[2] Over time the condition inevitably progresses without treatment: lesions increase in size and distribution throughout the body, behaving physiologically like a severe burn.

Other mucosal surfaces, the conjunctiva, nose, esophagus, penis, vulva, vagina, cervix, and anus, may also be affected.

The process is classified as a type II hypersensitivity reaction (in which antibodies bind to antigens on the body's own tissues).

On histology, the basal keratinocytes are usually still attached to the basement membrane leading to a characteristic appearance called "tombstoning".

Transudative fluid accumulates in between the keratinocytes and the basal layer (suprabasal split), forming a blister that is easily dislodged when a lateral force is applied, resulting in what is known as a positive Nikolsky's sign.

[6] This is a contrasting feature from bullous pemphigoid, which is thought to be due to anti-hemidesmosome antibodies, and where the detachment occurs between the epidermis and dermis (subepidermal bullae).

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.

[7] Corticosteroids and other immunosuppressive medications have historically been employed to reduce pemphigus symptoms, yet steroids are associated with serious and long-lasting side effects and their use should be limited as much as possible.

Intravenous immunoglobulin, mycophenolate mofetil, methotrexate, azathioprine, and cyclophosphamide have also been used with varying degrees of success.

In summer 2018, the FDA granted full approval to rituximab for this application, following successful fast track evaluation.

[citation needed] Rituximab demonstrated superior efficacy compared to mycophenolate mofetil in a Phase III clinical trial, results of which were published in 2021.

[14] If left untreated, 8 of 10 people with the disease die within a year with a cause of death being infection or loss of fluids, which is very common for raw, open sores that are characteristic of P. vulgaris.

In PV, autoreactive B cells produce antibodies against Dsg3, disrupting its adhesive function and causing skin blistering.