• anaphylaxis;
  • bismuth subsalicylate;
  • Pepto-Bismol

Salicylates are frequently used medications, and reactions to these medications and other nonsteroidal anti-inflammatory drugs (NSAIDs) are common, involving both allergic and nonallergic mechanisms (1,2). These reactions can be due to drug-specific IgE, or may be related to the nonspecific depletion of prostaglandin E2 via inhibition of the cyclooxygenase enzyme (1).

Bismuth subsalicylate, the active compound in Pepto-Bismol (Proctor and Gamble, Cincinnati, OH), is frequently used in the US for the prevention of traveller's diarrhoea and in the treatment of dyspepsia (3). Reactions known to be caused by bismuth-containing compounds include encephalopathy, erythroderma, and other skin reactions (3,4). To date, anaphylaxis to Pepto-Bismol has not been described. We present a case of anaphylaxis to Pepto-Bismol and demonstrate positive, reproducible skin prick testing (SPT) to this drug.

A 25-year-old man presented to our emergency department with acute urticaria. He had symptoms of acute gastroenteritis on the day before presentation, including nausea, vomiting and diarrhoea. He self-medicated with Pepto-Bismol, taking a total of eight caplets over the next 6 h. Approximately 30 min after the final dose, he experienced generalized urticaria for which he sought medical care. He denied symptoms of shortness of breath, wheezing, syncope, rhinorrhea, metallic taste or sensation of impending doom. The patient had tolerated Pepto-Bismol in the past, as well as other NSAIDs, denied the use of other medications, and had not taken anything else by mouth (except water) for at least 12 h before the onset of urticaria.

Physical examination was notable only for generalized urticaria. The patient was admitted and treated with intravenous fluids and H1-blockers. Total serum tryptase at admission was elevated to 17 ng/ml (normal = 2–10 ng/ml).

The patient returned to our allergy clinic one month later for SPT to Pepto-Bismol. The skin test material was prepared in the following manner: two Pepto-Bismol caplets, each containing 262 mg of bismuth subsalicylate, were crushed and added to 10 ml of phosphate-buffered saline. After obtaining informed consent, SPT were performed using a prick and wipe method on the volar surface of the patient's forearm, using histamine sulfate 1 mg/ml and normal saline as positive and negative controls, respectively. SPT to the Pepto-Bismol solution caused a 9 × 12 mm wheal, surrounded by 20 × 25 mm erythema, along with appropriate responses to positive and negative controls. Five control subjects tolerant to Pepto-Bismol had negative SPT to the same solution. SPT were repeated two weeks later, showing a 6 × 8 mm wheal and a surrounding 14 × 18 mm erythema. A dot blot assay, as described previously (5), was unsuccessful in demonstrating in vitro IgE to Pepto-Bismol in the patient's serum.

It was concluded that our patient had allergic anaphylaxis to Pepto-Bismol based on the result of the serum tryptase as well as positive reproducible SPT (2). Our inability to demonstrate in vitro IgE is not surprising, given the inconsistent and difficult nature of measuring IgE antibodies against NSAIDs (6). Based on the proposed classification of reactions to cyclooxygenase inhibitors by Stevenson (6), our patient's reaction would be categorized as “single-drug anaphylaxis”. In this type of reaction, previous sensitization has occurred, with the formation of drug-specific IgE, and cross-reactivity with other NSAIDs is unlikely (6).


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  2. References
  • 1
    Stevenson DD, Simon RA. Sensitivity to aspirin and non-steroidal anti-inflammatory drugs. In: Middleton, E, Reed, CE, Ellis, EF et al, editors. Allergy: Principles and Practice. St. . Louis: CV Mosby Co., 1998, 12251234.
  • 2
    Johansson SGO, O'B Hourihane J, Bousquet J et al. A revised nomenclature for allergy. Allergy 2001;56:813824.
  • 3
    Lambert JR. Pharmacol bismuth-containing compounds. Rev Infect Dis 1991;13:S691S695.
  • 4
    Burnett JW. Bismuth. Cutis 1990;45:220.
  • 5
    Stott DI. Immunoblotting and dot blotting. J Immunol Meth 1989;119:153187.
  • 6
    Stevenson DD, Sanchez-Borges M, Szczeklik A. Classification of allergic and pseudoallergic reactions to drugs that inhibit cyclooxygenase enzymes. Ann Allergy 2001;87:177180.