Toxic Epidermal Necrolysis JOSEPH A. LACY, R.D., L.D., M.S. University of Cincinnati Medical Center, Cincinnati,
Ohio
epidermal necrolysis is a rapidly progressive dermatologic condition associated with high mortality. Several factors have been implicated in the development of toxic epidermal necrolysis including drugs, vaccinations, infections, and neoplasia. Toxic epidermal necrolysis therapy has been compared with partial-thickness burn injury treatment. The absence of burned tissue can dampen fluid requirements and metabolic needs of toxic epidermal necrolysis in comparison to equivalent burn injury. In the following case report, a 69-year-old woman with multiple medical problems developed toxic epidermal necrolysis after treatment with metolazone and phenytoin. Her measured energy expenditure (3360 kcal) was considerably higher than previously reported caloric expenditure in toxic epidermal necrolysis patients (2500 kcal). ABSTRACT: Toxic
ble some aspects of burns, the absence of burned tissue mutes the physiological response in quantitative terms. Fluid requirements and metabolic needs are often less in TEN than in an equivalent burn injury.’ The following case report describes a patient whose energy needs were higher than predicted. CASE REPORT
H.K., a 69-year-old white woman, was transferred University Hospital’s Burns Special Care Unit from an outlying hospital in September 1990, suffering from 55% total body surface area skin slough secondary to presumed TEN. Her past medical problems included a history of seizure disorder, peptic ulcer disease, hypothyroidism, obesity, chronic obstructive pulmonary disease, and congestive heart failure. Before her transfer, the patient had experienced a generalized seizure. Her CT scan was nonspecific. The seizure activity was believed to be secondary to acid/base abnormalities, and the patient was subsequently given phenytoin. TEN manifestation was suspected to be secondary to drug therapy, with the culpable agent being either metolazone or phenytoin. to
epidermal necrolysis (TEN), first described by Lyell in 1956,1 is a serious, rapidly progressive dermatologic condition with mortality ranging from 20 to 70% in patients who require hospitalization.~-4 Toxic
The incidence of TEN has been associated with pharmacotherapy, including sulfonamides, anticonvulsants, penicillins, and nonsteroidal anti-inflam-
matory drugs (Table 1).
On examination, the patient was found to have 90 epidermal skin loss consistent with TEN. Nutritional assessment revealed the following: height, 5 feet 7 inches; weight, 100 kg; basal energy expenditure, 1,305 kcal (adjusted for obesity) per HarrisBenedict equation; resting energy expenditure, 2,740 kcal (basal energy expenditure X 1.2 X 1.75), serum albumin, 2.3. On hospital day (HD) 2, a full-strength, high-nitrogen isotonic tube feeding (Impact’) was instituted at 30ml/h continuously after successful insertion of a nasogastric feeding tube. The tube feeding
Treatment for TEN has been compared with the management of partial-thickness burn injury. Injury to the skin-the largest organ of the body-is associated with a marked change in the body’s need for and use of nutrients. The magnitude and persistence of hypermetabolic response after burn injury is the most significant of any insult that the human body sustains’. Although the characteristics of TEN resem-
to 95%
changed to a full-strength, high-fiber product to provide less of a nitrogen load and promote bowel tolerance. By HD 3, a dermatologic examination revealed essentially 100% of body surface area sloughed. The patient’s hypokalemia, hypomagnesemia, and hypophosphatemia were corrected by
was
(Jevity’)
Address requests for reprints to Joseph A. Lacy, University of Cincinnati Medical Center, Cincinnati, OH 45267-0771.
18 Downloaded from ncp.sagepub.com at FLORIDA INTERNATIONAL UNIV on May 29, 2015
19 Table 1. Factors Associated with TEN
quent in TEN. Dietary modifications
Development.
supplemental intravenous infusions. An indirect calorimetric measurement on HD 4 revealed a respiratory quotient of 0.89 and a 24-h caloric expenditure of 3,360 kcal. The feeding was advanced to a target tube feeding rate of 140 ml/h. On HD 7 the patient developed an ileus possibly secondary to sepsis. The feeding was decreased to 20 ml/h. During the next 24 h the patient suffered significant deterioration in major organ
systems and died on HD 8.
DISCUSSION
Patients with TEN or burns share commonalities of fluid resuscitation needs, methods of organ systems support, and types of wound care management. The control of infection is the cornerstone of treatment. TEN is characterized by widespread epidermal necrosis and a profound systemic toxic condition.’ Major sloughs of skin (often in sheets) occur in TEN at the dermoepidermal junction. The disorder occurs as an adverse reaction to a spectrum of drugs and infectious agents.’ Drug-related cases typically begin within 3 weeks of initiation of therapy; in cases of reexposure to a drug, the reaction may begin within hours of restarting therapy.’ Several recent reviews have listed culprit drugs suspected of causing TEN.9-12 The incidence of TEN and similar diseases severe enough to require hospitalization is estimated to be fewer than 1 per
100,000 patients.8
The
goals
of
therapy
are
to
provide
intensive sup-
can be made to increase intake of soft foods and liquids for patients able to take an oral diet.18 Often, therapy includes placement of a nasogastric or nasoenteric feeding tube to supply adequate nutrition. Nutrition support should be given by the enteral route whenever possible. Although ileus is uncommon,6 it can occur, and parenteral nutrition may be required in some patients.’ The risk of central venous catheters, however, can outweigh the benefit; their use should be avoided if at all possible. Careful fluid and electrolyte monitoring is required. Daily evaporative water loss can be extremely high if the patient is on air-fluidized bed or if fever is persistent.’ A paucity of research involving TEN and nutrition leaves many questions unanswered regarding precise nutrient requirements of affected patients. Lechner-Gruskay et al. describe nutritional deficiencies of children with epidermolysis bullosa, a genetic skin disorder in which denudation of skin occurs and the gastrointestinal tract is affected. Nutrient deficiencies were reported for zinc, magnesium, calcium, potassium, iron, vitamins A, D, E, thiamin, B12, and B6, protein, and calories.19 Although differences are evident in these two diseases, TEN patients may be affected by similar deficiencies. H.K.’s laboratory values reflected classical symptoms of refeeding syn-
drome.2o Prevention of malnutrition appears to be an integral part of avoiding short-term and long-term complications of TEN. Indirect calorimetric measurements are reported to be in the high end of normal range in comparison to burns of similar size. Heimbach et al. have reported that adult patients achieve weight stability and positive nitrogen balance when provided with approximately 2500 kcal/day.’ In pediatric patients, Hildreth reports that a previously published surface area formula for pediatric burn patients appears to overestimate the caloric needs of pediatric patients with TEN.21 In the case of H.K., her actual energy expenditure exceeded a liberal estimate of energy expenditure by 23%. H.K. was febrile (100.6°F
axillary temperature during measurement). Elevated energy expenditure could be expressed as a function of lack of biological dressing, which has been reported
port while the epidermis regenerates and to minimize
to decrease energy needs in the TEN
the potential for subsequent morbidity. Few clinical conditions constitute &dquo;nutritional emergencies&dquo;; however, the burn patient population requires prompt nutritional intervention.13-15 Burn care management appears appropriate for the unburned in the case of TEN. Although information about the nutritional requirements of TEN patients is scant when compared with that of burn patients, swift intervention seems
Nutritional care for TEN patients should include metabolic cart measurement if possible, monitoring of fluid and electrolyte balance, attention to dietary modifications in patients taking oral nutrition, and individualized administration of nutrients for reepithelialization as necessary. One important consideration as yet to be defined is the indication/contraindication for purported immunoenhancing/immunosuppressive nutrients in a disease state some postulate to involve circulating im-
appropriate.16,17 Early nutritional support is of paramount imporpatients with poor oral intake. Involvement of the gastrointestinal mucosa is less common; how-
tance to
ever, oral mucositis and mouth discomfort
are
fre-
population
complexes.&dquo; In the arena of pharmacotherapy, clinicians had recommended early use of steroids until progression of skin lesions had been arrested, mune
some
Downloaded from ncp.sagepub.com at FLORIDA INTERNATIONAL UNIV on May 29, 2015
20
but later reports show growing reluctance to administer steroids because of infectious complica-
8. Chan
tions.3°’~ ls° 2s Limited data are available on the nutritional care of TEN patients. Some parallels exist between TEN and burn manifestation. Prompt nutrition support appears indicated; enteral nutrition is preferred over parenteral nutrition support. Nitrogen needs may be elevated. Several micronutrient deficiencies can be present. Ascorbic acid, vitamin A, and zinc may be of particular importance for wound healing. Although energy expenditure in TEN patients is reportedly lower when compared with that in equivalent burn injury, H.K.’s energy expenditure was measured considerably higher than estimated needs. As more research is completed on TEN patients, nutritional pre-
9.
HL, Stern RS, Arndt KA. The incidence of erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. A population-based study with particular reference to reactions caused by drugs among outpatients. Arch Dermatol 1990;126:43-7. Guillaume JC, Roujeau JC, Revuz J. The culprit drugs in 87
of toxic epidermal necrolysis (Lyell’s syndrome). Arch Dermatol 1987;123:1166-70. 10. Roujeau JC, Huynh TH, Bracq C. Genetic susceptibility to toxic epidermal necrolysis. Arch Dermatol 1987;123:1171-3. 11. Roujeau JC, Guillaume JC, Fabre JP. Toxic epidermal necrolysis (Lyell syndrome). Incidence and drug etiology in France, 1981-5. Arch Dermatol 1990;126:37-42. 12. Fansidar-associated fatal reaction in an HIV-infected man. Reported by: Malaria Br and Parasitic Diseases Br, Division of Parasitic Diseases; AIDS Program, Center for Infectious Diseases, Centers for Disease Control. J Am Med Assoc cases
1988;260:2193.
scription will be further clarified.
13. Alexander JW, Gottschlich MM. Nutritional immunodulation in burn patients. Crit Care Med 1990;18:S149-S153. 14. Gottschlich MM, Jenkins M, Warden GD, et al. Differential effects of three enteral regimens on selected outcome variables.
REFERENCES
15. Deitch EA. The management of burns. N
JPEN 1990;14:225-36.
Engl
J Med
1990;323:1249-53.
Lyell A. Toxic epidermal necrolysis: an eruption resembling scalding of the skin. Br J Dermatol 1956;68:355-61. Massullo RE, Welton WA, Jacobsen E. Toxic epidermal necrolysis: report of two cases. J Am Acad Dermatol 1988;
16.
19:358-9. 3. Prendiville JS, Hebert AA, Greenwald MJ, et al. Management of Stevens-Johnson syndrome and toxic epidermal necrolysis in children. J Pediatr 1989;115:881-7. 4. Goldstein SM, Wintroub BW, Elias PM, et al. Toxic epidermal necrolysis. Unmuddying the waters. Arch Dermatol
18.
1. 2.
1987;123:1153-5. 5. Gamelli RL. Nutritional problems of the acute and chronic burn patient. Relevance to epidermolysis bullosa. Arch Dermatol
1988;124:756-9. 6. Pruitt BA. Burn treatment for the unburned. J Am Med Assoc
1987;257:2207-8. DM, Engrav LH, Marvin JA. Toxic epidermal necrolysis. A step forward in treatment. J Am Med Assoc 1987;257:2171-5.
7. Heimbach
17.
19.
Taylor JA, Grube B, Heimbach DM. Toxic epidermal necrolysis. A comprehensive approach. Clin Pediatr 1989;28:404-7. Revuz J, Roujeau JC, Guillaume JC, et al. Treatment of toxic epidermal necrolysis. Arch Dermatol 1987;123:1156-8. Nowak AJ. Oropharyngeal lesions and their management in epidermolysis bullosa. Arch Dermatol 1988;124:742-4. Lechner-Gruskay D, Honig PJ, Pereira G. Nutritional and metabolic profile of children with epidermolysis bullosa. Pediatr
Dermatol 1988;5:22-7. 20. Solomon SM, Kirby DF. The refeeding syndrome: A review. JPEN 1990;14:90-7. 21. Hildreth MA. Caloric needs of pediatric patients with toxic epidermal necrolysis. Poster session: clinical nutrition practice and research. J Am Diet Assoc 1990;9. 22. Birchall N, Langdon R, Cuono C. Toxic epidermal necrolysis: an approach to management using cryopreserved allograft skin. J Am Acad Dermatol 1987;16:368-72. 23. Parsons JM. Management of toxic epidermal necrolysis. Cutis
1985;10:305-11.
Downloaded from ncp.sagepub.com at FLORIDA INTERNATIONAL UNIV on May 29, 2015
Ohio
epidermal necrolysis is a rapidly progressive dermatologic condition associated with high mortality. Several factors have been implicated in the development of toxic epidermal necrolysis including drugs, vaccinations, infections, and neoplasia. Toxic epidermal necrolysis therapy has been compared with partial-thickness burn injury treatment. The absence of burned tissue can dampen fluid requirements and metabolic needs of toxic epidermal necrolysis in comparison to equivalent burn injury. In the following case report, a 69-year-old woman with multiple medical problems developed toxic epidermal necrolysis after treatment with metolazone and phenytoin. Her measured energy expenditure (3360 kcal) was considerably higher than previously reported caloric expenditure in toxic epidermal necrolysis patients (2500 kcal). ABSTRACT: Toxic
ble some aspects of burns, the absence of burned tissue mutes the physiological response in quantitative terms. Fluid requirements and metabolic needs are often less in TEN than in an equivalent burn injury.’ The following case report describes a patient whose energy needs were higher than predicted. CASE REPORT
H.K., a 69-year-old white woman, was transferred University Hospital’s Burns Special Care Unit from an outlying hospital in September 1990, suffering from 55% total body surface area skin slough secondary to presumed TEN. Her past medical problems included a history of seizure disorder, peptic ulcer disease, hypothyroidism, obesity, chronic obstructive pulmonary disease, and congestive heart failure. Before her transfer, the patient had experienced a generalized seizure. Her CT scan was nonspecific. The seizure activity was believed to be secondary to acid/base abnormalities, and the patient was subsequently given phenytoin. TEN manifestation was suspected to be secondary to drug therapy, with the culpable agent being either metolazone or phenytoin. to
epidermal necrolysis (TEN), first described by Lyell in 1956,1 is a serious, rapidly progressive dermatologic condition with mortality ranging from 20 to 70% in patients who require hospitalization.~-4 Toxic
The incidence of TEN has been associated with pharmacotherapy, including sulfonamides, anticonvulsants, penicillins, and nonsteroidal anti-inflam-
matory drugs (Table 1).
On examination, the patient was found to have 90 epidermal skin loss consistent with TEN. Nutritional assessment revealed the following: height, 5 feet 7 inches; weight, 100 kg; basal energy expenditure, 1,305 kcal (adjusted for obesity) per HarrisBenedict equation; resting energy expenditure, 2,740 kcal (basal energy expenditure X 1.2 X 1.75), serum albumin, 2.3. On hospital day (HD) 2, a full-strength, high-nitrogen isotonic tube feeding (Impact’) was instituted at 30ml/h continuously after successful insertion of a nasogastric feeding tube. The tube feeding
Treatment for TEN has been compared with the management of partial-thickness burn injury. Injury to the skin-the largest organ of the body-is associated with a marked change in the body’s need for and use of nutrients. The magnitude and persistence of hypermetabolic response after burn injury is the most significant of any insult that the human body sustains’. Although the characteristics of TEN resem-
to 95%
changed to a full-strength, high-fiber product to provide less of a nitrogen load and promote bowel tolerance. By HD 3, a dermatologic examination revealed essentially 100% of body surface area sloughed. The patient’s hypokalemia, hypomagnesemia, and hypophosphatemia were corrected by
was
(Jevity’)
Address requests for reprints to Joseph A. Lacy, University of Cincinnati Medical Center, Cincinnati, OH 45267-0771.
18 Downloaded from ncp.sagepub.com at FLORIDA INTERNATIONAL UNIV on May 29, 2015
19 Table 1. Factors Associated with TEN
quent in TEN. Dietary modifications
Development.
supplemental intravenous infusions. An indirect calorimetric measurement on HD 4 revealed a respiratory quotient of 0.89 and a 24-h caloric expenditure of 3,360 kcal. The feeding was advanced to a target tube feeding rate of 140 ml/h. On HD 7 the patient developed an ileus possibly secondary to sepsis. The feeding was decreased to 20 ml/h. During the next 24 h the patient suffered significant deterioration in major organ
systems and died on HD 8.
DISCUSSION
Patients with TEN or burns share commonalities of fluid resuscitation needs, methods of organ systems support, and types of wound care management. The control of infection is the cornerstone of treatment. TEN is characterized by widespread epidermal necrosis and a profound systemic toxic condition.’ Major sloughs of skin (often in sheets) occur in TEN at the dermoepidermal junction. The disorder occurs as an adverse reaction to a spectrum of drugs and infectious agents.’ Drug-related cases typically begin within 3 weeks of initiation of therapy; in cases of reexposure to a drug, the reaction may begin within hours of restarting therapy.’ Several recent reviews have listed culprit drugs suspected of causing TEN.9-12 The incidence of TEN and similar diseases severe enough to require hospitalization is estimated to be fewer than 1 per
100,000 patients.8
The
goals
of
therapy
are
to
provide
intensive sup-
can be made to increase intake of soft foods and liquids for patients able to take an oral diet.18 Often, therapy includes placement of a nasogastric or nasoenteric feeding tube to supply adequate nutrition. Nutrition support should be given by the enteral route whenever possible. Although ileus is uncommon,6 it can occur, and parenteral nutrition may be required in some patients.’ The risk of central venous catheters, however, can outweigh the benefit; their use should be avoided if at all possible. Careful fluid and electrolyte monitoring is required. Daily evaporative water loss can be extremely high if the patient is on air-fluidized bed or if fever is persistent.’ A paucity of research involving TEN and nutrition leaves many questions unanswered regarding precise nutrient requirements of affected patients. Lechner-Gruskay et al. describe nutritional deficiencies of children with epidermolysis bullosa, a genetic skin disorder in which denudation of skin occurs and the gastrointestinal tract is affected. Nutrient deficiencies were reported for zinc, magnesium, calcium, potassium, iron, vitamins A, D, E, thiamin, B12, and B6, protein, and calories.19 Although differences are evident in these two diseases, TEN patients may be affected by similar deficiencies. H.K.’s laboratory values reflected classical symptoms of refeeding syn-
drome.2o Prevention of malnutrition appears to be an integral part of avoiding short-term and long-term complications of TEN. Indirect calorimetric measurements are reported to be in the high end of normal range in comparison to burns of similar size. Heimbach et al. have reported that adult patients achieve weight stability and positive nitrogen balance when provided with approximately 2500 kcal/day.’ In pediatric patients, Hildreth reports that a previously published surface area formula for pediatric burn patients appears to overestimate the caloric needs of pediatric patients with TEN.21 In the case of H.K., her actual energy expenditure exceeded a liberal estimate of energy expenditure by 23%. H.K. was febrile (100.6°F
axillary temperature during measurement). Elevated energy expenditure could be expressed as a function of lack of biological dressing, which has been reported
port while the epidermis regenerates and to minimize
to decrease energy needs in the TEN
the potential for subsequent morbidity. Few clinical conditions constitute &dquo;nutritional emergencies&dquo;; however, the burn patient population requires prompt nutritional intervention.13-15 Burn care management appears appropriate for the unburned in the case of TEN. Although information about the nutritional requirements of TEN patients is scant when compared with that of burn patients, swift intervention seems
Nutritional care for TEN patients should include metabolic cart measurement if possible, monitoring of fluid and electrolyte balance, attention to dietary modifications in patients taking oral nutrition, and individualized administration of nutrients for reepithelialization as necessary. One important consideration as yet to be defined is the indication/contraindication for purported immunoenhancing/immunosuppressive nutrients in a disease state some postulate to involve circulating im-
appropriate.16,17 Early nutritional support is of paramount imporpatients with poor oral intake. Involvement of the gastrointestinal mucosa is less common; how-
tance to
ever, oral mucositis and mouth discomfort
are
fre-
population
complexes.&dquo; In the arena of pharmacotherapy, clinicians had recommended early use of steroids until progression of skin lesions had been arrested, mune
some
Downloaded from ncp.sagepub.com at FLORIDA INTERNATIONAL UNIV on May 29, 2015
20
but later reports show growing reluctance to administer steroids because of infectious complica-
8. Chan
tions.3°’~ ls° 2s Limited data are available on the nutritional care of TEN patients. Some parallels exist between TEN and burn manifestation. Prompt nutrition support appears indicated; enteral nutrition is preferred over parenteral nutrition support. Nitrogen needs may be elevated. Several micronutrient deficiencies can be present. Ascorbic acid, vitamin A, and zinc may be of particular importance for wound healing. Although energy expenditure in TEN patients is reportedly lower when compared with that in equivalent burn injury, H.K.’s energy expenditure was measured considerably higher than estimated needs. As more research is completed on TEN patients, nutritional pre-
9.
HL, Stern RS, Arndt KA. The incidence of erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. A population-based study with particular reference to reactions caused by drugs among outpatients. Arch Dermatol 1990;126:43-7. Guillaume JC, Roujeau JC, Revuz J. The culprit drugs in 87
of toxic epidermal necrolysis (Lyell’s syndrome). Arch Dermatol 1987;123:1166-70. 10. Roujeau JC, Huynh TH, Bracq C. Genetic susceptibility to toxic epidermal necrolysis. Arch Dermatol 1987;123:1171-3. 11. Roujeau JC, Guillaume JC, Fabre JP. Toxic epidermal necrolysis (Lyell syndrome). Incidence and drug etiology in France, 1981-5. Arch Dermatol 1990;126:37-42. 12. Fansidar-associated fatal reaction in an HIV-infected man. Reported by: Malaria Br and Parasitic Diseases Br, Division of Parasitic Diseases; AIDS Program, Center for Infectious Diseases, Centers for Disease Control. J Am Med Assoc cases
1988;260:2193.
scription will be further clarified.
13. Alexander JW, Gottschlich MM. Nutritional immunodulation in burn patients. Crit Care Med 1990;18:S149-S153. 14. Gottschlich MM, Jenkins M, Warden GD, et al. Differential effects of three enteral regimens on selected outcome variables.
REFERENCES
15. Deitch EA. The management of burns. N
JPEN 1990;14:225-36.
Engl
J Med
1990;323:1249-53.
Lyell A. Toxic epidermal necrolysis: an eruption resembling scalding of the skin. Br J Dermatol 1956;68:355-61. Massullo RE, Welton WA, Jacobsen E. Toxic epidermal necrolysis: report of two cases. J Am Acad Dermatol 1988;
16.
19:358-9. 3. Prendiville JS, Hebert AA, Greenwald MJ, et al. Management of Stevens-Johnson syndrome and toxic epidermal necrolysis in children. J Pediatr 1989;115:881-7. 4. Goldstein SM, Wintroub BW, Elias PM, et al. Toxic epidermal necrolysis. Unmuddying the waters. Arch Dermatol
18.
1. 2.
1987;123:1153-5. 5. Gamelli RL. Nutritional problems of the acute and chronic burn patient. Relevance to epidermolysis bullosa. Arch Dermatol
1988;124:756-9. 6. Pruitt BA. Burn treatment for the unburned. J Am Med Assoc
1987;257:2207-8. DM, Engrav LH, Marvin JA. Toxic epidermal necrolysis. A step forward in treatment. J Am Med Assoc 1987;257:2171-5.
7. Heimbach
17.
19.
Taylor JA, Grube B, Heimbach DM. Toxic epidermal necrolysis. A comprehensive approach. Clin Pediatr 1989;28:404-7. Revuz J, Roujeau JC, Guillaume JC, et al. Treatment of toxic epidermal necrolysis. Arch Dermatol 1987;123:1156-8. Nowak AJ. Oropharyngeal lesions and their management in epidermolysis bullosa. Arch Dermatol 1988;124:742-4. Lechner-Gruskay D, Honig PJ, Pereira G. Nutritional and metabolic profile of children with epidermolysis bullosa. Pediatr
Dermatol 1988;5:22-7. 20. Solomon SM, Kirby DF. The refeeding syndrome: A review. JPEN 1990;14:90-7. 21. Hildreth MA. Caloric needs of pediatric patients with toxic epidermal necrolysis. Poster session: clinical nutrition practice and research. J Am Diet Assoc 1990;9. 22. Birchall N, Langdon R, Cuono C. Toxic epidermal necrolysis: an approach to management using cryopreserved allograft skin. J Am Acad Dermatol 1987;16:368-72. 23. Parsons JM. Management of toxic epidermal necrolysis. Cutis
1985;10:305-11.
Downloaded from ncp.sagepub.com at FLORIDA INTERNATIONAL UNIV on May 29, 2015
