Skin Changes and Cancer Treatments: Tips for Healthy Skin and Hair
This is a summary of a lecture that was presented on September 14, 2010.
Why address issues of the skin? – Dr. Carolyn Goh
It may seem obvious, but both patients and physicians often do not address the issue of skin care as part of regular cancer care. Cancer and its treatments often impact skin quality, especially when there are appearance changes and discomforts such as pain and itching. Most importantly, skin changes that cannot be controlled might lead to a dose adjustment of medication, which may alter the likelihood of optimal response to therapy.
There are many causes of skin changes in patients with cancer. For some patients the skin changes are related to the malignancy itself including metastases, primary cancers and some immune disorders. They can also be related to cancer therapy as well as non-cancer therapy conditions. Finally, they can be related to being immunosuppressed, which is a result of many cancer treatments. It is important to have an accurate diagnosis and to understand what may be causing the skin changes.
Cancer Therapy and the Skin, Hair, and Nails – Dr. Carolyn Goh
There are 52 distinct skin toxicities that have been reported as a result of 41 unique agents or their combination. This includes chemotherapy, radiation therapy and newer targeted agents. The two agents that cause the most skin toxicities include cetuximab (Erbitux) and sorafenib (Nexavar). Both traditional chemotherapies and the newer targeted treatments can affect skin, though the profile of side effects may be different. Skin, hair and nails are affected by chemotherapy because they have rapidly dividing cells; cancer tends to also have rapidly dividing cells so most chemotherapies target these cells. The skin, hair and nails become innocent bystanders. Radiation can have direct toxic effects on the skin as can chemotherapy that leaks out of the IV and has contact with the skin. The newer targeted therapies that block the epidermal growth factor receptor (EGFR) to inhibit cancer cells from growing also affect the skin because EGFR is crucial for the normal development and physiology of the epidermis (skin). Blocking EGFR receptors can affect the cells of the epidermis (skin), causing inflammation and sensitization of the epidermis to ultraviolet (UV) radiation.
CHANGES IN HAIR
Alopecia (hair loss) is a common side effect for many but not all chemotherapy agents. Hair has a natural cycle that involves three phases of growing, resting and falling out. Not all hair is synchronized on the same cycles, which is why hair is maintained. Usually about 90% of hair is in the active growing phase and these are the ones that are affected by chemotherapies that affect rapidly dividing cells. Hair usually starts to fall out within days to weeks of starting therapy and completely in 1-2 months. It mostly affects the scalp, but can also affect eyelashes, eyebrows and beards. It is usually reversible and hair re-grows 3-6 months after stopping therapy. Hair may be different in color, structure and or texture. Sometimes the density of the hair may remain low after chemotherapy. There are only a few cases of permanent hair loss reported. When permanent hair loss occurs it may be due to some other process that is unmasked from the treatment.
Combination therapy is more toxic and the duration and intensity of the treatment are also factors in hair loss. Anti-microtubule agents, such as paclitaxel, cause hair loss 80% of the time. Topoisomerase inhibitors, such as doxorubicin (Adriamycin), cause hair loss 60-100% of the time. Alkylators, such as cyclophosphamide (Cytoxan), cause hair loss in 60% of the patients who receive it. Antimetabolite chemotherapy, such as 5-fluorouracil (5-FU), causes hair loss about 10-50% of the time. Epidermal growth factor receptor inhibitors, such as cetuximab, only cause hair loss 5-6% of the time.
Radiation therapy can also cause alopecia in the area that is irradiated. Sometimes radiation causes scarring and, therefore, the hair loss in a particular area can become permanent. Some patients have experienced a delayed response 4-6 months later in which the stress of the treatment causes the phases to become synchronized for all hair and their hair all falls out. It is usually temporary.
Many patients facing hair loss want to know if any treatments prevent or lessen the severity of hair loss. Scalp cooling caps have been used, but are not recommended in leukemia or lymphoma and there is some concern about the possibility of scalp metastases. These cooling caps may induce headaches, claustrophobia and discomfort due to the cold. Minoxidil (Rogaine) can also be helpful and it comes in 2% or 5% solutions or 5% foam. The 2% solution was found to decrease the severity and/or shortened the duration of hair loss in some patients. There are more side effects for women than for men. Other coping strategies include hats, scarves, wigs and hairpieces.
Hypertrichosis/eyelash trichomegaly is a condition in which the eyelashes continue to grow. They do not stop and tend to grow quite long and often become a bit unwieldy and out of control. It appears 100 days after starting EGFR inhibitors. Patients who develop this should have an ophthalmology evaluation because they are at an increased risk for corneal ulcerations, which is also associated with contact lens use. It may persist through treatment and may not stabilize, thus the eyelashes continue to grow.
COMMON SIDE EFFECTS OF THE SKIN
A rash known by a variety of names, including papulopustular eruption, can develop with some treatments. It is most notably associated with epidermal growth factor receptor inhibitors (EGFRI) and occurs in 60-80% of patients. It can also occur in monoclonal antibody therapies (treatments in which the name ends in “ab”) and in tyrosine inhibitors (treatments in which the name ends in “ib”). It can be associated with taxanes and steroids. When it appears in conjunction with EGFRI’s, the severity of the rash is ironically associated with better tumor response. It is usually, bumpy, red and the bumps can be pus filled. It tends to develop on the face chest, back, scalp, palms and soles. It may or may not be itchy and or tender. It is often dose dependent; the higher the dose, the greater the rash. Lesions occur within 1-3 weeks of initiation of the EGFRI therapy. The maximal skin toxicity occurs by 3 to 5 weeks. Lesions tend to resolve within 4 weeks of EGFRI cessation. Spontaneous improvement or stabilization of lesions can occur with continued EGFRI therapy.
There are a variety of treatments depending on the severity of the rash. Topical applications of hydrocortisone and clindamycin are often used for mild forms. More significant forms may require the use of systemic antibiotics and very severe forms may need a short course of steroids. Make-up is often used to cover it when it occurs on the face. Colloidal oatmeal lotion is also helpful as are topical steroids. Pre-emptive treatment has also been shown to be beneficial. For example, patients on cetuximab who also took 100 mg of minocycline once a day experienced less severe rash during their first month of treatment. For patients on panitimumab there was a 50% risk reduction in developing more severe (grade 2 or worse) rash by following specific steps that included the following steps:
- Using a skin moisturizer and applying it to face, hands, feet, neck, back and chest each day in the morning upon rising.
- Sunscreen that is PABA free with an SPF greater than or equal to 15 with both UVA and UVB protection should be applied to exposed skin areas before gong outdoors.
- Topical steroid (1% hydrocortisone cream) can be applied to the face, hands feet, neck, back and chest at bedtime.
- Doxycycline (100 mg) can be taken twice a day.
When a dermatologist sees a patient with these rashes they are categorized into 4 levels of severity which include:
- Grade I: Papules and/or pustules covering less than 10% of body surface area which may or may not be associated with symptoms of pruritus (itching) or tenderness.
- Grade II: Papules and or pustules covering 10-20% of body surface area which may or may not be associated with symptoms of pruritus or tenderness; associated with psychosocial impact limiting instrumental activities of daily living.
- Grade III: Papules and or pustules covering greater than 30% of body surface area which may or may not be associated with symptoms of pruritus or tenderness; limiting self-care and activities of daily living; associated with local super-infection with oral antibiotics indicated.
- Grade IV: Papules and/or pustules covering any % of the body surface area which may or may not be associated with symptoms of pruritus or tenderness and are associated with extensive super-infection with IV antibiotics indicated; life threatening consequences.
In summary, treatments include counseling about the condition and self-care of the skin, doxycycline or minocycline twice per day at 100 mg, mometasone cream (topical steroid) twice per day for 2-3 weeks, a transition to topical pimecrolimus or tacrolimus (steroid sparing cream) for the face, higher potency topical steroids for non-facial skin, and a wash for the face that is used as an acne treatment called sodium sulfacetamide wash.
Some chemotherapies (cytarabine, 5-fluorouracil, doxorubicin, and methotrexate) can cause hand-foot syndrome, another significant skin effect. It occurs in 6-42% of patients and is characterized by red, burning, tender lesions on the palms and the soles of the feet. Blisters may develop and the risk increases with higher dose chemotherapy, cumulative doses, increased age and when used in women. It happens due to secretion of the medication in ecrrine glands. Eccrine glands (or merocrine glands) are the major sweat glands of the human body, found in virtually all skin. Hand-foot syndrome is treated with regional cooling topical moisturizers, urea, corticosteroids, and dose modification.
There is a slightly different hand-foot syndrome associated with targeted therapies such as sorafenib (Nexavar) and sunitinib (Sutent). In this condition, the inhibition of growth factor receptors may prevent the normal repair of skin in high-pressure areas which are often exposed to a low level subclinical trauma. It develops 2-4 weeks after the onset of therapy and is more likely to occur when there is a combination therapy. Before treatment with these agents it is important the patient have a consult with a podiatrist and a dermatologist. If there is abnormal weight bearing on certain parts of the feet it may be a good idea to get orthotics. Also reduce exposure to hot water (i.e., dishwashing and baths). Reducing calluses may reduce potential risk. During the first month of therapy it is a good idea to prevent trauma by resting and wearing thick cotton socks and gloves to minimize trauma. Once symptoms start, urea cream and salicylic acid can be helpful. In addition, topical corticosteroids, topical analgesics, and non-steroidal anti-inflammatories, such as Advil and Motrin, are also beneficial. Patients may need a dose modification of their treatment. This syndrome has not been found to be related to the efficacy of the treatment. Fissures can develop in localized areas such as the tips of the fingers and heels. It usually starts around the third week with EGFRIs. It is important to use thick moisturizers (creams rather than lotions) at least twice daily. Liquid bandage, Krazy Glue or Dermabond are sometimes used to fill the fissures and reduce discomfort.
There are two types of radiation-induced skin problems. One is acute and one is chronic. In the acute phase there is redness, swelling, edema, itching, tenderness, necrosis desquamation and ulceration. In addition, the acute reaction can be reactivated 2 days to 15 years later with the administration of some chemotherapeutics. This is called a “recall” reaction in which the skin has a memory. Emollients are helpful. Chronic conditions develop months to years after radiation exposure. There may be changes in the pigmentation of the skin, either lightening or darkening, scaling, dry skin, thick skin, swelling, or dilated blood vessels. Treatments include laser, oxygen therapy and keratolytics.
Mucositis can occur 5-9 days after chemotherapy and last 7-14 days. It develops because the body is unable to repair the mucosal lining of the mouth. Ice chips and specific mouthwashes can be helpful.
Nail changes are common with the taxanes, capecitabine, bleomycin, hydroxyurea and EFGRI’s. Common nail changes include Beau’s lines which creates a groove in the nail, brittle nails, loss of nails, and hyperpigmentation. Non-specific changes such as beau’s lines and hyperpigmentation result from acute stress on the nail matrix where the nail grows. Approximately 20-44% of patients getting docetaxel and paclitaxel lose their nails or have darkening under their nails from debris, blood and pus under the nails.
Paronychia is inflammation of the areas around the nails. It develops in 12-58% of patients on EGFRIs. It usually occurs after 4-8 weeks of therapy, is associated with tenderness and it usually impairs daily activities.
Taxane-induced nail changes are sometimes prevented or reduced with frozen gloves worn 15 minutes before administration of taxane, during the one hour infusion, and for 15 minutes after. Moisturizer and gentle hand and foot care are important.
EGFRI nail changes benefit from moisturizer and many oncologists recommend that you refrain from manicures and pedicures as well as any “wet” work such as dishwashing. Vinegar soaks (1 part water to 1 part white vinegar) for about 5-10 minutes daily can be helpful for both taxane-based and EGFRI-based nail conditions. Beau’s lines usually resolve with time.
In sum, there are many cancer therapies that affect the skin, hair and nails. Combination therapy and higher doses lead to higher risk of developing most reactions. Preventative measures can be taken and treatments are available. Studies are currently ongoing, particularly for hand-foot syndrome and papulopustular eruption, in order to improve treatment options.
Tips for Healthy Skin – Dr. Jenny Kim
What are the basic issues of normal aging and skincare? There are two major factors of associated with aging skin. The first are the intrinsic ones which are genetically programmed, occur with time and differ significantly by individual. There is nothing to be done about these. The extrinsic factors include environmental factors such as ultraviolet radiation, pollution, harsh weather and smoking as well as medical factors such as surgery, chemotherapy, radiation and medication. Aging in the face can come from surface changes such as brown spots, broken vessels and lines. Soft tissue changes include thinning of the skin, less collagen, loss of elasticity, and the loss or gain of fat. Muscle changes can lead to wasting and thickening. Skeletal changes include coarsening of bony prominences or loss of bone such as in the jaw.
Dry skin care is very important. Skin can be protected by not showering too frequently as this washes away the body’s natural good oils. Warm showers are better than hot water showers because fewer oils are washed away. Skin cleansers should be used rather than soap because soap has drying effects. When drying off after a shower it is better to pat the skin dry lightly rather than rubbing it vigorously. Applying emollients on the skin helps to maintain moisture. Creams are better than lotion because they are thicker and hold in more moisture. Consider using extra treatment at night. Use ointments on extremely dry areas overnight such as on the lips, feet and hands. Wearing cotton gloves or socks over the ointments help to keep them on the skin for longer, providing more protection.
Skin has a circadian rhythm. Oil production is highest at noon. The temperature of the skin is higher at night and, therefore, there is more water loss at night. Thus, it makes sense to replenish moisture more in the evening.
Suntans may look nice but they are not good for your skin. They are the single most aging event that affects your skin. Sun tanning became popular in 1923 when Gabrielle “Coco” Chanel was seen cruising on Duke Wellington’s yacht from Paris to Cannes. Ultraviolet B rays (UVB) cause immediate sunburn. Ultra violet A rays can cause chronic aging. Our skin is like a grape; when put in the sun it becomes wrinkled and old looking like raisins. There are many harmful effects of the sun plus it down regulates the immune response. Sun ages the skin causing wrinkles, uneven complexion or pigmentation and can give the skin a leathery texture. It can also cause eye damage such as cataracts. . Sun exposure causes skin cancers such as melanoma, basal cell and squamous cell carcinomas. It is important to note that not all melanomas are related to sun exposure and there is a growing interest in the genetics associated with BRCA genes and their association to melanoma.
It is very important to protect your skin from the sun. To do this, avoid direct sun especially between 10 am and 4 pm. Wear protective clothing including hats, covers and sun glasses. Sunscreens should include protection for UVA and UVB rays. They now make clothes that are tightly woven to reduce sun exposure and there is soap that can be put into clothes that increases its SPF factor. The best sun protection comes from physical blockers that contain micronized zinc and titanium, although zinc is better. Parsol 1789 and mexoryl are also important. Always use an SPF of 15 or greater. Apply sunscreen every 2 hours when outdoors and use sunscreen daily. Do not ever use sunlamps or tanning beds. No matter what you have heard, no tan is safe. In addition, examine your skin regularly and see your dermatologists for skin checks.
Many people wonder whether topicals applied to the skin can help with reducing the impact of already damaged skin. There are a variety of these including retinoids, hydroxyl acids, growth factors, peptides, and antioxidants. The retinoids are the most superior products.
DOES EATING HEALTHY HELP THE SKIN?
There are no studies that suggest that eating specific foods will help to reduce damage caused by the skin, but healthy eating helps your organs and body be healthy. Your skin is important and is the largest organ of your body. Yes, your skin is an organ! Vitamin A, found in foods such as liver, milk and eggs is the most biologically active. Carotenoids (provitamin A) are found in carrots, tomatoes, and other colorful vegetables and fruits. All of these foods are part of a healthy diet. Vitamin A does help with reversing photo damage, increases collagen and the anti-oxidant effects may help reduce wrinkling, but these benefits are most likely found when it is applied directly to the skin.
Vitamin C (ascorbic acid) is found in citrus fruits and dark leafy vegetables. Vitamin C is a co-factor for collagen and elastin synthesis. It is also an anti-oxidant and increases collagen I and III. No clinical research to date has established that Vitamin C is good for the skin, but it is important in an overall healthy diet.
Vitamin D is found in liver, beef, and egg yolks. Large amounts are found in oily fish such as wild caught salmon. Vitamin D3 can be synthesized from 7-dehydrocholesterolin skin cell membranes and UVB exposure; however this also creates the risk of sun damage. Many people are vitamin D deficient and it is needed for good bone health. Research indicates that Individuals who have sufficient vitamin D levels have fewer falls. Vitamin D3 is being given in higher doses than ever to elevate and sustain people’s levels because of the many health benefits that good vitamin D levels are associated with, including reductions in cancer and osteoporosis. Vitamin D appears to have benefits on the bones, heart, cancer risk and the immune system. Vitamin D levels are affected by skin color (darker skin is equated with lower D levels in the blood serum), latitude, diet and sun exposure. The US government is currently recommending significantly lower levels of Vitamin D than Americans probably need. There is a growing consensus that individuals need between 2000 and 4000 IUs per day. It would require drinking 40 glasses of milk per day to get 2000 IUs of vitamin D. There are no large controlled studies to demonstrate clinical efficacy of oral vitamins and antioxidants in skin rejuvenation or reversal of photo aging of the skin. However, your skin reflects your health and well-being; vitamins (often found in a rich and healthy diet) are important for your health.
There are a variety of age-related skin problems and skin disease that can develop including actinic keratosis (scaly or crusty bump), melanoma, non-melanoma skin cancers, acrochordans (skin tag), cherry angiomas (small red bumps, vascular in nature), seborrhea keratosis (raised growth), lentigenes (sun spots or liver spots), pruritus (itching), bullous pemphigoid (chronic blistering of the skin), herpes zoster (shingles), xerosis (abnormal dryness), purpura (red or purple spots) and rhytides (wrinkles). There are many common non-surgical and aesthetic treatments that are used including botulinum toxin, fillers, laser hair removals, microdermabrasion and laser skin rejuvenation. Approximately 10 million of these treatments are performed each year. Broken blood vessels in the face are treated with pulsed dye laser or an intense pulse light (IPL). Freckles are treated with lasers, IPL liquid nitrogen and chemical peels. Botulinum toxin (Botox) is used to treat the bunny lines on the nose, lip lines, the chin, the lower mouth, neck and frown lines in the forehead. Fillers can be used to improve the shape and size of lips. Collagen was used but is no longer made. Other types of fillers include hyaluronic acid, polymethylmethacrylate (PMMA) calcium hydroylapetite, poly-L lactic acid, and silicone. Some are considered better than others. Scars can be a problem for some cancer survivors. They can sometimes be flattened out or the redness reduced using steroid injection, pulsed dye laser, fractional photothermolysis lasers and surgical revision.
It is important for survivors to know that there are no contraindications for them in using these techniques. Having cancer does not mean that you cannot be concerned about your appearance or want to make aesthetic improvements. Fillers are only contraindicated if you are allergic. Botulinum toxin is contraindicated if you are allergic or have any neurodegenerative conditions.
Chemotherapy induced hair loss is a distressing side effect for patients that often affects quality of life. It is important to use sun protection on the scalp during this time. Avoid harsh chemical products as much as possible; using topical treatment to replace oil can also be helpful. Most patients use hats, scarves, wigs or other hair pieces. Eyelash regrowth could take longer because of the longer resting phase for eyelashes. Bimatoprost has been used to help make eyelashes grow longer, fuller and darker. It has not been studied in patients with cancer as of yet. It was originally used as a treatment for glaucoma and was found to have this effect on eyelashes.
To protect nails, whether on chemotherapy or not, cut nails short. Don’t cut your cuticles, instead push them back or use cuticle removal creams. Wear gloves for chores and avoid excessive water on skin which can cause fungal infection. During treatment use clear or light polish to keep nails strong but also allow you to see any potential color change. Use non-acetone based polish remover. Avoid acrylic nails which can trap bacteria. Oncologists often recommend you avoid manicures, but if you do have them done bring your own instruments. If you experience persistent irritation and or inflammation around the nails, see your doctor.
In sum, good skin care is important during and after treatment. It is always important to minimize sun exposure. Antioxidants can be used topically. Having a healthy diet is good for all parts of your body and vitamin D is especially important. Exercise is also good for good health and may be helpful for a healthy mind as well. Almost all skin rejuvenation treatments can be used after a cancer diagnosis.
For reprint authorization, contact SimmsMannCenter@mednet.ucla.edu.