Am J Clin Dermatol (2014) 15:101113

DOI 10.1007/s40257-014-0067-7

REVIEW ARTICLE

Perioral Dermatitis: A Review of the Condition

with Special Attention to Treatment Options
Therdpong Tempark Tor A. Shwayder

Published online: 13 March 2014

Springer International Publishing Switzerland 2014

Abstract Perioral dermatitis is a common acneiform

facial eruption found in both adults and children. Its variants are periorificial and granulomatous periorificial dermatitis. The etiology of perioral dermatitis remains
unknown; however, topical corticosteroid use on the face
commonly precedes the manifestation of this condition.
There are an overwhelming number of treatment options
for perioral dermatitis, and the options in children are
slightly different from those in adults for both systemic
medications and topical treatment. This article provides a
literature review of the various applicable treatments
available based on the level and quality of the evidence by
the US Preventive Service Task Force. Oral tetracycline
reveals the best valid evidence. However, if the patient is
less than 8 years old, then this oral therapy may not be
suitable. Topical metronidazole, erythromycin, and pimecrolimus also represent effective treatment choices with
good evidence. Topical corticosteroid use is common in
these cases and the question of whether it is a good treatment or a cause remains unanswered. Corticosteroid cream
can improve the clinical picture, but there is a risk of
rebound when treatment is stopped. We propose a treatment algorithm to assist dermatologists, pediatric dermatologists, and general practitioners encountering this
condition.

T. Tempark (&)
Department of Pediatrics, Faculty of Medicine,
Chulalongkorn University, Sor Kor 11th Building,
Pathumwan, Bangkok, Thailand
e-mail: therdpmhu@yahoo.com
T. Tempark
T. A. Shwayder
Department of Dermatology, Henry Ford Hospital,
Detroit, MI, USA

1 Introduction
Perioral dermatitis is a chronic dermatosis that is usually
characterized by non-itchy, erythematous papules or papulopustules around the perioral area. If the lesions involve
perinasal and periorbital areas, the term periorificial dermatitis is often, but not always, used [1].
Perioral dermatitis is often found among women
between the ages of 16 and 45 years. However, it has also
been reported to occur among children between the ages of
7 months and 13 years [2]. The frequency of occurrence of
perioral dermatitis is not significantly different between the
sexes or between ethnic groups [3].
Because the knowledge and recognition of this
recalcitrant disease is potentially important, we
reviewed and summarized several articles, aiming to
enhance such literature, experiences, knowledge, and
recognition for the best and most appropriate management under the care of both dermatologists and general
practitioners.
1.1 Literature Review
The following databases were searched up to January 2014:
the US National Library of Medicine (PubMed), Ovid
MEDLINE, and Scopus. Search terms included perioral
dermatitis, periorificial dermatitis, and treatment of
perioral dermatitis.
The topic and abstracts of original articles, reports,
documents, and review articles in English, including male
or female patients of any ages or ethnic origins, were
screened and analyzed separately by the authors. Related
articles and reports on topics such as treatment of perioral
dermatitis or periorificial dermatitis were included and full
texts were reviewed.

102

T. Tempark, T. A. Shwayder

We found English references from Scopus (883), PubMed (428), and Ovid MEDLINE (266) databases; 88 articles were identified as related to our findings.

2 Pathogenesis/Etiology
The exact pathogenesis of this condition is unknown.
Topical corticosteroid use on the face commonly precedes
the manifestation of this condition [4], and risk factors
include long-term use of corticosteroids [5]. If perioral
dermatitis has been diagnosed, corticosteroid cream can
improve the clinical picture, but carries a risk of rebound
when the cream is stopped. It is not definitely known how
topical steroids may lead to perioral dermatitis. The presumptive pathogenesis is direct influence on the pilosebaceous unit or alteration of the follicular microflora, with a
subsequent increase in proliferation and metabolic activity
of infectious agents and skin biota [6, 7].
There is a long list of possible causes for perioral dermatitis such as infectious agents (Demodex spp. [2, 8],
Candida albicans [6], Fusiform bacteria [9]), medication
(topical corticosteroids [10], inhaled corticosteroids [11
13], oral corticosteroids [14], tacrolimus, pimecrolimus),
fluoride and anti-tartar toothpaste [15, 16], cosmetics/
moisturizers [17, 18], sunscreens [19], dental fillings [20],
orthognathic surgery [21], and chewing gum [22]. However, it should also be noted that there is another group of
factors associated with perioral dermatitis such as hormones (premenstrual flare, contraceptive pills, and pregnancy [2]), skin barrier dysfunction (atopic dermatitis) [23,
24], systemic corticosteroids in renal transplantation [25],
Crohns disease [26, 27], and myasthenia gravis [28].
Hence, it is reasonable to assume that perioral dermatitis is
a combination of the persons genes, environment, and
response to multiple different stimuli.

3 Clinical Presentation
Perioral dermatitis is characterized by a facial eruption of
erythematous papules, papulovesicles, and/or papulopustules around a narrow zone of the perioral area and sparingly around the vermilion border of the lips. Erythematous
papules and papulopustules may occur around the chin,
perinasal, and perioral area. The lesions are usually
accompanied by a diffused erythema and scaling. Burning
sensations have been reported in the literature to occur
more frequently than pruritus [29]. However, in our clinical
experience of more than 25 years, none of our pediatric
patients have reported a burning sensation. There is a wide
range of severity and chronicity in this disease.

Fig. 1 A 12-year-old Black female who has had perioral dermatitis

for the past 23 years. Note the monomorphic papular component
around the mouth, the side of the nose, and the inner eyelids of both
the upper and lower eyes

Fig. 2 A 6-year-old Hispanic male who has had perioral dermatitis

for the past year. More erythematous papules noted more prominently
around the mouth

A variant of perioral dermatitis is frequently detected

around the perioral, perinasal, and periorbital areas in
prepubertal children [30] (Figs. 1, 2), whereas extra-facial
granulomatous papules and typical periorificial papules
have been reported to occasionally occur around the neck,
trunk, extremities, and the genital area [30, 31]. Histopathology results indicate that the upper dermal and perifollicular granuloma are infiltrated by lymphocytes. Some
investigators term this variant as granulomatous periorificial dermatitis [32].

Perioral Dermatitis

Fig. 3 Biopsy from a patient clinically similar to the boy in Fig. 2,

taken from the chin. Pathology shows superficial perivascular mixed
inflammatory infiltrates with perifollicular accentuation

4 Histopathology
Histopathology examinations commonly show non-specific
inflammation with varied amounts of perifollicular or
perivascular lymphohistiocytic infiltration [2] (Fig. 3).
Perifollicular sarcoid-like granuloma and lymphocytic
infiltration [32, 33] are sometimes found in perioral
dermatitis.

5 Differential Diagnosis
The differential diagnosis for perioral dermatitis are the
facial dermatoses, which can be broken down into various
other forms such as acne, contact dermatitis, seborrheic
dermatitis, rosacea, sarcoidosis, eruptive syringoma, and
lupus miliaris disseminatus faciei (LMDF) [2, 3436].
Rosacea usually occurs in adults. The characteristics of
rosacea are facial erythema; telangiectasia; and flushing
papules and pustules around the cheeks, chin, and central
face (nasolabial area) [37, 38]. The nose and cheeks are the
most common sites afflicted. It is difficult to differentiate
granulomatous rosacea from sarcoidosis and granulomatous perioral dermatitis (GPD) [3941].
Sarcoidosis shares several features with rosacea. Physical examination reveals red-brown papules on the face and
lips. Sarcoidosis can also occur in the eye, causing uveitis,

103

retinitis, and keratitis. The lesions may even extend to the

neck and trunk area. This condition is often associated with
systemic findings such as fatigue, joint pain, weight loss,
and pulmonary symptoms [34, 38].
GPD is characterized by groups of papules, pustules,
and diffused erythema around the mouth, eyes, and nose in
prepubertal children. It may be difficult to differentiate this
from non-GPD by clinical findings alone. Histopathology
is needed in diagnosing this variant.
LMDF is a rare chronic caseating granulomatous condition with erythematous or flesh-colored papules distributed symmetrically across the eyelids, nose, upper lips, and
in the central area of the face [42]. The lesions can persist
for 12 years with spontaneous healing and often resulting
in scarring [34, 42]. However, it should be noted, that in
our experience, we have never witnessed scarring in children with perioral dermatitis. It should be noted that some
investigators have proposed that LMDF is the same as GPD
because of its clinical histopathology [34].
Facial Afro-Caribbean Eruption (FACE) is a sarcoidlike granulomatous dermatosis. This condition is often seen
in children with dark-colored skin. The characteristic feature is flesh-colored monomorphic papules in the perioral,
perinasal, and periocular area, particularly around the
upper eyelids and outer helix of the ears [43]. Histological
tests usually reveal a granulomatous infiltration that often
results in a differential diagnosis for sarcoidosis [44]. Some
investigators have proposed that FACE is a variant of
rosacea [43].
Table 1 details the different terminologies used for
perioral dermatitis and its variants.
An algorithm approach to investigate and manage perioral dermatitis is shown in Fig. 4.
History and physical examinations are the most helpful
tools in diagnosing perioral dermatitis. Additional investigations using potassium hydroxide (KOH), skin scrapings
for Demodex spp. [8], bacterial culture from pustular
lesions [9], patch testing for suspected allergens [45], and
skin biopsies are all optional and can be conducted at the
discretion of the attending physician.

6 Treatment
There are many treatment options available for perioral
dermatitis based on the theoretical etiologies of the disease.
However, most of the treatment protocols have mainly
been developed through trial and error.
Topical corticosteroids are often used as the first-line
therapy for perioral dermatitis. The one exception is in
patients whose perioral dermatitis developed while using
topical steroid creams. For these patients, the use of topical
steroid creams may be the cause of the disease, and

104

T. Tempark, T. A. Shwayder

Table 1 Differential diagnosis of perioral dermatitis and its variants

Term

Age group

Area involvement

Clinical features

Histopathology

Remarks

Perioral
dermatitis
(POD)

Children,
young
women

Perioral

Erythematous papules,
papulovesicles, and
papulopustules on
erythematous base

Perifollicular lymphocytic
infiltration, perivascular
infiltration

No scarring

Granulomatous
periorificial
dermatitis
(GPD)

Prepubertal

Perioral, perinasal,
periorbital, and/or
extrafacial

Dome-shaped
erythematous, yellowbrown papules (lack of
pustules)

Perifollicular granulomatous
infiltration is usually
detected on the upper half of
the body

Results in some
scarring

Lupus miliaris
disseminatus
faciei
(LMDF)

Adolescent,
adult

Symmetrical across
eyelids, nose, upper
lips (central area of
face)

Erythematous/fleshcolored papules

Perifollicular granulomatous
lymphohistiocytic
infiltration and occasionally
some neutrophils
The most characteristic
feature is the epithelioid cell
granuloma with central
caseated necrosis

Results in scarring

Perifollicular granulomatous
infiltration

No scarring
Some authors suggest
this is a variant of
rosacea

Facial AfroCaribbean
eruption
(FACE)

Black
children

Perioral, periorbital,
perinasal, especially
upper eyelid, outer
helix of the ear

Multiple, 13 mm in size

Flesh-colored
monomorphic papules
(no pustules, erythema,
comedone)

Often referred to as a
juvenile form of
rosacea

Some authors suggest

that this is a variant
of granulomatous
rosacea
Some authors suggest
this is a variant of
granulomatous
rosacea
Not related to
tuberculosis

Perioral lesion
Perioral dermatitis
(spare vermilion border)

Infection

-Demodex
-Candida
-Fusiform
bacteria

Scraping, KOH,
culture

Irritant / Allergy

-Topical CS/ Inhale CS

-Toothpaste: fluoride, tartar
-Cosmetics/Moisturizer
-Sunscreen
-Dental filling
-Orthognathic surgery
-Chewing gum

Patch test

Others: lip dermatitis, cheilitis

(involve vermilion border or commissure of lip)

Others

Idiopathic

-Hormonal factors
-Pregnancy
-Skin barrier
dysfunction: AD
-Drug :
contraceptive
pills, systemic CS

Allergic contact dermatitis

Irritant contact dermatittis

Atopy

Patch test /
Photo patch test

Avoid and
treatment

History taking

Avoid and
treatment

Treat atopy and 2nd

infection

Skin biopsy

Treat infection

Avoid suspected cause

Treat cause

Treatment

Fig. 4 Algorithm of approach, management, and investigation of perioral dermatitis. AD atopic dermatitis, CS corticosteroid, KOH potassium
hydroxide

discontinuation of the creams is recommended. We place

cause in quotation marks because whether topical steroids
cause or cure perioral dermatitis is unanswered in the literature (see below). It should be noted that, upon discontinuation of the topical corticosteroid, symptoms will

reappear within the first few weeks due to rebound flares.

Therefore, it is important to slowly reduce the use of the
topical corticosteroid over a span of several weeks to
prevent this rebound flare from occurring [46]. Aside from
topical corticosteroids, anti-tartar toothpastes have also

Perioral Dermatitis

been reported to aggravate perioral dermatitis [15, 16].

Even the paste itself and its occlusive effect have been
reported to somehow precipitate this eruption [18].
On the other hand, if topical contacts are suspected as
the cause of perioral dermatitis, then it is probably prudent
to discontinue all topical applications [2] including, but not
limited to, topical corticosteroids, cosmetics, moisturizers,
and sunscreens. Instead, the physician should recommend
that patients use bland emollients without any additives or
preservatives, if possible. It has been shown that occlusive
topical creams or ointments can sometimes somehow precipitate this eruption [18]. Lastly, two separate reports have
shown that topical corticosteroids used for the treatment of
atopic dermatitis caused the childrens perioral dermatitis
[24, 47].
Clinical trials evaluating different treatment protocols
for perioral, periorificial, and granulomatous periorificial
dermatitis are detailed in Tables 2 and 3. The level and
quality of the different treatment regimens are evaluated in
Table 4 based on the grading systems reported in the
documents issued by the US Task Force on Preventive
Health Care (retrieved 20 December 2013 from http://
www.uspreventiveservicestaskforce.org/uspstf/grade.htm).
Information such as the level and quality of the evidence
based on the study design, risks, and benefits of the medications were used to develop the grading scale shown in
Table 4.
6.1 Oral Tetracycline
Oral tetracycline is one of the treatments of choice for
perioral dermatitis. It is used in children older than 8 years
because it can severely stain developing teeth. The exact
mechanism of action is unknown.
The performance and efficacy of oral tetracycline has
been well documented. When oral tetracycline was compared with topical metronidazole in a prospective, doubleblind, randomized, multicenter trial, it was shown that oral
tetracycline was significantly more effective than topical
metronidazole [60].
Another prospective, randomized therapeutic study
compared the effectiveness of oral tetracycline to that of a
placebo, and showed that oral tetracycline was effective in
reducing the symptoms. In the same study, another antibiotic, topical erythromycin, was also compared with the
placebo and yielded the same results as the oral tetracycline. However, when oral tetracycline was compared with
topical erythromycin, it was shown that neither of the
antibiotics outperformed each other [62].
Many studies evaluated the performance of oral tetracycline used with other various topical medicines. All of
these studies showed a positive effect; however, because
there were many different variables in the mix, it was

105

difficult to definitively conclude whether oral tetracycline

outperformed the other medications. The common
denominator in all of the studies was oral tetracycline
(Table 2).
The dose of tetracycline varied from 250 mg twice daily
to four times daily [55] and 500 mg twice daily in severe
cases [42, 73]. The duration of the treatment varied
according to the response, which was usually around
48 weeks.
Adverse short-term effects (e.g. gastrointestinal upset,
diarrhea, and rarely photosensitivity) and long-term effects
(rare elevated liver function tests) should be discussed with
the patient thoroughly before initiating treatment.
6.2 Oral Erythromycin/Oral Macrolides
Pregnant women and pediatric patients are not allowed to
take oral tetracycline. In these cases, an alternative such as
oral erythromycin may be used. There are no efficacy data
for oral erythromycin from randomized controlled trials.
Nevertheless, several publications have reported the successful use of oral erythromycin. For example, Urbatsch
et al. [30] reported that oral erythromycin administered
concomitantly with another topical medication was effective in pediatric patients with extra-facial and generalized
granulomatous periorificial dermatitis. In another study,
oral erythromycin 250 mg administered two to three times
daily was less effective than tetracycline 250 mg administered twice daily, yet it still worked to some degree [78].
In two further studies, erythromycin 500 mg/day has been
reported to be effective [74]. The time to cure varied from
1 to 12 months [30, 74].
6.3 Oral Doxycycline/Oral Minocycline
Doxycycline and minocycline are second-generation tetracyclines. These medications exhibit greater bioavailability and absorption and broader anti-bacterial activity
than tetracycline [79]. Systemic medications have been
used in multiple dermatologic conditions, including acne,
acne rosacea, and perioral dermatitis.
A few cases have reported using minocycline [34] or
doxycycline [13] for the treatment of perioral dermatitis. It
is difficult to deduce the effectiveness of minocycline and
doxycycline because they were co-administered with other
topical medications. Cure time could not be ascertained, as
these studies were not randomized, double-blinded, placebo-controlled trials. Side effects of minocycline have
been reported to possibly include pseudotumor cerebri,
blue-gray hyperpigmentation, vertigo, and lupus-like syndrome in female patients. Doxycycline may cause gastrointestinal upset and esophageal irritation, especially when
taken as doxycycline hyclate.

Oral TET ? PL
Oral TET ? various
topicals

Oral TET

Oral TET ? topical CS

: Oral TET ? topicals

(56)
: Topical sulfacetamidesulfur-HC lotion (25)
: Various topicals (25)
Oral TET ? oral
CS ? topical CS

: Oral TET ? topical HC

(15)
: Oral TET ? topical
desonide (12)
: Topical HC (6)/desonide
(7)
Oral TET ? topical CS
Topical TET

Oral TET

Topical HC ? topical
ERY
Oral TET/ERY ? topical
HC
: Topical MET (54)
: Oral TET (54)

Report
Report

Report

Single blinded trial

Report

Report

Report
Report

Report

Series

Series

Randomized,
double-blinded,
multicenter

Report

Various topicals (MET,

ERY, HC)

Oral
antimalarials ? topicals

Report

Report

Regimen

Study design

9 months
6.5 years

1759
(median
35)

108

14

28

1833

32.2
1859

1861
(mean
45)
1545
(mean
22.6)

2.560
(median
29)

30

1148
(mean
26.4)

1839
(mean
27)
28

Age (y)

87

116

43
30

40

95 (11
lost to
F/U)

73

3
29

92

No. of
patients

Yes

[6 weeks

8 weeks

8 weeks

12 weeks

Yes

Yes

Yes

Yes

Yes
Yes

[612 weeks
4 weeks

8 weeks

No

Yes

No

Yes

Yes

Yes
Yes

No

Stop
CS

612 weeks

12 weeks

Several
months
25 weeks
(not clear)
[4 weeks

68 weeks
812 weeks

Not clear

Duration of
tx

No

No

No

No

No

No
No

No

No

Yes

No

No

No
No

No

Stop
cosmetic

Papule count
: Topical MET resolved in [8 weeks
: Oral TET resolved in 48 weeks
Resolved in 18 weeks (5 weeks)

Resolved in 812 weeks (12 weeks)

Resolved in 28 weeks (5 weeks)

Data not clear

: 80 % resolved in 528 days
: Half of the lesions resolved in 10 % of pts in
28 days
: 10 % discontinued medication
Resolved in [6 weeks

: Oral TET ? topical HC resolved in

\12 weeks
: Oral TET ? topical desonide resolved in
\12 weeks
: Topicalscompletely cleared

Resolved

: Oral TET ? topicals resolved in 10 days

4 weeks
: Topicalsdata not clear
: Various topicalsresolved in [4 weeks

Data not clear

Data not clear

Resolved
Resolved

93.5 % cleared

Endpoint/outcome

Duration of remission was

116 months after
completion of tx

Significant difference was

detected between two
groups

Repeated courses were done

for 8 pts
HC prevented flare from
rebounding

[61]

[60]

[59]

[58]

[46]

[56]
[57]

[55]

[54]

[53]

[52]

[51]

[49]
[50]

[48]

References

Moisturizing products were

indicated to cause the
disease

Various topicals were

alternatively used

63.2 % had no recurrence

after 423 months tx

Remark

Table 2 Different treatment regimens reported for perioral and periorificial dermatitis. If a paper utilized more than one regimen, the colon symbol (:) is used to represent each therapy or arm

106
T. Tempark, T. A. Shwayder

: Topical ERY (33)

: Oral TET (35)
: Oral PL (31)

Topical MET

Topical adapalene

Topical ERY ointment

(ERY, TiO2, talc,
paraffin, etc.)
Topical azelaic acid

Randomized

Series

Report

Series

: Topical PIM (20)

: Topical vehicle cream
(20)
: Topical PIM (60)
: Topical vehicle cream
(64)
Oral
doxycycline ? topical
clindamycin/MET
Topical MET
Topical azelaic acid

Oral cefcapene pivoxil

hydrochloride

Randomized,
double-blinded,
single-center

Report

1
10

124

40

14

10

10

6
312
(mean
7.7)
1037
25 weeks

16 weeks
48 weeks

8 weeks

4 weeks

[18

13

4 weeks

2 weeks

4 weeks

26 weeks

12 weeks

4 weeks

Yes

Yes
Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

3 weeks

16 weeks

Stop
CS

Duration of
tx

1870

22

1070
(mean
36.5)

877
(median
48)
3265

32

412

31
30
24

99

Age (y)

No. of
patients

Yes
Yes

Yes

Yes

No

Yes

Yes

Yes

No

Yes

Stop
cosmetic

Resolved in 25 weeks

Resolved
Resolved in 48 weeks (5.4 weeks)

PODSI score decreased for more than 50 % at

baseline
: Score topical PIM \ vehicle
Resolved

[50 % PODSI score decreased from baseline

: Score topical PIM \ vehicle

Resolved

Erythema or palpable lesions, mean clearance

of ALA PDT (92.1 %) [ topical
clindamycin (80.9 %)

Resolved in 26 weeks

Papule count resolved in 312 weeks

(5 weeks)

Resolved

Papule count
: Topical ERY resolved after 50 days
: Oral TET resolved after 40 days
: Oral PL resolved after 80 days
Resolved in 1224 weeks

Endpoint/outcome

Identify fusobacteria by using

tape-stripping toluidine blue
method

Mild PIH
No recurrence in 28 months
after tx completed

Assessed by PODSI
Significant difference
detected between 2 groups
Authors considered disease
caused by inhaled CS

Underlying CD
No recurrence in 4 months
after tx completed
Assessed by PODSI

No recurrence in
410 months after tx
completed
Significant difference
detected between 2 groups

[71]

[69]
[70]

[13]

[68]

[67]

[27]

[66]

[65]

[64]

[23]

[63]

[62]

Significant difference was

detected between 3 groups

No recurrence in 24 months
after tx completed
No recurrence in 8 months
after tx completed
Failure detected in 1030 %
who used topical tx

References

Remark

ALA PDT 5 aminolevulinic acid and photodynamic therapy, CS corticosteroid, CD Crohns disease, ERY erythromycin, F/U follow-up, HC hydrocortisone, MET metronidazole, PIH post-inflammatory
hyperpigmentation, PIM pimecrolimus, PL placebo, PODSI perioral dermatitis severity index, pts patients, TET tetracycline, TiO2 titanium dioxide, tx treatment
a
Periorificial dermatitis

Reporta
Seriesa

Report

Randomized,
double-blinded,
multicenter

Report

: ALA PDT (14 times/

week)
: Topical clindamycin
Topical PIM

Seriesselective
split face

Report

Regimen

Study design

Table 2 continued

Perioral Dermatitis
107

108

T. Tempark, T. A. Shwayder

Table 3 Different treatment regimens reported for granulomatous periorificial dermatitis

Study
design

Regimen

No. of
pts

Age (y)

Treatment
duration
(weeks)

Stop
CS

Stop
cosmetic

Endpoint/
outcome

Remark

References

Report

Multiple txs

311

Not clear

Spontaneously
resolved

[32]

Series

Oral ERY

910
(mean
9.5)

12

Resolved

FACE

[43]

Report

Oral isotretinoin

23

20

Resolved

Resulted in pitted,
atrophic scarring

[39]

No recurrence in
6 months after tx
completed
Report

Topical MET

7.7

14

Resolved

[72]

Report

Topical MET

12

Yes

Yes

Resolved

[44]

Series

Oral ERY/macrolide
? topical antibiotics/CS
(mixture of therapies no consistent regimens)

212

224

Resolved

Extrafacial and
generalized GPD

[30]

Report

Oral TET ? oral CS ?

topical clindamycin

12

[3

Resolved in
[3 weeks

[42]

Report

Oral
minocycline ? topical
TAC

11

Resolved

No recurrence in
2 months after tx
completed

[34]

Report

Oral TET ? topical MET

14

Yes

Resolved

No recurrence in
12 months after tx
completed

[73]

Report

Oral ERY

11

52

Resolved

[74]

Report

Topical TAC

11

[2

Resolved

[75]

Report

Oral ERY ? topical MET

16

Resolved

GPD with extrafacial

lesions

[76]

Report

Topical MET ? oral MET

Yes

Resolved

GPD

[77]

No recurrence in
12 months after tx
completed
CS corticosteroid, ERY erythromycin, FACE facial Afro-Caribbean eruption, GPD granulomatous periorificial dermatitis, MET metronidazole,
pts patients, TAC tacrolimus, TET tetracycline, tx treatment

6.4 Oral Isotretinoin

We found only one report on the use of isotretinoin for the
treatment of GPD [39]. This patient had tried various other
combination therapies with no success. As a result, the
investigator decided to prescribe 0.7 mg/kg/day isotretinoin for 20 weeks; after which the patient was cured of
GPD. However, the investigator pointed out that the results
obtained from isotretinoin could actually be due to the
spontaneous recovery of the patient who had received a
series of combination therapies. This patient had used oral
tetracycline for 5 months in combination with oral metronidazole for 2 months, and several other topical medications. Other medications the patient had tried were 2 %
erythromycin solution, 0.05 % tretinoin cream, and 5 %

benzoyl peroxide gel [39]. If the physician should decide to

prescribe isotretinoin to a patient, it is important to monitor
the long-term adverse effects, especially in sexually active
women regarding pregnancy and potential adverse effects
on the fetus.
6.5 Oral Cefcapene Pivoxil Hydrochloride
Only one report concerned the treatment of perioral dermatitis using cefcapene pivoxil [71]. Three Japanese
patients with this condition had been examined for Fusobacteria using the tape-stripping toluidine blue method
both before and after treatment. Fusobacteria was positive
before treatment and became negative within 3 weeks after
treatment with this medication. These patients showed

Perioral Dermatitis

109

Table 4 Authors evaluation of the different treatments available

according to the level and quality of evidence reporteda
Medication

Grades for level and

quality of evidence

Systemic medication
Tetracycline

IA

Erythromycin
Doxycycline/minocycline

II-3C
IIIC

Cefcapene pivoxil hydrochloride

IIIC

Isotretinoin

IIID

Topical medication
Metronidazole

IB

Erythromycin

IB

Pimecrolimus

IB

Clindamycin

II-3B

Azelaic acid

II-3B

Sulfacetamide/sulfur

II-3C

Tacrolimus

IIIB

Adapalene

IIIC

Corticosteroid

IIIC

Grading scales for levels of clinical service and evidence about the
effectiveness of the treatments were based on the documents issued
by the US Preventive Service Task Force (Retrieved 20 December
2013 from http://www.uspreventiveservicestaskforce.org/uspstf/
grades.htm)

a lot longer (16 weeks.) Higher concentrations of the

medication did not decrease the time to cure [63].
Generally, topical metronidazole was found to be less
effective than oral tetracycline [60] and therefore is used as
optional medication for the treatment of perioral, periorificial dermatitis in pediatric patients. The mean time to cure
varied from 8 to 16 weeks [44, 60, 63, 69, 72].
6.7 Topical Erythromycin
According to one randomized prospective therapeutic
study, 1 % topical erythromycin was effective after
7 weeks of use, whereas for oral tetracycline it was less
than 6 weeks [62]. Topical erythromycin was less effective
than oral tetracycline. In another report, 1.5 % topical
erythromycin solution was used concomitantly with topical
hydrocortisone valerate cream of 0.2 % to prevent acute
rebound flare of the disease while stepping down from
higher potency steroid creams [58]. The time to cure with
this combination therapy was 28 weeks (mean 5 weeks)
[58]. It should be noted that systemic oral erythromycin
had a greater efficacy than the topical treatment [78].
Having said this, topical erythromycin treatment is often
used as the first-line medication because it has no gastrointestinal side effects, unlike oral erythromycins.
6.8 Topical Clindamycin

improvement in 12 weeks and were cured after

25 weeks without adverse effects during treatment.
Cefcapene pivoxil hydrochloride, a b-lactam antibiotic,
is effective on Fusobacteria, which is presumed to be a
cause of perioral dermatitis. Although this report reveals
the effectiveness of this medication, further studies should
be performed in cases where tests for Fusobacteria are
absent or negative.

A few studies have investigated the use of topical clindamycin. Topical clindamycin is often used concomitantly
with oral antibiotics [13]. One report used topical clindamycin as the control medication for split face photodynamic therapy (PDT) [66]. The efficacy and mean cure
times were unclear from this article. The rationale for the
use of topical clindamycin for the treatment of perioral
dermatitis may have derived from its effectiveness in adult
rosacea patients.

6.6 Topical Metronidazole

6.9 Topical Pimecrolimus
The presumptive mechanisms of action for topical metronidazole for the treatment of perioral dermatitis are its
ability to suppress the activity of the bacterial skin flora,
and counter the activities of Demodex spp. and inflammation. The latter is by way of reducing hydrogen peroxide
into hydroxyl radicals [72]. Various concentrations
(0.752 %) and preparation forms of metronidazole (gel,
cream) have been investigated. Topical metronidazole has
been reported to be effective with or without oral medication. 1 % metronidazole cream used for 8 weeks was
shown to be effective [60]. Similarly, but at the lower
concentration of 0.75 %, metronidazole gel used for
14 weeks resolved the symptoms [72]. However, when a
higher concentration of 2 % was used, the time to cure was

Two 4-week randomized, double-blind, vehicle-controlled

(single and multicenter) studies showed that topical pimecrolimus was effective in improving the Finlays Dermatology Life Quality Index (DLQI) when the Perioral
Dermatitis Severity Index (PODSI) decreased more than
50 % compared with baseline [67, 68]. However, only the
results from the multicenter study showed statistical significance [68].
The presumptive pathomechanism of topical pimecrolimus is its ability to block the induction of pro-inflammatory cytokines by the nuclear factor of activated T cells
(NFAT). This blockage suppresses the T-cell responses to
proteins and inflammatory pathogens [67, 80]. Because of

110

this anti-inflammatory effect, and because it is a non-steroid-based cream, pimecrolimus is suitable as an optional
treatment for corticosteroid-induced perioral dermatitis
[68]. Pimecrolimus does not have an effect on Demodex
spp. nor does it have any vasoactive properties [81, 82].
Pimecrolimus is generally well tolerated. A small number
of patients have complained of a burning or smarting
sensation upon application [68].
6.10 Topical Tacrolimus
There were only two reports of topical tacrolimus in the
literature. One report was from a patient with granulomatous periorificial dermatitis [75]. In the other reported case,
the patient used topical tacrolimus concomitantly with oral
minocycline [34]. For both reports, the lesions resolved in
2 weeks when the topical tacrolimus was used and in
3 weeks if the topicals were used with oral antibiotics. The
presumptive mechanism of action is the same as that of
pimecrolimus.
6.11 Topical Adapalene
The rationale for the use of adapalene may derive from the
use of systemic oral isotretinoin for the treatment of
granulomatous periorificial dermatitis [39]. Jansen [23]
reported on the successful use of topical adapalene in a
patient with perioral dermatitis. The dermatitis resolved in
4 weeks.
This medication is a synthetic naphthoic acid derivative
that causes fewer skin irritations than retinoic acid. The
investigators suggested that the most likely pathomechanism of adapalene is its anti-inflammatory activity or
ability to interfere with the functions of polymorphonuclear
leukocyte and its arachidonic acid metabolism [23].
6.12 Topical Azelaic Acid
Two reports covered the use of topical azelaic acid, both
from open-label studies. One report was obtained from
adult patients with perioral dermatitis [65] and the other
from pediatric patients with periorificial dermatitis [70].
The cure time for the adult and pediatric patients were 26
and 48 weeks, respectively.
The exact mechanism of action of azelaic acid is
unknown, although it has been suggested that its antibacterial and anti-inflammatory effect and immunomodulatory
activity could prevent the neutrophilic pro-inflammatory
reactive oxygen species from being released [83]. As a
result of this suppression, inflammatory lesions and erythema disappeared [83].
The common adverse effects reported were transient
burning sensation, increased erythema, and scaling after

T. Tempark, T. A. Shwayder

application, especially in the first 2 weeks of treatment [65,

70]. Additional clinical randomized, double-blind, placebocontrolled and comparative studies are warranted to confirm the efficacy of this topical medication.
6.13 Topical Sulfacetamide and Sulfur
Sodium sulfacetamide 10 % and sulfur 5 % combination
is available as a cream, lotion, suspension, and cleanser.
The rationale for the use of this medication may derive
from its use for the treatment of acne, rosacea, and seborrheic dermatitis [8487]. One report had combined this
topical medication concomitantly with another topical
hydrocortisone lotion for the treatment of perioral dermatitis [53]. The efficacy of this combination could not be
ascertained.
The presumptive mechanism of sodium sulfacetamide is
its anti-microbial and anti-inflammatory properties [88].
Sulfur is known as a mild keratolytic agent [84]. The most
common side effect of this combination therapy is its
unpleasant odor. Serious side effects have not been
reported.

7 Summary and Recommendations

There were many reports for the treatment of perioral,
periorificial, and granulomatous periorificial dermatitis but
none of the medications appeared to be a clear winner in
completely curing the disease. Therefore, a practical
approach in treating perioral dermatitis should be established. First, the physician should try to ascertain whether
there are any aggravating factors involved that can be
teased out from the patients history. Oral tetracycline is
the first line of treatment for perioral dermatitis and its
variants for patients older than 8 years. According to the
grades, level, and quality of evidence, oral tetracycline
reveals the best valid evidence (randomized, double-blind,
multicenter, randomized report). The number of patients
in several studies increases the reliability of its efficacy.
However, if the patient is younger than 8 years, this oral
therapy may not be suitable. Instead, this regimen can
become problematic because of its usual side effects,
week upon week of dosing, and patient or parental fatigue
in administering oral medicines without obvious and
quick clearing of the skin. Topical metronidazole, erythromycin, and pimecrolimus are effective treatments (randomized, double-blind, multicenter/single center, case
series/report). These topical agents have been used alone
and/or combined with oral treatments in previous studies.
Hence, we recommend that physicians use topical treatments that have been evaluated to be effective and rotate
them every 68 weeks if the patient fails to respond. It is

Perioral Dermatitis

111

Fig. 5 Algorithm treatment of

perioral dermatitis based on our
evidentiary analysis of the
literature and our practice
experience in the clinic. ALA
PDT 5 aminolevulinic acid and
photodynamic therapy

Perioral dermatitis

Age < 8 years

Systemic treatment

Age

Topical treatment

- Non-Fluorinated
topical steroid

8 years

Systemic treatment

- Tetracycline

- Metronidazole
- Erythromycin

- Pimecrolimus

- Erythromycin

- Azelaic acid
- Clindamycin

- Erythromycin

- Tacrolimus
- Adapalene

- Doxycycline /
Minocycline

-Sulfacetamide /
Sulfur

- Spontaneous
recovery
- ALA- PDT
(5 aminolevulinic acid
photodynamic therapy)

not uncommon for many physicians to resort to using

several low-potency topical corticosteroids, topical
immune modulators, topical sulfurs, topical erythromycin,
topical clindamycin, topical metronidazole, and others in
succession. Oral erythromycin can certainly be used in
children.
In addition to discontinuing any possible items that may
aggravate the disease, appropriate care should be taken
according to the severity, age, sex, and individual concerns
of the patient. Above all, it is the duty of the physician to
reassure the patients at each visit that this condition is
neither infectious nor fatal. Based on our clinical experience and reported evidence-based treatment for perioral
dermatitis, we have developed a treatment algorithm that
we hope will assist physicians encountering patients with
this disease (Fig. 5).
Statement of Funding

None.

Conflict of Interest Disclosures Dr. Tor A. Shwayder: None.

Dr. Therdpong Tempark: None.

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