Efficacy of borneol-gypsum in skin regeneration and pain control in toxic epidermal necrolysis:A case report

BACKGROUND Toxic epidermal necrolysis(TEN)is a life-threatening dermatological emergency mainly induced by drug hypersensitivity reactions.Standard management includes discontinuation of culprit drug and application of immunomodulatory therapy.However,mortality remains high due to complications like septic shock and multiorgan failures.Innovative approaches for skin care are crucial.This report introduces borneol-gypsum,a traditional Chinese drug but a novel dressing serving as an adjuvant of TEN therapy,might significantly improve skin conditions and patient outcomes in TEN.CASE SUMMARY A 38-year-old woman diagnosed with eosinophilic granulomatosis with polyangiitis experienced gangrenous complications and motor nerve involvement.After initial treatment of high-dose corticosteroids and cyclophosphamide,symptom of foot drop improved,absolute eosinophil counts decreased,while limb pain sustained.Duloxetine was added to alleviate her symptom.Subsequently,TEN developed.Additional topical application of borneol-gypsum dressing not only protected the skin lesions from infection but also significantly eased localized pain.This approach demonstrated its merit in TEN management by promoting skin healing and potentially reducing infection risks.CONCLUSION Borneol-gypsum dressing is a promising adjuvant that could significantly improve TEN management,skin regeneration,and patient comfort.

Double plasma molecular adsorption system for Stevens–Johnson syndrome/toxic epidermal necrolysis:A case report

BACKGROUND Stevens–Johnson syndrome and toxic epidermal necrolysis(SJS/TEN)are very serious skin allergies,with an etiology related to infections and medication.Since the coronavirus disease 2019(COVID-19)pandemic,severe acute respiratory syndrome coronavirus-2 has also been considered to cause SJS/TEN.CASE SUMMARY We report the case of a woman in her thirties who took acetaminophen after contracting COVID-19.After 3 d of fever relief,she experienced high fever and presented with SJS/TEN symptoms,accompanied by intrahepatic cholestasis.Three days of corticosteroid treatment did not alleviate the skin damage;therefore,double plasma molecular adsorption system(DPMAS)therapy was initiated,with treatment intervals of 48 h.Her skin symptoms improved gradually and were resolved after seven DPMAS treatments.CONCLUSION DPMAS therapy is beneficial for abrogating SJS/TEN because plasma adsorption and perfusion techniques reduce the inflammatory mediators(e.g.,tumor necrosis factor-alpha and interleukin-10 and-12)speculated to be involved in the pathology of the skin conditions.

Successful treatment after toxic epidermal necrolysis induced by AZD-9291 in a patient with non-small cell lung cancer:A case report

BACKGROUND Toxic epidermal necrolysis and Stevens-Johnson syndrome are acute lifethreatening skin reactions.AZD9291 has been developed as a third-generation epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitor(TKI)with activity against T790M mutation.CASE SUMMARY Herein we report a 68-year-old woman who developed a large area of skin necrosis and was diagnosed with toxic epidermal necrolysis after AZD-9291 ingestion.To the best of our knowledge,this is the first case reported in patients with EGFR T790M mutation in non-small cell lung cancer(NSCLC).Cabozantinib combined with erlotinib had clinically meaningful effectiveness,with additional toxicity that was generally manageable.CONCLUSION Treatment with AZD-9261 is effective in regressing the growth of the NSCLC and can bring some hope to despairing patients.We hope that more research will be carried out on the association between severe rashes and EGFR-TKIs,and more safe and effective drugs can be developed.

Combination therapy(toripalimab and lenvatinib)-associated toxic epidermal necrolysis in a patient with metastatic liver cancer:A case report

BACKGROUND Both programmed cell death-1(PD-1)inhibitors and lenvatinib,which have a synergistic effect,are promising drugs for tumor treatment.It is generally believed that combination therapy with a PD-1 inhibitor and lenvatinib is safe and effective.However,we report a case of toxic epidermal necrolysis(TEN),a grade 4 toxicity,after this combination therapy.CASE SUMMARY A 39-year-old male presented with erythema,blisters and erosions on the face,neck,trunk and limbs 1 wk after receiving combination therapy with lenvatinib and toripalimab,a PD-1 inhibitor.The skin injury covered more than 70%of the body surface area.He was previously diagnosed with liver cancer with cervical vertebra metastasis.Histologically,prominent necrotic keratinocytes,hyperkeratosis,liquefaction of basal cells and acantholytic bullae were observed in the epidermis.Blood vessels in the dermis were infiltrated by lymphocytes and eosinophils.Direct immunofluorescence staining was negative.Thus,the diagnosis was confirmed to be TEN(associated with combination therapy with toripalimab and lenvatinib).Full-dose and long-term corticosteroids,high-dose intravenous immunoglobulin and targeted antibiotic drugs were administered.The rashes gradually faded;however,as expected,the tumor progressed.Therefore, sorafenib and regorafenib were given in succession, and the patient was still alive at the10-mo follow-up.CONCLUSIONCautious attention should be given to rashes that develop after combination therapy with PD-1inhibitors and lenvatinib. Large-dose and long-course glucocorticoids may be crucial for thetreatment of TEN associated with this combination treatment.

Toxic epidermal necrolysis induced by ritodrine in pregnancy:A case report

BACKGROUND Preterm birth accounts for about 12%of all pregnancies worldwide and is the leading cause of neonatal morbidity and mortality.In order to avoid premature birth and prolong gestational age,tocolytics are the first and the best choice.Ritodrine is the most commonly used tocolytic medication.However,side effects such as pulmonary edema,hypokalemia,and hyperglycemia are known.Here we report a rare but serious side effect–toxic epidermal necrolysis(TEN)–caused by ritodrine.CASE SUMMARY A woman(31 years,gravida 4,para 2)was hospitalized because of premature contractions at 27+6 wk of gestation.A skin rash with pruritus appeared at 32+3 wk of gestation after administration of ritodrine,indomethacin,and dexamethasone,and it spread throughout the whole body in 3 d,particularly the four limbs.After 11 d’treatment,she was diagnosed with TEN.An emergency cesarean section was performed immediately to deliver the baby and intensive symptomatic treatment was promptly commenced after delivery.She recovered from the severe condition without any sequelae except for slight pigmentation after symptomatic treatment.CONCLUSION When a skin rash appears during the administration of ritodrine,we are supposed to consider the risk of TEN.

Autologous scalp skin grafting to treat toxic epidermal necrolysis in a patient with a large skin injury:A case report

BACKGROUND Toxic epidermal necrolysis(TEN)is often associated with skin wounds affecting large areas.Healing of this type of wound is difficult because of pressure,infection and other factors.It can increase the length of hospital stay and result in wound sepsis and even death.CASE SUMMARY A 49-year-old woman developed a skin lesion covering 80%of the total body surface area after using a kind of Chinese medicinal ointment on a burn wound on her back;she developed life-threatening wound sepsis and septic shock.Methicillin-resistant Staphylococcus aureus,carbapenem-resistant Acinetobacter baumannii,carbapenem-resistant Pseudomonas aeruginosa and other bacteria were cultured from wound tissue,deep venous catheter and blood samples.Imipenem cilastatin sodium,tigecycline and teicoplanin were used for anti-infection therapy.Finally,the patient was transferred to the burn department because of severe wound sepsis.In the burn intensive care unit,pain-free dressing changes and autologous scalp skin grafting were performed to heal the wound in addition to reasonable and effective antibacterial treatment according to microbial susceptibility test results.After three operations within 2 wk,the wound healed and sepsis resolved.CONCLUSION TEN patients with large areas of skin injury may develop wound infection and life-threatening wound sepsis.Autologous scalp skin grafting may be beneficial for rapid wound healing and reducing the risk of sepsis in TEN patients,and it leaves no scar at the donor site.

Significant impact of cryopreserved amniotic membrane on acute ocular Stevens-Johnson syndrome and toxic epidermal necrolysis

The ocular surface is covered by an epithelium encompassing an area including the cornea,the limbus and the conjunctiva bordered by the upper and lower lids.The healthy state of the ocular surface epithelium depends on a stable and protective preocular tear film when the eye is open.A stable preocular tear film is governed by sound ocular surface defense that involves effective

Enzalutamide Associated with Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) Overlap: A Case Report

Enzalutamide is a hormonal therapy that blocks the action of androgens, such as testosterone in the treatment of metastatic castration-resistant prostate cancer. Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) overlap and are part of an adverse drug reaction continuum of disease, in which there is a 10% - 30% involvement of the skin surface with mucositis, blisters, skin slough, and a macular rash. A 66-year-old male was treated with enzalutamide for metastatic prostate cancer and developed SJS/TEN overlap with 25% total body surface area skin involvement. The patient received a seven-day course of cyclosporine to which he responded by re-epithelialization but succumbed to multi-organ failure. While SJS/TEN has been reported with apalutamide, to our knowledge, this is the first case of SJS/TEN overlap with enzalutamide.

Pneumatosis cystoides intestinalis associated with toxic epidermal necrolysis: A case report

Toxic epidermal necrolysis(TEN) is a severe adverse drug reaction, which is characterized by erythema, blisters, and/or erosions of the mucous membranes and skin, but intestinal involvement is rare. In contrast, pneumatosis cystoides intestinalis(PCI) is a rare condition associated with a wide variety of underlying diseases, but to date no patient has presented with PCI associated with TEN. A 55-year-old man was admitted to intensive care unit for treatment of TEN caused by phenobarbital. On day 8 after admission, he presented with progressive abdominal distention and hypotension. Computed tomography(CT) showed gas in the superior mesenteric vein and air filled cysts in the walls of the small intestine. He was suspected of having septic shock due to PCI. As there were no indications of bowel ischemia or necrosis, the patient was managed conservatively with antibiotics and oxygen therapy. On day 10 after admission, he was weaned off catecholamines, with CT on day 11 showing complete resolution of gas in the superior mesenteric vein and air filled cysts. To our knowledge, this article describes the first patient presenting with PCI associated with TEN.

Nursing Care of Stevens Johnson Syndrome and Toxic Epidermal Necrolysis: Case Study of Dermatology Unit of Referral Hospital, Kenya

Introduction: Stevens Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are adverse reaction to drugs whose manifestation affect the skin and mucous membranes whose outcomes may be life threatening and fatal. Supportive management has been proven to be the mainstay with well executed nursing care resulting in quality clinical outcomes. The aim was to evaluate the nursing care interventions in management of patients with SJS/TEN in the dermatology unit. Methods: Qualitative design was used, data were collected through observation of nursing care activities, informant interviews and focus group discussion with the nurses. Qualitative data were recorded in audio tapes and transcribed. Qualitative content analysis was used for the analysis of the transcribed texts. Study was approved by KNH/ERC and informed written consent from participants. Funding was obtained from KNH through the Research and Programs department. Findings: 20 nurses participated in the study. The commonest nursing care interventions were described as routine tasks initiated at clinical diagnosis and routinely performed. They include aggressive skin care, wound care, mucosal and eye care, infection surveillance and prevention practices and general patient monitoring for complications. Skin and wound care were most challenging part of nursing care due to severe erosion or exfoliation. Nurses do not use any specific guidelines of care but consider their role a key in quality outcomes for patients with SJS/TEN in this hospital.

Toxic epidermal necrolysis related to AP(pemetrexed plus cisplatin)and gefitinib combination therapy in a patient with metastatic non-small cell lung cancer

Toxic epidermal necrolysis(TEN) is a rare acute life-threatening mucocutaneous disorder that is mostly drug-related(80%-95%). It is clinically characterized as a widespread sloughing of the skin and mucosa. AP regimen(pemetrexed plus cisplatin) has been the preferred first-line chemotherapy for metastatic non-squamous non-small cell lung cancer(NSCLC). Gefitinib, a small-molecule epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor(TKI), has already been recommended as a first-line treatment in EGFR-mutant metastatic NSCLC. We report rare presentation of TEN involving adverse effects of AP and gefitinib combination treatment in a 42-year-old woman diagnosed with metastatic NSCLC harboring an EGFR mutation. On the 21 st day after administration of the first cycle of AP regimen and the 8th day after the initiation of gefitinib treatment, she developed an acne-like rash, oral ulcer, and conjunctivitis, which later became blisters and ultimately denuded. The characteristic clinical courses were decisive for the diagnosis of TEN. Treatment with systemic steroids and immunoglobulin as well as supportive treatment led to an improvement of her general condition and a remarkable recovery.

Retrospective Analysis of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in 88 Chinese Patients

Background： Stevens-Johnson syndrome （SJS） and toxic epidennal necrolysis （TEN） are life-threatening diseases with high mortality rates. This study was designed to analyze the pathogenic factors, clinical manifestations, complications, treatment, and prognosis of SJS/TEN and to explore the differences between surviving and deceased patients. Methods： SJS/TEN patients admitted to Beijing Friendship Hospital from January 2006 to December 2015 were included in the study. Patients＇ data were retrospectively analyzed. Comparative studies were performed on the survival group and the deceased group, and Fisher＇s exact probability test was used for statistical analysis. Results： Among the 88 patients included, 40 （45.5%） were male with a mean age of 45 - 18 years. Forty-eight （54.5%） had SJS, 34 （38.6%） had SJS/TEN, and 6 （6.8%） had TEN. Fifty-three （60.2%） cases were caused by medications, mainly antibiotics （n = 24） followed by traditional Chinese medicines 97 - 7）. Forty-two cases （47.7%） developed visceral damage. Eighty-two patients improved or recovered and were discharged from hospital, and six patients died. Comparative studies on the survival group and the deceased group showed that the presence of malignant tumor （Z2 = 27.969, P 〈 0.001）, connective tissue diseases （x^2 - 9.187, P = 0.002）, previous abnormal liver/kidney functions （x^2 = 6.006, P = 0.014）, heart rate 〉100 times/rain （x^2 = 6.347, P = 0.012）, detached skin area 〉20% （x^2 = 5.594, P = 0.018）, concurrent mucosal involvement at the mouth, eyes, and external genitals （Z2 = 4.945, P = 0.026）, subsequent accompanying liver/kidney damage （x^ = 11.839, P = 0.001, and x^2 = 36.302, P 〈 0.00 l, respectively）, and SCORTEN score 〉2 （x^2 = 37.148, P 〈 0.001 ） increased the risk of death. Conclusions： SJS/TEN is mainly caused by medications, and nearly half of patients develop visceral damage. Multiple factors increase the mortality risk.

Cohort study of patients with Stevens-Johnson syndrome and toxic epidermal necrolysis in China:evaluation of risk models and new predictor of pulmonary consolidation on computed tomography

Stevens-Johnson syndrome(SJS)and toxic epidermal necrolysis(TEN)are rare but severe diseases.This study aimed to validate the predictive ability of risk models in patients with SJS/TEN and propose possible refinement in China.Patients in the Department of Dermatology of Huashan Hospital from January 2008 to January 2019 were included.Results showed that the severity-of-illness score for TEN(SCORTEN)had a good discrimination(area under the receiver operating characteristic curve(AUC),0.78),and it was superior to auxiliary score(AS)and ABCD-10,which indicates age,bicarbonate level,cancer,dialysis,and 10%involved body surface area(AUC,0.69 and 0.68,respectively).The calibration of SCORTEN(Hosmer-Lemeshow goodness-of-fit test,P=0.69)was also better than that of AS(P=0.25)and ABCD-10(P=0.55).SCORTEN and ABCD-10 were similar(Brier score(BS),0.04 and 0.04)in terms of accuracy of predictions.In addition,the imaging appearance of pulmonary consolidation on computed tomography was associated with high mortality.Refined models were formed using the variables and this imaging appearance.The refined AS and ABCD-10 models were similar in discrimination compared with the original SCORTEN(0.74 vs.0.78,P=0.23;0.74 vs.0.78,P=0.30,respectively).Therefore,SCORTEN showed good discrimination performance,calibration,and accuracy,and refined AS or ABCD-10 model may be an option when SCORTEN variables are not available.

Stevens-Johnson syndrome/toxic epidermal necrolysis successfully treated with Chinese herbal medicine Pi-Yan-Ning: A case report

Stevens-Johnson syndrome/toxic epidermal necrolysis(SJS/TEN)is a rare adverse cutaneous reaction with a low incidence and high mortality.Despite posing a serious threat to patients’health and lives,there is no high-quality evidence for a standard treatment regimen.Here we report the case of a 62-year-old man with stage IV pancreatic cancer who experienced immunotherapy-induced SJS/TEN.After consensus-based regular treatments at a local hospital,his symptoms became worse.Thus,he consented to receive Chinese herbal medicine(CHM)therapy.The affected parts of the patient were treated with the CHM Pi-Yan-Ning which was applied externally for 20 min twice a day.After 7 days of treatment,the dead skin began peeling away from the former lesions that had covered his hands,feet,and lips,indicating that skin had regenerated.After 12 days of treatment,the patient’s skin was completely recovered.In this case,SJS/TEN was successfully treated with Pi-Yan-Ning,suggesting that there might be tremendous potential for the use of Pi-Yan-Ning in the treatment of severe skin reactions to drug treatments.Further basic investigations and clinical trials to explore the mechanism and efficacy are needed.

Biomarkers of skin toxicity induced by anti-epidermal growthfactor receptor antibody treatment in colorectal cancer

Skin toxicity is a common symptom of anti-epidermal rowth factor receptor(EGFR) antibody treatment and is also a predictive marker of its efficacy in colorectal cancer patients. However, severe skin disorders induced by such antibodies negatively impact on the quality of life of patients and decreases drug compliance during treatment. If we can predict the high-risk group susceptible to severe skin toxicity before treatment, we can undertake the early management of any arising skin disorders and formulate a more accurate prognosis for anti-EGFR antibody treatment. Previous studies have identified molecular markers of skin toxicity induced by anti-EGFR antibody, such as EGFR polymorphisms, the expression of inflammatory chemokines and serum levels of EGFR ligands. A clinical trial was undertaken involving the escalation of cetuximab doses, guided by the grade of skin toxicity observed, such as no or low-grade, in metastatic colorectal cancer(the EVEREST study). The dose escalation of cetuximab was confirmed by a safety profile and had the tendency to achieve a higher response rate in KRAS wild-type patients. A large, prospective randomized trial is now ongoing(EVEREST 2) and the results of this trial may contribute to personalized medicine in KRAS wild-type colorectal cancer patients.

Toxic epidermal necrolysis after percutaneous coronary intervention： which drug is the culprit？

Toxic epidermal necrolysis （TEN） is a serious, usually drug-induced, dermatosis characterized by extensive erythema,necrosis, bullous detachment of the epidermis, constitutional symptoms, and visceral involvement. We report a 62-year-old man who was diagnosed TEN after percutaneous coronary intervention （PCI）. After consulting with a cardiologist, all pre-hospital medication was discontinued except clopidogrel. With supportive care, the patient recovered.

Drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in children: 20 years study in a tertiary care hospital

Background:Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe life-threatening skin conditions.The most common cause of these manifestations is medications.Beside discontinued of the culprit drug,systemic corticosteroids were used as a primary treatment option among pediatric population.This study aimed to explore causative drugs (drug group/ latent period),treaments,complications,and treatment outcome (morbidity,mortality,length of hospital stay) of SJS and TEN in children.Methods:A retrospective chart was reviewed during the period of 1992 to 2012 at Srinagarind Hospital,Faculty of Medicine,Khon Kaen University,Thailand.SJS and TEN were clinically diagnosed and confirmed by pediatric dermatologists.Other possible causes other than drug-induced SJS and TEN were excluded.Results:A total of 30 patients was recorded,including 24 (80%) SJS patients and 6 (20%) TEN patients.The mean age was 6.9 years (SD 4.4).Male to female ratio was 1.5:1.Antiepileptic drug group was the most common causative drug (n=18,60%),followed by antibiotic drug group (n=8,26.6%),and others (n=4,13.3%) which included nonsteroidal antiinflammtory drugs (NSAIDs) and chemotherapy drugs.Systemic corticosteroids were used in 29 patients (96.6%).Intravenous immunoglobulin was used in one TEN patient (3.3%).There was a medium correlation between time to treatment (systemic corticosteroids) and the length of hospital stay (Spearman correlation coefficient=0.63,P=0.005).Two TEN patients (6.6%) died.Conclusions:Carbamazepine was the most common causative drug of SJS and TEN in our study.The severity of skin detachment is not correlated to severity of ocular findings.However,the persistent of ocular complications up to one year is suggested for promptly appropriate ocular treatment in all SJS and TEN patients.Our data suggested that early administration of systemic corticosteroid may reduce the length of hospital stay and should be considered for the treatment of pediatric drug-induced SJS and TEN.

Successful treatment of a female pediatric patient with carbamazepine-induced toxic epidermal necrolysis: Active wound care and systemic therapy

We describe a 6-year-old female patient who developed carbamazepine-associated toxic epidermal necrolysis.With active wound care,systemic methylprednisolone and intravenous immunoglobulin pulse therapies and multidisciplinary supportive care,the patient improved significantly.This case indicates that improving the management of Stevens-Johnson syndrome/Toxic epidermal necrolysis patients requires attention not only to the process of wound management but also to individual supportive care and active therapeutic intervention.Only through this can standardized care,including muco-cutaneous and visceral wound care,be delivered to provide high-quality care with improved clinical prognosis and quality of life.

Treatment and Nursing of a 90% Bullous Epidermal Necrolysis Drug Eruption Complicated with Diabetes, Hypoproteinemia and Bilateral Pneumonia

Bullous epidermal necrolysis drug eruption is mainly caused by drug allergy, also known as toxic epidermal necrolysis, TEN, first reported by Lyell A in 1956, also known as Lyell syndrome, is the most serious type of drug eruption, the fatality rate is about 25%-50%[1]. The disease is characterized by acute onset, obvious systemic toxic symptoms, and flaccid blisters of varying sizes on the skin of the whole body. At the beginning of the disease, the skin rash is dark red or dark red. It quickly fuses into flakes and develops into the whole body. There are flaccid blisters and epidermolysis in the lesions, which are slightly rubbed or broken, and the tenderness is obvious and accompanied by a large amount of exudation. Severe cases may involve various organs and tissues of the body, accompanied by oral, conjunctival, respiratory, gastrointestinal mucosa erosion, ulcer, some patients may have liver and kidney function damage, serious cases may die of infection, liver and kidney failure, toxicemia, electrolyte disorders or visceral bleeding.

Management of skin toxicities during panitumumab treatment in metastatic colorectal cancer

BACKGROUND Anti-epidermal growth factor receptor therapy is associated with skin adverse events not previously reported with conventional chemotherapy. Prophylactic actions are recommended, but routine clinical management of these toxicities and their impact on quality of life remain unknown. AIM To assess the dermatological toxicities reported after panitumumab initiation, their impact on the quality of life and the clinical practices for their management. METHODS Patients included in this prospective multicenter observational study were over 18 years of age and began treatment with panitumumab for wild-type KRAS metastatic colorectal cancer. The incidence of dermatological toxicities, clinical practices for their management and impact on quality of life were recorded during a 6-mo follow-up. RESULTS Overall, 229 patients (males, 57.6%;mean age, 66.2 years) were included. At day 15, 59.3% of patients had dermatological toxicity;the rate peaked at month 2 (74.7%) and decreased at month 6 (46.5%). The most frequent dermatological toxicities were rash/acneiform rash, xerosis and skin cracks. At least one preventive treatment was administered to 65.9% of patients (oral antibiotics, 84.1%;emollients, 75.5%;both, 62.9%). The rates of patients who received at least one curative treatment peaked at month 2 (63.4%) and decreased at month 6 (44.8%). The impact of the dermatological toxicities on quality of life was limited as assessed with Dermatology Life Quality Index scores and inconvenience visual analogic scale score. The rates of topical corticosteroids administration and visits to specialists were low. CONCLUSION The rates of the different skin toxicities peaked at various times and were improved at the end of follow-up. Nevertheless, their clinical management could be optimized with a better adherence to current recommendations. The impact of skin toxicities on patient’s quality of life appeared to be limited.