Toxic Epidermal Necrolysis Clinical Presentation

  • Author: Victor Cohen, PharmD; Chief Editor: Michael Stuart Bronze, MD   more...
 
Updated: Sep 15, 2011
 

History

Patients with toxic epidermal necrolysis (TEN) may describe an influenzalike prodrome characterized by the following:

  • Malaise
  • Rash
  • Fever
  • Cough
  • Arthralgia
  • Myalgia
  • Rhinitis
  • Headache
  • Anorexia
  • Nausea and vomiting, with or without diarrhea

Other prodromal signs and symptoms include conjunctivitis (32%), pharyngitis (25%), and pruritus (28%). The prodrome typically lasts from 1 day to as long as 3 weeks.

The cutaneous eruption begins as a poorly defined, erythematous macular rash with purpuric centers. Over a period of hours to days, the rash coalesces to form flaccid blisters and sheetlike epidermal detachment. The lesions predominate on the torso and face, sparing the scalp. Pain at the site of the skin lesions is often the predominating symptom and is often out of proportion to physical findings in early disease.

Mucous membrane erosions (seen in 90% of cases) generally precede the skin lesions by 1-3 days. The most frequently affected mucosal membrane is the oropharynx, followed by the eyes and genitalia. Oral cavity involvement typically presents as a sore or burning sensation. Intake may be limited because of pain associated with the oropharyngeal lesions.

Ocular manifestations range from acute conjunctivitis to corneal erosions and ulcers. Genital involvement may result in painful urination. Other mucosal surfaces such as the esophagus, intestinal tract, or respiratory epithelium may be affected. Bronchial epithelial sloughing may result in dyspnea and hypoxemia.

Most cases of TEN are drug induced, typically occurring within 1-3 weeks of therapy initiation and rarely occurring after more than 8 weeks. Therefore, a detailed medication history, focusing on medications that have been recently started, is a vital component of the patient's history.

More than 220 different medications have been suggested. The most commonly implicated agents include the following:

  • Sulfonamide antibiotics
  • Antiepileptic drugs
  • Oxicam nonsteroidal anti-inflammatory drugs
  • Allopurinol
  • Nevirapine
  • Abacavir
  • Lamotrigine

Fewer than 5% of patients report no history of medication use.

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Physical Examination

Vital signs in toxic epidermal necrolysis may include hyperpyrexia, hypotension secondary to hypovolemia, and tachycardia.

Skin examination

Skin lesions begin as painful/burning, warm, erythematous, morbilliform macules that are initially discrete. They begin symmetrically on the face and thorax before spreading to the entire body. The skin lesions coalesce and fill with fluid-producing large, flaccid blisters. The epidermis sloughs in sheets, leaving a characteristic moist, denuded dermis (see images below). Conjunctivitis and denudation and erosions of other mucous membranes precede epidermal necrolysis.

Epidermal sloughing in toxic epidermal necrolysis Epidermal sloughing in toxic epidermal necrolysis (TEN). Toxic epidermal necrolysis (TEN) ulcer in great toToxic epidermal necrolysis (TEN) ulcer in great toe (initial infection).

A positive Nikolsky sign is evident when the application of slight lateral pressure to the epidermal surface results in the epidermis easily separating from its underlying surface.

The usual course is an intense erythema that progresses rapidly to epidermolysis and stops within 2-3 days. Dermatologic recovery typically takes 1-3 weeks, with mucosal lesions taking longer. Rarely, necrolysis recurs in areas that began to heal.

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. Hemorrhagic crusting of the lips is a common finding (as seen in the image below).

Hemorrhagic crusting of mucous membranes in toxic Hemorrhagic crusting of mucous membranes in toxic epidermal necrolysis (TEN).

Ocular involvement varies in severity and can result in mild inflammation, conjunctival erosion, purulent exudates, or pseudomembrane formation.

Involvement of respiratory epithelium may result in bronchial hypersecretion, hypoxemia, interstitial infiltrates, pulmonary edema, bacterial pneumonia, or bronchiolitis obliterans.

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Complications

Numerous complications of TEN can arise as a result of the widespread cutaneous and mucosal membrane inflammation and necrosis. Stomatitis and mucositis, which are painful and hinder oral intake, can place patients at risk for dehydration and malnutrition.

Epithelial loss predisposes to septicemia (Pseudomonas aeruginosa, Staphylococcus aureus, gram-negative species, and Candida albicans). Renal hypoperfusion, acute tubular necrosis, and renal insufficiency may develop subsequent to septic shock.

Ulceration of various mucosal membranes may result in pain, scarring, and stricture formation. Affected surfaces include oral, ocular, and urogenital mucosa. Barrera and colleagues reported a case of hypopharyngeal stenosis and dysphagia with recurrent aspiration.[27] Miscellaneous complications include hypovolemia, massive gut bleeding, and pulmonary emboli.

Mild-to-severe eye complications can occur, such as the following:

  • Lid edema
  • Persistent dry eyes
  • Chronic photosensitivity
  • Conjunctivitis
  • Keratitis
  • Conjunctival fornix foreshortening
  • Ectropion or entropion with subsequent trichiasis
  • Symblepharon
  • Corneal ulceration and scarring
  • Blindness

Pulmonary complications may occur. Mucous retention and sloughing of tracheobronchial mucosa may occur, with aspiration of mucosal debris. Pneumonia and pneumonitis are common and sometimes fatal complications of TEN. Pulmonary embolism and acute respiratory distress syndrome (ARDS) have also been reported.

GI hemorrhage results from intestinal inflammation.

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Contributor Information and Disclosures
Author

Victor Cohen, PharmD  Clinical Pharmacy Manager, Department of Emergency Medicine, Maimonides Medical Center, Assistant Professor, Division of Pharmacy Practice, Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University

Victor Cohen, PharmD is a member of the following medical societies: American Association of Colleges of Pharmacy, American College of Clinical Pharmacy, American Society of Health-System Pharmacists, and Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Samantha P Jellinek, PharmD, BCPS  Clinical Coordinator of Pharmacy Practice Residency Program, Manager of Medication Reconciliation and Safety, Maimonides Medical Center

Samantha P Jellinek, PharmD, BCPS is a member of the following medical societies: American College of Clinical Pharmacy and American Society of Health-System Pharmacists

Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH  Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi

Disclosure: Nothing to disclose.

Chief Editor

Michael Stuart Bronze, MD  Professor, Stewart G Wolf Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Medical Association, Association of Professors of Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, and Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Additional Contributors

Theodore J Gaeta, DO, MPH, FACEP Clinical Associate Professor, Department of Emergency Medicine, Joan and Sanford Weill Medical College at Cornell University; Vice Chairman and Program Director of Emergency Medicine Residency Program, Department of Emergency Medicine, New York Methodist Hospital; Academic Chair, Adjunct Professor, Department of Emergency Medicine, St George's University School of Medicine

Theodore J Gaeta, DO, MPH, FACEP is a member of the following medical societies: Alliance for Clinical Education, American College of Emergency Physicians, Clerkship Directors in Emergency Medicine, Council of Emergency Medicine Residency Directors, New York Academy of Medicine, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Gregory P Garra, DO Clinical Assistant Professor, Department of Emergency Medicine, Stony Brook University School of Medicine; Residency Program Director, Department of Emergency Medicine, Stony Brook University Hospital

Gregory P Garra, DO is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Fred A Lopez, MD Associate Professor and Vice Chair, Department of Medicine, Assistant Dean for Student Affairs, Louisiana State University School of Medicine

Fred A Lopez, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, Infectious Diseases Society of America, and Louisiana State Medical Society

Disclosure: Nothing to disclose.

Mark L Plaster, MD, JD Executive Editor, Emergency Physicians Monthly

Mark L Plaster, MD, JD is a member of the following medical societies: American Academy of Emergency Medicine and American College of Emergency Physicians

Disclosure: M L Plaster Publishing Co LLC Ownership interest Management position

Jennifer Stellke, DO Resident Physician, Department of Emergency Medicine, Stony Brook University Medical Center

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Charles V Sanders, MD Edgar Hull Professor and Chairman, Department of Internal Medicine, Professor of Microbiology, Immunology and Parasitology, Louisiana State University School of Medicine at New Orleans; Medical Director, Medicine Hospital Center, Charity Hospital and Medical Center of Louisiana at New Orleans; Consulting Staff, Ochsner Medical Center

Charles V Sanders, MD is a member of the following medical societies: Alliance for the Prudent Use of Antibiotics, Alpha Omega Alpha, American Association for the Advancement of Science, American Association of University Professors, American Clinical and Climatological Association, American College of Physician Executives, American College of Physicians, American Federation for Medical Research, American Foundation for AIDS Research, American GeriatricsSociety, American Lung Association, American Medical Association, American Society for Microbiology, American Thoracic Society, American Venereal Disease Association, Association for Professionals in Infection Control and Epidemiology, Association of American Medical Colleges, Association of American Physicians, Association of Professors of Medicine, Infectious Disease Society for Obstetrics and Gynecology, Infectious Diseases Societyof America, Louisiana State Medical Society, Orleans Parish Medical Society, Royal Society of Medicine, Sigma Xi, Society of General Internal Medicine, Southeastern Clinical Club, Southern Medical Association, Southern Society for Clinical Investigation, and Southwestern Association of Clinical Microbiology

Disclosure: Baxter International and Johnson & Johnson Royalty Other

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Toxic epidermal necrolysis (TEN) ulcer in great toe (initial infection).
Hemorrhagic crusting of mucous membranes in toxic epidermal necrolysis (TEN).
Maculopapular rash in toxic epidermal necrolysis (TEN).
Diffuse maculopapular rash in toxic epidermal necrolysis (TEN).
Toxic epidermal necrolysis (TEN) blister on the index finger.
Epidermal sloughing in toxic epidermal necrolysis (TEN).
 
 
 
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