756376
case-report2018
CMSXXX10.1177/1203475418756376Journal of Cutaneous Medicine and SurgeryWong et al
Case Report
Drug Eruption to Rosuvastatin
With Recurrence on
Simvastatin: A Case Report
Ian T. Y. Wong1, Yuanshen Huang2 , and Youwen Zhou2
Keywords
lichenoid drug eruption, fixed drug eruption, cross-reactivity, rosuvastatin, simvastatin
Statins are a class of medications that work as competitive
inhibitors of the 3-hydroxy-3-methylglutaryl-coenzyme A
(HMG-CoA) reductase, a key rate-controlling enzyme in the
mevalonate pathway leading to cholesterol production. On
the Canadian market, there are 6 available statins commonly
grouped as either type 1 fermentation-derived statins (lovas-
tatin, simvastatin, pravastatin) or type 2 synthetic statins
(fluvastatin, atorvastatin, rosuvastatin). The 2 types that are
structurally differentiated as type 1 statins have a butyryl
group, whereas type 2 statins have a fluorophenyl group that
facilitates tighter binding to HMG-CoA reductase. Altogether,
statins represent an integral class of medications in the arma-
mentarium of physicians for the management of hyperlipid-
emia and prevention of cardiovascular events, including
myocardial infarction and stroke.
Adverse reactions reported with statin use include serious
(myopathy/rhabdomyolysis, elevated hepatic enzymes, inter-
stitial lung disease), gastrointestinal (abdominal pain/cramps,
constipation, diarrhea, dry mouth, flatulence, heartburn, nau-
sea, vomiting, taste perversion), central nervous system (diz-
ziness, headache, insomnia, paresthesia), and dermatologic
(rash, pruritus) findings.1 There are no reports of lichenoid or
fixed drug eruptions in the drug monograph for HMG-CoA
reductase inhibitors (statins).1 We present a case of a drug
reaction to rosuvastatin with clinical and histopathologic
findings that suggest either a lichenoid or fixed drug eruption
with recurrence following simvastatin therapy.
Case Report
In September 2016, a 55-year-old woman of South Asian
descent was referred to our clinic for evaluation of ery-
thematous to grey telangiectatic patches on the right thigh
with epidermal atrophy that had persisted for 5 months
(Figure 1A).
In April 2016, she was prescribed oral rosuvastatin
(Crestor) 10 mg once daily following a diagnosis of hyper-
cholesterolemia. One week after initiating rosuvastatin ther-
apy, she developed red to grey, pruritic lesions on the right
thigh measuring 10 cm × 11 cm. She was otherwise healthy
Journal of Cutaneous Medicine and Surgery
1­–3
© The Author(s) 2018
Reprints and permissions:
sagepub.com/journalsPermissions.nav
DOI: 10.1177/1203475418756376
https://doi.org/10.1177/1203475418756376
jcms.sagepub.com
and not on any other over-the-counter products, prescription
medications, or herbal products.
The patient was prescribed clobetasol propionate 0.05%
cream, which provided little improvement for the skin
lesions. Skin biopsies were performed on 2 of her patches on
the right thigh. The histopathologic findings, including the
presence of mild basal vacuolar changes and slight focal
parakeratosis in conjunction with the absence of necrotic
keratinocytes throughout all layers of the epidermis, sug-
gested a type of lichen planus, a drug eruption, or lupus ery-
thematosus (Figure 1B).
After her follow-up visit in November 2016, rosuvastatin
was discontinued, and she continued to apply clobetasol pro-
pionate 0.05% cream on her skin lesions. She returned for
follow-up on January 2017 and her skin lesions had resolved
(Figure 1C).
In April 2017, the patient was prescribed oral simvastatin
10 mg once daily as an alternative to rosuvastatin. Her skin
lesions recurred on the right thigh, and new lesions were seen
on the back, left flank, and oral mucosa (Figure 2A-D).
In May 2017, it was recommended that the patient discon-
tinue simvastatin. However, the patient’s cardiologist recom-
mended continuation of the medication. She developed more
numerous lesions on follow-up examination in July 2017.
Discussion
To date, case reports have described an association
between lichenoid drug eruptions with simvastatin, pravas-
tatin, fluvastatin, and lovastatin.2-6 Furthermore, Lareb, a
1
Faculty of Medicine, University of British Columbia, Vancouver, BC,
Canada
2
Department of Dermatology & Skin Science, Faculty of Medicine,
University of British Columbia, Vancouver, BC, Canada
Corresponding Author:
Youwen Zhou, Department of Dermatology & Skin Science, Faculty
of Medicine, 835 West 10th Avenue, 3rd Floor Academic Offices,
Vancouver, BC V5Z 4E8, Canada.
Email: youwen.zhou@ubc.ca
2 Journal of Cutaneous Medicine and Surgery 00(0)

Figure 1.  (A) Ill-defined, erythematous to grey telangiectatic patches on the right thigh with epidermal atrophy presenting while on
rosuvastatin therapy (September 29, 2016). (B) Dermatopathology findings suggestive of a type of lichen planus, a drug eruption, or lupus
erythematosus (September 29, 2016; hematoxylin and eosin stain). (C) Resolution of skin lesion upon discontinuation of rosuvastatin
therapy (January 25, 2017).

Figure 2.  (A-D) Ill-defined, erythematous to grey telangiectatic patches on the right thigh (recurrence), back, left flank, and oral mucosa
with initiation of simvastatin therapy (May 18, 2017).
Wong et al 3
pharmacovigilance centre based in the Netherlands, received
13 national reports of lichen planus or lichenoid dermatitis
associated with statin use during the period from July 18,
1996, to April 3, 2014.7 Of the 13 reports, 5 were associated
with atorvastatin and 8 associated with simvastatin.7 In addi-
tion, there has been a single reported case of fixed drug erup-
tion associated with atorvastatin use.8
Up to this present time, there have only been 2 reported
cutaneous findings in rosuvastatin. Oda et al9 recently
reported a maculopapular-type drug eruption due to rosuvas-
tatin in a 78-year-old woman presenting with generalized
erythematous eruption after starting rosuvastatin for 1 month.
Murad et al10 also reported pemphigoid induced by rosuvas-
tatin in a 58-year-old woman presenting with itchy blistering
eruption on her legs, without systemic involvement, after
starting rosuvastatin for 2 weeks. However, there has been no
report of lichenoid drug eruptions associated with rosuvas-
tatin use in the literature. We present a case of a drug reaction
to rosuvastatin with clinical and histopathologic findings that
suggest either a lichenoid or fixed drug eruption with recur-
rence following simvastatin therapy.
Delineating between lichenoid drug eruptions and fixed
drug eruptions can be challenging and relies on clinical fea-
tures and histopathological findings. Clinically, lichenoid
drug eruptions appear similar to lichen planus and generally
show focal parakeratosis, necrotic keratinocytes, mild basal
vacuolar changes, eosinophils in the infiltrate, and deep
perivascular infiltrate of lymphocytes.11 In contrast, fixed
drug eruptions uniquely recur at the same site each time the
offending drug is administered.11 Also, fixed drug eruptions
commonly demonstrate necrotic keratinocytes throughout
all layers of the epidermis, which was not observed in this
case.11
Rosuvastatin is the last remaining available statin to be
associated with lichenoid drug eruptions. As a result, there is
significant value in sharing our case associated with rosuvas-
tatin and simvastatin use. Our case also suggests there is
cross-reactivity between simvastatin and rosuvastatin, a type
1 and type 2 statin, respectively. Cross-reactivity has previ-
ously been reported between fluvastatin and rosuvastatin,
both of which are type 2 statins, and atorvastatin and simvas-
tatin, a type 1 and type 2 statin, respectively.6,8 It is conceiv-
able that clinicians may have favored prescribing rosuvastatin
in part due to its limited history of lichenoid drug eruption
along with its efficacy profile over other available statins
with documented reports of lichenoid drug eruptions.
Therefore, reporting the findings of lichenoid drug eruption
or fixed drug eruption in rosuvastatin use may aid the deci-
sion-making process for clinicians prescribing rosuvastatin.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, author-
ship, and/or publication of this article.
Declaration of Informed Consent
Verbal informed consent was obtained from the patient for her ano-
nymized information to be published in this article.
ORCID iD
Yuanshen Huang https://orcid.org/0000-0003-4603-1294
References
1. RxTx. https://www-myrxtx-ca.ezproxy.library.ubc.ca/search.
Accessed February 8, 2017.
2. Roger D, Rolle F, Labrousse F, Brosset A, Bonnetblanc
JM. Simvastatin-induced lichenoid drug eruption. Clin Exp
Dermatol. 1994;19(1):88-89.
3. Stoebner P-E, Michot C, Ligeron C, Durand L, Meynadier J,
Meunier L. Simvastatin-induced lichen planus pemphigoides [in
French]. Ann Dermatol Venereol. 2003;130(2, pt 1):187-190.
4. Keough GC, Richardson TT, Grabski WJ. Pravastatin-induced
lichenoid drug eruption. Cutis. 1998;61(2):98-100.
5. Pua VS, Scolyer RA, Barnetson RS. Pravastatin-induced lichen-
oid drug eruption. Australas J Dermatol. 2006;47(1):57-59.
6. Sebök B, Tóth M, Anga B, Harangi F, Schneider I. Lichenoid
drug eruption with HMG-CoA reductase inhibitors (fluvastatin
and lovastatin). Acta Derm Venereol. 2004;84(3):229-230.
7. Netherlands Pharmacovigilance Centre. Lareb. Statins and lichen-
oid drug eruption. 2014. https://databankws.lareb.nl/Downloads/
KWB_2014_3_statin1.pdf. Accessed February 8, 2017.
8. Huertas AJ, Ramírez-Hernández M, Mérida-Fernández C,
Chica-Marchal A, Pajarón-Fernández MJ, Carreño-Rojo A.
Fixed drug eruption due to atorvastatin. J Investig Allergol Clin
Immunol. 2015;25(2):155-156.
9. Oda T, Sawada Y, Yamaguchi T, et al. Drug eruption caused by
rosuvastatin. J Investig Allergol Clin Immunol. 2017;27(2):140-
141.
10. Murad AA, Connolly M, Tobin A-M. Rosuvastatin-induced
pemphigoid. BMJ Case Rep. 2012;2012:bcr1120115180.
11. Joshi R. Interface dermatitis. Indian J Dermatol Venereol
Leprol. 2013;79(3):349-359.