Tag Archives: pemphigus

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Many times when seeing a physician for pemphigus or pemphigoid they are quick to prescribe a systemic treatment that will hopefully help you reach remission. This can be a good thing. However, sometimes the obvious may be overlooked.  For example, if you are in pain,  having trouble eating or swallowing, your clothes are sticking to your lesions, the blisters on your scalp make bathing and showering difficult, or perhaps you are having chronic nosebleeds. These symptoms can be managed with topical treatments, but they are often forgotten. There are different options available for different body locations in many different strengths. Be candid with your doctor and let them know where you are having disease activity and how severe it is. Although, ultimately, the systemic treatment is going to make the difference in the long run.  Topical treatment can help relieve many of your symptoms along the way!

If you’re not sure which medications to ask for or their strengths, just “Ask a Coach”!

Remember, when you need us we are in your corner!

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In February of 1995 I noticed some eruptions on my chest which I ignored. The week after I notice them, I went to a week-long school for the Air National Guard in Virginia. While at the school, the eruptions increased on my chest, as well as in my nose, mouth, and face. I was extremely frightened; I did not know what was happening to me. I thought of going to “Sick Call” but decided not to, since the school was only for one week and I wanted to finish it. When I flew home from attending the school, my family took a look at me and begged me to go to an Emergency Room immediately. Since I was very tired from the trip, I waited until the next day.

The next day I went to the Emergency Room of one of the local hospitals. The physician in the ER admitted that he really did not know what was wrong with me. My wife suggested that he call a dermatologist at a bigger hospital which he did. The dermatologist made an appointment for me for the following Monday.

On that Monday I went to the dermatologist who diagnosed me with a disease that I never had heard of–pemphigus. He told me it was a very serious disease, one that was rare and very expensive to treat. I did not know where to turn. I did not know of anyone who had this disease or of any organization who dealt with this malady. He prescribed a mild dose of steroids and sent me home. The eruptions on my skin (which I learned were called “lesions”) increased. Despite many visits to the dermatologist and increases in the medication, the condition worsened. The dermatologist that I was going to suggested that I go to either New York City or Boston for treatment since the doctors in those cities had more experience in treating this strange disease. I opted for New York City.

After visiting a dermatologist in New York City, I was admitted to New York University Medical Center for treatment in April of 1995. The dermatologist in New York City was very aggressive in treating my disease with high doses of steroids, along with other medications and blood treatments. After a week of the aggressive treatment, the spreading of my pemphigus condition stopped. After three weeks I was sent home to recover.

Slowly I was weaned off of my medications in order to determine what my “maintenance level” was. By May of 1996 I was completely off all medications and have not seen a reocrurrence of pemphigus.

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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.