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Acta Dermatoven APA Vol 18, 2009, No 1 39
Toxic epidermal necrolysis probably due
to cosmetic cream: a case report
I. Kokcam
Toxic epidermal necrolysis (TEN) is a severe and life-threatening cutaneous reaction usually caused by
systemic drug administration. Preparations applied to the skin and mucous membranes topically very
rarely induce TEN. We present a case of TEN in a 35-year-old woman probably due to facial application
of an over-the-counter (OTC) cosmetic cream.
toxic epidermal
necrolysis,
over-the-
counter
cosmetic
preparation,
adverse effect
K E Y
W O R D S
S U M M A R Y
Introduction
Toxic epidermal necrolysis (TEN), or Lyell’s Syn-
drome, is an unusual, acute, and life-threatening der-
matological disease. It is characterized by wide-
spread erythematous macules, vesicles, blisters, and
full-thickness epidermal necrosis with sloughing; it
often involves more than 30% of the body’s surface
area. It also involves the mucous membranes. It mainly
occurs as an adverse reaction to drugs (1, 2). The inci-
dence is approximately one case per million people
per year (3). The mortality rate varies from 25 to
80%, with a mean of about 30% (4, 5). In the available
literature only a few cases of TEN have been attributed
to a topical preparation. Here we present a patient that
developed TEN 1 week after beginning treatment for
melasma with an over-the-counter (OTC) cosmetic
cream.
Case report
A previously healthy 35-year-old woman, 1 week
after beginning self-treatment for melasma with an OTC
cosmetic cream (“Ideal Cream,” of Middle Eastern ori-
gin), initially developed general malaise, followed by
pruritus and a burning maculopapular, erythematous
rash beginning on her face and neck and then extend-
ing to her arms. She visited a local hospital where the
lesions were diagnosed as contact dermatitis and treated
with a topical steroid and an oral antihistaminic drug.
Unfortunately the rash spread to the rest of her body,
her extremities, and her ocular, oral, and vaginal mu-
cosa, so she was admitted to Firat University Hospital’s
dermatology clinic. Initially she denied taking any medi-
cation or having a recent infection. All vital signs were
within the normal range except for a temperature of
38.5 °C. Dermatological examination revealed
C a s e r e p o r t Toxic epidermal necrolysis due to cosmetic cream
40 Acta Dermatoven APA Vol 18, 2009, No 1
erythema, edema, and erosions on her face, upper
trunk, and extremities. Mucosal ulcerations of her oral,
ocular, and genital mucosa were observed (Fig. 1, 2).
Nikolsky’s sign was positive. Her skin as a whole had
become reddened, with marked itching and pain in the
lesions. Later, a detailed interrogation revealed the use
of “Ideal Cream” for melasma as the presumptive cause.
Despite the discontinuation of all previously prescribed
medications, her rash progressed over the following
week.
Laboratory tests included a complete blood cell
count with differential, liver panel, electrolytes, blood
sugar, renal function, and urinalysis, which were all within
the normal ranges. At the onset of disease her level of
C-reactive protein (CRP) was 185 mg/L (normal range:
0–5 mg/L), and her sedimentation rate was 66 mm/h
(normal range: 0–20 mm/h). Serology for infectious
agents including Mycoplasma pneumoniae was nega-
tive. Histopathological examination of the skin biopsy
stained with HE revealed full-thickness epidermal ne-
crosis and detachment, consistent with a diagnosis of
TEN.
The patient was treated by intravenous administra-
tion of 120 mg/day prednisolone and parenteral fluid.
A bacterial culture test from her skin lesions revealed
Staphylococcus aureus and, in accordance with the
sensitivity test, levofloxacin was administered intrave-
nously. The skin lesions were covered with petrola-
tum-impregnated gauze.
The lesions on her eyes were treated with ointment
containing oxytetracycline. The intravenous adminis-
tration of prednisolone was reduced gradually as the
patient’s condition improved. She recovered after 6
weeks of therapy and was discharged almost without
sequelae. Follow-up examinations revealed post-in-
flammatory hyperpigmentation of the skin. The
patient’s eyes and mucous membranes had recovered
completely.
Discussion
Drugs, antibiotics, and anticonvulsants are the most
frequent triggers of TEN (5, 6). Other possible causes
include immunization, viral infection, graft versus host
disease, connective tissue disorders, and exposure to
industrial chemicals (3, 7).
The disease started with general malaise, myalgia,
and prodromal symptoms. A burning, painful eruption
spread from the face to the neck and shoulders and
later to the entire trunk and proximal parts of limbs.
The peak manifestation of lesions usually occurs in a
week. In nearly all cases, mucous membranes are in-
volved. Nikolsky’s sign is usually positive (1, 2, 7).
TEN caused by the application of topical prepara-
tions to the skin and mucous membranes is very un-
usual. Flórez et al. reported a case of TEN occurring
Figure 2. Oral mucous membrane involvement.
Figure 1. Epidermal detachment of the face and
the eyelids.
Toxic epidermal necrolysis due to cosmetic cream C a s e r e p o r t
Acta Dermatoven APA Vol 18, 2009, No 1 41
after ophthalmic use of timolol, dorzolamide, and
latanoprost (8). Praz et al. reported a case of TEN in-
duced by topical intranasal application of mupirocin (9).
Radimer et al. reported 4 patients with TEN related to
exposure to a fumigant mixture containing acrylonitrile
and carbon tetrachloride (10). Thompson and Wansker
described a young female patient in whom erythema
multiforme and TEN developed after two exposures to
a locally applied perfume (11). In our case, the patient
had used an OTC cosmetic cream 1 week prior to the
onset of cutaneous eruptions, and declared that she had
not taken any other kind of medication. Detailed ques-
tioning and the time course strongly suggested the OTC
cosmetic cream as the responsible agent.
It is often difficult to determine causative drugs.
There is no reliable laboratory test to confirm TEN. Patch
testing and lymphocyte transformation may show weak
positivity (12). Detailed disclosure of ingredients in
cosmetic products is not required by law in several coun-
tries, including Turkey. Thus, defining appropriate test
concentrations of ingredients is not possible. In our case,
the patient was using only “Ideal Cream,” had no infec-
tion, and was not using another medication. “Ideal
Cream” is an over-the-counter drug whose contents are
unknown. It is used to eliminate freckles and acne, in-
cluding melasma. We have to take into account, how-
ever, that patients’ histories concerning their drug in-
take are not reliable. The patient refused the applica-
tion of patch tests.
The use of traditional drugs is increasing in various
populations (14). Many users of traditional medicines
generally regard them as “natural,” and therefore in-
nocuous, without major side effects.
Treatment of TEN is mostly conservative and in-
cludes fluid and electrolyte replacement, nutritional
support, temperature regulation, prevention and treat-
ment of infection using daily dressings and broad-spec-
trum antibiotics, and ophthalmic and oral care. A role is
suggested for specific therapies such as a short course
of corticosteroids, cyclosporine, and intravenous gamma
globulin (IVIG), but there is no universal consensus on
their efficacy for treating this disease (15). In light of
this, we chose to treat the patient conservatively.
The increased use of cosmetics in modern society
may be responsible for the rise in the incidence of ad-
verse reactions. Our presentation suggests the need for
increased awareness of the possible severe cutaneous
adverse effects of topical OTC drugs.
1. Avakian R, Flowers FP, Araujo OE, Ramos-Caro FA. Toxic epidermal necrolysis: a review. J Am Acad
Dermatol. 1991;25:69–79.
2. Fritsch PO, Ruiz-Maldonado R. Erythema multiforme, Stevens-Johnson syndrome and toxic epider-
mal necrolysis. In: Freedberg IM, Eisen AZ, Wolff K, Austen K, Goldsmith L, Katz S, editors. Fitzpatrick’s
Dermatology in General Medicine. 6th ed. Vol. 1. New York: McGraw-Hill; 2003. p. 548–57.
3. Wolkenstein P, Revuz J. Toxic epidermal necrolysis. Dermatol Clin. 2000;18:485–95.
4. Ghislain PD, Roujeau JC. Treatment of severe drug reactions: Stevens-Johnson syndrome, toxic
epidermal necrolysis and hypersensitivity syndrome. Dermatol Online J. 2002;8:5.
5. Roujeau JC, Chosidow O, Saiag P, Guillaume JC. Toxic epidermal necrolysis (Lyell syndrome). J Am
Acad Dermatol. 1990;23:1039–58.
6. Guillaume JC,Roujeau JC, Revuz J, Pnso D, Touraine R. The culprit drugs in 87 cases of toxic
epidermal necrolysis (Lyell syndrome). Arch Dermatol. 1987;123:1166–70.
7. Pereira FA, Mudgil AV, Rosmarin DM. Toxic epidermal necrolysis. J Am Acad Dermatol.
2007;56(2):181–200.
8. Flórez A, Rosón E, Conde A, González B, García-Doval I, de la Torre C, Cruces M. Toxic epidermal
necrolysis secondary to timolol, dorzolamide, and latanoprost eyedrops. J Am Acad Dermatol.
2005;53(5):909–11.
9. Praz SM, de Torrente A, Zender H, Schmied E, Schleppy CA, Genne D. Toxic epidermal necrolysis
after topical intranasal application of mupirocin. Infect Control Hosp Epidemiol. 2003;24:459–60.
10. Radimer GF, Davis JH, Ackerman AB. Fumigant-induced toxic epidermal necrolysis. Arch Dermatol.
1974;110:103–4.
11.Thompson JA Jr, Wansker BA. A case of contact dermatitis, erythema multiforme, and toxic epider-
mal necrolysis. J Am Acad Dermatol. 1981;5:666–9.
12.Wolkenstein P, Chosidow O, Fléchet ML, et al. Patch testing in severe cutaneous adverse drug
reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis. Contact Dermatitis.
1996;35:234–6.
RE F E R E N C E S
C a s e r e p o r t Toxic epidermal necrolysis due to cosmetic cream
42 Acta Dermatoven APA Vol 18, 2009, No 1
13. Bygum A, Gregersen JW, Buus SK. Acetaminophen-Induced Toxic Epidermal Necrolysis. Pediatr
Dermatol. 2004;21(3):236–8.
14. Lim YL, Thirumoorthy T. Serious cutaneous adverse reactions to traditional Chinese medicines.
Singapore Med J. 2005;46:714–7.
15. Craven NM, Toxic Epidermal Necrolysis and Stevens-Johnson Syndrome. In: Lebwohl MG, Heymann
WR, Berth-Jones J, Coulson I, editors. Treatment of Skin Disease. 2nd ed. London: Mosby Elsever;
2006. p. 657–60.
Ibrahim Kokcam MD, Assoc Prof., Department of Dermatology, Firat
University School of medicine, 23119 Elazig, Turkey,
e-mail:ibrahimkokcam@gmail.com, corresponding author
A U T H O R ' S
A D D R E S S
Toxic epidermal necrolysis due to cosmetic cream C a s e r e p o r t

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Toxic Epidermal Necrolysis Probably Due to Cosmetic Cream

  • 1. Acta Dermatoven APA Vol 18, 2009, No 1 39 Toxic epidermal necrolysis probably due to cosmetic cream: a case report I. Kokcam Toxic epidermal necrolysis (TEN) is a severe and life-threatening cutaneous reaction usually caused by systemic drug administration. Preparations applied to the skin and mucous membranes topically very rarely induce TEN. We present a case of TEN in a 35-year-old woman probably due to facial application of an over-the-counter (OTC) cosmetic cream. toxic epidermal necrolysis, over-the- counter cosmetic preparation, adverse effect K E Y W O R D S S U M M A R Y Introduction Toxic epidermal necrolysis (TEN), or Lyell’s Syn- drome, is an unusual, acute, and life-threatening der- matological disease. It is characterized by wide- spread erythematous macules, vesicles, blisters, and full-thickness epidermal necrosis with sloughing; it often involves more than 30% of the body’s surface area. It also involves the mucous membranes. It mainly occurs as an adverse reaction to drugs (1, 2). The inci- dence is approximately one case per million people per year (3). The mortality rate varies from 25 to 80%, with a mean of about 30% (4, 5). In the available literature only a few cases of TEN have been attributed to a topical preparation. Here we present a patient that developed TEN 1 week after beginning treatment for melasma with an over-the-counter (OTC) cosmetic cream. Case report A previously healthy 35-year-old woman, 1 week after beginning self-treatment for melasma with an OTC cosmetic cream (“Ideal Cream,” of Middle Eastern ori- gin), initially developed general malaise, followed by pruritus and a burning maculopapular, erythematous rash beginning on her face and neck and then extend- ing to her arms. She visited a local hospital where the lesions were diagnosed as contact dermatitis and treated with a topical steroid and an oral antihistaminic drug. Unfortunately the rash spread to the rest of her body, her extremities, and her ocular, oral, and vaginal mu- cosa, so she was admitted to Firat University Hospital’s dermatology clinic. Initially she denied taking any medi- cation or having a recent infection. All vital signs were within the normal range except for a temperature of 38.5 °C. Dermatological examination revealed C a s e r e p o r t Toxic epidermal necrolysis due to cosmetic cream
  • 2. 40 Acta Dermatoven APA Vol 18, 2009, No 1 erythema, edema, and erosions on her face, upper trunk, and extremities. Mucosal ulcerations of her oral, ocular, and genital mucosa were observed (Fig. 1, 2). Nikolsky’s sign was positive. Her skin as a whole had become reddened, with marked itching and pain in the lesions. Later, a detailed interrogation revealed the use of “Ideal Cream” for melasma as the presumptive cause. Despite the discontinuation of all previously prescribed medications, her rash progressed over the following week. Laboratory tests included a complete blood cell count with differential, liver panel, electrolytes, blood sugar, renal function, and urinalysis, which were all within the normal ranges. At the onset of disease her level of C-reactive protein (CRP) was 185 mg/L (normal range: 0–5 mg/L), and her sedimentation rate was 66 mm/h (normal range: 0–20 mm/h). Serology for infectious agents including Mycoplasma pneumoniae was nega- tive. Histopathological examination of the skin biopsy stained with HE revealed full-thickness epidermal ne- crosis and detachment, consistent with a diagnosis of TEN. The patient was treated by intravenous administra- tion of 120 mg/day prednisolone and parenteral fluid. A bacterial culture test from her skin lesions revealed Staphylococcus aureus and, in accordance with the sensitivity test, levofloxacin was administered intrave- nously. The skin lesions were covered with petrola- tum-impregnated gauze. The lesions on her eyes were treated with ointment containing oxytetracycline. The intravenous adminis- tration of prednisolone was reduced gradually as the patient’s condition improved. She recovered after 6 weeks of therapy and was discharged almost without sequelae. Follow-up examinations revealed post-in- flammatory hyperpigmentation of the skin. The patient’s eyes and mucous membranes had recovered completely. Discussion Drugs, antibiotics, and anticonvulsants are the most frequent triggers of TEN (5, 6). Other possible causes include immunization, viral infection, graft versus host disease, connective tissue disorders, and exposure to industrial chemicals (3, 7). The disease started with general malaise, myalgia, and prodromal symptoms. A burning, painful eruption spread from the face to the neck and shoulders and later to the entire trunk and proximal parts of limbs. The peak manifestation of lesions usually occurs in a week. In nearly all cases, mucous membranes are in- volved. Nikolsky’s sign is usually positive (1, 2, 7). TEN caused by the application of topical prepara- tions to the skin and mucous membranes is very un- usual. Flórez et al. reported a case of TEN occurring Figure 2. Oral mucous membrane involvement. Figure 1. Epidermal detachment of the face and the eyelids. Toxic epidermal necrolysis due to cosmetic cream C a s e r e p o r t
  • 3. Acta Dermatoven APA Vol 18, 2009, No 1 41 after ophthalmic use of timolol, dorzolamide, and latanoprost (8). Praz et al. reported a case of TEN in- duced by topical intranasal application of mupirocin (9). Radimer et al. reported 4 patients with TEN related to exposure to a fumigant mixture containing acrylonitrile and carbon tetrachloride (10). Thompson and Wansker described a young female patient in whom erythema multiforme and TEN developed after two exposures to a locally applied perfume (11). In our case, the patient had used an OTC cosmetic cream 1 week prior to the onset of cutaneous eruptions, and declared that she had not taken any other kind of medication. Detailed ques- tioning and the time course strongly suggested the OTC cosmetic cream as the responsible agent. It is often difficult to determine causative drugs. There is no reliable laboratory test to confirm TEN. Patch testing and lymphocyte transformation may show weak positivity (12). Detailed disclosure of ingredients in cosmetic products is not required by law in several coun- tries, including Turkey. Thus, defining appropriate test concentrations of ingredients is not possible. In our case, the patient was using only “Ideal Cream,” had no infec- tion, and was not using another medication. “Ideal Cream” is an over-the-counter drug whose contents are unknown. It is used to eliminate freckles and acne, in- cluding melasma. We have to take into account, how- ever, that patients’ histories concerning their drug in- take are not reliable. The patient refused the applica- tion of patch tests. The use of traditional drugs is increasing in various populations (14). Many users of traditional medicines generally regard them as “natural,” and therefore in- nocuous, without major side effects. Treatment of TEN is mostly conservative and in- cludes fluid and electrolyte replacement, nutritional support, temperature regulation, prevention and treat- ment of infection using daily dressings and broad-spec- trum antibiotics, and ophthalmic and oral care. A role is suggested for specific therapies such as a short course of corticosteroids, cyclosporine, and intravenous gamma globulin (IVIG), but there is no universal consensus on their efficacy for treating this disease (15). In light of this, we chose to treat the patient conservatively. The increased use of cosmetics in modern society may be responsible for the rise in the incidence of ad- verse reactions. Our presentation suggests the need for increased awareness of the possible severe cutaneous adverse effects of topical OTC drugs. 1. Avakian R, Flowers FP, Araujo OE, Ramos-Caro FA. Toxic epidermal necrolysis: a review. J Am Acad Dermatol. 1991;25:69–79. 2. Fritsch PO, Ruiz-Maldonado R. Erythema multiforme, Stevens-Johnson syndrome and toxic epider- mal necrolysis. In: Freedberg IM, Eisen AZ, Wolff K, Austen K, Goldsmith L, Katz S, editors. Fitzpatrick’s Dermatology in General Medicine. 6th ed. Vol. 1. New York: McGraw-Hill; 2003. p. 548–57. 3. Wolkenstein P, Revuz J. Toxic epidermal necrolysis. Dermatol Clin. 2000;18:485–95. 4. Ghislain PD, Roujeau JC. Treatment of severe drug reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis and hypersensitivity syndrome. Dermatol Online J. 2002;8:5. 5. Roujeau JC, Chosidow O, Saiag P, Guillaume JC. Toxic epidermal necrolysis (Lyell syndrome). J Am Acad Dermatol. 1990;23:1039–58. 6. Guillaume JC,Roujeau JC, Revuz J, Pnso D, Touraine R. The culprit drugs in 87 cases of toxic epidermal necrolysis (Lyell syndrome). Arch Dermatol. 1987;123:1166–70. 7. Pereira FA, Mudgil AV, Rosmarin DM. Toxic epidermal necrolysis. J Am Acad Dermatol. 2007;56(2):181–200. 8. Flórez A, Rosón E, Conde A, González B, García-Doval I, de la Torre C, Cruces M. Toxic epidermal necrolysis secondary to timolol, dorzolamide, and latanoprost eyedrops. J Am Acad Dermatol. 2005;53(5):909–11. 9. Praz SM, de Torrente A, Zender H, Schmied E, Schleppy CA, Genne D. Toxic epidermal necrolysis after topical intranasal application of mupirocin. Infect Control Hosp Epidemiol. 2003;24:459–60. 10. Radimer GF, Davis JH, Ackerman AB. Fumigant-induced toxic epidermal necrolysis. Arch Dermatol. 1974;110:103–4. 11.Thompson JA Jr, Wansker BA. A case of contact dermatitis, erythema multiforme, and toxic epider- mal necrolysis. J Am Acad Dermatol. 1981;5:666–9. 12.Wolkenstein P, Chosidow O, Fléchet ML, et al. Patch testing in severe cutaneous adverse drug reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis. Contact Dermatitis. 1996;35:234–6. RE F E R E N C E S C a s e r e p o r t Toxic epidermal necrolysis due to cosmetic cream
  • 4. 42 Acta Dermatoven APA Vol 18, 2009, No 1 13. Bygum A, Gregersen JW, Buus SK. Acetaminophen-Induced Toxic Epidermal Necrolysis. Pediatr Dermatol. 2004;21(3):236–8. 14. Lim YL, Thirumoorthy T. Serious cutaneous adverse reactions to traditional Chinese medicines. Singapore Med J. 2005;46:714–7. 15. Craven NM, Toxic Epidermal Necrolysis and Stevens-Johnson Syndrome. In: Lebwohl MG, Heymann WR, Berth-Jones J, Coulson I, editors. Treatment of Skin Disease. 2nd ed. London: Mosby Elsever; 2006. p. 657–60. Ibrahim Kokcam MD, Assoc Prof., Department of Dermatology, Firat University School of medicine, 23119 Elazig, Turkey, e-mail:ibrahimkokcam@gmail.com, corresponding author A U T H O R ' S A D D R E S S Toxic epidermal necrolysis due to cosmetic cream C a s e r e p o r t