Topical corticosteroids (TCS) are efficacious treatments for inflammatory skin conditions, however, there is a risk of adverse effects; understanding how best to use these treatments is an unmet research priority shared by patients and healthcare professionals.
To develop non-invasive biomarkers of local adverse effects to facilitate the optimisation of topical therapy.
An observer-blind randomised within-subject controlled trial in atopic dermatitis patients was undertaken (NCT04194814) comparing betamethasone valerate 0.1% cream (BMV) to a non-steroidal anti-inflammatory treatment, crisaborole 2% ointment (CRB). Participants underwent 4 weeks twice-daily treatment with CRB on one forearm and BMV on the other (left/right randomised). Skin properties were assessed on days 1, 15, 29 of treatment and again on day 57, including imaging of skin microstructure using Optical Coherence Tomography (OCT) and Attenuated Total Reflectance (ATR)-Fourier Transform Infrared (FTIR) spectroscopic assessment of stratum corneum molecular structure. The primary outcome was the difference in the change in epidermal thickness from days 1 to 29.
Thirty-seven participants received the first dose, of which 32 completed the study (all 37 were included in the analysis). Pathologic epidermal thinning at day 29 was significantly greater (p < 0.0001) at sites treated with BMV (−31.66; 95% confidence interval: −35.31, −28.01 µm) compared to CRB (−13.76; −17.42, −10.10 µm). From a panel of exploratory biomarkers, superficial plexus depth and stratum corneum carboxyl group levels had the greatest ability to discriminate the effects of the TCS treatment (p < 0.0001).
BMV induced 2.3x more pathologic epidermal thinning than CRB after 4 weeks of treatment, suggesting that CRB may be more appropriate for longer-term, proactive-based, treatment strategies where the risks of adverse effects are greatest. By monitoring treatment effects using OCT and ATR-FTIR spectroscopy, two new non-invasive biomarkers of skin health have been identified with the potential to help optimise future safe treatment strategies.
Interleukins are central in the modulation of immune responses. This narrative review aims to summarize the growing evidence on their significance as key drivers of numerous cutaneous diseases with a special focus in some of the more prevalent chronic inflammatory dermatologic diseases such as psoriasis, atopic dermatitis, allergic contact dermatitis, urticaria, and hidradenitis suppurativa. Additionally, we discuss their relevance in the recent developments in targeted therapies that have significantly transformed the management of these skin conditions. To this end, we have conducted a comprehensive search through the Cochrane Library and Database of Systematic Reviews and the MEDLINE search engine, and we have summarized the available clinical evidence considering up to 466 records including meta-analyses, systematic reviews, reviews and clinical trials. Ultimately, this review intents to foster both dermatologist and non-dermatologist physicians' understanding of the immunology behind the clinical manifestations of some of the most common inflammatory skin diseases and engage with the novel therapeutic approaches by providing accessible insights into the implications of interleukin pathways dysregulation.
Biologics are therapeutic options for the management of moderate−severe plaque psoriasis. Some patients need to switch biologic treatment to achieve satisfactory outcomes, which might have a considerable economic impact.
We assessed the characteristics and switch rates of patients with plaque psoriasis initiating biologic treatment and compared healthcare resource utilization (HCRU) and associated costs for switching and non-switching.
This study was a retrospective claims-based analysis comprising a 182-day baseline period to identify patient characteristics and a 365-day follow-up to assess switch rates, HCRU and associated costs. Data covering claims activity from 2016 to 2021 in a representative sample of four million individuals with statutory insurance in Germany was used.
We identified 2565 patients with psoriasis initiating biologic treatment with anti-IL-17 (n = 1037), anti-IL-23 (n = 704), anti-TNF-α (n = 583) and anti-IL-12/23 (n = 241) agents. A total of 9.2% of patients switched therapy to another biologic during follow-up, ranging from 4.9% (secukinumab) to 16.5% (etanercept). The probability of treatment switching was significantly lower in patients treated with risankizumab (p < 0.05) than in patients treated with other biologics except guselkumab (p = 0.14). HCRU and associated costs during the follow-up were generally higher with a therapy switch (all-cause: 32,263 ± 15,381€) than without (25,041 ± 12,090€). This applied to direct costs (outpatient services, hospitalization, drug treatment) and indirect costs (sickness benefits). Drug treatment accounted for the largest share of costs.
Treatment switching is frequent in patients with moderate−severe plaque psoriasis initiating biologic therapy and is associated with increased HCRU and associated costs. As the probability that a switch occurs within 365 days after treatment initiation widely differs between biologic agents, further research is warranted to determine the underlying reasons for switching to help establish clinically and economically sound therapy sequences.
Pyoderma gangrenosum (PG) in Caucasians with Takayasu's arteritis (TA) is uncommon. We described a case of refractory PG in an 18-year-old Caucasian man with TA since the age of 10 and was treated with corticosteroids, methotrexate, anti-TNF therapy (adalimumab), anti-CD20 therapy (rituximab), cyclophosphamide and most latterly tocilizumab and leflunomide. He has vascular stenosis complicated with renovascular hypertension and is steroid-dependent. He presented with a 6-week history of a left cheek rapidly enlarging lesion associated with pain, bleeding and purulent discharge not responding to flucloxacillin. Incisional biopsy suggested PG. He later developed similar lesions on the volar aspect of the right hand and at venepuncture sites. Despite topical immunosuppressive medication and high-dose pulsed intravenous methylprednisolone, the left cheek lesion continued to grow rapidly. These painful, unsightly ulcers caused significant psychosocial stress and limited his daily life. Following a multidisciplinary team (MDT) discussion, tocilizumab was switched to abrocitinib. While initial improvement of lesions was observed, he subsequently developed an acneiform eruption which evolved into PG and became superinfected with herpes zoster virus and Staphylococcus aureus, requiring hospitalisation for intravenous (IV) acyclovir and antibiotics. Following several MDT discussions, abrocitinib was discontinued and a new regimen consisting of ciclosporin, dapsone and enhanced frequency IV immunoglobulin (IVIg) every 2 weeks was initiated, effectively stabilising his PG. This case highlights the rare association of PG and TA in Caucasians, the complexities of managing PG complicated by severe infections and underlying immunodeficiency, and the significant psychosocial burden of PG.
Vitiligo is described with a prevalence of 0.5%−1%. Recent studies suggest an increasing prevalence, but there is a scarcity of studies that have systematically evaluated the global incidence and prevalence. We examined the incidence and the global, regional, and country-specific prevalence of vitiligo in the general population (PROSPERO: CRD42021261643). We systematically searched PubMed, EMBASE, and Web of Science. Each study was categorised in subgroups. The overall analysis comprised all studies, except for studies only examining children and adolescents. Pooled proportions were calculated with the DerSimonian-Laird method for random-effects models with 95% confidence intervals (CI). Of the 7,838 identified studies, 171 were eligible for analysis (participants n = 572,334,973). The overall incidence was 1.59 per 10,000 person-years (95% CI: 0.70−2.83). The overall prevalence was 0.40% (95% CI: 0.37−0.44); no difference was observed between females (0.50%, 95% CI: 0.36−0.66) and males (0.49%, 95% CI: 0.35−0.65). West Asia showed the highest prevalence (0.77%, 95% CI: 0.44−1.10) and East Asia the lowest (0.12%, 95% CI: 0.10−0.14). The highest country-specific prevalence was reported in Jordan (1.34%, 95% CI: 0.12−3.87) and the lowest in Sweden (0.19%, 95% CI: 0.08−0.34). Children and adolescents showed a lower prevalence (0.27%, 95% CI: 0.24−0.31) compared to adults (0.70%, 95% CI: 0.59−0.81). Questionnaire-based studies showed a higher prevalence (0.73%, 95% CI: 0.52−0.98) compared to examination-based studies (0.59%, 95% CI: 0.46−0.73) and register-based studies (0.13%, 95% CI: 0.10−0.17). The prevalence in examination-based studies increased from 0.40% (95% CI: 0.17−0.73) between 1943 and 1979 to 0.89% (95% CI: 0.68−1.13) between 2020 and 2023. Questionnaire-based studies also showed an increasing prevalence, while in register-based studies, the prevalence was continuously low. This study shows the global impact of vitiligo and how subgroup analyses influence the prevalence. The overall prevalence of vitiligo is lower than previously assumed; females and males are equally affected, and vitiligo is more common in adults.
Should oral isotretinoin be considered contraindicated in patients with peanut, soybean, and cashew allergies? A systematic literature search of PubMed, EMBASE and The Cochrane Library up to July 2023 was conducted to identify randomised control trials (RCTs), cohort studies, case reports, and cross-sectional studies investigating if isotretinoin should be contraindicated in patients with various allergies including peanut, soybean, and cashew allergies. Primary outcomes explored included relapse, adverse effects, and safety profiles of oral isotretinoin at varying doses. Secondary outcomes included efficacy as well as economic considerations. The quality of studies, including risk of bias, was assessed using GRADE (Grading of Recommendations, Assessment, Development and Evaluations). A total of eight studies were included. The majority of studies suggested that isotretinoin should not be considered inadvisable. In cases with peanut allergies, minimal adverse effects were noted with various dosages of isotretinoin and prolonged treatment duration. In cases with soybean allergies, similar results and conclusions were obtained to the cases with peanut allergies, however the number of studies were not of similar value to those of peanut allergies. Comparison between studies was challenging due to differing methods of assessment, subjective interpretation of severity and duration of follow-up. This review highlights the need for an adequately powered RCT, to decipher whether isotretinoin should not be given to patients with peanut, soybean or cashew allergies.
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