Toxic epidermal necrolysis usually begins with flu-like prodrome, with a high-grade fever, sore-throat, cough, runny nose, redness of eyes, decreased appetite, malaise, arthralgia, myalgia, and generalized body aches. This is usually followed by drug exposure on average 14 days prior to the onset of symptoms. There is then an abrupt onset of red-purple, dusky, flat spots known as macules on the face and trunk, often spreading later to the rest of the body in an irregular fashion . The maximum extent is usually reached after 4 days. These skin lesions then transform into large blisters. Sheets of blisters coalesce and denude with the underlying skin becoming painful and erythematous. Large areas of affected skin become necrotic and peel off with just a gentle touch. In toxic epidermal necrolysis, more than 30% of the skin area is involved. The blisters most often damage the mucous membranes lining the mouth, throat, anus, genitals and eyes. It makes eating difficult. Closing the mouth may be painful. Nikolsky sign is positive in these patients; that is, the epidermis easily separates from its underlying surface when gentle pressure is applied   . Hypotension and tachycardia can develop after dehydration and hypovolemia. In addition to skin, other organs including liver, kidney, lungs and those of the urinary system may also be involved. A person who has this disorder is very susceptible to chronic infections, which if not untreated might lead to death.
Entire Body System
Prior to this, she complained of fever and discomfort upon swallowing. Skin biopsy had shown epidermal necrosis compatible with Stevens Johnson Syndrome and Toxic Epidermal Necrolysis. [ncbi.nlm.nih.gov]
TEN usually starts with 2-3 days of flu-like symptoms including fever, cough, sore throat, runny nose, and general aches and pains. This is followed by the critical phase that generally lasts 8-12 days. [web.archive.org]
[…] lead to SJS, here are a just few: Sulfonamides Penicillin Quinolones NSAIDS, such as aspirin Acetamenophen Corticosteroids Certain seizure drugs such as Carbamazepine, Phenytoin, Valproic Acid SJS Symptoms Below are the most common symptoms of SJS: fever [sjs-legal.com]
SJS/TEN manifest with an "influenza-like" prodromal phase (malaise, fever), followed by painful cutaneous and mucous membrane (ocular, oral, and genital) lesions, and other systemic symptoms. [ncbi.nlm.nih.gov]
Toxic epidermal necrolysis usually begins with flu-like prodrome, with a high-grade fever, sore-throat, cough, runny nose, redness of eyes, decreased appetite, malaise, arthralgia, myalgia, and generalized body aches. [symptoma.com]
Clinical Presentation • Prodromal phase of fever, cough, malaise • Nikolsky-positive macules (epidermal separation induced by gentle lateral pressure on skin surface) • Mucosal surface often involved, systemic involvement is variable (30% of cases have [slideshare.net]
Clinical record A 44-year-old woman presented to the emergency department with a 3-day history of a progressive rash, fever, malaise and mucosal ulceration. [mja.com.au]
Symptoms and Signs Within 1 to 3 wk after the start of the offending drug, patients develop a prodrome of malaise, fever, headache, cough, and keratoconjunctivitis. [merckmanuals.com]
They include: Sloughing of the mucous membranes in the mouth, throat, and digestive tract: this creates difficulty in eating and drinking and leads to dehydration and malnutrition Bacterial skin infections Conjunctival sloughing and other eye problems [web.archive.org]
Intravenous vitamins B and C (Pabrinex®) were added because of concern over malnutrition (BMI 16 kg/m2 at presentation). By the third hospital day approximately half the body surface area was denuded of epithelium. [bmj.com]
During the acute phase, potentially fatal complications include: Dehydration and acute malnutrition Infection of skin, mucous membranes, lungs (pneumonia), septicaemia (blood poisoning) Acute respiratory distress syndrome Gastrointestinal ulceration, [dermnetnz.org]
- Weight Loss
Center | Bascom Palmer Eye Institute Font Size Group 30 Group 30 Contrast logo Menu Search University of Miami Health System Close Search Find a Doctor Treatments Page 1 Featured Treatments For Allergy and Immunology Arthritis (Rheumatology) Bariatrics (Weight [uhealthsystem.com]
Signs and Symptoms Approximate number of patients (when available) Abnormal blistering of the skin 90% Abnormality of temperature regulation 90% Acantholysis 90% Hypermelanotic macule 90% Malabsorption 90% Nausea and vomiting 90% Weight loss 90% Abnormality [web.archive.org]
He denied any history of fever, weight loss or anorexia. His background history revealed that he was a smoker and had quit smoking three months earlier, and was taking antihypertensive medicines for the last three years. [ncbi.nlm.nih.gov]
Nutrition Poor oral intake in combination with increased calorie requirements can result in weight loss. [bjaed.oxfordjournals.org]
Hypothermia can also develop. TEN usually involves the eyes and the mucous membranes such as the mouth, nose, genitalia and anus. Description of the intervention There is no clear agreement on the treatment for TEN. [doi.org]
A positive-pressure environment (to decrease infection), with a temperature of 30 degrees Centigrade (to mitigate against hypothermia), is also recommended. Wound care should involve the initial aspiration of tense bullae. [clinicaladvisor.com]
Re-epithelization begins 1 week after onset, takes up to 3 weeks; faster in children 30 Mucosal and other complications Large wound area leads to severe pain, massive fluid and protein loss, electrolyte imbalances, bleeding, evaporative heat loss with subsequent hypothermia [emdocs.net]
Jaw & Teeth
- Conjunctival Injection
The initial symptoms included conjunctivitis ranging from mild conjunctival injection to purulent conjunctivitis with subsequent pseudomembrane formation (7/17, 41.1%), dry eye (2/17, 11.7%) and ocular pain (2/17, 11.7%). [panafrican-med-journal.com]
Symptoms and signs of mucous membrane involvement include blood-streaked rhinorrhea, conjunctival injection, hemorrhagic crusting of the lips, burning on urination, pain on defecation, and oral and genital erosions. [clinicaladvisor.com]
SJS-TEN overlap: note purulent discharge and oral erosions; crusting at the eyelid margins with conjunctival injection Figure 2. [pulmonologyadvisor.com]
The areas of rash enlarge and spread, often forming blisters in their center. The skin of the blisters is very loose and easy to rub off, often with just a gentle touch or pull, and the blisters peel off over a period of 1 to 3 days. [merck.com]
These skin lesions then transform into large blisters. Sheets of blisters coalesce and denude with the underlying skin becoming painful and erythematous. Large areas of affected skin become necrotic and peel off with just a gentle touch. [symptoma.com]
Pressing on a tense blister or scratching the skin next to a blister will extend the blister and make it larger. This is a common feature of these skin disorders. Blisters can involve any or all of the mucous membranes just listed. [webmd.com]
Involvement of the oral mucosa results in edema and erythema, followed by blistering. Ruptured blisters may form extensive hemorrhagic erosions with grayish white pseudomembranes or shallow aphthouslike ulcers. [web.archive.org]
Stevens Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are life-threatening and severe adverse cutaneous drug reactions characterized by epidermal detachment presenting as blisters and areas of denuded skin. [ncbi.nlm.nih.gov]
unspecified L52 Erythema nodosum L53 Other erythematous conditions L53.1 Erythema annulare centrifugum L53.2 Erythema marginatum L53.3 Other chronic figurate erythema L53.8 Other specified erythematous conditions Reimbursement claims with a date of [icd10data.com]
Both patients presented erythema after hospital discharge following initial paraquat poisoning and then developed a widespread eruption of diffuse erythema on almost the whole body, with bullae, epidermal necrosis and sloughing. [ncbi.nlm.nih.gov]
[…] multiforme, EM, bullous erythema multiforme, Stevens-Johnson syndrome, SJS, mucocutaneous reaction, widespread erythema, necrosis, bullous detachment of the epidermis, SJS-TEN, TEN with spots, TEN without spots, drug-induced skin disorder Background [web.archive.org]
Eruptions are deemed "fixed" because upon repeated exposure they recur at previously affected sites. Generalized bullous fixed drug eruption (GBFDE) is a rare FDE variant occurring in patients with a previous history of FDE. [ncbi.nlm.nih.gov]
[…] just few: Sulfonamides Penicillin Quinolones NSAIDS, such as aspirin Acetamenophen Corticosteroids Certain seizure drugs such as Carbamazepine, Phenytoin, Valproic Acid SJS Symptoms Below are the most common symptoms of SJS: fever sore throat fatigue ulcers [sjs-legal.com]
We describe a case of oxcarbazepine induced TEN, who presented with erythematous ulcerative maculopapular rash. [ncbi.nlm.nih.gov]
- Nikolsky's Sign
A 63-year-old woman treated with trimethoprim-sulfamethoxazole for Pneumocystis jirovecii infection developed a generalized maculopapular rash with herpetiform lesions, rosette-like lesions, and tense bullae with Nikolsky sign. [ncbi.nlm.nih.gov]
In severe cases of toxic epidermal necrolysis, large sheets of epithelium slide off the entire body at pressure points (Nikolsky sign), exposing weepy, painful, and erythematous skin. [merckmanuals.com]
Facts : Generally seen in adults History / PE : Erythematous morbilliform eruption Exfoliation of skin Positive Nikolsky's sign (skin falls off with slightest touch/pressure) Diagnosis : Biopsy shows full-thickness eosinophilic epidermal necrosis Greater [medlibes.com]
The diagnosis of toxic epidermal necrolysis is based on both clinical and histological findings. A recent history of drug reactions can indicate a high risk for this disorder. Skin examination shows painful, burning, erythematous macules that coalesce and form large fluid-filled blisters all over the skin. The Nikolsky sign is positive in such patients.
The laboratory tests that help confirm the diagnosis include the following.
- Complete blood count: Leukopenia, thrombocytopenia and neutropenia are present in severe infections.
- Hematologic studies: These include erythrocyte sedimentation rate and circulating immune complexes. They are found to be raised in chronic infections and sepsis.
- Coagulation studies: These include prothrombin time and activated partial thromboplastin time. These help assess the degree of severity of the disorder.
- Skin biopsy: It is usually required to confirm the clinical diagnosis. A frozen section specimen is taken to exclude Staphylococcal Scalded Skin Syndrome and other generalized rashes with blisters.
- Histology: The histopathology suggests full thickness epidermal necrosis with keratinocyte death. It often shows scant inflammatory infiltrate in the papillary dermis. Epidermal detachment and sloughing may also be evident.
- Serum biomarkers: It is a new technique for early diagnosis of toxic epidermal necrolysis. Serum granulysin and serum high-mobility group protein B1 are among a few of the markers being used in early research.
- To assess fluid and electrolyte losses, blood urea nitrogen, albumin and total protein should be assessed. Chest radiography should be performed in severe cases with respiratory distress. Patch testing also identifies the case and is often recommended.
The management of toxic epidermal necrolysis requires prompt diagnosis of the disorder and cessation of all causative agents. The patient should be hospitalized immediately in burn unit or intensive care center . The supportive measures include isolation of the patient with fluid and electrolyte replacement, nutritional support, temperature maintenance, pain management and protective dressing. Crystalloids are given by intravenous or nasogastric routes. On average, 3-4 liters are needed in patients with 50% of the body surface area affected. Parenteral feeding should be advised. Opiate analgesics for pain relief are essential for comforting patients. Proper skin care should be provided by daily skin examination, skin culture, use of topical anesthetics, for example silver nitrate or chlorhexidine and sterile dressings such as gauze with petroleum. Other supportive measures include frequent use of eye-drops, mouthwashes, aerosols, bronchial aspiration and urinary catheterization. Regular assessment for infection including skin, mucous membrane and catheter sites is essential. Psychiatric support and physiotherapy to maintain joint movements may also be helpful.
Drug therapy should be initiated within the first 24-48 hours of illness. This includes:
- Antibiotics: Staphylococcal infection is common and appropriate antibiotic should be given. Ciclosporin 3-5mg/kg/day and cyclophosphamide have been proved effective.
- Immunoglobulin: Intravenous immunoglobulin (IVIG) 2-3g/kg inhibits keratinocyte apoptosis and may be beneficial if started early.
- Adjuvant therapies: These include corticosteroids, plasmapheresis, pentoxifylline, ulinastatin, anti-TNF alpha, N-acetylcysteine, etanercept and infliximab. Moreover, heparin has also been recommended to prevent thromboembolism.
The mortality for toxic epidermal necrolysis is 25-30%. With early diagnosis and good care, the outlook is very good. However, the untreated cases become vulnerable to chronic infections from fungi and bacteria, and can result in sepsis and death of the patient. Mortality rates are higher in elderly patients than in children and adults. The various complications include hypopigmentation, hypohidrosis, scarring, alopecia, chronic xerostomia, phimosis and nail dystrophy.
A disease severity score (SCORTEN) is used to predict outcome   . It includes various factors such as age > 40 years, heart rate > 120 beats/min, hematological malignancies, involved body surface area > 10%, blood urea > 10mmol/L, serum bicarbonate <20mmol/L and blood glucose >14mmol/L. The mortality rates increase up to 90% if more than 5 factors are present. Other negative prognostic factors include respiratory failure, lymphopenia, neutropenia, multiple drugs intake and sepsis.
More than 85-90% cases of toxic epidermal necrolysis have been reported to be caused by drug reactions . Numerous drug groups have been implicated in this case. Antibacterial drugs associated with toxic epidermal necrolysis include sulfonamides, penicillins, macrolides, quinolones and chloramphenicol. The anticonvulsants associated with the disorder include phenobarbital, phenytoin, carbamazepine, valproic acid and lamotrigine. NSAIDs include sulindac, tolmetin, indomethacin, ibuprofen, phenylbutazone, oxybutazone and oxicams   . The genetic factors, for example certain HLA-types and HIV-positive individuals are at increased risk of toxic epidermal necrolysis. Moreover, certain infectious agents such as mycoplasma pneumoniae, herpes simplex virus, hepatitis A, dengue virus, various immunizations, contrast agents used in imaging studies and bone marrow transplantations have also been associated with toxic epidermal necrolysis.
The incidence of toxic epidermal necrolysis is 1-2 cases per million population a year. In the HIV-positive population, the incidence increases to 1 case per thousand a year. It can affect people of all age groups but is more common in the elderly. There is a genetic predilection towards individuals with HLA-types. The mean age of patients with this disorder is reported to be between 46 and 63 years. The female to male ratio is 1.5:1. Toxic epidermal necrolysis is a severe form of Stevens-Johnson syndrome. The condition is called toxic epidermal necrolysis when >30% of the body surface is involved. However, it is called Stevens-Johnson syndrome when <10% of body surface is involved.
Toxic epidermal necrolysis is usually caused by drugs or a bacterial infection. Usually 1-4 weeks after drug commencement, the patient becomes systemically unwell and often runs a fever. Soon after, erythema and blistering develop, initially on the trunk but rapidly involving all skin. The toxic drug reactions weaken the immune system of the body. Certain type of immune cells including cytotoxic CD8 and helper T cells are primarily responsible for keratinocyte death and subsequent skin detachment  . Drug induced secretion of granulysin and the release of destructive proteins from cytotoxic T lymphocytes involves an immunopathologic pathway that leads to keratinocyte apoptosis. CD8 immune cells become overactive by stimulation from drug metabolites. Other agents, including tumor necrosis factor alpha and fas ligand also appear to be involved in the pathogenesis of toxic epidermal necrolysis.
The most effective way to prevent toxic epidermal necrolysis and its recurrence is by proper skin care and avoid taking the causative drugs and related medications. Cross reactions have been reported between different anti-convulsant agents or non-steroidal anti-inflammatory drugs, such as the oxicams. Specialized nursing care is essential in people who have survived the lethal disorder. It should be predicted early using genetic screening, as specific at-risk HLA alleles have been recognized in certain populations. The first degree relatives of the patient should be alerted to their elevated risk of such reactions to the same drug. Patients requiring management should be monitored carefully in sterile environment. Areas of skin erosion should be covered with non-adherent protective dressings such as petroleum gauze. The patients with respiratory distress should be facilitated with endotracheal intubation and proper ventilation. The long term complications such as dry eyes, photophobia, symblepharon, corneal scarring, xerosis, vulvovaginal stenosis and skin eruptive lesions should also be treated immediately. In patients with worsening renal functions, allopurinol should be prescribed for good indications and commenced at low doses.
Toxic epidermal necrolysis is a rare, life-threatening skin disorder associated with a high mortality rate. The disease is characterized by extensive mucocutaneous blistering that causes rash, skin peeling and soreness on the mucous membranes. It is usually drug-induced, particularly associated with anticonvulsants, sulphonamides, sulphonylureas, anxiolytics, beta-lactams, barbiturates, NSAIDs, allopurinol and antiretroviral therapy. Typical symptoms for disease include flu-like prodrome with a cough, runny nose, fever, body-aches, decreased appetite, malaise and a flat red rash. It usually co-exists with Stevens-Johnson syndrome. Treatment involves discontinuing the use of causative agents, and supportive care in the intensive care unit of a hospital. Untreated cases of toxic epidermal necrolysis often suffer long-term complications affecting the skin and eyes.
Toxic epidermal necrolysis is a life-threatening skin disorder that is usually caused by a reaction to drugs. It causes rash, skin peeling and sores on the mucous membrane. The patients usually presents with fever, cough, body aches, generalized weakness, a flat red rash and blisters all over the skin. It affects the face and trunk, and later spreads to the rest of the body. It is a medical emergency and the patient requires proper treatment in burn unit. With early diagnosis and supportive care, the prognosis is good.
- Roujeau JC, Guillaume JC, Fabre JP, Penso D, Flechet ML, Girre JP. Toxic epidermal necrolysis (Lyell syndrome). Incidence and drug etiology in France, 1981-1985. Archives of dermatology. Jan 1990;126(1):37-42.
- Faninger A. [Contribution to the knowledge of the etiology of "toxic epidermal necrolysis (Lyell)"]. Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete. Dec 1961;12:554-555.
- Mockenhaupt M. Stevens-Johnson syndrome and toxic epidermal necrolysis: clinical patterns, diagnostic considerations, etiology, and therapeutic management. Seminars in cutaneous medicine and surgery. Mar 2014;33(1):10-16.
- Schwartz RA, McDonough PH, Lee BW. Toxic epidermal necrolysis: Part I. Introduction, history, classification, clinical features, systemic manifestations, etiology, and immunopathogenesis. Journal of the American Academy of Dermatology. Aug 2013;69(2):173 e171-113; quiz 185-176.
- Khalili B, Bahna SL. Pathogenesis and recent therapeutic trends in Stevens-Johnson syndrome and toxic epidermal necrolysis. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. Sep 2006;97(3):272-280; quiz 281-273, 320.
- Downey A, Jackson C, Harun N, Cooper A. Toxic epidermal necrolysis: review of pathogenesis and management. Journal of the American Academy of Dermatology. Jun 2012;66(6):995-1003.
- Collin B, Marshall T, Heagerty A. Scoring with SCORTEN. Archives of dermatology. Sep 2003;139(9):1215; author reply 1215-1216.
- Bastuji-Garin S, Fouchard N, Bertocchi M, Roujeau JC, Revuz J, Wolkenstein P. SCORTEN: a severity-of-illness score for toxic epidermal necrolysis. The Journal of investigative dermatology. Aug 2000;115(2):149-153.
- Cartotto R, Mayich M, Nickerson D, Gomez M. SCORTEN accurately predicts mortality among toxic epidermal necrolysis patients treated in a burn center. Journal of burn care & research : official publication of the American Burn Association. Jan-Feb 2008;29(1):141-146.
- Soloshenko EN, Brailovskii A. [Clinical picture and pathogenesis of toxic epidermal necrolysis (Lyell's syndrome)]. Vestnik dermatologii i venerologii. 1971;45(4):72-74.
- van Gijn J, Gijselhart JP. [Nikolsky and his sign]. Nederlands tijdschrift voor geneeskunde. 2011;155:A2846.
- Doubleday CW. Who is Nikolsky and what does his sign mean? Journal of the American Academy of Dermatology. May 1987;16(5 Pt 1):1054-1055.
- Goodman H. Nikolsky sign; page from notable contributors to the knowledge of dermatology. A.M.A. archives of dermatology and syphilology. Sep 1953;68(3):334-335.
- Hensen E. [Pathogenesis and treatment of toxic epidermal necrolysis]. Tijdschrift voor ziekenverpleging. Jun 23 1981;34(13):563-567.