Eczema medical therapy: Difference between revisions

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__NOTOC__
{{Eczema}}
{{Eczema}}
{{CMG}}, {{AE}} [[User:Edzelco|Edzel Lorraine Co, D.M.D., M.D.]]
{{CMG}}, {{AE}} [[User:Edzelco|Edzel Lorraine Co, D.M.D., M.D.]]
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**[[Eczema]] can be exacerbated by dryness of the [[skin]].  
**[[Eczema]] can be exacerbated by dryness of the [[skin]].  
**[[Moisture]] content is the main factor that determines the occurrence of [[eczema]].
**[[Moisture]] content is the main factor that determines the occurrence of [[eczema]].
**Thicker moisturizing ointments have a better effect on a [[dry]], [[flaky]] [[skin]]. 
** European [[emollients]] such as''Oilatum'', ''Balneum'', ''Medi Oil'', ''Diprobase'', ''Sebexol'', ''Epaderm'' [[ointment]], ''Eucerin'' lotion, bath oils and aqueous cream can relieve [[eczema]] itchiness.  
** European [[emollients]] such as''Oilatum'', ''Balneum'', ''Medi Oil'', ''Diprobase'', ''Sebexol'', ''Epaderm'' [[ointment]], ''Eucerin'' lotion, bath oils and aqueous cream can relieve [[eczema]] itchiness.  
** [[Topical]] application of [[sulfur]] gains popularity as an alternative treatment to steroids. However, no evidence-based publications are available yet on this matter. <ref>{{cite web |title=Sulfur |url=http://www.umm.edu/altmed/articles/000328.htm |date=4/1/2002 |publisher=University of Maryland Medical Center |accessdate=2007-10-15}}</ref>
** [[Topical]] application of [[sulfur]] gains popularity as an alternative treatment to steroids. However, no evidence-based publications are available yet on this matter. <ref>{{cite web |title=Sulfur |url=http://www.umm.edu/altmed/articles/000328.htm |date=4/1/2002 |publisher=University of Maryland Medical Center |accessdate=2007-10-15}}</ref>
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*[[Antibiotics]]
*[[Antibiotics]]
**Dry and cracked [[skin]] allows entry of [[bacteria]].  
**Dry and cracked [[skin]] allows entry of [[bacteria]].  
**[[Skin infection]] could develop, which can further irritate the [[skin]].
**[[Skin infection]] may arise and could irritate the [[skin]].
**An appropriate [[antibiotic]] regimen should be given.
**[[Antibiotics]] should be prescribed to cover the [[microorganism]].


*[[Immunosuppressants]]
*[[Immunosuppressants]]
**These work by dampening the immune system to improve [[eczema]].  
**These work by dampening the [[immune system]] to improve [[eczema]].  
** Commonly-used immunosuppressants for eczema include [[ciclosporin]], [[azathioprine]] and [[methotrexate]].  
** Commonly used [[immunosuppressants]] for [[eczema]] include [[ciclosporin]], [[azathioprine]], and [[methotrexate]].  
**[[Patients]] should undergo regular complete blood tests as side effects may develop.
**Laboratory workup such as a complete [[blood test]] must be done by the [[patient]] since [[drug]] side effects may develop.


===Light therapy===
===Light therapy===
[[Phototherapy|Light therapy]] using [[ultraviolet]] light can help control eczema.<ref name="pmid15752127">{{cite journal |author=Polderman MC, Wintzen M, le Cessie S, Pavel S |title=UVA-1 cold light therapy in the treatment of atopic dermatitis: 61 patients treated in the Leiden University Medical Center |journal=Photodermatology, photoimmunology & photomedicine |volume=21 |issue=2 |pages=93–6 |year=2005 |pmid=15752127 |doi=10.1111/j.1600-0781.2005.00150.x}}</ref> [[UVA]] is mostly used, but UVB and Narrow Band UVB are also used. Ultraviolet light exposure carries its own risks, particularly eventual skin cancer from exposure.<ref>{{cite news |author=Stöppler MC |title=Psoriasis PUVA Treatment Can Increase Melanoma Risk |url=http://www.medicinenet.com/script/main/art.asp?articlekey=548 |date=31 May 2007 |publisher=MedicineNet |accessdate=2007-10-17}}</ref>
*When [[light therapy]] alone is found to be ineffective, the [[treatment]] is performed with the application (or ingestion) of a substance called [[psoralen]].
*[[PUVA]] (Psoralen + UVA) combination [[therapy]] also known as [[photo-chemotherapy]] can increase the [[sensitivity]] to [[UV light]], which can lead to [[skin cancer]].<ref name="pmid11312420">{{cite journal |author=Stern RS |title=The risk of melanoma in association with long-term exposure to PUVA |journal=J. Am. Acad. Dermatol. |volume=44 |issue=5 |pages=755–61 |year=2001 |pmid=11312420 |doi=10.1067/mjd.2001.114576}}</ref>


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.<ref name="pmid11312420">{{cite journal |author=Stern RS |title=The risk of melanoma in association with long-term exposure to PUVA |journal=J. Am. Acad. Dermatol. |volume=44 |issue=5 |pages=755–61 |year=2001 |pmid=11312420 |doi=10.1067/mjd.2001.114576}}</ref>
===Herbal Medicine===
 
Some of these topical [[remedies]] include:
===Diet and nutrition===
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. <ref name="pmid15984300">{{cite journal |author=Kanny G |title=[Atopic dermatitis in children and food allergy: combination or causality? Should avoidance diets be initiated?] |language=French |journal=Annales de dermatologie et de vénéréologie |volume=132 Spec No 1 |issue= |pages=1S90–103 |year=2005 |pmid=15984300 |doi=}}</ref>
 
Dietary elements that have been reported to trigger eczema include dairy products and coffee (both caffeinated and decaffeinated), soybean products, eggs, nuts, wheat and maize (sweet corn), though food allergies may vary from person to person.
 
===Alternative therapies===
Non-conventional medical approaches include traditional herbal medicine and others. Patients should inform their doctor/allergist/dermatologist if they are pursuing one of these treatment routes. Patients can also wear clothing designed specifically to manage the itching, scratching and peeling associated with eczema.
[[Sulfur]] has been used for many years as a treatment in the alleviation of eczema, although this could be suppressive.
Many patients find that swimming in the ocean will relieve symptoms and clear up the red patchy scales.
[[Oatmeal]] is a common kitchen remedy to relieve itching, and can be applied topically as a cream or, as a [[colloid]], in the bath. Add 2tbl to a square of muslin and fasten securely with elastic band. Submerge in the bath and when the organic porridge oats are saturated, squeeze. The bath water becomes opaque with a soothing scent of oats.
 
===Pseudoceramides===
On August 27, 2007, [[scientists]] led by Jeung-Hoon Lee created in the [[laboratory]] synthetic lipids called pseudoceramides which are involved in [[skin cell]] growth and could be used in treating [[skin diseases]] such as [[atopic dermatitis]], a form of eczema characterized by red, flaky and very itchy skin; [[psoriasis]], a disease that causes red scaly patches on the skin; and glucocorticoid-induced epidermal atrophy, in which the skin shrinks due to skin cell loss.<ref>{{cite web |author= |title=New Skin-healing Chemicals |url=http://www.sciencedaily.com/releases/2007/08/070827184713.htm |date= August 30, 2007 |publisher=Science Daily |accessdate=2007-10-06}}</ref>
 
====Herbal Medicine====
Historical sources - notably [[traditional Chinese medicine]] and Western [[herbalism]] - suggest a wide variety of treatments, each of which may vary from individual to individual as to efficacy or harm. [[Toxicity]] may be present in some. Some of these remedies are for topical use.
*''Potentilla chinensis''
*''Potentilla chinensis''
*''Aebia clematidis''
*''Aebia clematidis''
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*''[[Rehmannia glutinosa]]''
*''[[Rehmannia glutinosa]]''
*''[[Paeonia lactiflora]]'' (Chinese Peony)
*''[[Paeonia lactiflora]]'' (Chinese Peony)
*''Schizonepeta tenuifolia'' (Neem)
*''Schizonepeta tennuifolia''
*''Lophatherum gracile''
*''Lophatherum gracile''
*''[[Calamine]]''
*''[[Oatmeal]]''
*''[[Glycyrrhiza uralensis]]''
*''[[Glycyrrhiza glabra]]'' (Licorice)
*''[[Burdock]]''
*''[[Rooibos]]''
*''Dictamnus dasycarpus''
*''Dictamnus dasycarpus''
*''[[Tribulus terrestris]]''
*''[[Tribulus terrestris]]''
*''[[Glycyrrhiza uralensis]]''
*''[[Glycyrrhiza glabra]]'' (Licorice)
*''Schizonepeta tenuifolia'' (Neem)
*''Schizonepeta tennuifolia''
*''[[Azadirachta indica]]''
*''[[Azadirachta indica]]''
*''Evening primrose oil''
*''Evening primrose oil''
*''[[Tea tree oil]]''
*''[[Tea tree oil]]''
*''[[Burdock]]''
*''[[Rooibos]]''
*''[[Linseed oil]]''
*''[[Linseed oil]]''
*''[[Calamine]]''
*''[[Oatmeal]]''
*''[[Cod liver oil]]''
*''[[Cod liver oil]]''
*''[[Neem oil]]''
*''[[Neem oil]]''
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*''Guto Kola''
*''Guto Kola''


===Behavioural approach===
===2014 Clinical Practice Guidelines for the Management of [[Eczema]] by American Academy of Dermatology <ref name="pmid24813302">{{cite journal| author=Eichenfield LF, Tom WL, Berger TG, Krol A, Paller AS, Schwarzenberger K | display-authors=etal| title=Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies. | journal=J Am Acad Dermatol | year= 2014 | volume= 71 | issue= 1 | pages= 116-32 | pmid=24813302 | doi=10.1016/j.jaad.2014.03.023 | pmc=4326095 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24813302  }} </ref> ===
In the 1980's, a Swedish [[dermatologist]] (Dr Peter Noren) developed a behavioural approach to the treatment of long term atopic eczema. This approach has been further developed by a dermatologist (Dr Richard Staughton) and [[psychiatrist]] (Christopher Bridgett) at the [[Chelsea and Westminster Hospital]] in London.<ref>{{cite journal |author=Bridgett C |title=Psychodermatology and Atopic Skin Disease in London 1989-1999 - Helping Patients to Help Themselves |journal=Dermatology and Psychosomatics |volume=1 |issue=4 |year=2000}}</ref><ref name="pmid17147570">{{cite journal |author=Bridgett C |title=Psychocutaneous medicine |journal=Journal of cosmetic dermatology |volume=3 |issue=2 |pages=116 |year=2004 |pmid=17147570 |doi=10.1111/j.1473-2130.2004.00047.x}}</ref>
 
{|class="wikitable" style="width:80%"
|-
|colspan="1" style="text-align:center; background:LightCyan"| [[AAD guidelines classification scheme#Strength of Recommendation|Class A]]
|-
| bgcolor="Beige"|<nowiki>"</nowiki>'''1.'''Use of [[moisturizers]]. ''([[AAD guidelines classification scheme#Strength of Recommendation|Level of Evidence: I]])'' <nowiki>"</nowiki>
 
|-
| bgcolor="Beige"|<nowiki>"</nowiki>'''2.'''Use of [[topical corticosteroids]]. ''([[AAD guidelines classification scheme#Strength of Recommendation|Level of Evidence: I]])'' <nowiki>"</nowiki>
 
|-
| bgcolor="Beige"|<nowiki>"</nowiki>'''2a.'''Need for consideration of side effects with use. ''([[AAD guidelines classification scheme#Strength of Recommendation|Level of Evidence: I]])'' <nowiki>"</nowiki>
 
|-
| bgcolor="Beige"|<nowiki>"</nowiki>'''3.'''Use of [[topical calcineurin inhibitors]] ''([[AAD guidelines classification scheme#Strength of Recommendation|Level of Evidence: I]])'' <nowiki>"</nowiki>
 
|-
| bgcolor="Beige"|<nowiki>"</nowiki>'''3a.'''Use as [[steroid]] sparing agents. ''([[AAD guidelines classification scheme#Strength of Recommendation|Level of Evidence: I]])'' <nowiki>"</nowiki>
 
|-
| bgcolor="Beige"|<nowiki>"</nowiki>'''3b.'''Off-label use of [[topical calcineurin inhibitors]] in those age less than 2 years. ''([[AAD guidelines classification scheme#Strength of Recommendation|Level of Evidence: I]])'' <nowiki>"</nowiki>
 
|-
| bgcolor="Beige"|<nowiki>"</nowiki>'''3c.'''Proactive use of [[topical calcineurin inhibitors]] for maintenance. ''([[AAD guidelines classification scheme#Strength of Recommendation|Level of Evidence: I]])'' <nowiki>"</nowiki>
 
|-
| bgcolor="Beige"|<nowiki>"</nowiki>'''3d.'''Routine monitoring of [[topical calcineurin inhibitors]] blood levels not needed. ''([[AAD guidelines classification scheme#Strength of Recommendation|Level of Evidence: I]])'' <nowiki>"</nowiki>
 
|-
| bgcolor="Beige"|<nowiki>"</nowiki>'''4.'''Against routine use of [[topical]] anti-''[[Staphylococcal]]'' [[treatment]]. ''([[AAD guidelines classification scheme#Strength of Recommendation|Level of Evidence: I]])'' <nowiki>"</nowiki>
|}
 
 
{|class="wikitable" style="width:80%"
|-
|colspan="1" style="text-align:center; background:LightCyan"| [[AAD guidelines classification scheme#Strength of Recommendation|Class B]]
|-
| bgcolor="Beige"|<nowiki>"</nowiki>'''1.'''Application of [[moisturizers]] after bathing. ''([[AAD guidelines classification scheme#Strength of Recommendation|Level of Evidence: II]])'' <nowiki>"</nowiki>
 
|-
| bgcolor="Beige"|<nowiki>"</nowiki>'''2.'''Wet-wrap [[therapy]]. ''([[AAD guidelines classification scheme#Strength of Recommendation|Level of Evidence: II]])'' <nowiki>"</nowiki>
 
|-
| bgcolor="Beige"|<nowiki>"</nowiki>'''3.'''Frequency of application of [[topical corticosteroids]]. ''([[AAD guidelines classification scheme#Strength of Recommendation|Level of Evidence: II]])'' <nowiki>"</nowiki>
 
|-
| bgcolor="Beige"|<nowiki>"</nowiki>'''3a.'''Proactive use of [[topical corticosteroids]] for maintenance. ''([[AAD guidelines classification scheme#Strength of Recommendation|Level of Evidence: II]])'' <nowiki>"</nowiki>
 
|-
| bgcolor="Beige"|<nowiki>"</nowiki>'''3b.'''Need for monitoring for [[cutaneous]] side effects with potent [[topical corticosteroids]]. ''([[AAD guidelines classification scheme#Strength of Recommendation|Level of Evidence: III]])'' <nowiki>"</nowiki>
 
|-
| bgcolor="Beige"|<nowiki>"</nowiki>'''3c.'''Addressing fears with use. ''([[AAD guidelines classification scheme#Strength of Recommendation|Level of Evidence: III]])'' <nowiki>"</nowiki>
 
|-
| bgcolor="Beige"|<nowiki>"</nowiki>'''4.'''Counseling on local reactions with [[topical calcineurin inhibitors]] and the preceding use of [[topical corticosteroids]]. ''([[AAD guidelines classification scheme#Strength of Recommendation|Level of Evidence: II]])'' <nowiki>"</nowiki>
 
|-
| bgcolor="Beige"|<nowiki>"</nowiki>'''4a.'''Concomitant [[topical corticosteroids]] and [[topical calcineurin inhibitors]] use.''([[AAD guidelines classification scheme#Strength of Recommendation|Level of Evidence: II]])'' <nowiki>"</nowiki>
 
|-
| bgcolor="Beige"|<nowiki>"</nowiki>'''5.'''Bleach baths and [[intranasal]] [[mupirocin]] for those with moderate to severe [[AD]] and [[clinical infection]]. ''([[AAD guidelines classification scheme#Strength of Recommendation|Level of Evidence: I]])'' <nowiki>"</nowiki>
 
|-
| bgcolor="Beige"|<nowiki>"</nowiki>'''6.'''Against use of [[topical antihistamines]]. ''([[AAD guidelines classification scheme#Strength of Recommendation|Level of Evidence: II]])'' <nowiki>"</nowiki>
|}
 
 
{|class="wikitable" style="width:80%"
|-
|colspan="1" style="text-align:center; background:LightCyan"| [[AAD guidelines classification scheme#Strength of Recommendation|Class C]]
|-
| bgcolor="Beige"|<nowiki>"</nowiki>'''1.'''Bathing and bathing practices ''([[AAD guidelines classification scheme#Strength of Recommendation|Level of Evidence: III]])'' <nowiki>"</nowiki>
 
|-
| bgcolor="Beige"|<nowiki>"</nowiki>'''2.'''Limited use of nonsoap cleansers. ''([[AAD guidelines classification scheme#Strength of Recommendation|Level of Evidence: III]])'' <nowiki>"</nowiki>
 
|-
| bgcolor="Beige"|<nowiki>"</nowiki>'''3.'''Against use of bath additives, acidic spring water. ''([[AAD guidelines classification scheme#Strength of Recommendation|Level of Evidence: III]])'' <nowiki>"</nowiki>
 
|-
| bgcolor="Beige"|<nowiki>"</nowiki>'''4.'''Consideration of a variety of factors in [[topical corticosteroids]] selection. ''([[AAD guidelines classification scheme#Strength of Recommendation|Level of Evidence: II]])'' <nowiki>"</nowiki>
 
|-
| bgcolor="Beige"|<nowiki>"</nowiki>'''4a.'''Specific routine monitoring for [[systemic]] [[side effects]] with [[topical corticosteroids]] not needed. ''([[AAD guidelines classification scheme#Strength of Recommendation|Level of Evidence: III]])'' <nowiki>"</nowiki>
 
|-
| bgcolor="Beige"|<nowiki>"</nowiki>'''5.'''Informing [[patients]] regarding theoretical risk of [[cutaneous]] [[viral infections]] with use. ''([[AAD guidelines classification scheme#Strength of Recommendation|Level of Evidence: III]])'' <nowiki>"</nowiki>


Patients undergo a 6 week monitored programme involving scratch habit reversal and self awareness of scratching levels. For long term eczema sufferers, scratching can become habitual. Sometimes scratching becomes a reflex (scratching without conscious awareness), and not always from the feeling of itchiness itself. The habit reversal programme 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.
|-
| bgcolor="Beige"|<nowiki>"</nowiki>'''6.'''Awareness of black-box warning of [[topical calcineurin inhibitors]]. ''([[AAD guidelines classification scheme#Strength of Recommendation|Level of Evidence: III]])'' <nowiki>"</nowiki>
|}


==References==
==References==
{{reflist|2}}
{{Reflist|2}}
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Latest revision as of 18:32, 14 July 2022

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1], Associate Editor(s)-in-Chief: Edzel Lorraine Co, D.M.D., M.D.

Overview

Topical corticosteroids are the mainline treatment for eczema. Different potencies of steroids are rendered specifically for the severity of eczema. Other drug treatments often used for eczema include topical calcineurin inhibitors, crisaborole, antimicrobials, and antifungals.

Medical Therapy

Pharmacotherapy

  • Moisturizers
    • Eczema can be exacerbated by dryness of the skin.
    • Moisture content is the main factor that determines the occurrence of eczema.
    • European emollients such asOilatum, Balneum, Medi Oil, Diprobase, Sebexol, Epaderm ointment, Eucerin lotion, bath oils and aqueous cream can relieve eczema itchiness.
    • Topical application of sulfur gains popularity as an alternative treatment to steroids. However, no evidence-based publications are available yet on this matter. [1]

Light therapy

Herbal Medicine

Some of these topical remedies include:

2014 Clinical Practice Guidelines for the Management of Eczema by American Academy of Dermatology [7]

Class A
"1.Use of moisturizers. (Level of Evidence: I) "
"2.Use of topical corticosteroids. (Level of Evidence: I) "
"2a.Need for consideration of side effects with use. (Level of Evidence: I) "
"3.Use of topical calcineurin inhibitors (Level of Evidence: I) "
"3a.Use as steroid sparing agents. (Level of Evidence: I) "
"3b.Off-label use of topical calcineurin inhibitors in those age less than 2 years. (Level of Evidence: I) "
"3c.Proactive use of topical calcineurin inhibitors for maintenance. (Level of Evidence: I) "
"3d.Routine monitoring of topical calcineurin inhibitors blood levels not needed. (Level of Evidence: I) "
"4.Against routine use of topical anti-Staphylococcal treatment. (Level of Evidence: I) "


Class B
"1.Application of moisturizers after bathing. (Level of Evidence: II) "
"2.Wet-wrap therapy. (Level of Evidence: II) "
"3.Frequency of application of topical corticosteroids. (Level of Evidence: II) "
"3a.Proactive use of topical corticosteroids for maintenance. (Level of Evidence: II) "
"3b.Need for monitoring for cutaneous side effects with potent topical corticosteroids. (Level of Evidence: III) "
"3c.Addressing fears with use. (Level of Evidence: III) "
"4.Counseling on local reactions with topical calcineurin inhibitors and the preceding use of topical corticosteroids. (Level of Evidence: II) "
"4a.Concomitant topical corticosteroids and topical calcineurin inhibitors use.(Level of Evidence: II) "
"5.Bleach baths and intranasal mupirocin for those with moderate to severe AD and clinical infection. (Level of Evidence: I) "
"6.Against use of topical antihistamines. (Level of Evidence: II) "


Class C
"1.Bathing and bathing practices (Level of Evidence: III) "
"2.Limited use of nonsoap cleansers. (Level of Evidence: III) "
"3.Against use of bath additives, acidic spring water. (Level of Evidence: III) "
"4.Consideration of a variety of factors in topical corticosteroids selection. (Level of Evidence: II) "
"4a.Specific routine monitoring for systemic side effects with topical corticosteroids not needed. (Level of Evidence: III) "
"5.Informing patients regarding theoretical risk of cutaneous viral infections with use. (Level of Evidence: III) "
"6.Awareness of black-box warning of topical calcineurin inhibitors. (Level of Evidence: III) "

References

  1. ↑ "Sulfur". University of Maryland Medical Center. 4/1/2002. Retrieved 2007-10-15. Check date values in: |date= (help)
  2. ↑ Hoare C, Li Wan Po A, Williams H (2000). "Systematic review of treatments for atopic eczema". Health technology assessment (Winchester, England). 4 (37): 1–191. PMID 11134919.
  3. ↑ Atherton DJ (2003). "Topical corticosteroids in atopic dermatitis". BMJ. 327 (7421): 942–3. doi:10.1136/bmj.327.7421.942. PMID 14576221.
  4. ↑ Lee NP, Arriola ER (1999). "Topical corticosteroids: back to basics" ("Scanned & PDF"). West. J. Med. 171 (5–6): 351–3. PMID 10639873.
  5. ↑ Martins GA, Arruda L (2004). "Systemic treatment of psoriasis - Part I: methotrexate and acitretin". An. Bras. Dermatol (in English translation). 79 (3): 263–278. Unknown parameter |month= ignored (help)
  6. ↑ Stern RS (2001). "The risk of melanoma in association with long-term exposure to PUVA". J. Am. Acad. Dermatol. 44 (5): 755–61. doi:10.1067/mjd.2001.114576. PMID 11312420.
  7. ↑ Eichenfield LF, Tom WL, Berger TG, Krol A, Paller AS, Schwarzenberger K; et al. (2014). "Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies". J Am Acad Dermatol. 71 (1): 116–32. doi:10.1016/j.jaad.2014.03.023. PMC 4326095. PMID 24813302.
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