Effects of Isotretinoin on Smell

Isotretinoin is a systemic retinoid widely used for the treatment of moderate to severe acne that does not respond adequately to conventional topical or oral therapies. Although highly effective, isotretinoin is known to cause mucocutaneous dryness, which may alter the nasal environment and potentially influence olfactory function. The sense of smell depends on the integrity of the olfactory epithelium, the moisture of the nasal mucosa, and the ability of odorant molecules to reach and dissolve within the mucus layer. Changes in these factors may lead to measurable reductions in olfactory sensitivity or identification ability.

Previous studies examining the effects of isotretinoin on olfaction have produced conflicting results. One investigation reported an increase in olfactory sensitivity during treatment, while another found a decrease in smell function using a different testing method. These inconsistent findings, combined with the limited number of available studies, highlight the need for further research using standardized and reproducible assessment tools.

This prospective clinical study will evaluate olfactory function in adults initiating isotretinoin therapy for dermatologic indications. Participants will undergo a structured olfactory assessment using the Connecticut Chemosensory Clinical Research Center (CCCRC) smell test, which includes both odor identification and discrimination components. In parallel, patient-reported nasal symptoms and sinonasal-related quality of life will be assessed using the NOSE and SNOT-22 questionnaires, allowing a broader understanding of subjective nasal changes that may accompany isotretinoin use.

All assessments will be performed at two time points: before the start of isotretinoin therapy and after a minimum of four weeks of continuous treatment. This within-subject design will allow comparison of pre-treatment and post-treatment measurements to determine whether isotretinoin produces quantifiable changes in olfactory performance. The study hypothesis is that isotretinoin may negatively affect olfactory function due to its well-recognized drying effects on the nasal mucosa.

The findings of this research may assist clinicians in counseling patients regarding potential sensory side effects of isotretinoin and may provide a basis for further investigations into the mechanisms by which systemic medications influence nasal physiology and smell perception.

Inclusion criteria

• Diagnosed with acne and scheduled to start oral isotretinoin as part of routine dermatology care
• Willing to participate and able to give informed consent
• Not currently smoking
• No history of allergic rhinitis, sinusitis, or active upper respiratory infection
• No medical condition known to affect the sense of smell

Exclusion criteria

• Younger than 18 years or older than 45 years
• Current cigarette smoking
• History of chronic sinonasal disease
• Any condition that would prevent completing the smell test
• Not willing to continue participation or withdrawal of consent at any time