Anti-inflammatory Effect of Novel Herbal Composition Containing Licorice Root Extract in The Management of Dermatitis

Dermatitis is an inflammation of the skin that causes recurring itchy rashes. Dermatitis impacts everyone from infants to seniors, significantly impacting their mental health and daily lives(1). It's prevalent worldwide among children and adults alike, affecting up to 20% of kids and 3-10% of adults. Symptoms include redness, itching, and disrupted sleep for those who suffer from this condition(2). These issues tend to worsen over time, especially after puberty. Many cases resolve naturally but persist into adulthood in about half of sufferers(4).The underlying causes involve compromised skin barriers, immune system imbalances, and environmental factors like exposure to water, chemicals, and harsh substances(5).Managing dermatitis requires effective treatments that help control flare-ups and improve overall quality of life. Early intervention is crucial, typically starting within the first six months of life when symptoms usually appear(6)Common triggers include water contact, soaps, detergents, and certain types of oil(7) Occupations like cleaning, butchery, cooking, beauty treatments, and healthcare professionals are high-risk jobs that involve working in water(8) Differences in how dermatitis manifests can be influenced by factors like skin type, leading to potential challenges in diagnosing cases(9) Additionally, dermatitis often emerges during childhood when individuals experience symptoms such as itching, inflammation, and distinctive skin patterns. These conditions typically persist over extended periods, suggesting a link to early life experiences and predispositions towards allergies or dryness(10)Thus, identifying dermatitis requires careful observation of both current symptoms and past medical histories(11)Early recognition of these signs is crucial for accurate diagnosis and effective treatment. Lesions may lead to skin peeling, hardening, and intense irritation(12) Dermatitis can be grouped by various clinical measures. EASI was developed in 1998(13).Steroids decrease inflammation that causes dermatitis. This reduces lesions and aids healing(14).Skin damage from dermatitis results from skin barriers, immune issues, and external factors like allergens, irritants, and bacteria(15) Clinical presentations and severities of dermatitis differ greatly; diagnosing them isn't easy, particularly for adults. The condition lasts for an extended period but has breaks in between. Active, the intense itchiness and rash become very troublesome. Symptoms' severity causes great distress(16) ) QOL suffers notably, especially in more serious cases. Fortunately, thanks to the availability of the Finnish celiac disease guideline online, which is accessible to all doctors, the diagnostic delay has been reduced recently. This guideline includes detailed descriptions of dermatitis along with clinical images and offers guidance on making the diagnosis at various locations(17)

Most recently, a PDE4 inhibitor called crisaborole was approved by the FDA in 2016. Early studies indicate it has an excellent safety profile for treating and managing dermatitis. This improvement in skin barrier function, hydration, and thickness is observed in patients who have used tacrolimus(18) Additionally, a Korean study from 1995 showed that the incidence of adverse events was 7%. In the six to twelve-year-old category, there was an increase of three percent. 9% in the 12-15 age group. In 2000, the number of people affected by AE increased to ten. Seven percent of children between six and twelve years old make up six people.Rephrase One percent of teenagers between twelve and fifteen years old. Parents' allergies could affect how often their kids get an ear infection. The results of the Korean study matched those from word wide investigations(19)

TYPES OF DERMATITIS

ATROPIC DERMATITIS: Atopic dermatitis (AD), also known as (atopic) eczema, is a common long-term skin condition that causes itching.It is a varied disease with different ways it can appear, and these can change over time(20)AD may be linked to metal allergies, possibly connected with a deficiency in a protein called suprabasin(21) It is a complex condition that comes from the interaction of genetic and other factors, such as environmental influences, immune system problems, and weakened skin barriers(22-23)According to criteria set by a UK working group, AD is diagnosed when someone has itchy skin along with three or more of these signs: skin rash in the bends of the body, a history of dry skin, asthma, or a rash that started before the age of two(24).

CONTACT DERMATITIS: Contact dermatitis is a type of skin inflammation caused by substances like chemicals or metals.These can either irritate the skin directly without causing an immune reaction or trigger a reaction by changing proteins and prompting the body's immune system to respond(25) Contact dermatitis often happens when the skin is damaged by outside factors or environmental influences(26)It typically affects the hands and can affect people of any age or sex. It is a delayed-type immune reaction, where the body reacts after being exposed to an allergen it already knows Irritant contact dermatitis (ICD) is a skin condition that happens when the skin's barrier is broken down(27)and the body's innate immune system is activated.ICD is more common than allergic contact dermatitis(28)Allergists often note that people can develop allergies to materials used in medical devices, such as implants. This is a serious concern for patients, doctors, dentists, and surgeons(29)

SEBORRHEIC DERMATITIS: Seborrheic dermatitis is a common long-term skin condition that causes inflammation. It mostly affects young adults and appears in areas of the body where there are a lot of oil glands, like the scalp, face, and torso. In teenagers and adults, the symptoms can range from small patches to widespread flaking on the scalp(30) In babies, it usually shows up on the scalp as yellow, scaly patches. Infants often have severe cases, which can look like thick, greasy scales on the top and front of the head, causing worry for parents Seborrheic dermatitis in infants typically occurs in the first three months of life(31) Seborrheic dermatitis is an inflammatory skin condition that causes red, scaly patches, mainly on the scalp, face, and skin folds. The flakes are usually white or yellow and can be oily or dry. It is thought that seborrheic dermatitis and dandruff together affect about half of all adults. Although it is very common, the exact causes are not fully understood. Factors like oil production from the skin and the presence of fungi on the skin surface may play a role(32) Scalp seborrheic dermatitis has two main periods of occurrence: one in newborns up to three months old, and another in adults between 30 and 60 years of age. Men are more likely to be affected than women, and there is no particular ethnic preference(33)The adult form of seborrheic dermatitis is much more common than the infantile type and tends to affect men more than women. It often starts around puberty, which is linked to increased oil production due to the development of oil glands and the release of sebum caused by androgen hormones. The course of seborrheic dermatitis in adults can vary over time, with some people experiencing only occasional flare-ups and others having chronic conditions with more frequent recurrences(34)

NUMMULAR DERMATITIS: Nummular dermatitis, also known as discoid eczema or nummular eczema, is a skin condition that causes itching and red, coin-shaped patches. It is a long-term inflammatory skin disease that usually affects the arms and legs, though it can also occur on the trunk(35)Nummular eczema is an allergic condition that causes itchy, coin-shaped patches on the skin. It can sometimes be confused with fungal infections like ringworm or psoriasis. Men usually develop nummular eczema later in life, while women tend to get it at a younger age(36) Skin examination showed dry skin with red, round patches that had yellowish discharge and crusting on the front of the right lower leg. Nummular dermatitis is considered a distinct type of eczema that is either caused internally or has no known cause, although some experts suggest it may be a subtype of atopic dermatitis(37) It mainly affects adults, especially women, with the highest number of cases starting in the third and fourth decades of life. Lesions may come back or last for years. The main treatment is using topical medications, but more intensive treatments may be needed for severe cases(38)

STASIS DERMATITIS:Stasis dermatitis, also called venous eczema or gravitational dermatitis, is a long-term skin condition caused by chronic venous insufficiency. It usually affects the legs, especially in older people(39)The main symptoms come from inflammation in the skin. People often have red, irritated patches and plaques on their lower legs, particularly around the inner part of the ankle(40) A substance called hemosiderin, which comes from broken down red blood cells, can build up in the skin, causing dark pigmentation and lasting discoloration(41) Stasis dermatitis is a common issue linked to chronic venous insufficiency, and it shows up as red and irritated patches on the lower legs(42)

DYSHIDROTIC DERMATITIS:Dyshidrotic dermatitis, also known as dyshidrotic eczema or acute palmoplantar eczema, is a common type of hand rash in adults.It accounts for 5 to 20% of hand skin problems(43) It is a condition that causes small blisters on the hands and feet. Its exact cause is not clear, but it is likely due to multiple factors and may be connected to atopic conditions(44) It can come on suddenly and cause intense itching, with small, deep blisters forming on the fingers, palms, and soles. Over time, these may turn into dry, scaly patches, cracks, and sometimes thickened skin(45)Dyshidrotic eczema is a long-term skin condition that is hard to treat, especially when the skin becomes thickened(46) The exact reason it happens is not well understood. Clinically, it is seen as sudden outbreaks of small, sterile blisters on red, scaly skin. It can come with thickened skin, redness, scaling, and cracking. It most often happens in middle-aged people, usually between the ages of 40 and 58years(47)

CAUSES OF DERMATITIS:

1-Itching: Itching is a core symptoms of dermatitis scratching and itching can trigger skin rashes.It can be worse the condition by breaking down the skin barriers leading skin infections.(48)

2-Burning or stinging sensation: A burning feeling in the skin is a common issue in dermatitis.When this pain is on the skin it suggests possible involvement of small nerve fibers, which should be considered in the possible causes.(49)

3-Temperature: Climate change is a global threat to public health and causes or worsens various diseases including dermatitis allergic, infectious, cardiovascular diseases, physical injuries, and mental disorders.(50)

4-Redness: The most common early symptom is red, dry, itching skin. Severe cases can include crusty scales, painful cracks in your skin, or blisters that ooze fluid. Since a range of things can irritate your skin, your doctor will try to narrow their diagnosis to a specific kind of dermatitis(51)

5-Allergic reaction: Allergic reactions in dental settings are a big problem, causing many different symptoms and affecting the quality of skin disease.This study looked at various aspects of allergies, including their causes, how they develop, and how common they are in skin disease(52)

6-Environmental factors: The rapidly increasing prevalence of and epigenetic alterations observed in dermatitis indicate a strong role of dynamic environmental factors.Environmental factors that have been shown to negatively affect skin diseases include pollution in water, air, and soil, as well as electromagnetic fields and ionizing radiation.(53)

7-Food additives: There is a wide held belief that food additives are the cause of many skin problems. The evidence, however, that food additives cause skin problems is weak. Even foods themselves seldom cause problems. Studies suggest atopic dermatitis may be aggravated by a dietary factor a small percentage (10–15%) (54)

8-Hormonal changes: Seborrheic dermatitis is especially common during periods of significant hormonal changes like puberty and middle age, affecting areas with more sebaceous glands like the scalp, face, and chest, and research suggests multiple factors including hormones and yeast overgrowth contribute to the condition(55)

ETIOLOGY OF DERMATITIS:The exact cause of eczema is not fully known, but it is thought to come from a mix of genetic and environmental factors.

Genetic Factors: Eczema has a strong genetic link, and people with a family history of eczema, asthma, or allergies are more likely to develop it.Researchers have found several genes related to eczema, especially those that affect the skin's ability to protect itself and how the immune system works (56).

Environmental Exposure: The impact of environmental factors and skin stressors is very important in understanding why eczema is becoming more common.Modern life has changed how people are exposed to various substances, such as household products, cosmetics, tobacco, processed foods, and air pollution. These exposures are believed to play a key role (57).

Skin Barrier Function: Eczema is linked to a weakened skin barrier.This happens because certain genes, like FLG, which help form the outer layer of skin, are not working properly. This leads to lower levels of ceramide, which is important for keeping skin moisturized. It also causes more activity of enzymes that break down proteins inside the skin and increases water loss from the skin (TEWL). Filaggrin is a protein that helps maintain the skin barrier and keeps the outer layer of skin (stratum corneum) hydrated (58). Mutations in the filaggrin gene are connected to higher levels of interleukin (IL)-1, a substance that starts the body's inflammatory response in eczema (59).

SYMPTOMS OF DERMATITIS:

1. Viral infection or illness: Viral infections require isolating cases, quarantining people who may have been exposed, using personal protection methods like infection control, and vaccinating large groups. This is because there are usually no specific treatments for most viral infections.(60)

2.Swollen lymph nodes: Lymphadenopathy refers to when lymph nodes become larger or change in some way. This is usually a sign of an infection, a non-infectious condition, or, in rare cases.(61)

3.Emotional stress: When the body experiences infection, illness, or fever, it goes through stress, which raises cortisol levels, leading to flare-ups of dermatitis. Psychological stress can also increase cortisol levels, causing skin irritation.(62)

4.Insect bites: Insect bites are common and can cause various skin reactions. One insect can lead to different types of skin problems, and each skin issue might come from a different insect, making it difficult to identify which insect caused a specific reaction.(63)

5.Water: Dermatitis caused by water can show in different forms, including swimmer's itch, hot tub rash, and conditions made worse by hard water, each needing special treatment.(64)

6.Redness and blanching: Blanching is a heat treatment done before some food preservation methods like drying, canning, and freezing. It plays a big role in how good the final product turns out.(65)

7.Pollen: People who are only allergic to pollen usually experience symptoms during the spring. Those allergic to multiple things might have symptoms for several months or all year round.(66)

8.Drug reactions: Adverse drug reactions are any harmful or unwanted effects that occur when taking a medicine. These can be expected or unexpected and can happen even at normal doses used for treating diseases or for other medical purposes.(67)

9.Food allergies: Food allergies are immune system reactions that happen every time a person eats a certain food. They are different from food intolerance, which is not an immune response and can be caused by various non-immune factors like digestion issues or toxicity.(68)

Pathogenesis

The development of dermatitis is complicated and involves exposure to environmental factors in people who are genetically at risk.A problem with the skin barrier is often the first step in causing dermatitis, though it can be disrupted later by inflammation or from scratching.(69) This leads to an inflammatory response that activates the body's innate immune system through the release of certain cytokines by skin cells, such as IL-1α, IL-1β, tumor necrosis factor-α, IL-8, IL-18, and granulocyte-macrophage colony-stimulating factor. Allergens are then taken in by cells that present them to the immune system, like Langerhans cells and dermal dendritic cells, and travel to nearby lymph nodes.(70) Genetic studies have also found that certain gene clusters linked to skin barrier problems, such as the filaggrin (FLG) gene, are strongly connected to dermatitis.(71)

Epidemiology: Dermatitis has become more common over the past 30 years.Current estimates suggest that the condition affects 1–3% of adults and 10–20% of children in developed countries (72). Around 45% of all dermatitis cases start within the first six months of life, 60% by the first year, and 85% before the age of five. Dermatitis often begins in early infancy. Many newborns who are at risk of developing dermatitis already show increased levels of transepidermal water loss on their second day of life (73), and this finding strongly suggests a future food allergy (74). Fortunately, up to 70% of children with dermatitis will see a clinical improvement before reaching adolescence (75). As previously mentioned, children with dermatitis are at a higher risk of developing allergic rhinitis, asthma, and food allergies. A major risk factor for severe dermatitis in infancy is having allergies to peanuts and eggs (76). A recent systematic review found that food allergies are specifically linked to more severe and long-lasting dermatitis, with dermatitis often occurring before food allergies, indicating a possible cause-and-effect relationship (77). Additionally, research shows that about 50% of people who develop dermatitis before the age of two will go on to develop asthma later in life. Children with dermatitis who also have allergic rhinitis or asthma are more likely to suffer from severe disease (78).

Diagnosis:There are no specific tests that can diagnose dermatitis.Instead, the condition is diagnosed based on specific criteria that take into account the patient’s medical history and symptoms. Although there are several established and validated diagnostic criteria for dermatitis, applying many of them can be time-consuming and often requires invasive testing. Williams et al. proposed simplified criteria in (Table 1) that are easy to use, do not require invasive testing, and have been shown to have high sensitivity and specificity for diagnosing dermatitis (79–81). These criteria state that a child must have an itchy skin condition (or parental/caregiver reports of scratching or rubbing) along with three or more minor criteria.

RISK FACTORS:

Common risk factors for dermatitis include:

Age.Dermatitis can happen to anyone, but atopic dermatitis is more often seen in children than in adults. It usually starts during infancy.

Allergies, atopic dermatitis, and asthma.People with a personal or family history of atopic dermatitis, allergies, hay fever, or asthma are more likely to develop atopic dermatitis.

Occupation.Certain jobs that involve exposure to metals, solvents, or cleaning products can increase the risk of contact dermatitis. For example, healthcare workers are more likely to develop hand eczema.

Other health conditions.Some health issues, such as Parkinson’s disease,immunodeficiency, and HIV/AIDS, are linked to an increased risk of seborrheic dermatitis.

TREATMENT: The treatment for dermatitis should focus on restoring the skin barrier. This includes keeping the skin hydrated and repaired, reducing itching, and lowering inflammation when necessary. Since dermatitis is a long-term condition, it's important for patients and caregivers to follow treatment plans consistently. Managing dermatitis effectively needs a comprehensive approach that involves educating patients and caregivers, using proper skin care routines, and applying anti-inflammatory treatments like topical corticosteroids (which are usually the first choice) and/or topical calcineurin inhibitors (TCIs). Treating skin infections is also important. In more severe cases that don't respond to good skin care and topical treatments, systemic immunosuppressive drugs might be considered. While first-generation antihistamines are not typically recommended for dermatitis because they can cause drowsiness and other side effects, they may be used short-term in people who have severe flare-ups, especially if these flares are causing serious sleep problems.

Education:Patients and their caregivers need to understand that the illness is long-term, so they can handle it effectively.It is important to keep up with proper skin care routines and use topical treatments as instructed. Not following these treatments, especially topical ones, often leads to worse results. This usually happens because people don't have enough information or are worried about side effects(82) Studies have shown that spending more time teaching patients and caregivers about these issues can make a big difference in how well the illness is managed. Patients can also get clear instructions on how to use medications, take care of their skin, and avoid flare-ups, which helps them understand better(83)

Skin care: Taking good care of the skin is a key part of managing dermatitis.Most experts suggest taking a bath every day, even though this is sometimes debated. Soaking in warm water for 10 to 15 minutes each day can help hydrate, clean, and improve the skin, especially when the skin is infected or needs treatment. This soaking time can vary based on how severe the dermatitis is(84) For people with mild, moderate, or severe dermatitis, using plenty of moisturizers or emollients is strongly recommended(85) Some studies show that using moisturizers from birth can help high-risk babies avoid developing dermatitis. This can reduce the need for topical steroids by easing itching and dryness and helping control flare-ups(86)Moisturizing helps the skin keep its moisture by reducing water loss, which is important for healing a damaged skin barrier. The type of moisturizer—whether cream, lotion, or ointment—can depend on the patient’s preference, the area being treated, the climate, and how dry the skin(87)

Topical anti-inflammatory treatments: The main treatment for dermatitis is using topical corticosteroids.These medicines have anti-inflammatory, antiproliferative, and immunosuppressive effects, which help control atopic skin issues. However, improper use can lead to side effects like thinning of the skin, purple spots, stretch marks, visible blood vessels, changes in skin color, and acne-like breakouts. (88) Systemic side effects from topical corticosteroids are rare but can include problems with the hypothalamic-pituitary-adrenal axis and slowed growth. (89)

Phototherapy: Ultraviolet (UV) light has antimicrobial properties and helps reduce the presence of Staphylococcus aureus on atopic skin.Studies have also shown that UVA1 treatment can suppress interleukin (IL)-5, IL-13, and IL-31, which are involved in inflammation. (25) Recent research suggests that vitamin D plays a key role in healing atopic skin during phototherapy. (90) After two weeks of treatment, there was a noticeable change in vitamin D levels, with increased serum calcidiol helping to treat dermatitis effectively. The use of UV light also helps by reducing and impairing the function of dendritic cells in the outer and deeper layers of the skin. (91)

Antihistamines: First-generation antihistamines, such as hydroxyzine, diphenhydramine, and chlorpheniramine, do not directly relieve the itching from dermatitis.However, their sedative effect can help patients with dermatitis sleep better. On the other hand, these medications may reduce rapid eye movement (REM) sleep, affect learning, and lower work performance. (92)

OTHER TREATMENTS OF DERMATITIS:

Table 2 Potency of common topical corticosteroid therapies