SpringerLink
Log in

Management and Long-Term Outcomes of Drug Reaction with Eosinophilia and Systemic Symptoms (DReSS) in Children: A Sco** Review

  • Review Article
  • Published:
American Journal of Clinical Dermatology Aims and scope Submit manuscript

Abstract

Drug reaction with eosinophilia and systemic symptoms (DReSS) is known to cause mortality and long-term sequelae in the pediatric population, however there are no established clinical practice guidelines for the management of pediatric DReSS. We conducted a sco** review, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to summarize the currently available data on treatment, mortality, and long-term sequelae of DReSS in children (aged 0–18 years). Data from 644 individuals revealed that various treatment strategies are being used in the management of pediatric DReSS, and strategies were often used in combination. The diversity in treatment approaches cannot be solely attributed to age or disease severity and reflects the lack of evidence-based management guidelines for DReSS. Children are also at risk of develo** autoimmune sequelae following DReSS, most commonly thyroid disease and type 1 diabetes mellitus. We found that the eventual development of autoimmune disease was more often associated with DReSS caused by antibiotics, especially minocycline and sulfamethoxazole, in comparison with individuals who did not develop sequelae. In this study, we identify strengths and weaknesses in the currently available literature and highlight that future prospective studies with structured and long-term follow-up of children with DReSS are needed to better understand potential risk factors for mortality and development of sequelae after DReSS.

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
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Kim GY, Anderson KR, Davis DMR, Hand JL, Tollefson MM. Drug reaction with eosinophilia and systemic symptoms (DRESS) in the pediatric population: a systematic review of the literature. J Am Acad Dermatol. 2020;83(5):1323–30.

    Article  CAS  PubMed  Google Scholar 

  2. Afiouni R, Zeinaty P, Kechichian E, Zoghaib S, Matar S, Helou-Mallat J, et al. Pediatric drug reaction with eosinophilia and systemic symptoms: a systematic review of the literature, with a focus on relapsing cases. Pediatr Dermatol. 2021;38(1):125–31.

    Article  PubMed  Google Scholar 

  3. Metterle L, Hatch L, Seminario-Vidal L. Pediatric drug reaction with eosinophilia and systemic symptoms: a systematic review of the literature. Pediatr Dermatol. 2020;37(1):124–9.

    Article  PubMed  Google Scholar 

  4. Stirton H, Shear NH, Dodiuk-Gad RP. Drug reaction with eosinophilia and systemic symptoms (DReSS)/drug-induced hypersensitivity syndrome (DiHS)-readdressing the DReSS. Biomedicines. 2022;10(5):999.

  5. Funck-Brentano E, Duong TA, Bouvresse S, Bagot M, Wolkenstein P, Roujeau JC, et al. Therapeutic management of DRESS: a retrospective study of 38 cases. J Am Acad Dermatol. 2015;72(2):246–52.

    Article  PubMed  Google Scholar 

  6. Schunkert EM, Divito SJ. Updates and insights in the diagnosis and management of DRESS syndrome. Curr Dermatol Rep. 2021;10(4):192–204.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Chen YC, Chang CY, Cho YT, Chiu HC, Chu CY. Long-term sequelae of drug reaction with eosinophilia and systemic symptoms: a retrospective cohort study from Taiwan. J Am Acad Dermatol. 2013;68(3):459–65.

    Article  PubMed  Google Scholar 

  8. Ushigome Y, Kano Y, Ishida T, Hirahara K, Shiohara T. Short- and long-term outcomes of 34 patients with drug-induced hypersensitivity syndrome in a single institution. J Am Acad Dermatol. 2013;68(5):721–8.

    Article  PubMed  Google Scholar 

  9. Deng M, Wu H, Yu M, Tian Y, Li Y, **ao X. Co-occurrence of multiple endocrine abnormalities induced by the DIHS/DRESS. Int J Endocrinol. 2019;2019:7959615.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Tempark T, Deekajorndech T, Chatproedprai S, Supornsilchai V, Wananukul S. Late sequelae of drug reaction with eosinophilia and systemic symptoms (DRESS) cause thyroid dysfunction and thyroiditis: review of literature. J Pediatr Endocrinol Metab. 2022;35(5):567–75.

    Article  CAS  PubMed  Google Scholar 

  11. Tricco AC, Lillie E, Zarin W, O’Brien KK, Colquhoun H, Levac D, et al. PRISMA extension for sco** reviews (PRISMA-ScR): checklist and explanation. Ann Intern Med. 2018;169(7):467–73.

    Article  PubMed  Google Scholar 

  12. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap): a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377–81.

    Article  PubMed  Google Scholar 

  13. Kardaun SH, Sekula P, Valeyrie-Allanore L, Liss Y, Chu CY, Creamer D, et al. Drug reaction with eosinophilia and systemic symptoms (DRESS): an original multisystem adverse drug reaction. Results from the prospective RegiSCAR study. Br J Dermatol. 2013;169(5):1071–80.

    Article  CAS  PubMed  Google Scholar 

  14. Cacoub P, Musette P, Descamps V, Meyer O, Speirs C, Finzi L, et al. The DRESS syndrome: a literature review. Am J Med. 2011;124(7):588–97.

    Article  CAS  PubMed  Google Scholar 

  15. Awad A, Goh MS, Trubiano JA. Drug reaction with eosinophilia and systemic symptoms: a systematic review. J Allergy Clin Immunol Pract. 2023;11(6):1856–68.

    Article  CAS  PubMed  Google Scholar 

  16. St George-Hyslop F, Cherepacha N, Chugani B, Alabdeen Y, Sanchez-Espino LF, Mahood Q, et al. Clinical presentation and diagnosis of drug reaction with eosinophilia and systemic symptoms (DReSS) in children: a sco** review. Clin Rev Allergy Immunol. 2024;66(1):112–23.

    Article  PubMed  Google Scholar 

  17. Shah SV, Vora NS, Dave JN, Goel R, Chakraborty N, Bhagat S. Phenytoin hypersensitivity syndrome. Indian J Dermatol Venereol Leprol. 1997;63(1):68–9.

    CAS  PubMed  Google Scholar 

  18. Hicks RA, Murphy JV, Jackson MA. Kawasaki-like syndrome caused by carbamazepine. Pediatr Infect Dis J. 1988;7(7):525–6.

    Article  CAS  PubMed  Google Scholar 

  19. Santos RP, Ramilo O, Barton T. Nevirapine-associated rash with eosinophilia and systemic symptoms in a child with human immunodeficiency virus infection. Pediatr Infect Dis J. 2007;26(11):1053–6.

    Article  PubMed  Google Scholar 

  20. Yoo SD, Kim SG, Kim SH, Kim HY. Drug rash with eosinophilia and systemic symptoms syndrome induced by chloral hydrate in early childhood. Allergy Asthma Immunol Res. 2014;6(3):270–2.

    Article  PubMed  Google Scholar 

  21. Bedouelle E, Ben Said B, Tetart F, Milpied B, Welfringer-Morin A, Maruani A, et al. Drug reaction with eosinophilia and systemic symptoms (DRESS): series of 49 French pediatric cases. J Allergy Clin Immunol Pract. 2022;10(1):267-74.e5.

    Article  CAS  PubMed  Google Scholar 

  22. Verstegen RHJ, Phillips EJ, Juurlink DN. First-line therapy in drug reaction with eosinophilia and systemic symptoms (DReSS): thinking beyond corticosteroids. Front Med. 2023;10:1138464.

    Article  Google Scholar 

  23. Newell BD, Moinfar M, Mancini AJ, Nopper AJ. Retrospective analysis of 32 pediatric patients with anticonvulsant hypersensitivity syndrome (ACHSS). Pediatr Dermatol. 2009;26(5):536–46.

    Article  PubMed  Google Scholar 

  24. Aihara Y, Ito S, Aihara M, Kobayashi Y, Yokota S. Different patterns of cytokines, ECP and immunoglobulin profiles at two adverse drug reactions in a patient. Pediatr Int. 2005;47(6):616–21.

    Article  PubMed  Google Scholar 

  25. Aouam K, Ben Romdhane F, Loussaief C, Salem R, Toumi A, Belhadjali H, et al. Hypersensitivity syndrome induced by anticonvulsants: possible cross-reactivity between carbamazepine and lamotrigine. J Clin Pharmacol. 2009;49(12):1488–91.

    Article  CAS  PubMed  Google Scholar 

  26. Troost RJ, Oranje AP, Lijnen RL, Benner R, Prens EP. Exfoliative dermatitis due to immunologically confirmed carbamazepine hypersensitivity. Pediatr Dermatol. 1996;13(4):316–20.

    Article  CAS  PubMed  Google Scholar 

  27. Chaabane A, Aouam K, Fredj NB, Boughattas NA. DRESS syndrome : étude de 11 cas et revue de la littérature. Therapies. 2010;65(6):543–50.

    Article  Google Scholar 

  28. Ben Salem C, Slim R, Denguezli M, Nouira R, Hmouda H, Bouraoui K. A recurrent drug rash with eosinophilia and systemic symptoms. Pediatr Dermatol. 2007;24(6):666–8.

    Article  PubMed  Google Scholar 

  29. Semic-Jusufagic A, Ogese MO, Edwards C, Wilkinson M, Nissenbaum C, Lee T, et al. T-cell-mediated hypersensitivity to lumacaftor and ivacaftor in cystic fibrosis. Pediatr Allergy Immunol. 2022;33(6): e13815.

    Article  CAS  PubMed  Google Scholar 

  30. Mendiratta V, Bhushan P. Phenytoin-induced DRESS with cross-reactivity to carbamazepine in a 10-year-old Indian child. Clin Exp Dermatol. 2006;31(5):720–1.

    Article  CAS  PubMed  Google Scholar 

  31. Carroll MC, Yueng-Yue KA, Esterly NB, Drolet BA. Drug-induced hypersensitivity syndrome in pediatric patients. Pediatrics. 2001;108(2):485–92.

    Article  CAS  PubMed  Google Scholar 

  32. Mittal RR, Jain C, Walia RL, Chopra A. Drug-induced pseudolymphoma syndrome. Indian J Dermatol Venereol Leprol. 1995;61(2):94–5.

    CAS  PubMed  Google Scholar 

  33. Bessmertny O, Hatton RC, Gonzalez-Peralta RP. Antiepileptic hypersensitivity syndrome in children. Ann Pharmacother. 2001;35(5):533–8.

    Article  CAS  PubMed  Google Scholar 

  34. Chan AL. Pediatric fatality due to anticonvulsant hypersensitivity syndrome. Ann Pharmacother. 2003;37(6):918.

    Article  PubMed  Google Scholar 

  35. Chen CJ, Huang YC, Wang CY, Lin TY. Fatal anticonvulsant hypersensitivity syndrome in an infant. Eur J Pediatr. 2003;162(12):893–4.

    Article  PubMed  Google Scholar 

  36. Huang YL, Hong HS, Wang ZW, Kuo TT. Fatal sodium valproate-induced hypersensitivity syndrome with lichenoid dermatitis and fulminant hepatitis. J Am Acad Dermatol. 2003;49(2):316–9.

    Article  PubMed  Google Scholar 

  37. Mahe E, Bodemer C, Dupic L, Hubert P, Lacaille F, Goulet O, et al. Drug-induced hypersensitivity syndrome associated with primary Epstein-Barr virus and human herpesvirus 6 infections in a child intestinal transplant recipient. Transplantation. 2004;77(3):479–80.

    Article  PubMed  Google Scholar 

  38. Yu MK, Yu MC, Lee F. Association of DRESS syndrome with chylous ascites. Nephrol Dial Transplant. 2006;21(11):3301–3.

    Article  PubMed  Google Scholar 

  39. Eshki M, Allanore L, Musette P, Milpied B, Grange A, Guillaume JC, et al. Twelve-year analysis of severe cases of drug reaction with eosinophilia and systemic symptoms: a cause of unpredictable multiorgan failure. Arch Dermatol. 2009;145(1):67–72.

    Article  PubMed  Google Scholar 

  40. Kitcharoensakkul M, Ree N, Bloomberg GR, Dehner LP, Heidingsfelder JA, White AJ, et al. Vancomycin-induced DRESS with evidence of T-cell activation in a 22-month-old patient. Ann Allergy Asthma Immunol. 2012;109(4):280–1.

    Article  PubMed  Google Scholar 

  41. Pereira CM, Vaz M, Kotha S, Santosh NH. Dapsone hypersensitivity syndrome with myocarditis. J Assoc Physicians India. 2014;62(8):728–31.

    PubMed  Google Scholar 

  42. Correa-de-Castro B, Paniago AM, Takita LC, Murback ND, Hans-Filho G. Drug reaction with eosinophilia and systemic symptoms: a clinicopathological study of six cases at a teaching hospital in midwestern Brazil. Int J Dermatol. 2016;55(3):328–34.

    Article  PubMed  Google Scholar 

  43. Goswami JN, Vaidya PC, Saini AG, De D, Radotra BD, Singhi PD. Drug reaction with eosinophilia and systemic symptoms in a child on multiple antiepileptics. Turk J Pediatr. 2017;59(2):197–9.

    Article  PubMed  Google Scholar 

  44. Rioualen S, Dufau J, Flatres C, Lavenant P, Misery L, Roue JM. DRESS complicated by hemophagocytic lymphohistiocytosis in an infant treated for congenital toxoplasmosis. Ann Dermatol Venereol. 2017;144(12):784–7.

    Article  CAS  PubMed  Google Scholar 

  45. Chua GT, Rosa Duque JS, Chong PCY, Lee PPW, Lau YL, Ho MHK. Paediatric case series of drug reaction with eosinophilia and systemic symptoms (DRESS): 12-year experience at a single referral centre in Hong Kong and the first reported use of infliximab. Eur Ann Allergy Clin Immunol. 2018;50(6):273–6.

    Article  CAS  PubMed  Google Scholar 

  46. Aljundi N, Utz Petry S, Moossavi M, Daveluy S. Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms following nivolumab and ipilimumab in a pediatric patient with melanoma. Pediatr Dermatol. 2022;39(3):486–7.

    Article  PubMed  Google Scholar 

  47. Brown RJ, Rother KI, Artman H, Mercurio MG, Wang R, Looney RJ, et al. Minocycline-induced drug hypersensitivity syndrome followed by multiple autoimmune sequelae. Arch Dermatol. 2009;145(1):63–6.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Lan J, Lahoti A, Lew DB. A severe case of minocycline-induced DRESS resulting in liver transplantation and autoimmune sequelae. Ann Allergy Asthma Immunol. 2016;116(4):367–8.

    Article  PubMed  Google Scholar 

  49. Coughlin CC, Jen MV, Boos MD. Drug hypersensitivity syndrome with prolonged course complicated by parvovirus infection. Pediatr Dermatol. 2016;33(6):e364–5.

    Article  PubMed  Google Scholar 

  50. Han XD, Koh MJ, Wong SMY. Drug reaction with eosinophilia and systemic symptoms in a cohort of Asian children. Pediatr Dermatol. 2019;36(3):324–9.

    Article  PubMed  Google Scholar 

  51. Werbel T, Castrovinci P, Contestable J. Ethosuximide-induced drug reaction with eosinophilia and systemic symptoms with mediastinal lymphadenopathy. Pediatr Dermatol. 2019;36(4):e99–101.

    Article  PubMed  Google Scholar 

  52. Satake M, Kudo K, Masuda A, Onoyama S, Furuno K, Furue M. Drug-induced hypersensitivity syndrome by iv immunoglobulin administration for Kawasaki disease. J Dermatol. 2020;47(3):e74–5.

    Article  PubMed  Google Scholar 

  53. Morita C, Yanase T, Shiohara T, Aoyama Y. Aggressive treatment in paediatric or young patients with drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) is associated with future development of type III polyglandular autoimmune syndrome. BMJ Case Rep. 2018;2018:bcr-2018-225528.

  54. Tempark T, Tangthanapalakul A, Deekajorndech T, Chatproedprai S, Supornsilchai V, Wananukul S. Graves’ disease: an uncommon cause of late sequelae following DRESS (drug reaction with eosinophilia and systemic symptoms). Clin Exp Pediatr. 2022;65(12):602–4.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Zhu B, Wu J, Chen G, Yang Y, Yi C. Fulminant type 1 diabetes mellitus caused by drug reaction with eosinophilia and systemic symptoms (DRESS): a case report and review of the literature. Front Endocrinol (Lausanne). 2019;10:474.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Dibek Misirlioglu E, Guvenir H, Bahceci S, Haktanir Abul M, Can D, Usta Guc BE, et al. Severe cutaneous adverse drug reactions in pediatric patients: a multicenter study. J Allergy Clin Immunol Pract. 2017;5(3):757–63.

    Article  PubMed  Google Scholar 

  57. Huang YL, Hsieh MY, Hsiao PF, Sheen JM, Yu HR, Kuo HC, et al. Alopecia areata universalis after phenobarbital-induced anti-convulsant hypersensitivity syndrome. Immunol Invest. 2009;38(5):383–97.

    Article  CAS  PubMed  Google Scholar 

  58. Hollingsworth P, Paci K, Evans M, Miedema J, Morrell DS. Alopecia universalis after drug reaction with eosinophilia and systemic symptoms (Dress). Pediatr Dermatol. 2020;37(5):947–9.

    Article  PubMed  Google Scholar 

  59. Shastry V, Betkerur J. Hypothyroidism as a late manifestation of drug hypersensitivity syndrome. Indian J Dermatol. 2010;55(4):405–6.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Alexander T, Iglesia E, Park Y, Duncan D, Peden D, Sheikh S, et al. Severe DRESS syndrome managed with therapeutic plasma exchange. Pediatrics. 2013;131(3):e945–9.

    Article  PubMed  Google Scholar 

  61. Martanto W, Pan JY. Severe DRESS syndrome secondary to sulfamethoxazole/trimethoprim complicated by hyperthyroidism, photosensitivity, anhidrosis, and juvenile idiopathic arthritis. Dermatol Sin. 2015;33(1):33–4.

    Article  Google Scholar 

  62. Dahl AR, Knoebel EE, Lloyd RM. DRESS following FIRES: a clinical conundrum. Clin Pediatr (Phila). 2018;57(12):1479–82.

    Article  PubMed  Google Scholar 

  63. Song SM, Cho MS, Oh SH, Kim KM, Park YS, Kim DY, et al. Liver transplantation in a child with acute liver failure resulting from drug rash with eosinophilia and systemic symptoms syndrome. Korean J Pediatr. 2013;56(5):224–6.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Garcia A, Yi NJ, Lee KB, Lee JM, Choi YR, Suh SW, et al. Fulminant hepatitis linked to dapsone hypersensitivity syndrome requiring urgent living donor liver transplantation: a case report. Pediatr Transplant. 2014;18(7):E240–5.

    Article  CAS  PubMed  Google Scholar 

  65. Álvarez-García L, López Amor L, Escudero AD. Liver transplantation in a patient with fulminant hepatitis by DRESS syndrome. Med Clín (Barc). 2021;156(7):363–4.

    Article  PubMed  Google Scholar 

  66. Erdem SB, Nacaroglu HT, Bag O, Karkiner CS, Korkmaz HA, Can D. DRESS syndrome associated with type 2 diabetes in a child. Cent Eur J Immunol. 2015;40(4):493–6.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors are grateful for library support by Catharine Pajunen and Jessie Cunningham (The Hospital for Sick Children, Toronto, ON, Canada).

Author information

Authors and Affiliations

  1. Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada

    Nicole Cherepacha & Frances St George-Hyslop

  2. Division of Clinical Pharmacology and Toxicology, Department of Paediatrics, The Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Canada

    Nicole Cherepacha, Frances St George-Hyslop, Bindiya Chugani & Ruud H. J. Verstegen

  3. Division of Immunology and Allergy, Department of Paediatrics, University of Toronto, Toronto, ON, Canada

    Yousef Alabdeen

  4. Division of Dermatology, Department of Paediatrics, Stollery Children’s Hospital, Edmonton, AB, Canada

    Luis F. Sanchez-Espino

  5. Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada

    Luis F. Sanchez-Espino

  6. Hospital Library, The Hospital for Sick Children, Toronto, ON, Canada

    Quenby Mahood

  7. Department of Paediatrics, University of Toronto, Toronto, ON, Canada

    Cathryn Sibbald & Ruud H. J. Verstegen

  8. Division of Dermatology, Department of Paediatrics, The Hospital for Sick Children, Toronto, ON, Canada

    Cathryn Sibbald

  9. Division of Rheumatology, Department of Paediatrics, The Hospital for Sick Children, Toronto, ON, Canada

    Ruud H. J. Verstegen

Authors
  1. Nicole Cherepacha
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Frances St George-Hyslop
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bindiya Chugani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yousef Alabdeen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Luis F. Sanchez-Espino
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Quenby Mahood
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Cathryn Sibbald
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ruud H. J. Verstegen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ruud H. J. Verstegen.

Ethics declarations

Funding

No funding was received to conduct this study.

Conflict of interest

Nicole Cherepacha, Frances St George-Hyslop, Bindiya Chugani, Yousef Alabdeen, Luis F. Sanchez-Espino, Quenby Mahood, Cathryn Sibbald, and Ruud Verstegen have no conflicts of interest to declare that are relevant to the contents of this article.

Ethics

Ethics approval was not required for this study.

Patient consent to participate/publish

Not applicable.

Data availability

The data that support the findings of this study are available from the corresponding author (RV), upon reasonable request.

Code availability

Not applicable.

Author contributions

NC, FS, YA, LS and QM performed the data collection. NC analyzed the data and prepared the draft manuscript. CS and RV supervised the project and edited the manuscript. All authors read and approved the final manuscript.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 28 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cherepacha, N., St George-Hyslop, F., Chugani, B. et al. Management and Long-Term Outcomes of Drug Reaction with Eosinophilia and Systemic Symptoms (DReSS) in Children: A Sco** Review. Am J Clin Dermatol (2024). https://doi.org/10.1007/s40257-024-00867-y

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s40257-024-00867-y

Search

Navigation