Fixed Drug Eruption: A Rare Case of Polysensitivity between Two Unrelated Fixed Dose Combination Preparations - A Case Report
Keywords:Drug Eruptions, Delated Hypersensitivity, Gliptins, Antimicrobial Agents, Titanium dioxide
Background: A fixed drug eruption is a type IV hypersensitivity reaction to a medication that characteristically re-emerges on the same site each time the specific drug is taken. Antimicrobials (including fixed dose combinations) are frequently implicated in fixed drug eruption while gliptins (as separate drugs or as combined preparations) on the other hand are infrequent triggers. Drugs belonging to similar classification and having similar chemical structures can show cross reactivity, but here we describe a case of cross reactivity between unrelated drug classes, also known as polysensitivity.
The Case: A 58-year-old man presented with painful, burning, and pruritic blisters with ulcerations on the oral mucosa of lips, hard palate, and tip of the tongue. The patient had been on vildagliptin - metformin fixed dose combination tablets for one year. He was asked to stop the drug and lesions started improving thereafter. A week later he suffered from gastroenteritis for which he took a combined preparation of ofloxacin and ornidazole and lesions re-appeared at the same site as before with severe itching and burning.
Conclusion: This case highlights polysensitivity amongst chemically unrelated drugs, especially available in fixed-dose combination. It is an extremely rare occurrence (less than 0.2%). Moreover, there have only been a few cases of such delayed reactions occurring to gliptins, especially vildagliptin. A clinician must keep a high index of suspicion to identify this phenomenon.
Jhaj R, Chaudhary D, Asati D, Sadasivam B. Fixed-drug Eruptions: What can we Learn from a Case Series? Indian J Dermatol. Jul-Aug 2018;63(4):332-337.
Scheen AJ. DPP-4 inhibitors in the management of type 2 diabetes: a critical review of head-to-head trials. Diabetes Metab. 2012 Apr;38(2):89-101.
Ahrén B. Novel combination treatment of type 2 diabetes DPP-4 inhibition + metformin. Vasc Health Risk Manag. 2008 Apr;4(2):383-94.
Karagiannis T, Paschos P, Paletas K, Matthews DR, Tsapas A. Dipeptidyl peptidase-4 inhibitors for treatment of type 2 diabetes mellitus in the clinical setting: systematic review and meta-analysis. BMJ. 2012 Mar 12;344: e1369.
Lukashevich V, Del Prato S, Araga M, Kothny W. Efficacy and safety of vildagliptin in patients with type 2 diabetes mellitus inadequately controlled with dual combination of metformin and sulphonylurea. Diabetes Obes Metab. 2014 May;16(5):403-9.
Stein SA, Lamos EM, Davis SN. A review of the efficacy and safety of oral antidiabetic drugs. Expert Opin Drug Saf. 2013 Mar;12(2):153-75.
Mathieu C, Degrande E. Vildagliptin: a new oral treatment for type 2 diabetes mellitus. Vasc Health Risk Manag. 2008;4(6):1349-60.
Moon C, Oh E. Rationale and strategies for formulation development of oral fixed dose combination drug products. Int J Pharm Investig. 2016;46:615-31.
Tyers M, Wright GD. Drug combinations: a strategy to extend the life of antibiotics in the 21st century. Nat Rev Microbiol. 2019 Mar;17(3):141-155.
Korkij W, Soltani K. Fixed drug eruption. A brief review. Arch Dermatol. 1984 Apr;120(4):520-4.
Davis EC, Callender VD. Postinflammatory hyperpigmentation: a review of the epidemiology, clinical features, and treatment options in skin of color. J Clin Aesthet Dermatol. 2010 Jul;3(7):20-31.
Nakatani K, Kurose T, Hyo T, Watanabe K, Yabe D, Kawamoto T, et al. Drug-induced generalized skin eruption in a diabetes mellitus patient receiving a dipeptidyl peptidase-4 inhibitor plus metformin. Diabetes Ther. 2012 Dec;3(1):14.
Chan HL, Tan KC. Fixed Drug Eruption to Three Anticonvulsant Drugs: An Unusual Case of Polysensitivity. J Am Acad Dermatol. 1997 Feb;36(2 Pt 1):259.
Myakalwar AK, Sreedhar S, Barman I, Dingari NC, Venugopal Rao S, Prem Kiran P, et al. Laser-induced breakdown spectroscopy-based investigation and classification of pharmaceutical tablets using multivariate chemometric analysis. Talanta. 2011 Dec 15;87:53-9.
Auffan M, Rose J, Bottero JY, Lowry GV, Jolivet JP, Wiesner MR, et al. Towards a definition of inorganic nanoparticles from an environmental, health and safety perspective. Nat Nanotechnol. 2009 Oct;4(10):634-41.
Peters RJB, van Bemmel G, Herrera-Rivera Z, Helsper HPFG, Marvin HJP, Weigel S, et al. Characterization of titanium dioxide nanoparticles in food products: Analytical methods to define nanoparticles. J Agric Food Chem. 2014 Jul 9;62(27):6285-93.
Skocaj M, Filipic M, Petkovic J, Novak S. Titanium dioxide in our everyday life; is it safe? Radiol Oncol. 2011 Dec;45(4):227-47.
Bettini S, Boutet-Robinet E, Cartier C, Coméra C, Gaultier E, Dupuy J, et al. Food-grade TiO2 impairs intestinal and systemic immune homeostasis, initiates preneoplastic lesions and promotes aberrant crypt development in the rat colon. Sci Rep. 2017 Jan 20;7:40373.
How to Cite
Authors who publish with this journal agree to the following terms:
- The Author retains copyright in the Work, where the term “Work” shall include all digital objects that may result in subsequent electronic publication or distribution.
- Upon acceptance of the Work, the author shall grant to the Publisher the right of first publication of the Work.
- The Author shall grant to the Publisher and its agents the nonexclusive perpetual right and license to publish, archive, and make accessible the Work in whole or in part in all forms of media now or hereafter known under a Creative Commons Attribution 4.0 International License or its equivalent, which, for the avoidance of doubt, allows others to copy, distribute, and transmit the Work under the following conditions:
- Attribution—other users must attribute the Work in the manner specified by the author as indicated on the journal Web site; with the understanding that the above condition can be waived with permission from the Author and that where the Work or any of its elements is in the public domain under applicable law, that status is in no way affected by the license.
- The Author is able to enter into separate, additional contractual arrangements for the nonexclusive distribution of the journal's published version of the Work (e.g., post it to an institutional repository or publish it in a book), as long as there is provided in the document an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post online a prepublication manuscript (but not the Publisher’s final formatted PDF version of the Work) in institutional repositories or on their Websites prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work. Any such posting made before acceptance and publication of the Work shall be updated upon publication to include a reference to the Publisher-assigned DOI (Digital Object Identifier) and a link to the online abstract for the final published Work in the Journal.
- Upon Publisher’s request, the Author agrees to furnish promptly to Publisher, at the Author’s own expense, written evidence of the permissions, licenses, and consents for use of third-party material included within the Work, except as determined by Publisher to be covered by the principles of Fair Use.
- The Author represents and warrants that:
- the Work is the Author’s original work;
- the Author has not transferred, and will not transfer, exclusive rights in the Work to any third party;
- the Work is not pending review or under consideration by another publisher;
- the Work has not previously been published;
- the Work contains no misrepresentation or infringement of the Work or property of other authors or third parties; and
- the Work contains no libel, invasion of privacy, or other unlawful matter.
- The Author agrees to indemnify and hold Publisher harmless from the Author’s breach of the representations and warranties contained in Paragraph 6 above, as well as any claim or proceeding relating to Publisher’s use and publication of any content contained in the Work, including third-party content.
Enforcement of copyright
The IJMS takes the protection of copyright very seriously.
If the IJMS discovers that you have used its copyright materials in contravention of the license above, the IJMS may bring legal proceedings against you seeking reparation and an injunction to stop you using those materials. You could also be ordered to pay legal costs.
If you become aware of any use of the IJMS' copyright materials that contravenes or may contravene the license above, please report this by email to firstname.lastname@example.org
If you become aware of any material on the website that you believe infringes your or any other person's copyright, please report this by email to email@example.com