Clinically, the earliest lesions may appear urticarial (like hives). Tense bullae eventually erupt, most commonly at the inner thighs and upper arms, but the trunk and extremities are frequently both involved. Any part of the skin surface can be involved. Oral lesions are present in a minority of cases. The disease may be acute, but typically will wax and wane. Several other skin diseases may have similar symptoms. However, milia are more common with epidermolysis bullosa acquisita, because of the deeper antigenic targets. A more ring-like configuration, with a central depression or centrally collapsed bullae may indicate linear IgA disease. Nikolsky's sign is negative unlike pemphigus vulgaris where it is positive.
Very rarely seen in children, bullous pemphigoid most commonly occurs in people 70 years of age and older. Estimated frequency is seven to 14 cases per million per year, but has been reported to be as high as 472 cases per million per year in Scottish men older than 85. At least one study indicates the incidence might be increasing in the United Kingdom. Some sources report it affects men twice as frequently as women, while others report no difference between the sexes.
Many mammals can be afflicted, including dogs, cats, pigs, and horses, as well as humans. It is very rare in dogs; on average, three cases are diagnosed around the world each year.
In most cases of bullous pemphigoid, no clear precipitating factors are identified. Potential precipitating events that have been reported include exposure to ultraviolet light and radiation therapy. Onset of bullous pemphigoid has also been associated with certain drugs, including furosemide, ibuprofen and other nonsteroidal anti-inflammatory agents, captopril, penicillamine, and antibiotics.
The bullae are formed by an immune reaction, initiated by the formation of IgG autoantibodies targeting Dystonin, also called Bullous Pemphigoid Antigen 1, and/or type XVII collagen, also called Bullous Pemphigoid Antigen 2, which is a component of hemidesmosomes. A different form of dystonin is associated with neuropathy. Following antibody targeting, a cascade of immunomodulators results in a variable surge of immune cells, including neutrophils, lymphocytes and eosinophils coming to the affected area. Unclear events subsequently result in a separation along the dermoepidermal junction and eventually stretch bullae.
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.
Animal models of bullous pemphigoid have been developed using transgenic techniques to produce mice lacking the genes for the two known autoantigens, dystonin and collagen XVII.