Effectiveness and Safety of Azathioprine versus PUVA-SOL as Steroid-Sparing Agents in the Treatment of Unstable Vitiligo.

Vitiligo is an acquired chronic loss of skin pigmentation characterized by white and frequent symmetric patches, for which corticosteroids are the mainstay of treatment. Regular intake of steroids for prolonged periods is frequently associated with severe and sometimes irreversible adverse events. This study was designed to compare the effectiveness and safety profiles of azathioprine versus psoralen+ultraviolet light A (PUVA)-solar light (SOL; sunlight) to determine which agent reduces the length and adverse effects of vitiligo therapy in a better manner. This single-center, randomized, open-label, prospective case-control study recruited 100 patients. Oral mini-pulse (OMP) corticosteroid therapy was administered to all patients during the first month of the study. The first group of patients (group A) continued with azathioprine 50-mg tablet twice a day (BID), and the second group (group B) was given PUVA-SOL for 2 months with concurrent OMP. Disease activity was monitored. At the end of the study period, 58% (group A) and 50% (group B) of patients had their improved vitiligo area severity index (VASI) scores by 25%-50%. Similarly, 36% (group A) and 50% (group B) of patients improved their VASI score by more than 50%. On the global physician assessment scale, 42% (group A) and 54% (group B) patients had a good to excellent response. Based on these findings, both azathioprine and PUVA-SOL were considered as good steroid-sparing agents, primarily if used with an initial phase of concomitant oral corticosteroids.

The Impact of Psoriasis Treatments on the Risk of Skin Cancer: A Narrative Review.

Several studies have described increased risk ratios of certain types of malignancies in patients with severe psoriasis. Among these, the lymphoproliferative disorders, including non-Hodgkin's lymphoma, cutaneous T-cell lymphoma and non-melanoma skin cancer, have been described most frequently. In addition to traditional cancer risk factors, some psoriasis treatments may also be implicated as potential carcinogens. The aim of this study was to perform a review of current literature on the association between psoriasis, the therapies against this disease and skin cancer, focusing on both epidemiology and the potential mechanism involved. Some psoriasis treatments, such as psoralen and ultraviolet A (PUVA) therapy and cyclosporine, have been associated with increased risk of skin cancer. Variable data have been reported for anti-tumour necrosis factor (TNF) drugs, whereas other class of biologics, like anti-IL17 and IL23, as well as ustekinumab, seem not to be related to skin cancer risk, such as the case of currently available small molecules.

Phototherapy for the treatment of cutaneous graft-versus-host disease: A systematic review.

BACKGROUND: Cutaneous graft-versus-host disease (GVHD) is a common complication of allogeneic hematopoietic stem cell transplantation. Phototherapy has been used to treat cutaneous GVHD, but data on its safety and efficacy are sparse. AIM: Review the current medical literature regarding the efficacy, dosing, and safety of various types of phototherapies for the treatment of cutaneous GVHD. METHODS: A systematic review of PubMed, Embase, Cochrane, and ClinicalTrials databases was performed. Publications were screened according to the PRISMA guidelines. Exclusion criteria comprised case reports and case series reporting less than five patients, review articles, and articles not published in English. RESULTS: A total of 28/1304 (2.5%) studies were included. Fifteen studies (n = 267 patients) focused on psoralen and ultraviolet (UV) A (PUVA), in which 65.5% of patients received concomitantly other systemic treatments. The response rate was 89.9%, with a mean of 33.2 treatments. Adverse events were recorded in 54% but were mainly mild. Eight studies, encompassing 95 patients, focused on narrow-band (NB) UVB. A response was observed in 94%, with a mean number of 26 treatments and 8.6% adverse effects. UVA1 was reported in six studies (n = 132 patients). A response was recorded in 89.3% with a mean of 26.2 treatments. Adverse events were noted in 70.1%, with a discontinuation rate of 10.9%. It should be noted that adverse events were recorded during the follow-up period of the studies, which varied significantly, ranging from no follow-up to 31 months. CONCLUSIONS: Current data regarding the use of phototherapy for the treatment of cutaneous GVHD are based on retrospective studies and case series. The present report advocates the use of one of the three modalities of phototherapy as an effective and safe adjunctive treatment for cutaneous GVHD, especially NB UVB phototherapy.

The efficacy of long-term psoralen plus ultraviolet A and low-dose interferon-a combination therapy in mycosis fungoides: A literature review.

BACKGROUND/PURPOSE: Interferon (IFN)-a is often used in combination with psoralen plus ultraviolet A (PUVA) in patients with mycosis fungoides (MF) refractory to skin-targeted therapies in early or advanced stages. The main objective is to evaluate the effectiveness of combined PUVA and low-dose IFN-α-2a therapy in patients with early- and advanced-stage MF. METHODS: Sixty-eight patients who received a combination of PUVA twice or thrice a week and INF-a 3 MU thrice a week for at least 3 months were reviewed retrospectively. The treatment response was evaluated as complete remission (CR), partial remission, stable disease, or progression. RESULTS: At the initiation, the majority of patients (66.2%) had early-stage disease. In 27.9% of cases, this was the initial treatment administered following the diagnosis of MF. The median duration of combination therapy was 11 months. Complete remission was achieved in 45.6% of the patients with an overall response rate of 60.3%. The mean duration of response was 5 months. Complete remission was statistically significantly higher in early-stage patients (p < .05). No statistically significant correlation was observed between CR and gender, histopathological features, or laboratory parameters. In patients with CR, 80% experienced relapse, significantly higher in early-stage patients (p < .05). However, there was no significant difference in disease-free survival between early and advanced stages (p > .05). CONCLUSIONS: The study results indicated that PUVA + low-dose INF-a combination therapy was more effective in the early stage than in the advanced stage. Additionally, there was a high relapse rate after the cessation of treatment in patients who achieved CR.

Phototherapy for Psoriasis in the Age of Biologics.

Phototherapy has utility as a psoriatic therapy, given its relatively high clinical efficacy, low side effect profile, and lower cost compared to newer effective treatments like biologics and small molecules. Phototherapy has shown Psoriasis Area and Severity Index (PASI)-75 and PASI-90 rates comparable to those of biologics and small molecules, with similarly rapid onsets of action, rates of remission, and quality of life scores. Certain patients may particularly benefit from phototherapy, such as those with localized disease or contraindications to systemic immunomodulatory medication. Phototherapy can be more cost-effective than biologics and conveniently administered at home, making it a valuable therapeutic option for the right patient.

Risks of glaucoma among individuals with psoriasis: a population-based cohort study.

BACKGROUND: Psoriasis is a chronic systemic disorder with ocular involvement. OBJECTIVES: To evaluate the risk of glaucoma among patients with psoriasis. METHODS: Participants in this cohort study were selected based on Chang Gung Research Database from 1 January 2003 to 31 December 2012. Follow-up ended on 31 December 2017. The participants in the control group were matched with the psoriasis group by sex, age and index date with a 4 : 1 ratio. The hazard ratios of glaucoma were estimated using Cox regression analysis. We also evaluated the relationship between the risk of glaucoma and systemic therapies as well as phototherapy and topical corticosteroid in patients with psoriasis. RESULTS: In total, 6682 patients with psoriasis and 26 728 matched controls were enrolled. The study population was composed mainly of males accounting for 64.2% (21 445/33 410) of the study population. The psoriasis group had higher incidence rates than the control group for glaucoma (adjusted hazard ratio 1.405, 95% confidence interval, 1.051-1.879). Patients with psoriasis receiving psoralen-ultraviolet A (PUVA) therapy for > 200 sessions had an increased risk of glaucoma. CONCLUSIONS: Patients with psoriasis had an increased risk of glaucoma. Long-term PUVA therapy raised the risk of glaucoma in people with psoriasis.

Does the risk of basal cell carcinoma increase in patients with psoriasis under treatment?

BACKGROUND: Psoriasis is a common, chronic, inflammatory disease. Although it mainly affects the skin, it has been associated with a large number of comorbidities. In addition to comorbidities such as depression and psoriatic arthritis, it is known that there is an increased prevalence of cancer in psoriasis patients. Skin cancers, particularly squamous cell carcinoma, have been associated with psoriasis. However, basal cell carcinoma data are limited. METHODS: 346 psoriasis patients and 306 individuals were selected as the control group. There were no differences between the patient and control groups in terms of age and gender. The mean age of the psoriasis patients was 49.9 ± 15.8 years and the control group was 49.4 ± 13.4 years. Sociodemographic data of the patients were recorded. Pharmacological agents used in the treatment of psoriasis were included in the analysis. Disease severity was assessed by the psoriasis area severity index (PASI). In the physical examination of the patients, biopsies were taken from lesions suspicious for BCC. BCC diagnosis was made by histopathologically. RESULTS: The frequency of BCC was higher in psoriasis patients than in the control group (6.6% vs. 2.9%, p < .001). Advanced age (p < .001), smoking (p = .003), and arthritis (p < .001) were associated with BCC in psoriasis patients. However, there was no relationship between PASI and BCC (p = .142). Among the psoriasis treatments, only UV therapy was associated with BCC (p = .038). The frequency of PUVA (p < .001) and number of PUVA session (p = .010) was higher in psoriasis patients with BCC rather than NB-UVB. CONCLUSION: The frequency of BCC is increased in psoriasis patients. Psoriasis is associated with an increased risk of BCC, especially when treated with PUVA therapy for a long time.

Risk of progression of early-stage mycosis fungoides, 10-year experience.

BACKGROUND: Mycosis fungoides is the most frequent form of cutaneous T-cell lymphoma. It is characterized by a chronic, slow, and progressive course, and is associated with mortality rates that depend on several factors, such as clinical staging. A median survival time of up to 13 months is found in patients with advanced stages that require more aggressive treatments, with greater toxicity and higher costs. In Latin America, few prognostic studies of the disease are available. OBJECTIVE: To determine the rate of progression from early stages (IA, IB, IIA) to more advanced stages (> IIB) in patients older than 18 years with mycosis fungoides treated at two medical centers in Colombia between January 1, 2010, and December 31, 2019. METHODS: Retrospective cohort study with a longitudinal design. RESULTS: 112 patients diagnosed with early mycosis fungoides were included. 56.2% were male (n = 63), with a median age of 53 years (IQR 43‒67). The most frequent clinical variant was classic (67.9%; n = 76), followed by folliculotropic (16%; n = 18), and hypopigmented (10.7%; n = 12). The most common first-line treatment was NB-UVB phototherapy (27.7%; n = 31), followed by PUVA phototherapy (25.8%; n = 29%), and topical corticosteroids (25%; n = 28). The global rate of disease progression was 8% (n = 9), with an overall mortality of 12.5% (n = 14). STUDY LIMITATIONS: Its retrospective design and the lack of molecular studies for case characterization. CONCLUSIONS: Early mycosis fungoides is a disease with a good prognosis in most patients, with a progression rate of 8% (n = 9).

Clinical, histopathological and immunohistochemical evaluation of ultraviolet A1 treatment in early-stage mycosis fungoides.

BACKGROUND/PURPOSE: Mycosis fungoides (MF) is the most common variant of cutaneous T-cell lymphomas primarily involving the skin. Early-stage MF is characterised by non-specific skin lesions and non-diagnostic biopsies. While skin-focused treatments, such as PUVA and narrowband UVB (nbUVB), are the most frequently recommended treatments, the UVA1 efficacy has been researched in recent years. The purpose of this study was to evaluate the clinical, histopathological and immunohistochemical aspects of UVA1 treatment in patients with early-stage MF. METHODS: The modified severity weighted assessment scale (mSWAT) was used for total skin body scoring before and after treatment. Skin punch biopsies were taken from the patients before and after treatment. UVA1 therapy was performed five times each week. RESULTS: This study included 26 patients with early-stage MF. The total number of UVA1 sessions varied between 15 and 34. Complete response was observed in 8 (30.8%) of 26 patients (30.8%). The median mSWAT score decreased statistically significantly from 7.1 to 2.0 after treatment (p < .001). Histopathological complete response was observed in 2 (9.5%) of 21 patients. A statistically significant decrease in dermal interstitial infiltrate was observed on histopathological examination after treatment (p = .039). Epidermal CD4/CD8 levels decreased statistically significantly higher from a median of 2.5-1.2 in the complete clinical response group after treatment (p = .043). CONCLUSION: According to our results, UVA1 treatment has an effect on early-stage MF in terms of clinical, histopathological and immunohistochemistry.

Melanocyte transplantation to skin prepared by controlled PUVA-induced sunburn-like blistering for vitiligo treatment - A pilot clinical trial.

Vitiligo is a common acquired disease of pigment loss. In lesions recalcitrant to non-invasive treatment, transplantation of cultured autologous melanocytes is an emerging choice. Conventionally, the recipient site is often prepared by laser-mediated or mechanical dermabrasion. Such preparation procedures have disadvantages including prolonged transplantation duration, long period for reepithelialization and potential scarring. We propose a method of preparing recipient sites by psoralen and controlled ultraviolet A (PUVA)-induced blistering followed by transplanting suspended melanocytes. We introduced this method in 10 patients with segmental vitiligo on their recipient site 3 to 5 days before transplantation and blistering developed in 2 to 3 days afterwards. On the day of transplantation, the blister roof could be peeled off easily without bleeding and the recipient site preparation could be completed in 20 min. The recipient site became reepithelialized within 1 week. Progressive repigmentation was observed for up to 6 months, with an average of 65.06% repigmentation in the recipient site without scarring at the end of follow-up. Hence, preparation of the recipient site by controlled PUVA-induced sunburn-like blistering can potentially facilitate melanocyte transplantation and prevent scarring.

Effects of psoriasis and psoralen exposure on the somatic mutation landscape of the skin.

Somatic mutations are hypothesized to play a role in many non-neoplastic diseases. We performed whole-exome sequencing of 1,182 microbiopsies dissected from lesional and nonlesional epidermis from 111 patients with psoriasis to search for evidence that somatic mutations in keratinocytes may influence the disease process. Lesional skin remained highly polyclonal, showing no evidence of large-scale spread of clones carrying potentially pathogenic mutations. The mutation rate of keratinocytes was similarly only modestly affected by the disease. We found evidence of positive selection in previously reported driver genes NOTCH1, NOTCH2, TP53, FAT1 and PPM1D and also identified mutations in four genes (GXYLT1, CHEK2, ZFP36L2 and EEF1A1) that we hypothesize are selected for in squamous epithelium irrespective of disease status. Finally, we describe a mutational signature of psoralens-a class of chemicals previously found in some sunscreens and which are used as part of PUVA (psoralens and ultraviolet-A) photochemotherapy treatment for psoriasis.

Bath psoralen plus ultraviolet-A photochemotherapy for chronic graft-versus-host disease: a retrospective cohort study.

BACKGROUND: Chronic graft-versus-host disease is a severe complication of allogeneic stem cell and bone marrow transplantation. First-line immunosuppressive agents, such as steroids, are used to prevent this disease; however, they have multiple side effects. Therefore, bath psoralen plus ultraviolet-A (PUVA) is an alternative second-line treatment. This study aimed to evaluate the clinical efficacy of bath PUVA for managing chronic graft-versus-host disease. METHODS: This retrospective, case-control study included 14 patients with extensive cutaneous chronic graft-versus-host disease, resistant to systemic corticosteroid, treated with bath PUVA. Major and partial responses were defined as clinical improvements of >70% and 50-70%, respectively. We analyzed the graft-versus-host disease clinical presentation and timing after allogeneic stem cell and bone marrow transplantation, bath PUVA doses, background diseases, additional treatments, and adverse effects. RESULTS: We observed eight major (three lichenoid and five sclerodermatoid) and six partial (three lichenoid and three sclerodermatoid) responses after a mean of 28 treatment sessions. After 6 to 25 months, four of the eight patients with sclerodermatoid lesions and all those with lichenoid lesions experienced relapse but responded to additional treatment cycles. CONCLUSIONS: Bath PUVA is well-tolerated and effective for extensive cutaneous chronic graft-versus-host disease. It allows rapid tapering of adjuvant immunosuppressants; however, most patients require prolonged maintenance phototherapy.

Phototherapy: Theory and practice.

Despite the development of highly effective biologics for skin diseases such as psoriasis or atopic dermatitis, UVA and UVB therapy, alone or in combination, are still essential components of various guidelines. Phototherapy is not only a first-line treatment and highly effective for a number of skin diseases, but is also economical and has few side effects. The targeted use of UVA and UVB, if necessary, in combination with the photosensitizer psoralen in the context of PUVA therapy, enables the dermatologist to effectively treat a wide variety of skin diseases. Indications for phototherapy include epidermal diseases such as atopic dermatitis, psoriasis and vitiligo, as well as photodermatoses, mycosis fungoides, graft-versus-host disease and deep dermal diseases such as scleroderma. This article reviews the physical principles, molecular mechanisms, current treatment regimens, and individual indications for phototherapy and photochemotherapy.

Risk of skin cancers in mycosis fungoides patients receiving PUVA therapy: A real-life experience from a single tertiary center.

BACKGROUND: Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma. Skin-directed therapies, including phototherapy, are the first-line treatment modalities. Psoralen plus ultraviolet A light photochemotherapy (PUVA) is quite effective in controlling the disease; however, long-term adverse effects, particularly carcinogenesis, are the cons of this treatment. OBJECTIVE: There are various studies on the negative impact of PUVA on skin cancer in patients with autoimmune skin diseases. The data on the long-term effects of phototherapy on MF patients are scarce. METHODS: All MF cases that received PUVA alone or combined with other treatments at a single tertiary center were analyzed. This study compared the development of non-melanoma skin cancers, melanoma, and solid organ tumors in MF patients with at least 5-year follow-up data with age- and sex-matched controls. RESULTS: A total of 104 patients were included in the study. Ninety-two malignancies were detected in 16 (15.4%) patients, and six developed multiple malignancies. Skin cancers consisted of 56 basal cell carcinomas, 16 Bowen's disease, four squamous cell carcinomas, three melanomas, two basosquamous cell carcinomas, one Kaposi sarcoma, and one keratoacanthoma were found in nine (8.7%) patients. Eight patients developed three solid cancers and six lymphomas. The risk of developing skin cancer was associated with the total number of PUVA sessions (<250 vs ≥250 sessions; hazard ratio (HR) 4.44, 95% confidence interval (CI) 1.033-19.068; p = .045). 9 (13.2%) of 68 patients who had follow-ups for at least 5 years developed skin cancer. Compared to an age- and sex-matched cohort, the prevalence of new skin cancer was considerably greater (p = .009). CONCLUSIONS: Patients with MF are predisposed to develop secondary malignancies, and continual exposure to PUVA may potentiate this risk. Annual digital dermoscopic follow-up in MF patients treated with UVA is advised for early diagnosis and treatment of secondary cutaneous malignancies.

Spontaneous Reversal of Vitiligo, a Rare Phenomenon Reported in a Case in Saudi Arabia with an Insight into Metabolic Biochemical Derangements.

Background and Objectives: Vitiligo is a skin disorder characterized by hypopigmented macules occurring due to melanocyte destruction. An interplay of several biochemical mechanisms has been proposed to explain the etiopathogenesis of vitiligo, such as genetic, autoimmune responses, generation of inflammatory mediators, oxidative stress, and melanocyte detachment mechanisms. There is no cure for vitiligo; however, pharmacological treatment measures (cosmetic camouflage creams, steroids, psoralen and ultraviolet A (PUVA) therapy, narrowband UVB) are available, but they could have certain side effects. We reported an interesting case of vitiligo in Saudi Arabia that showed reversal of vitiligo, which is an extremely rare phenomenon, with the objective of probing the probable reasons for this reversal. To the best of our knowledge, there is no study on vitiligo that has reported spontaneous reversal of vitiligo in Saudi Arabia so far. Materials and Method: The patient presented to the Family Medicine clinic with a history of restoration of melanin pigment in his lesions after 3 years of the onset of vitiligo. Patients history was taken carefully along with clinical examination, carried out necessary biomedical lab investigations and compiled the data. The data at the time of pigment restoration were compared to the previous data when he developed the lesions. Result: The probable reasons for vitiligo reversal could be markedly decreased psychological stress, regular consumption of an antioxidant-rich herbal drink made of curcumin and honey, and dietary switchover to vegetarianism and an alcohol-free lifestyle. Conclusions: Curcumin-based herbal remedies could be an alternative option to treat vitiligo. These methods must be further explored through clinical trials as they are safer, easily available, and more affordable.

Nb-UVB and PUVA therapy in treating early stages of Mycosis Fungoides: A single-center cross-sectional study.

INTRODUCTION: Mycosis fungoides (MF) and Sezary Syndrome are the most common forms of cutaneous T-cell lymphoma. Early-stage MF is known to have an indolent behavior, and the EORTC guidelines recommend treating patients with skin-directed therapies, such as phototherapy, instead of systemic therapies. Phototherapy is a popular therapeutic option, with two commonly used light sources-PUVA and narrow band-nb UVB. PUVA is less commonly used due to its potential carcinogenic role, but it has systemic effects, while nb-UVB has mostly skin-limited effects. There is ongoing debate regarding the role of UVB light, and in 2021, the Cutaneous Lymphoma Italian Study Group reached a consensus on technical schedules for NB-UVB and PUVA for MF. This study aims to analyze and compare the efficacy of the two phototherapy options in treating early-MF patients. MATERIALS AND METHODS: The study included patients diagnosed with stage IA/B MF in the last 10 years, who had at least 12 months of follow-up data and a minimum of 24 phototherapy sessions (PUVA or nb UVB) and treated with topical steroids apart from phototherapy. RESULTS: Results showed that the two phototherapy options were similarly effective in treating early MF, with no significant differences in clinical response, although PUVA was associated with more adverse effects. CONCLUSIONS: The study provides valuable insights into the use of phototherapy in early MF, and the results can be used to guide treatment decisions and improve patient outcomes.

PUVA therapy in persistent cutaneous histiocytosis: Case report and literature review.

BACKGROUND: Cutaneous and mucocutaneous histiocytosis (group C) comprise a wide variety of entities affecting skin and/or mucosae. Although they are considered as reactive proliferations, their exact pathophysiology remains unknown and, therefore, they lack a specific treatment. AIMS: The aim of this study is to review the evidence on cases of histiocytosis treated with UVB and/or UVA and to report a new case of relapsing group C histiocytosis that has been successfully treated with PUVA therapy. MATERIALS & METHODS: We have conducted a review of the literature published over the last 40 years on the treatment of histiocytosis with phototherapy in the online PubMed database. We also describe a new case of successful treatment of histiocytosis with PUVA therapy. RESULTS: Our patient was a 27-year-old man with persistent outbreaks of cutaneous histiocytosis over the previous 8 years. He responded successfully to PUVA therapy, and no relapse has been detected after one year of follow-up. DISCUSSION: Self-involution is usual in group C histiocytosis, so conservative management is usually the first approach. Relapsing cases pose a therapeutic challenge. Reported treatment options for these patients include isotretinoin, cryotherapy, immunosuppressants, low-dose chemotherapy, CO2 laser, radiotherapy, and surgery. Phototherapy and photochemotherapy have been used in a small number of patients with considerable success. The main limitation to provide firm recommendations on histiocytosis therapy is the absence of solid evidence, as the articles published are mainly case reports with a short follow-up. In our patient, despite the short follow-up we have considered photochemotherapy to be effective since no spontaneous remission had been achieved in the previous 8 years. CONCLUSION: PUVA therapy could be a safe and effective option to treat persistent cutaneous manifestations in patients with histiocytosis, although more evidence is required to support this statement.