Acute hemorrhagic conjunctivitis (AHC) is characterized by conjunctival congestion, vascular dilatation, and onset of edema. Viral infections usually elicit a mononuclear cell response. In AHC, a prominent hemorrhagic component soon appears that is characteristic of this infection. (See Etiology, History, and Physical Examination.)
AHC was first described in 1969. Since the first reports from Ghana, the infection has been described in numerous other countries, including China, India, Egypt, Cuba, Singapore, Taiwan, Japan, Pakistan, Thailand, and the United States.[1, 2, 3, 4] An epidemic involving more than 200,000 people was reported as occurring in Brazil in 2006.[5] Serologic studies have been useful in showing the presence of neutralizing antibodies to Coxsackie group A24 (CA24) and enterovirus E70 (EV70) strains as the causative agent.[4, 6] (See Epidemiology and Workup.)
Humans are the sole host for the enteroviruses. The virus spreads easily through fecal-oral channels. The rates of AHC infection typically are highest where hygiene is deficient. (See Etiology.)
Spread can occur between mother and child.
No treatment is available. Management consists of symptomatic treatment while waiting for the disease to run its 5- to 7-day course. AHC almost always resolves without sequelae, having a good visual prognosis. However, corneal microbial superinfection has been reported after treatment with topical steroids and requires appropriate antimicrobial therapy. (See Treatment.)
A secondary corneal ulcer is shown below.
View Image
Secondary corneal ulcer in a case of acute hemorrhagic conjunctivitis treated with steroids.
Rarely, neurologic sequelae have been noted in AHC. A poliolike paralysis has been reported in 1 case per 10,000. Also, human enteroviral infection is recognized as a major cause of aseptic meningitis in children.
Neutralizing antibodies are present for several years and confer a degree of resistance and immunity.
Change of neutralizing antibody with time was described after the 1984 epidemic of AHC in Sapporo, Japan. A study found that the level of EV70 neutralizing antibody decreased steadily during the first 2 years after infection and that by 7 years, 92% of the population studied had steadily decreasing titers to the point that resistance to reinfection probably was lost.
Some investigators speculate that epidemics can begin when group immunity falls below a safe level.
The prevalence of AHC is not influenced by sex or race, but children aged 10-14 years are at highest risk. (See Epidemiology.)
The viruses in the family Picornaviridae (picornaviruses) cause acute hemorrhagic conjunctivitis (AHC). Specifically, CA24 and EV70 have been linked as the causative agents of AHC. The results from polymerase chain reaction (PCR) testing have been positive for CA24 and EV70, and neutralizing antibodies to CA24 and EV70 have been shown to be present in patients with AHC.
Shedding of the viruses occurs without evidence of infection.
The prevalence of acute hemorrhagic conjunctivitis (AHC) is lower in the United States than in developing countries. Because of its occurrence in epidemics and its contagious nature, estimates of the incidence of the disease in a given population have been difficult. The disease has been reported most often in the southwestern areas of the United States.
International occurrence
AHC has been the cause of worldwide pandemics. Outbreaks have been described in India, Ghana, and throughout equatorial Africa, as well as in Taiwan, China, Japan, Singapore, and Cuba. It also has been reported in Pakistan, Thailand, and the Middle East.[1, 2, 3, 4]
Epidemics of AHC are most common in developing countries. Incidence has been estimated to be as high as one half of the population in endemic areas. The study of the seroepidemiology of AHC during an epidemic in 1983 showed neutralizing antibody of 19% to CA24 and 66.6% to EV70.
Race-, sex-, and age-related demographics
AHC has been noted throughout the tropical regions of the world without regard to race or ethnic background. AHC has no sex predilection.
Epidemic hemorrhagic conjunctivitis is prevalent in all age groups, but the highest predilection is for persons in their early teenaged years. Children aged 10-14 years have been found to have the highest rate of positive neutralizing antibodies to CA24 and EV70.
Recent studies in Changsa, China have assessed the efficacy of a quarantine method to help control outbreaks of AHC in schools. It was estimated that without intervention, almost all students would have become infected in 23 days. Using what the authors termed a susceptive-infective-quarantine removal (SIQR) model, the authors concluded that in the absence of definitive treatment, quarantine programs could be used to curtail AHC outbreaks at schools and reduce the number of accumulated cases.[7]
Patient education is important in acute hemorrhagic conjunctivitis (AHC) to help ease fears and to prevent undue alarm. The contagious nature, yet essentially benign outcome, of the disorder should be emphasized, with a view toward preventing the spread of the infection. Acceptance of the fact that the infection must run its course can be encouraged in the absence of an effective treatment modality.
Patient education is also indicated to avoid the spread of this highly contagious infection.
For patient education information, see the Eye and Vision Center, as well as Pinkeye and Subconjunctival Hemorrhage (Bleeding in Eye).
Acute hemorrhagic conjunctivitis (AHC) is a rapidly progressive and contagious viral infection.[8, 9]
AHC begins with an initial period of catarrhal inflammation.[10, 11] The presentation becomes more dramatic with the rapid appearance of conjunctival petechiae. These conjunctival petechiae soon coalesce to form subconjunctival hemorrhages. These are associated with a painful, rapidly progressive follicular conjunctivitis. The lids often become swollen and indurated. The infection resolves within 5-7 days, during which the symptoms of pain and irritation are present.
Punctate corneal epithelial defects have been noted and subepithelial corneal opacities have been described.
The most common manifestation of enteroviral infection is a low-grade fever of unknown etiology in infants. While concerned mainly with conjunctivitis here, it should be noted that numerous organ systems can be involved. They range from the myocardium to the central nervous system and can also include the respiratory system and the skin.
The presentation of acute hemorrhagic conjunctivitis (AHC) can be dramatic. Findings include swollen lids, conjunctival follicles, chemosis, and, depending on the stage at which the patient is seen initially, subconjunctival hemorrhages, which can range from petechiae to large areas of conjunctival involvement. The cornea can exhibit superficial epithelial changes.
The symptoms also include are pain and irritation, and the lids and periocular tissues present with marked inflammation.
The rapid course and the benign outcome of acute hemorrhagic conjunctivitis (AHC), as well as the difficulty of performing rapid viral studies, make laboratory testing impractical in the clinical setting. More rapid diagnostic tests have been developed and continue to be improved. Neutralizing assays with standardized antisera have been used with good results. These are being supplanted by PCR assay methods, which reduce the time needed for viral typing. These methods involve amplification of the viral nucleotide sequences and their comparison with the sequences of the 66 known serotypes of human enterovirus.
Park and colleagues reported on a rapid identification method to determine the causative agents of acute hemorrhagic conjunctivitis (AHC).[13] This method uses PCR analysis from conjunctival swab specimens obtained from patients with AHC.
The PCR assay is an in vitro test, which can be used to diagnose AHC by producing large amounts of specific deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) from the infectious agent.[14, 15]
While reliance on virus culture methods persists, rapid identification by molecular serotyping, directly using clinical specimens rather than cell cultures, was evaluated and found to be effective by Park and colleagues in an outbreak in South Korea.[13]
Culture and sensitivity assessment
Culture and sensitivity studies should be obtained in all cases of corneal superinfection and appropriate antibiotics given.[16] A sensitive real-time (RT) PCR test has been used to aid in the rapid clinical diagnosis in cases of this contagious epidemic.[17]
Histologic findings
The initial response to the viral infection in acute hemorrhagic conjunctivitis (AHC) is a mononuclear cell inflammatory response. A watery intercellular exudate is present, which is replaced by subconjunctival blood as the infection progresses.[18]
Currently, no treatment is available for acute hemorrhagic conjunctivitis (AHC). AHC usually exhibits a self-limited course. Although rare sequelae, such as radiculomyelitis, have been reported, the infection usually has no complications. Treatment with topical steroids should be avoided because of reported microbial superinfection of the cornea.
Acute hemorrhagic conjunctivitis (AHC) usually is treated in an outpatient setting, since no medical treatment is available. After a 24- to 72-hour period of incubation, the infection runs its relatively short, but uncomfortable, course.
Hygiene, education, and avoidance of infectious contact are the most effective preventive measures for AHC available.
Recent studies in Changsa, China have assessed the efficacy of a quarantine method to help control outbreaks of AHC in schools. It was estimated that without intervention, almost all students would have become infected in 23 days. Using what the authors termed a susceptive-infective-quarantine removal (SIQR) model, the authors concluded that in the absence of definitive treatment, quarantine programs could be used to curtail AHC outbreaks at schools and reduce the number of accumulated cases.[7]
There has been some development in the use of RNA interference (RNAi) to target regions of the EV70 genome.[19, 20] Replication of enterovirus has been shown to be reduced when these agents were used in an experimental laboratory cell line by Tan, Marcus, and Pohl in Singapore in 1980.
Outpatient care of patients with acute hemorrhagic conjunctivitis (AHC) consists of careful follow-up exams to ensure that no complications occur and that the infection runs a benign, self-limited course.
The practitioner should be vigilant with regard to any complications in this essentially benign condition. Be aware that rare, but consequential, sequelae can occur. For this reason, it is wise to schedule a final examination after the infection has subsided to check for any residual effects.
A consultation would be appropriate in acute hemorrhagic conjunctivitis (AHC) only if the patient develops enteroviral infection in other organ systems. In this case, a second opinion would be of benefit depending on the nature of the systemic involvement.
In rare cases, consultation could be indicated with a pediatrician or pediatric subspecialist.
Symptomatic treatment to make the patient as comfortable as possible is recommended. In the laboratory, benzimidazole agents have been shown to inhibit viral cultures in vitro, but this has not been tested clinically.
Treatment remains symptomatic only (eg, warm compresses); steroids are contraindicated and antibiotics are not needed except in the presence of bacterial superinfection.
A recent study by Jun et al may lead to a medication using antiviral small-interfering RNA to decrease viral replication and thus shorten the course of the symptoms and disease.[21]
Jean Deschênes, MD, FRCSC, Professor, Research Associate, Director, Uveitis Program, Department of Ophthalmology, McGill University Faculty of Medicine; Senior Ophthalmologist, Clinical Director, Department of Ophthalmology, Royal Victoria Hospital, Canada
Disclosure: Nothing to disclose.
Coauthor(s)
Ayman J Aljohani, MBBS, Resident Physician, Department of Ophthalmology, McGill University Faculty of Medicine, Canada
Disclosure: Nothing to disclose.
Specialty Editors
Simon K Law, MD, PharmD, Clinical Professor of Health Sciences, Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine
Disclosure: Nothing to disclose.
Christopher J Rapuano, MD, Professor, Department of Ophthalmology, Sidney Kimmel Medical College of Thomas Jefferson University; Director of the Cornea Service, Co-Director of Refractive Surgery Department, Wills Eye Hospital
Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cornea Society, AAO, OMIC, Avedro; Bio-Tissue; GSK, Kala, Novartis; Shire; Sun Ophthalmics; TearLab<br/>Serve(d) as a speaker or a member of a speakers bureau for: Avedro; Bio-Tissue; Shire<br/>Received income in an amount equal to or greater than $250 from: AAO, OMIC, Avedro; Bio-Tissue; GSK, Kala, Novartis; Shire; Sun Ophthalmics; TearLab.
Chief Editor
Hampton Roy, Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Disclosure: Nothing to disclose.
Additional Contributors
Fernando H Murillo-Lopez, MD, Senior Surgeon, Unidad Privada de Oftalmologia CEMES
Disclosure: Nothing to disclose.
George Plechaty, MD, Clinical Assistant Professor, Department of Surgery, Division of Ophthalmology, University of Hawaii, John A Burns School of Medicine
Disclosure: Nothing to disclose.
Acknowledgements
The authors and editors of Medscape Reference gratefully acknowledge the assistance of Ryan I Huffman, MD, with the literature review and referencing for this article.
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