Consensus Workshop on the Toxic Effects of Long-term PUVA Therapy

Morison, Warwick L.; Baughman, Richard D.; Day, Robert M.; Forbes, P. Donald; Hoenigsmann, Herbert; Krueger, Gerald G.; Lebwohl, Mark; Lew, Robert A.; Naldi, Luigi; Parrish, John A.; Piepkorn, Michael; Stern, Robert S.; Weinstein, Gerald D.; Whitmore, S. Elizabeth

doi:10.1001/archderm.134.5.595

Cited by 131 publications

(73 citation statements)

References 48 publications

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“…However, cocarcinogenic influences like arsenic, MTX, UVB and ionizing radiation are considered to carry additive effects in the development of SCC in long-term PUVA patients. As to immunosuppressive drugs, in contrast to cyclosporin, MTX is regarded to represent only a relative contraindication to PUVA therapy with marginal effects on SCC occurrence [9]. In our 2 patients the first skin cancer occurred 1 year after the beginning of MTX therapy following cessation of long-term PUVA therapy (fig.…”

Section: Discussionmentioning

confidence: 90%

“…Although initially large-scale European studies, in contrast to US studies, did not reveal an increased risk of SCC unless the patient belonged to the risk group with prior exposure to other potential carcinogens, a positive correlation has been found lately [7]. Reports of an increased risk of melanoma in patients with psoriasis treated with high doses of PUVA have reinforced concerns about its long-term safety [8, 9]. …”

Section: Introductionmentioning

confidence: 99%

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Widespread Cutaneous Carcinomas Associated with Human Papillomaviruses 5, 14 and 20 after Introduction of Methotrexate in Two Long-Term PUVA-Treated Patients

et al. 2001

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Background: PUVA treatment for patients with severe psoriasis has been demonstrated to be highly effective. However, an increased risk of nonmelanoma and melanoma skin cancers has been reported. It is generally accepted that the risk of squamous-cell carcinoma (SCC) is significantly increased in patients with long-term PUVA therapy. The role of methotrexate (MTX) and infection with oncogenic human papillomaviruses which may act as cocarcinogens is poorly documented. Case Reports: Two cases of multiple SCCs associated with numerous PUVA keratoses and PUVA freckles after long-term PUVA therapy and subsequent treatment with MTX are presented. In 1 case, the tumor progressed to metastatic SCC. Tumors and scrapings of psoriatic skin lesions were analyzed for the presence of oncogenic human papillomavirus (HPV) genotypes. The genotype of HPV-5, -14 and -20 was detected in scrapings and skin tumors using PCR amplification. Conclusion: These observations support the concept that long-term PUVA treatment is carcinogenic and rise questions concerning an additional influence of MTX in the development and progression of skin cancer. The risk of metastatic SCC seems to be underestimated in high-dose PUVA-treated patients due to longer latency for developing metastases and the small number of studies with long-term follow-up. Treatment with MTX should be considered cautiously in patients previously exposed to high doses of PUVA. The presence of oncogenic HPVs in carcinomas and psoriatic skin lesions detected only with the highly sensitive nested PCR method is not necessarily a proof of their implication in skin carcinogenesis.

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Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Widespread Cutaneous Carcinomas Associated with Human Papillomaviruses 5, 14 and 20 after Introduction of Methotrexate in Two Long-Term PUVA-Treated Patients

et al. 2001

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“…Typically, the lymphocytes display the immunophenotype of mature memory T-cells (CD 31 , CD 41 , CD45RO 1 , CD 8 À ) and clonal rearrangement of the T-cell receptor gene is detectable in most cases. Clinically, the disease presents with erythematous, sometimes poikilodermatous and scaly patches and plaques with an occasional itch (1,6).…”

Section: Mycosis Fungoides (Mf): Epidemiology Classification Staginmentioning

confidence: 99%

Phototherapy of mycosis fungoides

Trautinger

2011

Photoderm Photoimm Photomed

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SummaryBackground/purpose: Among the primary cutaneous T-cell lymphomas, mycosis fungoides (MF) is the most common disease entity. Recently, an improved understanding of the pathology, clinical presentation, and prognosis of MF has lead to the development of new and practically useful classification and staging systems. In most patients, MF presents with patches and plaques and remains confined to the skin for years and decades, making it an ideal target for phototherapy. However, treatment schedules vary widely and this review describes the current knowledge about phototherapy of MF focusing mainly on narrow-and broadband UVB and 8-methoxypsoralen plus UVA, its indications, practical aspects, and clinical outcome. Methods: Review and summary of the pertinent literature. Results and conclusions: Since 1976, when the first report on phototherapy for MF was published, sufficient evidence has accumulated to make narrowband UVB and PUVA safe and effective treatment options for early stages of the disease. In refractory cases or more advanced stages, combination of phototherapy with systemic treatments including mainly interferons and retinoids might be valuable. Additional research is required to further define the optimal treatment schedules and the role of maintenance.

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“…An increased risk of LPD observed in patients receiving long-term cyclosporine or methotrexate therapy has been attributed to the immunosuppressive nature of these agents. Factors that influence the risk of cutaneous malignancy in psoriasis patients include exposure to sunlight and other carcinogens, skin type, history of malignancy and the type of psoriatic treatment received [34,35,36,37,38,39,40]. …”

Section: Introductionmentioning

confidence: 99%

A Review of Malignancies Observed during Efalizumab (Raptiva®) Clinical Trials for Plaque Psoriasis

Toth¹,

Cather²,

Langley³

et al. 2006

Dermatology

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

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Consensus Workshop on the Toxic Effects of Long-term PUVA Therapy

Cited by 131 publications

References 48 publications

Widespread Cutaneous Carcinomas Associated with Human Papillomaviruses 5, 14 and 20 after Introduction of Methotrexate in Two Long-Term PUVA-Treated Patients

Widespread Cutaneous Carcinomas Associated with Human Papillomaviruses 5, 14 and 20 after Introduction of Methotrexate in Two Long-Term PUVA-Treated Patients

Phototherapy of mycosis fungoides

A Review of Malignancies Observed during Efalizumab (Raptiva®) Clinical Trials for Plaque Psoriasis

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