Lazareth, Victoria L.
Dermatology nurses are sensitive to the need for careful skin cancer screenings in patients who have a history of significant ultraviolet (UV) radiation exposure, be it from the sun or from medical therapeutics, including phototherapy. However, it is important for dermatology nurses to be made aware of the extremely high risk of the development of skin cancer in the patient who is an organ transplant recipient.
Patients who have received a donated heart, lung, kidney, liver, or pancreas are commonly identified as having been given "the gift of life." Having survived life-threatening organ failure, thanks to the transplantation of a healthy donor organ, these patients then depend on both the continued function of the organ and on the suppression of the host defenses to prevent rejection of the new organ.
Unfortunately, this suppression compromises the host's immune system to defend itself against the development of skin cancers and skin infections. Immunosuppressant medications impair the capacity of the immune system to repair or to destroy UV-damaged cells, allowing damaged cells to develop into cutaneous cancers.
The goal of this article is to provide a review of the works of experts in transplant medicine and dermatology for dermatology nursing professionals caring for organ transplant recipients.
RISK AND INCIDENCE
By the end of 2006, there were 223,000 Americans living with functioning solid organ transplants. With approximately 29,000 organs transplanted in the United States annually, that number will continue to climb (Burfeind, 2008).
Due largely to the medications organ transplant recipients must take to prevent their immune systems from rejecting the transplanted organs, these patients are at significantly increased risk of developing skin cancer (Lindorf, Sigurgeirsson, Gabel, & Stern, 2003). The higher dose and/or the quantity of antirejection medication required, the higher the risk of developing skin cancer. The rate of squamous cell carcinoma in transplant patients ranges from 65-fold to 250-fold that of nontransplant age-matched controls (Brennan, Rodeheffer, & Ambinder, 2006).
Physicians who attend to the dermatologic needs of transplant recipients have identified a crucial need for care dedicated to the unique problems of this patient population. Surveyed physicians reported that 10% to 50% of their transplant recipients develop 1 to 5 skin cancers annually, and one physician reported that approximately 18% of his transplant recipients have more than 10 new skin cancers annually (Carroll et al., 2003).
The risk of developing skin cancer increases as the duration of immunosuppressant therapy increases (Euvrard, Kanitakis, Decullier, Butnaru, Lefrancois, Boissonnat, et al., 2006). According to the American Academy of Dermatology (2009), some dermatologists reported diagnosing skin cancer after just 2 years of antirejection medications. For most skin cancers, the incidence increases significantly 5 to 7 years after transplantation (Otley et al., 2005). A study of 1,098 renal transplant patients in Queensland, Australia, reported that the cumulative incidence of developing skin cancer increased progressively from 7% after 1 year of immunosupression (Bouwes Bavinck et al., 1996) to 82% after 20 years (Gale, Cengage Learning, 2008).
In addition to the increased risk of developing squamous cell carcinoma and basal cell carcinoma, there is a reported increased risk of developing melanoma and anogenital carcinomas in pediatric solid organ transplant recipients. Although the occurrence of melanoma and nonmelanoma skin cancers is extremely rare in childhood, the cancers tend to develop in this population at an average age of 27 years (Euvrard, Kanitakis, Cochat, & Claudy, 2004). Many transplant recipients will develop a limited number of malignant cutaneous lesions, but some will develop hundreds of skin cancers, which can become very difficult to treat (International Transplant Skin Cancer Collaborative [ITSCC], 2009). The cancers may also be more aggressive than in the nontransplant population. These aggressive cancers are more likely to recur after treatment or to metastasize. A study of Australian transplant recipients found that 27% of deaths occurring 4 years after transplant were due to skin cancer (Burfeind, 2008). Metastatic skin cancer in organ transplant recipients is known to have a poor prognosis, with a 3-year disease-free specific survival rate of 56% (Christenson et al., 2004).
The long-term use of immunosuppressant medications taken to prevent organ rejection not only increases the risk for transplant patients to develop skin cancer, but some may also actually directly cause cancer-generating changes in skin cells. The higher doses of immunosuppressant medications required for heart and lung organ transplant recipients increase their risk even more. Lanza, Wang, Simon, and Irish (2009) called for increased uniformity in the conduction and reporting of clinical trials studying the risk and incidence of posttransplant neoplasms to improve comparison of results of one study with those of another.
Within the 15-year period from 1986 to 2001, the age-adapted incidence of Merkel cell carcinoma (MCC) rose within the general population, with a statistically significant annual increase of 8%. Furthermore, the mortality rate of MCC is about 33% higher than that of melanoma. There is also a striking epidemiological association between immunosuppression and MCC, with MCC ranking 15 times more likely and occurring at a significantly younger age in patients with organ transplants (Becker, 2009).
Organ transplant recipients are also at risk for the human papillomavirus that causes warts and may also be involved in the development of skin cancers in this population. Low CD4 counts have also been identified as a risk factor. However, UV exposure is the main factor in the development of skin cancers in transplant and nontransplant patients alike (DermNet NZ, 2009). As mentioned, the risk is heightened in the transplant population due to the suppressed capacity of the immune system to repair or to destroy UV-damaged cells, allowing damaged cells to develop into skin cancer.
Therefore, transplant patients at the highest risk are those with fair skin (Fitzpatrick Skin Type I-III), a history of significant UV exposure, advanced age (the increased risk possibly due to greater cumulative sun exposure), or a history of skin cancers or precancerous lesions prior to the transplantation. These factors underscore the need for more proactive approaches and vigilant ongoing care of patients with potentially preventable disease. Other patient characteristics which are associated with increased risk include male gender and outdoor work or hobbies.
Preventing skin cancer in transplant patients starts at the time of transplantation. Avoiding sun exposure is the principal method to prevent skin cancer that the transplant recipient can control (Gorgos, 2004). Preventive measures are important for all transplant patients, but they are particularly important for those who have additional risk factors. In a single-center, matched-pairs, observational study, a group of 60 organ transplant recipients using a highly protective liposomal sunscreen were compared with a control group matched for age, gender, skin type, transplant duration, previous posttransplant skin malignancies, and type of transplant. The results indicated remission of actinic keratoses when the patients received sunscreen and a marked reduction in the proportion of patients who developed a squamous cell carcinoma in the intent-to-treat group (Ulrich, Degen, Patel, and Stockfleth, 2008).
As outlined by the ITSCC (2009), sun-smart behaviors include the following:
1. Always wear sunscreen. Sunscreen should be rated SPF30+ and should be broad spectrum (blocking both UVA and UVB radiation). It should be applied 15-30 minutes before going outside. Sunscreen needs to be reapplied regularly during the day (every 2 hours in sunny weather, otherwise, every 3 to 4 hours).
2. Avoid sun exposure. This is especially important during the middle of the day, between 11 a.m. and 4 p.m., when UV radiation levels are at their highest.
3. Cover up well. Wearing long-sleeved shirts and pants of dark-colored, tightly woven material provides the most UV protection. Wearing sun-protective clothing that has a UV protection factor rating of 40-50+ also provides good protection.
4. Always wear a wide-brimmed hat when outdoors. Wearing a hat made of tightly woven material that shades the face, nose, neck, and ears provides protection to the head and neck.
5. Wear sunglasses. UV-protective sunglasses provide the best protection to the delicate skin around the eyes and may help to prevent ocular melanoma. Wraparound, close-fitting glasses with large lenses provide the best protection.
6. Avoid tanning beds, sunlamps, and any indoor tanning devices. Tanning lamps emit UV rays that can be up to 15 times stronger than that of the sun.
7. Schedule skin examinations. Scheduling annual full-body skin examinations with a dermatology professional is advised. During those visits, patients should be taught and encouraged to perform monthly self-examinations. Contacting the dermatology office immediately if a suspicious lesion is detected may prevent it from spreading or recurring.
Early detection of precancerous and cancerous lesions is vital to assuring the best care and the best long-term outcome. Dermatologists recommend that the patient undergo a complete skin examination prior to the transplant operation. All patients on transplant waiting lists should receive a baseline examination and counseling regarding sun-smart behaviors. This allows for detection of cancerous and precancerous lesions prior to the initiation of immunosuppressant medications, which would allow any preexisting lesions to grow rapidly and possibly more aggressively. Routine screening examinations are then scheduled regularly thereafter (ITSCC, 2009).
There are several organizational approaches that have been created to provide dermatology subspecialty clinical services to transplant patients (Christenson et al., 2004; Medical News Today, 2005). The Mayo Clinic (Rochester, MN) has organized a multidisciplinary transplant clinic that consists of physicians from transplant surgery, nephrology, hepatology, cardiology, infectious diseases, endocrinology, psychiatry, and dermatology. Comprehensive dermatologic care is provided, with emphasis on education, prevention, and early detection and treatment of cutaneous malignancies. After the recipient has been examined by the dermatologist, the interval between follow-up appointments is determined according to the guidelines recommended by Otley et al. (2005) (Dapprich et al., 2008):
1. No history of skin cancer or actinic keratoses: 12 months
2. History of actinic keratoses or one non-melanoma skin cancer: 6 months
3. History of multiple nonmelanoma skin cancers: 4 months
4. History of high-risk squamous cell cancer or melanoma: 3 months
5. History of metastatic squamous cell cancer or melanoma: 2 months
Another format is to designate dermatology clinics for transplant recipients. The largest clinic of this type is the Charite University Hospital, established in Berlin in 1998, where 6,000 transplant recipients receive care (Christenson et al., 2004). Extensive research is being performed at this clinic, including building an extensive database to record all malignancies, infections, and other dermatoses occurring in the patients. This database, Skin Care in Organ Transplant Patients, is being networked throughout Europe and at some sites in the United States. In addition to epidemiological studies, there are investigations on immunology of skin cancers, human papillomavirus or oncogenic viruses, herpes simplex virus and mycoses, and immunoresponse modifiers in the treatment of actinic keratoses.
A third option presented by Christenson et al. (2004) is to integrate transplant recipients into existing dermatology clinics. The number of patients seen per week ranges from 1 to 20, fewer than that seen in the multidisciplinary and designated clinics. Over half of the physicians provide comprehensive dermatologic care, but primary emphasis is on the diagnosis and treatment of skin cancer. Many of the differences in the management of transplant recipients in this clinical setting compared with the settings described earlier may be explained by most of the physicians being dermatologic surgeons; thus, their patients are referred specifically for the care of skin cancer.
Regardless of the clinic design used for the care of transplant recipients, Christenson et al. (2004) concluded that the following components are vital in providing the best care:
1. Close communication with the team of transplant physicians and nurse coordinators is essential in establishing effective care models and dermatology transplant subspecialty clinics.
2. Grand rounds and lecture series to educate other care providers about the unique dermatologic concerns of transplant recipients and the need for preventive care are effective ways to initiate the necessary working relationships.
3. Establishing an effective scheduling mechanism for seeing transplant recipients in dermatology is important. Incorporating a baseline dermatologic examination into the routine care of all transplant recipients or using a triage system for early referral to dermatology of high-risk patients is recommended.
4. Patient education is key to skin cancer prevention. Education efforts include reviewing sun-smart behaviors and the ABCDEs of self skin examinations at each visit. Offering encouragement may help to motivate patients to incorporate these behaviors into their daily routines.
5. Chemoprophylaxis (the use of medications that can reduce the tumor burden) is important and is used by nearly all physicians who care for transplant recipients.
6. Comprehensive dermatologic care is important for these complex immunosuppressed patients.
7. Close follow-up determined by the risk of skin cancer is necessary.
In its Web site on skin cancer, the American Academy of Dermatology (2009) acknowledges that, although these steps can be frustrating for patients, they remain the best means to control the aggressive skin cancers that often develop in transplant recipients. Early detection resulting from regular screenings can improve the patient's quality of life by reducing the number of invasive lesions and by preventing their spread.
A study conducted by Dr. Summer Youker (Burfeind, 2008) surveyed 298 solid organ transplant patients who attended the outpatient transplant clinics at Saint Louis University. Participants completed a two-page survey to evaluate their comprehension of skin cancer risk, their compliance with skin cancer preventive measures, and their attitudes about sunscreen use and skin screenings. Dr. Youker reported that 62% of respondents did not know they were at risk for skin cancer, and 73% of respondents stated that they were not informed about the risk of skin cancer after their organ transplantations. In fact, only 21% of patients had seen a dermatologist since their transplant, with even fewer (14%) receiving annual skin examinations.
"Educating transplant patients about the risk of skin cancer is essential, but multiple studies have shown that education during their postimplantation hospital stay is not retained by patients and is not enough to change patient behavior regarding sun protection," said Dr. Youker. "Because the time around an organ transplantation is consumed with the more pressing issues of rejection and infection, patients cannot be expected to recall information regarding the risks of sun exposure," explained Dr. Youker. "Clearly, another method of informing patients of this risk is needed, preferably one involving dermatologists, who can assist the transplant team with strategies to educate and treat this high-risk patient population."
Dr. Youker cited a related study, Educational Outcomes Regarding Skin Cancer in Organ Transplant Recipients, published in the June 2006 issue of the Archives of Dermatology, that found that the patients who received an intensive educational program in which written reminders reinforced the risk of skin cancer fared significantly better in terms of complying with the recommended sun-protection tips than those patients who did not receive this education (Burfeind, 2008).
Over a 10-month period, 202 high-risk patients presenting for transplant dermatologic consultation at the von Liebig Transplant Center at the Mayo Clinic were randomly assigned to receive standard episode-of-care-based education or intensive repetitive written education about skin cancer after organ transplantation. Patients who received the intensive educational intervention were significantly more compliant with recommendations for sun-protective behavior than were those who received standard education, although differences in knowledge were not apparent (Clowers-Webb et al., 2004).
Nurses are especially well positioned to provide effective education regarding the risks, prevention, and early detection of skin cancers in organ transplant recipient patients (Gorgos, 2002). Karen Lario, RN, presented a poster reviewing the importance of sun protection in organ transplant recipients at the Dermatology Nurses' Association conference in San Francisco in 2009, the abstract of which was published in the Journal of the Dermatology Nurses' Association (Lario, 2009). Lario noted that, although skin cancer is one of the most significant causes of morbidity and mortality in the organ transplant patient, many transplant clinics do not include dermatology care in their preoperative and postoperative teaching. She concluded that dermatology nurses who understand the potential for antirejection medications to predispose organ recipients to dermatologic disease have a unique opportunity to teach patients and other healthcare professionals about the importance of sun protection and regular complete skin examinations. Preventive measures and early detection may reduce the burden of skin cancer and may improve the quality of life in the solid organ transplant recipient.
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