Tag Archives: pemphigus vulgaris

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While you are seeing a qualified dermatologist who is treating you for your Pemphigus Vulgaris, Bullous Pemphigoid, Pemphigus Foliaceus, Mucous Membrane Pemphigoid, etc. you might also be seeing your own dentist, OB/GYN, internist, ophthalmologist or ear/nose/throat specialist.

Please be sure that all of your doctors are aware of your condition and that they have access to your dermatologist.  It is important that they know the medications and dosage that you are taking for each medication.

All of your doctors need to be able to communicate with one another if necessary.  Being left in the dark will leave you at a disadvantage.  Also, if you are going to be scheduled for any major dental work, advise your dermatologist.  Depending on the procedure, your medications may be adjusted for a few days prior and a few days following to prevent any flare-ups.

Remember when you need us we are in your corner!

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By Mirella Bucci, PhD

The main physical manisfestation of the P/P diseases is the presence of blisters on the skin and mucous membranes. Underlying those blisters are numerous molecular processes including recognition of keratinocyte cells of the skin and cell death. But how these blisters actually form, that is, what is the order of events leading up to their formation, has not been clear. A recent study by scientists Parviz Deyhimi and Payam Tavakoli suggests that in pemphigus vulgaris (PV), cell death comes first, then the formation of blisters (Journal of Oral Pathology and Medicine, doi: 10.1111/jop.12022).

The blisters that form in PV are referred to as lesions, or suprabasal vesicles, because of where they are found within the layers of the epidermis (supra meaning above, so above the basal layer, see Figure 1a). Because they are found so deep within the tissue, the blisters formed and PV disease itself is considered more severe than pemphigus foliaceus, where the blisters appear within the granular layer. The lesions formed during PV and in other mucocutaneous autoimmune blistering diseases are formed when the rogue antibodies formed during disease recognize proteins found at junctions formed by keratinocyte cells interacting with one another. The loss of these junctions that generates the tear in the skin is called acantholysis. Acantholysis is more than a tearing of the skin.

There is also cell death (also called apoptosis) within the lesions. But it has been unclear when and where apoptosis occurs with relation to acantholysis and to recognition of the junctions by antibodies generated by the immune system of the patient. Besides the ordering of events, it has been unclear which of the various types of apoptosis are at play. In the intrinsic pathway of apoptosis, a cell essentially commits suicide because of an internal trigger, perhaps as part of a genetic program as occurs during cell or tissue development. In the extrinsic pathway, the trigger to commit suicide is external. Perhaps this is where the antibodies of PV patients play a role, then? At least two models, both with excellent experimental support, exist for the ordering of events.

The first suggests that apoptosis is a late event in pemphigus and that it is not required for acantholysis and blister formation, while the second suggests that apoptosis occurs early, before significant acantholysis. A related viewpoint to the second is that the two occur simultaneously, though independently, though evidence exists for apoptosis actually causing acantholysis. For instance, chemical inhibitors of apoptosis have been shown to prevent lesion formation and a time-course study has shown that apoptotic cells were present before blisters in pemphigus foliaceus. The current authors looked at tissue samples from 25 patients with oral lesions due to PV. They used immunohistochemistry, the same technique that is used to diagnose PV.

Looking closely for regions where normal lesion-free tissue was adjacent to lesions, so-called peri-lesional regions, they found that 100% of the cells within lesions had fragmented DNA, the hallmark of apoptosis. In the adjacent normal tissue (in the parabasal region) of most of the samples, 75% of the cells had the marker of apoptosis. Looking at the acantholytic cells within the lesion, the result was strikingly close to 75%, at 76% and at the roof of the vesicle, it was even higher, at 80%. Given the presence of apoptotic cells in the lesion-free patient tissue, the authors concluded that apoptosis is not a late event, but an early one that may cause acantholysis. Recognizing that the structural damage (acantholysis) and death (apoptosis) of keratinocytes are mediated by the same molecular players – the caspase enzymes.

Research led by Sergei Grando has proposed a novel theory of“apoptolysis”, combining the two terms. The work of Deyhimi and Tavakoli supports this model and suggests that once a threshold level of apoptotic cells exist in the basal cell layer, somewhere north of 80%, then a lesion will form. According to the authors, conventional therapy of PV consisting of high-dose corticosteroids is based on the hypothesis that acantholysis leads to apoptosis, so it will be critical to unravel the current results and to determine if treatments might be tailored differently in the future. How apoptosis leads to formation of blisters and how antibodies to desmogleins may promote apoptosis is still under investigation, but one additional piece of information from the current work is that based on the absence of another cell death marker, Bax, the authors suspect the extrinsic cell death pathway.

The pieces to the pemphigus puzzle are beginning to be unraveled. Driven by the fact that the more we learn about the molecular events leading up to blisters, the more chances there will be to intervene before debilitating blisters can occur.

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Pemphigus vulgaris (PV) is a paradigm of autoimmune disease affecting intercellular adhesion. The mechanisms that lead to cell–cell detachment (acantholysis) have crucial therapeutic implications and are currently undergoing major scrutiny. The first part of this review focuses on the classical view of the pathogenesis of PV, which is dominated by the cell adhesion molecules of the desmosome, namely desmogleins (Dsgs). Cloning of the DSG3 gene, generation DSG3 knock-out mice and isolation of monoclonal anti-Dsg3 IgG have aided to clarify the pathogenic mechanisms of PV, which are in part dependent on the fate of desmosomal molecules. These include perturbation of the desmosomal network at the transcriptional, translational, and interaction level, kinase activation, proteinase-mediated degradation, and hyper-adhesion. By the use of PV models, translational research has in turn helped shed light into the basic structure, function, and dynamics of assembly of desmosomal cadherins. The combined efforts of basic and applied research has resulted in tremendous advance into the understanding of epidermal adhesion and helped debunk old myths on the supposedly unique role of desmogleins in the mechanisms of cell–cell detachment in PV.

From: http://informahealthcare.com/doi/abs/10.3109/15419061.2013.763799