PUVA Treatment Research Articles

Efficacy of Bath PUVA in the treatment of Palmoplantar hyperkeratosis

Background: Palmoplantar hyperkeratosis, or palmoplantar keratoderma, is a combination of skin conditions that are characterized by excessive thickening of the skin, mainly on the soles and palms. There are various treatment methods for keratoderma, and one of those methods are treatment through bathwater PUVA. It is a type of photochemotherapy. Objective of the study: The aim of the study was to observe the efficacy of bath PUVA treatment for palmoplantar hyperkeratosis. Methodology: This randomized clinical trial study was conducted at the Department of Dermatology and Venereology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. The study duration was 6 months, from September 2007 to February 2008. A total of 30 patients presented with with palmoplantar hyperkeratosis were enrolled in this study through random sampling method following the inclusion and exclusion criteria. Results: Majority of participant (33.3%) were from the age group of 31-40 years. The mean ±SD age was 38.40±10.89 years, and the age range of the participants was 20-58 years. 70% of the participants were male, 83.3% were from low socioeconomic class, and 36.7% were businessmen respectively. Histopathological diagnosis revealed that 52% patients had psoriasis, 33% had nonspecific dermatitis, and 10% patients had chronic inflammatory dermatitis. Gradual improvement was observed from baseline to 8 weeks follow-up in regards to palmoplantar surface area involvement, erythema, and hyperkeratosis. 46.7% of the participants reported skin tenderness, and 93.3% have a burning sensation and no other side effects. Conclusion: Bath PUVA may be an effective option in the treatment palmoplantar keratosis particularly of psoriatic patients. A mild form of nonspecific dermatitis may be treated with bath PUVA. Mugda Med Coll J. 2022; 5(2): 76-81

Effect of PUVA and NB-UVB Therapy on the Skin Cytokine Profile in Patients with Mycosis Fungoides.

Background Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma. The aim of the present study was to produce up-to-date information on different phototherapy approaches on skin cytokines in patients with MF. Methods A total of 27 patients with mycosis fungoides were treated with phototherapy: NB-UVB (narrow‐band ultraviolet B therapy) (10 patients) and PUVA (long-wavelength ultraviolet radiation of spectrum A with the use of skin-photosensitizing furocoumarins) therapy (17 patients). Evaluation of the effectiveness of treatment was carried out using BSA (body surface area) and the modified assessment of the severity of the skin lesions scale (mSWAT) used to quantify tumor mass in cutaneous T-cell lymphomas. Average numbers of procedures were 30.2 and 27.8 in the NB-UVB and PUVA groups, respectively. The median total dose of NB-UVB irradiation was 19.9 J/cm2 and PUVA therapy was 104.0 J/cm2. The overall response to therapy including complete and partial remission was 74.9% in the total group; 70% in the NB-UVB group, and 77.7% in the PUVA therapy group. In the obtained biopsies from lesions, surrounding tissue before treatment and skin samples of four healthy volunteers, the concentration of the IL-1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, IFN-γ, sCD40L, and TNF-α cytokines was studied. An increase in IL-4 and TNF-α levels was shown in the lesional skin of patients compared to the skin of healthy controls. After the treatment, positive correlations of mSWAT with the levels of IL22, IL33, and TNF-α in the tumor tissue were found. The levels of IL10 and IFN-γ after PUVA treatment were increased in comparison to baseline. There was no difference in cytokine levels before/after NB-UVB therapy.

Few X-ray and PUVA treatments accelerate photocarcinogenesis in hairless mice.

PUVA is a treatment that combines oral methoxypsoralen (8-MOP) with ultraviolet radiation A (UVA). It is used for severe psoriasis and the early stages of T-cell lymphoma. X-rays are an effective treatment for skin cancers. Both treatments are in higher doses used to treat skin malignancies and simultaneously increase the risk of keratinocyte cancer. The main objective of this study was to test whether a few PUVA or X-ray treatments could delay the development of ultraviolet radiation (UVR)-induced skin tumors in a well-established hairless mouse model. Three groups of immunocompetent mice (total, N = 75) were included in the study. All groups were UVR-exposed during the study period. In addition, one group was treated with PUVA and another group was treated with X-rays at days 45, 52, 90 and 97. A control group was treated with UVR only. We recorded when the first, second and third skin tumors were induced in each mouse. Skin tumors developed significantly earlier in both the PUVA and X-ray groups (median, 188days) than in the control mice (median, 215days; p < 0.001). Therefore, a few X-ray and PUVA treatments both significantly accelerated the development of skin tumors in hairless mice, compared to UVR controls. Neither treatment showed a delay of UVR-induced skin tumors and caution should be exercised before applying these treatments to sun-damaged skin.

Skin cancers in skin types IV-VI: Does the Fitzpatrick scale give a false sense of security?

The Fitzpatrick scale has been in use for skin colour typing according to the tanning potential of skin since its inception in 1975–1976. Thomas Fitzpatrick developed the scale to classify persons with ‘white skin’ in order to select the correct amount of UVA in Joules/cm2 for PUVA treatment for psoriasis. Since then, it has been widely used in Dermatology to gauge the skin's reaction to UV exposure, tanning potential, assessment of sunburn risk and amount of sun protection required for individual patients. However, the use of this scale has been of limited utility because of different self‐perception in different areas of the world, particularly among those with skin of colour. Skin cancer risk is loosely inversely correlated with the initial genetic/inherent amount of melanin (most research has focused on eumelanin) present in the skin, although the pattern of exposure and amount of UV radiation required causing DNA damage varies widely according to different cancers. In this review, we have shown that the Fitzpatrick scale is neither correct nor adequate to reflect sunburn and tanning risk for skin of colour. Therefore, it may give both patients and physicians a false sense of security that there is little risk that people of colour can develop skin cancers. We have reviewed the small but not insignificant risk of skin of colour developing skin cancers and emphasise that there remains much research that needs to be done in this field.

Cutan T-sejtes lymphomák bőrre irányuló kezelése (skin directed treatment) egy eset kapcsán

Cutaneous T-cell lymphomas are rare diseases with significant differences in their clinical course and prognosis. The choice of treatment basically depends on the stage, in the early stages of the disease only skin directed treatment is recommended. With most of the treatment modalities, complete cure is not possible, only long-term remission can be achieved. The authors report the case of a 52-year-old female patient who developed extensive annular, erythematous, infiltrated plaques in the spring of 2019. Histological examination confirmed mycosis fungoides, imaging did not show lymph node or other organ involvement. Given the disease (stage IB), PUVA treatment was initiated. After a total of 21 sessions of phototherapy from September 2019, the patient underwent complete remission. The authors provide a detailed review of skin directed treatment options for mycosis fungoides based on current international recommendations.

A cross-sectional analysis of skin cancer risk in patients receiving narrow-band ultraviolet B phototherapy: an evaluation of 100 patients.

Narrow-band ultraviolet B (NB-UVB) phototherapy is an effective and widely used treatment modality for psoriasis and other inflammatory skin diseases. The carcinogenic effect of PUVA treatment has been investigated extensively, but there is very scarce data about the role of NB-UVB in the development of skin cancer. The aim of this study was to investigate the potential carcinogenic risk of NB-UVB therapy in various skin disorders. In this cross-sectional study, we evaluated 100 patients who had received whole-body NB-UVB treatment and 100 age- and sex-matched controls. Phototherapy unit database was used to identify patients. A total of 100 patients (53 males and 47 females) treated with NB-UVB and 100 controls were included in the study. The patient group revealed no cases of melanoma or non-melanoma skin cancer, while ten of them were found to have solar lentigines. Basal cell carcinoma in a patient and nine patients with solar lentigines were detected in the control group. There was no statistically significant difference between patient and control groups in terms of skin cancer and solar lentigines. This study does not provide evidence for an increased skin cancer risk in patients treated with NB-UVB phototherapy. However, we have detected the occurence of 10 cases of solar lentigines. Still, definitive prospective longitudinal studies with a greater number of patients and prolonged follow-up are required to specifically address skin cancer risk in relation to NB-UVB phototherapy.

The Effect of Narrow Band UVB and PUVA Treatment on Serum Folate Levels

The Effect of Narrow Band UVB and PUVA Treatment on Serum Folate Levels

PUVA AND INTERFERON α2b COMBINED THERAPY FOR PATIENTS WITH MYCOSIS FUNGOIDES: A SEVEN‐YEAR RETROSPECTIVE STUDY IN RUSSIA

Introduction: Cutaneous T-Cell Lymphomas (CTCLs) are characterized by proliferation and accumulation of malignant monoclonal T lymphocytes or Natural Killer cells in the skin, which may also sequentially involve lymph nodes, internal organs and bone marrow. There are still only a limited number of controlled studies to support treatment decisions for MF patients with therapy being frequently determined by institutional experience and availability. The aim of our survey was to investigate the efficacy and tolerability of combined PUVA and IFN-α2b therapy in patients with different stages of MF, refractory to first line treatment with PUVA. Methods: We observed 31 patients with MF. The diagnoses were verified with histological, immunohictochemical methods and molecular analysis. The following combined IFN-α2b - PUVA treatment protocol was used: IFN-α2b was administered at a dose of 3 MU three times weekly. The dose was increased according to patient's tolerance up to 6 MU three times weekly. For PUVA therapy, 0.8 mg/kg oral 8-methoxypsoralen was given 1.5 hours before UVA radiation, three times a week with gradually increasing dose of 0.5-1.0 J/cm2 in every 2 sessions starting from a dose of 0.5-2 J/cm2 depending on skin phototype. Treatment toxicity was graded according to World Health Organization (WHO) criteria. Results: In terms of the stage of the disease, patients were distributed as follows: IB – 3 (10%), IIA – 7 (23%), IIB – 6 (19%), IIIA – 4 (12%), IIIB – 3 (10%), IVA – 3 (10%), IVB – 5 (16%). The mean total IFN-α2b dose was 275 MU (range 171-576 MU). Conversely, the median PUVA sessions for the entire group of patients was 81 with the median joules/ cm2 being 177.13 (range 127-204 joules/ cm2) and the median combination treatment period being 189 days (range 133–254 days). The overall response rate was 93%, including complete response (CR) (73%) and partial response (PR) (20%). CR was found in 100% stage IIB-IIIA group respect 0% in stage IIIB-IV, P<0.05; the CR rate was in line with the mean CR percentage reported in previous studies (76.5%). Patients with early stage disease had a 2-year progression free survival of 100% vs. 82% for the advanced stage group (P<0.001). In our study, combined treatment showed a 2- and 5-year progression free survival (PFS) of 90% and 43%, respectively; obviously, patients with early stage disease had a superior 2-year PFS respect to the advanced stage group (100% vs 82%) (P < 0.001). Сonclusion: IFN-α2b + PUVA combined treatment seemed to be an efficacious therapy option for MF patients refractory to PUVA ± topical corticosteroids, presenting also a convenient tolerability profile, especially in patients with IB-IIB stage. This combined therapy protocol showed to be effective in both early and advanced MF disease stage, even if significantly better outcomes were observed for early stage disease. Keywords: interferon (INF); mycosis fungoides (MF); phototherapy.

In vitro PUVA treatment triggers calreticulin exposition and HMGB1 release by dying T lymphocytes in GVHD: New insights in extracorporeal photopheresis.

Extracorporeal photopheresis (ECP) is an effective therapy for graft vs host disease (GVHD), based on infusion of UVA-irradiated and 8 methoxy-psoralen (PUVA)-treated leukocytes. Reinfusion of these apoptosing cells affects the functionality of pathogenic T cells through poorly understood immunomodulatory mechanisms. Apoptosis is usually a silent, tolerance-associated process, but can also be immunogenic, depending on death-inducers and environmental context. To understand ECP mechanisms of action, human alloreactive T cells generated in an in vitro model mimicking GVHD were used, as well as primary cells from GVHD patients. Cells were submitted to PUVA treatment and their phenotype and immunogenicity were analyzed, using cell culture and flow cytometry. In vitro PUVA treatment induced the expression of several damage-associated molecular patterns (DAMPs) by dying T cells (calreticulin, high-mobility group box-1, and to a lesser extent heat shock proteins 70 and 90), especially upon T cell activation, leading to their phagocytosis by macrophages and dendritic cells (DCs). Allogeneic DCs preincubated with PUVA treated T cells induced comparable naive T cell proliferation and polarization as control allogeneic DC. Altogether, in our experimental settings, in vitro PUVA-treatment induces a partially immunogenic phenotype allowing phagocytosis of apoptotic cells by macrophages and DC, however not sufficient to induce dendritic cell maturation and T cell activation. These data refine current models of ECP-mediated immune modulation and emphasize the need to further analyze PUVA-treated cell interactions with immune cells.

Phototherapy as a first-line treatment for early-stage mycosis fungoides: The results of a large retrospective analysis.

Phototherapy is one of the main treatments for mycosis fungoides (MF). In this study, we analyzed the efficacy and safety of phototherapy as a first-line treatment in patients with early-stage disease. We analyzed treatment outcomes in a group of 227 early-stage patients. The chi-squared test, the parametric t test, and ANOVA test and the non-parametric tests of Mann-Whitney and Kruskal-Wallis were applied for data analysis. 55.9% of patients treated with UVB-NB reached complete remission (CR), while analog rates after PUVA treatment were 74.5% (P=.015). Patients with patch-stage disease showed better response rates to PUVA compared to UVB-NB therapy (CRs 56.7% vs 91.3%, P<.001). Regarding the latter, long-lasting disease was proven as an independent negative prognostic factor for treatment outcome. Phototypes I and II were found to be favorable prognostic factors for patients treated with PUVA. Maintenance treatment did not alter final relapse rates but led to prolonged time to relapse compared to no-maintenance treated cases (19.5months, vs 32.3, P<.002). Our analysis indicates that PUVA leads to better responses and longer relapse-free intervals both in patch- and plaque-stage disease. UVB-NB could be a valid therapeutic alternative for patients with recent disease presentation.

579 PUVA and maintenance treatment in mycosis fungoides: Systemic aberrant cytokine expression is a predictor of outcome

579 PUVA and maintenance treatment in mycosis fungoides: Systemic aberrant cytokine expression is a predictor of outcome

The Patient's Guide to Psoriasis Treatment. Part 2: PUVA Phototherapy.

BackgroundPUVA treatment is photochemotherapy for psoriasis that combines psoralen with UVA radiation. Although PUVA is a very effective treatment option for psoriasis, there is an absence of patient resources explaining and demonstrating the process of PUVA. Studies have shown that patients who viewed videos explaining the treatment procedures for various medical conditions had a greater understanding of their treatment and were more active participants in their health.ObjectiveTo present a freely available online guide and video on PUVA treatment designed for patient education on PUVA.MethodsThe PUVA treatment protocol used at the University of California—San Francisco Psoriasis and Skin Treatment Center as well as available information from the literature was reviewed to design a comprehensive guide for patients receiving PUVA treatment.ResultsWe created a printable guide and video resource that reviews the benefits and risks of PUVA, discusses the three types of PUVA (hand–foot soak, full body soak, and systemic), demonstrates the PUVA process, and provides practical tips for safe use.ConclusionOnline media and video delivers material in a way that is flexible and often familiar to patients. This new format is beneficial for prospective patients planning to undergo PUVA treatment, health-care providers, and trainees who want to learn more about this treatment.

SNEV(Prp19/PSO4) deficiency increases PUVA-induced senescence in mouse skin.

Senescent cells accumulate during ageing in various tissues and contribute to organismal ageing. However, factors that are involved in the induction of senescence in vivo are still not well understood. SNEVP rp19/ PSO 4 is a multifaceted protein, known to be involved in DNA damage repair and senescence, albeit only in vitro. In this study, we used heterozygous SNEV +/− mice (SNEV‐knockout results in early embryonic lethality) and wild‐type littermate controls as a model to elucidate the role of SNEVP rp19/ PSO 4 in DNA damage repair and senescence in vivo. We performed PUVA treatment as model system for potently inducing cellular senescence, consisting of 8‐methoxypsoralen in combination with UVA on mouse skin to induce DNA damage and premature skin ageing. We show that SNEVP rp19/ PSO 4 expression decreases during organismal ageing, while p16, a marker of ageing in vivo, increases. In response to PUVA treatment, we observed in the skin of both SNEVP rp19/ PSO 4 and wild‐type mice an increase in γ‐H2AX levels, a DNA damage marker. In old SNEVP rp19/ PSO 4 mice, this increase is accompanied by reduced epidermis thickening and increase in p16 and collagenase levels. Thus, the DNA damage response occurring in the mouse skin upon PUVA treatment is dependent on SNEVP rp19/ PSO 4 expression and lower levels of SNEVP rp19/ PSO 4, as in old SNEV +/− mice, result in increase in cellular senescence and acceleration of premature skin ageing.

Efficacy and safety of topical PUVA treatment for refractory lesions of mycosis fungoides

To evaluate the efficacy and safety of topical PUVA treatment of refractory lesions of mycosis fungoides. From January 2008 to 2014, a total of 10 patients (4 males and 6 females) with mycosis fungoides were treated with topical PUVA in Peking Union Medical College Hospital, including 7 cases in plaque stage and 3 cases in tumor stage. The average number of lesions were 1.9±0.9. The median age of these patients was (46.0±9.4) years. The average course of disease was (12.4±7.7) years. Psoralen was applied topically on treatment area 30 min before total body UVA irradiation treatment, 3 times a week. And the efficiency and safety of the therapy were evaluated. All the patients were treated with topical PUVA with a median total dose of (161.60±135.96) J/cm2 in an average of (18.10±14.61) fractions. Total dose of UVA was (1 953.25±829.73) J/cm2, and total number of treatment was (261.90±116.79) fractions. The total treatment time was (45.80±26.64) months. Complete clinical response (CR) rate was 60.0%, partial response (PR) rate was 30.0%, and the overall response rate (CR+PR) was 90.0%. One patient showed no response. No severe acute or chronic side effects were observed. Topical PUVA therapy is effective in the treatment of refractory lesions of mycosis fungoides with little severe side effects.

Treatment of localized mycosis fungoides with digital UV photochemotherapy.

Photochemochemotherapy with 8-methoxypsoralen and UV-A light (PUVA) is a well-established treatment for mycosis fungoides (MF), although evidence for this therapy by means of prospective studies is scarce. However, long-term risks of PUVA are premature skin aging and development of nonmelanoma skin cancer. We therefore evaluated a device for targeted UV therapy, which reduces irradiation of unaffected skin in MF patients. Ten patients with patch- or plaque-type MF affecting less than 10% body surface area were included in a prospective study. A total of 14 lesions were treated with cream PUVA using the digital phototherapy device skintrek(®) PT3. Seven of ten patients showed response to treatment. Complete clinical remission was achieved in four of ten patients (complete remission of seven of fourteen treated lesions) after an average of 13.4weeks and an average cumulative UV dose of 42.6J/cm(2) in a mean of 31.2 treatment sessions. Adverse events were rare and of mild severity. This study is the first prospective trial demonstrating efficacy and safety of cream PUVA in MF patients. As healthy adjacent skin remains unaffected, the potential to reduce the carcinogenic risk of PUVA treatment makes this new method a promising therapeutic option for localized MF.

Hosszú távú PUVA kezelés bôröregítô hatásának vizsgálata egereken

Hosszú távú PUVA kezelés bôröregítô hatásának vizsgálata egereken

Dermatophyte infection encircling vitiligo.

Dermatophyte infection encircling vitiligo.

PEGYLATED LIPOSOMAL ENCAPSULATED DOXORUBICIN AND BRENTUXIMAB VEDOTIN IN STAGE IIB MYCOSIS FUNGOIDES – A CASE REPORT

Mycosis fungoides in advanced stages becomes a therapeutic challenge. During the course of the disease, the tumor may become treatment resistant. We report the use of pegylated liposomal encapsulated doxorubicin in a CD30-positive patient, who had become resistant to skin targeted PUVA treatment (psoralen plus UVA irradiation) and methotrexate. We achieved an objective global response lasting for seven months. Later on, the patient had a relapse and was no longer responding to doxorubicin, even with a dose escalation. A re-biopsy demonstrated the continuous expression of CD30, allowing a shift to CD-targeted treatment with brentuximab vedotine, a monoclonal antibody conjugate with monomethyl auristatin E. His objective global response lasted for six months, before he eventually deceased. CD30-targeted treatment is an option for mycosis fungoides with CD30 transformation. Key words: mycosis fungoides, CD30-transformation, pegylated liposomal encapsulated doxorubicin, brentuximab vedotine. Cite this article : Uwe Wollina, Gesina Hansel, Erich Zschuppe, Jacqueline Schonlebe. Pegylated liposomal encapsulated doxorubicin and brentuximab vedotin in stage IIB mycosis fungoides – case report. RoJCED 2017;3(4): 126-128. https://doi.org/10.26574/rojced.2017.4.3.126

Hsa-miR-4516 Mediated Downregulation of STAT3/CDK6/UBE2N Plays a Role in PUVA Induced Apoptosis in Keratinocytes

Psoriasis is a chronic inflammatory skin disorder mediated by cross-talk occurring between epidermal keratinocytes, dermal vascular cells and immunocytes. Literature reveals that Signal transducer and activator of transcription 3 (STAT3), a protein involved in transmitting extracellular signals to the nucleus, is a possible important link between keratinocytes and immunocytes and is crucial to the development of psoriasis. Although photochemotherapy using UV in combination with 8 methoxypsoralen is one of the most effective therapy for moderate to severe plaque psoriasis, its mechanism of action is largely unknown. Herein, we studied the change in miRNA profiles of cultured human keratinocytes (HaCaT cells) before and after in vitro PUVA treatment by 8 methoxypsoralen and found significant up regulation of hsa-miR-4516. We for the first time demonstrate that ectopic expression of hsa-miR-4516 directly targets STAT3 protein by binding to its 3'UTR in HaCaT cells as confirmed by Luciferase reporter assays and Western blot analysis. We further show that overexpression of hsa-miR-4516 downregulates STAT3, p-STAT3, CDK6, and UBE2N proteins that are consistently upregulated in psoriasis and induces apoptosis in HaCaT cells. We also observed that anti-miR-4516 treatment was able to partially inhibit PUVA-induced apoptosis, suggesting that miR-4516 is involved in PUVA-induced apoptosis. Taken together, these results not only indicate the mechanistic involvement of hsa-miR-4516 in PUVA mediated effects by down-regulating STAT3 in HaCaT keratinocytes, but also highlight the potential of hsa-miR-4516 in development of novel therapeutic strategies. J. Cell. Physiol. 229: 1630-1638, 2014. © 2014 Wiley Periodicals, Inc.

Circulating cell-free DNA levels in Portuguese patients with psoriasis vulgaris according to severity and therapy

Inflammation has a key role in the pathogenesis of psoriasis. Circulating cell-free DNA (CFD) is a marker of tissue cell damage closely associated with inflammation. We aimed to understand the relation of CFD levels with psoriasis severity, defined by the Psoriasis Area and Severity Index (PASI), with inflammation and with psoriasis therapy. Forty-six patients with psoriasis vulgaris were evaluated before (T0) and after 12weeks (T12) of treatment with narrowband ultraviolet light B (NB-UVB; n=17), psoralen plus UVA (PUVA; n=20) or topical therapy (n=9). We evaluated interleukin (IL)-6 and circulating CFD levels. Compared with controls, at T0, patients presented significantly higher levels of circulating CFD. CFD presented a significant positive correlation with IL-6 and a trend towards a positive correlation with PASI. Multiple linear regression analysis identified IL-6 as an independent variable associated with CFD circulating levels. As shown by the PASI score, a trend towards higher values of CFD was observed in the severe psoriasis forms; moderate and severe psoriasis presented also significantly higher CFD values, compared with control. Both NB-UVB and PUVA treatments significantly decreased the levels of CFD. Patients with psoriasis, at the active stage of the disease, presented an increased inflammation associated with raised circulating CFD levels, which seem to be linked to psoriasis severity. Both NB-UVB and PUVA, anti-inflammatory therapies, were effective in decreasing CFD values. We propose that the evaluation of circulating CFD may provide a new biomarker to monitor psoriasis, its severity and its treatment.