Solid organ transplantation refers to the removal of living and functioning organs from a donor’s body and then their transfer back into a recipient’s body. Solid organ transplantation involves major surgery and the risk for serious complications, including death.
In 2008 in the United States, about 200,000 people were living with a functioning transplanted organ, or graft, while about 100,750 were waiting on the active national transplant list and around 25,100 solid organ transplantations had been performed. In Australia, there were 799 organ transplant recipients in 2009, with 4,285 individuals receiving an organ transplant between 1989 and 2009.
Transplant rejection is one of the major post transplant complication. Rejection is the destruction of the transplanted organ by the recipient’s immune system; the network of cells, tissues, and organs that defend the human body against foreign substances. The immune system recognizes the transplanted organ as foreign tissue and destroys it in order to eliminate it from the body.
Rejection can be controlled with drugs that suppress the immune system and the body’s ability to recognize and destroy the transplanted organ. Patients who undergo a solid organ transplant, also called organ transplant recipients (OTRs), must continue lifelong treatment with immunosuppressive drugs which prevent their immune system from rejecting the newly transplanted organ.
While allowing the new organ to be tolerated by the OTR’s body and function, lifelong immunosuppressive treatment results in the modification of the recipient’s immune system ability to recognize and destroy foreign substances, thus reducing the body’s ability to fight against certain medical conditions, including tumours and infections.
As a result, there is an increased risk of developing various cancers in OTRs. Both systemic and cutaneous cancers develop, with an overall increased risk 3 to 4 fold greater than in the general population. Studies have shown that, compared to the general population, OTR patients have a 65 to 250 times greater incidence of certain types of skin cancer, with non melanoma skin cancers being the most common post transplant malignancy seen, affecting up to 82% of OTRs. The more invasive squamous cell carcinoma (SCC) skin cancer is more commonly seen in OTR patients than the more benign basal cell carcinoma (BCCs), with a ratio of 4:1, an inverse compared to the general population. It has also been shown that actinic keratoses (AKs), a precancerous lesion caused by UV light exposure, have an increased tendency to metastasize, and progress more rapidly into SCC skin cancer, in OTR patients.
Actinic keratosis and skin cancers in OTRs have been associated with defined extrinsic and intrinsic risk factors such as:
- Cumulative UV exposure;
- Fair skin type;
- The level, type and duration of immunosuppressive therapy;
- The age of transplantation;
- The type of transplanted organ.
The percentage of OTR patients who have skin cancers increases dramatically with time after transplantation as well as with decreasing latitude. Indeed, there is a correlation between increased age at the time of receiving an organ transplant and the incidence of skin cancer in OTR patients, which has been accredited to accumulated sun exposure, and thus skin damage, prior to transplantation. OTR patients at increasing latitudes have also been shown to have a much higher incidence of skin cancers.
In Australia, 45% of OTR patients have a skin cancer within 10 years of transplantation. In temperate climates countries (Holland, England, Italy), this incidence is 10 to 15%.
Role of the immune system in preventing skin cancer
Cumulative UV exposure results in damaged skin cells and DNA; UV exposure is the primary cause of non melanoma skin cancers. The immune system plays a vital role in responding to these damages by instigating targeted cell death (apoptosis), reducing the accumulation of damaged cells in the skin. Cells of the immune system provide continuous surveillance, recognizing and eliminating cells that undergo pre cancerous or cancerous transformation. Without a functioning immune system, the body is less able to defend against these damaged cells replicating unchecked, meaning that cancerous cells can more easily proliferate and metastasize (spread).
In OTR patients, the chronic immunosuppression resulting from immunosuppressive drugs creates a state in the body in which the immune surveillance and eradication of damaged skin cells and precancerous changes are impaired. In addition to that, the impaired immune surveillance leads to higher susceptibility to infection with viruses such as Epstein Barr virus, herpes Simplex virus, herpes zoster virus or human papilloma virus; infections associated with cancer formation. Indeed, squamous cell carcinoma in OTR has been associated with viral infections with herpes simplex virus and human papilloma virus.
Vitamin D and OTRs
Vitamin D is an essential component of human nutrition and has long being recognized for its role in healthy bone growth, development and maintenance. Scores of studies have also implicated vitamin D deficiency in the development of a number of diseases (including diabetes mellitus, cardiovascular disease and several types of internal cancer). Significantly, most of the vitamin D utilised by the human body is obtained through dermal contact with direct sunlight.
This poses an unexpected dilemma for OTRs as it is vital that they practice strict photoprotection due to their high risk of UV-induced SCC. As previously mentioned, immunosupression in these patients, particularly for long periods of time results in cancers which are more numerous, aggressive and tend to metastasise more often. However, stringent photoprotection is likely to result in vitamin D deficiency.
Therefore, while it is imperative that OTRs consult with a dermatologist to understand of their increased risk of skin cancer and the need for thorough photoprotection and precautionary skin examinations. Equally important is the detection and treatment of any resulting vitamin D deficiency. The usual treatment is supplementation in an oral form, as dietary changes rarely provide adequate sources of vitamin D.
For more information, see our article on vitamin D.
- Australia & New Zealand Organ Donation Registry (2009). Summary of organ donation. [Online]. Available online. [Accessed 17/4/2010].
- Bavnick JN, et al (1995). “Prevention of skin cancer and reduction of keratotic skin lesions during acitretin therapy in renal transplant recipients: a double- blind, placebo-controlled study.” Journal of Clinical Oncology. 13: 1933-38.
- Berg D & Otley CC (2002). “Skin cancer in organ transplant recipients: Epidemiology, pathogenesis, and management.” Journal of the American Academy of Dermatology. 47 (1): 1-17.
- Murphy GM (2009). “Ultraviolet radiation and immunosuppression.” British Journal of Dermatology. 161 (s3): 90-5.
- Ulrich C, et al (2003). “Cutaneous precancers in organ transplant recipients: an old enemy in a new surrounding”. British Journal of Dermatology. 149 (s66): 40-2.
- Zafar SY, Howell DN & Gockerman JP (2008). “Malignancy After Solid Organ Transplantation: An Overview.” The Oncologist. 13 (7): 769-778.