Safety Assessment of Conventional and Biological Systemic Therapy in Older Adults with Psoriasis, a Real-world Multicentre Cohort Study.

Optimal selection of systemic therapy in older adults with psoriasis can be challenging, due to sparse evidence-based guidance. This multicentre retrospective study investigated the safety of systemic therapy with causality assessment in a real-world cohort of older adults (≥ 65 years) with psoriasis. Data from 6 hospitals on (serious) adverse events were collected, causality assessment performed and incidence rate ratios calculated. Potential predictors for adverse events-occurrence were studied using multivariable logistic regression analysis. In total, 117 patients with 176 treatment episodes and 390 patient-years were included, comprising 115 (65.3%) and 61 (34.7%) treatment episodes with conventional systemic therapy and biologics/apremilast, respectively. After causality assessment, 232 of 319 (72.7%) adverse events remained and were analysed further, including 12 serious adverse events. No significant differences in incidence rate ratios were found between the systemic treatment types. In regression analysis, increasing age was associated with causality assessed adverse events-occurrence (odds ratio 1.195; p=0.022). Comorbidity, polypharmacy, and treatment type were not associated with causality assessed adverse events-occurrence. In conclusion, increasing age was associated with a higher causality assessed adverse events-occurrence. Causality assessed serious adverse events were rare, reversible and/or manageable in clinical practice. In conclusion, the safety profile of systemic antipsoriatic therapy within this population is reassuring.

Direct Comparison of Real-world Effectiveness of Biologics for Psoriasis using Absolute and Relative Psoriasis Area and Severity Index Scores in a Prospective Multicentre Cohort.

Real-world evidence, directly comparing the effectiveness of interleukin (IL)17-inhibitors, IL23-inhibitors, tumour necrosis factor alpha (TNF-α)-inhibitors and an IL12/23-inhibitor in psoriasis, is scarce. The aim of this study was to directly compare the first-year effectiveness of biologic therapies for psoriasis, corrected for confounders. This prospective, multicentre cohort study assessed BioCAPTURE data on etanercept, adalimumab, ustekinumab, secukinumab, ixekizumab, and guselkumab in 1,080 treatment episodes of 700 patients with psoriasis. The course of the mean absolute Psoriasis Area and Severity Index (PASI) and the proportion of patients who achieved PASI90/PASI75 were compared using linear mixed models and mixed logistic regression models respectively, corrected for baseline PASI, biologic naivety, and weight. Patients treated with adalimumab, ustekinumab, secukinumab, ixekizumab, or guselkumab all had a significantly lower mean PASI after 12 months compared with etanercept, and significantly higher overall odds of reaching PASI90 than those treated with etanercept. Patients treated with ixekizumab or guselkumab also had higher probabilities of reaching PASI90 than adalimumab, ustekinumab, and secukinumab. Relative to randomized controlled trials, the proportions of patients who reached PASI90/75 were lower in this real-world study.

Impairment in work and activities of daily life in patients with psoriasis: results of the prospective BioCAPTURE registry.

Background: Little is known about the extent of impairments in work and activities of daily life (ADL) in patients with psoriasis, and the influence of contextual factors such as disease-related characteristics and treatment. Therefore, this study aimed to assess these impairments in patients with psoriasis who started using biologicals/small molecule inhibitors.Methods: Using data from the prospective BioCAPTURE registry, we collected patient, disease, and treatment parameters, as well as work/ADL impairments at baseline, 6 and 12 months. Changes in impairment parameters and correlations between impairment and patient/disease characteristics were assessed using generalized estimating equations.Results: We included 194 patients in our analysis. After biological initiation, disease activity decreased significantly (PASI 11.2 at baseline versus 3.9 at 12 months, p < 0.001). Work-for-pay in this cohort was lower than in the Dutch general population (53% versus 67%, p = 0.01). In patients who had work-for-pay, presenteeism improved over time (5% at baseline versus 0% at 12 months, p = 0.04). Up to half of the patients reported impairments in ADL, which did not change over time. Associations between impairments and contextual factors varied, but all impairments were associated with worse mental/physical general functioning.Conclusion: Patients with psoriasis using biologicals are less likely to have work-for-pay. Treatment improves the work productivity of employed patients, but we were unable to detect changes in ADL performance.

Fluorescence diagnosis in actinic keratosis and squamous cell carcinoma.

BACKGROUND: As different tissue types have distinct capabilities to accumulate protoporphyrin IX, fluorescence diagnosis with aminolevulinic acid-induced porphyrins (FDAP) could be used to discriminate between different types of tissue. Previous results demonstrated higher fluorescence ratios in squamous cell carcinoma (SCC) compared with actinic keratoses (AKs). OBJECTIVES: The lesional : non-lesional fluorescence ratio of AKs was compared with the ratio of SCC. Other factors influencing macroscopic fluorescence were also assessed, including stratum corneum thickness, which has been demonstrated to account for heterogeneous fluorescence in psoriasis and in AKs. METHODS: After 1 week of keratolytic pretreatment, FDAP was performed in 13 patients with 36 lesions suspected for AK or SCC. Biopsies were taken for histopathological diagnosis and measurement of stratum corneum thickness. RESULTS: No significant differences were found in the fluorescence ratio (lesional : non-lesional skin) between AKs and SCCs, although macroscopic fluorescence was significantly higher in Bowen's disease and micro-invasive SCCs. CONCLUSIONS: There could be a potential applicability of FDAP to differentiate premalignant lesions with a tendency to progress into SCC and squamous cutaneous lesions already progressing into early invasive cancer from other squamous cutaneous (pre)malignancies. The amount of hyperkeratosis, invasiveness and degree of differentiation seem to be responsible for variations in fluorescence intensity.

Clinical and histological effects of blue light on normal skin.

INTRODUCTION: Phototherapy with visible light is gaining interest in dermatological practice. Theoretically, blue light could induce biological effects comparable to ultraviolet A (UVA) radiation. OBJECTIVES: To study the effects of blue light on normal skin in terms of photodamage, skin ageing and melanogenesis. METHODS: Eight healthy volunteers were included and irradiation with visible blue light was given on five consecutive days. Skin biopsies were analysed with respect to photodamage (p53, vacuolization, sunburn cells), skin ageing (elastosis, MMP-1) and melanogenesis (Melan-A). RESULTS: No inflammatory cells and sunburn cells were visible before or after irradiation. A significant increase in the perinuclear vacuolization of keratinocytes was demonstrated during treatment (P=0.02) with a tendency towards significance after cessation of treatment (P=0.09). No significant change in p53 expression was seen. Signs of elastosis and changes in MMP-1 expression were absent. Minimal clinical hyperpigmentation of the irradiated skin was confirmed histologically with a significant increase in Melan-A-positive cells (P=0.03). CONCLUSIONS: Visible blue light, as given in the present study, does not cause deoxyribonucleic acid damage or early photo-ageing. The biological effects of blue light on normal skin are transient melanogenesis and inexplicable vacuolization without resulting apoptosis. In conclusion, the (short-term) use of visible blue light in dermatological practice is safe.

Fluorescence diagnosis in keratinocytic intraepidermal neoplasias.

BACKGROUND: As different tissue types have distinct capabilities to accumulate protoporphyrin-IX, fluorescence diagnosis with aminolevulinic acid-induced porphyrin (FDAP) could be used to discriminate between different tissue types. OBJECTIVE: Protoporphyrin-IX accumulation and proliferation were studied in cutaneous squamous (pre)malignancies to see whether FDAP could be used to discriminate between different stages of keratinocytic intraepidermal neoplasia or proliferative status. METHODS: FDAP was performed in 14 patients (86 lesions) and biopsy specimens were taken, on which (immuno)histochemistry was performed for histopathologic classification and assessment of Ki67-antigen expression. Stratum corneum thickness was also measured. RESULTS: The fluorescence ratio (lesional:nonlesional skin) showed neither significant differences between the different keratinocytic intraepidermal neoplasia stages, nor between different levels of Ki67-antigen expression. Macroscopic fluorescence intensity and stratum corneum thickness were negatively correlated. LIMITATIONS: Relatively few malignancies were biopsied. CONCLUSIONS: With FDAP we were not able to discriminate between keratinocytic intraepidermal neoplasia lesions or proliferative activity. However, hyperkeratosis appeared to be an important determinant in variations in macroscopic fluorescence intensity.

Current and future treatment options for acne.

Acne is a frequent skin disease with abnormalities in the process of keratinization, sebaceous gland functioning and inflammation. In this review, our understanding of the pathogenesis of acne has been updated. An overview of efficacy and side effects of available anti-acne treatments is presented. Based on the present overview a recommendation for the treatment of various manifestations of acne is provided, also reconciling beneficial combinations of treatments. It is attractive to speculate that the increased insight into the pathogenesis of acne will create new treatment options. Challenging new options comprise blue light, photodynamic therapy, retinoic acid metabolism blocking agents and inhibitors of Th-1 cytokines.

Severe pyoderma gangrenosum unresponsive to etanercept and adalimumab.

BACKGROUND: A 74-year-old female with severe and therapy-resistant pyoderma gangrenosum (PG) was treated for more than 40 years with topical antibacterial ointments, topical and systemic corticosteroids, dapsone and azathioprine. Generally, immunosuppression is the mainstay of treatment of PG, but in our patient cyclosporine had to be discontinued because of significant serious side effects. An attempt was made to decrease the amount of steroids, but tapering of the prednisone dose resulted in relapses of PG. OBSERVATION: Off-label use of etanercept resulted in a temporary limited clinical improvement. After 6 months, initial clinical improvement reduced and adalimumab was started. Unfortunately, after 6 months of adalimumab no clinical improvement was seen. Therefore, systemic corticosteroids had to be continued with very good clinical results. CONCLUSION: In concordance with previous results of several other studies, reviews and case reports, we presume that possibly both etanercept and adalimumab could be excellent therapeutic alternatives in the treatment of PG. Unfortunately, the effectiveness of both etanercept and adalimumab were very limited in our case. Literature research revealed no other successful studies on the off-label use of other immunomodulators as an alternative treatment option for PG. However, infliximab or ustekinumab could be alternative treatment options.

The clinical efficacy of topical methyl-aminolevulinate photodynamic therapy in moderate to severe actinic keratoses of the face and scalp.

INTRODUCTION: Since actinic keratoses (AKs) often appear in areas with field cancerization, photodynamic therapy (PDT) may have significant advantages over the standard treatment options. OBJECTIVES: Clinical efficacy of PDT with topical methyl aminolevulinate (MAL-PDT) in field cancerization was evaluated with respect to the number of AKs and photodamage. METHODS: A total of 14 patients with 223 AKs on the face or scalp were treated with MAL-PDT. Two treatments with a 3-monthly interval were given. At baseline, before the second treatment and 3 months after the end of therapy, the number of AKs were counted and photodamage was assessed with respect to skin roughness, hyperpigmentation, hypopigmentation, scarring, atrophy, telangiectasia and wrinkling. RESULTS: Complete clearance was reached in patients with a moderate degree of actinic damage, whereas a severe degree of field cancerization demonstrated only partial clearance. The global score for photodamage improved significantly. After the follow-up period, none of the patients reaching clearance had developed relapsing or new AKs. CONCLUSIONS: MAL-PDT induces a high clearance rate of AKs, dependent on the degree of field cancerization, with a good improvement in photodamage and prevention of developing new AKs. Thus, more PDT sessions are needed in patients with a severe degree of field cancerization.

The effects of keratolytic pretreatment prior to fluorescence diagnosis and photodynamic therapy with aminolevulinic acid-induced porphyrins in psoriasis.

BACKGROUND: Psoriasis lesions accumulate protoporphyrin IX (PpIX) with a variable distribution within plaques due to variations in hyperkeratosis causing differences in penetration of cream or light. OBJECTIVES: To study the effects of different keratolytic pretreatments in PpIX-induced fluorescence diagnosis (FDAP) and during photodynamic therapy (PDT). METHODS: Two psoriasis plaques of 10 patients were treated with either topical retinoic acid or with a hydrocolloid dressing. The hydrocolloid dressing gave the best results. Subsequently, two different contralateral plaques of eight patients were pretreated with a hydrocolloid dressing or the standard pretreatment, salicylic acid in petrolatum, during the 6 weeks of PDT. Biopsies were investigated with respect to stratum corneum thickness, proliferation, differentiation and inflammation. RESULTS: Irritation and point bleedings were noticed after retinoic acid. A hydrocolloid dressing induced the best clinical improvement. Therefore, it was used as alternative pretreatment for psoriasis prior to PDT. We observed significant clinical and immunohistochemical improvement of psoriasis in the salicylic acid as well as the hydrocolloid dressing pretreated plaques. CONCLUSIONS: Salicylic acid in petrolatum and a hydrocolloid dressing prior to FDAP and PDT induce improvement of hyperkeratosis. Thus, a hydrocolloid dressing is a good alternative to the current keratolytic pretreatment regime.

Aneuploidy and proliferation in keratinocytic intraepidermal neoplasias.

Cutaneous squamous (pre)malignancies can be classified according to the keratinocytic intraepidermal neoplasia (KIN) classification. Aneuploidy can be seen as the result of chromosomal aberrations leading to altered DNA content and has been strongly associated with malignancy. Hyperproliferation is also strongly associated with tumorigenesis. The aim of the study was to analyse the presence and the amount of aneuploidy and proliferation in the progression from intraepithelial neoplasm to microinvasive carcinoma (miSCC). For this purpose, nuclei were isolated from 116 formalin-fixed KIN lesions from 68 patients in which DNA content was measured by flow cytometry. Proliferation was assessed by immunohistochemical staining for Ki67 as well as by flow cytometry. Aneuploidy was increasingly found in higher KIN lesions, but not in normal skin. However, in miSCC aneuploidy was relatively less frequently found. DNA indices (mean +/- SE) of KIN III-lesions (1.57 +/- 0.05) were significantly lower compared with KIN I/II lesions (1.71 +/- 0.05). Ki67 expression was strongly positively correlated with KIN grade, and proved to be a good adjunct in the classification of KINs. Thus, aneuploidy occurred more frequently in higher KIN lesions, indicating cumulative damage during KIN progression. The lower frequency of aneuploidy in miSCC compared with KIN III may point at alternative routes towards invasive carcinoma besides serial progression through all three KIN stages. Ki67 expression appears a valuable marker in the classification of KINs.