# Perioral dermatitis

Perioral dermatitis, also known as periorificial dermatitis, is a common type of inflammatory skin rash. Symptoms include multiple small (1–2 mm) bumps and blisters sometimes with background redness and scale, localized to the skin around the mouth and nostrils. Less commonly, the eyes and genitalia may be involved. It can be persistent or recurring, and resembles particularly rosacea and to some extent acne and allergic dermatitis. The term "dermatitis" is a misnomer because this is not an eczematous process.
The cause is unclear. Topical steroids are associated with the condition and moisturizers and cosmetics may contribute. The underlying mechanism may involve blockage of the skin surface followed by subsequent excessive growth of skin flora. Fluoridated toothpaste and some micro-organisms including Candida may also worsen the condition, but their roles in this condition are unclear. It is considered a disease of the hair follicle with biopsy samples showing microscopic changes around the hair follicle. Diagnosis is based on symptoms.
Treatment is typically by stopping topical steroids, changing cosmetics, and in more severe cases, taking tetracyclines by mouth. Stopping steroids may initially worsen the rash. The condition is estimated to affect 0.5-1% of people a year in the developed world. Up to 90% of those affected are women between the ages of 16 and 45 years, though it also affects children and the elderly, and has an increasing incidence in men.

## History

The disorder appears to have made a sudden appearance with a case of 'light sensitive seborrhoeid' in 1957, which is said to be the first nearest description of the condition. By 1964, the condition in adults became popularly known as perioral dermatitis, but without clear clinical criteria. In 1970, the condition was recognized in children. That all rashes around the mouth are perioral dermatitis has since been frequently debated. That this condition should be renamed periorificial dermatitis has been proposed. Darrell Wilkinson was a British dermatologist who gave one of the earliest 'definitive' descriptions of 'perioral dermatitis' and noted that the condition was not always associated with the use of fluoridated steroid creams.

## Signs and symptoms

A stinging and burning sensation with rash is often felt and noticed, but itching is less common. Often the rash is steroid responsive, initially improving with application of topical steroid. The redness caused by perioral dermatitis has been associated with variable level of depression and anxiety.
Initially, there may be small pinpoint papules either side of the nostrils. Multiple small (1-2mm) papules and pustules then occur around the mouth, nose and sometimes cheeks. The area of skin directly adjacent to the lips, also called the vermillion border, is spared and looks normal. There may be some mild background redness and occasional scale. These areas of skin are felt to be drier and therefore there is a tendency to moisturize them more frequently. Hence, they do not tolerate drying agents well and the rash can be worsened by them.
Perioral dermatitis is also known by other names including rosacea-like dermatoses, periorofacial dermatitis and periorificial dermatitis. Unlike rosacea which involves mainly the nose and cheeks, there is no telangiectasia in perioral dermatitis. Rosacea also has a tendency to be present in older people. Acne can be distinguished by the presence of comedones and by its wider distribution on the face and chest. There are no comedones in perioral dermatitis.
A variant of perioral dermatitis called granulomatous perioral dermatitis (GPD) is often seen in prepubertal children or in darker skin phenotypes. GPD lesions may appear yellow on a diascopy. Patients report irritation but are usually asymptomatic. For children with GPD, a skin biopsy showing granulomatous infiltrate is needed to confirm diagnosis in an atypical patient. If the GPD is mild, treatment is not mandatory.

## Causes

The exact cause of perioral dermatitis is unclear; however there are some associations that are suspected. There have been clinical trials to look at the link between perioral dermatitis and steroids, infections, and typical face products. These factors may play a role in the development of perioral dermatitis. Although light exposure has been discounted as a causal factor, some reports of perioral dermatitis have been made by some patients receiving Psoralen and ultraviolet A therapy. It is important to note that an underlying cause can not always be known for patients as the exact mechanism of action to develop perioral dermatitis is not known.

### Corticosteroids

Perioral dermatitis can occur with corticosteroids, which is often shortened to steroids. Steroids are anti-inflammatory drugs so they are used to reduce swelling and redness that is caused by the body. There are different forms of steroids, many of which can contribute to the development of perioral dermatitis. Some of these are topical corticosteroids, oral corticosteroids, and inhaled corticosteroids. There have been clinical trials that show a correlation between these corticosteroids; however, a direct cause has not been confirmed. The highest link seems to be with topical corticosteroids in comparison to the others and there seems to be a higher chance of development of perioral dermatitis with greater strength steroids. It has also been seen that chronic use of steroids show a higher rate of developing perioral dermatitis. Discontinuing the steroids often initially worsens the dermatitis, which leads to some conflicting beliefs as some people believe the steroids were initially controlling the condition. Perioral dermatitis has a tendency to occur on the drier parts of the face and can be aggravated by drying agents including topical benzoyl peroxide, tretinoin and lotions with an alcohol base.Reports of perioral dermatitis in renal transplant recipients treated with oral corticosteroids and azathioprine have been documented.

### Infections

Topical corticosteroids may lead to increase micro-organism density in the hair follicle. Micro-organisms are small living things that a person is not able to see without a microscope. Normally people have micro-organisms all over their body but the type and amount can be quickly changed by corticosteroids. This may lead to an infection. The role of infectious agents such as Candida species, Demodex folliculorum, and fusobacteria has not been confirmed, but could be potential causes for development as well. There are different types of the infections such as bacterial, yeast, and parasitic. From different clinical trials, it seems that a bacteria infection is more like to lead to perioral dermatitis than the other types.

### Cosmetics

Cosmetics play an important role as potential causal factors for perioral dermatitis. Cosmetics in this case include a variety of products that are applied to the face such as moisturizer, foundation, and sunscreen. It is especially seen when these products contain petroleum, paraffin, or isopropyl myristate. Applying large quantities of a moisturizing creams regularly causes persistent hydration of the layer which may cause impairment and occlusion of the barrier function, irritation of the hair follicle, and proliferation of skin flora. Occlusion is the sealing of the moisture. Proliferation is the cells continuing to divide to create usually new healthy cells. This is a process that cells of all kinds normally and often do. For some people, this act of moisturizing excessive can affect the typically proliferation of skin flora. Skin flora is the typical bacteria and cells that sits on a person's face. Transepidermal water loss is also seen as associated to perioral dermatitis. Transepidermal water loss is water that is lost from the inside of the body by doing through the skin to the outside world. There are associations that water loss is greater with older adults but perioral dermatitis can still occur in younger people. Barrier dysfunction is seen as a large cosmetic association to perioral dermatitis. Combining this with night cream and foundation significantly increases risk of perioral dermatitis 13-fold. In a similar fashion, foundation and sunscreen also create extra occlusive layers that may affect the skin. Physical sunscreens also have been seen to have an associations These are potential associations to perioral dermatitis and thoughts of how it may cause perioral dermatitis; however, the exact pathology is still unknown. This also does not mean that those that use these products will be sure to develop perioral dermatitis.

### Other Potential Causes

There are a variety of other potential factors that are suspected to cause or worsen perioral dermatitis; however, enough research has not been done to shown a link as strong as that with corticosteroids. Hormonal changes may be linked to causing perioral dermatitis. Oral contraceptives (birth control pills) may also have a link as they significantly impact the hormonal balance of the people taking them. Hormones are nature chemicals in the body that act as messengers by relaying information to different parts of the body. These levels are normally regulated by the body; however, they can be changed by other factors such as oral contraceptives. Gastrointestinal (GI) changes may also be linked with perioral dermatitis. The GI system includes all the organs for food to be broken down, absorbed, and excreted out of the body. The condition may be potentially worsened by fluoridate toothpaste, excessive wind, or heat. The possibility of an association with wearing a veil has been documented as well. Some other miscellaneous factors include emotional stress, malabsorption, and latex gloves.
Perioral dermatitis can also be caused by other factors, such as stress, oily secretions, and intake of fluids, all of which were impacted as COVID cases increased, which further increased the rates of wearing masks. This, in turn, resulted in an increased level of stress and oil secretions along the face and decreased intake of water.

## Pathophysiology

The pathophysiology of perioral dermatitis is related to disease of the hair follicle as is now included in the ICD-11 due to be finalized in 2018. Lip licker's dermatitis or perioral irritant contact dermatitis due to lip-licking is considered a separate disease categorized under irritant contact dermatitis due to saliva.
Perioral dermatitis is frequently histologically similar to rosacea with the two conditions overlapping considerably. There is a lymphohistiocytic infiltrate with perifollicular localization and marked granulomatous inflammation. Occasionally, perifollicular abscesses may be present when pustules and papules are the dominant clinical findings.
There is a possible discovery of new information that the perioral dermatitis develops due to damage to the skin barrier in the facial area, which possibly led to the patients become expose to both the internal and external factors that may contributes to the development of the perioral dermatitis.

## Diagnosis

A diagnosis of perioral dermatitis is typically made based on the characteristics of the rash. A skin biopsy is usually not required to make the diagnosis but can be helpful to rule out other skin diseases which may resemble perioral dermatitis. Extended patch testing may be useful to also rule out allergic contact causes. If the skin biopsy show signs of other components such as bacteria, the healthcare workers can do further lab testing such as culture or other test like a diascopy.
Other skin diseases that may resemble perioral dermatitis include:
* Rosacea
* Acne vulgaris
* Seborrheic dermatitis
* Allergic contact dermatitis
* Irritant contact dermatitis
* Angular cheilitis
* Sarcoidosis
* Lip licker's cheilitis
* Demodex folliculitis
* Tinea faciei
* Syringomas

## Treatment

Multiple treatment regimes are available and treatment algorithms have been proposed.
Treatment regimens are advised to treat perioral dermatitis using the lowest possible dose for antibiotics and other therapies.
Most treatment plans were developed through trial and error. Treatment plans usually consist of a systemic treatment such as an oral antibiotic or a topical treatment like metronidazole.
However, many factors can play a role in the development of perioral dermatitis in patients, as well as their severity of the disease. This can cause to develop many treatment plans that would cater the best towards the patient.
Perioral dermatitis will usually resolve within a few months without medication, by limiting the use of irritants, including products with fragrance, cosmetics, benzoyl peroxide, occlusive sunscreens, and various acne products. This is called zero treatment. Topical corticosteroids should be stopped entirely if possible. Abrupt discontinuation of a topical corticosteroid may lead to rebound flares that can be worse than the primary dermatitis. If the flare proves intolerable, temporary use of a less potent topical corticosteroid can often be helpful. Slowly reducing the use of topical corticosteroids over time can help prevent rebound flares.
Topical retinoids and benzoyl peroxide are potentially irritating products that can cause inflammation of the skin and should be avoided.

### Medication

A number of medications, either applied directly to the skin or taken by mouth, may hasten recovery. These include tetracycline, doxycycline, and erythromycin. Tetracycline is given at a daily dosage of 250 to 500 mg twice a day for 4 to 8 weeks. Gastrointestinal issues, diarrhea, and photosensitivity are possible short term side effects when taking tetracycline. Sarecycline, a narrow-spectrum tetracycline antibiotic, has a lower potential of causing bacterial resistance and gastrointestinal issues compared to other tetracycline medications. Possible side effects of sarecycline include mainly nausea and sunburn being very rare. Pregnant women and pediatric patients can not take tetracycline due to possible harm to the fetus and severe staining of developing teeth. Erythromycin is often given as an alternative to those that can't take tetracycline, given at a daily dosage of 250 to 500 mg. Erythromycin may be used as a cream. Doxycycline is a second generation tetracycline with improved absorption and a broader anti-bacterial spectrum. Doxycycline is most often the first antibiotic drug choice, given at a daily dosage of 100 mg for up to a month before considering tapering off or stopping. Sometimes, longer duration of low doses of doxycycline are required. Possible side effects of doxycycline include gastrointestinal issues and irritation in the esophagus.
Metronidazole is less effective, but is available in a gel and can be applied twice daily. For pediatric patients, metronidazole can be used as an alternative to tetracycline. Metronidazole comes in various concentrations ranging from 0.75% to 2%. Higher concentrated metronidazole did not equate to shorter time to cure times. If the perioral dermatitis was triggered by a topical steroid then pimecrolimus cream has been suggested as effective in improving symptoms. However, this has also been documented to cause the condition. Topical pimecrolimus is often used in treating corticosteroid induced perioral dermatitis due to it being a non-steroid based cream. Pimecrolimus is generally well tolerated with a rare side effect of a burning sensation at the application site.
Topical adapalene has been reported to resolve a case of perioral dermatitis in 4 weeks without any side effects. The dose used was 1% adapalene gel once a day at night. The patient did not have recurrence during the 8-month follow up period.
The most common medications to help treat perioral dermatitis are oral tetracycline, pimecrolimus cream, and azelaic gel. However, some of these medications can't be used for prolonged periods of time, otherwise they will no longer be effective against the disease. For example, use of pimecrolimus cream for more than four weeks will be ineffective, while use of azelaic gel for more than six weeks will be ineffective. While these two medications previously mentioned decrease in effectiveness after a certain period of time, oral tetracycline, on the other hand, have been shown to have decreased effectiveness if used prior to twenty days of disease diagnosis.
While there may be other topical medications that can be effective against perioral dermatitis, such as erythromycin emulsion or metronidazole cream, studies have shown that their effectiveness varied amongst different random controlled trials. As a result, these two topical medications, amongst others, may not be the ideal solution for perioral dermatitis.
For more rare cases, cefcapene pivoxil hydrochloride, a beta lactam antibiotic, has been used in treating perioral dermatitis presumably caused by Fusobacteria. Improvement was visible in 1 to 2 weeks and cured in 2 to 5 weeks. Isotretinoin was used in treating granulomatous perioral dermatitis at a dose of 0.7 mg/kg/day isotretinoin for 20 weeks. However, the patient was also taking a series of combination therapies. Isotretinoin also requires long term monitoring for potential side effects.
More studies lately shows other possible solutions to use for the treatment, one such study shows the use of TRPV1 inhibitor 4-t butylcyclohexanol. The TPRV receptor activates as a defense against possible pain like inflammatory reactions, which could lead to the possible development of the perioral dermatitis. The study presents that the symptoms of perioral dermatitis in patients take it shows improvement within 8 weeks.
When giving patients their medication, healthcare workers need to be aware of the possibility of the perioral dermatitis coming back to the patient again, as well as exacerbation. If the perioral dermatitis comes back again, the medication that they took prior may not work the second time around, so the healthcare workers may need to create a secondary treatment plan around the return of the disease.

## Prognosis

Perioral dermatitis is likely to fully resolve with short courses of antibiotics but if left untreated it can persist for years and take on a chronic form.
In some cases, it can be resolve for the patient to stop taking external factors that may play a role in the development of perioral dermatitis.
Improvement with tetracyclines is usually seen after 4 days and significantly so after 2 weeks. In severe cases, longer periods of treatment may be required to achieve cosmetic satisfaction.

## Epidemiology

Most commonly in females between the ages of 16 and 45 years, perioral dermatitis also occurs equally in all racial and ethnic backgrounds and include children as young as three months and is increasingly reported in male. In children, females are more likely affected. It has an incidence of up to 1% in developed countries. While perioral dermatitis is more prevalent amongst young females compared to male, the reason behind why is unclear.
There are findings that in the adult age, women dominate the affected population over the men, and the most affected age are those in their twenties or thirties. However, those in the children age range, the majority of the affected populations are those before puberty, and there are more affected male than female.
Amongst the few adult men who find themselves diagnosed with perioral dermatitis, it has been shown in multiple studies the reason behind it is due to them taking volatile alkyl nitrates, an inhaled product used to relax muscles.

## Impacts

Many individuals who have perioral dermatitis, amongst other skin issues, have an increase risk of experiencing mental health issues, such as, depression, anxiety, and stress. This is particularly more prevalent in adolescents, compared to adults, due to the presence of more social stigmas during one's teen years as opposed to one's adulthood.
Individuals who use topical steroids long past standard treatment plans or chronically may increase the risk of developing other severe diseases such as severe dermatitis.