Abstract
The consequences of atopic dermatitis reach beyond the skin and past childhood. Patients with atopic dermatitis are at risk of developing allergic comorbidities, but less is known about the associations between atopic dermatitis and non-allergic conditions. Understanding these non-allergic comorbidities has the potential to improve patient outcomes and to help mitigate the cost and burdens associated with these conditions. Atopic dermatitis is associated with cutaneous bacterial infections, more severe forms/courses of cutaneous viral infections, and extra-cutaneous infections. Atopic dermatitis is also associated with several mental health comorbidities particularly attention-deficit hyperactivity disorder, anxiety, and depression. Data are largely inconsistent for specific cancers, but atopic dermatitis appears to protect against malignancy overall; severe long-term atopic dermatitis is associated with adult lymphomas. Atopic dermatitis may also be associated with obesity, cardiovascular disease, and autoimmune disease, particularly alopecia areata and gastrointestinal immune-mediated disorders. Although the causative mechanisms underlying these associations are poorly understood, treating physicians should be aware of associations in seeking to alleviate the burden for patients with atopic dermatitis.
Similar content being viewed by others
References
Odhiambo JA, Williams HC, Clayton TO, ISAAC Phase Three Study Group, et al. Global variations in prevalence of eczema symptoms in children from ISAAC Phase Three. J Allergy Clin Immunol. 2009;124(6):1251–8.
Thyssen JP, Hamann CR, Linneberg A, et al. Atopic dermatitis is associated with anxiety, depression, and suicidal ideation, but not with psychiatric hospitalization or suicide. Allergy. 2018;73(1):214–20.
Egeberg A, Andersen YM, Gislason GH, et al. Prevalence of comorbidity and associated risk factors in adults with atopic dermatitis. Allergy. 2017;72(5):783–91.
Schneider L, Hanifin J, Boguniewicz M, et al. Study of the atopic march: development of atopic comorbidities. Pediatr Dermatol. 2016;33(4):388–98.
Simpson EL, Eichenfield LF, Ellis CN, et al. Current issues in atopic comorbidities and preventing the atopic march. Semin Cutan Med Surg. 2012;31(3 Suppl.):S6–9.
Thyssen JP, McFadden JP, Kimber I. The multiple factors affecting the association between atopic dermatitis and contact sensitization. Allergy. 2014;69(1):28–36.
Ruff SMD, Engebretsen KA, Zachariae C, et al. The association between atopic dermatitis and hand eczema: a systematic review and meta-analysis. Br J Dermatol. 2018;178(4):879–88.
Leonard A, Guttman-Yassky E. The unique molecular signatures of contact dermatitis and implications for treatment. Clin Rev Allergy Immunol. 2018. https://doi.org/10.1007/s12016-018-8685-0 (Epub ahead of print).
Brunner PM, Silverberg JI, Guttman-Yassky E, et al. Councilors of the International Eczema Council. Increasing comorbidities suggest that atopic dermatitis is a systemic disorder. J Investig Dermatol. 2017;137(1):18–25.
Thijs JL, Strickland I, Bruijnzeel-Koomen C, et al. Serum biomarker profiles suggest that atopic dermatitis is a systemic disease. J Allergy Clin Immunol. 2018;141(4):1523–6.
Hayashida S, Furusho N, Uchi H, et al. Are lifetime prevalence of impetigo, molluscum and herpes infection really increased in children having atopic dermatitis? J Dermatol Sci. 2010;60(3):173–8.
Langan SM, Abuabara K, Henrickson SE, et al. Increased risk of cutaneous and systemic infections in atopic dermatitis: a cohort study. J Investig Dermatol. 2017;137(6):1375–7.
Chen CF, Wu KG, Hsu MC, et al. Prevalence and relationship between allergic diseases and infectious diseases. J Microbiol Immunol Infect. 2001;34(1):57–62.
Bell MC, Stovall SH, Scurlock AM, et al. Addressing antimicrobial resistance to treat children with atopic dermatitis in a tertiary pediatric allergy clinic. Clin Pediatr (Phila). 2012;51(11):1025–9.
Early GJ, Seifried SE. Risk factors for community-associated Staphylococcus aureus skin infection in children of Maui. Hawaii J Med Public Health. 2012;71(8):218–23.
Ortega-Loayza AG, Diamantis SA, Gilligan P, et al. Characterization of Staphylococcus aureus cutaneous infections in a pediatric dermatology tertiary health care outpatient facility. J Am Acad Dermatol. 2010;62(5):804–11.
Matiz C, Tom WL, Eichenfield LF, et al. Children with atopic dermatitis appear less likely to be infected with community acquired methicillin-resistant Staphylococcus aureus: the San Diego experience. Pediatr Dermatol. 2011;28(1):6–11.
Narla S, Silverberg JI. Association between atopic dermatitis and serious cutaneous, multiorgan and systemic infections in US adults. Ann Allergy Asthma Immunol. 2018;120(1):66–72.
Beck LA, Boguniewicz M, Hata T, et al. Phenotype of atopic dermatitis subjects with a history of eczema herpeticum. J Allergy Clin Immunol. 2009;124(2):260–9 (269.e1–7).
Leung DY. Why is eczema herpeticum unexpectedly rare? Antiviral Res. 2013;98(2):153–7.
Hsu DY, Shinkai K, Silverberg JI. Epidemiology of eczema herpeticum in hospitalized US children: analysis of a nationwide cohort. J Investig Dermatol. 2018;138(2):265–72.
Wollenberg A, Zoch C, Wetzel S, et al. Predisposing factors and clinical features of eczema herpeticum: a retrospective analysis of 100 cases. J Am Acad Dermatol. 2003;49(2):198–205.
Mathes EF, Oza V, Frieden IJ, et al. “Eczema coxsackium” and unusual cutaneous findings in an enterovirus outbreak. Pediatrics. 2013;132(1):e149–57.
Olsen JR, Gallacher J, Piguet V, et al. Epidemiology of molluscum contagiosum in children: a systematic review. Fam Pract. 2014;31(2):130–6.
McCollum AM, Holman RC, Hughes CM, et al. Molluscum contagiosum in a pediatric American Indian population: incidence and risk factors. PLoS One. 2014;9(7):e103419.
Dohil MA, Lin P, Lee J, et al. The epidemiology of molluscum contagiosum in children. J Am Acad Dermatol. 2006;54(1):47–54.
Osio A, Deslandes E, Saada V, et al. Clinical characteristics of molluscum contagiosum in children in a private dermatology practice in the greater Paris area, France: a prospective study in 661 patients. Dermatology. 2011;222(4):314–20.
Seize MB, Ianhez M, Cestari Sda C. A study of the correlation between molluscum contagiosum and atopic dermatitis in children. An Bras Dermatol. 2011;86(4):663–8.
Berger EM, Orlow SJ, Patel RR, et al. Experience with molluscum contagiosum and associated inflammatory reactions in a pediatric dermatology practice: the bump that rashes. Arch Dermatol. 2012;148(11):1257–64.
Montgomery SM, Ehlin AG, Sparen P, et al. Childhood indicators of susceptibility to subsequent cervical cancer. Br J Cancer. 2002;87(9):989–93.
Strom MA, Silverberg JI. Association between atopic dermatitis and extracutaneous infections in US adults. Br J Dermatol. 2017;176(2):495–7.
Silverberg JI, Silverberg NB. Childhood atopic dermatitis and warts are associated with increased risk of infection: a US population-based study. J Allergy Clin Immunol. 2014;133(4):1041–7.
Bohme M, Lannero E, Wickman M, et al. Atopic dermatitis and concomitant disease patterns in children up to 2 years of age. Acta Derm Venereol. 2002;82(2):98–103.
Jung JA, Kita H, Yawn BP, et al. Increased risk of serious pneumococcal disease in patients with atopic conditions other than asthma. J Allergy Clin Immunol. 2010;125(1):217–21.
Bentdal YE, Nafstad P, Karevold G, et al. Acute otitis media in schoolchildren: allergic diseases and skin prick test positivity. Acta Otolaryngol. 2007;127(5):480–5.
Juhn YJ, Frey D, Li X, et al. Streptococcus pyogenes upper respiratory infection and atopic conditions other than asthma: a retrospective cohort study. Prim Care Respir J. 2012;21(2):153–8.
Silverberg JI, Simpson EL. Association between severe eczema in children and multiple comorbid conditions and increased healthcare utilization. Pediatr Allergy Immunol. 2013;24(5):476–86.
Rotsztejn H, Frankowska J, Kamer B, et al. Infection cases in infants and small children with atopic dermatitis—own observations. Postepy Hig Med Dosw (Online). 2012;66:96–103.
Ong PY, Leung DY. The infectious aspects of atopic dermatitis. Immunol Allergy Clin N Am. 2010;30(3):309–21.
Grice K, Sattar H, Baker H, et al. The relationship of transepidermal water loss to skin temperature in psoriasis and eczema. J Investig Dermatol. 1975;64(5):313–5.
Nomura I, Goleva E, Howell MD, et al. Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes. J Immunol. 2003;171(6):3262–9.
Guttman-Yassky E, Nograles KE, Krueger JG. Contrasting pathogenesis of atopic dermatitis and psoriasis. Part I. Clinical and pathologic concepts. J Allergy Clin Immunol. 2011;127(5):1110–8.
Wilsmann-Theis D, Hagemann T, Jordan J, et al. Facing psoriasis and atopic dermatitis: are there more similarities or more differences? Eur J Dermatol. 2008;18(2):172–80.
Rantala A, Jaakkola JJ, Jaakkola MS. Respiratory infections in adults with atopic disease and IgE antibodies to common aeroallergens. PLoS One. 2013;8(7):e68582.
Warner JA, McGirt LY, Beck LA. Biomarkers of Th2 polarity are predictive of staphylococcal colonization in subjects with atopic dermatitis. Br J Dermatol. 2009;160(1):183–5.
Peng WM, Jenneck C, Bussmann C, et al. Risk factors of atopic dermatitis patients for eczema herpeticum. J Investig Dermatol. 2007;127(5):1261–3.
Guzik TJ, Bzowska M, Kasprowicz A, et al. Persistent skin colonization with Staphylococcus aureus in atopic dermatitis: relationship to clinical and immunological parameters. Clin Exp Allergy. 2005;35(4):448–55.
Bunikowski R, Mielke M, Skarabis H, et al. Prevalence and role of serum IgE antibodies to the Staphylococcus aureus-derived superantigens SEA and SEB in children with atopic dermatitis. J Allergy Clin Immunol. 1999;103(1 Pt 1):119–24.
Simpson EL, Villarreal M, Jepson B, et al. Atopic dermatitis subjects colonized with Staphylococcus aureus have a distinct phenotype and endotype. J Investig Dermatol. 2018. https://doi.org/10.1016/j.jid.2018.03.1517 (Epub ahead of print).
Harder J, Dressel S, Wittersheim M, et al. Enhanced expression and secretion of antimicrobial peptides in atopic dermatitis and after superficial skin injury. J Investig Dermatol. 2010;130(5):1355–64.
de Jongh GJ, Zeeuwen PL, Kucharekova M, et al. High expression levels of keratinocyte antimicrobial proteins in psoriasis compared with atopic dermatitis. J Investig Dermatol. 2005;125(6):1163–73.
Ong PY, Ohtake T, Brandt C, et al. Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N Engl J Med. 2002;347(15):1151–60.
Esaki H, Brunner PM, Renert-Yuval Y, et al. Early-onset pediatric atopic dermatitis is TH2 but also TH17 polarized in skin. J Allergy Clin Immunol. 2016;138(6):1639–51.
Rieg S, Steffen H, Seeber S, et al. Deficiency of dermcidin-derived antimicrobial peptides in sweat of patients with atopic dermatitis correlates with an impaired innate defense of human skin in vivo. J Immunol. 2005;174(12):8003–10.
Howell MD, Wollenberg A, Gallo RL, et al. Cathelicidin deficiency predisposes to eczema herpeticum. J Allergy Clin Immunol. 2006;117(4):836–41.
Gao PS, Rafaels NM, Hand T, et al. Filaggrin mutations that confer risk of atopic dermatitis confer greater risk for eczema herpeticum. J Allergy Clin Immunol. 2009;124(3):507–13 (513.e1–7).
Gao PS, Leung DY, Rafaels NM, et al. Genetic variants in interferon regulatory factor 2 (IRF2) are associated with atopic dermatitis and eczema herpeticum. J Investig Dermatol. 2012;132(3 Pt 1):650–7.
Cho SH, Strickland I, Boguniewicz M, et al. Fibronectin and fibrinogen contribute to the enhanced binding of Staphylococcus aureus to atopic skin. J Allergy Clin Immunol. 2001;108(2):269–74.
Kobayashi T, Glatz M, Horiuchi K, et al. Dysbiosis and Staphylococcus aureus colonization drives inflammation in atopic dermatitis. Immunity. 2015;42(4):756–66.
Kong HH, Oh J, Deming C, NISC Comparative Sequence Program, et al. Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis. Genome Res. 2012;22(5):850–9.
Nakatsuji T, Chen TH, Narala S, et al. Antimicrobials from human skin commensal bacteria protect against Staphylococcus aureus and are deficient in atopic dermatitis. Sci Transl Med. 2017. https://doi.org/10.1126/scitranslmed.aah4680.
Cho SH, Strickland I, Tomkinson A, et al. Preferential binding of Staphylococcus aureus to skin sites of Th2-mediated inflammation in a murine model. J Investig Dermatol. 2001;116(5):658–63.
Hata TR, Gallo RL. Antimicrobial peptides, skin infections, and atopic dermatitis. Semin Cutan Med Surg. 2008;27(2):144–50.
Miajlovic H, Fallon PG, Irvine AD, et al. Effect of filaggrin breakdown products on growth of and protein expression by Staphylococcus aureus. J Allergy Clin Immunol. 2010;126(6):1184–1190.e3.
Strange P, Skov L, Lisby S, et al. Staphylococcal enterotoxin B applied on intact normal and intact atopic skin induces dermatitis. Arch Dermatol. 1996;132(1):27–33.
Silverberg JI. Association between childhood atopic dermatitis, malnutrition, and low bone mineral density: a US population-based study. Pediatr Allergy Immunol. 2015;26(1):54–61.
Jolliffe DA, Griffiths CJ, Martineau AR. Vitamin D in the prevention of acute respiratory infection: systematic review of clinical studies. J Steroid Biochem Mol Biol. 2013;136:321–9.
Ahn K. The role of air pollutants in atopic dermatitis. J Allergy Clin Immunol. 2014;134(5):993–9.
Ghio AJ. Particle exposures and infections. Infection. 2014;42(3):459–67.
Schmitt J, Apfelbacher C, Chen CM, German Infant Nutrition Intervention plus Study Group, et al. Infant-onset eczema in relation to mental health problems at age 10 years: results from a prospective birth cohort study (German Infant Nutrition Intervention plus). J Allergy Clin Immunol. 2010;125(2):404–10.
Garg N, Silverberg JI. Association between childhood allergic disease, psychological comorbidity, and injury requiring medical attention. Ann Allergy Asthma Immunol. 2014;112(6):525–32.
Yaghmaie P, Koudelka CW, Simpson EL. Mental health comorbidity in patients with atopic dermatitis. J Allergy Clin Immunol. 2013;131(2):428–33.
Whiteley J, Emir B, Seitzman R, et al. The burden of atopic dermatitis in US adults: results from the 2013 National Health and Wellness Survey. Curr Med Res Opin. 2016;21:1–7 (Epub ahead of print).
Augustin M, Radtke MA, Glaeske G, et al. Epidemiology and comorbidity in children with psoriasis and atopic eczema. Dermatology. 2015;231(1):35–40.
Radtke MA, Schafer I, Glaeske G, et al. Prevalence and comorbidities in adults with psoriasis compared to atopic eczema. J Eur Acad Dermatol Venereol. 2017;31(1):151–7.
Strom MA, Fishbein AB, Paller AS, et al. Association between atopic dermatitis and attention deficit hyperactivity disorder in US children and adults. Br J Dermatol. 2016;175(5):920–9.
Tsai JD, Chang SN, Mou CH, et al. Association between atopic diseases and attention-deficit/hyperactivity disorder in childhood: a population-based case–control study. Ann Epidemiol. 2013;23(4):185–8.
Genuneit J, Braig S, Brandt S, et al. Infant atopic eczema and subsequent attention-deficit/hyperactivity disorder: a prospective birth cohort study. Pediatr Allergy Immunol. 2014;25(1):51–6.
Schmitt J, Romanos M, Schmitt NM, et al. Atopic eczema and attention-deficit/hyperactivity disorder in a population-based sample of children and adolescents. JAMA. 2009;301(7):724–6.
Schmitt J, Buske-Kirschbaum A, Roessner V. Is atopic disease a risk factor for attention-deficit/hyperactivity disorder? A systematic review. Allergy. 2010;65(12):1506–24.
Chen MH, Su TP, Chen YS, et al. Comorbidity of allergic and autoimmune diseases among patients with ADHD. J Atten Disord. 2013;21(3):219–27.
Yu SH, Silverberg JI. Association between atopic dermatitis and depression in US adults. J Investig Dermatol. 2015;135(12):3183–6.
Yang YW, Tseng KC, Chen YH, et al. Associations among eczema, asthma, serum immunoglobulin E and depression in adults: a population-based study. Allergy. 2010;65(6):801–2.
Halvorsen JA, Lien L, Dalgard F, et al. Suicidal ideation, mental health problems, and social function in adolescents with eczema: a population-based study. J Investig Dermatol. 2014;134(7):1847–54.
Singhal A, Ross J, Seminog O, et al. Risk of self-harm and suicide in people with specific psychiatric and physical disorders: comparisons between disorders using English national record linkage. J R Soc Med. 2014;107(5):194–204.
Chen MH, Su TP, Chen YS, et al. Is atopy in early childhood a risk factor for ADHD and ASD? A longitudinal study. J Psychosom Res. 2014;77(4):316–21.
Shyu CS, Lin HK, Lin CH, et al. Prevalence of attention-deficit/hyperactivity disorder in patients with pediatric allergic disorders: a nationwide, population-based study. J Microbiol Immunol Infect. 2012;45(3):237–42.
Schmitt J, Chen CM, Apfelbacher C, LISA-plus Study Group, et al. Infant eczema, infant sleeping problems, and mental health at 10 years of age: the prospective birth cohort study LISAplus. Allergy. 2011;66(3):404–11.
Goodwin RD, Sourander A, Duarte CS, et al. Do mental health problems in childhood predict chronic physical conditions among males in early adulthood? Evidence from a community-based prospective study. Psychol Med. 2009;39(2):301–11.
Chida Y, Hamer M, Steptoe A. A bidirectional relationship between psychosocial factors and atopic disorders: a systematic review and meta-analysis. Psychosom Med. 2008;70(1):102–16.
Archer T, Kostrzewa RM. Physical exercise alleviates ADHD symptoms: regional deficits and development trajectory. Neurotox Res. 2012;21(2):195–209.
Sanna L, Stuart AL, Pasco JA, et al. Atopic disorders and depression: findings from a large, population-based study. J Affect Disord. 2014;155:261–5.
Thomsen SF, Kyvik KO, Backer V. Etiological relationships in atopy: a review of twin studies. Twin Res Hum Genet. 2008;11(2):112–20.
Slattery MJ, Klein DF, Mannuzza S, et al. Relationship between separation anxiety disorder, parental panic disorder, and atopic disorders in children: a controlled high-risk study. J Am Acad Child Adolesc Psychiatry. 2002;41(8):947–54.
Wamboldt MZ, Hewitt JK, Schmitz S, et al. Familial association between allergic disorders and depression in adult Finnish twins. Am J Med Genet. 2000;96(2):146–53.
Slattery MJ, Essex MJ, Paletz EM, et al. Depression, anxiety, and dermatologic quality of life in adolescents with atopic dermatitis. J Allergy Clin Immunol. 2011;128(3):668–71.
Klokk M, Gotestam KG, Mykletun A. Factors accounting for the association between anxiety and depression, and eczema: the Hordaland health study (HUSK). BMC Dermatol. 2010;10:3.
Romanos M, Gerlach M, Warnke A, et al. Association of attention-deficit/hyperactivity disorder and atopic eczema modified by sleep disturbance in a large population-based sample. J Epidemiol Community Health. 2010;64(3):269–73.
Chang YT, Li YF, Muo CH, et al. Correlation of Tourette syndrome and allergic disease: nationwide population-based case–control study. J Dev Behav Pediatr. 2011;32(2):98–102.
Chen MH, Su TP, Chen YS, et al. Attention deficit hyperactivity disorder, tic disorder, and allergy: is there a link? A nationwide population-based study. J Child Psychol Psychiatry. 2013;54(5):545–51.
Khandaker GM, Zammit S, Lewis G, et al. A population-based study of atopic disorders and inflammatory markers in childhood before psychotic experiences in adolescence. Schizophr Res. 2014;152(1):139–45.
Liao TC, Lien YT, Wang S, et al. Comorbidity of atopic disorders with autism spectrum disorder and attention deficit/hyperactivity disorder. J Pediatr. 2016;171:24–55.
Mostafa GA, Hamza RT, El-Shahawi HH. Allergic manifestations in autistic children: relation to disease severity. J Pediatr Neurol. 2008;6(2):115–23.
Pedersen MS, Benros ME, Agerbo E, et al. Schizophrenia in patients with atopic disorders with particular emphasis on asthma: a Danish population-based study. Schizophr Res. 2012;138(1):58–62.
Chen YH, Lee HC, Lin HC. Prevalence and risk of atopic disorders among schizophrenia patients: a nationwide population based study. Schizophr Res. 2009;108(1–3):191–6.
Chen MH, Wu YH, Su TP, et al. Risk of epilepsy among patients with atopic dermatitis: a nationwide longitudinal study. Epilepsia. 2014;55(8):1307–12.
Silverberg JI, Joks R, Durkin HG. Allergic disease is associated with epilepsy in childhood: a US population-based study. Allergy. 2014;69(1):95–103.
Gaitatzis A, Carroll K, Majeed A, et al. The epidemiology of the comorbidity of epilepsy in the general population. Epilepsia. 2004;45(12):1613–22.
Garg N, Silverberg JI. Association between eczema and increased fracture and bone or joint injury in adults: a US population-based study. JAMA Dermatol. 2015;151(1):33–41.
Seiffert K, Hilbert E, Schaechinger H, et al. Psychophysiological reactivity under mental stress in atopic dermatitis. Dermatology. 2005;210(4):286–93.
Silverberg JI. Selected comorbidities of atopic dermatitis: atopy, neuropsychiatric, and musculoskeletal disorders. Clin Dermatol. 2017;35(4):360–6.
Silverberg JI, Simpson EL. Association between obesity and eczema prevalence, severity and poorer health in US adolescents. Dermatitis. 2014;25(4):172–81.
Silverberg JI. Atopic disease and cardiovascular risk factors in US children. J Allergy Clin Immunol. 2016;137(3):938–40.
Zhang A, Silverberg JI. Association of atopic dermatitis with being overweight and obese: a systematic review and metaanalysis. J Am Acad Dermatol. 2015;72(4):606–16.
Baumann S, Lorentz A. Obesity: a promoter of allergy? Int Arch Allergy Immunol. 2013;162(3):205–13.
Mitchell EA, Beasley R, Bjorksten B, ISAAC Phase Three Study Group, et al. The association between BMI, vigorous physical activity and television viewing and the risk of symptoms of asthma, rhinoconjunctivitis and eczema in children and adolescents: ISAAC Phase Three. Clin Exp Allergy. 2013;43(1):73–84.
Silverberg JI, Kleiman E, Lev-Tov H, et al. Association between obesity and atopic dermatitis in childhood: a case–control study. J Allergy Clin Immunol. 2011;127(5):1180–6.
Shaheen SO, Sterne JA, Montgomery SM, et al. Birth weight, body mass index and asthma in young adults. Thorax. 1999;54(5):396–402.
O’Donovan SM, Hourihane JOB, Murray DM, et al. Neonatal adiposity increases the risk of atopic dermatitis during the first year of life. J Allergy Clin Immunol. 2016;137(1):108–17.
Musso G, Gambino R, Cassader M. Obesity, diabetes, and gut microbiota: the hygiene hypothesis expanded? Diabetes Care. 2010;33(10):2277–84.
Isolauri E, Kalliomaki M, Rautava S, et al. Obesity: extending the hygiene hypothesis. Nestle Nutr Workshop Ser Pediatr Program. 2009;64:75–85.
Song H, Yoo Y, Hwang J, et al. Faecalibacterium prausnitzii subspecies-level dysbiosis in the human gut microbiome underlying atopic dermatitis. J Allergy Clin Immunol. 2016;137(3):852–60.
Irei AV, Takahashi K, Le DS, et al. Obesity is associated with increased risk of allergy in Vietnamese adolescents. Eur J Clin Nutr. 2005;59(4):571–7.
Silverberg JI, Greenland P. Eczema and cardiovascular risk factors in 2 US adult population studies. J Allergy Clin Immunol. 2015;135(3):721–8.
Nino M, Franzese A, Ruggiero Perrino N, et al. The effect of obesity on skin disease and epidermal permeability barrier status in children. Pediatr Dermatol. 2012;29(5):567–70.
Loffler H, Aramaki JU, Effendy I. The influence of body mass index on skin susceptibility to sodium lauryl sulphate. Skin Res Technol. 2002;8(1):19–22.
Andersen YMF, Egeberg A, Gislason GH, et al. Adult atopic dermatitis and the risk of type 2 diabetes. J Allergy Clin Immunol. 2017;139(3):1057–9.
Silverberg JI. Association between adult atopic dermatitis, cardiovascular disease, and increased heart attacks in three population-based studies. Allergy. 2015;70(10):1300–8.
Hjuler KF, Bottcher M, Vestergaard C, et al. Increased prevalence of coronary artery disease in severe psoriasis and severe atopic dermatitis. Am J Med. 2015;128(12):1325–34.
Riis JL, Vestergaard C, Hjuler KF, et al. Hospital-diagnosed atopic dermatitis and long-term risk of myocardial infarction: a population-based follow-up study. BMJ Open. 2016;6(11):e011870.
Drucker AM, Qureshi AA, Dummer TJB, et al. Atopic dermatitis and risk of hypertension, type 2 diabetes, myocardial infarction and stroke in a cross-sectional analysis from the Canadian Partnership for Tomorrow Project. Br J Dermatol. 2017;177(4):1043–51.
Treudler R, Zeynalova S, Walther F, et al. Atopic dermatitis is associated with autoimmune but not with cardiovascular comorbidities in a random sample of the general population in Leipzig, Germany. J Eur Acad Dermatol Venereol. 2018;32(2):e44–6.
Andersen YM, Egeberg A, Gislason GH, et al. Risk of myocardial infarction, ischemic stroke, and cardiovascular death in patients with atopic dermatitis. J Allergy Clin Immunol. 2016;138(1):310–2.
Standl M, Tesch F, Baurecht H, et al. Association of atopic dermatitis with cardiovascular risk factors and diseases. J Investig Dermatol. 2017;137(5):1074–81.
Su VY, Chen TJ, Yeh CM, et al. Atopic dermatitis and risk of ischemic stroke: a nationwide population-based study. Ann Med. 2014;46(2):84–9.
Silverberg JI, Becker L, Kwasny M, et al. Central obesity and high blood pressure in pediatric patients with atopic dermatitis. JAMA Dermatol. 2015;151(2):144–52.
Nastalek M, Wojas-Pelc A, Undas A. Plasma fibrin clot properties in atopic dermatitis: links between thrombosis and atopy. J Thromb Thrombolysis. 2010;30(2):121–6.
Thyssen JP, Linneberg A, Carlsen BC, et al. A possible association between a dysfunctional skin barrier (filaggrin null-mutation status) and diabetes: a cross-sectional study. BMJ Open. 2011;1(1):e000062.
Tang TS, Bieber T, Williams HC. Does “autoreactivity” play a role in atopic dermatitis? J Allergy Clin Immunol. 2012;129(5):1209–15.e2.
Andersen YM, Egeberg A, Gislason GH, et al. Autoimmune diseases in adults with atopic dermatitis. J Am Acad Dermatol. 2017;76(2):274–80.
Kappelman MD, Galanko JA, Porter CQ, et al. Association of paediatric inflammatory bowel disease with other immune-mediated diseases. Arch Dis Child. 2011;96(11):1042–6.
Schmitt J, Schwarz K, Baurecht H, et al. Atopic dermatitis is associated with an increased risk for rheumatoid arthritis and inflammatory bowel disease, and a decreased risk for type 1 diabetes. J Allergy Clin Immunol. 2016;137(1):130–6.
Feeney MA, Murphy F, Clegg AJ, et al. A case–control study of childhood environmental risk factors for the development of inflammatory bowel disease. Eur J Gastroenterol Hepatol. 2002;14(5):529–34.
Baron S, Turck D, Leplat C, et al. Environmental risk factors in paediatric inflammatory bowel diseases: a population based case control study. Gut. 2005;54(3):357–63.
Ress K, Annus T, Putnik U, et al. Celiac disease in children with atopic dermatitis. Pediatr Dermatol. 2014;31(4):483–8.
Mohan GC, Silverberg JI. Association of vitiligo and alopecia areata with atopic dermatitis: a systematic review and meta-analysis. JAMA Dermatol. 2015;151(5):522–8.
Lee NR, Kim BK, Yoon NY, et al. Differences in comorbidity profiles between early-onset and late-onset alopecia areata patients: a retrospective study of 871 Korean patients. Ann Dermatol. 2014;26(6):722–6.
Cho HH, Jo SJ, Paik SH, et al. Clinical characteristics and prognostic factors in early-onset alopecia totalis and alopecia universalis. J Korean Med Sci. 2012;27(7):799–802.
Chu SY, Chen YJ, Tseng WC, et al. Comorbidity profiles among patients with alopecia areata: the importance of onset age, a nationwide population-based study. J Am Acad Dermatol. 2011;65(5):949–56.
Betz RC, Pforr J, Flaquer A, et al. Loss-of-function mutations in the filaggrin gene and alopecia areata: strong risk factor for a severe course of disease in patients comorbid for atopic disease. J Investig Dermatol. 2007;127(11):2539–43.
Goh C, Finkel M, Christos PJ, et al. Profile of 513 patients with alopecia areata: associations of disease subtypes with atopy, autoimmune disease and positive family history. J Eur Acad Dermatol Venereol. 2006;20(9):1055–60.
Paternoster L, Standl M, Waage J, Australian Asthma Genetics Consortium (AAGC), et al. Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis. Nat Genet. 2015;47(12):1449–56.
Wang H, Diepgen TL. Is atopy a protective or a risk factor for cancer? A review of epidemiological studies. Allergy. 2005;60(9):1098–111.
Hwang CY, Chen YJ, Lin MW, et al. Cancer risk in patients with allergic rhinitis, asthma and atopic dermatitis: a nationwide cohort study in Taiwan. Int J Cancer. 2012;130(5):1160–7.
Vena JE, Bona JR, Byers TE, et al. Allergy-related diseases and cancer: an inverse association. Am J Epidemiol. 1985;122(1):66–74.
Morton LM, Slager SL, Cerhan JR, et al. Etiologic heterogeneity among non-Hodgkin lymphoma subtypes: the InterLymph Non-Hodgkin Lymphoma Subtypes Project. J Natl Cancer Inst Monogr. 2014;2014(48):130–44.
Sherman PW, Holland E, Sherman JS. Allergies: their role in cancer prevention. Q Rev Biol. 2008;83(4):339–62.
Merrill RM, Isakson RT, Beck RE. The association between allergies and cancer: what is currently known? Ann Allergy Asthma Immunol. 2007;99(2):102–16 (quiz 117–9, 150).
Arana A, Wentworth CE, Fernandez-Vidaurre C, et al. Incidence of cancer in the general population and in patients with or without atopic dermatitis in the UK. Br J Dermatol. 2010;163(5):1036–43.
Zhang Y, Zhou B. Functions of thymic stromal lymphopoietin in immunity and disease. Immunol Res. 2012;52(3):211–23.
Josephs DH, Spicer JF, Corrigan CJ, et al. Epidemiological associations of allergy, IgE and cancer. Clin Exp Allergy. 2013;43(10):1110–23.
Rittmeyer D, Lorentz A. Relationship between allergy and cancer: an overview. Int Arch Allergy Immunol. 2012;159(3):216–25.
Legendre L, Barnetche T, Mazereeuw-Hautier J, et al. Risk of lymphoma in patients with atopic dermatitis and the role of topical treatment: a systematic review and meta-analysis. J Am Acad Dermatol. 2015;72(6):992–1002.
Tennis P, Gelfand JM, Rothman KJ. Evaluation of cancer risk related to atopic dermatitis and use of topical calcineurin inhibitors. Br J Dermatol. 2011;165(3):465–73.
Ruff S, Egeberg A, Andersen YMF, et al. Prevalence of cancer in adult patients with atopic dermatitis: a nationwide study. Acta Dermovenereol. 2017;97(9):1127–9.
Vajdic CM, Falster MO, de Sanjose S, et al. Atopic disease and risk of non-Hodgkin lymphoma: an InterLymph pooled analysis. Cancer Res. 2009;69(16):6482–9.
Wang H, Diepgen TL. Atopic dermatitis and cancer risk. Br J Dermatol. 2006;154(2):205–10.
Grulich AE, Vajdic CM, Cozen W. Altered immunity as a risk factor for non-Hodgkin lymphoma. Cancer Epidemiol Biomark Prev. 2007;16(3):405–8.
Soderberg KC, Hagmar L, Schwartzbaum J, et al. Allergic conditions and risk of hematological malignancies in adults: a cohort study. BMC Public Health. 2004;4:51.
Wang SS, Flowers CR, Kadin ME, et al. Medical history, lifestyle, family history, and occupational risk factors for peripheral T-cell lymphomas: the InterLymph Non-Hodgkin Lymphoma Subtypes Project. J Natl Cancer Inst Monogr. 2014;2014(48):66–75.
Aschebrook-Kilfoy B, Cocco P, La Vecchia C, et al. Medical history, lifestyle, family history, and occupational risk factors for mycosis fungoides and Sezary syndrome: the InterLymph Non-Hodgkin Lymphoma Subtypes Project. J Natl Cancer Inst Monogr. 2014;2014(48):98–105.
Gandini S, Stanganelli I, Palli D, et al. Atopic dermatitis, naevi count and skin cancer risk: a meta-analysis. J Dermatol Sci. 2016;84(2):137–43.
Jensen AO, Svaerke C, Kormendine Farkas D, et al. Atopic dermatitis and risk of skin cancer: a Danish nationwide cohort study (1977–2006). Am J Clin Dermatol. 2012;13(1):29–36.
Cheng J, Zens MS, Duell E, et al. History of allergy and atopic dermatitis in relation to squamous cell and basal cell carcinoma of the skin. Cancer Epidemiol Biomark Prev. 2015;24(4):749–54.
Andersen YMF, Egeberg A, Balslev E, et al. Filaggrin loss-of-function mutations, atopic dermatitis and risk of actinic keratosis: results from two cross-sectional studies. J Eur Acad Dermatol Venereol. 2017;31(6):1038–43.
Hajdarbegovic E, Blom H, Verkouteren JA, et al. Atopic dermatitis is not associated with actinic keratosis: cross-sectional results from the Rotterdam study. Br J Dermatol. 2016;175(1):89–94.
Hajdarbegovic E, Atiq N, van der Leest R, et al. Atopic dermatitis is not a protective factor for melanoma but asthma may be. Int J Clin Oncol. 2014;19(4):708–11.
Synnerstad I, Fredrikson M, Ternesten-Bratel A, et al. Low risk of melanoma in patients with atopic dermatitis. J Eur Acad Dermatol Venereol. 2008;22(12):1423–8.
Kallas M, Rosdahl I, Fredriksson M, et al. Frequency and distribution pattern of melanocytic naevi in Estonian children and the influence of atopic dermatitis. J Eur Acad Dermatol Venereol. 2006;20(2):143–8.
Author information
Authors and Affiliations
Contributions
AP directed the development of the manuscript text and table content, reviewed the literature related to mental health comorbidities, critically reviewed each draft, and approved the final version for submission. JCJ performed literature searches, drafted the manuscript without financial compensation, and approved the final version for submission. ELS reviewed included articles for appropriateness, critically reviewed each draft of the manuscript, and approved the final version for submission. MB reviewed the literature related to infectious comorbidities, critically reviewed each draft of the manuscript, and approved the final version for submission. JJR reviewed the literature related to neurologic, obesity, cardiovascular, and autoimmune comorbidities, critically reviewed each draft of the manuscript, and approved the final version for submission. JKB critically reviewed each draft of the manuscript and approved the final version for submission. ST reviewed included articles for appropriateness, critically reviewed each draft of the manuscript, and approved the final version for submission. JDD critically reviewed each draft of the manuscript and approved the final version for submission. SRF reviewed included articles for appropriateness, critically reviewed each draft of the manuscript, and approved the final version for submission. ARC critically reviewed each draft of the manuscript and approved the final version for submission. GS reviewed the included literature for odds ratios, reviewed and edited the manuscript, and approved the final version for submission. LE reviewed the literature related to malignancy comorbidities, critically reviewed each draft, and approved the final version as submitted.
Corresponding author
Ethics declarations
Funding
This article was conceived during a 2013 roundtable in which all authors were engaged. The roundtable was supported by Valeant Pharmaceuticals North America LLC; however, there was no funding source for writing this article.
Conflict of interest
Amy Paller is a principal investigator without personal compensation for atopic dermatitis clinical trials with Incyte, LEO Pharma, and Sanofi-Regeneron, and served as a consultant for AbbVie, Dermira, Eli Lilly, Expanscience, GSK-Stiefel, Menlo Therapeutics, Novartis, Pfizer, Sanofi-Regeneron, and Valeant. Jennifer C. Jaworski was a full-time employee of Prescott Medical Communications Group, which received financial compensation for organizing the 2013 roundtable at which this manuscript was conceived. Eric L. Simpson is an investigator for AbbVie, Anacor (now part of Pfizer), Celgene, Dermira, Eli Lilly, Galderma, Genentech, LEO Pharma, Menlo Therapeutics, Pfizer, Regeneron, and Sanofi, and has served as a consultant for Amgen, Anacor, Chugai, Eli Lilly, GlaxoSmithKline, LEO Pharma, Novartis, Regeneron, Roivant, Tioga, and Vanda. Mark Boguniewicz has received research grants from Anacor (now part of Pfizer) and Regeneron, and has served as a consultant for Valeant, Pfizer, Regeneron, and Sanofi-Genzyme. John J. Russell has served as a consultant and a Speakers Bureau member for Sanofi-Aventis. Julie K. Block is a salaried executive of National Eczema Association, which has received grants and sponsorship awards from a variety of industry partners including Valeant (full list at: http://nationaleczema.org/corporate-partners/). Susan Tofte has served as a consultant for Valeant and as an Advisory Board member for Amgen, Johnson & Johnson Consumer & Personal Products Worldwide, Novartis, Sanofi-Regeneron, Pfizer, and LEO Pharma. Steven R. Feldman has served as a consultant for AbbVie, Boehringer Ingelheim, Celgene, Ely Lilly, Galderma, Janssen, LEO Pharma, Pfizer, Mylan, Novartis, Qurient, and Samsung, and a Speakers Bureau member for AbbVie, Celgene, Janssen, Eli Lilly, Novartis, and Ortho Dermatologics (formerly Valeant). He has received grants from Pfizer, Sanofi, Regeneron, AbbVie, Celgene, Novartis, and Eli Lilly. Steven R. Feldman is a founder and part owner of Causa Research, a company dedicated to enhancing patients’ adherence to treatment. Adele R. Clark has been a sub-investigator without personal compensation for Astellas, Medicis (now part of Valeant), Galderma, Anacor (now part of Pfizer), GSK-Stiefel, Maruho, Merz, Regeneron, and HanAll Biopharma. She has received financial compensation for her work as a consultant for Valeant Pharmaceuticals North America LLC. Lawrence Eichenfield has been a principal investigator for Astellas, Galderma, and GSK-Stiefel. He has received compensation for his work as a consultant for Valeant, Anacor (now part of Pfizer), Galderma, Promius GSK-Stiefel, and TopMD. Jeffrey D. Dunn and Gene Schwartz have no conflicts of interest that are directly relevant to the content of this article.
Rights and permissions
About this article
Cite this article
Paller, A., Jaworski, J.C., Simpson, E.L. et al. Major Comorbidities of Atopic Dermatitis: Beyond Allergic Disorders. Am J Clin Dermatol 19, 821–838 (2018). https://doi.org/10.1007/s40257-018-0383-4
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40257-018-0383-4