Observational Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Methodol. Mar 26, 2017; 7(1): 25-32
Published online Mar 26, 2017. doi: 10.5662/wjm.v7.i1.25
Patch testing and cross sensitivity study of adverse cutaneous drug reactions due to anticonvulsants: A preliminary report
T N Shiny, Vikram K Mahajan, Karaninder S Mehta, Pushpinder S Chauhan, Ritu Rawat, Rajni Sharma
T N Shiny, Vikram K Mahajan, Karaninder S Mehta, Pushpinder S Chauhan, Ritu Rawat, Rajni Sharma, Department of Dermatology, Venereology and Leprosy, Dr. R. P. Govt. Medical College, Kangra, Himachal Pradesh 176001, India
Author contributions: Shiny TN collected patients’ data, performed patch testing, analyzed and interpreted data, and drafted preliminary manuscript; Mahajan VK conceptualized, analyzed, interpreted data, and designed, re-drafted, and critically evaluated the manuscript for important intellectual content; Mehta KS helped in manuscript drafting, data collection, analysis and interpretation of data; Chauhan PS helped in analysis and interpretation of data and manuscript drafting; Rawat R and Sharma R helped in clinical material, editing, and drafting of manuscript; all these authors were involved in the revision of the draft manuscript and have agreed to the final content.
Institutional review board statement: The study was reviewed and approved by the Institutional Scientific Protocol Review Committee, Dr R. P. Govt. Medical College, Kangra (Tanda), H.P. 176001 (India).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: No potential conflict of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Vikram K Mahajan, MBBS, MD, Department of Dermatology, Venereology and Leprosy, Dr. R. P. Govt. Medical College, Tanda Hospital Rd, Kangra, Himachal Pradesh 176001, India. vkm1@rediffmail.com
Telephone: +91-1892-287161 Fax: +91-1892-267115
Received: November 17, 2016
Peer-review started: November 22, 2016
First decision: January 14, 2017
Revised: January 21, 2017
Accepted: March 12, 2017
Article in press: March 13, 2017
Published online: March 26, 2017
Processing time: 127 Days and 9.4 Hours
Abstract
AIM

To evaluate the utility of patch test and cross-sensitivity patterns in patients with adverse cutaneous drug reactions (ACDR) from common anticonvulsants.

METHODS

Twenty-four (M:F = 13:11) patients aged 18-75 years with ACDR from anticonvulsants were patch tested 3-27 mo after complete recovery using carbamazepine, phenytoin, phenobarbitone, lamotrigine, and sodium valproate in 10%, 20% and 30% conc. in pet. after informed consent. Positive reactions persisting on D3 and D4 were considered significant.

RESULTS

Clinical patterns were exanthematous drug rash with or without systemic involvement (DRESS) in 18 (75%), Stevens-Johnsons syndrome/toxic epidermal necrolysis (SJS/TEN) overlap and TEN in 2 (8.3%) patients each, SJS and lichenoid drug eruption in 1 (4.2%) patient each, respectively. The implicated drugs were phenytoin in 14 (58.3%), carbamazepine in 9 (37.5%), phenobarbitone in 2 (8.3%), and lamotrigine in 1 (4.7%) patients, respectively. Twelve (50%) patients elicited positive reactions to implicated drugs; carbamazepine in 6 (50%), phenytoin alone in 4 (33.3%), phenobarbitone alone in 1 (8.3%), and both phenytoin and phenobarbitone in 1 (8.33%) patients, respectively. Cross-reactions occurred in 11 (92%) patients. Six patients with carbamazepine positive patch test reaction showed cross sensitivity with phenobarbitone, sodium valproate and/or lamotrigine. Three (75%) patients among positive phenytoin patch test reactions had cross reactions with phenobarbitone, lamotrigine, and/or valproate.

CONCLUSION

Carbamazepine remains the commonest anticonvulsant causing ACDRs and cross-reactions with other anticonvulsants are possible. Drug patch testing appears useful in DRESS for drug imputability and cross-reactions established clinically.

Keywords: Anticonvulsant hypersensitivity syndrome; Carbamazepine; Sodium valproate; Drug rash with eosinophilia with or without systemic involvement; Drug patch test; Lamotrigine; Phenobarbitone; Phenytoin; Stevens-Johnsons syndrome; Toxic epidermal necrolysis

Core tip: Anticonvulsants account for 20% of all adverse cutaneous drug reactions (ACDRs) while cross-reactions occur frequently among carbamazepine, phenytoin, phenobarbitone necessitating careful prescriptions. The clinical presentation alone is not diagnostic and identification of offending drug needs causality assessment that may be misleading in patients on multiple medications. Drug provocation, skin prick or intradermal tests have ethical issues for possibility of precipitating more severe reactions. Basophil degranulation/lymphocyte activation or drug specific IgE radioallergosorbent tests, histamine release and passive haemagglutination tests have limited use in clinical practice. Drug patch testing appears useful in anticonvulsant ACDRs, drug imputability and cross-reactions established clinically.