CASE REPORT

Rosaceiform dermatitis associated with topical

tacrolimus treatment
Shoko Fujiwara, MD, Yukari Okubo, MD, Ryokichi Irisawa, MD, and Ryoji Tsuboi, MD
Tokyo, Japan

We describe herein 3 patients who developed rosacea-like dermatitis eruptions while using 0.03% or
0.1% tacrolimus ointment for facial dermatitis. Skin biopsy specimens showed telangiectasia and
noncaseating epithelioid granulomatous tissue formation in the papillary to mid dermis. Continuous
topical use of immunomodulators such as tacrolimus or pimecrolimus should be regarded as a potential
cause of rosaceiform dermatitis, although many cases have not been reported. ( J Am Acad Dermatol
2010;62:1050-2.)

Key words: rosaceiform dermatitis; tacrolimus treatment.

steroid-aggravated rosacea and perioral dermatitis.7

L ong-term topical corticosteroid therapy for

facial eruptions is widely known to cause
rosacea-like symptoms or perioral dermatitis,
manifested as epidermal atrophy, telangiectasia, er-
ythema, and erythematous papules and pustules.
Discontinuation of topical steroids results in sudden
aggravation of symptoms.1 The histologic features of
this condition are epidermal atrophy, spongiosis,
and a lymphohistiocytic infiltrate surrounding the
follicular infundibulum. Telangiectasia and granu-
lomatous inflammation are frequently found.2
Corticosteroids are a well-known cause of skin
atrophy and telangiectasia.2 The pathogenesis of
steroid-induced rosacea is multifactorial. The immu-
nosuppressive effects of corticosteroids facilitate an
overgrowth of bacteria, which may act as superan-
tigens to form follicular granulomatous lesions.3
Tacrolimus ointment, an immunosuppressive
macrolide, has been used for various skin diseases
such as atopic dermatitis, seborrheic dermatitis,
asteatotic eczema, contact dermatitis, psoriasis, and
oral lichen planus.4,5
Numerous clinical trials have demonstrated the
relative efficacy and safety of topical tacrolimus over
corticosteroids in the treatment of moderate to
severe atopic dermatitis.6 Recent observations indi-
cate that tacrolimus is also effective in ameliorating
From the Department of Dermatology, Tokyo Medical University.
Funding sources: None.
Conflicts of interest: None declared.
Reprint requests: Yukari Okubo, MD, Department of Dermatology,
Tokyo Medical University, 6-7-1 Nishi-Shinjuku, Shinjuku-ku,
Tokyo 166-0023, Japan. E-mail: yukari-o@tokyo-med.ac.jp.
0190-9622/$36.00
ª 2009 by the American Academy of Dermatology, Inc.
doi:10.1016/j.jaad.2009.01.029
The deciding factor in the choice of this ointment in
various diseases is the predominantly inflammatory
nature of the lesions, combined with the ineffective-
ness of other standard topical therapies. Tacrolimus
inhibits cytokine transcription and activation of T
cells by binding to FK506 binding protein and
blocking calcineurin phosphatase activity, resulting
in reduction of cytokines from helper T cells and
histamine from skin mast cells.4 Unlike topical
steroids, tacrolimus does not induce skin atrophy
and telangiectasia.
In this report, we describe 3 patients who devel-
oped rosacea-like granulomatous lesions while us-
ing tacrolimus ointment for facial dermatitis.
CASE REPORT
Case 1
A 57-year-old Japanese man with perioral ery-
thema unresponsive to various topical ointments
was treated with 0.1% tacrolimus and showed rapid
improvement 1 year before his most recent consul-
tation. Approximately 2 months before returning to
our clinic, he experienced a relapse with slight
erythema and extensive pustulation. Physical exam-
ination at this time revealed diffuse edematous
erythema and milia-sized erythematous papules in
the perioral area (Fig 1, A). Demodex folliculorum
mites were not detected in the affected area, and a
patch test for tacrolimus produced negative find-
ings. A skin biopsy specimen showed telangiectasia
in the papillary to mid dermis and a perifollicular
lymphohistiocytic infiltrate with noncaseating epi-
thelioid granulomas around the follicles (Fig 1, B).
Discontinuation of tacrolimus treatment and the
resumption of minocycline therapy (100 mg/d)

1050
J AM ACAD DERMATOL
VOLUME 62, NUMBER 6
Fig 1. A, Diffuse edematous erythema and milia-sized red
papules. B, Noncaseating epithelioid granulomas around
follicles.
triggered a relapse with intense erythema and
numerous pustular lesions after 1 week. After 2
months, however, the affected area improved with
only slight erythema, although the red papules were
still visible.
Case 2
A 48-year-old Japanese woman with a 2-year
history of pruritic erythema on the face and neck
was treated intermittently with steroid ointments and
0.1% tacrolimus ointment without improvement.
Although she was treated with 0.03% tacrolimus
ointment for the previous 4 months, the eruption
worsened. When she visited our hospital, she
presented with pruritic erythema, red papules, pus-
tules, and telangiectasia on the cheeks, neck, and
upper aspect of her chest (Fig 2, A). A smear of the
pustules on her cheeks revealed an abundance of
D folliculorum mites, although a patch test for
tacrolimus ointment produced negative findings.
Case report 1051
Fig 2. A, Red papules, pustules, and telangiectasia on
cheeks and neck. B, Telangiectasia in papillary dermis and
epithelioid granulomas around follicles.
A biopsy specimen of tissue from her neck showed
telangiectasia in the papillary to mid dermis and
noncaseating epithelioid granulomas around the
follicles (Fig 2, B). Tacrolimus was discontinued,
and the flareup resolved after treatment including
topical zinc oxide ointment and systemic minocy-
cline (100 mg/d).
Case 3
A 71-year-old Japanese woman, previously trea-
ted for rosacea using topical hydrocortisone butyrate
and systemic minocycline (200 mg/d), had been
prescribed 0.1% tacrolimus ointment for 2 months
before her visit. An acute flareup manifested as 2- to
3-mm diameter red papules with intense erythema
1052 Case report
Table I. Histologic features of 8 cases of rosaceiform dermatitis cased by topical tacrolimus
Year Author Age, y/sex Epithelioid granulomas
2003 Bernard et al10 54/F
2004 Yajima et al8 52/F
60/F
2005 Kakurai et al13 46/M
2006 Koizumi et al14 37/F
2010 Current study 57/M
48/F
71/F
F, Female; M, male.
on the cheeks and chin. A skin biopsy specimen
showed mild epidermal atrophy, telangiectasia, and
small noncaseating epithelioid granulomas in the
papillary dermis. The facial rash significantly im-
proved with oral roxithromycin (300 mg/d) for 2
months, and did not recur after discontinuation of
the therapy.
DISCUSSION
In this report, the continuous use of topical
tacrolimus was identified as the cause of rosacea-
like symptoms, previously defined as one of the
major side effects of the long-term use of topical
corticosteroids. In all of 3 cases, replacement of
topical tacrolimus with systemic minocycline or
roxithromycin resolved most of the symptoms.
We reviewed 24 cases of rosaceiform dermatitis
(including the current 3 cases) reported in the
literature that occurred after the use of topical
tacrolimus.8-14 Seventeen cases have been reported
in Japan, 6 in Switzerland, and one in the United
States. Four patients were men and 20 were women.
The average age was 47.5 years (range: 27-71 years).
The period of tacrolimus use was 10 days to 23
months. Smears of the pustules revealed an abun-
dance of D folliculorum mites in 12 of 20 patients.
The immunosuppressive properties of tacrolimus
might facilitate the overgrowth of follicular
D folliculorum mites and bacteria in susceptible
patients. Skin biopsy specimens taken in 8 cases,
including the current cases, showed telangiectasia
and noncaseating epithelioid granuloma formation
in the papillary to mid dermis. Epidermal atrophy
appeared in only one case (Table I). The absence of
skin atrophy is a noteworthy fact because, unlike
corticosteroids, tacrolimus ointment does not cause
skin atrophy.8
We view rosaceiform dermatitis as an iatrogenic
skin disease that results from facial application of
ointments with immunosuppressive properties.
Although only few cases of rosaceiform dermatitis
J AM ACAD DERMATOL
JUNE 2010
Epidermal atrophy Telangiectasia
1 Not mentioned 1
1 e 1
1 e 1
1 e e
1 Not mentioned Not mentioned
1 e 1
1 e 1
1 1 1
caused by tacrolimus ointment have been reported
thus far, caution should be exercised in the long-term
use of it and other topical immunomodulators for the
treatment of facial skin disorders.
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