Acute and Chronic Laryngopharyngitis

Viral Etiologies of Acute Laryngopharyngitis

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. 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 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 .

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 neuraminidase 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. 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. 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 laboratory diagnosis, the sensitivity and specificity of these tests range from 62% to 73% and from 80% to 99%, respectively. 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. 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. 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.

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. 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 differential 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 manifestations less commonly observed include ulcers (29%) and candidiasis (17%).

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. The high viral titer associated with ARS is reflective of the initial burst of viremia 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. 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.

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. 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 progressively enlarge, have destructive behavior, and are extremely painful; they have a propensity for the tonsillar fossa, floor of the mouth, and epiglottis. 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 ulcers and systemic thalidomide. Early recognition of these ulcers through expert physical examination 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 pharyngoconjunctival fever in children and an adult febrile respiratory illness in situations involving overcrowding and physical stress, such as in military recruits. 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. 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. 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. 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. Immunologic studies include the heterophile antibody test and EBV-specific antibody tests. 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. 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. 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 infection. 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. 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.