doi: 10.1111/1346-8138.

15695 Journal of Dermatology 2020; : 1–3

CONCISE COMMUNICATION
Treatment of pediatric periorificial dermatitis with topical
calcineurin inhibitor and topical/oral metronidazole
Hanjae LEE,1 Kyu Han KIM1,2,3
1
Department of Dermatology, Seoul National University College of Medicine, 2Institute of Human-Environment Interface Biology, Seoul
National University Medical Research Center, Seoul National University, 3Laboratory of Cutaneous Aging and Hair Research,
Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea

ABSTRACT
Pediatric periorificial dermatitis is a papulopustular eruption found around the facial orifices in children. Although
the treatment of the disease has been largely anecdotal and experience-based, studies have shown that topical
calcineurin inhibitors, as well as other topical and oral antibiotics, such as metronidazole, can be effective treat-
ment options. However, most of the studies with a sizable number of patients have been based on the Caucasian
population. Herein, we evaluated the clinical efficacy of topical calcineurin inhibitors and topical/oral metronida-
zole in 24 Korean patients with pediatric periorificial dermatitis. The majority of the patients showed a complete
response to treatment.

Key words: metronidazole, pediatric dermatology, pediatric periorificial dermatitis, perioral dermatitis,
topical calcineurin inhibitor.

INTRODUCTION received pimecrolimus 1% cream, and one received tacrolimus

Pediatric periorificial dermatitis (POD) is a facial eruption
characterized by erythematous to skin-colored papules and
papulopustules located around the facial orifices.1 It has been
reported in pediatric patients as young as 3 months, with a
slightly higher prevalence in girls.2 There have been anecdotal
cases where POD was successfully treated with topical/oral
metronidazole or oral azithromycin.3,4 Also, a recent retrospec-
tive study by Ollech et al.,5 reported that the majority of the 72
largely Caucasian patients with POD showed excellent response
to topical calcineurin inhibitors (TCIs) as the main therapy. In this
study, we evaluated the clinical efficacy of TCI and topical/oral
metronidazole in 24 Korean patients diagnosed with POD.
METHODS
A retrospective review of the electronic medical records was
conducted for patients diagnosed with POD at Seoul National
University Hospital between January 2016 and June 2020.
Among 37 patients identified, 24 were eligible for our study
based on the following inclusion criteria: (1) had sufficient pho-
tographic records for the evaluation of the baseline disease
severity and treatment response; (2) had at least one follow-up
visit after treatment was initiated. Among the 22 patients who
received TCI therapy, either as monotherapy or combination
therapy, 18 received tacrolimus 0.03% ointment, three
0.1% ointment. This study was reviewed and approved by the
Institutional Review Board of Seoul National University (IRB no.
1907-092-1048).
A severity index for adult perioral dermatitis has been pro-
posed,6 but there is no adequate severity index for POD to date.
The severity index for adult perioral dermatitis, which is based
on erythema, papules, and scaling, does not include the extent
of facial eruption as one of its scoring components. This index,
naturally, is appropriate for adult perioral dermatitis as the facial
eruption is generally confined to the lower half of the face,
around the mouth. On the contrary, periorificial dermatitis found
in pediatric patients frequently involves periocular areas and
sometimes even extra-facial areas. Therefore, we believe that
the extent of skin eruption is clinically more important in evaluat-
ing the severity of the disease in pediatric patients; we devel-
oped a new severity index for pediatric periorificial dermatitis on
a 7-point scale, based on erythema, type of lesions, and extent
of eruption (1–3 mild, 4–5 moderate, 6–7 severe; Table 1).
RESULTS
General characteristics
Of the 24 patients identified, 14 (58.3%) were male and 10
(41.7%) were female with the median age at diagnosis of
7.5 years (Table 2). Based on our severity index, 15 (62.5%)
patients had moderate to severe disease. The median

Correspondence: Kyu Han Kim, M.D., Ph.D., Department of Dermatology, Seoul National University College of Medicine, 101 Daehak-ro,
Jongno-gu, Seoul 03080, Korea. Email: kyuhkim@snu.ac.kr
Received 22 July 2020; accepted 20 October 2020.

© 2020 Japanese Dermatological Association 1

H. Lee and K.H. Kim

Table 1. Pediatric periorificial dermatitis severity index TCI combined with oral metronidazole or other systemic
antibiotics. Overall, five of the 14 (35.7%) patients, whose treat-
Parameter Points
ments were completed and stopped after achieving a complete
Erythema response, experienced a recurrence of the disease.
Mild or barely visible erythema 1
Moderate red erythema 2 Adverse events
Severe, violaceous, diffuse erythema 3
There was no severe side effect reported. One patient reported
Type of lesions
mild diarrhea after taking oral metronidazole, and the symptom
Few scattered papules 1
Multiple papules with occasional pustules and/or 2 was eliminated after the dosage was reduced from 500 mg per
crust day to 250 mg per day.
Disseminated, aggregated papulopustules with crust 3
Extent of eruption
DISCUSSION
All three periorificial areas extensively involved or 1
concurrent extra-facial manifestation presented Pediatric periorificial dermatitis includes several other variants
such as childhood granulomatous periorificial dermatitis
Severity as the sum of all points: 1-3 mild, 4-5 moderate, 6-7 severe. (CGPD) and lupus miliaris disseminatus faciei (LMDF).1 Nota-
bly, there has been a slight ambiguity among the diagnostic
treatment period was 5.5 months, and 14 (58.3%) patients
terms such as CGPD, LMDF, and perioral dermatitis in the lit-
showed a complete response to treatment while 10 (41.7%)
erature.7,8 However, ever since the term periorificial dermatitis
showed a partial response. Notably, the history of previous
was suggested as the most accurate terminology for the spec-
steroid therapy preceding POD was highly prevalent (62.5%).
trum of periorificial eruptions in children and adolescents by
Nguyen and Eichenfield,9 it has been adopted by multiple stud-
Treatment response
ies to describe the disease entity in the pediatric population.2,5
Among the 24 patients, 18 received either TCI, as well as topical
We also agree that the diagnosis of POD is more appropriate
and oral metronidazole (500 mg per day) or TCI and topical
for the array of periorificial dermatitis found in children, espe-
metronidazole only (Table 3). Five of the 12 (41.7%) patients
cially because a diagnosis such as CGPD requires a facial
who received oral metronidazole in addition to the two topical
biopsy,10 which parents, as well as physicians, often want to
agents had severe disease while only one out of the six (16.7%)
avoid. Also, specifying POD as CGPD via a histological analy-
patients who received TCI and only topical metronidazole had
sis, for example, does not necessarily change the treatment
severe disease. A small number of patients received either only
approach. Overall, most of our patients who were clinically
one of the two topical agents, topical and oral metronidazole, or
diagnosed with POD responded well to the empirical treatment
Table 2. General characteristics of the patients without the need to perform a biopsy.
The general characteristics of the patients in our study are
Characteristic Value mostly in line with the previous reports in terms of age, the preva-
Age, y (interquartile range) lent use of steroid preceding POD, and a high complete response
Median 7.5 (4.3–10.7) rate.2,5 Although there is no universal consensus on the treatment
Sex, n (%) of POD, studies have reported that topical and oral metronida-
Male 14 (58.3) zole,3 as well as TCIs can be good therapeutic options.11 In our
Female 10 (41.7) institution, we have adopted the two topicals, metronidazole and
Severity, n (%) calcineurin inhibitors, as the mainstay therapy and added oral
Severe 7 (29.2)
metronidazole when the disease was severe or the patient had a
Moderate 8 (33.3)
long history of POD, resistant to other treatment modalities. Both
Mild 9 (37.5)
Location at lesions, n (%) treatment regimens showed good results with the complete
All three orifices 18 (75.0) response rates of 66.7% and 58.3%, respectively. Although the
Two orifices 6 (25.0) complete response rate was slightly lower in the group where oral
Treatment period, m (range) metronidazole was used in addition to the two topical agents, the
Median 5.5 (1–24) lower rate was probably due to the target group having more
Treatment response, n (%) patients with severe POD. Overall, 13 of the 22 (59%) patients
Complete response 14 (58.3) who received TCI therapy as the main or part of the treatment
Partial response 10 (41.7) regimen achieved a complete response. Regardless of the treat-
No response 0
ment modalities, all the patients included in our study showed at
Recurrence, n (%) 5 (35.7)†
least a partial response, and of the 14 patients who achieved a
Previous steroid therapy, n (%)
Yes 15 (62.5) complete response, 5 (35.7%) experienced recurrence. Lastly,
No/Unknown 9 (37.5) there was no severe side effect reported except for transient diar-
rhea after taking oral metronidazole. In conclusion, based on our
†
Five patients out of the 14 patients who achieved a complete findings, we suggest TCI and topical/oral metronidazole as effec-
response. tive treatment modalities for POD.

2 © 2020 Japanese Dermatological Association

 Treatment of pediatric periorificial dermatitis

Table 3. Treatment response based on treatment regimen

Treatment response, n (%)

Severity, n
Complete Partial severe/ Recurrence, n
Treatment regimen response response Total moderate/mild (%)‡
TCI + TMZ + OMZ 7 (58.3) 5 (41.7) 12 5/3/4 3 (42.9)
(50.0)
TCI + TMZ 4 (66.7) 2 (33.3) 6 (25.0) 1/2/3 1 (25.0)
TCI + OMZ or other systemic 1 (50.0) 1 (50.0) 2 (8.3) 1/1/0 1 (100)
antibiotics†
TCI 1 (50.0) 1 (50.0) 2 (8.3) 0/1/1 0
TMZ + OMZ 0 1 (100) 1 (4.2) 0/1/0 0
TMZ 1 (100) 0 1 (4.2) 0/0/1 0
Total 14 (58.3) 10 (41.7) 24 (100) 7/8/9 5 (35.7)

Abbreviations: OMZ, oral metronidazole; TCI, topical calcineurin inhibitor; TMZ, topical metronidazole.
†
Roxithromycin was used as a systemic antibiotic, instead of metronidazole, in one patient.
‡
Recurrence from the patients who achieved a complete response.

Our study has limitations that are inherent to retrospective
observational studies with small sample size. Although we did
not find any statistically meaningful differences between the
patients with and without previous steroid therapy in terms of
treatment response, the baseline severity of the disease, and
the recurrence rate (data not shown), a study with a larger
sample size might yield different results. Also, given that the
study was performed at a single tertiary hospital, referral bias
may have overestimated the general severity of the disease.
Lastly, the severity index we developed is not validated yet.
Despite the limitations, our study provides meaningful evidence
that the favorable efficacy of TCI and topical/oral metronida-
zole for POD holds true for non-Caucasian patients as well.
Prospective, well-controlled future studies are warranted to
find the optimal combination therapy for POD.
ACKNOWLEDGMENTS: Funding sources: None
CONFLICTS OF INTEREST: None declared.
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© 2020 Japanese Dermatological Association 3