Successful treatment of multiple actinic keratoses in organ transplant patients with topical 5% imiquimod: a report of six cases.

BACKGROUND: Nonmelanoma skin cancer represents a significant cause of morbidity in organ transplant recipients (OTRs). Cutaneous malignancies, mainly invasive squamous cell carcinoma and its precursor actinic keratosis (AK), appear approximately 5-10 years after organ transplantation. Impaired wound healing and high recurrence rates in immunocompromised patients treated with destructive therapies such as cryosurgery or topical 5-fluorouracil represent frequently known complications. OBJECTIVES: To evaluate the safety and efficacy of imiqimod 5% in the treatment of AKs in OTRs. METHODS: Six OTRs (two kidney, two heart, one lung and one liver) with extensive AKs were treated with imiquimod 5% cream two to three times weekly in an open-label uncontrolled, nonrandomized pilot study. RESULTS: In five of six patients treated with imiquimod 5% cream all AK lesions were cleared after 12-16 weeks. One patient showed partial response. Local adverse events at the site of application included erythema, oedema and mild erosion. No wound infection or scarring was observed in any of these patients. All graft-related laboratory parameters were stable during and after treatment. Immunosuppressive therapy remained unchanged throughout the treatment. CONCLUSIONS: These results suggest that imiquimod 5% cream may be useful for the local treatment of precancerous AK lesions in OTRs.

Induction of apoptosis by Toll-like receptor-7 agonist in tissue cultures.

Toll-like receptor (TLR)-7 agonists represent a new group of immune response modifiers, which include imiquimod and resiquimod (R-848). Topically applied imiquimod is used for the treatment of both external and perianal genital warts, and benign and malignant epithelial lesions. Based on the induction of interferons and other cytokines in vitro and in vivo, regression of epithelial lesions probably depends on induction of both innate and cellular immune responses. As clinical remission is not always associated with inflammation, other mechanisms may also be involved. Using two different assays for detection of apoptosis (TUNEL test and gel analysis of DNA fragmentation), we observed induction of apoptosis by imiquimod in human epithelial cell lines (HeLa S3) and keratinocytes (HaCaT, A431 cells), as well as in mouse fibroblasts (McCoy cells). These findings suggest that the mode of action of imiquimod to eliminate virus-infected, dysplastic or neoplastic epithelial cells may also include the induction of apoptotic processes.

Viral warts in organ transplant recipients: new aspects in therapy.

The long-term success of organ transplantation depends on the prevention of allograft rejection and improvement in quality of life for the patients. This has been achieved through better immunosuppressive regimens with lower dosages and a new generation of immunosuppressive drugs. However, these immunosuppressive agents not only impair the patient's reactivity to the graft, but also to infectious organisms, thereby making them more susceptible to opportunistic pathogens. Because of this, organ transplant recipients are predisposed to epithelial malignancies and infections. The majority of transplant recipients will develop warts induced by human papillomavirus (HPV). Some of these viral warts may present with atypical histological features and may progress into squamous cell carcinomas. The risk for cutaneous cancers after transplantation is much higher than in the immunocompetent population. Current therapies for HPV-associated skin tumours mainly depend on the destruction of affected skin areas. These treatment modalities are of limited efficacy and are usually painful for the patients. A promising novel therapeutic agent is imiquimod, an immune response modifier. Clinical efficacy of imiquimod has been observed for different skin lesions, including viral warts in both immunocompetent and immunosuppressed patients.

Cutaneous precancers in organ transplant recipients: an old enemy in a new surrounding.

Premalignant and malignant epithelial lesions are acknowledged as being the most frequent neoplasia in long-term immunosuppressed patients such as organ-transplant recipients. Paralleling the constant improvement in modern transplant techniques, their incidence increases together with the growing survival time post-transplantation, reaching 40% to 60% after 20 years. Against the background of lifelong immunosuppression, the impact of accepted cancer inducers and promoters such as ultraviolet radiation, oncogenic viruses and individual susceptibility has to be closely scrutinized. Precancerous lesions such as actinic keratoses in transplant patients progress more rapidly into squamous cell carcinomas, showing an increased tendency to metastasize. As it remains impossible to identify and consequently treat those lesions that may progress into invasive carcinoma, the best prophylaxis for nonmelanoma skin cancer in organ-transplant recipients may be the treatment of all existing precancerous lesions. As reduction of the immunosuppressive therapy is rarely practicable, other terms of prophylaxis and treatment, such as immune response modifiers, have to be considered.

The use of Toll-like receptor-7 agonist in the treatment of basal cell carcinoma: an overview.

Basal cell carcinoma (BCC) is a subtype of nonmelanoma skin cancer (NMSC), with an increasing incidence worldwide. Currently, excision of the tumour with histological control is the standard therapy. However, high incidence rates have led to concern about the economic burden imposed by BCC management in many countries. Imiquimod is a member of a novel class of immune response modifiers (IRM), which works by using the toll-like receptor (TLR)-7. Although the exact mode of action is so far unknown, it is suggested to induce the expression of different cytokines like interleukin (IL)-1, IL-6, IL-12, interferon (IFN)-alpha and tumour necrosis factor (TNF)-alpha, which stimulate or enhance both the innate immune system and the cell-mediated immune response. Pre-clinical studies have indicated the potential of this TLR-7 agonist for the treatment of precancers and tumours in humans. A number of Phase II trials have demonstrated the efficacy of imiquimod for the treatment of BCC, although the most appropriate dosing regimen is being confirmed in Phase III studies. Imiquimod 5% cream for the treatment of mainly superficial BCC appears to be an effective and well-tolerated treatment option.

Current treatment patterns in non-melanoma skin cancer across Europe.

With marked increases in the annual incidence of non-melanoma skin cancer (NMSC) across the globe, its management is of increasing concern to dermatologists. This paper summarises the epidemiology and risk factors and provides an overview of treatment approaches in NMSC across Europe, including surgery, topical 5-fluorouracil and cryotherapy, in the context of the trade-offs that exist in finding optimal treatment outcomes. The paper will also briefly examine new approaches such as immunomodulators and the growing body of data on photodynamic therapy (PDT) using methyl aminolevulinate (MAL), including the authors' personal experience of the efficacy and cosmetic results obtained with these newer therapies.

Remarkable remission of a follicular lymphoma treated with rituximab and polychemotherapy (CHOP).

We describe a 50-year-old female patient who developed extensive lymphomatous infiltrates on her forehead, scalp and face within a few months. Histology and immunohistochemistry of skin tumours revealed a CD20 positive follicular B-cell lymphoma. Subsequently, extracutaneous manifestations were detected by computed tomography scans and bone marrow biopsy. The patient suffered from a primary nodular malignant lymphoma with extraordinary cutaneous infiltration of the head. Therefore, combination treatment with a monoclonal antibody against the CD20 antigen, rituximab, and polychemotherapy (CHOP scheme) was administered every 3 weeks. After the second course of treatment a complete regression of cutaneous infiltrates was noticed. Follow-up biopsies on the forehead showed no evidence of CD20 positive lymphoma cells, now. Despite mild leucocytopaenia therapy was well tolerated.

[Granulomatous slack skin: partial remission following intralesional administration of interferon-alpha and PUVA]. / Granulomatous slack skin. Partielle Remission unter intraläsionärer Gabe von Interferon-alpha und PUVA.

Granulomatous slack skin (GSS) is a rare cutaneous T-cell lymphoma which typically runs a protracted and indolent course. On histopathological assessment lymphoid infiltrates with multinucleated giant cells in the dermis and subcutis with elastophagocytosis can be observed. Skin lesions are characterized by pendulous folds. We report on the successful response of the lesions to intralesional interferon alpha combined with PUVA.