Advertisement

Archives of Dermatological Research

, Volume 311, Issue 3, pp 173–182 | Cite as

Determinants of disease severity among patients with atopic dermatitis: association with components of the atopic march

  • Jesper Grønlund HolmEmail author
  • Tove Agner
  • Maja-Lisa Clausen
  • Simon Francis Thomsen
Original Paper
  • 126 Downloads

Abstract

We aimed to explore the association of key clinical characteristics with disease severity in atopic dermatitis (AD) and its relation to components of the atopic march in a large hospital cohort. Outpatients with AD referred to the Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark, between January 2012 and December 2017, were compared based on disease severity (SCORAD); mild (< 25), moderate (25–50) and severe (> 50). A total of 470 AD patients were included: 122 small children (< 4 years of age), 103 children/adolescents (age 4–15 years) and 245 adults (> 15 years of age). A significant difference between severity groups in small children was observed for FLG mutation carrier status (16.7 vs. 30.2 vs. 60.0% mutation carriers among patients with mild, moderate and severe AD, respectively, p = 0.012) and self-rated health (3.2 vs. 2.7 vs. 2.8 with 4 being excellent health, p = 0.022). A significant difference between severity groups in adults was observed for male sex (24.4 vs. 39.8 vs. 52.9%, p = 0.003), serum total IgE (577 vs. 1269 vs. 2379 × 103 IU/L, p < 0.001), blood eosinophil count (0.28 vs. 0.39 vs. 0.61 × 109/L, p < 0.001) and asthma (42.9 vs. 38.8 vs. 72.0%, p < 0.001). Early onset of AD (< 1 year of age) and FLG mutation was associated with more severe disease and high serum total IgE levels. In conclusion, the distribution of key clinical characteristics varies significantly according to the severity of AD measured by SCORAD. Sub-typing of AD patients related to determinants of disease severity may be helpful in establishing prognosis and targeted treatment of AD.

Keywords

Atopic dermatitis Disease characteristics Determinants Severity Atopic march 

Notes

Funding

There is no funding source.

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

This study was approved by the Committee of Biomedical Research Ethics of the Capital Region of Denmark. For this type of study formal consent is not required.

References

  1. 1.
    Leung DYM, Bieber T (2003) Atopic dermatitis. Lancet 361:151–160.  https://doi.org/10.1016/S0140-6736(03)12193-9 CrossRefGoogle Scholar
  2. 2.
    Flohr C, Mann J (2014) New insights into the epidemiology of childhood atopic dermatitis. Allergy Eur J Allergy Clin Immunol 69:3–16CrossRefGoogle Scholar
  3. 3.
    Garg N, Silverberg JI (2015) Epidemiology of childhood atopic dermatitis. Clin Dermatol 33:281–288CrossRefGoogle Scholar
  4. 4.
    Brown SJ, McLean WHI (2012) One remarkable molecule: filaggrin. J Investig Dermatol 132:751–762.  https://doi.org/10.1038/jid.2011.393 CrossRefGoogle Scholar
  5. 5.
    Palmer CNa, Irvine AD, Terron-Kwiatkowski A et al (2006) Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet 38:441–446.  https://doi.org/10.1038/ng1767 CrossRefGoogle Scholar
  6. 6.
    Weidinger S, Illig T, Baurecht H et al (2006) Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations. J Allergy Clin Immunol 118:214–219.  https://doi.org/10.1016/j.jaci.2006.05.004 CrossRefGoogle Scholar
  7. 7.
    Kezic S, Jakasa I (2017) Filaggrin and skin barrier function. Curr Probl Dermatol 49:1–7Google Scholar
  8. 8.
    Brown SJ, Asai Y, Cordell HJ et al (2011) Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy. J Allergy Clin Immunol 127:661–667.  https://doi.org/10.1016/j.jaci.2011.01.031 CrossRefGoogle Scholar
  9. 9.
    McAleer M, Irvine AD (2013) The multifunctional role of filaggrin in allergic skin disease. J Allergy Clin Immunol 131:280–291.  https://doi.org/10.1016/j.jaci.2012.12.668 CrossRefGoogle Scholar
  10. 10.
    Nomura T, Akiyama M, Sandilands A et al (2008) Specific filaggrin mutations cause ichthyosis vulgaris and are significantly associated with atopic dermatitis in Japan. J Investig Dermatol 128:1436–1441.  https://doi.org/10.1038/sj.jid.5701205 CrossRefGoogle Scholar
  11. 11.
    Johansson SGO, Bieber T, Dahl R (2003) Rostrums revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organization, October 2003. J Allergy Clin Immun 113(5):832–836CrossRefGoogle Scholar
  12. 12.
    Clausen M-L, Agner T, Thomsen SF (2015) Skin barrier dysfunction and the atopic march. Curr Treat Options Allergy 218–227.  https://doi.org/10.1007/s40521-015-0056-y
  13. 13.
    Bowcock AM, Cookson WOCM (2004) The genetics of psoriasis, psoriatic arthritis and atopic dermatitis. Hum Mol Genet 13 Spec No:R43–R55.  https://doi.org/10.1093/hmg/ddh094 CrossRefGoogle Scholar
  14. 14.
    Howell MD, Kim BE, Gao P et al (2009) Cytokine modulation of atopic dermatitis filaggrin skin expression. J Allergy Clin Immunol 124:R7–R12.  https://doi.org/10.1016/j.jaci.2009.07.012 CrossRefGoogle Scholar
  15. 15.
    Holm J, Agner T, Clausen ML, Thomsen SF (2016) Quality of life and disease severity in patients with atopic dermatitis. J Eur Acad Dermatol Venereol 30(10):1760–1767CrossRefGoogle Scholar
  16. 16.
    Hanifin J, Rajka G (1980) Diagnostic features of atopic dermatitis. Acta Derm Venereol 92:44–47Google Scholar
  17. 17.
    Asher MI, Keil U, Anderson HR, Beasley R, Crane J, Martinez F, Mitchell EA, Pearce N, Sibbald B, Stewart AW, Strachen D, Weiland SKWH (1995) International study of asthma and allergies in childhood (ISAAC) written questionnaire: validation of the asthma component among Brazilian children. Eur Respir J 8:483–491CrossRefGoogle Scholar
  18. 18.
    Burney PGJ, Luczynska C, Chinn S, Jarvis D (1994) The European community respiratory health survey. Eur Respir J 7:954–960.  https://doi.org/10.1183/09031936.94.07050954 CrossRefGoogle Scholar
  19. 19.
    Eriksen L, Curtis T, Grønbæk M et al (2013) The association between physical activity, cardiorespiratory fitness and self-rated health. Prev Med (Baltim) 57:900–902.  https://doi.org/10.1016/j.ypmed.2013.09.024 CrossRefGoogle Scholar
  20. 20.
    Wards K (1993) Clinical and laboratory investigations European task force on atopic dermatitis atopic dermatitis eczema scoring composite index severity. Dermatology 186:23–31CrossRefGoogle Scholar
  21. 21.
    Rajka G, Langeland T (1989) Grading of the severity of atopic dermatitis. Acta Derm Venereol Suppl (Stockh) 144:13–14Google Scholar
  22. 22.
    Chalmers J, Deckert S, Schmitt J, HOM for AD (HOME) IEB (2015) Reaching clinically relevant outcome measures for new pharmacotherapy and immunotherapy of atopic eczema. Curr Opin Allergy Clin Immunol 15(3):227–233.  https://doi.org/10.1097/ACI.0000000000000158 Google Scholar
  23. 23.
    Rehal B, Armstrong A (2011) Health outcome measures in atopic dermatitis: a systematic review of trends in disease severity and quality-of-life instruments 1985–2010. PLoS One 6:e17520.  https://doi.org/10.1371/journal.pone.0017520 CrossRefGoogle Scholar
  24. 24.
    El Taieb MA, Fayed HM, Aly SSIA (2013) Assessment of serum 25-hydroxyvitamin d levels in children with atopic dermatitis: correlationwith SCORAD index. Dermatitis 24(6):296–301CrossRefGoogle Scholar
  25. 25.
    Oranje AP (2011) Practical issues on interpretation of scoring atopic dermatitis: SCORAD index, objective SCORAD, patient-oriented SCORAD and three-item severity score. Curr Probl Dermatol 41:149–155.  https://doi.org/10.1159/000323308 CrossRefGoogle Scholar
  26. 26.
    Wollenberg A, Barbarot S, T BT et al (2018) Consensus based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children part I. JEADV 32:657–682.  https://doi.org/10.1111/jdv.14891 Google Scholar
  27. 27.
    Zachariae R, Zachariae C, Ibsen H et al (2000) Dermatology life quality index: data from Danish inpatients and outpatients. Acta Derm Venereol 80:272–276.  https://doi.org/10.1080/000155500750012153 CrossRefGoogle Scholar
  28. 28.
    Lewis-Jones MS, Finlay aY (1995) The Children’s Dermatology Life Quality Index (CDLQI): initial validation and practical use. Br J Dermatol 132:942–949CrossRefGoogle Scholar
  29. 29.
    Radhakrishnan DK, Dell SD, Guttmann A et al (2014) Trends in the age of diagnosis of childhood asthma. J Allergy Clin Immunol 134:1057–1062.e5CrossRefGoogle Scholar
  30. 30.
    Emerson RM, Williams HC, Allen BR (1998) Severity distribution of atopic dermatitis in the community and its relationship to secondary referral. Br J Dermatol 139:73–76CrossRefGoogle Scholar
  31. 31.
    Emerson RM, Charman CRWH (2000) The Nottingham Eczema Severity Score: preliminary refinement of the Rajka and Langeland grading. Br J Dermatol 142:288–297CrossRefGoogle Scholar
  32. 32.
    Silverberg JI, Simpson EL (2013) Association between severe eczema in children and multiple comorbid conditions and increased healthcare utilization. Pediatr Allergy Immunol 24(5):476–486CrossRefGoogle Scholar
  33. 33.
    Akan A, Azkur D, Civelek E et al (2014) Risk factors of severe atopic dermatitis in childhood: single-center experience. Turk J Pediatr 56:121–126Google Scholar
  34. 34.
    Orfali RL, Shimizu MM, Takaoka R et al (2013) Atopic dermatitis in adults: clinical and epidemiological considerations. Rev Assoc Med Bras 59:270–275CrossRefGoogle Scholar
  35. 35.
    Ballardini N, Kull I, Söderhäll C et al (2013) Eczema severity in preadolescent children and its relation to sex, filaggrin mutations, asthma, rhinitis, aggravating factors and topical treatment: a report from the BAMSE birth cohort. Br J Dermatol 168:588–594CrossRefGoogle Scholar
  36. 36.
    Schäfer T, Heinrich J, Wjst M et al (1999) Association between severity of atopic eczema and degree of sensitization to aeroallergens in schoolchildren. J Allergy Clin Immunol 104:1280–1284CrossRefGoogle Scholar
  37. 37.
    Flohr C, Weiland SK, Weinmayr G et al (2008) The role of atopic sensitization in flexural eczema: findings from the International Study of Asthma and Allergies in Childhood Phase Two. J Allergy Clin Immunol 121(1):141–147CrossRefGoogle Scholar
  38. 38.
    Grönhagen C, Lidén C, Wahlgren CF et al (2015) Hand eczema and atopic dermatitis in adolescents: a prospective cohort study from the BAMSE project. Br J Dermatol 173:1175–1182CrossRefGoogle Scholar
  39. 39.
    Chernyshov P, Jirakova A, Ho R et al (2013) An international multicenter study on quality of life and family quality of life in children with atopic dermatitis. Indian J Dermatol Venereol Leprol 79:52CrossRefGoogle Scholar
  40. 40.
    Chernyshov PV (2012) Gender differences in health-related and family quality of life in young children with atopic dermatitis. Int J Dermatol 51:290–294CrossRefGoogle Scholar
  41. 41.
    Henderson J, Northstone K, Lee SP, Liao H, Zhao Y, Pembrey M, Mukhopadhyay S, Smith GD, Palmer CN, McLean WH, Irvine A (2008) The burden of disease associated with filaggrin mutations: a population-based, longitudinal birth cohort study. J Allergy Clin Immunol 121(4):872–877CrossRefGoogle Scholar
  42. 42.
    Rodríguez E, Baurecht H, Herberich E, Wagenpfeil S, Brown SJ, Cordell HJ, Irvine ADWS (2009) Meta-analysis of filaggrin polymorphisms in eczema and asthma: robust risk factors in atopic disease. J Allergy Clin Immunol 123(6):1361–1370CrossRefGoogle Scholar
  43. 43.
    van den Oord RA, Sheikh A (2009) Filaggrin gene defects and risk of developing allergic sensitisation and allergic disorders: systematic review and meta-analysis. BMJ 339:b2433CrossRefGoogle Scholar
  44. 44.
    Nutten S (2015) Atopic dermatitis: global epidemiology and risk factors. Ann Nutr Metab 66:8–16CrossRefGoogle Scholar
  45. 45.
    Dębińska A, Danielewicz H, Drabik-chamerska A, Kalita DBA (2017) Filaggrin loss-of-function mutations as a predictor for atopic eczema, allergic sensitization and eczema-associated asthma in Polish children population. Adv Clin Exp Med 26(6):991–998CrossRefGoogle Scholar
  46. 46.
    Brown SJ, Relton CL, Liao H, Zhao Y, Sandilands A, Wilson IJ, Burn J, Reynolds NJ, McLean WH, Cordell H (2008) Filaggrin null mutations and childhood atopic eczema: a population-based case-control study. J Allergy Clin Immunol 121(4):940–946CrossRefGoogle Scholar
  47. 47.
    Marenholz I, Nickel R, Rüschendorf F, Schulz F, Esparza-Gordillo J, Kerscher T, Grüber C, Lau S, Worm M, Keil T, Kurek M, Zaluga E, Wahn ULY (2006) Information A Filaggrin loss-of-function mutations predispose to phenotypes involved in the atopic march. J Allergy Clin Immunol 118(4):866–871CrossRefGoogle Scholar
  48. 48.
    Palmer CN, Ismail T, Lee SP, Terron-Kwiatkowski A, Zhao Y, Liao H, Smith FJ, McLean WH, Mukhopadhyay S (2007) Filaggrin null mutations are associated with increased asthma severity in children and young adults. J Allergy Clin Immunol 120(1):64–68CrossRefGoogle Scholar
  49. 49.
    Weidinger S, O’Sullivan M, Illig T, Baurecht H, Depner M, Rodriguez E, Ruether A, Klopp N, Vogelberg C, Weiland SK, McLean WH, von Mutius E, Irvine AD (2008) Filaggrin mutations, atopic eczema, hay fever, and asthma in children. J Allergy Clin Immunol 121(5):1203–1209CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Dermato-venereology, Bispebjerg HospitalUniversity of CopenhagenCopenhagenDenmark
  2. 2.Department of Biomedical Sciences, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark

Personalised recommendations