Bath psoralen+ultraviolet A photochemotherapy vs. narrow band‐ultraviolet B in psoriasis: a comparison of clinical outcome and effect on circulating T‐helper and T‐suppressor/cytotoxic cells

Background: Comparative success rates of bath psoralen+ultraviolet A (PUVA) and narrow band‐ultraviolet B (NB‐UVB) in psoriasis treatment are variably reported with no previous studies on the possible effect of bath PUVA on circulating CD4+ and CD8+ T cells. Objective: We aimed to compare the effect of bath PUVA and NB‐UVB clinically and on circulating T‐helper and T‐suppressor/cytotoxic cells in psoriasis. Patients and methods: Thirty‐four psoriatic patients divided into a bath PUVA‐treated group (18 patients) and a NB‐UVB‐treated group (16 patients) were compared regarding the disease severity by psoriasis area and severity index (PASI) score and percentage of circulating CD4+ and CD8+ T cells by flowcytometry before and after treatment. Results: After treatment, the bath PUVA group showed a significantly higher reduction of PASI score (85.44%) than the NB‐UVB group (58.72%). Mean peripheral CD4+ T‐cell percentage was significantly lower after [36.8; 95% confidence interval (CI) 33.80, 39.97] compared with before treatment (42.06; 95% CI 38.29, 45.83) (P<0.05) in the bath PUVA group while this difference was insignificant in the NB‐UVB group (P>0.05). Conclusion: Bath PUVA therapy is superior to NB‐UVB in the treatment of moderate and severe psoriasis with mild reversible side effects. Both modalities have a systemic effect decreasing peripheral CD4+ T cells, which is more with bath PUVA.     

Comparison of clinical effects of psoriasis treatment regimens among calcipotriol alone,narrowband ultraviolet B phototherapy alone,combination of calcipotriol and narrowband ultraviolet B phototherapy once a week,and combination of calcipotriol and narrowband ultraviolet B phototherapy more than twice a week

We compared the clinical efficacy of various psoriasis treatments among: (i) topical application of calcipotriol ointment twice daily (group I); (ii) topical application of calcipotriol ointment twice daily and narrowband ultraviolet B NB‐UVB phototherapy once a week (group II); (iii) topical application of heparinoid ointment twice daily and NB‐UVB phototherapy more than twice a week (group III); and (iv) topical application of calcipotriol ointment twice daily and NB‐UVB phototherapy more than twice a week (group IV). Ten patients were randomly selected for each group and treated by the indicated regimens for 12 weeks. All treatments were effective and significantly improved Psoriasis Area and Severity Index (PASI) scores, self‐administered PASI scores and visual analog scale scores of pruritus. Group IV showed most marked and rapid reduction in PASI and self‐PASI scores among the four regimens. Although the serum levels of interleukin (IL)‐17, IL‐20 and IL‐22 and psoriasis disability index were significantly decreased after the treatments, no significant difference was detected among the four groups. Our study indicates that combination of calcipotriol ointment plus NB‐UVB more than twice a week is superior to other treatment regimens, rapidly improving psoriasis lesions.     

IL‐33 is secreted by psoriatic keratinocytes and induces pro‐inflammatory cytokines via keratinocyte and mast cell activation

IL‐33 is a novel pro‐inflammatory cytokine and ligand for the orphan receptor ST2. Although originally defined as an inducer of Th2‐mediated responses, IL‐33 was recently found to be involved in arthritis, a Th1/Th17‐mediated disease. Here, we assessed the ability of IL‐33 to promote inflammation via mast cells (MCs) and keratinocytes (KCs) activation in psoriasis. IL‐33 resulted elevated in the skin but not in the serum of psoriasis patients. IL‐33 was secreted by psoriasis KCs and HaCaT cells after TNF‐α stimulation. In HMC‐1, TNF‐α, but not IL‐17, could induce a robust increase in IL‐33 expression. In HaCaT cells, TNF‐α was able to induce IL‐6, MCP‐1 and VEGF, and the addition of IL‐33 reinforced these increases. TNF‐α + IL‐33 combination showed similar results in primary KCs and ex vivo skin organ culture. In conclusion, our study suggests that IL‐33 may be involved in psoriasis biology via MCs and KCs.     

Circulating adipokine levels in Portuguese patients with psoriasis vulgaris according to body mass index,severity and therapy

Background Psoriasis vulgaris is associated with overweight/obesity and with increased C‐reactive protein (CRP), tumour necrosis factor (TNF)‐α, interleukin (IL)‐6, leptin and resistin levels and decreased adiponectin levels. Objectives To understand the role/relationship of adipokines, as well as CRP, in a Portuguese psoriatic population, by assessing the relationship of their levels with psoriasis severity, defined by Psoriasis Area and Severity Index (PASI), with obesity, defined by body mass index (BMI), and psoriasis therapy. Methods A cross‐sectional (n = 66) and longitudinal study (before and after 12 weeks of therapy; n = 44) was performed; 10 patients started topical treatment, 17 narrow‐band ultraviolet B (NBUVB) and 17 psolaren associated with UVA (PUVA). Results Patients presented significantly higher BMI, leptin, resistin, TNF‐α, IL‐6 and CRP and significantly lower adiponectin values. CRP and IL‐6 correlated with PASI. Adiponectin and leptin were more altered in patients with higher BMI. Concerning severity, CRP, resistin and adiponectin were more altered in the severer forms. After treatment, a significant reduction in PASI, CRP, resistin, TNF‐α and IL‐6, and a significant rise in adiponectin were observed. Nonetheless, CRP and adiponectin remained different from those of control. Concerning therapies, topical therapy was not associated with any significant change, except for TNF‐α. After NBUVB, a significant reduction was observed in TNF‐α and in CRP. For PUVA, we observed a significant reduction in TNF‐α, IL‐6 and CRP, and a significant increase in adiponectin. Conclusion In psoriatic patients, increased overweight/obesity was associated with raised leptin levels and decreased adiponectin levels. Leptin may contribute to enhance the inflammatory process in overweight/obese psoriatic patients. Resistin, IL‐6, CRP and adiponectin levels appear to be dependent on psoriasis severity. CRP, together with IL‐6, appears to be a useful marker of psoriasis severity. Both NBUVB and PUVA were effective; however, PUVA results seem to be more successful. Nonetheless, after NBUVB and PUVA, a low‐grade inflammation still persists.     

High‐fat diet exacerbates imiquimod‐induced psoriasis‐like dermatitis in mice

Psoriasis, a chronic inflammatory skin disease, is closely related to systemic metabolism. An elevated body mass index (BMI) is a risk factor for psoriasis; inflammasomes are activated by adipose tissue macrophages in obese subjects. We hypothesized that hyperlipidaemia is involved in the pathogenesis of psoriasis and examined the role of a high‐fat diet (HFD) in the development of psoriasis in imiquimod (IMQ)‐treated mice. The body weight and serum level of cholesterol were significantly higher in mice fed an HFD than in a regular diet (RD). HFD mice had higher psoriasis skin scores, and the number of neutrophils infiltrating into the lesional skin was elevated. IL‐17A mRNA expression was significantly increased in the skin of IMQ‐treated HFD mice; the expression of IL‐22, IL‐23 and TNF‐α mRNA was not enhanced. Caspase‐1 and IL‐1β were activated in the skin of IMQ‐treated HFD mice, and their serum level of IL‐17A, TNF‐α and IL‐1β was significantly upregulated. Our findings strongly suggest that hyperlipidaemia is involved in the development and progression of psoriasis via systemic inflammation and inflammasome activation.     

Narrowband ultraviolet B treatment improves vitamin D balance and alters antimicrobial peptide expression in skin lesions of psoriasis and atopic dermatitis

Background Narrowband ultraviolet B (NB‐UVB) is a routine treatment for psoriasis and atopic dermatitis (AD) but its effect on vitamin D balance is not well studied. Objectives To examine whether NB‐UVB treatment in winter improves vitamin D balance in psoriasis and AD, and to study the effects of NB‐UVB on antimicrobial peptide and cytokine expression in the skin. Methods Eighteen adult patients with psoriasis, 18 with AD and 15 healthy subjects received a total of 15 NB‐UVB exposures on the whole body, given three times a week. Serum calcidiol (25‐hydroxyvitamin D) was measured by radioimmunoassay. Antimicrobial peptide and cytokine expression in skin lesions was examined by real‐time quantitative polymerase chain reaction. Results At onset 16 (89%) patients with psoriasis, 17 (94%) patients with AD and eight (53%) healthy subjects had vitamin D insufficiency (calcidiol < 50 nmol L^?1). NB‐UVB treatment significantly increased (P < 0·001) serum calcidiol. The increase was 59·9 nmol L^?1 (95% confidence interval, CI 53·5–66·9) in psoriasis, 68·2 nmol L^?1 (95% CI 55·4–80·1) in AD and 90·7 nmol L^?1 (95% CI 63·8–123·4) in healthy subjects. Psoriasis Area and Severity Index and SCORAD improved significantly (P < 0·001) but no correlation to the increase of serum calcidiol was found. Cathelicidin and human β‐defensin 2 (HBD2) expression was high in skin lesions of psoriasis. After six NB‐UVB treatments cathelicidin increased further while HBD2 expression decreased. A similar trend was observed in AD lesions. NB‐UVB caused a marked but nonsignificant decrease of interleukin (IL)‐1β and IL‐17 in psoriasis lesions. Conclusions The present study shows that in addition to a significant improvement of psoriasis and AD, NB‐UVB treatment effectively corrects vitamin D insufficiency. It also increases cathelicidin and decreases HBD2 levels in healing skin lesions of psoriasis and AD. This effect might be mediated by improved vitamin D balance and the local cytokine network.     

Mechanism of pathogenesis of imiquimod‐induced skin inflammation in the mouse: A role for interferon‐alpha in dendritic cell activation by imiquimod

Topical application of imiquimod (IMQ), a Toll‐like receptor (TLR)7 ligand, can induce and exacerbate psoriasis, a chronic inflammatory skin disorder. In a mouse model of IMQ‐induced psoriasis‐like skin inflammation, T‐helper (Th)17 cells and interleukin (IL)‐17/IL‐22‐producing γδ‐T cells have been shown to play a pivotal role. However, the mechanisms of induction of the Th17 pathway and development of psoriasis‐like skin inflammation by IMQ treatment remain unclear. In this study, we investigated pathogenic mechanisms of IMQ‐induced psoriasis‐like skin inflammation in mice. We first confirmed that, together with an increase in IL‐17 and IL‐22 production, application of IMQ to mouse skin induced the expression of cytokines required for activation of the Th17 pathway, and pro‐inflammatory mediators involved in the pathology of psoriasis. Analysis of Tlr7^?/? mice demonstrated that most of the in vivo effects of IMQ were mediated via TLR7. In an in vitro study using plasmacytoid dendritic cells (DCs), IMQ induced production of interferon (IFN)‐α, IL‐23, IL‐6 and tumor necrosis factor (TNF)‐α. Furthermore, when we analyzed in vitro‐generated bone marrow‐derived DCs with features similar to TNF‐α and inducible nitric oxide synthase (iNOS)‐producing DCs, IL‐23, IL‐6, IL‐1β, TNF‐α and iNOS/NO production was weakly induced by IMQ alone and further enhanced after co‐stimulation with IMQ and IFN‐α. These in vitro effects of IMQ were also mediated via TLR7 and the synergistic effect of IMQ, and IFN‐α was suggested to be caused by upregulation of TLR7 expression by IFN‐α. These results demonstrate part of the mechanism by which the Th17 pathway and psoriasis‐like skin inflammation are induced by IMQ and IFN‐α in a mouse model.     

Research in practice: IL‐22 and IL‐20: significance for epithelial homeostasis and psoriasis pathogenesis

Psoriasis vulgaris is a frequent, chronically relapsing, immune‐mediated, systemic disease with characteristic skin changes. Despite the importance of this disease there are currently limited therapeutic options indicating a need for effective, long‐lasting treatment strategies with few side effects. The most recent discoveries regarding psoriasis pathogenesis, particularly our results regarding two cytokines – IL‐22 and IL‐20 – could prove to be the foundation for such therapies. Whereas IL‐22 is mainly produced by activated T‐cell sub‐populations (Th22, Th1, Th17), monocytes, dendritic cells and keratinocytes produce IL‐20. Blood and lesional skin samples from psoriasis patients demonstrate high levels of IL‐22 and IL‐20. Interestingly, both cytokines act principally on keratinocytes and do not impact the immune system. Similar to the changes in the psoriasis epidermis these cytokines inhibit the terminal differentiation of keratinocytes although they simultaneously increase their innate defense, mobility, and the production of some chemokines. Some IL‐22 effects are amplified by TNF‐α, IL‐17, and IFN‐α. IL‐22/IL‐20 lends the reconstructed epidermis a psoriasis‐like appearance with acanthosis, hypogranularity, and hyperkeratosis. In addition, mice that constitutively express high levels of IL‐22 or IL‐20 demonstrate a psoriasis‐like appearance. A therapy counteracting IL‐22 and IL‐20 would be an innovative treatment with the potential for few side effects that would act on the final phase of psoriasis pathogenesis.     

Reduction of inflammatory slan (6‐sulfo LacNAc) dendritic cells in psoriatic skin of patients treated with etanercept

Dermal dendritic cells (DCs) play a central role in the immunopathology of psoriasis. We previously identified slanDCs as pro‐inflammatory TNF‐α, IL‐23‐ and IL‐12‐producing DCs in human blood and as prominent inflammatory dermal TNF‐α secreting and CD11c‐positive DC subset in psoriasis. Here, we ask for the effects of TNF‐α‐inhibition on inflammatory slanDCs in skin and blood of 10 patients with psoriasis during 24 weeks of treatment with etanercept. Treatment with etanercept reduced the frequency of dermal slanDCs but did not induce apoptosis as determined by lack of increased active caspase‐3‐expression. In parallel, we found increased frequencies of slanDCs in blood which expressed lower levels of HLA‐DR. Stimulating slanDCs isolated from the blood of healthy donors in vitro induced a strong production of IL‐1β, IL‐6, IL‐23 and IL‐12p70. This capacity was efficiently reduced in the presence of etanercept, thereby indicating that TNF‐α is an autocrine stimulus for maturation and pro‐inflammatory cytokine production of slanDCs. In vivo, we noticed that treatment with etanercept did reduce the number of dermal slanDCs in parallel to the overall expression of TNF‐α and IL‐23p19. However, successful treatment did not down‐regulated the percentage of dermal slanDCs that stained positive for TNF‐α and IL‐23p19 indicating that remaining slanDCs kept their pro‐inflammatory capacity. This study provides novel insights into the immune regulatory properties of etanercept at the level of inflammatory slanDCs in vivo in skin and blood as well as in vitro.     

Narrowband ultraviolet B versus psoralen plus ultraviolet A therapy for severe plaque psoriasis: an Indian perspective

There is a dearth of studies comparing the efficacy of psoralen ultraviolet A (PUVA) and narrowband (NB)‐UVB in psoriasis in South Asian patients. Patients having plaque psoriasis with > 20% body surface area involvement were randomly assigned to one of two groups (group A: NB‐UVB, group B: PUVA). The response to treatment was assessed by the Psoriasis Area and Severity Index (PASI) at baseline and every 2 weeks thereafter. The maximum possible treatment duration was 16 weeks. In total, 43 patients (21 NB‐UVB, 22 PUVA) completed the study. Marked improvement was seen in 80.9% of the patients in group A and 81.8% in group B (NS: P > 0.05). The mean ± SD time taken to achieve marked improvement was 9.9 ± 3.3 and 9.9 ± 3.5 weeks, respectively. In total, 29 patients were available for the analysis of the remission data at 6 months after treatment completion; 26.7% of the patients in group A and 42.8% in group B were in remission (NS: P > 0.05). Both methods seem to be equally effective in achieving clearance and maintaining remission of severe chronic plaque psoriasis in patients with Fitzpatrick skin type 4 and 5.     

A large scale analytical study on efficacy of different photo(chemo)therapeutic modalities in the treatment of psoriasis,vitiligo and mycosis fungoides

Psoriasis, vitiligo, and mycosis fungoides (MF) are among the most frequently treated dermatological diseases by photo(chemo)therapy. The objectives are to determine which photo (chemo) therapeutic modality could achieve the best response in the treatment of psoriasis, vitiligo, and MF. The design used in this study is retrospective analytical study. The study included 745 patients' records; 293 with psoriasis, 309 with vitiligo, and 143 with early MF, treated in the Phototherapy Unit, Dermatology Department, Kasr El‐Aini Hospital, Cairo University by either psoralen and ultraviolet A (PUVA), narrow band ultraviolet B (NB‐UVB), psoralen and narrow band UVB (P‐NBUVB), broad band UVB (BB‐UVB), or broad band UVA (ΒΒ‐UVA). Data were retrieved from the computer database of the unit and statistically analyzed. In psoriasis, oral and topical PUVA and NB‐UVB were found to be equally effective, whereas oral PUVA had significantly better results than both UVA and BB‐UVB at the end of therapy. In generalized vitiligo, PUVA and P‐NBUVB had significantly better results than NB‐UVB alone. In early MF, there was no statistically significant difference between the response to oral PUVA and NB‐UVB. PUVA and NB‐UVB are good choices in patients with psoriasis and early stage MF, whereas PUVA appears the best choice in the treatment of vitiligo.     

Incidence of skin cancers in 3867 patients treated with narrow-band ultraviolet B phototherapy

Background  Narrow‐band ultraviolet B (NB‐UVB) phototherapy is a widely used treatment. Psoralen‐UVA photochemotherapy (PUVA) increases skin cancer risk and some animal studies have raised the possibility of an increased risk with NB‐UVB. The risk of skin cancer in humans following treatment with NB‐UVB is unknown. Objectives  This current analysis forms part of an ongoing study ultimately aiming to define the long‐term carcinogenic risk of NB‐UVB treatment in humans. Methods  Details of all patients receiving NB‐UVB treatment until 31/12/2002 in Tayside, Scotland, were accessed from a treatment database and linked to the Scottish Cancer Registry. Indirect standardization was used to compare skin cancer incidence in the study population with age and sex matched cancer registry data for the Tayside population. We also assessed the effect of NB‐UVB exposure treatment numbers on the risk of developing skin cancer. Results  Of 4690 records reviewed, 4665 were suitable for analysis with 3886 records linked with the cancer registry and 3867 followed‐up for at least 6 months before 31/12/02 (the date at which cancer registration was deemed to be complete). The median number of NB‐UVB treatments was 29 with 352 patients receiving ≥ 100 treatments. The study gave 24 753 person‐years of follow up. First skin cancers recorded in study patients were 27 basal cell carcinomas (BCC), seven squamous cell carcinomas (SCC) and six melanomas. No association was found between NB‐UVB exposure alone (without PUVA) and any skin cancer. For NB‐UVB and PUVA treated patients there was an association with BCC, with 27 BCCs found compared with 14·1 expected in the matched population. Conclusion  We found no significant association between NB‐UVB treatment and BCC, SCC or melanoma. There was a small increase in BCCs amongst those also treated with PUVA. These reassuring results do not demonstrate the early increase in skin cancers that was found associated with PUVA treatment. However, cautious interpretation is required as the cohort contained relatively few patients who had a high treatment number and because the slow evolution of skin cancers may result in a delayed incidence peak. Ongoing risk assessment is therefore essential.     

Efficacy and safety of guselkumab in psoriasis patients who failed ustekinumab and/or anti‐interleukin‐17 treatment: A real‐life 52‐week retrospective study

Recent major research advancements have significantly expanded our understanding of psoriasis pathophysiology, resulting in the development of highly effective, targeted therapies. Guselkumab is the first interleukin (IL)‐23 inhibitor approved for the treatment of moderate‐to‐severe‐psoriasis, providing a new therapeutical option for psoriasis. The aim of our study was to evaluate the efficacy of guselkumab in psoriatic patients who previously failed anti‐IL‐12/23 and/or anti‐IL‐17 treatment. A 52‐week single‐center retrospective study was performed enrolling moderate‐to‐severe patients attending our Psoriasis Care Center from October 2018 to May 2020. Study population included 13 patients; 46.1% have been previously treated with ustekinumab, while 69.2% have previously failed an anti‐IL‐17 treatment (38.5% secukinumab, 30.8% ixekizumab, and 38.5% both). At baseline, mean Psoriasis Area and Severity Index was 13.2 ± 6.8, reducing up to 0.5 ± 0.7 at week 52 (P < .001). Body surface area reduced from 22.3 ± 10.5 (baseline) to 0.8 ± 1.1 at week 52 (P < .001). No statistically significant differences have been found between patients previously treated with anti‐IL‐12/23 compared to anti‐IL‐17 or both. Only one patient discontinued guselkumab at week 36 due to secondary inefficacy. This is a single institution study with a relatively small sample size. Our real‐life data confirm trial results, showing guselkumab as a safe and effective option in patients with moderate‐to‐severe psoriasis even in those who previously failed ustekinumab and/or anti‐IL‐17 treatment.     

IL6 −174G>C polymorphism is associated with an increased risk of psoriasis but not response to treatment

Interleukin‐6 (IL‐6) is implicated in the pathogenesis of psoriasis as well as in its treatment efficacy. The aim of this study of 406 patients with psoriasis and 203 healthy controls was to evaluate the association between the IL6 ?174G>C (rs1800795) polymorphism and psoriasis susceptibility, as well as treatment efficacy. The frequency of genotype GG (33.7% vs 20.7%; P = 0.00022; OR = 0.51, 95% confidence interval 0.34–0.76) and of allele G (56.2% vs 46.8%; P = 0.0023) was significantly higher in the psoriasis group compared with controls. No polymorphism variants were associated with better response to topical or combined topical/narrow‐band ultraviolet B (NB‐UVB) treatment. We conclude that the IL6 ?174G>C polymorphism can be a marker of susceptibility to psoriasis, with an almost twofold increased risk of the disease in individuals carrying the GG genotype; however, it was not associated with treatment response to topical and/or NB‐UVB therapy.     

Interleukin‐21 receptor signalling is not critically required for imiquimod‐induced psoriasiform dermatitis in mice

Psoriasis is largely mediated by interleukin (IL)‐23/T helper (Th) 17 axis, and IL‐21 is a pleiotropic cytokine expressed by Th17 cells. Despite previously reported possible pathogenic roles of IL‐21 in human psoriasis, we found that IL‐21 receptor (IL‐21R) signalling was not crucial for imiquimod‐induced psoriatic inflammation, using IL‐21R^?/? mice. The severity of imiquimod‐induced psoriatic manifestation and pro‐inflammatory Th17 cytokine levels, IL‐17A‐producing γδ T cells and CD4+ T cells, and in vitro IL‐17A production by γδ T cells after IL‐23 stimulation was comparable between wild‐type and IL‐21R^?/? mice. Collectively, IL‐21R signalling was not critically involved in IMQ‐induced psoriatic inflammation despite an increased IL‐21 expression in the IMQ‐treated mouse skin. Our data may represent the significant differences between human psoriasis and murine psoriasis model, and further studies using other models will be required to elucidate the role of IL‐21 in psoriasis pathogenesis.     

Skin‐penetrating methotrexate alleviates imiquimod‐induced psoriasiform dermatitis via decreasing IL‐17‐producing gamma delta T cells

Accumulating evidence has shown that the Toll‐like receptor 7 agonist imiquimod (IMQ) induces psoriasiform skin inflammation in mice and that this inflammation is dependent on the IL‐23/IL‐17 axis. Moreover, it has been demonstrated that the main source of IL‐17 is not Th17 but is dermal gamma delta (γδ) T cells in mouse psoriasiform skin. Recent advances in the understanding of immunopathogenesis of psoriasis led to an alteration in the treatment paradigm to the use of highly efficacious biologics. However, their high cost impedes the extensive use of these agents. Thus, inexpensive and safe medications are still considered valuable. In this study, we introduce the therapeutic efficacy of a newly formulated methotrexate (MTX), a chemical conjugate of MTX with cell permeable peptide, for the treatment of psoriasis. Topically applied skin‐penetrating (SP)‐MTX reduced the psoriasiform skin phenomenon, epidermal thickness and infiltrating immune cells into the dermis. IL‐17A‐producing dermal γδ T cells in the cellular infiltrate that contribute IL‐23/IL‐17 axis were well abrogated by SP‐MTX. Furthermore, SP‐MTX had no toxic effects on liver, kidney or myeloid cells, unlike systemic administration of MTX. In conclusion, topically applied SP‐MTX ameliorated psoriasiform skin inflammation in mice with the criteria of clinical phenomenon, histopathology and immunology, without inducing systemic toxic effects.     

Etanercept plus narrowband ultraviolet B phototherapy of psoriasis is more effective than etanercept monotherapy at 6 weeks

Background A substantial portion of patients with psoriasis does not achieve a satisfactory response under antitumour necrosis factor (TNF)‐α biological therapies. Objectives We aimed to evaluate whether etanercept plus narrowband ultraviolet B (NB‐UVB) phototherapy is superior to etanercept monotherapy in the management of psoriasis. Methods In this prospective study, patients with psoriasis were treated with etanercept 25 mg twice weekly. Two marker lesions were selected for determination of the modified Psoriasis Area and Severity Index (M‐PASI). NB‐UVB was administered thrice weekly whereby one marker lesion was covered as nonirradiated control. Skin biopsies for histology and immunohistochemistry were performed in both marker lesions after a 6‐week treatment course. Results After 6 weeks of therapy, the relative M‐PASI reduction (mean ± SD) in etanercept‐treated sites (53·7 ± 36·9%) was significantly lower than the reduction in etanercept plus NB‐UVB‐treated lesions (64 ± 27·8%; P = 0·011). At the end of treatment, histology scores of etanercept‐treated psoriatic plaques were significantly higher than scores of etanercept plus NB‐UVB‐treated sites (4·6 ± 2·7 vs. 3·7 ± 2·4; P = 0·045). Epidermal immunoreactivity for CD1a, CD4 and CD8 was significantly lower in etanercept plus NB‐UVB‐treated lesions when compared with etanercept monotherapy. Conclusions Etanercept combined with NB‐UVB is more effective than etanercept monotherapy at 6 weeks as demonstrated at a clinical, histological and immunohistological level. However, as there is an increased risk for malignancy by treatment with TNF‐α blockers alone or in combination with phototherapy, we recommend to restrict this highly effective combination to short periods of time, for instance to obtain a quicker response, and to avoid long‐term treatment.     

When IL‐17 inhibitors fail: Real‐life evidence to switch from secukinumab to adalimumab or ustekinumab

Psoriasis is a chronic, systemic inflammatory disease that in the moderate to severe forms may benefit of biologics, namely TNF and IL‐12/23 and IL‐17 inhibitors. Loss of response, lack of response, or discontinuation due to adverse events represent a concrete therapeutic challenge for dermatologists that have to switch patients to other treatments. Although some evidences already exist toward the switch from IL‐12/23 and TNF inhibitors to IL‐17 inhibitors, conversely nothing is present toward the switch from IL‐17 inhibitors to IL‐12/23 and TNF inhibitors. We performed a real‐life study enrolling 50 patients randomly switched to adalimuamb, a TNF inhibitor, or ustekinumab, an IL‐12/23 inhibitor. Our observational study suggests that switching from IL‐17i to TNFi and IL‐12/23i is a safe and effective therapeutic strategy.     

Brodalumab: A new way to inhibit IL‐17 in psoriasis

Psoriasis is a chronic inflammatory disease that affects 2% to 4% of the population; about 20% of the patients present a moderate‐to‐severe form. The IL‐23/Th17/IL‐17 molecular axis is considered crucial in the pathogenesis of psoriasis and IL‐17 is fundamental in the maintenance of the immune and inflammatory alterations causing psoriasis. Expression of IL‐17A, IL‐17F, and IL‐17C is strongly increased in psoriatic plaques. Effective therapy leads to restoration of the expression of a wide range of genes (including effector cytokines and chemokines downstream of IL‐17) to near normal levels. Brodalumab is the first biologic drug targeting specifically the subunit A of the IL‐17 receptor (IL‐17RA) and thus inhibiting not only IL‐17A but also other members of the IL‐17 family. Brodalumab is very effective and safe in treating moderate‐to severe psoriasis.     

Topical silver and gold nanoparticles complexed with Cornus mas suppress inflammation in human psoriasis plaques by inhibiting NF‐κB activity

New biomaterials based on nanoparticles (NPs) carrying polyphenols‐rich extracts (Cornus mas) recently showed promising anti‐inflammatory activity in psoriasis. We aimed to understand how topically delivered silver and gold nanoparticles complexed with Cornus mas (Ag‐NPs‐CM, Au‐NPs‐CM) modulate inflammation in psoriasis at cellular and molecular level. The impact on psoriatic inflammation was assessed in vitro on pro‐inflammatory macrophages, by clinical score, high‐frequency ultrasonography and immunohistology of psoriasis plaques treated with Ag‐NPs‐CM, Au‐NPs‐CM or control. Incubation of pro‐inflammatory macrophages with nanoparticles significantly decreased the release of NO, IL‐12 and TNF‐α. Immunofluorescence confirmed that nanoparticles significantly reduced CD68‐positive macrophages and their IL‐12 and TNF‐α production in human psoriasis plaques. NPs‐CM appear to repress NF‐κB activation in macrophages, inhibiting the production of pro‐inflammatory factors with causal role in psoriasis. Ag and Au NPs‐CM represent a novel nanoparticle‐based “green” technology which may provide an efficient tool for modern psoriasis therapy, circumventing immunosuppression‐related side effects of biologicals.