Postgrad Med J 2000;76:501–502 501 Postgrad Med J: first published as 10.1136/pmj.76.898.501 on 1 August 2000. Downloaded from ADVERSE DRUG REACTION

Anaphylactoid reactions to paracetamol

Oyekoya T Ayonrinde, Barry M Saker

Abstract oxygen and intravenous colloid. Intravenous The toxic eVects of paracetamol in over- heparin was started until pulmonary embolism dose quantities are well recognised but the and myocardial infarction were excluded. A occurrence of anaphylactoid reactions to generalised pruritic rash evolved over about an paracetamol is infrequently identified by hour. Her cardiopulmonary status normalised consumers and health care professionals. over two hours but the rash resolved over three Nevertheless adverse reactions to this days. The flucloxacillin was continued the next drug, even in therapeutic doses, can have day after a test dose without incident. fatal or near fatal consequences. A case of Her full blood count and serum biochemis- an anaphylactoid reaction to paracetamol try remained unchanged. In light of a normal is described. chest radiograph, normal range serial cardiac (Postgrad Med J 2000;76:501–502) enzyme levels and electrocardiograms (ECGs), and low probability V/Q scan heparin was dis- Keywords: paracetamol; anaphylaxis; allergy; hypersen- sitivity continued. Review of a previous volume of her medical records from four years earlier confirmed a Paracetamol, one of the world’s most fre- fever treated with1gofparacetamol. About 30 quently consumed drugs, is generally freely minutes later she developed acute onset available over-the-counter, on account of its dyspnoea, diaphoresis, truncal flushing, and relative safety in therapeutic doses.1 It is a generalised pruritus. She remained normoten- component of numerous prescription and sive and ECGs were normal. There had been non-prescription drugs in common use. Based no clinical or radiological pulmonary oedema on its popularity some local brands are nearly and no wheeze. She promptly responded to synonymous with oral analgesics. nebulised salbutamol, and fully recovered over Paracetamol hepatotoxicity is well described a few hours after that event. The possibility that but there are few reports of adverse reactions paracetamol was responsible was considered. after the ingestion of paracetamol within However she had previously consumed para- recommended doses. Unlike aspirin, little is cetamol without incident, hence a causal http://pmj.bmj.com/ known about hypersensitivity, anaphylactic, or relationship could not be established with cer- anaphylactoid reactions to paracetamol. tainty despite the temporal association. No We report a case of an anaphylactoid definite diagnosis was made but a “possible reaction after ingestion of1gofparacetamol. reaction” to paracetamol was proposed. She had since not required use of this drug and was Case report thus left unsure. A 65 year old caucasian woman treated with The unintentional rechallenge with para- chronic ambulatory peritoneal dialysis cetamol had reproduced a similar anaphylac- on September 27, 2021 by guest. Protected copyright. (CAPD) for end stage renal failure was hospi- toid reaction. Allergy to paracetamol was talised for treatment of gangrene of two toes. clearly documented in her medical records and She was a type II diabetic with peripheral vas- pharmaceutical charts in order to avoid further cular disease. Her usual medications included adverse events or doubt. The case was reported calcitriol, calcium carbonate, and gliclazide. to the Australian Adverse Drug Reaction Advi- Her CAPD had remained uncomplicated since sory Committee (ADRAC). onset three years earlier. On admission she was started on intravenous flucloxacillin. She men- Discussion tioned a remote possible reaction to paraceta- The English language medical literature con- mol. tains few cases of anaphylactoid reactions/ anaphylaxis to paracetamol. These predomi- Royal Perth Hospital, During hospitalisation an on-call medical GPO Box X2213, oYcer, unaware of her possible allergy, gave her nantly appear in journals of allergy or Perth, Western 1 g of paracetamol to treat a fever. Over the dermatology as individual case reports or series Australia 6000, next 30 minutes she became anxious, flushed, describing hypersensitivity or allergic reactions Australia weak, faint, and intensely dyspnoeic. Assess- to paracetamol. Clinical features covering the O T Ayonrinde ment by a diVerent medical oYcer at this stage spectrum of anaphylaxis have been described, B M Saker described a woman in respiratory distress, notably generalised pruritus, fixed drug erup- Correspondence to: hypotensive (blood pressure 85/50 mm Hg), tions, urticaria, hypotension, dyspnoea, and Dr Ayonrinde (email: tachycardic (pulse 130/min), and with occa- bronchospasm.1–10 The dyspnoea and hypoten- [email protected]) sional inspiratory crackles but no wheeze on sion may be severe, necessitating cardiopul- 23 Submitted 20 July 1999 chest auscultation. She was hypoxic breathing monary support. The intensity of reaction Accepted 22 December 1999 room air but improved on resuscitation with has been found to be dose related, increasing

www.postgradmedj.com 502 Ayonrinde, Saker Postgrad Med J: first published as 10.1136/pmj.76.898.501 on 1 August 2000. Downloaded from with dose beyond individual threshold, and is often unrelated to aspirin hypersensitivity or a Summary points history of atopy.124 There is an age unrelated x Importance of a complete drug history. 1 5–10 female preponderance in reported cases. x Adverse drug reactions can occur to any Paracetamol is excreted in breast milk and a medication no matter how seemingly reproducible rash has been reported in a innocuous. breastfeeding infant each time her mother x Recognition of anaphylactoid/ ingested paracetamol.8 anaphylactic reactions and appropriate While the toxic eVects of paracetamol are management. Recommended treatment well recognised, these allergic-like reactions are 1–5910 for anaphylaxis, particularly if manifest generally considered to be rare. People by cardiopulmonary compromise, is who have previously ingested paracetamol with parenteral adrenaline. impunity may be aVected.7 Most reports detailed onset of symptoms within 30–60 min- x Importance of clear documentation of utes of ingesting paracetamol, as occurs with suspected or confirmed adverse drug immediate hypersensitivity reactions, but that reactions. association has not been confirmed.12479 x Significance of reporting adverse drug We reviewed the records of the Australian events to the appropriate local drug ADRAC registry (1973 to July 1998), selecting monitoring bodies in order to establish a cases reporting allergy, hypersensitivity, ana- reliable database for future reference. phylaxis, cutaneous, respiratory and cardiovas- cular reactions to paracetamol. Altogether 350 reports were identified. antihistamines, glucocorticoids, and parenteral Cases where other drugs were concurrently adrenaline were required. administered or where the primary condition A similar pattern of reports notified to other adverse drug reaction monitoring bodies has could potentially have resulted in the reported 5910 clinical features were excluded. This left 68 been discussed by other authors. The mechanism of the anaphylactoid reac- reports causally associating paracetamol inges- 17 tion with the described reactions. The distribu- tion to paracetamol remains uncertain. The varied presentations indicate that it may often tion of anaphylactic-like reactions reported are remain unsuspected. The possibility of this, listed in table 1. Sixty per cent of these reportedly, rare drug reaction should be borne reactions occurred in females and mostly in mind when taking a drug history and when involved a rash. Ages ranged from 2 months to challenged by cases of unexplained “collapse” 92 years old. Most reports where the outcome or features suggestive of anaphylaxis. It is sug- was recorded indicated recovery on cessation gested that such adverse drug reactions be of paracetamol alone. In other instances single unequivocally represented within the past drug or combinations of oral or parenteral medical history and perhaps on a medical alert bracelet. http://pmj.bmj.com/

Table 1 Summary of range of anaphylactoid-type We thank the Secretary, Adverse Drug Reaction Section, reactions to paracetamol reported to ADRAC between 1973 Therapeutic Goods Administration, Woden, ACT, Australia. and July 1998 1 Le Van Diem, Grilliat JP. Anaphylactic shock induced by Type of reaction No of reports paracetamol. Eur J Clin Pharmacol 1990;38:389–90. 2 Kumar RK, Byard I. Paracetamol as a cause of anaphylaxis. Rash (including urticaria and fixed 44 Hospital Medicine 1999;60:66–7. drug eruptions) 3 Brown G. Acetaminophen-induced hypotension. Heart Facial and periorbital oedema/angioedema 24 Lung 1996;25:137–40. Pruritus 16 4 Leung R, Plomley R, Czarny D. Paracetamol anaphylaxis. on September 27, 2021 by guest. Protected copyright. Clin Exp Allergy 1992;22:831–3. Dyspnoea/bronchospasm 15 5 Rademaker M, Salmon P. Fixed drug eruption to paraceta- Increased sweating 5 mol. NZMedJ1994;107:295–6. Hypotension/faintness 4 6 Kalyoncu AF. Acetaminophen hypersensitivity and other Syncope 3 analgesics (letter). Ann Allergy 1994;72:285. Anaphylactoid reactions 3 7 Doan T, Greenburger PA. Nearly fatal episodes of hypoten- Flushing 1 sion, flushing and dyspnoea in a 47 year old woman. Ann Stridor 1 Allergy 1993;70:439–44. Allergic reactions 1 8 Matheson I, Lunde PKM, Notorianni L. Infant rash caused by paracetamol in breast milk? (letter). Pediatrics 1985;76: Note: 651. 9 Stricker BHCH, Meyboom RHB, Linquist TM. Acute 1. Several reports described combinations of above features in hypersensitivity reactions to paracetamol. BMJ 1985;291: the same individual. 938–9. 2. Description of adverse reactions listed is based on name given 10 Thomas RHM, Munro DD. Fixed drug eruption due to in actual reports. paracetamol. Br J Dermatol 1986;115:357–9.

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