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Background: Anti-tumor necrosis factor (TNF) therapy in psoriasis has been associated with an increased risk of serious infections compared with nonbiologic systemic therapies., Objective: We sought to quantify the risk of: (1) serious infections (leading to hospitalization, sequelae, or death); and (2) "any infection," bacterial cutaneous infections, and granulomatous infections among patients receiving anti-TNF therapy compared with nonbiologics (acitretin, methotrexate, cyclosporine)., Methods: We used prospective meta-analysis to combine data from the Psocare registry (Italy), Biobadaderm registry (Spain), and Clalit Health Services database (Israel), including 17,739 patients and 23,357.5 person-years of follow-up., Results: For serious infections, age, gender, and Charlson morbidity index adjusted hazard ratio of exposure to anti-TNFs compared with nonbiologics was 0.98 (95% confidence interval 0.80-1.19), for bacterial cutaneous infections it was 1.00 (95% confidence interval 0.62-1.61), and for granulomatous infections it was 1.23 (95% confidence interval 0.82-1.84). Using methotrexate as comparator and comparing first year of exposure with later exposure did not modify the results. For any infectious episode, risks and relative risks were heterogeneous among registries, probably because of different definitions of outcome., Limitations: There was lack of power to describe risk of single drugs., Conclusion: In current clinical practice, treatment with anti-TNF drugs was not associated with a higher risk of serious infections than treatment with nonbiologic systemic therapy., (Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

It has been hypothesized that severe psoriasis is an independent risk factor for cardiovascular disease (CVD). We prospectively studied patients with severe psoriasis treated with psoralens and ultraviolet-A therapy (PUVA) who enrolled in a cohort study in 1975-1976. From 1977 to 2005, 617 of the 1,376 patients (45%) died. Compared with the general population, cohort death rates were significantly higher than expected (standard mortality ratio (SMR) = 1.1, 95% confidence interval (CI) = 1.02-1.20). The number of deaths due to CVD (SMR = 1.02, 95% CI = 0.9-1.6) was nearly identical to the expected number. Deaths due to liver disease were significantly elevated (SMR = 4.04, 95% CI = 2.76-5.70). Patients with exceptionally severe psoriasis at entry (>42% body surface area (BSA)) had a significantly increased risk of death compared with less severely affected cohort members (all-cause hazard ratio (HR) = 1.42, 95% CI = 1.18-1.69) as well as for deaths because of causes other than cancer or CVD (multivariate HR 1.56, 95% CI = 1.14-2.13). Only patients with exceptionally severe psoriasis had an increased mortality risk compared with both the general population and other cohort members with less extensive but still severe psoriasis. These increases were not significant for CVD. Our data do not support the hypothesis that severe psoriasis is an independent risk factor for CVD. However, exceptionally severe psoriasis is associated with increased all-cause mortality.

A large number of clinical measures of psoriasis are used in clinical trials and daily practice. These measures lack uniformity and validation. However, valid outcome and severity measures for psoriasis are a prerequisite for fully informative clinical research and evidence-based medicine. The purpose of this study was to identify all clinical measures of psoriasis severity and outcome in use and to evaluate the quality of these measures using clinimetric criteria; we identified 53 separate clinical measures, which were regrouped into 11 measures for quality analysis. No measure could be scored on all items used in the clinimetric analysis. The Lattice System Physician's Global Assessment and Physician's Global Assessment were most highly noted. We conclude that none of the psoriasis measures is adequately validated. The Psoriasis Area and Severity Index is the most commonly used clinical measure in research, but it has substantial limitations such as low response distribution, no consensus on interpretability, and low responsiveness in mild disease. Nevertheless, because of its widespread use the Psoriasis Area and Severity Index permits some degree of comparison of results among clinical trials. Overall, no best instrument was identified, and different situations may call for different measures.

Since Gelfand's 2006 publication, the hypothesis that psoriasis is a risk factor for myocardial infarction (MI) and cardiovascular disease (CVD) has drawn substantial attention (Gelfand et al., 2006). Makers of biologic therapies for psoriasis, whose products cost $15,000 to $25,000 per patient treated per year, are prominent sponsors of symposia and publications that have advanced this hypothesis (Strober et al., 2008; Friedewald et al., 2008). A company-supported clinical trial testing the hypothesis that tumor necrosis factor (TNF) inhibitor therapy of psoriasis may also reduce cardiovascular risk is under way (ClinicalTrials.gov, 2007). In this issue, Wakkee et al. provide additional evidence that it is unlikely that either psoriasis or severe psoriasis is a relevant risk factor for MI. Even if--after accounting for confounding and bias--psoriasis is significantly associated with CVD risk, psoriasis is unlikely to be a clinically useful independent risk factor for CVD.

Objective: To assess the severity of psoriasis over time., Design: We analyzed the results of structured dermatologic examinations administered over a 20-year period beginning 10 years after study enrollment., Setting: The PUVA [psoralen-UV-A] Follow-up Study, which is a prospective cohort study., Patients: The analyses were restricted to 815 patients (83.2% of those eligible) who underwent at least 2 of 4 possible examinations between 1985 and 2005., Main Outcome Measure: A 4-point physician global assessment (PGA)., Results: The distribution of the PGA levels in the study group did not change significantly over time, except that in 2005 more patients had no psoriasis compared with patients who underwent examinations in the previous study years (9.6% vs < 5.1%, P < .03). The PGA level changed more than 1 level between examinations in only 14% of patients. Multistate Markov models estimated that patients had a likelihood of about 80% to remain at the same PGA level 1 year later. After 10 years, this likelihood varied between 19% and 53%, depending on the PGA level. Except for patients who were clear of disease at baseline, on average patients had about 1 year without psoriasis over 20 years. On average, individuals with moderate to severe disease remained at these levels for 11 or more years. Conclusion Three decades after a large and diverse group of patients sought a cure for their psoriasis, consistent control of their psoriasis often had not been achieved.

Background: In some animal species, exposure of the unprotected eye to psoralen plus ultraviolet A (PUVA) therapy induces lens opacities. The relevance of these animal findings to human beings is not established. However, some case reports suggest that PUVA in human beings may increase the risk of lens abnormalities., Objective: Our aim was to evaluate any possible associations between exposure to PUVA and increased risk of ocular lens abnormalities., Methods: Since 1977 the PUVA follow-up study has periodically monitored the ocular status of 1237 cohort members with psoriasis using structured eye examinations. In our previous report we presented data results of the first 10 years of prospective study. This report includes data from two additional cycles of eye examinations that span an additional 14 years of follow-up., Results: Based on our data from the last pre-1993 to final eye examination (2004), compared with that observed for the earlier period (first ever to last pre-1993 eye examination), the age-adjusted incidence of cataract did not increase significantly (incidence rate ratio = 1.04, 95% confidence interval = 0.82-1.31). In both the univariate and multivariate analyses increasing exposure to PUVA was not associated with a higher risk of cataract., Limitations: Our cohort principally enrolled middle-aged or older patients so our data do not permit us to assess the effects of PUVA on the eyes of younger persons., Conclusions: Increasing exposure to PUVA does not increase cataract risk among persons using eye protection at the rates used in our cohort.

Objective: To compare characteristics of patients enrolled in a long-term multicenter cohort trial who had used biological therapies for treatment of psoriasis with those who had not used these agents., Design: Retrospective analysis of users vs nonusers of biological therapies., Setting: Database from the PUVA Follow-up Study, a multicenter, 30-year study of patients originally treated with psoralen UV-A (PUVA) for moderate to severe psoriasis. Patients A total of 521 patients who completed the last cycle of follow-up of the PUVA Follow-up Study., Main Outcome Measures: Demographic data, severity data (physician global assessment), type of biological therapy used, patients' opinions about their therapy, and their best treatment., Results: Seventy-four of 521 patients (14%) used biological therapies: 65% etanercept (n = 48), 22% infliximab (n = 16), 11% efalizumab (n = 8), and 8% alefacept (n = 6). Users of biological therapies were younger, had more formal education, and were more likely to have had a greater extent of psoriasis at entry than the other cohort members. In 1998, those who used biological treatments were more likely than other cohort members to have been assessed as having severe psoriasis. In 2004, no significant difference was noted. Users of etanercept considered this agent to be as effective as methotrexate and more effective in clearing their skin and having fewer adverse effects than PUVA or UV-B. The proportion of patients originally enrolled in the 16 centers who had used biological agents varied greatly (0%-33%)., Conclusion: After short durations of therapy, patients' opinions about biological agents tended to be positive.

Background: A recent refinement study suggested that a Rasch reduced version of the Impact of Psoriasis Questionnaire (IPSO) of 11 items most adequately assessed the psychosocial impact of US psoriasis patients., Objective: To test whether the IPSO would also behave well in a different population that varies culturally, demographically, and in disease severity., Methods: The psychometric properties of the IPSO, using classical test and item response theory (Rasch analysis), were assessed in 805 Italian psoriasis patients., Results: Patients with more severe psoriasis reported significantly higher impact on their HRQOL (p < 0.001) and the IPSO correlated well with the Skindex-29 (r = 0.74) confirming its validity. The response distribution was adequate for all items, except item 9. The Cronbach's alphas were excellent and the high item-rest correlations confirmed its homogeneity. Principal component analysis demonstrated one dominant factor with an eigenvalue of 4.47 (items loading >0.40). Overall, the 11 IPSO items fitted the Rasch model (p = 0.07) and all items demonstrated a logical threshold order. Of the 11 items, 2 items showed significant individual misfit and only 1 item demonstrated significant differential item functioning for age but none for gender or global severity score., Conclusion: The 11-item IPSO is a valuable psoriasis-specific HRQOL instrument in different populations., (2007 S. Karger AG, Basel)

Objective: To assess the risk of lymphoma in patients with psoriasis., Design: Prospective cohort study that spans 30 years and a systematic review of the literature., Setting: Sixteen university medical centers., Patients: A total of 1380 patients with psoriasis who were initially treated with psoralen-UV-A (PUVA) from 1975 through 1976 and who underwent periodic interviews and physician examinations irrespective of their use of any treatment., Main Outcome Measure: Incidence of lymphoma relative to that expected in the general US population (original primary end point of the study)., Results: The incidence of lymphoma in patients who received PUVA and were not exposed to high levels of methotrexate was comparable to that expected in the general population (incidence rate ratio, 0.85; 95% confidence interval, 0.37-1.67) but was elevated among those exposed to high levels of methotrexate (> or =36 months) (incidence rate ratio, 4.39; 95% confidence interval, 1.59-12.06)., Conclusion: Unless exposed to high levels of methotrexate, the risk of lymphoma among members of the PUVA Follow-up Study was comparable to that observed in the general population.

Although psoriasis typically affects patients for many years, studies quantifying impairment in health-related quality of life (HRQOL) owing to psoriasis over long periods are lacking. This study, which interviewed patients independent of psoriasis care, investigates change in the impact of psoriasis on HRQOL over 11 years and factors associated with change among 484 patients using the Impact of Psoriasis Questionnaire (IPSO). We determined changes in the impact of psoriasis on HRQOL using a psychometrically optimized version of the IPSO. In 1993, the patients were 53+/-11.4 years and 61.8% males. From 1993 to 2004, impact on most social aspects of HRQOL remained stable, but concerns related to physical appearance decreased (e.g., 36-13%, P = 0.001). Over 11 years, the proportion of patients with low overall impact of psoriasis increased significantly (43-53%, P < 0.001). Mean IPSO scores (range 0-22) decreased by one-fifth (5-4, P < 0.001). At follow-up, patients reporting poor health had mean improvement in HRQOL about three times greater than those in good health (P < 0.05). In this large cohort interviewed independent of treatments and psoriasis status, impact of psoriasis on HRQOL decreases over time. For chronic diseases, HRQOL is best measured over time and independently of seeking treatment.

Although it has had only limited psychometric assessment in one country (the UK), the Psoriasis Disability Index (PDI) is a commonly used measure of the impact of psoriasis on patients. This study's objective was to analyze the psychometric properties of the PDI in 1196 US patients. High Cronbach's alpha coefficients suggested that the PDI's internal consistency is good. The validity of the PDI was tested using a global question on disease burden and self-assessed extent of disease and both appeared to be good predictors of the PDI. Large floor effects and the suboptimal response distribution of most items, however, suggested that the PDI is insensitive to mild functional limitation. Factor analyses indicated that the current PDI subscales are suboptimal. In the Rasch analysis, the PDI and its subscales appeared to measure multiple constructs, making the validity of deriving a single overall score questionable. The frequent presence of differential item functioning related to several patient characteristics confirmed the instrument's multidimensionality. These findings suggest that the PDI is not an optimal measure for use in US study populations. The psychometric properties of instruments designed to measure the impact of psoriasis should be tested in populations in which the instrument is to be applied.

Background: Many psoriasis patients are dissatisfied with current therapies. However, patient-centered levels of satisfaction with individual treatments have not been well described., Objective: To assess patients' satisfaction with 4 systemic treatment options available before 2002., Methods: We used data from a recent national survey. Psoriasis patients were randomly recruited from the general US population, members of the Psoriasis Foundation, and persons who contacted the Psoriasis Foundation but did not join. The interview included questions about use and satisfaction with specific Psoriasis therapy., Results: Of 1197 psoriasis patients interviewed, 311 (26%) indicated current or past use of methotrexate, psoralen plus ultaviolet A (PUVA), cyclosporin, and/or acitretin (users). Compared with those who had never used any of these systemic therapies, users reported more extensive disease (adjusted odds ratio [OR] = 2.90, 95% confidence interval [CI] = 1.87-4.49) and higher Psoriasis Disability Index scores (category V: adjusted OR = 2.31, 95% CI = 1.22-4.36). After adjusting for these variables, more than one third of patients were dissatisfied with each therapy, except for PUVA (14%). Patients were most satisfied with methotrexate and PUVA. However, less than 40% of the users indicated they were very satisfied with any of the 4 therapies assessed. Only 10% of persons who ever used cyclosporin were currently using it. In a paired analysis, cyclosporin users were significantly less satisfied with cyclosporin than with other therapies ( P = .01)., Conclusion: For most patients, none of the 4 systemic therapies widely utilized in 2002 for psoriasis were highly satisfactory. If we are to learn whether new treatments satisfy patients' needs, long term, prospective, comparative studies of heterogeneous patient populations that include patients' assessments are needed.

Sunlight and psoralen and ultraviolet A (PUVA) are risk factors for the development of squamous cell carcinoma (SCC) and, to a lesser extent, basal cell carcinoma (BCC). Ultraviolet B (UVB) therapy, used for the treatment of psoriasis, might also increase the risk of these tumors. We studied the relation of skin cancer incidence to UVB use among 1380 adult subjects enrolled in a long-term safety trial of PUVA therapy. We used negative binomial regression models to quantify the association between UVB and the development of non-melanoma skin cancer (NMSC), controlling for known confounders. High UVB exposure (> or =300 treatments vs <300 treatments) was associated with a modest but significant increase in SCC (adjusted incidence rate ratio (IRR)=1.37, 95% confidence interval (CI)=1.03-1.83) and BCC (adjusted IRR=1.45, 95% CI=1.07-1.96) risk. Among patients with <100 PUVA treatments, high UVB exposure was significantly associated with the development of SCC (adjusted IRR=2.75, 95% CI=1.11-6.84) and BCC (adjusted IRR=3.00, 95% CI=1.30-6.91) on body sites typically exposed to UVB therapy but not on chronically sun-exposed sites typically covered during therapy. For adults with high UVB exposure levels, UVB confers a modest increase in NMSC risk, much less than that observed with PUVA. Therefore, UVB remains a relatively low-risk treatment for psoriasis.

Background: Psoriasis is a common disease with substantial effects on quality of life. The prevalence of psoriasis in African Americans has been previously reported as rare. However, there have been no population-based studies to assess the prevalence and burden of psoriasis in African Americans., Objective: We sought to measure the prevalence and burden of psoriasis in African Americans compared with Caucasians., Methods: Patients were randomly selected from the United States population and were asked standard demographic questions. Patients who reported a physician diagnosis of psoriasis were asked additional questions related to quality of life., Results: The total sample included 27,220 individuals of which 21,921 were Caucasian and 2443 were African American. The prevalence of psoriasis was 2.5% in Caucasian patients and was 1.3% in African American patients. African Americans had an approximately 52% reduction in the prevalence of psoriasis compared with Caucasians ( P < .0001). African Americans and Caucasians had similar impacts on quality of life and treatment satisfaction based on single global questions., Conclusion: Although psoriasis is less common in African Americans than in Caucasians, it is not rare in either demographic and carries a substantial burden in both groups.

Objective: Patient advocacy groups such as the National Psoriasis Foundation (NPF) serve as representatives of those affected by disease and provide information about the condition. Our objective was to assess the extent to which NPF members differ from nonmember patients with psoriasis in their knowledge and use of therapies., Participants: Using random-digit dialing, we identified and interviewed patients with psoriasis in the general US population. Randomly selected NPF members were also interviewed., Main Outcome Measures: Multivariate logistic regression models were used to estimate differences (odds ratios and 95% confidence intervals) in demographic and clinical characteristics and in awareness and use of therapies between members and others diagnosed as having psoriasis., Results: Of 601 individuals with psoriasis identified from the general population survey, 185 provided a second interview and were defined as nonmembers. We interviewed 289 randomly selected members of the NPF. Although members were significantly older and wealthier and had more extensive disease, they reported the disease to be significantly less of a burden and were more satisfied with therapy than others affected. Compared with nonmembers, members were significantly more likely to have heard of and used most of the 10 therapies assessed. However, the proportion of respondents who were aware of a therapy and who also used it did not differ between groups., Conclusion: Members of the NPF are better informed and more satisfied with available treatment options than nonmember affected patients.

Background: Psoriasis is a common disease with substantial effects on quality of life. Few quality of life studies have been performed in psoriasis patients from the general US population., Objective: To describe the determinants of quality of life in psoriasis patients from the US population., Methods: Patients were randomly selected from the US population. Patients who identified themselves as having been diagnosed with psoriasis by a physician were invited to complete a more detailed survey about quality of life., Results: Two hundred sixty-six psoriasis patients from the US population completed the detailed survey. Body surface area showed the strongest association with decrements in quality of life (Spearman 0.50, P < .0001). Younger patients and female patients also had statistically significant reductions in quality of life. Increasing psoriasis severity was associated with seeking care from multiple physicians and having decrements in income., Conclusion: Patients with more extensive skin involvement have greater reductions in quality of life. Female patients and young patients are affected to a greater extent.

The impact of psoriasis on quality of life has been studied in select patient populations. Population-based data detailing the distribution of extent of disease, associated problems in everyday life, and treatment satisfaction for the US population have been lacking. Our population-based survey indicates that approximately 4.5 million adults have been diagnosed as having psoriasis. Most (59%) have little or no involvement, but 650,000 adults have at least three palms of body surface involved and more than 1,000,000 indicate substantial dissatisfaction with their treatment. Only 5% of patients (56,000) who report severe dissatisfaction with current therapy have extensive disease (10 palms). Many individuals with little psoriasis at the time of interview considered the disease to be a large problem in everyday life.

Background: Small open studies of patients at high risk for squamous cell carcinoma (SCC) of the skin suggest that oral retinoid use reduces the risk of these tumors. Among patients at lower risk, randomized trials of low doses of retinoids did not demonstrate significant chemopreventive effects. Patients with psoriasis treated with oral psoralen-UVA have a high risk of SCC development. Oral retinoids are used to treat psoriasis. We performed a nested cohort study to assess whether oral retinoids reduce skin cancer risk among patients with psoriasis exposed to psoralen-UVA., Methods: From 1985 to 2000, 135 patients (11.3% of surviving patients in our cohort) used retinoids for at least 26 weeks in 1 year or more. For these 135 patients, we compared each person's SCC and basal cell carcinoma incidence during years of substantial oral retinoid use and other years. We used Poisson regression models to adjust for potential confounders., Results: In a paired analysis, which compared each patient's own tumor experience while using and not using retinoids, retinoid use was associated with a 30% reduction in SCC incidence (196 SCCs/1000 and 302 SCCs/1000 years of use and no use, respectively; P =.002). After adjusting for other factors associated with SCC risk, the incidence of SCC was significantly decreased during years of substantial retinoid use (incidence rate ratio = 0.79; 95% confidence interval = 0.65, 0.95). Oral retinoid use and basal cell carcinoma incidence were not significantly associated., Conclusion: In patients with psoriasis treated with psoralen-UVA, systemic retinoid use reduced SCC risk but did not significantly alter basal cell carcinoma incidence.

Background: Inpatient hospital care was a traditional approach to treat severe psoriasis. Since 1980, only modest innovations in psoriasis therapy have been introduced, but regulation and financing of inpatient hospital care have changed greatly., Objective: We documented changes in the use of inpatient care in acute care hospitals for psoriasis in a cohort of individuals with severe psoriasis and nationally., Methods: Using interviews, we quantified hospitalizations for psoriasis and other reasons among the PUVA Follow-up Study cohort. We used National Hospital Discharge Survey data to determine national trends in hospitalization rates., Results: In 2 decades, national rates of hospitalization primarily for psoriasis decreased more than 80%. Among our cohort of persons with severe psoriasis, the age-adjusted rate of hospital days for psoriasis decreased more than 60% during this period., Conclusion: Currently, hospitalization in acute care hospitals is seldom used to care for persons with psoriasis.

Background: In the general population, squamous cell carcinomas (SCCs) of the male genitalia are rare. Ten years ago, we documented a significant dose-dependent increase in the risk of malignant genital neoplasms among men treated with psoralen plus ultraviolet A (PUVA). Since that time, fewer cohort patients have used PUVA, and genital protection among PUVA users is likely to be frequent., Objective: Our aim was to determine the incidence and risk factors for genital neoplasms since 1989 and risk factors for these neoplasms among patients treated with PUVA., Methods: We conducted a prospective cohort study of 892 men first treated with PUVA in 1975-1976., Results: Twenty-four men (2.7%) had 51 genital neoplasms, including 10 patients with a first tumor after May 1, 1989 (the ending date for our 1990 report). Since May 1, 1989, the incidence of invasive penile and scrotal SCCs was elevated 52.6-fold (95% confidence interval, 19.3-114.6) compared with that expected for the general white population. Multivariate models revealed the highest genital tumor risk among men with high-dose exposure to both PUVA and topical tar/ultraviolet B, with an incidence rate ratio of 4.5 (95% confidence interval, 1.3-16.1) compared with the low-dose exposure group., Conclusion: Although use of PUVA has decreased and genital shielding in our cohort has increased, the dose-dependent increase in the risk of genital tumors in men treated with PUVA has persisted. Particularly high risks occur among those with high-dose exposures to both PUVA and topical tar/ultraviolet B.

Psoralen + ultraviolet A-treated psoriasis patients are at increased risk for squamous cell carcinomas and basal cell carcinomas; however, the incidence and risk factors associated with second squamous cell carcinomas and basal cell carcinomas in this population are not well qualified. Incidence and risk factors for second squamous cell carcinomas and basal cell carcinomas were studied in a cohort of 1380 psoralen + ultraviolet A-treated psoriasis patients prospectively followed for over 20 y; 264 had a squamous cell carcinoma and 258 a basal cell carcinoma after beginning psoralen + ultraviolet A therapy. After a first squamous cell carcinoma, the risk of a second squamous cell carcinoma was 26% at 1 y, 62% at 5 y, and 75% at 10 y. Risk increased with high psoralen + ultraviolet A exposure prior to the first squamous cell carcinoma (hazard ratio 3.32, 95% confidence interval 1.53, 7.18). Higher rates of post-first squamous cell carcinoma psoralen + ultraviolet A treatment also were associated with greater risk (hazard ratio 1.56 for every additional 10 treatments per year for patients with low pre-first squamous cell carcinoma psoralen + ultraviolet A exposure, 95% confidence interval 1.35, 1.81). Patients exposed to high levels of tar and/or ultraviolet B before a first squamous cell carcinoma were also at higher risk (hazard ratio 1.72, 95% confidence interval 1.14-2.60). Risk of a second basal cell carcinoma was 21% at 1 y, 49% at 5 y, and 61% at 10 y. There was some evidence that high exposure to psoralen + ultraviolet A before a first basal cell carcinoma was associated with increased risk of second basal cell carcinoma (hazard ratio 1.45, 95% confidence interval 0.97-2.17). Higher post-first tumor psoralen + ultraviolet A treatment rates also increased risk (hazard ratio 1.24 for every additional 10 treatments per year, 95% confidence interval 1.06-1.47). Psoralen + ultraviolet A-treated psoriasis patients appear to have a greatly increased incidence of second squamous cell carcinoma compared with the general population. Patients who develop a squamous cell carcinoma after starting psoralen + ultraviolet A therapy should be closely monitored for a subsequent squamous cell carcinoma.

Background: By 1977, psoralen and ultraviolet A (PUVA) was established as a highly effective therapy for psoriasis. Because of concerns about potential long-term adverse effects, particularly cancer, the PUVA Follow-Up Study was established to assess long-term risk and benefits of PUVA. Objective: We sought to determine the association of certain squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) risk with exposure to PUVA. Methods: For nearly 30 years, this prospective cohort study of 1380 patients with psoriasis first treated with PUVA in 1975 to 1976 documented exposures and incident events including biopsy-proven skin cancers. Results: From 1975 to 2005, 351 of 1380 (25%) cohort patients developed 2973 biopsy-proven SCC and 330 (24%) developed 1729 BCCs. After adjusting for age, gender, and significant confounders, the risk of developing one or more SCC in a year was strongly associated with total number of PUVA treatments (350-450 vs <50 treatments, incidence rate ratio [IRR] = 6.01, 95% confidence interval [CI] = 4.41-8.20). When all tumors are included this risk is significantly higher (IRR = 20.92, 95% CI = 14.08-31.08). Corresponding risks for BCC were much lower (person counts IRR = 3.09, 95% CI = 2.36-4.06; tumor counts IRR = 2.12, 95% CI = 1.47-3.05). Limitations: This was an observational prospective study of a cohort with severe psoriasis. An unknown factor associated with higher dose exposure to PUVA in our cohort that was not included in our analysis could account for the observed associations. Conclusion: Exposure to more than 350 PUVA treatments greatly increases the risk of SCC. Exposure to fewer than 150 PUVA treatments has, at most, modest effects on SCC risk. Even high-dose exposure to PUVA does not greatly increase BCC risk. The risks of SCC in long-term PUVA-treated patients should be considered in determining the risk of this therapy relative to other treatments for severe psoriasis. [ABSTRACT FROM AUTHOR]

Psoralen+ultraviolet A-treated psoriasis patients are at increased risk for nonmelanoma skin cancer. To assess the persistence of cancer risk among patients who have discontinued psoralen+ultraviolet A and the risk of a first tumor with the passage of time, we prospectively studied the incidence in a cohort of 1,380 psoriasis patients treated with psoralen+ultraviolet A. We observed a total of 27,840 person-years of which 59.4% were considered years without psoralen+ultraviolet. No significant decrease in risk was noted during the first 15 years after psoralen+ultraviolet A was discontinued. Subsequently, the risk of squamous cell carcinoma was reduced (incidence rate ratio=0.79; 95%CI=0.62, 1.01 on treatment vs >15 years off). After 25 years, about 7% of patients with ≤200 psoralen+ultraviolet A treatments and more than half of the patients with >=400 treatments develop at least one squamous cell carcinoma. After 25 years, almost one third of the patients exposed to >=200 treatments developed at least one basal cell carcinoma. In conclusion, substantial exposure to psoralen+ultraviolet A dramatically increases the risk of nonmelanoma skin cancer and prior exposure to psoralen+ultraviolet A remains an important issue in the management of patients because the cancer risk associated with psoralen+ultraviolet A is persistent. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Psoriasis can have a profound impact on a patient's quality of life. Objectives: To assess patients' perspectives on the impact of psoriasis on their lifestyle and emotional well-being and the social ramifications of living with the disease; to determine the range of therapies available; and to ascertain patients' satisfaction with the management of their disease. Design: A 4-page, self-administered questionnaire was mailed on July 13 and 14, 1998, to the entire membership of the National Psoriasis Foundation (N =40350), and followed by a telephone survey of responders with severe psoriasis. Main Outcome Measures: Patients' perspectives on the psychosocial impact of psoriasis and the effectiveness of the management of their disease. Results: Of the 40 350 questionnaires mailed out, a response rate of 43% was realized. The most frequent symptoms experienced by the mail-survey respondents were scaling (94%), itching (79%), and skin redness (71%); 39% reported that psoriasis covered 10% or more of their bodies. A total of 6194 patients with severe psoriasis were entered into the database for the telephone survey. Of these, 79% reported that psoriasis had a negative impact on their lives, 40% felt frustrated with the ineffectiveness of their current therapies, and 32% reported that treatment was not aggressive enough. Conclusions: The unprecedented response to the survey provides compelling evidence that individuals with psoriasis believe that the disease has a profound emotional and social as well as physical impact on their quality of life. Many patients with psoriasis, particularly those with severe disease, are frustrated with the management of their disease and by the perceived ineffectiveness of their therapies. Physicians may need to improve communication with their patients and should reevaluate their management of psoriasis. [ABSTRACT FROM AUTHOR]

Background/methods: The treatment of psoriasis with high-dose exposure to oral psoralen and ultraviolet-A light (i.e., PUVA) substantially increases the risk of cutaneous squamous cell cancer, but not of basal cell cancer, within a decade of beginning treatment. To assess the persistence of cancer risk among individuals treated with PUVA, including those who discontinued therapy long ago and those without substantial exposure to other carcinogens, we prospectively studied a cohort of 1380 patients with psoriasis who were first treated during the period from January 1, 1975, through October 1, 1976, and evaluated risk factors associated with the development of cutaneous squamous cell cancers and basal cell cancers after 1985.Results: From 1975 through 1996, 237 patients developed 1422 cutaneous squamous cell cancers. From 1986 through 1996, 135 (12.5%) of 1081 patients without a prior squamous cell cancer developed 593 such tumors. From 1975 through 1997, 247 patients developed 1042 basal cell cancers; these patients included 151 individuals with a first basal cell cancer after 1985. Among those without a squamous cell or a basal cell cancer in the first decade of the prospective study, a strong dose-related increase in the risk of squamous cell cancer was observed in the subsequent decade (adjusted relative risk [> or =337 treatments versus <100 treatments] = 8.6; 95% confidence interval = 4.9-15.2). Risk of basal cell cancer was substantially increased only in those patients exposed to very high levels of PUVA (> or =337 treatments).Conclusions: High-dose exposure to PUVA is associated with a persistent, dose-related increase in the risk of squamous cell cancer, even among patients lacking substantial exposure to other carcinogens and among patients without substantial recent exposure to PUVA. Exposure to PUVA has far less effect on the risk of basal cell cancer. The use of PUVA for psoriasis should be weighed against the increased cancer risk. [ABSTRACT FROM AUTHOR]

Discusses psoriasis. Explanation of the condition; Its four distinct pathological alterations; Symptoms; Differential diagnosis; Clinical subtypes; Associated diseases and exacerbating factors; Management; Types of vehicles for topical preparations used for psoriasis; Annual wholesale medication and direct treatment costs; References; Further reading.

After 10 years of prospective study of a cohort of 1,380 patients with psoriasis enrolled in the Photochemotherapy (PUVA) Follow-up Study, our data show that the incidence of death and causes of death were comparable to those expected in the general population. We noted no increase in cardiovascular mortality, nut observed that cirrhosis caused more deaths among our cohort than in the general population ( Standard Mortality Ratio: 4.7, P < 0.05). The overall incidence of non-cutaneous cancer was slightly but not significantly elevated in our population ( Standard Mortality Ratio=1.2, P > 0.05). In an analysis of individual sites, we observed significant increases in the incidence of colonic cancer and primary neoplasms of the central nervous system. We found no significant increase in the incidence of lymphoma, leukemia, or malignant melanoma within our cohort. Because of the possible long latency time and the low incidence of these malignancies only continued follow-up of this cohort van assure us that PUVA therapy does not substantially alter the risk for the development of these condition. [ABSTRACT FROM AUTHOR]

This 5-year prospective study of ophthalmologic findings in 1299 patients treated with oral 8-methoxypsoralen photochemotherapy (PUVA) for psoriasis failed to demonstrate a significant dose-dependent increase in the risk of developing symptomatic cataracts. These patients were instructed to wear UVA-blocking eye-glasses when exposed to sunlight and during treatment for a 12-h period beginning from the time of 8-methoxypsoralen ingestion. However, we did observe a small increase in the risk for development of nuclear sclerosis and posterior subcapsular opacities among patients who received at least 100 PUVA treatments, compared to patients with fewer than 100 treatments (relative risk = 2.3 and 3.0, respectively; p < .05 both comparisons). We compared our results to those of a large, population-based study and found, after adjusting for differences in methods, that the prevalence of cataracts in our study patients, aged 52-75 years, was not significantly different. Since the latency period for development of symptomatic ocular abnormalities may be longer than 5 years, continued surveillance of our cohort and continued use of appropriate ocular protection by all patients treated with PUVA is indicated. [ABSTRACT FROM AUTHOR]

Pigmented macules appearing in sun-protected sites of psoriatic patients treated chronically with oral methoxsalen photochemotherapy (PUVA) have been characterized as a lentiginous proliferation of relatively large, sometimes cytologically atypical, melanocytes (i.e., PUVA lentigines). In 1380 psoriatic adults followed prospectively, PUVA lentigines of any degree (slight, moderate, or extensive) were noted on the buttocks of 53% of patients at the most recent examination (an average of 5.7 years after starting PUVA). The frequency of moderate or extensive buttock lentigines at the most recent examination was positively associated with a greater number of PUVA treatments, an older age at starting PUVA, and male sex, and negatively associated with skin types V and VI. Moderate or extensive buttock lentigines were present in 17% of 693 patients who had not had PUVA for 1-2 years or longer. According to a regression analysis, the persistence of buttock lentigines was related in greatest measure to the total number of PUVA treatments received and was relatively independent of the time interval from the last PUVA treatment to the most recent examination or to "other" UV radiation therapy (predominantly UVB) received after PUVA was discontinued. Until the long- term course of PUVA lentigines is known, individuals who develop "fixed" pigmented lesions while on PUVA should be monitored continually for melanocytic dysplasias, including melanoma. [ABSTRACT FROM AUTHOR]

The prevalence of psoriasis among first-degree relatives of 1209 patients with severe psoriasis was studied by means of a questionnaire survey. Siblings of patients with an affected parent were more than 4 times as likely to have psoriasis as siblings of patients without an affected parent. Siblings of patients with onset before age 15 were more than 3 times as likely to have psoriasis as siblings of patients with onset after age 30. The increased prevalence associated with each factor was independent of the other factor. This relation suggests that determinants of susceptibility to psoriasis are separate from factors that influence age at onset in those who are susceptible. This separation is important because the genetics and biochemistry of susceptibility may be less complex than for age at onset. Prevalence among offspring was less than age-adjusted prevalence among siblings with an affected parent which suggests the major determinant of susceptibility is not a single dominant allele. [ABSTRACT FROM AUTHOR]

There is concern about possible association between PUVA treatment and an increased risk of noncutaneous cancer. An alteration in the risk of cancer among persons with psoriasis has also been postulated. To test this hypothesis, for nearly two decades we have prospectively followed 1380 patients who first began PUVA treatment for psoriasis in 1975-1976. We compare the risk of noncutaneous cancer in our cohort with that expected based on general population incidence rates. The overall risk of noncutaneous cancer was nearly identical to that expected in general population. For three separate sites, we noted significant increases: thyroid cancer (RR = 3.57, 95% CI = 1.16-8.34), breast cancer (RR = 1.81, 95% CI = 1.19-2.64), and central nervous system neoplasms (RR = 2.80, 95% CI = 1.13-5.57). Since 1987, however, the risk of central nervous system neoplasnis has not been elevated (RR = 0.00, 95% CI = 0.00- 3.35) and the relative risk of breast cancer was lower than in the prior decade and not statistically significant. There was no association between higher levels of exposure to PUVA and the risk of any of these cancers. We did not detect any significant increase in the risk of lymphoma or leukemia. Our study does not support the hypothesis that long-term PUVA treatment increases the risk of noncutaneous cancer. [ABSTRACT FROM AUTHOR]

In some animal species, exposure of the ocular lens to 8-methoxypsoralen (8-MOP) and ultraviolet-A radiation (PUVA) induces lens opacities. Case reports have suggested that PUVA therapy in humans may be associated with an increased risk of ocular lens abnormalities. To examine this risk, we compared the results of the initial and final examinations, which were performed on an average of 10 years apart in 1,235 individuals enrolled in the PUVA Follow-up Study. After adjustment for age and sex, there was no significant relation between the risk of developing an ocular lens abnormality or cataract and the level of exposure to PUVA. A higher incidence of cataract was noted, however, in the PUVA cohort compared to a large population-based study. In addition, rates of cataract extraction were significantly higher among male members of the PUVA study compared to enrollees in the Physician Health Study. Overall, our data strongly argue against a dose-dependent increase in the risk of cataract or other lens abnormality in association with PUVA therapy in a cohort most of whose members we believe usually used recommended eye protection. Our data do not explain the higher incidence and prevalence of ocular lens pathology in our cohort compared to groups without psoriasis. These differences could reflect differences in criteria for defining these abnormalities, other exposures, or PUVA. [ABSTRACT FROM AUTHOR]

To test the validity of the common hypothesis that patients with psoriasis have an inherently lower susceptibility to cancer, we prospectively studied 1367 patients with severe psoriasis who enrolled in a clinical trial of oral methoxsalen photochemotherapy for treatment of psoriasis for an average of 3.2 yr. The incidence of noncutaneous cancers and the number of deaths from such cancers were slightly but not significantly higher than that expected for the general population (relative risk = 1.1; standard mortality ratio = 1.3). Among 318 patients (23%) in this cohort who were over 35 yr of age and who lacked appreciable exposure to suspected cutaneous carcinogens, the observed incidence for cutaneous carcinoma was 1.4 times that expected, based on rates for the general population (90% confidence interval = .8 to 2.7). These data suggest that patients with psoriasis have a risk of systemic and cutaneous cancer that is comparable to the risk for the general population. [ABSTRACT FROM AUTHOR]

Background: Estimates of the prevalence of psoriatic arthritis vary widely and are usually not determined by population-based studies.Objectives: We sought to determine the prevalence of psoriatic arthritis and the impact of the disease on quality of life in the US population.Methods: Patients were selected randomly from the US population and were interviewed by telephone. Cases were defined as patients who reported a physician diagnosis of psoriasis and psoriatic arthritis.Results: Interviews of 27,220 persons were conducted; 601 of the interviewees had psoriasis and 71 had psoriasis and psoriatic arthritis. The prevalence of psoriatic arthritis was 0.25% (95% confidence interval [CI]: 0.18%, 0.31%). The prevalence of psoriatic arthritis among patients with psoriasis was 11% (95% CI: 9%, 14%) and varied substantially based on self-reporting of the extent of skin involvement with psoriasis. Thirty-nine percent of patients with psoriatic arthritis indicated that it was a large problem in everyday life.Limitations: Psoriatic arthritis was classified on the basis of the patient's self-report.Conclusion: Psoriatic arthritis affects an estimated 520,000 patients in the US population, and many rate it as a large problem in everyday life. The prevalence varies widely based on the extent of skin involvement, which demonstrates the importance of performing broadly representative studies to measure the prevalence of psoriatic arthritis. [ABSTRACT FROM AUTHOR]