Generality
Pemphigus is a serious autoimmune disease that affects the skin and / or mucous membranes; it is a bullous dermatosis characterized by the detachment of the epidermal cells that make up the stratified epithelium (acantholysis). Pemphigus develops following an interaction between endogenous (genetic) and environmental factors. The course of the disease can be subacute or chronically progressive.
Symptoms
To learn more: Symptoms Pemphigus
The primary lesions of the pemphigus are represented by extremely fragile bubbles of varying dimensions (from one to several centimeters). Their content is clear and similar to serum.
Bullous lesions of pemphigus have two peculiar clinical features:
- they arise on normal skin, so they are not associated with a perilesional inflammatory phenomenon;
- rubbing the healthy skin near a bubble with a finger, a characteristic detachment of the epidermis is manifested, known as Nikolsky's sign . This reaction shows the impairment of the cohesion normally existing between the cells that form the epidermis.
Generally, the blisters appear initially at the level of the mucous membranes (50% of patients have oral lesions), or they can affect the scalp, the face, the trunk, the axillary cords or the inguinal region. Pemphigus lesions usually appear on apparently healthy skin. When the bubbles break, they cause the onset of painful erosions and de-epithelialized areas that are covered with scabs. These formations remain as chronic, often painful, lesions for a variable period and can undergo infection. Any area of the stratified squamous epithelium can be affected by pemphigus (for example, lesions can affect the oropharynx and upper portion of the esophagus), but the extent of skin lesions and mucosal involvement are extremely variable.
Some signs and symptoms differ depending on the clinical variants:
- Pemphigus vulgaris and vegetative pemphigus: affecting the spinous layer of the epidermis. These forms are characterized by the formation of lesions in the mucous membranes, with painful ulcerations, and in the skin, with flaccid bubbles (similar to those caused by burns) that break easily and leave an area of low-cut epidermis on the margins. Lesions can localize over the entire body surface, but especially in areas subjected to friction, such as armpits, inguinal and genital regions. The erosions of the oral cavity are more often present.
- In pemphigus vulgaris, the bubbles appear initially on the mucous membranes, break easily, are covered with scabs and tend to resolve without scarring. The epidermis is easily detached from the underlying layers (Nikolsky's sign) and the biopsy generally shows a typical detachment of suprabasal epidermal cells.
- In vegetative pemphigus vulgaris, on the other hand, after breaking, the bubbles are occupied by soft and exuding vegetations, bounded by an epithelial border.
- Pemphigus foliaceus and pemphigus erythematosus: In pemphigus foliaceus and erythematous lesions do not occur in the suprabasal region, but in the superficial portions of the spinous layer and in the granular layer.
- In pemphigus foliaceus, flat, flaccid, low-liquid bubbles appear, which do not tend to break, but to flow together. Generally, pemphigus foliaceus does not affect the mucous membranes: the blisters usually begin on the face and scalp, and then appear on the chest and back. Injuries are usually not painful, but can sometimes be itchy (when the blisters become covered with scabs). Furthermore, pemphigus foliaceus can simulate psoriasis, a drug eruption or some form of dermatitis.
- Seborrheic or erythematous pemphigus has bubbles that evolve into oily squamous crusts, located in typically seborrheic sites and with aspects similar to seborrheic dermatitis and subacute cutaneous lupus erythematosus.
Diagnosis
Pemphigus is not immediate to diagnose, since it is a rare disease and the presence of lesions is not sufficient to define the pathology with certainty (since the appearance of bubbles and chronic ulceration of the mucous membranes may be associated with several other conditions). The diagnosis of pemphigus is established on the basis of the histopathological findings on the lesions and by means of immunofluorescence techniques on serum or skin of the patients, which show the presence of autoantibodies directed against the desmogleins of keratinocyte membranes. These exams will also be investigated through blood tests. The differential diagnosis must be made with respect to other chronic ulcerative lesions of the oral cavity and other bullous dermatoses.
Clinical-anamnestic data
Clinical history of the patient, presence of signs on physical examination, appearance and distribution of skin lesions, etc.
- Nikolsky sign . The doctor rubs sideways an area of unaltered skin with a cotton swab or finger: in the case of pemphigus the upper layers of the skin are easily separated by detachment from the deep ones after the slight pressure.
- Asboe-Hansen sign. It consists in the possibility of extending a bullous lesion of the pemphigus, by pressing on the lateral edge, to demonstrate its enlargement.
Cytodiagnostics of Tzanck and histological examination
The cytodiagnostic examination of Tzanck is a rapid and easy to perform diagnostic technique. The material to be examined is obtained by scarifying the lesion or by scraping at its base. The collected sample is then crawled on a slide that will be colored (usually with May Grunwald Giemsa or Wright staining) to be examined by light microscopy.
The cytodiagnostic examination of Tzanck allows obtaining numerous diagnostic indications, including:
- The acantholytic cells, a typical pemphigus finding: they are keratinocytes larger than normal, similar to the basal ones, with a large central nucleus and abundant condensed basophilic cytoplasm.
- Mosaic arrangement of keratinocytes and poor inflammatory infiltrate.
- Free keratinocytes and some haematia.
This finding allows a rapid differential diagnosis between pathologies of the pemphigus group and reactions characterized by subepidermal bubbles, such as bullous pemphigoid and herpetiform dermatitis. A biopsy of the skin lesion can help confirm the diagnosis: the histological examination (hematoxylin-eosin staining) allows to characterize the dermal level of origin of the bubble and its location.
For example:
- Pemphigus foliaceus : bubbles that originate superficially, at the level of the granular layer;
- Pemphigus vulgaris : lesions that arise at the level of the deep epidermis, above the basal layer.
Direct and indirect immunofluorescence
Immunofluorescence is a laboratory method based on the use of anti-immunoglobulin immune sera, labeled with fluorescent substances that allow their detection with special UV-source microscopes.
- Search for circulating autoantibodies (indirect immunofluorescence) : a known substrate is used (example: human skin or monkey esophagus) and is placed in contact with the patient's serum . Then, anti-human Ig antibodies labeled with a fluorescent substance are added. If the patient's serum contains the autoantibodies, the presence of the latter will be revealed by the persistence of the fluorescence after the elution (ie the operations of washing of the non-immunological molecules). Indirect immunofluorescence allows also to perform useful quantitative measurements, by titration: the antibody titre may be related to the severity of the disease and may also be useful to monitor the clinical course in response to therapy.
- Tissue autoantibody research (direct immunofluorescence) : a biopsy is performed at the perilesional (or mucosal) skin level and is placed in contact with an anti-Ig serum; if autoantibodies are present, these will be revealed by the persistence of the fluorescence after the elution. The direct immunofluorescence allows to highlight a typical "net" (or hive) design, since the IgG are arranged around the keratinocytes, in the intercellular spaces.
- Blood tests. Among the diagnostic investigations that confirm pemphigus, the ELISA test was recently introduced , which allows the detection and identification of anti-desmoglein antibodies present in a patient's blood sample (levels increase in the acute phase and decrease in dependence of therapeutic control of symptoms).
