Toxic epidermal necrolysis is a severe polyethological disease of an allergic nature, characterized by an acute violation of the general condition of the patient, bullous lesion of the entire skin and mucous membranes. The rapid development of dehydration, toxic damage to the kidneys and other internal organs, and the addition of an infectious process often lead to a fatal outcome of the disease. Diagnosis includes an objective examination of the patient, constant monitoring of coagulogram data, clinical and biochemical blood and urine tests. Treatment includes emergency measures, methods of extracorporeal blood purification, infusion therapy, administration of large doses of prednisone, antibiotic therapy, correction of water-salt disorders, etc.
ICD 10
L51.2 Toxic epidermal necrolysis [Lyell’s syndrome]
General information
Toxic epidermal necrolysis (Lyell’s syndrome) belongs to the group of bullous dermatitis. It got its main name in honor of the doctor Lyell, who in 1956 first described the syndrome as a severe form of toxicoderma. The clinical picture is similar to a grade II skin burn, which is why the disease is called burn skin syndrome. Another common name for the syndrome — malignant pemphigus — is due to the formation of blisters on the skin, similar to the elements of pemphigus.
Toxic epidermal necrolysis occurs in 0.3% of cases of drug allergies. After anaphylactic shock, it is the most severe allergic reaction. Disease is most often observed in young people and children. Symptoms of the disease may appear in a couple of hours or within a week after the administration of the medication. According to various data, mortality in toxic epidermal necrolysis ranges from 30% to 70%.
Causes
Depending on the cause of the development of toxic epidermal necrolysis, modern dermatology identifies 4 variants of the disease.
- The first is an allergic reaction to an infectious process and is most often caused by group II Staphylococcus aureus. As a rule, it develops in children and is characterized by the most severe course.
- The second is toxic epidermal necrolysis, which is observed in connection with the use of medications (sulfonamides, antibiotics, anticonvulsants, acetylsalicylic acid, painkillers, anti-inflammatory and anti-tuberculosis drugs). Most often, the development of the syndrome is caused by the simultaneous administration of several drugs, one of which was sulfonamide. In recent years, cases of the development of toxic epidermal necrolysis on the use of biologically active additives, vitamins, contrast agents for radiography, etc. have been described.
- The third variant of toxic epidermal necrolysis consists of ideopathic cases of the disease, the cause of which remains unclear. The fourth is toxic epidermal necrolysis, caused by combined causes: infectious and medicinal, develops against the background of therapy of an infectious disease.
Pathogenesis
A large role in the development of toxic epidermal necrolysis is assigned to the genetically determined predisposition of the body to various allergic reactions. In the anamnesis of many patients there are indications of allergic diseases: allergic rhinitis, pollinosis, allergic contact dermatitis, eczema, bronchial asthma, etc. In such persons, due to a violation of the mechanisms of neutralization of toxic metabolic products, the drug introduced into the body is combined with a protein contained in the cells of the epidermis. This newly formed substance is an antigen in toxic epidermal necrolysis. Thus, the immune response of the body is directed not only to the injected medicine, but also to the patient’s skin. The process resembles a graft rejection reaction, in which the immune system takes the patient’s own skin for a graft.
The basis of toxic epidermal necrolysis is the Schwartzman-Sanarelli phenomenon — an immunological reaction that leads to a violation of the regulation of the breakdown of protein substances and the accumulation of products of this decay in the body. As a result, toxic damage to organs and systems occurs. This disrupts the work of detoxifying and detoxifying organs, which aggravates intoxication, leads to pronounced changes in the water-salt and electrolyte balance in the body. These processes lead to a rapid deterioration of the patient’s condition in toxic epidermal necrolysis and can cause a fatal outcome.
Symptoms
Disease begins with a sudden and causeless increase in body temperature to 39-40 ° C. In a few hours, slightly edematous and painful erythematous spots of various sizes appear on the skin of the trunk, limbs, face, oral mucosa and genitals. They may partially merge.
After some time (an average of 12 hours), the epidermis begins to peel off in areas of externally healthy skin. In this case, thin-walled sluggish bubbles of irregular shape are formed, the size of which varies from the size of a hazelnut to 10-15 cm in diameter. After the bubbles are opened, large erosions remain, along the periphery they are covered with fragments of bubble tires. Erosions are surrounded by edematous and hyperemic skin. They secrete abundant serous-bloody exudate, which is the cause of rapid dehydration of the patient’s body.
In toxic epidermal necrolysis, Nikolsky’s symptom characteristic of pemphigus is noted — peeling of the epidermis in response to a slight surface effect on the skin. Due to the detachment of the epidermis, in those areas of the skin that have undergone compression, friction or maceration, erosion forms immediately, without the formation of bubbles.
Pretty quickly, the entire skin of a patient with toxic epidermal necrolysis becomes red and sharply painful when touched, its appearance resembles a burn with boiling water of II-III degree. There is a characteristic symptom of “wet laundry” when the skin is easily shifted and wrinkled when touched. In some cases of toxic epidermal necrolysis, its main manifestations are accompanied by the appearance of a small petechial rash throughout the patient’s body. In children, the disease usually begins with symptoms of conjunctivitis and is combined with an infectious skin lesion with staphylococcal flora.
The defeat of the mucous membranes in toxic epidermal necrolysis is manifested by the formation of painful surface defects on them, bleeding even with minor injury. The process can affect not only the mouth and lips, but also the mucous membrane of the eyes, pharynx, larynx, trachea, bronchi, bladder and urethra, stomach and intestines.
Complications
The general condition of patients with toxic epidermal necrolysis progressively worsens and becomes extremely severe in a short period of time. Excruciating thirst, decreased sweating and saliva production are signs of dehydration of the body. Patients complain of severe headache, lose orientation, become drowsy. There is a hair loss and nails. Dehydration leads to blood thickening and disruption of blood supply to internal organs. Along with toxic damage to the body, this leads to disruption of the liver, heart, lungs and kidneys. Anuria and acute renal failure develop. It is possible to attach a secondary infection.
Diagnostics
A clinical blood test for toxic epidermal necrolysis indicates an inflammatory process. There is an increase in ESR, leukocytosis with the appearance of immature forms. A decrease or complete absence of eosinophils in the blood test is a diagnostic sign that allows you to distinguish toxic epidermal necrolysis from other allergic conditions. Coagulogram data indicate increased blood clotting. Urine analysis and biochemical blood analysis allow to identify disorders occurring on the part of the kidneys and monitor the state of the body during treatment.
An important task is to determine the medication that led to the development of toxic epidermal necrolysis, because its repeated use during treatment can be disastrous for the patient. Immunological tests help to identify the provoking substance. The provoking drug is indicated by the rapid multiplication of immune cells that occurs in response to its introduction into the patient’s blood sample.
A skin biopsy and histological examination of the obtained sample in a patient with toxic epidermal necrolysis reveals complete cell death of the surface layer of the epidermis. In the deeper layers, there is the formation of large blisters, swelling and accumulation of immune cells with the highest concentration in the area of skin vessels.
Toxic epidermal necrolysis is differentiated from other acute dermatitis accompanied by the formation of blisters: actinic dermatitis, pemphigus, contact dermatitis, Stevens-Johnson syndrome, epidermolysis bullosa, During’s herpetiform dermatitis, herpes simplex.
Treatment
Treatment of patients is carried out in the intensive care unit and includes a whole range of urgent measures. At the same time, taking into account the toxic-allergic nature of the disease, the use of medicines should be carried out with strict consideration of indications and contraindications.
Toxic epidermal necrolysis is treated by injecting large doses of corticosteroids (prednisone). With improvement, the patient is transferred to taking the drug in tablet form with a gradual decrease in its dose. The use of extracorporeal hemocorrection methods (plasmapheresis, hemosorption) makes it possible to purify the blood from toxic substances formed in toxic epidermal necrolysis. Constant infusion therapy (physical solution, dextran, saline solutions) is aimed at combating dehydration and normalizing the water-salt balance. It is carried out under strict control of the volume of urine secreted by the patient.
In the complex therapy of toxic epidermal necrolysis, medications are used to support the functioning of the kidneys and liver; inhibitors of enzymes involved in the destruction of tissues; minerals (potassium, calcium and magnesium); drugs that reduce clotting; diuretics; broad-spectrum antibiotics.
Local treatment includes the use of aerosols with corticosteroids, wet-drying dressings, antibacterial lotions. It is carried out in accordance with the principles of treatment of burns. To prevent infection with toxic epidermal necrolysis, it is necessary to change underwear to sterile several times a day, to treat not only the skin, but also the mucous membranes. Given the pronounced soreness, local therapy should be carried out with appropriate anesthesia. If necessary, bandages are performed under anesthesia.
Forecast
The prognosis of the disease is determined by the nature of its course. In this regard, there are 3 variants of the course of toxic epidermal necrolysis: lightning-fast with a fatal outcome, acute with a possible fatal outcome when an infectious process is attached, and favorable, usually resolved after 7-10 days. Earlier initiation of therapeutic measures and their careful implementation improve the prognosis of the disease.