In conversation with Dr. John E Harris, Chair and Professor, UMass Chan Medical School, Dermatology.
About S Rao: I am a rising senior in high school from Cupertino, CA. I am passionate about vitiligo, in part due to having been diagnosed with segmental vitiligo a couple of years ago. I have been reading and researching vitiligo, including following Dr. Harris’s research and other blogs such as TheVitpro.com from Caroline Haye.
From the onset of vitiligo, I have gone through many years and many different types of treatments. Each step got me curious about how the human body operates, what happens in each cell and how medication, nutrition or therapies like excimer laser work. My interest continues far and beyond vitiligo into other areas in dermatology, nutrition and even broader medicine. I intend to pursue these fields in college.
Recently, I had the opportunity to visit the UMass Chan Medical School (UMass Chan), Vitiligo Clinic and Research Center in Worcester, MA. The visit gave me the privilege to interview Dr. John E. Harris, about his research, tour his lab, and even learn from his team of researchers. The session was not only educational but also an eye opener. I wanted to share what I learnt with others who follow his research.
I initiated my conversation with Dr. Harris, with the very superficial question about vitiligo and the key types - Segmental vs. Non-segmental.
“If we draw a line dividing our body from head to toe, segmental vitiligo appears on one side of the line while general vitiligo is symmetrical on both sides,” Dr. Harris replied. As an example, if one eye is largely affected by vitiligo, then in segmental vitiligo, it is only that eye that is affected, while in generic vitiligo the condition is seen across the line affecting the other eye as well.
Segmental Vitiligo is actually the less common of the two varieties. Dr. Harris says, “In kids, 20% of all vitiligo is Segmental while in adults only 5% of all vitiligo is of the Segmental type.” With segmental vitiligo, there is good news, bad news and more good news. The first good news is that with this type of vitiligo, from the onset of vitiligo to stability, is about six months. Furthermore, there are no further outbreaks - it is almost like the vitiligo spreads really fast for about six months and comes to a screeching halt. However, it is also the type of vitiligo that is much more difficult to treat. Segmental vitiligo loves to affect the hair, and once the hair follicles and the skin underneath is affected, it is extremely difficult to treat. Dr. Harris says, “The only way to treat segmental vitiligo is to get to it extremely early - jump on it at the onset and there is a great chance with treatments like excimer laser and topical steroids. This is what made the treatments very effective on you - as you jumped on it very early.” But the best news about segmental vitiligo is that since it stabilizes quickly, after six months, segmental vitiligo tends to become a great candidate for surgical treatments like MKTP or blister grafts.
Vitiligo has been around for ages. I was amazed to hear when Dr. Harris said that the early treatment for vitiligo appeared in the Indian Vedic texts, where the patient with vitiligo was fed an herb called “bakuchi” and made to sit in the midday sun till the patient sweats - the ancient origin of “PUVA” therapy. Psoralen, the chemical found in “bakuchi,” and the Ultraviolet “A” rays from the sun was the ancient PUVA treatment for vitiligo. However, researchers found that PUVA therapy increased the risk of skin cancer and is therefore not used to treat vitiligo anymore. Luckily, Ultraviolet “B” (UVB) rays, also found in the sun, can be used to treat vitiligo with no increased risk of cancer. The excimer laser treatments commonly used to treat vitiligo today are of the UVB type.
Dr. Harris and I went on to discuss topical steroid treatments for vitiligo. We spoke extensively about how they work. He said, “Essentially, topical steroid creams work by suppressing the skin’s immune response to kill the pigment causing melanocytes. Suppressing the immune response enables the skin to not kill the melanocytes, thereby helping the skin with re-pigmentation.” It is interesting that there are various ways in which one can suppress the skin’s immune response. In addition to topical steroids, there is a pill form as well. Dr. Brett King at Yale used a pill form, called JAK inhibitor, that was meant for rheumatoid arthritis on a vitiligo patient based on one of the research papers from Dr. Harris’s research. Dr. King found that the JAK inhibitor worked well on that patient for vitiligo. Other dermatologists have successfully tried the JAK inhibitor in a cream form as well. The key issue with these JAK inhibitors is that it only works when in use - once the patient stops the treatment, the vitiligo re-appears. The team of dermatologists continued to research the reasons when they found memory cells. These memory cells were responsible for the continued killing of the melanocytes after stopping the JAK inhibitor treatment.
In addition to topical steroids or JAK inhibitors, stable vitiligo can also be treated via surgical methods. The most popular methods for surgical treatments are blister grafting and Melanocyte-Keratinocyte Transplantation (MKTP). As we have learnt, segmental vitiligo quickly reaches stability. I was curious about the surgical treatment options for vitiligo, such as MKTP and blister grafting. “With the blister graft, a portion of healthy skin is extracted from the donor area - typically an area which is not visible like buttocks and surgically transplanted to the recipient area, generally visible like the face or hands. A thin slice of skin is removed, almost like peeling off the outer skin of a tomato, and transplanting it to the vitiligo affected area. In this type of transplant surgery, the donor and recipient area have a 1:1 relationship, i.e. an identical portion of skin is extracted from the donor area to fill the recipient area.”
With a 1:1 relationship between the donor and recipient area, it is clear that skin grafts can be inordinate if the recipient area is too large. Think of getting a graft to an entire arm, the graft will probably have to be from an entire leg, which is not really an effective way to surgically treat. This is precisely where MKTP is used. It is a more effective surgical treatment for large areas compared with grafts. With MKTP, a piece or two of skin, typically the size of a postage stamp, is extracted and placed in a petri-dish with an enzyme called trypsin. Trypsin digests the skin and allows for the extraction of melanocytes and keratinocytes - the pigment cells from the top layer of the skin. Once the melanocytes are extracted, the surgeon spreads the cells onto a much larger recipient area, similar to spreading butter over toast, and enabling the melanocyte cells to grow and provide pigmentation. With this type of surgery, a much larger area, almost 10 times the size of the donor area can be covered, making it a very effective treatment for larger areas. In addition, MKTP has a slight advantage that the cells blend better with the rest of the area giving a more cohesive look.
“MKTP is, however, more expensive, and can be “overkill” when skin grafts like blister grafts can work. You are a prime candidate for blister grafting and Dr. Pandya is an expert at it and can talk to you about it.” Dr. Harris said. I was excited to hear Dr. Pandya’s name because I am his patient and see him at the Palo Alto Medical Foundation clinic in Sunnyvale, CA. It was very comforting to know that the simpler option of blister grafting was more appropriate as I am dealing with a much smaller unpigmented area. Every other patch I had has healed well with excimer laser therapy and topical steroids as we jumped on the vitiligo patch quite early.
Given that MKTP is the latest in the surgical treatments for stable vitiligo, I was curious to know how many doctors perform MKTP in the world because I heard there are only a couple of clinics in the US that perform this surgery. “In the US it is only 2 to 4. We do it, and Detroit does it. Dr. Amit Pandya used to do it in Dallas and another Dr. Ganesan from UC Irvine also did MKTP procedures in the past. However, in India there are a lot more doctors who do MKTP. Dr. Sanjeev V. Mulekar came from India to Detroit and taught the Detroit doctors MKTP, and they in turn taught us at UMass. Dr. Davinder Parsad, from Chandigarh, India who is one of the world leaders, does the surgery as well.” Dr. Harris’s explanation made total sense as vitiligo seems much more common in India.
The word surgery generally sends shivers through anyone’s spine. It is generally the last resort for anyone experiencing any debilitating disease. It was for me as well, so I got curious about the surgery itself and its success factors. I went on to ask if MKTP was permanent or was there a possibility of a recurrence in areas addressed by surgery? “If it works and if it still looks good after a year then it is not likely to come back. However, we have seen some patients where it stabilized for 4 months and then after ten months it has come back. Those have never been with segmental vitiligo patients.” With segmental vitiligo being stable after six months, they respond beautifully to MKTP - anywhere from 70 to 100%. When one gets that level of improvement as long as it sticks around for a year it appears to be permanent.
With any surgery, I felt it was important to learn about any side effects. Dr. Harris gave me the good news here - “Usually if an experienced doctor does the surgery, the scar and the pain at the donor area is minimal. Blister grafting does not scar, but the skin can get hyper-pigmented and take a long time to fully heal - but will not be a permanent scar. Recipient site needs to be prepared as well. We do it in a number of ways: something like dermabrasion, or some form of laser treatment for the recipient site.”
All these surgical procedures sparked my interest. Wanting to learn more, I asked Dr. Harris whether people can notice the color variation in a vitiligo patient who went through surgical treatment. He again pointed me in the direction of Dr. Pandya, the expert in blister grafts. “I don’t think color mismatch really happens with Blister Grafting,” said Dr. Harris as he expressed his trust in Dr. Pandya’s expertise. “I think it has to do with the fact that we use split skin grafting where only the epidermis is grafted to the recipient area and the cells in the dermis below tell that epidermis how dark to be.”
With segmental vitiligo, it is quite common that the vitiligo attacks the hair follicles. I saw this to be the case with my own vitiligo. Wanting to see if the surgeries have any impact on the hair follicle, I inquired about it. “There is no real data on gray hair picking up pigment.” Dr. Harris continued, “Dr. Davinder Parsad kept an overall track of the hair repigmentation, and said that in about 10-15% of the cases, the hairs turn to the original color with MKTP. The number is even lower, 0 - 15%, with blister grafts.”
Talking to Dr. Harris was the icing on the cake for the long day I had at UMass Chan Medical School. As a prospective student of medicine, I could not have asked for a better day. Having understood vitiligo and the available treatment options, I wanted to dive into the science behind autoimmune conditions and its treatments. Dr. Harris provided me with a tremendous amount of information and pointed me in the direction of additional research. The science behind treatments is so rich and fascinating that I will be back to you all with another blog.
Finally, I would like to leave the readers with this. When I first realized I have this condition I was devastated like every other patient. But with the right guidance and exposure that fear turned into education and curiosity. It gave me the opportunity, at such a young age, to delve into science, look for the research, listen to the experts, understand the options and stay with the course of treatments. I wanted to share my writing because like someone said, sharing knowledge builds strong communities. I look at this as a new beginning of my journey and I can’t wait to start it.
