title: Psychoneuroimmunology of psychological stress and atopic dermatitis: pathophysiologic and therapeutic updates.
abstract: Atopic dermatitis is a chronic inflammatory skin disease characterized by impaired epidermal barrier function, inflammatory infiltration, extensive pruritus and a clinical course defined by symptomatic flares and remissions. The mechanisms of disease exacerbation are still poorly understood. Clinical occurrence of atopic dermatitis is often associated with psychological stress. In response to stress, upregulation of neuropeptide mediators in the brain, endocrine organs, and peripheral nervous system directly affect immune and resident cells in the skin. Lesional and non-lesional skin of patients with atopic dermatitis demonstrates increased mast cells and mast cell-nerve fiber contacts. In the setting of stress, sensory nerves release neuromediators that regulate inflammatory and immune responses, as well as barrier function. Progress towards elucidating these neuroimmune connections will refine our understanding of how emotional stress influences atopic dermatitis. Moreover, psychopharmacologic agents that modulate neuronal receptors or the amplification circuits of inflammation are attractive options for the treatment of not only atopic dermatitis, but also other stress-mediated inflammatory skin diseases.
authors.affiliation: Department of Dermatology, University of Colorado Denver, School of Medicine, Aurora, USA.
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Suárez
authors.forename: Jamison D
authors.initials: JD
authors.lastname: Feramisco
authors.forename: John
authors.initials: J
authors.lastname: Koo
authors.forename: Martin
authors.initials: M
authors.lastname: Steinhoff
mesh_terms: D016207:Cytokines / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D008407:Mast Cells; D015213:Neuroimmunomodulation; D010913:Pituitary-Adrenal System / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D013315:Stress, Psychological / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes
chemical_list: D016207:Cytokines; D017981:Receptors, Neurotransmitter
references.citation: FASEB J. 2001 Dec;15(14):2754-6
references.pmid: 11606483
references.citation: Arch Dermatol Res. 2003 Apr;295(1):2-7
references.pmid: 12709813
references.citation: Neuroreport. 2001 Nov 16;12(16):3475-8
references.pmid: 11733694
references.citation: Clin Dermatol. 1998 Nov-Dec;16(6):711-4
references.pmid: 9949917
references.citation: Br J Dermatol. 1986 Oct;115(4):467-74
references.pmid: 3778815
references.citation: Int Arch Allergy Immunol. 2007;144(1):1-9
references.pmid: 17449959
references.citation: Reprod Biomed Online. 2008 Jul;17(1):101-13
references.pmid: 18616898
references.citation: Physiol Rev. 2006 Oct;86(4):1309-79
references.pmid: 17015491
references.citation: Nat Med. 2000 Feb;6(2):151-8
references.pmid: 10655102
references.citation: J Invest Dermatol. 2008 Feb;128(2):426-33
references.pmid: 17657239
references.citation: Curr Opin Allergy Clin Immunol. 2009 Oct;9(5):427-30
references.pmid: 19550301
references.citation: J Mol Med (Berl). 2005 May;83(5):386-96
references.pmid: 15759104
references.citation: Nat Immunol. 2010 Jul;11(7):561-4
references.pmid: 20562838
references.citation: J Hepatol. 2003 Jul;39(1):131-3
references.pmid: 12821057
references.citation: J Pharmacol Exp Ther. 1998 Sep;286(3):1140-5
references.pmid: 9732370
references.citation: J Pain. 2009 Sep;10(9):895-926
references.pmid: 19712899
references.citation: Acta Derm Venereol. 2010 Nov;90(6):582-8
references.pmid: 21057740
references.citation: Arch Dermatol. 2001 Jan;137(1):78-82
references.pmid: 11176665
references.citation: Br J Dermatol. 1989 Sep;121(3):359-66
references.pmid: 2679856
references.citation: Am J Physiol Regul Integr Comp Physiol. 2006 Dec;291(6):R1657-62
references.pmid: 16857896
references.citation: Nature. 1999 Nov 25;402(6760 Suppl):B5-11
references.pmid: 10586889
references.citation: JAMA. 2000 Aug 2;284(5):592-7
references.pmid: 10918705
references.citation: J Allergy Clin Immunol. 1992 Oct;90(4 Pt 1):613-22
references.pmid: 1383306
references.citation: Exp Dermatol. 1998 Apr-Jun;7(2-3):81-96
references.pmid: 9583747
references.citation: J Clin Invest. 2004 Mar;113(5):651-7
references.pmid: 14991059
references.citation: J Neuroimmunol. 2002 Aug;129(1-2):161-7
references.pmid: 12161032
references.citation: Allergy. 2010 Jul;65(7):805-21
references.pmid: 20384615
references.citation: Blood. 2002 Apr 1;99(7):2627
references.pmid: 11926187
references.citation: Br J Dermatol. 2002 Jul;147(1):71-9
references.pmid: 12100187
references.citation: Psychother Psychosom. 2000 May-Jun;69(3):165-6
references.pmid: 10773782
references.citation: J Allergy Clin Immunol. 2001 Jan;107(1):171-7
references.pmid: 11150008
references.citation: J Invest Dermatol. 2006 Aug;126(8):1697-704
references.pmid: 16845409
references.citation: Clin Exp Dermatol. 1990 Jul;15(4):264-6
references.pmid: 2208775
references.citation: J Eur Acad Dermatol Venereol. 2008 Jan;22(1):11-8
references.pmid: 18181968
references.citation: Neurosci Res. 1999 Nov;35(2):77-83
references.pmid: 10616911
references.citation: J Allergy Clin Immunol. 2004 Oct;114(4):977-8
references.pmid: 15480346
references.citation: Ann N Y Acad Sci. 1998 May 1;840:664-73
references.pmid: 9629293
references.citation: J Clin Invest. 1997 Sep 15;100(6):1513-9
references.pmid: 9294119
references.citation: Eur J Pain. 2008 Oct;12(7):834-41
references.pmid: 18203636
references.citation: Endocrinology. 2004 Jan;145(1):43-8
references.pmid: 14576187
references.citation: Psychother Psychosom. 1993;60(3-4):168-76
references.pmid: 8272475
references.citation: Arch Dermatol Res. 1997 Apr;289(5):292-302
references.pmid: 9164640
references.citation: Curr Opin Immunol. 2009 Dec;21(6):666-78
references.pmid: 19828304
references.citation: Ann N Y Acad Sci. 2004 Jun;1024:138-46
references.pmid: 15265778
references.citation: Br J Dermatol. 2008 Sep;159(4):834-8
references.pmid: 18652587
references.citation: Dermatologica. 1991;183(2):100-5
references.pmid: 1660414
references.citation: Acta Derm Venereol. 2009;89(1):45-51
references.pmid: 19197541
references.citation: J Clin Psychopharmacol. 1990 Jun;10(3 Suppl):67S-76S
references.pmid: 2198303
references.citation: J Invest Dermatol. 2008 May;128(5):1067-70
references.pmid: 18408746
references.citation: J Ethnopharmacol. 2011 Jan 27;133(2):810-7
references.pmid: 21094681
references.citation: Br J Haematol. 2001 Dec;115(3):619-21
references.pmid: 11736946
references.citation: Exp Dermatol. 2008 Apr;17(4):301-11
references.pmid: 18177349
references.citation: Nat Rev Neurosci. 2006 Jul;7(7):535-47
references.pmid: 16791143
references.citation: J Invest Dermatol. 2006 Dec;126(12):2673-8
references.pmid: 17008877
references.citation: Ann N Y Acad Sci. 1999 Jun 22;876:1-11; discussion 11-3
references.pmid: 10415589
references.citation: Appl Psychophysiol Biofeedback. 2007 Mar;32(1):1-10
references.pmid: 17219062
references.citation: J Invest Dermatol. 2009 May;129(5):1071-87
references.pmid: 19110541
references.citation: Lancet. 2003 Jan 11;361(9352):151-60
references.pmid: 12531593
references.citation: J Consult Clin Psychol. 1995 Aug;63(4):624-35
references.pmid: 7673540
references.citation: J Am Acad Dermatol. 1993 May;28(5 Pt 1):719-23
references.pmid: 8496415
references.citation: Exp Dermatol. 2009 Mar;18(3):199-204
references.pmid: 18803662
references.citation: Ann Allergy Asthma Immunol. 2004 Sep;93(3 Suppl 2):S1-21
references.pmid: 15478395
references.citation: Przegl Lek. 2006;63(9):743-7
references.pmid: 17479861
references.citation: Exp Dermatol. 2002 Apr;11(2):159-87
references.pmid: 11994143
references.citation: FASEB J. 2005 Feb;19(2):176-94
references.pmid: 15677341
references.citation: J Pain Symptom Manage. 1998 Aug;16(2):121-4
references.pmid: 9737103
references.citation: Drugs. 2004;64(7):777-94
references.pmid: 15025555
references.citation: J Allergy Clin Immunol. 2008 Jun;121(6):1337-43
references.pmid: 18329087
references.citation: Int Arch Allergy Immunol. 2001 Jan-Mar;124(1-3):326-31
references.pmid: 11307006
references.citation: Proc Natl Acad Sci U S A. 2009 Jun 2;106(22):8865-70
references.pmid: 19451642
references.citation: Pharmacopsychiatry. 2006 Nov;39(6):229
references.pmid: 17124645
references.citation: Allergy. 2010 Jan;65(1):84-94
references.pmid: 19804445
references.citation: J Allergy Clin Immunol. 2004 Jun;113(6):1051-7
references.pmid: 15208584
references.citation: J Clin Invest. 2007 Nov;117(11):3339-49
references.pmid: 17975669
references.citation: Curr Allergy Asthma Rep. 2008 Jul;8(4):312-7
references.pmid: 18606083
references.citation: Allergy. 1992 Apr;47(2 Pt 1):65-75
references.pmid: 1632481
references.citation: J Clin Endocrinol Metab. 2002 Sep;87(9):4245-51
references.pmid: 12213879
references.citation: N Engl J Med. 2011 Feb 3;364(5):487
references.pmid: 21288111
references.citation: J Invest Dermatol. 2008 Feb;128(2):434-46
references.pmid: 17914449
references.citation: Biochemistry. 1975 Nov 18;14(23):5135-40
references.pmid: 41
references.citation: PLoS One. 2010 Jun 04;5(6):e10968
references.pmid: 20532044
references.citation: Virchows Arch. 1998 Apr;432(4):363-70
references.pmid: 9565347
references.citation: J Allergy Clin Immunol. 2001 Sep;108(3):455-62
references.pmid: 11544468
references.citation: Leuk Res. 2005 Dec;29(12):1459-63
references.pmid: 15964626
references.citation: Clin Exp Allergy. 2008 Aug;38(8):1302-8
references.pmid: 18510693
references.citation: Pharmacol Res. 2003 Oct;48(4):335-45
references.pmid: 12902204
references.citation: Clin Exp Dermatol. 2010 Dec;35(8):835-40
references.pmid: 20089082
references.citation: J Invest Dermatol. 2006 Aug;126(8):1705-18
references.pmid: 16845410
references.citation: Pain. 2007 Sep;131(1-2):4-7
references.pmid: 17524558
references.citation: Trends Immunol. 2004 May;25(5):235-41
references.pmid: 15099563
references.citation: Acta Derm Venereol. 2010 Jul;90(4):354-61
references.pmid: 20574599
references.citation: Acta Derm Venereol. 1995 Sep;75(5):348-52
references.pmid: 8615049
references.citation: Nat Rev Immunol. 2005 Mar;5(3):243-51
references.pmid: 15738954
references.citation: Dermatology. 2005;210(4):286-93
references.pmid: 15942214
references.citation: J Am Acad Dermatol. 1994 Sep;31(3 Pt 1):467-73
references.pmid: 8077475
references.citation: J Neurosci. 2003 Jul 16;23(15):6176-80
references.pmid: 12867500
references.citation: Pflugers Arch. 1974 Mar 11;347(3):209-22
references.pmid: 4857072
references.citation: Neurology. 2004 Jan 27;62(2):212-7
references.pmid: 14745056
references.citation: Neuropsychopharmacology. 1999 Aug;21(2 Suppl):33S-45S
references.pmid: 10432487
references.citation: Br J Dermatol. 2005 Jun;152(6):1161-4
references.pmid: 15948976
references.citation: J Pain Symptom Manage. 2003 Dec;26(6):1105-12
references.pmid: 14654262
references.citation: J Clin Gastroenterol. 2006 Oct;40(9):814-20
references.pmid: 17016138
references.citation: Ann N Y Acad Sci. 2006 Nov;1088:78-99
references.pmid: 17192558
references.citation: Am J Med Sci. 1966 Oct;252(4):478-96
references.pmid: 5332067
references.citation: Muscle Nerve. 1997 Nov;20(11):1389-95
references.pmid: 9342155
references.citation: Clin Exp Allergy. 1997 Nov;27(11):1261-9
references.pmid: 9420129
references.citation: Am J Gastroenterol. 2003 Dec;98(12):2736-41
references.pmid: 14687826
references.citation: J Am Acad Dermatol. 1986 Sep;15(3):487-94
references.pmid: 3760273
references.citation: Neuroimmunomodulation. 2006;13(5-6):347-56
references.pmid: 17709957
references.citation: J Clin Immunol. 2005 May;25(3):177-88
references.pmid: 16118915
references.citation: Arch Dermatol. 1998 Nov;134(11):1422-5
references.pmid: 9828879
references.citation: Acta Derm Venereol. 1995 Nov;75(6):434-6
references.pmid: 8651018
references.citation: Psychosomatics. 2005 Jul-Aug;46(4):373-4
references.pmid: 16000683
references.citation: J Invest Dermatol. 2009 Jan;129(1):14-30
references.pmid: 19078985
references.citation: Gastroenterology. 2001 Nov;121(5):1260-1
references.pmid: 11706830
references.citation: Gastroenterology. 2003 Oct;125(4):1290
references.pmid: 14552325
references.citation: J Cell Physiol. 2003 Jul;196(1):144-53
references.pmid: 12767050
references.citation: J Dermatol. 2009 Apr;36(4):185-90
references.pmid: 19348655
references.citation: Brain Behav Immun. 2010 Nov;24(8):1347-53
references.pmid: 20633637
references.citation: Psychosom Med. 2002 Sep-Oct;64(5):835-40
references.pmid: 12271115
references.citation: Brain Res. 1981 Apr 6;210(1-2):407-12
references.pmid: 6164445
references.citation: J Allergy Clin Immunol. 2010 Jan;125(1):273-5.e1-4
references.pmid: 20109756
references.citation: G Ital Dermatol Venereol. 2010 Apr;145(2):195-204
references.pmid: 20467393
references.citation: Curr Opin Allergy Clin Immunol. 2005 Feb;5(1):23-9
references.pmid: 15643340
references.citation: Stem Cell Rev. 2006;2(2):143-54
references.pmid: 17237553
references.citation: J Invest Dermatol. 2003 Mar;120(3):456-64
references.pmid: 12603860
references.citation: J Allergy Clin Immunol. 2009 Sep;124(3 Suppl 2):R2-6
references.pmid: 19720209
references.citation: Eur J Pharmacol. 2004 May 3;491(2-3):191-4
references.pmid: 15140636
references.citation: Indian J Dermatol. 2010 Apr-Jun;55(2):135-9
references.pmid: 20606880
references.citation: Br J Dermatol. 2011 Mar;164(3):665-7
references.pmid: 21039410
references.citation: Arch Dermatol Res. 2002 Dec;294(9):393-8
references.pmid: 12522576
references.citation: Curr Opin Allergy Clin Immunol. 2007 Oct;7(5):365-73
references.pmid: 17873574
references.citation: Ann Dermatol. 2010 Aug;22(3):245-54
references.pmid: 20711259
references.citation: Int J Dermatol. 1999 Sep;38(9):673-5
references.pmid: 10517683
references.citation: N Engl J Med. 2009 Oct 1;361(14):1415-6
references.pmid: 19797294
references.citation: Clin Exp Dermatol. 2010 Jul;35(5):531-6
references.pmid: 19874365
references.citation: J Am Acad Dermatol. 2008 Mar;58(3):415-20
references.pmid: 18280338
references.citation: Psychoneuroendocrinology. 2004 Jul;29(6):705-11
references.pmid: 15110919
references.citation: J Allergy Clin Immunol. 2010 Jan;125(1):16-29.e1-11; quiz 30-1
references.pmid: 20109730
references.citation: Clin Exp Rheumatol. 2001 Jan-Feb;19(1):1-3
references.pmid: 11247309
references.citation: Nat Genet. 2009 May;41(5):596-601
references.pmid: 19349984
references.citation: Hautarzt. 2008 Apr;59(4):314-8
references.pmid: 18389157
references.citation: Endocr Rev. 2000 Oct;21(5):457-87
references.pmid: 11041445
references.citation: J Eur Acad Dermatol Venereol. 2008 Feb;22(2):223-8
references.pmid: 18211417
references.citation: Arch Dermatol. 2001 Jan;137(1):53-9
references.pmid: 11176661
references.citation: Arch Dermatol. 2003 Nov;139(11):1479-88
references.pmid: 14623709
references.citation: Acta Dermatovenerol Croat. 2005;13(1):54-62
references.pmid: 15788148
references.citation: Psychosom Med. 1997 Jul-Aug;59(4):419-26
references.pmid: 9251162
references.citation: J Investig Allergol Clin Immunol. 2009;19(6):481-7
references.pmid: 20128423
references.citation: N Engl J Med. 2010 Jul 22;363(4):397-8
references.pmid: 20660413
references.citation: Arch Dermatol. 2009 Dec;145(12):1384-8
references.pmid: 20026846
references.citation: PLoS Genet. 2008 Aug;4(8):e1000166
references.pmid: 18846228
references.citation: Hepatology. 2007 Mar;45(3):666-74
references.pmid: 17326161
references.citation: J Allergy Clin Immunol. 2006 Jul;118(1):178-89
references.pmid: 16815153
references.citation: Curr Opin Allergy Clin Immunol. 2005 Oct;5(5):419-24
references.pmid: 16131917
references.citation: Curr Allergy Asthma Rep. 2008 Jul;8(4):306-11
references.pmid: 18606082