Generality
Lyell syndrome is a serious inflammatory pathology, fortunately rare. This condition is characterized by an extensive necrolysis, ie a destruction of the superficial layer of the skin and mucous membranes that leads to their detachment .
The underlying reaction of Lyell syndrome is evident with the formation of rashes with red plaques and blisters, mucosal erosions and epidermal detachments on different parts of the body, as if the skin had been exposed to a burning substance .
In most cases, Lyell syndrome is drug induced and appears to be associated with the use of particular types of medicines. Less often, the clinical picture can be triggered by an infection, an allergy or a bone marrow transplant.
From a clinical point of view, Lyell syndrome constitutes an emergency situation due to the risks related to the destruction of the skin and the general consequences (dehydration, infectious complications, electrolyte imbalance etc.). If it is not managed with intensive care, Lyell syndrome is potentially fatal.
What's this
Lyell syndrome: what is it?
Lyell syndrome is an inflammatory dermatological disorder that mainly affects the mucous membranes and the skin . This condition is characterized by the destruction and detachment of the skin epithelium and mucous membranes ( dermo-epidermal necrolysis ), secondary to an abnormal activation of the immune system. This reaction is extensive, as Lyell syndrome involves at least 30% of the body surface area .
Lyell syndrome: synonyms and terminology
Lyell syndrome is also known as toxic epidermal necrolysis ( TEN, which stands for " Toxic Epidermal Necrolysis "). Less often, the condition is referred to as erythema multiforme plaques.
Lyell syndrome is considered the most severe variant of polymorphic erythema.
To learn more: Polymorphic Erythema - Characteristic Signs, Types and Causes »Causes
Lyell syndrome is a muco-cutaneous inflammation induced by a cell-mediated immune reaction, which results in extensive tissue damage . In practice, widespread necrolysis occurs which leads to the destruction and detachment of the skin epithelium and mucous membranes.
The consequences of Lyell syndrome can be extremely serious: the people affected are equated with burns.
What can trigger Lyell Syndrome?
In about 70% of cases, Lyell syndrome is drug-induced; less often, toxic epidermal necrolysis is related to infections, bone marrow transplantation or other causes. Sometimes, however, Lyell's syndrome is idiopathic, so the reason it manifests itself is not identifiable.
DRUGS
In most cases, Lyell syndrome is related to the use of some medicines.
A higher risk of developing toxic epidermal necrolysis is associated in particular with the following drugs:
- allopurinol;
- Anti-infectives and antibiotics:
- Sulfonamides (eg cotrimoxazole and sulfasalazine);
- Nevirapine;
- Antiepileptic drugs:
- Carbamazepine;
- Phenobarbital;
- Phenytoin;
- Lamotrigine;
- Non-steroidal anti-inflammatory drugs (NSAIDs of the oxicam-derived family);
The medicines that can potentially cause Lyell syndrome also include:
- Amoxicillin, ampicillin and other penicillins;
- Cephalosporins;
- Valproic acid;
- Barbiturates;
- Quinolone.
Less often, toxic epidermal necrolysis has been found after the administration of diphtheria, tetanus, smallpox, hepatitis B, poliomyelitis and tuberculosis vaccines .
OTHER CAUSES
Lyell's syndrome can also be caused by:
- Infections (herpes simplex virus and Mycoplasma pneumoniae );
- Allergies;
- Bone marrow transplant;
- Systemic lupus erythematosus.
Lyell syndrome: pathogenetic mechanism
The mechanism underlying the onset of toxic epidermal necrolysis is not yet fully known, but several factors appear to be involved.
Drug-induced Lyell syndrome appears to be triggered by an abnormal immune response to a given medicine ( hypersensitivity reaction or allergy ) or to certain metabolites derived from it.
These reactive products determine the production of an inflammatory mediator, tumor necrosis factor alfa (TNF-α), capable of causing tissue damage and lesions either directly (through the induction of apoptosis in keratinocytes, ie their death from which the detachment of the skin), and indirect (recruiting other components of the immune system, such as cytokines, chemokines, cytotoxic T cells and NK).
Recently, it has been observed that the selective destruction of keratinocytes (apoptosis) during Lyell syndrome is caused by an altered interaction between FAS membrane receptors - responsible for the programmed suicide of these cells - and their respective ligand ( FAS L or CD95L), which is expressed in excess. In simpler terms, Lyell syndrome would be the consequence of an exaggerated activation of the messages of programmed death of epidermal cells, which react to the command with a " mass suicide ".
The tendency to develop this reaction probably recognizes a genetic predisposition. It should be emphasized that, in each individual subject, Lyell syndrome is specific for a given drug, so the abnormal immune response is induced only when a specific medicine or its analogue is taken.
Lyell syndrome: how widespread is it?
Fortunately, Lyell syndrome is very rare: the incidence is around 1 / 1, 000, 000 cases per year.
Symptoms and Complications
Lyell's syndrome is characterized by:
- Mucous erosions ;
- Large areas of dermo-epidermal detachment ;
To be clear, the patient with toxic epidermal necrolysis presents a condition very similar to that of a large burn . For this reason, Lyell syndrome requires prompt diagnosis and adequate intensive treatment in an emergency regime.
Prodromal manifestations of Lyell Syndrome
The lesions that characterize Lyell's syndrome, that is the marked desquamation of skin tissue, followed by mucosal involvement, are anticipated by systemic and non-specific symptoms . These prodromal manifestations consist mainly of fever and generalized malaise .
Earlier, an erythema and a painful hand and foot edema may also appear.
Onset times of Lyell Syndrome
- When Lyell syndrome is drug induced, between 4 and 28 days can elapse between taking the responsible medicine and the first clinical signs.
- Lesions of Lyell syndrome include skin rashes and epidermal detachments, all of which are acute. Mucosal involvement, as a rule, is simultaneous with cutaneous involvement.
Lesions of Lyell syndrome affecting skin and mucous membranes
After the onset of prodromal symptoms, Lyell syndrome involves a rash, composed of reddish patches, macules and papules. This generally starts from the face, neck and trunk, and then spreads to the rest of the body.
The rash is followed by the formation of blisters or blisters, and, within 1-3 days, the peeling of the skin and epidermal detachments begin. At this stage, many patients may also experience a marked burning sensation and itchy skin .
These signs are accompanied by erosive lesions of the mucous membranes, involving the mouth, throat, nose, ocular conjunctiva and genitals.
Lyell syndrome: which sites are affected?
In Lyell syndrome, the eruption of skin and mucous membranes affects more than 30% of the body surface.
The lesions mainly affect the face, limbs (back and palms, extensor surfaces of the extremities and soles of the feet) and trunk, but the involvement of genitals, eyes and internal epithelia is possible, such as those in the airways or urinary tract.
Lyell syndrome also affects the mucous membranes of the oral cavity, causing erosive lesions, vesicles, pain and burning on the lips, palate and gum.
Complications of Lyell Syndrome
The dermo-epidermal detachment that characterizes Lyell syndrome can give rise to various emergency situations, such as:
- Haemodynamic repercussions for electrolyte loss, respiratory problems and dehydration;
- Very intense pain;
- Septic risk;
- Multi-organ failure.
The dermis discovered predisposes to infectious complications, including sepsis.
Even after healing it is possible to run into sequelae of Lyell's syndrome, especially in the eyes and genitals, such as:
- trichiasis;
- Punctata keratitis (inflammation of the cornea);
- Simblefaron (adherence between palpebral and bulbar conjunctiva);
- phimosis;
- Vaginal synechiae.
Diagnosis
How is Lyell Syndrome Diagnosed?
The diagnosis of Lyell syndrome is clinical and is based on the patient's objective examination, that is on the observation of lesions at the level of skin and mucous membranes, possibly assisted by histological examination after performing a skin biopsy.
If necessary, to identify the exact cause of Lyell syndrome, your doctor may use some support tests, such as:
- Complete blood count;
- Measurement of urea in the blood;
- Dosage of electrolytes;
- VES;
- Liver function test;
- Microbiological cultures from blood, saliva and samples taken from lesions;
- Serological tests for HSV, Mycoplasma pneumoniae or other microorganisms suspected to be involved in the pathology.
Unfortunately, when Lyell's syndrome is still in its initial phase and manifests itself with non-specific prodromal symptoms, early diagnosis is not always possible, from which it may result in a delay in identifying the causes and treatment.
Lyell syndrome: what should be distinguished?
Stevens-Johnson syndrome is considered a limited variant of Lyell syndrome: the symptomatic pictures of these conditions are very similar to each other, with the difference that the latter is more extensive and severe. In fact, Stevens-Johnson syndrome affects less than 10% of the entire body surface, while Lyell's syndrome may involve more than 30% of the same .
Read more: Stevens-Johnson Syndrome - Definition, Symptoms and Causes »Treatment
Patients with Lyell syndrome should be admitted to the intensive care unit or wards for large burns as soon as the diagnosis is suspected.
First aid and support measures
Lyell syndrome requires hospitalization, in intensive care, in order to avoid the onset of potentially fatal complications (such as sepsis or multi-organ failure).
The patient is equated with a large burn and, as such, is treated, ie with asepsis of the skin, correction of electrolyte imbalances, rehydration and feeding of the patient intravenously.
The first operations that must be addressed to the patient suffering from Lyell syndrome include:
- Administration of intravenous fluids (note: the vascular approach is performed in the healthy area);
- Maintenance of the patient in a warm environment, with a constant temperature (between 26 and 28 ° C) to prevent thermal losses;
- Control of vital signs (heart rate, urine output, etc.);
- Evaluation of the extent of epidermal detachment;
- Immediate suspension of all drugs (when possible);
- Short time transfer of the patient to the burn unit or intensive care unit.
Skin lesions typical of Lyell syndrome should be treated daily in the same way as partial thickness burns. Toxic epidermal necrolysis can be extremely painful, therefore a suitable analgesic treatment can be given in the absence of contraindications.
To counteract the worsening of the clinical picture, intravenous immunoglobulins, cyclosporine, cyclophosphamide, pentoxifylline and thalidomide can be used. The use of corticosteroids is very controversial and, in the later stages of Lyell syndrome, can even be harmful.
Prognosis
- The prognosis of Lyell syndrome is not favorable and, in general, is closely related to the extent of dermo-epidermal detachment. The condition is associated with a mortality rate of around 25-40%.
- If treatment is early, Lyell syndrome may correlate with a favorable evolution. In the latter case, skin regrowth is observed after a few weeks.
