Toxic epidermal necrolysis
Encyclopedia
Toxic epidermal necrolysis (also known as "Lyell's syndrome") is a rare, life-threatening dermatological
condition that is usually induced by a reaction to medications. It is characterized by the detachment of the top layer of skin (the epidermis) from the lower layers of the skin (the dermis
) all over the body.
There is broad agreement in medical literature that TEN can be considered a more severe form of Stevens–Johnson syndrome, and debate whether it falls on a spectrum of disease that includes erythema multiforme
. Some authors consider that there is an overlap between the two syndromes (usually between 10% and 30% of skin detachment).
The incidence
is between 0.4 and 1.3 cases per million each year.
s, such as the mouth
, eyes, and vagina
. The severe findings of TEN are often preceded by 1 to 2 weeks of fever
. These symptoms may mimic those of a common upper respiratory tract infection
. When the rash
appears it may be over large and varied parts of the body, and it is usually warm and appears red. The dermal layer fills with fluid being deposited there by the body's immune system, usually as a result of a negative reaction to an antibiotic. The skin then begins to sag from the body and can be peeled off in great swaths. The mouth becomes blistered and eroded, making eating difficult and sometimes necessitating feeding through a nasogastric tube through the nose or a gastric tube directly into the stomach. The eyes are affected, becoming swollen, crusted, and ulcerated and blindness may occur.
, are characterized by confluent epidermal necrosis
with minimal associated inflammation. The acuity is apparent from the (normal) basket weave-like pattern of the stratum corneum
.
, antimetabolites (methotrexate
), antiretroviral drugs, corticosteroids, chlormezanone
(anxiolytic
) and anticonvulsant
s such as phenobarbital
, phenytoin
, carbamazepine
, and valproic acid
.
The condition might also result from infection with agents such as Mycoplasma pneumoniae
or the herpes virus
; and transplant
s of bone marrow
or organs.
(cell death).
. Typical histological criteria of TEN include mild infiltrate of lymphocytes which may obscure the dermoepidermal junction
and prominent cell death with basal vacuolar change and individual cell necrosis.
Nikolsky's sign
is almost always present in toxic epidermal necrolysis
s, supportive management, and nutritional support.
The second line is Intravenous immunoglobulin
(IVIG). Uncontrolled trials showed promising effect of IVIG on treatment of TEN; a randomized control trial is needed in the future to determine the efficacy of IVIG in TEN.
The third line is cyclosporin, cyclophosphamide
, plasmapheresis
, pentoxifylline, N-acetylcysteine, ulinastatin
, infliximab
, and/or Granulocyte colony-stimulating factors (if TEN associated-leukopenia
exists).
, and can result in sepsis
, the leading cause of death in the disease. Death is caused either by infection
or by respiratory distress
which is either due to pneumonia
or damage to the linings of the airway. Microscopic analysis of tissue (especially the degree of dermal mononuclear inflammation and the degree of inflammation in general) can play a role in determining the prognosis of individual cases.
A Swiss medical study recorded the day to day evolution of the epidermis in a TEN patient. Pictures show the initial bullous stage as well as the skin healing.
Dermatology
Dermatology is the branch of medicine dealing with the skin and its diseases, a unique specialty with both medical and surgical aspects. A dermatologist takes care of diseases, in the widest sense, and some cosmetic problems of the skin, scalp, hair, and nails....
condition that is usually induced by a reaction to medications. It is characterized by the detachment of the top layer of skin (the epidermis) from the lower layers of the skin (the dermis
Dermis
The dermis is a layer of skin between the epidermis and subcutaneous tissues, and is composed of two layers, the papillary and reticular dermis...
) all over the body.
There is broad agreement in medical literature that TEN can be considered a more severe form of Stevens–Johnson syndrome, and debate whether it falls on a spectrum of disease that includes erythema multiforme
Erythema multiforme
Erythema multiforme is a skin condition of unknown cause, possibly mediated by deposition of immune complex in the superficial microvasculature of the skin and oral mucous membrane that usually follows an infection or drug exposure...
. Some authors consider that there is an overlap between the two syndromes (usually between 10% and 30% of skin detachment).
The incidence
Incidence (epidemiology)
Incidence is a measure of the risk of developing some new condition within a specified period of time. Although sometimes loosely expressed simply as the number of new cases during some time period, it is better expressed as a proportion or a rate with a denominator.Incidence proportion is the...
is between 0.4 and 1.3 cases per million each year.
Signs and symptoms
TEN affects many parts of the body, but it most severely affects the mucous membraneMucous membrane
The mucous membranes are linings of mostly endodermal origin, covered in epithelium, which are involved in absorption and secretion. They line cavities that are exposed to the external environment and internal organs...
s, such as the mouth
Mouth
The mouth is the first portion of the alimentary canal that receives food andsaliva. The oral mucosa is the mucous membrane epithelium lining the inside of the mouth....
, eyes, and vagina
Vagina
The vagina is a fibromuscular tubular tract leading from the uterus to the exterior of the body in female placental mammals and marsupials, or to the cloaca in female birds, monotremes, and some reptiles. Female insects and other invertebrates also have a vagina, which is the terminal part of the...
. The severe findings of TEN are often preceded by 1 to 2 weeks of fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
. These symptoms may mimic those of a common upper respiratory tract infection
Upper respiratory tract infection
Upper respiratory tract infections are the illnesses caused by an acute infection which involves the upper respiratory tract: nose, sinuses, pharynx or larynx...
. When the rash
Rash
A rash is a change of the skin which affects its color, appearance or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracked or blistered, swell and may be painful. The causes, and...
appears it may be over large and varied parts of the body, and it is usually warm and appears red. The dermal layer fills with fluid being deposited there by the body's immune system, usually as a result of a negative reaction to an antibiotic. The skin then begins to sag from the body and can be peeled off in great swaths. The mouth becomes blistered and eroded, making eating difficult and sometimes necessitating feeding through a nasogastric tube through the nose or a gastric tube directly into the stomach. The eyes are affected, becoming swollen, crusted, and ulcerated and blindness may occur.
Pathology
TEN, like Steven-Johnson syndrome and erythema multiformeErythema multiforme
Erythema multiforme is a skin condition of unknown cause, possibly mediated by deposition of immune complex in the superficial microvasculature of the skin and oral mucous membrane that usually follows an infection or drug exposure...
, are characterized by confluent epidermal necrosis
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
with minimal associated inflammation. The acuity is apparent from the (normal) basket weave-like pattern of the stratum corneum
Stratum corneum
The stratum corneum is the outermost layer of the epidermis, consisting of dead cells that lack nuclei and organelles. The purpose of the stratum corneum is to form a barrier to protect underlying tissue from infection, dehydration, chemicals and mechanical stress...
.
Cause
Toxic epidermal necrolysis is a rare and usually severe adverse reaction to certain drugs. History of medication use exists in over 95% of patients with TEN. The drugs most often implicated in TEN are antibiotics such as sulfonamides, nonsteroidal anti-inflammatory drugs, allopurinolAllopurinol
Allopurinol is a drug used primarily to treat hyperuricemia and its complications, including chronic gout.- Mechanism of action :...
, antimetabolites (methotrexate
Methotrexate
Methotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate...
), antiretroviral drugs, corticosteroids, chlormezanone
Chlormezanone
Chlormezanone is a drug used as an anxiolytic and a muscle relaxant.Its use was discontinued in many countries in 1996, due to rare but serious cases of toxic epidermal necrolysis.- Chemistry :...
(anxiolytic
Anxiolytic
An anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...
) and anticonvulsant
Anticonvulsant
The anticonvulsants are a diverse group of pharmaceuticals used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder, since many seem to act as mood stabilizers, and in the treatment of neuropathic pain. The goal of an...
s such as phenobarbital
Phenobarbital
Phenobarbital or phenobarbitone is a barbiturate, first marketed as Luminal by Friedr. Bayer et comp. It is the most widely used anticonvulsant worldwide, and the oldest still commonly used. It also has sedative and hypnotic properties but, as with other barbiturates, has been superseded by the...
, phenytoin
Phenytoin
Phenytoin sodium is a commonly used antiepileptic. Phenytoin acts to suppress the abnormal brain activity seen in seizure by reducing electrical conductance among brain cells by stabilizing the inactive state of voltage-gated sodium channels...
, carbamazepine
Carbamazepine
Carbamazepine is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder, as well as trigeminal neuralgia...
, and valproic acid
Valproic acid
Valproic acid is a chemical compound that has found clinical use as an anticonvulsant and mood-stabilizing drug, primarily in the treatment of epilepsy, bipolar disorder, and, less commonly, major depression. It is also used to treat migraine headaches and schizophrenia...
.
The condition might also result from infection with agents such as Mycoplasma pneumoniae
Mycoplasma pneumoniae
Mycoplasma pneumoniae is a very small bacterium in the class Mollicutes.It causes the disease mycoplasma pneumonia, a form of atypical bacterial pneumonia, and is related to cold agglutinin disease.-Cell wall/Treatment:...
or the herpes virus
Herpes virus
In colloquial use, herpes virus refers to the herpes simplex virus, particularly when transmitted sexually.In scientific use, herpesvirus refers to a virus of the taxonomic family herpesviridae....
; and transplant
Organ transplant
Organ transplantation is the moving of an organ from one body to another or from a donor site on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative medicine is allowing scientists and engineers to create organs to be...
s of bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
or organs.
Pathogenesis
Microscopically, TEN causes cell death throughout the epidermis. Keratinocytes, which are the cells found lower in the epidermis, specializing in holding the skin cells together, undergo necrosisNecrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
(cell death).
Diagnosis
Often, the diagnosis can be made clinically. Generally, if the clinical history is consistent with Stevens–Johnson syndrome, and the skin lesion covers greater than 30% of the body surface area, the diagnosis of TEN is appropriate. Sometimes, however, examination of affected tissue under the microscope may be needed to distinguish it between other entities such as staphylococcal scalded skin syndromeStaphylococcal scalded skin syndrome
Staphylococcal scalded skin syndrome, SSSS, also known as Pemphigus neonatorum or Ritter's disease, or Localized bullous impetigo is a dermatological condition caused by Staphylococcus aureus.-Pathophysiology:...
. Typical histological criteria of TEN include mild infiltrate of lymphocytes which may obscure the dermoepidermal junction
Dermoepidermal junction
The dermoepidermal junction is the area of tissue that joins the epidermal and the dermal layers of the skin. The basal cells in the stratum basale of the epidermis connect to the basement membrane by hemidesmosomes; the cells of the papillary layer of the dermis are attached to the basement...
and prominent cell death with basal vacuolar change and individual cell necrosis.
Nikolsky's sign
Nikolsky's sign
Nikolsky's sign is a clinical dermatological sign, named after the Russian physician Pyotr Nikolsky . The sign is positive when slight rubbing of the skin results in exfoliation of the outermost layer....
is almost always present in toxic epidermal necrolysis
Treatment
The first line of treatment is early withdrawal of culprit drugs, early referral and management in burn units or intensive care unitIntensive Care Unit
thumb|220px|ICU roomAn intensive-care unit , critical-care unit , intensive-therapy unit/intensive-treatment unit is a specialized department in a hospital that provides intensive-care medicine...
s, supportive management, and nutritional support.
The second line is Intravenous immunoglobulin
Intravenous immunoglobulin
Intravenous immunoglobulin is a blood product administered intravenously. It contains the pooled IgG extracted from the plasma of over one thousand blood donors. IVIG's effects last between 2 weeks and 3 months...
(IVIG). Uncontrolled trials showed promising effect of IVIG on treatment of TEN; a randomized control trial is needed in the future to determine the efficacy of IVIG in TEN.
The third line is cyclosporin, cyclophosphamide
Cyclophosphamide
Cyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....
, plasmapheresis
Plasmapheresis
Plasmapheresis is the removal, treatment, and return of blood plasma from blood circulation. It is thus an extracorporeal therapy...
, pentoxifylline, N-acetylcysteine, ulinastatin
Ulinastatin
Ulinastatin is a glycoprotein which acts as a trypsin inhibitor. It can be derived from urine or it can be synthetically produced. It may be effective in treatment of acute pancreatitis, chronic pancreatitis, toxic shock, Stevens–Johnson syndrome and toxic epidermal necrolysis . Currently, the...
, infliximab
Infliximab
Infliximab is a monoclonal antibody against tumour necrosis factor alpha . It is used to treat autoimmune diseases. Remicade is marketed by Janssen Biotech, Inc...
, and/or Granulocyte colony-stimulating factors (if TEN associated-leukopenia
Leukopenia
Leukopenia is a decrease in the number of white blood cells found in the blood, which places individuals at increased risk of infection....
exists).
Prognosis
The mortality for toxic epidermal necrolysis is 30-40 percent. Loss of the skin leaves patients vulnerable to infections from fungi and bacteriaBacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
, and can result in sepsis
Sepsis
Sepsis is a potentially deadly medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection. The body may develop this inflammatory response by the immune system to microbes in the blood, urine, lungs, skin, or other tissues...
, the leading cause of death in the disease. Death is caused either by infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
or by respiratory distress
Respiratory distress
Respiratory distress may refer to either/both:* Labored breathing, the physical presentation of respiratory distress*Shortness of breath or dyspnea - a sensation of respiratory distress-See also:*List of terms of lung size and activity...
which is either due to pneumonia
Pneumonia
Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...
or damage to the linings of the airway. Microscopic analysis of tissue (especially the degree of dermal mononuclear inflammation and the degree of inflammation in general) can play a role in determining the prognosis of individual cases.
A Swiss medical study recorded the day to day evolution of the epidermis in a TEN patient. Pictures show the initial bullous stage as well as the skin healing.
See also
- Erythema multiforme majorErythema multiforme majorErythema multiforme major is a term that may be used to refer to two conditions that constitute a spectrum of the same disease process:* Stevens–Johnson syndrome...
- Stevens–Johnson syndrome
- Alan LyellAlan LyellAlan Lyell was a Scottish dermatologist who described Lyell's syndrome.-References:...
- List of cutaneous conditions