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Pediatrics International (2014) 56, e52–e54
doi: 10.1111/ped.12410
Patient Report
Toxic epidermal necrolysis treated with N-acetylcysteine Haluk Yavuz and Melike Emiroglu Department of Pediatrics, Necmettin Erbakan University Meram Medical Faculty, Konya, Turkey Abstract
Adverse drug reactions are the major cause of morbidity and mortality worldwide. Cutaneous drug reaction is the most common type of adverse reaction. Toxic epidermal necrolysis (TEN) is a rare, life-threatening mucocutaneous disease, usually attributable to drugs. There is no proven therapy for TEN. The mainstay of therapy is immediate withdrawal of the culprit drug, using disease-modifying agents, and meticulous supportive care. Several disease-modifying agents have been used such as steroid, i.v. human immunoglobulin (IVIg), plasmapheresis. A 10-year-old epileptic girl was admitted with lamotrigine-induced TEN. She was unresponsive to steroid. Her condition deteriorated despite IVIg treatment. She was treated with N-acetylcysteine (NAC). To our knowledge this is the first report of a child with TEN, a potentially lethal disorder, treated with NAC. NAC may be effective for children with TEN.
Key words cutaneous drug reaction, i.v. human immunoglobulin, lamotrigine, N-acetylcysteine, toxic epidermal necrolysis.
Adverse drug reactions caused by immune or non-immune mechanisms are the major cause of morbidity and mortality worldwide. They have been shown to complicate 5–15% of drug treatment courses. Cutaneous drug reaction is the most common type of adverse reaction, and occurs in 8% of the general population and 2–3% of hospitalized patients. Most of these reactions manifest as generalized morbilliform eruptions (50–95%) or urticaria (5–20%). The morbilliform eruptions may be the first presentation of severe cutaneous adverse conditions such as Stevens–Johnson syndrome (SJS), or toxic epidermal necrolysis (TEN).1,2 Toxic epidermal necrolysis is a life-threatening mucocutaneous disease, usually attributable to drugs, especially antibiotics, non-steroidal anti-inflammatory drugs, and anticonvulsants including lamotrigine (LTG). TEN has an annual incidence of 0.4–1.2 cases per million per year. The primary lesions of SJS/TEN are flat, irregular, atypical target lesions of two zones or purpuric macules with a predilection for the trunk, face and proximal limbs. These initial dusky macular lesions become confluent and develop into flaccid blisters. The blisters then coalesce to result in large areas of epidermal detachment as a result of full-thickness epidermal necrosis. Sloughing of the epidermis leaves characteristic moist, denuded dermis. This progression may occur in hours or over a few days. There is intense pain in the affected areas. Mucosal involvement is present in most patients and is typified by erythema and painful erosions of the buccal, ocular and genital mucosa.3 The mortality rates for SJS and TEN are 13% and 39% respectively.4
Correspondence: Melike Emiroglu, MD, Necmettin Erbakan University Meram Medical Faculty, Department of Pediatrics, 42080 Konya, Turkey. Email: [email protected] Received 11 October 2013; revised 4 April 2014; accepted 10 April 2014.
© 2014 Japan Pediatric Society
There is no proven therapy for SJS/TEN. We describe a child with TEN unresponsive to steroid. Her condition deteriorated despite the use of i.v. human immunoglobulin (IVIg). She was treated with N-acetylcysteine (NAC). This is the first report of a child with TEN treated with NAC. NAC may be effective for children with TEN.
Case report A 10-year-old epileptic girl had taken valproate without any serious side-effects. LTG was added to treatment because of recurrence of seizures. In the fourth week of the LTG treatment, she was hospitalized with erythematous rash on the face and chest, sore throat and toothache. On physical examination weight was 26 kg, height 132 cm, body temperature 39.1°C, heart rate 130 beats/min, respiration rate 28 breaths/min, and blood pressure 100/60 mmHg. Also noted were periorbital edema, erythematous maculopapular rash affecting most of the body with augmentation on the chest, aphthous stomatitis, tonsillary and pharyngeal hyperemia. LTG was discontinued immediately. The patient was given i.v. fluids; 30 mg/day prednisolone, ranitidine, setirizine and hydroxyzine, and amoxicillin/clavulanic acid were added for tonsillitis. Laboratory data on admission were as follows: hemoglobin, 11.1 g/dL; thrombocyte count, 110 × 103/μL; white blood cells, 13.5 × 103/μL; 57.1% neutrophils, 21.2% lymphocytes, 11.8% monocytes, 13.8% eosinophils, 1.5% basophils; lactate dehydrogenase, 361 U/L (normal, 98–192 IU/L); and serum sodium, 133 mEq/L (normal, 136–144 mEq/L). The other routine hematological and biochemical tests were normal. The blood and urine cultures, cold agglutination, IgG and IgM serum antibody for Epstein–Barr virus, Herpes simplex virus type II, parvovirus B19 were all negative, IgGs for cytomegalovirus and rubella were positive, while IgMs were negative, and serum total
TEN treated with NAC
e53
Fig. 1 Generalized maculopapular skin lesions and mucosal involvement.
immunoglobulin E, complement C3 and C4 were within the normal range. Although on the third day of hospitalization temporary relative improvement was seen, on the next day the skin rashes worsened and fever increased. Amoxicillin/clavulanic acid was discontinued because throat culture was negative. Steroid therapy was stopped. On the fifth day of hospitalization the patient developed bullous lesions on her body and spiking fever to 40.0°C unresponsive to acetaminophen infusions. Ciprofloxacin was started for suspected nosocomial bacteremia. Over the following 24 h, sloughing of skin and purulent exudation from eyes were noted, and IVIg approximately 0.4 g/kg once daily for 5 days was initiated and valproate was discontinued. On hospital day 8 the rashes became generalized and reached the end of the lower extremities. More than 90% of the patient’s total body surface area was involved, in addition to mucous membranes (Fig. 1). C-reactive protein was 61.5 mg/L (normal, 0–10 mg/L). Crusting on eyelids, ancyloblepharon was noted and fever persisted at approximately 40°C, thus high-dose NAC was prescribed, with the permission of the family. (The i.v. loading dose was 150 mg/kg over 15 min, followed by 50 mg/kg over the next 4 h and 100 mg/kg over the 16 h thereafter. The total dose was 300 mg/kg.5). The next day the rash had stabilized, the shiny red color of the rash had darkened, and fever slightly regressed. A second dose of NAC was given (150 mg/kg per day i.v.). On the 10th day fever decreased. On hospital day 13 her general condition improved in that the fever had gone, but Acinetobacter baumanni, susceptible only to tygecycline and colistin, was isolated from blood cultures taken on the 10th day of hospitalization, and ciprofloxacin was changed to colistin. In the course of time oral, conjunctival and dermal lesions improved substantially and affected skin areas underwent widespread re-epithelialization in the week following NAC treatment (Fig. 2). The patient was discharged in stable condition after Acinetobacter treatment was completed (Fig. 3). A scoring system for grading the severity of TEN, SCORTEN, could not be calculated because of insufficient data.
During hospitalization hyponatremia, hypocalcemia, hypomagnesemia, and hypoalbuminemia were identified and treated. The seizures were treated with continuous midazolam infusion and oral topiramate. Tulle gras dressing with 0.5% chlorhexidine acetate BP and 2% fucidic acide pomade were applied to all open skin lesions. Airflow bed was used. Tramadol and acetaminophen were used for pain control. Total parenteral nutrition and enteral nutrition were given until oral lesions improved.
Discussion Stevens–Johnson syndrome and TEN occurs most frequently on first exposure to the drug, with initial symptoms starting 2–8 weeks after drug exposure.2,6 The present patient’s complaints developed 4 weeks after the beginning of LTG treatment. LTG is an anticonvulsant drug approved for the treatment of focal and generalized epilepsy. The most common side-effect of LTG is exanthema, but it can induce SJS or TEN.6,7
Fig. 2
Re-epithelialization of the affected skin. © 2014 Japan Pediatric Society
e54
H Yavuz and M Emiroglu In the literature five adults have been treated with NAC, and rapid improvement was seen in all cases.8–10 Claes et al. used the combination of IVIg and NAC.9 We do not know whether the improvement in the present patient was due solely to NAC or IVIg or to the combined effect of IVIg and NAC. There is controversy over the use of IVIg in the treatment of SJS/TEN. Randomized controlled trials to assess the benefits and risks of IVIg in TEN are lacking.11 N-acetylcysteine is a non-toxic and inexpensive drug with well-documented pharmacokinetics and safety. It is an advantage of NAC that it can be given for a short time, such as 1 or 2 days, as a minimally invasive application for the treatment of TEN. Moreover, to our knowledge, this is the first case describing combined treatment with IVIg and high-dose NAC for TEN in a child. NAC is a safe intervention in extremely ill TEN patients and may reduce the mortality in this severe disease. Prospective studies are needed to further define its usefulness.
Fig. 3 The course of fever (°C) and involved area (%) according to treatment modalities. Fever was measured via the axillary route until day 6 of hospitalization, after which the rectal route was preferred due to presence of lesions. IVIg, i.v. human immunoglobulin; NAC, N-acetylcysteine.
Treatment of SJS and TEN includes supportive procedures and several disease-modifying agents. Discontinuation of a suspected drug, rigorous adjustment of fluid, protein and electrolyte balance, strict thermoregulation, control of infection, care of eye, oral and nasal mucosa, supportive pulmonary care and regular surveillance with sepsis screening are essential. Although several disease-modifying agents such as corticosteroids, IVIg and plasmapheresis have been used, there is no clear consensus on treatment.2–4 Given that the clinical situation of the present patient continued to deteriorate in spite of steroid and IVIg therapies, we decided to carry out another promising therapeutic option, NAC, as proposed for the treatment of acetaminophen overdose.5 The pathophysiology of TEN is still unknown, but most hypotheses are based on a specific immunologic reaction against keratinocytes modified by the drug or its metabolites. The reactive metabolites are intracellularly scavenged by the oxidant-buffering capacity of glutathione, the main molecule involved in the detoxification of drugs.8 NAC is a cysteine derivative precursor of glutathione. It increases glutathione stores, it acts as a glutathione substitute, and it enhances sulphate conjugation. NAC also has antioxidant, antiinflammatory, inotropic, and vasodilating effects that may further benefit the patient. NAC may be effective in severe drug reactions in three ways: (i) reacting with oxidative intermediates and replenishing intracellular cysteine necessary for the production of glutathione; (ii) inhibiting production of tumor necrosis factor-α and interleukin-1; and (iii) blocking expression of the skin homing receptor cutaneous lymphocyteassociated antigen.5,8
© 2014 Japan Pediatric Society
Acknowledgment The authors state that there is no conflict of interest.
References 1 Seth D, Kamat D, Montejo J. DRESS syndrome: A practical approach for primary care practitioners. Clin. Pediatr. (Phila). 2008; 47: 947–52. 2 Knowles SR, Shear NH. Recognition and management of severe cutaneous drug reactions. Dermatol. Clin. 2007; 25: 245–53. 3 Mukasa Y, Craven N. Management of toxic epidermal necrolysis and related syndromes. Postgrad. Med. J. 2008; 84: 60–65. 4 Schneck J, Fagot JP, Sekula P, Sassolas B, Roujeau JC, Mockenhaupt M. Effects of treatments on the mortality of StevensJohnson syndrome and toxic epidermal necrolysis: A retrospective study on patients included in the prospective EuroSCAR Study. J. Am. Acad. Dermatol. 2008; 58: 33–40. 5 Larson AM. Acetaminophen hepatotoxicity. Clin. Liver Dis. 2007; 11: 525–48. 6 Mockenhaupt M, Viboud C, Dunant A et al. Stevens-Johnson syndrome and toxic epidermal necrolysis: Assessment of medication risks with emphasis on recently marketed drugs. The EuroSCARstudy. J. Invest. Dermatol. 2008; 128: 35–44. 7 P-Codrea (Tigaran) S, Sidenius P, Dam M. Lamotrigine-induced rash: Worth a rechallenge. Acta Neurol. Scand. 2005; 111: 191–4. 8 Vélez A, Moreno JC. Toxic epidermal necrolysis treated with N-acetylcysteine. J. Am. Acad. Dermatol. 2002; 46: 469–70. 9 Claes P, Wintzen M, Allard S, Simons P, De Coninck A, Lacor P. Nevirapine-induced toxic epidermal necrolysis and toxic hepatitis treated successfully with a combination of intravenous immunoglobulins and N-acetylcysteine. Eur. J. Intern. Med. 2004; 15: 255–8. 10 Redondo P, de Felipe I, de la Peña A, Aramendia JM, Vanaclocha V. Drug-induced hypersensitivity syndrome and toxic epidermal necrolysis. Treatment with N-acetylcysteine. Br. J. Dermatol. 1997; 136: 645–6. 11 Momin SB, Del Rosso JQ. Review of intravenous immunoglobulin in the treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis. J. Clin. Aesthet. Dermatol. 2009; 2: 51–8.
Pediatrics International (2014) 56, e52–e54
doi: 10.1111/ped.12410
Patient Report
Toxic epidermal necrolysis treated with N-acetylcysteine Haluk Yavuz and Melike Emiroglu Department of Pediatrics, Necmettin Erbakan University Meram Medical Faculty, Konya, Turkey Abstract
Adverse drug reactions are the major cause of morbidity and mortality worldwide. Cutaneous drug reaction is the most common type of adverse reaction. Toxic epidermal necrolysis (TEN) is a rare, life-threatening mucocutaneous disease, usually attributable to drugs. There is no proven therapy for TEN. The mainstay of therapy is immediate withdrawal of the culprit drug, using disease-modifying agents, and meticulous supportive care. Several disease-modifying agents have been used such as steroid, i.v. human immunoglobulin (IVIg), plasmapheresis. A 10-year-old epileptic girl was admitted with lamotrigine-induced TEN. She was unresponsive to steroid. Her condition deteriorated despite IVIg treatment. She was treated with N-acetylcysteine (NAC). To our knowledge this is the first report of a child with TEN, a potentially lethal disorder, treated with NAC. NAC may be effective for children with TEN.
Key words cutaneous drug reaction, i.v. human immunoglobulin, lamotrigine, N-acetylcysteine, toxic epidermal necrolysis.
Adverse drug reactions caused by immune or non-immune mechanisms are the major cause of morbidity and mortality worldwide. They have been shown to complicate 5–15% of drug treatment courses. Cutaneous drug reaction is the most common type of adverse reaction, and occurs in 8% of the general population and 2–3% of hospitalized patients. Most of these reactions manifest as generalized morbilliform eruptions (50–95%) or urticaria (5–20%). The morbilliform eruptions may be the first presentation of severe cutaneous adverse conditions such as Stevens–Johnson syndrome (SJS), or toxic epidermal necrolysis (TEN).1,2 Toxic epidermal necrolysis is a life-threatening mucocutaneous disease, usually attributable to drugs, especially antibiotics, non-steroidal anti-inflammatory drugs, and anticonvulsants including lamotrigine (LTG). TEN has an annual incidence of 0.4–1.2 cases per million per year. The primary lesions of SJS/TEN are flat, irregular, atypical target lesions of two zones or purpuric macules with a predilection for the trunk, face and proximal limbs. These initial dusky macular lesions become confluent and develop into flaccid blisters. The blisters then coalesce to result in large areas of epidermal detachment as a result of full-thickness epidermal necrosis. Sloughing of the epidermis leaves characteristic moist, denuded dermis. This progression may occur in hours or over a few days. There is intense pain in the affected areas. Mucosal involvement is present in most patients and is typified by erythema and painful erosions of the buccal, ocular and genital mucosa.3 The mortality rates for SJS and TEN are 13% and 39% respectively.4
Correspondence: Melike Emiroglu, MD, Necmettin Erbakan University Meram Medical Faculty, Department of Pediatrics, 42080 Konya, Turkey. Email: [email protected] Received 11 October 2013; revised 4 April 2014; accepted 10 April 2014.
© 2014 Japan Pediatric Society
There is no proven therapy for SJS/TEN. We describe a child with TEN unresponsive to steroid. Her condition deteriorated despite the use of i.v. human immunoglobulin (IVIg). She was treated with N-acetylcysteine (NAC). This is the first report of a child with TEN treated with NAC. NAC may be effective for children with TEN.
Case report A 10-year-old epileptic girl had taken valproate without any serious side-effects. LTG was added to treatment because of recurrence of seizures. In the fourth week of the LTG treatment, she was hospitalized with erythematous rash on the face and chest, sore throat and toothache. On physical examination weight was 26 kg, height 132 cm, body temperature 39.1°C, heart rate 130 beats/min, respiration rate 28 breaths/min, and blood pressure 100/60 mmHg. Also noted were periorbital edema, erythematous maculopapular rash affecting most of the body with augmentation on the chest, aphthous stomatitis, tonsillary and pharyngeal hyperemia. LTG was discontinued immediately. The patient was given i.v. fluids; 30 mg/day prednisolone, ranitidine, setirizine and hydroxyzine, and amoxicillin/clavulanic acid were added for tonsillitis. Laboratory data on admission were as follows: hemoglobin, 11.1 g/dL; thrombocyte count, 110 × 103/μL; white blood cells, 13.5 × 103/μL; 57.1% neutrophils, 21.2% lymphocytes, 11.8% monocytes, 13.8% eosinophils, 1.5% basophils; lactate dehydrogenase, 361 U/L (normal, 98–192 IU/L); and serum sodium, 133 mEq/L (normal, 136–144 mEq/L). The other routine hematological and biochemical tests were normal. The blood and urine cultures, cold agglutination, IgG and IgM serum antibody for Epstein–Barr virus, Herpes simplex virus type II, parvovirus B19 were all negative, IgGs for cytomegalovirus and rubella were positive, while IgMs were negative, and serum total
TEN treated with NAC
e53
Fig. 1 Generalized maculopapular skin lesions and mucosal involvement.
immunoglobulin E, complement C3 and C4 were within the normal range. Although on the third day of hospitalization temporary relative improvement was seen, on the next day the skin rashes worsened and fever increased. Amoxicillin/clavulanic acid was discontinued because throat culture was negative. Steroid therapy was stopped. On the fifth day of hospitalization the patient developed bullous lesions on her body and spiking fever to 40.0°C unresponsive to acetaminophen infusions. Ciprofloxacin was started for suspected nosocomial bacteremia. Over the following 24 h, sloughing of skin and purulent exudation from eyes were noted, and IVIg approximately 0.4 g/kg once daily for 5 days was initiated and valproate was discontinued. On hospital day 8 the rashes became generalized and reached the end of the lower extremities. More than 90% of the patient’s total body surface area was involved, in addition to mucous membranes (Fig. 1). C-reactive protein was 61.5 mg/L (normal, 0–10 mg/L). Crusting on eyelids, ancyloblepharon was noted and fever persisted at approximately 40°C, thus high-dose NAC was prescribed, with the permission of the family. (The i.v. loading dose was 150 mg/kg over 15 min, followed by 50 mg/kg over the next 4 h and 100 mg/kg over the 16 h thereafter. The total dose was 300 mg/kg.5). The next day the rash had stabilized, the shiny red color of the rash had darkened, and fever slightly regressed. A second dose of NAC was given (150 mg/kg per day i.v.). On the 10th day fever decreased. On hospital day 13 her general condition improved in that the fever had gone, but Acinetobacter baumanni, susceptible only to tygecycline and colistin, was isolated from blood cultures taken on the 10th day of hospitalization, and ciprofloxacin was changed to colistin. In the course of time oral, conjunctival and dermal lesions improved substantially and affected skin areas underwent widespread re-epithelialization in the week following NAC treatment (Fig. 2). The patient was discharged in stable condition after Acinetobacter treatment was completed (Fig. 3). A scoring system for grading the severity of TEN, SCORTEN, could not be calculated because of insufficient data.
During hospitalization hyponatremia, hypocalcemia, hypomagnesemia, and hypoalbuminemia were identified and treated. The seizures were treated with continuous midazolam infusion and oral topiramate. Tulle gras dressing with 0.5% chlorhexidine acetate BP and 2% fucidic acide pomade were applied to all open skin lesions. Airflow bed was used. Tramadol and acetaminophen were used for pain control. Total parenteral nutrition and enteral nutrition were given until oral lesions improved.
Discussion Stevens–Johnson syndrome and TEN occurs most frequently on first exposure to the drug, with initial symptoms starting 2–8 weeks after drug exposure.2,6 The present patient’s complaints developed 4 weeks after the beginning of LTG treatment. LTG is an anticonvulsant drug approved for the treatment of focal and generalized epilepsy. The most common side-effect of LTG is exanthema, but it can induce SJS or TEN.6,7
Fig. 2
Re-epithelialization of the affected skin. © 2014 Japan Pediatric Society
e54
H Yavuz and M Emiroglu In the literature five adults have been treated with NAC, and rapid improvement was seen in all cases.8–10 Claes et al. used the combination of IVIg and NAC.9 We do not know whether the improvement in the present patient was due solely to NAC or IVIg or to the combined effect of IVIg and NAC. There is controversy over the use of IVIg in the treatment of SJS/TEN. Randomized controlled trials to assess the benefits and risks of IVIg in TEN are lacking.11 N-acetylcysteine is a non-toxic and inexpensive drug with well-documented pharmacokinetics and safety. It is an advantage of NAC that it can be given for a short time, such as 1 or 2 days, as a minimally invasive application for the treatment of TEN. Moreover, to our knowledge, this is the first case describing combined treatment with IVIg and high-dose NAC for TEN in a child. NAC is a safe intervention in extremely ill TEN patients and may reduce the mortality in this severe disease. Prospective studies are needed to further define its usefulness.
Fig. 3 The course of fever (°C) and involved area (%) according to treatment modalities. Fever was measured via the axillary route until day 6 of hospitalization, after which the rectal route was preferred due to presence of lesions. IVIg, i.v. human immunoglobulin; NAC, N-acetylcysteine.
Treatment of SJS and TEN includes supportive procedures and several disease-modifying agents. Discontinuation of a suspected drug, rigorous adjustment of fluid, protein and electrolyte balance, strict thermoregulation, control of infection, care of eye, oral and nasal mucosa, supportive pulmonary care and regular surveillance with sepsis screening are essential. Although several disease-modifying agents such as corticosteroids, IVIg and plasmapheresis have been used, there is no clear consensus on treatment.2–4 Given that the clinical situation of the present patient continued to deteriorate in spite of steroid and IVIg therapies, we decided to carry out another promising therapeutic option, NAC, as proposed for the treatment of acetaminophen overdose.5 The pathophysiology of TEN is still unknown, but most hypotheses are based on a specific immunologic reaction against keratinocytes modified by the drug or its metabolites. The reactive metabolites are intracellularly scavenged by the oxidant-buffering capacity of glutathione, the main molecule involved in the detoxification of drugs.8 NAC is a cysteine derivative precursor of glutathione. It increases glutathione stores, it acts as a glutathione substitute, and it enhances sulphate conjugation. NAC also has antioxidant, antiinflammatory, inotropic, and vasodilating effects that may further benefit the patient. NAC may be effective in severe drug reactions in three ways: (i) reacting with oxidative intermediates and replenishing intracellular cysteine necessary for the production of glutathione; (ii) inhibiting production of tumor necrosis factor-α and interleukin-1; and (iii) blocking expression of the skin homing receptor cutaneous lymphocyteassociated antigen.5,8
© 2014 Japan Pediatric Society
Acknowledgment The authors state that there is no conflict of interest.
References 1 Seth D, Kamat D, Montejo J. DRESS syndrome: A practical approach for primary care practitioners. Clin. Pediatr. (Phila). 2008; 47: 947–52. 2 Knowles SR, Shear NH. Recognition and management of severe cutaneous drug reactions. Dermatol. Clin. 2007; 25: 245–53. 3 Mukasa Y, Craven N. Management of toxic epidermal necrolysis and related syndromes. Postgrad. Med. J. 2008; 84: 60–65. 4 Schneck J, Fagot JP, Sekula P, Sassolas B, Roujeau JC, Mockenhaupt M. Effects of treatments on the mortality of StevensJohnson syndrome and toxic epidermal necrolysis: A retrospective study on patients included in the prospective EuroSCAR Study. J. Am. Acad. Dermatol. 2008; 58: 33–40. 5 Larson AM. Acetaminophen hepatotoxicity. Clin. Liver Dis. 2007; 11: 525–48. 6 Mockenhaupt M, Viboud C, Dunant A et al. Stevens-Johnson syndrome and toxic epidermal necrolysis: Assessment of medication risks with emphasis on recently marketed drugs. The EuroSCARstudy. J. Invest. Dermatol. 2008; 128: 35–44. 7 P-Codrea (Tigaran) S, Sidenius P, Dam M. Lamotrigine-induced rash: Worth a rechallenge. Acta Neurol. Scand. 2005; 111: 191–4. 8 Vélez A, Moreno JC. Toxic epidermal necrolysis treated with N-acetylcysteine. J. Am. Acad. Dermatol. 2002; 46: 469–70. 9 Claes P, Wintzen M, Allard S, Simons P, De Coninck A, Lacor P. Nevirapine-induced toxic epidermal necrolysis and toxic hepatitis treated successfully with a combination of intravenous immunoglobulins and N-acetylcysteine. Eur. J. Intern. Med. 2004; 15: 255–8. 10 Redondo P, de Felipe I, de la Peña A, Aramendia JM, Vanaclocha V. Drug-induced hypersensitivity syndrome and toxic epidermal necrolysis. Treatment with N-acetylcysteine. Br. J. Dermatol. 1997; 136: 645–6. 11 Momin SB, Del Rosso JQ. Review of intravenous immunoglobulin in the treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis. J. Clin. Aesthet. Dermatol. 2009; 2: 51–8.
