Stevens‐Johnson syndrome: Pathogenesis,diagnosis, and management

Cutaneous drug reactions are the most common type of adverse drug reaction. These reactions, ranging from simple pruritic eruptions to potentially life‐threatening events, are a significant cause of iatrogenic morbidity and mortality. Stevens‐Johnson syndrome (SJS) is a serious and potentially life‐threatening cutaneous drug reaction. Although progress has been made in the management of SJS through early detection, prompt hospitalization, and immediate cessation of offending agents, the prevalence of permanent disabilities associated with SJS remains unchanged. Nevertheless, despite being a problem that is global in scope, government and health care agencies worldwide have yet to find a consensus on either diagnostic criteria or therapy for this disorder. Here, we provide the internist and emergency room physician with a brief review the SJS literature and summarize the latest recommended interventions with the hope of improving early recognition of this disease and prevention of permanent sequelae and mortality that frequently complicate SJS.     

Warfarin‐induced Stevens–Johnson syndrome with severe liver injury

Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a life-threatening mucocutaneous disease that is predominantly drug-induced. Warfarin is the most commonly used drug for long-term anti-coagulant therapy; however, warfarin-induced SJS/TEN is seldom reported. In this study, we presented the case of a 61-year-old man who developed SJS after receiving multiple-drug therapy following aortic valve replacement surgery. The patient was diagnosed with drug-induced liver injury (DILI) based on significantly abnormal liver function test results. Warfarin was identified as the culprit drug using the algorithm of drug causality for epidermal necrolysis (ALDEN) score, enzyme-linked immunospot (ELISPOT) assay, and Roussel Uclaf Causality Assessment Method (RUCAM). After warfarin discontinuation and corticosteroid therapy, the lesions and liver function test findings improved. Human leukocyte antigen typing was conducted to detect the risk allele. To our knowledge, this is the first reported case of warfarin-induced SJS/TEN with DILI. This case suggests that commonly used and safe pharmaceutical agents such as warfarin can potentially cause serious adverse events, including SJS/TEN and DILI. The application of ALDEN, the ELISPOT assay, and RUCAM could be useful in identifying culprit drugs.     

Stevens-Johnson syndrome and concurrent hand foot syndrome during treatment with capecitabine: A case report

BACKGROUNDCapecitabine is used in combination with lapatinib as palliative treatment for human epidermal growth factor receptor 2 - positive metastatic breast cancer. The most frequently reported adverse events attributed to capecitabine include diarrhea, hyperbilirubinemia, and hand-foot syndrome (HFS). A number of cutaneous adverse events have been attributed to capecitabine, including Stevens-Johnson syndrome (SJS) as a rare and potentially life-threatening mucocutaneous condition. We report the first case involving concurrent SJS and HFS after capecitabine and lapatinib treatment.CASE SUMMARYA 70-year-old woman with a history of breast cancer treatment visited our hospital for evaluation of painful skin lesions. Six weeks earlier, she had been prescribed capecitabine plus lapatinib as treatment for metastatic breast cancer. She subsequently developed worsening erythema and bullae on her palms and soles, as well as reddish macules on her back and chest wall. Histopathological evaluation of the chest wall lesions revealed extensive eosinophilic epidermal necrosis and separation of the epidermis from the dermis. The capecitabine plus lapatinib treatment was discontinued immediately and treatment was started using systemic steroids. This treatment resolved most lesions, although the lesions on her palms and soles required Vaseline gauze dressings, which resulted in re-epithelialization. Therefore, we determined that the patient had concurrent SJS and HFS. Although the dermatological problems resolved, the patient ultimately died because of multiple organ failure.CONCLUSIONOral capecitabine treatment carries a risk of both HFS and also life-threatening adverse cutaneous drug reactions, such as SJS.     

Purpura fulminans,TEN, and disseminated herpes simplex: An unexpected combination

Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and purpura fulminans (PF) are all rare conditions. A combination of these 3 conditions together with a viral infection is very rare. A 52‐year‐old, previously healthy woman which developed SJS, potentially due to a reaction to CT contrast, although this is still unknown. This developed into TEN on day 10 of the initial admission, the patient scored 3 points on SCORTEN. On day 12 from initial admission, she developed unexpected multiorgan failure and PF. The patient passed away 2 days later, the autopsy demonstrates herpes simplex virus in the bladder and lungs on immunohistological staining. Our clinical case encountered the challenge of differentiating TEN and PF. The microscopic and immunochemical examination confirmed the clinical suspicion of PF but also a disseminated herpes simplex infection. We speculate the clinical route of this case started SJS and TEN, leading to superimposed infection with three different types of bacteria, confirmed in blood cultures, and a disseminated viral infection. The combination of all these diagnoses are very rare, no similar case has been described in adults to the authors’ knowledge. We recommend a prompt diagnosis and early recognition of both bacterial and viral infections to prevent the development of PF.     

Stevens-Johnson syndrome and toxic epidermal necrolysis: oncologic considerations

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe skin toxicities that may occur in patients with cancer. They are caused by infection or a drug reaction and can result in sepsis, severe ocular complications, and even death. Skin lesions usually are preceded by prodromal flulike symptoms. A rash with subsequent blistering and denudation follows. Diagnosis is made by skin biopsy, and classification is based on body surface area and visceral organ involvement. Because many of the drugs associated with SJS and TEN are used to treat cancer, early recognition and intervention are critical to achieving a favorable outcome. Interventions include stopping the suspected offending agent. The use of steroids is controversial. Healthcare professionals always should consider an early transfer to a burn unit for patients with a comorbid condition such as cancer because this action is associated with improved outcomes. Implications for oncology nurses and a case study are presented in this article.     

重症多形红斑与中毒性表皮坏死松解症的临床分析

目的探讨重症多形红斑(SJS)与中毒性表皮坏死松解症(TEN)的致病因素、发生规律、临床特点和治疗措施。方法对42例SJS和20例TEN住院患者的临床资料进行回顾性分析。结果 SJS组和TEN组患者中,药物为最常见病因。致敏药物中排在前三位的分别是抗癫痫药(29.03%)、别嘌呤醇(16.13%)及抗生素(16.13%)。SJS与TEN的黏膜损害率均为100%,TEN组的皮损范围、损害程度、黏膜病变均较SJS组更广泛、更严重,TEN的日、最大糖皮质激素用量均高于SJS。结论药物是SJS和TEN发病最主要的原因。TEN患者较SJS患者病变广泛且严重。别嘌呤醇与卡马西平应用需谨慎,激素联合免疫球蛋白IVIG治疗有效。     

Radiologic Contrast Reactions and Transfusion Reactions: Recognition,Differentiation, and Treatment

Acutely ill patients receive many treatments, some of which can cause serious reactions. It is not unusual for a critically ill patient to receive blood products and low osmolar nonionic iodine-based contrast material in close proximity to one another. If the patient appears to develop a reaction during the administration of either iodine-based contrast or transfusion, it may be difficult to determine whether the patient is experiencing a transfusion reaction or a contrast reaction. This article explores different types of acute reactions resulting from administration of blood products or iodine-based contrast and how to differentiate between these reactions. Only iodine-based contrast reactions and acute transfusion reactions are discussed, as these are by far the most common and most serious types of reactions that will occur. Bedside management of both types of reactions is also explored. In conclusion, timely recognition of acute transfusion and iodine-based reactions, along with an understanding of the differences and similarities between these reactions, enables the clinical team to appropriately evaluate and treat the patient for these potentially life-threatening events.     

糖皮质激素联合人免疫球蛋白治疗Stevens-Johnson综合征和中毒性表皮松解症

  目的  探讨Stevens-Johnson综合征(Stevens-Johnson syndrome, SJS)和中毒性表皮松解症(toxic epidermal necrolysis, TEN)的临床特征及治疗方法, 以提高对SJS/TEN的认识。  方法  回顾性分析北京协和医院7例SJS/TEN患者的临床表现、疾病严重程度、眼部受累程度、致敏药物、治疗方案及临床结局。  结果  患者年龄26~81岁, 均伴有黏膜损害, 致敏药物以非甾体类抗炎药、抗惊厥药及别嘌醇为主, 7例均使用大剂量糖皮质激素联合人免疫球蛋白治疗, 治愈6例, 死亡1例。  结论  SJS/TEN是一组累及全身皮肤黏膜严重威胁患者生命的疾病, 病死率高, 早期足量使用大剂量糖皮质激素联合人免疫球蛋白为主要的治疗手段, 伴有系统疾病的患者预后较差。眼部损伤与疾病严重程度具有不同步性, 需及早给予针对性治疗。     

Cephalexin-induced Stevens-Johnson syndrome.

OBJECTIVE: To report a case of cephalexin-induced Stevens-Johnson syndrome (SJS), a devastating adverse drug reaction that involves the entire skin surface and mucosal areas of the body. DATA SOURCES: MEDLINE search (key terms cephalosporins, Stevens-Johnson syndrome, erythema multiforme, and systemic lupus erythematosus) and references identified from bibliographies of pertinent articles. DATA SYNTHESIS: Clinical presentation and manifestations of SJS include the skin, eyes, gastrointestinal tract, and pulmonary system. Infectious complications are the leading cause of mortality. Early intervention is important to prevent progression of SJS. The case described is consistent with the features of this syndrome. The patient presented with fever, arthralgias, and malaise. Skin lesions included a diffuse violet macular rash with erythema and multiple bullous lesions on her neck and abdomen. The skin biopsy was consistent with SJS. Multiple mucocutaneous ulcers were found in her mouth, but no evidence of lower gastrointestinal tract involvement was documented. She remained relatively free of pulmonary complaints except for the presenting bronchitis. CONCLUSIONS: Cephalexin should be added to the list of agents to consider as iatrogenic causes of SJS.     

Adverse reactions to contrast material: recognition,prevention, and treatment

Adverse reactions to contrast agents range from a mild inconvenience, such as itching associated with hives, to a life-threatening emergency. Renal toxicity is a well known adverse reaction associated with the use of intravenous contrast material. Other forms of adverse reactions include delayed allergic reactions, anaphylactic reactions, and local tissue damage. Previous allergic reactions to contrast material, asthma, and allergies are factors associated with an increased risk of developing an adverse reaction. Pretreatment of patients who have such risk factors with a corticosteroid and diphenhydramine decreases the chance of allergic reactions, including anaphylaxis, renal failure, or a possible life-threatening emergency. Awareness of the different types of risk factors and prescreening for their presence allows for early recognition and prompt treatment. Prophylactic treatment before administration of contrast material can prevent potential adverse reactions. If such reactions do occur, prompt recognition allows them to be treated immediately. Using the smallest amount of contrast material possible and low-molecular, nonionic agents also decreases the relative risk of reactions. Renal insufficiency induced by contrast material may be prevented by ensuring adequate hydration and discontinuing other nephrotoxic medications before the procedure. Low-osmolar, nonionic agents are helpful in patients with known conditions associated with adverse reactions.     

Atteintes bronchopulmonaires au cours des toxidermies graves

Skin is one of the most common targets of adverse drug reactions. Life-threatening skin adverse reactions include Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS). SJS and TEN are characterized by skin and mucous membrane detachments. Respiratory complications occur in about 40% of the cases, and can be related to specific bronchial epithelial injuries as well as to nonspecific manifestations like infection, pulmonary edema, and atelectasis. Mechanical ventilation is required in about 25% of cases. Bronchoscopy is warranted in mechanically ventilated patients to remove detached mucous membranes and prevent airway obstruction. Pulmonary involvement in DRESS is rare and related to lung infiltration by eosinophils, which rarely leads to the acute respiratory distress syndrome. The most severe cases of DRESS usually present other organ involvement like cytolytic hepatitis and are usually reversible after steroid treatment. Removal of the involved drug is warranted.     

HLA‐B*1502 Strongly Predicts Carbamazepine‐Induced Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis in Thai Patients with Neuropathic Pain

Background: Carbamazepine (CBZ) is one of the standard pharmacological treatments for neuropathic pain. However, its serious adverse drug reactions include Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Recently, HLA‐B*1502 allele was implicated as a genetic marker of CBZ‐induced SJS/TEN in some Asian epilepsy populations. Methods: This is a case control study to describe the clinical characteristics of SJS/TEN in Thai patients with neuropathic pain who were treated with CBZ, and to determine the association of HLA‐B*1502 in these patients, comparing with those who exposed to CBZ for at least 6 months without any cutaneous reactions. Results: Thirty‐four SJS/TEN patients and 40 control patients were included in this study. Mean age of SJS/TEN patients was 47 years. SJS/TEN was developed in 10.8 ± 1.4 days after initiation of CBZ. HLA‐B*1502 allele was found in 32 of 34 SJS/TEN patients (94.1%) but it was found only in 7 of 40 control patients (17.5%). The association was very strong with an odds ratio of 75.4. Sensitivity and specificity of this HLA‐B*1502 genotype test were 94.1% and 82.5%, respectively, while the positive predictive value and negative predictive value were 1.43% and 99.98%, respectively. Positive and negative likelihood ratios were 5.37 and 0.07, respectively. Conclusions: HLA‐B*1502 is a strong genetic marker for CBZ‐induced SJS/TEN in Thai patients with neuropathic pain. The screening for this marker should be performed prior to initiation of CBZ treatment to assess the risk of this serious side effect.     

Geropharmacology: a primer for advanced practice. Acute care and critical care nurses, part II

In the first part of this 2-part continuing education series, sources of medication errors were discussed. A predominant source of errors was the prescribing of potentially inappropriate medications for older adults. In this second part, drug classifications and drugs posing problems for older adults and cautions for advanced practice acute care and critical care nurses in their medication therapy management are highlighted. Cautions are advanced for anticholinergics, antihypertensives, analgesics, and psychotropics because of the severity of adverse reactions, including anticholinergic symptoms; mental status changes (especially confusion, sedation, delirium, and cognitive impairment); orthostatic hypotension; gastrointestinal tract problems (especially hemorrhage); depression; and neurobehavioral disturbances (agitation and aggressiveness). Risks of life-threatening outcomes associated with medications and adverse reactions are highlighted.     

Overlap Stevens Johnson Syndrome/Toxic Epidermal Necrolysis developed due to the use of toxic-dose vinblastine in case of Langerhans Cell Histiocytosis(Letterer-Siwe)

Except for side effects expected standart dose use of the chemotherapeutics agents, toxic effects (poisoning) may occur if high doses of are mistakenly used in the treatment of haemato-oncological diseases and these toxic doses are usually fatal. Here, we report a case of Stevens Johnson Syndrome (SJS) / Toxic Epidermal Necrolysis (TEN) following administration of toxic dose of vinblastine by mistake. A 20-month-old male patient with a diagnosis of Langerhans Cell Histiocytosis (Letterer-Siwe) at the pediatric oncology department was admitted to intensive care unit, after having received treatment protocol consisting of vinblastine, etoposide and prednisolone, with fever, altered consciousness and decompensated shock findings. Skin biopsy which performed from bullous lesions in the perianal, neck and axillary regions was resulted compatible with SJS / TEN in the patient with multiple organ failure, at 48 h of admission. It was later determined that the patient has been mistakenly given 10 times the normal dose of vinblastine he needed (60 mg/m²), which was 6 mg/m². Plasma exchange was performed 3 times for vinblastine toxicity, intravenous immunoglobulin was administered for SJS / TEN therapy and phenobarbital was initiated to increase drug metabolism. The patient whose clinical picture fully improved, was transferred to the oncology department on the 30th day of intensive care hospitalization. Vinblastine toxicity is a life-threatening condition that can cause multiple organ failure, SJS / TEN. Plasma exchange is an effective treatment method for the removal of vinblastine from the body and in these cases of toxicity.     

Omnipaque (iohexol).

The largest nationwide comparative clinical study evaluated 337,647 patients receiving high-osmolar ionic contrast media or low-osmolar nonionic contrast media and the incidence of adverse drug reactions. The overall prevalence of adverse drug reactions was 12.66% in the ionic contrast media group and 3.13% in the nonionic contrast media group. Severe adverse drug reactions occurred in 0.22% of examinations in the ionic contrast media group and in 0.04% of examinations in the nonionic contrast media group. Thus, the use of nonionic contrast medium significantly reduces the frequency of severe and potentially life-threatening adverse drug reactions to contrast media.     

Morbidity and mortality of mucocutaneous diseases in the pediatric population at a tertiary care center.

Toxic epidermal necrolysis (TEN) is a life threatening desquamating disease that is often an adverse reaction to drugs. Because mortality is so high, up to 30% nationally, and the morbidity significant, these cases are managed in burn centers. This study was conducted to evaluate what drugs were given to children who developed exfoliating skin disease and to identify the complications that these patients suffered. Thirty-two pediatric cases of erythema multiforme, Stevens-Johnson syndrome (SJS), and TEN were identified during a period of 8 years in which the average number of admissions to the burn center was 200 per year. Age, sex, drug history before admission, drug treatment during hospital stay, and clinical outcomes were noted. Several drugs were identified as probable causative agents. The most common cause of exfoliating disease was a combination of azithromycin and ibuprofen, followed by ibuprofen alone. Notably, the combination of ibuprofen and another drug was responsible for four additional cases, making the total percentage of pediatric cases involving ibuprofen 47%. Although no children died, several children with TEN and SJS suffered severe ocular involvement, sepsis, pneumonia, and genitourinary complications. All of the children who experienced complications had received ibuprofen. Chi-square analysis showed the correlation between ibuprofen and complications to be statistically significant (<0.05). This association was not observed with any other drug administered. Not only is ibuprofen a potential etiologic agent of exfoliating skin disease in children, it also may contribute to the development of complications in pediatric patients with the disease. Although this association does not prove that ibuprofen is the definitive cause of complications in these cases, caution is advised when giving this drug to children with suspected erythema multiforme, SJS, and TEN.     

Toxic Epidermal Necrolysis associated with COVID‐19 infection: A case report

Toxic Epidermal Necrolysis/Steven–Johnson Syndrome (TEN/SJS) is one of the most serious dermatological adverse reactions triggered mainly by drugs and less likely by infections. COVID‐19 disease is caused by Sever Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) with a wide range of clinical manifestations. Skin involvement is common in COVID‐19 patients including urticaria, purpura, and vasculitis. There were reported cases of TEN/SJS in adults with COVID‐19 infections and only two reported cases in pediatric patients. The causality relationship between COVID‐19 infection and TEN/SJS was not established in most cases due to history of drug usage that could be the trigger. In this study, we are reporting a case of previously healthy child apart from COVID‐19 infection who was admitted to the intensive care unit with TEN involving more than 30% of body surface area confirmed by skin biopsy. The child was treated with intravenous immunoglobulins, steroids, and cyclosporin with a very good outcome.     

Possible cefotaxime-induced Stevens-Johnson syndrome

OBJECTIVE: To report a case of possible cefotaxime-induced Stevens-Johnson syndrome (SJS). CASE SUMMARY: A 72-year-old woman with an upper urinary tract infection developed erosions and blisters on the skin and the mucous membranes, as well as fever and prostration, soon after the administration of cefotaxime. This presentation is consistent with the features of SJS. Resolution of the clinical manifestations was observed after discontinuation of the drug; all other drugs, infections, or immunologic disorders that could have caused this syndrome were carefully excluded. An objective causality assessment revealed that SJS was possibly associated with the use of cefotaxime. DISCUSSION: Although cephalosporins have been associated with an increased risk for SJS and cefotaxime has been suspected of being associated with SJS in a previous case-control study, this is the first full report for cefotaxime-related SJS in the literature. An immunologically mediated reaction may be the underlying mechanism. CONCLUSIONS: Although cefotaxime administration seems to be the underlying cause of the SJS observed in our patient, establishment of a definite causal relationship requires additional cases and supportive data.     

Stevens-Johnson syndrome

Stevens-Johnson Syndrome (SJS), or erythema multiforme, is a severe, acute, adverse, cutaneous reaction to certain medications, such as phenytoin and topical nitrogen mustard. The risk of developing SJS is high when phenytoin and steroids are administered during cranial irradiation. SJS produces headache, malaise, sore throat, fever, and sloughing of the skin and mucous membranes. Prompt recognition of SJS and withdrawal of the offending medication is key to treating this disorder. Nurses play an important role in assessing patients and educating them about signs and symptoms of SJS.     

Rare case of rhabdomyolysis with therapeutic doses of phendimetrazine tartrate

Phendimetrazine tartrate is a newer drug that acts as a central stimulant and indirectly acting sympathomimetic with a host of uses similar to the class amphetamines. Its main use is as an anorectic in the short-term treatment of obesity, although stimulants are no longer indicated for this purpose. This drug appeals to the younger American population for immediate weight loss through decreased appetite and early satiety. The European Union markets have already withdrawn this medication as well as other countries, but phendimetrazine is still used within the United States. Rhabdomyolysis is a potentially life-threatening complication reported with higher doses of amphetamines. We present a case of rhabdomyolysis and myoglobinuria developing in a 23-year-old patient after oral administration of phendimetrazine tartrate for 3 days in suggested therapeutic doses. The medication was taken for short-term treatment of obesity, and patient did not have any predisposing factors to precipitate rhabdomyolysis. Rhabdomyolysis resolved within 5 days. To our knowledge, this is the first reported case of rhabdomyolysis from administration of therapeutic amounts of phendimetrazine tartrate. The purpose of this case report is to create an awareness among physicians about the potentially life-threatening complications associated with phendimetrazine use as an anorectic even in suggested therapeutic doses as was the case in our patient. Additional awareness is needed to educate their patients about the side effects associated with these drugs and to strongly discourage their unsupervised use.