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Vesiculobullous drug eruptions in children
Vesiculobullous Drug Eruptions in Children ALBERT0 GIANNETTI, MD MARCELLA MALMUSI, MD GIAMPIERO GIROLOMONI,
MD
V
ery few data are available on the actual incidence of adverse reactions to drugs in children, especially among nonhospitalized patients. It is generally believed that side effects from drugs are rarer in children than in adults and increase progressively with age, paralleling drug consumption; however, other factors, including the difference in pharmacokinetics of drugs in children and adults, may be relevant to the reduced rate of adverse drug reactions in younger subjects. These factors may explain the low incidence of drug reactions in newborns receiving many drugs.’ It has been estimated that adverse reactions to drugs occur in 2 to 5% of hospitalized children.2*3 Antineoplastics, antimicrobials, and anticonvulsants have been identified as the drugs most frequently responsible for hospital admissions for adverse reactions*“; however, as antibiotics account for approximately 50% of all drug prescriptions for children, this is the group of drugs most commonly implicated in adverse reactions in the pediatric age group. In addition, newborns and infants can develop adverse reactions to drugs taken by the mother that cross the placenta or are eliminated through the milk.’ Among adverse drug reactions, cutaneous manifestations are certainly the most common. In this article, we limit our discussion to vesiculobullous drug reactions encountered in the pediatric age group, emphasizing peculiar clinical and epidemiologic aspects. The reader is referred to other articles in this issue for more detailed information concerning pathogenesis and immunologic mechanisms.
From the Department of Dermatology, University of Modena, Modena, Italy. Address correspondence to Albert0 Giannetti, MD, Clinica Dermatologica, Universitd di Modena, Via de1 Pouo 71, 41100 Modena, Italy.
0 1993 by Elsevier Science Publishing
Co., Inc.
l
0738-081x/93/$6.00
Fixed Drug Eruption Fixed drug eruption (FDE) is characterized by round erythematous patches that recur at the same site of the skin or mucous membranes following repeated exposure to the same drug. The lesions resolve, leaving residual marked hyperpigmentationP FDE is probably the only cutaneous eruption the exclusive etiology of which is drug exposure. The lesions are usually macules, but as epidermal necrosis and inflammation evolve, they may become bullous and ulcerate. When numerous bullous lesions occur (generalized bullous FDE) the differential diagnosis with erythema multiforme may be difficult.‘j FDE of oral (lips) and genital mucous membranes is most often bullous and easily evolves into erosive and crusted lesions that are to be clinically differentiated from herpes simplex (Fig 1). FDE is rarer in childhood than adulthood and affects mainly school-age children.6*7 The drugs most commonly responsible for FDE in children are sulfonamides, phenazone, aspirin, and penicillin.6~7 In contrast to adults, tetracyclines are very rarely the cause of FDE in children.
Toxic Epidermal Necrolysis (Lyell’s Syndrome) Toxic epidermal necrolysis (TEN) is a severe exfoliative disease of skin and mucous membranes with a high rate of morta1ity.s TEN probably represents the most severe form of a disease spectrum that includes erythema multiforme and Stevens- Johnson syndrome.9 The incidence of TEN is extremely low and has been estimated to be around one case per million per year in European countries.lO,ll TEN has been reported in all age groups, including newborns. ** In general, children seem to be affected only slightly less than adults. Of 333 cases reported in a French series collected in a 5-year period, only 13.8% were below 16 years of age. lo In a following series of 90 French cases, 5.5% were under the age of 16.13 In an
551
552
GIANNETTI,
MALMUSI,
AND
Clinics in Dermatology 1993;11:551-555
GIROLOMONI
Figure 1. Bullous fixed drug eruption of the lips caused by cotrimoxazole in an S-year-old boy.
Italian study conducted by the Gruppo Italian0 di Studi Epidemiologici in Dermatologia (GISED) on 47 consecutive cases of TEN, about 10% were younger than 14 years (Locati F. Personal communication). The incidence of drug-induced TEN in children has been reported to be much higher in other studies.” The female-to-male ratio varies from 3 : 1 to 2 : 1 in adults, whereas it is more balanced in children. The drugs most commonly associated with TEN in children are anticonvulsants (phenytoin, barbiturates, carbamazepine), antibiotics (penicillin, sulfonamides), and nonsteroidal anti-inflammatory agents (aspirin, pyrazolones), but a larger proportion of TEN in children remains idiopathic. 8~12~15~16 The clinical manifestations of TEN in children do not substantially differ from those in adult cases (Fig 2). Prognosis in children appears to be much better compared with adults, with a similar extension of lesions. In the largest series from France, only one death occurred among 35 childhood cases, whereas 5 1% of patients above the age of 60 diedlo; however, other authors believe that the prognosis in children may be as severe as in adults.15 Mortality is related mainly to the extent of denuded skin and blood urea nitrogen, which together with age are well-known prognostic factors for burn patients, and, in fact, TEN children can be managed as burn patients. W’ Another factor that seems to affect prognosis negatively is the development of persistent leukopenia and neutropenia, probably because this increases the risk of septicemia.‘* The most important differential diagnosis of TEN in children is the staphylococ-
Figure 2. Erithema multiforme in a IO-year-old boy following intake of ampicillin.
Clinics in Dermatology
GIANNETTI, MALMUSI, AND VESICULOBULLOUS DRUG ERUPTIONS
1993:11:551-555
GIROLOMONI IN CHILDREN
553
cal scalded skin syndrome (SSSS), caused by phage group II, type 51, or 70/71 Staphylococcus mreus.*g SSSS usually arises in children under age 5 and does not affect mucous membranes, with the exception of frequent conjunctivitis. The rash starts and is more prominent on body flexures and periorificial regions; there are no target, erythema multiforme-like lesions. Peeling is very superficial, showing little or no oozing. Microscopic examination of a frozen section reveals an intraepidermal detachment in SSSS, whereas in TEN there is full-thickness epidermal necrosis with subepidermal cleavage. Another pediatric condition that may be misdiagnosed with early TEN is Kawasaki disease; however, in Kawasaki disease there is no cutaneous blistering. Treatment of TEN in children includes supportive measures such as reverse barrier isolation, intravenous fluids and nutritional support, meticmous care, earIy detection and treatment of infection, and frequent ophthalmologic examination. The use of systemic corticosteroids is controversial. Steroids do not seem to improve prognosis and may adversely affect the outcome by increasing the risk of complications, including secondary infections and gastrointestinal bleeding.16,17 Also, systemic antibiotics are not indicated on a prophylactic basis and should be used only when infection is proved or neutropenia develops.16
Erythema Multiforme Syndrome
and Stevens- Johnson
Erythema multiforme (EM) and Stevens-Johnson syndrome (SJS) represent two variants of the same disease and similar etiopathogenetic mechanisms are recognized. They are more common than TEN among adolescents and young adults. WO In two studies on 138 and 266 cases, 43 and 56%, respectively, were under the age of 19 .21*22In two pediatric series of SJS, the mean ages were 6 and 8 years, respectively. 15,23In addition, a series of 51 children with SJS, 18% of whom were 12 months of age or younger, has been described.” Unlike in TEN, a large percentage of EM/SJS cases are not drug related, and may develop following a variety of other precipitating conditions such as infections, neoplasia, and autoimmune diseases. Infections are more common causes of EM in children than in adults. Drugs are indicated as the causative factor in 15 to 65% of pediatric patients.22-25 The most frequent drugs cited as a cause of EM/SJS in children are the same as those described for TEN and include anticonvulsants (phenytoin, carbamazepine), antibiotics (sulfonamides, penicillin), and nonsteroidal anti-inflammatory drugs (pyrazolones, aspirin) (Figs 3 -5) whereas the infectious diseases most frequently implicated in childhood are Mycoplasma pneumoniae,26
Figure 3. Samepatient
of
Figure 2. Bullous lesions of the feet.
staphylococcal and streptococcal upper respiratory tract infections,23,25 and herpes simplex. It is, however, often difficult to establish the actual relevance of drug versus infective etiology, especially when a child presents with a history of drug intake for an infectious disease. In addition, the prodromal symptoms of EM/SJS may easily simulate an infectious disease. In general, SJS and EM cases with more prominent epidermal injury are more likely to be drug induced. In contrast, EM showing very limited epidermal necrosis and relatively more dermal inflammation is more commonly observed following infections (eg, herpes).27 Finally, in a varying percentage of patients with EM/SJS no etiologic factors can be found. Differential diagnosis of SJS in children includes bullous generalized FDE, Kawasaki disease, vasculitis, and SSSS. The use of systemic corticosteroids in treatment of SJS in children is not recommended because it does not shorten the recovery time and increases the risk of secondary infections and gastrointestinal bleeding.23,24,2K2g Other authors believe steroids are of appreciable help when administered early (within 2 days of disease onset
554
GIANNETTI,
MALMUSI,
Figure
AND
4. Stevens-Johnson syndrome caused by phenytoin in a U-year-old girl.
or when the rash is in the crescendo phase), at relatively high dosage, and to hospitalized patients.2**29
Pemphigus Pemphigus is a group of mucocutaneous diseases characterized by intraepithelial blisters caused by loss of normal cell-cell adhesion and associated with autoantibodies Figure
Clinics in Dermatology 2993;21:552-555
GIROLOMONI
against various surface glycoproteins of stratified squamous epithelia. Pemphigus is very rare in children, with pemphigus foliaceus being more common than pemphigus vulgaris. 3o Transient PV has also been described in neonates and is due to placental transport of autoantibodies from the mother with active pemphigus. Most pemphigus are idiopathic; however, in some cases inducing or triggering factors can be found. These include
5. Toxic epidermal necrolysiscaused by amoxicillin in a 2-year-old infant.
Clinics in Dermatology 2993;12:551-555 physical agents, neoplasia, and especially drugs.3* Druginduced pemphigus has been described in two children of 7 and 4 years. In both cases the clinical and histologic features were those of a superficial, erythematous form and amoxicillin was the drug incriminated. In the first case, drug discontinuation and topical steroids were sufficient to induce complete recovery3*; the second case required systemic steroids.33
References 1. Mitchell AA, Goldman P, Shapiro S, Slone D. Drug utiIization and reported adverse reactions in hospitalized children Am J Epidemiol 1979;110:196-204. 2. McKenzie MW, Marchall GL, Netzloff ML, Cluff LE. Adverse drug reactions leading to hospitalization in children. J Pediatr 1976;89:487-90. 3. Choonara IA, Harris F. Adverse drug reactions in medical inpatients. Arch Dis Child 1984;59:578-80. 4. Wilson JT, Brown RD, Cherek DR. Drug excretion in human breast milk: Principles, pharmacokinetics, and projected consequences. Clin Pharmacokinet 1980;5:1-5. 5. Korkij W, Soltani K. Fixed drug eruption: A brief review. Arch Dermatol 1984;120:520-4. 6. Kanwar AJ, Bharija SC, Belhaj MS. Fixed drug eruptions in children: A series of 23 cases with provocative tests. Dermatologica 1986;172:315-9. 7. Bonifazi E, Meneghini CL. Eritema tisso da medicamenti. Boll Dermatol Pediatr 1984;1:93-9. 8. Avakian R, Flowers FP, Araujo OE, Ramos-Caro FA. Toxic epidermal necrolysis: A review. J Am Acad Dermatol 1991;25:69-79. S, Rzany B, Stem RS, Shear NH, Naldi L, 9. Bastuji-Garin Roujeau JC. Clinical classification of cases of toxic epiderma1 necrolysis, Stevens- Johnson syndrome, and erythema multiforme. Arch Dermatol 1993;129:92-6. J-C, Fabre J-P, Penso D, FlCchet 10. Roujeau J-C, Guillaume M-L, Girre J-P, Toxic epidermal necrolysis (Lye11 syndrome). Arch Dermatol 1990;126:37-42. 11. Schiipf E, Stiihmer A, Rzany B, Victor N, Zentgraf R, Kapp JF. Toxic epidermal necrolysis and Stevens- Johnson syndrome. Arch Dermatol 1991;127:839-42. 13 _-. Scully MC, Frieden IJ. Toxic epidermal necrolysis in early infancy. J Am Acad Dermatol 1992;27:340-4. 13. Correia 0, Chosidow 0, Saiag Ph, Bastuji-Garin S, Revuz J, Roujeau JC. Evolving pattern of drug-induced toxic epiderma1 necrolysis. Dermatology 1993;186:32-7. 14. Chan H-L, Stem RS, Amdt KA, et al. The incidence of erythema multifonne, Stevens- Johnson syndrome, and toxic epidermal necrolysis. Arch Dermatol1990;126:43 - 7. 15. Ruiz-Maldonado R. Acute disseminated epidermal necrolysis types 1, 2, and 3: Study of sixty cases. J Am Acad Dermatol 1985;13:623-35.
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16. Prendville JS,Hebert AA, Greenwald MJ, Esterly NB. Management of Stevens- Johnson syndrome and toxic epiderma1 necrolysis in children. J Pediatr 1989;115:881-7. 17. Adzick NS, Kim SH, Bondoc CC, Quinby WC, RemenSnyder JP. Management of toxic epidermal necrolysis in a pediatric bum center. Am J Dis Child 1985;139:499-552. 18. Goens J, Song M, Fondu P, Blum D, Achten G. Haematological disturbances and immune mechanisms in toxic epidermal necrolysis. Br J Dermatol 1986;114:255-9. 19. Hansen RC. Staphylococcal scalded skin syndrome, toxic shock syndrome and Kawasaki disease. Pediatr CIin North
Am 1983;30:533-44. 20. Hemborg A. Stevens- Johnson syndrome after mass prophylaxis with sulfadoxine for cholera in Mozambique. Lancet 1985;1:1072-3. 21. Strom J, Aetiology of febrile mucocutaneous syndromes with special reference to the provocative role of infections and drugs. Acta Med Stand 1977;201:131-6. 22. Bianchine JR, Macareg PVJ, Lasagna L, et al. Drugs as etiologic factors in the Stevens- Johnson syndrome. Am J Med 1968;44:390-405. 23. Rasmussen JE. Erythema multiforme in children. Br J Dermatol 1976;95:181-6. 24. /Ginsburg CM. Stevens- Johnson syndrome in children, Pediatr Infect Dis 1982;1:155-8. 25. D&land WJ, Oranje AP, Stolz E, van Joost Th. Erythema multiforme in childhood and early infancy. Pediatr Dermato1 1986;3:135-9. 26. McCormack JG. Mycoplasma pneumonia and the erythema multiforme-Stevens-Johnson syndrome. J Infect 1981;3:32-6. 27. Howland WW, Golitz LE, Weston WL, Huff JC. Erythema multiforme: Clinical, histopathologic, and immunologic study. J Am Acad Dermatol 1984;10:438-46. 28 Weston WL., Oranje AP, Rasmussen JE, et al. Corticosteroids for erythema multiforme? Pediatr Dermatol 1989;6:229-50. 29. Lynch PJ. Vascular reactions. In: Schachner LA, Hansen RC, editors. Pediatric dermatology. New York: Churchill Livingstone, 1988: 959-1014. 30. Smitt JH. Pemphigus vulgaris in childhood: Clinical features, treatment and prognosis. Pediatr Dermatol 1985;2:185-90. 31. Ruocco V, Sacerdoti G. Pemphigus and bullous pemphigoid due to drugs. Int J Dermatol 1991;30:307-12. 32. Toan ND, Morel P, Ramel F, Puissant A. Pemphigus superticiel de l’enfant. Induction par l’amoxicilline? Ann Dermato1 Venereol 1983;110:917-9. 33. Escallier F, Gaudard S, Boulitrop-Morvan C, et al. Pemphigus superficiel de l’enfant. Rale declenchant de l’amoxicil line? Ann Dermatol Venereol 1991;118:381-4.
MD
V
ery few data are available on the actual incidence of adverse reactions to drugs in children, especially among nonhospitalized patients. It is generally believed that side effects from drugs are rarer in children than in adults and increase progressively with age, paralleling drug consumption; however, other factors, including the difference in pharmacokinetics of drugs in children and adults, may be relevant to the reduced rate of adverse drug reactions in younger subjects. These factors may explain the low incidence of drug reactions in newborns receiving many drugs.’ It has been estimated that adverse reactions to drugs occur in 2 to 5% of hospitalized children.2*3 Antineoplastics, antimicrobials, and anticonvulsants have been identified as the drugs most frequently responsible for hospital admissions for adverse reactions*“; however, as antibiotics account for approximately 50% of all drug prescriptions for children, this is the group of drugs most commonly implicated in adverse reactions in the pediatric age group. In addition, newborns and infants can develop adverse reactions to drugs taken by the mother that cross the placenta or are eliminated through the milk.’ Among adverse drug reactions, cutaneous manifestations are certainly the most common. In this article, we limit our discussion to vesiculobullous drug reactions encountered in the pediatric age group, emphasizing peculiar clinical and epidemiologic aspects. The reader is referred to other articles in this issue for more detailed information concerning pathogenesis and immunologic mechanisms.
From the Department of Dermatology, University of Modena, Modena, Italy. Address correspondence to Albert0 Giannetti, MD, Clinica Dermatologica, Universitd di Modena, Via de1 Pouo 71, 41100 Modena, Italy.
0 1993 by Elsevier Science Publishing
Co., Inc.
l
0738-081x/93/$6.00
Fixed Drug Eruption Fixed drug eruption (FDE) is characterized by round erythematous patches that recur at the same site of the skin or mucous membranes following repeated exposure to the same drug. The lesions resolve, leaving residual marked hyperpigmentationP FDE is probably the only cutaneous eruption the exclusive etiology of which is drug exposure. The lesions are usually macules, but as epidermal necrosis and inflammation evolve, they may become bullous and ulcerate. When numerous bullous lesions occur (generalized bullous FDE) the differential diagnosis with erythema multiforme may be difficult.‘j FDE of oral (lips) and genital mucous membranes is most often bullous and easily evolves into erosive and crusted lesions that are to be clinically differentiated from herpes simplex (Fig 1). FDE is rarer in childhood than adulthood and affects mainly school-age children.6*7 The drugs most commonly responsible for FDE in children are sulfonamides, phenazone, aspirin, and penicillin.6~7 In contrast to adults, tetracyclines are very rarely the cause of FDE in children.
Toxic Epidermal Necrolysis (Lyell’s Syndrome) Toxic epidermal necrolysis (TEN) is a severe exfoliative disease of skin and mucous membranes with a high rate of morta1ity.s TEN probably represents the most severe form of a disease spectrum that includes erythema multiforme and Stevens- Johnson syndrome.9 The incidence of TEN is extremely low and has been estimated to be around one case per million per year in European countries.lO,ll TEN has been reported in all age groups, including newborns. ** In general, children seem to be affected only slightly less than adults. Of 333 cases reported in a French series collected in a 5-year period, only 13.8% were below 16 years of age. lo In a following series of 90 French cases, 5.5% were under the age of 16.13 In an
551
552
GIANNETTI,
MALMUSI,
AND
Clinics in Dermatology 1993;11:551-555
GIROLOMONI
Figure 1. Bullous fixed drug eruption of the lips caused by cotrimoxazole in an S-year-old boy.
Italian study conducted by the Gruppo Italian0 di Studi Epidemiologici in Dermatologia (GISED) on 47 consecutive cases of TEN, about 10% were younger than 14 years (Locati F. Personal communication). The incidence of drug-induced TEN in children has been reported to be much higher in other studies.” The female-to-male ratio varies from 3 : 1 to 2 : 1 in adults, whereas it is more balanced in children. The drugs most commonly associated with TEN in children are anticonvulsants (phenytoin, barbiturates, carbamazepine), antibiotics (penicillin, sulfonamides), and nonsteroidal anti-inflammatory agents (aspirin, pyrazolones), but a larger proportion of TEN in children remains idiopathic. 8~12~15~16 The clinical manifestations of TEN in children do not substantially differ from those in adult cases (Fig 2). Prognosis in children appears to be much better compared with adults, with a similar extension of lesions. In the largest series from France, only one death occurred among 35 childhood cases, whereas 5 1% of patients above the age of 60 diedlo; however, other authors believe that the prognosis in children may be as severe as in adults.15 Mortality is related mainly to the extent of denuded skin and blood urea nitrogen, which together with age are well-known prognostic factors for burn patients, and, in fact, TEN children can be managed as burn patients. W’ Another factor that seems to affect prognosis negatively is the development of persistent leukopenia and neutropenia, probably because this increases the risk of septicemia.‘* The most important differential diagnosis of TEN in children is the staphylococ-
Figure 2. Erithema multiforme in a IO-year-old boy following intake of ampicillin.
Clinics in Dermatology
GIANNETTI, MALMUSI, AND VESICULOBULLOUS DRUG ERUPTIONS
1993:11:551-555
GIROLOMONI IN CHILDREN
553
cal scalded skin syndrome (SSSS), caused by phage group II, type 51, or 70/71 Staphylococcus mreus.*g SSSS usually arises in children under age 5 and does not affect mucous membranes, with the exception of frequent conjunctivitis. The rash starts and is more prominent on body flexures and periorificial regions; there are no target, erythema multiforme-like lesions. Peeling is very superficial, showing little or no oozing. Microscopic examination of a frozen section reveals an intraepidermal detachment in SSSS, whereas in TEN there is full-thickness epidermal necrosis with subepidermal cleavage. Another pediatric condition that may be misdiagnosed with early TEN is Kawasaki disease; however, in Kawasaki disease there is no cutaneous blistering. Treatment of TEN in children includes supportive measures such as reverse barrier isolation, intravenous fluids and nutritional support, meticmous care, earIy detection and treatment of infection, and frequent ophthalmologic examination. The use of systemic corticosteroids is controversial. Steroids do not seem to improve prognosis and may adversely affect the outcome by increasing the risk of complications, including secondary infections and gastrointestinal bleeding.16,17 Also, systemic antibiotics are not indicated on a prophylactic basis and should be used only when infection is proved or neutropenia develops.16
Erythema Multiforme Syndrome
and Stevens- Johnson
Erythema multiforme (EM) and Stevens-Johnson syndrome (SJS) represent two variants of the same disease and similar etiopathogenetic mechanisms are recognized. They are more common than TEN among adolescents and young adults. WO In two studies on 138 and 266 cases, 43 and 56%, respectively, were under the age of 19 .21*22In two pediatric series of SJS, the mean ages were 6 and 8 years, respectively. 15,23In addition, a series of 51 children with SJS, 18% of whom were 12 months of age or younger, has been described.” Unlike in TEN, a large percentage of EM/SJS cases are not drug related, and may develop following a variety of other precipitating conditions such as infections, neoplasia, and autoimmune diseases. Infections are more common causes of EM in children than in adults. Drugs are indicated as the causative factor in 15 to 65% of pediatric patients.22-25 The most frequent drugs cited as a cause of EM/SJS in children are the same as those described for TEN and include anticonvulsants (phenytoin, carbamazepine), antibiotics (sulfonamides, penicillin), and nonsteroidal anti-inflammatory drugs (pyrazolones, aspirin) (Figs 3 -5) whereas the infectious diseases most frequently implicated in childhood are Mycoplasma pneumoniae,26
Figure 3. Samepatient
of
Figure 2. Bullous lesions of the feet.
staphylococcal and streptococcal upper respiratory tract infections,23,25 and herpes simplex. It is, however, often difficult to establish the actual relevance of drug versus infective etiology, especially when a child presents with a history of drug intake for an infectious disease. In addition, the prodromal symptoms of EM/SJS may easily simulate an infectious disease. In general, SJS and EM cases with more prominent epidermal injury are more likely to be drug induced. In contrast, EM showing very limited epidermal necrosis and relatively more dermal inflammation is more commonly observed following infections (eg, herpes).27 Finally, in a varying percentage of patients with EM/SJS no etiologic factors can be found. Differential diagnosis of SJS in children includes bullous generalized FDE, Kawasaki disease, vasculitis, and SSSS. The use of systemic corticosteroids in treatment of SJS in children is not recommended because it does not shorten the recovery time and increases the risk of secondary infections and gastrointestinal bleeding.23,24,2K2g Other authors believe steroids are of appreciable help when administered early (within 2 days of disease onset
554
GIANNETTI,
MALMUSI,
Figure
AND
4. Stevens-Johnson syndrome caused by phenytoin in a U-year-old girl.
or when the rash is in the crescendo phase), at relatively high dosage, and to hospitalized patients.2**29
Pemphigus Pemphigus is a group of mucocutaneous diseases characterized by intraepithelial blisters caused by loss of normal cell-cell adhesion and associated with autoantibodies Figure
Clinics in Dermatology 2993;21:552-555
GIROLOMONI
against various surface glycoproteins of stratified squamous epithelia. Pemphigus is very rare in children, with pemphigus foliaceus being more common than pemphigus vulgaris. 3o Transient PV has also been described in neonates and is due to placental transport of autoantibodies from the mother with active pemphigus. Most pemphigus are idiopathic; however, in some cases inducing or triggering factors can be found. These include
5. Toxic epidermal necrolysiscaused by amoxicillin in a 2-year-old infant.
Clinics in Dermatology 2993;12:551-555 physical agents, neoplasia, and especially drugs.3* Druginduced pemphigus has been described in two children of 7 and 4 years. In both cases the clinical and histologic features were those of a superficial, erythematous form and amoxicillin was the drug incriminated. In the first case, drug discontinuation and topical steroids were sufficient to induce complete recovery3*; the second case required systemic steroids.33
References 1. Mitchell AA, Goldman P, Shapiro S, Slone D. Drug utiIization and reported adverse reactions in hospitalized children Am J Epidemiol 1979;110:196-204. 2. McKenzie MW, Marchall GL, Netzloff ML, Cluff LE. Adverse drug reactions leading to hospitalization in children. J Pediatr 1976;89:487-90. 3. Choonara IA, Harris F. Adverse drug reactions in medical inpatients. Arch Dis Child 1984;59:578-80. 4. Wilson JT, Brown RD, Cherek DR. Drug excretion in human breast milk: Principles, pharmacokinetics, and projected consequences. Clin Pharmacokinet 1980;5:1-5. 5. Korkij W, Soltani K. Fixed drug eruption: A brief review. Arch Dermatol 1984;120:520-4. 6. Kanwar AJ, Bharija SC, Belhaj MS. Fixed drug eruptions in children: A series of 23 cases with provocative tests. Dermatologica 1986;172:315-9. 7. Bonifazi E, Meneghini CL. Eritema tisso da medicamenti. Boll Dermatol Pediatr 1984;1:93-9. 8. Avakian R, Flowers FP, Araujo OE, Ramos-Caro FA. Toxic epidermal necrolysis: A review. J Am Acad Dermatol 1991;25:69-79. S, Rzany B, Stem RS, Shear NH, Naldi L, 9. Bastuji-Garin Roujeau JC. Clinical classification of cases of toxic epiderma1 necrolysis, Stevens- Johnson syndrome, and erythema multiforme. Arch Dermatol 1993;129:92-6. J-C, Fabre J-P, Penso D, FlCchet 10. Roujeau J-C, Guillaume M-L, Girre J-P, Toxic epidermal necrolysis (Lye11 syndrome). Arch Dermatol 1990;126:37-42. 11. Schiipf E, Stiihmer A, Rzany B, Victor N, Zentgraf R, Kapp JF. Toxic epidermal necrolysis and Stevens- Johnson syndrome. Arch Dermatol 1991;127:839-42. 13 _-. Scully MC, Frieden IJ. Toxic epidermal necrolysis in early infancy. J Am Acad Dermatol 1992;27:340-4. 13. Correia 0, Chosidow 0, Saiag Ph, Bastuji-Garin S, Revuz J, Roujeau JC. Evolving pattern of drug-induced toxic epiderma1 necrolysis. Dermatology 1993;186:32-7. 14. Chan H-L, Stem RS, Amdt KA, et al. The incidence of erythema multifonne, Stevens- Johnson syndrome, and toxic epidermal necrolysis. Arch Dermatol1990;126:43 - 7. 15. Ruiz-Maldonado R. Acute disseminated epidermal necrolysis types 1, 2, and 3: Study of sixty cases. J Am Acad Dermatol 1985;13:623-35.
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16. Prendville JS,Hebert AA, Greenwald MJ, Esterly NB. Management of Stevens- Johnson syndrome and toxic epiderma1 necrolysis in children. J Pediatr 1989;115:881-7. 17. Adzick NS, Kim SH, Bondoc CC, Quinby WC, RemenSnyder JP. Management of toxic epidermal necrolysis in a pediatric bum center. Am J Dis Child 1985;139:499-552. 18. Goens J, Song M, Fondu P, Blum D, Achten G. Haematological disturbances and immune mechanisms in toxic epidermal necrolysis. Br J Dermatol 1986;114:255-9. 19. Hansen RC. Staphylococcal scalded skin syndrome, toxic shock syndrome and Kawasaki disease. Pediatr CIin North
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