RICSA, 3(1),67-72. (2026)

Etoricoxib-Induced Fixed Drug Eruption with Cutaneous and Mucosal Involvement: A Case Report

Eritema pigmentado fijo en brazos y mucosa oral posterior a la ingesta de etoricoxib: reporte de caso.

Luz M. Moyano Vidal1,2,3,a,b; Lucia M. Bolivar-Herrada4,c; Martha P. Diaz-Guevara5,b; from the INERTROP working group.

Filiación:

1. Unidad Médico Legal Contralmirante Villar, Instituto de Medicina Legal y Ciencias Forenses, Tumbes, Perú.

2. Escuela Profesional de Medicina Humana, Facultad de Ciencias de la Salud, Universidad Nacional de Tumbes, Tumbes, Perú.

3. Doctora en Ciencias de Medio Ambiente y Sociedad, con mención en Medio Ambiente y Salud Pública, Tumbes, Perú.

4. Establecimiento de Salud Pampa Grande, Dirección Regional de Salud de Tumbes, Tumbes, Perú.

5. Unidad Médico Legal II Tumbes, Instituto de Medicina Legal y Ciencias Forenses, Tumbes, Perú.

a. Médica cirujana investigadora Renacyt nivel I.

b. Médica Legista

c. Medica especialista en medicina familiar y comunitaria

Correspondencia: Luz María Moyano Vidal, luzmariamoyano@gmail.com

ID ORCID de los autores

Luz María Moyano Vidal https://orcid.org/0000-0002-5878-5782 Lucia Margarita Bolivar Herrada https://orcid.org/0009-0007-3337-1560 Martha Patricia Diaz Guevara https://orcid.org/0009-0009-7771-6086

Authorship statement: Writing–original draft: LMMV, LMBH, MPDG. Writing–review & editing: LMMV, LMBH, MPDG. Supervision: LMMV, LMBH, MPDG. Final approval of the manuscript: all authors.

Conflict of interest statement: The author declares that they have no financial, personal, or institutional conflicts of interest that could influence the results or interpretation of the study.

Funding: This study was funded with the author’s own resources and did not receive external funding from

public or private institutions.

Ethical Considerations: The patient described in this case report is the corresponding author. Informed written consent was obtained prior to submission for the publication of clinical data and photographic material with full anonymization. The corresponding author acknowledges the potential for reporting bias inherent in first-person case descriptions and has ensured objective documentation of clinical findings based on contemporaneous medical records. No institutional ethics committee approval was required, as this constitutes a particular case report without experimental intervention. The present study was conducted in accordance with the Declaration of Helsinki and applicable national regulations.

Artificial Intelligence Use Declaration: During the preparation of this manuscript, Luz M. Moyano (LMMV) used Claude AI Pro (Anthropic), Perplexity AI Pro, Open Evidence, Medsearch, and Scopus AI for the following purposes: integrating clinical history data, reducing word redundancy, improving spelling and grammar, enhancing paragraph clarity, conducting real and updated scientific evidence searches, structuring the discussion section, and confirming references. After using these tools/technologies, the authors reviewed and edited the content as needed and assumed full responsibility for the last version of the publication.

Recibido: 20-03-2026.

Aceptado: 30-03-2026.

Publicado: 31-03-2026.

Esta obra está publicada bajo la licencia CC BY 4.0

DOI: http://doi.org/10.57188/ricsa.2026.010

ABSTRACT

Introduction: Fixed drug eruption (FDE) is a delayed hypersensitivity reaction characterized by erythematous- violaceous plaques recurring at identical anatomical sites upon re-exposure to the causative drug, with persistent residual hyperpigmentation. Etoricoxib, a widely used COX-2 inhibitor, is an increasingly recognized trigger. Case Report: A 49-year-old woman developed hyperpigmented plaques on the arms and oral mucosa eight hours after a single dose of etoricoxib 120 mg for acute low back pain. A clinically identical episode had occurred two years earlier at the same sites, initially misdiagnosed as herpetic infection. Diagnosis was established by temporal chronology, exact anatomical recurrence, and a Naranjo score of 10 (definite causal relationship). Management comprised drug discontinuation, oral antihistamine, and topical corticosteroid, with favorable outpatient evolution. Conclusion: This case illustrates etoricoxib-induced FDE with cutaneous and mucosal involvement and exact site recurrence. Early recognition, definitive discontinuation, and pharmacovigilance reporting are clinical imperatives to prevent recurrence and ensure safe alternatives.

Keywords: Fixed drug eruption; Etoricoxib; Cyclooxygenase-2 Inhibitors; Drug Hypersensitivity; Pharmacovigilance. (Source: MeSH-NLM

RESUMEN

Introducción: La erupcio´n fija medicamentosa (EFM) es una reaccio´n de hipersensibilidad retardada caracterizada por placas eritematoviola´ceas recurrentes en los mismos sitios anato´micos tras la reexposicio´n al fa´rmaco causal, dejando hiperpigmentacio´n residual. Etoricoxib, inhibidor selectivo de COX-2, es un desencadenante. Reporte del caso: Mujer de 49 an˜os desarrollo´ placas hiperpigmentadas en brazos y mucosa oral ocho horas despue´s de etoricoxib 120 mg para lumbalgia aguda. Un episodio ide´ntico ocurrio´ dos an˜os antes en las mismas localizaciones, interpretado como infeccio´n herpe´tica. El diagno´stico de EFM se establecio´ por cronologí´a temporal, recurrencia exacta y puntuacio´n de 10/13 del Naranjo Probability Scale. El manejo incluyo´ suspensio´n del fa´rmaco, antihistamí´nico oral y corticoide to´pico, con evolucio´n favorable. Conclusión: Este caso ilustra un EFM por etoricoxib con compromiso cuta´neo y mucoso, de recurrencia exacta. El reconocimiento temprano, suspensio´n definitiva y reporte a farmacovigilancia son imperativos clí´nicos para prevenir recurrencias y garantizar alternativas seguras.

Palabras clave: Erupcio´n fija medicamentosa; Etoricoxib; Inhibidores de ciclooxigenasa-2; Hipersensibilidad a medicamentos; Farmacovigilancia.

INTRODUCTION

Etoricoxib is a selective cyclooxygenase-2 (COX-2) inhibitor widely prescribed for musculoskeletal pain and chronic inflammatory conditions, often perceived as a safer alternative to non-selective NSAIDs in terms of gastrointestinal tolerability.(1,2) However, multiple adverse cutaneous reactions have been described in association with its use, ranging from localized eruptions to severe toxic epidermal necrolysis, prompting reassessment of its dermatological safety profile.(1,3-5)

Among these reactions, fixed drug eruption (FDE) is characterized by well-demarcated erythematous-violaceous macules or plaques that invariably recur at the same anatomical sites upon re-exposure to the causative drug and leave persistent residual hyperpigmentation.(1–4) In clinical practice, NSAIDs and particularly selective COX-2 inhibitors are recognized as frequent triggers of this delayed hypersensitivity pattern, with a growing number of reports specifically linking etoricoxib to both cutaneous and mucosal FDE.(1-4,7)

Several recent cases have documented etoricoxib- induced FDE with localized and generalized distribution, including bullous lesions and

oromucosal involvement, thereby broadening the clinical spectrum associated with this agent and highlighting the importance of including it in the differential diagnosis of recurrent hyperpigmented lesions and probable drug-induced oral erosions.(1-4) Cross-reactivity with other NSAIDs, varying clinical severity, and, in the most extreme circumstances, life-threatening cutaneous toxicity have also been reported.(2,3,5)

Current drug allergy guidelines emphasize that early recognition of these patterns, timely withdrawal of the suspected drug, and identification of safe alternatives are fundamental to preventing recurrences and reducing the risk of serious complications.(6) In this context, case reports including those from Latin American primary care settings where etoricoxib is widely prescribed remain a key source for characterizing the clinical presentation, latency, and natural course of etoricoxib-associated cutaneous reactions.(1-4,7) This report describes two documented episodes of etoricoxib-induced FDE with cutaneous and mucosal involvement, diagnosed in the primary care setting after an initial misdiagnosis, with the aim of expanding recognition of this entity at the first level of care.

CASE PRESENTATION

A 49-year-old woman and university professor, with a history of myomectomy (June 2015) and regular use of tranexamic acid for metrorrhagia secondary to uterine myomatosis, presented on 12 March 2026 with acute onset of hyperpigmented plaques on the upper limbs and oral mucosa, appearing eight hours after a single dose of etoricoxib 120 mg for acute low back pain, administered concomitantly with orphenadrine 100 mg. Relevant past medical history included an adverse reaction to epidural anesthesia and tachycardia following a third dose of aspirin 75 mg in 2021. Her mother had a known hypersensitivity reaction to tramadol.

First episode (August 2024). The patient reported a clinically identical episode in August 2024 following several days of etoricoxib 120 mg. Lesions appeared on the oral mucosa (left lower lip), initially diagnosed as herpes zoster, and treated with antiviral therapy for seven days. Simultaneously, three hyperpigmented plaques appeared on the distal third of the left arm, one at the anatomical snuffbox of the right hand, and

intense bilateral palmar erythema in the hypothenar regions (VAS pruritus: 8/10). Lesions resolved over 30 – 60 days with residual hyperpigmentation lasting more than one month. No causal link with etoricoxib was established at that time.

Second episode and current presentation (March 2026). Eight hours after etoricoxib 120 mg on 11 March 2026, the patient identified reappearance of lesions at anatomically identical sites. Physical examination revealed three hyperpigmented plaques on the distal third of the lateral left arm: primary lesion 1.0 × 1.3 cm, dark violaceous, well- demarcated, smooth surface; two satellite lesions

1.0 × 1.2 cm (medial) and 1.0 × 1.5 cm (lateral), less intense pigmentation, diffuse borders. A 1.0 × 1.2 cm plaque was observed at the right anatomical snuffbox. Mucosal involvement of the left lower lip, bilateral palmar thenar erythema with local burning, no genital or plantar lesions. Pruritus mild (VAS 1/10) notably lower than the prior episode. Nikolsky sign negative. (see Figure 01)

Vital signs: BP 110/65 mmHg, HR 75 bpm, RR 19 rpm, axillary temperature 36.5 °C, SpO₂ 99%. Alert, oriented, hemodynamically stable, no lymphadenopathy, no hepatosplenomegaly.

Table 1. Naranjo Algorithm Adverse Drug Reaction Probability Scale in the case report.

Questions yes no Score
Previous reports of this reaction Reaction after suspected	+1 +2
drug: Improved on withdrawal:	+1
Recurred on re- administration Alternative causes:	+2	+1
Reaction with placebo:		+1
Drug at toxic level:		0*
More severe at higher dose Similar reaction to same	+1	0*
drug before Confirmed by objective	+1

evidence Total score 10

DEFINITE causal relationship (≥9 = definite); Naranjo et al., (Clin Pharmacol Ther 1981). Total Score ≥9: Definitive; Total Score 5 to 8. Probable; Total Score 1 to 4 Possible; Total Score ≤0. Doubtful (10)

Differential diagnosis: Contact dermatitis excluded (no relevant contactant exposure). Recurrent herpetic infection ruled out (morphology, distribution, and absence of vesicles inconsistent). Stevens-Johnson syndrome excluded (limited extent, no epidermal detachment, negative Nikolsky sign). Orphenadrine-induced FDE excluded: orphenadrine is not a recognized FDE trigger, and exact lesion recurrence across both episodes in which etoricoxib was the common denominator firmly attributes causality to etoricoxib. No skin biopsy, patch testing, or oral provocation challenge was performed; the clinical diagnosis was conclusive, and re-exposure would represent unnecessary risk.(see table 01).

Management. Immediate and permanent discontinuation of etoricoxib. Ambulatory regimen: desloratadine 5 mg orally once daily × 7 days; betamethasone 0.05% topical cream twice daily × 7 days. No hospitalization required. Patients

were instructed to avoid all selective COX-2 inhibitors. Weekly outpatient follow-up scheduled. Follow-up at 15 days. Satellite lesions resolved with progressive attenuation of hyperpigmentation. Primary left arm plaque persists with gradual reduction. For reference, the first episode (2024) required approximately 60 days for complete resolution. Patient adherent, with adequate understanding of permanent avoidance of the causative agent.(see table 2).

Table 2. Clinical timeline of two episodes of etoricoxib-induced fixed drug eruption. gradual reduction

The present case is consistent with an expanding body of literature documenting etoricoxib-induced FDE in high-impact dermatology, allergology, and oral surgery journals, as well as in Latin American clinical publications.(1-5,7-10) Across these reports, the clinical presentation is relatively uniform: well-demarcated erythematous- violaceous macules or plaques appearing hours to

days after drug administration, exact recurrence at identical anatomical sites upon re-exposure, and resolution with persistent post-inflammatory hyperpigmentation.(1-4,9) (see Table 3) In our patient, the latency of approximately eight hours after a single 120 mg dose, together with exact recurrence of hyperpigmented plaques on the arms and oral mucosa at anatomically identical locations to the 2024 episode, reproduces this classical FDE pattern precisely.(1-3)

The cases reported by Porr et al. and Makris et al. provide the closest clinical parallels.(1,2) Porr et al. describe a woman who developed well-demarcated plaques eight hours after a single 60 mg dose of etoricoxib, with confirmation by oral provocation challenge.(1) Makris et al. report cross-reactivity between nimesulide and etoricoxib, with bullous lesions, underscoring that sensitization may extend across chemically related or even unrelated NSAIDs.(2) Relevant to the present report is the Peruvian case documented by Dextre-Vilchez (2025), which describes etoricoxib-induced FDE with genital and mucosal involvement confirming that this adverse reaction is recognized in our region and that local pharmacovigilance data are beginning to emerge.(9)

The oral mucosal involvement in this case has been documented by Rawlings et al. and Perks et al., who

report etoricoxib-induced FDE presenting as oral erosions at high risk of misdiagnosis as herpetic or idiopathic ulcerative conditions.(3,4) The initial management of our patient as a herpetic infection later corrected when the second episode disclosed the causative pattern reflects precisely this diagnostic pitfall, and underscores the value of detailed drug history review in recurrent oral lesions.(3,4)

Regarding the concomitant use of orphenadrine 100 mg during the second episode: orphenadrine, a centrally acting skeletal muscle relaxant with anticholinergic properties, is not recognized as an FDE trigger in published literature. The occurrence of clinically identical lesions at the same sites during the first episode in which orphenadrine was not documented firmly attributes causal responsibility to etoricoxib rather than to the concomitant agent.

The Naranjo probability scale yielded a score of 10/13, classifying the causal relationship as definite (score ≥9).(11) This systematic assessment supports the diagnostic conclusion even in the absence of skin biopsy, epicutaneous patch testing, or oral drug provocation challenge procedures that, while used in confirmatory series,(1,2,8,10) carry procedural risk and are generally not required when clinical diagnosis is unambiguous.(6)

From a pharmacovigilance perspective, most published etoricoxib-induced FDE cases arise from specialized services, suggesting significant underreporting from primary care settings.(3,6–9) The present report originates in a general outpatient setting and follows the sequence described by Makris et al. and others: initial misdiagnosis of the first episode, followed by pattern recognition only when a second episode occurred.(2,6) In Peru, adverse drug reactions can be reported to DIGEMID (Direccio´n General de

This report documents two consecutive episodes of etoricoxib-induced fixed drug eruption with cutaneous involvement of the upper limbs and mucosal involvement of the lip, characterized by short latency (~8 hours), exact anatomical recurrence, and prolonged post-inflammatory hyperpigmentation. A definite causal relationship was established by Naranjo score (10-13), achieved through detailed clinical history and two-episode temporal concordance, without requiring biopsy or provocative testing. Early recognition of FDE at the primary care level is essential to prevent unnecessary re-exposure, avoid potentially more severe reactions, and ensure safe substitution of the causative anti-inflammatory agent. Clinicians

should maintain a high index of suspicion for drug- induced FDE when evaluating recurrent hyperpigmented lesions or oral erosions temporally associated with NSAID use.

The absence of pharmacovigilance reporting in this case highlights a persistent gap in primary care adverse drug reaction surveillance. Healthcare providers in Peru are encouraged to report adverse reactions including those to widely used COX-2 inhibitors through DIGEMID's national pharmacovigilance system, contributing to regional drug safety monitoring and evidence generation.

1. Porr C, Harris DM, Vidrighin A, et al. Etoricoxib- induced fixed erythema. J Clin Med. 2025;14(23):8504. doi:10.3390/jcm14238504

2. Makris M, Papapostolou N, Koumprentziotis IA, Pappa G, Katoulis AC. Nimesulide-induced fixed drug eruption followed by etoricoxib-induced fixed drug eruption: an unusual case report and review of the literature. J Clin Med. 2024;13(6):1583. doi:10.3390/jcm13061583

3. Rawlings N, Joshi S, Sandison A, Carey B. Fixed drug eruption secondary to etoricoxib. Br J Oral Maxillofac Surg. 2024;62(6):571-574. doi:10.1016/j.bjoms.2024.05.001

4. Perks A, Bates TJ, Velangi S, Brown RM, Poveda- Gallego A. Probable etoricoxib-induced fixed drug eruption involving the oral mucosa: a case report. Oral Surg Oral Med Oral Pathol Oral Radiol. 2021;131(4):e100-e107.

doi:10.1016/j.oooo.2020.12.019

5. Roy SS, Mukherjee S, Era N, Mukherjee M. Etoricoxib-induced toxic epidermal necrolysis: a fatal case report. Indian J Pharmacol. 2018;50(3):139-142. doi:10.4103/ijp.IJP_39_17

6. Khan DA, Banerji A, Blumenthal KG, et al. Drug allergy: a 2022 practice parameter update. J Allergy Clin Immunol. 2022;150(6):1333-1393. doi:10.1016/j.jaci.2022.08.028

7. Dextre-Vilchez, Rí´os-Lozano. Eritema medicamentoso pigmentado fijo por etoricoxib. Iatreia. 2025. doi:10.17533/udea.iatreia.280

8. Siriwattanasatorn M, Kamudhamas A, Sivapornpan N, Noonpugdee M, Kamalashiran C, Phetkate P. Fixed drug eruption induced by etoricoxib in Thailand: a case report. Toxicol Rep. 2025;14:102010.

doi:10.1016/j.toxrep.2025.102010

9. Mota D, Coutinho RM, Mesquita M, Cernadas J, Carneiro-Lea˜o L. Generalized fixed drug eruption secondary to etoricoxib. Dermatitis. 2025;36(4):e405-e406.

doi:10.1089/derm.2024.0324.

10. Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Adverse Drug Reaction Probability Scale (Naranjo) in Drug Induced Liver Injury. [Updated 2019 May 4]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK548069.

11. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30(2):239-245. doi:10.1038/clpt.1981.154.

12. Sousa AS, Gonçalo M. Fixed drug eruption by etoricoxib confirmed by patch test. An Bras Dermatol. 2016;91(6):777-779. doi:10.1590/abd1806-4841.20164777

13. Martí´nez Anto´n MD, Gala´n Gimeno C, Sa´nchez de Vicente J, Ja´uregui Presa I, Gamboa Setie´n PM. Etoricoxib-induced fixed drug eruption: Report of seven cases. Contact Dermatitis. 2020 Aug 18; doi: 10.1111/cod.13659

Etoricoxib-Induced Fixed Drug Eruption with Cutaneous and Mucosal Involvement: A Case Report

Luz M. Moyano Vidal1,2,3,a,b; Lucia M. Bolivar-Herrada4,c; Martha P. Diaz-Guevara5,b; from the INERTROP working group.

ABSTRACT

RESUMEN

INTRODUCTION

CASE PRESENTATION

DISCUSION

CONCLUSION

REFERENCIAS BIBLIOGRÁFICAS