Perioral (periorificial) dermatitis

INTRODUCTION — Perioral dermatitis (POD), also known as periorificial dermatitis, is a skin disorder that typically presents with multiple small, inflammatory papules around the mouth, nose, or eyes (picture 1A-L). Although the name "perioral dermatitis" suggests a primarily eczematous condition, POD most often resembles an acneiform or rosacea-like eruption with or without associated features of a mild, eczematous dermatitis.

The pathogenesis of POD is poorly understood; both intrinsic factors and extrinsic factors, such as irritants and topical corticosteroids, may contribute to this disorder. Topical anti-inflammatory agents and topical or systemic antibiotics constitute the major pharmacologic treatment options (algorithm 1).

The clinical features, diagnosis, and management of POD will be discussed here. The differential diagnosis of disorders that present with inflammation of facial skin is reviewed separately. (See "Approach to the patient with facial erythema".)

TERMINOLOGY — POD was first described in 1957 under the moniker "light sensitive seborrheid" [1]. Since then, an association with light exposure has largely been discounted [2,3]. In 1964, "perioral dermatitis" was introduced as the preferred term to refer to this disease [4]. Some authors have advocated for utilization of the term "periorificial dermatitis," a name that reflects the various potential sites of POD [5,6]. (See 'Clinical manifestations' below.)

EPIDEMIOLOGY — POD occurs worldwide and in individuals of all racial and ethnic backgrounds. Although women between the ages of 16 and 45 constitute the vast majority of patients affected by POD, POD may also occur in older individuals, men, and children [7,8].

Childhood POD often occurs in young children. A retrospective study of 222 children with POD seen at an academic dermatology department found an average age of presentation of 6.6 years [9]. POD may develop in infants as young as three months of age [9]. Girls may be slightly more likely to develop POD than boys. In a retrospective study, 46 of 79 children and adolescents with POD (58 percent) were female [5].

ETIOLOGY AND PATHOGENESIS — The pathways that lead to the development of POD are not well understood. Deficiencies in skin barrier function and features of atopy have been detected at increased frequency in patients with POD [10,11]. Although it is conceivable that these factors could augment the risk for persistent cutaneous inflammation after exposures to external irritants [10-12], a definitive role for skin barrier dysfunction and atopic diatheses in POD has not been established.

Topical corticosteroid use is frequently reported in association with POD, with the classic history being a papular and slightly scaly facial eruption that initially improves with topical corticosteroid use, but recurs or worsens with continued use or attempts to discontinue corticosteroid therapy [2,5,13,14]. Whether topical corticosteroids are capable of inducing POD during treatment of unrelated facial dermatoses or whether they may simply exacerbate preexisting POD remains uncertain. Reports vary widely on the proportion of patients who recount a history of topical corticosteroid therapy [2,5,11,15,16].

Despite the uncertainty in the specific role of corticosteroids in POD, there appears to be a connection between POD and topical corticosteroid use, particularly with potent formulations. There is an impression that fluorinated topical corticosteroids are particularly likely to contribute to POD, which may be related to their high potencies, rather than a specific effect of fluorination [2,17,18]. Further support for a contributory role of corticosteroids arises from reports of POD that developed after the administration of oral [19,20] or inhaled corticosteroids [21,22].

The reason for an association between POD and corticosteroids remains unclear. Some authors have suggested that corticosteroid-induced damage to the epidermal barrier may be a contributing factor [7].

In addition to topical corticosteroids, several other factors have been proposed as potential contributors to POD, including fluoridated toothpaste, skin moisturizers and cosmetic products, fusobacteria, Candida albicans, hormonal fluctuations in women, and oral contraceptive therapy [2,3,13,23-28]. Whether these factors truly contribute to the development of POD is uncertain [2,15]. During the coronavirus disease 2019 (COVID-19) pandemic, there have been reports of increased mask use resulting in skin conditions often confused with POD, such as acne, rosacea, and dermatitis [29,30]. This may be due to changes in the local microbiome of the skin under occlusion [31].

CLINICAL MANIFESTATIONS

Classic perioral dermatitis — POD typically manifests as multiple 1 to 2 mm, clustered, erythematous papules, papulovesicles, or papulopustules with or without mild scale (picture 1A-L). In some patients, features consistent with a mild, eczematous dermatitis are also present. Occasionally, the eczematous component is prominent.

The inflammatory papules and scaling of POD occur most frequently in the perioral region, but a narrow zone around the vermilion border of the lip is usually spared [3]. Less often, the perinasal and periorbital areas are sites of significant involvement (picture 1K-L). In a retrospective study of 79 children and adolescents with POD, perioral, perinasal, or periocular lesions were present in 70, 43, and 25 percent of patients, respectively [5]. Lesions in these classic locations may also be accompanied by lesions in other areas, such as the cheeks, chin, forehead, and neck [5].

POD may be asymptomatic or may be accompanied by mild to moderate stinging or burning sensations in the affected areas [7]. The skin lesions usually resolve without scarring.

Granulomatous periorificial dermatitis — Granulomatous periorificial dermatitis represents a clinical variant of POD that typically occurs in prepubescent children [32-35]. Children typically develop numerous small, flesh-colored, red-brown, or yellow-brown, inflammatory papules in perioral, perinasal, or periocular areas (picture 2). Papulopustules and papulovesicles are typically absent, and, occasionally, sites other than the face are affected [36,37].

Disease course — POD is generally considered a benign and self-limited disorder. In some patients, POD resolves within a few months without pharmacologic therapy, while in others, the disorder may persist for several years [38].

Topical corticosteroid use may contribute to the chronicity of POD. Although improvement may be noted early in the course of corticosteroid treatment, continued use may perpetuate or exacerbate the disorder [2,5]. (See 'Elimination of corticosteroids and irritants (zero therapy)' below.)

DIAGNOSIS — The diagnosis of POD can usually be made via assessment of the patient history and recognition of the classic clinical features. The presence of multiple small, inflammatory papules, papulovesicles, or papulopustules clustered on the perioral, perinasal, or periocular skin suggests this diagnosis (picture 1A-L). The following additional findings also support a diagnosis of POD:

●Sparing of the skin immediately adjacent to the vermilion border of the lip

●Coexisting features of eczematous dermatitis

●Burning or stinging sensations

●Recent use of topical, nasal, or inhaled corticosteroids

●History of disease flares after topical corticosteroid withdrawal

●Absence of comedones (comedones are a manifestation of acne vulgaris)

Skin biopsies are rarely necessary, but a small punch biopsy (eg, 3 mm punch) can be used to differentiate POD from other disorders when the diagnosis is uncertain. The histopathologic findings of POD are nonspecific and vary with the type of lesion biopsied: Scaling, eczematous-appearing areas show parakeratosis, epidermal spongiosis, and mild acanthosis, and biopsies of papules typically exhibit perifollicular and perivascular lymphocytic infiltrates. Biopsies taken from lesions of granulomatous periorificial dermatitis demonstrate epithelioid granulomas that resemble those found in granulomatous rosacea [39-41]. (See "Approach to the patient with facial erythema", section on 'Biopsy' and "Rosacea: Pathogenesis, clinical features, and diagnosis", section on 'Granulomatous rosacea'.)

Serologic studies are not useful for confirming a diagnosis of POD. A potassium hydroxide (KOH) or mineral oil scraping may be helpful if infection is under consideration, specifically from fungus or Demodex mites, respectively. (See 'Differential diagnosis' below.)

DIFFERENTIAL DIAGNOSIS — Multiple other skin disorders may present with inflammatory eruptions around the mouth, nose, or eyes. Examples include the following:

●Acne vulgaris – Acne vulgaris is a common disorder that manifests as comedones and inflammatory papules or pustules (picture 3A-B). Although the detection of comedones on the skin supports a diagnosis of acne vulgaris, acne vulgaris and POD may coexist. Unlike acne vulgaris, scarring is uncommon in POD. (See "Pathogenesis, clinical manifestations, and diagnosis of acne vulgaris", section on 'Clinical manifestations'.)

●Rosacea – Papulopustular rosacea presents with inflammatory papules and pustules that are primarily distributed on the central face (picture 4). Centrofacial erythema and telangiectasias may also be present. A predilection for the cheeks rather than periorificial sites suggests a diagnosis of papulopustular rosacea. In the absence of other findings consistent with rosacea, lesions of granulomatous rosacea may be impossible to distinguish from granulomatous periorificial dermatitis. (See "Rosacea: Pathogenesis, clinical features, and diagnosis".)

●Seborrheic dermatitis – Seborrheic dermatitis is a common inflammatory condition that frequently presents with erythema and scale involving the perinasal skin (picture 5). Scaling macules and patches are typically present. In contrast to POD, small papules are not a typical feature of seborrheic dermatitis, and a perioral distribution is unusual in seborrheic dermatitis. The detection of seborrheic dermatitis in other commonly affected sites, such as the scalp, eyebrows, nasolabial folds, and chest, can be useful for diagnosis. (See "Seborrheic dermatitis in adolescents and adults".)

●Allergic contact dermatitis – Allergic contact dermatitis is a manifestation of a type IV hypersensitivity reaction to agents that come in contact with the skin. Patients may present with inflammatory papules, vesicles, weeping, or crusting (picture 6). The distribution of lesions is dependent upon the specific sites of contact with the inciting agent. Unlike POD, intense pruritus is usually present, scale is often prominent, and lesions fail to improve with antibiotic therapy. (See "Clinical features and diagnosis of allergic contact dermatitis".)

●Irritant contact dermatitis – The clinical findings of irritant contact dermatitis vary based upon the nature of the external insult and site of involvement. Papules, vesicles, scale, erythema, or edema may be seen. Unlike allergic contact dermatitis, but similar to POD, a burning sensation, rather than pruritus, is often the predominating symptom. The patient history is of value for identifying this diagnosis. As an example, irritant dermatitis related to chronic lip-licking behavior can resemble POD (picture 7). (See "Irritant contact dermatitis in adults".)

●Impetigo – Impetigo is a common staphylococcal or streptococcal skin infection that most frequently occurs in children. The perinasal skin is a common site for involvement. Erosions, vesicles, and yellow crusts may be present (picture 8). Scaling and acne-like papules are uncommon. Gram stains and bacterial cultures can be used to confirm this diagnosis. (See "Impetigo".)

●Dermatophyte infections – Tinea corporis and tinea barbae may present with inflammatory papules or pustules on the face (picture 9). Unlike POD, dermatophyte infections almost always have an asymmetrical distribution. A potassium hydroxide (KOH) preparation is useful for diagnosis. (See "Dermatophyte (tinea) infections" and "Office-based dermatologic diagnostic procedures", section on 'Potassium hydroxide preparation'.)

●Demodex folliculitis – Demodex folliculitis often presents as multiple monomorphic, facial papules, refractory to common antibiotics (picture 10). A KOH or mineral oil preparation can demonstrate numerous Demodex mites on microscopy (picture 11). (See "Infectious folliculitis", section on 'Demodex folliculitis'.)

●"Maskne" – Respiratory mask-related exacerbations of other common facial dermatoses, such as acne, rosacea, seborrheic dermatitis, and folliculitis, have been reported. (See "COVID-19: Cutaneous manifestations and issues related to dermatologic care", section on 'Personal protective equipment-induced skin injury'.)

Less common causes of facial lesions that may exhibit features suggestive of POD include respiratory mask-related exacerbations of common facial dermatoses (eg, acne vulgaris, rosacea), lupus miliaris disseminatus faciei (which may represent a variant of rosacea) (picture 12), cutaneous sarcoidosis (picture 13), gram-negative folliculitis, eosinophilic folliculitis with or without associated human immunodeficiency virus (HIV) infection, and cutaneous syringomas. (See "Infectious folliculitis" and "HIV-associated eosinophilic folliculitis".)

MANAGEMENT — The management of POD generally involves the discontinuation of topical corticosteroids, avoidance of topical products that may promote or exacerbate POD, and pharmacologic therapy (algorithm 1). Although POD may improve within a few months with the first two interventions, distress over the appearance of POD and the disease's unpredictable course cause most patients to desire intervention to reduce the duration of symptoms. Limited data suggest that some pharmacologic therapies are useful; disease severity influences the selection of treatment. (See 'Disease course' above and 'Elimination of corticosteroids and irritants (zero therapy)' below and 'Mild disease' below and 'Moderate to severe disease' below.)

All patients — Elimination of corticosteroids and skin irritants is considered an important therapeutic measure for all patients with POD.

Elimination of corticosteroids and irritants (zero therapy) — The discontinuation of topical corticosteroids and avoidance of skin care products and cosmetics that may irritate or occlude the skin is also referred to as "zero therapy." This approach is supported by the observation that many vehicle- or placebo-treated patients in randomized trials have improved within two to three months without active therapy [12,42,43].

Although the cessation of topical corticosteroid use is accepted as an important component of management, patients typically become distressed when disease flares occur following cessation. Some clinicians attempt to reduce the likelihood of a rebound flare by either transitioning patients utilizing high- or medium-potency topical corticosteroids to low-potency agents (eg, hydrocortisone 1%) or slowly tapering the frequency of corticosteroid application prior to treatment cessation [3,6,8,16]. The benefit of these techniques is unproven.

An effort to minimize potential skin irritants and allergens typically involves [8,24]:

●Gentle skin cleansing practices (gently cleansing the skin with a fragrance-free, nonsoap cleanser promptly followed by complete and gentle rinsing of the cleanser from the skin)

●Limiting the use of topical products (eg, cosmetics, sunscreens, emollients) on the face to the occasional "only as needed" application of a bland, nonocclusive moisturizing lotion

Once stable remission is attained, skin care products may be slowly restarted (eg, one product per week). The patient should pay close attention to the skin's response to each product. Products that seem to induce recurrences should be promptly discontinued.

Mild disease — Mild POD may be considered the presence of lesions that involve a relatively small area of facial skin and do not cause the patient significant emotional distress (picture 1A-B, 1D, 1F). In an attempt to accelerate clinical improvement in children and adults with mild disease, we usually prescribe topical medication in addition to zero therapy.

Initial therapy — We prefer topical therapy rather than systemic therapy for the initial treatment of mild POD due to the relatively low risk for drug-induced systemic adverse effects. Topical calcineurin inhibitors and topical antibiotics are the primary modes of therapy.

The relative efficacy of different topical agents is unclear. Therefore, selection of a topical therapy is primarily based upon other factors, such as availability, cost, clinician familiarity with particular agents, and patient preference. Compared with topical calcineurin inhibitors, topical erythromycin and topical metronidazole are typically less expensive therapies.

Topical calcineurin inhibitors — Topical calcineurin inhibitors that have been used for POD include topical pimecrolimus cream and topical tacrolimus ointment. We typically utilize pimecrolimus because efficacy data for tacrolimus ointment are more limited. In addition, many of our patients prefer a cream vehicle for facial use over an ointment:

●Administration – Pimecrolimus 1% cream is applied to the affected area twice daily. Topical tacrolimus ointment is used similarly and is commercially available as a 0.03% or 0.1% ointment. The 0.03% concentration, rather than the 0.1% concentration, is typically used for children. Signs of improvement from topical calcineurin inhibitors typically occur within the first month of therapy. (See 'Moderate to severe disease' below.)

Treatment with topical calcineurin inhibitors is usually well tolerated. Although the US Food and Drug Administration has placed a boxed warning on topical calcineurin inhibitors due to concerns about an association between these agents and malignancies, the risk for such events appears to be minimal [44]. (See "Treatment of atopic dermatitis (eczema)", section on 'Topical calcineurin inhibitors'.)

●Efficacy – In a multicenter randomized trial in which 124 adults were treated for up to four weeks with twice-daily applications of pimecrolimus 1% cream or a vehicle cream, pimecrolimus therapy was associated with more rapid improvement [12]. After eight days, greater than 50 percent reductions in disease severity scores occurred in 24 of 60 patients in the pimecrolimus group (40 percent) and only 7 of 64 patients in the vehicle group (11 percent). In addition, the median time to response was 14 versus 28 days. Patients with a history of topical corticosteroid use appeared to respond best to pimecrolimus. However, the benefit of pimecrolimus dissipated over time; by day 29, disease severity scores were similar in both groups.

The efficacy of pimecrolimus for POD was also supported by a smaller randomized trial in which 40 adults were treated with either pimecrolimus 1% cream or vehicle cream applied twice daily [42]. Throughout the four weeks of treatment, the reduction in disease severity was greater in patients treated with pimecrolimus, and after the first week of treatment, at least a 50 percent reduction in the disease severity score was present in 50 versus 15 percent of patients. As in the larger trial, the duration of treatment benefit was limited. Four weeks after the end of treatment, the response rates were similar in both groups.

In the randomized trials, adverse effects were mild and primarily limited to the sites of treatment, and post-treatment disease flares did not appear to occur after the cessation of pimecrolimus [12,42].

No randomized trials of pimecrolimus therapy have been performed in children. A retrospective study that assessed outcomes for 72 children (ages 0 to 17 years) with POD who received topical tacrolimus 0.03% (53 patients), tacrolimus 0.1% (7 patients), or pimecrolimus 1% cream (12 patients) suggests benefit [45]. Complete responses, as assessed through medical record review or telephone call, occurred in 33 of 48 patients (69 percent) treated with either topical tacrolimus or topical pimecrolimus as monotherapy. In addition, among the patients prescribed combination therapy, 9 of 12 patients (75 percent) also using topical metronidazole and 7 of 9 patients (78 percent) also taking an oral antibiotic had complete responses. Two of three patients treated with triple therapy (a topical calcineurin inhibitor, topical metronidazole, and an oral antibiotic) achieved complete responses. The median time to partial or complete improvement during topical calcineurin inhibitor therapy was 14 days. Adverse events were mild and rare. Recurrences were documented in 13 patients (18 percent).

Topical tacrolimus therapy has also been associated with clinical improvement in granulomatous POD in case reports [7,35,46].

Topical erythromycin

●Administration – We typically prescribe twice-daily application of erythromycin 2% gel. Improvement is usually evident within four to eight weeks.

●Efficacy – The efficacy of topical erythromycin for POD is supported by an 80-day randomized trial and documentation of clinical experience [43,47]. In the randomized trial, 99 patients who were treated with either a topical erythromycin emulsion containing 1% erythromycin base (treatment regimen unspecified), oral tetracycline (500 mg twice daily for 10 days and 250 mg twice daily for 10 days), or a placebo pill returned for the assessment of the response to therapy [43]. Both drugs were superior to placebo, and statistically significant differences between the response to topical erythromycin and oral tetracycline were not detected. (See 'Oral tetracyclines' below.)

Topical metronidazole

●Administration – We typically prescribe metronidazole lotion, gel, or cream (0.75% or 1%) once daily and continue treatment for at least eight weeks. Improvement is often noted within this period, but longer periods of treatment may be required for complete clearing [5,16].

●Efficacy – Metronidazole 1% cream was compared with oral tetracycline (250 mg twice daily) in an eight-week randomized trial of 108 patients [38]. Patients in both groups improved, but the response of papular lesions was slower with metronidazole therapy (see 'Oral tetracyclines' below). Additional data on topical metronidazole come from small case series and case reports that document efficacy in children [15,48].

Course and follow-up — Patients who demonstrate progressive improvement with topical therapy may discontinue treatment upon resolution. We typically advise these patients to continue gentle skin care practices and to engage in cautious reintroduction of skin care products. (See 'Elimination of corticosteroids and irritants (zero therapy)' above.)

Patients who do not demonstrate progressive improvement within four to eight weeks with topical pimecrolimus, erythromycin, or metronidazole may proceed to the oral therapies used for more severe disease (algorithm 1). (See 'Moderate to severe disease' below.)

Moderate to severe disease — Moderate to severe POD may be considered POD with numerous papules, large areas of confluent involvement, or bothersome symptoms or significantly emotionally distressing POD (picture 1E-G, 1I-J). This category may also include milder disease that has failed to resolve with topical therapy.

Adolescents and adults — Oral tetracyclines are the most common agents used for systemic treatment of POD and are the preferred therapies for adolescents or adults with moderate to severe POD. Oral erythromycin is an alternative for patients who cannot tolerate tetracyclines. (See 'Children' below.)

Oral tetracyclines — Although oral tetracyclines (eg, tetracycline, doxycycline, minocycline) are accepted as effective treatments for POD [2,49-52], the mechanism through which these agents improve POD is unknown. Anti-inflammatory effects may account for their efficacy:

●Administration – A typical course of oral tetracyclines for POD is approximately eight weeks.

Typical doses for adolescent and adult patients with POD are:

•Tetracycline (250 to 500 mg twice daily)

•Doxycycline (50 to 100 mg twice daily or 100 mg once daily)

•Minocycline (50 to 100 mg twice daily or 100 mg once daily)

Treatment with tetracyclines is generally well tolerated. Gastrointestinal distress is a common adverse effect. Other potential side effects include photosensitivity and skin dyspigmentation.

●Efficacy – Two randomized trials support the use of tetracycline in POD:

•Tetracycline (500 mg twice daily for 10 days followed by 250 mg twice daily for 10 days) was compared with a topical erythromycin emulsion (treatment regimen unspecified) and a placebo pill in an 80-day unblinded randomized trial in which 99 out of 120 patients returned for follow-up evaluation [43]. Papule counts were significantly lower in the tetracycline group than in the placebo group between days 20 to 40, suggesting tetracycline therapy increased the rate of improvement. At day 40, more than 80 percent of patients in the placebo group had more than 10 papules remaining, compared with none of the patients treated with tetracycline. The trial did not find significant differences in the efficacy of oral tetracycline and topical erythromycin. (See 'Topical erythromycin' above.)

•An eight-week multicenter randomized trial of 108 adult patients with moderate POD compared oral tetracycline (250 mg twice daily) with twice-daily applications of metronidazole 1% cream [38]. Although both agents were associated with reduced lesion counts, patients treated with tetracycline improved more quickly. Significantly greater reductions in lesion counts were present in patients treated with tetracycline at four weeks (96 versus 67 percent) and eight weeks (100 versus 92 percent). Improvement in skin erythema was similar in the two groups.

A third randomized trial failed to find a difference in efficacy between oral tetracycline and no therapy [53]. However, the quality of this trial was poor, and the results were inconsistent with the findings of other studies [49].

No randomized trials have evaluated the efficacy of doxycycline and minocycline, and their wide use is primarily based upon the evidence from the studies of tetracycline and a few case reports [19,46].

Alternative therapy — Treatment with a macrolide, similar to the approach in young children, is an option for adolescents and adults who cannot tolerate tetracyclines (algorithm 1). We generally treat adults with erythromycin base (333 mg three times per day or 500 mg twice daily). Administration with food may help to decrease associated gastrointestinal discomfort. (See 'Children' below.)

Children — In children, topical therapy is often tried prior to systemic therapy because of ease of administration and concern for side effects. (See 'Initial therapy' above.)

If systemic therapy is necessary, the age of the child impacts drug selection (algorithm 1).

Although older children may be treated with tetracyclines, oral erythromycin is the preferred systemic agent for young children and other patients who cannot tolerate tetracyclines. Tetracyclines are contraindicated in children under eight years of age because of adverse effects on permanent teeth and bone. Although durations of tetracycline treatment under 22 days are generally considered safe in young children, longer courses are generally used for POD. (See "Tetracyclines", section on 'Young children' and 'Oral tetracyclines' above.)

The optimal dose of erythromycin for POD has not been established. We generally treat children over four years of age with 40 mg/kg per day divided into three doses up to a maximum dose of 1000 mg per day. Administration with food may help to decrease associated gastrointestinal discomfort.

Oral erythromycin has not been evaluated in randomized trials, but, based upon case reports and case series, the drug may be effective [5,36,54-57]. Gastrointestinal distress is an adverse effect that may limit use of erythromycin in some patients. Administration with food may help to decrease associated gastrointestinal discomfort. Oral azithromycin may be an alternative; azithromycin appeared effective for POD in a case series [9].

Course and follow-up — Treatment with oral antibiotics is generally continued for eight weeks. For patients who respond within this period, the antibiotic can be discontinued at the end of this course of treatment. We typically advise these patients to continue gentle skin care practices and to engage in cautious reintroduction of skin care products. (See 'Elimination of corticosteroids and irritants (zero therapy)' above.)

The best approach to patients who fail treatment with oral tetracyclines or oral erythromycin is unclear. In general, if improvement has not occurred within eight weeks, reevaluation to confirm the diagnosis and review of patient adherence to management recommendations is prudent. If POD remains the most likely diagnosis and there has been appropriate adherence to treatment, trials of less commonly used therapies are reasonable. In our experience, we have found topical ivermectin or topical sulfur-sulfacetamide sodium helpful. (See 'Other therapies' below.)

Other therapies — Limited data suggest that other therapies may be effective for POD.

Clinical use of ivermectin for POD is increasing. However, no randomized trials have evaluated use of topical or oral ivermectin for POD. In a retrospective study that included four children treated with compounded topical 1% ivermectin (applied once daily for three months), all achieved complete or almost complete clearance of POD [58]. Treatment was well tolerated; one child experienced transient, mild desquamation. In the same study, all of three children treated with a single dose of oral ivermectin (200 to 250 micrograms/kg) achieved complete or almost complete clearance of disease. Oral ivermectin also was well tolerated. Two children had transient, mild desquamation.

Additional local therapies reported to be of benefit in small uncontrolled or case report studies include azelaic acid 20% cream [59,60], topical clindamycin with or without hydrocortisone 1% lotion [54,61], topical tetracycline [62], adapalene 0.1% gel [63], and topical sulfacetamide-sulfur combined with oral tetracycline [64]. Efficacy of oral isotretinoin for refractory granulomatous periorificial dermatitis has been described in case reports [65,66], and oral metronidazole appeared to resolve granulomatous periorificial dermatitis in a child [67]. Marked improvement of POD linked to fusobacteria after treatment with oral beta-lactam antibiotics has been reported in three children [68]. In addition, we have anecdotally noted good responses of POD to topical precipitated sulfur in patients with contraindications to standard treatments.

Photodynamic therapy may be another option for the treatment of POD. This intervention was more effective than clindamycin gel in a split-face study of 21 patients [61]. However, seven patients dropped out of the study due to skin irritation related to photodynamic therapy, and three patients developed treatment-related postinflammatory hyperpigmentation.

Further study is necessary to determine the efficacy of all of these agents.

PROGNOSIS — Prognostic data on POD are limited. In a retrospective study of 222 children with POD, of the 131 children who presented for follow-up visits, 94 (72 percent) had complete resolution of symptoms, and the average time to resolution of POD was 3.8 months [9]. Children in the study received topical and/or oral therapy.

The risk for disease recurrence after resolution has not been established. In our experience, recurrences are common and can occur a few years after successful treatment.

SUMMARY AND RECOMMENDATIONS

●Epidemiology – Perioral dermatitis (POD), also known as periorificial dermatitis, is an inflammatory condition of facial skin that primarily affects young women. Less frequently, the disorder occurs in older individuals, men, and children. (See 'Epidemiology' above.)

●Pathogenesis – Although a variety of intrinsic and extrinsic factors have been proposed as contributors to POD, the pathogenesis of this disorder is not well understood. The factor most frequently reported in association with the occurrence or persistence of POD is topical corticosteroid use. (See 'Etiology and pathogenesis' above.)

●Clinical manifestations:

•Classic perioral dermatitis – Patients with classic POD typically present with small, inflammatory papules, papulovesicles, or papulopustules and scaling surrounding the mouth, nose, or eyes (picture 1A-L). In patients with perioral lesions, the skin adjacent to the lip border is typically spared. (See 'Clinical manifestations' above.)

•Granulomatous periorificial dermatitis – Granulomatous periorificial dermatitis is a variant of POD that is typically seen in prepubertal children (picture 2). Histopathologic examination of lesional skin reveals a granulomatous infiltrate in these patients. (See 'Clinical manifestations' above.)

●Diagnosis – The clinical history and physical examination is usually sufficient for the diagnosis of POD. The histopathologic findings of POD are nonspecific, and skin biopsies are rarely necessary. (See 'Diagnosis' above.)

●Treatment – The treatment of POD involves the discontinuation of topical corticosteroids and the avoidance of skin irritants. Although patients may eventually improve without additional interventions, pharmacologic therapy is often instituted in an attempt to accelerate lesion resolution (algorithm 1) (see 'Management' above):

•Mild disease – For adults and children with mild POD who desire an attempt to accelerate improvement, we suggest treatment with topical therapy rather than systemic therapy (Grade 2C). Our preferred topical therapies include topical pimecrolimus, topical erythromycin, and topical metronidazole. Topical tacrolimus is an additional option for therapy. (See 'Mild disease' above.)

•Moderate to severe disease – For adolescents and adults with moderate to severe POD or with milder disease refractory to topical agents who desire an attempt to accelerate improvement, we suggest treatment with an oral tetracycline (Grade 2B). Examples include tetracycline, doxycycline, and minocycline. The response to oral antibiotic therapy is often slow; a typical course of treatment is eight weeks. (See 'Moderate to severe disease' above.)

For children under the age of eight with moderate to severe POD or who fail treatment with topical agents, we suggest treatment with oral erythromycin (Grade 2C). Oral azithromycin is an alternative. Young children should not be treated with oral tetracyclines due to the potential for adverse effects on tooth and bone development. (See 'Children' above.)