Combination therapy of oral methoxypsoralen: photochemotherapy (PUVA) and an aromatic retinoid (etretinate, tigason) in the treatment of psoriasis

RePUVA is the combination of an oral aromatic retinoid, etretinate, with oral photochemotherapy, PUVA. This combination therapy has the advantage of faster clearance with fewer side effects. In Middle Road Hospital, we treated 29 patients with extensive psoriasis (more than 30% involvement) with a total 32 RePUVA treatments. There was complete clearance in 69% of patients with an average of 19 irradiations and an average total ultraviolet A (UVA) dose of 183 J/cm². This compared well with standard PUVA which needed 25 radiations and a total UVA dose of 346 J/cm². The main side effects were cheilitis, exfoliation of skin and pruritus. Biochemically, 41% of the patients showed elevations of serum triglyceride.     

Comparison of the efficacy of local narrowband ultraviolet B (NB-UVB) phototherapy versus psoralen plus ultraviolet A (PUVA) paint for palmoplantar psoriasis

Palmoplantar psoriasis is an idiopathic disabling condition, often resistant to conventional therapies. The purpose of this study was to evaluate the efficacy and safety of local narrowband ultraviolet B (NB-UVB) phototherapy and to compare it with local psoralen plus ultraviolet A (PUVA) paint in patients with palmoplantar psoriasis unresponsive to conventional therapies other than phototherapy. A cohort of 25 patients with palmoplantar psoriasis were included in this study, which was based on a left-to-right comparison pattern. The treatments were administered with local narrowband UVB irradiation on one side and local PUVA on the other side three times a week over 9 weeks. Clinical assessments were performed at baseline and every 3 weeks during the 9-week treatment. There was a statistically significant decrease in the mean clinical scores at the third, sixth and ninth week with both treatments. The difference in clinical response between the two treatment modalities was statistically significant at the end of the treatment period, with the percentage reduction in severity index scores with the PUVA-paint-treated side being 85.45% compared with 61.08% for the NB-UVB treated side (t = 5.379, P = 0.0001, Student's t-test for unpaired samples). Our results show that, although some clinical improvement was achieved with local NB-UVB phototherapy, the results were better with local PUVA, and such a treatment option may be reserved for patients with palmoplantar psoriasis who experience phototoxic reaction to psoralens.     

A comparison of psoralen plus ultraviolet A (PUVA) monotherapy,tacalcitol plus PUVA and tazarotene plus PUVA in patients with chronic plaque-type psoriasis

BACKGROUND: Numerous studies have shown that the additional administration of topical or systemic antipsoriatic agents might serve as an effective means to increase the efficacy of photochemotherapy [psoralen plus ultraviolet (UV) A (PUVA)] for psoriasis. OBJECTIVES: To compare the therapeutic response to tacalcitol plus PUVA, tazarotene plus PUVA and PUVA monotherapy in patients with chronic plaque-type psoriasis. In addition, we also assessed the duration of remission induced by each regimen and the tolerability of the two combination treatments. METHODS: Thirty-one patients with chronic plaque-type psoriasis were included in this observer-blinded, intrapatient comparison trial. PUVA treatment was given four times weekly. Additionally, tacalcitol ointment and 0.1% tazarotene gel were applied separately on two target areas once daily in the evening. At the onset of therapy and every 2 weeks thereafter the response to treatment was determined by the Psoriasis Severity Index score, which assesses the degree of erythema, infiltration and scaling of the psoriatic lesions. After complete or near complete clearing patients were followed-up until relapse. RESULTS: Twenty-four patients completed the study. The treatment requirements to induce complete or near complete clearing were significantly lower for both combination treatments than for PUVA monotherapy (P < 0.01). The median cumulative UVA dose and number of exposures were 30.6 J cm-2 (95% confidence interval, CI 22.5-71.2) and 14 (95% CI 11-16) for tacalcitol plus PUVA, 32.3 J cm-2 (95% CI 22.5-73.8) and 14 (95% CI 11-19) for tazarotene plus PUVA, and 37.0 J cm-2 (95% CI 29.5-83.9) and 16 (95% CI 14-22) for PUVA monotherapy. No difference between the three regimens was observed with regard to duration of remission. Adverse reactions occurred more often with 0.1% tazarotene than with tacalcitol but were in general mild and completely reversible upon using a lower concentration of 0.05% tazarotene. CONCLUSIONS: Tacalcitol ointment and tazarotene gel are both comparably effective in improving the therapeutic result of PUVA therapy in patients with chronic plaque-type psoriasis. Besides accelerating the treatment response, both agents, by virtue of their UVA dose-sparing effect, might also help to reduce possible long-term hazards of PUVA treatment.     

Narrow band UVB (311 nm), psoralen UVB (311 nm) and PUVA therapy in the treatment of early-stage mycosis fungoides: a right-left comparative study

BACKGROUND: Psoralen ultraviolet A (PUVA) is a widely used first-line therapy for treatment of early cutaneous T-cell lymphoma. Narrow band UVB (UVB-NB) (311 nm) has been recently introduced as another effective line of treatment. It is postulated that the efficacy of UVB-NB could be enhanced by addition of psoralen. AIM: The aim of the present work was to compare the clinical and histopathologic efficacy of PUVA and UVB-NB in the treatment of early-stage MF (stages IA, IB and IIA), and to evaluate whether psoralen adds to the efficacy of UVB-NB or not. Patients and Methods: Twenty patients (stage IA, IB or IIA) were divided into two equal groups: group I received UVB-NB on the right body half vs. PUVA on the left side of the body for 48 sessions, and group II received PUVB-NB on the right side of the body vs. PUVA on the left side for 36 sessions. The sessions were administered three times weekly. RESULTS: In group I, almost equal results were obtained on both sides, i.e., UVB-NB and PUVA were equally effective in the treatment of early stages of MF, both clinically and histopathologically. In group II, PUVB-NB was found to be as effective as conventional PUVA in the treatment of early-stage mycosis fungoides, also on both clinical and histopathological grounds. CONCLUSION: UVB-NB phototherapy should be included among the initial therapeutic options of mycosis fungoides in view of its efficacy, convenience, and likelihood of fewer long-term adverse effects. Addition of psoralen does not seem to enhance its therapeutic efficacy.     

Influence of wetness on the ultraviolet protection factor (UPF) of textiles: in vitro and in vivo measurements

BACKGROUND/PURPOSE: Clothing is an important product for sunburn protection and skin cancer prevention. The moisture content of a fabric, which can increase during its wearing, may decrease the fabric's capability of protecting the skin from solar UV radiation, that is, lower its UPF (ultraviolet protection factor). Due to limited data about the effect of fabric wetness on UPF, this study was undertaken to investigate the following: (a) the effect of saturating a variety of fabrics with tap water and with salt water on fabric UPF and (b) whether wetted-fabric UPF values reflect only the fact that the fabric is wet during testing or the fact that the skin is hydrated and the fabric is wet. METHODS: For objective a, 69 summer fabrics were spectrophotometrically (in vitro) assessed when "dry" and when saturated with tap and salt water. In vitro UPFs, percent UVA transmission and percent UVB transmission values were calculated from the transmission data. For objective b, 100% cotton and 100% polyester fabrics were tested in vivo to determine in vivo UPF values. The minimal erythema dose (MED) was determined for each of the 12 subjects on unprotected "dry" skin and on "hydrated" unprotected skin. MEDprotected was determined when the subject's skin was covered with "dry" and with saturated fabric. In vivo UPFs were calculated using this data. Student's paired t-tests were used to determine the effect of wetting. RESULTS: With one exception, in vitro UPF values were the same when the fabrics were saturated with tap water and when they were saturated with salt water. However, saturating the fabrics with water had different effects on the UPF, UVA transmission, and UVB transmission values. For linen, viscose and polyester fabrics, UPF significantly increased. For the cotton fabrics and the polyester + TiO2 fabrics, UPF significantly decreased. For the modal + TiO2 fabrics and the polyester crepe + TiO2 fabrics, UPF significantly increased. From the in vivo testing, the MED of the "hydrated unprotected" skin was not different than the MED of "dry unprotected skin." Values obtained from subtracting dry-fabric in vivo UPF values from dry-fabric in vitro values and subtracting wet-fabric in vivo UPF values from wet-fabric in vitro values are not different. CONCLUSION: Fabrics do not need to be tested when saturated with tap and with salt water. Testing fabrics wet and dry should be done, as the effect of saturating fabric on UPF value varies. Fortunately, UPF values for wetted fabrics reveal only the effect of increased moisture content in the fabric and have nothing to do with wetting of the skin by the fabric.     

A randomized clinical trial in psoriasis: synchronous balneophototherapy with bathing in Dead Sea salt solution plus narrowband UVB vs. narrowband UVB alone (TOMESA‐study group)

Background Synchronous balneophototherapy (sBPT) simulates treatment conditions at the Dead Sea for outpatient use. In the past, sBPT proved to be an effective treatment for psoriasis. However, there is a lack of sufficiently large randomized controlled clinical trials evaluating the additional benefit of sBPT compared with ultraviolet B (UVB) monotherapy. Objectives The purpose of this study was to compare the effectiveness and safety of sBPT with UVB phototherapy (PT) alone in a randomized controlled effectiveness study. Methods In this phase III, multicentre effectiveness study, 367 patients with moderate to severe psoriasis were randomly allocated in a 1 : 1 ratio to receive either sBPT consisting of narrowband UVB PT with 311 nm and synchronous bathing in 10% Dead Sea salt solution or PT with 311 nm alone. Primary endpoint, analysed on an intention‐to‐treat basis (n = 356), was the relative improvement of the Psoriasis Area and Severity Index (PASI) from baseline to end of treatment (35 sessions or clearance). Sample size calculation aimed at the detection of superiority of at least 10%. Results Median PASI values were comparable at baseline (sBPT: 15.1, interquartile range: 10.9–24.3; PT: 15.3, interquartile range: 10.0–23.7). A clinically relevant and statistically significant difference of 49.5% between sBPT and PT could be proven at the end of the therapy phase (P < 0.001; Wilcoxon–Mann–Whitney test). Exploratory testing showed a statistically significant superiority of sBPT after 6 months. Conclusions In routine clinical practice, sBPT is superior to PT alone after 35 treatment sessions and a follow‐up of 6 months. Both treatments demonstrated to be safe.     

A network meta‐analysis for the comparison of efficacy and safety of interleukin (IL)‐23 targeted drugs in the treatment of moderate to severe psoriasis

A variety of interleukin‐23 targeted drugs have been used to treat moderate to severe psoriasis, but it is not clear which is most effective. This network meta‐analysis compared and summarized the short‐term efficacy and safety of interleukin‐23 (IL‐23) targeted drugs in the treatment of moderate to severe psoriasis. PubMed, Embase, Web of Science, and Cochrane Library were used to search randomized controlled trials (RCTs) about the treatment of moderate to severe psoriasis with ustekinumab (Ust), guselkumab (Gus), tildrakizumab (Til), and risankizumab (Ris). Bayesian Network Meta‐analysis (NMA) was used to calculate Psoriasis Area and Severity Index 75%, 90%; Physician Global Assessment score of 0 or 1 (PGA 0/1); Dermatology Life Quality Index of 0 or 1 (DLQI 0/1), and safety (adverse events [AEs]) effect estimates (odds ratio OR) and 95% confidence intervals. Direct, indirect, and network meta‐analysis estimates were calculated using a random‐effects model. The GRADE method was used to assess the quality of evidence for each pair‐wise comparison. In addition, the surface under the cumulative ranking curve (SUCRA) analysis was used to rank the treatment level for each outcome indicator. This network meta‐analysis included 14 RCTs with 8402 patients. The results indicate that the curative effect of the IL‐23 targeted drugs is better than that of a placebo. Network meta‐analysis showed that Ris90 mg and Ris180 mg were significantly more effective than Til (5, 25, 100, and 200 mg), Ust (45 mg, 90 mg, body weight‐based administration), Gus 100 mg and Ris (75 and 150 mg). Regarding safety, there is no significant difference in the risk of adverse events between drugs targeting IL‐23 and placebo. In addition, according to the ranking of SUCRA, Ris 90 mg has the best efficacy index for PASI 75 and PGA 0/1, with SUCRA values of 97.6% and 97.1%, respectively. Ris 180 mg ranked first in PASI 90 (91.1%), while Ris 75 mg performed best in DLQI 0/1 (73.7%). In this network meta‐analysis, risankizumab showed the best curative effect in the short‐term treatment of moderate to severe psoriasis, and the risk of adverse events was not significantly different from placebo. However, more research data are needed for further study in the field of cost to evaluate which drug strikes the most favorable balance among efficacy, safety, and cost of access.     

Interleukin (IL)‐22, IL‐17, IL‐23, IL‐8, vascular endothelial growth factor and tumour necrosis factor‐α levels in patients with psoriasis before,during and after psoralen–ultraviolet A and narrowband ultraviolet B therapy

Background Several cross‐sectional studies have shown that different cytokines and growth factors are enhanced in psoriasis. Objectives We aimed to understand the role/relation of interleukin (IL)‐22, IL‐17, IL‐23, IL‐8, vascular endothelial growth factor (VEGF) and tumour necrosis factor (TNF)‐α in psoriasis vulgaris, addressing their levels and changes before, during and after psoralen–ultraviolet A (PUVA) and narrowband ultraviolet B (NB‐UVB) treatment. Methods A cross‐sectional and a longitudinal study (n = 34) – before (T0) and at 3 (T3), 6 (T6) and 12 (T12) weeks of NB‐UVB and PUVA therapy – were performed; 17 patients started NB‐UVB and 17 PUVA, and IL‐22, IL‐17, IL‐23, IL‐8, TNF‐α and VEGF levels were evaluated. Results At T0, compared with controls (n = 20), all the parameters were significantly higher in patients, except for TNF‐α. Both NB‐UVB and PUVA treatment gave, at T3, a significant decrease in TNF‐α and IL‐23; IL‐22 and IL‐17 decreased significantly at T6; all parameters and Psoriasis Area and Severity Index decreased significantly at T12. However, in both groups, at T12, VEGF was still significantly higher than control. Conclusions Psoriasis seems to be a complex disease in which the cytokine network is disturbed, namely in levels of IL‐22, IL‐17, IL‐23, IL‐8, TNF‐α and VEGF. NB‐UVB and PUVA follow‐up studies suggested that the reduction in the IL‐23/Th17 axis might be important in the pathogenic mechanisms of psoriasis. Further follow‐up studies of patients with psoriasis treated with these and other therapies could be very helpful for the understanding of the disturbance in the cytokine network in psoriasis and indirectly in its pathogenesis.     

A cross‐sectional study using the Children’s Dermatology Life Quality Index (CDLQI) in childhood psoriasis: negative effect on quality of life and moderate correlation of CDLQI with severity scores

Background Juvenile psoriasis is a chronic and incurable skin disease that affects approximately 0·7% of children. Objectives To achieve more insight into the quality of life (QoL) in childhood psoriasis and to investigate whether disease severity scores correlate with QoL scores. Methods All consecutive patients with juvenile plaque psoriasis (≤ 18 years old) who visited our outpatient department were included. At baseline, the Children’s Dermatology Life Quality Index (CDLQI) questionnaire was completed and disease severity was assessed by the Psoriasis Area and Severity Index (PASI) and the Physician Global Assessment (PGA). Results Thirty‐nine patients were included in the study. A median CDLQI of 6 [interquartile range (IQR) 5–9] was reported. Median PASI was 6·3 (IQR 3·3–8·2) and median PGA was 2 (IQR 1–3). The correlation coefficient between PASI and CDLQI was 0·47 (P = 0·003), whereas the correlation coefficient between PGA and CDLQI was 0·51 (P = 0·001). Conclusions The negative effect on QoL in juvenile psoriasis was confirmed in the largest cohort presented up to now. The correlation between disease severity scores and disease‐related QoL in children with psoriasis is only moderate. Therefore, both clinical outcome parameters (PASI, PGA) and measures of QoL (CDLQI) should be included in adequate, patient‐oriented clinical decision making.