Orbital, Ear, and Skin Lesions in a Healthy Laboratory Research Assistant
A 24-year-old male presented in July with swelling and pain of his right ear and left eye. Six days prior to admission, the patient was stung by a bee on the left hand while vacationing in North Carolina. He subsequently developed swelling and pain of his right ear lobe, followed the next day by swelling around his left eye. The swelling at both sites worsened over several days, and small white dots formed on the right ear lobe. He had trouble seeing that he attributed to the swelling of his eyelids, which was accompanied by an opaque, yellow discharge. He described malaise and subjective fevers, and his symptoms did not respond to cephalexin and prednisone. He presented to the emergency department where he was noted to have some pain with eye movement, and he was admitted with a presumed diagnosis of orbital cellulitis. The patient denied any past medical problems, and had tested negative for HIV a few months prior to admission. He worked as a cancer and immunology research assistant at a hospital-affiliated research laboratory.
On physical examination, the patient was afebrile but in obvious discomfort due to right ear and eye pain. The lobe of his right ear was coated in crusted, purulent material, with a crop of vesicles inferior to his ear (Figure 11f.1a). The vesicles were all at the same stage of development. His left periorbital soft tissue was edematous and erythematous (Figure 11f.1b). A thick purulent discharge covered his sclera and cornea. There was no scleral injection. Pupils were equal, round, and reactive to light when the left palpebrae were parted. There was some pain with extraocular movement but no proptosis. Other cranial nerve functions were intact. His left hand (the reported site of the bee sting) had no lesions, but there were two small vesicular lesions on his chest and one on his flank. There was erythema of the skin surrounding each vesicle, but the remainder of his physical examination and laboratory studies was normal.
CT scan of the left orbit showed severe inflammation restricted to the preseptal tissues. The consulting ophthalmologist described conjunctivitis and blepharitis, with possible mild keratitis. Cellular culture of a swab taken from the purulent exudate from his eye showed a cytopathic effect (Figure 11f.2). Polymerase chain reaction for vaccinia virus was performed on the cultured material and was positive. When the diagnosis was suspected, the patient’s lesions had already begun to improve and, thus, systemic therapy was not required. The patient recovered with some madarosis but without visual sequelae.
Case 11f Discussion: Vaccinia Virus Infection
Live vaccinia virus, an orthopoxvirus, is the immunogenic component of the smallpox vaccine, which is used to induce immunity to variola, the causative agent of smallpox. Since routine civilian vaccination was stopped in 1972, vaccination has been limited to those with a risk of exposure to orthopoxviruses through laboratory work or first response to a bioterrorist attack.1 Intentional inoculation with vaccinia, for the purpose of vaccination, results in an inflammatory lesion that crusts and separates within approximately 14 days.2 Live vaccinia is shed from the inoculation site for approximately 21 days. During this period, the virus may be transmitted to other susceptible individuals (accidental inoculation) or to other parts of the body of the vaccinated individual (autoinoculation). Covering the wound with a semipermeable dressing and adherence to hand-washing practices reduces the risk of transmission. In the described case, accidental acquisition from a laboratory animal had occurred, and subsequently spread to multiple sites, likely by autoinoculation.
Multiple complications of vaccination with vaccinia have been reported. Progressive vaccinia, or vaccinia gangrenosum, is fatal without treatment and occurs in infants and in immunocompromised hosts, usually with deficient cellular immune response. This severe disease is characterized by expansion of vaccinia lesions from the site of vaccination, or spread of lesions to distant sites.3 There is a lack of inflammation, pain, or evidence of healing after 14 days. Lesions progress and develop into deep, necrotic ulcerations. Amputation of affected limbs is often required, and superinfection may occur. Eczema vaccinatum, a complication that occurred in 14–44 cases per million vaccinees prior to 1968, can occur in patients with atopic dermatitis even in the absence of active lesions or prior diagnosis of atopy. This complication may be acquired through vaccination or contact with a recently vaccinated individual, and manifests as either a localized or widespread, potentially fatal, cutaneous disease.4
In contrast to progressive vaccinia and eczema vaccinatum, generalized vaccinia occurs in immunocompetent individuals, and is a self-limited illness characterized by systemic symptoms and scattered vesicular lesions with surrounding erythema indicative of a proper inflammatory response. Postvaccination encephalomyelitis carries a high rate of death (up to 30%) and permanent neurologic sequelae (up to 20%). Myopericarditis may complicate vaccination, and was reported more frequently during military and civilian vaccination programs in 2003, instituted in response to the threat of bioterrorism. During this period, attention was also drawn to a risk of postvaccination cardiac ischemic events in patients with preexisting cardiac risk factors.
As in the case above, ocular manifestations occur as a result of accidental inoculation or autoinoculation. Blepharitis and conjunctivitis do not frequently result in serious long-term sequelae. While long-term sequelae are more likely to occur after keratitis (18%), the largest prospective study of vaccinia keratitis found minimal residual corneal defects 5 years after infection in the 7 patients that were available for evaluation.5
Diagnosis and Treatment
Polymerase chain reaction of infected exudate is used for definitive, molecular diagnosis. Electron microscopy can be used to identify intracellular viral particles after growth of the virus in cell culture. The typical cytopathic effect of vaccinia consists of rounding, granularity without vacuolation, and expanding cytolysis with fibrinous material at the site of dead cells.
Vaccinia immune globulin (VIG) has decreased mortality from severe complications, with the exception of vaccinia-induced encephalitis. VIG is contraindicated in cases of isolated vaccinia keratitis, because it may increase the likelihood of corneal scarring, although the data are mixed. Cidofovir, and the experimental antiviral, ST-246, have in vitro activity against vaccinia and have been used in combination.6 Topical trifluorothymidine and vidarabine are active against vaccinia in vitro, and are used to treat keratitis. Progressive vaccinia requires combined therapy with VIG, antiviral medications, and aggressive debridement.
1. Wharton M, Strikas RA, Harpaz R, et al. Recommendations for using smallpox vaccine in a pre-event vaccination program. Supplemental recommendations of the Advisory Committee on Immunization Practices (ACIP) and the Healthcare Infection Control Practices Advisory Committee (HICPAC). MMWR Recomm Rep. 2003 Apr;52(RR-7):1–16.Find this resource:
2. Lane JM and Goldstein J. Adverse events occurring after smallpox vaccination. Semin Pediatr Infect Dis. 2003 Jul;14(3):189–195.Find this resource:
3. Barbero GJ, Gray A, Scott TF, Kempe CH. Vaccinia gangrenosa treated with hyperimmune vaccinal gamma globulin. Pediatrics. 1955 Nov;16(5):609–618.Find this resource:
4. Kempe CH. Studies of smallpox and complications of smallpox vaccination. Pediatrics. 1960 Aug;26;176–189.Find this resource:
5. Ruben FL and Lane JM. Ocular vaccinia. An epidemiologic analysis of 348 cases. Arch Ophthalmol. 1970 Jul;84(1):45–48.Find this resource:
6. Vora S, Damon I, Fulginiti V, et al. Severe eczema vaccinatum in a household contact of a smallpox vaccinee. Clin Infect Dis. 2008;46(10):1555–1561.Find this resource: