Description

• Bullous pemphigoid (BP) is a chronic, acquired autoimmune subepidermal blistering skin disorder caused by linear deposition of autoantibodies against the epithelial basal membrane zone.
• Pruritic, tense, symmetric, localized, widespread bullae, or urticarial plaques
• Flexural surface (80%), axillary, inguinal folds, and abdomen (20%)
• Oral lesions develop in 10–20% of cases, rarely affecting mucosae of eyes, nose, pharynx, and anogenital zones.

Epidemiology

• Most common autoimmune blistering disease
• Typical between 60 and 80 years old, but juvenile BP can occur
• Affects both females and males, possibly with higher incidence in females
• No association with race or geographic location

Incidence

• BP incidence increases with age (1).
• 14 to 42 new cases per million per year (2)

Etiology and Pathophysiology

• Autoantibodies react against hemidesmosomal proteins: the 230-kDa BP antigen (BPAg1) within basal keratinocytes and 180-kDa (BPAg2 or type XVII collagen) in the basement membrane zone (BMZ).
• IgG is usually the predominant autoantibody leading to C3 complement activation, recruitment of inflammatory cells, and liberation of proteolytic enzymes that break down the dermoepidermal junction.
• The noncollagenous 16A domain (NC16A) located at the membrane proximal region of BP180 is considered the major target epitope and is recognized in 80–90% of BP patients.
• It has recently been shown that IgE antibodies correlate with a severe form of BP, and those who test positive for IgE anti-BP180 antibodies required longer duration for remission and therapy.

Genetics

• Certain class II antigens of the major histocompatibility complex (MHC) alleles DQB1*0301 predominate in the United States.
• Expression of this allele on antigen-presenting cells is thought to be involved in the presentation to autoreactive T cells in patients with BP.
• Molecular mimicry has been proposed as a mechanism by which exogenous agents may trigger the immune response.

Risk Factors

• Advanced age
• Associated with autoimmune disorders and inflammatory dermatoses like lichen planus, psoriasis, and other forms of bullous disease
• Increased risk in patients with neurologic disorders such as multiple sclerosis, dementia, stroke, Parkinson disease, demyelinating disorders, epilepsy, depression, and schizophrenia (3)
• Although drug-induced BP is rare, chronic intake of neuroleptics, aldosterone antagonists, furosemide, dopaminergic drugs, opioids, salicylates, NSAIDs, and phenacetin have been associated.
• Less frequent: trauma, burns, surgical scars, UV radiation, and x-ray therapy

Commonly Associated Conditions

• Underlying malignancy can be found in patients with BP, but it may be age related, and the correlation is marginal.
• Several autoimmune disorders such as rheumatoid arthritis, Hashimoto thyroiditis, dermatomyositis, lupus erythematosus, inflammatory dermatoses–like psoriasis, and lichen planus have been reported but are rare.
• Increased risk of septicemia, pneumonia, UTI, and pulmonary embolism (3)