State sees rash of false-positive reactions from skin test reagent
Experts say Aplisol reactions seem to be subsiding quickly
Did someone say "Aplisol"? Did they mention false-positive reactions, complete with itching, redness, and swelling? According to the experts, those reactions shouldn’t be happening, but TB controllers in Massachusetts say they are. And although the reactions seem to be subsiding quickly, in the meantime, patients and test readers alike are collectively freaking out, administrators report.
"One hospital called us and said they were going to throw out all the Aplisol we gave them and buy Tubersol," says Edward Nardell, MD, chief of pulmonary medicine at the Cambridge Hospital and TB control officer of the Massachusetts Department of Public Health. "They had tested hundreds of people, and they had 30 to 40 of them complaining of itchy redness and large reactions."
One patient injected with the tuberculin skin-test reagent (which is made by Parkdale Pharmaceuticals of Rochester, MI, and distributed by King Pharmaceuticals in Bristol, TN) showed up with her entire forearm swollen, says Denise O’Connor, RN, program director for TB control in Boston. "She had a huge reaction, which we presume was allergic in nature," says O’Connor. "Within 24 hours, though, the swelling was gone."
In another instance, a nursing home called to report that this year’s annual skin-testing, conducted with Aplisol instead of Tubersol (made by Pasteur Merieux Connaught in Swiftwater, PA), seemed to show a rash of conversions. "We’ve been getting a lot of reports like this since we switched," says O’Connor.
According to O’Connor, the reactions tend to develop within hours and consist chiefly of erythema (ranging from about 20 mm to "someone’s entire forearm") and induration (ranging from about 10 mm to, again, an entire forearm). The reactions reportedly occur across all skin types, not just the fair-haired, light-skinned people O’Connor says she usually warns about such reactions.
It takes experience
The signs and symptoms aren’t the kind experienced clinicians would mistake for a positive result, adds Nardell. "We had a house officer come in with a reaction that several nurses had assured her was positive," he recounts. "And indeed, you could measure some induration, but it wasn’t the vigorous response you’d expect in someone who’s young and healthy." A subsequent test with Tubersol provoked no reaction at all.
But asking nurses without a lot of experience to make that kind of distinction is "asking a lot," Nardell adds. "It’s hard enough to get people to read a test with Tubersol correctly — to get them to disregard the redness, measure across the arm, record in millimeters, all of that."
Right this minute, Nardell’s biggest headache stems from the fact that last year, he bought a year’s supply of the stuff, after the company offered a big price break predicated on a high-volume sale. "They were offering it literally at a tenth the price we pay for Tubersol," adds Nardell.
His state program, like many others, is struggling to do the right thing, he adds, by offering prophylaxis to more of its latently infected populations; plus, there was that recently published double-blind trial comparing Aplisol to Tubersol, which concluded the two products were substantially equal in terms of specificity.1 At the time, Nardell sighs, it seemed like a great idea. "It took a while for our supply of Tubersol to get used up," he adds. "Now that we’re starting to use the Aplisol, we’re getting all these reports."
Other TB controllers, apprised of the situation, are "tsk-tsking" sympathetically. Some say, price break or not, they’ll stick with Tubersol. "Let’s say we’ve had some problems with Aplisol before, and we prefer not to use it because of the unusual reactions," says Carol Pozsik, RN, MPH, chief of TB control for North Carolina. If hospitals in the state call asking for advice, Pozsik adds, she advises them not to switch if they’re already using Aplisol — but otherwise, to stick with Tubersol.
A spokesman for King Pharmaceuticals, who responded by fax to queries about the Massachu setts incidents, noted that the best way to avoid false positives with the product is for test readers to make sure they abide by parameters noted in the product literature, a point a Centers for Disease Control and Prevention expert says is worth bearing in mind.
"With skilled, well-trained nurses doing the reading, people shouldn’t be troubled by this soft, mushy induration, which is the kind of cross-reaction you usually see with Aplisol," says Rick O’Brien, MD, chief of the research and evaluation branch at the CDC’s Division of TB Elimination. "These kinds of reactions haven’t been well described in the literature, but surveys suggest it’s the hard induration that’s associated with greater risk of TB."
If in doubt, the thing to do is re-test with Tubersol, counsels John Sbarbaro, MD, professor of medicine at the University of Colorado Health Sciences Center in Denver. "The CDC, I’m sure, would like to see a product that competes well [with Tubersol], so prices stay down," Sbarbaro adds. "So I urge people to buy Aplisol or Tubersol, but if the results don’t fit, re-test with Tubersol."
That’s small consolation to Nardell, who is currently facing two contact investigations in area high schools.
To Sbarbaro, the moral is clear. "A skin test that can identify someone with TB infection — that’s the single most important thing this country needs if we’re ever going to eliminate TB."
Reference
1. Villarino M, Burman W, Wang Y-C, et al. Comparable specificity of 2 commercial tuberculin reagents in persons at low risk for tuberculosis infection. JAMA 1999; 281:169-171.
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