Histamine-Mediated Emergencies



The wheel and flare of urticaria is the pathognomonic feature of histamine-mediated cutaneous lesions. In fact, urticaria is one of the most common chief complaints encountered by dermatologists. Fortunately, their life-threatening sequelae, namely, anaphylaxis and shock, are exceedingly rare. Understanding the mechanisms through which histamine release occurs and its subsequent physiologic and potentially pathologic impact is vital to our ability to triage and treat appropriately. All dermatologists should be proficient at recognizing and diagnosing both common and unusual histamine-mediated emergencies in order to implement timely and directed therapy that could be potentially lifesaving.


Mast Cell Chronic Urticaria Peanut Allergy Systemic Mastocytosis Basophil Activation 
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  1. 1.
    Maintz L, Novak N. Histamine and histamine intolerance. Am J Clin Nutr. 2007;85(5):1185–96.PubMedGoogle Scholar
  2. 2.
    Ogawa Y, Grant JA. Mediators of anaphylaxis. Immunol Allergy Clin North Am. 2007;27(2):249–60. vii.PubMedCrossRefGoogle Scholar
  3. 3.
    Lieberman P. Clinical aspects and diagnosis of anaphylaxis. In: Pawankar R, Holgate ST, Rosenwasser LJ, editors. Allergy frontiers: diagnosis and health economics. Springer: Tokyo; 2009. p. 319–33.CrossRefGoogle Scholar
  4. 4.
    Tole JW, Lieberman P. Biphasic anaphylaxis: review of incidence, clinical predictors, and observation recommendations. Immunol Allergy Clin North Am. 2007;27(2):309–26. viii.PubMedCrossRefGoogle Scholar
  5. 5.
    Viale PH, Yamamoto DS. Biphasic and delayed hypersensitivity reactions: implications for oncology nursing. Clin J Oncol Nurs. 2010;14(3):347–56.PubMedCrossRefGoogle Scholar
  6. 6.
    James WD, et al. Andrews’ diseases of the skin clinical dermatology. London: Saunders Elsevier; 2011. p. 138–54.Google Scholar
  7. 7.
    Fisher AA. Contact dermatitis. Philadelphia: Lea and Febiger; 1973.Google Scholar
  8. 8.
    Gober LM, Saini SS. Allergic urticaria. In: Tyring SK, Gaspari AA, editors. Clinical and basic immunodermatology. London: Springer; 2008. p. 459–77.CrossRefGoogle Scholar
  9. 9.
    Sampson HA, et al. Symposium on the definition and management of anaphylaxis: summary report. J Allergy Clin Immunol. 2005;115(3):584–91.PubMedCrossRefGoogle Scholar
  10. 10.
    Sampson HA, et al. Second symposium on the definition and management of anaphylaxis: summary report–Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin Immunol. 2006;117(2):391–7.PubMedCrossRefGoogle Scholar
  11. 11.
    Kanji S, Chant C. Allergic and hypersensitivity reactions in the intensive care unit. Crit Care Med. 2010;38:S162–8. doi: 10.1097/CCM.0b013e3181de0c99.PubMedCrossRefGoogle Scholar
  12. 12.
    Sampson HA, Mendelson L, Rosen JP. Fatal and near-fatal anaphylactic reactions to food in children and Adolescents. N Engl J Med. 1992;327(6):380–4.PubMedCrossRefGoogle Scholar
  13. 13.
    Zuberbier T. Urticaria. Allergy. 2003;58(12):1224–34.PubMedCrossRefGoogle Scholar
  14. 14.
    Volcheck, G.W. Anaphylaxis and anaphylactoid reactions, in clinical allergy: diagnosis and Management. Humana Press; 2009. p. 433–63.Google Scholar
  15. 15.
    Lieberman P, et al. Epidemiology of anaphylaxis: findings of the American College of Allergy, Asthma and Immunology Epidemiology of Anaphylaxis Working Group. Ann Allergy Asthma Immunol. 2006;97(5):596–602.PubMedCrossRefGoogle Scholar
  16. 16.
    Clark S, Camargo Jr CA. Epidemiology of anaphylaxis. Immunol Allergy Clin North Am. 2007;27(2):145–63. v.PubMedCrossRefGoogle Scholar
  17. 17.
    Wolf R. Emergency dermatology. Cambridge: Cambridge University Press; 2010. p. 178–83. xi, 363.Google Scholar
  18. 18.
    Hall JE, Guyton AC. Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders/Elsevier; 2011. p. xix, 1091 p.Google Scholar
  19. 19.
    Brown SG. The pathophysiology of shock in anaphylaxis. Immunol Allergy Clin North Am. 2007;27(2):165–75. v.PubMedCrossRefGoogle Scholar
  20. 20.
    Pumphrey RS. Lessons for management of anaphylaxis from a study of fatal reactions. Clin Exp Allergy. 2000;30(8):1144–50.PubMedCrossRefGoogle Scholar
  21. 21.
    Simons FE. Anaphylaxis. J Allergy Clin Immunol. 2010;125(2 Suppl 2):S161–81.PubMedCrossRefGoogle Scholar
  22. 22.
    Bhatia R, Alikhan A, Maibach HI. Contact urticaria: present scenario. Indian J Dermatol. 2009;54(3): 264–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Novembre E, et al. Urticaria and urticaria related skin condition/disease in children. Eur Ann Allergy Clin Immunol. 2008;40(1):5–13.PubMedGoogle Scholar
  24. 24.
    Finn AA. Urticaria and angioedema. In: Lieberman P, Anderson JA, editors. Allergic diseases. London: Humana Press; 2007. p. 199–215.CrossRefGoogle Scholar
  25. 25.
    Yang MS, et al. Epidemiologic and clinical features of anaphylaxis in Korea. Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology. 2008;100(1):31–6.CrossRefGoogle Scholar
  26. 26.
    Frigas E, Park MA. Acute urticaria and angioedema: diagnostic and treatment considerations. Am J Clin Dermatol. 2009;10(4):239–50.PubMedCrossRefGoogle Scholar
  27. 27.
    Simons FER. Anaphylaxis pathogenesis and treatment. Allergy. 2011;66:31–4.PubMedCrossRefGoogle Scholar
  28. 28.
    Gonzalez-Perez A, et al. Anaphylaxis epidemiology in patients with and patients without asthma: a United Kingdom database review. J Allergy Clin Immunol. 2010;125(5):1098.e1–104.CrossRefGoogle Scholar
  29. 29.
    Krishna MT, et al. Diagnosis and management of hymenoptera venom allergy: British Society for Allergy and Clinical Immunology (BSACI) guidelines. Clin Exp Allergy. 2011;41(9):1201–20.PubMedCrossRefGoogle Scholar
  30. 30.
    Bilò MB. Anaphylaxis caused by Hymenoptera stings: from epidemiology to treatment. Allergy. 2011;66: 35–7.PubMedCrossRefGoogle Scholar
  31. 31.
    Keet CA, Wood RA. Food allergy and anaphylaxis. Immunol Allergy Clin North Am. 2007;27(2):193–212. vi.PubMedCrossRefGoogle Scholar
  32. 32.
    Ayuso R. Update on the diagnosis and treatment of shellfish allergy. Curr Allergy Asthma Rep. 2011;11(4):309–16.PubMedCrossRefGoogle Scholar
  33. 33.
    Hungerford JM. Scombroid poisoning: A review. Toxicon. 2010;56(2):231–43.PubMedCrossRefGoogle Scholar
  34. 34.
    Taylor SL, Stratton JE, Nordlee JA. Histamine poisoning (scombroid fish poisoning): an allergy-like intoxication. J Toxicol Clin Toxicol. 1989;27(4–5):225–40.PubMedCrossRefGoogle Scholar
  35. 35.
    Sicherer SH, Leung DYM. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2010. J Allergy Clin Immunol. 2011;127(2):326–35.PubMedCrossRefGoogle Scholar
  36. 36.
    Venter C, Arshad SH. Epidemiology of food allergy. Pediatr Clin North Am. 2011;58(2):327–49. ix.PubMedCrossRefGoogle Scholar
  37. 37.
    Bochner BS, Lichtenstein LM. Anaphylaxis. N Engl J Med. 1991;324(25):1785–90.PubMedCrossRefGoogle Scholar
  38. 38.
    Novembre E, et al. Anaphylaxis in children: clinical and allergologic features. Pediatrics. 1998;101(4):E8.PubMedCrossRefGoogle Scholar
  39. 39.
    Blumchen K, et al. Oral peanut immunotherapy in children with peanut anaphylaxis. J Allergy Clin Immunol. 2010;126(1):83.e1–91.CrossRefGoogle Scholar
  40. 40.
    Thyagarajan A, et al. Peanut oral immunotherapy is not ready for clinical use. J Allergy Clin Immunol. 2010;126(1):31–2.PubMedCrossRefGoogle Scholar
  41. 41.
    Khan DA, Solensky R. Drug allergy. J Allergy Clin Immunol. 2010;125(2 Suppl 2):S126–37.PubMedCrossRefGoogle Scholar
  42. 42.
    Doeglas HM. Reactions to aspirin and food additives in patients with chronic urticaria, including the physical urticarias. Br J Dermatol. 1975;93(2):135–44.PubMedCrossRefGoogle Scholar
  43. 43.
    Sanchez-Borges M. NSAID hypersensitivity (respiratory, cutaneous, and generalized anaphylactic symptoms). Med Clin North Am. 2010;94(4):853–64. xiii.PubMedCrossRefGoogle Scholar
  44. 44.
    An SY, et al. Vancomycin-associated spontaneous cutaneous adverse drug reactions. Allergy Asthma Immunol Res. 2011;3(3):194–8.PubMedCrossRefGoogle Scholar
  45. 45.
    Polk RE, et al. Vancomycin and the red-man syndrome: pharmacodynamics of histamine release. J Infect Dis. 1988;157(3):502–7.PubMedCrossRefGoogle Scholar
  46. 46.
    Renz C, et al. Histamine release during rapid vancomycin administration. Inflamm Res. 1998;47(13):69–70.CrossRefGoogle Scholar
  47. 47.
    Bircher AJ, Scherer K. Delayed cutaneous manifestations of drug hypersensitivity. Med Clin North Am. 2010;94(4):711–25. x.PubMedCrossRefGoogle Scholar
  48. 48.
    Shah D, Chowdhury MM. Rubber allergy. Clin Dermatol. 2011;29(3):278–86.PubMedCrossRefGoogle Scholar
  49. 49.
    Freeman TM. Clinical practice. Hypersensitivity to hymenoptera stings. N Engl J Med. 2004;351(19):1978–84.PubMedCrossRefGoogle Scholar
  50. 50.
    Brockow K, Ring J. Update on Diagnosis and Treatment of Mastocytosis. Curr Allergy Asthma Rep. 2011;11(4):292–9.PubMedCrossRefGoogle Scholar
  51. 51.
    Rueff F, et al. Predictors of severe systemic anaphylactic reactions in patients with Hymenoptera venom allergy: importance of baseline serum tryptase-a study of the European Academy of Allergology and Clinical Immunology Interest Group on Insect Venom Hypersensitivity. J Allergy Clin Immunol. 2009;124(5):1047–54.PubMedCrossRefGoogle Scholar
  52. 52.
    Tanus T, et al. Serum tryptase in idiopathic anaphylaxis: a case report and review of the literature. Ann Emerg Med. 1994;24(1):104–7.PubMedCrossRefGoogle Scholar
  53. 53.
    Dice JP. Physical urticaria. Immunol Allergy Clin North Am. 2004;24(2):225–46. vi.PubMedCrossRefGoogle Scholar
  54. 54.
    Sackeyfio A, et al. Diagnosis and assessment of food allergy in children and young people: summary of NICE guidance. BMJ. 2011;342:d747.PubMedCrossRefGoogle Scholar
  55. 55.
    Staevska M, et al. The effectiveness of levocetirizine and desloratadine in up to 4 times conventional doses in difficult-to-treat urticaria. J Allergy Clin Immunol. 2010;125(3):676–82.PubMedCrossRefGoogle Scholar
  56. 56.
    Zuberbier T, et al. EAACI/GA(2)LEN/EDF/WAO guideline: management of urticaria. Allergy. 2009;64(10):1427–43.PubMedCrossRefGoogle Scholar
  57. 57.
    Erbagci Z. The leukotriene receptor antagonist montelukast in the treatment of chronic idiopathic urticaria: a single-blind, placebo-controlled, crossover clinical study. J Allergy Clin Immunol. 2002;110(3): 484–8.PubMedCrossRefGoogle Scholar
  58. 58.
    Kosnik M, Subic T. Add-on montelukast in antihistamine-resistant chronic idiopathic urticaria. Respir Med. 2011;105 Suppl 1:S84–8.PubMedCrossRefGoogle Scholar
  59. 59.
    Anand MK, Nelson HS, Dreskin SC. A possible role for cyclooxygenase 2 inhibitors in the treatment of chronic urticaria. J Allergy Clin Immunol. 2003;111(5):1133–6.PubMedCrossRefGoogle Scholar
  60. 60.
    Spector S, Tan RA. Antileukotrienes in chronic urticaria. J Allergy Clin Immunol. 1998;101(4 Pt 1):572.PubMedGoogle Scholar
  61. 61.
    Smith PF, Corelli RL. Doxepin in the management of pruritus associated with allergic cutaneous reactions. Ann Pharmacother. 1997;31(5):633–5.PubMedGoogle Scholar
  62. 62.
    Asero R, Tedeschi A. Usefulness of a short course of oral prednisone in antihistamine-resistant chronic urticaria: a retrospective analysis. J Investig Allergol Clin Immunol. 2010;20(5):386–90.PubMedGoogle Scholar
  63. 63.
    Buchman AL. Side effects of corticosteroid therapy. J Clin Gastroenterol. 2001;33(4):289–94.PubMedCrossRefGoogle Scholar
  64. 64.
    Di Leo E, et al. Cyclosporin-A efficacy in chronic idiopathic urticaria. Int J Immunopathol Pharmacol. 2011;24(1):195–200.PubMedGoogle Scholar
  65. 65.
    Grattan CE, et al. Randomized double-blind study of cyclosporin in chronic ‘idiopathic’ urticaria. Br J Dermatol. 2000;143(2):365–72.PubMedCrossRefGoogle Scholar
  66. 66.
    Vena GA, et al. Cyclosporine in chronic idiopathic urticaria: a double-blind, randomized, placebo-controlled trial. J Am Acad Dermatol. 2006;55(4):705–9.PubMedCrossRefGoogle Scholar
  67. 67.
    Stellato C, et al. Anti-inflammatory effect of cyclosporin A on human skin mast cells. J Invest Dermatol. 1992;98(5):800–4.PubMedCrossRefGoogle Scholar
  68. 68.
    Harvey RP, Wegs J, Schocket AL. A controlled trial of therapy in chronic urticaria. J Allergy Clin Immunol. 1981;68(4):262–6.PubMedCrossRefGoogle Scholar
  69. 69.
    Cassano N, et al. Low-dose dapsone in chronic idiopathic urticaria: preliminary results of an open study. Acta Derm Venereol. 2005;85(3):254–5.PubMedGoogle Scholar
  70. 70.
    Engin B, Ozdemir M. Prospective randomized non-blinded clinical trial on the use of dapsone plus antihistamine vs. antihistamine in patients with chronic idiopathic urticaria. J Eur Acad Dermatol Venereol. 2008;22(4):481–6.PubMedCrossRefGoogle Scholar
  71. 71.
    Chakravarty SD, Yee AF, Paget SA. Rituximab successfully treats refractory chronic autoimmune urticaria caused by IgE receptor autoantibodies. J Allergy Clin Immunol. 2011;128(6):1354–5.PubMedCrossRefGoogle Scholar
  72. 72.
    Maurer M, et al. Efficacy and safety of omalizumab in patients with chronic urticaria who exhibit IgE against thyroperoxidase. J Allergy Clin Immunol. 2011;128(1):202.e5–9.CrossRefGoogle Scholar
  73. 73.
    Saini S, et al. A randomized, placebo-controlled, dose-ranging study of single-dose omalizumab in patients with H1-antihistamine-refractory chronic idiopathic urticaria. J Allergy Clin Immunol. 2011;128(3):567.e1–73.CrossRefGoogle Scholar
  74. 74.
    Sagi L, et al. Evidence for methotrexate as a useful treatment for steroid-dependent chronic urticaria. Acta Derm Venereol. 2011;91(3):303–6.PubMedCrossRefGoogle Scholar
  75. 75.
    Kemp SF, Lockey RF, Simons FE. Epinephrine: the drug of choice for anaphylaxis. A statement of the World Allergy Organization. Allergy. 2008;63(8):1061–70.PubMedCrossRefGoogle Scholar
  76. 76.
    Simons FE, et al. Epinephrine absorption in children with a history of anaphylaxis. J Allergy Clin Immunol. 1998;101(1 Pt 1):33–7.PubMedCrossRefGoogle Scholar
  77. 77.
    Simons KJ, Simons FE. Epinephrine and its use in anaphylaxis: current issues. Curr Opin Allergy Clin Immunol. 2010;10(4):354–61.PubMedCrossRefGoogle Scholar
  78. 78.
    Pumphrey R. When should self-injectible epinephrine be prescribed for food allergy and when should it be used? Curr Opin Allergy Clin Immunol. 2008;8(3):254–60.PubMedCrossRefGoogle Scholar
  79. 79.
    Ogden CL, Carroll MD, Flegal KM. High body mass index for age among US children and adolescents, 2003–2006. JAMA. 2008;299(20):2401–5.PubMedCrossRefGoogle Scholar
  80. 80.
    Song TT, et al. Adequacy of the epinephrine autoinjector needle length in delivering epinephrine to the intramuscular tissues. Ann Allergy Asthma Immunol. 2005;94(5):539–42.PubMedCrossRefGoogle Scholar
  81. 81.
    Stecher D, et al. Epinephrine auto-injectors: is needle length adequate for delivery of epinephrine intramuscularly? Pediatrics. 2009;124(1):65–70.PubMedCrossRefGoogle Scholar
  82. 82.
    Pumphrey RS. Fatal posture in anaphylactic shock. J Allergy Clin Immunol. 2003;112(2):451–2.PubMedCrossRefGoogle Scholar
  83. 83.
    Sicherer SH, Simons FE. Quandaries in prescribing an emergency action plan and self-injectable epinephrine for first-aid management of anaphylaxis in the community. J Allergy Clin Immunol. 2005;115(3):575–83.PubMedCrossRefGoogle Scholar
  84. 84.
    Soar J, et al. Emergency treatment of anaphylactic reactions–guidelines for healthcare providers. Resuscitation. 2008;77(2):157–69.PubMedCrossRefGoogle Scholar
  85. 85.
    Mueller UR. Cardiovascular disease and anaphylaxis. Curr Opin Allergy Clin Immunol. 2007;7(4):337–41.PubMedCrossRefGoogle Scholar
  86. 86.
    Arock M, Valent P. Pathogenesis, classification and treatment of mastocytosis: state of the art in 2010 and future perspectives. Expert Rev Hematol. 2010;3(4):497–516.PubMedCrossRefGoogle Scholar
  87. 87.
    Tharp MD. Mastocytosis. In: Bolognia J, Jorizzo JL, Rapini RP, editors. Dermatology. St. Louis, Mo: Mosby; 2008.Google Scholar
  88. 88.
    Wedi B, Frieri M. Mastocytosis. In: Mahmoudi M, editor. Challenging cases in allergy and immunology. London: Humana Press; 2009. p. 193–212.CrossRefGoogle Scholar
  89. 89.
    Valent P, et al. Standards and standardization in mastocytosis: consensus statements on diagnostics, treatment recommendations and response criteria. Eur J Clin Invest. 2007;37(6):435–53.PubMedCrossRefGoogle Scholar
  90. 90.
    Valent P, et al. Diagnosis and classification of mast cell proliferative disorders: delineation from immunologic diseases and non-mast cell hematopoietic neoplasms. J Allergy Clin Immunol. 2004;114(1):3–11. quiz 12.PubMedCrossRefGoogle Scholar
  91. 91.
    Briley LD, Phillips CM. Cutaneous mastocytosis: a review focusing on the pediatric population. Clin Pediatr. 2008;47(8):757–61.CrossRefGoogle Scholar
  92. 92.
    Lim KH, et al. Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors. Blood. 2009;113(23):5727–36.PubMedCrossRefGoogle Scholar
  93. 93.
    Castells M, Metcalfe DD, Escribano L. Diagnosis and treatment of cutaneous mastocytosis in children: practical recommendations. Am J Clin Dermatol. 2011;12(4):259–70.PubMedCrossRefGoogle Scholar
  94. 94.
    George TI, Horny HP. Systemic mastocytosis. Hematol Oncol Clin North Am. 2011;25(5): 1067–83.PubMedCrossRefGoogle Scholar
  95. 95.
    Longley Jr BJ, et al. Activating and dominant inactivating c-KIT catalytic domain mutations in distinct clinical forms of human mastocytosis. Proc Natl Acad Sci USA. 1999;96(4):1609–14.PubMedCrossRefGoogle Scholar
  96. 96.
    Heide R, Tank B, Oranje AP. Mastocytosis in childhood. Pediatr Dermatol. 2002;19(5):375–81.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media, LLC 2013

Authors and Affiliations

  1. 1.Albert Einstein College of MedicineNew YorkUSA
  2. 2.Division of Dermatology, Department of MedicineAlbert Einstein College of MedicineBronxUSA
  3. 3.Division of Dermatology, Department of MedicineMontefiore Medical Center, Albert Einstein College of MedicineBronxUSA

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