Tag Archives: pemphigus

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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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This article is meant for those of you who have recently or about to move to a new area. After living in the greater Seattle area for 58 years, I moved to the San Francisco Bay area in August ‘14.

I encountered more challenges that I had expected. I had to find new medical insurance, since the company that I was with in WA isn’t licensed to cover in California. I also had to find a new dermatologist and general practitioner.
First, I had to decide on what kind of insurance to get. In WA I was with a company for around four years. They were much like Kaiser in the west. You can only go to Kaiser providers, labs and prescription services. I was used to this system, however it felt restrictive. The other option was to pick an insurance company that was a PPO.

Finding a GP was probably the hardest, in the sense that I felt a bit like I was shooting in the dark. My insurance agent unofficially suggested I look for a doctor within the John Muir system. They are close, and generally good. It was much easier to find a dermatologist, because I already knew who I wanted. When moving though you should always contact the IPPF and have them re-send you the physician’s referral list. This way you can see the doctors in your new area.

I was familiar with Dr. Peter Marinkovich at Stanford Medical Center. He is on the medical advisory with the IPPF and I have heard him speak before. I felt great about working with him, and his staff. It’s over an hour drive away from me, but worth it.
I have a few suggestions to keep in mind. If you are moving due to a job change, or your spouse’s, then I believe you are more restricted if you don’t want to self-pay. Read up on what kind of choices you have for a dermatologist in your area. Talk to your insurance company’s customer service if you have any questions regarding coverages. Find out how much experience the dermatologist has treating pemphigus/pemphigoid. In addition to that, it’s important to be able to feel connected, and your doctor understands you.
If you need help finding a dermatologist, feel free to contact Noelle Madsen at the IPPF office. She can make some recommendations, as well as send you a list we have. She can be reached by phone at 916-922-1288 x105 or by email at noelle@pemphigus.org.
Remember, when you need us we are in your corner!

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Having a rare disease like pemphigus or pemphigoid can make you feel like you have lost control of your life. After being diagnosed you may experience fear, confusion, and you may feel unclear about your future. You may even feel helpless, vulnerable, and at the mercy of others. Your self- esteem may be compromised along with your immune system. The anxiety or stress that can bring may be overwhelming. The good news is that these feelings are normal and more importantly that you truly do have the power to stay in control!

Here are a few tips on how to keep calm and stay in control:

1.      Offer help to others – this will help you keep your disease in perspective

2.      Find the “silver-lining,” in every situation – there is always something positive to gain

3.      Respect and accept that you can’t control everything – the sooner you realize this, the better!

4.      Don’t be a victim, be a contender!

5.      Be proud of yourself – every day is a step in the right direction

6.      Learn about your disease – knowledge is power

7.      Be self-determined – you are the master of your fate

8.      Speak up for yourself – being heard builds affirmation

9.      Consider how your disease will help you grow as an individual

10.  Don’t be afraid to ask for help and support!

You are not in this alone and there are many patients that are experiencing the struggles that you are going through. If you reach out to others through the IPPF you will find that you really are in control and together with other patients like you we have the power to overcome this disease.

Not sure how to connect with others?  Just “Ask a Coach!” Remember, when you need us, we are in your corner!