By Leonard M.Milstone, MD

The goal of immunization programs is simple: to reduce the chance of serious illness or death in people who are at risk. Smallpox is a highly contagious disease that is usually transmitted by inhalation. Most people who contract smallpox will have a serious illness, but will recover without long-lasting effects. Up to 20-30% of those who get widespread blisters on their skin will die from the disease. There is no curative treatment for smallpox. There are few infectious diseases in which the risk of death is as great.

Smallpox is caused by the variola virus. Two closely related viruses, the cowpox virus and the vaccinia virus, cause localized blisters in people, calves, and other animals. More than 200 years ago, William Jenner recognized that people exposed to cowpox virus were protected against infection with variola. During much of the twentieth century, vaccinia virus was used to “vaccinate” people in order to protect them against variola (smallpox) and in 1980, the disease smallpox was declared eradicated from the world. Vaccination involves scratching the skin, inoculating the vaccinia virus, and allowing it to produce a local infection. Long-lasting immunity to reinfection is the result of successful vaccination. Vaccination is very effective and, by comparison with smallpox, is safe. However, 1 in 1,000,000 individuals will die from their vaccination. Less severe complications, including widespread blisters may occur in as many as 1 in 50,000 vaccinated individuals.

Making decisions about the relative risks and benefits from an immunization program is never easy. The seriousness of smallpox, balanced against the real risks from vaccinations, make this particularly true for programs designed to prevent epidemics of smallpox. Prevention programs rely on “herd immunity,” meaning that epidemics are prevented when a very large fraction, but not necessarily all, of the people in a community are immunized. The smallpox program is made more complicated by the implied goal of preventing risk to individuals. Not everyone shares equally the risks from vaccination or from smallpox. People whose immune systems do not function well comprise the majority of people who die from vaccination. People with some, but not all, skin diseases are at higher risk than most to develop widespread blisters.

Unfortunately, there is little hard data that would allow us to quantify the increased risk or to identify all groups of patients that are at increased risk. The additional risk conferred by skin disease makes the current debate about reinstitution of vaccination programs of special interest to the ichthyosis community. The risk of developing widespread disease after local infection with the vaccinia or herpes simplex viruses is definitely increased in individuals who have atopic dermatitis and Darier’s Disease. It is less certain that the risk is increased in other skin diseases. However, it would not be surprising if individuals with some forms of ichthyosis were at greater risk. One might expect that individuals with Netherton Syndrome are at greater risk because of their poor skin barrier function and their atopic-like immune responses. Individuals with epidermolytic hyperkeratosis, whose skin blisters easily, might be expected to be more at risk from virus infections that cause blistering. Unfortunately, we cannot quantify the risks for individuals with Netherton Syndrome and EHK because they are such rare diseases.

On the other hand, it is notable that there have not been reports of widespread, serious illness following vaccination in individuals with ichthyosis vulgaris or X-linked ichthyosis. Because these forms of ichthyosis are common, we can be cautiously optimistic that lack of reported problems probably means lack of increased risk. While reports of severe reaction to vaccination in individuals with inflammatory form of ichthyosis, such as lamellar ichthyosis/CIE or erythrokeratoderma variabilis, are extremely rare or absent, it may well be that most individuals with those problems were never vaccinated in the past because of their inflamed skin. When assessing risks, we should remember that individuals with greater risk from complications of vaccination are also likely to have a greater risk of having a severe case of smallpox.

Should individuals with ichthyosis get vaccinated? The answer depends on the type of ichthyosis and upon the perceived risk of getting smallpox. The risk of a smallpox epidemic in the general population seems quite low at this time. If the risk were great, for example if you found yourself in the middle of an epidemic, the recommendations would be different. At present, my recommendation is that individuals with any form of inflammatory ichthyosis, ichthyosis that is red as well as scaly, should not be vaccinated. In addition, those individuals should avoid close contact, for at least three weeks, with individuals who have been vaccinated. There are no compelling reasons to recommend against vaccinating individuals with ichthyosis vulgaris (unless they also have atopic dermatitis), X-linked ichthyosis, or those with most palmoplantar keratodermas.

As with many things in medicine, there are always good reasons why general recommendations might not apply to individuals. Patients with ichthyosis should discuss their particular case with their dermatologist.

Editor’s Note: For the latest information on smallpox, the vaccine, and our nation’s planned response to a smallpox threat, click here to visit the Center for Disease Control website. If you do not have access to a computer or the Internet, call the national office, 1-800-545-3286, and ask for a printout of the information from this site.