Skin surveillance in organ transplant recipients

Transplant patients need dermatological surveillance, writes Dr Joy Osbourne.

Approximately 2,700 organ transplants are performed each year in the UK and waiting lists are growing by 3 per cent per year.

Patient and organ survival is increasing as a result of better immunosuppressive regimens, improved treatment of infectious diseases and improved national sharing of HLA-matched cadaveric organs.

IMMUNOSUPPRESSION
Immediately after transplant, intense multi-agent immunosuppressive therapy is used to prevent acute rejection. The therapy is then tapered over three to six months to a maintenance level.

However, chronic immunosuppression increases the risk of developing cancer, particularly skin cancer. Non-melanoma skin cancer (NMSC) is the most common post-transplant malignancy in white-skinned populations.

Immunosuppressants accelerate the development of skin cancers through direct carcinogenesis and chronic immunosuppression, which impairs immune surveillance and eradication of pre-cancerous changes.

Other carcinogenic co-factors and promoters include ultraviolet radiation and HPV.

RISK FACTORS
Sun exposure is an important risk factor. Most tumours (80 per cent) develop in sun-exposed areas, but they can also occur on covered sites.

Distribution appears to be related to the age at transplantation. In patients receiving transplants before the age of 40 years, 80 per cent of tumours develop on the dorsa of the hands and forearms or on the upper trunk. In older transplant recipients, 80 per cent of lesions develop on the head.

The percentage of patients developing skin cancer increases with time after transplantation. In the UK, risk is around 30 per cent after 10 years and 60 per cent after 20 years. The mean interval between transplantation and diagnosis of skin cancer is eight years if transplanted before the age of 40 and only three years if transplanted after the age of 60.

Rejection in the first year post-transplant may be predictive of skin cancer risk, possibly because higher levels of immunosuppressive treatment are required.

Other risk factors include fair skin, HPV infection, the duration of pre-transplant dialysis and possibly smoking.

A history of skin cancer before transplantation increases the risk of new lesions and metastasis afterwards.

Paediatric recipients are particularly at risk of aggressive skin tumours.

PRE-MALIGNANT LESIONS
The relative risk of skin tumours in organ recipients is shown in the box, left.

Actinic keratoses are very common pre-malignant lesions developing on sun-exposed sites and can also progress to invasive squamous cell carcinoma (SCC).

Clinical diagnosis can be complicated by the development of numerous warty lesions on the dorsa of hands.

These lesions can be a mixture of actinic keratoses, viral warts, squamous papillomas or even early SCCs. If the clinical diagnosis is in doubt excision biopsy must be undertaken.

SCC is the most common type of skin cancer. An unfavourable prognosis is associated with multiple tumours, a cephalic location, the presence of extra-cutaneous tumours, older age and exposure to sun.

The risk of developing skin cancer with time appears to increase linearly for basal cell carcinoma (BCC) and exponentially for SCC.

The usual SCC to BCC ratio of 1:4 is reversed in transplant recipients, although in the first years after transplantation BCC may be more common.

There is an increased risk of malignant melanoma in transplant patients. It accounts for 6.2 per cent of skin cancers in adults and 15 per cent in children post-transplant.

In patients with a history of melanoma, the risk of post-transplant recurrence is high (20 per cent). Melanoma can also be transmitted from the donor to the recipient.

There is also a high incidence of Kaposi's sarcoma, reflecting the effect of immunosuppression on this infection-related tumour.

OTHER TUMOURS
Anogenital cancers account for 2.8 per cent of post-transplant tumours. They are associated with transplantation in childhood and are twice as common in females.

Cutaneous T- and B-cell lymphomas are among the most common complications of transplantation, affecting up to 5 per cent of patients.

A variety of other more rare tumours can also develop, including atypical fibroxanthoma, angiosarcoma, verrucous carcinoma, Merckel cell tumour and leiomyosarcoma.

TRANSPLANT RECIPIENTS
Transplant patients should be educated about the risk, signs of skin cancer and about sun protection measures prior to undergoing transplantation.

The transplant team should liaise closely with the dermatologist and refer patients for annual skin surveillance at the first anniversary of their transplant.

Patients should also have open access to the dermatologist to allow prompt diagnosis and treatment of any developing lesions. High-risk patients should be offered more frequent follow-up (see box).

Actinic keratoses should be treated aggressively to minimise the risk of progression to SCC. Solitary lesions can be treated with cryotherapy, but topical or oral retinoids, topical 5 per cent fluorouracil or imiquimod should be considered in patients with multiple actinic keratoses.

Oral retinoids, which modulate cellular proliferation and apoptosis, should be considered in patients who develop multiple SCCs.

Acitretin (30mg/daily or 0.3mg/kg) has been shown to decrease the rate of development of new skin cancers, with no effect on renal function or rejection risk, although hyperlipidaemia has often been a side-effect.

CONCLUSION
Regular skin surveillance by a dermatologist is now considered to be an integral part of the gold standard of care for organ recipients.

It can be challenging and time-consuming, but there is a high pick-up rate for tumours and improved outcome from early diagnosis and treatment.

SKIN TUMOURS
Risk of skin tumours in organ recipients
Actinic keratoses: >250
SCC: >100
BCC: 10
Kaposi's sarcoma: 85-500
Anogenital tumours: 100
Melanoma: 2-5

CANCER SURVEILLANCE

  • Chronic immunosuppression increases cancer risk, particularly skin cancer.
  • Transplant patients can develop numerous warty lesions on the dorsa of the hands. Excision biopsy must be undertaken if the clinical diagnosis is in doubt.
  • Anogenital cancers are common in transplant patients, especially following transplantation in childhood. Persistent wart-like lesions should be biopsied to exclude this diagnosis.
  • Transplant patients should be educated about the risk, signs and symptoms of skin cancer and about sun protection measures.
  • Patients should also have open access to the dermatologist to allow prompt diagnosis and treatment of any developing lesions.

FOLLOW UP SCHEDULE FOR TRANSPLANT PATIENTS
Patient history Examination schedule
No skin cancer/actinic keratoses 12 months
Actinic keratoses 6 months
Single NMSC 6 months
Multiple NMSCs 2-4 months
High risk of malignant melanoma/SCC 3 months
Metastatic malignant melanoma/SCC 2 months

REFERENCES

- Bouwes Bavinck J N, Feltkamp M, Struijk L, ter Schegget J. Human papillomavirus infection and skin cancer risk in organ transplant recipients. J Investig Dermatol Symp Proc 2001; 6: 207-11.

- McKenna D B, Murphy G M. Skin cancer chemoprophylaxis in renal transplant recipients: 5 years of experience using low-dose acitretin. Br J Dermatol 1999; 140: 656-60.

Dr Joy Osbourne is associate specialist in dermatology at Leicester Royal Infirmary, Leicester.

This article was first published in MIMS Dermatology, March 2006. To register to receive copies go to www.hayreg.co.uk/specials.

 

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