Reduction of Immunosuppression for Transplant-Associated Skin Cancer: Rationale and Evidence of Efficacy

BACKGROUND: Solid organ transplant recipients may develop numerous or life-threatening skin cancers. In addition to aggressive standard treatment of skin cancer, reduction of immunosuppression has been considered an adjuvant therapeutic strategy, albeit without direct proof of efficacy. OBJECTIVE: To review the rationale for and evidence supporting the efficacy of reduction of immunosuppression for severe skin cancer in transplant recipients. METHODS: Review of the literature regarding direct and indirect evidence on reduction of immunosuppression for transplant-associated skin cancer. RESULTS: Although there are no randomized controlled trials of reduction of immunosuppression as a therapeutic intervention for transplant patients with skin cancer, multiple lines of evidence suggest that this strategy may be an effective adjuvant therapy. A randomized trial has demonstrated a lower incidence of skin cancer in transplant recipients after reduction of immunosuppression, albeit in a cohort not previously affected by skin cancer. Case series of reduction or cessation of immunosuppression demonstrate a lower incidence of skin cancer or improved outcomes of preexisting skin cancer. Lower overall immunosuppression is associated with a lower incidence of skin cancer. Multiple cancers affecting the skin have been shown to regress with reduction of immunosuppression. CONCLUSIONS: Reduction of immunosuppression may be an effective adjuvant therapeutic strategy when confronting severe transplant-associated skin cancer. The risks of reduction of immunosuppression must be better defined, and randomized trials of this strategy are necessary.     

Fragrance material review on cinnamyl alcohol.

A toxicologic and dermatologic review of cinnamyl alcohol when used as a fragrance ingredient is presented.     

High-resolution immunophenotyping of subcellular compartments in tissue microarrays by enzyme metallography.

Ultrasensitive bright field in situ hybridization assays using enzyme metallography (EnzMet) have been developed and validated, but little is known regarding the applicability of EnzMet for immunophenotypic detection of protein via IHC. Superior resolution via discrete metallographic deposits offers the potential for enhancing high-resolution immunophenotyping. Using high-complexity tissue microarrays (TMAs), 88 common solid tumors were evaluated by automated EnzMet (Nanoprobes and Ventana). Targets were chosen to assess the ability of EnzMet to specifically localize encoded antigens in the nucleus (estrogen receptor), cytoplasm (cytokeratins), and cytoplasmic membrane (HER2) in TMAs. Results were compared with conventional IHC diaminobenzidine (DAB) immunostaining. There was full concordance between the EnzMet and conventional IHC results. Furthermore, the EnzMet reaction products did not appreciably diffuse, were dense and sharply defined, and provided excellent high-resolution differentiation of cellular compartments in paraffin sections for the nuclear, cytoplasmic, and cell membrane-localized antigens evaluated. The higher density of elemental silver deposited during enzyme metallography permitted evaluation of core immunophenotypes at a relatively low magnification, allowing more tissue to be screened in an efficient manner. This preliminary study shows the utility of using enzyme metallography for high-resolution immunophenotyping in TMAs.     

The tetracyclines in dermatology.

Tetracycline is one of the most widely used antibiotics. It may share some properties with conventional immunosuppressive drugs and act as an anti-inflammatory agent in the treatment of inflammatory disease. This article reviews cutaneous diseases that have been treated with tetracyclines and their antiinflammatory and immunosuppressive properties.