A Double-Blind Randomized Study of Two Doses of Oral Isotretinoin in the Treatment of Recalcitrant Facial Flat Warts: Impact on Quality of Life, Anxiety, and Depression

María Guadalupe Olguín-García; María Luisa Peralta-Pedrero; Martha Alejandra Morales-Sánchez; Elisa Vega-Memije; Víctor Manuel Bautista-de Lucio

doi:10.1002/hsr2.70684

A Double-Blind Randomized Study of Two Doses of Oral Isotretinoin in the Treatment of Recalcitrant Facial Flat Warts: Impact on Quality of Life, Anxiety, and Depression

Health Sci Rep. 2025 Apr 21;8(4):e70684. doi: 10.1002/hsr2.70684. eCollection 2025 Apr.

Authors

María Guadalupe Olguín-García^{1

2

3}, María Luisa Peralta-Pedrero^{1

2}, Martha Alejandra Morales-Sánchez², Elisa Vega-Memije⁴, Víctor Manuel Bautista-de Lucio⁵

Affiliations

¹ Programa de Maestría y Doctorado en Ciencias Médicas, Odontológicas y de la Salud Universidad Nacional Autónoma de México Mexico City Mexico.
² Education and Research Department Centro Dermatológico Dr. Ladislao de la Pascua (CDP) Secretaría de Salud de la Ciudad de México Mexico City Mexico.
³ Internal Medicine Department Hospital General Dr. Darío Fernández Fierro, ISSSTE Mexico City Mexico.
⁴ Dermatology Department Hospital General Dr. Manuel Gea González Secretaria de Salud Mexico City Mexico.
⁵ Microbiology and Ocular Proteomics, Research Unit, Institute of Ophthalmology Fundación de Asistencia Privada Conde de Valenciana Mexico City Mexico.

Abstract

Background and aims: Recalcitrant facial flat warts are caused by human papillomavirus and may persist for years despite treatment. Oral isotretinoin administered at a dose of 0.5 mg/kg/day is effective and safe. However, the adverse effects reported are dose-dependent behaviors and they could limit their use. We aim to compare the efficacy and safety of two doses of oral isotretinoin for the treatment of recalcitrant facial flat warts and to assess the quality of life, anxiety, and depression in the individuals studied.

Methods: Isotretinoin 0.3 mg/kg/day or isotretinoin 0.5 mg/kg/day was administered to 21 and 19 adult patients, respectively, in a double-blind, randomized fashion for 12 weeks. Cutaneous lesions were assessed, and adverse events, including serologic changes, were recorded. It is considered that warts were recalcitrant if the patient was treated for at least 3 years with at least two of the following options: retinoids, 5-fluorouracil, imiquimod, and cryotherapy. In addition, quality of life, anxiety, and depression were assessed at the beginning and end of follow-up.

Results: In the isotretinoin 0.3 mg/kg/day group, 35% of the patients had a complete response, and 66% had a partial response, while in the isotretinoin 0.5 mg/kg/day group, 73.7% presented a complete response, and 26.31% presented a partial response (p = 0.015). The most frequent adverse event was cheilitis. There was an elevation of aspartate aminotransferase (p = 0.020) and total bilirubin (p = 0.015) in the isotretinoin 0.5 mg/kg/day group. Improvement in the quality-of-life score (p = 0.0001) and a reduction in the anxiety (p = 0.00) score was observed in both groups.

Conclusion: Oral isotretinoin at a dose of 0.5 mg/kg/day is safe and effective for the treatment of recalcitrant facial flat warts in adults, with lower recurrence rates than 0.3 mg/kg/day. Prolonged treatment with isotretinoin for over 12 weeks in adults can increase the overall response rate. Trial Registration: Registry of ClinicalTrials.gov identifier: NTC04290572; https://classic.clinicaltrials.gov/.

Keywords: oral isotretinoin; recalcitrant flat warts; treatment.