• antispasmodic;
  • Buscapina®;
  • hyoscine butylbromide;
  • urticaria

Hyoscine butylbromide (Buscapina®; Boehringer Ingelheim, Barcelona, Spain) is an anticholinergic antispasmodic agent with quaternary ammonium structure. Although it is widely used, reports of immediate hypersensitivity reactions after hyoscine administration are scarce (1, 2). The mechanism implicated is still unknown. We describe a probable IgE-mediated case of acute urticaria after administration of hyoscine butylbromide.

A 23-year-old atopic woman was diagnosed of an acute appendicitis. Before the operation, the patient was treated symptomatically with intravenous Buscapina® 20 mg once. Twenty minutes later, developed urticarial lesions on trunk and extremities. Lesions disappeared within an hour after the administration of a parenteral antihistaminic and a corticosteroid. The patient did not remember previous ingestion of Buscapina® or Buscapina Compositum® (hyoscine butylbromide and metamizol). Afterwards, she tolerated Nolotil® (metamizol).

After informed consent was obtained, skin prick test (SPT) was performed using Buscapina® for parenteral administration (20 mg/ml). Histamine phosphate (10 mg/ml) was used as positive control and NaCl (0.9%) as negative control. Five non-atopic and five atopic subjects served as controls. A 4 mm wheal was obtained in the patient and was negative in control subjects. NaCl was negative and histamine was 11 mm in the patient.

A single-blind placebo-controlled oral challenge was performed with increasing doses of Buscapina®, starting with 2.5 mg with an hour interval. One hour after the administration of 5 mg, she presented headache, pruritus and rash in face, neck and upper area of thorax. Lesions disappeared in an hour after parenteral administration of 40 mg of prednisone. No late response was detected.

SPTs with a battery of commercially available common inhalant allergens and latex were also performed. The result was positive for grass and tree pollens and negative for the rest of allergens.

Histamine releasing test (HRT) according to Siraganian method (3) gave a negative result.

Tolerance to a different antispasmodic agent was needed to give the patient an alternative of treatment. Therapeutic doses (135 mg) of mebeverine were well tolerated.

On the one hand, the short period of latency added to the result of SPT, guide us to consider it an IgE-mediated reaction to hyoscine butylbromide. On the other hand, the result of HRT does not confirm this mechanism. However, some studies reveal a rate of 19% false negatives in HRT (4).

The patient was not sure she had taken this drug before. Quaternary ion ammonium might be the epitope responsible of the IgE-mediated reaction, as it happens with muscle relaxants used in general anesthesia. The ubiquity of the quaternary ion ammonium group could be the reason of previous sensitization in our patient. The union to specific IgE and the consequent release of mediators, takes place when there are at least two quaternary ion ammonium groups. Hyoscine butylbromide has only one quaternary ion ammonium group in its molecule. For this reason, other antigenic structures might be implicated in the origin of the reaction.

Among antispasmodic agents with anticholinergic action, there are compounds with quaternary ion ammonium structure, as hyoscine butylbromide and compounds with tertiary amine structure, like mebeverine. The tolerance of mebeverine could rule out the existence of in vivo cross-reactivity between both drugs.

In conclusion, we describe a rare case of urticaria due to hyoscine butylbromide. Positive SPT and oral provocation with this drug suggest an allergic IgE-mediated mechanism. However, more evidences are necessary to corroborate such mechanism.


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  2. References
  • 1
    Robinson ACR, Teeling M. Angioneurotic oedema and urticaria induced by hyoscine butylbromide. Postgrad Med J 1982;58: 316.
  • 2
    Watanabe T, Funayama M, Morita M. Fatal anaphylactic shock to hyoscine and diphenhydramine. J Toxicol Clin Toxicol 1994;32: 593594.
  • 3
    Siraganian RP, Brodsky MJ. Automated histamine analysis for in vitro allergy testing I. A method utilizing allergen-induced histamine release from whole blood. J Allergy Clin Immunol 1976;57: 525540.
  • 4
    Siraganian RP, Hook WA. Histamine release and assay methods for the study of human allergy. In: RoseNR, deMacarioEC, FaheyJL, FriedmanH, PennGM, editors. Manual of clinical laboratory immunology, 4th edn. Washington DC: American Society for Microbiology, 1992: 709716.