Skip to main content

Advertisement

SpringerLink
Log in

Systemic Contact Dermatitis

  • Published:
Clinical Reviews in Allergy & Immunology Aims and scope Submit manuscript

Abstract

Systemic contact dermatitis (SCD) traditionally refers to a skin condition where an individual who is cutaneously sensitized to an allergen will subsequently react to that same allergen or a cross reacting allergen via a different route. It occurs to allergens including metals, medications, and foods. The exact pathophysiology underlying this disease remains unknown, although it appears to be mediated by type 4 hypersensitivity reactions and possibly type 3 hypersensitivity reactions. The p-I concept (pharmacologic interaction with immunoreceptors) hypothesized that drugs are able to bind directly to a T cell receptor without first being presented by MHC (major histocompatibility complex) molecules and without prior metabolism, which would help explain why SCD can be seen on first exposure to medications. Nomenclature remains a challenge as SCD can be subcategorized using terms such as ACDS (allergic contact dermatitis syndrome) and its four clinical stages, Baboon syndrome, and SDRIFE (symmetrical drug-related intertriginous and flexural exanthema), which share many overlapping features. Food allergens may be responsible for uncontrolled or persistent symptoms in patients with contact dermatitis who do not respond to topical avoidance. With medications, symptoms may be induced by topical application versus systemic administration. Patch testing (PT) may be beneficial in diagnosing SCD caused by metals and many topical medications including corticosteroids, antimicrobials (ampicillin, bacitracin, erythromycin, neomycin, nystatin), NSAIDs (diclofenac, ibuprofen), anesthetics, and antihistamines (chlorphenamine, piperazine). Current treatment options include topical steroids and oral antihistamines for symptom relief and dietary avoidance to causative foods or metals.

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

Similar content being viewed by others

Abbreviations

ACD:

Allergic contact dermatitis

ACDS:

Allergic contact dermatitis syndrome

BOP:

Balsam of Peru

BS:

Baboon syndrome

CS:

Corticosteroids

LND:

Low nickel diet

PT:

Patch test

MHC:

Major histocompatibility complex

SCD:

Systemic contact dermatitis

SDRIFE:

Symmetrical drug-related intertriginous and flexural exanthema

References

  1. Winnicki M, Shear NH (2011) A systematic approach to systemic contact dermatitis and symmetric drug-related intertriginous and flexural exanthema (SDRIFE): a closer look at these conditions and an approach to intertriginous eruptions. Am J Clin Dermatol 12(3):171–180

    Article  Google Scholar 

  2. Veien NK (2011) Systemic contact dermatitis. Int J Dermatol 50(12):1445–1456

    Article  CAS  Google Scholar 

  3. Kaaber K, Sjolin KE, Menne T (1983) Elbow eruptions in nickel and chromate dermatitis. Contact Dermatitis 9(3):213–216

    Article  CAS  Google Scholar 

  4. Fabbro SK, Zirwas MJ (2014) Systemic contact dermatitis to foods: nickel, BOP, and more. Curr Allergy Asthma Rep 14:463

    Article  Google Scholar 

  5. Menne T et al (1994) Systemic contact dermatitis. Am J Contact Dermat 5:1–12

    Article  Google Scholar 

  6. Andersen KE, Hjorth N, Menne T (1984) The baboon syndrome: systemically-induced allergic contact dermatitis. Contact Dermatitis 10(2):97–100

    Article  CAS  Google Scholar 

  7. Gawkrodger DJ, McVittie E, Hunter JA (1987) Immunophenotyping of the eczematous flare-up reaction in a nickel-sensitive subject. Dermatologica 175(4):171–177

    Article  CAS  Google Scholar 

  8. Di Gioacchino M et al (1995) Immuno-histopathologic changes in the gastrointestinal mucosa in patients with nickel contact allergy. G Ital Med Lav 17(1–6):33–36

    PubMed  Google Scholar 

  9. Boscolo P, Andreassi M, Sabbioni E, Reale M, Conti P, Amerio P, di Gioacchino M (1999) Systemic effects of ingested nickel on the immune system of nickel sensitised women. Life Sci 64(17):1485–1491

    Article  CAS  Google Scholar 

  10. Di Gioacchino M et al (2000) Lymphocyte subset changes in blood and gastrointestinal mucosa after oral nickel challenge in nickel-sensitized women. Contact Dermatitis 43(4):206–211

    Article  Google Scholar 

  11. Roychowdhury S, Svensson CK (2005) Mechanisms of drug-induced delayed-type hypersensitivity reactions in the skin. AAPS J 7(4):E834–E846

    Article  CAS  Google Scholar 

  12. Jensen CS, Lisby S, Larsen JK, Veien NK, Menne T (2004) Characterization of lymphocyte subpopulations and cytokine profiles in peripheral blood of nickel-sensitive individuals with systemic contact dermatitis after oral nickel exposure. Contact Dermatitis 50(1):31–38

    Article  CAS  Google Scholar 

  13. Posadas SJ, Pichler WJ (2007) Delayed drug hypersensitivity reactions - new concepts. Clin Exp Allergy 37(7):989–999

    Article  CAS  Google Scholar 

  14. Lachapelle JM The Spectrum of diseases for which patch testing is recommended. In: Patch Testing & Prick Testing: A Practical Guide Official Publication of the ICDRG, springer-Verlag, editor. 2009. Springer Berlin Heidelberg, Berlin, pp 7–31

  15. Hausermann P, Harr T, Bircher AJ (2004) Baboon syndrome resulting from systemic drugs: is there strife between SDRIFE and allergic contact dermatitis syndrome? Contact Dermatitis 51(5–6):297–310

    Article  CAS  Google Scholar 

  16. Ozkaya E (2014) Current understanding of baboon syndrome. Expert Rev Dermatol 4(2):163–175

    Article  Google Scholar 

  17. Miyahara A, Kawashima H, Okubo Y, Hoshika A (2011) A new proposal for a clinical-oriented subclassification of baboon syndrome and a review of baboon syndrome. Asian Pac J Allergy Immunol 29:150–160

    PubMed  Google Scholar 

  18. Veien NK, Christiansen AH, Svejgaard E, Kaaber K (1979) Antibodies against nickel-albumin in rabbits and man. Contact Dermatitis 5(6):378–382

    Article  CAS  Google Scholar 

  19. Polak L, Turk JL (1968) Studies on the effect of systemic administration of sensitizers in Guinea-pigs with contact sensitivity to inorganic metal compounds. I. The induction of immunological unresponsiveness in already sensitized animals. Clin Exp Immunol 3(3):245–251

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Tan S-C, Tan JW-l (2011) Symmetrical drug related intertriginous and flexural exanthema. Curr Opin Allergy Clin Immunol 11:313–318

    Article  Google Scholar 

  21. Gallo R, Parodi A (2002) Baboon syndrome from 5-aminosalicyclic acid. Contact Dermatitis 46(2):110

    Article  CAS  Google Scholar 

  22. Nakada T, Matsuzawa Y, Matsuzawa Y (2012) Allergic Contact Dermatitis Syndrome From Bufexamac for Nursing Infant. Dermatitis 23(4):185–186

    Article  Google Scholar 

  23. Proske S, Uter W, Schnuch A, Hartschuh W (2003) Severe allergic contact dermatitis with generalized spread due to bufexamac presenting as the "baboon" syndrome. Dtsch Med Wochenschr 128(11):545–547

    Article  CAS  Google Scholar 

  24. European Medicines Agency recommends revocation of marketing authorisations for bufexamac. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2010/04/WC500089623.pdf#search=‘eu,%20bufexamac’

  25. Lakshmi C, Srinivas C (2011) Systemic (allergic) contact dermatitis to diclofenac. Indian J Dermatol Venereol Leprol 77(4):536

    Article  Google Scholar 

  26. Rajan JP, Cornell R, White AA (2015) A case of systemic contact dermatitis secondary to edetate disodium. J Allergy Clin Immunol Pract 3(4):607–608

    Article  Google Scholar 

  27. Mussani F, Poon D, Skotnicki-Grant S (2013) Systemic contact dermatitis to topical clioquinol/hydrocortisone combination cream. Dermatitis 24(4):196–197

    Article  Google Scholar 

  28. Oliveira A, Rosmaninho A, Lobo I, Selores M (2011) Intertriginous and flexural exanthema after application of a topical anesthetic cream: a case of baboon syndrome. Dermatitis 22(6):360–362

    PubMed  Google Scholar 

  29. Erdmann S, Sachs B, Merk H (2001) Systemic contact dermatitis from cinchocaine. Contact Dermatitis 44(4):260261

    Article  Google Scholar 

  30. Malinauskiene L, Isaksson M, Bruze M (2013) Systemic contact dermatitis in a gold-allergic patient after treatment with an oral homeopathic drug. J Am Acad Dermatol 68(2):e58

    Article  Google Scholar 

  31. Moller H et al (1996) Flare up at contact allergy sites in a gold treated rheumatic patient. Acta Derm Venerol 76(1):55–58

    CAS  PubMed  Google Scholar 

  32. Klein-Gitelman MS, Pachman LM (1998) Intravenous corticosteroids: adverse reactions are more variable than expected in children. J Rheumatol 25(10):1995–2002

    CAS  PubMed  Google Scholar 

  33. Baeck M, Goossens A (2012) Systemic contact dermatitis to corticosteroids. Allergy 67(12):1580–1585

    CAS  PubMed  Google Scholar 

  34. Barbaud A, Waton J (2016) Systemic allergy to corticosteroids: clinical features and cross reactivity. Curr Pharm Des 22(45):6825–6831

    Article  CAS  Google Scholar 

  35. Garcia-Bravo B, Repiso JB, Camacho F (2000) Systemic Contact Dermatitis to Deflazacort. Contact Derm 43:359–360

    Article  CAS  Google Scholar 

  36. Bianchi L, Hansel K, Antonelli E, Bellini V, Rigano L, Stingeni L (2016) Deflazacort hypersensitivity: a difficult-to-manage case of systemic allergic dermatitis and literature review. Contact Dermatitis 75(1):54–56

    Article  Google Scholar 

  37. Treudler R, Simon J (2006) Symmetric, drug-related, intertriginous, and flexural exanthema in a patient with polyvalent intolerance to corticosteroids. J Allergy Clin Immunol 118:965–967

    Article  Google Scholar 

  38. DeKoven JG, Warshaw EM, Belsito DV, Sasseville D, Maibach HI, Taylor JS, Marks JG, Fowler JF Jr, Mathias CGT, DeLeo VA, Pratt MD, Zirwas MJ, Zug KA (2017) North American contact dermatitis group patch test results 2013-2014. Dermatitis 28(1):33–46

    Article  Google Scholar 

  39. Guin JD, Phillips D (1989) Erythroderma from systemic contact dermatitis: a complication of systemic gentamicin in a patient with contact allergy to neomycin. Cutis 43(6):564–567

    CAS  PubMed  Google Scholar 

  40. Haeberle M, Wittner B (2009) Is gentamicin-loaded bone cement a risk factor for developing systemic allergic dermatitis? Contact Dermatitis 60:176–177

    Article  Google Scholar 

  41. Wolf R, Orion E, Matz H (2003) The baboon syndrome or intertriginous drug eruption: a report of eleven cases and a second look at its pathomechanism. Dermatol Online J 9(3):2

    PubMed  Google Scholar 

  42. Goossens C, Sass U, Song M (1997) Baboon syndrome. Dermatology 194:421–422

    Article  CAS  Google Scholar 

  43. Wolf R, Elman M, Brenner S (1993) Drug-induced "intertrigo". Int J Dermatol 32(7):515–516

    Article  CAS  Google Scholar 

  44. Ash S, Scheman AJ (1997) Systemic contact dermatitis to hydroxyzine. Am J Contact Dermat 8(1):2–5

    CAS  PubMed  Google Scholar 

  45. Cusano F, Ferrara G, Crisman G, Sarracco G, Zalaudek I, Argenziano G (2006) Clinicopathologic features of systemic contact dermatitis from ethylenediamine in cetrizine and levocetrizine. Dermatology 213(4):353–355

    Article  Google Scholar 

  46. Isaksson M, Ljunggren B (2003) Systemic contact dermatitis from ethylenediamine in an aminophylline preparation presenting as the baboon syndrome. Acta Derm Venereol 83(1):69–70

    Article  CAS  Google Scholar 

  47. Walker S, Ferguson S (2004) Systemic allergic contact dermatitis due to ethylenediamine following administration of oral aminophylline. Br J Dermatol 150(3):594

    Article  CAS  Google Scholar 

  48. Sharma AD (2007) Relationship between nickel allergy and diet. Indian J Dermatol Venereol Leprol 73(5):307–312

    Article  Google Scholar 

  49. Brandao MH et al (2010) Ear piercing as a risk factor for contact allergy to nickel. J Pediatr 86(2):149–154

    Article  Google Scholar 

  50. Thyssen JP (2011) Nickel and cobalt allergy before and after nickel regulation--evaluation of a public health intervention. Contact Dermatitis 65(Suppl 1):1–68

    Article  Google Scholar 

  51. Kulberg A, Schliemann S, Elsner P (2014) Contact dermatitis as a systemic disease. Clin Dermatol 32:414–419

    Article  Google Scholar 

  52. Lerch M, Bircher AJ (2004) Systemically induced allergic exanthem from mercury. Contact Dermatitis 50(6):349–353

    Article  CAS  Google Scholar 

  53. Audicana M, Bernedo N, Gonzalez I, Munoz D, Fernandez E, Gastaminza G (2001) An unusual case of baboon syndrome due to mercury present in a homeopathic medicine. Contact Dermatitis 45(3):185

    Article  CAS  Google Scholar 

  54. Shimizu T, Kobayashi S, Tanaka M (2003) Systemic contact dermatitis to zinc in dental fillings. Clin Exp Dermatol 28(676):675

    Article  CAS  Google Scholar 

  55. Saito N, Yamane N, Matsumura W, Fujita Y, Inokuma D, Kuroshima SI, Hamasaka K, Shimizu H (2010) Generalized exacerbation of systemic allergic dermatitis due to zinc patch test and dental treatments. Contact Dermatitis 62(6):372–373

    Article  Google Scholar 

  56. Pigatto PD, Guzzi G (2004) Systemic contact dermatitis from nickel associated with orthodontic appliances. Contact Dermatitis 50(2):100–101

    Article  CAS  Google Scholar 

  57. Hausen BM et al (1995) Identification of new allergenic constituents and proof of evidence for coniferyl benzoate in balsam of Peru. Am J Contact Dermatitis 6(4):199–208

    Article  Google Scholar 

  58. Belsito DV (2001) Surviving on a balsam-restricted diet: cruel and unusual punishment or medically necessary therapy? J Am Acad Dermatol 45(3):470–472

    Article  CAS  Google Scholar 

  59. Hill AM, Belsito DV (2003) Systemic contact dermatitis of the eyelids caused by formaldehyde derived from aspartame? Contact Dermatitis 49(5):258–259

    Article  Google Scholar 

  60. Nijhawan RI et al (2009) Systemic contact dermatitis. Dermatol Clin 27(3):355–364 vii

    Article  CAS  Google Scholar 

  61. Matiz C, Jacob SE (2011) Systemic contact dermatitis in children: how an avoidance diet can make a difference. Pediatr Dermatol 28(4):368–374

    Article  Google Scholar 

  62. Dejobert Y, Delaporte E, Piette F, Thomas P (2001) Vesicular eczema and systemic contact dermatitis from sorbic acid. Contact Dermatitis 45(5):291

    Article  CAS  Google Scholar 

  63. Giordano-Labadie F, Pech-Ormieres C, Bazex J (1996) Systemic contact dermatitis from sorbic acid. Contact Dermatitis 34(1):61–62

    Article  CAS  Google Scholar 

  64. Scheman A, Cha C, Jacob SE, Nedorost S (2012) Food avoidance diets for systemic, lip, and oral contact allergy: an american contact alternatives group article. Dermatitis 23(6):248–257

    Article  CAS  Google Scholar 

  65. Burden AD, Wilkinson SM, Beck MH, Chalmers RJG (1994) Garlic-induced systemic contact dermatitis. Contact Dermatitis 30(5):299–300

    Article  CAS  Google Scholar 

  66. Veien NK (1997) Ingested food in systemic allergic contact dermatitis. Clin Dermatol 15(4):547–555

    Article  CAS  Google Scholar 

  67. Cho E, Lee JD, Cho SH (2011) Systemic contact dermatitis from propolis ingestion. Ann Dermatol 23(1):85–88

    Article  Google Scholar 

  68. Jacob SE, Scheman A, McGowan MA (2017) Allergen of the year: propylene glycol. Dermatitis 29(1):3–5

  69. Warshaw EM, Botto NC, Zug KA, Belsito DV, Maibach HI, Sasseville D, Fowler JF Jr, Storrs FJ, Taylor JS, DeLeo V, Marks JG Jr, Mathias CG, Pratt MD, Rietschel RL (2008) Contact dermatitis associated with food: retrospective cross-sectional analysis of north American contact dermatitis group data, 2001-2004. Dermatitis 19(5):252–260

    Article  CAS  Google Scholar 

  70. Lowther A, McCormick T, Nedorost S (2008) Systemic contact dermatitis from propylene glycol. Dermatitis 19(2):105–108

    Article  Google Scholar 

  71. Pereira F, Santos R, Pereira A (1997) Contact dermatitis from chamomile tea. Contact Dermatitis 36(6):307

    Article  CAS  Google Scholar 

  72. Rodriguez-Serna M, Sanchez-Motilla JM, Ramon R, Aliaga A (1998) Allergic and systemic contact dermatitis from Matricaria chamomilla tea. Contact Dermatitis 39(4):192–193

    Article  CAS  Google Scholar 

  73. Rycroft RJ (2003) Recurrent facial dermatitis from chamomile tea. Contact Dermatitis 48(4):229

    Article  Google Scholar 

  74. Barbaud A, Gonçalo M, Bruynzeel D, Bircher A, European Society of Contact Dermatitis (2001) Guidelines for performing skin tests with drugs in the investigation of cutaneous adverse drug reactions. Contact Dermatitis 45(6):321–328

    Article  CAS  Google Scholar 

  75. Brockow K et al (2002) General considerations for skin test procedures in the diagnosis of drug hypersensitivity. Allergy 57(1):45–51

    CAS  PubMed  Google Scholar 

  76. Sharma AD (2006) Disulfiram and low nickel diet in the management of hand eczema: a clinical study. Indian J Dermatol Venereol Leprol 72(2):113–118

    Article  Google Scholar 

  77. Christensen OB, Kristensen M (1982) Treatment with disulfiram in chronic nickel hand dermatitis. Contact Dermatitis 8(1):59–63

    Article  CAS  Google Scholar 

  78. Veien NK, Hattel T, Laurberg G (1993) Low nickel diet: an open, prospective trial. J Am Acad Dermatol 29(6):1002–1007

    Article  CAS  Google Scholar 

  79. Mislankar M, Zirwas MJ (2013) Low-nickel diet scoring system for systemic nickel allergy. Dermatitis 24(4):190–195

    Article  CAS  Google Scholar 

  80. Joneja JM (1995) Specific food restrictions nickel allergy. In: Managing food allergy & intolerance: a practical guide. J.A. Hall Publications, Port Coquitlam (BC), pp 247–262

  81. Salam TN, Fowler JF Jr (2001) Balsam-related systemic contact dermatitis. J Am Acad Dermatol 45(3):377–381

    Article  CAS  Google Scholar 

  82. Sharma AD (2009) Low chromate diet in dermatology. Indian J Dermatol 54(3):293–295

    Article  Google Scholar 

  83. Stuckert J, Nedorost S (2008) Low-cobalt diet for dyshidrotic eczema patients. Contact Dermatitis 59(6):361–365

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. SUNY at Stony Brook, Stony Brook, NY, USA

    Marcella Aquino

  2. Division of Rheumatology, Allergy & Immunology, NYU Winthrop University Hospital, 120 Mineola Blvd, Suite 410, Mineola, NY, 11501, USA

    Marcella Aquino & Greg Rosner

Authors
  1. Marcella Aquino
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Greg Rosner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marcella Aquino.

Ethics declarations

Conflicts of Interest

Dr. Marcella Aquino is immediate past president and a board member of the Long Island Allergy & Asthma Society; she has served as principal investigator on asthma clinical trials for Merck & Co. (SPIRO) and F. Hoffmann-La Roche (Study 1159871); has served as a sub-investigator on clinical trials for Novartis, Genentech, Shire, and Regeneron; has been paid for giving lectures by the ACAAI and WAO; has had travel expenses covered/reimbursed for travel to meetings by the ACAAI and WAO.

Dr. Gregory Rosner declares that he has no conflict of interest.

Ethical Approval and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Aquino, M., Rosner, G. Systemic Contact Dermatitis. Clinic Rev Allerg Immunol 56, 9–18 (2019). https://doi.org/10.1007/s12016-018-8686-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12016-018-8686-z

Keywords

Search

Navigation