Pharyngoconjunctival Fever (PCF) 

Updated: Sep 05, 2017
Author: Ingrid U Scott, MD, MPH; Chief Editor: Hampton Roy, Sr, MD 

Overview

Background

Pharyngoconjunctival fever (PCF) is an acute and highly infectious illness characterized by fever, pharyngitis, acute follicular conjunctivitis, and regional lymphoid hyperplasia with tender, enlarged preauricular adenopathy.

Adenoviruses are the most common cause of acute viral infections of the conjunctiva, occurring epidemically or sporadically throughout all seasons. Clinically, 4 syndromes of adenoviral ocular infection have been recognized, as follows: epidemic keratoconjunctivitis, pharyngoconjunctival fever (PCF), nonspecific sporadic follicular conjunctivitis, and chronic papillary conjunctivitis.

Pathophysiology

The adenoviruses consist of a group of 35 morphologically similar but antigenically distinct DNA viruses that share a common complement-fixing antigen. Ubiquitous throughout the world, these extremely stable, ether-resistant organisms cause infections of the upper respiratory tract and the eye. PCF most frequently is caused by adenovirus serotypes 3 and 7, but serotypes 2, 4, and 14 also have been documented as etiologic agents. In addition, sporadic outbreaks caused by serotypes 1, 5, 6, 8, 11, and 19 have been reported.[1, 2, 3, 4]

Transmission occurs through contact with infected upper respiratory droplets or fomites, or through swimming pools, in which fecal excretion of the virus is believed to be responsible. Communicability ranges from 100% during the first few days to 0% by 10-15 days after the onset of symptoms. The incubation period after exposure is 5-12 days (average, 8 d).

Epidemiology

Frequency

United States

Because PCF occurs epidemically and sporadically, the frequency is not known.

Mortality/Morbidity

Many cases of PCF are self-limited and mild, although chronic infections have been reported. Long-term ocular sequelae are rare.

Sex

PCF occurs equally in men and in women.

Age

Disease is seen predominantly in children and institutionalized individuals, with epidemics occurring within families, schools, prisons, ships, and military organizations.

 

Presentation

History

Patients may give a history of recent exposure to an individual with red eye at home, school, or work, or they may have a history of recent symptoms of an upper respiratory tract infection.

PCF is characterized by its associated systemic manifestations. Patients experience a sudden or gradual onset of fever ranging from 100-104°F, lasting up to 10 days. Myalgia, malaise, and GI disturbances frequently are associated with the fever. The pharyngitis may be mild or quite painful.

Initial symptoms of conjunctivitis range from slight itching and burning to marked irritation and tearing, but little photophobia. Swelling of the lids may occur within 48 hours.

Signs of disease include epiphora, conjunctival hyperemia and chemosis, subconjunctival hemorrhage, follicular or mild papillary conjunctival reaction, and eyelid edema.

Mild crusting of the lids and discharge may occur; if present, it usually is serous.

PCF most frequently is bilateral, with one eye typically having onset 1-3 days prior to the second eye. With bilateral disease, the first eye generally is affected more severely.

Physical

On general examination, look for a reddened posterior oropharynx covered with glassy follicles. Nontender cervical lymphadenopathy and tender, enlarged preauricular adenopathy may be present.

On ophthalmic examination, the conjunctivitis presents initially as a diffuse hyperemia that is generally more pronounced in the lower fornix but extends throughout the palpebral mucosa and onto the bulbar conjunctiva. It may be sufficiently boggy to give a slightly gelatinous appearance to the tissue.

The lower lid may be tender to palpation and ecchymotic, giving the appearance of recent ocular trauma. Conjunctival membranes and pseudomembranes are infrequent but may be present.

Causes

Adenoviruses are the most common cause of acute viral infections.

 

DDx

Diagnostic Considerations

Epidemic keratoconjunctivitis

Vernal keratoconjunctivitis

Punctate keratitis, although not frequent, may develop a few days to a week after the onset of symptoms. The keratitis progresses through stages characterized by an orderly sequence of superficial epithelial keratitis, deep epithelial keratitis, and subepithelial infiltrates. Superficial epithelial keratitis begins as small epithelial dots that stain with fluorescein. Deep epithelial keratitis is characterized by focal epithelial and subepithelial whitish lesions that may stain and subepithelial infiltrates that characteristically do not stain.

Although the entire illness usually is acute and transient, resolving over a few days to 3 weeks, subepithelial infiltrates may persist for several months, and, if in the visual axis, they may cause glare and decreased visual acuity.

Differential Diagnoses

 

Workup

Laboratory Studies

Diagnosis of PCF generally is made based on clinical presentation alone. Virus may be cultured during the acute epithelial stage only, because the stromal infiltrates that occur later in the disease are thought to be immune complexes against residual viral antigen.

Without positive viral cultures taken during the first 8-10 days, proof of diagnosis beyond clinical impression may be obtained from paired blood specimens; one specimen drawn 1 week after the onset of symptoms and the second specimen drawn 2-3 weeks later. A 4-fold or greater increase in humoral antibody to adenovirus, measured by complement fixation, indicates recent adenoviral infection.

Other diagnostic tests include electron microscopy, immunofluorescence, immunoperoxidase, polymerase chain reaction, and enzyme-linked immunosorbent assay (ELISA) testing. Several commercially available tests may provide a diagnosis, although laboratory processing time may be several days to over a week.

 

Treatment

Medical Care

Because PCF usually is a self-limited disease, treatment is mainly symptomatic, as follows:

  • Cold compresses several times per day for 1-2 weeks

  • Artificial tears 4-8 times per day for 1-3 weeks

Drug therapy

Drug therapy may be used but is rarely indicated.

A topical vasoconstrictor/antihistamine may be instilled 4 times per day for severe itching only, because it may cause a rebounding of symptoms and it has a high incidence of local toxicity and hypersensitivity.

A topical astringent or antibiotic may be instilled 4 times per day to prevent bacterial superinfection.

Topical steroids dramatically suppress conjunctival inflammatory signs, relieve symptoms, and are associated with resolution of the corneal subepithelial infiltrates. However, due to their adverse effects, topical steroids should only be used for pseudomembranes or when subepithelial infiltrates severely reduce vision. Subepithelial infiltrates may recur after discontinuing the steroids. Therapy should be maintained for one to a few weeks and then slowly tapered over months. Extreme caution must be taken when giving steroids to any patient with follicular conjunctivitis because it may worsen an underlying herpes simplex viral infection. Furthermore, topical steroids should be avoided during the first 2 weeks of infection during active viral replication.

Although adenovirus has been found to be sensitive to idoxuridine and trifluorothymidine in vitro, none of the commercially available antivirals have been shown to be effective clinically. On the other hand, topical cidofovir has been shown to be highly effective in the eradication of actively replicating viruses and limiting the time of symptomatology. Further clinical study is warranted to determine the long-term adverse effects of topical cidofovir, including the possibility of epithelial toxicity, secondary corneal infiltrates, and punctal stenosis. Topical cidofovir is also effective clinically against herpes simplex, molluscum contagiosum, and human papilloma virus.

Topical human fibroblast interferon has been shown to have some success, but it is still an experimental treatment.

An in vitro study using adenovirus 8 and A549 human epithelial cell cultures demonstrated that povidone-iodine at a concentration of 1:10 (0.8%) is highly effective against free adenovirus, less effective against intracellular adenoviral particles in already infected cells, and not significantly cytotoxic for healthy cells. Thus, povidone-iodine 0.8% may represent a potential option to reduce contagiousness in cases of adenoviral infections.

Surgical Care

If a membrane or pseudomembrane is present, it may be peeled off gently, and a topical steroid may be prescribed. If a symblepharon is forming, the membrane or the pseudomembrane should be removed. Frequent ointment therapy is also useful.

Consultations

Corneal consultation may be needed for nonresolving or severe keratitis or for steroid-related complications.

Activity

Families should be forewarned of the extremely contagious nature of this infection. Fomites, including napkins, towels, pillowcases, and clothing, should not be shared. Hand washing is also essential to avoid transmission. Health care workers may be precluded from patient contact for up to 2 weeks because of this infection, particularly if they work regularly with individuals who are immunocompromised. In general, workers with significant contact with people should not work until the weeping stops, which typically takes 1-2 weeks.

 

Medication

Medication Summary

Medications currently used in the treatment of PCF include the following: topical artificial tears 4-8 times per day for 1-3 weeks, topical vasoconstrictor/antihistamine 4 times per day for severe itching, topical steroids for pseudomembranes and subepithelial infiltrates, and topical antibiotic to prevent bacterial superinfection.[5, 6]

Ocular lubricants

Class Summary

Used for symptomatic relief.

Artificial tears (Celluvisc, Murine, Artificial Tears, Tears Naturale, Refresh)

Acts to stabilize and thicken precorneal tear film and prolong tear film breakup time, which occurs with dry eye states. Preservative-free tear preparations may be particularly appropriate.

Antihistamines

Class Summary

For severe itching; these include first-generation antihistamines prescribed over the counter (eg, naphazoline), second-generation therapy with agents (eg, levocabastine [Livostin], lodoxamide [Alomide]), and third-generation drugs (eg, olopatadine [Patanol], nedocromil [Alocril], pemirolast [Alamast], ketotifen [Zaditor]). Third-generation drugs may have antihistamine, mast cell stabilizing, and cell-mediated immunity inhibitory effects.

Levocabastine (Livostin)

Potent histamine H1-receptor antagonist, for ophthalmic use.

Corticosteroids

Class Summary

Have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli. For pseudomembranes and subepithelial infiltrates, which cause glare and/or decreased vision.

Prednisolone ophthalmic (AK-Pred, Pred Forte)

Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.

In cases of bacterial infections, concomitant use of anti-infective agents is mandatory; if signs and symptoms do not improve after 2 days, reevaluate patient. Dosing may be reduced, but advise patients not to discontinue therapy prematurely.

Loteprednol etabonate (Lotemax, Alrex)

Unique retromolecular engineering design ester steroid is metabolized rapidly when unbound to glucocorticoid receptor. Decreased incidence of significant intraocular pressure elevations in FDA study protocols. Efficacy similar to dexamethasone and prednisolone.

Nonsteroidal anti-inflammatory agents (NSAIDs)

Class Summary

Have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action is not known but may inhibit cyclooxygenase activity and prostaglandin synthesis. Other mechanisms may exist as well, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell membrane functions.

Diclofenac ophthalmic (Voltaren)

Inhibits prostaglandin synthesis by decreasing activity of enzyme cyclooxygenase, which, in turn, decreases formation of prostaglandin precursors.

Ketorolac ophthalmic (Acular)

Potent prostaglandin inhibitor. Acular also is available in a preservative-free single-dose unit preparation at additional cost. Formulation is extremely useful in patients with ocular surface disease, including adenovirus infection, as well as in the perioperative period.

 

Follow-up

Further Outpatient Care

Patients should return in 1-3 weeks for follow-up care but sooner if the condition worsens.

Deterrence/Prevention

Prevention of transmission, especially in the health care facility, is extremely important.

Careful hand washing before seeing every patient, proper cleansing of instruments, and frequent changing of multiuse ophthalmic drops are vital.

Using a single infective examination room and educating the staff and the patient are also essential.

Patients should be instructed to take contagion and isolation precautions for at least 2 weeks or as long as the eyes are red and weeping.

Complications

Potential complications include the following:

  • Punctate keratitis with subepithelial infiltrates

  • Bacterial superinfection

  • Chronic infection

  • Steroid drop dependence: Many ophthalmologists with this disease who have access to topical steroid samples have become dependent upon steroids and experience a protracted clinical course with prolonged corneal opacification.

Prognosis

Most cases of PCF are acute, benign, and self-limited. The infection usually resolves spontaneously within 2-3 weeks. Subepithelial infiltrates may last for several months (or longer), and, if in the visual axis, they may cause glare or decreased vision. Specific adenovirus serotypes, including 8, 19, 29, and 37, may be associated with keratitis.

Patient Education

To allay patient anxiety, patients should be informed that their symptoms may worsen during the first 4-7 days after onset before they begin to improve, and they may not resolve for 2-3 weeks. The contagiousness of the infection also should be emphasized, and proper isolation from work or school is advisable to prevent epidemics in the office and at school.

For patient education resources, see the Eye and Vision Center, as well as Pinkeye.