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.

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.

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.

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.

Bath-PUVA still represents a valuable treatment option for the subsets of psoriatic patients who are not eligible to or rejecting systemic treatments and are not responsive to NB-UVB phototherapy.

BACKGROUND: Photochemotherapy with bathwater delivery of psoralens plus UVA exposures (bath-PUVA) is mainly used for those psoriatic patients who are not responsive to narrowband (NB)-UVB phototherapy and oral-PUVA therapy and belong to two categories (1) patients with psoriasis without systemic comorbidities who do not need long-term continuous treatment and (2) patients who have contraindications to immunosuppressive drugs and oral-PUVA or refuse systemic drugs, including oral ingestion of psoralens, for personal reasons. However, it is not known how many patients belong to the second group and how much bath-PUVA is effective and safe for them. METHODS: We have reviewed the treatment results of a cohort of 120 patients with clinical indication to bath-PUVA for the above-mentioned reasons between 2010 and 2019. These patients were selected among 2640 patients with moderate and severe psoriasis who were treated in our department in the same time interval. RESULTS: Ninety-six patients completed at least one treatment cycle with bath-PUVA. A per-protocol analysis showed that average number of treatment sessions was 21.3 ± 9.0 and the cumulative UVA dose was 80.4 ± 60.0 J/cm2 . The average PASI scores decreased from 20.8 ± 7.9 to 5.1 ± 5.4 (p < .01). Sixty-seven (69.7%) patients achieved at least a 75% improvement (PASI75 ) and, of them, 38 (39.6%) had an improvement greater than 90% (PASI90 ). Adverse effects were mild and transitory. CONCLUSION: These findings demonstrate that bath-PUVA is still a valuable treatment option for a high number of patients who reject systemic treatments or have contraindications to systemic immune-modifying drugs and have had a limited or no improvement with NB-UVB phototherapy.

Prognosis in early stage cutaneous T-cell lymphoma treated with psoralen plus ultraviolet A irradiation and low-dose interferon-α: Long-term efficacy and survival according to conventional and emerging clinical endpoints.

Patients with early stage cutaneous T cell lymphoma (CTCL) usually have a benign and chronic disease course, characterized by temporally response to conventional skin directed therapies and intrinsic possibility to evolve. Using the combination of psoralen plus ultraviolet A irradiation (PUVA) and low-dose interferon-α (INF), the principal treatment goal is to keep confined the disease to the skin, preventing disease progression. Among 87 patients with early stage IA to IIA MF treated with low-dose IFN-α2b and PUVA in our center, complete remission (CR) were reported in 70 patients (80.5%) and the overall response rate (ORR) was 97.8% (n = 85), with a median time to best response to therapy of 5 months (range, 1-30). Among the responders, only the 8% of patients had a relapse with major event. The median follow-up was 207 months (range, 6-295). Survival data showed a median overall survival (OS) not reached (95% CI; 235-NR months), a disease free survival (DFS) of 210 months (95% CI; 200-226 months) and a median time to next treatment (TTNT) of 38.5 months (95% CI, 33-46 months). The long follow up of this study verifies our preliminary results already published in 2006 and confirms the efficacy of INF-PUVA combination therapy in a real world setting, according conventional (OS and DFS) and emerging (TTNT) clinical endpoint of treatment efficacy.

Frequency of phototherapy for treating psoriasis: a systematic review.

INTRODUCTION: Narrow band ultraviolet B (NB-UVB) and psoralen-ultraviolet A (PUVA) remain inexpensive and effective anti-psoriatic therapies adopted worldwide with different frequency protocols. We aimed to systematically assess the evidence on the effects of different frequency protocols of phototherapy in treating psoriasis. EVIDENCE ACQUISITION: We used the following terms, namely "photochemotherapy," "phototherapy," "psoriasis," "UVB," "UVA" and "ultraviolet therapy," to search the Cochrane Controlled Register of Trials, MEDLINE and Embase databases on August 1, 2019. We organized results using a PRISMA diagram and analyzed bias risks with RoB-2 tool. EVIDENCE SYNTHESIS: We included five randomized controlled trials (RCTs) on oral PUVA and three RCTs on NB-UVB. The five studies on PUVA included a total of 1452 patients with plaque psoriasis and did not find any significant difference in efficacy comparing two- vs. three- vs. four times weekly protocols. The three studies on NB-UVB included a total of 248 patients with plaque psoriasis. No differences in efficacy were reported in comparing different frequencies in delivering NB-UVB, namely twice vs. thrice weekly, twice vs. four times weekly, and thrice- vs. five times weekly protocols. Although protocols with higher treatments frequency per week achieved clearance faster than lower frequency ones, but they did not differ in terms of efficacy. CONCLUSIONS: PUVA and NB-UVB remain effective anti-psoriatic treatments; however further studies are needed to elucidate which protocol may be more effective in different skin phototypes.

Light- and laser-based treatments for granuloma annulare: A systematic review.

BACKGROUND: Granuloma annulare (GA) is challenging to treat, especially when generalized. A systematic review to support the use of light- and laser-based treatments for GA is lacking. METHODS: We performed a systematic review by searching Cochrane, MEDLINE, and Embase. Title, abstract, full-text screening, and data extraction were done in duplicate. Quality appraisal was performed using the Joanna Briggs Institute critical appraisal tool for case series. RESULTS: Thirty-one case series met the inclusion criteria, representing a total of 336 patients. Overall, psoralen ultraviolet light A (PUVA) showed the greatest frequency of cases with complete response (59%, n = 77/131), followed by photodynamic therapy (PDT) (52%, n = 13/25), ultraviolet light B (UVB)/narrowband UVB (nbUVB)/excimer laser (40%, n = 19/47), UVA1 (31%, n = 27/86), and lasers (29%, n = 8/28). Overall across treatment modalities, higher response rates were seen in localized GA compared to generalized GA. CONCLUSIONS: The body of evidence for light- and laser-based treatment of GA is sparse. Our results suggest that PUVA has a high clearance rate for GA but its use may be limited by concerns of carcinogenesis. Although PDT has the second highest clearance rate, adverse effects, small sample sizes, impractical treatment delivery (especially with generalized disease), and long-term concerns of carcinogenesis may limit its use. Although UVB/nbUVB/excimer laser appeared slightly less effective than other light therapies, we recommend UVB/nbUVB/excimer laser therapy as a first-line treatment for patients with generalized GA given wider availability and a favorable long-term safety profile.

Clinical Trial of High-Dose Pegylated-Interferon-Alfa-2b Combined With Phototherapy in Advanced Stage Mycosis Fungoides.

The combination of Interferon-α-2b (IFN-α-2b) and phototherapy is highly effective in treating mycosis fungoides (MF) but side effects often lead to discontinuation of therapy.1.

Efficacy of doxycycline in the treatment of early stages of mycosis fungoides: a randomized controlled trial.

BACKGROUND: Mycosis fungoides is the most common type of primary cutaneous T cell lymphomas. Doxycycline promoted apoptosis in different human malignant cell lines and in vivo models. OBJECTIVES: To test for the therapeutic efficacy of doxycycline in comparison to PUVA in early stages of classic MF and its effect on T cell apoptosis. METHODS: Thirty-six patients were randomized into either: doxycycline 200 mg daily (n = 18) or PUVA (3 weekly sessions) (n = 18) for 12 weeks. The primary outcome (therapeutic efficacy) was defined in terms of objective response rate (ORR) which was measured according to changes in the modified severity weighted assessment tool (mSWAT). RESULTS: Doxycycline achieved significantly less ORR (partial response) in comparison to PUVA (11.1%, 50%, respectively, p = .016). The percent reduction in mSWAT, CAILS, histopathology score and CD3 expression was significantly less in the doxycycline group (p = .001, p = .001, p ˂ .001, and p = .004, respectively). Within the doxycycline group, changes in mSWAT and CAILS showed no correlation with changes in the CD3 or Bcl-2 expression. Gastric upset was significantly more encountered in the doxycycline group (p = .001). CONCLUSION: Doxycycline is not suitable as a sole agent in the treatment of early stages of classic MF, acting mainly by anti-inflammatory rather apoptotic function. REGISTER NUMBER: NCT03454945 (www.clinicaltrials.gov).

Interventions for mycosis fungoides.

BACKGROUND: Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, a malignant, chronic disease initially affecting the skin. Several therapies are available, which may induce clinical remission for a time. This is an update of a Cochrane Review first published in 2012: we wanted to assess new trials, some of which investigated new interventions. OBJECTIVES: To assess the effects of interventions for MF in all stages of the disease. SEARCH METHODS: We updated our searches of the following databases to May 2019: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We searched 2 trials registries for additional references. For adverse event outcomes, we undertook separate searches in MEDLINE in April, July and November 2017. SELECTION CRITERIA: Randomised controlled trials (RCTs) of local or systemic interventions for MF in adults with any stage of the disease compared with either another local or systemic intervention or with placebo. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. The primary outcomes were improvement in health-related quality of life as defined by participants, and common adverse effects of the treatments. Key secondary outcomes were complete response (CR), defined as complete disappearance of all clinical evidence of disease, and objective response rate (ORR), defined as proportion of patients with a partial or complete response. We used GRADE to assess the certainty of evidence and considered comparisons of psoralen plus ultraviolet A (PUVA) light treatment as most important because this is first-line treatment for MF in most guidelines. MAIN RESULTS: This review includes 20 RCTs (1369 participants) covering a wide range of interventions. The following were assessed as either treatments or comparators: imiquimod, peldesine, hypericin, mechlorethamine, nitrogen mustard and intralesional injections of interferon-α (IFN-α) (topical applications); PUVA, extracorporeal photopheresis (ECP: photochemotherapy), and visible light (light applications); acitretin, bexarotene, lenalidomide, methotrexate and vorinostat (oral agents); brentuximab vedotin; denileukin diftitox; mogamulizumab; chemotherapy with cyclophosphamide, doxorubicin, etoposide, and vincristine; a combination of chemotherapy with electron beam radiation; subcutaneous injection of IFN-α; and intramuscular injections of active transfer factor (parenteral systemics). Thirteen trials used an active comparator, five were placebo-controlled, and two compared an active operator to observation only. In 14 trials, participants had MF in clinical stages IA to IIB. All participants were treated in secondary and tertiary care settings, mainly in Europe, North America or Australia. Trials recruited both men and women, with more male participants overall. Trial duration varied from four weeks to 12 months, with one longer-term study lasting more than six years. We judged 16 trials as at high risk of bias in at least one domain, most commonly performance bias (blinding of participants and investigators), attrition bias and reporting bias. None of our key comparisons measured quality of life, and the two studies that did presented no usable data. Eighteen studies reported common adverse effects of the treatments. Adverse effects ranged from mild symptoms to lethal complications depending upon the treatment type. More aggressive treatments like systemic chemotherapy generally resulted in more severe adverse effects. In the included studies, CR rates ranged from 0% to 83% (median 31%), and ORR ranged from 0% to 88% (median 47%). Five trials assessed PUVA treatment, alone or combined, summarised below. There may be little to no difference between intralesional IFN-α and PUVA compared with PUVA alone for 24 to 52 weeks in CR (risk ratio (RR) 1.07, 95% confidence interval (CI) 0.87 to 1.31; 2 trials; 122 participants; low-certainty evidence). Common adverse events and ORR were not measured. One small cross-over trial found once-monthly ECP for six months may be less effective than twice-weekly PUVA for three months, reporting CR in two of eight participants and ORR in six of eight participants after PUVA, compared with no CR or ORR after ECP (very low-certainty evidence). Some participants reported mild nausea after PUVA but no numerical data were given. One participant in the ECP group withdrew due to hypotension. However, we are unsure of the results due to very low-certainty evidence. One trial comparing bexarotene plus PUVA versus PUVA alone for up to 16 weeks reported one case of photosensitivity in the bexarotene plus PUVA group compared to none in the PUVA-alone group (87 participants; low-certainty evidence). There may be little to no difference between bexarotene plus PUVA and PUVA alone in CR (RR 1.41, 95% CI 0.71 to 2.80) and ORR (RR 0.94, 95% CI 0.61 to 1.44) (93 participants; low-certainty evidence). One trial comparing subcutaneous IFN-α injections combined with either acitretin or PUVA for up to 48 weeks or until CR indicated there may be little to no difference in the common IFN-α adverse effect of flu-like symptoms (RR 1.32, 95% CI 0.92 to 1.88; 82 participants). There may be lower CR with IFN-α and acitretin compared with IFN-α and PUVA (RR 0.54, 95% CI 0.35 to 0.84; 82 participants) (both outcomes: low-certainty evidence). This trial did not measure ORR. One trial comparing PUVA maintenance treatment to no maintenance treatment, in participants who had already had CR, did report common adverse effects. However, the distribution was not evaluable. CR and OR were not assessable. The range of treatment options meant that rare adverse effects consequently occurred in a variety of organs. AUTHORS' CONCLUSIONS: ​​There is a lack of high-certainty evidence to support decision making in the treatment of MF. Because of substantial heterogeneity in design, missing data, small sample sizes, and low methodological quality, the comparative safety and efficacy of these interventions cannot be reliably established on the basis of the included RCTs. PUVA is commonly recommended as first-line treatment for MF, and we did not find evidence to challenge this recommendation. There was an absence of evidence to support the use of intralesional IFN-α or bexarotene in people receiving PUVA and an absence of evidence to support the use of acitretin or ECP for treating MF. Future trials should compare the safety and efficacy of treatments to PUVA, as the current standard of care, and should measure quality of life and common adverse effects.

Indoor salt water baths followed by artificial ultraviolet B light for chronic plaque psoriasis.

BACKGROUND: Chronic plaque psoriasis is an immune-mediated, chronic, inflammatory skin disease, which can impair quality of life and social interaction. Disease severity can be classified by the psoriasis area and severity index (PASI) score ranging from 0 to 72 points. Indoor artificial salt bath with or without artificial ultraviolet B (UVB) light is used to treat psoriasis, simulating sea bathing and sunlight exposure; however, the evidence base needs clear evaluation. OBJECTIVES: To assess the effects of indoor (artificial) salt water baths followed by exposure to artificial UVB for treating chronic plaque psoriasis in adults. SEARCH METHODS: We searched the following databases up to June 2019: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trial registers, and checked the reference lists of included studies, recent reviews, and relevant papers for further references to relevant trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) of salt bath indoors followed by exposure to artificial UVB in adults who have been diagnosed with chronic plaque type psoriasis. We included studies reporting between-participant data and within-participant data. We evaluated two different comparisons: 1) salt bath + UVB versus other treatment without UVB; eligible comparators were exposure to psoralen bath, psoralen bath + artificial ultraviolet A UVA) light, topical treatment, systemic treatment, or placebo, and 2) salt bath + UVB versus other treatment + UVB or UVB only; eligible comparators were exposure to bath containing other compositions or concentrations + UVB or UVB only. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We used GRADE to assess the certainty of the evidence. The primary efficacy outcome was PASI-75, to detect people with a 75% or more reduction in PASI score from baseline. The primary adverse outcome was treatment-related adverse events requiring withdrawal. For the dichotomous variables PASI-75 and treatment-related adverse events requiring withdrawal, we estimated the proportion of events among the assessed participants. The secondary outcomes were health-related quality of life using the Dermatology Life Quality Index, (DLQI) pruritus severity measured using a visual analogue scale, time to relapse, and secondary malignancies. MAIN RESULTS: We included eight RCTs: six reported between-participant data (2035 participants; 1908 analysed), and two reported within-participant data (70 participants, 68 analysed; 140 limbs; 136 analysed). One study reported data for the comparison salt bath with UVB versus other treatment without UVB; and eight studies reported data for salt bath with UVB versus other treatment with UVB or UVB only. Of these eight studies, only five reported any of our pre-specified outcomes and assessed the comparison of salt bath with UVB versus UVB only. The one included trial that assessed salt bath plus UVB versus other treatment without UVB (psoralen bath + UVA) did not report any of our primary outcomes. The mean age of the participants ranged from 41 to 50 years of age in 75% of the studies. None of the included studies reported on the predefined secondary outcomes of this review. We judged seven of the eight studies as at high risk of bias in at least one domain, most commonly performance bias. Total trial duration ranged between at least two months and up to 13 months. In five studies, the median participant PASI score at baseline ranged from 15 to 18 and was balanced between treatment arms. Three studies did not report PASI score. Most studies were conducted in Germany; all were set in Europe. Half of the studies were multi-centred (set in spa centres or outpatient clinics); half were set in a single centre in either an unspecified settings, a psoriasis daycare centre, or a spa centre. Commercial spa or salt companies sponsored three of eight studies, health insurance companies funded another, the association of dermatologists funded another, and three did not report on funding. When comparing salt bath plus UVB versus UVB only, two between-participant studies found that salt bath plus UVB may improve psoriasis when measured using PASI 75 (achieving a 75% or more reduction in PASI score from baseline) (risk ratio (RR) 1.71, 95% confidence interval (CI) 1.24 to 2.35; 278 participants; low-certainty evidence). Assessment was conducted at the end of treatment, which was equivalent to six to eight weeks after start of treatment. The two trials which contributed data for the primary efficacy outcome were conducted by the same group, and did not blind outcome assessors. The German Spas Association funded one of the trials and the funding source was not stated for the other trial. Two other between-participant studies found salt bath plus UVB may make little to no difference to outcome treatment-related adverse events requiring withdrawal compared with UVB only (RR 0.96, 95% CI 0.35 to 2.64; 404 participants; low-certainty evidence). One of the studies reported adverse events, but did not specify the type of events; the other study reported skin irritation. One within-participant study found similar results, with one participant reporting severe itch immediately after Dead Sea salt soak in the salt bath and UVB group and two instances of inadequate response to phototherapy and conversion to psoralen bath + UVA reported in the UVB only group (low-certainty evidence). AUTHORS' CONCLUSIONS: Salt bath with artificial ultraviolet B (UVB) light may improve psoriasis in people with chronic plaque psoriasis compared with UVB light treatment alone, and there may be no difference in the occurrence of treatment-related adverse events requiring withdrawal. Both results are based on data from a limited number of studies, which provided low-certainty evidence, so we cannot draw any clear conclusions. The reporting of our pre-specified outcomes was either non-existent or limited, with a maximum of two studies reporting a given outcome. The same group conducted the two trials which contributed data for the primary efficacy outcome, and the German Spas Association funded one of these trials. We recommend further RCTs that assess PASI-75, with detailed reporting of the outcome and time point, as well as treatment-related adverse events. Risk of bias was an issue; future studies should ensure blinding of outcome assessors and full reporting.

Efficacy and safety of bexarotene combined with photo(chemo)therapy for cutaneous T-cell lymphoma.

Cutaneous T-cell lymphoma (CTCL) is a chronic condition with low malignancy. International treatment guidelines for CTCL are widely followed in Europe and the USA. Combination therapy with therapeutic agents for CTCL and phototherapy is effective on the basis of European data. The efficacy and safety of combination therapy for Japanese CTCL patients are not established. We investigated the efficacy and safety of combination therapy with photo(chemo)therapy and bexarotene in Japanese CTCL patients. Twenty-five patients received daily oral bexarotene (300 mg/m2 body surface), followed by bath-psoralen plus ultraviolet (UV)-A (PUVA) or narrowband UV-B. Treatment results were evaluated using the modified Severity-Weighted Assessment Tool (mSWAT) and the Physician Global Assessment of Clinical Condition (PGA) up to week 24. Safety was also assessed. Twenty-four weeks after initiating treatment, the total response rate was 80.0% (mSWAT) and 84.0% (PGA). Response rates did not differ when stratified by disease stage. Number of days (mean ± standard deviation) for time to response, duration of response and time to progression determined by the mSWAT were 20.7 ± 9.62, 117.0 ± 43.0 and 163.6 ± 28.8, respectively. T-helper 2 chemokine levels in patients at stage IIA or more decreased significantly at weeks 12 and 24. All patients experienced adverse events and adverse drug reactions. Serious adverse drug reactions included sepsis, anemia and congestive cardiac insufficiency (n = 1 each). Other adverse drug reactions were of mild to moderate severity. Combination therapy with bexarotene and PUVA was safe and effective in Japanese CTCL patients.

The Science and (Lost) Art of Psoralen Plus UVA Phototherapy.

PUVA phototherapy is the therapeutic use of psoralens and UVA light to treat inflammatory skin diseases, with psoriasis the prototype disease. Naturally occurring phototoxic compounds, psoralens interact with UVA to suppress DNA synthesis and cell proliferation and induce apoptosis of inflammatory cells. Well-developed therapeutic protocols for psoriasis guide psoralen and UVA doses, treatment frequency, and safety measures, and these protocols also may be used to treat other inflammatory dermatoses.

Evaluation of serum folate level before and after bath PUVA therapy in patients referred to Razi Hospital, Rasht, Iran.

Ultraviolet (UV) radiation could disintegrate folate molecule, so phototherapy may reduce folate levels in the patients. The effect of phototherapy on serum folate in human body is questionable. We investigated the effect of bath PUVA therapy on serum folate level. This study was designed as a before-after study. Thirty-two patients completed study during 2 years. Our variables were demographic data, folate levels before and 8 weeks after treatment and cumulative dosage of UVA during 8 weeks of treatment. Serum folate was evaluated with chemiluminescence immunoassay technique. All data were analyzed using SPSS 18 software. Folate level changes were statistically significant before and after bath PUVA therapy. There was no significant difference in folate levels in psoriasis patients compared with nonpsoriasis patients. In psoriasis patients, folate levels had no significant correlation with psoriasis activity index before treatment. Decrease in folate levels was more significant in fair-skinned patients. There was no association between folate status and cumulative dosage of UVA. Bath PUVA therapy reduced serum folate level in our patients although none of them were folate deficient. Folate deficiency should be evaluated and corrected especially in fair-skinned cases, as it may be aggravated by phototherapy.

Drug survival and reasons for drug discontinuation in palmoplantar pustulosis: a retrospective multicenter study.

BACKGROUND: Palmoplantar pustulosis (PPP) is a chronic inflammatory skin disease-related to psoriasis. Its treatment is challenging, and little is known about the sustainability of different medications. The aim of this study was to analyze drug survival rates and drug discontinuation in the treatment of PPP under real-world conditions. PATIENTS AND METHODS: Patients with PPP treated in the dermatology departments of five German university medical centers between 01/2005 and 08/2017 were included in our retrospective study. Drug survival of systemic therapies was assessed with Kaplan-Meier analysis and multivariate regression. RESULTS: Overall, 347 patients with 935 treatment courses were identified. Within the group of non-biologic systemic agents, apremilast showed the highest median drug survival (15 months), followed by cyclosporine (12 months), the combination of acitretin and topical PUVA (9 months), MTX (8 months), acitretin monotherapy (6 months), alitretinoin (5 months), and fumaric acid esters (3 months). Among biologicals, the highest maintenance rate was detected for certolizumab pegol (restricted mean: 47.4 months), followed by infliximab (median: 26 months), golimumab (22 months), ustekinumab (21 months), adalimumab (18 months), secukinumab (9 months), and etanercept (8 months). CONCLUSIONS: Biologicals and apremilast may serve as second-line options for treatment of PPP and should be further evaluated.

Evaluation of Low-Dose, Low-Frequency Oral Psoralen-UV-A Treatment With or Without Maintenance on Early-Stage Mycosis Fungoides: A Randomized Clinical Trial.

Importance: Psoralen-UV-A (PUVA) photochemotherapy is standard first-line treatment for skin-limited, early-stage mycosis fungoides capable of producing high initial complete response (CR) rates. However, much remains unknown about PUVA's therapeutic mechanisms, optimal duration and frequency of treatment, dose escalation, or use as maintenance therapy. Objectives: To evaluate low-dose, low-frequency PUVA, and whether maintenance treatment extends disease-free remission in patients with mycosis fungoides. Design, Setting, and Participants: This prospective randomized clinical trial with defined PUVA dosing regimen was carried out in 5 centers (Graz, Vienna, Hietzing, Innsbruck, and Salzburg) across Austria. Patients with stage IA to IIA mycosis fungoides (n = 27) were enrolled in the study beginning March 13, 2013, with the last patient enrolled March 21, 2016. These patients were treated with oral 8-methoxypsoralen followed by UV-A exposure 2 times per week for 12 to 24 weeks until CR. Patients with CR were randomized to PUVA maintenance for 9 months (14 total exposures) or no maintenance. The study was conducted from April 27, 2012, to July 27, 2018. Data analysis of the primary end point was of the intention-to-treat population, and the secondary end point analysis was of the evaluable population. Main Outcomes and Measures: Efficacy of the PUVA regimen was determined by the rate of CR as defined by a modified severity-weighted assessment tool (mSWAT) score reduction to 0. Levels of proinflammatory molecules in serum and histologic features and percentage of clonal T cells in skin were assessed to search for biomarkers of clinical response. Results: In 27 patients with mycosis fungoides, 19 (70%) were male with mean (range) age 61 (30-80) years. At baseline, patients with CR had a mean (range) mSWAT score of 18.6 (1-66) compared with 16.8 (3-46) in patients with partial response. The 12- to 24-week PUVA induction regimen reduced the mSWAT score in all patients and led to CR in 19 (70%) of 27 patients and a low mean cumulative UV-A dose of 78.5 J/cm2. The subsequent standardized 9-month PUVA maintenance phase prolonged median (range) disease-free remission from 4 (1-20) months to 15 (1-54) months (P = .02). High density of histologic infiltrate and high percentage of clonal TCR sequences in skin biopsy specimens at baseline were inversely associated with therapeutic response. No severe adverse effects were seen during the PUVA induction or maintenance phase. Conclusions and Relevance: This proof-of-concept study identifies potential biomarkers for therapeutic response to PUVA in mycosis fungoides; it also demonstrates that low-dose, low-frequency PUVA appears to be highly effective, and maintenance treatment may extend disease-free remission. Trial Registration: ClinicalTrials.gov identifier: NCT01686594.