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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]

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 <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 <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. [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]

To determine the extent of clinical actinic damage that occurred in association with exposure to oral methoxsalen photochemotherapy (PUVA), dermatologists at 16 university centers assessed the wrinkling, telangiectasia, and altered skin markings on the buttocks and the dorsa of the hands among 1380 patients treated with PUVA. These changes are similar to those seen in skin that is chronically exposed to sunlight. After more than 5 years of prospective study, patients with psoriasis exposed to PUVA Showed a significant dose-dependent increase in the prevalence of clinical actinic degeneration of the skin of the buttocks (p < .05, F-test). The prevalence of moderate or severe change among those patients exposed to high doses of PUVA (more than 160 treatments) was low (11%). The degree of increased clinical actinic degeneration noted on the dorsa of the hands was also significantly related to total exposure to PUVA (p < .05, F-test). Our findings indicate that long-term PUVA exposure is associated with an increase in clinical actinic degeneration of the skin. However, the magnitude of this increase is small and, after more than 5 years, is of limited clinical consequence to most patients. [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]

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. [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]

Presents a letter to the editor in the May 2005 issue of the "Journal of Investigative Dermatology."

Presents a response by Robert S. Stern to a letter to the editor about his article "Cardiovascular Disease, Cancer, and Cause of Death in Patients With Psoriasis: 10 Years' in a Cohort of 1,380 Patients," published in the 1988 issue of "The Journal of Investigative Dermatology."

We examined two manifestations of coal tar phototoxicity: delayed erythema and skin pain (tar smarts) by quantifying the amount (dose) of UVA and exposure conditions required to induce these phenomena in normal human skin. The minimal UVA dose required to induce delayed erythema (minimal phototoxic dose or MPD) and the minimal UVA dose required to induce an immediate smarting reaction (minimal smarting dose or MSD) were recorded in 32 subjects in a variety of settings. A log-log dose-response model described the relation between the interval of time tar was left on the skin and lowering of MPD. We examined 4 different methods of tar removal and showed that several methods using more than water alone were equally effective-judging by resultant phototoxicity. The time between tar removal and UVA irradiation is important. Even 30 mm was sufficient for the MPD to increase from 3.77 ± 1.55 to 6.1 ± 4.0 J/cm² (p. < 0.02). The smarting reaction shows a similar dependence on the time interval between tar removal and exposure. The mean MSD was less than the mean MPD at all times tested. Both manifestations of coal tar phototoxicity, reduced delayed erythema threshold and susceptibility to the smarting reaction, persisted at least 30 h after tar removal. [ABSTRACT FROM AUTHOR]

We studied the mechanism of repair following exposure of normal skin to the CO2 laser in a focused mode. Exposed areas were biopsied at 0, 24, 48 h; 1, 2 weeks; 1, 2½ months (pulse width varying from 0.1 to 1 .0 s) after irradiation. The initial pattern was a V-shaped zone of cauterized collagen with a central crevice, the depth of which correlated with the total energy applied. The epidermal changes consisted of transepidermal cauterization and basal vacuolar changes lateral to the site of impact. Over a period of 1 week, the wound crevice decreased in depth and width and the central margins of the zone of cauterized collagen approximated. The cauterized collagen was extruded and was noted in the epidermal crust; minimal granulation tissue was present. Biopsies at later time periods showed formation of granulation tissue and retention of small amounts of necrotic collagen; the process of collagen extrusion was largely prevented by suturing. These observations show that dermal contraction and necrotic collagen extrusion are important components of initial tissue repair following limited dermal destruction produced by CO2 irradiation. [ABSTRACT FROM AUTHOR]

The interaction of normal human skin with low-fluence CO2 laser irradiation was studied using a three-phase approach. In phase one, freshly excised skin was observed immediately after impact. In phase two, skin irradiated 2 h prior to excision was studied. In phase three, human volunteers were irradiated and biopsied at time zero, 24 h and 48 h. Seventy-five sites were exposed and 60 biopsies were performed. The earliest histologic changes were observed in the 6-10 J/cm2 fluence (radiant exposure) range and these changes included spindle and vacuolar changes in the basal layer of the epidermis. Papillary dermal coagulation was present to a maximum of 0.03 mm. At fluences of 10-25 J/cm2, superficial dermal necrosis (0.06-0.08 mm) was observed. At fluences above 25 J/cm2, transepidermal necrosis was present with increasing papillary dermal necrosis that was in proportion to the energy density delivered. At 2 h, basal vacuolar changes were accompanied by diffuse keratinocytic cell death where contact was maintained between the epidermis and dermis, while where separation occurred limited keratinocytic death was observed. The earliest changes occurred at lower threshold fluences (4-6 J/cm2). After 24 h, these doses resulted in extensive epidermal necrosis with focal acute inflammatory infiltrates. At 48 h, the degree of epidermal "slough" was proportional to the energy density delivered and was maximal with a fluence of 5.7 J/cm2 delivered whereas with a fluence of 3.8 J/cm2 thin slough (0.02 mm) was observed. These findings suggest that low-dose CO2 laser irradiation may provide a new approach to selectively damage the epidermis with minimal dermal damage. [ABSTRACT FROM AUTHOR]