They are postulated to release proteolytic enzymes which degrade the hemidesmosomal proteins, resulting in blister formation.Other potential contributory factors including genetic factors, environmental exposures to infections and drugs as well as the phenomenon of epitope spreading are also known to cause bullous pemphigoid. Diagnosis
Diagnosis of bullous pemphigoid includes clinical assessment, skin biopsy for histopathology and direct immunofluorescence, indirect immunofluorescence and ELISA test. Among all, direct immunofluorescence is the gold standard for diagnosis of bullous pemphigoid. Clinical assessment
For patients greater than 70 years old 
Blistering skin disease characterized by the presence of tense blisters and erosions that occur without another identifiable cause and rarely on mucosa. Unexplained pruritus, pruritic eczematous eruptions, or urticarial plaques

Histopathology
Lesional tissue, preferably of an intact vesicle or the edge of an intact bulla is obtained using punch biopsy for Haemotoxylin and Eosin (H&E)staining. Typical histopathologic findings include:
Sub-epidermal split with numerous eosinophils within the cleft. A superficial dermal inflammatory cell infiltrate of variable intensity with lymphocytes, eosinophils, and neutrophils. Eosinophlic spongiosis (Specifically in early lesion or may be seen in clinically erythematous skin surrounding the blister)

Direct immunofluorescence
Direct immunofluorescence (DIF) studies involves directly detecting tissue bound antibodies. Biopsy specimens for DIF should be taken from perilesional skin instead of lesional skin for H&E histopathologic evaluation. DIF specimens should be placed in Michels solution or Zeuss transport media instead of formalin. DIF of bullous pemphigoid will show the presence of fine, continuous and linear deposits of IgG and/or C3 along the epidermal basement membrane.
Intravenous immunoglobulin
ii. Rituximab
Among all, topical or systemic corticosteroids are considered as the first line therapy in controlling bullous pemphigoid. Other drugs and immunomodulatory therapies are often used as adjunct to minimize the adverse effect of long term use of corticosteroids and improve the healing of the disease. There are several factors that have to be taken into account when choosing the therapies given to the patient: (a) patients age (b) underlying disease such as hypertension, diabetes mellitus and other cardiovascular disease (c) side effect with the use of drugs (d) patients ability to compliant to the therapy (d) severity and extent of disease (e) cost of drugs. Corticosteroids
High potency topical corticosteroid is preferred as the first line treatment due to its efficacy and fewer systemic adverse effects when compared to systemic corticosteroids. Studies have shown that patients with extensive bullous pemphigoid (defined as >10 new bullae per day) treated with topical corticosteroids (Topical Clobetasol Propionate 0.05% cream) had better clinical outcomes than patients with extensive bullae pemphigoid who were treated with systemic glucocorticoid therapy (Prednisone).Systemic glucocorticoids can be used for patients when there are factors that make the use of topical corticosteroids not feasible, such as elderly patient inability to apply the cream on their own, cost or patients own preference. Topical Corticosteroids
Topical Clobetasol Propionate 0.05% cream is usually used and applied twice daily. A study by Joly et al.