Pharyngoconjunctival fever (PCF) is an acute viral infectious disease characterized by the three main symptoms of fever, pharyngitis, and conjunctivitis. Commonly called “pool fever,” it often occurs in outbreaks among children through swimming pools in the summer. In cases without conjunctivitis, it is often diagnosed as “summer cold” in pediatric settings.
Viral conjunctivitis caused by adenovirus (AdV) has two main clinical forms: epidemic keratoconjunctivitis (EKC) and pharyngoconjunctival fever (PCF). While EKC is primarily characterized by local ocular symptoms (keratitis and multiple corneal subepithelial infiltrates), PCF is characterized by systemic symptoms such as pharyngitis and fever being more prominent1).
The complete form (all three main symptoms of fever, pharyngitis, and conjunctivitis) is rare, and incomplete forms presenting with only “pharyngitis and conjunctivitis” or “fever and conjunctivitis” are more common. Since incomplete forms do not meet the reporting criteria, they are not included in statistical patient counts, but in reality, incomplete forms are often present around patients with the complete form1).
The trend in the number of PCF patients over the past 10 years is shown below1).
| Period | Number of patients per PCF sentinel site (patients/year) |
|---|---|
| Pre-pandemic (2013–2019 average) | 23.3 ± 3.2 |
| Pandemic period (2020–2022 average) | 11.0 ± 0.17 (approximately halved) |
| 2023 (Post-pandemic) | 56.7 (resurgence at approximately 2x normal) |
Due to COVID-19 control measures (handwashing, mask-wearing, pool closures, etc.), the number of PCF patients approximately halved during the pandemic period. In 2023, a rebound resurgence of approximately twice the normal level was reported, and continued vigilance is needed1).
Pharyngoconjunctival fever is also called “pool fever” because infection spreads easily through swimming pools in summer. When pool water is contaminated with adenovirus, the virus can easily enter through the eyes, nose, and mouth during swimming. Another factor is that children have more opportunities to play in water together in groups during summer. Cases are also observed in winter, and this is an infection that can be contracted year-round through droplet and contact transmission.
Onset occurs acutely after an incubation period of 3–5 days from infection (shorter than the 7–14 days for EKC)1).
Systemic symptoms (predominant)：
Local ocular symptoms (relatively mild):
Conjunctival Findings in PCF
Incubation period: 3–5 days (shorter than 7–14 days for EKC)
Follicular conjunctivitis: Moderate hyperemia and follicle formation. Similar to EKC but generally milder
Eyelid swelling: Relatively mild
Preauricular lymph nodes: Accompanied by swelling and tenderness
Course of conjunctivitis: Generally resolves within 1–2 weeks
Key differences from EKC
No MSI: Multiple subepithelial infiltrates (MSI) do not occur (in EKC, they appear from 4–5 days after onset)
Keratitis is minimal: Only transient punctate keratitis in the superior peripheral cornea. Resolves in about 1 week, no steroid treatment needed
Few sequelae: Almost never leaves corneal opacity or long-term visual impairment
Systemic symptoms dominate: Fever and pharyngitis are prominent
Adenoviral conjunctivitis in infants presents with a different clinical picture from adults and school-age children1).
The main differences are the presence of corneal subepithelial infiltrates (MSI) and the degree of systemic symptoms. Epidemic keratoconjunctivitis (EKC) is caused by species D adenovirus and produces multiple subepithelial infiltrates in the cornea around one week after onset; if not treated appropriately, it can leave photophobia and visual impairment lasting for years. In contrast, pharyngoconjunctival fever (PCF) is caused by species B (mainly AdV type 3), does not produce MSI, and is characterized by prominent systemic symptoms such as fever and sore throat. Under the School Health and Safety Act, PCF is classified as Category 2 (return to school 2 days after defervescence is the guideline), whereas EKC is Category 3 (until determined by a physician).
Adenoviruses (AdV) are non-enveloped icosahedral (70-90 nm in diameter) double-stranded DNA viruses classified into 7 species (A through G). The main cause of PCF is AdV type 3, which belongs to species B, with AdV2, AdV1, AdV5 (species C), AdV4 (species E), AdV7, and AdV11 also detected1).
Number of detections in the Infectious Disease Surveillance from 2015 to 2023 (in descending order): AdV3 > AdV2 > AdV1 > AdV5 > AdV41).
| Species | Main types | Associated diseases |
|---|---|---|
| B (B1) | 3, 7 | Pharyngoconjunctival fever (PCF), acute respiratory infection |
| B (B2) | 11 | Hemorrhagic cystitis |
| C | 1, 2, 5, 6 | Acute respiratory infection |
| D | 8, 37, 53, 54, 56, 64, 85 | Epidemic keratoconjunctivitis (EKC) |
| E | 4 | Acute respiratory infection / conjunctivitis (mild form) |
AdV3 (species B) has a high rate of approximately 80% of conjunctivitis accompanied by extraocular symptoms. Meanwhile, AdV4 (species E) is approximately 50% and presents a wide range of clinical manifestations from EKC to PCF1).
The most important transmission route is contact infection via the hands1).
Adenoviruses are biologically very robust and can remain infectious for 10 days or more even in dry environments1).
The 2025 Japanese Guidelines for the Management of Viral Conjunctivitis define the diagnostic criteria for adenoviral conjunctivitis as follows1).
| Category | Item |
|---|---|
| A. Microbiological testing | A-1. AdV antigen positive by rapid antigen detection kit (immunochromatography) A-2. Detection of AdV gene by PCR |
| B. Objective findings | B-1. Acute follicular conjunctivitis B-2. Conjunctival petechiae B-3. Conjunctival pseudomembrane B-4. Diffuse superficial keratitis or multiple corneal subepithelial infiltrates |
| C. Preauricular lymph node findings | Swelling or tenderness |
| D. Systemic findings | Any one of fever, sore throat, or bronchitis (particularly important finding in PCF) |
| E. Intrafamilial infection | Present |
In PCF, D (fever, sore throat) is a particularly typical finding, and clinical diagnosis of PCF with conjunctivitis accompanied by fever and sore throat is often relatively easy.
Immunochromatography (rapid antigen detection kit)
The most widely used rapid AdV diagnostic method in clinical settings. An antigen-antibody reaction using adenovirus hexon monoclonal antibody that yields results in 5–15 minutes1).
In recent years, minimally invasive kits (such as QuickChaser® Adeno Eye) that allow tear fluid collection simply by placing filter paper on the lower eyelid have been developed. They do not require topical anesthesia and are easy to use even in pediatric cases1). Furthermore, silver amplification automated kits (QuickChaser® Auto Adeno Eye, Fuji Dri-Chem IMMUNO AG Cartridge Adeno OPH) that improve sensitivity by amplifying labeled gold colloid approximately 100-fold via silver amplification are also available1).
PCR method
It can identify AdV with higher sensitivity than rapid antigen detection kits. It is also possible to determine the AdV serotype. It is not covered by insurance and must be outsourced to a testing laboratory or requested at a specialized facility1).
Conjunctival smear microscopy
Conjunctival discharge collected with a swab is Giemsa-stained and examined for cells. A predominance of mononuclear cells (lymphocytes) suggests viral conjunctivitis and is useful as an adjunctive diagnostic tool1).
Virus isolation culture
It is the virological gold standard, but it is not suitable for clinical diagnosis because it takes several weeks to obtain results. It is useful for serotype identification1).
The diseases that should be considered when differentiating PCF are listed below.
| Disease | Key differentiating features |
|---|---|
| EKC (Epidemic Keratoconjunctivitis) | MSI (multiple subepithelial infiltrates) present. Predominantly ocular symptoms. Class 3 under School Health Law. |
| Bacterial conjunctivitis | Characterized by mucopurulent discharge. Lymphadenopathy is usually absent. |
| HSV conjunctivitis | Often unilateral. Eyelid rash (vesicles, crusts). Dendritic or geographic keratitis. |
| Chlamydial conjunctivitis | Unilateral. Subacute (≥2 weeks). History of urethritis/cervicitis. Large solid follicles. |
| Allergic conjunctivitis | Itching predominates. Papillary (not follicular). No fever or lymphadenopathy. |
| Acute hemorrhagic conjunctivitis (AHC) | Extremely short incubation period of half a day to 1 day. Bulbar conjunctival hemorrhage is characteristic. |
| Influenza | Systemic symptoms such as high fever and myalgia are prominent. Conjunctival symptoms are mild. |
Yes, it is possible. The sensitivity of rapid antigen detection kits (immunochromatography) is approximately 70–80%, and false negatives can occur when the viral load is low or specimen collection is inadequate. When the three main symptoms of fever, sore throat, and conjunctival injection are present, along with information on household infection or cluster outbreaks, it is appropriate to make a clinical diagnosis of pharyngoconjunctival fever even if the test is negative. The 2025 Guidelines for the Management of Viral Conjunctivitis establish criteria for a “clinical diagnosis” that allows diagnosis even when microbiological tests are negative.
No specific antiviral drug currently exists for pharyngoconjunctival fever. Treatment mainly consists of symptomatic therapy and infection prevention1). Since pharyngoconjunctival fever does not cause MSI as seen in EKC, MSI treatment (long-term steroid use) is generally unnecessary.
Along with treatment, be sure to provide guidance on preventing the spread of infection.
1. Antibacterial eye drops
Antibacterial agents are inherently ineffective against adenovirus, but they are used to prevent secondary bacterial infection1).
2. Steroid eye drops
Use is limited to severe cases (pseudomembrane formation, severe inflammation, marked eyelid swelling, etc.)1).
3. Iodine eye drops (PVA-I eye drops)
Polyvinyl alcohol-iodine (PVA-I) ophthalmic solution (Sanyodo® ophthalmic solution 0.4% PVA-I), launched as an OTC drug in Japan in 2022, is available for use1).
4. Nonsteroidal anti-inflammatory drug (NSAID) eye drops
Used adjunctively when subjective symptoms such as tearing and foreign body sensation are severe. It has no antiviral effect1).
5. Systemic Administration (Severe Cases in Infants)
In severe cases in infants aged 3 years or younger for whom eye drops are difficult to administer, oral steroids may be considered1).
Based on the School Health and Safety Act Enforcement Regulations, measures are taken as follows.
Even after symptoms disappear, you should avoid going to the pool right away. The adenovirus that causes pharyngoconjunctival fever continues to be shed in feces for about one month after symptoms resolve. Entering the pool poses a risk of spreading the infection to other users. The 2025 Guidelines for the Management of Viral Conjunctivitis also recommend instructing PCF patients to refrain from swimming for about one month after conjunctivitis has resolved.
Adenovirus (AdV) is a non-enveloped icosahedral (diameter 70–90 nm) double-stranded DNA virus. Seven species (A through G) and over 100 types have been identified. The binding mode to receptors differs between species B (such as AdV3), the main cause of PCF, and species D (such as AdV8, 37, 53, and 54), the main cause of EKC.
The fiber protein of AdV attaches to receptors on the surface of conjunctival epithelial cells to initiate infection. These receptors differ depending on the AdV serotype, which determines the tissues and organs each serotype tends to infect. Species B (AdV type 3), which causes PCF, has lower affinity for ocular tissues compared to species D (AdV type 8, etc.) that causes EKC, and primarily infects the upper respiratory tract mucosa including the pharynx and airways. This relationship between receptors and viral fibers determines the difference in clinical presentation between PCF (predominantly systemic symptoms) and EKC (predominantly ocular symptoms).
Adenovirus replicates not only in the conjunctiva but also in the pharynx, intestinal tract, and urinary tract. Therefore, PCF patients continue to excrete the virus in their stool for approximately 1 month after symptoms have resolved1). This is the basis for the prohibition of swimming.
After infection, neutralizing antibodies rise approximately 10 days after onset, coinciding with the resolution of clinical symptoms. Neutralizing antibodies are type-specific (e.g., antibodies against type 3 do not neutralize type 4), so reinfection with a different AdV serotype can occur.
In EKC, the virus (mainly species D) infects the corneal stroma, and approximately one week after onset, a delayed-type hypersensitivity reaction to AdV antigens occurs in the superficial corneal stroma, leading to the formation of MSI. In contrast, species B AdV, which causes PCF, is less likely to trigger this corneal reaction, and MSI formation does not occur1).
Currently, there are no specific antiviral agents in ophthalmology against AdV. The following are at the research or clinical trial stage1).
Ganciclovir (GCV) ophthalmic solution
GCV is an antiviral agent with DNA polymerase inhibitory activity, and its efficacy against AdV has been demonstrated in in vitro and animal studies. However, there are no adequate randomized controlled trials (RCTs) in humans, and it has not been established as a standard treatment.
Famciclovir (FCV)
It is a nucleoside analog with broad-spectrum antiviral activity, and potent inhibitory effects have been reported particularly against AdV5. Phase I clinical trials have been conducted, and no serious adverse effects have been confirmed, but phase II trials and beyond are needed1).
Cidofovir (CDV) ophthalmic solution
Preventive and therapeutic effects against AdV have been reported in animal models and phase I/II clinical trials, but some reports indicate that RCTs did not show significant improvement in clinical course. Concerns also exist regarding the emergence of CDV-resistant strains and local adverse effects (lacrimal duct stenosis, conjunctival inflammation, etc.)1).
In 2023, the number of PCF patients reached approximately twice the usual level. This is thought to be due to reduced herd immunity (immunity debt) following the lifting of COVID-19 restrictions, and continued monitoring of epidemic fluctuations is necessary1).
