RESUMO
BACKGROUND: Supportive care is the cornerstone of management of adult and paediatric Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, consensus on the modalities of supportive care is lacking. OBJECTIVES: Our aim in this international multicentric Delphi exercise was to establish a multidisciplinary expert consensus to standardize recommendations regarding supportive care in the acute phase of SJS/TEN. METHODS: Participants were sent a survey via the online tool SurveyMonkey, consisting of 103 statements organized into 11 topics: multidisciplinary team composition, suspect drug management, infection prevention, fluid resuscitation and prevention of hypothermia, nutritional support, pain and psychological distress management, management of acute respiratory failure, local skincare, ophthalmological management, management of other mucosa, and additional measures. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). The results were analysed according to the RAND/UCLA Appropriateness Method. RESULTS: Forty-five participants from 13 countries (on three continents) participated. After the first round, a consensus was obtained for 82.5% of the 103 initially proposed statements. After the second round, a final consensus was obtained for 102 statements. CONCLUSIONS: We have reached an international Delphi-based consensus on best supportive care practice for SJS/TEN. Our expert consensus should help guide physicians in treating patients with SJS/TEN and thereby improve short-term prognosis and the risk of sequelae.
Assuntos
Síndrome de Stevens-Johnson , Adulto , Criança , Consenso , Humanos , Pesquisa , Estudos Retrospectivos , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/terapiaRESUMO
BACKGROUND: The high prevalence of actinic keratosis (AK) requires the optimal use of healthcare resources. OBJECTIVES: To gain insight in to the healthcare utilization of people with AK in a population-based cohort, and the management of AK in a primary and secondary care setting. METHODS: A retrospective cohort study using three complementary data sources was conducted to describe the use of care, diagnosis, treatment and follow-up of patients with AK in the Netherlands. Data sources consisted of a population-based cohort study (Rotterdam Study), routine general practitioner (GP) records (Integrated Primary Care Information) and nationwide claims data (DRG Information System). RESULTS: In the population-based cohort (Rotterdam Study), 69% (918 of 1322) of participants diagnosed with AK during a skin-screening visit had no previous AK-related visit in their GP record. This proportion was 50% for participants with extensive AK (i.e. ≥ 10 AKs; n = 270). Cryotherapy was the most used AK treatment by both GPs (78%) and dermatologists (41-56%). Topical agents were the second most used treatment by dermatologists (13-21%) but were rarely applied in primary care (2%). During the first AK-related GP visit, 31% (171 of 554) were referred to a dermatologist, and the likelihood of being referred was comparable between low- and high-risk patients, which is inconsistent with the Dutch general practitioner guidelines for 'suspicious skin lesions' from 2017. Annually, 40 000 new claims representing 13% of all dermatology claims were labelled as cutaneous premalignancy. Extensive follow-up rates (56%) in secondary care were registered, while only 18% received a claim for a subsequent cutaneous malignancy in 5 years. CONCLUSIONS: AK management seems to diverge from guidelines in both primary and secondary care. Underutilization of field treatments, inappropriate treatments and high referral rates without proper risk stratification in primary care, combined with extensive follow-up in secondary care result in the inefficient use of healthcare resources and overburdening in secondary care. Efforts directed to better risk differentiation and guideline adherence may prove useful in increasing the efficiency in AK management. What's already known about this topic? The prevalence of actinic keratosis (AK) is high and, in particular, multiple AKs are a strong skin cancer predictor. The high prevalence of AK requires optimal use of healthcare resources. Nevertheless, (population based) AK healthcare utilization and management data are very rare. What does this study add? Although AK-related care already consumes substantial resources, about 70% of the AK population has never received care. Primary care AK management demonstrated underutilization of topical therapies and high referral rates without proper risk stratification, while in secondary care the extensive follow-up schedules were applied. This inefficient use of healthcare resources highlights the need for better harmonization and risk stratification to increase the efficiency of AK care.
Assuntos
Ceratose Actínica/terapia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Atenção Primária à Saúde/estatística & dados numéricos , Atenção Secundária à Saúde/estatística & dados numéricos , Demandas Administrativas em Assistência à Saúde/estatística & dados numéricos , Assistência ao Convalescente/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Crioterapia/estatística & dados numéricos , Bases de Dados Factuais/estatística & dados numéricos , Fármacos Dermatológicos/uso terapêutico , Dermatologistas/normas , Dermatologistas/estatística & dados numéricos , Feminino , Clínicos Gerais/normas , Clínicos Gerais/estatística & dados numéricos , Fidelidade a Diretrizes/estatística & dados numéricos , Humanos , Ceratose Actínica/diagnóstico , Masculino , Pessoa de Meia-Idade , Países Baixos , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/normas , Atenção Primária à Saúde/normas , Encaminhamento e Consulta/normas , Encaminhamento e Consulta/estatística & dados numéricos , Estudos Retrospectivos , Medição de Risco/normas , Medição de Risco/estatística & dados numéricos , Atenção Secundária à Saúde/normasRESUMO
BACKGROUND: Cancer risk following long-term exposure to systemic immunomodulatory therapies in patients with psoriasis is possible. OBJECTIVES: To assess a dose-response relationship between cumulative length of exposure to biological therapy and risk of cancer. METHODS: Four national studies (a healthcare database from Israel, and prospective cohorts form Italy, Spain and the U.K. and Republic of Ireland) collaborating through Psonet (European Registry of Psoriasis) participated in these nested case-control studies, including nearly 60 000 person-years of observation. 'Cases' were patients who developed an incident cancer. Patients with previous cancers and benign or in situ tumours were excluded. Four cancer-free controls were matched to each case on year of birth, sex, geographic area and registration year. Follow-up for controls was censored at the date of cancer diagnosis for the matched case. Conditional logistic regression was performed by each registry. Results were pooled using random-effects meta-analysis. RESULTS: A total of 728 cases and 2671 controls were identified. After matching, differences between cases and controls were present for the Charlson Comorbidity Index in all three registries, and in the prevalence of previous exposure to psoralen-ultraviolet A and smoking (the British Association of Dermatologists Biologic Interventions Register only). The risk of first cancers was not significantly associated with cumulative exposure to biologics (adjusted odds ratio per year of exposure 1·02, 95% confidence interval 0·92-1·13). Results were similar if squamous and basal cell carcinomas were included in the outcome. CONCLUSIONS: Cumulative length of exposure to biological therapies in patients with psoriasis in real-world clinical practice does not appear to be linked to a higher risk of cancer after several years of use.
Assuntos
Produtos Biológicos/efeitos adversos , Fármacos Dermatológicos/efeitos adversos , Fatores Imunológicos/efeitos adversos , Neoplasias/epidemiologia , Psoríase/tratamento farmacológico , Produtos Biológicos/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Relação Dose-Resposta a Droga , Europa (Continente)/epidemiologia , Humanos , Fatores Imunológicos/administração & dosagem , Incidência , Israel/epidemiologia , Neoplasias/induzido quimicamente , Neoplasias/imunologia , Psoríase/imunologia , Sistema de Registros/estatística & dados numéricos , Fatores de TempoRESUMO
BACKGROUND: Biologics have greatly improved psoriasis management. However, primary and secondary non-response to treatment requires innovative strategies to optimize outcomes. OBJECTIVE: To describe the use of combined treatment of biologics with conventional systemic agents or phototherapy in daily clinical practice. METHODS: We collected data on frequency of use, demographics, treatment characteristics and drug survival of biologics combined with conventional systemic agents or phototherapy in five PSONET registries. RESULTS: Of 9922 biologic treatment cycles, 982 (9.9%) were identified as combination treatment. 72.9% of treatment cycles concerned concomitant use of methotrexate, 25.3% concerned concomitant UVB therapy, acitretin or cyclosporin and 1.8% concerned combined treatment with PUVA, fumaric acids or a second biologic. Substantial variation was detected in type and frequency of combination treatments prescribed across registries. Patients initiated on combined treatment had generally severe disease and were affected with psoriasis for many years. The extent to which patients had been priory treated with biologic monotherapy and the proportion of patients affected with psoriatic arthritis differed between registries. Survival rates for etanercept, adalimumab, infliximab and ustekinumab with methotrexate ranged between 43 and 92%, 28 and 83%, 65 and 87% and 53 and 77%, respectively, across registries after one year with no consistent superior survival for a particular biologic. Longest survival on a biologic combined with methotrexate, acitretin or cyclosporin was 103, 78 and 34 months, respectively. CONCLUSION: Methotrexate was the most commonly used concomitant treatment for patients on a biologic. Wide geographical variations in treatment selection and persistence of combination treatment exist. Data derived from ongoing studies may help to determine whether combined treatment is superior to biologic monotherapy.
Assuntos
Produtos Biológicos/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Terapia PUVA , Psoríase/terapia , Acitretina/uso terapêutico , Adalimumab/uso terapêutico , Áustria , Terapia Combinada , Ciclosporina/uso terapêutico , República Tcheca , Quimioterapia Combinada , Etanercepte/uso terapêutico , Feminino , Fumaratos/uso terapêutico , Humanos , Infliximab/uso terapêutico , Israel , Itália , Estimativa de Kaplan-Meier , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Países Baixos , Sistema de Registros , Índice de Gravidade de Doença , Ustekinumab/uso terapêuticoRESUMO
About 11 million people suffer from psoriasis in Europe. This chronic condition may have a dramatic impact on quality of life. About 20% of patients may need systemic treatment to effectively control their disease activity. The introduction of biological agents greatly increased the options of systemic therapies for psoriasis. However, clinical experience with newer systemic therapies is relatively limited, and available data are mostly derived from short-term phase III trials. Except for PUVA and ciclosporin, long-term safety data from formal postmarketing studies are also largely lacking conventional treatment options. Registries provide one mechanism to monitor the long-term safety and effectiveness of treatment in the 'natural environment'. Several European countries have established registries to collect data on systemic psoriasis treatment. Even though different in some aspects of study design and monitoring, the registries share a number of common features: they include all the biological drugs and sometimes all the licensed systemic agents for psoriasis, and they observe the patients for a defined period of time irrespective of the drug given. Combining the results from these registries would increase their power and impact. We are developing an international collaboration called 'Psonet' that will perform a joint analysis of data from 9 individual national psoriasis registries.
Assuntos
Psoríase/tratamento farmacológico , Sistema de Registros , Europa (Continente) , Humanos , Prontuários Médicos , Terapia PUVA , Vigilância de Produtos ComercializadosRESUMO
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.
Assuntos
Carcinoma Basocelular/etiologia , Carcinoma de Células Escamosas/etiologia , Ficusina/efeitos adversos , Fotoquimioterapia/efeitos adversos , Fármacos Fotossensibilizantes/efeitos adversos , Psoríase/tratamento farmacológico , Neoplasias Cutâneas/etiologia , Raios Ultravioleta/efeitos adversos , Administração Oral , Adulto , Análise de Variância , Carcinoma Basocelular/induzido quimicamente , Carcinoma de Células Escamosas/induzido quimicamente , Relação Dose-Resposta à Radiação , Feminino , Ficusina/uso terapêutico , Seguimentos , Humanos , Masculino , Fármacos Fotossensibilizantes/uso terapêutico , Estudos Prospectivos , Fatores de Risco , Neoplasias Cutâneas/induzido quimicamenteRESUMO
PUVA therapy has radically altered the management of severe psoriasis. It is of greatest benefit in those patients with extensive involvement, and in those unresponsive to conventional therapy. The long term side effects of PUVA currently limit its use to patients with disabling disease. The full extent of long term side effects has yet to be defined. In order to reduce the toxicity and improve the efficacy of PUVA, a better understanding of the molecular aspects of psoralen-DNA interaction, DNA repair, and mutagenesis is required. The action spectrum of PUVA in clearing psoriasis has yet to be defined. By limiting the spectrum of UVA exposure it may be possible to reduce some of the toxic effects of PUVA. The recent advances in the formulation of 8-MOP preparations has yielded a drug with more predictable pharmacokinetics and clinical response. Further research with newer psoralens may produce more effective and less toxic compounds. In the last ten years, PUVA has been both a valuable addition to dermatologists' clinical armamentarium and a useful tool in increasing our understanding of cellular biology and the interaction between ultraviolet radiation and biologic systems.
Assuntos
Furocumarinas , Terapia PUVA , Psoríase/tratamento farmacológico , Animais , Terapia Combinada , Furocumarinas/efeitos adversos , Furocumarinas/metabolismo , Furocumarinas/farmacocinética , Humanos , Imunidade/efeitos dos fármacos , Terapia PUVA/efeitos adversosRESUMO
Forty-five chronic agoraphobics were randomly assigned to treatment by placebo or imipramine in doses up to 200 mg/day for 28 weeks. All patients also had systematic self-exposure homework with an instruction manual. In addition, half of each drug group had therapist-aided exposure and half had therapist-aided relaxation, each totalling three hours. Patients in both drug groups improved substantially and maintained their gains for one year of follow-up. Imipramine had no significant therapeutic effect despite satisfactory plasma levels and significant drug side effects. Patients' low initial Hamilton depression scores might explain the absence of any drug effect. Antidepressants may be ineffective for agoraphobics who have normal mood. Brief therapist-aided exposure improved phobias and panics to a significant but limited extent, and is a useful adjuvant to self-exposure homework, which can be a powerful therapeutic agency by itself.
Assuntos
Agorafobia/terapia , Terapia Comportamental/métodos , Imipramina/uso terapêutico , Transtornos Fóbicos/terapia , Adulto , Agorafobia/tratamento farmacológico , Agorafobia/psicologia , Dessensibilização Psicológica , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Placebos , Escalas de Graduação Psiquiátrica , Terapia de Relaxamento , AutocuidadoRESUMO
Enrollees of health maintenance organizations (HMOs) are less frequently hospitalized than are patients cared for by fee-for-service physicians. To determine if care provided to HMO and fee-for-service patient is different once they are hospitalized, we compared length of stay, total costs, and severity of illness for 617 HMO and fee-for-service patients hospitalized during the period 1983 through 1985 at a major teaching hospital. Severity was gauged in the following two ways: the Severity of Illness Index developed by Horn, and ratings by two physicians who were given all records from the first day of each patient's hospitalization. Length of stay was shorter and total costs were less for HMO patients in 7 of 11 diagnosis related groups. Using regression analysis to adjust for age, sex, emergency ward admission, diagnosis related group, and severity, we found that overall length of stay was 14% shorter for HMO patients than for fee-for-service patients (6.2 vs 5.3 days, P less than .01), whereas total costs were only 4% less ($4251 vs $4090, P greater than .2). These findings indicate that while patterns of utilization may vary by diagnosis related groups, HMO patients had shorter lengths of stay but comparable overall costs. Whether shorter lengths of stay represent greater efficiency, substitution of outpatient for inpatient care, or diminution in the quality of care is not clear.
Assuntos
Sistemas Pré-Pagos de Saúde/economia , Seguro Saúde/economia , Tempo de Internação/economia , Boston , Estudos de Coortes , Custos e Análise de Custo , Grupos Diagnósticos Relacionados , Recursos em Saúde/economia , Índice de Gravidade de DoençaRESUMO
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.
Assuntos
Catarata/etiologia , Terapia PUVA/efeitos adversos , Idoso , Catarata/diagnóstico , Catarata/epidemiologia , Estudos de Coortes , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
The medical literature suggests that persons infected with human immunodeficiency virus (HIV) have an increased risk of many common and uncommon cutaneous diseases. Further, it has been suggested that in HIV-infected people these conditions may be more persistent and they may be more prone to developing adverse cutaneous reactions to drugs. We have identified a cohort of 684 HIV-infected persons who were members of a large Massachusetts health maintenance organization. Based on review of hospital records, automated ambulatory records, and automated prescription data for these patients, we determined the occurrence of skin disease including adverse reactions to drugs. In this 2.8-year study, these HIV-infected persons averaged 3.7 separate skin diagnoses each, a significantly higher rate (p < 0.001) than in a comparable uninfected group of enrollees in this health maintenance organization. The rate of visits for many common skin diagnoses increased as HIV infection progressed. Cutaneous drug reactions were also significantly more frequent (per course of drug) in AIDS patients compared to patients with asymptomatic HIV infection. Skin disease is a frequent and important cause of morbidity in HIV-infected persons. The development of a specific cutaneous disease may act as a prognostic marker for progression of HIV infection. In HIV-infected persons, adverse cutaneous reactions to drugs frequently limit treatment with essential drugs.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/complicações , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Síndrome da Imunodeficiência Adquirida/complicações , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Dermatopatias Infecciosas/complicações , Dermatopatias Infecciosas/epidemiologia , Adulto , Estudos de Coortes , Feminino , Sistemas Pré-Pagos de Saúde , Humanos , Masculino , Massachusetts/epidemiologia , Pessoa de Meia-Idade , PrognósticoRESUMO
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.
Assuntos
Psoríase/genética , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-IdadeRESUMO
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, but observed that cirrhosis caused more deaths among our cohort than in the general population (Standard Mortality Ratio: 4.7, P less than 0.05). The overall incidence of non-cutaneous cancer was slightly but not significantly elevated in our population (Standard Mortality Ratio = 1.2, P greater than 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 can assure us that PUVA therapy does not substantially alter the risk for the development of these conditions.
Assuntos
Doenças Cardiovasculares/etiologia , Causas de Morte , Neoplasias/etiologia , Psoríase/complicações , Adulto , Idoso , Feminino , Humanos , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Terapia PUVA/efeitos adversos , Estudos Prospectivos , Psoríase/mortalidade , Psoríase/terapia , RiscoRESUMO
Continued prospective study of the 1,380 patients enrolled in the PUVA study for 10 years after first exposure to PUVA demonstrates a strong association between cumulative exposure to PUVA and an increased risk of squamous cell carcinoma of the skin. For tumors occurring at least 58 months after first treatment, after adjustment for age, sex, and area of residence, we observed that patients with more than 260 treatments had an 11-fold increase in risk compared to patients who had received 160 or fewer treatments during the same interval (P less than 0.01). Comparable increases in relative risk were noted in patients of all skin types, irrespective of prior ionizing radiation exposure. We also noted a modest dose-dependent increase in the risk for the development of basal cell carcinoma for patients who received an excess of 200 treatments compared to those who had received fewer than 160 treatments within the same time period (P less than 0.05). Tumors detected in our cohort exhibit biologic behavior similar to non-melanoma skin cancers associated with sun exposure. Careful monitoring and early detection should limit the morbidity associated with these tumors.
Assuntos
Carcinoma de Células Escamosas/etiologia , Neoplasias Induzidas por Radiação/etiologia , Terapia PUVA/efeitos adversos , Neoplasias Cutâneas/etiologia , Carcinoma Basocelular/etiologia , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Fatores de TempoRESUMO
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 neoplasms 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.