Oculo-respiratory syndrome

Oculo-respiratory syndrome (ORS) is a rare and usually transient condition characterized by bilateral conjunctivitis, facial edema, and upper respiratory symptoms following influenza immunization. Symptoms typically appear 2 to 24 hours after vaccination and resolve within 48-72 hours of onset. ORS was noted first in the 2000-2001 flu season in Canada. This was due to a manufacturing error in the trivalent influenza vaccine (TIV) and has since been resolved. This condition has only been recorded mostly among middle-age white women in Canada, but the reason behind this phenomenon is not yet known. This condition can be treated with over-the-counter pain medication and cough medication.

Signs and symptoms

Presentation of swollen eyelids

The most common symptoms with ORS are bilateral red eyes, facial edema, and respiratory symptoms as described in the table below. These symptoms typically occur 2-24 hours after administration of the vaccine and they are typically resolved between 48 and 72 hours onset. All of these symptoms are not required to diagnose ORS. The symptoms experienced mimic those of any flu vaccination, but they are a little more moderate in severity; there have not been any reported cases of hospitalization due to ORS.

Affected Area	Symptoms
Eyes	bilateral red eyes
Face	swollen eyes lids, swollen lips, swollen tongue
Respiratory	coughing, wheezing, sore throat, difficulty breathing, difficulty swallowing, horseness, chest tightness

Cause

The cause of ORS is the influenza vaccine. Studies have shown that the cases from the 2000-2001 flu season related ORS to TIV. When investigated further, a manufacturing error occurred in the vaccines. Upon investigation using electron microscopy, the vaccine presented with a disproportionate number of virion aggregates that were unsplit in the vaccine. Coupled with the manufacturing error, the patients that presented with ORS were tested for cytokine levels in peripheral blood after vaccination. The study concluded that those that had ORS presented with elevated levels of IL-10 and IL-3 and that amount was constant for 9-12 months after. This indicated that the vaccine did not cause the elevated amounts of IL-10 and IL-3, the population of people were predisposed to ORS.

Mechanism

Although the specific mechanism is not understood, the research demonstrates that there is a correlation between contracting ORS and having elevated amounts of IL-10 and IL-3. These immune cells are important with imflammation in the body. Although studies show that patients with elevated IL-10 and IL-3 are predisposed to contracting ORS, the elevated amounts of these cells are in line with the symptoms patients have presented with. As the body is fighting off this condition and there is inflammation of both the respiratory system and in the face these immune cells would need to work extra hard in order to combat the inflammation in these affected areas.

In the respiratory system, there is inflammation of the lungs or the airway that leads from the mouth to the lungs when contracting ORS. When there is inflammation anywhere in the body, the body's reaction to this is to send white blood cells and immune cells in order to control the inflammation. This is where the IL-10 and IL-3 cells come in. When the body is fighting off an infection or inflammation there are elevated amounts of white blood cells and immune cells because they are working overtime in order to contain the infection or inflammation. Since the inflammation in the respiratory tract is more internal, this process of fighting off inflammation can be seen more with patients that present with facial edema. The inflammation of the face triggers these immune cells to come to the sight of inflammation and try and suppress this issue before it become severe. The main symptom in this condition is inflammation of the affected area whether that be the conjunctiva in the eyes, the face, or the respiratory tract. With these issues, the body must attack the inflammation by increasing the amount of immune cells (IL-10 and IL-3) in order to suppress this inflammation.

Diagnosis

Presentation of a child with facial edema

Although there is no diagnostic test, a patient would be diagnosed based on symptoms and history.

Treatment

There is no treatment for ORS. The only advice given to patients experiencing these symptoms would be to take over-the-counter cough medication and pain medication and wait for the symptoms to subside.

Prognosis

Patients who have contracted ORS are at a higher risk of reoccurrence with revaccination. This is dependent on the type of symptoms the individual experiences. Those who have contracted ORS and did not expererience any respiratory symptoms are safe to get reimmunized against influenza. Those who have contracted ORS and did experience respiratory symptoms should contact a physician before reimmuninization as they are at risk of reoccurrence. Studies have also shown that those who have had a reoccurrence of ORS upon revaccination are not necessarily going to experience future symptoms with revaccination.

Epidemiology

There have been limited cases involving ORS; however from the cases it was noted that this condition affected women more than men and was typical in people 40-59 years old. These cases arrised in Canada during the 2000-2001 flu season and was seen primarily in white Canadians. There was a similar issue that occurred in Europe in the mid 1990s however this was not ORS. The reason behind why white Canadian women in their 40-50's are more susceptible to this condition is still not yet known.

References

• Skowronski, Danuta M.; Strauss, Barbara; De Serres, Gaston; MacDonald, Diane; Marion, Stephen A.; Naus, Monika; Patrick, David M.; Kendall, Perry (2003). "Oculo‐respiratory Syndrome: A New Influenza Vaccine–Associated Adverse Event?". Clinical Infectious Diseases. 36 (6): 705–13. doi:10.1086/367667. PMID 12627354.
• Al-Dabbagh M, Lapphra K, Scheifele DW, Halperin SA, Langley JM, Cho P, Kollmann TR, Li Y, De Serres G, Fortuno ES 3rd, Bettinger JA. Elevated inflammatory mediators in adults with oculorespiratory syndrome following influenza immunization: a public health agency of Canada/Canadian Institutes of Health Research Influenza Research Network Study. Clin Vaccine Immunol. 2013 Aug;20(8):1108-14. doi: 10.1128/CVI.00659-12.
• Zepf MD, Bill (2003). "Oculorespiratory Syndrome: Adverse Effects of Flu Vaccine." Am Fam Physician. 68 (12): 2450.
• "Oculorespiratory Syndrome." World Health Organization. January 2003. https://www.who.int/groups/global-advisory-committee-on-vaccine-safety/topics/oculorespiratory-syndrome

http://cvi.asm.org/content/early/2013/05/16/CVI.00659-12.abstract Copyright © 2013, American Society for Microbiology. All Rights Reserved.