Patel Punita s*, Patel Brilina M, Arora Bhoomi
Institute of clinical research India
Bullous Pemphigoid (BP) is an autoimmune subepidermal blistering disease appearing predominantly in the elderly. Bullous Pemphigoidcharacterized by an autoimmune response to 2 hemidesmosomal proteins within the dermal–epidermal junction, These proteins, called BP antigen 1 (BPAG1 or AgBP230), and BPAG2 (or AgBP180 or collagen XVII) have respective molecular masses of 230 and 180. While BP180 is a transmembrane glycoprotein with an extracellular domain BP230 localizes intracellularly and associates with the hemidesmosomal plaque. The disease is characterized clinically by tight bullae, with clear content, often large, developing primarily on the edge of erythematous plaques. Intense itching is common. The disease is primarily treated with systemic corticosteroids. Now,The increased knowledge of the development of noveltherapeutic strategies for Bullous Pemphigoids.
Reference Id: PHARMATUTOR-ART-1329
In 1953, Lever  was the first to distinguish, on the basis of distinctive clinical and histological features, bullous pemphigoid (BP) from pemphigus. In 1967, Jordon et al .demonstrated by immunofluorescence analysis that patients with bullous pemphigoid (BP) produce circulating autoantibodies directed against the cutaneous basement membrane zone. Bullous Pemphigoid (BP) is a subepidermal autoimmune disease presenting as pruritus, papulovesicles and tenseblisters. Autoantibodies mainly IgG (rarely IgM, IgE) in BP are directed against two hemidesmosomalproteins designated BP230 and BP180.The autoantibodies are localized in vivoalong the epidermal basement membrane. Bullous Pemphigoid is mostly found in the elderly. However, cases have also been reported in children.Bullous pemphigoid is not only the most common disorder but also represents the most frequent autoimmune blistering disease in general. In this review, we will focus on recent progress in our understanding of the novel drug therapy of bullous pemphigoid.
Auto-antibodies are directed against 2 hemidesmosomal proteins, designated BP180 and BP230. While BP230 localises intracellularly and associates with the hemidesmosomal plaque, BP180 is a transmembrane glycoprotein with an extracellular domain consisting of approximately 1000 amino acids. The non-collagenous 16A domain that encompasses 76 amino acids and localises directly adjacent to the transmembrane region has been identified as an immunodominant region of the BP180 ectodomain .
In most bullous pemphigoid sera, circulating antibodies to BP180NC16A are detected with serum levels correlating with disease activity. Bullous pemphigoid auto-antibodies (with the help of complement activation), the infiltration of inflammatory cells, and the release of proteases and various inflammatory mediators, including cytokines, are essential for lesion formation. Further studies using a similar approach revealed that antihuman BP180NC16A antibodies and neutrophils are responsible for this tissue injury .Using an IgG passive transfer approach, there exists in vivo evidence that rabbit antibodies directed against the murine BP180NC16A homologue are pathogenic in mice . These in vitro and in vivo data demonstrate that antibodies specific for the BP180NC16A domain are pathogenic. It is clear that the binding of anti-BP180 antibody to its target is the critical first step in sub-epidermal blister formation in bullous pemphigoid. It is unclear as to the sub-class of IgG that is pathogenic and directly related to the severity of the disease. New findings identify anti-BP180-N IgG1 auto-antibodies as the predominant IgG sub-class associated with acute onset of bullous pemphigoid. Because IgG1 antibodies are capable of fixing complement, the link between anti-BP180 auto-antibodies and complement in their pathogenic role in bullous pemphigoid is revealed.
Bullous pemphigoid often provokes blood and tissue eosinophilia, which suggests chemoattractants may modulate the eosinophil infiltration. Eotaxin and interleukin (IL)-5 are strongly associated with the tissue eosinophilia of bullous pemphigoid. These findings suggest that eotaxin and IL-5 may be important for eosinophil migration in bullous pemphigoid lesions and that therapies that aim to inhibit production of eotaxin and IL-5 may improve inflammation and blister formation.
Bullous Pemphigoid is the most common autoimmune blistering disease in the West with an estimated incidence of six to seven cases per million population per year in France and Germany.The prevalence of bullous pemphigoid in the US is reported as 6 to 10 cases per million with a mean age of onset of 65 years. North East Scotland appears to have a relatively high incidence of bullous pemphigoid (14 cases per million per year) when compared with incidence rates in continental Europe.It occurs equally in both sexes and is usually a disease of the elderly (> 70 years) but can also affect younger patients and children. Men are more frequently affected than women.BP has been reported in association with malignancies; however, most large series have concluded that there is no increased incidence of malignancy in patients with Bullous Pemphigoid in western countries compared with age- and sex-matched controls.
The disease is characterized clinically by tight bullae, with clear content, often large, developing primarily on the edge of erythematous plaques. Intense itching is common. Mouth sores and bleeding gums are also common. The lesions are symmetrical with a predilection for the flexor sides of the limbs, the anterior-internal face of the thighs and abdomen. Mucosal lesions are rare, predominantly affecting the buccal mucosa (10-20% of the cases). Nikolsky's sign is absent. The disease progresses by successive bouts, the bullae healing without scarring. Affect on the patient's general status is variable; it depends on the extent of the lesions, and the severity and duration of itching. Oral lesions consist of small blisters orerosions and are found mainly on the palatal mucosa.The blister formation may be preceded by an urticarialor eczematous rash. The degree of itch varies fromnone to intense and may precede the appearance ofblisters by weeks, months or occasionally years.
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