Psoralen And Ultraviolet A Radiation Research Articles

Psoriasis: a brief overview

Psoriasis is a clinically heterogeneous lifelong skin disease that presents in multiple forms such as plaque, flexural, guttate, pustular or erythrodermic. An estimated 60 million people have psoriasis worldwide, with 1.52% of the general population affected in the UK. An immune-mediated inflammatory disease, psoriasis has a major genetic component. Its association with psoriatic arthritis and increased rates of cardiometabolic, hepatic and psychological comorbidity requires a holistic and multidisciplinary care approach. Psoriasis treatments include topical agents (vitamin D analogues and corticosteroids), phototherapy (narrowband ultraviolet B radiation (NB-UVB) and psoralen and ultraviolet A radiation (PUVA)), standard systemic (methotrexate, ciclosporin and acitretin), biologic (tumour necrosis factor (TNF), interleukin (IL)-17 and IL-23 inhibitors) or small molecule inhibitor (dimethyl fumarate and apremilast) therapies. Advances in the understanding of its pathophysiology have led to development of highly effective and targeted treatments.

Aggressive mycosis fungoides/sézary syndrome in Nigeria: case report and literature review

<p class="abstract">Mycosis fungoides and its variant, sézary syndrome are rare neoplastic conditions which are part of a larger group of lymphomas that primarily affect the skin known as cutaneous T-cell lymphomas. We report a case of fatal aggressive mycosis fungoides/sézary syndrome in a 55-year old Nigerian man who initially developed pruritic hyperpigmented spots on his skin which progressed over the course of 5 years to widespread scaly mixed hyperpigmented and hypopigmented plaques and nodules with features of organ involvement despite being managed with Psoralen and ultraviolet A radiation (PUVA), total skin electron-beam (TSEB), local electron-beam radiation, bexarotene, and oral prednisolone and chlorambucil (Winklemann regimen). In the process, we highlight the rarity of the condition, its ease of misdiagnosis and its predilection for people of Sub-Saharan decent.</p>

Necrobiosis lipoidica treated with intense pulsed light

<p class="SectionHeading1"><span lang="EN-US">Necrobiosis Lipoidica (NL) is a chronic degenerative disease of the collagen with higher incidence on the anterior part of lower extremities, especially the tibial area. There were a number of proposed treatments, but none is 100% effective. We present a case of a fifty-year-old female patient with a suspected diagnosis of necrobiosis lipoidica, confirmed by histopathological examination. After two years of treatment with topical corticosteroids and weekly applications of Psoralen and ultraviolet A radiation (PUVA), there were no signs of improvement and we decided to perform a treatment with intense pulsed light therapy. Over a period of 14 months, a total of 13 sessions were carried out and a satisfactory treatment result was obtained.</span></p>

Repair efficiency and PUVA therapeutic response variation in patients with vitiligo

Vitiligo is an acquired depigmentation disorder affecting 0.1% to >8.8% in Indian population. Psoralen and ultraviolet A radiation (PUVA) is a gold standard treatment for vitiligo, however, response is still empirical. In order to investigate whether drug response variation is influenced by the repair ability of PUVA treated vitiligo subjects, single cell gel electrophoresis (SCGE) for genotoxicity and serum malonaldehyde (MDA) for cytotoxicity were performed on 107 subjects (77 cases and 30 healthy controls) in South Indian population. In vitro repair ability was assessed by considering the residual damage.A significant difference was observed between the patients and controls with regard to their mean values of DNA damage and MDA levels (p<0.05). On categorization to fast and slow responders based on the time of response, patients exhibited a significant deviation in residual DNA damage, suggestive of variation with respect to DNA repair efficiency (p<0.05). This is the first study to our knowledge with respect to PUVA drug response variation in vitiligo in relation to DNA repair. Large systematic studies on DNA repair may help in a better understanding of the mechanisms involved in the PUVA drug response variation.

Up-regulation of Notch-1 in psoriasis: an immunohistochemical study

The Notch pathway plays a key role in differentiation, proliferation, and influencing cell fate decision in multiple organisms and tissues including the epidermis and its appendages. The role of Notch-1 in psoriasis has not been widely evaluated; therefore, the current study aimed to evaluate its role in etiopathogenesis of this common skin disease. The current study used immunohistochemical technique to evaluate Notch-1 expression in 35 lesional biopsies of patients having chronic plaque psoriasis in comparison with normal skin biopsies, representing the control group. Notch-1 was expressed in the epidermis of both normal and psoriatic skins; however, the intensity was in favor of psoriatic lesion, and the nuclear form of Notch-1 was more frequently and diffusely seen in psoriasis. Exacerbation of psoriasis as assessed by the Psoriasis Area and Severity Index score was significantly associated with intense (P = .005) and nuclear form of Notch-1 expression (P = .0001). The nuclear form of Notch-1 was also correlated with female sex (P = .043). From this study, up-regulation and not down-regulation of Notch-1 may have a role in pathogenesis of psoriasis. The nuclear form is responsible for the exacerbation of symptoms, and it is the one that may disappear by the effect of psoralen and ultraviolet A radiation (PUVA) therapy.

Report of the Topical Calcineurin Inhibitor Task Force of the American College of Allergy, Asthma and Immunology and the American Academy of Allergy, Asthma and Immunology

Atopic dermatitis (AD) is a common chronic inflammatory skin disease that causes significant suffering and has limited treatment options. It is often the first step in the atopic march and might contribute to the severitypersistence of asthma. On February 15, 2005, the Pediatric Advisory Committee of the US Food and Drug Administration (FDA) recommended ‘‘black box’’ warnings for pimecrolimus (Elidel; Novartis, Basel, Switzerland) and tacrolimus (Protopic; Astellas Pharma, Tokyo, Japan) because of a potential risk of cancer. The American College of Allergy, Asthma and Immunology and the American Academy of Allergy, Asthma and

Genital squamous cell carcinoma in men treated by photochemotherapy. A cancer registry-based study from 1978 to 1998.

One single report from the U.S. 16-centre-trial indicated that psoralen and ultraviolet A radiation (PUVA) therapy may induce an increased risk of genital tumours in men, and protection of the genital area is, therefore, recommended. To evaluate the relevance of this risk in routine clinical practice. Two groups of patients were included in a 1978-98 retrospective study. Case records of men with genital squamous cell carcinoma (SCC) identified from the Cancer Registry of the Doubs area of France were examined for a history of PUVA therapy, topical tar treatment, psoriasis, human papillomavirus infection or genital dermatitis. In addition, all the dermatologists of the Doubs area (in public and private practice) using PUVA therapy were asked to provide information on the number of patients having received PUVA therapy and whether the genital area was exposed during treatment. Between 1978 and 1998, among the 48 men who had developed a genital SCC in the Doubs area, only one had a history of intensive PUVA therapy. About 150,000 treatments with PUVA therapy had been performed by 15 dermatologists in the Doubs area for 5400 patients since 1978. No case of genital SCC had been reported, despite the fact that the genital area had not been protected during UVA exposure. Although retrospective, our study demonstrates that the occurrence of genital SCC in men treated with PUVA therapy is a very rare event in common dermatological practice.

The risk of melanoma in association with long-term exposure to PUVA

Background: Oral methoxsalen (psoralen) and ultraviolet A radiation (PUVA) is a highly effective therapy for psoriasis and many other skin conditions. It is carcinogenic. Previously we reported an increased risk of melanoma that first emerged 15 years after first treatment. Objective: Our purpose is to present additional data concerning the associations of previous exposure to PUVA, the passage of time, and the risk of malignant melanoma. Methods: We have prospectively studied a cohort of 1380 patients first treated with PUVA in 1975 and 1976. We have documented the occurrence of melanoma and in this report compare the observed and expected incidence of melanoma in this cohort, particularly melanomas developing since our earlier report (ie, after March 1996). Results: Since 1975, 23 patients have developed 26 invasive or in situ cutaneous melanomas. In an average of 2.25 years since our last report, we detected 7 additional invasive melanomas (incidence rate ratio, 8.4; 95% confidence interval, 3.4-17.3). Conclusion: Beginning 15 years after first exposure to PUVA, an increased risk of melanoma is observed in our cohort of PUVA-treated patients. This risk is greater in patients exposed to high doses of PUVA, appears to be increasing with the passage of time, and should be considered in determining the risks and benefits of this therapy. (J Am Acad Dermatol 2001;44:755-61.)

PUVA and cancer risk: the Swedish follow-up study.

There is concern about the long-term carcinogenic effects of psoralen and ultraviolet A radiation (PUVA) for treatment of skin disorders. Many authors have found an increased risk for cutaneous squamous cell carcinoma (SCC). Except in anecdotal reports, malignant melanoma had not been observed in patients treated with PUVA until recently. In the U.S.A., a 16-centre prospective study of 1380 patients showed for the first time that there might also be an increased risk for malignant melanoma in patients treated with high cumulative dosages of PUVA. We have therefore followed up the Swedish PUVA cohort until 1994. This cohort had previously been followed up until 1985. Information from 4799 Swedish patients (2343 men, 2456 women) who had received PUVA between 1974 and 1985 was linked to the compulsory Swedish Cancer Registry in order to identify individuals with cancer. The average follow-up period was 15.9 years for men and 16.2 for women. We did not find any increased risk for malignant melanoma in our total cohort of 4799 patients treated with PUVA or in a subcohort comprising 1867 patients followed for 15-21 years. For cutaneous SCC there was an increase in the risk: the relative risk was 5.6 (95% confidence interval, CI 4. 4-7.1) for men and 3.6 (95% CI 2.1-5.8) for women. Significant (P < 0.05) increases were also found in the incidence of respiratory cancer in men and women and of kidney cancer in women. In conclusion, we did not find any increased risk for malignant melanoma in our patients treated with high doses of PUVA and followed up for a long time. We confirm previous reports of an increase in the incidence of cutaneous SCC in patients treated with PUVA, and recommend that patients should be carefully selected for PUVA and rigorously followed up.

Malignant melanoma in patients treated for psoriasis with PUVA.

Photodermatology, Photoimmunology & PhotomedicineVolume 15, Issue 1 p. 37-38 Free Access Malignant melanoma in patients treated for psoriasis with PUVA R. S. Stern, Corresponding Author R. S. Stern Harvard Medical School, Boston, Massachusetts, USABeth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA, USASearch for more papers by this author R. S. Stern, Corresponding Author R. S. Stern Harvard Medical School, Boston, Massachusetts, USABeth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA, USASearch for more papers by this author First published: 13 February 2009 https://doi.org/10.1111/j.1600-0781.1999.tb00052.xCitations: 18AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1 Stern RS, Laird N. The carcinogenic risk of treatments for severe psoriasis. Photochemotherapy follow-up study. Cancer 1994: 73: 2759– 2764. 2 Klecak G., Urbach F., Urwyler H. Fluoroquinolone antibacterials enhance UVA-induced skin tumors. J Photochem Photobiol 1997: 37: 174– 181. 3 Abdel-Naser MB, Hann SK, Bystryn JC. Oral psoralen with UV-A therapy releases circulating growth factor(s) that stimulates cell proliferation. Arch Dermatol 1997: 133: 1530– 1533. 4 Roelandts R. Mutagenicity and carcinogenicity of methoxsalen plus UV-A. Arch Dermatol 1984: 120: 662– 669. 5 Rhodes AR, Stern RS, Melski JW. The PUVA lentigo: analysis of predisposing factors. J Invest Dermatol 1983: 81: 459– 463. 6 Stern RS, Nichols KT, Väkevä LH. Malignant melanoma in patients treated for psoriasis with methoxsalen (psoralen) and ultraviolet A radiation (PUVA). N Engl J Med 1997: 336: 1041– 1045. Citing Literature Volume15, Issue1February 1999Pages 37-38 ReferencesRelatedInformation

Malignant melanoma in patients treated for psoriasis with methoxsalen (psoralen) and ultraviolet A radiation (PUVA). The PUVA Follow-Up Study.

Photochemotherapy with oral methoxsalen (psoralen) and ultraviolet A radiation (PUVA) is an effective treatment for psoriasis. However, PUVA is mutagenic, increases the risk of squamous-cell skin cancer, and can cause irregular, pigmented skin lesions. We studied the occurrence of melanoma among patients treated with PUVA. We prospectively identified cases of melanoma and documented the extent of exposure to PUVA among 1380 patients with psoriasis who were first treated with PUVA in 1975 or 1976. Using incidence data, we calculated the expected incidence of melanoma in this cohort and compared it with the observed incidence. Using regression models, we assessed the risks of melanoma associated with a long time (> or = 15 years) since the first treatment and with a large number of PUVA treatments (> or = 250). From 1975 through 1990, we detected four malignant melanomas, about the number expected in the overall population (relative risk, 1.1). From 1991 through 1996, we detected seven malignant melanomas (relative risk, 5.4; 95 percent confidence interval, 2.2 to 11.1). The risk of melanoma was higher in the later period than in the earlier one (incidence-rate ratio, 3.8) and higher among patients who received at least 250 PUVA treatments than among those who received fewer treatments (incidence-rate ratio, 3.1). About 15 years after the first treatment with PUVA, the risk of malignant melanoma increases, especially among patients who receive 250 treatments or more.

Signature p53 mutation at DNA cross-linking sites in 8-methoxypsoralen and ultraviolet A (PUVA)-induced murine skin cancers.

A combination of psoralen and ultraviolet A radiation (PUVA) is widely used in the treatment of psoriasis. However, PUVA treatment increases the risk of developing skin cancer in psoriasis patients and induces skin cancer in mice. Since the DNA damage induced by PUVA is quite different from that induced by UV, we investigated whether PUVA-induced mouse skin cancers display carcinogen-specific mutations in the p53 tumor suppressor gene. The results indicated that 10 of 13 (77%) PUVA-induced skin tumors contained missense mutations predominantly at exons 6 and 7. In contrast, tumor-adjacent, PUVA-exposed skin from tumor-bearing animals did not exhibit p53 mutation in exons 4-8. Interestingly, about 40% of all mutations in PUVA-induced skin tumors occurred at 5'-TA sites, and an equal number of mutations occurred at one base flanking 5'TA or 5'-TAT sites. Since PUVA induces DNA cross-links exclusively at these sites and since UV "signature" mutations were rarely detected in PUVA-induced skin cancers, we can conclude that PUVA acts as a carcinogen by inducing unique PUVA signature mutations in p53. This finding may have implications for identifying the etiology of skin cancer in psoriasis patients who have undergone PUVA therapy.

The carcinogenic risk of treatments for severe psoriasis

Common treatments used for severe psoriasis include psoralen and ultraviolet A radiation (PUVA), methotrexate, ultraviolet B (UVB), and tar. These therapies are often used for prolonged periods and may be carcinogenic. For more than 13 years, the authors have prospectively determined the incidence of skin cancer and use of treatments for psoriasis in a 1380 patient cohort originally enrolled in a therapeutic trial of PUVA at 16 university centers. Squamous cell carcinoma (SCC) developed in more than one fourth of patients exposed to high doses of PUVA. In this group, the standard morbidity ratio for these tumors was 83 (95% confidence interval [CI], 72-96) compared with the expected number of these tumors in the general population. High-level exposure to methotrexate is a significant independent risk factor for developing SCC (relative risk, 2.1 for high versus low or no exposure; 95% CI, 1.4-2.8). Metastatic disease developed in seven patients with SCC. No significant increase in the risk of SCC was associated with long term exposure to UVB or topical tar, and no substantial increase in the risk of basal cell carcinoma was noted in association with prolonged use of any of these treatments. Long term exposure to PUVA and methotrexate significantly increases the risk of SCC in patients with psoriasis. This risk should be considered in selection of treatment. The ultimate morbidity of these tumors is undetermined.

PUVA and cancer: a large-scale epidemiological study

There is concern about the long-term carcinogenic effects of psoralen and ultraviolet A radiation (PUVA) therapy for treatment of skin disorders. A study of 4799 Swedish patients (2343 males, 2056 females; mean age at first treatment 45·3 years, range 6-93; mean follow-up 6·9 years males, 7·2 years females) who received PUVA between 1974 and 1985 showed a dose-dependent increase in the risk of squamous cell cancer of the skin. Male patients who had received more than 200 treatments had over 30 times the incidence of squamous cell cancer found in the general population. Significant increases (p<0·05) were also found in the incidences of respiratory cancer in males and females, pancreatic cancer in males, and kidney and colonic cancer in females. This study confirms previous reports of a dose-dependent increase in the incidence of squamous cell cancer in patients treated with PUVA.

Risk Assessment of PUVA and Cyclosporine

In 1974, a new therapeutic approach to psoriasis based on photochemotherapy with psoralen and ultraviolet A radiation (PUVA) was introduced. 1 Assessments of its long-term safety continue. Adding to earlier observations about cyclosporine and cutaneous psoriasis, 2 in this issue of theArchivesdata supporting the efficacy of therapy for psoriatic arthritis based on immunosuppression with cyclosporine are presented. 3 There are likely to be many parallels in the evolution of the role of PUVA and cyclosporine as treatments for psoriasis. Since psoriasis is a chronic disease, initial clearing is only the first step in a continued effort to control both the cutaneous and extracutaneous manifestations of this disease. Previous experience with these treatments and knowledge about their mechanism of action raise substantial concern about their safety in long-term use for a chronic, often disabling, but not life-threatening disease. Today, with cyclosporine therapy we are at a point similar to where we were