Atopic dermatitis

Source: Wikipedia, the free encyclopedia.
(Redirected from
Atopic eczema
)
Atopic dermatitis
Other namesAtopic eczema, infantile eczema, prurigo Besnier, allergic eczema, neurodermatitis
moisturising cream, steroid creams for flares[3] Humidifier
Frequency~20% at some time[2][4]

Atopic dermatitis (AD), also known as atopic eczema, is a long-term type of inflammation of the skin (

eczema, a term that generally refers to a larger group of skin conditions.[2][5]

Atopic dermatitis affects about 20% of people at some point in their lives.[2][4] It is more common in younger children.[3] Females are slightly more affected than males.[6] Many people outgrow the condition.[3]

While the condition may occur at any age, it typically starts in childhood, with changing severity over the years.

hay fever or asthma.[2]

The cause is unknown but believed to involve

identical twin is affected, the other has an 85% chance of having the condition.[7] Those who live in cities and dry climates are more commonly affected.[2] Exposure to certain chemicals or frequent hand washing makes symptoms worse.[2] While emotional stress may make the symptoms worse, it is not a cause.[2] The disorder is not contagious.[2] A diagnosis is typically based on the signs, symptoms and family history.[3]
ECLARE ANG IS ONE OF THE MAIN CARRIER OF ECZEMA

Treatment involves avoiding things that make the condition worse, enhancing the skin barrier through skin care and treating the underlying skin inflammation.

Phototherapy may be useful in some people.[2] Antibiotics (either by mouth or topically) are usually not helpful unless there is secondary bacterial infection or the person is unwell.[10] Dietary exclusion does not benefit most people and it is only needed if food allergies are suspected.[11] 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".[1]

Signs and symptoms

Child with atopic dermatitis

Symptoms refer to the sensations that people with AD feel, whereas signs refers to a description of the visible changes that result from AD.

The pattern of atopic eczema varies with age.

The main symptom of AD is itching which can be intense. Some people experience burning or soreness or pain.[2]

People with AD often have a generally dry skin that can look greyish in people with darker skin tones of colour. Areas of AD are not well defined, and they are typically inflamed (red in a light coloured skin or purple or dark brown in people with dark skin of colour).[12] Surface changes include:

  • scaling cracking (fissures)
  • swelling (oedema)
  • scratch marks (excoriation)
  • bumpiness (papulation)
  • oozing of clear fluid
  • thickening of the skin (lichenification) where the AD has been present for a long time.[2]

Eczema often starts on the cheeks and outer limbs and body in infants and frequently settles in the folds of the skin such as behind the knees, folds of the elbows, around the neck, wrists and under the buttock folds as the child grows.[13] Any part of the body can be affected by AD.[14]

AD commonly affects the eyelids, where an extra prominent crease can form under the eyelid due to skin swelling known as Dennie-Morgan infraorbital folds.[15] Cracks can form under the ears which can be painful (infra-auricular fissure).[16][15]

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 a period of months providing the underlying AD is treated effectively.[17]

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 to form in the bends of the arms or legs, face, and neck.[18][19][20][21][22]

Causes

The cause of AD is not known, although some evidence indicates environmental, immunologic, and potential genetic factors.[23]

Pollution

Since 1970, the rates of atopic dermatitis in the US and UK have increased 3-6 fold.[24] Even today, people who migrate from developing nations before the age of 4 years 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.[25] Recent work has shed light on these and other data strongly suggesting that early life industrial exposures may cause atopic dermatitis.[24][26] Chemicals such as (di)isocyanates and xylene prevent the skin bacteria from producing ceramide-sphingolipid family lipids.[24][26] Early life deficiency in these lipids predictive which children will go on to develop atopic dermatitis.[27][28][29][30] These chemicals also directly activate an itch receptor in the skin known as TRPA1.[31] 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.[25][24][26]

Climate

Low humidity, and low temperature increase the prevalence and risk of flares in patients with atopic dermatitis.[32]

Genetics

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.[18][19] Up to 80% of people with atopic dermatitis have elevated total or allergen-specific IgE levels.[33]

About 30% of people with atopic dermatitis have mutations in the gene for the production of filaggrin (FLG), which increase the risk for early onset of atopic dermatitis and developing asthma.[34][35] However, expression of filaggrin protein or breakdown products offer no predictive utility in atopic dermatitis risk.[28]

Hygiene hypothesis

According to the

helminth parasites) protects against allergic diseases by contributing to the development of the immune system.[36]
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.[37] Those exposed to dogs while growing up have a lower risk of atopic dermatitis.[38] Also, epidemiological studies support a protective role for helminths against AD.[39] Likewise, children with poor hygiene are at a lower risk for developing AD, as are children who drink unpasteurized milk.[39]

Allergens

In a small percentage of cases, atopic dermatitis is caused by sensitization to foods

coeliac disease and non-coeliac gluten sensitivity. Because a gluten-free diet (GFD) improves symptoms in these cases, gluten seems to be the cause of AD in these cases.[42][43] A diet high in fruits seems to have a protective effect against AD, whereas the opposite seems true for heavily processed foods.[39]

Exposure to allergens, either from food or the environment, can exacerbate existing atopic dermatitis.[44] Exposure to dust mites, for example, is believed to contribute to the risk of developing AD.[45]

Role of Staphylococcus aureus

Colonization of the skin by the bacterium S. aureus is extremely prevalent in those with atopic dermatitis.[46] Abnormalities in the skin barrier of persons with AD are exploited by S. aureus to trigger cytokine expression, thus aggravating the condition.[47] 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.[48]

Hard water

The prevalence of atopic dermatitis in children may be linked to the level of calcium carbonate or "hardness" of household drinking water.[49][50] 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.[50]

Pathophysiology

Excessive type 2 inflammation underlies the pathophysiology of atopic dermatitis.[51][52]

Disruption of the epidermal barrier is thought to play an integral role in the

IgE contributing to further inflammation.[33] Other CD4+ helper T-cell pathways thought to be involved in atopic dermatitis inflammation include the Th1, Th17, and Th22 pathways.[33] Some specific CD4+ helper T-cell inflammatory pathways are more commonly activated in specific ethnic groups with AD (for example, the Th-2 and Th-17 pathways are commonly activated in Asian people) possibly explaining the differences in phenotypic presentation of atopic dermatitis in specific populations.[33]

Mutations in the filaggrin gene, FLG, also cause impairment in the skin barrier that contributes to the pathogenesis of AD.

xerosis or dry skin commonly seen in AD) and antigen and allergen penetration of the epidermal layer.[33] 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 (commonly Staphylococcus aureus overgrowth or colonization).[33]

Atopic dermatitis is also associated with the release of pruritogens (molecules that stimulate

lichenification of the skin or prurigo nodularis (generalized nodules that are severely itchy).[33]

Diagnosis

AD is typically

diagnosed clinically, meaning it is based on signs and symptoms alone, without special testing.[53] Several different criteria developed for research have also been validated to aid in diagnosis.[54] Of these, the UK Diagnostic Criteria, based on the work of Hanifin and Rajka, has been the most widely validated.[54][55]

UK diagnostic criteria[55]
People must have itchy skin, or evidence of rubbing or scratching, plus three or more of:
Skin creases are involved - flexural dermatitis of fronts of ankles, antecubital fossae, popliteal fossae, skin around eyes, or neck, (or cheeks for children under 10)
History of asthma or allergic rhinitis (or family history of these conditions if patient is a child ≤4 years old)
Symptoms began before age 2 (can only be applied to patients ≥4 years old)
History of dry skin (within the past year)
Dermatitis is visible on flexural surfaces (patients ≥age 4) or on the cheeks, forehead, and extensor surfaces (patients<age 4)

Other diseases that must be excluded before making a diagnosis include

seborrheic dermatitis.[3]

Treatments

No cure for AD is known, although treatments may reduce the severity and frequency of flares.[18] The most commonly used topical treatments for AD are topical corticosteroids (to get control of flare-ups) and moisturisers (emollients) to help keep control.[56] Clinical trials often measure the efficacy of treatments with a severity scale such as the SCORAD index or the Eczema Area and Severity Index.[53][57]

Moisturisers

Daily basic care is intended to stabilize the barrier function of the skin to mitigate its sensitivity to irritation and penetration of allergens. Affected persons often report that improvement of skin hydration parallels with improvement in AD symptoms. Moisturisers (or emollients) can improve skin comfort and may reduce disease flares.[58] They can be used as leave-on treatments, bath additives or soap substitutes. There are many different products but the majority of leave-on treatments (least to most greasy) are lotions, creams, gels or ointments. All of the different types of moisturisers are equally effective so people need to choose one or more products based on what suits them, according to their age, body site effected, climate/season and personal preference.[59] Non-medicated prescription moisturisers may also be no more effective than over-the-counter moisturisers.[60]

There is no evidence that the additional use of emollient bath additives is beneficial.[61]

Medication

Topical

Corticosteroids applied directly on skin (topical) have proven effective in managing atopic dermatitis.[18][19][60][62] Newer (second generation) corticosteroids, such as fluticasone propionate and mometasone furoate, are more effective and safer than older ones. Strong and moderate corticosteroids work better than weaker ones. They are also generally safe when used in intermittent bursts to treat AD flare-ups. Applying once daily is as effective as twice or more daily application.[60][62]

In addition to topical corticosteroids, topical

calcineurin inhibitors such as tacrolimus or pimecrolimus are also recommended as first-line therapies for managing atopic dermatitis.[60][63] Both tacrolimus and pimecrolimus are effective and safe to use in AD.[64][65] Crisaborole, an inhibitor of PDE-4, is also effective and safe as a topical treatment for mild-to-moderate AD.[66][67] Ruxolitinib, a Janus kinase inhibitor, has uncertain efficacy and safety.[60][63]

Systemic

Oral medications used for AD include systemic

mycophenolate mofetil, and azathioprine.[18][68] Antidepressants and naltrexone may be used to control pruritus (itchiness).[69]

Leukotriene receptor antagonists such as montelukast might be a useful for the treatment of AD but their effectiveness has not yet been proven by research.[70][71][72]

Certain monoclonal antibodies (mAb) are highly effective for managing atopic dermatitis, but modestly increase the risk of conjunctivitis.[63][73] Among monoclonal antibodies, dupilumab (Dupixent) and tralokinumab (Adtralza, Adbry) are approved to treat moderate-to-severe eczema in the US and the EU.[74][75][76][77] Lebrikizumab (Ebglyss) is also approved in the EU for treating moderate-to-severe AC[78] but in the US its approval was declined due to manufacturing issues.[79]

Some JAK inhibitors such as abrocitinib, trade name Cibinqo,[80] and upadacitinib, trade name Rinvoq,[81] have been approved in the US for the treatment of moderate-to-severe eczema as of January 2022. These treatments are among the most effective systemic treatments, but have uncertain serious harms.[63][73]

Allergen immunotherapy may be effective in relieving symptoms of AD but it also comes with an increased risk of adverse events.[82] This treatment consists of a series of injections or drops under the tongue of a solution containing the allergen.[83]

Antibiotics, either by mouth or applied topically, are commonly used to target overgrowth of S. aureus in the skin of people with AD, but there is insufficient evidence for the effectiveness of anti-staphylococcal treatments for treating S. aureus in infected or uninfected eczema.[48]

Diet

The role of vitamin D on atopic dermatitis is not clear, but vitamin D supplementation may improve its symptoms.[84][85][86]

There is no clear benefit for pregnant mothers taking omega 3 long-chain polyunsaturated fatty acid (LCPUFA) in preventing the development of AD in their child.[87][88]

Several

probiotics seem to have a positive effect, with a roughly 20% reduction in the rate of AD.[89][90][91] Probiotics containing multiple strains of bacteria seem to work the best.[92]

In people with celiac disease or nonceliac gluten sensitivity, a gluten-free diet improves their symptoms and prevents the occurrence of new outbreaks.[42][43]

Use of blood specific IgE or skin prick tests to guide dietary exclusions with the aim of improving disease severity or control is controversial. Clinicians vary in their use of these tests for this purpose and there are very limited evidence of any benefit.[93]

Lifestyle

Health professionals often recommend that people with AD bathe regularly in lukewarm baths, especially in salt water, to moisten their skin.[19][94] Dilute bleach baths may be helpful for people with moderate and severe eczema, but only for patients with Staphylococcus aureus.[95]

Avoiding woolen clothing or scratchy fibres is usually recommended for people with AD as they can trigger a flare.[96][97]

Self-management

Treatment regimens can be confusing and written action plans may support people to know what treatments to use where and when.[98]

A website supporting self-management has been shown to improve AD symptoms for parents, children, adolescents and young adults.[99][100]

Light

UV phototherapy is not indicated in young adults and children due to this risk of skin cancer with prolonged use or exposure.[33]

Alternative medicine

While several

Chinese herbal medicines are intended for treating atopic eczema, no conclusive evidence shows that these treatments, taken by mouth or applied topically, reduce the severity of eczema in children or adults.[105]

Burden of disease

Atopic dermatitis significantly impairs the quality of life of affected individuals. [106][107] The impact of AD extends beyond physical symptoms, encompassing substantial humanistic and psychosocial effects. Its burden is significant, especially given the high indirect costs and psychological impacts on quality of life.[106][108]

According to the Global Burden of Disease Study, AD is the skin disease with the highest disability-adjusted life year burden and ranks in the top 15 of all nonfatal diseases. In comparison with other dermatological conditions like psoriasis and urticaria, AD presents a significantly higher burden.[107]

While AD remains incurable, reducing its severity can significantly alleviate its burden. Understanding the extent of the burden of AD can aid in better resource allocation and prioritization of interventions, benefiting both patients and healthcare systems.[109]

Humanistic burden

AD significantly decreases the quality of life by affecting various aspects of people's lives. The psychological impact, often resulting in conditions like depression and anxiety, is a major factor leading to decreased quality of life. Sleep disturbances, commonly reported in people with AD, further contribute to the humanistic burden, affecting daily productivity and concentration.[106][110]

Clinical and economic burden

Economically, AD imposes a substantial burden on healthcare systems, with the average direct cost per patient estimated at 4411 USD and the average indirect cost reaching 9068 USD annually.[106] These figures highlight the considerable financial impact of the disease on healthcare systems and people with the condition.[111][112]

Productivity loss

AD also has a marked impact on productivity. The total number of days lost annually due to these factors is about 68.8 days for the general AD population, with presenteeism accounting for the majority of these days.[106] The impact on productivity varies significantly with the severity of AD, with more severe cases resulting in higher numbers of days lost.[106][113]

Burden of disease in the Middle East and Africa

Atopic dermatitis leads to the highest loss in disability-adjusted life years compared to other skin diseases in the Middle East and Africa.[114] Patients with AD in these regions lose approximately 0.19 quality-adjusted life years (QALYs) annually due to the disease. Egypt experiences the highest QALY loss and Kuwait the lowest.[114]

The average annual healthcare cost per patient varies is highest in the United Arab Emirates, estimated at US $3569, and lowest in Algeria at US $312. These costs are influenced by the economic status of each country and the cost of healthcare. Advanced treatments like targeted therapies and phototherapy are among the main cost drivers.[114]

Indirect costs, primarily due to productivity loss from absenteeism and presenteeism average about 67% in these countries. Indirect costs in Saudi Arabia are the highest in the area, estimated at US $364 million.[114] Factors like mental health impact, side effects of treatments, and other indirect costs such as personal care products are not fully accounted for in these estimates, suggesting that the actual burden might be even higher.[114]

Epidemiology

Since the beginning of the 20th century, many inflammatory skin disorders have become more common; AD is a classic example of such a disease. Although AD was previously considered primarily a childhood disease, it is now recognized as highly prevalent in adults, with an estimated adult prevalence of 3-5% globally.[106][107] It now affects 15–30% of children and 2–10% of adults in developed countries, and in the United States has nearly tripled in the past 30–40 years.[19][115] Over 15 million American adults and children have AD.[116]

Society and culture

Conspiracy theories

A number of false and conspiratorial claims about AD have emerged on the internet and have been amplified by social media. These

vegan diets, apple cider vinegar, calendula, and witch hazel can cure AD and that air purifiers reduce the risk of developing AD.[117]

Research

Staphylococcus aureus may have a role in producing atopic dermatitis by colonizing on the skin.[118]

See also

References

  1. ^
    S2CID 31546363. Archived
    from the original on 2015-06-19.
  2. ^ a b c d e f g h i j k l m n o p q r s t u v w x "Handout on Health: Atopic Dermatitis (A type of eczema)". National Institute of Arthritis and Musculoskeletal and Skin Diseases. May 2013. Archived from the original on 30 May 2015. Retrieved 19 June 2015.
  3. ^
    PMID 25422009
    .
  4. ^
    PMID 25006501
    .
  5. PMID 15131563
    .
  6. ^ "Atopic Dermatitis". National Institute of Arthritis and Musculoskeletal and Skin Diseases. September 2019. Retrieved 29 August 2022.
  7. ISBN 978-1-4443-0017-8. Archived
    from the original on 2017-09-08.
  8. PMID 23549982
    .
  9. S2CID 43247714
    .
  10. S2CID 256222372
    .
  11. S2CID 250710625
    .
  12. S2CID 3379280
    .
  13. OCLC 605909001
    .
  14. ISBN 978-0-470-75052-0
    .
  15. ^
    PMID 22583715
    .
  16. S2CID 220873055
    .
  17. ^ Lambert A (2021-02-09). "Skin pigmentation and eczema". National Eczema Society. Retrieved 2023-04-06.
  18. ^
    PMID 22962911. Archived
    (PDF) from the original on 2015-09-06.
  19. ^ a b c d e Kim BS (21 January 2014). Fritsch P, Vinson RP, Perry V, Quirk CM, James WD (eds.). "Atopic Dermatitis". Medscape Reference. WebMD. Archived from the original on 10 February 2014. Retrieved 3 March 2014.
  20. ISBN 978-3-540-67136-7
    .
  21. S2CID 28538214
    .
  22. PMID 24035157
    .
  23. PMID 27517355
    .
  24. ^ a b c d "NIAID Researchers Identify Link Between Common Chemicals and Eczema | NIH: National Institute of Allergy and Infectious Diseases". www.niaid.nih.gov. 2023-01-23. Retrieved 2023-11-23.
  25. ^
    PMID 36608129
    .
  26. ^ a b c "Eczema's cause could be in the air we breathe". NBC News. 2023-03-26. Retrieved 2023-11-23.
  27. PMID 37422700
    .
  28. ^
    S2CID 255078763
    .
  29. PMID 36112082
    .
  30. PMID 36897437
    .
  31. PMID 36877675
    .
  32. S2CID 12378072
    .
  33. ^
    S2CID 232355341
    .
  34. PMID 28025545
    .
  35. PMID 21991953
    .
  36. PMID 28196925
    .
  37. PMID 18385500
    .
  38. PMID 23711545
    .
  39. ^
    S2CID 32645590
    .
  40. PMID 27583103
    .
  41. PMID 32249942
    .
  42. ^
    PMID 25583468
    . Many patients with celiac disease also have atopic disorders. About 30% of patients' allergies with gastrointestinal (GI) symptoms and mucosal lesions, but negative results from serologic (TG2 antibodies) or genetic tests (DQ2 or DQ8 genotype) for celiac disease, had reduced GI and atopic symptoms when they were placed on GFDs. These findings indicated that their symptoms were related to gluten ingestion.
  43. ^
    S2CID 22521576
    .
  44. PMID 16815157. Archived from the original
    (PDF) on 2018-07-19. Retrieved 2019-02-05.
  45. PMID 22361514
    .
  46. S2CID 3112669
    .
  47. PMID 27381887
    .
  48. ^
    PMID 31684694
    .
  49. PMID 24049611
    .
  50. ^
    S2CID 227245344
    .
  51. S2CID 2421591
    .
  52. PMID 32319104
    .
  53. ^
    PMID 24290431
    .
  54. ^
    S2CID 453564
    .
  55. ^
    S2CID 37406163
    .
  56. ^ "What are Topical Treatments for Eczema and How Should They Be Used?". National Eczema Association. Retrieved 2023-06-22.
  57. S2CID 52277845
    .
  58. S2CID 204882682
    .
  59. S2CID 249024141
    .
  60. ^
    S2CID 261610152
    .
  61. PMID 29724749
    .
  62. ^
    PMID 35275399
    .
  63. ^
    PMID 38108679
    .
  64. PMID 26132597
    .
  65. S2CID 253470127
    .
  66. PMID 34861031
    .
  67. ISSN 1529-8019
    .
  68. PMID 23551368
    .
  69. PMID 24009842
    .
  70. S2CID 21753181
    .
  71. PMID 30343498
    .
  72. PMID 38607671
    .
  73. ^
    PMID 37678577
    .
  74. ^ "FDA approves new eczema drug Dupixent". US Food & Drug Administration. 28 March 2017. Archived from the original on 28 March 2017. Retrieved 29 March 2017.
  75. ^ EMA (2018-09-17). "Dupixent". European Medicines Agency. Retrieved 2023-03-22.
  76. ^ "Adtralza EPAR". European Medicines Agency (EMA). 20 April 2021. Retrieved 9 July 2021. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  77. ^ "Drug Approval Package: ADBRY". US Food & Drug Administration. December 27, 2021. Retrieved March 6, 2022.
  78. ^ "Ebglyss". European Medicines Agency. Retrieved 2024-04-15.
  79. ^ "FDA Rejects Lilly's Eczema Treatment Over Third-Party Manufacturing Issues". BioSpace. Retrieved 2023-10-03.
  80. ^ "U.S. FDA Approves Pfizer's Cibinqo (abrocitinib) for Adults with Moderate-to-Severe Atopic Dermatitis". Pfizer Inc. (Press release). 14 January 2022. Retrieved 16 January 2022.
  81. ^ "U.S. FDA Approves RINVOQ® (upadacitinib) to Treat Adults and Children 12 Years and Older with Refractory, Moderate to Severe Atopic Dermatitis". AbbeVie (Press release). Retrieved March 6, 2022.
  82. S2CID 252656283
    .
  83. PMID 26871981
    .
  84. S2CID 35345939
    .
  85. PMID 27061361
    .
  86. PMID 31405041
    .
  87. PMID 32524677
    .
  88. PMID 33585361
    .
  89. PMID 30480774
    .
  90. PMID 31384325
    .
  91. PMID 35978397
    .
  92. PMID 26810481
    .
  93. S2CID 244872550
    .
  94. S2CID 40875822
    .
  95. S2CID 247847598
    .
  96. S2CID 218761019
    .
  97. ^ "Clothing and eczema". National Eczema Society. 2020-02-11. Retrieved 2023-04-10.
  98. S2CID 257729897
    .
  99. S2CID 258094184
    .
  100. S2CID 254367009
    .
  101. PMID 21762976
    .
  102. S2CID 22191753
    .
  103. PMID 34709669
    .
  104. PMID 16966369
    .
  105. PMID 24018636
    .
  106. ^
    PMID 36197589
    .
  107. ^
    PMID 33782057
    .
  108. PMID 32401725
    .
  109. PMID 33516523
    .
  110. PMID 18436948
    .
  111. PMID 33861780
    .
  112. ^ "World Bank Country and Lending Groups – World Bank Data Help Desk". datahelpdesk.worldbank.org. Retrieved 2024-01-14.
  113. PMID 28978208
    .
  114. ^
    PMID 36445612
    .
  115. S2CID 20040720
    .
  116. ^ "Atopic Dermatitis". www.uchospitals.edu. 1 January 2015. Archived from the original on 2015-04-08. Retrieved 2 April 2015.
  117. S2CID 233278383
    .
  118. S2CID 23617550
    .

External links

Wikimedia Commons has media related to Atopic dermatitis.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Atopic_dermatitis&oldid=1220514578"