Effect of Systemic Isotretinoin Therapy on Mucociliary Clearance and Nasal Surface Mucosa in Acne Patients

August 2013 | Volume 12 | Issue 8 | Original Article | 124 | Copyright © August 2013

Zennure Takci MD,a Gulcin Guler Simsek MD,b Hayriye Karabulut MD,c
Yunus Buran MD,c and Ayse Serap Karadag MDd

aKecioren Research and Training Hospital, Department of Dermatology, Ankara, Turkey
bKecioren Research and Training Hospital, Department of Pathology, Ankara, Turkey
cKecioren Research and Training Hospital, Department of Otolaryngology and Audiology, Ankara, Turkey
dYuzuncu yil University, Faculty of Medicine, Department of Dermatology, Van, Turkey

Abstract
BACKGROUND: Currently, there are no studies investigating the topical or systemic effects of retinoids on human nasal mucosa. We aimed to investigate the effect of systemic isotretinoin therapy on mucociliary transport and nasal surface mucosa using the saccharine test (ST) and nasal cytology techniques.
METHODS: A total of 30 patients with severe or moderate acne were enrolled in this study. The median prescribed dose of isotretinoin was 0.75 mg per kg per day. Clinical and biochemical examinations were carried out periodically. The ST and nasal cytology were performed before treatment and during the third month of therapy.
RESULTS: Of the 30 patients who initially agreed to participate in the research, 21 completed the study (18 female and 3 male, mean ± standard deviation (SD) aged 20.9 ± 4.7 years, range 15-32 years). There was a significant difference between the mucociliary clearance time for subjects in the pre- and post-treatment periods (173.8 ± 89.2 seconds vs 245.2 ± 191.6 seconds, respectively; P=.009). Cytological examination revealed that the squamous cell ratio was significantly lower and the reactive changes of the respiratory epithelium were significantly higher 3 months after isotretinoin therapy than before therapy (P=.010, P=.002, respectively). There were mild signs of inflammation according to the number of neutrophilic leukocytes (8.3% vs 26.6%, P=.06) after 3 months of isotretinoin therapy.
CONCLUSION: Systemic isotretinoin alters the mucociliary transport, decreases the squamous cell ratio, increases the reactive changes in the respiratory epithelium significantly, and increases neutrophils in the nasal surface mucosa in the third month of treatment.

J Drugs Dermatol. 2013;12(8):e124-e128.

INTRODUCTION

Since the 1980s, retinoids have been used to treat acne and various other skin disorders, such as psoriasis, keratinization anomalies, and keratotic genodermatosis.1 The synthetic retinoid 13-cis-retinoic acid, or isotretinoin, is the most effective choice for the treatment of extensive, nodulocystic acne, and can also be used for moderate acne that is unresponsive to conventional treatment and in patients with obvious scarring.2,3 Isotretinoin is a generally well-tolerated medication; however, it has a broad side effect profile that includes mucocutaneous side effects such as chelitis, xerosis, conjunctivitis, and dry nasal mucosa, which are experienced by nearly all patients.4
The nasal mucosa is one of the first areas attacked by foreign inhaled particles, including a variety of pathogens and toxins, and it has evolved a very effective defense system to protect itself.5 An essential part of this defense system is mucociliary clearance, which transports the foreign particles from the anterior part of the nose to the nasopharynx.6 Retinoic acid has been found to promote epithelial proliferation, induce mucociliary differentiation, and inhibit the squamous cell differentiation of the epithelial cells.7 A report by Gorpelioglu et al showed a significant impairment of mucociliary clearance in the nasal passage after 3 months of systemic isotretinoin therapy.8 There are studies examining the effect of topical retinoic acid on surgically demucosalized animal paranasal sinuses, but there are no studies that have investigated the topical or systemic effects of retinoids on human nasal or paranasal sinus mucosa. Therefore, in this study we aimed to investigate the effect of systemic isotretinoin therapy on mucociliary transport and nasal surface mucosa using the saccharine test (ST) and nasal cytology techniques.

Patients and Methods

A total of 30 patients with severe or moderate acne were enrolled in this study. The patients had all been admitted to the dermatology outpatient clinic of the Kecioren Research and Training Hospital during the period November 2010 to July 2011. The study group was selected from a group of men and non-pregnant women having therapeutic failure with topical remedies and tetracyclines. The women of childbearing potential were using at least 2 separate and effective methods of birth control, and had a negative serum pregnancy test 1 week before the initiation of isotretinoin therapy.