Atopic dermatitis
Atopic dermatitis, also known as atopic eczema, is a long-term type of inflammation of the skin. Atopic dermatitis is also often called simply eczema, but "eczema" is also used to refer to dermatitis, the larger group of skin conditions. Atopic dermatitis results in itchy, red, swollen, and cracked skin. Clear fluid may come from the affected areas, which can thicken over time.
Atopic dermatitis affects about 20% of people at some point in their lives. It is more common in younger children. Females are affected slightly more often than males. Many people outgrow the condition.
While the condition may occur at any age, it typically begins in childhood, with varying severity over the years. In children under one year of age, the face and limbs and much of the body may be affected. As children get older, the areas on the insides of the knees and folds of the elbows and around the neck are most commonly affected. In adults, the hands and feet are commonly affected. Scratching the affected areas worsens the eczema and increases the risk of skin infections. Many people with atopic dermatitis develop hay fever or asthma.
The cause is unknown but is believed to involve genetics, immune system dysfunction, environmental exposures, and difficulties with the permeability of the skin. If one identical twin is affected, the other has an 85% chance of having the condition. Those who live in cities and dry climates are more commonly affected. Exposure to certain chemicals or frequent hand washing makes symptoms worse. While emotional stress may make the symptoms worse, it is not a cause. The disorder is not contagious. A diagnosis is typically based on the signs, symptoms, and family history.
Treatment involves avoiding things that make the condition worse, enhancing the skin barrier through skin care, and treating the underlying skin inflammation. Moisturising creams are used to make the skin less dry and prevent AD flare-ups. Anti-inflammatory corticosteroid creams are used to control flare-ups. Creams based on calcineurin inhibitors may also be used to control flares if other measures are not effective. Certain antihistamine pills might help with itchiness. Things that commonly make it worse include house dust mite, stress, and seasonal factors. Phototherapy may be useful in some people. Antibiotics are usually not helpful unless there is secondary bacterial infection or the person is unwell. Dietary exclusion does not benefit most people, and it is only needed if food allergies are suspected. More severe AD cases may need systemic medicines such as cyclosporin, methotrexate, dupilumab, or baricitinib.
Other names of the condition include "infantile eczema", "flexural eczema", "prurigo Besnier", "allergic eczema", and "neurodermatitis".
Signs and symptoms
Symptoms refer to the sensations that people with AD feel, whereas signs refer to a description of the visible changes that result from AD.The main symptom of AD is itching which can be intense. Some people experience burning, soreness, or pain.People with AD often have generally dry skin that can look greyish in people with darker skin tones. Areas of AD are not well-defined, and they are typically inflamed. Surface changes include:
- scaling cracking
- swelling
- scratch marks
- bumpiness
- oozing of clear fluid
- thickening of the skin where the AD has been present for a long time.
Atopic dermatitis commonly affects the eyelids, where an extra prominent crease can form under the eyelid due to skin swelling known as Dennie-Morgan infraorbital folds. Cracks can form under the ears, which can be painful.
The inflammation from AD often leaves "footprints" known as postinflammatory pigmentation that can be lighter than the normal skin or darker. These marks are not scars and eventually go back to normal over months, provided the underlying AD is treated effectively.
People with AD often have dry and scaly skin that spans the entire body, except perhaps the diaper area, and intensely itchy red, splotchy, raised lesions that form in the bends of the arms or legs, face, and neck.
Causes
The cause of AD is not known, although evidence indicates environmental, immunologic, bacterial, and potential genetic factors.Pollution
Since 1970 the rates of atopic dermatitis in the US and UK have increased three- to sixfold. Even today, people who migrate from developing nations before the age of 4 years old to industrialized nations experience a dramatic rise in the risk of atopic dermatitis and have an additional risk when living in urbanized areas of the industrial nation. Recent work has shed light on these and other data, strongly suggesting that early life industrial exposures may cause atopic dermatitis. Chemicals such as isocyanates and xylene prevent the skin bacteria from producing ceramide-sphingolipid family lipids. Early life deficiency in these lipids predicts which children will go on to develop atopic dermatitis. These chemicals also directly activate an itch receptor in the skin known as TRPA1. The industrial manufacturing and use of both xylene and diisocyanates greatly increased starting in 1970, which greatly expanded the average exposure to these substances. For example, these chemicals are components of several exposures known to increase the risk of atopic dermatitis or worsen symptoms including: wildfires, automobile exhaust, wallpaper adhesives, paints, non-latex foam furniture, cigarette smoke, and are elements of fabrics like polyester, nylon, and spandex.Climate
Low humidity and low temperature increase the prevalence and risk of flare-ups in people with atopic dermatitis.Genetics
Genes that may contribute to AD are mainly those responsible for immune response and the skin barrier.Immune response: Many people with AD have a family history or a personal history of atopy. Atopy is a term used to describe individuals who produce substantial amounts of IgE. Such individuals have an increased tendency to develop asthma, hay fever, eczema, urticaria, and allergic rhinitis. Up to 80% of people with atopic dermatitis have elevated total or allergen-specific IgE levels.
Skin barrier: About 30% of people with AD have mutations in the gene for the production of filaggrin, which increases the risk for the early onset of atopic dermatitis and developing asthma. However, expression of filaggrin protein or breakdown products offers no predictive utility in atopic dermatitis risk.
People with atopic dermatitis also have decreased expression of tight junction protein Claudin-1, which deteriorates the bioelectric barrier function in the epidermis.
Hygiene hypothesis
According to the hygiene hypothesis, early childhood exposure to certain microorganisms protects against allergic diseases by contributing to the development of the immune system. This exposure is limited in a modern "sanitary" environment, and the incorrectly developed immune system is prone to develop allergies to harmless substances.Some support exists for this hypothesis with respect to AD. Those exposed to dogs while growing up have a lower risk of atopic dermatitis. Also, epidemiological studies support a protective role for helminths against AD. Likewise, children with poor hygiene are at a lower risk for developing AD, as are children who drink unpasteurized milk.
Allergens
In a small percentage of cases, atopic dermatitis is caused by sensitization to foods such as milk, but there is growing consensus that food allergy most likely arises as a result of skin barrier dysfunction resulting from AD, rather than food allergy causing the skin problems. Atopic dermatitis sometimes appears associated with coeliac disease and non-coeliac gluten sensitivity. Because a gluten-free diet improves symptoms in these cases, gluten seems to be the cause of AD in these cases. A diet high in fruits seems to have a protective effect against AD, whereas the opposite seems true for heavily processed foods.Exposure to allergens, either from food or the environment, can exacerbate existing atopic dermatitis. Exposure to dust mites, for example, is believed to contribute to the risk of developing AD.
Hard water
The prevalence of atopic dermatitis in children may be linked to the level of calcium carbonate or "hardness" of household drinking water. Living in areas with hard water may also play a part in the development of AD in early life. However, when AD is already established, using water softeners at home does not reduce the severity of the symptoms.Role of ''Staphylococcus aureus''
Colonization of the skin by the bacterium S. aureus is prevalent in those with atopic dermatitis. Abnormalities in the skin barrier of persons with AD are exploited by S. aureus to trigger cytokine expression, thus aggravating the condition.However, atopic dermatitis is non-communicable and therefore could not be directly caused by a highly infectious organism. Furthermore, there is insufficient evidence for the effectiveness of anti-staphylococcal treatments for treating S. aureus in infected or uninfected eczema.
The role of S. aureus in skin irritation occurs via inflammation factors that induce itching, which may damage the skin, further driving inflammation, and facilitating the growth of S. aureus, thus promoting a chronic cycle.
Pathophysiology
Excessive type 2 inflammation underlies the pathophysiology of atopic dermatitis.Disruption of the epidermal barrier is thought to play an integral role in the pathogenesis of AD. Disruptions of the epidermal barrier allows allergens to penetrate the epidermis to deeper layers of the skin. This leads to activation of epidermal inflammatory dendritic and innate lymphoid cells, which subsequently attract Th2 CD4+ helper T cells to the skin. This dysregulated Th2 inflammatory response is thought to lead to the eczematous lesions. The Th2 helper T cells become activated, leading to the release of inflammatory cytokines including IL-4, IL-13, and IL-31 which activate downstream Janus kinase pathways. The active Jak pathways lead to inflammation and downstream activation of plasma cells and B lymphocytes, which release antigen-specific IgE, contributing to further inflammation. Other CD4+ helper T-cell pathways thought to be involved in atopic dermatitis inflammation include the Th1, Th17, and Th22 pathways. Some specific CD4+ helper T-cell inflammatory pathways are more commonly activated in specific ethnic groups with AD possibly explaining the differences in phenotypic presentation of atopic dermatitis in specific populations.
Mutations in the filaggrin gene, FLG, also cause impairment in the skin barrier that contributes to the pathogenesis of AD. Filaggrin is produced by epidermal skin cells in the horny layer of the epidermis. Filaggrin stimulates skin cells to release moisturizing factors and lipid matrix material, which cause adhesion of adjacent keratinocytes and contribute to the skin barrier. A loss-of-function mutation of filaggrin causes loss of this lipid matrix and external moisturizing factors, subsequently leading to disruption of the skin barrier. The disrupted skin barrier leads to transdermal water loss and antigen and allergen penetration of the epidermal layer. Filaggrin mutations are also associated with a decrease in natural antimicrobial peptides found on the skin; subsequently leading to disruption of skin flora and bacterial overgrowth.
Atopic dermatitis is also associated with the release of pruritogens in the skin. Keratinocytes, mast cells, eosinophils and T-cells release pruritogens in the skin; leading to activation of Aδ fibers and Group C nerve fibers in the epidermis and dermis contributing to sensations of pruritus and pain. The pruritogens include the Th2 cytokines IL-4, IL-13, IL-31, histamine, and various neuropeptides. Mechanical stimulation from scratching lesions can also lead to the release of pruritogens contributing to the itch-scratch cycle, whereby there is increased pruritus or itch after scratching a lesion. Chronic scratching of lesions can cause thickening or lichenification of the skin or prurigo nodularis.
Another factor in the barrier failure and immunological dysregulation in people with atopic dermatitis may be due to decreases in tight junction protein Claudin-1. Inhibiting Claudin-1 expression in human keratinocytes has been shown to both reduce tight junction function, as well as increase keratinocyte proliferation in vitro. It has also been discovered that this deteriorates the bioelectric barrier function in the epidermis.