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26 Dermatologic Changes Related toPatients withObstructive Sleep Apnea
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26.4 Conclusion
In conclusion, skin diseases have various epidemiologic associations with
OSA.However, four etiopathogenic mechanisms that may explain the relationship
of many dermatologic processes with OSA are as follows:
1. Systemic bidirectional inammation associated with OSA and inammatory
skin disease (best exemplied by psoriasis) in each condition exacerbates
the other.
2. Obesity itself and the conditions associated with obesity (such as type 2 diabe-
tes) in which skin manifestations and concurrent OSA are frequently observed.
Type 2 diabetes is an interesting example as it is believed that OSA induces
decient wound healing and may contribute to diabetic ulcers becoming
infected.
3. Mechanical obstruction of the upper airways may be due to obesity and other
specic conditions such as lipodystrophy in which fat deposits accumulate adjacent to the airways.
4. The hypoxia related to OSA may be associated with skin cancer, particularly
melanoma. The intermittent hypoxia may produce proliferative neovascular signals which favor tumor growth. Joining these mechanisms is the autonomic dysfunction due to OSA.Excessive sympathetic ow toward the skin may accelerate
aging and uncover or exacerbate preexisting skin disorders.
Concerning the secondary effects, continuous positive pressure in the airways
may be locally associated with skin irritation, folliculitis, rosacea, irritative dermatitis, seborrheic dermatitis, and, very rarely, contact allergic dermatitis. However,
the benets of CPAP clearly outweigh the risks.
Many of these associations are clear and have been well studied and documented.
However, more research is needed to describe better the mechanisms underlying the
clinical associations between skin diseases and OSA and the potential therapeutic
effects on skin diseases when treating OSA with CPAP or other interventions.
Furthermore, it is likely that in everyday clinical practice, specialists come across
OSA in complex dermatologic patients who have one or more medical or psychiatric disorders, which are also associated with a greater risk for OSA.
Finally, dermatologists should be aware of the possible impact of OSA on the
course of skin diseases, especially those associated with a mainly inammatory
physiopathology, and the great benet offered by CPAP for the integumentary system.
Take-Home Messages
• Skin disorders are a common comorbidity of sleep apnea
• Sleep apnea itself may deteriorate the skin.
• Four ethiopathogenic mechanisms may explain the relationship of many derma-
tologic processes with OSA:
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– systemic bi-directional inammation associated with OSA and inammatory
skin disease (best exemplied by psoriasis and atopic dermatitis) in which
each condition exacerbates the other.
– obesity itself and the conditions associated with it (diabetes, hidradenitis sup-
purativa, polycystic ovary syndrome);
– Mechanical obstruction of the upper airways
– Hypoxia related to OSA may be associated with skin cancer, in particular
melanoma.
• Many of these associations are clear and have been well studied and documented.
• More research is needed to describe better the mechanisms underlying the clinical associations between skin diseases and OSA and the potential therapeutic
effects on skin diseases when treating OSA with CPAP or other interventions.
References
1. American Academy of Sleep Medicine. International classication of sleep disorders. 3rd ed.
Darien, IL: American Academy of Sleep Medicine; 2014.
2. Jennum P, Ibsen R, Kjellberg J.Morbidity prior to a diagnosis of sleep-disordered breathing:
a controlled national study. J Clin Sleep Med. 2013;9:103–8.
3. Jennum P, Ibsen R, Kjellberg J.Morbidity and mortality in children with obstructive sleep
apnoea: a controlled national study. Thorax. 2013;68:949–54.
4. Drager LF, Togeiro SM, Polotsky VY, etal. Obstructive sleep apnea: a cardiometabolic risk in
obesity and the metabolic syndrome. J Am Coll Cardiol. 2013;62:569–76.
5. Gupta MA, Gupta AK.Psychiatric and psychological co-morbidity in patients with dermatologic disorders: epidemiology and management. Am J Clin Dermatol. 2003;4:833–42.
6. Gupta MA, Simpson FC.Obstructive sleep apnea and psychiatric disorders: a systematic
review. J Clin Sleep Med. 2015;11:165–75.
7. Gupta MA, Gupta AK. Sleep-wake disorders and dermatology. Clin Dermatol.
2013;31:118–26.
8. Savransky V, Jun J, Li J, etal. Dyslipidemia and atherosclerosis induced by chronic intermittent hypoxia are attenuated by deciency of stearoyl coenzyme A desaturase. Circ Res.
2008;103:1173–80.
9. McNicholas WT, Bonsigore MR. Management Committee of ECAB. Sleep apnoea as an
independent risk factor for cardiovascular disease: current evidence, basic mechanisms and
research priorities. Eur Respir J. 2007;29:156–78.
10. Hirotsu C, Nogueira H, Albuquerque RG, Tomimori J, Tuk S, Andersen ML.The bidirectional interactions between psoriasis and obstructive sleep apnea. Int J Dermatol.
2015;54:1352–8.
11. Gaines J, Vgontzas AN, Fernandez-Mendoza J, et al. Inammation mediates the association between visceral adiposity and obstructive sleep apnea in adolescents. Am J Physiol
Endocrinol Metab. 2016;311:E851–8.
12. Can M, Uygur F, Tanriverdi H, etal. Effect of continuous positive airway pressure (CPAP)
therapy on IL-23in patients with obstructive sleep apnea. Immunol Res. 2016;64:1179–84.
13. Phillips BG, Wang Y, Ambati S, Ma P, Meagher RB. Airways therapy of obstructive sleep
apnea dramatically improves aberrant levels of soluble cytokines involved in autoimmune
disease. Clin Immunol. 2020;221:108601.
14. Polat D, Demirtaş E, Ahmet B, Yarali H.Decreased serum paraoxonase 1 (PON1) activity: an
additional risk factor for atherosclerotic heart disease in patients with PCOS? Hum Reprod.
2006;21:104–8.
26 Dermatologic Changes Related toPatients withObstructive Sleep Apnea
https://t.me/medicina_free
15. Van Cauter E.Sleep disturbances and insulin resistance. Diabet Med. 2011;28:1455–62.
16. Gupta MA, Simpson FC, Gupta AK.Psoriasis and sleep disorders: a systematic review. Sleep
Med Rev. 2015;29:63–75.
17. Gowda S, Goldblum OM, McCall WV, etal. Factors affecting sleep quality in patients with
psoriasis. J Am Acad Dermatol. 2010;63:114–23.
18. Machado-Pinto J, Diniz Mdos S, Bavoso NC. Psoriasis: new comorbidities. An Bras
Dermatol. 2016;91:8–14.
19. Egeberg A, Khalid U, Gislason GH, etal. Psoriasis and sleep apnea: a Danish nationwide
cohort study. J Clin Sleep Med. 2016;12:663–71.
20. Bissonnette R, Maari C, Bolduc C, etal. Prevalence of obstructive sleep apnea in obese
patients with psoriasis. J Am Acad Dermatol. 2012;66:AB133.
21. Chiu HY, Hsieh CF, Chiang YT, etal. Concomitant sleep disorders signicantly increase the
risk of cardiovascular disease in patients with psoriasis. PloS One. 2016;11:e0146462.
22. Cohen JM, Jackson CL, Li TY, etal. Sleep disordered breathing and the risk of psoriasis
among US women. Arch Dermatol Res. 2015;307:433–8.
23. Dufn KC, Woodcock J, Walsh J, etal. Increased prevalence of sleep apnea in patients with
psoriasis compared to matched controls. Clin Transl Sci. 2012;5:170.
24. Papadavid E, Vlami K, Dalamaga M, etal. Sleep apnea as a comorbidity in obese psoriasis
patients: a cross-sectional study. Do psoriasis characteristics and metabolic parameters play
a role? J Eur Acad Dermatol Venereol. 2013;27:820–6.
25. Tsai TF, Wang TS, Hung ST, etal. Epidemiology and comorbidities of psoriasis patients in a
national database in Taiwan. J Dermatol Sci. 2011;63:40–6.
26. Yang YW, Kang JH, Lin HC.Increased risk of psoriasis following obstructive sleep apnea: a
longitudinal population-based study. Sleep Med. 2012;13:285–9.
27. Papadavid E, Dalamaga M, Vlami K, Koumaki D, Gyftopoulos S, Christodoulatos GS, etal.
Psoriasis is associated with risk of obstructive sleep apnea independently from metabolic
parameters and other comorbidities: a large hospital-based case-control study. Sleep Breath.
2017;21:949–58.
28. Shalom G, Dreiher J, Cohen A. Psoriasis and obstructive sleep apnea. Int J Dermatol.
2016;55:e579–84.
29. Castello-Branco RC, Cerqueira-Silva T, Andrade AL, Gonçalves BM, Pereira CB, Felix IF,
Santos LS, Porto LM, Marques ME, Catto MB, etal. Association between risk of obstructive sleep apnea and cerebrovascular reactivity in stroke patients. J Am Heart Assoc.
2020;9:e015313.
30. Saçmaci H, Gürel G.Sleep disorders in patients with psoriasis: across-sectional study using
non-polysomnographical methods. Sleep Breath. 2019;23:893–8.
31. Gabryelska A, Białasiewicz P. Is autonomic activation a middleman between obstructive
sleep apnea syndrome and psoriasis? J Clin Sleep Med. 2018;14:1087–8.
32. Gowda S, Goldblum OM, McCall WV, Feldman SR. Factors affecting sleep quality in
patients with psoriasis. J Am Acad Dermatol. 2010;63:114–23.
33. Maari C, Bolduc C, Nigen S, Marchessault P, Bissonnette R.Effect of adalimumab on sleep
parameters in patients with psoriasis and obstructive sleep apnea: a randomized controlled
trial. J Dermatol Treat. 2014;25:57–60.
34. Vakil M, Park S, Broder A.The complex associations between obstructive sleep apnea and
auto-immune disorders: a review. Med Hypotheses. 2018;110:138–43.
35. Kim J, Kim BE, Leung DYM.Pathophysiology of atopic dermatitis: Clinical implications.
Allergy Asthma Proc. 2019;40:84–92.
36. Cabanillas B, Brehler AC, Novak N.Atopic dermatitis phenotypes and the need for personalized medicine. Curr Opin Allergy Clin Immunol. 2017;17:309–15.
37. Darsow U, Raap U, Ständer S.Atopic dermatitis. In: Carstens E, Akiyama T, editors. Itch:
mechanisms and treatment. Boca Raton, FL: CRC Press; 2014. Chapter 3.
38. Wolter S, Price HN.Atopic dermatitis. Pediatr Clin North Am. 2014;61:241–60.
39. Tien KJ, Chou CW, Lee SY, Yeh NC, Yang CY, Yen FC, etal. Obstructive sleep apnea and the
risk of atopic dermatitis: a population-based case control study. PloS One. 2014;9:e89656.
463
464
https://t.me/medicina_free
40. Arens R, Marcus CL.Pathophysiology of upper airway obstruction: a developmental perspective. Sleep. 2004;27:997–1019.
41. Olusesi AD, Undie NB, Amodu JE.Allergy history as a predictor of early onset adenoids/
adenotonsillar hypertrophy among Nigerian children. Int J Pediatr Otorhinolaryngol.
2013;77:1032–5.
42. Alexopoulos EI, Bizakis J, Gourgoulianis K, Kaditis AG.Atopy does not affect the frequency of adenotonsillar hypertrophy and sleep apnoea in children who snore. Acta Paediatr.
2014;103:1239–43.
43. Huo Z, Shi J, Shu Y, Xiang M, Lu J, Wu H.The relationship between allergic status and
adenotonsillar regrowth: a retrospective research on children after adenotonsillectomy. Sci
Rep. 2017;7:46,615.
44. Kheirandish-Gozal L, Bandla HP, Gozal D.Montelukast for children with obstructive sleep
apnea: results of a double-blind, randomized, placebo-controlled trial. Ann Am Thorac Soc.
2016;13:1736–41.
45. Dayyat E, Serpero LD, Kheirandish-Gozal L, Goldman JL, Snow A, Bhattacharjee R, etal.
Leukotriene pathways and invitro adenotonsillar cell proliferation in children with obstructive sleep apnea. Chest. 2009;135:1142–9.
46. Fishbein AB, Lor J, Penedo FJ, Forrest CB, Grifth JW, Paller AS.Patient-reported outcomes for measuring sleep disturbance in pediatric atopic dermatitis: cross sectional study of
PROMIS pediatric sleep measures and actigraphy. J Am Acad Dermatol. 2020;
47. Association between obstructive sleep apnea and atopic dermatitis in children: a nationwide,
population-based cohort study. Pediatr Allergy Immunol. 2018;29:260–6.
48. Fishbein AB, Mueller K, Kruse L, Boor P, Sheldon S, Zee P, etal. Sleep disturbance in
children with moderate/severe atopic dermatitis: a case-control study. J Am Acad Dermatol.
2018;78:336–41.
49. Treister AD, Stefek H, Grimaldi D, Rupani N, Zee P, Yob J, etal. Sleep and limb movement
characteristics of children with atopic dermatitis coincidentally undergoing clinical polysomnography. J Clin Sleep Med. 2019;15:1107–13.
50. Reuveni H, Chapnick G, Tal A, etal. Sleep fragmentation in children with atopic dermatitis.
Arch Pediatr Adolesc Med. 1999;153:249–53.
51. Bozkurt B, Serife Ugur K, Karamanli H, etal. Polysomnographic ndings in persistent allergic rhinitis. Sleep Breath. 2016. [Epub ahead of print].
52. Tahrani AA, Ali A, Raymond NT, Begum S, Dubb K, Mughal S, etal. Obstructive sleep
apnea and diabetic neuropathy: a novel association in patients with type 2 diabetes. Am J
Respir Crit Care Med. 2012;186:434–41.
53. Altaf QA, Ali A, Piya MK, Raymond NT, Tahrani AA.The relationship between obstructive
sleep apnea and intra-epidermal nerve ber density, PARP activation and foot ulceration in
patients with type 2 diabetes. J Diabetes Complications. 2016;30:1315–20.
54. Vas PR, Ahluwalia R, Manas AB, Manu CA, Kavarthapu V, Edmonds ME.Undiagnosed
severe sleep apnoea and diabetic foot ulceration—a case series based hypothesis: a hitherto
under emphasized factor in failure to heal. Diabet Med. 2016;33:e1–4.
55. van der Zee HH, de Ruiter L, van den Broecke DG, etal. Elevated levels of tumour necrosis
factor (TNF)-a, interleukin (IL)-1b and IL-10in hidradenitis suppurativa skin: a rationale for
targeting TNF-a and IL-1b. Br J Dermatol. 2011;164:1292–8.
56. Alberti A, Sarchielli P, Gallinella E, etal. Plasma cytokine levels in patients with obstructive
sleep apnea syndrome: a preliminary study. J Sleep Res. 2003;12:305–11.
57. Irwin MR, Olmstead R, Carroll JE.Sleep disturbance, sleep duration, and inammation: a
systematic review and meta-analysis of cohort studies and experimental sleep deprivation.
Biol Psychiatry. 2016;80:40–52.
58. Wertenteil S, Strunk A, Garg A.Incidence of obstructive sleep apnoea in patients with
hidradenitis suppurativa: a retrospective population-based cohort analysis. Br J Dermatol.
2018;179:1398–9.
59. Vinkel C, Thomsen SF.Risk factors for cardiovascular disease in patients with hidradenitis
suppurativa. J Eur Acad Dermatol Venereol. 2017;31:e411–3.
P. Redondo
26 Dermatologic Changes Related toPatients withObstructive Sleep Apnea
https://t.me/medicina_free
60. Drager LF, Togeiro SM, Polotsky VY, Lorenzi-Filho G. Obstructive sleep apnea: a cardiometabolic risk in obesity and the metabolic syndrome. J Am Coll Cardiol. 2013;62:569–76.
61. Matusiak L, Bieniek A, Szepietowski JC.Increased serum tumour necrosis factor-alpha in
hidradenitis suppurativa patients: is there a basis for treatment with anti-tumour necrosis
factor-alpha agents? Acta Dermatovenereol. 2009;89:601–3.
62. Kelly A, Meurling J, Kirthi Jeyarajah S, Ryan C, Hughes R, Garvey J, Kirby B.Obstructive
sleep apnoea in psoriasis and hidradenitis suppurativa. Br J Dermatol. 2021;184:1183–5.
63. Fogel RB, Malhotra A, Pillar G, et al. Increased prevalence of obstructive sleep apnea
syndrome in obese women with polycystic ovary syndrome. J Clin Endocrinol Metab.
2001;86:1175–80.
64. Vgontzas AN, Legro RS, Bixler EO, etal. Polycystic ovary syndrome is associated with
obstructive sleep apnea and daytime sleepiness: role of insulin resistance. J Clin Endocrinol
Metab. 2001;86:517–20.
65. Tasali E, Van Cauter E, Ehrmann DA.Relationships between sleep disordered breathing and
glucose metabolism in polycystic ovary syndrome. J Clin Endocrinol Metab. 2006;91:36–42.
66. Gopal M, Duntley S, Uhles M, etal. The role of obesity in the increased prevalence of
obstructive sleep apnea syndrome in patients with polycystic ovarian syndrome. Sleep Med.
2002;3:401–4.
67. Chatterjee B, Suri J, Suri JC, etal. Impact of sleep-disordered breathing on metabolic dysfunctions in patients with polycystic ovary syndrome. Sleep Med. 2014;15:1547–53.
68. Nandalike K, Agarwal C, Strauss T, etal. Sleep and cardiometabolic function in obese adolescent girls with polycystic ovary syndrome. Sleep Med. 2012;13:1307–12.
69. Kahal H, Kyrou I, Tahrani A, Randeva H.Obstructive sleep apnoea and polycystic ovary
syndrome: a comprehensive review of clinical interactions and underlying pathophysiology.
Clin Endocrinol (Oxf). 2017;87:313–9.
70. Heinzer R, Vat S, Marques-Vidal P, et al. Prevalence of sleep-disordered breathing in the
general population: the HypnoLaus study. Lancet. Respir Med. 2015;3:310–8.
71. Tasali E, Chapotot F, Leproult R, et al. Treatment of obstructive sleep apnea improves
cardiometabolic function in young obese women with polycystic ovary syndrome. J Clin
Endocrinol Metab. 2011;96:365–74.
72. Tasali E, Van Cauter E, Hoffman L, etal. Impact of obstructive sleep apnea on insulin resistance and glucose tolerance in women with polycystic ovary syndrome. J Clin Endocrinol
Metab. 2008;93:3878–84.
73. Mokhlesi B, Scoccia B, Mazzone T, etal. Risk of obstructive sleep apnea in obese and nonobese women with polycystic ovary syndrome and healthy reproductively normal women.
Fertil Steril. 2012;97:786–91.
74. Yang HP, Kang JH, Su HY, etal. Apnea-hypopnea index in nonobese women with polycystic
ovary syndrome. Int J Gynaecol Obstet. 2009;105:226–9.
75. Lin TY, Lin PY, Su TP, et al. Risk of developing obstructive sleep apnea among women
with polycystic ovarian syndrome: a nationwide longitudinal follow-up study. Sleep Med.
2017;36:165–9.
76. Analysis of the proportion and clinical characteristics of obstructive sleep apnea in women
with polycystic ovary syndrome. Sleep Breath. 2022;26:497–503.
77. Hoppin AG, Katz ES, Kaplan LM, etal. Case records of the Massachusetts General Hospital.
Case 31–2006. A 15-year-old girl with severe obesity. N Engl J Med. 2006;355:1593–602.
78. Ismailogullari S, Ferahbas A, Aksu M, et al. Effects of isotretinoin treatment on sleep in
patients with severe acne: a pilot study. J Eur Acad Dermatol Venereol. 2012;26:778–81.
79. Haynes D, Topham C, Greiling T.Acne keloidalis nuchae and obstructive sleep apnoea: a
retrospective case series. Clin Exp Dermatol. 2019;44:e214–5.
80. Kelly AP. Pseudofolliculitis barbae and acne keloidalis nuchae. Dermatol Clin.
2003;21:645–53.
81. Verma SB, Wollina U.Acne keloidalis nuchae: another cutaneous symptom of metabolic
syndrome, truncal obesity, and impending/overt diabetes mellitus? Am J Clin Dermatol.
2010;11:433–6.
465
466
https://t.me/medicina_free
82. Buyuktas D, Arslan E, Celik O, Tasan E, Demirkesen C, Gundogdu S.Elephantiasis nostras
verrucosa on the abdomen of a Turkish female patient caused by morbid obesity. Dermatol
Online J. 2010;16:14.
83. Shanmugam VK, Tsagaris KC, Attinger CE.Leg ulcers associated with Klinefelter's syndrome: a case report and review of the literature. Int Wound J. 2012;9:104–7.
84. Hegele RA, Al-Attar SA, Rutt BK.Obstructive sleep apnea in 2 women with familial partial
lipodystrophy due to a heterozygous LMNA R482Q mutation. CMAJ. 2007;177:743–5.
85. Carr A, Cooper DA.Adverse effects of antiretroviral therapy. Lancet. 2000;356(9239):1423–30.
86. Epstein LJ, Strollo PJ Jr, Donegan RB, Delmar J, Hendrix C, Westbrook PR.Obstructive sleep
apnea in patients with human immunodeciency virus (HIV) disease. Sleep. 1995;18:368–76.
87. Abdeen Y, Al-Halawani M, Kaako A, Hao IFY, Dazley J, Katpally R, Klukowicz A, Miller R,
Slim J.Effect of the duration of protease inhibitor therapy in HIV-infected individuals on the
severity of obstructive sleep apnea. J Res Med Sci. 2019;24:65.
88. Harsch IA, Bergmann T, Koebnick C, Wiedmann R, Ruderich F, Hahn EG, etal. Adiponectin,
resistin and subclinical inammation—the metabolic burden in Launois Bensaude Syndrome,
a rare form of obesity. J Physiol Pharmacol. 2007;58(Suppl 1):65–76.
89. Hanson RD, Olsen KD, Rogers RS III.Upper aerodigestive tract manifestations of cicatricial
pemphigoid. Ann Otol Rhinol Laryngol. 1988;97:493–9.
90. Hubbard M, Masters IB, Williams GR, etal. Severe obstructive sleep apnea secondary to pressure garments used in the treatment of hypertrophic burn scars. Eur Respir J. 2000;16:1205–7.
91. Gozal D, Ham SA, Mokhlesi B.Sleep apnea and cancer: analysis of a nationwide population
sample. Sleep. 2016;39:1493–500.
92. Gozal D, Farré R, Nieto FJ.Putative links between sleep apnea and cancer from hypotheses
to evolving evidence. Chest. 2015;148:1140–7.
93. Martínez-García MÁ, Campos-Rodriguez F, Barbé F.Cancer and OSA: current evidence
from human studies. Chest. 2016;150:451–63.
94. Martínez-García MA, Martorell-Calatayud A, Nagore E, etal. Association between sleep disordered breathing and aggressiveness markers of malignant cutaneous melanoma. Eur Respir
J. 2014;43:1661–8.
95. Almendros I, Montserrat JM, Torres M, etal. Intermittent hypoxia increases melanoma metastasis to the lung in a mouse model of sleep apnea. Respir Physiol Neurobiol. 2013;186:303–7.
96. Santamaria-Martos F, Benítez I, Girón C, Barbé F, Martínez-García MA, Hernández L, etal.
Biomarkers of carcinogenesis and tumour growth in patients with cutaneous melanoma and
obstructive sleep apnoea. Eur Respir J. 2018;51:1701885.
97. Almendros I, Martínez-García M, Campos-Rodríguez F, Riveiro-Falkenbach E, RodríguezPeralto JL, Nagore E, etal. Intermittent hypoxia is associated with high hypoxia inducible
factor-1α but not high vascular endothelial growth factor cell expression in tumors of cutaneous melanoma patients. Front Neurol. 2018;9:272.
98. Martinez-Garcia MA, Campos-Rodriguez F, Nagore E, Martorell A, Rodriguez-Peralto JL,
Riveiro-Falkenbach E, etal. Sleep-disordered breathing is independently associated with
increased aggressiveness of cutaneous melanoma: a multicenter observational study in 443
patients. Chest. 2018;154:1348–58.
99. Martinez-Garcia MA, Campos-Rodriguez F, Almendros I, etal. Relationship between sleep
apnea and cancer. Arch Bronconeumol. 2015;51:456–61.
100. Tan NKW, Yap DWT, Tan BKJ, et al. The association of obstructive sleep apnea with
melanoma incidence and mortality: a meta-analysis of 5,276,451 patients. Sleep Med.
2021;88:213–20.
101. Almendros I, Martínez-García MA, Campos-Rodríguez F, etal. Intermittent hypoxia is associated with high hypoxia inducible factor-1a but not high vascular endothelial growth factor
cell expression in tumors of cutaneous melanoma patients. Front Neurol. 2018:9.
102. Hunyor I, Cook KM.Models of intermittent hypoxia and obstructive sleep apnea: molecular pathways and their contribution to cancer. Am J Physiol Regul Integr Comp Physiol.
2018;315(R669):r87.
P. Redondo
26 Dermatologic Changes Related toPatients withObstructive Sleep Apnea
https://t.me/medicina_free
103. Li H, Chen J, Wang X, etal. Nodal induced by hypoxia exposure contributes todacarbazine
resistance and the maintenance of stemness in melanoma cancer stem-like cells. Oncol Rep.
2018;39:2855–64.
104. Sun X, Lv X, Yan Y, etal. Hypoxia-mediated cancer stem cell resistance and targeted therapy.
Biomed Pharmacother. 2020;130:110623.
105. Lin Y, Xu J, Lan H.Tumor-associated macrophages in tumor metastasis: biological roles and
clinical therapeutic applications. J Hematol Oncol. 2019;12:76.
106. Cole SW, Sood AK.Molecular pathways: beta-adrenergic signaling in cancer. Clin Cancer
Res. 2012;18:1201–6.
107. Moretti S, Massi D, Farini V, etal. b-adrenoceptors are upregulated in humanmelanoma and
their activation releases pro-tumorigenic cytokines and metalloproteases in melanoma cell
lines. Lab Invest. 2013;93:279–90.
108. Dal Monte M, Calvani M, Cammalleri M, etal. b-Adrenoceptors as drug targets in melanoma: novel preclinical evidence for a role of b (3) -adrenoceptors. Br J Pharmacol.
2019;176:2496–508.
109. Baik I, Lee S, Thomas RJ, Shin C.Obstructive sleep apnea, low transferrin saturation levels,
and male-pattern baldness. Int J Dermatol. 2019;58:67–74.
110. Reintgen C, Leavitt A, Pace E, Molas-Pierson J, Mast BA.Risk factor analysis for mastectomy skin ap necrosis. implications for intraoperative vascular analysis. Ann Plast Surg.
2016;76(Suppl 4):S336–9.
111. Pépin JL, Leger P, Veale D, Langevin B, Robert D, Lévy P.Side effects of nasal continuous
positive airway pressure in sleep apnea syndrome. Study of 193 patients in two French sleep
centers. Chest. 1995;107:375–81.
112. Pepin JL, Leger P, Veale D, et al. Side effects of nasal continuous positive airway pressure in sleep apnea syndrome. Study of 193 patients in two French sleep centers. Chest.
1995;107:375–81.
113. Reynaerts A, Bruze M, Erikstam U, etal. Allergic contact dermatitis from a medical device,
followed by depigmentation. Contact Dermatitis. 1998;39:204–5.
114. Elkin PL, Mullin S, Sakilay S.Rosacea patients are at higher risk for obstructive sleep apnea:
automated retrospective research. Stud Health Technol Inform. 2020;270:1381–2.
115. Logger JGM, Peppelman M, Vugt RV, Driessen RJB.Rosacea and use of continuous positive airway pressure mask for obstructive sleep apnea syndrome: report of ve cases. Ann
Dermatol. 2020;32:3.
116. Matin A, Bliwise DL, Wellman JJ, Ewing HA, Rasmuson P.Resolution of dyshidrotic dermatitis of the hand after treatment with continuous positive airway pressure for obstructive sleep
apnea. South Med J. 2002;95:253–4.
117. Nino G, Singareddy R.Severe onychophagia and nger mutilation associated with obstructive sleep apnea. J Clin Sleep Med. 2013;9:379–81.
118. Arnardottir ES, Thorleifsdottir B, Svanborg E, etal. Sleep-related sweating in obstructive
sleep apnoea: association with sleep stages and blood pressure. J Sleep Res. 2010;19:122–30.
119. Schlaud M, Urschitz MS, Urschitz-Duprat PM, etal. The German study on sleep-disordered
breathing in primary school children: epidemiological approach, representativeness of study
sample, and preliminary screening results. Paediatr Perinat Epidemiol. 2004;18:431–40.
120. Eitner S, Urschitz MS, Guenther A, etal. Sleep problems and daytime somnolence in a German
population-based sample of snoring school-aged children. J Sleep Res. 2007;16:96–101.
121. Arnardottir ES, Janson C, Bjornsdottir E, etal. Nocturnal sweating–a common symptom of
obstructive sleep apnoea: The Icelandic sleep apnoea cohort. BMJ Open. 2013;3:e002795.
122. Gabryelska A, Sochal M, Wasik B, Bialasiewicz P.Patients with obstructive sleep apnea are
over four times more likely to suffer from psoriasis than the general population. J Clin Sleep
Med. 2018;14:153.
123. Martinez-Garcia MA, Campos-Rodriguez F, Almendros I, Garcia-Rio F, Sanchez-de-la-Torre
M, Farre R, etal. Cancer and sleep apnea: cutaneous melanoma as a case study. Am J Respir
Crit Care Med. 2019;200:1345–53.
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Laboratory Parameters Changes
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27
CamiloSilvaFroján, JuanaKarinaZapataCárdenas,
SaioaEcheverríaAndueza, andPatriciaAndradaÁlvarez
27.1 Complete Blood Cell Count
Complete blood cell count (CBC) is a medical laboratory test widely available, easy
to obtain, and cheap. Systemic inammation and altered platelet function are two
mechanisms involved in the increased cardiovascular risk associated with obstructive sleep apnea (OSA). Through a hemogram, we can obtain a series of parameters
related to these two physiopathological mechanisms. Red cell distribution width
(RDW) is a measurement of the range in the volume and size of the erythrocytes.
Inammation can shorten erythrocytes survival, and elevated RDW has been
described in OSA patients.
Nevertheless, this fact may be related to age or obesity. A signicant positive
correlation between RDW and apnea–hypopnea index (AHI) and oxygen desaturation index (ODI) has been found. Furthermore, RDW might be used as a marker of
the response to continuous positive airway pressure (CPAP) treatment [1].
It is well known that hypoxia stimulates erythropoiesis and is associated with
inammation [2]. Hemoglobin and hematocrit are signicantly increased in patients
with severe OSA, but values remain within the normal clinical range. A negative
C. S. Froján (*)
Department of Endocrinology & Nutrition, Clínica Universidad de Navarra, Pamplona, Spain
Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición
(CIBEROBN), Instituto de Salud Carlos III, Pamplona, Spain
Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA),
Pamplona, Spain
e-mail: csilvafr@unav.es
J. K. Z. Cárdenas · S. E. Andueza · P. A. Álvarez
Department of Endocrinology & Nutrition, Clínica Universidad de Navarra, Pamplona, Spain
e-mail: jzapatac@unav.es; secheverriaa@unav.es; pandrada@unav.es
© The Author(s), under exclusive license to Springer Nature
Switzerland AG 2023
P. M. Baptista et al. (eds.), Obstructive Sleep Apnea,
https://doi.org/10.1007/978-3-031-35225-6_27
469
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association exists between hemoglobin, hematocrit, mean corpuscular volume
(MCV), and mean peripheral oxygen saturation (SpO2) [3]. One possible explanation are the high blood levels of erythropoietin (EPO) seen in OSA patients [4].
Atrial natriuretic peptide (ANP) is secreted by the cardiac muscle cells in response
to an expanded extracellular uid, and its natriuretic effect can contribute to hemoconcentration. The atrial natriuretic peptide is increased in untreated OSA patients
and levels decrease during treatment with CPAP, suggesting a possible role in
increased hemoglobin and hematocrit levels due to hemoconcentration [5].
Platelets play a crucial role in hemostasis and thrombosis. Platelet activation can
increase blood viscosity which mediates between systemic inammation and cardiovascular risk. Several platelet indices are usually part of the hemogram that can
be used as markers of activity. Mean platelet volume (MPV) refers to the average
size of circulating platelets and is associated with several cardiometabolic risk factors and cardiovascular events.
MPV is signicantly increased in patients with OSA and could be used as a
marker to predict cardiovascular disease in this group [6]. Furthermore, one study
showed that six months of CPAP therapy causes signicant reductions in the MPV
values in patients with severe OSA [7]. However, MPV can be inuenced by many
factors such as age, gender, or blood sample processing, reducing the specicity of
this parameter [8].
Platelet distribution width (PDW) refers to the variance in the size of circulating
platelets. High PDW has been correlated with AHI in OSA, and CPAP can decrease
this parameter [9].
Activated platelets can interact with leukocytes and neutrophils forming aggregates. Also, activated platelets can stimulate neutrophils, promoting the formation
of neutrophil–lymphocyte complexes. Among other situations, the neutrophil to
lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) increase in systemic inammation and cardiovascular diseases. The PLR value in OSA patients
has been found to be less than the control group, showing an inverse correlation
with AHI.In the same study, NLR increased as the time spent during the sleep with
a lowering of arterial oxygen saturation below 90% [10].
C. S. Froján et al.
27.2 Inflammatory Markers
OSA, inammation, and cardiovascular risk are interconnected. It is well known
that chronic vascular inammation is related to the development of atherosclerosis,
which is now considered an inammatory disease. In addition to activating the sympathetic nervous system and derangement in endothelial function, OSA patients
have a higher expression of systemic inammatory markers [11]. The proinammatory state associated with OSA is related to intermittent hypoxia, since cycles of
hypoxia and reoxygenation are similar to ischemia-reperfusion injury which promotes oxidative stress [12]. Therefore, it is not easy to determine whether OSA
itself or the obesity usually associated is responsible for this rise since obesity is
associated with a proinammatory state.
27 Laboratory Parameters Changes
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C-reactive protein (CRP), produced in the liver through interleukin-6 (IL-6)
activity, is one of the most used inammatory markers in clinical practice, and its
elevated levels have been associated, among others, with diabetes or cardiovascular
disease. Several studies have reported increased levels of CRP in OSA patients, and
these levels tend to decrease with effective treatment. However, other studies have
failed to conrm this relationship, suggesting that the association between OSA and
CRP levels is inuenced by other factors like obesity or diabetes [13].
IL-6 is an important proinammatory cytokine that induces the synthesis of all
acute-phase proteins, including CRP.Other biological activities of IL-6 are proliferation and differentiation of lymphocytes or immunoglobulin secretion. Similar to
CRP, elevated levels of IL-6 are associated with higher cardiovascular risk through
the propitiation of a proinammatory state. Several meta-analyses conrm an
increase in IL-6in patients with OSA [14].
Tumor Necrosis Factor Alpha (TNF-α) is a proinammatory cytokine secreted
by immune cells and mediates the pathogenesis of several diseases such as cancer,
atherosclerosis, or autoimmune diseases. A recent meta-analysis found a signicant
association between OSA and elevated TNF-α levels in adults. In this investigation,
TNF-α levels were correlated with OSA severity [15].
Fibrinogen is a glycoprotein involved in the thrombogenesis process. Fibrinogen
also acts as an acute-phase protein, and high levels are associated with inammation
and cardiovascular disease. Recently two meta-analysis showed that circulating
brinogen levels are elevated in patients with OSA [16] and that CPAP treatment
can reduce plasma brinogen levels in OSA patients, suggesting that elevated
brinogen levels may be a link between OSA and cardiovascular disease [17].
Other inammatory markers such as interleukin 8 (IL-8), intercellular adhesion
molecule (ICAM), vascular cell adhesion molecule (VCAM), and selectins have
also been found to be increased in patients with OSA [11].
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27.3 Glucose Metabolism
Type 2 diabetes is associated with an increased risk of developing OSA.Patients
with type 2 diabetes (T2D) have an increased adjusted incidence rate ratio (1.48) of
OSA compared with those without [18]. However, positive airway pressure (PAP)
therapy has failed to improve glycemic control in type 2 diabetes patients [19]. One
mechanism that may mediate this association is insulin resistance, which is independently associated with OSA [20].
Diabetes mellitus is a heterogeneous disease of glucose metabolism characterized by impaired ability to produce or respond to insulin. Diabetes is characterized
an elevated blood glucose level that, sustained over time, can be associated with the
development of microvascular and macrovascular complications (retinopathy,
nephropathy, neuropathy, and vascular disease). The most common form of diabetes
is type 2 diabetes (T2D), which occurs more frequently in middle-aged and elderly
people. There are several pathophysiological factors involved in T2D, among which
the presence of obesity and insulin resistance stands out. Diabetes may be
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