Kate Johnson

November 19, 2013

BALTIMORE — The chance of an indeterminate penicillin skin test is 10 times higher in patients in intensive care than in other hospitalized patients. This suggests that the test is not worth performing in this setting, according to a new study.

"We need to inform our colleagues in critical care that while it may be important for them to determine whether they can use penicillin urgently, the ICU setting might not be the best condition for skin testing because it may not provide the most conclusive information," said investigator Bob Geng, MD, from the University of California at Los Angeles.

"For patients who are critically ill and have a suspected penicillin allergy, "we don't really want to waste time and money getting the skin test done," Dr. Geng told Medscape Medical News. "Perhaps we should just go directly to a different drug or, if we definitely need the penicillin, perhaps we should go directly to desensitization."

He presented results from the retrospective case–control study here at the American College of Allergy, Asthma & Immunology 2013 Annual Scientific Meeting.

The study was undertaken after an analysis of the previous decade showed that 20% of penicillin skin tests had indeterminate results, he explained.

 
When 20% of tests were coming back with indeterminate results, we felt there had to be something strange going on."
 

"At UCLA, penicillin allergy skin testing includes all the major and minor penicillin determinants, but we also include a histamine positive control and a saline negative control. When 20% of tests were coming back with indeterminate results, we felt there had to be something strange going on because we are very meticulous in ensuring that patients have not been on antihistamines at least 72 hours prior to the test," he said.

The researchers reviewed the inpatient penicillin skin test database and identified 52 cases of an indeterminate penicillin skin test, defined as the absence of a reaction to the histamine control. They also randomly selected 125 control subjects from the database.

They evaluated ICU status before or during the skin test and the use of vasopressors, H₂ blockers, short-term steroids, leukotriene inhibitors, immunosuppressives, thyroid replacement therapy, proton pump inhibitors, amiodarone, psychotropic medications, and diuretics.

Diuretic use was chosen as "a surrogate for any condition that could cause volume overload. An edematous state can influence skin testing because the skin may not be able to respond with a wheal and flare," Dr. Geng explained.

On bivariate analysis, being in the ICU was the only significant variable (odds ratio [OR], 6.46), but the use of amiodarone or an H₂ blocker both approached significance.

On multivariable logistic regression analysis, being in the ICU was still significant (OR, 10.6), as was steroid use (OR, 3.4), but the use of an H₂ blocker still did not reach significance.

"Doing the skin test in the ICU setting is probably not a good idea," concluded Dr. Geng. "The cause may be multifactorial, and could be the result of cumulative individual factors, such as sedatives, vasopressors, severe illness, and edematous state. We looked at those factors individually and none of them really added up, but the ICU stay itself may have a whole cumulative effect."

The findings also dispel some common assumptions about medications believed to interfere with skin testing, including one very unexpected finding.

Immunosuppressives Protect

"Paradoxically, immunosuppressive agents actually had significance in the opposite direction, which we did not anticipate," Dr. Geng noted. "We found patients were less likely to have an indeterminate result if they were taking these drugs than if they weren't (OR, 0.165). This was completely the opposite of what we had hypothesized. It's very counterintuitive and we don't have a good explanation. Typically, immunosuppressives dampen the immune response, and we use immunosuppressants to treat chronic hives. For these data to show that they are almost protective is very perplexing."

In addition, although conventional wisdom has held that H₂ blockers, leukotriene inhibitors, vasopressors, and psychotropic drugs might interfere with skin testing, the study found no evidence of this.

Session moderator Janna Tuck, MD, an allergist and immunologist in Cape Girardeau, Missouri, raised the issue of subsequent testing. Why were patients whose histamine prick test was inconclusive not given either a repeat prick test or an intradermal histamine test?

 
We use immunosuppressants to treat chronic hives. For these data to show that they are almost protective is very perplexing.
 

Dr. Geng and senior investigator Marc Riedl, MD, from the University of California at San Diego, both explained that an intradermal histamine test could pose a risk to some patients.

"A negative histamine skin prick test means that the skin prick penicillin tests are uninterpretable, and could be negative due to nonreactive skin," Dr. Riedl told Medscape Medical News. "Therefore, this step cannot be relied on to identify a penicillin-allergic patient. Advancing to intradermal histamine and penicillin testing without a reliable skin prick test exposes the patient to the added risk of an induced allergic reaction from the test itself."

Dr. Tuck acknowledged that the approach was a wise course of action, given the serious condition of patients in the ICU.

"I agree it's more about the patient's safety," she told Medscape Medical News. "If it was in the office, we would bring them back on another day and test them until we got a good histamine response. But these people were critical, so you either have to choose another drug or do a desensitization."

Dr. Geng has disclosed no relevant financial relationships. Dr. Riedl reports financial relationships with Shire, CSL Behring, Dyax, Isis, Pharming, Santaurus, and ViroPharma. Dr. Tuck reports owning stock in Advanced Cell Technology, Cel-Sci, and Synergy.

American College of Allergy, Asthma & Immunology (ACAAI) 2013 Annual Scientific Meeting: Abstract 19. Presented November 10, 2013.

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