Post-acute phase and sequelae management of epidermal necrolysis: an international, multidisciplinary DELPHI-based consensus.

BACKGROUND: Long-term sequelae are frequent and often disabling after epidermal necrolysis (Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)). However, consensus on the modalities of management of these sequelae is lacking. OBJECTIVES: We conducted an international multicentric DELPHI exercise to establish a multidisciplinary expert consensus to standardize recommendations regarding management of SJS/TEN sequelae. METHODS: Participants were sent a survey via the online tool "Survey Monkey" consisting of 54 statements organized into 8 topics: general recommendations, professionals involved, skin, oral mucosa and teeth, eyes, genital area, mental health, and allergy workup. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). Results were analyzed according to the RAND/UCLA Appropriateness Method. RESULTS: Fifty-two healthcare professionals participated. After the first round, a consensus was obtained for 100% of 54 initially proposed statements (disagreement index < 1). Among them, 50 statements were agreed upon as 'appropriate'; four statements were considered 'uncertain', and ultimately finally discarded. CONCLUSIONS: Our DELPHI-based expert consensus should help guide physicians in conducting a prolonged multidisciplinary follow-up of sequelae in SJS-TEN.

Supportive care in the acute phase of Stevens-Johnson syndrome and toxic epidermal necrolysis: an international, multidisciplinary Delphi-based consensus.

BACKGROUND: Supportive care is the cornerstone of management of adult and paediatric Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, consensus on the modalities of supportive care is lacking. OBJECTIVES: Our aim in this international multicentric Delphi exercise was to establish a multidisciplinary expert consensus to standardize recommendations regarding supportive care in the acute phase of SJS/TEN. METHODS: Participants were sent a survey via the online tool SurveyMonkey, consisting of 103 statements organized into 11 topics: multidisciplinary team composition, suspect drug management, infection prevention, fluid resuscitation and prevention of hypothermia, nutritional support, pain and psychological distress management, management of acute respiratory failure, local skincare, ophthalmological management, management of other mucosa, and additional measures. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). The results were analysed according to the RAND/UCLA Appropriateness Method. RESULTS: Forty-five participants from 13 countries (on three continents) participated. After the first round, a consensus was obtained for 82.5% of the 103 initially proposed statements. After the second round, a final consensus was obtained for 102 statements. CONCLUSIONS: We have reached an international Delphi-based consensus on best supportive care practice for SJS/TEN. Our expert consensus should help guide physicians in treating patients with SJS/TEN and thereby improve short-term prognosis and the risk of sequelae.

Severe hypokalemia as a cause of acute transient paraplegia following electrical shock.

Transient lower extremity paralysis has been previously reported following high voltage electrical injury. The following case report describes an unusual presentation of transient acute flaccid lower extremity paralysis following a high voltage electrical injury associated with profound hypokalemia and acid/base abnormalities similar to the periodic paralysis syndrome. The patient's symptoms resolved with correction of severe hypokalemia. Potential mechanisms for a metabolic neuromuscular disorder induced by electrical injury are proposed.

Cutaneous herpetic infections complicating burns.

Many people harbor herpes simplex virus, often with a known history of "cold sores". During the relatively immunosuppressed state associated with a serious burn, recrudescence of such infections can occur. We report four adults and two children who developed severe herpetic ulceration, over the face and neck in five patients and in a partial thickness wound in one patient. Herpetic infection was diagnosed by culture and direct immunofluorescence testing and treatment was immediately instituted with systemic and topical Acylovir(R) (Zovirax, Glaxo Wellcome). Ulceration healed under treatment and did not leave visible scarring in any of the patients. Although these infections are rapidly progressive, they respond to prompt treatment with antiviral chemotherapy. Rapidly progressive vesicles and ulceration appearing on the face or in the wounds of burn patients should prompt immediate evaluation for herpetic infection.

A 10-year experience with toxic epidermal necrolysis.

Toxic epidermal necrolysis is a devastating medication-induced desquamation disorder with a reported mortality rate of 30% to 60% in adults. Data from previously reported series suggest that age, delay in referral to a burn center, total body surface area (TBSA) involvement, and systemic steroid treatment are poor prognostic indicators. We reviewed the records of 39 patients treated in our burn center over the past 10 years and found that the mortality rate was significantly correlated with age, thrombocytopenia, and delay in presentation. Steroid treatment and TBSA involvement were not significantly related to the mortality rate. Thirty-nine adult patients with greater than 20% TBSA epithelial necrosis were cared for in our center from January 1987 to March 1998. Wounds were treated with topical antimicrobial medications and porcine xenografts in a bacteria-controlled nursing unit. We reviewed the records of these patients for 28 clinical characteristics and looked for clinical correlates of mortality by single analysis of variance. The mortality rate was 44% (17 of 39 patients); the cause of death was most commonly multiple-organ dysfunction syndrome, for which a microbial etiologic agent was not always identified. Autopsies were performed on 11 of the 17 patients who died; there was evidence of multiple-organ damage. The patients who survived and the patients who died did not differ significantly in TBSA epithelial necrosis (66%+/-6% vs 72%+/-5%, respectively), admission platelets, number of nosocomial infections, number of complications, preadmission exposure to steroids, or extent of mucosal involvement. When compared with the patients who died, the patients who survived were (1) 20 years younger (47.5+/-4.2 years vs 64.5+/-5.3 years), (2) admitted to the hospital sooner after the onset of their rash (3.5+/-0.4 days vs 5.9+/-1.0 days), (3) much less likely to experience early thrombocytopenia (platelet nadir, 154+/-24 vs 70+/-18), (4) more likely to be febrile on presentation, and (5) less likely to have been treated with antibiotics before referral to our unit. These differences were statistically significant. The most common etiologic agents were antibiotics, anticonvulsants, and nonsteroidal anti-inflammatory drugs. Our results for a group of older patients with toxic epidermal necrolysis with extensive skin involvement suggest that age, delay in hospitalization, thrombocytopenia, and early empiric antibiotic treatment are associated with a poor prognosis.

Artificial skin.

The skin is a complex organ that is difficult to replace when it is irreversibly damaged by burns, trauma, or disease. Although autologous skin transplantation remains the most common form of treatment in patients with significant skin loss, there are now a number of commercially available products that can be used to replace the skin temporarily or permanently. Here we describe several such products under the rubric "artificial skin," focusing on two types of technology that have been applied to the problem of permanent skin replacement.

Current expectations for survival in pediatric burns.

BACKGROUND: Conventional wisdom and published reports suggest that children, particularly those younger than 48 months, have higher mortality rates after burns than young adults. However, coincident with refinements in resuscitation, operative techniques, and critical care, survival rates for children with burns seem to have improved. To document this change and to define current expectations, a review of deaths during two 7-year intervals separated by a decade was done. DESIGN: We examined the clinical course of children who died after admission for care of acute thermal burns during two 7-year intervals: calendar years 1974 to 1980 inclusive (group 1) and 1991 to 1997 inclusive (group 2). Dying children were stratified by total body surface area (TBSA) burned: small (0%-39%), midsize (40%-59%), and large (60%-100%) TBSA burns. Children who arrived with anoxic brain injury or in a moribund state with refractory shock were excluded from analysis (4 children in group 1 and 5 in group 2); 2 of these children in group 2 died and became solid organ donors. SETTING: Regional pediatric burn center. PATIENTS: Six hundred seventy-eight children in group 1 and 1150 children in group 2. MAIN OUTCOME MEASURE: Survival. RESULTS: In children with 0% to 39% TBSA burns, mortality was 0.6% in group 1 and 0% in group 2 (Fisher exact test, P = .04; chi2 test, P = .02). In children with 40% to 59% TBSA burns, mortality was 7.7% in group 1 and 0% in group 2 (Fisher exact test, P = .07; chi2 test, P = .047). In children with 60% to 100% TBSA bums, mortality was 33.3% ingroup 1 and 14.3% in group 2 (Fisher exact test, P = .04; chi2 test, P = .02). Although 59% of the children in group 2 were younger than 48 months, including 55% of those with 40% to 59% TBSA burns and 41% of those with 60% to 100% TBSA burns, there were no deaths in this age group. CONCLUSION: Survival rates after burns have improved significantly for children. At present, most children, even young children and children with large burns, should survive.

Management of severe toxic epidermal necrolysis in children.

Toxic epidermal necrolysis (TEN) is a severe form of erythema multiforme that results in extensive epidermal sloughing; the condition is associated with a mortality of up to 70%. From 1991 to 1998, 10 children with severe toxic epidermal necrolysis were referred to a regional pediatric burn facility. Wounds were managed with strategy involving prevention of wound desiccation and superinfection, including the frequent use of biologic wound coverings. Children unable to guard their airway because of extensive oropharyngeal involvement were prophylactically intubated. Enteral nutrition was stressed. Steroids were not used and antibiotics were administered to managed specific foci of infection only. The 2 boys and 8 girls had an average age of 7.2+/-1.8 years (range 6 months to 15 years) and sloughed surface area of 76+/-6% of the body surface (range 50 to 95%). Antibiotics (3 children), anticonvulsants (3 children), nonsteroidals (2 children), and viral syndrome or unknown agents (2 children) were felt to have triggered the syndrome. Six children (60%) required intubation for an average of 9.7+/-1.8 days (range 2 to 14 days). Buccal mucosal involvement occurred in 9 (90%) and ocular involvement in 9 (90%). Although infectious complications were common (2 pneumonias, 2 urinary infections, 1 bacteremia, 2 central line infections, and 2 candidemias), all children survived after lengths of stay in the burn unit averaging 19+/-3 (range 6 to 40) days. The most common long-term morbidity was keratitis sicca (2 children, 20%), finger nail deformities (3 children, 30%), and variegated skin pigment changes (5 children, 50%). Although having both a cutaneous and visceral wound that predispose them to infectious complications, most children with TEN will survive if managed with a strategy emphasizing biologic wound closure, intensive nutritional support, and early detection and treatment of septic foci. Burn units have the resource set required to manage severe TEN and early referral of such children may have a favorable impact on survival.

Acute hand burns in children: management and long-term outcome based on a 10-year experience with 698 injured hands.

OBJECTIVE: To document long-term results associated with an coordinated plan of care for acutely burned hands in children. SUMMARY AND BACKGROUND DATA: Optimal hand function is a crucial component of a high-quality survival after burn injury. This can be achieved only with a coordinated approach to the injuries. Long-term outcomes associated with such a plan of care have not been previously reported. METHODS: Over a 10-year period, 495 children with 698 acutely burned hands were managed at a regional pediatric burn facility; 219 children with 395 injured hands were followed in the authors' outpatient clinic for at least 1 year and an average of >5 years. The authors' approach to the acutely burned hand emphasizes ranging and splinting throughout the hospital stay, prompt sheet autograft wound closure as soon as practical, and the selective use of axial pin fixation and flaps. Long-term follow-up, hand therapy, and reconstructive surgery are emphasized. RESULTS: Normal functional results were seen in 97% of second-degree and 85% of third-degree injuries; in children with burns involving underlying tendon and bone, 70% could perform activities of daily living and 20% had normal function. Reconstructive hand surgery was required in 4.4% of second-degree burns, 32% of third-degree burns, and 65% of those with injuries involving underlying bone and tendon. CONCLUSIONS: When managed in a coordinated long-term program, the large majority of children with serious hand burns can be expected to have excellent functional results.

Characterization and purification of membrane-associated phosphatidylinositol-4-phosphate kinase from human red blood cells.

The membrane-bound form of phosphatidylinositol-4-phosphate (PtdInsP) kinase was purified 4,300-fold from human red blood cells to a specific activity of 117 nmol min-1 mg-1. Although this enzyme copurified with red blood cell membranes, it was solubilized by high salt extraction in the absence of detergent indicating that it is a peripheral membrane protein. The major protein seen in the most purified preparation migrated at 53,000 daltons on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The major PtdInsP kinase activity in this preparation was also coincident with this 53,000-dalton band upon renaturation of activity from SDS-PAGE. To test further whether the 53,000-dalton protein contained PtdInsP kinase activity, antibodies were prepared against the gel-purified 53,000-dalton protein. This antiserum was able to precipitate both the 53,000-dalton peptide and PtdInsP kinase activity from red blood cell membranes. The apparent size of the native enzyme in the most purified preparation was determined to be 150,000 +/- 25,000 daltons by gel filtration. This PtdInsP kinase activity was at least 100-fold more active in phosphorylating PtdInsP than phosphatidylinositol and was easily separated from the red cell membrane phosphatidylinositol kinase by salt extraction. Analysis of the reaction product, phosphatidylinositol 4,5-bisphosphate, indicates that the enzyme phosphorylates phosphatidylinositol 4-phosphate specifically at the 5'-hydroxyl of the inositol ring. The apparent Km for ATP was 2 microM, and the concentrations of Mg2+ and Mn2+ giving half-maximal activity were 2 and 0.2 mM, respectively. Mg2+ supported 3-fold higher activity than Mn2+ at optimal concentrations. The enzymatic activity was inhibited by its product, phosphatidylinositol 4,5-bisphosphate and enhanced by phosphatidylserine.

CV-1 cell recipients of the mouse ouabain resistance gene express a ouabain-insensitive Na,K-ATPase after growth in cardioactive steroids.

The cation-transporting activity and Na,K-ATPase activity of CV-1 cell recipients of the mouse ouabain resistance gene (ouaR6, or OR6 cells; see Levenson, R., Racaniello, V., Albritton, L., and Housman, D. (1984) Proc. Natl. Acad. Sci. U. S. A. 81, 1489-1493) have been further characterized. OR6 cells grown in strophanthidin (a cardiac aglycon which may be removed rapidly from the Na,K-ATPase) possess both ouabain-sensitive and -insensitive 86Rb+ uptake activities. The ouabain-sensitive 86Rb+ uptake activity of these cells (OR6-S cells) exhibits the same Ki for ouabain as that of the CV-1 parent cells (Ki(app) = 3 x 10(-7) M ouabain), but accounts for only approximately 30% of total 86Rb+ uptake into Na+-loaded OR6-S cells, compared to 80% for CV-1 cells. Most of the ouabain-resistant 86Rb+ uptake in OR6-S cells is dependent on internal Na+ and is insensitive to furosemide, suggesting that it is due to an ouabain-resistant Na,K pump. In OR6-S cell lysates, 50% of Na+-dependent ATPase activity is insensitive to 1 mM ouabain, compared to less than 5% in CV-1 cell lysates. In addition, purified plasma membranes from OR6-S cells contain a 100-kDa protein which is transiently phosphorylated by ATP in an Na+-dependent, K+-sensitive manner, like the alpha subunit of the CV-1 Na,K-ATPase and the canine renal Na,K-ATPase, but which is unaffected by preincubation in 1 mM ouabain. All of these data suggest that OR6-S cells possess a ouabain-insensitive Na,K pump with characteristics similar to the ouabain-sensitive pump of CV-1 parent cells. Since the mouse ouabain resistance gene does not encode either subunit of the Na,K-ATPase, these results suggest that the ouabain resistance gene product may modify the ouabain sensitivity of the endogenous CV-1 Na,K pump.