vocal fold hemorrhage and edema in addition
to changes incurred at the molecular level.38 Although this process
does not represent the usual concept of infectious or “exogenous”
sources of inflammation, the tissue response to injury can be quite
profound. The problem of vocal abuse and strain may be exacer-
bated by dehydration through its effect on phonation threshold
pressure.39 On the basis of common clinical experience, many
practitioners believe that vascular lesions of the vocal fold may
begin, or be exacerbated by, acute phonotrauma. In the case
illustrated in Fig. 61.3, a young singer noted the moment her
voice changed during a performance. Examination of her vocal
folds in the clinic revealed a left true vocal fold lesion with feeding
vessels. Despite excellent hygiene, voice therapy, and conservative
management, the lesion did not resolve, and she required pho-
nosurgical intervention.
In the great majority of cases that involve phonotrauma,
medical attention is not sought. A patient who does seek care
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CHAPTER 61 Acute and Chronic Laryngopharyngitis 901
61
Fig. 61.3 Intraoperative image from a 70-degree telescope of the left
true vocal fold of a young singer who reported acute vocal changes
during a performance. Clinical examination revealed this pedunculated
lesion with surrounding inflammatory vessels. Medical and speech
language intervention did not resolve the condition, so the patient
underwent successful phonosurgical removal of the lesion. Note the
absence of pathologic vessels on the right vocal fold.
from an otolaryngologist is most likely to have recurrent or
severe symptoms or to be particularly sensitive to his or her vocal
health. Clinical examination should include a detailed history,
laryngoscopic examination, and stroboscopy, if available. There
is little to no scientific basis for the usual treatments utilized for
vocal fold trauma—voice rest, steroids, and other medications.
Anecdotally, however, voice rest is quite useful to reduce further
acute injury, particularly if the laryngeal injury has a hemorrhagic
component. Paradoxically, some degree of mechanical strain, in
the truest physical sense of the word, may be beneficial to appro-
priate vocal fold healing. Branski and colleagues have elegantly
shown that low levels of mechanical activity reduce interleukin
1β (IL-1β)-induced proinflammatory signaling in vocal fold
fibroblasts.40 This finding may be elucidated by further investiga-
tion as our understanding of the molecular basis of vocal fold
injury improves.
CHRONIC LARYNGOPHARYNGITIS
Generally speaking, chronic infectious and inflammatory disorders
are more likely to afflict the larynx than the pharynx. The distinction
between acute and chronic laryngitis is not necessarily a strict one;
many of the disorders discussed in the section on acute laryngo-
pharyngitis may also contribute to chronic dysfunction. In this
section, several key infectious causes of chronic laryngopharyngitis
are reviewed along with reflux-associated inflammation.
Chronic Bacterial Laryngitis
Although most otolaryngologists associate bacterial infection of
the larynx with an acute process, chronic, even life-threatening
disease may arise in this situation. Superinfection of the larynx
may complicate intubation injuries or larynges already damaged
from relapsing polychondritis (RP), for example. Eliashar and
colleagues41 presented several case examples of this occurrence.
In each of the three cases outlined, purulent chondritis was noted
in patients with prolonged hoarseness and stridor lasting more
than 1 month. These patients required surgical drainage and
ongoing medical treatment. In two of the three cases, the pathogen
902 PART V Laryngology and Bronchoesophagology

was S. aureus. Lipopolysaccharide of bacterial origin induces

proinflammatory cytokine (IL-8) expression and alters mucin gene
expression in laryngeal goblet cells.42 Clinicians should suspect
bacterial infection, regardless of its relative rarity, in patients who
have persistent chronic inflammation of the larynx. Culture and
drainage of abscess spaces may be required. The role of hyperbaric
oxygen in the treatment of this disorder, similar to treatment for
chondroradionecrosis of the larynx, deserves consideration and is
discussed elsewhere in this volume.

Chronic Fungal Laryngitis

The larynx may also become infected chronically with pathogenic
fungal species. Representative organisms include Blastomyces,
Histoplasma, Coccidioides, Paracoccidioides, and Cryptococcus species.
In general, the clinical presentation of laryngeal fungal infection
is not specific to the pathogen but reflects a general disturbance
of laryngeal function—that is, it consists of hoarseness and throat
discomfort. Tissue biopsy and fungal stains are needed to confirm
Fig. 61.4 Hematoxylin and eosin stain of laryngeal tuberculosis
the diagnosis. Less common pathogens are not discussed in detail,
demonstrating granuloma formation. (Courtesy Hong-Shik Choi,
although laryngeal infections with Sporothrix, Aspergillus, and
MD, Yonsei University College of Medicine, Seoul, Korea.)
Cryptococcus species have been reported.
More common chronic laryngeal fungal infections include:

• Blastomycosis is endemic in several areas, including the southern

United States.43 Although this fungus enters the system by
inhalation, laryngeal infestation is thought to arise, similar
to infestation of other organs, from hematogenous spread.
While laryngeal involvement with blastomycosis infection is
rare (<5% of cases)44, diagnosis of blastomycosis should be
considered when atypical but suspicious lesions are noted in the
larynx. Fungal stains of the involved tissue reveal broad-based
budding yeast. Treatment includes systemic therapy, such as with
amphotericin B, ketoconazole, or itraconazole. The practitioner
must be particularly cautious to distinguish blastomycosis from
laryngeal carcinoma; like many inflammatory disorders, fungal
laryngitis may manifest in a clinical picture similar to that seen
in a new laryngeal cancer. Furthermore, biopsies of involved
tissue may reveal pseudoepitheliomatous hyperplasia, which may be
mistaken for the advancing front of an epithelial malignancy.45
• Paracoccidioides appears to be one of the leading pathogens in
invasive fungal laryngitis. Although not common in comparison
with other laryngeal maladies, paracoccidioidal infection of
the larynx affects a significant fraction of patients in South
America. As in most of these disorders, the primary manifestation
is dysphonia with dyspnea. Laryngeal examination revealed
both ulcerative and exophytic lesions, which can resemble
carcinoma, like those in blastomycosis. In patients with granu-
lomatous laryngitis, paracoccidioidal infection should be
considered.46,47 Treatment is with systemic antifungals.
• The causative agent in histoplasmosis, Histoplasma capsulatum,
is a fungus endemic to the Ohio and Mississippi River valleys,
and its spores may be inhaled, leading to localized pulmonary
infection or systemic dissemination. It is possible for this
infection to occur outside of endemic areas, but such occurrences
are rare. Few cases of laryngeal histoplasmosis have been
reported. Gerber and colleagues48 reviewed a series of 115
patients with disseminated disease to characterize the incidence
of otolaryngologic findings. Seven of these patients had oral
cavity/oropharyngeal infection; only two cases featured laryngeal
disease, and eight of the nine patients with otolaryngologic
manifestations were immunocompromised secondary to HIV
infection, post-transplant iatrogenic immunosuppression, or
diabetes. Fungal staining of an acquired tissue sample was
positive in eight of nine patients. Further, treatment results
were better with amphotericin compared with fluconazole. As
with other fungal and atypical laryngeal infections, histoplas-
mosis can be misdiagnosed as carcinoma.49
Chronic Mycobacterial Laryngitis
Patients with and without disseminated tuberculosis (TB) may
develop laryngeal manifestations of the disease. The bulk of this
discussion reviews existing knowledge regarding laryngeal TB.
One other mycobacterial infection, leprosy, also deserves mention
here. In this generally tropical disease, the causative agent,
Mycobacterium leprae, is transmitted via aerosolized droplets that
are highly contagious but do not always lead to clinical disease.
This disease is most often encountered in South America, Africa,
and the Asian subcontinent; countries with the highest incidence
include Brazil, Mozambique, and India. More than a third of
patients with disseminated leprosy in India were noted to have
laryngeal involvement.50 Similar to TB, staining of tissue biopsy
specimens demonstrates acid-fast bacilli and granuloma formation
(Fig. 61.4). Multiple-drug regimens may be required for extended
periods of treatment to eradicate the disease.
The recognition and treatment of laryngeal TB requires an
awareness of the typical clinical scenario and laryngeal findings
associated with the disorder. Lim and colleagues reviewed 60 cases
of laryngeal TB over a 10-year period.51 Hoarseness was nearly
uniform, and laryngoscopic findings were divided between granu-
lomatous and ulcerative lesions. True and false vocal folds were
the most commonly affected sites. Of these 60 patients, 28 (47%)
had active pulmonary disease; 20 of the 60 (33%) had inactive
pulmonary TB, and 9 (15%) had isolated laryngeal TB. Lim and
colleagues made special note of the focal, atypical, and unilateral
laryngeal findings in patients without active pulmonary disease.
NONINFECTIOUS CHRONIC LARYNGITIS
The most clinically significant causes of laryngitis in the otolar-
yngologist’s practice are often related to poor laryngeal hygiene
(tobacco, alcohol, and caffeine consumption) or to the refluxate
of gastric and duodenal contents. Although a detailed description
of the impact of reflux on the larynx, as well as other organs in
the head and neck, is given elsewhere in this text, the topic deserves
some discussion here. In addition, we review the major autoimmune
and systemic inflammatory disorders that often manifest as laryngeal
disease and dysfunction.
Reflux Laryngitis
The larynx may be affected by contact with refluxed material from
the lower foregut, and the vast majority of such contact events

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Fig. 61.5 Pepsin (arrow) within an intracellular vesicle of human
laryngeal epithelium from a patient with laryngopharyngeal reflux
(bar = 0.2 µm). (Courtesy Nikki Johnston, PhD, Medical College of
Wisconsin, Milwaukee.)
are thought to be acidic in nature. The recognition of acidic injury
to the larynx has been one of the key advancements in laryngology
in the past few decades.52 Little controversy surrounds the ability
of extraesophageal reflux to induce changes in the epithelium and
stroma of laryngeal tissue that leads to organ dysfunction,53-55 but
controversy does surround the incidence and diagnosis of this
disorder. The rates of medical management of presumed reflux
that affects the larynx and pharynx have risen despite the lack of
compelling evidence in double-blind, placebo-controlled trials that
such therapy works.56,57 It is possible, however, that investigation
into nonacidic reflux, as well as into the significance of variable
patient susceptibility to reflux-associated mucosal injury (and
perhaps other laryngeal disorders), will yield a deeper understanding
of this issue.
Bile and pepsin have been implicated as possible sources of
laryngeal injury for many years. The presence of biliary- and/or
pepsin-containing reflux continues to be a possible explanation
for the lack of response to antacid therapy in chronic reflux lar-
yngitis. Bile causes significant injury to laryngeal mucosa in an
acid environment.58 Animal studies have clearly demonstrated the
ability of pepsin to create laryngeal epithelial injury in acidic
environments.58,59 Importantly, pepsin was found to maintain
damaging activity at pH above 4 and was able to be “reactivated”
after some time in a pH-neutral environment.60,61 The significance
of these findings may prove to be great, because the current para-
digm for treating reflux-associated injury of the larynx has focused
on neutralization of the proton pump in the stomach. If pepsin
can indeed maintain the ability to damage tissue even after
neutralization, particularly after receptor-mediated uptake into
epithelial cells, current strategies aimed at treating reflux-associated
laryngitis must be reconsidered (Fig. 61.5).
LARYNGITIS ASSOCIATED WITH
AUTOIMMUNE DISEASE
• Pemphigoid and Pemphigus The larynx may be the end organ
affected by autoimmune disorders, such as pemphigoid and
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CHAPTER 61 Acute and Chronic Laryngopharyngitis 903
61
Fig. 61.6 Pemphigus vulgaris in a 57-year-old woman who came to
medical attention with throat pain and hoarseness. This image of the
left false and true vocal folds was obtained with a 70-degree
telescope during direct laryngoscopy.
pemphigus (Fig. 61.6). Severe epithelial loss and resulting
inflammation may occur from the effect of either intraepithelial
(pemphigus vulgaris) or subepithelial (pemphigoid) autoantibod-
ies. Up to 80% of the patients with pemphigus had otolaryn-
gologic signs and symptoms, of which 40% were laryngeal in
nature.62 Evidence suggests that laryngeal manifestations of
pemphigus respond well to high-dose corticosteroids combined
with immunosuppressives.63 Of patients with pemphigoid, 35%
were found to have some symptoms related to the head and
neck, and half of these patients had discoverable laryngeal
lesions at the time of examination.64 Interestingly, only 10 of
38 (26%) had laryngeal symptoms, indicating that laryngeal
involvement was asymptomatic in a significant fraction of
patients.
• Granulomatosis with Polyangiitis (GPA) Formerly known as
Wegener granulomatosis, this disease is a small- and medium-vessel
vasculitis associated with autoantibodies against proteinase 3
(cytoplasmic antineutrophil cytoplasmic antibody [c-ANCA])
and myeloperoxidase (perinuclear antineutrophil cytoplasmic
antibody [p-ANCA]) proteins found in neutrophils. Patients
may demonstrate either systemic or localized disease; of patients
with systemic disease, 95% are ANCA-positive, whereas 75%
of patients with disease manifestations localized to the head
and neck are positive on serology.65 Overall, 90% of patients
with GPA will have some form of head and neck manifesta-
tion, the most common being subglottic stenosis (20%).65,66
Airway obstruction resulting from chronic inflammation is
treated with either endoscopic airway dilation or open resec-
tion of diseased tissue.65,67 Benefits of systemic immunosup-
pression, in terms of prevention of restenosis, have not been
demonstrated.
• A rarer disorder, relapsing polychondritis (RP), deserves
discussion. This disorder involves episodes of inflammation in
cartilages high in glycosaminoglycans and in surrounding tissues.
It is felt to be an autoimmune disorder, and autoantibodies
directed against type II collagen can frequently be identified
in patients who demonstrate the clinical hallmarks of RP.68 Of
patients with RP, 25% to 50% demonstrate symptoms of
laryngeal dysfunction or objective changes in the larynx that
range from hoarseness, pain, and cough to lethal airway obstruc-
tion.68,69 Treatment often includes combinations of both medical
management and surgical intervention.
904 PART V Laryngology and Bronchoesophagology

LARYNGITIS ASSOCIATED WITH SYSTEMIC
INFLAMMATORY DISEASE
Two systemic inflammatory disorders, sarcoidosis and amyloidosis,
may affect the larynx and should be included in the differential
diagnosis in a patient with laryngeal dysfunction of unclear
etiology.
• Sarcoidosis is a rare disorder that involves the development
of collections of chronic inflammatory cells (noncaseating
granulomas) in tissues throughout the body. The cause is
unknown. Laryngeal involvement occurs in less than 1% of
patients.70 Laryngeal sarcoid is often limited to the supraglottic
and glottic larynx in the form of diffuse edema, whereas subglot-
tic extension is very rare. Diagnosis is often achieved only
through histologic analysis of representative tissue.71 Systemic
medical treatment is often used for systemic disease, but selective
endoscopic resection of obstructing laryngeal disease and
intralesional steroid injection can be utilized for disease limited
to the larynx.72
• Amyloidosis is a disorder broadly characterized as the extracel-
lular deposition of abnormal proteinaceous debris. This can
occur in tissues throughout the body secondary to systemic
lymphoproliferative or chronic inflammatory disorders such
as multiple myeloma. Conversely, representing a biologically
distinct process, focal, isolated amyloid deposits can form, often
secondary to extramedullary plasmacytomas.73 These rare plasma
cell neoplasms and their associated focal amyloid deposits can
occur in the mucosal-associated lymphoid tissue (MALT) of
the larynx. Laryngeal amyloidosis is rare and accounts for less
than 1% of all benign laryngeal lesions. The diagnosis is
suspected with the presence of a nonulcerated, submucosal
mass or nodule that often demonstrates a yellow or orange
hue. Treatment depends on the underlying cause, but laryngeal
symptoms can often be palliated with selective endoscopic
resection of disease that affects the voice or obstructs the airway
(Fig. 61.7).74
BROAD CONCEPTS: THE LARYNX AS A COMPLEX
IMMUNOLOGIC ORGAN
Immune Anatomy
Apart from its role in protecting the lower airways and facilitating
respiration and phonation, emerging evidence now points to an
active immunologic role for the larynx. The “immune anatomy”
of the larynx is complex. Major histocompatibility (MHC) class
II proteins necessary for presentation of extracellular antigenic
material to the adaptive immune system are expressed on cells in
the lamina propria and to a lesser degree on epithelial cells in
laryngeal mucosa. Expression of MHC class I proteins, critical
for intracellular protein homeostasis and antigen detection,
demonstrates a similar pattern,75 suggesting that the laryngeal
mucosa has necessary components to detect and potentially initiate
immune responses to foreign or antigenic material. Not only critical
for response to pathogens, this has significant implications for
potential laryngeal transplantation, because MHC molecules are
the major source of antigenic material responsible for recipient
immune rejection of transplanted tissue.
Expression of MHC components in the mucosa of the larynx
is dependent at least in part on the presence of mucosal leukocytes.
When cultured in vitro, laryngeal epithelial cells do not express
MHC; in fact, they do so only when artificially stimulated with
interferon-γ.76 At baseline, T lymphocytes, as well as MHC class
II–expressing antigen presenting cells, are present in variable
degrees in the epithelium and lamina propria of the supraglottic
and subglottic larynx.77 Other studies have demonstrated remarkable
accumulation of immune cells in response to viral, bacterial, and
environmental antigenic exposure in the larynx. Following exposure,
neutrophils, T and B lymphocytes, natural killer cells, and, most
robustly, dendritic cells (DCs) accumulate primarily in the subglottic
larynx.77,78 Of note, macrophage accumulation in response to
antigenic stimulation primarily occurs in the glottis as opposed
to the subglottis. Colocalization studies that have matched the
physical locations of CD8-positive T lymphocytes with MHC
class I–expressing cells79 and CD4-positive T lymphocytes with
MHC class II–expressing cells bolster the evidence that suggests
that the larynx is capable of generating a physiologically active
immune response.
Immune Tolerance
The above evidence demonstrates that many of the key components
required to elicit an immune response within the larynx are present;
yet the larynx does not exist in a perpetual state of inflammation
in response to the constant barrage of inhaled, pathogenic, and
food antigenic material that it encounters given its unique location
at the junction of the respiratory and gastrointestinal tracts. Several
findings suggest that the larynx may play a significant functional
role in the development of immune tolerance. First, the expression
of MHC molecules is highly compartmentalized in the laryngeal
epithelium, with classic MHC class I components—that respond
to virus, for example—expressed in the deep, basal layers and the
nonclassic MHC molecule CD1d (involved in tolerance) expressed

A B
Fig. 61.7 Representative images from in-office endoscopic examinations. (A) Severe supraglottic edema
and inflammation secondary to laryngeal sarcoidosis that caused pain, hoarseness, and airway obstruction.
(B) Diffuse, painless laryngeal amyloid deposits that caused hoarseness.

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 CHAPTER 61 Acute and Chronic Laryngopharyngitis 905

in the more superficial layers.79-81 Second, laryngeal mucosa lacks
expression of T-cell receptor costimulatory proteins (CD80, CD86)
required for MHC-antigen complex T-lymphocyte activation. In
the absence of such coreceptor stimulation, engaged T cells become
inactive, and tolerance is induced. Third, whereas activated DCs
are critical for the presentation of extracellular antigen to T
lymphocytes, immature DCs induce T-cell tolerance and recruit
immunosuppressive regulatory T cells. Although several studies
have demonstrated the robust infiltration of DCs in laryngeal
epithelium at baseline and following antigenic exposure, whether
these are mature, functional DCs has not been fully evaluated.
Further research must be done on the immune components
in the laryngopharynx to understand how these structures not 61
only respond to pathogen-associated antigenic stimuli but do not
respond to environmental antigen; this will be critical for under-
standing the delicate balance between inflammatory response to
harmful pathogens and tolerance that allows normal laryngo­
pharyngeal function. These findings are likely to have wide
implications in the care of patients with food and other environ-
mental allergy, asthma, reflux, and malignancy.
For a complete list of references, visit ExpertConsult.com.

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