Eczema Explained

Eczema
Icd10:-
Omim:603165
Medlineplus:000853
Emedicinesubj:Derm
Emedicinetopic:38
Meshid:D004485

Eczema (from Greek ἔκζεμα ēkzema, "to boil over") is a form of dermatitis, or inflammation of the epidermis (the outer layer of the skin). In England, an estimated 5.7 million or about one in every nine people have been diagnosed with the disease by a clinician at some point in their lives.[1]

The term eczema is broadly applied to a range of persistent skin conditions. These include dryness and recurring skin rashes that are characterized by one or more of these symptoms: redness, skin edema (swelling), itching and dryness, crusting, flaking, blistering, cracking, oozing, or bleeding. Areas of temporary skin discoloration may appear and are sometimes due to healed injuries. Scratching open a healing lesion may result in scarring and may enlarge the rash.

The word eczema comes from Greek words, that mean "to boil over". Dermatitis comes from the Greek word for skinand both terms refer to exactly the same skin condition. In some languages, dermatitis and eczema are synonymous, while in other languages dermatitis implies an acute condition and "eczema" a chronic one.[2] The two conditions are often classified together.

Classification

The term eczema refers to a set of clinical characteristics. Classification of the underlying diseases has been haphazard and unsystematic, with many synonyms used to describe the same condition. A type of eczema may be described by location (e.g., hand eczema), by specific appearance (eczema craquele or discoid), or by possible cause (varicose eczema). Further adding to the confusion, many sources use the term eczema for the most common type of eczema (atopic dermatitis) interchangeably.

The European Academy of Allergology and Clinical Immunology (EAACI) published a position paper in 2001 which simplifies the nomenclature of allergy-related diseases including atopic and allergic contact eczemas.[3] Non-allergic eczemas are not affected by this proposal.

The classifications below is ordered by incidence frequency.

Common

Less common

Cause

The cause of eczema is unknown but is presumed to be a combination of genetic and environmental factors.[4]

The hygiene hypothesis postulates that the cause of asthma, eczema, and other allergic diseases is an unusually clean environment. It is supported by epidemiologic studies for asthma.[5] The hypothesis states that exposure to bacteria and other immune system modulators is important during development, and missing out on this exposure increases risk for asthma and allergy.

While it has been suggested that eczema may sometimes be an allergic reaction to the excrement from house dust mites,[6] with up to 5% of people showing antibodies to the mites,[7] the overall role this plays awaits further corroboration.

Researchers have compared the prevalence of eczema in people who also suffer from celiac disease to eczema prevalence in control subjects, and they've found that eczema occurs about three times more frequently in celiac disease patients and about two times more frequently in relatives of celiac patients, potentially indicating a genetic link between the two conditions.[8] [9]

Eczema is known to have a strong connection to Candidiasis fungal infection, so many physicians prefer an antifungal-and-corticosteroid combination creams.

Diagnosis

Diagnosis of eczema is based mostly on history and physical examination. However, in uncertain cases, skin biopsy may be useful.

Prevention

Those with eczema should not get the smallpox vaccination due to risk of developing eczema vaccinatum, a potentially severe and sometimes fatal complication.[10]

Treatment

There is no known cure for eczema; therefore, treatments aim to control the symptoms by reducing inflammation and relieving itching.

Medications

Corticosteroids

Corticosteroids are highly effective in controlling or suppressing symptoms in most cases.[11] For mild-moderate eczema a weak steroid may be used (e.g. hydrocortisone), while in more severe cases a higher-potency steroid (e.g. clobetasol propionate) may be used. In severe cases, oral or injectable corticosteroids may be used. While these usually bring about rapid improvements, they have greater side effects. Candidiasis is a yeast or fungal infection that often develop on skin with eczema, so many physicians prefer an antifungal-and-corticosteroid combination creams.[12] [13] [14] [15]

Side effects

Prolonged use of topical corticosteroids is thought to increase the risk of side effects, the most common of which is the skin becoming thin and fragile (atrophy).[16] Because of this, if used on the face or other delicate skin, only a low-strength steroid should be used. Additionally, high-strength steroids used over large areas, or under occlusion, may be significantly absorbed into the body, causing hypothalamic-pituitary-adrenal axis suppression (HPA axis suppression).[17] Finally by their immunosuppressive action they can, if used without antibiotics or antifungal drugs, lead to some skin infections (fungal or bacterial). Care must be taken to avoid the eyes, as topical corticosteroids applied to the eye can cause glaucoma [18] or cataracts.

Because of the risks associated with this type of drug, a steroid of an appropriate strength should be sparingly applied only to control an episode of eczema. Once the desired response has been achieved, it should be discontinued and replaced with emollients as maintenance therapy. Corticosteroids are generally considered safe to use in the short- to medium-term for controlling eczema, with no significant side effects differing from treatment with non-steroidal ointment.[19]

Some recent research claims that topically applied corticosteroids did not significantly increase the risk of skin thinning, stretch marks or HPA axis suppression (and where such suppression did occur, it was mild and reversible where the corticosteroids were used for limited periods of time). Further, skin conditions are often under-treated because of fears of side effects. This has led some researchers to suggest that the usual dosage instructions should be changed from "Use sparingly" to "Apply enough to cover affected areas", and that specific dosage directions using "fingertip units" or FTUs be provided, along with photos to illustrate FTUs.[20] However, caution must always be used as long-term use, prolonged widespread coverage, or use with occlusion, can create side effects that are permanent and resistant to treatment.[21]

Topical immunosuppressants

Topical immunosuppressants like pimecrolimus (Elidel and Douglan) and tacrolimus (Protopic) were developed after topical corticosteroids had come into widespread use. These newer agents effectively suppress the immune system in the affected area, and appear to yield better results in some populations.The U.S. Food and Drug Administration has issued a public health advisory about the possible risk of lymph node or skin cancer from use of these products,[22] but many professional medical organizations disagree with the FDA's findings;

Oral and parenteral immunosuppressants

When eczema is severe and does not respond to other forms of treatment, immunosuppressant drugs are sometimes prescribed. These dampen the immune system and can result in dramatic improvements to the patient's eczema. However, immunosuppressants can cause side effects on the body. As such, patients must undergo regular blood tests and be closely monitored by a doctor. In the UK, the most commonly used immunosuppressants for eczema are ciclosporin, azathioprine and methotrexate. These drugs were generally designed for other medical conditions but have been found to be effective against eczema.

Itch relief

Anti-itch drugs, often antihistamine, may reduce the itch during a flare up of eczema, and the reduced scratching in turn reduces damage and irritation to the skin (the "itch cycle"). However, in some cases, significant benefit may be due to the sedative side effects of these drugs, rather than their specific antihistamine effect. Thus sedating antihistamines such as promethazine (Phenergan) or diphenhydramine (Benadryl) may be more effective at preventing night time scratching than the newer, nonsedating antihistamines.[27]

Capsaicin applied to the skin acts as a counter irritant (see gate control theory of nerve signal transmission).

Hydrocortisone applied to the skin aids in temporary itch relief.

Temporary yet significant and fast-acting relief can be found by cooling the skin via water (swimming, cool water bath or wet washcloth), air (direct output of an air conditioning vent), or careful use of an ice pack (wrapped in soft smooth cloth, e.g., pillow case, to protect skin from damage).

Moisturizers

Eczema can be exacerbated by dryness of the skin. Moisturizing is one of the most important self-care treatments for eczema. Keeping the affected area moistened can promote skin healing and relief of symptoms. Soaps and detergents should not be used on affected skin because they can strip natural skin oils and lead to excessive dryness.

Moistening agents are called emollients. In general, it is best to match thicker ointments to the driest, flakiest skin. Light emollients may not have any effect on severely dry skin. Moisturizing gloves (gloves which keep emollients in contact with skin on the hands) can be worn while sleeping. Generally, twice-daily applications of emollients work best. Ointments, with less water content, stay on the skin longer and need fewer applications, but they can be greasy and inconvenient. Steroids may also be mixed in with ointments.

For unbroken skin, direct application of waterproof tape with or without an emollient or prescription ointment can improve moisture levels and skin integrity which allows the skin to heal. This treatment regimen can also help prevent the skin from cracking, as well as put a stop to the itch cycle. The end result is reduced lichenification (the roughening of skin from repeated scratching). Taping works best on skin away from joints.

There is a disagreement whether baths are desirable or a necessary evil. For example, the Mayo Clinic advises against daily baths to avoid skin drying.[28] On the other hand,the American Academy of Dermatology claims "it is a common misconception that bathing dries the skin and should be kept to a bare minimum" and recommends bathing to hydrate skin. They even suggest up to 3 short baths a day for people with severe eczema. According to them, a moisturizer should be applied within 3 minutes to trap the moisture from bath in the skin.[29] U.S. National Eczema Associationand the Eczema Society of Canada make similar recommendations.[30] [31]

Anecdotal evidence suggested that soft water could have therapeutic effects for people with eczema currently using hard water.[32] However, a trial involving 336 children with eczema showed no objective difference in outcomes between the children whose homes were fitted with a water softener and those without.[33]

Recently, ceramides, which are the major lipid constituent of the stratum corneum, have been used in the treatment of eczema.[34] [35] [36] They are often one of the ingredients of modern moisturizers. These lipids were also successfully produced synthetically in the laboratory.[37]

However, detergents are so ubiquitous in modern environments in items like tissues, and so persistent on surfaces, "safe" soaps are necessary to remove them from the skin in order to control eczema. Although most eczema recommendations use the terms "detergents" and "soaps" interchangeably, and tell eczema sufferers to avoid both, detergents and soaps are not the same and are not equally problematic to eczema sufferers. Detergents, which differ from soap in that they commonly have a sulfate polar group, increase the permeability of skin membranes in a way that soaps and water alone do not. Sodium lauryl sulfate, the most common household detergent, has been shown to amplify the allergenicity of other substances ("increase antigen penetration").[38]

Unfortunately there is no one agreed-upon best kind of skin cleanser for eczema sufferers. Different clinical tests, sponsored by different personal product companies, unsurprisingly tout various brands as the most skin-friendly based on specific properties of various products and different underlying assumptions as to what really determines skin friendliness. The terms "hypoallergenic" and "doctor tested" are not regulated,[39] and no research has been done showing that products labeled "hypoallergenic" are in fact less problematic than any others. It may be best to avoid soaps and detergent cleansers altogether, except for the armpits, groin and perianal areas, and use cheap bland emollients in the bath or shower.

Lifestyle

Various measures may reduce the amount of mite antigens, in particular swapping carpets for hard surfaces.[40] However it is not clear whether such measures actually help with eczema. A controlled study suggested that a number of environmental factors such as air exchange rates, relative humidity and room temperature (but not the level of house dust mites) might have an effect on the condition.[41]

Light therapy

Light therapy (or deep penetrating light therapy) using ultraviolet light can help control eczema.[42] UVA is mostly used, but UVB and Narrow Band UVB are also used. Overexposure to ultraviolet light carries its own risks, particularly potential skin cancer from exposure.[43]

When light therapy alone is found to be ineffective, the treatment is performed with the application (or ingestion) of a substance called psoralen. This PUVA (Psoralen + UVA) combination therapy is termed photo-chemotherapy. Psoralens make the skin more sensitive to UV light, thus allowing lower doses of UVA to be used. However, the increased sensitivity to UV light also puts the patient at greater risk for skin cancer.[44]

Natural sunlight therapy or climatotherapy

This type of light therapy is available in the Dead Sea region in Israel [45] and is the natural alternative to artifical light therapy mentioned above which does not require the use of the drug Psoralen.The sun shines throughout the year at the dead sea region but it shines through an extra atmospheric layer. The Dead Sea area lies 400 metres below sea level and combines a natural sunscreen of evaporating water and chemicals from the body of water as well as a thick ozone layer. This weakens the harsh and dangerous ultraviolet B (UV-B) rays chiefly responsible for sunburn and greatly increases the amount of safe sun-exposure time. This makes the region ideal for helio- (sunlight) therapy.This type of natural light therapy requires a gradual daily increase to sunlight using an individual timetable according to skin disorder and skin type.Typically patients will start with one 10 minute sunbathing session in the morning and one 10 minute sunbathing session in the afternoon building gradually over 2 weeks to a maximum of 4 x 40 minute separate sunbathing sessions between the hours of 8 -11 am and 2 - 4 pm.

Diet

Recent studies provide hints that food allergy may trigger atopic dermatitis. For these people, identifying the allergens could lead to an avoidance diet to help minimize symptoms, although this approach is still in an experimental stage.[46] Dietary elements that have been reported to trigger eczema include dairy products, coffee (both caffeinated and decaffeinated), soybean products, eggs, nuts, wheat and maize (sweet corn), though food allergies may vary from person to person.However, in 2009, researchers at National Jewish Medical and Research Center found that eczema patients were especially prone to misdiagnosis of food allergies.[47] [48]

A study led by researchers at the University of California, San Diego School of Medicine suggests that use of oral vitamin D3 supplements bolsters production of a protective chemical normally found in the skin, and may help prevent skin infections that are a common result of atopic dermatitis, the most common form of eczema.[49] It can be noted that the production of vitamin D3 is catalyzed by UV radiation and may influence histocompatibility expression, correlating with both the seasonality of eczema and its relation to the immune system. Also, hemp seed oil has been shown to relieve the symptoms of atopic eczema.[50]

Alternative therapies

A number of alternative therapies are used for eczema including:

there is some anecdotal evidence that salt water baths may help some children with atopic eczema.[51] One reason might be that seawater has antiseptic properties. The Dead sea is popular for alleviating skin problems including eczema but it is mainly exposure to the type of sunlight in the dead sea region climatotherapy which helps the eczema rather than the sea water. Any benefits of dead sea water treatment must also be weighed against the extreme discomfort and burning sensations suffered as the salt water contacts raw skin

Patients can also wear clothing designed specifically to manage the itching, scratching and peeling associated with eczema.[60]

Behavioural approach

In the 1980s, Swedish dermatologist Peter Noren developed a behavioural approach to the treatment of long term atopic eczema. This approach has been further developed by dermatologist Richard Staughton and psychiatrist Christopher Bridgett at the Chelsea and Westminster Hospital in London.[61] [62] Patients undergo a six-week monitored program involving scratch habit reversal and self-awareness of scratching levels. For long-term eczema sufferers, scratching can become habitual. Sometimes scratching becomes a reflex, resulting in scratching without conscious awareness, rather than from the feeling of itchiness itself. The habit reversal program is done in conjunction with the standard applied emollient/corticosteroid treatments so that the skin can heal. It also reduces future scratching, as well as reduces the likelihood of further flareups. The behavioural approach can give an eczema sufferer some control over the degree of severity of eczema.

Epidemiology

The lifetime clinician-recorded prevalence of eczema has been seen to peak in infancy, with female predominance of eczema presentations occurring during the reproductive period of 15–49 years.[63] Although little data on the trend of eczema prevalence over time exists prior to the Second World War (1939–45), the prevalence of eczema has been found to have increased substantially in the latter half of the 20th Century, with eczema in school-aged children being found to increase between the late 1940s and 2000.[64] A review of epidemiological data in the UK has also found an inexorable rise in the prevalence of eczema over time.[65] Further recent increases in the incidence and lifetime prevalence of eczema in England have also been reported, such that an estimated 5,773,700 or about one in every nine people have been diagnosed with the disease by a clinician at some point in their lives.[1]

Research

Other than direct treatments of the symptoms, no cure is presently known for most types of dermatitis; even cortisone treatments and immunomodulation may often have only minor effects on what may be a complex problem. As the condition is often related to family history of allergies (and thus heredity), it is probable that gene therapy or genetic engineering might help.

Damage from the enzymatic activity of allergens is usually prevented by the body's own protease inhibitors, such as, LEKTI, produced from the gene SPINK5. Mutations in this gene are known to cause Netherton's syndrome, which is a congenital erythroderma. These patients nearly always develop atopic disease, including hay fever, food allergy, urticaria and asthma. Such evidence supports the hypothesis that skin damage from allergens may be the cause of eczema, and may provide a venue for further treatment.[66]

Another study identified a gene that the researchers believe to be the cause of inherited eczema and some related disorders. The gene produces the protein filaggrin, the lack of which causes dry skin and impaired skin barrier function.[67]

A recent study indicated that two specific chemicals found in the blood are connected to the itching sensations associated with eczema. The chemicals are Brain-derived neurotrophic factor (BDNF) and Substance P.[68]

In a genome-wide study published on Dec 25, 2011 in Nature Genetics, researchers reported discovery of three new genetic variants associated with eczema. They are OVOL1, ACTL9 and IL4-KIF3A.[69]

Eczema has increased dramatically in England as a study showed a 42% rise in diagnosis of the condition between 2001 and 2005, by which time it was estimated to affect 5.7 million adults and children. A paper in the Journal of the Royal Society of Medicine says Eczema is thought to be a trigger for other allergic conditions. GP records show over 9 million patients were used by researchers to assess how many people have the skin disorder.[70]

External links

Notes and References

  1. Simpson CR, Newton J, Hippisley-Cox J, Sheikh A. Trends in the epidemiology and prescribing of medication for eczema in England. Journal of the Royal Society of Medicine. 102. 3. 108–17. 2009. March. 19297652. 2746851. 10.1258/jrsm.2009.080211.
  2. Book: Johannes Ring. Bernhard Przybilla. Thomas Ruzicka. Handbook of atopic eczema. 4 May 2010. 2006. Birkhäuser. 978-3-540-23133-2. 4.
  3. Johansson SG, Hourihane JO, Bousquet J, et al.. A revised nomenclature for allergy. An EAACI position statement from the EAACI nomenclature task force. Allergy. 56. 9. 813–24. 2001. September. 11551246. 10.1034/j.1398-9995.2001.t01-1-00001.x.
  4. Web site: Atopic dermatitis. National Institute of Health. 27 September 2011.
  5. Bufford. JD. Gern JE. The hygiene hypothesis revisited. Immunology and Allergy Clinics of North America. 25. 2. 247–262. May. 2005. 15878454. 10.1016/j.iac.2005.03.005.
  6. Carswell F, Thompson S. Does natural sensitisation in eczema occur through the skin?. Lancet. 2. 8497. 13–5. 1986. 2873316. 10.1016/S0140-6736(86)92560-2.
  7. Henszel Ł, Kuźna-Grygiel W. [House dust mites in the etiology of allergic diseases]. Polish. Annales Academiae Medicae Stetinensis. 52. 2. 123–7. 2006. 17633128.
  8. Web site: Anderson. Jane. Can Eating Gluten-Free Help with Your Eczema Treatment?. About.com Health's Disease and Condition. 27 September 2011.
  9. Ciacci. C. Cavallaro R, Iovino P, Sabbatini F, Palumbo A, Amoruso D, Tortora R, Mazzacca G.. Allergy prevalence in adult celiac disease. J Allergy Clin Immunol. 2004. June. 113(6). 1199–203. 27 September 2011.
  10. Web site: CDC Smallpox | Smallpox (Vaccinia) Vaccine Contraindications (Info for Clinicians). Emergency.cdc.gov. 2007-02-07. 2010-02-07.
  11. Hoare C, Li Wan Po A, Williams H. Systematic review of treatments for atopic eczema. Health Technology Assessment. 4. 37. 1–191. 2000. 11134919.
  12. Web site: Evaluation of Candida albicans allergens reactive with specific IgE in asthma and atopic eczema patients.
  13. Web site: THE ASSOCIATION BETWEEN CANDIDA ALBICANS AND LESIONS OF SEBORRHOEIC ECZEMA.
  14. Web site: Infection and eczema. Sue Ward.
  15. Web site: CANDIDA OVERGROWTH AND HOW IT IS RELATED TO SKIN CONDITIONS SUCH AS PSORIASIS ECZEMA DERMATITIS AND FUNGAL INFECTIONS.
  16. Atherton DJ. Topical corticosteroids in atopic dermatitis. BMJ. 327. 7421. 942–3. 2003. October. 14576221. 259155. 10.1136/bmj.327.7421.942.
  17. Lee NP, Arriola ER. Topical corticosteroids: back to basics. The Western Journal of Medicine. 171. 5-6. 351–3. 1999. 10639873. 1308757.
  18. Web site: neomycin and polymyxin b sulfates and bacitracin zinc with hydrocortisone acetate (Neomycin sulfate and Polymyxin B Sulfate, Bacitracin zinc and Hydrocortisone Acetate) ointment -- Warnings. U.S. Food and Drug Administration.
  19. Van Der Meer JB, Glazenburg EJ, Mulder PG, Eggink HF, Coenraads PJ. The management of moderate to severe atopic dermatitis in adults with topical fluticasone propionate. The Netherlands Adult Atopic DermatitisStudy Group. British Journal of Dermatology. 140. 6. 1114–21. 1999. June. 10354080.
  20. Bewley A. Expert consensus: time for a change in the way we advise our patients to use topical corticosteroids. The British Journal of Dermatology. 158. 5. 917–20. 2008. May. 18294314. 10.1111/j.1365-2133.2008.08479.x. Dermatology Working. Group.
  21. Atrophic patches. 1783752. College of Family Physicians of Canada.
  22. Web site: FDA Issues Public Health Advisory Informing Health Care Providers of Safety Concerns Associated with the Use of Two Eczema Drugs, Elidel and Protopic. March 10, 2005. FDA. 2007-10-16. http://web.archive.org/web/20070917075450/http://www.fda.gov/bbs/topics/ANSWERS/2005/ANS01343.html . 2007-09-17.
  23. Web site: N H Cox and Catherine H Smith. Advice to dermatologists re topical tacrolimus. DOC. 2002. December. Therapy Guidelines Committee. British Association of Dermatologists.
  24. Pimecrolimus cream for atopic dermatitis. Drug and Therapeutics Bulletin. 41. 5. 33–6. 2003. May. 12789846. 10.1136/dtb.2003.41533.
  25. Web site: Microsoft Word - package insert and med guide June 2009.doc. PDF. 2011-03-27.
  26. 10.1590/S0365-05962004000300002. Tratamento sistêmico da psoríase - Parte I: metotrexato e acitretina. 2004. Martins. Gladys Aires. Arruda. Lucia. Anais Brasileiros de Dermatologia. 79.
  27. http://www.cks.nhs.uk/eczema_atopic/evidence/supporting_evidence/antihistamines | Retrieved 14 November 2011
  28. Web site: Atopic dermatitis (eczema) - Prevention at Mayoclinic]'s website]. 2011-10-10.
  29. Web site: Daily Skin Care Essential to Control Atopic Dermatitis article at American Academy of Dermatology]'s EczemaNet website]. 2009-03-24.
  30. Web site: Bathing and Moisturizing at National Eczema Association's EASE website. 2008-05-07.
  31. Web site: Treating Eczema at The Eczema Society of Canada's website. 2008-05-07.
  32. News: Water softener eczema relief hope. 2009-12-19. BBC News. 2009-01-11.
  33. Web site: Softened Water Eczema Trial, A clinical trial to see if water softeners help children with eczema. 2009-12-19.
  34. Coderch L, López O, de la Maza A, Parra JL. Ceramides and skin function. American Journal of Clinical Dermatology. 4. 2. 107–29. 2003. 12553851. 10.2165/00128071-200304020-00004.
  35. Bouwstra JA, Ponec M. The skin barrier in healthy and diseased state. Biochimica et Biophysica Acta. 1758. 12. 2080–95. 2006. December. 16945325. 10.1016/j.bbamem.2006.06.021.
  36. Choi MJ, Maibach HI. Role of ceramides in barrier function of healthy and diseased skin. American Journal of Clinical Dermatology. 6. 4. 215–23. 2005. 16060709. 10.2165/00128071-200506040-00002.
  37. Web site: New Skin-healing Chemicals. August 30, 2007. Science Daily. 2007-10-06.
  38. Corazza M, Virgili A. Allergic contact dermatitis from ophthalmic products: can pre-treatment with sodium lauryl sulfate increase patch test sensitivity?. Contact Dermatitis. 52. 5. 239–41. 2005. May. 15898995. 10.1111/j.0105-1873.2005.00606.x.
  39. Murphy LA, White IR, Rastogi SC. Is hypoallergenic a credible term?. Clinical and Experimental Dermatology. 29. 3. 325–7. 2004. May. 15115531. 10.1111/j.1365-2230.2004.01521.x.
  40. Mihrshahi S, Marks G, Vanlaar C, Tovey E, Peat J. Predictors of high house dust mite allergen concentrations in residential homes in Sydney. Allergy. 57. 2. 137–42. 2002. 11929416. 10.1034/j.1398-9995.2002.5720999.x.
  41. Beck HI, Bjerring P, Harving H. Atopic dermatitis and the indoor climate. The effect from preventive measures. Acta Dermato-venereologica. 69. 2. 162–5. 1989. 2564236.
  42. Polderman MC, Wintzen M, le Cessie S, Pavel S. UVA-1 cold light therapy in the treatment of atopic dermatitis: 61 patients treated in the Leiden University Medical Center. Photodermatology, photoimmunology & photomedicine. 21. 2. 93–6. 2005. 15752127. 10.1111/j.1600-0781.2005.00150.x.
  43. News: Stöppler MC. Psoriasis PUVA Treatment Can Increase Melanoma Risk. 31 May 2007. MedicineNet. 2007-10-17.
  44. Stern RS. The risk of melanoma in association with long-term exposure to PUVA. Journal of the American Academy of Dermatology. 44. 5. 755–61. 2001. May. 11312420. 10.1067/mjd.2001.114576. Puva Follow Up. Study.
  45. name="pmid15752127"((cite journal=http://www.mfa.gov.il/MFA/MFAArchive/1990_1999/1999/4/FOCUS+on+Israel-+The+Living+Dead+Sea.htm))
  46. Kanny G. [Atopic dermatitis in children and food allergy: combination or causality? Should avoidance diets be initiated?]. French. Annales de dermatologie et de vénéréologie. 132. Spec No 1. 1S90–103. 2005. January. 15984300.
  47. Food allergies commonly misdiagnosed, especially among eczema patients. 16 March 2009. National Jewish Medical and Research Center. 2009-03-20.
  48. Atkins D. Food allergy: diagnosis and management. Primary Care. 35. 1. 119–40, vii. 2008. March. 18206721. 10.1016/j.pop.2007.09.003.
  49. News: Oral Vitamin D May Help Prevent Some Skin Infections. October 6, 2008. University of California, San Diego. 2010-11-29.
  50. Callaway, JC, Schwab U, Harvimaa I, Halonen P, Mykkänen O, Hyvönen P & Järvinen T (2005). Efficacy of dietary hempseed oil in patients with atopic dermatitis. Journal of Dermatological Treatment 16: 87-94.
  51. Web site: Atopic Eczema - British Association of Dermatologists. 2011-03-27. http://web.archive.org/web/20080802230737/http://www.bad.org.uk/patients/disease/atopic/salt.asp. 2008-08-02.
  52. Web site: Sulfur. 4/1/2002. University of Maryland Medical Center. 2007-10-15.
  53. Boyle RJ, Bath-Hextall FJ, Leonardi-Bee J, Murrell DF, Tang ML. Boyle. Robert John. Probiotics for treating eczema. Cochrane Database of Systematic Reviews (Online). 4. CD006135. 2008. 18843705. 10.1002/14651858.CD006135.pub2.
  54. Flohr C, Pascoe D, Williams HC. Atopic dermatitis and the 'hygiene hypothesis': too clean to be true?. The British Journal of Dermatology. 152. 2. 202–16. 2005. February. 15727630. 10.1111/j.1365-2133.2004.06436.x.
  55. Web site: Complementary Therapies. American Academy of Dermatology. 2008-08-01.
  56. http://www.acupuncturetoday.com/archives2005/mar/03glick.html
  57. News: Chinese medicine 'eases eczema'. BBC News. 13 March 2008.
  58. Armstrong NC, Ernst E. The treatment of eczema with Chinese herbs: a systematic review of randomized clinical trials. British Journal of Clinical Pharmacology. 48. 2. 262–4. 1999. August. 10417508. 2014284. 10.1046/j.1365-2125.1999.00004.x.
  59. Eldred DC, Tuchin PJ. Treatment of acute atopic eczema by chiropractic care. A case study. Australasian Chiropractic & Osteopathy. 8. 3. 96–101. 1999. November. 17987197. 2051093.
  60. Ricci G, Patrizi A, Bellini F, Medri M. Use of textiles in atopic dermatitis: care of atopic dermatitis. Current Problems in Dermatology. 33. 127–43. 2006. 16766885. 10.1159/000093940.
  61. 10.1159/000057975. Psychodermatology and Atopic Skin Disease in London 1989 - 1999  - Helping Patients to Help Themselves. 2000. Bridgett. C.. Dermatology and Psychosomatics / Dermatologie und Psychosomatik. 1. 183.
  62. Bridgett C. Psychocutaneous medicine. Journal of cosmetic dermatology. 3. 2. 116. 2004. 17147570. 10.1111/j.1473-2130.2004.00047.x.
  63. Osman M, Hansell AL, Simpson CR, Hollowell J, Helms PJ. Gender-specific presentations for asthma, allergic rhinitis and eczema in primary care. Primary Care Respiratory Journal. 16. 1. 28–35. 2007. February. 17297524. 10.3132/pcrj.2007.00006.
  64. Taylor B, Wadsworth J, Wadsworth M, Peckham C. Changes in the reported prevalence of childhood eczema since the 1939-45 war. Lancet. 2. 8414. 1255–7. 1984. December. 6150286. 10.1016/S0140-6736(84)92805-8.
  65. Gupta R, Sheikh A, Strachan DP, Anderson HR. Burden of allergic disease in the UK: secondary analyses of national databases. Clinical and Experimental Allergy. 34. 4. 520–6. 2004. April. 15080802. 10.1111/j.1365-2222.2004.1935.x.
  66. Walley AJ, Chavanas S, Moffatt MF, et al.. Gene polymorphism in Netherton and common atopic disease. Nat. Genet.. 29. 2. 175–8. 2001. 11544479. 10.1038/ng728.
  67. Palmer CN et al.. 2006. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nature Genetics. 38. 4. 441–6. 16550169. 10.1038/ng1767.
  68. News: 'Blood chemicals link' to eczema – Scientists have identified two blood chemicals linked to itchy eczema, offering new treatment possibilities.. 26 August 2007. BBC News. 2007-10-16.
  69. Paternoster et al.. 2011. Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis. Nature Genetics.
  70. News: Eczema cases rise dramatically. Wilkinson Emma. 23 March 2009. BBC News.