Humane Papillomvirus-assoziierte Warzen bei organtransplantierten Patienten

Human papillomaviruses infect the squamous epithelia of the skin and cause warts, and are occasionally found in squamous cell carcinomas. Since cell-mediated immunity plays a crucial role in the control of HPV-infections, organ transplant recipients, unable to mount an adequate T-helper 1 cell-mediated immune surveillance, frequently develop widespread and resistant induced warts. Skin tumors, especially squamous cell carcinomas, are the most common post-transplantation neoplasm. Warts, actinic keratoses and invasive squamous cell carcinomas are known to develop at the same time in the areas. The role of HPV in the development of invasive squamous cell carcinoma under immunosuppression, remains to be elucidated in respect to common risk factors and increased numbers of warts potentially indentifing patients at increased risk for carcinoma. We prospectively studied 1690 organ transplant recipients in the dermatology clinic at the Charité University Hospital in Berlin, to evaluate risk factors being involved in the development of HPV-induced warts and to assess a potential association of with the development of non-melanoma skin cancers in this population. The cumulative incidence of warts steadily increased throughout the post-transplant years. The presence of more than 10 verrucae was associated with the development of actinic keratoses, invasive squamous cell carcinoma and basal cell carcinoma. This study shows clear evidence that certain risk factors of skin carcinogenesis in organ transplant recipient such as increased age at transplantation, a high dose of immunosuppression related to a specific type of graft and use of azathioprine or cyclosporine are strongly associated with an increased incidence of warts. Furthermore, HPV-induced verrucae vulgares could be used as a potential predictor for the development of coincidental non melanoma skin cancer in organ transplant recipients and therefore could serve as an early identification marker of skin cancer high-risk patients. The challenging management of warts in organ transplantation patients is reviewed.     

Human papillomavirus infection and skin cancer risk in organ transplant recipients

Warts and squamous cell carcinomas are important cutaneous complications in organ transplant recipients. The role of infection with human papillomaviruses (HPV) in the development of cutaneous squamous cell carcinoma is still unclear. An extremely diverse group of HPV types, mainly consisting of epidermodysplasia-verruciformis (EV)-associated HPV types, can be detected in benign, premalignant, and malignant skin lesions of organ transplant recipients. Frequently, there are multiple HPV types present in single skin biopsies. Typically, the prevalence of viral warts rises steadily after transplantation and a strong association exists between the number of HPV-induced warts and the development of skin cancer. The interval between the transplantation to the development of warts is clearly shorter than the interval from transplantation to the diagnosis of the first skin cancer. A comparison of transplant recipients with and without skin cancer, however, showed an equally high prevalence of EV-HPV DNA in keratotic skin lesions in both groups of patients and the detection rate and spectrum of HPV infection in hyperkeratotic papillomas, actinic keratoses, and squamous cell carcinomas was also similar. HPV DNA can frequently be detected in patients with hyperproliferative disorders like psoriasis and antibodies against HPV in patients with regenerating skin (e.g., after extensive second degree burns). Latent infection with EV-HPV seems to be widespread. The hair follicle region might be the reservoir of EV-HPV. The E6 protein from a range of cutaneous HPV types effectively inhibits apoptosis in response to UV-light induced damage. It is therefore conceivable that individuals who are infected by EV-HPV are at an increased risk of developing actinic keratoses and squamous cell carcinomas, possibly by chronically preventing UV-light induced apoptosis.     

Evaluation of human papillomavirus type 5 on frozen sections of multiple lesions from transplant recipients with in situ hybridization and non-isotopic probes.

Transplant recipients are at high risk to develop multiple cutaneous lesions after grafting. The frequency of the potentially oncogenic human papillomavirus (HPV) type 5 DNA was evaluated in cutaneous lesions taken from sun-exposed areas in transplant recipients (92 lesions and 5 samples from normal skin) and compared with a nontransplanted population (22 lesions and 7 samples from normal skin) using in situ hybridization and biotinylated probes to HPV types 1, 2, 5, 16 and 18. HPV type 5 DNA was identified in 8/92 cutaneous lesions of transplanted recipients: 3 warts, 1 case of seborrheic keratosis, 2 actinic keratoses and 2 keratoacanthomas. HPV type 5 DNA was not detected in 27 malignant tumors (8 basal cell carcinomas and 19 squamous cell carcinomas) from transplant recipients. HPV DNA type 5 was detected in only 1 case of squamous cell carcinoma from the general population. The presence of HPV DNA 5 was confirmed with Southern blotting in 2 out of 6 cases from transplant recipients. The reaction was negative with the squamous cell carcinoma from nontransplant recipients. These data indicate that the presence of HPV DNA type 5 is not very frequent; it can be detected with in situ hybridization and nonisotopic probe, which is easier to handle than Southern blot.     

Human papillomavirus type 1-associated squamous cell carcinoma in a heart transplant recipient.

The occurrence of squamous cell carcinomas in organ transplant recipients with warts represents a good model to study viral carcinogenesis. Most of the cases were reported in renal transplant recipients. We present the case of a heart transplant recipient in whom multiple common warts, preepitheliomatous keratoses, and squamous cell carcinomas developed. The warts began 4 years after the transplantation and the first carcinoma occurred 2 years after the warts, all the lesions being on sun-exposed areas. Histologic signs of human papillomavirus infection were seen in all premalignant and malignant lesions. Furthermore, human papillomavirus type 1 DNA was detected by in situ molecular hybridization within one of the carcinomas. Human papillomaviruses, along with other carcinogenic factors, play an important role in the development of carcinomas, and benign types could be implicated. Further studies are required to evaluate the frequency of cutaneous malignant neoplasms in heart transplant recipients as compared with renal transplant recipients.     

Acitretin treatment of premalignant and malignant skin disorders in renal transplant recipients: clinical effects of a randomized trial comparing two doses of acitretin

INTRODUCTION: After renal transplantation, the incidence of premalignant and malignant skin lesions is high. Treatment with acitretin improves the number and aspect of actinic keratoses and appears to reduce the incidence of squamous cell carcinomas, but treatment is hampered by frequent side effects. No optimal long-term dosing advice is available. METHODS: A total of 26 long-term renal transplant recipients were randomized to 1-year treatment with acitretin, either 0.4 mg/kg/d throughout the whole year or 0.4 mg/kg/d during the first 3 months followed by 0.2 mg/kg/d for the remaining 9 months. At 9 different time points, the number of actinic keratoses and tumors was counted, and erythema and thickness of the lesions, and severity of side effects were scored. Patient's judgment was recorded using visual analog scores. RESULTS: In both groups, the number of actinic keratoses decreased by nearly 50%, but the number of new malignant tumors during the study year was similar to the number of tumors in the year before the study. Thickness of the keratoses decreased significantly in both groups. Acitretin dose had to be reduced in most patients because of the frequent occurrence of mucocutaneous side effects, such as cheilitis, excessive peeling of the skin, and hair disorders. In the 14 patients randomized to continuous treatment with a dose of 0.4 mg/kg/d, this dose could be maintained in 3 of 14 patients only. Temporary interruption of acitretin therapy was necessary in 7 of 26 patients. Patients' contentment about the aspect of their skin increased significantly, with no differences between groups. CONCLUSIONS: Acitretin therapy decreased the number of actinic keratoses in renal transplant recipients at a low maintenance dose of 0.2 mg/kg/d and significantly decreased the degree of thickness of the lesions. However, the incidence of new skin malignancies remained unchanged. Despite the high incidence of mucocutaneous side effects, patient's contentment with the aspect of their skin increased significantly.     

p53 immunoreactivity in non-melanoma skin cancer from immunosuppressed and immunocompetent individuals: a comparative study of 246 tumours

p53 immunoreactivity was examined in 132 cutaneous non-melanoma tumours from renal transplant recipients and in 114 histologically matched specimens from immunocompetent individuals. Skin lesions examined included 52 viral warts, 50 clysplastic keratoses, 51 intraepidermal carcinomas (IEC), 50 invasive squamous cell carcinomas (SCC) and 43 basal cell carcinomas (BCC). Overall, 51% (51/101) pre-malignant skin lesions and 45% (42/93) non-melanoma skin cancers (NMSC) showed p53 immunoreactivity, with extensive (> 50% cells positive) p53 staining in 27% (27/101) of pre-malignant and 20% (19/93) of malignant lesions. 17% (9/52) viral warts showed p53 immunoreactivity, but this was limited to focal or basal p53 staining. p53 immunoreactivity in all tumours was less in transplant than in non-transplant patients and this reached statistical significance for SCCs (p = 0.03).     

Hauterkrankungen bei organtransplantierten Patienten

In Germany 3273 visceral organs were transplanted in the year 2000. Together with patients grafted abroad, it is estimated that between 70,000 and 100,000 organ transplant patients are currently living in Germany. With the provision of lifelong immunosuppression the survival-time of these patients can exceed more than 20 years. In the first year following transplantation special emphasis is given to the prevention of viral, bacterial and fungal infections. Regular dermatological screening can provide early diagnosis of even systemic infections. An increased incidence of skin cancer parallels the extended survival rates of grafted patients. Within the first 5 years of immunosuppression 40% of these patients develop pre-malignant skin tumors such as actinic keratoses, dysplastic nevi, squamous cell carcinomas and basal cell carcinomas. Squamous cell carcinomas show an aggressive biology and an uncommon clinical morphology. The increased incidence of cancer is now responsible for a mortality rate of 5-8% in grafted patients. Against a background of lifelong immunosuppression, other risk factors include sun exposure and infections with oncogenic viruses. The rapidly growing numbers of allograft recipients as well as the rising long term survival rates of these patients demand the provision of high quality interdisciplinary and dermatological care in this field.     

Langerhans cells, inflammation markers and human papillomavirus infections in benign and malignant epithelial tumors from transplant recipients.

Organ transplant recipients frequently develop warts which progress toward premalignant or malignant lesions after a rather long grafting period. The local immune responses of such lesions (warts, condyloma acuminata, actinic keratoses, Bowen, basal and squamous cell carcinomas) was studied in 32 frozen skin specimens taken from 15 male transplant recipients and compared to similar lesions from the normal population. We studied the expression of T cell subsets, Langerhans cell phenotype, HLA class 1 (beta 2-microglobulin), HLA class 2 (DR antigen), and intercellular adhesion molecule 1 (ICAM 1). The presence of HPV infection was also considered, using in situ hybridization with biotinylated probes in order to examine the correlation with immunological markers. In the dermis, the lesions from grafted patients showed a moderate to intense inflammatory reaction of HLA-DR-positive cells. Most of these cells were CD4+ and CD8+ without any predominance of a single T cell subset. In the epidermis, most lesions were characterized by a reduced number of CD1-positive cells; this was concomitant with a decrease or a loss of beta 2-microglobulin expression by epithelial cells. HLA-DR antigen was not expressed by keratinocytes or tumoral cells in any specimen; ICAM 1 antigen was observed in a few cases. The expression of these markers was similarly modified with or without the presence of HPV DNA. Conversely, most lesions from non-immunocompromised patients, except warts, showed intense inflammatory reactions, with a predominance of CD4-positive cells and large foci of ICAM 1-positive cells. Expression of activation markers by keratinocytes occurred mainly in condylomas and squamous cell carcinomas. In the normal population, HPV infection was only detected in papilloma lesions. These data indicate, in lesions from grafted patients, a lack of effective immune response with partial inhibition of activation markers expressed by keratinocytes. It is conceivable that immunosuppressive treatment with solar exposure may also be responsible for the local immune deficiency and thus for the conversion of benign warts toward malignant lesions in grafted patients.     

Benign Human Papillomavirus Infection in Renal Transplant Recipients

Warts and cutaneous squamous cell carcinomas are common complications of immunosuppression. We studied a total of 189 renal transplant recipients clinically for such lesions. The incidence of warts increased steadily after transplant, such that of patients transplanted for more than 5 years, 92% were found to have warts and 65% had more than five warts each. DNA extracted from scrapings of their warts showed they carried the same human papillomavirus types as the general population, and not the unique set found on patients with epidermodysplasia verruciformis (who share with transplant recipients an increased incidence of warts and squamous cell carcinomas).     

The influence of painful sunburns and lifetime sun exposure on the risk of actinic keratoses,seborrheic warts,melanocytic nevi,atypical nevi,and skin cancer

Painful sunburns are implicated in the pathogenesis of squamous cell carcinoma, basal cell carcinoma, and malignant melanoma. Chronic exposure to ultraviolet radiation is known as the most important risk factor for the development of actinic keratoses and squamous cell carcinoma. The purpose of the study was to assess the effect of painful sunburns and lifetime sun exposure on the development of actinic keratoses and seborrheic warts in relation to the development of squamous cell carcinoma and basal cell carcinoma, and on the development of melanocytic nevi and atypical nevi in relation to the development of malignant melanoma. We made use of a cohort of 966 individuals who participated in a case-control study to investigate environmental and genetic risk factors for skin cancer. Exposure measurements for sunlight were collected and actinic keratoses, seborrheic warts, melanocytic nevi, and atypical nevi were counted. Relative risks were estimated using exposure odds ratios from cross-tabulation. Multivariate logistic regression was used to adjust for potential confounders. The recall of painful sunburns before the age of 20 y was associated with an increased risk of squamous cell carcinoma, nodular basal cell carcinoma, and multifocal superficial basal cell carcinoma as well as actinic keratoses. Odds ratios with 95% confidence intervals adjusted for age, sex, and skin type were 1.5 (0.97; 2.3); 1.6 (1.1; 2.2); 2.6 (1.7; 3.8); and 1.9 (1.4; 2.6) for the three types of nonmelanoma skin cancer and actinic keratoses, respectively. Painful sunburns before the age of 20 y were also associated with an increased risk of malignant melanoma and the development of its precursors, melanocytic nevi and atypical nevi. Odds ratios with 95% confidence intervals adjusted for age, sex, and skin type were 1.4 (0.86; 2.1); 1.5 (1.1; 2.0); and 1.4 (0.88; 2.3) for malignant melanoma and the two types of precursors, respectively. Lifetime sun exposure was predominantly associated with an increased risk of squamous cell carcinoma (p-value for trend=0.03) and actinic keratoses (p-value for trend <0.0001) and to a lesser degree with the two types of basal cell carcinoma. By contrast, lifetime sun exposure appeared to be associated with a lower risk of malignant melanoma, despite the fact that lifetime sun exposure did not diminish the number of melanocytic nevi or atypical nevi. Neither painful sunburns nor lifetime sun exposure were associated with an increased risk of seborrheic warts.     

Primär- und Sekundärprophylaxe von Hauttumoren nach Organtransplantation

Skin cancer constitutes the most frequently reported post-transplant malignancy in solid organ transplant recipients (OTR) worldwide. Whereas the risk for malignant melanoma is only moderately increased, non-melanoma skin cancers (NMSC) seem to thrive on chronic immunosuppression and account for up to 95% of post-transplant cutaneous malignancies. Compared to the general population cutaneous squamous cell carcinoma (SCC) and actinic keratoses (AK) characteristically show even higher incidences than basal cell carcinoma (BCC) and act as an indicator for the development of multiple primary cutaneous neoplasias and locally recurrent cancers (field cancerization). Early diagnosis and therapy of pre-malignant cutaneous lesions is crucial for the secondary prophylaxis of further invasive and highly aggressive skin cancers. High quality interdisciplinary care and prophylactic modalities, including consistent and sufficient UV protection, topical immunmodulatory therapies of UV-damaged skin areas, retinoid chemoprevention as well as tapering immunosuppressive treatment or the selection of immunosuppressants with proposed antiangiogenic properties like mTor-inhibitors may help to reduce the multiplicity of subsequent primary skin cancers in high-risk patients. Apart from the continuous need for educational intervention of OTR in the primary prophylaxis of post-transplant skin cancers, dermatologic care occupies a central position within the field of transplantation medicine in terms of pre- and post-transplanation dermatologic evaluation and therapy as well as the implication of timely and effective secondary preventive approaches in the management of this high-risk patient population.     

Acitretin treatment in (pre)malignant skin disorders of renal transplant recipients: Histologic and immunohistochemical effects

BACKGROUND: The incidence of (pre)malignant skin lesions after renal transplantation is high. Acitretin treatment appears to decrease the number of new squamous cell carcinomas and ameliorates the aspect and reduces the number of actinic keratoses. However, no histologic and immunohistochemical studies have been performed to further substantiate these observations. METHODS: In 33 renal transplant recipients, biopsies were taken before and after 3 months of treatment with acitretin in doses up to 0.4 mg/kg/day. Histologic and immunohistochemical parameters for dysplasia, epidermal thickness, proliferation, differentiation, apoptosis, and dermal inflammation were analyzed. RESULTS: Following acitretin treatment, a significant reduction in epidermal thickness (P =.002) and a significant increase in normal differentiation parameter K10 (P =.02) was observed. Epidermal proliferation did not change, nor did apoptosis, inflammation, keratinocytic epidermal neoplasia score, or transglutaminase staining. At baseline, in 8 actinic keratoses, a single cell expression pattern of K13 and/or K19 was found. This was associated with high levels of parameters indicative of high-risk lesions (P <.05). After acitretin treatment, an increase in K13 (P =.006) and K19 (P =.05) was found, together with a change in expression towards a focal or band-like staining pattern. CONCLUSION: Acitretin improves the aspect of actinic keratoses via alteration of keratinization, resulting in peeling of the stratum corneum. No significant change in proliferation was found, which may explain the rapid recurrence of actinic keratoses seen after cessation of acitretin treatment.     

A randomized controlled clinical trial of topical photodynamic therapy with methyl aminolaevulinate in the treatment of actinic keratoses in transplant recipients

BACKGROUND: Transplant recipients have an increased propensity to develop multiple actinic keratoses, which demonstrate an increased transformation rate into invasive squamous cell carcinoma. OBJECTIVE: To evaluate the efficacy and tolerability of topical photodynamic therapy with the new highly tumour-selective photosensitizer methyl aminolaevulinate vs. placebo in the treatment of actinic keratoses in transplant recipients. METHODS: Seventeen transplant recipients with a total number of 129 mild to moderate actinic keratoses were enrolled in a prospective, randomized, double-blind, placebo-controlled study. Two lesional areas within a patient were randomized for two consecutive treatments of topical photodynamic therapy 1 week apart using either methyl aminolaevulinate or placebo cream. Sites were illuminated with 75 J cm(-2) of visible light delivered at 80 mW cm(-2) by a noncoherent light source. Complete resolution and reduction in the number or size of actinic keratoses within the lesional area relative to the initial findings were evaluated at weeks 4, 8 and 16 after treatment. RESULTS: The lesional areas treated with methyl aminolaevulinate were clinically cleared in 13 of 17 patients at 16 weeks. A partial response was recorded in a further three. No reduction in the size or number of actinic keratoses was observed in one area treated with methyl aminolaevulinate and in all placebo-treated areas. Adverse events, such as erythema, oedema and crust formation, were mild to moderate, and treatment was well tolerated by all patients. CONCLUSION: Photodynamic therapy using methyl aminolaevulinate is a safe and effective treatment for actinic keratoses in transplant recipients. It may also reduce the risk of transformation of actinic keratoses to invasive, potentially fatal, squamous cell carcinoma.     

Photodynamic therapy: A targeted literature review focussing on outcomes and optimisation in solid organ transplant recipients

Squamous cell carcinoma incidence is 65- to 250-fold in solid organ transplant recipients, BCC is 10-fold and in Australia, rates of skin cancer in solid organ transplant recipients reach 70–82% prevalence within the first 20 years; hence, effective, evidence-based treatment of early and precancerous lesions is an essential tool in dermatological patient care. Photodynamic therapy is used to treat a range of conditions including actinic keratoses, squamous cell carcinoma in situ, superficial basal cell carcinoma and nodular basal cell carcinoma. A literature review was undertaken to examine the outcomes of photodynamic therapy in solid organ transplant recipients and methods of optimising outcomes in solid organ transplant recipients. Study sizes were small and protocols varied widely, so meta-analysis was not possible; however, photodynamic therapy appears to be an acceptable treatment for approved indications in solid organ transplant recipients in whom ongoing surveillance is maintained to ensure clearance and detect recurrence. Methods for improving efficacy were also reviewed for this population. Improved outcomes may be achieved by combining photodynamic therapy with other local methods such as 5-fluorouracil or ablative fractional laser.     

Twenty-eight-year incidence and characteristics of post-transplant skin cancers: Comparative analysis of past and recent 10-year experience

Because primary skin cancers in organ transplant recipients are rare, little is known about the characteristics and risk factors for skin cancers in organ transplant recipients. We searched the Asan Medical Center database of 13 469 organ transplant recipients for cases of all skin cancers from January 1990 to December 2018. Characteristics of and risk factors for skin cancers were analyzed and compared according to the period of transplantation. Of the identified 113 patients with skin cancers, squamous cell carcinoma was the most common cancer followed by basal cell carcinoma and Kaposi sarcoma. The cumulative incidence of skin cancers at 28 years was 5.3%. Over the 10-year period from January 2009 to December 2018, the standardized incidence ratio for premalignant in situ skin lesions increased, whereas the standardized incidence ratio for skin cancers decreased. Age at transplantation and treatment with more than two immunosuppressive agents were risk factors for the development of new skin cancers in organ transplant recipients. Over the most recent 10-year period, post-transplant skin cancers have been found earlier and diversified compared with in the previous period.     

High‐risk cutaneous squamous cell carcinoma in a Japanese allogeneic bone marrow transplant recipient on long‐term voriconazole

Cutaneous squamous cell carcinomas arise as secondary cancers in hematopoietic stem cell transplant survivors. They have been documented primarily in Western cohorts and relatively little is known about their occurrence in Asian hematopoietic stem cell transplant recipients, with no reports of squamous cell carcinomas with high‐risk features in Asian patients. We describe a case of a cutaneous squamous cell carcinoma with high‐risk features on the scalp of a Japanese bone marrow transplant recipient approximately 6.5 years post‐transplant, who was on long‐term voriconazole. The history of a photodistributed erythema followed by the appearance of multiple actinic keratoses and solar lentigines, together with the rarity of cutaneous squamous cell carcinomas in Asian hematopoietic stem cell transplant cohorts revealed in our literature review, suggest that voriconazole use contributed to the development of high‐risk squamous cell carcinoma in our patient.     

Skin cancers and other cutaneous diseases in renal transplant recipients: a single Italian center observational study

Kidney transplant recipients frequently suffer from skin infections and malignancies, due to the effects of long-term immunosuppressive therapy. Herein, a dermatological screening was performed to evaluate the relationship between risk factors, cutaneous tumours and other skin diseases in a group of 282 kidney transplant patients. Infectious diseases (16.7%) were the most frequent dermatological disorders, whereas cutaneous inflammatory and autoimmune diseases were relatively rare, probably due to an indirect therapeutic role of immunosuppressive regimens. Thirty patients experienced cutaneous side effects from immunosuppressants, mainly when receiving corticosteroids (p?=?0.0372). We identified 99 patients (35.1%) who developed cutaneous tumours after transplantation. Cumulative tumour incidence was observed during long-term immunosuppressive therapy; no relationships were identified between skin cancer risk and single class of drug or combination regimens. When we evaluated the eventual relevance of other risk factors for skin cancers, we demonstrated a statistical significance in univariate analysis for male gender, more advanced age at transplantation, long duration of immunosuppressive regimens, no sunscreen usage, outdoor job, absence of cherry angiomas and presence of actinic keratoses (AKs). Age at transplantation (p?=?0.0174), presence of AKs (p?=?0.0005) and duration of immunosuppression (p?=?0.0011) also confirmed their significance in multivariate analysis.     

Chemopreventative thoughts for photodynamic therapy

The concept of skin cancer prevention with photodynamic therapy has evolved over the past few years to include large surface application of aminolevulinic acid or methyl aminolevulinate followed by light exposure to prevent the development of new lesions. Pre-clinical studies using various mouse models have shown that large surface photodynamic therapy can prevent the appearance of actinic keratoses, squamous cell carcinomas, and basal cell carcinomas. Recent clinical studies also suggest that large surface photodynamic therapy can prevent the development of actinic keratoses and possibly skin cancer.     

Actinic Keratosis

Actinic keratoses are hyperkeratotic skin lesions that represent focal abnormal proliferation of epidermal keratinocytes. Some actinic keratoses evolve into squamous cell carcinoma of the skin, while others resolve spontaneously. The conversion rate of actinic keratosis to squamous cell carcinoma is not accurately known, but appears to be in the range of 0.25 to 1% per year. Although there is a low rate of conversion of actinic keratoses to squamous cell carcinoma, 60% of squamous cell carcinomas of the skin probably arise from actinic keratoses. The main cause of actinic keratoses in otherwise healthy Caucasians appears to be the sun. Therapy for actinic keratoses begins with prevention which starts with sun avoidance and physical protection. Sunprotection with sunscreens actually slows the return of actinic keratoses in patients already getting actinic keratoses. Interestingly, a few studies are available that demonstrate that a high fat diet is associated with the production of more actinic keratoses than is a low fat diet. One of the mainstays of therapy has been local destruction of the actinic keratoses with cryotherapy, and curettage and electrodesiccation. A new addition to this group of therapies to treat individual actinic keratoses is photodynamic therapy with topical aminolevulinic acid and light. In patients who have numerous actinic keratoses in an area of severely sun damaged skin, therapies which are applied to the whole actinic keratosis area are used. The goal of treating such an area of skin is to treat all of the early as well as the numerous clinically evident actinic keratoses at the same time. The classical approaches for treating areas of photodamaged skin without treating actinic keratoses individually include: the use of topically applied fluorouracil cream, dermabrasion, and cutaneous peels with various agents like trichloroacetic acid. Both topically as well as orally administered retinoids have been used to treat actinic keratoses but retinoids alone are probably not an optimal monotherapy. Photodynamic therapy with topical aminolevulinic acid and light is a new therapy for actinic keratoses. Aminolevulinic acid is a precursor of protoporphyrin IX (PpIX) which is synthesized in the actinic keratosis when it is treated with aminolevulinic acid, and the PpIX photosensitizes the actinic keratosis so that light exposure can lead to its destruction. Photodynamic therapy with topical aminolevulinic acid is approved in the US to treat multiple individual actinic keratoses on the face and scalp and has similar cure rates to those reported for cryotherapy and fluorouracil therapy.     

Cornu cutaneum

We report on 62 cases of cornu cutaneum. In contrast to the general opinion that the majority of these lesions arise on the basis of an underlying actinic keratosis or a squamous cell carcinoma, on histological examination we found actinic keratoses in only 25% and squamous cell carcinomas in only 3.2% of cases; 58% of all lesions were identified as common warts. We therefore recommend removal of these skin lesions by the shaving technique followed by electrodesiccation of the base. This has the advantage of supplying the histopathologist with a representative specimen for histological examination and avoiding an unnecessarily large surgical excision. In the rare cases of histologically confirmed squamous cell carcinoma, these lesions can be excised in a second session.