Management of Papulopustular Rosacea and Perioral Dermatitis With Emphasis on Iatrogenic Causation...

1/5/2014 Management of Papulopustular Rosacea and Perioral Dermatitis with Emphasis on Iatrogenic Causation or Exacerbation of Inflammatory Facial Derm…

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J Clin Aesthet Dermatol. Aug 2011; 4(8): 20–30. PMCID: PMC3168247

Management of Papulopustular Rosacea and Perioral Dermatitis with Emphasis on

Iatrogenic Causation or Exacerbation of Inflammatory Facial Dermatoses

Use of Doxycycline-modified Release 40mg Capsule Once Daily in Combination with Properly Selected Skin Care as an

Effective Therapeutic Approach

James Q. Del Rosso, DO, FAOCD

Dermatology Residency Program Director, Valley Hospital Medical Center, Las Vegas, Nevada; Clinical Professor (Dermatology), Touro University

College of Osteopathic Medicine, Henderson, Nevada; and Private Practice, Dermatology and Cutaneous Surgery, Las Vegas Skin & Cancer Clinics,

Las Vegas, Nevada and Henderson, Nevada

Corresponding author.

ADDRESS CORRESPONDENCE TO: James Q. Del Rosso, DO; E-mail: [email protected]

DISCLOSURE: Dr. Del Rosso serves as a consultant, researcher, and/or speaker for Allergan, Coria/Valeant, Galderma, Gracew ay, Intendis/Bayer,

LeoPharma, Medicis, Onset Dermatologics, Ortho Dermatology, Pharmaderm, Promius, Ranbaxy, TriaBeauty, Unilever, and Warner-Chilcott.

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Abstract

A variety of inflammatory facial dermatoses, such as papulopustular rosacea and perioral dermatitis, are

often idiopathic. However, prolonged continuous and/or repeated intermittent topical corticosteroid use can

exacerbate these disorders or, in some cases, induce them. This article discusses corticosteroid-induced

rosacea-like dermatitis and primary perioral dermatitis with regard to clinical presentations, including in both

adults and children, and management considerations. The rationale for use of an anti-inflammatory dose of

doxycycline that is subantimicrobial, doxycycline modified-release 40mg capsule once daily, along with

properly selected skin care, is discussed. Case illustrations are also included.

The category basket referred to as “common inflammatory facial dermatoses” comprises a diverse group of

disorders that includes acne vulgaris (AV), papulopustular rosacea (PPR), erythematotelangiectatic rosacea

(ETR), perioral dermatitis, seborrheic dermatitis (SD), and atopic dermatitis (AD). Despite some overlapping

visible features, these disorders are distinct in terms of clinical presentation and in their apparent pathogenic

mechanisms, although there may be some overlap of specific pathogenic pathways among some of these

disorders. In the case of eczematous dermatoses and seborrheic dermatitis, topical corticosteroid (TC) therapy

is an effective short-term approach to achieve rapid improvement, followed quickly by adjustment of its use

and discontinuation of application to avoid predictable adverse reactions associated with prolonged use.1

Nonsteroidal therapies also help to control flares and sustain remission.2 In the case of PPR, ETR, AV, and

perioral dermatitis, published treatment recommendations do not include use of a TC.3–9 In fact, it is

strongly suggested that these agents are best avoided for prolonged and frequently repeated facial use. Despite

initial visible improvement, prolonged use of TCs to the face, including intermittent repeated courses of

application, results in adverse outcomes that are predictable and often difficult to manage.4,8,10 These

adverse outcomes are well established in the literature and typically include exacerbation of several features

of the underlying dermatosis, rebound flaring after discontinuation of TC use (“red skin syndromes” and

“corticosteroid addiction and withdrawal”), and emergence of rosacea-like dermatitis induced by prolonged or

repeated episodes of TC application.4,8,10–13 The latter scenario often presents with symptomatic facial

erythema and a more intensified appearance of edematous inflammation and suffusion.4,8,10–13

For many of the common inflammatory facial dermatoses, such as AV, SD, AD, and PPR, there are multiple

studies supporting management recommendations, a reasonable body of scientific data on pathogenesis, and

some therapies that are approved by the United States Food and Drug Administration (FDA) for these

primary indications based on large-scale studies. However, for clinical presentations that are “rosaceaform” in

nature, such as corticosteroid-induced rosacea-like dermatitis (CIRD) and perioral dermatitis both with and

without a history of TC use, management is more dependent on “after-the-fact” case report collections,

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literature reviews, and anecdotal experience.5,7–11 In such cases, there is a conspicuous absence of

prospective clinical trials as well as an absence of large-scale pivotal studies, as no topical or oral agents are

FDA approved for these diagnoses as specific indications.5,7,9–11

Some cases of CIRD are clinically consistent with PPR or ETR that has been complicated by prolonged TC

use. If this historical scenario is confirmed, then the primary diagnosis is the initial PPR or ETR that was

erroneously treated with a TC, and the CIRD in such cases represents the secondary overlap of adverse effects

caused by repeated TC use. Figure 1 depicts an adult patient with a 10-year history of PPR who developed

CIRD secondary to chronic intermittent use of betamethasone dipropionate 0.05%-clotrimazole 1% cream

twice daily for three months followed by repeated courses of mometasone furoate 0.1% cream daily for six

months.

Figure 1

Topical corticosteroid-induced worsening of papulopustular rosacea

In other cases, CIRD is diagnosed without the ability to fully ascertain the primary diagnosis, although some

have reported that the most common initial diagnoses in patients with CIRD that prompted facial TC use

from the outset are AD, SD, and sometimes “dry skin” or rosacea.8,10,12,13 Perioral dermatitis and its variant

presentations (e.g., periocular dermatitis, perinasal dermatitis) may present as a clinical subset of CIRD or

may be idiopathic.8,9,11 Figure 2 illustrates a woman with perioral dermatitis who developed the perioral

subtype of CIRD induced by repeated courses of fluocinonide 0.05% cream twice daily over seven months.

Note the brisk inflammatory nature of the individual perioral papules and the more confluent infranasal foci

that were present bilaterally. Idiopathic perioral dermatitis has been described in adults and children without

a history of TC exposure on facial skin and is not uncommon. Figure 3 shows a woman with a two-month

history of idiopathic perioral dermatitis that was not responsive to treatment with metronidazole 0.75%

cream once daily for six weeks. Note the characteristic light pink hue of individual small papules and regions

of confluence, along with perivermillion sparing, as opposed to the more briskly inflamed and more swollen-

appearing papules of CIRD, which present more commonly with a red hue rather than “pink erythema.”

When encountering a patient with perioral dermatitis, it is important to recognize that topical exposure of

facial skin to a corticosteroid may occur not only during intentional application of TC-containing products,

but also unintentionally and insidiously during use of an inhaled corticosteroid for allergic airway disease

(e.g., asthma, allergic rhinitis). As many patients who develop CIRD have been reported to be atopic, this

history is not unlikely and requires an index of suspicion and directed questioning by the clinician to elicit this

potential cause of CIRD, including a presentation of perioral dermatitis associated with corticosteroid

exposure.10,12,13–15

Figure 2

Topical corticosteroid-induced worsening of perioral dermatitis

Figure 3

Idiopathic perioral dermatitis

A variety of therapeutic approaches have been suggested in the literature for patients with rosaceaform facial

eruptions and/or perioral dermatitis associated with TC use and for perioral dermatitis not associated with TC

exposure. As there is a dearth of prospective scientific evidence to support a consensus approach to these

distinct clinical disorders, much of what dermatologists do to manage these disorders is based on “recycled

dogma” derived from lectures or articles, or in many cases, spoken to the clinician from within their own

mind. Either way, we do our best to manage these disorders based on our best understanding from the

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information and experiences that we have, and from this we subliminally develop strong belief systems on

how to best manage such cases. This is simply human nature; however, each of us needs to maintain an open

mind as additional information or new perspectives may sometimes provide opportunities to modify how we

manage specific disorders and improve therapeutic outcomes with greater consistency.

In this article, the author suggests a simplified and practical management approach to both facial CIRD and

idiopathic perioral dermatitis based on his assessment of the best evidence from current publications and

clinical experience. A common theme of the management approach for these disorders is the concept of first

“priming the skin,” a concept initially presented by the author at the 2010 Fall Clinical Dermatology

Conference in Las Vegas, Nevada. Case studies will be used to illustrate important points felt to be worthy of

emphasis. Although it is recognized that cutaneous side effects associated with prolonged TC use can occur at

sites other than the face, this article specifically discusses facial involvement, which is the anatomic site most

commonly affected by CIRD.

CORTICOSTEROID-INDUCED ROSACEA-LIKE DERMATITIS (CIRD)

The untoward effects of prolonged and repeated TC use on facial skin have been thoroughly documented in

the literature and the clinical presentations of these effects have been well described in both adults and

children. 8,10,12–21 In many cases, the diagnosis of CIRD is made without knowledge of the initial diagnosis

that led to facial application of the TC in the first place. In other cases, the TC is used erroneously to treat PPR

or ETR leading to emergence of TC-exacerbated rosacea, which most simulates severe PPR. However, the

papular and erythematous components of the eruption tend to be more diffuse rather than predominantly

centrofacial. The designation CIRD will be used to describe both circumstances, although in some cases the

patient had PPR or ETR initially. Prolonged TC use can also exacerbate or induce perioral dermatitis, which if

associated with TC use is one of the subtypes of CIRD. Importantly, CIRD is categorized as an adverse drug

reaction pattern, and is not felt to be a clinical subtype or variant of rosacea.4,10,22,23

TC potency and development of CIRD. It is generally accepted that the risk for development of CIRD

correlates with TC potency, although CIRD may occur in association with prolonged use of TCs of any

potency ranking, including hydrocortisone 1%.10,12,13,20 CIRD may also occur after prolonged application

of both halogenated and nonhalogenated TCs.

Duration of TC application associated with CIRD. CIRD has been noted to occur over a broad range of

treatment durations, and CIRD may develop after a minimum of two months of TC application. However, in

many cases, six months or more of facial application of a TC has been noted prior to the development of

clinically evident CIRD.10 In another report, the duration of TC use associated with CIRD ranged from 3 to

480 months, with most cases occurring over 1 to 2 years of TC use.24

Clinical presentation of CIRD. Three subtypes of CIRD have been described based on anatomic location—

perioral, centrofacial, and diffuse.10 The perioral subtype is the most common presentation of CIRD

involving the face, has been noted in both adults and children, and represents a common subset of perioral

dermatitis.8,10 Children commonly present with perioral dermatitis, with or without perinasal and/or

periocular involvement.10,23 However, perinasal involvement, often misdiagnosed as SD, may be the only

anatomic site affected initially in many children. Figure 4 depicts an 11-year-old girl with CIRD presenting as

perinasal dermatitis, a clinical variant of perioral dermatitis that occurs without perioral or periocular

involvement. This eruption developed after repeated courses of application of mometasone furoate 0.1%

cream over a duration of 10 months. CIRD is reported to occur more commonly in female patients (72%),

often with a history of atopy (67%).24

Figure 4

Topical corticosteroid-induced perinasal dermatitis in an 11-year-old girl

CIRD is reported to occur more commonly in female patients (72%), often with a history of atopy (67%).24

It has been suggested that patients with PPR or ETR are more susceptible to CIRD.4 Patients with CIRD

often complain of sensitive or painful skin that is symptomatic, as typified by complaints of burning, stinging,






pruritus, or dryness.8,10 The primary lesions of CIRD are small flesh-colored, pink or red (most common)

papules, pustules, and/or papulovesicles (pseudovesicles) that often exhibit a perilesional flare of erythema.10

Areas of confluence are also commonly noted. Perivermillion sparing is common overall, but is not always a

complete finding. The eventual sequelae of resolved papules is erythema, which is persistent and edematous,

with a propensity to become more diffuse.10,12,13 Telangiectasias and deeper follicular papules and nodules

progressively increase with prolonged duration and/or continued episodes of TC use.

The perioral dermatitis subset of CIRD is the most common presentation in both adults and children (

Figure 2).8,10,21,23 In some cases, perinasal (Figure 4) and/or periocular involvement (Figure 5) is also

observed. The centrofacial subtype of CIRD involves the inner cheeks, lower eyelids, nose, and medial

forehead including the glabellar region, with usual absence of perioral involvement.10 In the diffuse subtype,

the entire face is involved with extension onto the neck a common finding (Figure 1).10,12,13

Figure 5

Topical corticosteroid-induced periocular dermatitis

Differential diagnosis of CIRD. Facial skin disorders that are to be considered in the differential diagnosis

of CIRD include idiopathic PPR or ETR, corticosteroid-induced acneiform eruptions, chronic cutaneous lupus

erythematosus (LE), systemic LE, sarcoidosis (simulant of CIRD with granulomatous changes),

polymorphous light eruption, tinea faciei (especially tinea incognito secondary to TC use), lupus miliaris, and

dermatomyositis. Most can be differentiated by clinical characteristics, history, physical examination, and

laboratory testing, including histological findings when the need for a skin biopsy is clinically applicable.8,10

Diagnosis of CIRD is based on clinical suspicion, history, and physical examination.8,10,12,13 There are no

confirmatory laboratory tests that definitively support the diagnosis of CIRD, and histological findings are not

specifically diagnostic.4,8,10,12,13

Clinical course of CIRD. The development and progression of CIRD is consistent among affected

patients.10,12,13,24 CIRD typically begins with either self-treatment with OTC hydrocortisone or a

prescription TC for a variety of possible underlying disorders. After initial clearance, the underlying disorder

flares within a few weeks, which leads to restarting of the TC. The repeated cycles of flaring and restarting of

TC therapy continues to lead to more frequent flaring with repeated episodes of TC application. Eventually,

the efficacy of TC application diminishes, sometimes leading to physicians increasing the potency of the TC or

prescribing systemic corticosteroid therapy.24 As the eruption progresses, symptoms of burning, stinging, and

itching increase in regularity and severity.10,24 Over time, the visible presentation of CIRD progresses,

usually associated with increased intensity of inflammation and erythema. The clinical subtype correlates

primarily with the facial locations where repeated intentional or insidious TC application occurs.

Pathogenic mechanisms of CIRD. Several cutaneous abnormalities occur as a result of TC exposure

based on studies completed in both human and animal models.25–28 Alterations in epidermal structure and

the permeability barrier of the epidermis have been associated with TC use, including decreased density and

maturation of lamellar body formation, downregulation of epidermal lipid synthesis-related enzymes,

decreased epidermal cellular layers, and reduced size of keratinocytes. Other epidermal and dermal changes

include thinning of the stratum corneum with loss of “basket-weave” appearance, diminution of the granular

layer, increased transepidermal water loss (TEWL), delayed response and recovery of permeability barrier,

decreased dermal collagen and mucopolysaccharide synthesis, thinning of upper dermal elastin fibers, and

reduced epidermal lipids including ceramides.26–28 In patients with CIRD and an underlying AD history,

additional innate stratum corneum abnormalities associated with AD and atopic skin are present, including a

decrease in specific ceramide subfractions and other lipids, and in some cases fillagrin gene mutations leading

to a decrease in natural moisturizing factor.29–31 In addition, increased facial TEWL has been noted as an

inherent characteristic of perioral dermatitis, ETR, and PPR, with atopic diathesis suggested as a possible risk

factor for development of perioral dermatitis.32 Signs and symptoms characteristic of facial skin sensitivity

inherent to untreated PPR have been documented, including dryness (65–69%), scaling (51–57%), edema

(32–38%), pruritus (49–52%), burning (33–36%), stinging (29–34%), and pain/discomfort (17–21%). Male

and female patients with rosacea find several skin care and personal use products to be irritating based on

large-scale surveys.6,33–35









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Chronic TC application leads to several functional and biological changes within the skin, which alter

cutaneous response. Reduction in collagen and elastin synthesis leads to degradation of dermal matrix with

reduced structural support for superficial vasculature leading to cutaneous vasodilation, which is visible

clinically as telangiectasias and diffuse erythema.4,10,12,13,26–28 TC-induced alterations in the normal

homeostatic balance of chemical mediators, which modify cutaneous blood flow, appears to be a major factor

in the pathogenesis of CIRD.10,12,13 The predominant force in creating symptomatic exacerbations of CIRD

that follow discontinuation of TC application appears to be release of accumulated cutaneous endothelial

nitric oxide stores leading to exaggerated dilatation of cutaneous vessels.10,12,13,24 Endothelial nitric oxide

(eNO), also referred to as endothelium-derived relaxing factor, is an endogenous vasodilator that is markedly

inhibited by glucocorticosteroids, including with TC application.24 During TC application, vasoconstriction

occurs, and release of eNO is inhibited. As a result, eNO accumulates and is stored. Upon discontinuation of

TC use, there is a surge of eNO release, which results in vascular “hyperdilation.” As a result, rebound flaring

with suffusion occurs characterized by brisk erythema, edema, and symptoms of discomfort—stinging,

burning, and pruritus.10,24 The repeated offset and onset of nonphysiological storage and release of eNO

creates what has been described as a “trampoline effect” or “neon sign” effect, ultimately resulting in

persistent vasodilatation as a sequelae of repeated episodes of vasoconstriction-vasoldilatation.12

PERIORAL DERMATITIS NOT ASSOCIATED WITH TOPICAL CORTICOSTEROID USE(IDIOPATHIC PERIORAL DERMATITIS)

As noted above, perioral dermatitis may be a subset of CIRD or can occur in the absence of previous TC

use.8–10 This disorder is estimated to affect female patients in 90 percent of cases, usually between the ages

of 20 to 45 years, although male patients may be affected.8,9 Occurrence in children has been noted without

an apparent gender predominance, with a variety of designations and variants described, such as Gianotti-

type perioral dermatitis, rosacea-like eruption of childhood, granulomatous periorificial dermatitis of

childhood, or facial Afro-Caribbean childhood eruption (FACE).21,23,36 Some reports in children and adults

include both the perioral subset of CIRD and cases of idiopathic perioral dermatitis. The granulomatous form

of perioral dermatitis (periorificial granulomatous dermatitis) is more commonly seen in African-American

children and may be associated with TC use, with both perioral (Figure 6a) and periocular involvement (

Figure 6b) noted in some cases.8 Perioral dermatitis is not classified as a subtype of rosacea despite clinical

similarities to PPR and response to many of the same therapeutic agents.4,22

Figure 6a

Periorificial granulomatous dermatitis in an 8-year-old Filipino girl

associated with repeated application of a mid-potency topical

corticosteroid over several months and occasional oral prednisone use:

perioral involvement

Figure 6b

Same patient as Figure 6a: Periocular involvement

Many potential etiologies of idiopathic perioral dermatitis have been suggested, including fluorinated

toothpaste, overuse of “heavy” cosmetic creams and moisturizers (e.g., petrolatum or paraffin-based

products), emotional stress, and microbiological factors. However, all of these suggested etiologies are

speculative, and none of these factors have been shown to be definitively causative.8

Clinical presentation. Idiopathic perioral dermatitis typically presents as small, discrete, pink-to-red

papules, papulovesicles, and less commonly pustules involving the perioral region. The lesions tend to form a

complete or partial circumoral ring of involvement, with a characteristic rim of perivermillion sparing (

Figure 3).8,9 Individual papules sometimes exhibit a microvesicular appearance, although the lesions are

solid. The primary lesions of idiopathic perioral dermatitis most commonly exhibit a characteristic pink color,

with areas of confluence commonly noted, and fine scaling sometimes present (Figure 7). Perinasal and/or

periocular involvement is sometimes present. Figures 8a–8c depict a nine-year-old girl with idiopathic

nongranulomatous perioral dermatitis involving multiple facial sites. In children, especially preteens,

perinasal involvement is often the only affected location, at least initially, and is frequently misdiagnosed as

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SD and erroneously treated with a TC. Figure 9 depicts an 11-year-old boy with idiopathic perioral dermatitis

presenting only with perinasal involvement. In some children, idiopathic nongranulomatous perioral

dermatitis often presents as noninflamed micropapular lesions, which, in some areas, may simulate lesions of

molluscum contagiosum.

Figure 7

Idiopathic perioral dermatitis with scaling

Figure 8a

Perioral dermatitis (idiopathic): Perioral involvement in a nine-year old

half-African American and half-Mexican girl not associated with topical

corticosteroid use

Figure 8c

Same patient as Figures 8a and 8b: Perinasal involvement

Figure 9

Perinasal dermatitis in an 11-year-old boy. Such cases are commonly

misdiagnosed as seborrheic dermatitis and are often erroneously treated

with a topical corticosteroid.

Figure 8b

Same patient as Figure 8a: Periocular involvement

Patients with untreated perioral dermatitis have been shown to exhibit higher levels of centrofacial TEWL

than patients with ETR and PPR, and an atopic history has been suggested as a potential predisposing

factor.32 The increased TEWL, reflective of an impaired permeability barrier, accounts at least partially for

the tendency of the facial skin of patients with perioral dermatitis to be easily irritated by several contactants,

such as skin care products and topical medications.6,33,35

MANAGEMENT OF CORTICOSTEROID-INDUCED ROSACEA-LIKE DERMATITIS ANDIDIOPATHIC PERIORAL DERMATITIS

Although there are important distinctions between CIRD, including the perioral subset, and idiopathic

perioral dermatitis, certain common characteristics suggest that a unified management plan is likely to be

efficacious. However, the time course of response may be more prolonged in CIRD.10,12 Importantly,

depending on the duration and severity of CIRD, rebound flaring once TC use is discontinued may result in

the need for continued support and encouragement and a longer course of therapy.8 In CIRD, to reduce the

intensity of rebound, some authors suggest tapering the frequency of TC use or “step down” to a lower

potency TC. However, there is no support for this approach other than anecdotal suggestion.10 Some authors,

including the author of this article, do not suggest this “tapering” approach and recommend abrupt

discontinuation of all TC application to the face and “working through” rebound flares—the so called “cold

turkey” approach.8,12,13,24

Medical therapy options. Several therapies, including oral antibiotics (e.g., tetracyclines), topical

antibiotics (e.g., erythromycin, clindamycin), topical metronidazole, topical azelaic acid, topical

sulfacetamide-sulfur, and topical calcineurin inhibitors (e.g., tacrolimus, pimecrolimus), have been used with

some success to treat perioral dermatitis, including the perioral CIRD subset, although cutaneous irritation

may be problematic in some patients treated with topical agents.4,5,8–11,36 For CIRD, some authors have

recommended the use of tacrolimus as the preferred topical agent; however, exacerbations may occur, and

the body of data supporting this approach is limited.

















Topical therapy considerations. Overall, the author agrees with the suggested “null therapy” approach to

the topical management of idiopathic perioral dermatitis.8 In addition, the author suggests this same

approach in the management of CIRD. Essentially, it is strongly recommended to limit as much as possible

what is applied to the skin, including both skin care products and topical medications, especially over the first

few weeks of treatment.8 Avoidance of soaps, astringents, abrasives, and patient-selected skin care products is

an important component of this approach, as the epidermal permeability barrier is perturbed in both CIRD

and in idiopathic perioral dermatitis, and facial skin is exquisitely sensitive.

Oral therapy considerations. Despite the absence of well-controlled clinical trials, among the available

therapeutic agents used to treat perioral dermatitis, the tetracyclines appear to be consistently efficacious.8,9

Additionally, as eNO appears to be an important mediator in the pathogenesis of at least the vascular

component of CIRD, the ability of tetracyclines to inhibit NO production, along with several other direct anti-

inflammatory properties, supports their role in the treatment of CIRD.37–40 As there is no definitive

evidence that a bacterium is causative in the etiology of either CIRD or PPR, the author has used the same

subantimicrobial dosing that is FDA-approved for PPR—doxycycline-modified release (MR) 40mg, one

capsule daily—to treat both CIRD and idiopathic perioral dermatitis with consistent success anecdotally. This

dosing regimen has been shown to exhibit anti-inflammatory activity without producing antibiotic selection

pressure or emergence of antibiotic-resistant bacterial strains, including with chronic administration over

nine months or greater.41–43

Although a comprehensive understanding of the pathophysiology of these disorders is not currently known,

certain features may be taken into account when considering treatment options. In both CIRD and idiopathic

perioral dermatitis, addressing repair of the altered permeability barrier of the stratum corneum and

reduction of increased TEWL is significant in order to reduce associated skin sensitivity, erythema, and

propensity for secondary inflammation.5–7,32,44,45 The ability of tetracyclines to inhibit many pathways of

inflammation (e.g., reduction in activity of reactive oxygen species, downregulated expression of some matrix

metalloproteinases, decreased serine protease activity, decreased eNO production) also seems to correlate with

therapeutic benefit in CIRD and idiopathic perioral dermatitis, as has been noted with PPR in both clinical

and basic science studies.4–7,37–41,43 In CIRD, inhibition of the altered vascular response produced by

episodes of eNO production, storage, and release appears to be a relevant component of the mode of action of

tetracyclines, as discussed above.10,12,13,24

Conceptual and rational approach to management. The major components of the management

approach used by the author in both CIRD and idiopathic perioral dermatitis are 1) “priming the skin” with

management of skin care for the outset, 2) consideration of the need for and selection of topical therapy after

skin priming, and 3) use of doxycycline-MR 40mg once daily from the outset. Although a controlled study

has not yet been initiated, the author has regularly used this approach for the past two years with consistent

success in the vast majority of cases, with experience in more than 50 adult and pediatric patients to date

with perioral dermatitis, CIRD, and PPR over the past 18 months.

Priming the skin. Due to innate permeability barrier impairment of the stratum corneum and facial skin

sensitivity associated with both CIRD and idiopathic perioral dermatitis, taking control of fundamental skin

care is a “rate-limiting step” in achieving a favorable therapeutic outcome. As it is difficult to fully know the

magnitude of permeability barrier impairment in patients at baseline, or be fully informed of their actual skin

care practices despite what they tell us, dermatologist-directed skin care is recommended to “reset” the

permeability barrier from the start of treatment, an approach the author refers to as “priming the skin.” That

is, you as the clinician direct the status of their epidermal permeability barrier from the start as an integral

part of the overall management of their facial problem. The patient is instructed to disband other cleansers

and moisturizers, astringents, facial scrubs, and any procedures, such as exfoliation procedures (e.g., facials,

superficial peels) or microdermabrasion, during treatment of their current disorder. Photoprotection with use

of a dermatologist-selected sunblock and avoidance of ultraviolet light exposure as much as possible is

recommended.

How is priming of the skin carried out by the patient? Priming the skin is done by incorporating a

gentle nonmedicated cleanser and moisturizer without initial use of topical medication for the first 3 to 5

days. In idiopathic perioral dermatitis, the addition of topical medication is often not needed, as oral therapy

alone is almost always sufficient. In CIRD, after initially priming the skin with gentle skin care, use of a

topical agent can then be initiated with less potential for cutaneous irritation. Priming the skin allows for this



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by first improving the functional integrity of the epidermal permeability barrier by incorporating proper skin

care from the outset of management and by removing any patient-directed improper skin care approaches

that augment damage to the stratum corneum and potentiate skin sensitivity. Also in CIRD, all TC agents are

discontinued abruptly so initial rebound flares are anticipated. The author has observed overall that the

frequency of rebound flares appears to be less, and the flares that do occur seem blunted in intensity with the

initial “priming” approach. However, marked rebound may still occur and facial sensitivity to even gentle skin

care products may be present in some cases, especially with intensely inflamed CIRD.

Selection of topical therapy. There is no single topical medication definitively shown to be most effective

in either idiopathic perioral dermatitis or CIRD. Topical options discussed in the literature include

metronidazole, azelaic acid, clindamycin (aqueous-based formulation), sulfacetamide 10% lotion,

sulfacetamide 10%-sulfur 5% formulations, and calcineurin inhibitors.9–1,36 The author most currently uses

only controlled skin care alone in combination with oral therapy from the outset for idiopathic perioral

dermatitis and has tried this approach in some cases of CIRD with success, including the perioral subtype and

in cases of PPR complicated by CIRD. In most cases of CIRD, the author initiates priming of the skin and

oral therapy from the outset. After five days of this regimen, proper skin care is continued along with oral

therapy, and in many cases a topical agent is added. The author has the most experience with adding either

topical sulfacetamide 10% lotion, azelaic acid 15% gel, or metronidazole 1% gel. However, there are no well-

controlled studies to differentiate the therapeutic impact or relative benefits among these topical therapies in

CIRD or perioral dermatitis. Available data are primarily anecdotal and based on small studies and case

report series.9–11,36

Selection of oral therapy. Oral tetracycline agents, including tetracycline, doxycycline, and minocycline,

exhibit anti-inflammatory properties that appear to contribute to their efficacy in disorders such as PPR and

perioral dermatitis.5,9,11 The author has elected to use doxycycline-MR 40mg once daily for treatment of

CIRD and idiopathic perioral dermatitis as anti-inflammatory activity is preserved with absence of antibiotic

selection pressure.37,39,41–43 In addition, doxycycline-MR 40mg once daily has been shown to be as

effective in reducing inflammatory lesions in PPR as doxycycline 100mg daily, with a markedly lower risk of

gastrointestinal side effects.46 None of the subjects treated with doxycycline-MR 40mg once daily in this

study experienced abdominal pain, nausea, vomiting, or diarrhea. Additionally, none of the female subjects

(n=185) actively treated for PPR in the two phase III pivotal trials with doxycycline-MR 40mg once daily

developed vaginal yeast infections.43 This latter factor is important as the majority of patients with CIRD and

perioral dermatitis are females.8,10,12,13,24

ILLUSTRATIVE CASE STUDIES

The following cases illustrate clinical presentations of CIRD and idiopathic perioral dermatitis with focus on a

simplified management approach selected to address underlying pathophysiological abnormalities occurring

in these disorders.

Case 1. A 22-year-old healthy, white, female college student presented with a three-month history of

erythematous papules with occasional pruritus on the chin and inner cheek region bilaterally. She related no

history of TC use and has no history of any skin disorders other than mild acne in her early teen years. She

did admit to picking at her facial lesions and recently had used a facial scrub along with an OTC benzoyl

peroxide (BP) product. Examination revealed erythematous papules on the inner cheeks and chin with some

light red diffuse erythema and diffuse scaling. Excoriated papules were also noted (Figure 10a). The diffuse

erythema and scaling was felt to be caused by cutaneous irritation from the facial scrub and/or the BP

product. A diagnosis of idiopathic perioral dermatitis was made. A diagnosis of acne vulgaris was also

considered, but was excluded clinically based on the “overall gestalt,” which took into account the absence of

comedones and other acne lesion types on the face and trunk, the monomorphic nature of the primary

lesions, and the distribution pattern of the eruption. Irritant dermatitis secondary to inappropriate skin care

and OTC treatment was also noted. The patient was treated with a ceramide-based gentle cleanser, a

ceramide-based physiological lipid moisturizer cream, and doxycycline-MR 40mg capsule once daily. One

month later, there was definite improvement with marked reduction in inflammatory lesions, absence of

pruritus, and absence of scaling and background erythema (Figure 10b). The patient was very pleased with

the results, and treatment was continued for four more weeks. No adverse reactions were reported or

observed.





Figure 10a

Perioral dermatitis before treatment in a 21-year-old white woman with

obvious visible signs of cutaneous irritation (diffuse erythema, scaling)

caused by overly aggressive skin care, and multiple secondarily

excoriated inflammatory papules

Figure 10b

Perioral dermatitis one month after use of a ceramide-based gentle

cleanser, a ceramide-based physiologic lipid moisturizer cream, and

doxycycline-MR 40mg capsule once daily. Note the clearance of diffuse

redness and scaling attributed to the change to ...

Case 2. A 50-year-old Caucasian male insurance agent presented with a two-month history of pink

erythematous pinpoint papules and papulopustules noted within a background of confluent pink erythema

involving the lateral third of the left upper and lower eyelid and the left lateral canthus (Figure 11a). The right

periocular region was minimally affected. A mild stinging sensation was noted intermittently. No other areas

of involvement were present. The patient had not used any TCs or other prescription or OTC topical

medications on the face, and there was no history of use of any prescription or OTC ophthalmic products. The

patient did not wear goggles of any type or contact lenses, and there was no history of this type of periocular

or facial eruption occurring in the past. Previous medical history was unremarkable except for hyperlipemia

treated for the last six years with atorvastatin 20mg daily and allergic rhinitis treated with cetirizine 10mg

daily. A diagnosis of idiopathic periocular dermatitis (variant of perioral dermatitis) was made. The patient

was treated with a gentle cleanser and moisturizer and doxycycline-MR capsule 40mg once daily. One

month later, the eruption was completely clear and no further therapy was needed (Figure 11b). No adverse

reactions were reported or observed.

Figure 11a

Periocular dermatitis before treatment in a 50-year-old white man

Figure 11b

Same patient as Figure 11a at one month after treatment with a gentle

cleanser and moisturizer and doxycycline-MR 40mg capsule once daily

Case 3. A 42-year-old white female office manager presented with a 10-year history of PPR that was treated

intermittently in the past with “an oral antibiotic” and sulfacetamide 10% lotion twice daily with some

success. Approximately nine months ago, her facial eruption flared extensively on the cheeks, forehead, and

chin. She saw a new physician who initially prescribed betamethasone dipropionate 0.05%-clotrimazole 1%

cream twice daily for three months. During this time, the eruption cleared, but would recur within 7 to 10

days of stopping treatment. Her medication was then changed to mometasone furoate 0.1% cream daily used

in repeated courses for six months to control flares. However, the patient noted that the flares became more

frequent, the eruption more extensive, and her skin became more sensitive with symptoms of burning and

itching over this six-month time period. Ultimately, the eruption became unresponsive to the TC treatment

she was repeatedly using.

On examination, multiple discrete papules and pustules were noted diffusely on the cheeks, jawline, anterior-

lateral neck, and central forehead with surrounding erythema (Figures 12a and 13a). The patient was treated

with a ceramide-based gentle cleanser, a prescription ceramide-based topical emulsion, and doxycycline-MR

40mg capsule once daily. After two months, marked improvement was noted with a decreased number of

inflammatory lesions, reduction in erythema, and clearance of symptoms (Figures 12b and 13b). The patient

stated she was very pleased with her response to therapy. Treatment was continued and no adverse reactions

were reported or observed.


















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Figure 12a

Topical corticosteroid-induced worsening of papulopustular rosacea before treatment in a

42-year-old white woman

Figure 12b

Marked improvement noted at two months after treatment with a

ceramide-based gentle cleanser, a prescription ceramide-based topical

emulsion, and doxycycline-MR 40mg capsule once daily

Figure 13a

Topical corticosteroid-induced worsening of papulopustular rosacea

before treatment in a 42-year-old white woman

Figure 13b

Marked improvement noted at two months after treatment with a

ceramide-based gentle cleanser, a prescription ceramide-based topical

emulsion, and doxycycline-MR 40mg capsule once daily

CONCLUSION

CIRD involving facial skin and idiopathic perioral dermatitis are two common inflammatory facial

dermatoses that have not been well studied prospectively with regard to treatment. Although there are

differences in the time course of response, and CIRD is associated with a propensity for rebound flaring, both

entities are responsive to a simple regimen involving “priming the skin” with appropriate skin care and use of

doxycycline-MR 40mg capsule once daily. This oral therapy approach provides anti-inflammatory effects

without antibiotic activity, thus avoiding the emergence of antibiotic-resistant bacterial strains.39–43 In

addition, doxycycline-MR 40mg capsule once daily is associated with a markedly lower risk of

gastrointestinal side effects as compared to an immediate-release formulation of doxycycline 100mg once

daily based on a comparative study.46 Anecdotal experience supports this therapeutic approach for CIRD and

idiopathic perioral dermatitis, which was conceptualized based on an understanding of apparent pathogenic

factors and clinical experience in managing such cases.

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Management of Papulopustular Rosacea and Perioral Dermatitis With Emphasis on Iatrogenic Causation...

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