Differentiating among mosquito-borne forms of uveitis

Reviewed by Emmett T. Cunningham, MD, PhD, MPH

Hillsborough, CA-Diagnosis of mosquito-borne forms of uveitis are occurring more often in developed countries, in addition to developing-world countries where their diagnosis is often expected-largely because of extensive global air travel and easy interconnectivity among the world's countries.

Mosquitos are the culprits in the spread of some of these diseases, specifically, West Nile virus, Dengue fever, and Chikungunya. 

Though the three diseases can appear similar, there are some characteristics that can help physicians distinguish among them, said Emmett Cunningham, MD, PhD, MPH
.

"Considering the three diseases, West Nile virus tends to be less severe than Dengue fever, which is less severe than Chikungunya," said Dr. Cunningham, director, Uveitis Service, California Pacific Medical Center, Hillsborough, CA.

West Nile virus

This is a flavivirus of about 12 kilodaltons in size that was first identified in 1937 in Uganda. The virus's natural reservoirs are birds, which, in turn, transmit the virus to mosquitos that then pass it to mammals.

The infection entered the United States in 1999, and the incidence has grown since that time, making the disease a global disorder. The incidence is less than one case per 100,000 people, according to Dr. Cunningham.

West Nile virus appears cyclically and seasonally, with outbreaks tending to occur more often in summer and fall.

Neurological component

The virus has a neurologic component, and most cases of neurologic disease are severe and occur in elderly patients and/or diabetics. These neuroinvasive cases-characterized by central nervous system involvement, severe headache, nausea, and vomiting-tend to be the ones in which there are ocular manifestations.

The typical presentations in symptomatic patients-who account for about 15% of affected patients with West Nile virus-are systemic in nature (i.e., fever, headache, myalgia, arthralgia, nausea, vomiting, skin rash, and pharyngitis). The virus generally has incubation periods ranging from 2 to 14 days and the fever is self-limited and lasts about 1 week.

Most patients (80%) are asymptomatic. At the other end of the spectrum are 5% of patients with encephalitis who have severe headaches, meningismus, confusion, stupor/coma, tremors, convulsions, and paralysis.

Ocular manifestations can vary among patients and included anterior chamber and vitreous inflammation, retinal vasculitis, retinitis, choroiditis (the most common finding), and multifocal chorioretinitis in a curvilinear pattern. The early retinal lesions are deep yellow-white. Fluorescein and indocyanine green angiography (ICGA) are valuable for identifying these lesions.

Dengue fever

Dengue fever is similar to West Nile virus in that it also is a flavivirus, about the same size as West Nile virus at 11 kilodaltons, the incubation periods range from 2 to 14 days, and the disease has a worldwide distribution.

A difference is that Dengue fever tends to be limited to tropical environs, where it is endemic and occurs less often than West Nile virus.  An estimate is that 50 to 100 million new cases develop each year. Cases do appear in the United States, largely in Florida and Texas, and these represent most of the cases. However, some are imported, i.e., acquired during travel, Dr. Cunningham explained.

Patients with Dengue fever also are affected systemically.

Classic Dengue fever is characterized by high fever, severe headache, myalgia, arthralgia, malaise, nausea, vomiting, and a maculopapular skin rash. Ten percent of patients may develop cutaneous, subconjunctival, or retinal hemorrhages. This form is referred to as dengue hemorrhagic fever.

The ocular disease is bilateral in 75% of patients. In addition to subconjunctival and retinal hemorrhages, findings include anterior chamber and vitreous inflammation, retinal vasculitis, and vascular occlusion, retinitis, deep retinal spots/foveolitis, retinal pigment epithelial mottling, serous retinal detachment, and choroiditis.

"Hemorrhage, yellow-white lesions, and vasculitis are seen most often," Dr. Cunningham said.

"Interestingly, the clinical fundus picture in these patients does not look nearly as bad as the vascular leakage on fluorescein angiography," he said. "A great deal of leakage is present in these patients and it can be seen on ICGA images as well. Typically, retinal vasculitis does not leak on ICGA, but it can in patients with Dengue fever."

Chikungunya

Chikungunya, an alphavirus and also a worldwide pathogen, was first reported in 1953 in East Africa in Tanzania and Mozambique. The disease now tends to be found mostly in Africa and East Asia, but recently has extended to South America, Caribbean nations, and the Southeastern United States. The name-which means "to walk bent over"-is characterized by severe arthritis.

The incubation period ranges from 2 to 14 days. The systemic manifestations in acute cases are similar-with patients complaining of fever, headache, low back pain, severe joint pain, myalgia, malaise, nausea, and vomiting.  Patients who are severely affected suffer multiorgan failure, central nervous system involvement, and death.

Ocular manifestations

The ocular manifestations include anterior chamber and vitreous inflammation with high intraocular pressure, retinal hemorrhage, retinal vasculitis, retinal vascular occlusion, retinitis, neuroretinitis, serous retinal detachments, and choroiditis.

Dr. Cunningham described a case of Chikungunya with focal areas of retinitis, such as are seen sometimes in patients with necrotizing retinitis due to syphilis or herpes virus infection. The patients tend to have panuveitis.

Because these mosquito-borne diseases can have similar appearances upon presentation, Dengue fever may be hard to differentiate from Chikungunya. He advised placing the diseases in the context of their endemic areas, areas of patient travel, and the systemic symptoms.

"Hemorrhages would suggest that the patient has Dengue fever, and profound arthritis suggests Chikungunya if the patients have been to areas that have those disorders," Dr. Cunningham said. "If they have been to South America, the chances of them having contracted Chikungunya are much lower."

Emmett T. Cunningham, MD, PhD, MPH

E: emmett_cunningham@yahoo.com

This article was adapted from Dr. Cunningham’s presentation at the 2015 meeting of the American Academy of Ophthalmology. Dr. Cunningham has no financial interest in the subject matter.