key: cord-0877390-26asfqab
authors: Wang, Yu; Lipner, Shari R.
title: Retrospective Analysis of Smell and Taste Disturbances Associated with Dermatological Medications Reported to the United States Food and Drug Administration and Relevance to COVID-19 Infections
date: 2020-05-17
journal: J Am Acad Dermatol
DOI: 10.1016/j.jaad.2020.05.057
sha: f1490b46959ed0be3123ae4f58a58a7107adee47
doc_id: 877390
cord_uid: 26asfqab

nan

. Many commonly used dermatological medications can also cause smell/taste changes. With COVID-19 testing shortages in the United States (US), these medication adverse events warrant careful consideration. In this study, we analyzed the US Food and Drug Administration (FDA) Adverse Event Reporting Database (FAERS) for the most common dermatological medications associated with smell/taste disturbances, and their relevance to COVID-19 infections.

The FAERS database was searched for the most common medications causing smell/taste disturbances [2] and then filtered for dermatologic drugs. The data was substantiated using two other databases and recorded. The National Institute of Health Clinical Studies Database was queried for clinical trial data and Pubmed was examined for case reports/series on smell/taste disturbances associated with these medications.

Taste disturbances were 6.11 times more common than smell disturbances, with 10,232 and 62,524, respectively, reported to FAERS, during the study periods (Tables 1, 2). Adalimumab was the most common dermatological medication associated with anosmia in FAERS (84 cases), which was not corroborated in clinical trials or in a Pubmed search (Table 1) .

Apremilast and methotrexate were associated with 223 and 176 cases of taste disturbances, respectively ( Table 2 ). An 83-year-old female reported bitter taste following 4 weeks of apremilast treatment, which resolved 3 months after discontinuation [3] . A 22-year-old female presented with reproducible dysgeusia 5-6 hours following methotrexate ingestion, with resolution 24-36 hours after folic acid administration [4] .

Sixty percent of the listed dermatological medications caused both smell and taste disturbances (Tables 1, 2). Vismodegib is well known for causing taste disturbances, reported in 67% of patients in phase III clinical trials; smell disturbances were reported in a phase IV trial. For terbinafine, taste disturbances were reported in 2.8% of phase III clinical trial patients; taste/smell changes were described in 17 patients from an Italian adverse event reporting database [5] . There are 2 case reports of smell/taste changes with isotretinoin treatment for acne; in a 23-year-old female after 4 weeks of therapy and in a 36-year-old female after 20 weeks of treatment, with resolution 6 months after discontinuation [6, 7] . While there is no clinical trial data describing smell/taste disturbances with etanercept, these changes were reported in a 31year-old female after several months of etanercept therapy for ankylosing spondylitis [8] .

This study is subject to several limitations. FAERS data is collected from patients, physicians, and pharmaceutical companies, without confirmation of adverse events or dosage information. While many of these dermatological medications are associated with smell/taste disturbances, there is no proof of causation.

In conclusion, smell and taste disturbances are reported in about 1/3 of COVID-19 patients and also with medications frequently used in dermatology. Taste disturbances are about six times more common than smell disturbances and the majority of dermatological medications listed cause both changes. Therefore, dermatologists should be familiar with these lists and review both current medication lists in patients presenting with anosmia or dysgeusia and counsel patients of the possibility of smell/taste disturbances when initiating new treatments. 

Smell and taste dysfunction in patients with COVID-19. The Lancet Infectious Diseases. Publised Online April 15th

Retrospective Analysis of Smell and Taste Disturbances Reported to the United States Food and Drug Administration and Relevance to COVID-19 Infections

Severe bitter taste associated with apremilast

Methotrexate-induced impairment of taste acuity

Drug-induced taste and smell alterations: a case/non-case evaluation of an italian database of spontaneous adverse drug reaction reporting

Loss of taste associated with isotretinoin

Taste and olfactory disturbances after treatment for acne with isotretinoin, a 13-cis-isomer of retinoic acid

Spelunking Meckel Cave: A 31-Year-Old With Diplopia and Loss of Taste and Smell