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Rheumatology Advance Access originally published online on March 20, 2008
Rheumatology 2008 47(5):733-734; doi:10.1093/rheumatology/ken075
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© The Author 2008. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org


LETTERS TO THE EDITOR

Purified protein derivative reaction is not augmented in Behçet's syndrome patients

G. Hatemi1, M. Melikoglu1, N. Sut2 and H. Yazici1

1Rheumatology Division, Department of Internal Medicine, Cerrahpasa Medical School, Istanbul University, Istanbul and 2Department of Biostatistics, Medical School, Trakya University, Edirne, Turkey.

Correspondence to: G. Hatemi, Cerrahpasa Tip Fakultesi, Ic Hastaliklari ABD, 34300 Aksaray, Istanbul, Turkey. E-mail: gulenhatemi{at}yahoo.com

SIR, In a recent position paper about the emerging role of TNF-{alpha} antagonists in managing Behçet's syndrome (BS), the importance of screening BS patients for latent tuberculosis before starting treatment with these agents has been emphasized [1]. This is especially important since in geographies where BS is endemic, the prevalence of tuberculosis is also relatively high. Guidelines recommend screening all patients with a tuberculin test and chest X-ray before starting treatment with TNF-{alpha} antagonists [2]. Case reports suggest that false positive results can be obtained with the tuberculin test due to the pathergy phenomenon observed in BS patients [3, 4]. However, this has not been formally surveyed.

During a recent study, in which we looked at the effect of infliximab on the tuberculin test [5], we had included 82 BS patients, 81 infliximab naive RA patients and 47 healthy subjects as controls. At the same time and apart from the purposes of that study, we also had done a pathergy test in those subjects who agreed to participate, with the aim of determining the effect of the pathergy phenomenon on the response of BS patients to the tuberculin test. Informed consent was obtained from all subjects. The study was approved by the ethical committee of Istanbul University, Cerrahpasa Medical School.

Eighty BS and 61 RA patients and 38 healthy controls participated. The tuberculin test was administered with the Mantoux technique, using 5 IU of purified protein derivative (PPD) solution, which was injected intradermally into the forearm by a nurse. The pathergy test was done at three sites on each forearm by inserting six sterile 20-gauge needles intradermally, on the same day as the tuberculin test. Both the tuberculin test and the pathergy reaction were evaluated 48 h later, by two independent observers in a blinded manner. Subjects put their arms through a curtain and their hands were covered to prevent the observers from recognizing the subjects, or any deformities revealing the diagnosis. PPD reaction was evaluated by measuring the transverse diameter of the induration. A positive pathergy test was defined as a papule or a pustule at the insertion site of the needle. The number of subjects with a positive PPD test (≥10 mm) in each group was compared and the relationship between PPD positivity and the pathergy phenomenon was sought.

The number of patients with a positive pathergy reaction, a positive PPD test and the mean PPD induration of each group are shown in Table 1. The mean diameter of the PPD induration was lower among RA patients (H2df = 20.1, P < 0.001, Kruskal–Wallis) when compared with BS patients and healthy controls. The mean indurations in BS patients and healthy controls were similar (H1df = 2.0, P = 0.163, Kruskal–Wallis). Inter-group comparisons revealed that mean PPD induration was similar among BS patients and healthy controls (Mann–Whitney U = 1207, P = 0.163). PPD indurations in both BS patients and healthy controls were higher than in RA patients (Mann–Whitney U = 1595, P < 0.001 and Mann–Whitney U = 568.5, P < 0.001, respectively).


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TABLE 1. Number of patients with a positive pathergy reaction, a positive PPD test and the mean PPD induration of each group

 
The number of patients with a positive PPD was also lower among RA patients than the other two groups ({chi}2 = 19.246, P < 0.001). Inter-group comparisons showed that the frequency of PPD positivity was similar among BS patients and healthy controls (P = 0.2), and higher in both BS patients and healthy controls when compared with RA patients (P = 0.002 and P < 0.001, respectively).

Then, we looked at the association between having a positive pathergy test and the size of the PPD reaction. The mean PPD induration was similar among BD patients with a positive pathergy test and among those with a negative test (9.8 ± 7.1 vs 11.9 ± 7.7 mm; P = 0.316). The number of patients with a positive PPD test was also similar among BS patients with and without a positive pathergy reaction (12/18, 67% vs 38/62, 63%; P = 0.79). Forty-seven of the BS patients were using immunosuppressive drugs such as AZA and CsA. The frequency of a positive PPD test was not different between the patients who were receiving immunosuppressives and those who were not (30/47 vs 21/33, P = 0.6). Similarly, the mean PPD induration was not different between those who were receiving immunsuppressives and those who were not (11.3 ± 7.5 vs 11.5 ± 7.5; P = 0.947).

The frequency of a positive pathergy test among BD patients was somewhat lower than peviously reported [6]. The patients we included were patients who were being followed in our clinic for some time. This might have resulted in a lower frequency of pathergy positivity when compared with a newly diagnosed group of patients.

Our findings showed that the PPD reaction was not augmented among BS patients and its induration size was not affected by having a positive pathergy test.

Formula

Disclosure statement: The authors have declared no conflicts of interest.


    References
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 References
 

  1. Sfikakis PP, Markomichelakis N, Alpsoy E, et al. Anti-TNF therapy in the management of Behcet's disease—review and basis for recommendations. Rheumatology (2007) 46:736–41.[Free Full Text]
  2. Furst DE, Cush J, Kaufmann S, Siegel J, Kurth R. Preliminary guidelines for diagnosing and treating tuberculosis in patients with rheumatoid arthritis in immunosuppressive trials or being treated with biological agents. Ann Rheum Dis (2002) 61(Suppl 2):ii62–3.[Free Full Text]
  3. Pickering MC, Haskard DO. False-positive results obtained using the Mantoux test in Behcet's syndrome: comment on the article by Garcia-Porrua et al. Arthritis Rheum (2000) 43:2855–6.[Web of Science][Medline]
  4. Kaplinsky N, Movshovits M, Frankel O. False-positive tuberculin test in Behçet's syndrome. Cutis (1980) 25:529–30.[Web of Science][Medline]
  5. Hatemi G, Melikoglu M, Fresko I, Masatlioglu S, Tascilar K, Yazici H. Infliximab does not suppress the tuberculin skin test (purified protein derivative). J Rheumatol (2007) 34:474–80.[Abstract/Free Full Text]
  6. Yazici H, Fresko I, Yurdakul S. Behcet's syndrome: disease manifestations, management, and advances in treatment. Nat Clin Pract Rheumatol (2007) 3:148–55.[CrossRef][Web of Science][Medline]
Accepted 31 January 2008


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