Skin Cancer & Immunosuppression Flashcards
Lifelong immunosuppression to stop graft rejection consists of 3 stages. What are these?
- Induction therapy
- Initial maintenance
- Long-term maintenance
What is the aim of induction therapy?
- Deplete or alter T-Cell Response to limit acute rejection and enhance efficiency.
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Biological agents are mainly used.
- These minimise IL-2 mediated lymphocyte activation.
In maintenance therapy, why are higher dosages of immunosuppressants used?
- Greater doses of immunosuppresants are given because chance of rejection are higher in the first 3 months.
What happens in long-term maintenance?
- Dosages are reduced gradually.
- The risk of rejection is less.
What are some commonly used biological agents in immunotherapy?
-
Calcineurin Inhibitors
- Ciclopsorin
- Tacrolimus
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Antiproliferative agents
- Azathioprine
- Mycofenolate mofetil
- Glucocorticoids.
What are the newer mTOR(mammalian target of rapamycin) agents and why are they useful?
- Sirolimus or Everlimus
- Improved tolerability
- Lack of nephrotoxicity
- Anti-tumour and anti-angiogenic properties.
- Lower incidence of malignancy.
What is the most prevalent malignancy after transplation?
Skin Cancer.
What is the most common skin cancer in OTRs (organ transplant recipients)?
- SCC - 65x (The most common)
- Highly Aggressive.
- Kaposi’s Sarcoma 84x increase.
At 10 years what is the risk of SCC?
At 20 years what is the risk of SCC?
(In OTR patients)
- 10 years = 10-27%
- 20 years = 40-60%
Why are rates of SCC higher in lung/heart transplant patients than in renal transplant patients?
- More aggressive immunosuppression.
- Older age at time of transplant (in heart and lung patients)
What can OTR patients do to significantly decrease their risk of SCC?
Stick to a strict sun protection protocol.
What are the main reasons for increased skin cancer in OTR(organ transplant recipients) patients?
- Genetics - p53 tumour suppressor gene mutations.
- UV Radiation - 75% of skin cancers arise in sun exposed areas.
- Oncogenic Viral Infections - HPV 8,9 and 15. They repress apoptosis and thus the cells that would have died stay around with mutated genes.
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Immunosuppressants
- azathioprine and ciclosporin are both carcinogenic.
- Azathioprine accelerates photo-carcinogenesis.
What virus is Kaposi’s Sarcoma linked to?
Human Herpes Virus 8 (HHV-8)
What virus is Merkel Cell Carcinoma linked to?
Merkel Cell Polyomavirus
How do Kaposi’s Sarcoma(s) present?
- 4 subtypes - non-HIV variant is most common in OTRs.
- Can regress if immunosuppression stops.
- Aggressive if not stopped.
- Affects the face and extremeties and mucosal areas.
- Lesions are multiple & can coalesce to form plaques.
- Ulceration can occur
- Involution and pigmented scars can occur.
How do Merkel Cell Carcinoma’s present?
- Arises from cutaneous neuroendocrine cells.
- Mortality rate is 50% due to high rate of recurrence.
- Most often found in the head, neck and arms.
- Presents as a firm, shiny red to purple nodule.
- Varies from 1-5cm in diameter.
What are the 3 ways that skin cancer in OTR patients are managed?
- Education and counselling (sun protection, self-examination, follow-up screenings)
- Topical treatments (surgical and non-surgical interventions such as topical 5-FU, imiquimod and PDT)
- Systemic treatments (oral retinoids, reduction or modification of immunosuppression)
What systemic oral agent is chemoprotective for OTRs?
Oral retinoids.
- Start at 10mg/day and increase to 20-25mg/day as a traget.
- Rebound with discontinuation is common.
- Thought to immunomodulate, anti-keratinisation and induction of apoptosis.
Why is capecitabine useful in OTRs?
capecitabine
- It is an oral prodrug of 5-FU
- Reports of resolution of AKs in patients.
