Understanding Dermatology Profile (IgG)

The dermatology profile IgG is based on the six most relevant structural proteins (BP180, BP230, desmoglein 1, desmoglein 3, envoplakin and collagen type VII) of the skin that are targeted in autoimmune bullous dermatoses. 

Bullous autoimmune dermatoses are a type of organ-specific autoimmune disease. In these conditions, the body's immune system mistakenly targets its own skin, forming autoantibodies against crucial structural proteins. 

These structural proteins establish the cell -to -cell contact in keratinocytes within the epidermis and the adhesion of the epidermis to the dermis. Bullous autoimmune dermatoses represent a diverse group of diseases, both clinically and immunopathologically. Patients typically experience blisters or erosions on the skin, and in some cases, even on mucous membranes, which can lead to considerable discomfort and potential complications if not properly managed.

Bullous autoimmune dermatoses are divided into four groups based on their target antigens and the localization of the blisters: 

1. Pemphigoid diseases 

2. Pemphigus diseases including paraneoplastic pemphigus, 

3. Epidermolysis bullosa acquisita (EBA) 

4. Dermatitis herpetiformis (DH) 

In pemphigus vulgaris, approximately 70–80% of patients are affected, while pemphigus foliaceus accounts for about 20%. Paraneoplastic pemphigus occurs in around 5% of cases, and IgA pemphigus is found in about 1–3% of patients.

In pemphigus diseases the blisters are formed intraepidermally, while in pemphigoid diseases, epidermolysis bullosa acquisita, dermatitis herpetiformes they are subepidermally. 

The diagnosis of bullous autoimmune dermatoses is based on a combination of the clinical picture with the detection of autoantibodies against structural proteins of the skin or against recombinant, biochemically purified antigens. 

Pemphigoid diseases: 

Pemphigoid diseases - characterised by subepidermal blister formation near the basement membrane - include bullous pemphigoid, pemphigoid gestations, linear IgA dermatoses, mucous membrane pemphigoid, lichen planus pemphigoids anti-laminin γ 1/p200 pemphigoid.

Bullous pemphigoid is the most common subepidermal blistering autoimmune disease worldwide, predominantly affecting older adults rather than younger individuals. Its hallmark symptom is the appearance of large, tense blisters on the skin, especially on the arms, legs, and abdomen. However, bullous pemphigoid can sometimes progress subtly, with symptoms such as itching and redness for weeks or even months before blisters actually appear. Therefore, elderly patients with irritating skin disorders persisting for long periods should be tested for BP in differential diagnosis. 

Autoantibodies in BP are directed against the hemidesmosomal proteins BP180 (type XVII collagen) and BP230. 

Epidermolysis bullosa acquisita (EBA): 

Autoantibodies against the skin protein collagen type VII of the anchoring fibrils cause the rare, severe blistering skin disease EBA. Collagen type VII is a long-chain protein that connects the skin’s basement layer to the underlying connective tissue in the dermis. When blisters develop, they are bulging, as in bullous pemphigoid. In most cases, other symptoms also occur, such as easily injured skin and nail disorders. ​

Dermatitis herpetiformis (DH): 

In DH, autoantibodies against epidermal transglutaminase or tissue transglutaminase/endomysium, and antibodies against gliadin play an indicative role. Evidence of sprue can be found in every patient with DH (but DH is not found in every case of sprue). 

Pemphigous diseases: 

In pemphigus diseases (blisters are formed intraepidermally by acantholysis), the autoimmune system targets primarily the calcium-dependent adhesion molecules (cadherins) desmoglein 1 and 3 (Dsg1 and Dsg3) of the prickle cell desmosomes, which connect the keratinocytes with  each other. Dsg1 is expressed more frequently on the epidermal and mucosal surfaces than in the stratum basale. For Dsg3 this is vice versa. Furthermore, Dsg3 is present along the entire length of the mucosal epithelium, but in the epidermis, it is mainly located near the basal cells.

Pemphigus foliaceus is associated with autoantibodies against Dsg1. This means that only the upper layers of the epidermis are affected. The mucosa is not involved since it contains enough Dsg3 (which is not targeted by the autoimmune response). A gap forms in the stratum granulosum, with thin flaccid blisters. In pemphigus foliaceus, the skin is primarily affected, leading to erosions and scaly crusts. These symptoms typically occur in seborrheic areas, particularly on the trunk and head, causing discomfort and requiring effective management. The incidence is estimated at 0.1 cases per 100,000 persons per year. 

Pemphigus vulgaris (PV) is caused by an autoimmune response to Dsg3. The disease manifests itself in two variants: If only autoantibodies against Dsg3 are present, the mucosa is primarily affected.  The cells of the epidermis are still anchored by Dsg1, which is not affected. If, however, the patient also develops autoantibodies against Dsg1, the epidermis is also involved in addition to the mucosa. In contrast to pemphigus foliaceus, the acantholysis takes place in the lower layers of the epidermis. The blisters are therefore slightly tenser. PV is the most frequently occurring disease of the pemphigus group, however the incidence of the disease varies depending on the region.

- In IgA pemphigus, autoantibodies of the immunoglobulin class IgA are found. The target antigens are Dsg1 or Dsg3 and desmocollin 1.

- In paraneoplastic pemphigus (PNP), besides the severe skin disease, there is an occult or manifest tumour, in most cases hematological neoplasia (in 84% of cases). 

Paraneoplastic pemphigus is linked to neoplasia and can clinically resemble pemphigus vulgaris. Characteristic features include pronounced stomatitis, lip involvement, and polymorphic skin changes that are often lichenoid. Of these cases, approximately 39% are linked to non-Hodgkin lymphoma, around 19% to lymphatic leukemia, another 19% to Castleman tumor, and about 6% to benign thymoma.

It can be associated with autoantibodies against various desmosomal and hemidesmosomal proteins: desmoplakin 1 and 2, BP230, envoplakin, periplakin, plectin, Dsg1, Dsg3 and against an unknown 170 kD antigen. 

Also included in the pemphigus group are pemphigus vegetans, herpetiformis, erythematosus and drug- induced pemphigus.