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Cryotherapy plus low-dose oral isotretinoin vs cryotherapy only for the treatment of anogenital warts: a randomized clinical trial

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Abstract

Background

Anogenital warts are a common human papillomavirus infection. They cause emotional distress, especially when they are in the anogenital region. Cryotherapy is a first-line treatment. Previous clinical trials and case series have reported variable results with retinoids (isotretinoin) as adjuvant therapy.

Objective

To determine the safety and efficacy of low-dose oral isotretinoin as adjuvant treatment of anogenital warts.

Methods

Forty-six patients with anogenital warts were randomly assigned to isotretinoin + cryotherapy (n = 23) or only cryotherapy (n = 23). Patients were allocated via an interactive web-based randomization system. Evaluators were blinded to treatments. Isotretinoin 20 mg/daily + cryotherapy or cryotherapy were prescribed for 6 weeks. Patients were followed for 4 months. Genotyping of lesions was performed before treatment started. Dermatology Life Quality Index (DLQI) and Columbia-Suicide Severity Rating Scale (C-SSRS) were measured at the beginning and end of therapy. All patients completed the study.

Results

Both Groups had 50% clearance at the end of treatment. Recurrence in the combined group was not significantly lower than in the cryotherapy group (P = 0.59). Improvement was observed in the DLQI of all patients in both groups (P = 0.001). No suicidal intention was detected with the C-SSRS. Two patients (one in each group) had liver function test abnormalities after treatment.

Conclusion

Combined therapy showed a slight not significant efficacy for anogenital warts in Hispanic patients. Low-dose isotretinoin seems to be safe even when it is used with cryotherapy on anogenital warts.

Trial registration

On April 25, 2019 with registration number DE19-00004, CONBIOÉTICA-19-CEI-001–20160404. Prospectively registered.

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Acknowledgements

We thank all the patients who participated in this study. Thanks to Dr Sergio Lozano, for his support in the English language writing.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Dermatology Department, Facultad de Medicina Y Hospital Universitario “Dr. José Eleuterio Gonzalez”, Universidad Autónoma de Nuevo León, Avenida Francisco I. Madero Y Avenida Gonzalitos S/N Colonia Mitras Centro, 64460, Monterrey, Nuevo Leon, Mexico

    Irving Llibran Reyna-Rodríguez, Sonia Chavez-Alvarez, Veronica Garza-Rodríguez, Gerardo Gonzalez-Martinez, Jorge Ocampo-Candiani & Alejandra Villarreal-Martinez

  2. Pathology Department, Facultad de Medicina Y Hospital Universitario “Dr. José Eleuterio Gonzalez”, Universidad Autónoma de Nuevo León, Monterrey, Mexico

    Rodolfo Franco-Marquez

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  1. Irving Llibran Reyna-Rodríguez
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Contributions

ILRR obtained compiled, analyzed all data, and prepared initial draft. ILRR, SCA, VGR and AVM analyzed and interpreted data, drafted, and critically evaluated the manuscript for important intellectual content. ILRR, SCA, VGR, AVM, GGM, RFM and JOC helped in obtaining, compiling and interpretation of data, and literature search. ILRR evaluated clinical response and SCA, VGR and AVM assessed pre- and post-treatment photographs. All authors were involved in the drafting and revision of the manuscript and have agreed to the final content.

Corresponding author

Correspondence to Alejandra Villarreal-Martinez.

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Conflict of interest

All authors declare that they have no competing interest and therefore nothing else to declare, and have contributed significantly and take full responsibility for the manuscript. The authors of the paper are obliged to confirm that it has not been previously published.

Ethical approval

This study was registered and approved (registration number: DE19-00004) by the Institutional Review Board Ethical Committee of the Dr. Jose Eleuterio González University Hospital of the Universidad Autónoma de Nuevo León, Mexico (CONBIOÉTICA-19-CEI-001-20160404).

Informed consent

Informed consent was obtained from study subjects for enrollment and publication of material with the understanding that their names and initials will not be published and due efforts will be made to conceal their identity but anonymity cannot be guaranteed. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki declaration of 1975 as revised in 1983.

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Reyna-Rodríguez, I.L., Chavez-Alvarez, S., Garza-Rodríguez, V. et al. Cryotherapy plus low-dose oral isotretinoin vs cryotherapy only for the treatment of anogenital warts: a randomized clinical trial. Arch Dermatol Res 313, 815–827 (2021). https://doi.org/10.1007/s00403-020-02182-y

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