Original article
High incidence of anergy in inflammatory bowel disease patients limits the usefulness of PPD screening before infliximab therapy☆

https://doi.org/10.1016/S1542-3565(04)00060-6Get rights and content

Abstract

Background & Aims: Reports of tuberculosis (TB) in patients administered infliximab prompted the Food and Drug Administration to recommend that all patients being considered for this therapy be evaluated for the risk for latent TB infection by means of a tuberculin skin test (TST). The aim of this study is to evaluate the utility of a TST as an adequate screen for TB exposure in patients with inflammatory bowel disease (IBD). Methods: Eighty-two consecutive patients with IBD (Crohn’s disease, 70 patients; ulcerative colitis, 4 patients; indeterminate colitis, 8 patients) seen at Cedars-Sinai Medical Center IBD Center (Los Angeles, CA) being treated with or considered for infliximab therapy underwent a standard intradermal purified protein derivative (PPD) TST before or between infusions of infliximab. One or more control antigens (Candida, tetanus, and/or mumps) were concurrently placed on 69 of these patients. Skin tests were read for induration at 48–72 hours after placement, and results were recorded. Results: None of 82 patients had a positive PPD TST result. Overall, 71% of patients (49 of 69 patients) with controls placed failed to react to any antigen. Eighty-three percent of patients (40 of 48 patients) who were administered corticosteroids and/or immunosuppressive medications, not including infliximab, for at least 1 month were anergic compared with 43% of patients (9 of 21 patients; P < 0.002) who were not administered those medications. Conclusions: Given the high prevalence of anergy, a negative TST result in patients with IBD administered infliximab is an unreliable indicator for TB exposure. Evaluation for TB risks should include not only a TST, but also a detailed history of travel, TB exposures, and such symptoms as chronic cough and weight loss, and a chest radiograph should be considered.

Section snippets

Patients

All patients with IBD seen at the Cedars-Sinai Medical Center IBD Center (Los Angeles, CA) between February 2001 and April 2002 who were considered good candidates for therapy with infliximab were eligible for this study. A total of 82 patients (70 patients, CD; 4 patients, ulcerative colitis [UC]; 8 patients, indeterminate colitis [IC]) were included. There were 45 men and 37 women (average age, 35 yr; range, 7–67 yr). The diagnosis of UC, CD, and IC was determined by standard methods of

Skin test results reflect high rate of anergy

Reflecting the low rate of TB in our population, none of 82 patients with IBD screened during this study had a positive PPD result according to the Centers for Disease Control and Prevention recommendations for TSTs in immunosuppressed patients.41, 42 Table 1 lists results of control skin tests among the 69 patients with at least 1 control test performed. Overall, 20 of 69 patients (29%) had a positive control skin test result, and 49 of 69 patients (71%) were anergic. There was a high rate of

Discussion

The manufacturer of infliximab currently recommends that all patients considering therapy with infliximab undergo a PPD TST before initiating infusions and has required that patients participating in clinical trials undergo a chest radiograph before the first infusion, if not done within the 3 months of study initiation.22, 24 This study shows a high incidence of anergy among patients with IBD, especially patients administered corticosteroids and/or traditional immunosuppressive medications,

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    ☆

    Supported in part by IBD program project grant no. DK46763 and GI training grant no. T32 DK07180-27 from the National Institutes of Health.

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    Copyright © 2004 American Gastroenterological Association. Published by Elsevier Ltd. All rights reserved.