Anaphylactoid Reactions to Mild Analgesics

  • B. Przybilla
  • A.-R. Bonnländer
  • J. Ring


“Mild” analgesic preparations (MAP), containing as main active compounds salicylates, pyrazolons, or p-aminophenol derivatives, are well-known elicitors of AR. The identification of the responsible agent is often difficult, as routine skin tests are only rarely conclusive.

The diagnostic value of skin tests (prick test, intracutaneous tests), challenge tests, and basophil histamine release tests was assessed in patients presenting with AR to MAP.

Prick testing with common components of MAP or commercial preparations (mostly in saturated solutions) yielded conclusive results (≥ 3 mm wheal diameter) in 19/282 patients. Positive reactions in more than 1% were observed only with the pyrazolons dipyrone (3.3%), propyphenazone (2.2%), and anti-pyrine (1.1%). The yield of conclusive results increased with the severity of the reactions reported in the history, reaching 25% in patients with a history of a full shock. — In 155 patients (mostly with negative prick test), oral challenge tests were performed. At least one conclusive positive result was obtained in 90 patients. The most frequent reactions were due to propyphenazone (in 39% of the patients tested), aspirin (23%), dipyrone (25%), acetaminophen (6%), and phenacetin (6%). In more than half of the patients with aspirin-induced AR there were additional reactions to pyrazolons and002For p-aminophenol derivatives. Among 71 patients reacting to dipyrone or propyphenazone, “cross reactivity” to both pyrazolon compounds occurred only in 12 cases. — Intracutaneous skin testing (ICT) with solutions of 10~2 M was compared with the oral challenge test results: with propyphenazone 4002F6 ICT reactions proved to be false positive, and in only 2/6 patients with a positive challenge test a conclusive ICT was found. 0/4 patients with AR to dipyrone were identifiable by ICT. In 3 patients showing conclusive positive prick test reactions to propyphenazone and/ or dipyrone oral challenges with these compounds were positive. — In 19 patients with positive oral challenge tests the histamine release from basophils was evaluated in vitro after incubation with the eliciting compounds. Only in 1 patient reactive to propyphenazone and dipyrone a concordant clearcut positive result was obtained.

These results indicate that at present oral challenge tests are the only reliable procedure to evaluate AR to MAP. They should include a battery of different drugs, since all mild analgesics, including acetaminophen, may elicit AR. Conclusive prick test results can be obtained with some pyrazolone derivatives, especially in patients with severe reactions. They probably are then sufficient for diagnosis. ICT as described does not seem to yield any advantage and bears the risk of false positive reactions. Positive results in the basophil histamine release test may be diagnostic, however, they are only observed in rare cases.


Anaphylactoid Reaction Oral Challenge Wheal Diameter Mild Analgesic Oral Challenge Test 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Capron A, Ameisen JC, Joseph M, Auriault C, Tonnel AB, Caen J (1985) New functions for platelets and their pathological implications. Int Arch Allergy Appl Immunol 77: 107–114PubMedCrossRefGoogle Scholar
  2. 2.
    Czerniawska-Mysik G, Szczeklik A (1981) Idiosyncrasy to pyrazolone drugs. Allergy 36: 381–384PubMedCrossRefGoogle Scholar
  3. 3.
    De Weck AL (1971) Immunological effects of aspirin anhydride, a contaminant of commercial acetylsalicylic acid preparations. Int Arch Allergy 41: 393–418PubMedCrossRefGoogle Scholar
  4. 4.
    Gottmann-Lückerath I, Steigleder GK (1974) Nachweis von Arzneimittelallergien durch Hauttests. In: Werner M, Ruppert V (eds) Praktische Allergiediagnostik. Methoden des direkten Allergennachweises. Thieme, Stuttgart, pp 115–128Google Scholar
  5. 5.
    Illig L (1982) Pseudo-allergische (anaphylactoide) Reaktionen der Haut auf Lebensmittel-farbstoffe. Allergologie 5: 193–198Google Scholar
  6. 6.
    Kleinhans D (1985) Reaktionen vom Soforttyp auf Analgetika-Wirkstoffe: Allergie und Intoleranz. Allergologie 8: 254–259Google Scholar
  7. 7.
    Maucher OM, Fuchs A (1983) Kontakturtikaria im Epikutantest bei Pyrazolonallergie. Hautarzt 34: 383–386PubMedGoogle Scholar
  8. 8.
    Merk H, Goerz G (1983) Analgetika-Intoleranz. Z Hautkr 58: 535–542PubMedGoogle Scholar
  9. 9.
    Patriarca G, Venuti A, Bonini W (1973) Allergy to pyramidon (aminopyrine). Ann Allergy 31: 84–86PubMedGoogle Scholar
  10. 10.
    Pleskow WW, Chenoweth DE, Simon RA, Stevenson DD, Curd JG (1983) The absence of detectable complement activation in aspirin-sensitive asthmatic patients during aspirin challenge. J Allergy Clin Immunol 72: 462–468PubMedCrossRefGoogle Scholar
  11. 11.
    Przybilla B, Ring J, Harle R (1984) Evaluation of anaphylactoid reactions (AR) to “mild” analgesics. J Allergy Clin Immunol 73: 164 (Abstract)Google Scholar
  12. 12.
    Ring J, Laubenthal H, Meßmer K (1982) Incidence and classification of adverse reactions to plasma substitutes. Klin Wochenschr 60: 997–1002PubMedCrossRefGoogle Scholar
  13. 13.
    Samter M, Beers RF (1968) Intolerance to aspirin. Clinical studies and consideration of its pathogenesis. Ann Intern Med 68: 975–983PubMedGoogle Scholar
  14. 14.
    Sertoli A, Marliani A, Lombardi P, Panconesi E (1980) Immediate sensitization to methamizole verified by patch tests. Contact Dermatitis 6: 294CrossRefGoogle Scholar
  15. 15.
    Settipane GA (1983) Aspirin and allergic diseases: a review. Am J Med 74 (6 A): 102–109PubMedCrossRefGoogle Scholar
  16. 16.
    Scheuer B (1983) Dermatologische Nebenwirkungen von Propyphenazon. Allergologie 6: 450–453Google Scholar
  17. 17.
    Schlumberger HD (1980) Drug-induced pseudo-allergic syndrome as exemplified by aeetylsalieylie acid intolerance. In: Dukor P, Kallós P, Schlumberger HD, West GB (eds) PAR. Pseudo-allergic reactions. Involvement of drugs and chemicals, vol 1. Karger, Basel, pp 125–203Google Scholar
  18. 18.
    Schulz KH (1979) Stellenwert und Aussagekraft von Testmethoden bei allergischen Arzneiexanthemen. In: Braun-Falco O, Wolff HH (eds) Fortschritte der praktischen Dermatologie und Venerologie, vol 9. Springer, Berlin Heidelberg New York, pp 71–80Google Scholar
  19. 19.
    Siraganian RP (1976) Histamine release and assay methods for the study of human allergy. In: Rose NR, Friedmann H (eds) Manual of clinical immunology. American Society for Microbiology, Washington, pp 603–615Google Scholar
  20. 20.
    Stevenson DD, Pleskow WW, Curd JG, Simon RA, Mathison DA (1982) Desensitization to aeetylsalieylie acid (ASA) in ASA-sensitive patients with rhinosinusitis/asthma. In: Dukor P, Kallós P, Schlumberger HD, West GB (eds) PAR. Pseudo-allergic reactions. Involvement of drugs and chemicals, vol 3. Karger, Basel, pp 133–156Google Scholar
  21. 21.
    Szczeklik A, Gryglewski RJ, Czerniawska-Mysik G (1977) Clinical patterns of hypersensitivity to nonsteroidal anti-inflammatory drugs and their pathogenesis. J Allergy Clin Immunol 6: 276–284CrossRefGoogle Scholar
  22. 22.
    Voigtländer V, Hänsch GM, Rother U (1980) Effect of aspirin on complement in vivo. Int Arch Allergy Appl Immunol 61: 145–149PubMedCrossRefGoogle Scholar
  23. 23.
    Woodbury DM, Fingl E (1975) Analgesic-antipyretics, anti-inflammatory agents, and drugs employed in the therapy of gout. In: Goodman LS, Gilman A (eds) The pharmacological basis of therapeutics. Macmillan, New York, pp 325–358Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1986

Authors and Affiliations

  • B. Przybilla
    • 1
  • A.-R. Bonnländer
    • 1
  • J. Ring
    • 1
  1. 1.Dermatologische Klinik und Poliklinik der Ludwig-Maximilians-Universität MünchenMunichFederal Republic of Germany

Personalised recommendations