Perioral Dermatitis

Practice Essentials

Perioral dermatitis (POD), also known as periorificial dermatitis, is a papulopustular facial dermatitis. It most commonly affects adolescent and young adult women, but can also occur in children, older adults, and men.^{[1, 2]}  The clinical and histologic features of the perioral dermatitis lesions resemble those of rosacea. Treatment involves avoiding potential triggers as well as systemic and/or topical medications.

See the image below.

View Image

Perioral dermatitis. Courtesy of Professor Raimo Suhonen and DermNet New Zealand (http://www.dermnetnz.org/assets/Uploads/acne/s/pod6.jpg).

• References

Pathophysiology

The etiology of perioral dermatitis (POD) is unknown. Skin barrier dysfunction is commonly observed in those with POD.^[3]  Topical or inhaled corticosteroids are often reported as potential triggers of perioral dermatitis. Other suggested triggers include fragrances, cosmeceutical products, and fluorinated toothpastes.

• References

Etiology of Perioral Dermatitis

The etiology of perioral dermatitis is unknown; however, long-term use of topical steroids for minor skin alterations of the face often precedes the manifestation of the disease. 

Drugs

Some patients may be overusing topical steroid preparations on the face.^[4] No clear correlation exists between the risk of perioral dermatitis and strength of the steroid or the duration of the use. Perioral dermatitis has also been reported after the use of nasal steroids^[5] and steroid inhalers.

Cosmeticeuticals

Fluorinated toothpaste use has been associated with perioral dermatitis.^[6]

Skin care ointments and creams, especially those with a petrolatum or paraffin base, and the vehicle isopropyl myristate are suggested to be causative factors. In an Australian study, applying foundation in addition to moisturizer and night cream resulted in a 13-fold increased risk for perioral dermatitis. The combination of moisturizer and foundation was associated with a lesser but significantly increased risk for perioral dermatitis, whereas moisturizer alone was not associated with an increased risk.^[7]  

• References

Epidemiology

There is limited data on the epidemiology of perioral dermatitis (POD). Most patients are women ages 20-45 years-old, but perioral dermatitis can also occur in children, older adults, and men

• References

Prognosis

Limited data is available regarding the long-term prognosis of perioral dermatitis. Some patients may achieve resolution of symptoms within a few months whereas others may have a more persistent disease course. Recurrences can occur after successful treatment. 

• References

Patient Education

Education about triggers and risk factors is important to address potential underlying causes of the eruption. This is particularly important for topical steroids; although patients may notice temporary improvement with topical steroid use, these can contribute to persistent disease activity if not discontinued. During treatment, use of other cosmeceutical and skin care products should be limited. Anticipatory guidance and setting appropriate expectations (e.g. treatment can take at least 4-8 weeks to see improvement) is important to ensure adherence to treatment.

• References

History

Subjective symptoms of perioral dermatitis (POD) may consist of a sensation of stinging and burning. Itching is rare.

Often, long-term use of topical steroids for minor or even undiagnosed skin alterations precedes the development of perioral dermatitis.

Perioral dermatitis often can be subacute to be chronic.

• References

Physical Examination

Patients with perioral dermatitis typically present with grouped, erythematous papules surrounding the mouth, eyes, and nose. Scaling, papulovesicles, and pustules can also be seen. Notably, the lesions often spare the vermillion border of the lips.

In granulomatous variants of perioral dermatitis, the lesions may have a yellow-brown color and also involve the ears and neck.

The development of a lupoid dermal infiltrate is considered to be a feature of more severe disease that presents with densely grouped red-brown papules. The diagnosis can be supported on the basis of the yellowish discoloration upon diascopy. Scarring may occur with the lupoid form of perioral dermatitis.^[8]

• References

Complications

• References

Laboratory Studies

The diagnosis is made clinically. No laboratory abnormalities can be expected.

• References

Histologic Findings

Histologic findings are similar to those of rosacea, but the signs of actinic skin damage are generally less intense and vary according to the patient's age. Thus, a lymphohistiocytic infiltrate with perifollicular localization can be expected in all stages. A marked granulomatous inflammation and, occasionally, perifollicular abscesses may be present when pustules and papules are the dominant clinical findings.

• References

Approach Considerations

For all patients with perioral dermatitis, provoking factors (e.g. topical or inhaled corticosteroids) should be eliminated. In addition, irritating skincare practices should be avoided and overall use of cosmeceutical products should be limited (i.e. "zero therapy"). Cosmeceutical products should be limited to those that are fragrance free. Some individuals with perioral dermatitis may find dimethicone containing products helpful. Some patients may improve with these supportive measures alone.

There is no Food and Drug Administration (FDA)-approved treatment for perioral dermatitis. For those with mild disease, treatment can be initiated with pimecrolimus^{[14, 15]} , erythromycin^[16] , clindamycin, or metronidazole^[17] , either individually or in combination. Topical sulfur or sulfacetamide may also be helpful for some patients. For those with more severe disease or who do not improve after 4-8 weeks of topical therapy, treatment with oral tetracyclines such as oral doxycycline or sarecycline should be considered.^[16]

For those with improvement after an initial 4-8 week course of therapy, treatment can be discontinued and the patient monitored for recurrence. For those with more refractory disease, oral and topical ivermectin^[18] , oral erythromycin^[19] , oral and topical Janus kinase (JAK) inhibitors ^{[20, 21]} , and oral isotretinoin^{[22, 23]} may be considered.

Some patients may notice some initial worsening with treatment, particularly if topical or inhaled steroids are being withdrawn. Slow tapering of the topical or inhaled steroid may help to reduce this initial flaring if applicable. In addition, patient counseling and anticipatory guidance can help to improve adherence to the treatment plan and avoid continued use of topical steroid exposure, which can perpetuate disease activity.

Consultation with a dermatologist may helpful in the evaluation of provoking factors and in determining the individualized treatment plan.^[24]

• References

Medical Care

• References

Medication Summary

For mild disease, treatment can involve pimecrolimus, erythromycin, or metronidazole, either individually or in combination. Several small randomized controlled trials in adults support the efficacy of pimecrolimus in the treatment of perioral dermatitis ^{[14, 15]} . Case reports have also suggested that tacrolimus may be effective.^[25] Small randomized trials also support the efficacy of topical antibiotics such as erythromycin and clindamycin^[16] and topical metronidazole.^[17]  Case reports and small series have also suggested a potential role for topical azelaic acid ^[26] and adapalene^[27] , though these should be used cautiously given the potential for causing irritation.

While randomized trials are lacking in pediatric populations, observational data suggest that pimecrolimus and metronidazole can be effective treatment options.^[28]

For those with more severe disease or who do not improve after 4-8 weeks of topical therapy, treatment with oral tetracyclines is often indicated.^[16] Doxycycline is typically preferred over minocycline due to the lower risk of severe adverse effects.^[29]  Emerging evidence suggests that sarecycline may also be a useful treatment option for perioral dermatitis.^{[30, 31]} Sarecycline has a narrower spectrum of antibacterial activity than standard broad-spectrum antibiotics, which may reduce negative effects on the microbiome and the development of antibiotic resistance.^[32]

Oral and topical ivermectin^[18] , oral erythromycin^[19] , oral and topical Janus kinase (JAK) inhibitors ^{[20, 21]} , and oral isotretinoin^{[22, 23]} have also been suggested as potential treatment options . 

• References

Metronidazole (Flagyl)

• Dosing, Interactions, etc.

Clinical Context:  Metronidazole is an imidazole ring-based antibiotic active against various anaerobic bacteria and protozoa. In concentrations of 0.75-2%, it is considered to be the drug of choice for topical treatment of perioral dermatitis. Metronidazole is available in a gel, lotion, or cream.

• References

Erythromycin (E.E.S., Erythrocin, Ery-Tab)

• Dosing, Interactions, etc.

Clinical Context:  Topical erythromycin in concentrations of 2-4% as a gel or cream is an alternative to metronidazole for topical treatment. It inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest. It is used to treat staphylococcal and streptococcal infections.

• References

Clindamycin topical (Cleocin T, Clindacin P, ClindaDerm)

• Dosing, Interactions, etc.

Clinical Context: 

• References

Class Summary

These drugs may have antibacterial and/or anti-inflammatory effects that are responsible for their effectiveness in perioral dermatitis.

• References

Isotretinoin (Amnesteem, Claravis, Sotret)

• Dosing, Interactions, etc.

Clinical Context:  Isotretinoin is an oral agent used to treat serious dermatologic conditions. It is a synthetic 13-cis isomer of naturally occurring tretinoin (trans -retinoic acid). Both agents are structurally related to vitamin A. Isotretinoin decreases sebaceous gland size and sebum production. It may inhibit sebaceous gland differentiation and abnormal keratinization. Isotretinoin is indicated for long-standing and refractory forms of perioral dermatitis. Because of adverse effects, therapy should be prescribed only by a physician familiar with this drug (ie, dermatologist).

A US Food and Drug Administration–mandated registry is now in place for all individuals prescribing, dispensing, or taking isotretinoin. For more information on this registry, see iPLEDGE. This registry aims to further decrease the risk of pregnancy and other unwanted and potentially dangerous adverse effects during a course of isotretinoin therapy.

• References

Class Summary

These agents reduce the size of the sebaceous glands, decrease sebum secretion, and inhibit keratinization.

• References

Tacrolimus ointment (Protopic)

• Dosing, Interactions, etc.

Clinical Context: 

• References

Pimecrolimus (Elidel)

• Dosing, Interactions, etc.

Clinical Context:  Pimecrolimus is the first nonsteroid cream approved in the United States for mild-to-moderate atopic dermatitis. It is derived from ascomycin, a natural substance produced by the fungus Streptomyces hygroscopicus var ascomyceticus. Pimecrolimus selectively inhibits the production and release of inflammatory cytokines from activated T-cells by binding to cytosolic immunophilin receptor macrophilin-12. The resulting complex inhibits phosphatase calcineurin, thus blocking T-cell activation and cytokine release. Cutaneous atrophy is not observed in clinical trials, a potential advantage over topical corticosteroids.

• References

Sarecycline (Seysara)

• Dosing, Interactions, etc.

Clinical Context: 

• References

Doxycycline (Oracea, Doryx, Vibramycin)

• Dosing, Interactions, etc.

Clinical Context:  Doxycycline is the drug of choice in nonpregnant women. It inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. Alternatively, one may use tetracycline in adapted dose.

• References

Ivermectin (Stromectol)

• Dosing, Interactions, etc.

Clinical Context: 

• References