What is Pemphigus
The term pemphigus identifies a group of bullous dermatoses with an autoimmune etiology. These rare skin disorders are characterized by the appearance of lesions on the skin and mucous membranes .
Causes
Today we know that pemphigus is mainly due to the alteration of the cellular adhesion mechanisms of the epidermis; in particular, the disease is caused by the presence of specific autoantibodies (IgA or IgG) that attack a component of the desmosomes, damaging these structures (connecting points) that tightly bind adjacent epidermal cells. The abnormal autoantibodies react with some glycoproteins present on keratinocyte desmosomes: desmogleines ( Dsg) ; when autoantibodies attack these components, the release of plasminogen (precursor of the plasmin protease) is induced, with consequent destruction of the intercellular bridges and lysis of the cells of the epidermal layer concerned: the phenomenon is called acantholysis . Afterwards, the transudation liquid is called by osmotic diffusion, to form a characteristic swelling below the outer layer of the epidermis ( bubble ).
In summary. Pathogenesis of bubble formation
Auto Ab link to Dsg → Activation of intracytoplasmic signals → Plasminogen activator production → Plasminogen → Plasmin → Acantholysis: rupture of the adhesion of epidermal cells → formation of bubbles characteristic of pemphigus
The presentation of the disease is variable, as it can be in localized or widespread form.
The two most common forms are distinguished by the location in which the "detachment" occurs between the cells:
- Pemphigus vulgaris : it is a form of deep pemphigus, in which the cells of the epidermis detach themselves in the thorny layer;
- Pemphigus foliaceus : the detachment of the cells takes place at the level of the granular layer, located at the most superficial level.
Pemphigus is characterized by a subacute or chronically progressive course . Generally, the disease is associated with a serious condition and can potentially lead to death: management is better if the diagnosis is made early, as is the treatment, which may include drugs or therapies similar to those used for severe burns.
Inducing factors
In most cases, the specific trigger factor, which causes the origin of the disease, is not known. The agents capable of inducing pemphigus are, in fact, numerous and heterogeneous .
In summary, the onset and course of pemphigus depend on the interaction between:
- predisposing factors (genetic) : the genetic predisposition is correlated to the presence of some particular antigens of the major histocompatibility system. In some ethnic groups, in fact, there is a strong association between this pathology and a particular allele of HLA-DR4, which binds to a peptide antigen originating from desmosomes. However, genetic predisposition alone is not sufficient to trigger the autoimmune reaction that determines the disease.
- heterogeneous inducing factors, present in the environment : external agents can intervene occasionally and in a non-specific way, triggering an immune mechanism already programmed and ready to start.
Sometimes, pemphigus develops as a side effect of some drugs, see for example ACE inhibitors, useful for the control of blood pressure, or chelating substances such as penicillin. In these cases, one speaks of drug-induced pemphigus . From a clinical point of view, drug-induced pemphigus resembles the autoimmune form (in most cases it takes the form of a superficial pemphigus); this variant of the disease therefore represents a condition in which environmental factors play a leading role: the disease resolves spontaneously, even without treatment, following the elimination of the inducing factor (after drug withdrawal).
In association with genetic predisposition, some factors inducing pemphigus may be: | |
drugs |
|
Physical agents | Burns, UV and ionizing radiation |
Virus | Herpes virus, paramyxovirus |
Malignant neoplasms | Carcinomas, lymphomas |
Pregnancy and hormones | Progesterone |
Contact allergens | Pesticides |
Dietary factors | Allyl compounds, tannins |
Pemphigus and diseases of the pemphigoid group
The term pemphigoid indicates some forms of autoimmune dermatosis, with features apparently similar to pemphigus (as expressed by the name).
Compared to pemphigus, pemphigoid disorders are :
- Less common;
- They do not have acantholysis : the acantholytic cells are absent, while an eosinophilic infiltrate is present (instead absent in pemphigus, which does not have an inflammatory infiltrate);
- Autoantibodies are directed towards normal antigens (Ag) in the skin and mucous membranes, located at the level of the epidermal basement membrane (while in pemphigus, Ag are found on the surface of keratinocytes).
The three best known types are:
- Bullous pemphigoid;
- Cicatricial pemphigoid;
- Pemphigoid gravidarum;
Classification
The forms of pemphigus
There are different types of pemphigus that vary depending on the type of desmoglein affected by autoantibodies, the severity and position of the bubbles in the different layers of the epidermis.
The main forms of pemphigus are:
- pemphigus vulgaris and related variants:
- vegetative pemphigus ;
- Hallopeau vegetating pemphigus;
- Neumann vegetative pemphigus.
- pemphigus foliaceus and its variants:
- pemphigus erythematosus (localized variant).
The forms of the most recent clinical classification are:
- Paraneoplastic pemphigus;
- Pemphigus at IgA deposition;
- Pemphigus herpetiformis;
- Superficial pemphigus.
Short note.
Hailey-Hailey disease, also called benign familial chronic pemphigus, is a rare hereditary dermatologic disease (genetic) and is not an autoimmune disease. For this reason, it is not generally considered part of the group of pemphigus diseases.
