A Brief Introduction to Diseases of Pemphigoid

Bullous pemphigoid (BP) is the most common skin autoimmune subcutaneous bullous disease. Occur in the elderly, the generalized itching of herpes characterized by large, mucosal involvement is relatively rare, with significant morbidity. However, the performance of Bullous pemphigoid is very diverse, beginning to be easily misdiagnosed, especially in early disease or atypical cases, patients can be completely without bullae. For these cases, the prerequisite for the diagnosis ofBullous pemphigoid first need a high degree of suspicion, and immediately take appropriate treatment. Bullous pemphigoid is an example of organ-specific autoimmune diseases. The target antigen of the patient's autoantibody is the two components of the connective complex-hemi-desmosomes in the skin and mucosa.

Pemphigoid disease history

Over the centuries, the description of bullous dermatology has used many terms. From the 18th century onwards, the term "pemphigus" is used to describe any type of bullous rash. Until 1953, Lever based on its special clinical and pathological features, that Bullous pemphigoid is a disease different from pemphigus.

Ten years later, Jordon, Bertner, and colleagues demonstrated thatBullous pemphigoid patients have autoantibodies against the skin basement membrane zone (BMZ) that binds to the tissue and resides in the circulation. This finding suggests that autoantibodies are responsible for the structural components of the skin that promote the adhesion of the dermis to the epidermis, leading to poor subepidermal adhesion. Other milestones that help us understand BULLOUS PEMPHIGOID include the immunohistochemical characterization of target proteins, gene cloning of these proteins, and establishment of disease animal models.

Pathogenesis of pemphigoid

Bullous pemphigoid is an immune-mediated disease in which humoral and cellular immunity occurs directly against two antigens: Bullous pemphigoid antigen 180 (Bullous pemphigoid 180, Bullous pemphigoidAG2 or XVII collagen) and Bullous pemphigoid antigen 230 (Bullous pemphigoid 230 or Bullous pemphigoid AG1). Bullous pemphigoid 180 is a transmembrane protein with extracellular domain as collagen. Bullous pemphigoid 230 is a cytoplasmic protein belonging to the family of plaques. Both antigens are components of hemi-desmosomes. Hemi-desmosomes are complexes that promote the adhesion of the epidermis to the stroma in a stratified epithelium or other complex epithelium, such as the skin or mucosa.

In vitro studies and in vivo studies of animal models provide substantial evidence of the pathogenic role of Bullous pemphigoid autoantibodies. In addition, pregnancy pemphigoid patients, the maternal body of Bullous pemphigoid 180 autoantibody through the placenta to the neonatal body, can lead to newborns with transient bullous lesions. Finally, the association of Bullous pemphigoid with a particular major histocompatibility complex (MHC) class II monomer and its response to immunosuppressive therapy indirectly supports the autoimmune etiology of Bullous pemphigoid.

Pemphigoid associated diseases

In most cases, Bullous pemphigoid patients with visceral malignancies may be associated with the elderly. Although the incidence of certain cancers (e.g. alimentary canal, bladder and lung) and lymphoproliferative disorders is higher in the three case-control studies, the risk of malignancy appears to be marginalized in Bullous pemphigoid patients. Occasionally individual cases, blister disease and malignant tumors occur simultaneously. Therefore, if the system performance and atypical performance such as Bullous pemphigoid occurred in middle-aged, it is recommended for cancer screening. Age-related cancer screening tests should be recommended for Bullous pemphigoid patients in the general population.

There are rare cases reported, Bullous pemphigoid patients with inflammatory bowel disease and other autoimmune diseases such as rheumatoid arthritis, Hashimoto thyroiditis, dermatomyositis, lupus erythematosus and autoimmune thrombocytopenia. These correlations are not accidental, and they reflect a genetic predisposition to autoimmune diseases. However, case-control studies did not find any evidence of a high risk of autoimmune disease in patients with Bullous pemphigoid.

Trauma, burns, radiation or UV radiation (including PUVA) can be an etiologic factor in some Bullous pemphigoid patients. Bullous pemphigoidcan also be associated with certain skin diseases, such as psoriasis, lichen planus. Bullae may be localized to psoriasis plaques, suggesting that chronic inflammation at the dermal-epidermal junction causes the antigen to be exposed to autoreactive T cells, causing a secondary immune response (epitope spreading).

Finally, Bullous pemphigoid patients can also be associated with neurological diseases such as multiple sclerosis, Shy-Drager syndrome or amyotrophic lateral sclerosis. The relevance of these correlations is unclear. However, it is notable that Bullous pemphigoid 230 neuronal variants are expressed in the central and peripheral nervous systems.

Treatment of pemphigoid disease

Bullous pemphigoid treatment is based on clinical experience, rather than controlled study.

The most commonly used system is corticosteroids. The generalized skin lesions, oral prednisone 0.5-1mg/kg/day, usually 1-2 weeks to control the disease, and then gradually reduced in the 6-9 months. However, the use of corticosteroids in the elderly is often accompanied by significant adverse reactions, such as hyperglycemia, infection, osteoporosis, congestive heart failure and so on. Recently, a large sample of controlled studies has emphasized that topical corticosteroids are effective not only for localized or light Bullous pemphigoid, but also for patients with generalized Bullous pemphigoid, as well as with oral corticosteroids, and most importantly, their systemic Fewer adverse reactions. Occasionally, in order to quickly control the disease, if necessary, the use of methylprednisolone pulse therapy.

The use of immunosuppressive agents is controversial. Some clinicians prefer to use corticosteroids as a second-line treatment if they can not control their condition or if they have contraindications to corticosteroids. The most commonly used are azathioprine, methotrexate, chlorambucil (0.1mg/kg/day, usually 4-6mg/day), cyclophosphamide (1-3mg/kg/day), cyclosporine (1-5mg/kg/day) and mycophenolate mofetil (1.5-3.0g/day). To increase efficacy and reduce side effects, the dose of azathioprine (0.5-2.5mg/kg/day) should be adjusted to the level of thiopurine methyltransferase (TPMT). Should be based on adverse drug reactions, the patient's overall condition and the doctor's experience to choose the appropriate immunosuppressant.

The combination of nicotinamide (500-2000mg/day) and minocycline or tetracycline has achieved some success in a small number of patients. Patients with a systematic contraindication to the use of corticosteroids may be selected as a treatment option. In the absence of glucose-6-phosphate dehydrogenase deficiency, ampicillin can also be used, particularly if there is mucosal involvement. Local topical immunomodulatory agents, such as the effect of his Demos need verification. IVIG, plasma exchange or anti-CD20 immunotherapy (rituximab) can also be tried.

In conclusion, for all Bullous pemphigoid patients, it is important to reduce the risk of skin lesions and systemic complications, including prevention of osteoporosis, protection of the stomach, assessment of cardiovascular function and reduction of infection.