Autoimmune Bullous Diseases and LRP Flashcards
What are autoimmune bullous disorders?
They are clinically characterized by the development of blisters sometimes even all over the body. They are immunologically characterized by the presence of autoantibodies which are directed at structures of the skin. Some of them have severe prognosis although mortality was higher before steroids where available.
What are the two main families of autoimmune bullous disorders?
Pemphigus which is characterized by autoantibodies directed against desmosomal proteins that connect neighboring keratinocytes. Forms intraepidermal blisters.
Pemphigoid which is characterized by autoantibodies which target the structural components of the dermal epidermal junction. Forms blisters in between the epidermis and dermis.
What are some immunological differences between pemphigoid and pemphigus? What techniques can be used?
Performing Direct ImmunoFluorescence an a skin lesion biopsy of pemphigoid we can notice autoantibodies deposited in the spaces between the keratinocytes in linear fashion while in pemphigus in a net like structure.
Indirect ImmunoFluorescence is used to detect circulating autoantibodies in the blood serum.
ELISA is a technique used to identify circulating IgG antibodies against the diseases.
Pemphigus family main ideas and pathogenesis?
In this disease the auto antibodies are directed against the desmosomal proteins that connect neighboring keratinocytes, mainly desmogleins which are adhesion molecules of the desmosomes.
There is the formation of an intraepideramal blister for the primary lysis of the desmosomes called acantholysis by IgG autoantibodies. The autoantibodies after binding to the desmolgein releases proteases which cause acantholysis.
There are several different clinical variants and different desmogleins attacked.
What is pemphigus vulgaris?
It is the most common form. Age of development is very important and it allows us to differentiate it from pemphigoid. This disease usually arises in 50 to 60 year old patients while for pemphigoid the mean age is 78. Most of patients present lesions in the oral mucosa as the first symptom. Following the first symptom there might be subsequent development of blisters all over the body with high risk of infection. Typical sites of involvement are the scalp, chest and a large folds. After the blisters break they may present with secondary Lesions such as crusts and erosions. Immunologically desmoglein 3 autoantibodies are typical. Intraepithelial blisters form above the basal layer. Steroids are used as treatment. Although death can still occur due to infections.
What is pemphigus vegetans?
Is is a very rare disease that causes the formation of vegetative lesions caused by friction. Usually found in the axillae or inguinal folds. Desmoglein 3. Deep type of pemphigus.
What is pemphigus foliaceus?
Less frequent than pemphigus vulgaris and also more benign. In this disease it is rare to have oral erosions. Patients are covered by scales and crusts because the blisters are superficial and break easily. Scales are only present on the trunk. In this diseases desmoglein 1 autoantibodies are the culprits.
What is fogo salvagem?
It is a particular type of superficial pemphigus which is endemic to some areas in Brazil. It is clinically and immunopathologically the same as pemphigus foliaceus. It is though to be due to an arbovirus but it still has not been proven yet.
What is seborrheic pemphigus?
Also known as erythematous pemphigus it is another type of superficial pemphigus charcaterized by scaly to crusted lesions mainly in seborrheic areas like the face, behind the ear and the zygomatic one.
What is paraneoplastic pemphigus?
It occurs in patients as a sign of cancer, usually lymphoma or leukemia. It is less common but it is the most serious and lethal. It presents painful blisters around the mouth, skin and esophagus. It is much worse compared to the vulgaris type as the skin of the patients detaches like in burnt patients. It is very difficult to find a balanced treatment. More there is the presence of autoantibodies against antigens of both pemphigus and pemphigoid. Tumors such as B cell lymphoma, lymphocytic leukemia, thymoma and others are implied in the development of this disease.
What are some common treatment for the pemphigus family?
Systemic Corticosteroids.
Rituximab: Anti CD20 monoclonal antibody against B lymphocytes.
Immunosuppressors: like Azathioprine and Cyclophospamides.
Immunomodulators: Like Cyclosporins and Mycophenolate Mofetil.
Pemphigoid family main ideas and pathogenesis?
They are autoimmune blistering diseases characterized by sub epithelial blister formation and auto antibodies against antigens which are essential for dermal epidermal adhesions. The auto antibodies are deposited in a linear way between the epidermis and dermis. There are two main antigens attacked by autoantibodies : BPAg2 which is the main one located in the lamina lucida and BPAg1 which is located intracellularly within the basal keratinocytes as a components of hemidesmosomal anchoring.
What is bullous pemphigoid of the lever?
It is the most common form of sub epidermal blistering diseases. It is still generally very rare. It presents genetic predispositions associated with HLA DQB1. It is characterized by the presence of large, tense bullae filled with fluid which rupture. Causes also rashes on trunk and inguinale folds. The tense bullae is what differentiates it form the flaccid bullae of pemphigus. There is a sub epidermal blister with eosinophils and linear deposition of Igs. Treated with corticosteroids, topical steroids and immunosuppressants.
What is membrane pemphigoid?
Usually affects mainly women over 60. Onset is usually in the oral mucosa with subepidermal blisters and erosions in the gums. Promotes severe ocular involvement and possible blindness. Autoantibodies against laminin 332 and type VII collagen. It is harder to treat than bullous pemphigoid of lever.
What is pemphigoid gestationis?
It gives rise to bullous pemphigoid during pregnancy. There are no differences except from the fact that it occurs during pregnancy at the 5th or 6th month. With each pregnancy it increases the severity. Genetic predisposition, HLA A1, B8 and DR3. Fathers HLA has influence as if partner changes it might not recur. Causes subepidermal blisters with eosinophils and shows linear deposits of IgG and C3.
