Pharyngoconjunctival Fever (PCF) is an acute and highly infectious adenoviral disease characterised by fever, pharyngitis, acute follicular conjunctivitis and regional lymphoid hyperplasia with tender, enlarged pre-auricular lymphadenopathy.
Adenoviruses are the commonest cause of acute viral infections of the conjunctiva, which may occur in epidemics or sporadically throughout the year.
Adenoviral ocular infections are:
- Pharyngoconjunctival fever.
- Epidemic keratoconjunctivitis.
- Non-specific sporadic follicular conjunctivitis.
- Chronic papillary conjunctivitis.
Pharyngoconjunctival fever is seen predominantly in children and institutionalised people, with epidemics taking place within families, schools, prisons or military organisations.
PCF is mostly bilateral, with one eye typically having onset 1-3 days prior to the involvement of other eye. With bilateral disease, involvement of second eye is milder than the first eye.
Many cases of PCF are self-limiting and mild, although chronic infections have been reported. Long-term sequelae of eyes are rare.
Kanski,Jack J. Clinical Ophthalmology, A Systematic Approach .Third Edition.UK. Butterworth Heinemann, 1994.
Paryngoconjunctival fever is characterised by:
Systemic features may be:
- Sudden or gradual onset of fever in the range of 100-104°F, which lasts for about 10 days.
- Pharyngitis may be mild or quite painful.
- Gastro-intestinal disturbances.
Ocular features may be:
- Conjunctival redness.
- Irritation of eyes.
- Burning sensation in eyes.
- Epiphora (watering from eyes).
- Chemosis (swelling of conjunctiva).
- Subconjunctival (below conjunctiva) haemorrhage.
- Swelling of lids.
- Ecchymosis (non-raised reddish or bluish discolouration) of lids.
- Cervical lymphadenopathy.
- Painful pre-auricular lymphadenopathy.
Causative adenoviruses consist of a group of morphologically similar but antigenically distinct deoxyribonucleic acid (DNA) viruses which share a common complement-fixing antigen. Extremely stable adenovirus is present throughout the world and cause infections of the upper respiratory tract and eye.
Pharyngoconjunctival fever is caused most frequently by adenovirus serotypes 3 and 7, but serotypes 2, 4 and 14 have also been documented as aetiologic agents. Sporadic outbreaks may be caused by serotypes 1, 5, 6, 8, 11 and 19.
Transmission of adenovirus occurs through contact with:
- Infected upper respiratory droplets.
- Through fomites (inanimate objects).
- Through swimming pools.
The incubation period after exposure to adenovirus is 5-12 days (average is 8 days). Communicability of infection ranges from 100% during first few days to nil by 10-15 days after the onset of symptoms.
Diagnosis generally depends upon the history of presentation and physical features of the disease.
Patients may give history of recent exposure to a patient with red eye at home, workplace or school or they may give history of recent symptoms of an upper respiratory tract infection.
On general examination, patient may have fever associated with pharyngitis and systemic features like myalgia, malaise or gastrointestinal disturbances. Pharyngitis shows a reddened posterior oro-pharynx covered with glassy follicles.
Non-tender cervical lymphadenopathy and tender pre-auricular lymphadenopathy may be present.
Ocular examination shows:
Slit-lamp examination by an eye specialist is required for diagnosis.
- Diffuse conjunctival hyperaemia, initially more pronounced in lower fornix (junction of eyelid and eyeball).
- Subconjunctival haemorrhage.
- Follicular conjunctival reaction.
- Papillary hypertrophy.
- Swelling of lids.
- Tenderness and ecchymosis of lower lid.
- Mild crusting of lids may be present.
Conjunctival membranes and pseudo-membranes may be present but are infrequent.
Keratitis and photophobia is less common.
Following tests may be used for diagnosis of PCF:
- Polymerase chain reaction assay (PCR assay):
- Fluorescent antibody test:
- Immunoperoxidase test:
- Complement fixation test: Paired blood specimens are taken at one week and at 2-3 weeks interval after the onset of symptoms. A four-fold or greater increase in humoral antibody to adenovirus indicates a recent adenoviral infection.
- Giemsa cytology: Giemsa cytology is microscopic examination of stained conjunctival scrapings for intranuclear inclusions and lymphocytes.
- Cell culture: Virus may be cultured during acute epithelial stage only, since stromal infiltrates are thought to be immune complexes against residual viral antigen.
- Enzyme immune assays:
- AdenoPlus test: AdenoPlus test, an enhanced device for Rapid Pathogen Screening (RPS), is an antigen-based immunoassay. This test detects the presence of adenoviral particles and thus allows patient a speedier return to school or work when the virus is no longer detectable. Ability to confirm adenoviral infection may allow the study and use of novel therapies for the disease.
PCR test is more sensitive test, and therefore, use of AdenoPlus test should be limited to diagnostically challenging patients.
Pharyngoconjunctival fever may be differentiated from conditions like:
- Allergic conjunctivitis.
- Acute haemorrhagic conjunctivitis.
- Bacterial conjunctivitis.
- Viral conjunctivitis.
- Chlamydial infections.
- Giant papillary conjunctivitis.
Management should be carried out under medical supervision.
PCF is usually a self-limiting disease and it tends to resolve spontaneously within 1-3 weeks without leaving any significant complications. There is no effective treatment for PCF.
Depending upon the severity of signs and symptoms, patients are followed up for several days to weeks.
Goals of pharmacotherapy (treatment with medicines) are to reduce morbidity and to prevent any complications.
Antiviral eye drops were tried in some patients, but there was no definite benefit of these.
Supportive medical management of PCF includes:
- Cold compresses.
- Artificial tears: Artificial tears stabilise and thicken pre-corneal tear film and prolong tear film break-up time (BUT), which occurs with dry eye.
- Topical vasoconstrictor/antihistamine: Topical vasoconstrictor/antihistamine may be used for severe itching. On discontinuation, it may cause rebound (recurrence) of symptoms.
- Topical non-steroidal anti-inflammatory agents (NSAIDs): Topical non-steroidal anti-inflammatory agents (NSAIDS) may be used to reduce inflammation.
- Topical antibiotic: Topical antibiotic may be used to prevent superadded bacterial infection.
- Cycloplegic agents: Cycloplegic agents may be used for severe photophobia.
- Mild topical corticosteroids: Mild topical corticosteroids may be used in severe membranous conjunctivitis or patients with marked reduction in vision due to late sub-epithelial opacities. While corticosteroids do assist in reducing inflammation, they do not have any significant impact on natural course of the disease. Taper this treatment slowly to avoid recurrence of corneal opacities. Any patient on topical corticosteroid should be observed for side effects such as elevated intraocular pressure and formation of cataract.
- Topical immune-suppressants (e.g.Tacrolimus ointment): Topical immune-suppressants can inhibit autoimmune inflammatory responses. Tacrolimus is a treatment option for sub-epithelial infiltrates in PCF. Tacrolimus suppresses cellular immunity.
- Ophthalmic antiseptics (e.g.Povidone-iodine): Ophthalmic antiseptics are broad-spectrum germicidal agents. Povidone-iodine has broad antibacterial and antiviral activity. Povidone iodine may be used to reduce the duration of disease.
Surgery is extremely rare for PCF and is reserved for severe cases with cicatricial conjunctivitis or symblepharon.
If surgery is necessary, it is mainly in the form of:
- Excimer laser photo-therapeutic keratectomy (PTK): Excimer laser photo-therapeutic keratectomy (PTK), along with low-dose mitomycin C (MMC), may be used to remove sub-epithelial opacities.
- Membrane or pseudomembrane removal: Membrane or pseudomembrane may be peeled off gently and a topical corticosteroid may be prescribed.
- Fornix reconstruction.
- Entropion repair.
Most cases of PCF are acute, benign and self-limiting. Infection usually resolves spontaneously within 2-3 weeks.
Sub-epithelial infiltrates may last for months together and may decrease vision if visual axis is involved.
Potential complications of PCF are:
- Punctate keratitis.
- Sub-epithelial infiltrates.
- Superadded bacterial infection.
- Chronic infection.
-Corticosteroid induced protracted clinical course with prolonged corneal opacification.
Pharyngoconjunctival fever is a highly contagious disease and since there is no effective treatment, prevention is important to tackle disease. Virus can spread by contact with infected surfaces or objects. A patient can spread disease agents by touching infected eyes and then touching objects. Objects that come into contact with eyes, such as cosmetics, should not be shared. A person may be contagious for two weeks or more after onset of symptoms, and therefore, should avoid return to work or school.
Preventive measures include:
- Patients should not touch others and not to share tissues, towels, pillows, clothing or handkerchiefs and should wash hands frequently as long as the eye is red.
- Eye care professionals should wash their hands thoroughly after examining any patient. As a routine, they should wash their hands before seeing all patients.
- Health care workers caring for immune-compromised individuals are precluded from patient contact for up to two weeks to avoid transmission of infection.
- Ophthalmic instruments should be properly cleaned and sterilised.
- A ‘red eye room’ may be created to separate out red eye patients from other patients.
-Other family members of the patient may be educated about the disease.