Anaphylactic Reaction to Oral Cefaclor in a Child ABSTRACT. Adverse drug reactions are a common diphenhydramine. He did not have any associated respiratory clinical problem. It has been estimated1 that 6% to 15% of symptoms, hypotension, or gastrointestinal symptoms. He had hospitalized patients experience some sort of adverse been treated with cefaclor on two previous additional occasions, drug reaction. Clinical manifestations of adverse drug without adverse reaction. Two months later, the patient redeveloped otitis media, and reactions include skin rash; a serum sickness-like reac- unfortunately, ignorant to the previous reaction, cefaclor was tion; drug fever; pulmonary, hepatic, and renal involve- prescribed. Thirty seconds after ingesting the first dose of the ment; and systemic anaphylaxis. Many of these adverse drug, he developed a severe systemic reaction comprised of vom- events are not immunologically mediated. Actual allergic iting, generalized hives, shortness of breath, and wheezing with or immunologic drug reactions probably account for grunting. He lost consciousness on the way to the local hospital. <25% of adverse drug reactions overall.1 The patient was not on any other medication at this time. He was Antibiotics are one of the major contributors to drug treated on arrival with subcutaneous epinephrine, intravenous hypersensitivity. Cefaclor, an oral second-generation diphenhydramine, intravenous fluids, and inhaled salbutamol cephalosporin with a b-lactam ring, is used against var- with oxygen. He was noted to have tachypnea (60 breaths/ minute); however, his blood pressure was unreported. He was ious infectious diseases of the respiratory tract, especially observed for 24 hours and discharged from the hospital in stable in children. Several cases of cefaclor hypersensitivity condition. Acute serum tryptase and urinary leukotriene E4 levels 2,3 have been reported. The most common presentations were not measured. are either erythematous or papular eruptions, although Subsequently we tested the patient for penicillin and cefaclor. serum sickness-like reactions have also been described. All penicillin tests were negative, including the epicutaneous, Anaphylactic reactions, although rare, have been ob- intradermal, and oral challenges. However, epicutaneous prick served in adults. Here we report a case of anaphylactic testing with histamine revealed a wheal-and-flare reaction of a 5 3 1 5 mm induration; and there was an 8 3 10 mm induration at the reaction to cefaclor in a 2 ⁄2-year-old patient. Pediatrics 1999;103(4). URL: http://www.pediatrics.org/cgi/content/ site of the cefaclor epicutaneous test. Epicutaneous and intrader- e mal testing with cefuroxime, cefazolin, and ceftazidime were also full/103/4/ 50; anaphylaxis, cefaclor, penicillin, cephalos- negative. A simultaneous cefaclor skin test on a control, whom porine, case report. was noted to be an atopic individual, was negative. METHODS efaclor, in a 1-mg/mL solution, was used for DISCUSSION epicutaneous prick testing. We also used ce- Hypersensitivity to cefaclor has been recognized Cfuroxime, cefazolin, and ceftazidime in a 2.5- since its early clinical introduction. In 1981, Kammer4 mg/mL solution for testing. A solution of phos- reviewed more than 3000 adult and pediatric pa- phate-buffered physiologic saline at pH 7.4 with tients treated with cefaclor and found an incidence of 0.4% phenol was used for negative control. For pos- hypersensitivity of 1.1%. Rash and diffuse pruritus itive control, we used histamine 1/200 in water were the most common findings. In 1980, McLinn5 (Bencard Allergy Laboratories, Mississauga, Ontario, reviewed the efficacy of cefaclor in the treatment of Canada). otitis media and noted no serious adverse reactions, We performed a battery of penicillin prick, intra- except for one case of vascular purpura. This oc- dermal, and oral challenge tests. As major determi- curred during the sixth day of treatment of a 5-year- nants, we used penicillin G at 1000 U/mL and 100 old boy with otitis media, who was taking cefaclor, U/mL, and benzylpenicilloyl polylysine 6 3 1025 M 250 mg, three times a day. Other reports suggested a (Pre-Pen; Richmond Pharmaceuticals, Richmond serum sickness-like syndrome, with symptoms in- Hill, Ontario, Canada). For minor determinants, we cluding malaise, fever, cutaneous eruption, and ar- used penicilloate and penicilloate sodium 10 mM. thralgias.6–8 For oral challenge, 250 mg of penicillin G was given. Penicillin remains the most common cause of The patient’s parent gave consent for us to carry out drug-induced anaphylaxis. It has been estimated2 the tests, which were done according to the guide- that nearly 75% of fatal anaphylactic reactions result lines of our hospital ethics board. from the administration of penicillin. Anaphylaxis because of cefaclor is rare. Nishioka and colleagues3 CASE REPORT described 3 adult patients who developed urticarial A 27-month-old, nonatopic, white boy, previously healthy, was rashes with asphyxiation immediately after an ad- referred to our allergy/adverse drug reaction service for assess- ministration of cefaclor. In 1988, Hama and Mori9 ment of his anaphylactic reaction to cefaclor. reported 4 adults with anaphylactic reactions. But At the age of 2 years, he developed generalized hives 1 day after ingesting cefaclor suspension for otitis media. The eruption never before were similar reactions reported in the was pruritic. The rash resolved the same day, after one dose of pediatric age group. We report a case of anaphylaxis to cefaclor in a child who developed urticarial rash, vomiting, respi- Received for publication May 15, 1998; accepted Nov 16, 1998. ratory distress, and loss of consciousness immedi- Reprint requests to (C.M.R.) Hospital for Sick Children, Division of Immu- nology/Allergy, 555 University Ave, Toronto, Ontario, M5G 1X8, Canada. ately after cefaclor ingestion, requiring immediate PEDIATRICS (ISSN 0031 4005). Copyright © 1999 by the American Acad- treatment. This reaction to cefaclor is most likely to emy of Pediatrics. be IgE-mediated, which was confirmed by a strongly http://www.pediatrics.org/cgi/content/full/103/4/Downloaded from www.aappublications.org/newse50 by guestPEDIATRICS on September Vol. 26, 2021 103 No. 4 April 1999 1of2 positive epicutaneous prick test. Because the break- Masoud Grouhi, MD down products of cefaclor are unknown, in vitro David Hummel, MD testing for this drug was not done. However, the Chaim M. Roifman, MD positive epicutaneous test is indicative of IgE in- University of Toronto volvement. Furthermore these IgE antibodies are Department of Paediatrics, Division of Immunology/ more likely to be side chain specific to cefaclor be- Allergy Hospital for Sick Children cause our patient did not show any reaction to other Toronto, Ontario, Canada M5G 1X8 cephalosporins including cefuroxime, cefazolin, and ceftazidime. Our patient gradually developed hypersensitivity REFERENCES to cefaclor; his first three exposures to cefaclor were 1. Patterson R, Anderson J. Allergic reactions to drugs and biologic agents. without significant reactions. This presentation is un- JAMA. 1982;248:2637–2645 usual compared with anaphylaxis from penicillin, 2. Shelter AL. Anaphylaxis. J Allergy Clin Immunol. 1985;75:227–233 3. Nishioka K, Katayama I, Kobayashi Y, Takijiri C. Anaphylaxis due to which usually appears after the first or second expo- cefaclor hypersensitivity. J Dermatol. 1986;13:226–227 sure. There is a risk of cross-reactivity between pen- 4. Kammer RB. Cefaclor in management of streptococcal pharyngitis, icillin and cephalosporins, occurring in 4% to 15% of otitis media, and skin infections. Ann Otol Rhinol Laryngol. 1981;90: cases10–12; therefore, most clinicians avoid cephalo- 79–81 sporins for patients with a history of immediate re- 5. McLinn SE. Cefaclor in the treatment of otitis media and pharyngitis in 12 children. Am J Dis Child. 1980;134:560–563 actions to a penicillin. In our patient penicillin test- 6. Lawley TJ, Frank MM. Immune complexes and allergic diseases. In: ing (including oral administration of penicillin was Middleton E, Reed CE, Ellis EF, Adkinson NF, eds. Allergy: Principles negative). and Practice. St Louis, MO: CV Mosby Co; 1993:990–1006 7. Murray DL, Singer DA, Singer AB. Cefaclor: a cluster of adverse reac- CONCLUSION tions. N Engl J Med. 1980;303:1003 8. Swedish Adverse Drug Reaction Advisory Committee. Hypersensitiv- In summary, we report a case of an anaphylactic ity reactions to cefaclor. Bull SADRAC. 1986;47:2–3 reaction to cefaclor in the pediatric population. Be- 9. Hama R, Mori K. High incidence of anaphylactic reaction to cefaclor. cause cefaclor is widely used in children for common Lancet. 1988;1:1331 infections such as otitis media, we will likely see 10. Anderson JA. Cross-sensitivity to cephalosporins in patients allergic to more cases of anaphylactic reaction to this antibiotic. penicillin. Pediatr Infect Dis J. 1986;5:557–561 11. Levine BB. Antigenicity and cross-reactivity of penicillin and cephalo- Physicians should anticipate the possibility of ana- sporins. J Infect Dis. 1973;128:S364–S366 phylactic reaction in children treated with this agent, 12. Lin RY. A perspective on penicillin allergy. Arch Intern Med. 1992;152: particularly in cases of multiple exposure. 930–937 2of2 ANAPHYLACTICDownloaded REACTION from TOwww.aappublications.org/news ORAL CEFACLOR IN by A guest CHILD on September 26, 2021 Anaphylactic Reaction to Oral Cefaclor in a Child Masoud Grouhi, David Hummel