Treatment of Toxic Epidermal Necrolysis With Moisture-Retentive Ointment: A Case Report and Review of the Literature

Toxic epidermal necrolysis (TEN) is a rare condition that was described by Lyell in 1956. It is a severe, acute, adverse, primarily drug-induced, potentially fatal, cutaneous reaction that is characterized by large areas of skin desquamation and sloughing, similar in many aspects to second-degree burns. The treatment of cutaneous drug reactions rests essentially on immediate diagnosis and recognition of the disease process, accurate history, thorough physical examination, prompt discontinuation of the offending drug, and supportive care. TEN patients are best managed in specialized burn units. Nevertheless, the management remains very much individualized, based on the clinical setting. Topical wound care remains an essential factor in the treatment of burn-like syndromes and is a main determining parameter for morbidity and mortality. As the value of moist environment in wound healing is being fully appreciated, we report on the use of a newly introduced ointment, the Moist Exposed Burn Ointment (Julphar; Gulf Pharmaceutical industries, Ras El-Khaymah, United Arab of Emirutes), a moisture-retentive ointment, in the successful management of a case of TEN.     

Bullous Lesions in a Patient with Systemic Lupus Erythematosus

Bullous eruptions in patients with lupus erythematosus can be difficult to diagnose as bullous lesions can develop in lupus-specific lesions, and primary blistering disorders can also occur. Additionally, these patients tend to have multiple co-morbidities making them more likely to be on many medications that can lead to bullous drug reactions. A thorough history, the clinical presentation, and histopathological findings along with direct immunofluorescence can be helpful in diagnosing most cases. The authors report the case of a woman with a long history of systemic lupus erythematosus who initially presented in their clinic for diagnosis and management of erythema dyschromicum perstans and one year later developed bullae in atypical targetoid lesions on the extremities and trunk. They discuss several blistering disorders that have been reported in patients with lupus erythematosus with a focus on features that help distinguish erythema multiforme, fixed drug eruption, and lupus erythematosus from Stevens-Johnson syndrome/toxic epidermal necrolysis. In the patient described herein, the authors favor a diagnosis of Stevens-Johnson syndrome, but the classification between erythema multiforme major and Stevens-Johnson syndrome/toxic epidermal necrolysis cannot be made in some cases.The diagnosis of bullous eruptions in patients with lupus erythematosus (LE) can be difficult to make as several different primary blistering disorders have been reported to occur in association with LE, including bullous pemphigoid, pemphigus vulgaris, dermatitis herpetiformis, epidermolysis bullosa acquisita, linear immunoglobulin A (IgA), porphyria cutanea tarda, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN).1-3 Bullous lesions can also occur in erythema multiforme (EM). These conditions must be differentiated from the bullous lesions that can occur in cutaneous lesions of LE, which can be due to extensive vacuolar degeneration of the basement membrane (BM) or from antibodies to type VII collagen in bullous systemic lupus erythematosus (BSLE).4 Patients with LE also tend to have multiple comorbidities, making them more likely to be on multiple medications that can lead to bullous drug eruptions. To add to the difficulty, many of these conditions may mimic SJS/TEN, which can be associated with significant morbidity and mortality. A thorough history, the clinical presentation, and histopathological findings along with direct immunofluorescence (DIF) can be used to diagnose most cases, but there are some cases where a clear diagnosis cannot be made. The authors report a case of a patient with systemic lupus erythematosus (SLE) who presented with a bullous eruption and focus on a discussion of features that help differentiate fixed drug eruption (FDE), LE, and erythema multiforme (EM) from SJS/TEN.     

Drug-induced toxic epidermal necrolysis with involvement of the intestinal and respiratory tract. A case report

Toxic epidermal necrolysis (TEN) is a disease occurring with low-incidence but has a relatively high mortality rate. Sepsis is the predominant cause for life-threatening complications in TEN but severe mucosal damage represents a further complication which may delay convalescence. We report a case of TEN in a 51-year-old man which eventually spread to include the whole skin surface. The long-term and comprehensive treatment focused on support of the organ failure as well as wound treatment. The extent of involvement of the intestinal tract, the sustained laryngeal stenosis and the pronounced saddle-nose were unusual. It appears necessary to treat TEN in facilities which offer intensive care and are able to manage extensive skin damage. Burns units offer the best conditions for its management.     

Toxic Epidermal Necrolysis in Pregnancy due to Ondansetron with a Favorable Outcome: A Case Report and Review of the Literature

Toxic epidermal necrolysis (TEN) is an uncommon, life-threatening hypersensitivity drug reaction with a high mortality rate that involves the skin and mucous membranes. Most reported cases involving pregnant patients were seen in those with human immunodeficiency virus. Here, we discuss a 21-year-old Iranian woman who presented at 18 weeks’ gestation with extensive TEN following the administration of ondansetron with no any other risk factors.     

Severe idiosyncratic drug reactions with epidermal necrolysis: A 5-year study

Introduction:

Idiosyncratic drug reactions (IDRs) are unexpected responses to a drug. The spectrums of severe cutaneous reactions include Stevens–Johnson Syndrome (SJS), SJS/Lyell Syndrome and Toxic Epidermal Necrolysis (TEN). The conditions are associated with high mortality. This study was designed to determine the causal agents, patterns of presentations, review the management and make recommendations to reduce the incidence and mortality of this class of drug reactions.

Materials and Methods:

A retrospective study was made of patients seen with IDR in the Lagos State University Teaching Hospital, LASUTH, between January, 2004 and December, 2008. They were cases admitted with bullous skin eruptions with associated systemic symptoms.

Results:

Sixty-seven patients were seen, with 45 (67.2%) satisfying the inclusion criteria. Fifteen males and 30 females were involved, giving a male to female (M:F) ratio of 1:2. Their ages ranged from 7 to 79 years (mean, 40.02 ± 17.89 years). Peak incidences occurred among the 20–24 and 30–34 year age groups. The causal agents were antibiotics (48.89%), sulphonamides (24.44%), herbal preparations (17.78%) and artemisinin drugs (8.89%).

Conclusions:

The age groups with the peak incidence are the most likely to indulge more in drug abuse in environments with poor drug control. Diagnosis of SJS, SJS/TEN and TEN were missed in many patients at first contact due to the progressive nature of the conditions. Patients needed reviews at regular intervals when IDR was suspected. Health education to prevent drug abuse is important and herbal preparations should be scientifically studied to determine the efficacy and side-effects.KEY WORDS: Idiosyncratic drug reactions, Stevens Johnson Syndrome, Toxic Epidermal Necrolysis, toxic epidermal necrolysis     

Treatment of toxic epidermal necrolysis with cyclosporin A

BACKGROUND: Toxic epidermal necrolysis (TEN) is a severe skin disorder characterized by separation of the dermal-epidermal junction, as is observed in second-degree superficial burns. It has been proposed that immunosuppressive treatment may improve prognosis of patients with TEN. METHODS: We report here a case series of patients with TEN treated with cyclosporin A (CSA) without other concomitant immunosuppressive agent. These patients (n = 11) were consecutively admitted to our Intensive Care Burn Unit because of severe TEN, involving a large body surface area (83 +/- 17% [mean +/- SD], median, 90%; range, 35-96%) and were treated with CSA 3 mg/kg per day enterally every 12 hours. We compared the series of patients treated with CSA with a historical series of patients admitted to our Intensive Care Burn Unit before CSA was introduced as part of the treatment protocol These patients (n = 6) were treated with cyclophosphamide (150 mg i.v. every 12 hours) and different doses of corticosteroids (> or =1 mg/kg per day of 6-methyl-prednisolone). Both groups of patients were similar in regard to age, delay from onset of disease to Intensive Care Burn Unit admission, and body surface area involved. RESULTS: Time from the onset of skin signs to arrest of the disease progression (1.4 +/- 0.3 days, vs. 3.6 +/- 1.5 days) and to complete reepithelialization (12.0 +/- 3.6 days, vs. 17.6 +/- 3.1 days) was significantly shorter in patients treated with CSA compared with those treated with cyclophosphamide and corticosteroids (p = 0.0002, and p = 0.0058, respectively). Significantly fewer patients in the CSA group had > or =4 organs failing (2 of 11 vs. 3 of 6, respectively, p = 0.029), had severe leukopenia (<1,000 cells/microL) (0 of 11 vs. 4 of 6, respectively, p = 0.006), or died (3 of 6 vs. 0 of 11, respectively, p = 0.0029). CONCLUSION: We conclude that immunosuppressive treatment with CSA is safe and is associated with a rapid reepithelialization rate and a low mortality rate in patients with severe TEN. Our data suggest that this regimen could be more effective than treatment with cyclophosphamide and corticosteroids. Prospective controlled trials are required to test the hypothesis that CSA is more effective than cyclophosphamide or other immunosuppressive regimens for the treatment of TEN.     

Development of bullous pemphigoid during the haemodialysis of a young man: case report and literature survey

Haemodialysis is the most frequent form of renal replacement therapy (RRT) in patients with end‐stage renal disorder (ESRD). Patients with ESRD frequently develop skin problems, mainly xerosis, pruritus and hyperpigmentation, as well as bullous diseases, mainly porphyria or pseudoporphyria and, in some cases, bullous pemphigoid (BP). BP is the most common autoimmune sub‐epidermal blistering disease, and it predominantly affects elderly people. Clinically, BP is characterised by generalised pruritic, bullous eruptions and urticaria‐like lesions. Usually, BP is an idiopathic disorder; however, in some cases, underlying internal disorders are present, like diabetes or neurological disorders. Herein, we present a 33‐year‐old man with ESRD, maintained on haemodialysis, who developed BP. There are only six cases with BP provoked by the placement of a fistula for haemodialysis. BP in the current patient was confirmed by direct immunofluorescence (DIF) and indirect immunofluorescence using BIOCHIP. The patient responded promptly to tertracycline and 0·05% clobetasol propionate lesionally. However, the relationship between BP and the fistula for haemodialisys still remains unknown. It is highly likely that the skin injury associated with fistula placement was responsible for the alteration of the basement membrane zone (BMZ) and the stimulation of the immune system, leading to BP development. To explain the real role of fistula placement as a provocative factor in BP, other such cases are required for assessment.     

Bullous pemphigoid-associated nephropathy: report of two cases and review of the literature

Bullous pemphigoid has previously been reported in association with a variety of renal lesions. Two additional cases are presented in this report in which the nephropathy preceded the onset of the skin disease: one case with membranous glomerulopathy and one case of renal allograft rejection with concurrent membranous pathology. Both patients had positive immunofluorescence of the skin, typical of bullous pemphigoid. Institution of systemic corticosteroid therapy resulted in a satisfactory clinical response and cessation of the blistering process. These cases and a review of the literature suggest that the occurrence of an immune process involving these two different basement membranes is not merely coincidental. Many cases have been described in which the severity of the skin lesions paralleled that of the renal disease. Although the possibility of multiple distinct autoimmune processes cannot be excluded, anti-basement-zone antibody interactions or allograft rejection-induced immune stimulation are possible unifying mechanisms for the simultaneous skin and renal involvement observed in these two cases.     

Chronic intrathecal baclofen administration for control of severe spasticity

Baclofen, the most effective drug for treating spasticity, is a specific agonist of gamma-aminobutyric acid-B receptors, and is very abundant in the superficial layers of the spinal cord. Given orally, baclofen does not easily penetrate the blood-brain barrier, and is distributed equally to the brain and spinal cord. Direct intrathecal administration was given in order to change the distribution of the drug by preferentially perfusing the spinal cord. Eighteen patients presenting a severe spastic syndrome were treated with chronic intrathecal infusion of baclofen in the lumbar cerebrospinal fluid. After clinical preselection, 38 patients were implanted with a lumbar access port allowing long-term trials in order to determine the efficacy of baclofen therapy and the effective 12-hour dose. The 18 patients selected for chronic administration were implanted with a programmable pump. The pathology in these cases was: multiple sclerosis (6 cases), posttrauma spastic syndrome (eight cases), and (one case each) cerebral palsy, ischemic cerebral lesion, spinal ischemia, and transverse myelitis. The mean follow-up period was 18 months (range 4 to 43 months). The clinical results were evaluated according to muscular hypertony on Ashworth's scale (changed for occurrence of painful spasms) and functional improvement. Results were better for spastic syndrome secondary to traumatic medullary lesion than for demyelinating disease. Hypertonia was improved in all cases as confirmed by the registration of the Hoffman (H) reflex. Painful muscular spasms disappeared in 14 of the 16 affected patients. Significant functional improvement was noted in nine patients and was considerable in three. The risk of side effects secondary to overdose (such as excessive hypotonia or central depression) and the absence of a specific baclofen antagonist stresses the necessity for accurate determination of the efficient dose. After an initial titration period and adjustment of the therapeutic dose, the individual doses were from 21 to 500 micrograms/24 hrs (mean 160 micrograms/24 hrs). This new conservative method is very effective, perfectly reversible, and safe when administered in conditions favorable to its use.     

Study on surgical treatment for lung cancer associated with giant bullous disease

Five patients of primary lung cancer with giant bullous diesase underwent surgery from April 1985 to December 1995. All patients were male and heavy smokers, and the median age was 50 years. The location of the tumor was in the right upper lobe in four patients and in the left upper lobe in the other. Three patients were treated by lobectomy and two by sleeve lobectomy. Histological examination showed large cell carcinoma in four patients and poorly-differentiated adenocarcinoma in the other. The pathological stage was I in three. IIIA in one, and IV in the other. Two of three in stage I have survived for more than 6 years postopertively without recurrence, and the other died of brain metastasis. The stage IIIA case and the IV case died 3 years and one year postoperatively, respectively. The clinical features of lung cancer associated with giant bullous disease was discussed by reviewing 33 patients reported in Japan, including our patients. In 13 patients, lung cancer and bullous disease were diagnosed simultaneously (group A), and in 20 patients, bullous disease were diagnosed prior to the appearance of an abnormal shadow due to lung cancer (group B). The patients in group B had a tendency to be diagnosed at an earlier stage of lung cancer than the patients in group A. In the patients of stage I, the 5-year survival rate was 78.6%, however, in the patients of more than stage IIIA, 3-year survival rate was 26.5% and the 5-year survival rate was 0%. Significant differences in the survival curves were demonstrated between the cases with stage I and the cases with more than stage IIIA. In conclusion, in order to improve the prognosis of lung cancer with giant bullous disease, it is considered to be important to detect giant bulla prior to lung cancer, and when a case of bullous disease is found, periodical follow-up must be done to find early stage lung cancer.     

Treatment of toxic epidermal necrolysis by a multidisciplinary team. A review of literature and treatment results

Background

Stevens–Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are mucocutaneous hypersensitivity reactions, usually to drugs or their metabolites. TEN is the most severe involving greater than 30% of the total body surface area (TBSA). Management of these patients usually benefits from a large multidisciplinary team for both wound and medical management. Treatment of these patients varies between centers and physicians and there is lack of a standardized treatment protocol in the medical literature.

Traitement des septicémies par le latamoxef: Etude multicentrique de soixante cas

Sixty patients including forty two males and eighteen females, age range: 18-87 years, received antibacterial single drug treatment with latamoxef for septicemia. Forty nine patients had underlying conditions including multiple trauma, neoplasm, cardiovascular, metabolic and respiratory tract diseases. Causative pathogens were isolated in all cases. The predominant isolates were E. coli (thirty), Klebsiella pneumoniae (tent) and Enterobacter (seven). A single organism was isolated in fifty seven cases; in the other three cases two organisms were isolated from blood cultures. Mean daily dosage was 46.6 +/- 6.1 mg . kg-1 (range: 14-113 mg . kg-1). In the majority of cases (fifty two) dosage was 3 g . d-1 or less; in thirty cases it was no higher than 2 g . d-1. Duration of therapy ranged from six to thirty eight days. Serum titer was measured in many cases and latamoxef blood levels were assayed in nine patients. A satisfactory clinical response was achieved in fifty eight cases and fifty eight bacteriological cures were also obtained. There was no statistically significant difference in therapeutic response between the 2 g and 3 g daily dosage groups. Tolerance was very good; untoward effects were few and required drug discontinuation in one case only.     

Une présentation rare du syndrome d’intolérance au greffon renal : la pemphigoïde bulleuse

Bullous pemphigoid is an autoimmune bullous cutaneous disease. We report the case of a 60 year-old male patient whose kidney allograft failed and was on hemodialysis for the previous 16 months. After tapering immunosuppressive medication, he presented simultaneous bullous eruption and kidney allograft intolerance syndrome. Investigation showed a positive BP180 anti-basement membrane zone antibody and skin biopsy was consistent with bullous pemphigoid. The patient was treated with corticotherapy and bullous pemphigoid resolved. The development of new onset diabetes and concerns over long term immunosuppression, halted the decision to continue corticotherapy and the patient underwent graft nephrectomy, with resolution of the kidney allograft intolerance syndrome without recurrence of the bullous disease. The occurrence of bullous pemphigoid in patients with failed renal allograft is rare, with only eleven cases reported in literature. This case illustrates how graft nephrectomy can provide a definitive cure to bullous pemphigoid in this setting.     

Percutaneous nephrostomy in children: diagnostic and therapeutic importance

The aim of this study was to evaluate the effectiveness and safety of percutaneous nephrostomy (PN) in terms of diagnostic and therapeutic approach in children with urological problems. PN was performed on 39 kidneys in 28 patients (12 girls, 16 boys) aged 4.5 months to 13 years (average 5.38±3.41 years) during the period from January 1996 to December 2003. Underlying abnormalities were ureteropelvic junction obstruction (UPJO) in 14 patients (17 kidneys), ureterovesical junction obstruction (UVJO) in six patients (eight kidneys), supravesical obstruction due to tumour or hydatid cyst or ureteral stone in three patients (five kidneys), and severe vesicoureteral reflux (VUR) with/without neurogenic bladder associated with pyonephrotic kidneys in five patients (nine kidneys). The duration of catheter insertion was between 2 and 160 days (average 80±65.01 days). The complications were haematuria (six cases), infection (five cases) and displacement of catheter (four cases). Radical surgical management was performed in 25 patients (33 kidneys): pyeloplasty in eight cases (ten kidneys), UVJO correction in six cases (eight kidneys), nephrectomy in five cases (five kidneys), ureteroneocystostomy in four cases (seven kidneys), hydatid cyst operation in one case (two kidneys) and stone extraction in one case (one kidney). PN is an easy, safe and efficient diagnostic and therapeutic procedure with few complications in childhood.     

The spectrum of renal involvement in epidermolysis bullosa dystrophica hereditaria: report of two cases

Epidermolysis bullosa dystrophica Hallopeau-Siemens (EBDH) is one of the most severe inherited epidermolyses, a group of mechanobullous dermatological disorders. We observed two patients presenting with a severely multilating type of EBDH who developed biopsy-proven renal disease, which substantially altered the evolution and pathogenesis of their disease. In a boy, chronic postinfectious glomerulonephritis developed, most probably due to recurring superinfections of bullous skin lesions. He also experienced acute oliguric renal failure due to severe diarrhea during exacerbation of EBDH. A female patient developed a nephrotic syndrome due to secondary amyloidosis. Hypoalbuminemia caused further fluid losses through bullous skin lesions, aggravating intravascular hypovolemia and leading to rapid renal failure secondary to bilateral renal vein thrombosis. The study shows that, although rare, renal complications may alter the natural course of EBDH.     

Skin Allograft in the Treatment of Toxic Epidermal Necrolysis (TEN)

BACKGROUND: TEN is a severe form of exfoliative dermatitis. Its course is acute and its outcome fatal in 40% of cases. Wound cover to prevent fluid/protein loss and infections and to control pain, is the first step, as for burns. Skin allograft can be successfully used for this purpose. OBJECTIVE: We report two cases of TEN with de-epithelialization of 50 and 70% of the total body surface area. The patients were given support therapy and treated with human glycerol-preserved skin allografts for wound cover. METHODS: Patients were grafted with glycerol-preserved donor skin, obtained from a skin bank. RESULTS: Re-epithelization of treated areas was complete in 8 days; pain relief was obtained soon after the graft. CONCLUSIONS: Glycerol-preserved skin allograft is an effective treatment in extensive skin loss, for its barrier and analgesic effect. Quality standards of this product ensure safety and simplicity of use at limited cost.     

Early enteral feeding, compared with parenteral, reduces postoperative septic complications. The results of a meta-analysis.

This two-part meta-analysis combined data from eight prospective randomized trials designed to compare the nutritional efficacy of early enteral (TEN) and parenteral (TPN) nutrition in high-risk surgical patients. The combined data gave sufficient patient numbers (TEN, n = 118; TPN, n = 112) to adequately address whether route of substrate delivery affected septic complication incidence. Phase I (dropouts excluded) meta-analysis confirmed data homogeneity across study sites, that TEN and TPN groups were comparable, and that significantly fewer TEN patients experienced septic complications (TEN, 18%; TPN, 35%; p = 0.01). Phase II meta-analysis, an intent-to-treat analysis (dropouts included), confirmed that fewer TEN patients developed septic complications. Further breakdown by patient type showed that all trauma and blunt trauma subgroups had the most significant reduction in septic complications when fed enterally. In conclusion, this meta-analysis attests to the feasibility of early postoperative TEN in high-risk surgical patients and that these patients have reduced septic morbidity rates compared with those administered TPN.     

Retrospective study of 213 cases of Stevens–Johnson syndrome and toxic epidermal necrolysis from China

BackgroundStevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe adverse drug reactions with high mortality. The use of corticosteroids and the management of complications (e.g. infection) in SJS/TEN remains controversial.MethodsA retrospective study was performed among 213 patients with SJS/TEN who were hospitalized in our department between 2008 and 2018, to investigate the causative agents, clinical characteristics, complications, and prognoses of SJS/TEN mainly treated by systemic corticosteroids combined with intravenous immunoglobulin (IVIG).ResultsThe causative drugs of SJS/TEN in these patients mainly consisted of antibiotics (61/213, 28.6%), anticonvulsants (52/213, 24.4%), and nonsteroidal anti-inflammation drugs (24/213, 11.3%), among which carbamazepine was the most frequently administered drug (39/213, 18.3%). There were significant differences in the maximum dosage, time to corticosteroid tapering, and the total dosage of corticosteroid between the SJS group and the TEN group, as well as among the three groups (P = 0.000), whereas in the initial dose of corticosteroid was not statistically significant among the three groups (P = 0.277). In a series of 213 cases, 18.4 cases (8.6%) were expected to die based on the score for the toxic epidermal necrolysis (SCORTEN) system, whereas eight deaths (3.8%) were observed; the difference was not statistically significant (P = 0.067; SMR = 0.43, 95% CI: 0.06, 0.48). The most common complications were electrolyte disturbance (174/213, 81.7%), drug-induced liver injury (64/213, 30.0%), infection (53/213, 24.9%), and fasting blood sugar above 10 mmol/L (33/213, 15.5%). Respiratory system (22/213, 10.3%) and wound (11/213, 5.2%) were the most common sites of infection. Multivariate logistic regression analysis indicated that the maximum blood sugar (≥10 mmol/L), the time to corticosteroid tapering (≥12 d), the maximum dosage of corticosteroid (≥1.5 mg/kg/d), and the total body surface area (TBSA) (≥10%) were defined as the most relevant factors of the infection.ConclusionThe mortality of patients in this study was lower than that predicted by SCORTEN, although there was no significant difference between them. Hyperglycemia, high-dose corticosteroid, and the TBSA were closely related to the infections of patients with SJS/TEN.     

AQUACEL Ag in the treatment of toxic epidermal necrolysis (TEN)

Toxic Epidermal Necrolysis (TEN) is life-threatening dermatological disease characterized by extensive destruction of the epidermis is associated with a 25-60% mortality rate in adults. We presented one patient with TEN with 86% skin slough treated successfully using AQUACEL Ag exclusively. All of the wounds were healed completely 8 days after onset of TEN. AQUACEL Ag is an efficient and cost-effective adjunct in the treatment of TEN.