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Transplantation dermatology: Race matters

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By Warren R. Heymann, MD
June 21, 2017

African American man with generalized vitiligo. Medial aspect of foot before (A) and 5 months after (B) melanocyte-keratinocyte transplantation procedure.
Credit: JAAD
December 3rd, 2017 will mark the 50th anniversary of the first human-to-human heart transplant performed by the late South African cardiothoracic surgeon, Christaan Barnard. On Dec. 2, 1967 Denise Darvall, a 25-year old accounting-machine operator, was struck by an automobile while crossing a street in Cape Town. She was found to be clinically brain dead but her heart was in good condition. She had the same blood type as Louis Washkansky, a grocer, who became the first cardiac transplant recipient. He died 18 days later of pneumonia attributed to immunosuppression from azathioprine and steroids (1).

Half a century of progress in transplantation has fostered tremendous progress — mortality following solid organ transplantation is decreasing due to improved immunosuppressant regimens and better surgical outcomes. Currently, there are 170,000 solid organ recipients in the USA. As transplanted patients live longer, their level of risk for acquiring malignancies, especially skin cancers, increases. More than 50% of solid organ recipients will be diagnosed with at least one skin cancer. There is also increased risk for squamous cell carcinoma (SCC) of 65–250 times and for basal cell carcinoma (BCC) of 10–16 times those of the general population (2). Although chronic graft rejection remains a leading cause of post-transplant mortality, death due to malignancy in organ transplant recipients (OTR) may occur in up to 12% of subjects in the United States, with nonmelanoma skin cancer (NMSC) being the most common. This is especially true for older, white, male patients who are thoracic transplant recipients (3).

What is the risk of NMSC in OTR patients of color?

Chung et al performed a retrospective review of 412 OTRs treated at Drexel University’s multidisciplinary transplantation clinic. Prevalence and characteristics of cutaneous disease were compared in 154 white and 258 nonwhite (Asian, Hispanic, and black) OTRs.

The 412 patients undergoing analysis included 264 men (64.1%) and 148 women (35.9%), with a mean age of 60.1 years. White OTRs more commonly had malignant disease at their first visit (82 [67.8%]), whereas nonwhite OTRs presented more commonly with infectious (63 [37.5%]) and inflammatory (82 [48.8%]) conditions [See the appendix below for a list of these disorders]. Skin cancer was diagnosed in 64 (41.6%) white OTRs and 15 (5.8%) nonwhite OTRs. Most lesions in white (294 of 370 [79.5%]) and Asian (5 of 6 [83.3%]) OTRs occurred in sun-exposed areas. Among black OTRs, 6 of 9 lesions (66.7%) occurred in sun-protected areas, specifically the genitals. Fewer nonwhite than white OTRs reported having regular dermatologic examinations (5 [11.4%] versus 8 [36.4%]) and knowing the signs of skin cancer (11 [25.0%] versus 10 [45.4%]).

The authors concluded that treatment of nonwhite OTRs should focus on inflammatory and infectious diseases. Sun protection should continue to be emphasized in white, Asian, and Hispanic OTRs. Black OTRs should be counseled to recognize the signs of genital human papillomavirus infection. Optimal posttransplant dermatologic care may be determined based on the race or ethnicity of the patients, but a baseline full-skin assessment should be performed in all patients. All nonwhite OTRs should be counseled more effectively on the signs of skin cancer, with focused discussion points contingent on skin type and race or ethnicity (4).

Regardless of race, long-term immunosuppression in organ transplant recipients (OTRs) leads to decreased immune-mediated tumor surveillance and development of malignancies. A delicate balance needs to be maintained in the intensity of immunosuppression to keep the risk of malignancy low without jeopardizing life-saving graft function. In addition to SCCs and BCCs, other reported skin cancers in OTRs include Kaposi’s sarcoma, Merkel cell carcinoma and malignant melanoma. Tumors in this high-risk population are aggressive and may respond poorly to standard therapies. Fortunately, new, targeted therapies are promising. Checkpoint inhibitor antibodies have been used for treatment of cutaneous SCC, Merkel cell carcinoma, and MM; epidermal growth factor receptor inhibitors for cutaneous SCC; hedgehog pathway inhibitors for BCC; and BRAF and MEK inhibitors are being used increasingly in the management of MM in OTRs. (5)

Vigilance in screening for skin cancer, sun protection, consideration for use of the HPV vaccine, and administration of retinoids (notably acetretin) are vital in preventing skin cancers in this high-risk group. Other chemoprevention therapies currently being studied include difluoromethylornithine, cyclooxygenase inhibitors, nicotinamide, and antioxidants.(2). Christina Chung and her group have offered a refined pathway for skin cancer prevention in our increasingly multicultural society. This should help reduce morbidity and mortality in transplant patients of all races and ethnic backgrounds.

1. Altman LK. Christiaan Barnard, 78, Surgeon for first heart transplant, dies. New York Times, Sept 3, 2001.
2. Perez HC, et al. Basic aspects of the pathogenesis and prevention of non-melanoma skin cancer in solid organ transplant recipients: A review. Int J Dermatol 2017; 56: 370-8.
3. Garrett GL, et al. Trends of skin cancer mortality after transplantation in the United States: 1987 to 2013. J Am Acad Dermatol 2016; 75: 106-12.
4. Chung CL, et al. Comparison of posttransplant dermatologic diseases by race. Arch Dermatol 2017; 153:552-8.
5. Mittal A, Colegio OR. Skin cancers in organ transplant recipients. Am J Transplant 2017. May 29 [Epub ahead of print]

Appendix from Chung CL, et al.

Primary Diagnostic Category Reference List

 Category  Diagnoses
 Malignant/Premalignant   AK, atypical intraepithelial melanocytic proliferation, BCC, KS, Merkel cell carcinoma, porokeratosis, SCC, SCCIS, sebaceous carcinoma
 Infectious candidiasis, dermatophytosis, HPV, HSV, malessezia, onychomycosis, VZV
 Inflammatory  acne vulgaris, alopecia areata, bullous pemphigoid, CCCA, eczematous dermatitis, erythema nodosum, folliculitis, hidradenitis suppurativa, lichen planus, nephrogenic systemic fibrosis, PCT, perioral dermatitis, PFB, pityriasis rosea, psoriasis vulgaris, prurigo nodularis, rosacea, seborrheic dermatitis, SLE, stasis dermatitis
 Other  alopecia, angioma, benign nevi, dermatofibroma, cyst, ichthyosis vulgaris, IGH, keloid, KP, lentigo, lipoma, NLS, PIH, rhytides, sebaceous hyperplasia, senile purpura, SK, xerosis



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