Graft-versus-Host Disease: Skin, Hair and Nails

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Graft-versus-Host Disease: Skin, Hair and Nails

Thursday, May 4, 2023

Presenter: Alina Markova MD, FAAD, Memorial Sloan Kettering Cancer Center

38 minutes of presentation, followed by 21 minutes of Q&A

Many thanks to Incyte and Sanofi, whose support, in part, helped make this video possible.

Summary:  Graft-versus-host disease (GVHD) is a common complication after a stem cell transplant with donor cells (allogeneic transplant). This presentation discusses the manifestations of chronic GVHD on the skin, hair, and nails; how skin GVHD can affect activities of daily living; and pharmacologic and non-pharmacological therapies that can help patients who have skin GVHD

Highlights:

• There are two types of skin GVHD: acute and chronic. They typically occur at different times and affect organs and tissues differently.
• Depending on the severity and extent of GVHD, the treatment may be localized, such as a cream, or systemic, such as steroids that affect the entire body.
• The FDA has approved three systemic therapies for chronic GVHD: ibrutinib (Imbruvica®) ruxolitinib (Jakafi®) and belumosudil (Rezurock®) which are helpful when treating skin GVHD.

Key Points:

(03:30): The first-line therapy for acute skin GVHD is usually a topical steroid or calcineurin inhibitor in the form or a cream, spray, gel or foam.

(06:36): For patients with widespread skin GVHD, systemic steroids or light therapy may be the preferred option.

(09:20): Chronic GVHD affects skin differently than acute GVHD and typically presents more than 100 days post-transplant. It can last for months-to-years, but eventually does burn out and becomes inactive.

(09:50): Chronic skin GVHD can be non-scarring or scarring. It can affect the skin, mouth, lips, genitals, palms of the hand and fingertips.

(12:13): Sclerotic GVHD, the scarring type of GVHD, can severely limit movement and range of motion. It often appears in areas of prior trauma or prior radiation.

(15:30): Systemic therapies are typically used to treat sclerotic GVHD. Topical therapies for sclerotic skin GVHD are only minimally effective.

(17:03): Because most sclerosis starts slowly, and we expect many therapies to act more slowly, the time to improvement in chronic GVHD can usually be a couple of months before you see any notable improvement.

(18:26): Stretch marks, also known as striae, may develop with prolonged systemic steroid use, and are very challenging to treat.

(26:12): When in the sun, it is important for GVHD patients to use a broad spectrum sunblock with an SPF of at least 30, applied every one to two hours, when in the sun.

(32:37): GVHD can cause temporary or permanent hair loss. Minoxidil (Rogaine®) often helps with hair loss.

Transcript:

(00:00): [Marla O’Keefe]: Good morning. My name is Marla O’Keefe and I will be your moderator for this workshop, Graft-versus-Host Disease: Skin, Hair, and Nails.

(00:08): I'd like to thank Incyte Corporation and Sanofi whose support helped make this workshop possible.

(00:14): Introduction of Speaker. It's my pleasure to introduce to today's speaker, Dr. Alina Markova. Dr. Markova is a board-certified dermatologist at Memorial Sloan Kettering Cancer Center, who specializes in treating skin conditions that result from bone marrow transplantation. Her outpatient clinical practice is devoted to caring for people affected by graft-versus-host disease. As Co-Director of the Multidisciplinary GVHD Clinic, she partners with oncologists, hematologists, nurses, and other experts to provide patients with comprehensive care to effectively address their symptoms. Please join me in welcoming Dr. Markova.

(00:56): [Dr. Alina Markova]: Topics covered in this presentation. Thank you so much, Marla, for the kind introduction. It's a pleasure to speak with all of you today about graft-versus-host disease (GVHD) of, the skin, hair, and nails. We will review the timeline of manifestations of chronic GVHD on the skin, hair, and nails. We'll describe how cutaneous GVHD can affect activities of daily living, and we will summarize pharmacologic and non-pharmacological therapies that can help patients who have cutaneous GVHD.

(01:35): There are two types of cutaneous (skin) GVHD: acute cutaneous GVHD and chronic cutaneous GVHD. I'm sure you've learned a little bit about GVHD already. There are two main presentations of cutaneous GVHD, one in the acute phase and one in the chronic phase. Traditionally, acute cutaneous GVHD presents in the first 100 days and chronic presents after 100 days post-transplant, but either type can present at any time. We really diagnose this based on the presentation on the skin, not based on the timeline.

(02:06): Acute GVHD of the skin typically presents with pink, flat raised areas on the face, neck or hands or other parts of the body.  I will first start by discussing acute cutaneous GVHD. Acute graft-versus-host disease of the skin may present with pink flat and raised areas. This may be itchy. It can be localized just to the face, neck or hands, or it can really be generalized. The symptoms can range. Some patients may be totally asymptomatic. Others may be very itchy, even have burning pain and have symptoms that disrupt their sleep. Rarely acute graft-versus-host disease may become bullets and blister, and this is considered to be stage four acute graft-versus-host disease.

(02:48): The severity of acute GVHD of the skin is determined by the percent of involved skin. So, if you have no involved skin, then it's stage zero. If less than a quarter of your skin is involved, it's stage one. If 25 to 50% of your skin is involved, it's stage two. Over 50% is stage three. Lastly, if you have over 50% of involvement of that redness and pinkness, plus about 5% of your skin is blistering, that's considered to be stage four. This staging really helps guide treatment. If it's an extensive rash, stage three and up, that's when the transplant physician will oftentimes use systemic therapy.

(03:30): The first-line therapy for acute skin GVHD is usually a topical steroid or calcineurin inhibitor in the form or a cream, spray, gel or foam. So, how do we manage acute graft-versus-host disease of the skin? The first line therapy for localized graft-versus-host disease is typically a topical approach We have creams in our armamentarium, and we also have light treatments. Topical steroids, topical calcineurin inhibitors are the creams that we have available, and also phototherapy. For acute graft-versus-host disease of the skin, we typically use narrow band UVB phototherapy.

(03:59): Topicals can come in different vehicles and the vehicle is really how the topical medication is presented to you. It can come as a solution or a spray, a gel or a foam, and these that I just mentioned contain alcohol. The alcohol makes them easier to apply. They're great for hair bearing areas. They're great for applying to an extensive body surface area, but because of the alcohol, if you have any broken skin, they can actually create a burning sensation.

(04:34): For patients with broken skin or localized areas and non-hair bearing skin, we oftentimes recommend creams, oils, or ointments. These do not have alcohol. They're water- and oil-based and are better tolerated. They also moisturize due to their oil or petrolatum base. If you're ever prescribed a topical and you find that it's not the right quantity or you don't like the vehicle that it comes in, you can always ask your provider to send you an alternate. You can ask for something that's less greasy, for something that's easier to apply for a larger quantity. That's something that can be easily prescribed as there are many topical steroids that have equal efficacy and they come in different preparations. So, always important to ask.

(05:26): Our topical approach for management of acute graft-versus-host disease, as I mentioned, most of the treatments are applied twice daily. Topical steroids can be applied twice daily. Topical steroids are effective. However, they can thin the skin with chronic use. They can cause bruising.

(05:45): Topical calcineurin inhibitors only come as a cream or ointment, so they're greasier. They're considered to be less effective than topical steroids when we're talking about high strength. But for areas like the face, the folds, topical calcineurin inhibitors are very effective. An example would be topical tacrolimus or topical pimecrolimus. The brand names are Protopic® and Elidel®.

(06:12): The one caveat to be aware of for topical calcineurin inhibitors is that they can burn with initial application. It doesn't cause any damage to the skin, but it can cause a burning sensation. Sometimes to mitigate that, we will first start with topical steroids and then eventually transition to topical calcineurin inhibitors when the initial severe inflammation of the skin is calmed down.

(06:36): For patients with widespread skin GVHD, systemic steroids or light therapy may be the preferred option. If a patient presents with widespread cutaneous GVHD, acute cutaneous GVHD, we always speak to the transplant physician, because at that point, systemic therapy is typically indicated.

(06:50): If the GVHD is widespread but not very symptomatic, and there is a reason not to give systemic therapy, there's a contraindication, then we may recommend narrow band ultraviolet-B phototherapy, which is off-label, but is approved for conditions like atopic dermatitis or eczema and psoriasis and can be effective. This can be administered both at home and at a dermatology office.

(07:18): Take a photo of any rash you develop after transplant and share it with your doctor. The other reminder for any rash that you experience post-transplant, now in the age of telehealth and easy communication with your physician, always take photos. Take photos because they timestamp when something happens. It's something that you can always reference if the rash changes, when it started and how it first presented, and they're really helpful. Send them to your provider through the portal or whatever communication method you have available to you. These will be very important for helping manage your disease.

(07:52): Ultraviolet B is the type of phototherapy typically prescribed for patients with acute skin GVHD. It’s typically administered three times a week for three to six weeks. How does phototherapy work? There are three main types of phototherapy that we prescribe. Ultraviolet-B is the type we prescribe for patients with both acute graft-versus-host disease of the skin and a non-scarring chronic. This one, as you can see with this arrow, really penetrates just down to the basal layer of the epidermis. So, the top where you can see these cells, that's the epidermis. Below it where you see blood vessels and veins and lymphatics and then fat, that's the dermis.

(08:23): Ultraviolet-B. It penetrates down just through the epidermis where the process of acute graft-versus-host disease is. This can be typically administered three times a week. For acute GVHD, most patients require about three to six weeks of treatment. Again, this can be done in the home or at a phototherapy office at a dermatologist provider.

(08:45): You can find a phototherapy center near you at aad.org/fad. How do you find a phototherapy center? The American Academy of Dermatology actually has a website that you can navigate and it's aad.org/fad. You can enter your zip code on this website. Then under procedures, you can select phototherapy and this will provide you a list of available phototherapy providers. Then you will have to call the office and make sure that they take your insurance and then you can set up a visit and be evaluated for potential initiation of phototherapy.

(09:20): Chronic GVHD affects skin differently than acute GVHD and typically presents after 100 days post-transplant. Moving on to chronic graft-versus-host disease. Chronic graft-versus-host disease classically presents after day 100, but again can present at any time depending on how the skin appears. When we say chronic graft-versus-host disease, it doesn't mean that it lasts forever. It just lasts for a longer period of time than acute graft-versus-host disease. Chronic GVHD can last for months- to-years, but eventually does burn out and becomes inactive.

(09:50): The first type of chronic skin GVHD is non-scarring or non-sclerotic, lichenoid chronic GVHD and is sometimes referred to as lichen planus or lichenoid. These are all interchangeable words. It can present with scaly, pink, raised areas and flat areas. Sometimes a network can develop on the neck that is also part of chronic GVHD. This can be itchy. This can crack and open or can be relatively asymptomatic. There's really a variety of presentations. The symptoms that you develop will impact how aggressive we may be with therapy.

(10:34): Lichenoid chronic GVHD can also be extensive. As you can see, it can affect the palms, the hands, the nails. It can cause discoloration and peeling. However, it can also be localized. So, there's really a spectrum. I want to just emphasize that.

(10:52): Chronic GVHD can affect the mouth, lips, genitals, palms of the hand and fingertips. Chronic GVHD can affect the mouth, it can affect the lips. Patients may develop these white lacy areas on the lips, on the genitalia, and on the skin. Again, this is all non-scarring and usually responds well to topical steroids.

(11:10): When it affects the palms or the fingertips, this can be more symptomatic. This is a time when we use topical steroid ointments in order to increase the penetration and to provide a coating of lubrication to minimize the symptoms associated with GVHD of the palms and fingertips.

(11:29): The treatment for chronic non-scarring skin or non-sclerotic skin GVHD is very similar to the treatment for acute GVHD. So, topical steroids, topical calcineurin inhibitors, and narrow band phototherapy. Of course, if it's more extensive or rapidly progressive or very symptomatic, that's when we really communicate with a transplant physician to recommend a systemic therapy.

(11:55): Now, we have three FDA-approved systemic therapies for chronic GVHD, including ibrutinib (Imbruvica®) ruxolitinib (Jakafi®) and belumosudil (Rezurock®). It's very exciting to have such great therapies available for patients with more extensive chronic cutaneous GVHD.

(12:13): Sclerotic GVHD is the scarring type of GVHD that can limit movement. Moving on to sclerotic, sclerotic GVHD is the scarring type of GVHD. This is when patients develop GVHD where the skin becomes hard to pinch and it becomes bound down. Patients may have limited involvement or more extensive involvement. Depending on where your involvement and how severe it is, this may impact how aggressive we are with therapy.

(12:40): So, again, just another photo of sclerotic. This is a little bit more superficial. This patient has shiny, scaly patches and plaques, but the skin is bound down.

(12:49): Sclerotic GVHD often appears in areas of prior trauma and prior radiation. One notable thing that you may notice when you first develop sclerotic GVHD is that it can appear in areas of prior trauma. You can see in this textbook photo on the prior bra line, the patient develops sclerotic GVHD within the bra line. Also, at the waistband in the right photo and in the axilla, and in the underarms just from the trauma of moving the arm. Also, in prior lines on the right neck and on the right chest from a port and a central line. You can develop within the scars, sclerotic GVHD.

(13:22): You may also develop sclerotic GVHD in areas of prior radiation. Those are some spots where you may start to see the GVHD first, and that's something where you really want to tune in and flag your physician to assess you entirely and look for other areas of GVHD and to initiate a management plan.

(13:46): Sclerotic GVHD can affect the joints, limiting their range of motion. Of course, this can be extensive to the point where the skin scarring affects the joints. While you can have joint GVHD, you can also have just extensive skin GVHD that reduces range of motion. You can see on the legs, it can be very tight, very bound down, hard to flex the ankle.

(14:04): We assess range of motion at every visit. The way we assess the range of motion is we ask patients to perform the position in the right most column. We ask the patient to raise their arms, and we look at the shoulder to make sure there's normal range of motion in the shoulder. We then ask them to extend their elbow, to make a prayer sign, so we can examine the wrist. And lastly, we examine the ankle by bringing the toes to the shin and making sure that the patient can go past the 90-degree mark. This will tell us if the patient has tightening of the skin or joint, because tightening in either may lead to decreased range of motion. We follow this at every visit.

(14:49): Sclerotic GVHD can lead to ulcers. Sclerotic GVHD, when the skin scars significantly enough, even with mild trauma or no trauma, can ulcerate and make a wound that can be chronic or short-lived. If you notice any small wound forming, there's great wound care that can be performed to minimize the progression of the wound, and we need even more aggressive systemic GVHD therapy. Definitely let your physician know, definitely take a picture, and bring this to the physician's attention as soon as possible.

(15:30): Systemic therapies are typically used to treat sclerotic GVHD. Topical therapies for chronic scarring or sclerotic skin GVHD are minimally effective. We rely on systemic therapy as per the transplant physician. Again, treatments that are approved and have efficacy in sclerotic GVHD include the ruxolitinib, the belumosudil, and the ibrutinib and off-label treatments like extracorporeal photopheresis.

(15:54): Topical steroids, because the scarring is deeper than the top layers of the skin, really don't penetrate well. There are very superficial forms of sclerotic GVHD where the topical steroids and topical calcineurin inhibitors may have some efficacy, but really most of the sclerosis is deeper. There's usually limited efficacy with the topicals.

(16:16): Wound care is very important to reduce risk for infection, to help heal the skin and improve the quality of life. Living with wounds can be painful, can be bleeding, can be malodorous. So, really, we want to treat these. And chronic wounds put a patient at increased risk for skin cancer within the wound. We definitely want to manage these.

(16:38): When a patient develops generalized sclerosis, the patient will typically be advised to start systemic therapist, per the transplant physician. If the disease is progressing rapidly in the skin. a patient may require system steroids to control the sclerosis as quickly as possible.

(17:03): Because most sclerosis starts slowly, and we expect many therapies to act more slowly, the time to improvement in chronic GVHD can usually be a couple of months before you see any notable improvement. If you are started on a systemic therapy, don't give up hope if you haven't seen changes in the first month. Really, depending on the therapy, usually, a couple of months is where you start to see improvement.

(17:34): UVA1 phototherapy is a treatment option. However, with the new FDA-approved systemic therapies, it is used less often to treat skin GVHD.  Historically, we did recommend PUVA, which is Psoralen with UVA, but that increases, significantly, the risk of skin cancer, both non-melanoma skin cancer and melanoma. We typically try to avoid PUVA these days because there is UVA1 that is available that does not require Psoralen. However, this is not readily available. There are few centers in the country that do provide it. So, that may be more challenging to find. However, now that we have these systemic therapies that are FDA approved, we typically rely on those in lieu of phototherapy.

(18:16): Now shifting gears away from GVHD to other side effects that we see in patients who are being treated with systemic steroids for GVHD.

(18:26): Stretch marks, also known as striae, may develop with prolonged systemic steroid use, and are very challenging to treat. You can see in this patient; the patient has atrophic skin or really thin skin and these can be quite extensive. The patient has these stretch marks on the arms, on the back. When the skin is so thin, the integrity is so poor that even light trauma or movement can cause an open wound.

(18:52): How do we treat this? We can treat stretch marks. They're very challenging to treat, but we can use certain treatments to help with the cosmesis, or how they look, and sometimes to help with the skin integrity so they're less likely to break down. Any stretch mark, on its own, remodels over a year and continues to improve with time. Even if you do not treat it, it will lighten and it will slowly improve, but treatment can expedite that.

(19:19): Topical tretinoin is a vitamin A derivative and it can improve early stretch marks, but it can cause dryness and redness or peeling skin. Treatments are available and have variable efficacy. For example, topical tretinoin is a vitamin A derivative and it can improve early stretch marks. So, when a patient first develops that stretch mark, if it's used daily or twice daily for six months or longer, it can reduce the length and the width of the stretch mark. You can see in this picture here, from a study back in 1996, this patient had used tretinoin for six months and then for nearly another year and had significant improvement. Keep in mind that the stretch mark is also improving on its own, and this is the best response in their series of patients.

(20:05): This is another patient who used tretinoin for half a year and had an impressive response. But again, they chose to show the best response and most patients have a mixed response that's not quite as good, but it is something that some patients may achieve.

(20:21): Tretinoin can cause side effects such as dryness and erythema, which is pinkness or skin peeling. Keep that in mind, that a stretch mark can be asymptomatic without any symptoms and then applying this tretinoin can actually make them symptomatic or cause itching and peeling. That's something to keep in mind, weighing the risks and benefits of any intervention.

(20:45): Stretch marks may also be treated with a laser. Depending on the type of stretch mark, we use different types of lasers. If you have a pink stretch mark, as you see in the top portion of this picture, we would typically use a pulsed dye laser. Pulsed dye laser targets the vessels in the stretch marks, and that's why it works well for this. The pulsed dye laser does not typically create sores in the skin, so it can even be used if a patient is on systemic therapy that's immunosuppressive.

(21:16): If you are trying to target the thin texture in a stretch mark, usually, a fractional CO2 laser or Er: YAG laser is used. The fractional lasers work by creating little, microscopic holes in the skin that stimulate collagen to rebuild, increase the strength of the skin there and reduce the thinness.

(21:40): Because this laser creates little holes, we typically advise patients to be on minimal immunosuppressive therapy, essentially no steroids or very low steroids, because with these holes, we do put a patient at risk for skin infections. This one we reserve for when the patient is mostly off of systemic immunosuppressive therapy.

(22:09): This is an example of the fractional CO2 laser. This is just after one treatment. Three months after the treatments on the left side, you can see the A and B photos. After one treatment, you can see that the stretch marks are minimized or less white. Similarly, on the right two photos, after just one treatment. It really does help the overall appearance.

(22:33): Another treatment for stretch marks can be micro needling and this can be safe and effective. In this case series, the stretch mark is improved by over 50% after just two treatments. The main side effects of micro needling, which is typically a roller with needles, is transient pinkness. This is another treatment.

(22:53): A lot of these treatments are not covered by insurance. That's something to keep in mind. One of the main side effects of all these treatments is really the financial cost. So, you must bear that in mind with any of these recommended treatments.

(23:09): Hand washing with lukewarm water and unscented soap, followed by moisturizing, is very important if you have GVHD. Now shifting gears to skincare when you have GVHD. When you have GVHD, hand washing is something that is very important to reduce the risk of infection. Of course, hand washing is also associated with dryness, and dryness and skin cracking can also increase risk for infection.

(23:29): How do we hand wash but keep our hands moisturized? Every time you wash your hands, we usually recommend washing less than 20 seconds with lukewarm water. Then you dry your hands with a clean towel, leave some water on your hands, and apply a fragrance-free moisturizer.

(23:44): The best soaps to use. We recommend you avoid anything with triclosan or anything that says antibacterial. Any soap is great, but an unscented bar soap is what we recommend.

(23:57): For the showers, we recommend showering or bathing less for less than 20 minutes, with lukewarm water, and using a gentle fragrance-free soap or cleanser and moisturizing immediately after the shower.

(24:11): Patients often ask, "In what order do I apply the skin products when I have GVHD?"

(24:17): If you have a medicated cream or ointment that you are supposed to be applying to treat the GVHD, that goes on first when you come out of the shower, while the skin is still damp, because we want the medication to be in direct contact with the rash that you are treating. You can let that dry and then you can apply a moisturizer, then a sunscreen, and then make up if that's something that you're interested in or if you have a social event, as long as you do not have broken skin.

(24:54): How do you choose a moisturizer? You choose an ointment or a cream. Lotions are typically less moisturizing because they have a little bit of alcohol, and they can evaporate. Apply a petroleum jelly or moisturizer when the skin is damp. It locks in the moisture under the moisturizer. That's important. If you want to further seal in the moisturizer, you can cover the moisturized hands or feet with cotton gloves or socks to seal that in further, especially overnight.

(25:30): How do we choose the sunblock when we have skin GVHD? There are two main categories of sunscreen. One is chemical and one is mineral. Chemical, if you look at the back of the sunblock, will have ingredients like octinoxate, oxybenzone, or avobenzone. These are typically easier to spread on the skin. They don't leave that white residue. They're available in water resistant options. They may be best if you do not have sensitive skin.

(25:56): However, if you have broken skin or sensitive skin, the best sunblocks are really zinc oxide or titanium dioxide. They're thicker. They do not rub into the skin very easily. They do leave a white or purplish residue, but they’re a better choice for sensitive skin.

(26:12): It is important for GVHD patients to use a broad spectrum sunblock with an SPF of at least 30, applied every one to two hours, when in the sun. We always recommend applying broad spectrum, which means it protects you against UVA and UVB light and SPF, that's at least 30 or above. Oftentimes, we recommend 50 and above SPF, to apply 20 minutes before you go outside. Choose a broad-spectrum sunblock, avoid the sun between the hours of 10:00 AM to 4:00 PM, and reapply the sunblock every one-to-two hours or if you feel you're burning.

(26:46): The most effective thing, really, is to wear clothing that protects your skin from the sun. So, regular clothing like long sleeve shirts, wide-brimmed hats, sunglasses all work. If you have access to ultraviolet protective factor clothing or UPF clothing, that's even easier, especially if you have broken skin because it's so effective at blocking out the light. The most important is just avoiding the sun during the peak hours of sunlight where the sun is strongest. So, 10:00 AM to 4:00 PM. If you want to go to the beach, that's something you could do early in the morning with a lot of UPF clothing, sun protection, and a big hat. The sunglasses also protect the eyelids and the periorbital area from skin cancer as well. So, really all-important areas.

(27:36): I do want to caution everyone that if any patient is ever treated with voriconazole, this is very, very photosensitizing, which means it makes your risk for burning very high. So, on that medication, you have to have even stricter precautions, even be more sun avoidant than other patients when you are on that medication.

(28:01): GVHD patients should use fragrance-free make up made for sensitive skin, and avoid products labeled natural or unpreserved. Then how do you use makeup when you have skin GVHD? We tell patients to choose fragrance-free products made for sensitive skin, and to avoid any products that are natural or unpreserved because these can have germs that can cause a skin infection. Try one product at a time every few days. You may have new allergies after the transplant, even to products you previously used.

(28:26): It's okay to use makeup to cover a rash as long as the skin is not broken, and it's okay to use concealer to cover dark spots or light spots that may have appeared after a rash has resolved.

(28:39): It's very important to replace makeup products when you have skin GVHD. Throw out your older products and buy new ones after your transplant. You really want to start fresh. Replace mascara every few months, eyeshadows at least every year, foundation at least every one to two years, and lipsticks and blushes at least every one to two years. This is important because these makeups can really harbor bacteria and little cracks in the skin, with the bacteria in the makeup, can lead to a skin infection. So, you really want to replace these things regularly.

(29:18): Many patients have nail changes due to GVHD which may be strictly a cosmetic problem, or they may make it difficult to do things like unbutton buttons, type or text. Now, nails. Many patients experience nail changes from their GVHD, and these can be non-scarring nail changes. They can be scarring nail changes. We see brittle nails oftentimes post-transplant even without GVHD.

(29:33): So, what do we do for these? These can be asymptomatic where it's just the appearance of the nails that's the problem, or they can be very uncomfortable, making it harder to unbutton buttons, harder to type, harder to text, et cetera. Some patients may experience loss of nails, which is rarer, and typically requires systemic therapy if it's in the setting of other systemic GVHD.

(30:02): For brittle, breaking, lifting, and scarring nails, we recommend two main products. Sally Hansen Hard as Nails® is readily available. This is a nail lacquer that can harden the nail and really just needs to be painted on a few times a week. This can help protect the nail. Nail Tek® has range of products for brittle soft nails, and these can also harden the nail and protect the nail.

(30:31): For nails that have cracked, if they've cracked somewhere in the middle, sometimes we employ things as simple as Band-Aids just to protect the nail from snagging on clothing. Oral biotin, even though it has not proven to be very effective for hair regrowth, is effective for nail hardening. So, that's something we do often recommend, over-the-counter oral biotin supplements. High potency topical steroids and be used if there's an inflammatory component.

(31:00): For example, if a patient has GVHD in the skin and other areas, and the nail is becoming thinner, like I showed in the prior photo, this is when the high potency topical steroids can help. If the patient's starting to lose their nail and it's not chemotherapy-related we can do some steroid injections into that nail fold, into the cuticle, which is painful, but can be effective. Then if a patient starts systemic therapy for other GVHD, then that would also typically help with the nails.

(31:40): Even if you have effective treatment of your nails, it takes six months to grow out a new fingernail and about 18 months to two years to grow out a new toenail. So, the area where you'll look for a new nail growing out normally is right at that closest cuticle to you. If the nail's looking normal there, that's a great sign and then you just must give it time to grow out normally.

(32:02): Most transplant recipients experience hair loss. Another term for hair loss is alopecia. Alopecia just means any type of hair loss. Most transplant recipients first experience anagen effluvium, and this is the hair loss in the first six months after chemotherapy. This is chemotherapy related. We call hair loss persistent chemotherapy-induced alopecia or hair loss if the hair loss has lasted more than six months after chemotherapy. There are other treatments we can employ to help it regrow.

(32:37): GVHD can cause temporary or permanent hair loss. Patients may also experience GVHD-associated hair loss and that can occur as part of chronic GVHD. GVHD hair loss may be scarring or non-scarring. You can see there's thinning in the leftmost photo, and on the scalp - this is a closeup on the scalp of the hair follicles. There's some pinkness but there's no scale. Then on the third photo, you can see scale and inflammation that we have to target. The rightmost photo is really scarring and that's where patients can lose the hair follicle. Once you lose the hair follicle, you cannot regrow the hair. If we start to see scarring in the scalp, we want to be aggressive in treatment.

(33:20): Topical treatments for GVHD of the scalp and the hair. If you see hair thinning, fine hair after transplant, if there's inflammation, there's scale or pinkness, we typically recommend a topical steroid solution, and usually, oral minoxidil, which is oral Rogaine®. Topical Rogaine® may also be used, but oral Rogaine is typically easier to take. It doesn't have to be applied to the whole scalp if you have some hair. It doesn't make it oily or greasy, et cetera.

(33:50): If you have no inflammation, we typically just recommend no topical steroid, but just the oral minoxidil and/or oral finasteride for males and postmenopausal females. If there is scarring, we still recommend that oral Rogaine® or minoxidil. Patients, once their GVHD is burned out, may be candidates for hair transplant.

(34:15): Rogaine® (Minoxidil) can sometimes help with hair re-growth. Minoxidil works by prolonging the growth phase of the hair cycle. It helps the hair cycle to grow thicker to the patient's baseline. It's not going to make it thicker than your other hairs, but if your hairs were thicker in the past than they are now, it'll thicken them up to that hair width. In this study, these two patients, the left column is someone who had received minoxidil. The right column is someone who had received placebo treatment. They took their minoxidil during their chemotherapy. The person who had minoxidil experienced hair regrowth faster by 50 days than the person who just took placebo. While it does not prevent alopecia, it really reduces the period of hair thinning and baldness.

(35:07): This is something that's usually well tolerated. We give it at very low doses. The main side effects are excess hair growth on the face, rarely some leg swelling. On higher doses, it could lower your blood pressure, but we really give very small doses.

(35:27): Minoxidil may also help the appearance of scarring graft-versus-host disease of the scalp by increasing the background hair density. This patient has scarring on the top of her scalp. While we can't reverse the scarring, what we can do is we can start minoxidil and we can thicken the background hair, so that she has more fullness, despite having areas of hair loss that we cannot regrow. This is after 12 months of minoxidil.

(35:56): How do we take care of our scalp when we have GVHD of the scalp? We recommend washing and conditioning your hair every two to four days, using a shampoo and a cream rinse or hair conditioner. Then when you brush your hair, start at the end, use a soft bristle brush or comb or even your fingers really to be gentle to your hair.

(36:17): If you have any scale, treat that dandruff. You can use an over-the-counter antifungal shampoo like Head & Shoulders® or Selsun Blue® or you can ask your provider for a prescription ketoconazole shampoo. Even though these antifungal shampoos are called shampoos, they're really to treat the scalp. It's important to lather that shampoo, the antifungal shampoo, onto the scalp for about three to five minutes, so the medication has time to work on the scalp. It does not need to go anywhere else on the hair. Then you can always apply whatever shampoo or conditioner you like to the hair itself.

(36:54): There are also products that mask hair loss. How else do we mask? There's makeup for hair, so we can mask hair loss in different ways. There are powders, lotions, and sprays. Pigmented concealing powders can camouflage hair thinning. This is just same-day application of a camouflage powder. You can see how much thicker this area appears. Hair transplantation may also be used once the GVHD is inactive. The advantage of hair transplantation is that it's effective and permanent and it's performed under local numbing. However, there's a risk of scalp swelling, scalp bleeding, minor infections. It can look unnatural in some patients. It can create a donor site scar. If they're removing hair from the back of the head, this can leave a scar and ultimately, it's expensive because it's not covered by insurance.

(37:50): Micro-pigmentation can be used to recreate the appearance of hair follicles. There's also micro-pigmentation. This is something that can really be used in darker skin types and recreates the appearance of hair follicles. An advantage is that it's relatively permanent, it can look like pores on the scalp. There is a small risk of infection from the procedure. A patient may develop an allergy to the pigment used for the micro-pigmentation and the natural hair has to be dyed to match the pigment, because there are only so many pigment colors and patients may need touchups over time as the pigment fades. So, this is a nice additional option.

(38:24): I'm going to end here and am happy to take questions, but in summary, acute graft-versus-host disease of the skin presents with a maculopapular rash or a pink rash. Chronic graft-versus-host disease may affect the skin, hair, or nails. Many treatments are available that improve quality of life and we encourage you to notify your care team if you develop signs or symptoms of skin, hair, or nail GVHD, so that we can address them.

(38:51): In the age of telehealth and readily accessible cameras, always document any new rashes with photos. Take more photos. We'd always be happy to see more photos to have a better timeline and understanding of what's going on with you and your skin. Our overall goal is to improve your quality of life and there are many things we can do for you, so I'm happy to take questions. Thank you.

Question and Answer Session

(39:16): [Marla O’Keefe]: Thank you, Dr. Markova, for this excellent presentation. The first question is, what is the difference between red light and phototherapy?

(39:28): [Dr. Alina Markova]: That's a great, great question. Phototherapy is used for the treatment of inflammatory skin conditions, things like eczema, psoriasis, and GVHD cutaneous lymphoma. This works by increasing the regulatory white blood cells in the skin to reduce the inflammation.

(39:50): Red light is really less well-studied, and it can be used for different things like in photo biomodulation to reduce onset of sores in the mouth. There are over-the-counter products available for hair regrowth, but they were mostly still experimental. Except in the setting of prevention of mucositis or mouth sores, they're experimental. So, the efficacy of red light isn't so well-established, and it has not been tested for the treatment of GVHD on the skin.

(40:24): [Marla O’Keefe]: Thank you. Next question is, do you have any recommendations for recurrent painful lip fissures that start to heal but then crack open easily again?

(40:38): [Dr. Alina Markova]: That's a frequent issue that our patients experience. The number one moisturizer for your lips is really Vaseline® or 100% petrolatum ointment. That's really important to apply many times a day. Always avoid lip licking. Our saliva has antibacterial components. The saliva is like a soap. It can really dry out the lips and irritate them. Then, if there's frequent lip cracking, it's really important to get assessed by a dermatologist. There are many different causes for lip cracking. Things like GVHD can affect the lips, and in which case, you would want to use a topical steroid.

(41:22): After transplant, patients are at increased risk for skin cancer. You can develop skin cancer on the lips, and they can be this pre-skin cancer on the lip that's called actinic colitis. So, it's important for a dermatologist to make sure that's not what's going on, because then we could treat it with a special blue light or red light for the treatment of skin cancer.

(41:45): Also, infections can occur. There can be candida infections, yeast infections, or viral infections. If it's not responding easily to Vaseline, petrolatum, or Aquaphor, I would reach out to a dermatologist in order to help you address that.

(42:08): [Marla O’Keefe]: Thank you. The next question is how do you assess trunk scleroderma? Have you seen any benefits with myofascial manual therapy for this?

(42:19): [Dr. Alina Markova]: That's a great question. Trunk scleroderma is very challenging to assess. As I'm sure your providers have done with you, we typically do try to pinch and see how much elasticity there is and follow it over time, follow the comfort in breathing over time, and really rely on the patient assessment. The patient oftentimes will feel like their eating is better, their breathing is better if their trunk scleroderma is very tight and starts to soften.

(42:51): There have been some experimental tools that have been investigated, like ultrasound and other devices, to improve the tightening. But we follow with photos, that's really what's best, and patient reports. As far as myofascial, it is something that, if it's available, we sometimes do incorporate if a patient is motivated. And patients have had some good responses to that therapy.

(43:23): [Marla O’Keefe]: Thank you. There are a few questions here about the treatment of your fingernails. I'm going to try to combine them. They want to know what particular treatment you might suggest for nails. Someone wanted to know if biotin was good for thinning nails. Will my nails ever come back to normal or will I eventually lose them?

(43:50): [Dr. Alina Markova]: Absolutely. It depends on what's going on with your nails. For brittle nails, biotin is very helpful. We prescribe anywhere from 2.5 milligrams to 5 milligrams daily to supplement this, and usually, about a two-month course is enough to provide that nail hardening.

(44:11): One thing to keep in mind with biotin, is that biotin is not dangerous in any way. But it does interact with one test that we use to check if you are experiencing any cardiac symptoms like symptoms of a heart attack. It affects the lab processing of the test. If you are taking biotin and you do take some supplementation, and you are being evaluated for anything cardiac, or you're just going to the emergency room for any reason, tell the providers there that you're on biotin. They will check you in a slightly different way, because it affects a lab test. Just one warning about the biotin. But anywhere from 2.5 to 5 milligrams per day is an adequate dose and we usually treat for two months.

(44:56): For the nail hardening, use the nail lacquers I mentioned. The Nail Tek® as well as the Sally Hansen Hard as Nails® do work well. Also, have an evaluation for certain nutritional deficiencies. Especially if you've had a history of graft-versus-host disease of the gut, that can predispose you to nail changes.

(45:24): If you have ongoing systemic GVHD and you have associated nail changes, when your GVHD responds to treatment, the nails typically also improve. But there's typically a six-month lag period because it takes six months to grow out the nails.

(45:40): If you have scarring of the nails, sometimes they do not regrow exactly the same way, and that is the one hard thing. If you have sclerotic GVHD, sometimes you can scar over the nail matrix, which is the cells that produce the nail. So, it really depends on the type of nail condition you have, how well they respond.

(46:01): If you have just the fingernail changes after the conditioning chemotherapy you had for the transplant, those typically all grow out in about six months. It really depends, but those are some of the treatment options.

(46:17): [Marla O’Keefe]: Thank you for that. I use a topical steroid ointment for mild GVHD on my back. If the spots fade and itching is reduced, should I continue to use the ointment?

(46:32): [Dr. Alina Markova]: A very good question. Because topical steroids over time do thin the skin. If the spot fades, we typically advise patients to switch to moisturizers and then, if anything recurs, or if there are any symptoms to restart.

(46:49): Some patients will also do a maintenance treatment. Basically if everything goes away, then once a week, they'll just put a topical steroid there just to maintain it if there's still active GVHD in other parts of their skin. But if you treat and it's gone, you do not need to keep using it, because again, there are side effects with the topical steroids, including skin thinning and bruising and those are really hard to reverse.

(47:16): [Marla O’Keefe]: Thank you. This is a two-parter. For dry skin, besides Aquaphor® ointment, is there anything that you can recommend that's not quite as thick? Then someone asked if you could use coconut oil as a moisturizer, so two parts there.

(47:35): [Dr. Alina Markova]: Absolutely. I always tell patients that the best moisturizer is the one you're willing to use. So, if it's coconut oil, if it's olive oil, if there is a moisturizer you like and you're going to use it every day or multiple times a day, that's the best one. But if you are very compliant and you're eager to use any moisturizer, then I typically recommend creams, so slightly less greasy than Aquaphor or Vaseline® or Cetaphil® or CeraVe® cream. There's an Aquaphor® spray that's less greasy than the Aquaphor itself, but it's still very moisturizing. The patients like as well. But really, if there's an oil that you would like to use, go for it. Just use it frequently. That's what's most important.

(48:22): [Marla O’Keefe]: Great, thank you. How effective have you found ECP treatment for scleroderma skin, GVHD?

(48:31): [Dr. Alina Markova]: That's an important question. For sclerotic GVHD, there're now the three FDA approved therapies, the ibrutinib and the belumosudil and the ruxolitinib. Typically, with our patients, we do initiate systemic therapy with one of the FDA-approved therapies first. But in patients who have a contraindication to one of the FDA-approved therapies, or prefer to try something like extracorporeal photopheresis, it is something we do recommend, and we see good responses with it.

(49:04): But keep in mind, it is something that requires a line. Typically, most patients are unable to receive it through the IV, because it really requires a big gauge needle, and the veins can scar over time.

(49:17): It requires a long period of treatment. - oftentimes at least a year of treatment - and it's a burden because it can require twice a week treatment for several hours each treatment. So, although it is tapered over time and can be used less frequently, it is great because it does not reduce your immune system and can really work and target all organs in chronic GVHD, it does require a time commitment and a line and sometimes puts you at risk for infection through that line. So, those are the general risks and benefits, but it is something that we have seen good responses with in sclerotic GVHD.

(50:09): [Marla O’Keefe]: Thank you. This goes back to some initial questions. Someone wants to know what myofascial treatment is.

(50:18): [Dr. Alina Markova]: That's a great question. This is not available in many places. It's something where we usually refer to a physical therapist. Really, it's a massage. It's a gentle massage that can help release tightness in the skin, but it's a medical massage and there are some physical therapists and lymphedema experts that are trained in this. This can improve the circulation and the lymphatic drainage, et cetera, especially in our patients who have sclerosis on the limbs where the lymphatic drainage of that limb is impaired. This myofascial release or massage can really be helpful in draining that fluid from that extremity.

(51:14): [Marla O’Keefe]: Thank you. What can we do with the stretch marks and cellulite produced by Jakafi®?

(51:26): [Dr. Alina Markova]: So typically, with Jakafi (ruxolitinib), it's an oral Janus Kinase 1 and 2 inhibitors, so an oral JAK inhibitor. We typically do not see stretch marks and cellulitis directly related to it. What we do see stretch marks related to is steroids. And the cellulite-like changes we see in sclerotic GVHD, that's typically a side effect of the GVHD itself.

(51:54): When the sclerotic GVHD affects the panniculus or the fat, it causes scarring within it, which can simulate an appearance of cellulite. I always tell patients, if you ever start to see new cellulite appear that is more rapid in onset or atypical, always reach out to your clinicians, so that we can assess it, because that might be evolving GVHD. But we don't typically see cellulite or the scarring with ruxolitinib, although we see it in patients who are being treated with ruxolitinib for sclerotic GVHD or who have had systemic steroids in the past.

(52:28): [Marla O’Keefe]: Yeah, thank you for that. Two hair questions. One, is it safe to dye my hair after transplant? The second part is do you recommend Nioxin® shampoo?

(52:42): [Dr. Alina Markova]: Great questions. As far as safe to dye your hair, as long as your skin is intact, it typically is safe to dye your hair. I still always advise you to confirm with your bone marrow transplant physician, because if you have an active rash on the skin or a previous rash on the scalp, sometimes we may avoid hair dying for a short period of time so that we don't stimulate another reaction in that site, and we can really stay on top of managing the GVHD. But once things are quiescent, and as long as you don't have broken skin, we encourage any sort of hair dye to allow you to really enjoy your survivorship.

(53:25): As far as the Nioxin®, there's no great evidence for it. It's not harmful, based on the ingredients.  If it's something you enjoy using, then it's okay to use. But as far as mechanistically, there's no great evidence for hair regrowth with that product.

(53:49): Thank you. This person is concerned. They would like to get a manicure after transplant, and they're concerned about the tools that they use at the manicurists.

(54:00): [Dr. Alina Markova]: Absolutely. If you get any manicures or pedicures after transplant, we always recommend bringing your own tools that you've pre-sterilized, either with alcohol or any hot soap and water. Only use your own tools. I also typically recommend you bringing your own nail polish as well.

(54:25): If you're using any water, do not use any of the sinks, like the tubs for the feet. Use a bowl of water for your hands or a bowl of water for the feet, so that you're not exposed to the bacteria in the plumbing in the tubs that they have there. But it is possible to get it done. I also advise against cutting any cuticles. Just stick to cutting the nails and minimizing any skin trauma.

(54:56): [Marla O’Keefe]: Thank you. Is there anything that can be done about steroid induced very thin skin?

(55:05): [Dr. Alina Markova]: This is one of the biggest challenges we have both with topical and systemic steroids and it is very hard to reverse. Really, the best thing we can do is moisturize. In some patients who can tolerate it, where there's a particular area, we can try the tretinoin cream, which is the Retin-A cream or the vitamin A derivative cream, which can help thicken the collagen, but it's otherwise very, very hard to reverse that steroid atrophy or the skin thinning that you get with steroids. So, the best thing you can do is protect the skin by moisturizing, so that it doesn't open up with light trauma.

(55:43): [Marla O’Keefe]: Thank you. This will have to be our last question. I had skin GVHD and now the areas are darkened in the affected areas. How long does this take to clear up? Is it months? Is there anything I can do to speed up the process?

(55:59): [Dr. Alina Markova]: Absolutely. This is something that we can treat. With dark spots, they do lighten group on their own over about a year, they really do fade over the year. Anytime you have sun exposure, they can re-darken. So, we strongly recommend wearing sunblock whenever you are outside.

(56:19): As far as lightning, there are over-the-counter treatments that are available., one that has hydroquinone 2%. But the best is to get a prescription for the stronger hydroquinone treatments, such as a hydroquinone 4%. One product that works well has hydroquinone, tretinoin and a steroid, and that's called Tri-Luma®. And some pharmacies compound it as well. Those work well for lightning. Patients can also receive chemical peels to treat the skin darkening. Depending on the skin type, we may recommend a different regimen for lightning those spots. So, that is something that can be treated.

(57:01): Great. Thank you, Dr. Markova. On behalf of BMT InfoNet and our partners, we'd like to thank you for a very helpful presentation. Thank you, the audience, for excellent questions. Please enjoy the rest of the symposium.