Validity of patient self-reported history of skin cancer

OBJECTIVE: To determine the validity of patient self-report of skin cancer history. DESIGN: A cohort of patients was randomly selected from the case group in a prior case-control study involving skin cancer, and a second cohort was randomly selected from the controls of that study. Patient self-reported history (as determined by responses to a survey) was compared with the gold standard of chart documentation of a pathology report or a procedure note from Mohs micrographic surgery demonstrating skin cancer. SETTING: University-based outpatient dermatology clinic. PATIENTS: Three hundred patients were selected. MAIN OUTCOME MEASURES: Patients were considered to have correctly classified their skin cancer history if their self-reported history was consistent with chart documentation. RESULTS: We obtained chart information for 258 patients.Of those patients, 183 (70.9%) had chart documentation of nonmelanoma skin cancer, and 16 (6.2%) had chart documentation of a melanoma. Using chart documentation as the gold standard, we found that patients correctly identified their basal cell carcinoma status in 84.3% of cases; their squamous cell carcinoma status in 81.5% of cases; their overall nonmelanoma skin cancer status in 91.8% of cases; their melanoma status in 94.8% of cases; and their overall skin cancer status in 92.6% of cases. Patients' self-reported history of skin cancer of any type had a positive predictive value of 95.1% and a negative predictive value of 85.9%. CONCLUSIONS: Self-reported history of skin cancer had a high degree of sensitivity and specificity and a high positive and negative predictive value within the study population. Obtaining medical information by patient report appears to be a useful tool for determining medical history of skin cancer.     

The risk of malignancy associated with psoriasis

OBJECTIVE: To measure the incidence of cancer in patients with psoriasis, stratified by the severity of their disease. DESIGN: A cohort study. SETTING: Administrative claims records obtained from Medicaid programs in 3 US states. PARTICIPANTS: All individuals in the claims database who qualified for 1 of the 5 following groups: severe psoriasis as defined by treatment with systemic medication, less severe psoriasis, severe eczema, history of organ transplantation, and hypertension. MAIN OUTCOME MEASURE: A diagnosis of cancer. RESULTS: Individuals with severe psoriasis were more likely to develop a malignancy than those with hypertension (risk ratio, 1.78; 95% confidence interval [CI], 1.32-2.40). The risk of malignancy in the severe psoriasis group approaches that in patients with organ transplants (risk ratio, 2.12; 95% CI, 1.80-2.50). Most of these cancers were nonmelanoma skin cancers and lymphoproliferative malignancies. Those with less severe psoriasis were only slightly more likely to develop a new malignancy than those with hypertension (risk ratio, 1.13; 95% CI, 1.03-1.25). CONCLUSIONS: Patients with psoriasis are at an increased risk of developing a malignancy compared with patients with hypertension. The increased risk is greatest for those with severe disease (ie, patients with psoriasis treated with systemic agents) and minimal (if an increased risk at all) for those with less severe disease compared with those in the hypertension group. The increased risk is mainly for lymphoproliferative cancers and nonmelanoma skin cancers.     

Sunscreen use before and after transplantation and assessment of risk factors associated with skin cancer development in renal transplant recipients

OBJECTIVE: To determine the degree of compliance with sunscreen use among renal transplant recipients before and after transplantation and to determine risk factors associated with skin carcinogenesis. DESIGN: Single-observer study with structured interview using a standardized questionnaire. Medical records and histology reports were examined for details of prior skin cancer. Cox proportional hazards regression was used for analysis of risk factors for developing skin cancer after transplantation. SETTING: Patients attending Beaumont Hospital, the national renal transplantation center in Dublin, Ireland. PATIENTS: The study population comprised 270 patients (182 male and 88 female). MAIN OUTCOME MEASURES: Patients' use of sunscreens before and after transplantation relative to known skin cancer risk factors and subsequent skin carcinogenesis. RESULTS: Prior to transplantation, 68.5% of patients never applied sunscreen on a sunny day compared with 25.9% after transplantation. Patients 50 years or younger were more likely to always apply sunscreen both before and after transplantation (P = .01), as were female patients prior to transplantation (P = .02). Those patients who participated in an outdoor recreation were more likely to subsequently develop nonmelanoma skin cancer (P = .04), as were those older than 50 years (P<.001) and those with a history of 2 or more painful sunburns (P = .03). CONCLUSIONS: Transplant recipients are poorly compliant with the use of sunscreens both before and after transplantation. Compliance is poorest in those groups at higher risk of nonmelanoma skin cancer.     

Nonmelanoma skin cancers and infection with the human immunodeficiency virus.

BACKGROUND AND DESIGN--Forty-eight human immunodeficiency virus-infected patients with nonmelanoma skin cancers seen during a four-year period were evaluated in a retrospective, case-control study. Patients were followed up after therapy and recurrence rates were determined. RESULTS--One hundred and sixteen nonmelanoma skin cancers were identified, 101 of which were basal cell carcinomas (87%), mostly superficial multicentric (67%) of the trunk (62%). There were 15 low-grade squamous cell carcinomas, most commonly of the head and neck. Half of the patients had multiple cancers. Compared with age-matched controls, the patients with skin cancer more commonly had blue/hazel eyes (89% vs 66%; odds ratio [OR] 4.1; confidence interval [CI], 1.25 to 13.44; P = .033), blond hair (42% vs 13%; OR = 4.53; CI, 1.40 to 13.74, P = .003), a family history of skin cancer (45% vs 5%; OR = 11.88; CI, 2.85 to 49.57; P = .00), and a history of regular sunbathing (92% vs 48%; OR = 11.24; CI, 3.17 to 39.83; P = .00). The number of cancers or the presence of squamous cell carcinoma did not correlate with the degree of immunosuppression. The recurrence rate for basal cell carcinomas following standard treatment methods (mostly curettage and electrodesiccation and excision) was 5.4% for those tumors followed up for longer than 12 months. Three of the 15 squamous cell carcinomas recurred, all following curettage and electrodesiccation. CONCLUSION--Nonmelanoma skin cancers are a not uncommon cutaneous finding in human immunodeficiency virus-infected patients. The major risk factors for developing skin cancer in association with human immunodeficiency virus disease seem to be the same as in the normal population--fair skin, a positive family history, and sun exposure. Standard treatment methods seem to be associated with acceptable cure rates, except for squamous cell carcinomas, which had a high (20%) recurrence rate following curettage and electrodesiccation.     

A family study of atopic dermatitis

Summary The history of 188 Caucasian patients with atopic dermatitis (AD) and of 2,151 family members has been analyzed. Of the AD patients 48% suffered from respiratory atopy (36% rhinitis, 28% asthma, and 15% both). AD showed by far the earliest onset of all atopic diseases: 50% of our patients had skin lesions before the age of 2 years and 60% before the age of 5 years. In contrast, symptoms of allergic asthma developed in 40% of AD patients before the age of 5 years in comparison with only 25% who had allergic rhinitis. AD affects females more frequently than males (male to female ratio 11.5), regardless of whether additional respiratory atopies are present or not. In contrast, respiratory atopies develop more frequently in males than in females (male to female ratio 1.51). Mothers with respiratory atopy more often have atopic children (26%) than do fathers with respiratory atopy (13%). Finally, risk figures for genetic counselling are given. In short, the general risk of developing AD (3%) and atopy (7%) increases by a factor of two with each first-degree family member already suffering from atopy.     

HLA alleles in renal transplant recipients with nonmelanoma skin cancer in southeastern Brazil

Background: Renal transplant recipients are submitted to immunosuppression to avoid graft rejection, which makes them susceptible to various conditions. Furthermore, these individuals present malignant tumors more frequently than the general population, including nonmelanoma skin cancer. The individual genetic basis that acts in the pathogenesis of cutaneous cancer may present a protection or susceptibility factor for disease development. One of these factors is the HLA complex.Objective: To investigate HLA alleles association to the occurrence of nonmelanoma skin cancer in renal transplant recipients from Sao Paulo State.Methods: A total of 213 patients (93 renal transplant recipients with nonmelanoma skin cancer and 120 renal transplant recipients without nonmelanoma skin cancer) were evaluated by retrospective and cross-sectional study. Epidemiological, clinical and HLA typing data were found in databases. HLA class I (A, B) and class II (DR) alleles were compared to establish their association with nonmelanoma skin cancer.Results: Comparing renal transplant recipients with and without nonmelanoma skin cancer, the HLA-B*13 allele was associated with higher risk of developing nonmelanoma skin cancer while B*45 and B*50 alleles were associated with protection.Study limitations: The HLA A, B and DR alleles identification for the kidney transplantation routine is done by low and medium resolution techniques that do not allow discrimination of specific alleles.Conclusion: The involvement of HLA alleles in nonmelanoma skin cancer in renal transplant recipients was confirmed in this study. Renal transplant recipients with HLA-B*13 showed higher risk for developing a skin cancer (OR= 7.29) and should be monitored for a long period of time after transplantation.     

RISK OF CANCER IN RELATIVES OF PATIENTS WITH CUTANEOUS MELANOMA

Background. Cutaneous malignant melanoma (CMM) is a recognized feature of the Lynch type II cancer-family syndrome and the Li-Fraumeni's syndrome. A significant contribution of these syndromes to the total burden of CMM would be reflected in an increased risk of nonmelanoma cancers in first degree relatives. Methods. Pedigrees were taken from 85 patients with CMM using a family history questionnaire. The relative risk of death from all cancers and individual cancers in first degree relatives was calculated. Results. Of the 85 questionnaires, those of 79 patients were completed and of adequate quality for analysis. The first degree relatives of CMM patients showed no increased risk of cancer death, the relative risk of cancer death being 1.0. Six patients (7.6%) had first degree relatives with CMM. One patient had a family history compatible with the dominant transmission of a predisposition to cancer. Conclusions. It is important to establish whether an increased cancer risk is present in relatives of patients with malignancies so that screening programs may be offered. This study provides little evidence to support seeing relatives for noncutaneous malignancies in the absence of a dominant family history of predisposition to cancers. The increased frequency of CMM in relatives suggests that relatives of CMM patients should be counseled on protection from the sun and examination of the skin for melanoma.     

Awareness of, knowledge of and attitudes to nonmelanoma skin cancer (NMSC) and actinic keratosis (AK) among physicians

BACKGROUND: Nonmelanoma skin cancer (NMSC) is the most common type of cancer that affects the Caucasian population. Approximately 80% of NMSCs are basal cell carcinoma (BCC) and 20% are squamous cell carcinoma (SCC). Actinic keratosis (AK) is a precancerous lesion that may develop into SCC. METHODS: A market research survey was conducted in which dermatologists and primary care physicians (PCPs) were randomly selected from seven countries (USA, Australia, UK, Italy, France, Germany and Spain). Their knowledge of nonmelanoma skin cancer and their current clinical practice were assessed. RESULTS: In total, 2100 physicians took part in the survey. They had practised medicine for between 1 and 30 years and saw at least 30 patients in a typical week. The majority of dermatologists (97%) were familiar with BCC and AK, and treated each condition with a minimum of referrals. PCPs were more familiar with BCC (90%) than with AK (74%). Of the PCPs that were aware of BCC, only 31% treated the condition, and of those aware of AK, 40% treated the condition. Surgery was the most common choice of treatment for BCC. The most popular treatment choice for AK lesions was cryotherapy. Eighty to 100% of physicians reported that they discussed skin cancer prevention with their patients. A much lower number of physicians (ranging from 5 to 37%) provided educational material to patients. Overall, PCPs in the two countries that have a high incidence of NMSC (USA and Australia) were more familiar with BCC and AK and more likely to treat each condition than PCPs in Europe. All physicians rated BCC as a more serious condition than AK. Facial lesions were considered more serious than lesions on the head or trunk for both conditions. CONCLUSIONS: As the burden of disease and the number of patients seeking treatment for NMSC increase, dermatologists are well placed to lead educational initiatives for PCPs and provide educational material for patients. This would increase awareness of AK and BCC and could improve early diagnosis.     

Incidence of cancer among patients with hidradenitis suppurativa

BACKGROUND: On the basis of some case reports, a relationship has been suggested between hidradenitis suppurativa (HS) and the development of nonmelanoma skin cancer. OBJECTIVES: To confirm this relationship and to explore the risk of other cancers among patients with HS. PATIENTS: Patients with a discharge diagnosis of HS were obtained from the computerized database of hospital discharge diagnoses from January 1, 1965, through December 31, 1997. A total of 2119 patients with HS were identified. SETTING: All hospitals in Sweden. DESIGN: With record linkage to the Swedish National Cancer Registry, standardized incidence ratios (SIR [the ratio of the observed to expected incidence]) were calculated to estimate relative risk. RESULTS: The risk of developing any cancer in the cohort with HS increased 50% (95% confidence interval of SIR, 1.1-1.8, based on 73 observed cases). Statistically significant risk elevations were observed for nonmelanoma skin cancer (5 cases; SIR, 4.6; 95% confidence interval, 1.5-10.7), buccal cancer (5 cases; SIR, 5.5; 95% confidence interval, 1.8-12.9), and primary liver cancer (3 cases; SIR, 10.0; 95% confidence interval, 2.1-29.2). CONCLUSIONS: This study confirms an increased risk of nonmelanoma skin cancer among patients with HS. The risk for buccal cancer and primary liver cancer was also elevated among this cohort, but these associations should be interpreted cautiously because the combination of multiple significance testing and the few observed cases may have generated chance findings.     

Increased risk of skin cancer associated with the presence of epidermodysplasia verruciformis human papillomavirus types in normal skin

BACKGROUND: Human papillomaviruses (HPVs) are found in normal skin and in benign and malignant skin conditions. Epidermodysplasia verruciformis (EV) HPV types are those most plausibly linked to the development of squamous cell carcinomas of the skin. OBJECTIVES: To assess the risk of nonmelanoma skin cancer (NMSC) associated with the presence of EV HPV in normal skin in immunocompetent (IC) individuals and renal transplant recipients (RTRs). METHODS: Using a degenerate and nested polymerase chain reaction technique, HPV DNA was sought in 124 normal skin samples from sun-exposed and nonsun-exposed sites, from 39 IC individuals and 38 RTRs, both with and without NMSC. Data were analysed using the Mantel-Haenszel test and by logistic regression analysis. RESULTS: HPV DNA was detected in 58/67 (87%) and 20/57 (35%) samples from renal transplant and IC patients, respectively. There was no difference in either the prevalence or spectrum of HPV types found in sun-exposed and nonsun-exposed normal skin. However, there was significant association between NMSC and the presence of EV HPV DNA. Multivariate analysis provided an odds ratio of 6.41 (95% confidence interval 1.79-22.9) for the association of EV HPV DNA in normal skin (irrespective of site) and NMSC status, even after stratifying for patient group and adjusting for the clustering effect of multiple sampling. Conversely, there was no association between skin cancer status and the presence of cutaneous or mucosal HPV types in either sun-exposed or nonsun-exposed skin. CONCLUSIONS: HPV DNA is widespread in normal adult skin, particularly in transplant patients. In our study, the presence of EV but not cutaneous HPV DNA in normal skin was significantly associated with NMSC status and may prove to be of predictive value for skin cancer risk. These data provide reason to focus on EV HPV types as causal agents in skin cancer.     

The risk of developing non‐melanoma skin cancer,lymphoma and melanoma in patients with psoriasis in Taiwan: a 10‐year,population‐based cohort study

Background Hospitalized psoriasis patients are known to have a higher risk of malignancy (e.g., nonmelanoma skin cancer [NMSC], lymphoma, and melanoma) than the general population; currently, it is unclear whether this risk is affected by psoriasis severity. The aim of this study was to compare the cancer risk of patients with mild and severe psoriasis and the general population. Methods Data for this retrospective population‐based cohort study were obtained from the Taiwan National Health Insurance Research Database. This study included 7061 patients with a first‐time diagnosis of psoriasis. All study individuals were followed up until the end of 2007. The crude incidence density ratio and standardized incidence ratio (SIR) of NMSC, melanoma, and lymphoma were determined. Results Among psoriasis patients, the most common cancer was NMSC (density ratio: 7.5); women were at a higher risk of NMSC than men (density ratios: 8.08 vs. 7.0). Psoriasis patients in the south geographic group or in the 50‐ to 59‐year‐old age group were most likely to develop NMSC. The NMSC SIR was higher among patients with severe psoriasis than among patients with mild psoriasis (SIR: 3.72 vs. 7.08). The lymphoma and melanoma SIR among patients with severe psoriasis was also high (lymphoma SIR: 4.85; melanoma: 11.01). Conclusions Psoriasis carries an elevated risk of NMSC and lymphoma. This effect is modified by the severity of psoriasis, age, gender, and geographic location.     

p53 mutation in nonmelanoma skin cancers occurring in psoralen ultraviolet a-treated patients: evidence for heterogeneity and field cancerization

A combination of psoralens and ultraviolet A radiation is widely used to treat psoriasis. Long-term, high-dose exposure to psoralen + ultraviolet A is associated with an increased risk of nonmelanoma skin cancer, particularly squamous cell carcinoma. In this study, we used p53 mutations as a molecular marker to determine the separate contributions of psoralen + ultraviolet A and other ultraviolet exposures, such as ultraviolet B for skin cancer development in psoralen + ultraviolet A-treated psoriasis patients. The results indicated that of 69 tumors analyzed, 37 (54%) tumors had one or more p53 mutations. Of 37 tumors with mutations, 17 (46%) tumors had only ultraviolet-type mutations, two (5%) tumors had only psoralen + ultraviolet A-type mutations, and 18 (49%) tumors had both types of mutations. Interestingly, psoralen + ultraviolet A-type p53 mutations were more frequent than ultraviolet type in tumors arising in patients with high-dose exposure to psoralen + ultraviolet A. Field cancerization and tumor heterogeneity appeared to occur frequently in the same patient and even in the same tumor. This study's data suggest that psoralen + ultraviolet A-induced p53 mutations may play an important part in the development of nonmelanoma skin cancer in psoralen + ultraviolet A-treated patients, but these mutations are likely to act in concert with the effects of other carcinogenic exposures, particularly ultraviolet B, in the development of skin cancer.     

Contact sensitization to common haptens is associated with atopic dermatitis: new insight

Background It has been much debated whether atopic dermatitis (AD) is associated with contact sensitization as past findings have been conflicting. A positive association might change our clinical practice. Objectives To investigate the association between AD and contact sensitization taking the likely route of allergen exposure into account. Methods Questionnaire and clinical data from a cross‐sectional study performed in a general population in Copenhagen. In total, 3202 adults aged 18–69 years were patch tested, filaggrin genotyped for 2282del4 and R501X and questioned about AD. Results The variable ‘contact sensitization to at least one allergen, but not nickel and thimerosal’ was significantly associated with AD (odds ratio 2·53, 95% confidence interval 1·59–4·04). The higher prevalence of contact sensitization was driven mainly by fragrance chemicals. In a subanalysis in nonpierced women, a positive association was also found for nickel sensitization. Nickel and thimerosal sensitization may introduce bias in data analysis as these allergies often develop following skin piercing where the skin compartments are bypassed. Conclusions We suspect that individuals with self‐reported AD from this study mainly had mild disease. However, clinicians should be aware of increased levels of contact sensitization in individuals with AD. Patch testing should therefore be considered at an early point in individuals with a history of AD and active disease. The fundamental relationship between atopic disease and environmental chemical exposure may be of a more complex and intimate nature than previously supposed.     

Tanning bed exposure increases the risk of malignant melanoma

BACKGROUND: Epidemiologic studies have associated tanning bed exposure and cutaneous melanoma. The relationship between the extent of tanning bed exposure and the risk of melanoma has not been elucidated in detail. METHODS: Surveys assessing the extent of tanning bed exposure and the history of skin cancer, including malignant melanoma, were collected from academic dermatology clinic patients (n = 1518). Of these, 551 (36.3%) completed all components of the survey. The available medical records, including pathology reports (n = 501; 33%), were reviewed to confirm cases of skin cancer. Data on potential confounding factors, including indoor vs. outdoor occupation and leisure activities, Fitzpatrick skin type, history of blistering sunburn, use of sunscreen and sun protective clothing, history of phototherapy, and level of education, were assessed and compared. RESULTS: Of the patients surveyed, 487 (32.1%) reported tanning bed exposure. Women aged 45 years or younger accounted for about 60% of all tanning bed users. Seventy-nine cases of malignant melanoma were reported, 22 in women aged 45 years or younger. In the entire cohort, the "ever-use" of tanning beds was found to be a significant risk factor for the development of melanoma [P < 0.05; odds ratio (OR), 1.64; 95% confidence interval (95% CI), 1.01-2.67]. The risk was greater in women aged 45 years or younger (P < 0.05; OR, 3.22; 95% CI, 1.01-11.46). Patients with a history of melanoma were significantly more likely to report tanning bed sessions exceeding 20 min (P < 0.01; OR, 3.18; 95% CI, 1.48-6.82); this association was even stronger for women aged 45 years or younger (OR, 4.12; 95% CI, 1.41-12.02). LIMITATIONS: The study was subject to recall bias, included only patients at a midwestern academic practice, and had a relatively low response rate. CONCLUSION: Exposure to tanning beds increases the risk of malignant melanoma, especially in women aged 45 years or younger. These findings reinforce the hazards of tanning bed exposure.     

Risk factors for basal cell carcinoma in a Mediterranean population: role of recreational sun exposure early in life

OBJECTIVE: To investigate the role of pigmentary traits, different patterns of sun exposure, artificial sources of UV radiation, and lifestyle-related factors on the risk of basal cell carcinoma (BCC) in a Mediterranean population from central-southern Italy. DESIGN: Hospital-based case-control study. SETTING: A referral dermatological hospital in Rome, Italy. PATIENTS: A convenience sample of 166 case patients with histologically confirmed BCC and 158 cancer-free control subjects with minor dermatological conditions observed between March 1995 and June 1997. RESULTS: In the multivariate analysis, the mean number of weeks per year spent at the beach before the age of 20 years was significantly associated with BCC. A dose-response trend was found for subjects who had spent 3 to 4 (odds ratio, 1.8; 95% confidence interval, 0.8-4.4), 5 to 8 (odds ratio, 3.7; 95% confidence interval, 1.5-9.0), or more than 8 (odds ratio, 4.5; 95% confidence interval, 1.9-10.5) weeks per year at the beach (P =.01 for trend). There was a significant association with the presence of actinic keratoses or solar lentigines, whereas no effect was found for skin type, history of sunburns, exposure to nonsolar UV radiation, and lifestyle-related habits such as cigarette smoking, alcohol consumption, and coffee drinking. Subjects reporting a family history of skin cancer had an extremely increased risk of BCC. CONCLUSION: The definite association with recreational sun exposure during childhood and adolescence and the strong relation with family history of skin cancer suggest that genetic predisposition and peculiar exposure patterns to UV radiation are key independent risk factors for the development of BCC in a southern European population.     

Efficacy of curettage before excision in clearing surgical margins of nonmelanoma skin cancer

OBJECTIVE: To determine whether curettage before excision of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) improves margin clearance rates. DESIGN: A retrospective, nonrandomized, case-control series of nonmelanoma skin cancers treated with preexcisional curettage followed by simple excision was identified using a computerized search of the database of a dermatopathology service. A validation cohort was established by manually identifying nonmelanoma skin cancers treated with wide excision on a given day. SETTING: All analyzed specimens were derived from the Dermatopathology Service at the University of California, San Francisco, a university-based laboratory that provides interpretation of skin biopsy specimens received directly from community (90%) and academic (10%) practices. PATIENTS: Our retrospective cohort consisted of all nonrecurrent nonmelanoma skin cancers diagnosed by biopsy and treated by simple excision between April 1, 1997, and April 30, 1999. There were 1983 BCCs and 849 SCCs included in our study. The validation cohort included skin cancers diagnosed by biopsy treated with simple excision on the 16th day of each month during the same period. INTERVENTION: Preexcisional curettage. MAIN OUTCOME MEASURE: We compared the frequency of tumor margin involvement of curetted vs noncuretted lesions. Margin involvement was considered surgical failure. RESULTS: Forty-two pecent of BCCs and 34% of SCCs were curetted before excision. In BCC, risks for surgical failure included head and neck lesions (P<.001), lesions treated by physicians performing fewer than 51 procedures (P<.001), and invasive subtypes (P<.01). Factors associated with surgical failure in SCC included in situ disease (P=.01) and an older (77 vs 74 years) patient population (P=.05). In univariate analysis, curettage before excision decreased the surgical failure rate for BCC by 24% (P=.03) but did not decrease the rate for SCC (P=.8). In multivariate analysis, curettage of BCC reduced surgical failure rates by 26% when the physician performed 50 skin cancer excisions or less during the study (odds ratio, 0.74; 95% confidence interval, 0.57-0.95;P=.02). CONCLUSION: Preoperative curettage decreases the frequency of positive margins in the management of BCC but not of SCC.     

A review of malignancies observed during efalizumab (Raptiva) clinical trials for plaque psoriasis

BACKGROUND: Psoriasis is a chronic, incurable immune-mediated disease. Most therapies used for moderate to severe psoriasis are immunosuppressive. Agents that depress immune function, including traditional psoriasis therapies, have been associated with an increased incidence of malignancies. Efalizumab is a recombinant monoclonal immunoglobulin G1 (IgG1) antibody approved for use in psoriasis patients. OBJECTIVES: To evaluate the incidence of malignancy in patients receiving efalizumab during clinical trials compared with placebo-treated patients, psoriasis patients from external cohorts and the general US population. METHODS: Patient data were pooled from multiple phase III placebo-controlled, open-label efalizumab clinical trials, and the incidence rate of reported malignancies was calculated as a function of patient years of observation. The results for the efalizumab-treated patients were compared with the data on psoriasis patients from insurance claims databases and a registry of events in the general population. RESULTS: The efalizumab- and placebo-treated patients had similar incidence rates of malignancy, including lymphoproliferative disease, solid tumor, malignant melanoma and nonmelanoma skin cancer. The incidence of nonmelanoma skin cancers, including basal cell carcinoma and squamous cell carcinoma, in patients receiving efalizumab or placebo was elevated relative to the external databases. CONCLUSIONS: These results suggest that efalizumab treatment does not increase a patient's risk for malignancy. The difference observed with nonmelanoma skin cancer may be due to biases introduced by the clinical trial methodology. Additional patient observation is necessary to ascertain whether a link exists between efalizumab therapy and nonmelanoma skin cancer above that normally observed in psoriasis patients.     

Multiple nonmelanoma skin cancer in an exposed Australian population

BACKGROUND: Patients with nonmelanoma skin cancer (NMSC) frequently develop multiple skin cancers. The study presents incidence rates and rates of excision of NMSC for a population living in a high-risk environment for skin cancer. METHODS: Between 1997 and 1999 a prospective population-based study collected information on all histologically confirmed NMSCs in Townsville, Australia. RESULTS: Of the 6708 patients recorded with NMSC, 38.5% had multiple lesions. Yearly age-standardized incidence rates (per 100,000 inhabitants) of basal cell carcinoma (BCC) were 1444.8 for men, 942.7 for women, and of squamous cell carcinoma (SCC) were 805.0 for men, and 423.6 for women. Compared to incidence rates, age-standardized rates of lesions of BCC were 2.1 times higher in men, 1.6 times higher in women, and of SCC were 1.8 times higher in men and 1.4 times higher in women. CONCLUSIONS: The occurrence of multiple NMSCs compromises results of short-term studies on incidence. Further discussions on the most appropriate strategies to describe the real burden of NMSC are warranted.     

Full-body skin examinations: the patient's perspective

OBJECTIVES: To determine (1). primary care practitioner (PCP) and dermatologist full-body skin examination (FBSE) rates by using a patient questionnaire and (2). whether patient risk factors for skin cancer alter these rates. DESIGN: Questionnaires pertaining to whether participants underwent regular FBSE, their feelings about this screening test, and their risks for developing skin cancer. SETTING: The primary care and dermatology clinics at the West Haven Veterans Affairs Medical Center. PARTICIPANTS: A convenience sample of 356 patients awaiting clinic appointments. Of those asked to participate, 251 (71%) agreed. MAIN OUTCOME MEASURES: Patient report of undergoing FBSE, attitudes regarding this examination, and risk factors for cutaneous malignancy. RESULTS: Thirty-two percent of all respondents reported undergoing regular FBSE by their PCP, whereas 55% of those with a history of skin cancer reported undergoing FBSE. Eight percent of participants reported embarrassment with FBSE, 83% reported that their PCP would be considered thorough by performing FBSE, and 87% would like their PCP to perform FBSE regularly. Only 2% of participants would refuse the examination if the PCP were of the opposite sex, whereas 8% would be more willing to be examined. CONCLUSIONS: Although patients report a low incidence of FBSE, those with a personal history of skin cancer are more likely to be screened. A low rate of embarrassment and a high rate of perceived PCP thoroughness are associated with FBSE. Patients have a strong preference to undergo FBSE. A sex difference between the PCP and the patient should not be a barrier to this examination.     

Bowen disease and risk of subsequent malignant neoplasms: a population-based cohort study of 1147 patients.

OBJECTIVE: To address the long-standing question of whether patients with Bowen disease are at increased risk of internal malignant neoplasms. PATIENTS: A total of 1147 Danish patients diagnosed between 1978 and 1993 as having Bowen disease at nongenital sites were followed up for 6463 person-years for cancer occurrence up to 16 years after the skin lesion. MAIN OUTCOME MEASURE: Standardized incidence ratios (SIRs)--the ratios of observed-to-expected numbers of cancer--served as measures of relative risk. RESULTS: The observed number of noncutaneous cancers occurring in the cohort (n = 115) was close to expected (n = 103.0) (SIR = 1.1; 95% confidence interval, [CI], 0.9-1.3). However, nonmelanoma skin cancer (SIR = 4.3; 95% CI, 3.5-5.4; n = 83), lip cancer (SIR = 8.2; 95% CI, 2.6-19.1; n = 5), and, among men, leukemia (SIR = 3.2; 95% CI, 1.04-7.5; n = 5) occurred in excess. CONCLUSIONS: Patients with Bowen disease do not appear to constitutionally be at any unusually high general cancer risk. The increased risk of invasive skin and lip cancers is likely due to the common risk factor of UV light.