Diagnostic techniques:

- antibodies (IgG) precipitates complement (C3) in the lamina lucida of the basement membrane.

- Circulating auto-antibodies to BP-1 antigen (located in hemidesmosome). 50% have BP-2.

- Positive Nikolsky sign.

- IgG, C3 deposition at BM creating smooth line in immunofluorescent analysis.

Pemphigus is a group of autoimmune blistering diseases that may be classified into the following types:

Diagnosis is based on two biopsies of the skin, one submitted for routine H&E staining and one for immunofluorescence studies.

The management depends upon the severity of the condition. For example, where there are lesions in the mouth alone, systemic drugs are less likely to be used. Where the condition is not limited to the mouth, or where there is poor response to Topical treatments, systemic drugs are more likely to be used.

Pemphigus defines a group of autoimmune interepithelial blistering diseases that are characterized by loss of normal cell-cell adhesion (acantholysis), and by the presence of pathogenic (predominantly IgG) autoantibodies reacting against epithelial adhesion molecules. Pemphigus is further divided in two major subtypes: pemphigus vulgaris (PV) and pemphigus foliaceus (PF). However, several other disorders such as IgA pemphigus, IgE pemphigus, pemphigus herpetiformis, drug induced pemphigus, Senear Usher syndrome and endemic pemphigus foliaceus exist;recognized by a dermatologist from the appearance and distribution of the skin lesions. It is also commonly diagnosed by specialists practicing otolaryngology- head and neck surgery, periodontists, oral and maxillofacial surgeons and eye doctors, as lesions can affect the eyes and mucous membrane of the oral cavity. Intraorally it resembles the more common diseases lichen planus and mucous membrane pemphigoid. Definitive diagnosis requires examination of a skin or mucous membrane biopsy by a dermatopathologist or oral pathologist. The skin biopsy is taken from the edge of a blister, prepared for histopathology and examined with a microscope. The pathologist looks for an intraepidermal vesicle caused by the breaking apart of epidermal cells (acantholysis). Thus, the superficial (upper) portion of the epidermis sloughs off, leaving the bottom layer of cells on the "floor" of the blister. This bottom layer of cells is said to have a "tombstone appearance".

Definitive diagnosis also requires the demonstration of anti-desmoglein autoantibodies by direct immunofluorescence on the skin biopsy. These antibodies appear as IgG deposits along the desmosomes between epidermal cells, a pattern reminiscent of chicken wire. Anti-desmoglein antibodies can also be detected in a blood sample using the ELISA technique.

Lichen planus has a unique microscopic appearance that is similar between cutaneous, mucosal and oral. A Periodic acid-Schiff stain of the biopsy may be used to visualise the specimen. Histological features seen include:

- thickening of the stratum corneum both with nuclei present (parakeratosis) and without (orthokeratosis). Parakeratosis is more common in oral variants of lichen planus.

- thickening of the stratum granulosum

- thickening of the stratum spinosum (acanthosis) with formation of colloid bodies (also known as Civatte bodies, Sabouraud bodies) that may stretch down to the lamina propria.

- liquefactive degeneration of the stratum basale, with separation from the underlying lamina propria, as a result of desmosome loss, creating small spaces (Max Joseph spaces).

- Infiltration of T cells in a band-like pattern into the dermis "hugging" the basal layer.

- Development of a "saw-tooth" appearance of the rete pegs, which is much more common in non-oral forms of lichen planus.

The differential diagnosis for OLP includes:

- Other oral vesiculo-ulcerative conditions such as Pemphigus vulgaris and Benign mucous membrane pemphigoid

- Lupus erythematosus, with lesions more commonly occur on the palate and appear as centrally ulcerated or erythematous with radiating white striae. In contrast, OLP and lichenoid reactions rarely occur on the palate, and the striae are randomly arranged rather than radial.

- Chronic ulcerative stomatitis

- Frictional keratosis and Morsicatio buccarum (chronic cheek biting)

- Oral leukoplakia

- Oral candidiasis

Because it is a rare disease, diagnosis is often complicated and takes a long time. Early in the disease patients may have erosions in the mouth or blisters on the skin. These blisters can be itchy or painful. Theoretically, the blisters should demonstrate a positive Nikolsky's sign, in which the skin sloughs off from slight rubbing, but this is not always reliable. The gold standard for diagnosis is a punch biopsy from the area around the lesion that is examined by direct immunofluorescent staining, in which cells are acantholytic, that is, lacking the normal intercellular connections that hold them together. These can also be seen on a Tzanck smear. These cells are basically rounded, nucleated keratinocytes formed due to antibody mediated damage to cell adhesion protein desmoglein.

Pemphigus vulgaris is easily confused with impetigo and candidiasis. IgG4 is considered pathogenic. The diagnosis can be confirmed by testing for the infections that cause these other conditions, and by a lack of response to antibiotic treatment.

Bullous pemphigoid may be self-resolving in a period ranging from several months to many years even without treatment. Poor general health related to old age is associated with a poorer prognosis.

Immunoprecipitation, immunoblotting and enzyme-link immunosorbent assay (ELISA)

Poot et al. 2013 determined that immunoprecipitation for antibodies against envoplakin and periplakin or alpha2-macroglobulin-like–1 is the most sensitive test. However, alpha2-macroglobulin-like-1 can also be detected in patients with toxic epidermal necrosis.

Patients with high concentration of antibodies show intercellular, intraepidermal antibodies as well as along the dermoepidermal junction. Patients with low concentration of antibodies only present with them inside the cells (intercellular).

If the results are negative, perform the additional assays regardless. Cases have been confirmed that reported with initial negative DIF and IDIF tests.

Erythema multiforme is frequently self-limiting and requires no treatment. The appropriateness of glucocorticoid therapy can be uncertain, because it is difficult to determine if the course will be a resolving one.

Pemphigoid is usually considered to be mediated by IgG, but IgA-mediated forms have also been described.

IgA-mediated immunobullous diseases can often be difficult to treat even with usually effective medications such as rituximab.

While the term pemphigus typically refers to "a rare group of blistering autoimmune diseases" affecting "the skin and mucous membranes", Hailey–Hailey disease is not an autoimmune disorder and there are no autoantibodies. According to Pemphigus Pemphigoid Foundation (IPPF), "familial benign chronic pemphigus, or Hailey-Hailey disease, is a different condition from Pemphigus".

Research into using genetically modified T-cells to treat pemphigus vulgaris in mice was reported in 2016. Rituximab indiscriminately attacks all B cells, which reduces the body's ability to control infections. In the experimental treatment, human T cells are genetically engineered to recognize only those B cells that produce antibodies to desmoglein 3.

The forms of pemphigoid are considered to be connective tissue autoimmune skin diseases. There are several types:

- Gestational pemphigoid or Pemphigoid gestationis (PG) (formerly called Herpes gestationis)

- Bullous pemphigoid (BP) Rarely affect the mouth

- Mucous membrane pemphigoid, also known as Cicatricial pemphigoid (CP) (No skin involvement)

Bullous and Cicatricial pemphigoids usually affect persons who are over age 60. Gestational pemphigoid occurs during pregnancy, typically in the second or third trimester, and/or immediately following pregnancy.

Topical steroid preparations often help outbreaks; use of the weakest corticosteroid that is effective is recommended to help prevent thinning of the skin. Drugs such as antibiotics, antifungals, corticosteroids, dapsone, methotrexate, thalidomide, etretinate, cyclosporine and, most recently, intramuscular alefacept may control the disease but are ineffective for severe chronic or relapsing forms of the disease. Intracutaneous injections of botulinum toxin to inhibit perspiration may be of benefit. Maintaining a healthy weight, avoiding heat and friction of affected areas, and keeping the area clean and dry may help prevent flares.

Some have found relief in laser resurfacing that burns off the top layer of the epidermis, allowing healthy non-affected skin to regrow in its place.

Secondary bacterial, fungal and/or viral infections are common and may exacerbate an outbreak. Some people have found that outbreaks are triggered by certain foods, hormone cycles and stress.

In a few cases naltrexone appears to help.

PG often is confused with pruritic urticarial papules and plaques of pregnancy (PUPPP), especially if it occurs in a first pregnancy. PUPPP typically begins in stretch mark areas of the abdomen and usually ends within two weeks after delivery. PUPPP is not an autoimmune disease.

Diagnosing PG is done by biopsy using direct immunofluorescence, appearance, and blood studies.

The physical examination of the skin and its appendages, as well as the mucous membranes, forms the cornerstone of an accurate diagnosis of cutaneous conditions. Most of these conditions present with cutaneous surface changes termed "lesions," which have more or less distinct characteristics. Often proper examination will lead the physician to obtain appropriate historical information and/or laboratory tests that are able to confirm the diagnosis. Upon examination, the important clinical observations are the (1) morphology, (2) configuration, and (3) distribution of the lesion(s). With regard to morphology, the initial lesion that characterizes a condition is known as the "primary lesion," and identification of such a lesions is the most important aspect of the cutaneous examination. Over time, these primary lesions may continue to develop or be modified by regression or trauma, producing "secondary lesions." However, with that being stated, the lack of standardization of basic dermatologic terminology has been one of the principal barriers to successful communication among physicians in describing cutaneous findings. Nevertheless, there are some commonly accepted terms used to describe the macroscopic morphology, configuration, and distribution of skin lesions, which are listed below.

The differential diagnosis includes oral lichen planus, erythematous candidiasis, leukoplakia, lupus erythematosus, glossitis, and chemical burns. Atrophic glossitis is usually distinguished from benign migratory glossitis on the basis of the migrating pattern of the lesions and the presence of a whitish border, features which are not present in atrophic glossitis, which instead shows lesions which enlarge rather than migrate. Rarely, blood tests may be required to distinguish from glossitis associated with anemia or other nutritional deficiencies. Since the appearance and the history of the condition (i.e. migrating areas of depapillation) are so striking, there is rarely any need for biopsy. When biopsy is taken, the histopathologic appearance is quite similar to psoriasis:

- Hyperparakeratosis.

- Acanthosis.

- Subepithelial T lymphocyte inflammatory infiltrate.

- Migration of neutrophilic granulocytes into the epithelial layer, which may create superficial microabscesses, similar to the Munro's microabscesses described in pustular psoriasis.

The most accepted way to treat PG is with the use of corticosteroids, i.e. prednisone; and/or topical steroids, i.e. clobetasol and betamethasone. Suppressing the immune system with corticosteroids helps by decreasing the number of antibodies attacking the skin. Treating PG can be difficult and can take several months. Some cases of PG persist for many years. In the" post partum" period, if necessary, the full range of immunosuppressive treatment may be administered for cases unresponsive to corticosteroid treatments, such as tetracyclines, nicotinamide, cyclophosphamide, ciclosporin, goserelin, azathioprine, dapsone, rituximumab, or plasmaphoresis, or intravenous immunoglobulin may sometimes be considered when the symptoms are severe.

There is no cure for PG. Women who have PG are considered in remission if they are no longer blistering. Remission can last indefinitely, or until a subsequent pregnancy. PG usually occurs in subsequent pregnancies; however, it often seems more manageable because it is anticipated.

The diagnosis is usually made by tissue biopsy, however this cannot reliably distinguish between the granulomas of OFG and those of Crohn's disease or sarcoidosis. Other causes of granulomatous inflammation are ruled out, such as sarcoidosis,

Crohn's disease, allergic or foreign body reactions and mycobacterial infections.

Many suspected aetiologic factors have been reported to cause EM.

- Infections: Bacterial (including Bacillus Calmette-Guérin (BCG) vaccination, haemolytic "Streptococci", legionellosis, leprosy, "Neisseria meningitidis, Mycobacterium, "Pneumococcus, "Salmonella" species, "Staphylococcus" species, "Mycoplasma pneumoniae), "Chlamydial.

- Fungal (Coccidioides immitis)

- Parasitic ("Trichomonas" species, "Toxoplasma gondii), "

- Viral (especially Herpes simplex)

- Drug reactions, most commonly to: antibiotics (including, sulphonamides, penicillin), anticonvulsants (phenytoin, barbiturates), aspirin, antituberculoids, and allopurinol and many others.

- Physical factors: radiotherapy, cold, sunlight

- Others: collagen diseases, vasculitides, non-Hodgkin lymphoma, leukaemia, multiple myeloma, myeloid metaplasia, polycythemia

EM minor is regarded as being triggered by HSV in almost all cases. A herpetic aetiology also accounts for 55% of cases of EM major. Among the other infections, "Mycoplasma" infection appears to be a common cause.

Herpes simplex virus suppression and even prophylaxis (with acyclovir) has been shown to prevent recurrent erythema multiforme eruption.

Vesicular pemphigoid is a cutaneous condition, a clinical variant of bullous pemphigoid, characterized by a dermatitis herpetiformis-like presentation with grouped small tense blisters.

Anti-tumour necrosis factor α antagonists (e.g. infliximab)

Dietary restriction of a particular suspected or proven antigen may be involved in the management of OFG, such as cinnamon or benzoate-free diets.