- Email: [email protected]
Drug eruptions in children with ENT infections
International Journal of Pediatric Otorhinolaryngology (2006) 70, 53—57
www.elsevier.com/locate/ijporl
Drug eruptions in children with ENT infections Efstathios Rallis a, Dimitrios G. Balatsouras b,*, Constantinos Kouskoukis c, Constantinos Verros a, Elias Homsioglou d a
Department of Dermatology of 401 General Military Hospital of Athens, 1 Kanelopoulou Street — Papagos, GR-11525 Athens, Greece b ENT Department of Tzanion General Hospital, 11 Zani & Afentouli Street, GR-18536 Piraeus, Greece c Department of Dermatology, Demokrition University of Thrace, 6 Ioacim Kavyri Street, GR-68100 Alexandroupolis, Greece d ENT Clinic of 492 Military Hospital of Alexandroupolis, 31 Venizelou Street, GR-68100 Alexandroupolis, Greece Received 19 March 2005; accepted 11 May 2005
KEYWORDS Drug eruptions; Cutaneous drug reactions; ENT infections
Summary Objective: A common problem for the clinician in an outpatient clinic is to distinguish a drug eruption from a viral exanthem in a child. The aim of this study was to describe the common drug eruptions seen in children with ENT infections, suggesting an approach to this problem. Methods: We studied the cases of ENT patients aged 15-years-old and below, with the clinical diagnosis of cutaneous adverse reactions. Main variables in the assessment of drug etiology in skin eruptions were previous experience with the drug in the general population, alternative explanation for the eruption, timing between the ingestion of the drug and the appearance of the lesions, drug levels or evidence of overdose or longacting drug, subsequent progression of the eruption and reactions to dechallenge and rechallenge. Results: A total of 47 children were examined during a period of 11 months. The indications for drug prescribed were tonsillitis, pharyngitis, rhinitis, otitis and sinusitis. The most usually implicated drugs were amoxycillin-clavulanic acid, cephalosporin, clindamycin, erythromycin, clarithromycin and paracetamol. The main clinical patterns of the eruptions seen were urticaria, maculopapular rash, fixed drug eruption and erythema multiforme. Conclusions: Careful clinical examination, detailed history, knowledge of the numerous clinical patterns of the eruptions and the drugs specific reaction rates, as well as oral drug rechallenge, RAST and patch tests if indicated, are essential factors in the management of patients with drug eruptions. # 2005 Elsevier Ireland Ltd. All rights reserved.
* Corresponding author. Present address: 23 Achaion Street — Ag. Paraskevi, GR-15343 Athens, Greece. Tel.: +30 210 600 4683; fax: +30 210 4592 671. E-mail address: [email protected] (D.G. Balatsouras). 0165-5876/$ — see front matter # 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijporl.2005.05.012
54
E. Rallis et al.
1. Introduction
3. Results
An adverse cutaneous drug reaction may be defined as an undesirable manifestation of the skin resulting from administration of a particular drug; this includes reactions due to overdose, predictable side-effects and unanticipated adverse manifestations [1]. There have been several studies of the incidence of drug reactions, but only a few in the pediatric population [2—5]. A drug eruption is a frequent diagnostic problem for the clinician in an outpatient clinic and commonly it has to be differentiated from a viral exanthem, especially in a diseased child [6]. The purpose of this study was to evaluate the druginduced reaction patterns seen among children presenting with various ear, nose, and throat (ENT) infections, suggesting an approach to this problem in the pediatric population.
Forty-seven children were examined during a period of 1-year. Twenty four of them were male and 23 female, with mean age at the time of diagnosis 9.1 years (range 6 months to 15 years). Indications for drugs prescribed were tonsillitis (36%), pharyngitis (23%), rhinitis (19%), otitis (14%), and sinusitis (8%). Implicated drugs included amoxycillin and clavulanic acid, cephalosporins, clindamycin, erythromycin, clarithromycin and paracetamol. Four clinical patterns of skin eruptions were recognized: maculopapular rash, urticaria (Fig. 1), fixed drug eruption, and erythema multiforme (Fig. 2). Occurrences of the pattern of skin rash according to the administered drug are shown in Table 1. The onset of the eruptions occurred in 40 of 47 patients (85.1%), within the first 8 days of the drug intake. In the remaining seven cases the eruptions appeared after the completion of the therapy and involved six patients with maculopapular rash and the child with erythema multiforme. In all patients, apart from skin eruptions no other symptoms or signs were associated with the medication administered for the ENT infections. None of the children was needed to be hospitalized because of the drug eruption. The cutaneous adverse reactions were treated with the cessation of the implicating drug (usually antibiotic) and the administration of another medication from a different drug category, in conjunction with oral antihistamines and topical corticosteroids. Only in one
2. Patients and methods This was a prospective study of 62 young patients consecutively treated in an outpatient setting, who presented with ENT infections and were, also, clinically diagnosed as having cutaneous adverse reactions. All of the patients were ambulatory and in all cases, the appropriate drugs had been adimistered orally. We excluded from the study patients in whom no medication was given, patients older than 15 years old, patients with eruption compatible with a viral exanthem and patients with rash that preceded the intake of any medication for the infection. Forty seven cases in total were finally available for evaluation during this study, which took place between December 2000 and November 2001. Additional data, collected from the subjects, were age, sex, implicated drugs, indication of use, time of onset, morphology, distribution and duration of the rash, withdrawal of the rash and assessment of probability. Main variables in the assessment of drug etiology in skin eruptions [6] were previous experience with the drug in the general population, alternative explanation for the eruption, time elapsed between drug intake and appearance of the lesions, drug levels or evidence of overdose or long-acting drug, subsequent progression of the eruption and reactions to dechallenge and rechallenge. The type of skin eruption in each patient was recorded. None of the patients underwent any laboratory tests, including radio-allergosorbent tests (RAST), during this study.
Fig. 1 Urticaria involving the trunk of a 14-year-old male, caused from treatment of acute sinusitis by amoxycilline-clavulanic acid.
Drug eruptions in children with ENT infections
55
Fig. 2 Erythema multiforme at the hands of a 9-year-old child owed to treatment of acute otitis media by cephalosporine.
case, the patient with erythema multiforme, treatment included oral administration of corticosteroids (methylprednizolone 20 mg) with gradual taper off.
4. Discussion Cutaneous drug reactions, apart from fixed drug eruption, have non specific clinical features and it is often impossible to identify the implicated drug with certainty, especially when a patient with a suspected reaction is receiving many drugs simultaneously [7]. Drug eruptions may be mistaken for naturally occurring conditions and may, therefore, be overlooked. A similar problem encountered by the clinician is to establish the diagnosis of drug eruption in a diseased child with a rash. In our study, history and physical examination were the most important tools in the assessment process. Assessment of probability of whether a given drug is responsible for a drug reaction necessitates a careful physical examination, information of the drugs intake and may involve drug elimina-
tion, as well as, in vitro and rechallenge tests. Skin tests, including prick and patch testing, are for the most part unreliable and probably hazardous [7,8]. In vitro tests are only applicable to real allergic reactions [7]. Drug challenge test is often not possible due to ethical and safety considerations [9]. Therefore, we avoided these three parameters for the assessment process and we used only the variables already mentioned. As expected, the most common indications for the prescription of the drugs were upper respiratory tract infections and the usually implicated drugs were antibiotics. Maculopapular eruptions were the most frequent pattern of cutaneous drug reaction seen, accounting for more than half of the cases. The rash involved mainly the trunk and extremities, symmetrically. In three patients, an erosive stomatitis was observed. The onset of the eruption occurred, in the majority of the patients, early in the course of treatment, but it has been reported that the rash may appear anytime between the first day and 3 weeks [6]. Exanthematic reactions are said to be the most common of all drug-induced cutaneous eruptions [7] and this is in agreement with the results reported in the Boston Collaborative Drug Surveillance Program [10]. Amoxycillin with clavulanic acid was the most commonly implicated drug in our study, followed by cephalosporin, which are in accordance with previous reports [5,6]. The second most common type of drug reaction was urticaria, accounting for almost 40/% of our patients. Urticaria is defined as an exanthematous eruption of transient, pruritic, edematous papules lasting less than 24 h and occurring within 36 h of drug administration [1,7]. In the majority of the cases, its onset was within the first 24 h of the administration of the drug. Urticaria is reported as the second most frequent exanthematous eruption in general [7,11] and this agrees, also, with our study, although its occurrence may vary in different settings [5,6]. Amoxycillin with clavulanic acid was, again, the most commonly implicated drug in our patients.
Table 1 Implicated drugs and drug reaction pattern Drugs
Patients (N = 47)
Maculopapular rash
Urticaria
Fixed drug eruption
Amoxicillin-clavulanic acid Cephalosporin Clindamycin Erythromycin Clarithromycin Paracetamol
18 (38.2%) 13 (27.6%) 7 (14.8%) 5 (10.9%) 2 (4.2%) 2 (4.2%)
9 8 5 1 1 1
7 4 2 3 1 1
2
Total
47 (100%)
25 (53.2%)
18 (38.3%)
3 (6.4%)
Erythema multiforme 1
1
1 (2.1%)
56
The third type of skin rash, fixed eruptions, usually develops 30 min to 8 h after exposure to the suspected drug. Lesions may be solitary initially, but after re-administration of the same drug, new lesions may appear and the existing lesions may increase in size [12,13]. Commonly involved sites are the extremities, genitalia, perianal, periorbital and perioral areas. A vast number of drugs can produce fixed drug eruptions, including trimethoprim-sulphamethoxazole, tetracyclines and analgesics [14]. In our study, the suspected drugs were amoxycillin with clavulanic acid in two cases and erythromycin in another one. A single case of erythema multiforme observed in one of our patients was attributed to cephalosporin. This drug was implicated in 59% of erythema multiforme patients and 68% of cases with Stevens-Johnson syndrome patients [15,16]. Other commonly implicated drugs include sulphonamides, barbiturates and pyrazolone derivatives [17]. Erythema multiforme is a well-recognized eruption characterized clinically by macular, papular, urticarial and ‘‘target’’-like lesions, which are distributed preferentially on the distal extremities and may involve the palms, the trunk, and the oral and genital mucous membranes. It is usually precipitated by a variety of infections, with only 10% of the cases being drug-related and its pathogenesis still remains obscure [7,17]. The issue of the underlying mechanisms responsible for the various drug reactions should be briefly mentioned. Drug reactions may arise as a result of immunological drug allergy or more commonly by non-immunological mechanisms and have been classified into four types [18,19]. Most commonly type A drug reactions occur, which are predictable, usually dose-related, are met in otherwise healthy individuals and are a function of the known pharmacological actions or metabolism of the drug. Unpredictable reactions (type B reactions) are uncommon, do not have an allergic pathogenesis, are not related to the pharmacological action of the drug and may have a genetic basis. Type C reactions are rare, immunologically mediated and develop as a consequence of previous exposure to the drug with resultant allergy. Finally, type D consists of delayed reactions (e.g. carcinogenesis, teratogenicity). Unfortunately, an extensive work-up is needed to define the pathogenetic mechanisms responsible for drug eruptions in each case, and currently, in most settings patients are usually treated based on history and physical findings only, as in the present study. It should be, finally, noted that extreme caution should be given in differentiating exanthematic drug eruptions from viral rashes, especially in chil-
E. Rallis et al.
dren. Viral exanthems may initiate on the face and progress to involve the trunk and are most often accompanied by conjunctivitis, lymphadenopathy and fever. Careful clinical examination, detailed history, knowledge of the numerous clinical patterns of the eruptions and the drugs specific reaction types, as well as, occasionally, oral drug rechallenge, RAST and patch tests if indicated, are essential factors in the management of children with drug eruptions.
References [1] S.M. Breathnach, H. Hintner, Introduction and incidence of drug reactions, in: S.M. Breathnach, H. Hintner (Eds.), Adverse Drug Reactions and the Skin, first ed., Blackwell Science Inc, London, 1992, pp. 3—13. [2] K. Kubota, N. Kubota, G.L. Pearce, P. Prescott, R.D. Mann, Signalling drug-induced rash with 36 drugs recently marketed in the United Kingdom and studied by prescriptionevent monitoring, Int. J. Clin. Pharmacol. Ther. 33 (1995) 219—225. [3] K.A. Arndt, H. Jick, Rates of cutaneous reactions to drugs. A report from the Boston Collaborative Drug Surveillance Program, JAMA 235 (1976) 918—923. [4] K. Kauppinen, S. Stubb, Drug eruptions: causative agents and clinical types. A series of in-patients during a 10-yearperiod, Acta Derm. Venereol. 64 (1984) 320—324. [5] V.K. Sharma, S. Dhar, Clinical pattern of cutaneous drug eruption among children and adolescents in North India, Pediatr. Dermatol. 12 (1995) 178—183. [6] B.P. Khoo, Y.C. Giam, Drug eruptions in children: a review of 111 cases seen in a tertiary skin referral center, Singapore Med. J. 41 (2000) 525—529. [7] S.M. Breathnach, Drug reactions, in: R.H. Champion, J.L. Burton, D.A. Burns, S.M. Breathnach (Eds.), sixth ed., Rook/ Wilkinson/Ebling Textbook of Dermatology, vol. 3, Blackwell Science, London, 1998, pp. 3340—3517. [8] D. Bruynzeel, W.G. van Ketel, Patch testing in drug eruptions, Semin. Dermatol. 8 (1989) 196—203. [9] P. Mortureux, C. Leaute-Labreze, V. Legrain-Lifermann, T. Lamireau, J. Sarlangue, A. Taieb, Acute urticaria in infancy and early childhood: a prospective study, Arch. Dermatol. 134 (1998) 319—323. [10] M. Bigby, S. Jick, H. Jick, K. Arndt, Drug-induced cutaneous reactions. A report from the Boston Collaborative Drug Surveillance Program on 15,438 consecutive inpatients, 1975 to 1982, JAMA 256 (1986) 3358—3363. [11] V. Legrain, A. Taieb, T. Sage, J. Maleville, Urticaria in infants: a study of 40 patients, Pediatr. Dermatol. 7 (1990) 101—107. [12] W. Korkij, K. Soltani, Fixed drug eruption. A brief review, Arch. Dermatol. 120 (1984) 520—524. [13] V.N. Sehgal, O.P. Gangwani, Fixed drug eruptions. Current concepts, Int. J. Dermatol. 26 (1987) 67—74. [14] T.P. Thankappan, J. Zachariah, Drug-specific clinical pattern in fixed drug eruptions, Int. J. Dermatol. 30 (1991) 867—870. [15] J.R. Nethercott, B.C. Choi, Erythema multiforme (StevensJohnson syndrome) — chart review of 123 hospitalized patients, Dermatologica 171 (1985) 383—396. [16] M.G. Stewart, NO. Duncan III, D.J. Franklin, E.M. Friedman, M. Sulek, Head and neck manifestations of erythema multi-
Drug eruptions in children with ENT infections
forme in children, Otolaryngol. Head Neck Surg. 111 (3 Pt 1) (1994) 236—242. [17] J.C. Huff, W.L. Weston, M.G. Tonnesen, Erythema multiforme: a critical review of characteristics, diagnostic criteria and causes, J. Am. Acad. Dermatol. 8 (1983) 763—765. [18] S.M. Breathnach, H. Hintner, Classification and mechanisms of drug reactions, in: S.M. Breathnach, H. Hintner (Eds.),
57
Adverse Drug Reactions and the Skin, first ed., Blackwell Science Inc, London, 1992, pp. 14—38. [19] P.H. McKee, E. Calonje, S.R. Granter, Cutaneous adverse reactions to drugs, in: P.H. McKee, E. Calonje, S.R. Granter (Eds.), third ed., Pathology of the Skin with Clinical Correlations, vol. I, Elsevier-Mosby, Boston, 2005, pp. 623— 672.
www.elsevier.com/locate/ijporl
Drug eruptions in children with ENT infections Efstathios Rallis a, Dimitrios G. Balatsouras b,*, Constantinos Kouskoukis c, Constantinos Verros a, Elias Homsioglou d a
Department of Dermatology of 401 General Military Hospital of Athens, 1 Kanelopoulou Street — Papagos, GR-11525 Athens, Greece b ENT Department of Tzanion General Hospital, 11 Zani & Afentouli Street, GR-18536 Piraeus, Greece c Department of Dermatology, Demokrition University of Thrace, 6 Ioacim Kavyri Street, GR-68100 Alexandroupolis, Greece d ENT Clinic of 492 Military Hospital of Alexandroupolis, 31 Venizelou Street, GR-68100 Alexandroupolis, Greece Received 19 March 2005; accepted 11 May 2005
KEYWORDS Drug eruptions; Cutaneous drug reactions; ENT infections
Summary Objective: A common problem for the clinician in an outpatient clinic is to distinguish a drug eruption from a viral exanthem in a child. The aim of this study was to describe the common drug eruptions seen in children with ENT infections, suggesting an approach to this problem. Methods: We studied the cases of ENT patients aged 15-years-old and below, with the clinical diagnosis of cutaneous adverse reactions. Main variables in the assessment of drug etiology in skin eruptions were previous experience with the drug in the general population, alternative explanation for the eruption, timing between the ingestion of the drug and the appearance of the lesions, drug levels or evidence of overdose or longacting drug, subsequent progression of the eruption and reactions to dechallenge and rechallenge. Results: A total of 47 children were examined during a period of 11 months. The indications for drug prescribed were tonsillitis, pharyngitis, rhinitis, otitis and sinusitis. The most usually implicated drugs were amoxycillin-clavulanic acid, cephalosporin, clindamycin, erythromycin, clarithromycin and paracetamol. The main clinical patterns of the eruptions seen were urticaria, maculopapular rash, fixed drug eruption and erythema multiforme. Conclusions: Careful clinical examination, detailed history, knowledge of the numerous clinical patterns of the eruptions and the drugs specific reaction rates, as well as oral drug rechallenge, RAST and patch tests if indicated, are essential factors in the management of patients with drug eruptions. # 2005 Elsevier Ireland Ltd. All rights reserved.
* Corresponding author. Present address: 23 Achaion Street — Ag. Paraskevi, GR-15343 Athens, Greece. Tel.: +30 210 600 4683; fax: +30 210 4592 671. E-mail address: [email protected] (D.G. Balatsouras). 0165-5876/$ — see front matter # 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijporl.2005.05.012
54
E. Rallis et al.
1. Introduction
3. Results
An adverse cutaneous drug reaction may be defined as an undesirable manifestation of the skin resulting from administration of a particular drug; this includes reactions due to overdose, predictable side-effects and unanticipated adverse manifestations [1]. There have been several studies of the incidence of drug reactions, but only a few in the pediatric population [2—5]. A drug eruption is a frequent diagnostic problem for the clinician in an outpatient clinic and commonly it has to be differentiated from a viral exanthem, especially in a diseased child [6]. The purpose of this study was to evaluate the druginduced reaction patterns seen among children presenting with various ear, nose, and throat (ENT) infections, suggesting an approach to this problem in the pediatric population.
Forty-seven children were examined during a period of 1-year. Twenty four of them were male and 23 female, with mean age at the time of diagnosis 9.1 years (range 6 months to 15 years). Indications for drugs prescribed were tonsillitis (36%), pharyngitis (23%), rhinitis (19%), otitis (14%), and sinusitis (8%). Implicated drugs included amoxycillin and clavulanic acid, cephalosporins, clindamycin, erythromycin, clarithromycin and paracetamol. Four clinical patterns of skin eruptions were recognized: maculopapular rash, urticaria (Fig. 1), fixed drug eruption, and erythema multiforme (Fig. 2). Occurrences of the pattern of skin rash according to the administered drug are shown in Table 1. The onset of the eruptions occurred in 40 of 47 patients (85.1%), within the first 8 days of the drug intake. In the remaining seven cases the eruptions appeared after the completion of the therapy and involved six patients with maculopapular rash and the child with erythema multiforme. In all patients, apart from skin eruptions no other symptoms or signs were associated with the medication administered for the ENT infections. None of the children was needed to be hospitalized because of the drug eruption. The cutaneous adverse reactions were treated with the cessation of the implicating drug (usually antibiotic) and the administration of another medication from a different drug category, in conjunction with oral antihistamines and topical corticosteroids. Only in one
2. Patients and methods This was a prospective study of 62 young patients consecutively treated in an outpatient setting, who presented with ENT infections and were, also, clinically diagnosed as having cutaneous adverse reactions. All of the patients were ambulatory and in all cases, the appropriate drugs had been adimistered orally. We excluded from the study patients in whom no medication was given, patients older than 15 years old, patients with eruption compatible with a viral exanthem and patients with rash that preceded the intake of any medication for the infection. Forty seven cases in total were finally available for evaluation during this study, which took place between December 2000 and November 2001. Additional data, collected from the subjects, were age, sex, implicated drugs, indication of use, time of onset, morphology, distribution and duration of the rash, withdrawal of the rash and assessment of probability. Main variables in the assessment of drug etiology in skin eruptions [6] were previous experience with the drug in the general population, alternative explanation for the eruption, time elapsed between drug intake and appearance of the lesions, drug levels or evidence of overdose or long-acting drug, subsequent progression of the eruption and reactions to dechallenge and rechallenge. The type of skin eruption in each patient was recorded. None of the patients underwent any laboratory tests, including radio-allergosorbent tests (RAST), during this study.
Fig. 1 Urticaria involving the trunk of a 14-year-old male, caused from treatment of acute sinusitis by amoxycilline-clavulanic acid.
Drug eruptions in children with ENT infections
55
Fig. 2 Erythema multiforme at the hands of a 9-year-old child owed to treatment of acute otitis media by cephalosporine.
case, the patient with erythema multiforme, treatment included oral administration of corticosteroids (methylprednizolone 20 mg) with gradual taper off.
4. Discussion Cutaneous drug reactions, apart from fixed drug eruption, have non specific clinical features and it is often impossible to identify the implicated drug with certainty, especially when a patient with a suspected reaction is receiving many drugs simultaneously [7]. Drug eruptions may be mistaken for naturally occurring conditions and may, therefore, be overlooked. A similar problem encountered by the clinician is to establish the diagnosis of drug eruption in a diseased child with a rash. In our study, history and physical examination were the most important tools in the assessment process. Assessment of probability of whether a given drug is responsible for a drug reaction necessitates a careful physical examination, information of the drugs intake and may involve drug elimina-
tion, as well as, in vitro and rechallenge tests. Skin tests, including prick and patch testing, are for the most part unreliable and probably hazardous [7,8]. In vitro tests are only applicable to real allergic reactions [7]. Drug challenge test is often not possible due to ethical and safety considerations [9]. Therefore, we avoided these three parameters for the assessment process and we used only the variables already mentioned. As expected, the most common indications for the prescription of the drugs were upper respiratory tract infections and the usually implicated drugs were antibiotics. Maculopapular eruptions were the most frequent pattern of cutaneous drug reaction seen, accounting for more than half of the cases. The rash involved mainly the trunk and extremities, symmetrically. In three patients, an erosive stomatitis was observed. The onset of the eruption occurred, in the majority of the patients, early in the course of treatment, but it has been reported that the rash may appear anytime between the first day and 3 weeks [6]. Exanthematic reactions are said to be the most common of all drug-induced cutaneous eruptions [7] and this is in agreement with the results reported in the Boston Collaborative Drug Surveillance Program [10]. Amoxycillin with clavulanic acid was the most commonly implicated drug in our study, followed by cephalosporin, which are in accordance with previous reports [5,6]. The second most common type of drug reaction was urticaria, accounting for almost 40/% of our patients. Urticaria is defined as an exanthematous eruption of transient, pruritic, edematous papules lasting less than 24 h and occurring within 36 h of drug administration [1,7]. In the majority of the cases, its onset was within the first 24 h of the administration of the drug. Urticaria is reported as the second most frequent exanthematous eruption in general [7,11] and this agrees, also, with our study, although its occurrence may vary in different settings [5,6]. Amoxycillin with clavulanic acid was, again, the most commonly implicated drug in our patients.
Table 1 Implicated drugs and drug reaction pattern Drugs
Patients (N = 47)
Maculopapular rash
Urticaria
Fixed drug eruption
Amoxicillin-clavulanic acid Cephalosporin Clindamycin Erythromycin Clarithromycin Paracetamol
18 (38.2%) 13 (27.6%) 7 (14.8%) 5 (10.9%) 2 (4.2%) 2 (4.2%)
9 8 5 1 1 1
7 4 2 3 1 1
2
Total
47 (100%)
25 (53.2%)
18 (38.3%)
3 (6.4%)
Erythema multiforme 1
1
1 (2.1%)
56
The third type of skin rash, fixed eruptions, usually develops 30 min to 8 h after exposure to the suspected drug. Lesions may be solitary initially, but after re-administration of the same drug, new lesions may appear and the existing lesions may increase in size [12,13]. Commonly involved sites are the extremities, genitalia, perianal, periorbital and perioral areas. A vast number of drugs can produce fixed drug eruptions, including trimethoprim-sulphamethoxazole, tetracyclines and analgesics [14]. In our study, the suspected drugs were amoxycillin with clavulanic acid in two cases and erythromycin in another one. A single case of erythema multiforme observed in one of our patients was attributed to cephalosporin. This drug was implicated in 59% of erythema multiforme patients and 68% of cases with Stevens-Johnson syndrome patients [15,16]. Other commonly implicated drugs include sulphonamides, barbiturates and pyrazolone derivatives [17]. Erythema multiforme is a well-recognized eruption characterized clinically by macular, papular, urticarial and ‘‘target’’-like lesions, which are distributed preferentially on the distal extremities and may involve the palms, the trunk, and the oral and genital mucous membranes. It is usually precipitated by a variety of infections, with only 10% of the cases being drug-related and its pathogenesis still remains obscure [7,17]. The issue of the underlying mechanisms responsible for the various drug reactions should be briefly mentioned. Drug reactions may arise as a result of immunological drug allergy or more commonly by non-immunological mechanisms and have been classified into four types [18,19]. Most commonly type A drug reactions occur, which are predictable, usually dose-related, are met in otherwise healthy individuals and are a function of the known pharmacological actions or metabolism of the drug. Unpredictable reactions (type B reactions) are uncommon, do not have an allergic pathogenesis, are not related to the pharmacological action of the drug and may have a genetic basis. Type C reactions are rare, immunologically mediated and develop as a consequence of previous exposure to the drug with resultant allergy. Finally, type D consists of delayed reactions (e.g. carcinogenesis, teratogenicity). Unfortunately, an extensive work-up is needed to define the pathogenetic mechanisms responsible for drug eruptions in each case, and currently, in most settings patients are usually treated based on history and physical findings only, as in the present study. It should be, finally, noted that extreme caution should be given in differentiating exanthematic drug eruptions from viral rashes, especially in chil-
E. Rallis et al.
dren. Viral exanthems may initiate on the face and progress to involve the trunk and are most often accompanied by conjunctivitis, lymphadenopathy and fever. Careful clinical examination, detailed history, knowledge of the numerous clinical patterns of the eruptions and the drugs specific reaction types, as well as, occasionally, oral drug rechallenge, RAST and patch tests if indicated, are essential factors in the management of children with drug eruptions.
References [1] S.M. Breathnach, H. Hintner, Introduction and incidence of drug reactions, in: S.M. Breathnach, H. Hintner (Eds.), Adverse Drug Reactions and the Skin, first ed., Blackwell Science Inc, London, 1992, pp. 3—13. [2] K. Kubota, N. Kubota, G.L. Pearce, P. Prescott, R.D. Mann, Signalling drug-induced rash with 36 drugs recently marketed in the United Kingdom and studied by prescriptionevent monitoring, Int. J. Clin. Pharmacol. Ther. 33 (1995) 219—225. [3] K.A. Arndt, H. Jick, Rates of cutaneous reactions to drugs. A report from the Boston Collaborative Drug Surveillance Program, JAMA 235 (1976) 918—923. [4] K. Kauppinen, S. Stubb, Drug eruptions: causative agents and clinical types. A series of in-patients during a 10-yearperiod, Acta Derm. Venereol. 64 (1984) 320—324. [5] V.K. Sharma, S. Dhar, Clinical pattern of cutaneous drug eruption among children and adolescents in North India, Pediatr. Dermatol. 12 (1995) 178—183. [6] B.P. Khoo, Y.C. Giam, Drug eruptions in children: a review of 111 cases seen in a tertiary skin referral center, Singapore Med. J. 41 (2000) 525—529. [7] S.M. Breathnach, Drug reactions, in: R.H. Champion, J.L. Burton, D.A. Burns, S.M. Breathnach (Eds.), sixth ed., Rook/ Wilkinson/Ebling Textbook of Dermatology, vol. 3, Blackwell Science, London, 1998, pp. 3340—3517. [8] D. Bruynzeel, W.G. van Ketel, Patch testing in drug eruptions, Semin. Dermatol. 8 (1989) 196—203. [9] P. Mortureux, C. Leaute-Labreze, V. Legrain-Lifermann, T. Lamireau, J. Sarlangue, A. Taieb, Acute urticaria in infancy and early childhood: a prospective study, Arch. Dermatol. 134 (1998) 319—323. [10] M. Bigby, S. Jick, H. Jick, K. Arndt, Drug-induced cutaneous reactions. A report from the Boston Collaborative Drug Surveillance Program on 15,438 consecutive inpatients, 1975 to 1982, JAMA 256 (1986) 3358—3363. [11] V. Legrain, A. Taieb, T. Sage, J. Maleville, Urticaria in infants: a study of 40 patients, Pediatr. Dermatol. 7 (1990) 101—107. [12] W. Korkij, K. Soltani, Fixed drug eruption. A brief review, Arch. Dermatol. 120 (1984) 520—524. [13] V.N. Sehgal, O.P. Gangwani, Fixed drug eruptions. Current concepts, Int. J. Dermatol. 26 (1987) 67—74. [14] T.P. Thankappan, J. Zachariah, Drug-specific clinical pattern in fixed drug eruptions, Int. J. Dermatol. 30 (1991) 867—870. [15] J.R. Nethercott, B.C. Choi, Erythema multiforme (StevensJohnson syndrome) — chart review of 123 hospitalized patients, Dermatologica 171 (1985) 383—396. [16] M.G. Stewart, NO. Duncan III, D.J. Franklin, E.M. Friedman, M. Sulek, Head and neck manifestations of erythema multi-
Drug eruptions in children with ENT infections
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