Aminopenicillin Allergy Arch Dis Child: First Published As 10.1136/Adc.76.6.513 on 1 June 1997

Archives of Disease in Childhood 1997;76:513–517 513 Aminopenicillin allergy Arch Dis Child: first published as 10.1136/adc.76.6.513 on 1 June 1997. Downloaded from A Romano, D Quaratino, G Papa, M Di Fonso, A Venuti Abstract drug has been started, are not associated with Eighty two children with histories of IgE antibodies, and do not appear to predis- maculopapular or urticarial rashes dur- pose the patient to urticarial reactions.1 Over ing aminopenicillin treatment underwent the last decade, however, various investigators skin tests, patch tests, radioallergosorbent have come to the conclusion that these rashes assays and, in some cases, oral challenges. often represent type IV (cell mediated) hyper- Hypersensitivity was diagnosed in eight sensitivity, which is associated with patch test (9.8%): immediate in four with urticarial and/or delayed (that is six or more hours after reactions and delayed (that is cell medi- administration) intradermal test positivity.8–13 ated) in four with maculopapular rashes. In some cases, tested skin has been biopsied In 49 children (38 with maculopapular and found to present histological features simi- eruptions, 11 with urticarial/angiooede- lar to those of allergic contact dermatitis,9–13 matous reactions), negative allergologic and oral challenges with the suspected drug findings were confirmed using oral chal- have provoked delayed onset skin rashes.9101213 lenges with the suspected drug. Maculo- This approach has proved to be capable of papular rashes may reflect delayed detecting delayed forms of aminopenicillin hypersensitivity to aminopenicillins, hypersensitivity even when several years have which can be diagnosed on the basis of late elapsed since the last exposure to the drug.12 intradermal reactions and/or patch test Nevertheless, in many other cases of amino- positivity. The allergen panel must include penicillin associated maculopapular rashes the suspected aminopenicillin itself, as there is no evidence of immune mediated many cases are side chain specific. Most mechanisms of any type, and challenges with patients with urticarial reactions (more the suspected aminopenicillin are well typical of immediate hypersensitivity) will tolerated.12 14 also react to penicilloyl polylysine and The present study was conducted to deter- minor determinant mixture. The time mine the incidence of true allergy in a group of elapsed between the reaction and testing children with histories of cutaneous eruptions must be considered if negative results during aminopenicillin treatment. emerge, because IgE mediated sensitivity http://adc.bmj.com/ (unlike cell mediated forms) declines in Patients and methods the absence of antigen exposure. This study included all children with histories (Arch Dis Child 1997;76:513–517) of adverse cutaneous reactions to aminopenicillins seen by our staV between January 1990 Keywords: aminopenicillins; hypersensitivity; maculopapular rash and December 1995. The following allergologic investigations were performed. on September 23, 2021 by guest. Protected copyright. Many patients who develop rashes, urticaria, or other skin symptoms during â-lactam treat- (1) PRICK AND INTRADERMAL SKIN TESTS ment are automatically labelled ‘allergic to These were done using: penicillin’, and subsequent use of these antibi- (A) Penicilloyl polylysine (PPL) (Allergo- otics is avoided, even if they appear to be the pen; Reinbeck, Germany). The undiluted solu- drugs of choice for treatment of serious tion was obtained by reconstituting the infections. Urticaria (or hives), which is one of lyophilised contents of a vial containing 0.175 the classic manifestations of type I (or IgE mg PPL plus 20 mg mannitol in 5 ml buVer. A Institute of Internal and Geriatric mediated) hypersensitivity in general, occurs in 1:10 dilution of this solution in 0.9% sodium Medicine, Catholic 4.5% of patients treated with penicillin or its chloride (NaCl) was initially used. When University of St Cuore, analogues.1 However, many patients who have results were negative, testing was repeated with Rome, Italy experienced urticarial reactions to â-lactams the undiluted solution. A Romano prove to be skin test negative for the major and (B) Minor determinant mixture (MDM) D Quaratino minor penicillin determinants, and in many (Allergopen), containing 0.6 mg benzylpenicil- G Papa M Di Fonso cases subsequent administration of penicillin lin and 0. 5 mg benzylpenicilloate/ml, initially 2–4 A Venuti or the suspected drug is well tolerated. diluted 1:10 000 in 0.9% NaCl. Tests were Maculopapular or morbilliform rashes are repeated with a 1:10 dilution when initial Correspondence to: even more common during treatment with results were negative. Dr Antonino Romano, 5–7 Ambulatorio di Allergologia, these drugs, particularly ampicillin. The (C) Potassium penicillin G (Bristol Italiana; Complesso Integrato incidence of morbilliform rashes during Sermoneta, Italy), diluted in 0.9% NaCl and Columbus, Via della Pineta therapy with the latter drug has been estimated administered at increasing concentrations Sacchetti 506, 00168 Rome, at 9.5%.1 Until recently, these rashes were ranging from 0.1 IU/ml to 10 000 IU/ml. Italy. thought to be late, idiopathic drug reactions. (D) Ampicillin (Amplital, Farmitalia; Milan, Accepted 13 January 1997 They usually appear 2–3 days or more after the Italy) and amoxycillin (Velamox, Zambeletti; 514 Romano, Quaratino, Papa, Di Fonso, Venuti Table 1 Clinical manifestations described by subjects studied and results of allergologic adverse cutaneous reactions to aminopenicil- tests lins. In over 90% of the cases, the antibiotic had Arch Dis Child: first published as 10.1136/adc.76.6.513 on 1 June 1997. Downloaded from been prescribed to treat upper respiratory tract No of patients No with immediate No with delayed Symptoms studied hypersensitivity* hypersensitivity† infections. Our investigation was performed at a mean (SD) 30.6 (28.4) months (range Maculopapular rash 42 – 4 Urticaria 29 2 – 1–120) after the most recent drug exposure. Angio-oedema 4 1 – Sixty one of the 82 children (74.4%) had Urticaria/angio-oedema 2 – – reportedly reacted to amoxycillin (in three Urticaria/angio-oedema and dyspnoea 1 1 – cases administered with clavulanic acid), 17 Erythema 4 – – (20.7%) had reacted to ampicillin (bacampicil- * Immediate hypersensitivity diagnosed on the basis of skin tests and RAST. lin in one case, ampicillin plus sulbactam in † Delayed hypersensitivity diagnosed on the basis of delayed intradermal reactivity and patch tests. another), and four had experienced reactions to more than one aminopenicillin (ampicillin Milan, Italy), both used at concentrations of 1 and amoxycillin in three cases, ampicillin and mg/ml and 20 mg/ml, after dilution in 0.9% bacampicillin in one). Thirteen (15.85%) had NaCl. also reacted to cephalosporins. All haptens were initially tested on the volar The reactive manifestations (based on par- forearm skin using the prick technique. Reac- ents’ descriptions and, in some cases, paediatri- tions were considered positive when a weal >3 cians’ reports) are summarised in table 1. In mm in diameter appeared within 15–20 81/82 cases, the symptoms had been exclu- minutes. When negative results were observed, sively cutaneous; the remaining child had 0.02 ml of the hapten solution was injected experienced both cutaneous and respiratory intradermally, and readings were made at 20 symptoms. Forty two of the children had minutes and 48 hours. Results were defined as suVered maculopapular reactions, 36 had positive when weals of >5 mm appeared. Posi- experienced urticaria/angio-oedema, and four tive controls for prick and intradermal tests had developed diVuse erythematous reactions. were performed with histamine (10 mg/ml and On the basis of these tests, four of the 82 1 mg/ml, respectively); normal saline was used children (4.9%) were diagnosed as having as a negative control. immediate hypersensitivity. All four had experienced their most recent reaction less than one (2) PATCH TESTS year before testing. Two had experienced urti- These were administered with (a) penicillin G carial reactions, one had developed angio- (5000 IU/g Vaseline), (b) ampicillin (5% in oedema, and the fourth had reacted with urti- Vaseline), and (c) amoxycillin (5% in Vaseline). caria, angio-oedema, and dyspnoea. In all four The patches were applied to the interscapular cases, the onset of symptoms had occurred region of the back and evaluated according to within one hour of the initial administration of the criteria of Wilkinson et al after 48 and 72 the drug and the rash had persisted for hours.15 approximately 24 hours after the antibiotic had http://adc.bmj.com/ been withdrawn and antihistaminic and steroid (3) RADIOALLERGOSORBENT TESTS (RASTS) treatment started. Two of these four children In vitro assays for antigen specific IgE to peni- presented skin test positivity for all of the aller- cilloyl G, penicilloyl V, ampicillin, and amoxy- gens tested, the third was positive for PPL and cillin were performed using the Phadebas penicillin G, and the fourth reacted only to RAST (Pharmacia; Uppsala, Sweden). penicillin G. RASTs were negative in 3/4; the (4) ORAL CHALLENGES fourth was positive for penicilloyls G and V. These were performed only in negative cases, Thirty six other children with histories of on September 23, 2021 by guest. Protected copyright. on children with histories of either maculopa- urticarial/angio-oedematous or diVuse ery- pular reactions or erythematous or urticarial/ thematous

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