Smallpox Vaccine Complications: The Dermatologist’s Role in Diagnosis and Management
In 2002, the United States implemented a new program for smallpox vaccinations among military personnel using a live vaccinia virus product. Approximately 2.4 million US military service members and health care workers have since been inoculated, with considerable numbers experiencing adverse reactions. Military dermatologists are at the forefront of describing and treating these reactions, from relatively benign generalized vaccinia (GV) and erythema multiforme (EM) to more severe progressive vaccinia (PV) and eczema vaccinatum (EV). A wide range of providers, including civilian dermatologists and primary care providers, also may see such reactions and must be aware of the spectrum of vaccine reactions. Given current world instability (eg, threats of nuclear war, rise of authoritarian regimes) and concerns for bioterrorism attacks, the smallpox vaccine program likely will continue indefinitely. As the brisk military deployment tempo continues, a larger population of new vaccinees will yield more cutaneous reactions and diagnostic challenges.
Practice Points
- Dermatologists should be aware that smallpox vaccinations are being administered to patients and may present with a myriad of cutaneous complications.
- Progressive vaccinia should be suspected if a smallpox inoculation has not healed after 14 days and, most specifically, if there is no inflammation surrounding the site.
- Generalized vaccinia generally is a benign condition seen in otherwise healthy patients and usually requires no treatment.
Atopic patients should be educated to avoid receiving routine smallpox vaccinations if they would be considered at risk for requiring the inoculation.
Localized Reactions Due to Viral Replication
Accidental autoinoculation can occur when patients touch the vaccination site and then themselves, transferring virus particles to areas of compromised skin integrity, most commonly on the face, eyes, hands, genitalia, anus, or any other broken skin. Autoinoculation happens with some frequency and is of limited clinical concern unless there is ocular involvement. Keratitis develops in 6% of ocular vaccinia cases, and VIGIV is contraindicated, as rabbit models suggest that antigen-antibody precipitates in the cornea can cause scarring.21 Instead, trifluorothymidine is an effective topical treatment available for ocular vaccinia.
A robust response or “take” is defined as a reaction having redness, swelling, and warmth more than 3 inches in diameter at the inoculation site, peaking 6 to 12 days after inoculation with spontaneous regression occurring 1 to 3 days after.22,23 A robust take frequently is of concern to the clinician, as it can be difficult to discern from secondary infection. Secondary infections are uncommon, and a robust take is secondary to viral, not bacterial, cellulitis. Unfortunately, there are no diagnostics that have utility in distinguishing between the two, and the decision to administer empiric antibiotics might be unavoidable in light of the consequences of an untreated, rapidly progressive bacterial cellulitis. Milder cases in the setting of no constitutional symptoms could be safely monitored if close follow-up is assured.
Generalized Skin Reactions Without Viral Replication
Development of erythematous, pruritic, urticarial, and diffuse targetlike lesions of EM is common in first-time vaccinees. Often misdiagnosed as GV, EM is an immunologically mediated, not virally mediated, process. The most common infectious cause prompting EM is herpes simplex virus type 1. In the setting of a live-virus vaccine, it is difficult to determine if the vaccine prompted herpes simplex virus type 1 viral shedding and associated EM or if the vaccinia vaccine is more directly the cause of EM.24 Symptoms typically are mild, but more severe reactions may require treatment with corticosteroids. Stevens-Johnson syndrome with a severe bullous eruption has been linked to vaccinia24 but fortunately is rare. Morbilliform eruptions, urticaria, and angioedema also can occur.
,Final Thoughts
Given current world events and ongoing bioterrorism threats, the smallpox vaccine program continues indefinitely. With a brisk military deployment tempo, a larger population of new vaccinees naturally will yield more cutaneous reactions. Military members, civilian health care workers, and members of the National Guard and National Reserves will develop complications and present to dermatologists for care. The historical pool of providers accustomed to seeing these complications from the 1960s eradication campaign is scant. Military and civilian dermatologists alike are uniquely poised to be the experts on protean manifestations of vaccinia reactions.
