Melatonin and Atopic Dermatitis: New Insights in Pathophysiology and its Role in Sleep Disturbance
Abstract
Sleep disturbance is common in children with atopic dermatitis, with a significant impact in their quality of life and negative effects on behavior and neurocognitive function. However, the pathophysiology of sleep disturbance in patients with atopic dermatitis is not well understood. It was thought to be consequence of pruritus and scratching, but nowadays we know to a consequence of multiple factors. Recent studies have suggested that melatonin could be involved, not only because of its primordial effect on sleep induction, but also its effects on immunomodulation and as anti-oxidant. In this review, the authors summarize the new insights about the sleep disturbances in children with atopic dermatitis, emphasizing the role of melatonin and its possible therapeutic implication.
Downloads
References
Bieber T. Atopic dermatitis. N Engl J Med.
;358:1483–94. doi: 10.1056/NEJMra074081.
Camfferman D, Kennedy JD, Gold M, Martin AJ,
Lushington K. Eczema and sleep and its relationship
to daytime functioning in children. Sleep Med Rev.
; 14:359-69. doi: 10.1016/j.smrv.2010.01.004
Ricci G, Bendandi B, Bellini F, Patrizi A, Masi M. Atopic
dermatitis: quality of life of young Italian children
and their families and correlation with severity
score. Pediatr Allergy Immunol. 2007; 18:245-9. doi:
1111/j.1399-3038.2006.00502.x
Lewis-Jones S. Quality of life and childhood atopic dermatitis:
the misery of living with childhood eczema.Int
J Clin Pract. 2006; 60:984-92. doi: 10.1111/j.1742-
-1241.2006.01047.x
Sadeh A, Gruber R, Raviv A. Sleep, neurobehavioral
functioning, and behavior problems in school-age
children.Child Dev. 2002; 73:405-17.
Touchette E, Petit D, Séguin JR, Boivin M, Tremblay
RE, Montplaisir JY. Associations between sleep duration
patterns and behavioral/cognitive functioning at
school entry. Sleep. 2007; 30:1213-9.
Chang YS, Chou YT, Lee JH, Lee PL, Dai YS, Sun C, et
al. Atopic dermatitis, melatonin, and sleep disturbance.
Pediatrics. 2014; 134:e397-405. doi: 10.1542/
peds.2014-0376.
Bender BG, Ballard R, Canono B, Murphy JR, Leung
DY. Disease severity, scratching, and sleep quality in
patients with atopic dermatitis. J Am Acad Dermatol.
; 58:415-20. doi: 10.1016/j.jaad.2007.10.010.
Hon KL, Lam MC, Wong KY, Leung TF, Ng PC. Pathophysiology
of nocturnal scratching in childhood atopic
dermatitis: the role of brain-derived neurotrophic factor
and substance P. Br J Dermatol. 2007; 157:922-5.
doi:10.1111/j.1365-2133.2007.08149.x
Hon KL, Lam MC, Leung TF, Wong KY, Chow CM, Fok
TF, et al. Are age-specific high serum IgE levels associated
with worse symptomatology in children with
atopic dermatitis? Int J Dermatol. 2007; 46:1258-62.
doi: 10.1111/j.1365-2133.2007.08149.x
Stores G, Burrows A, Crawford C. Physiological sleep
disturbance in children with atopic dermatitis: a case
control study. Pediatr Dermatol. 1998; 15:264-8.
Bender BG, Leung DY. Sleep disorders in patients with
asthma, atopic dermatitis, and allergic rhinitis. J Allergy
Clin Immunol. 2005; 116:1200-1. doi:10.1016/j.
jaci.2005.09.041
Reuveni H, Chapnick G, Tal A, Tarasiuk A. Sleep fragmentation
in children with atopic dermatitis. Arch Pediatr
Adolesc Med. 1999; 153:249-53.
Born J, Lange T, Hansen K, Mölle M, Fehm HL. Effects
of sleep and circadian rhythm on human circulating
immune cells. J Immunol. 1997; 158:4454-64.
Geiger SS, Fagundes CT, Siegel RM. Chrono-immunology:
progress and challenges in understanding links between the circadian and immune systems. Immunology.
; 146:349-58. doi: 10.1111/imm.12525.
Hon KL, Lam MC, Leung TF, Kam WY, Lee KC, Li
MC, et al. Nocturnal wrist movements are correlated
with objective clinical scores and plasma chemokine
levels in children with atopic dermatitis. Br J
Dermatol. 2006; 154:629-35. doi:10.1111/j.1365-
2006.07213.x
Sakami S, Ishikawa T, Kawakami N, Haratani T, Fukui
A, Kobayashi F, et al.Coemergence of insomnia and a
shift in the Th1/Th2 balance toward Th2 dominance.
Neuroimmunomodulation. 2002-2003; 10:337-43.
doi: 10.1159/000071474
Chang YS, Chiang BL. Mechanism of sleep disturbance
in children with atopic dermatitis and the role of the
circadian rhythm and melatonin. Int J Mol Sci. 2016;
:462. doi: 10.3390/ijms17040462.
Lee J, Lee H, Noh S, Bae BG, Shin JU, Park CO, et
al. Retrospective analysis on the effects of house dust
mite specific immunotherapy for more than 3 years in
atopic dermatitis. Yonsei Med J. 2016; 57:393-8. doi:
3349/ymj.2016.57.2.393.
Tam H, Calderon MA, Manikam L, Nankervis H, García
Núñez I, Williams HC, et al. Specific allergen
immunotherapy for the treatment of atopic eczema.
Cochrane Database Syst Rev. 2016; 2:CD008774.
doi: 10.1002/14651858.CD008774.pub2.
Brzezinski A. Melatonin in humans. N Engl J Med.
Jan 16; 336(3):186-95.
Chang YS, Lin MH, Lee JH, Lee PL, Dai YS, Chu KH, et
al. Melatonin supplementation for children with atopic
dermatitis and sleep disturbance: a randomized
clinical trial. JAMA Pediatr. 2016; 170:35-42. doi:
1001/jamapediatrics.2015.3092.
Abdelgadir IS, Gordon MA, Akobeng AK. Melatonin
for the management of sleep problems in children
with neurodevelopmental disorders: a systematic
review and meta-analysis. Arch Dis Child. 2018 (in
press). doi: 10.1136/archdischild-2017-314181.
Acuña-Castroviejo D, Escames G, Venegas C, Díaz-
-Casado ME, Lima-Cabello E, López LC, et al. Extrapineal
melatonin: sources, regulation, and potential
functions. Cell Mol Life Sci. 2014; 71:2997-3025.
doi: 10.1007/s00018-014-1579-2.
Carpentieri A, Díaz de Barboza G, Areco V, Peralta
López M, Tolosa de Talamoni N. New perspectives in
melatonin uses. Pharmacol Res. 2012; 65:437-44.
doi: 10.1016/j.phrs.2012.01.003.
Marseglia L, D'Angelo G, Manti S, Salpietro C, Arrigo
T, Barberi I, et al. Melatonin and atopy: role in
atopic dermatitis and asthma. Int J Mol Sci. 2014;
:13482-93. doi: 10.3390/ijms150813482.
Kim TH, Jung JA, Kim GD, Jang AH, Ahn HJ, Park YS, et
al. Melatonin inhibits the development of 2,4-dinitrofluorobenzene-
induced atopic dermatitis-like skin lesions
in NC/Nga mice. J Pineal Res. 2009; 47:324-9.
doi: 10.1111/j.1600-079X.2009.00718.x.
Chen L, Lin SX, Overbergh L, Mathieu C, Chan
LS. The disease progression in the keratin 14 IL-4-
-transgenic mouse model of atopic dermatitis parallels
the up-regulation of B cell activation molecules,
proliferation and surface and serum IgE. Clin Exp
Immunol. 2005; 142:21-30. doi: 10.1111/j.1365-
-2249.2005.02894.x
Gittler JK, Shemer A, Suarez-Farinas M, Fuentes-Duculan
J, Gulewicz KJ, Wang CQF, et al. Progressive
activation of T(H)2/T(H)22 cytokines and selective epidermal
proteins characterizes acute and chronic atopic
dermatitis. J Allergy Clin Immunol. 2012; 130:1344–
doi: 10.1016/j.jaci.2012.07.012.
Howell MD, Fairchild HR, Kim BE, Bin L, Boguniewicz
M, Redzic JS, et al. Th2 cytokines act on S100/
A11 to downregulate keratinocyte differentiation. J Investig
Dermatol. 2008; 128:2248-58. doi: 10.1038/
jid.2008.74.
Carrillo-Vico A, Lardone PJ, Alvarez-Sánchez N, Rodríguez-
Rodríguez A, Guerrero JM. Melatonin: buffering
the immune system. Int J Mol Sci. 2013; 14:8638-83.
doi: 10.3390/ijms14048638.
García JJ, López-Pingarrón L, Almeida-Souza P, Tres
A, Escudero P, García-Gil FA, et al. Protective effects
of melatonin in reducing oxidative stress and in preserving
the fluidity of biological membranes: a review.
J Pineal Res. 2014; 56:225-37. doi: 10.1111/
jpi.12128.
Fishbein AB, Vitaterna O, Haugh IM, Bavishi AA, Zee
PC, Turek FW, et al. Nocturnal eczema: Review of
sleep and circadian rhythms in children with atopic
dermatitis and future research directions. J Allergy
Clin Immunol. 2015; 136:1170-7. doi: 10.1016/j.
jaci.2015.08.028.
Gupta MA, Gupta AK. Sleep-wake disorders and
dermatology. Clin Dermatol. 2013; 31:118-26. doi:
1016/j.clindermatol.2011.11.016.
Kelsay K. Management of sleep disturbance associated
with atopic dermatitis. J Allergy Clin Immunol.
; 118:198-201.
Brown RE, Stevens DR, Haas HL. The physiology of
brain histamine. Prog Neurobiol. 2001; 63:637-72.
Tsujii T, Yamamoto E, Ohira T, Takahashi T, Watanabe
S. Antihistamine effects on prefrontal cortex activity
during working memory process in preschool
children: a near-infrared spectroscopy (NIRS) study.
Neurosci Res. 2010; 67:80-5. doi: 10.1016/j.neures.
01.010.
Richardson GS, Roehrs TA, Rosenthal L, Koshorek G,
Roth T. Tolerance to daytime sedative effects of H1 antihistamines.
J Clin Psychopharmacol. 2002; 22:511-5.
Motola D, Donati M, Biagi C, Calamelli E, Cipriani
F, Melis M, et al. Safety profile of H1-antihistamines
in pediatrics: an analysis based on data from VigiBase.
Pharmacoepidemiol Drug Saf. 2017; 26:1164-71. doi: 10.1002/pds.4246.
Slominski AT, Hardeland R, Zmijewski MA, Slominski
RM, Reiter RJ, Paus R. Melatonin: a cutaneous
perspective on its production, metabolism, and functions.
J Invest Dermatol. 2018;138:490-9. doi:
1016/j.jid.2017.10.025.
All articles in this journal are Open Access under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).