Skip to main content

Advertisement

SpringerLink
Log in

Systemic Treatment for Severe Atopic Dermatitis

  • Review
  • Published:
Archivum Immunologiae et Therapiae Experimentalis Aims and scope

Abstract

Atopic dermatitis (AD) is a chronic inflammatory, relapsing disease of the skin, characterized by intense pruritus, maculopapular or vesicular erythematous lesions and scaling, sometimes accompanied by oozing, crusts and/or lichenification that has a negative impact on patients’ quality of life. Prevalence is higher in children, around 15%, and approximately 5% in adults. Before introducing systemic therapy, it is mandatory to review patients’ adherence to the correct use of topical treatments (corticosteroids, calcineurin inhibitors or cresoborole) and/or phototherapy. Ensure that environmental measures are being taken care of, irritant or proven allergic substances are not in use and even if the diagnostic is correct. If all is being done and topical treatment with corticosteroid, emollients and phototherapy have not been sufficient to achieve a good control in AD of adults or children patients, it is time to consider systemic agents. Up to now, most of systemic treatments were based on immunosuppressive therapies, being cyclosporine A, the usually first choice for moderate-to-severe AD. Recently, biologic drugs have been developed and approved for AD, as dupilumab, and a whole new group of drugs is giving much hope for patients to have a better control of the disease with less side effects.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

AD:

Atopic dermatitis

CyA:

Cyclosporine A

SCS:

Systemic corticosteroids

MTX:

Methotrexate

AZA:

Azathioprine

MMF:

Mycophenolate mofetil

EC-MPS:

Enteric-coated mycophenolate sodium

JAK:

Janus-associated kinase

TSLP:

Thymic stromal lymphopoietin

References

  • Arm JP, Bottoli I, Skerjanec A et al (2014) Pharmacokinetics, pharmacodynamics and safety of QGE031 (ligelizumab), a novel high-affinity anti-IgE antibody, in atopic subjects. Clin Exp Allergy 44:1371–1385

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Balal M, Demir E, Paydas S et al (2005) Uncommon side effect of MMF in renal transplant recipients. Ren Fail 27:591–594

    Article  CAS  PubMed  Google Scholar 

  • Bantz SK, Zhu Z, Zheng T (2014) The atopic March: progression from atopic dermatitis to allergic rhinitis and asthma. J Clin Cell Immunol 5:202

    PubMed  PubMed Central  Google Scholar 

  • Benson AA, Toh JA, Vernon N et al (2012) The role of vitamin D in the immunopathogenesis of allergic skin diseases. Allergy 67:296–301

    Article  CAS  PubMed  Google Scholar 

  • Berth-Jones J, Takwale A, Tan E et al (2002) Azathioprine in severe adult atopic dermatitis: a double-blind, placebo-controlled, crossover trial. Br J Dermatol 147:324–330

    Article  CAS  PubMed  Google Scholar 

  • Bieber T (2008) Atopic dermatitis. N Engl J Med 358:1483–1494

    Article  CAS  PubMed  Google Scholar 

  • Doege K, Grajecki D, Zyriax BC et al (2012) Impact of maternal supplementation with probiotics during pregnancy on atopic eczema in childhood—a meta-analysis. Br J Nutr 107:1–6

    Article  CAS  PubMed  Google Scholar 

  • Eichenfield LF, Ahluwalia J, Waldman A et al (2017) Current guidelines for the evaluation and management of atopic dermatitis: a comparison of the Joint Task Force Practice Parameter and American Academy of Dermatology guidelines. J Allergy Clin Immunol 139:S49–S57

    Article  PubMed  Google Scholar 

  • El-Khalawany MA, Hassan H, Shaaban D et al (2013) Methotrexate versus cyclosporine in the treatment of severe atopic dermatitis in children: a multicenter experience from Egypt. Eur J Pediatr 172:351–356

    Article  CAS  PubMed  Google Scholar 

  • Fala L (2015) Otezla (Apremilast), an oral PDE-4 inhibitor, receives FDA approval for the treatment of patients with active psoriatic arthritis and plaque psoriasis. Am Health Drug Benefits 8:105–110

    PubMed  PubMed Central  Google Scholar 

  • Fernández-Antón Martínez MC, Alfageme Roldán F, Ciudad Blanco C et al (2014) Ustekinumab in the treatment of severe atopic dermatitis: a preliminary report of our experience with 4 patients. Actas Dermosifiliogr 105:312–313

    Article  PubMed  Google Scholar 

  • Flohr C, Mann J (2014) New insights into the epidemiology of childhood atopic dermatitis. Allergy 69:3–16

    Article  CAS  PubMed  Google Scholar 

  • Garmhausen D, Hagemann T, Bieber T et al (2013) Characterization of different courses of atopic dermatitis in adolescent and adult patients. Allergy 68:498–506

    Article  CAS  PubMed  Google Scholar 

  • Gooderham M, Lynde CW, Papp K et al (2017) Review of systemic treatment options for adult atopic dermatitis. J Cutan Med Surg 21:31–39

    Article  PubMed  Google Scholar 

  • Goujon C, Bérard F, Dahel K et al (2006) Methotrexate for the treatment of adult atopic dermatitis. Eur J Dermatol 16:155–158

    CAS  PubMed  Google Scholar 

  • Grahovac M, Molin S, Prinz JC et al (2010) Treatment of atopic eczema with oral alitretinoin. Br J Dermatol 162:217–218

    Article  CAS  PubMed  Google Scholar 

  • Grundmann-Kollmann M, Podda M, Ochsendorf F et al (2001) Mycophenolate mofetil is effective in the treatment of atopic dermatitis. Arch Dermatol 137:870–873

    CAS  PubMed  Google Scholar 

  • Haeck IM, Knol MJ, Ten Berge O et al (2011) Enteric-coated mycophenolate sodium versus cyclosporin A as long-term treatment in adult patients with severe atopic dermatitis: a randomized controlled trial. J Am Acad Dermatol 64:1074–1084

    Article  CAS  PubMed  Google Scholar 

  • Hamilton JD, Suárez-Fariñas M, Dhingra N et al (2014) Dupilumab improves the molecular signature in skin of patients with moderate-to-severe atopic dermatitis. J Allergy Clin Immunol 134:1293–1300

    Article  CAS  PubMed  Google Scholar 

  • Hanifin JM, Reed ML (2007) A population-based survey of eczema prevalence in the United States. Dermatitis 18:82–91

    Article  PubMed  Google Scholar 

  • Hata TR, Audish D, Kotol P et al (2014) A randomized controlled double-blind investigation of the effects of vitamin D dietary supplementation in subjects with atopic dermatitis. J Eur Acad Dermatol Venereol 28:781–789

    Article  CAS  PubMed  Google Scholar 

  • Heller M, Shin HT, Orlow SJ et al (2007) Mycophenolate mofetil for severe childhood atopic dermatitis: experience in 14 patients. Br J Dermatol 157:127–132

    Article  CAS  PubMed  Google Scholar 

  • Hoare C, Li Wan Po A, Williams H (2000) Systematic review of treatments for atopic eczema. Health Technol Assess 4:1–191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hotze M, Baurecht H, Rodríguez E et al (2014) Increased efficacy of omalizumab in atopic dermatitis patients with wild-type filaggrin status and higher serum levels of phosphatidylcholines. Allergy 69:132–135

    Article  CAS  PubMed  Google Scholar 

  • Howell MD, Kim BE, Gao P et al (2007) Cytokine modulation of atopic dermatitis filaggrin skin expression. J Allergy Clin Immunol 120:150–155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Irvine AD, Jones AP, Beattie P et al (2018) A randomised controlled trial protocol assessing the effectiveness, safety and cost-effectiveness of methotrexate versus ciclosporin in the treatment of severe atopic eczema in children: the treatment of severe Atopic eczema Trial (TREAT). Br J Dermatol. https://doi.org/10.1111/bjd.16717

    Article  PubMed  PubMed Central  Google Scholar 

  • Iyengar SR, Hoyte EG, Loza A et al (2013) Immunologic effects of omalizumab in children with severe refractory atopic dermatitis: a randomized, placebo-controlled clinical trial. Int Arch Allergy Immunol 162:89–93

    Article  CAS  PubMed  Google Scholar 

  • Javanbakht MH, Keshavarz SA, Djalali M et al (2011) Randomized controlled trial using vitamins E and D supplementation in atopic dermatitis. J Dermatol Treat 22:144–150

    Article  CAS  Google Scholar 

  • Katsarou A, Armenaka M (2011) Atopic dermatitis in older patients: particular points. J Eur Acad Dermatol Venereol 25:12–18

    Article  CAS  PubMed  Google Scholar 

  • Kay J, Gawkrodger DJ, Mortimer MJ et al (1994) The prevalence of childhood atopic eczema in a general population. J Am Acad Dermatol 30:35–39

    Article  CAS  PubMed  Google Scholar 

  • Khan N, Abbas AM, Lichtenstein GR et al (2013) Risk of lymphoma in patients with ulcerative colitis treated with thiopurines: a nationwide retrospective cohort study. Gastroenterology 145:1007–1015.e3

    Article  CAS  PubMed  Google Scholar 

  • Kim DH, Park KY, Kim BJ et al (2013) Anti-immunoglobulin E in the treatment of refractory atopic dermatitis. Clin Exp Dermatol 38:496–500

    Article  CAS  PubMed  Google Scholar 

  • Kim JE, Kim HJ, Lew BJ et al (2015) Consensus guidelines for the treatment of atopic dermatitis in Korea (Part II): systemic treatment. Ann Dermatol 27:578–592

    Article  PubMed  PubMed Central  Google Scholar 

  • Kirby B, Owen CM, Blewitt RW et al (2002) Cutaneous T-cell lymphoma developing in a patient on cyclosporin therapy. J Am Acad Dermatol 47(2 Suppl):S165–S167

    Article  PubMed  Google Scholar 

  • Klein PA, Clark RA (1999) An evidence-based review of the efficacy of antihistamines in relieving pruritus in atopic dermatitis. Arch Dermatol 135:1522–1525

    Article  CAS  PubMed  Google Scholar 

  • Laube S, Stephens M, Smith AG et al (2005) Lymphomatoid papulosis in a patient with atopic eczema on long-term ciclosporin therapy. Br J Dermatol 152:1346–1348

    Article  CAS  PubMed  Google Scholar 

  • Leung DY, Boguniewicz M, Howell MD et al (2004) New insights into atopic dermatitis. J Clin Invest 113:651–657

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Levy LL, Urban J, King BA (2015) Treatment of recalcitrant atopic dermatitis with the oral Janus kinase inhibitor tofacitinib citrate. J Am Acad Dermatol 73:395–399

    Article  CAS  PubMed  Google Scholar 

  • Lyakhovitsky A, Barzilai A, Heyman R et al (2010) Low-dose methotrexate treatment for moderate-to-severe atopic dermatitis in adults. J Eur Acad Dermatol Venereol 24:43–49

    Article  CAS  PubMed  Google Scholar 

  • Meggitt SJ, Gray JC, Reynolds NJ (2006) Azathioprine dosed by thiopurine methyltransferase activity for moderate-to-severe atopic eczema: a double-blind, randomised controlled trial. Lancet 367:839–846

    Article  CAS  PubMed  Google Scholar 

  • Megna M, Napolitano M, Patruno C et al (2017) Systemic treatment of adult atopic dermatitis: a review. Dermatol Ther 7:1–23

    Article  Google Scholar 

  • Moreno AS, McPhee R, Arruda LK et al (2016) Targeting the T helper 2 inflammatory axis in atopic dermatitis. Int Arch Allergy Immunol 171:71–80

    Article  CAS  PubMed  Google Scholar 

  • Moul DK, Routhouska SB, Robinson MR et al (2008) Alefacept for moderate to severe atopic dermatitis: a pilot study in adults. J Am Acad Dermatol 58:984–989

    Article  PubMed  Google Scholar 

  • Mutgi K, Koo J (2013) Update on the role of systemic vitamin D in atopic dermatitis. Pediatr Dermatol 30:303–307

    Article  PubMed  Google Scholar 

  • Napolitano M, Megna M, Patruno C et al (2016) Adult atopic dermatitis: a review. Dermatol Venereol 151:403–411

    Google Scholar 

  • Nguyen RH, Cruz PD Jr (2014) Hepatitis due to mycophenolate mofetil used to treat atopic dermatitis and allergic contact dermatitis. Dermatitis 25:284–285

    Article  PubMed  PubMed Central  Google Scholar 

  • Notaro ER, Sidbury R (2015) Systemic agents for severe atopic dermatitis in children. Paediatr Drugs 17:449–457

    Article  PubMed  Google Scholar 

  • Oldhoff JM, Darsow U, Werfel T et al (2005) Anti-IL-5 recombinant humanized monoclonal antibody (mepolizumab) for the treatment of atopic dermatitis. Allergy 60:693–696

    Article  CAS  PubMed  Google Scholar 

  • Pelucchi C, Chatenoud L, Turati F et al (2012) Probiotics supplementation during pregnancy or infancy for the prevention of atopic dermatitis: a meta-analysis. Epidemiology 23:402–414

    Article  PubMed  Google Scholar 

  • Peyrin-Biroulet L, Khosrotehrani K, Carrat F et al (2011) Increased risk for nonmelanoma skin cancers in patients who receive thiopurines for inflammatory bowel disease. Gastroenterology 141:1621–1628 (e1–5)

    Article  CAS  PubMed  Google Scholar 

  • Politiek K, van der Schaft J, Coenraads PJ et al (2016) Drug survival for methotrexate in a daily practice cohort of adult patients with severe atopic dermatitis. Br J Dermatol 174:201–203

    Article  PubMed  Google Scholar 

  • Puya R, Alvarez-López M, Velez A et al (2012) Treatment of severe refractory adult atopic dermatitis with ustekinumab. Int J Dermatol 51:115–116

    Article  PubMed  Google Scholar 

  • Ring J, Alomar A, Bieber T et al (2012) Guidelines for treatment of atopic eczema (atopic dermatitis) Part II. J Eur Acad Dermatol Venereol 26:1176–1193

    Article  CAS  PubMed  Google Scholar 

  • Roekevisch E, Spuls PI, Kuester D et al (2014) Efficacy and safety of systemic treatments for moderate-to-severe atopic dermatitis: a systematic review. J Allergy Clin Immunol 133:429–438

    Article  CAS  PubMed  Google Scholar 

  • Ruzicka T, Lynde CW, Jemec GB et al (2008) Efficacy and safety of oral alitretinoin (9-cis retinoic acid) in patients with severe chronic hand eczema refractory to topical corticosteroids: results of a randomized, double-blind, placebo-controlled, multicentre trial. Br J Dermatol 158:808–817

    Article  CAS  PubMed  Google Scholar 

  • Saeki H, Nakahara T, Tanaka A et al (2016) Clinical practice guidelines for the management of atopic dermatitis 2016. J Dermatol 43:1117–1145

    Article  PubMed  Google Scholar 

  • Saeki H, Kabashima K, Tokura Y et al (2017) Efficacy and safety of ustekinumab in Japanese patients with severe atopic dermatitis: a randomized, double-blind, placebo-controlled, phase II study. Br J Dermatol 177:419–427

    Article  CAS  PubMed  Google Scholar 

  • Samorano LP, Hanifin JM, Simpson EL et al (2016) Inadequate response to ustekinumab in atopic dermatitis—a report of two patients. J Eur Acad Dermatol Venereol 30:522–523

    Article  CAS  PubMed  Google Scholar 

  • Samrao A, Berry TM, Goreshi R et al (2012) A pilot study of an oral phosphodiesterase inhibitor (apremilast) for atopic dermatitis in adults. Arch Dermatol 148:890–897

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sánchez-Pérez J, Daudén-Tello E, Mora AM et al (2013) Impact of atopic dermatitis on health-related quality of life in Spanish children and adults: the PSEDA study. Actas Dermosifiliogr 104:44–52

    Article  PubMed  Google Scholar 

  • Schmitt J, Schmitt N, Meurer M (2007) Cyclosporin in the treatment of patients with atopic eczema—a systematic review and meta-analysis. J Eur Acad Dermatol Venereol 21:606–619

    CAS  PubMed  Google Scholar 

  • Schmitt J, Schäkel K, Fölster-Holst R et al (2010) Prednisolone vs. ciclosporin for severe adult eczema. An investigator-initiated double-blind placebo-controlled multicentre trial. Br J Dermatol 162:661–668

    Article  CAS  PubMed  Google Scholar 

  • Schram ME, Roekevisch E, Leeflang MM et al (2011) A randomized trial of methotrexate versus azathioprine for severe atopic eczema. J Allergy Clin Immunol 128:353–359

    Article  CAS  PubMed  Google Scholar 

  • Sedivá A, Kayserová J, Vernerová E et al (2008) Anti-CD20 (rituximab) treatment for atopic eczema. J Allergy Clin Immunol 121:1515–1516

    Article  PubMed  Google Scholar 

  • Shaw TE, Currie GP, Koudelka CW et al (2011) Eczema prevalence in the United States: data from the 2003 National Survey of Children’s Health. J Invest Dermatol 131:67–73

    Article  CAS  PubMed  Google Scholar 

  • Sheldon E, Schwickart M, Li J et al (2016) Pharmacokinetics, pharmacodynamics, and safety of MEDI4212, an anti-IgE monoclonal antibody, in subjects with atopy: a phase I study. Adv Ther 33:225–251

    Article  CAS  PubMed  Google Scholar 

  • Sidbury R, Davis DM, Cohen DE et al (2014a) Guidelines of care for the management of atopic dermatitis: Sect. 3. Management and treatment with phototherapy and systemic agents. J Am Acad Dermatol 71:327–349

    Article  PubMed  PubMed Central  Google Scholar 

  • Sidbury R, Tom WL, Bergman JN (2014b) Guidelines of care for the management of atopic dermatitis: Sect. 4. Prevention of disease flares and use of adjunctive therapies and approaches. J Am Acad Dermatol 71:1218–1233

    Article  PubMed  PubMed Central  Google Scholar 

  • Silverberg JI, Hanifin JM (2013) Adult eczema prevalence and associations with asthma and other health and demographic factors: a US population-based study. J Allergy Clin Immunol 132:1132–1138

    Article  PubMed  Google Scholar 

  • Simon D, Bieber T (2014) Systemic therapy for atopic dermatitis. Allergy 69:46–55

    Article  CAS  PubMed  Google Scholar 

  • Simon D, Hösli S, Kostylina G et al (2008) Anti-CD20 (rituximab) treatment improves atopic eczema. J Allergy Clin Immunol 121:122–128

    Article  CAS  PubMed  Google Scholar 

  • Simpson EL, Bieber T, Eckert L et al (2016) Patient burden of moderate to severe atopic dermatitis (AD): insights from a phase 2b clinical trial of dupilumab in adults. J Am Acad Dermatol 74:491–498

    Article  CAS  PubMed  Google Scholar 

  • Simpson EL, Akinlade B, Ardenalu M (2017) Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med 376:1090–1091

    Article  PubMed  Google Scholar 

  • Sinha A, Velangi S, Natarajan S (2004) Non-Hodgkin’s lymphoma following treatment of atopic eczema with cyclosporin A. Acta Derm Venereol 84:327–328

    Article  PubMed  Google Scholar 

  • Sollinger HW (2005) Enteric-coated mycophenolate sodium—current and future use in transplant patients. Expert Rev Clin Immunol 1:203–211

    Article  CAS  PubMed  Google Scholar 

  • Soumelis V, Reche PA, Kanzler H et al (2002) Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP. Nat Immunol 3:673–680

    Article  CAS  PubMed  Google Scholar 

  • Spergel JM, Mizoguchi E, Oettgen H et al (1999) Roles of TH1 and TH2 cytokines in a murine model of allergic dermatitis. J Clin Invest 103:1103–1111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Van der Schaft J, van Zuilen AD, Deinum J et al (2015) Serum creatinine levels during and after long-term treatment with cyclosporine A in patients with severe atopic dermatitis. Acta Derm Venereol 95:963–967

    Article  CAS  PubMed  Google Scholar 

  • Volf EM, Au SC, Dumont N et al (2012) A phase 2, open-label, investigator-initiated study to evaluate the safety and efficacy of apremilast in subjects with recalcitrant allergic contact or atopic dermatitis. J Drugs Dermatol 11:341–346

    CAS  PubMed  Google Scholar 

  • Wang YH, Liu YJ (2009) Thymic stromal lymphopoietin, OX40-ligand, and interleukin-25 in allergic responses. Clin Exp Allergy 39:798–806

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Waxweiler WT, Agans R, Morrell DS (2011) Systemic treatment of pediatric atopic dermatitis with azathioprine and mycophenolate mofetil. Pediatr Dermatol 28:689–694

    Article  PubMed  Google Scholar 

  • Weatherhead SC, Wahie S, Reynolds NJ et al (2007) An open-label, dose-ranging study of methotrexate for moderate-to-severe adult atopic eczema. Br J Dermatol 156:346–351

    Article  CAS  PubMed  Google Scholar 

  • Weidinger S, Novak N (2016) Atopic dermatitis. Lancet 387:1109–1122

    Article  PubMed  Google Scholar 

  • Werfel T, Aberer W, Augustin M et al (2009) [Atopic dermatitis: S2 guidelines]. J Dtsch Dermatol Ges 7(Suppl 1):S1–S46

    PubMed  Google Scholar 

  • Wilson SR, Thé L, Batia LM et al (2013) The epithelial cell-derived atopic dermatitis cytokine TSLP activates neurons to induce itch. Cell 155:285–295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wollenberg A, Bieber T (2009) Proactive therapy of atopic dermatitis—an emerging concept. Allergy 64:276–278

    Article  CAS  PubMed  Google Scholar 

  • Wollenberg A, Oranje A, Deleuran M et al (2016) ETFAD/EADV Eczema task force 2015 position paper on diagnosis and treatment of atopic dermatitis in adult and paediatric patients. J Eur Acad Dermatol Venereol 30:729–747

    Article  CAS  PubMed  Google Scholar 

  • Wollenberg A, Barbarot S, Bieber T et al (2018) Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part II. J Eur Acad Dermatol Venereol 32:850–878

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Clinical Immunology and Allergy, University of São Paulo School of Medicine, Artur Ramos 178 ap.211A, Jd. América, São Paulo, SP, CEP: 01454-904, Brazil

    Mara Giavina-Bianchi & Pedro Giavina-Bianchi

Authors
  1. Mara Giavina-Bianchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pedro Giavina-Bianchi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pedro Giavina-Bianchi.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Giavina-Bianchi, M., Giavina-Bianchi, P. Systemic Treatment for Severe Atopic Dermatitis. Arch. Immunol. Ther. Exp. 67, 69–78 (2019). https://doi.org/10.1007/s00005-018-0521-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00005-018-0521-y

Keywords

Search

Navigation