European Journal of Clinical Pharmacology

, Volume 73, Issue 12, pp 1523–1537 | Cite as

Drug-induced oral lichenoid reactions: a real clinical entity? A systematic review

  • Giulio Fortuna
  • Massimo Aria
  • Julie H. Schiavo



Drug-induced oral lichenoid reactions (DIOLRs) have been extensively reported in the literature, but the validity of the causality relationship between any drug and the oral lichenoid lesions (OLLs) still remains questionable. We sought to determine whether this causality relationship really exists, whether a resolution of the oral lesions upon withdrawal occurs, and what the most common alleged offending medications are.


Nine electronic databases from January 1966 to December 2016 were systematically searched to identify all relevant studies selected with specific inclusion criteria (a clinical and histopathological diagnosis of DIOLRs, and clearly statement on the systemic offending medication). Searched terms included but not limited to oral lichen planus/oral lichenoid lesions/oral lichenoid reactions, the adverse effects of medication, and drug-induced. Statistical analyses conducted.


The search retrieved a total of 817 articles, of which only 46 were included into a qualitative synthesis: 40 case reports/series and 6 studies. The causality assessment was done only in 14.8% of cases with the C-D-R protocol. The Naranjo algorithm was not reported in the majority of cases (98.2%). Culprit medication was withdrawn in 68.5% of the cases, obtaining a partial or complete resolution without treatment in 16.7% of cases and with treatment in 27.7% of cases. The median number of culprit medication(s) described was 1 with the most frequent ones being Methyldopa (20.37%), Interferon (IFN)-alpha (11.11%), and Imatinib and Infliximab (9.26%).


This systematic review demonstrated that there is no strong scientific evidence to support the causal relationship between any drug and oral lichenoid lesions; therefore, in all reviewed cases, we must question whether the DIOLRs represent a real and separate clinical entity. Further and more thorough investigations using one of the available algorithms for adverse drug reaction are warranted.


Oral lichen planus Oral lichenoid lesions Oral licheniod reactions Diagnosis Management Medication Drug 



We would like to thank Ms. Thelisia Davis, Department of Libraries, Louisiana State University Health Sciences Center, for her help in editing the manuscript.

Funding information

No funding source has been provided for this work.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

228_2017_2325_MOESM1_ESM.docx (18 kb)
ESM 1 (DOCX 17 kb)


  1. 1.
    WHO (1972) International drug monitoring: the role of national centres. Rep Ser 498Google Scholar
  2. 2.
    Edwards IR, Aronson JK (2000) Adverse drug reactions: definitions, diagnosis, and management. Lancet 356(9237):1255–1259. CrossRefPubMedGoogle Scholar
  3. 3.
    Zelickson BD, Rogers RS 3rd (1986) Drug reactions involving the mouth. Clin Dermatol 4(1):98–109CrossRefPubMedGoogle Scholar
  4. 4.
    Boras VV, Andabak-Rogulj A, Brailo V, Simunkovic SK, Gabric D, Vrdoljak DV (2015) Adverse drug reactions in the oral cavity. Acta Clin Croat 54(2):208–215PubMedGoogle Scholar
  5. 5.
    Yuan A, Woo SB (2015) Adverse drug events in the oral cavity. Oral Surg Oral Med Oral Pathol Oral Radiol 119(1):35–47. CrossRefPubMedGoogle Scholar
  6. 6.
    Femiano F, Lanza A, Buonaiuto C, Gombos F, Rullo R, Festa V, Cirillo N (2008) Oral manifestations of adverse drug reactions: guidelines. J Eur Acad Dermatol Venereol 22(6):681–691. CrossRefPubMedGoogle Scholar
  7. 7.
    Abdollahi M, Rahimi R, Radfar M (2008) Current opinion on drug-induced oral reactions: a comprehensive review. J Contemp Dent Pract 9(3):1–15PubMedGoogle Scholar
  8. 8.
    Belvederi Murri M, Guaglianone A, Bugliani M, Calcagno P, Respino M, Serafini G, Innamorati M, Pompili M, Amore M (2015) Second-generation antipsychotics and neuroleptic malignant syndrome: systematic review and case report analysis. Drugs R D 15(1):45–62. CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Healy CM, Smyth Y, Flint SR (2004) Persistent nicorandil induced oral ulceration. Heart 90(7):e38. CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Parkhill AL (2013) Oral mucositis and stomatitis associated with conventional and targeted anticancer therapy. Aust J Pharm 1:112. Google Scholar
  11. 11.
    Almeyda J, Levantine A (1971) Drug reactions. XVI Lichenoid drug eruptions. Br J Dermatol 85(6):604–607CrossRefPubMedGoogle Scholar
  12. 12.
    McCartan BE, McCreary CE (1997) Oral lichenoid drug eruptions. Oral Dis 3(2):58–63CrossRefPubMedGoogle Scholar
  13. 13.
    Serrano-Sánchez P, Bagán JV, Jiménez-Soriano SG (2010) Drug-induced oral lichenoid reactions. A literature review. J Clin Exp Dent 2:e71–e75CrossRefGoogle Scholar
  14. 14.
    Al-Hashimi I, Schifter M, Lockhart PB, Wray D, Brennan M, Migliorati CA, Axell T, Bruce AJ, Carpenter W, Eisenberg E, Epstein JB, Holmstrup P, Jontell M, Lozada-Nur F, Nair R, Silverman B, Thongprasom K, Thornhill M, Warnakulasuriya S, van der Waal I (2007) Oral lichen planus and oral lichenoid lesions: diagnostic and therapeutic considerations. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 103(Suppl 1):S25 e1–s25 e12. Google Scholar
  15. 15.
    van der Waal I (2009) Oral lichen planus and oral lichenoid lesions; a critical appraisal with emphasis on the diagnostic aspects. Med Oral Patol Oral Cir Bucal 14(7):E310–E314PubMedGoogle Scholar
  16. 16.
    Potts AJ, Hamburger J, Scully C (1987) The medication of patients with oral lichen planus and the association of nonsteroidal anti-inflammatory drugs with erosive lesions. Oral Surg Oral Med Oral Pathol 64(5):541–543CrossRefPubMedGoogle Scholar
  17. 17.
    Lamey PJ, McCartan BE, MacDonald DG, MacKie RM (1995) Basal cell cytoplasmic autoantibodies in oral lichenoid reactions. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 79(1):44–49CrossRefPubMedGoogle Scholar
  18. 18.
    Baris E, Senguven B, Tuzuner T, Gultekin SE (2014) Oral lichenoid lesions related to drugs: review of clinicopathological features and differential diagnosis. Eur J Inflamm 12(2):217–225CrossRefGoogle Scholar
  19. 19.
    Van den Haute V, Antoine JL, Lachapelle JM (1989) Histopathological discriminant criteria between lichenoid drug eruption and idiopathic lichen planus: retrospective study on selected samples. Dermatologica 179(1):10–13CrossRefPubMedGoogle Scholar
  20. 20.
    Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, Janecek E, Domecq C, Greenblatt DJ (1981) A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 30(2):239–245CrossRefPubMedGoogle Scholar
  21. 21.
    WHO (2014) World Health Organization. JAPST (1):22–35 (Accessed 22 June 2017)
  22. 22.
    Agbabiaka TB, Savovic J, Ernst E (2008) Methods for causality assessment of adverse drug reactions: a systematic review. Drug Saf 31(1):21–37CrossRefPubMedGoogle Scholar
  23. 23.
    Moher D, Liberati A, Tetzlaff J, Altman DG, Group P (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6(7):e1000097. CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Blasberg B, Dorey JL, Stein HB, Chalmers A, Conklin RJ (1984) Lichenoid lesions of the oral mucosa in rheumatoid arthritis patients treated with penicillamine. J Rheumatol 11(3):348–351PubMedGoogle Scholar
  25. 25.
    Clayton R, Chaudhry S, Ali I, Cooper S, Hodgson T, Wojnarowska F (2010) Mucosal (oral and vulval) lichen planus in women: are angiotensin-converting enzyme inhibitors protective, and beta-blockers and non-steroidal anti-inflammatory drugs associated with the condition? Clin Exp Dermatol 35(4):384–387. CrossRefPubMedGoogle Scholar
  26. 26.
    Gunes AT, Fetil E, Ilknur T, Birgin B, Ozkan S (2006) Naproxen-induced lichen planus: report of 55 cases. Int J Dermatol 45(6):709–712. CrossRefPubMedGoogle Scholar
  27. 27.
    Robertson WD, Wray D (1992) Ingestion of medication among patients with oral keratoses including lichen planus. Oral Surg Oral Med Oral Pathol 74(2):183–185CrossRefPubMedGoogle Scholar
  28. 28.
    Powell FC, Rogers RS 3rd, Dickson ER (1983) Primary biliary cirrhosis and lichen planus. J Am Acad Dermatol 9(4):540–545CrossRefPubMedGoogle Scholar
  29. 29.
    McCartan BE, McCreary CE, Healy CM (2003) Studies of drug-induced lichenoid reactions: criteria for case selection. Oral Dis 9(4):163–164CrossRefPubMedGoogle Scholar
  30. 30.
    American Society of Health-System Pharmacists (1995) ASHP guidelines on adverse drug reaction monitoring and reporting. Am J Health Syst Pharm 52(4):417–419Google Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Department of Diagnostic Science, New Orleans School of DentistryLouisiana State University Health Sciences CenterNew OrleansUSA
  2. 2.D.eb.RA. Mexico FoundationMonterreyMexico
  3. 3.Federico Navarro Institute – School of Orgonomy “Piero Borrelli”NaplesItaly
  4. 4.Department of Economics and StatisticsFederico II University of NaplesNaplesItaly
  5. 5.Department of Libraries, New Orleans School of DentistryLouisiana State University Health Sciences CenterNew OrleansUSA

Personalised recommendations