Biomarkers and patient-related factors associated with clinical outcomes in dupilumab-treated atopic dermatitis.

Background: Atopic dermatitis (AD) is a common chronic eczematous skin disease with severe pruritus. Several new therapeutic agents for AD such as dupilumab, an anti-IL-4Rα antibody, have been developed in recent years. We need to predict which agent is the best choice for each patient, but this remains difficult. Objective: Our aim was to examine clinical background factors and baseline biomarkers that could predict the achievement of improved clinical outcomes in patients with AD treated with dupilumab. Methods: A multicenter, prospective observational study was conducted on 110 patients with AD. The Eczema Area and Severity Index was used as an objective assessment, and the Patient-Oriented Eczema Measure and Numerical Rating Scale for Pruritus were used as patient-reported outcomes. In addition, some clinical background factors were evaluated. Results: The achievement of an absolute Eczema Area and Severity Index of 7 or less was negatively associated with current comorbidity of food allergy and baseline serum lactate dehydrogenase (LDH) levels. There were negative associations between achievement of a Patient-Oriented Eczema Measure score of 7 or less and duration of severe AD and between achievement of an itching Numerical Rating Scale for Pruritus score of 1 or less and current comorbidity of allergic conjunctivitis or baseline serum periostin level. Furthermore, signal detection analysis showed that a baseline serum LDH level less than 328 U/L could potentially be used as a cutoff value for predicting the efficacy of dupilumab. Conclusion: Baseline biomarkers such as LDH and periostin and clinical background factors such as current comorbidity of food allergy and a long period of severe disease may be useful indicators when choosing dupilumab for systemic treatment for AD, as they can predict the efficacy of dupilumab.

Three cases of subcorneal pustular dermatosis with immunohistochemical examinations.

Subcorneal pustular dermatosis, a rare, benign skin disease, is a type of neutrophilic dermatosis. The authors reported three cases of subcorneal pustular dermatosis. In case 1, a 9-year-old girl developed a skin rash with blisters following a mycoplasma infection and had a flare-up due to a common cold. She was successfully treated with a topical corticosteroid. In case 2, a 70-year-old woman who had been treated for rheumatoid arthritis with adalimumab, salazosulfapyridine, and leflunomide developed 3- to 5-mm pustules on her trunk and thighs 4 days after flu vaccination. The rash disappeared with drug withdrawal and treatment with diaminodiphenyl sulfone. In case 3, an 81-year-old man, who was diagnosed with pyoderma gangrenosum at 61 years old, developed multiple small flaccid pustules on his trunk and extremities due to an infection in the arteriovenous shunt area on the forearm. The pustule disappeared with intravenous antibiotic therapy; however, the pustules subsequently flared up along with ulcers typical of pyoderma gangrenosum. He was given oral prednisolone therapy, which was effective for the small pustules and some ulcers. Immunohistochemical examination of the three cases revealed neutrophilic infiltration in the subcorneal layer of the epidermis. The pustules contained neutrophils as well as some CD68+ and a few CD1a+ cells. The epidermis and dermis were more predominantly infiltrated by CD4+ cells than by CD8+ cells. Positive stainings for interleukin 8, interleukin 36γ, and phospho-extracellular signal-regulated kinases 1 and 2 were observed in the upper layers of the epidermis below the pustules. Although the pathogenesis of subcorneal pustular dermatosis has not been clarified, the current results suggest that a variety of inflammatory cells, including those responsible for both innate and acquired immunity, are involved in the accumulation of neutrophils in subcorneal pustular dermatosis.

Single-center survey of incidental imaging findings on computed tomography in patients with psoriasis on biologic therapy.

Psoriasis is an immune-mediated chronic inflammatory disease that predominantly affects the skin and joints. Systemic therapies are required for patients with moderate-to-severe psoriasis, and biologics can provide significant symptomatic improvement. Computed tomography (CT) analysis is recommended before and after biologic therapy to exclude the possibility of comorbid infections and malignancies; incidental findings are often detected in asymptomatic patients. In this study, we analyzed the common incidental findings on CT in 227 patients with psoriasis on biologic therapy and 219 living-kidney transplant donors at our hospital. Incidental findings on CT were observed in 176 (77.5%) patients with psoriasis. The most common were fatty liver (82 patients, 36.1%), urolithiasis (54 patients, 23.8%), pulmonary lesions (47 patients, 20.7%), gallstones or postoperative gallstones (38 patients, 16.7%), liver cysts (36 patients, 15.9%), renal cysts (33 patients, 14.5%), and colonic diverticulum (22 patients, 9.7%), which were observed in 38 (17.4%), eight (3.7%), 68 (31.1%), 12 (5.5%), 58 (26.5%), 88 (40.2%), and 10 (4.6%) donors, respectively. The prevalence of fatty liver, urolithiasis, gallstones, and postoperative gallstones was significantly higher in patients with psoriasis. Multivariate logistic regression showed that psoriasis was a risk factor for fatty liver disease, urolithiasis, and gallstones. Currently, incidental findings on CT in patients with psoriasis have not been well studied. The results of this survey will lead to increased awareness of the incidental findings on CT as a complication of psoriasis.

Drug Survival of Tumor Necrosis Factor-Alpha Inhibitors and Switched Subsequent Biologic Agents in Patients with Psoriasis: A Retrospective Study.

INTRODUCTION: This study aimed to retrospectively examine the drug survival of tumor necrosis factor (TNF)-alpha inhibitors and switched subsequent biologic agents after discontinuation of TNF inhibitors. METHODS: This real-world setting study was conducted at a single academic center. We included patients who were treated with adalimumab (n = 111), certolizumab pegol (n = 12), and infliximab (n = 74) at Jichi Medical University Hospital from 1 January 2010 to 31 July 2021. RESULTS: No significant differences were noted in drug survival between the three TNF inhibitors. The 10-year drug survival rate for adalimumab and infliximab was 14% and 18%, respectively. Of the patients who discontinued TNF inhibitors for any reason (n = 137), 105 chose biologics as their subsequent treatment. The subsequent biologics included 31 cases of TNF inhibitors (adalimumab in 20, certolizumab pegol in 1, and infliximab in 10), 19 of interleukin-12/23 inhibitor (ustekinumab), 42 of interleukin-17 inhibitors (secukinumab in 19, brodalumab in 9, and ixekizumab in 14) and 13 of interleukin-23 inhibitors (guselkumab in 11, risankizumab in 1, and tildrakizumab in 1). Cox proportional hazards analysis for the subsequent drugs in cases of discontinuation due to inadequate efficacy revealed that female sex was a predictor of drug discontinuation (hazard ratio 2.58, 95% confidence interval 1.17-5.70) and that taking interleukin-17 inhibitors rather than TNF inhibitors was a predictor of drug persistence (hazard ratio 0.37, 95% confidence interval 0.15-0.93). CONCLUSIONS: Interleukin-17 inhibitors may be a favorable option for patients who need to switch from TNF inhibitors due to inadequate efficacy. However, this study is limited by the small number of cases and its retrospective design.

With many biologic options available for the treatment of psoriasis, choosing the optimal drug can be challenging, especially when switching drugs. Tumor necrosis factor (TNF) inhibitors are the oldest category of biologics used for psoriasis, with adalimumab and infliximab being available since 2010 and certolizumab pegol since 2019 in Japan. In this study, we examined the drug survival of TNF inhibitors in patients treated with adalimumab (n = 111), certolizumab pegol (n = 12), and infliximab (n = 74) at Jichi Medical University Hospital from 1 January 2010 to 31 July 2021. No significant differences were noted in drug survival between the three TNF inhibitors, and the 10-year drug survival rate for adalimumab and infliximab was 14% and 18%, respectively. We examined the drug survival of subsequent biologics used by patients who discontinued TNF inhibitors for any reason (n = 137) and found that among patients who discontinued TNF inhibitors due to inadequate efficacy, female sex was a predictor of drug discontinuation and that taking interleukin-17 inhibitors rather than TNF inhibitors was a predictor of drug continuation. The study results suggest that interleukin-17 inhibitors is a favorable option for patients who discontinue TNF inhibitors due to inadequate efficacy and need to switch to other agents. However, this study has limitations, including the small number of cases and the single-center and retrospective study design.

Four-year drug survival of apremilast in patients with psoriasis.

This real-world study at a single academic center retrospectively examined the drug survival of apremilast for patients with psoriasis. Retrospective information was extracted from the medical records of patients with psoriasis treated with apremilast at the Department of Dermatology, Jichi Medical University Hospital, between March 1, 2017, and June 31, 2021. In total, 281 patients were included in this study. Of these patients, 22% had psoriatic arthritis and 57% had a history of prior systemic treatment, including biologics, before the initiation of apremilast. The 1-, 2-, 3-, and 4-year drug survival rates were 54%, 41%, 32%, and 30%, respectively. Cox regression analysis revealed that sex, duration of plaque psoriasis (<10 years vs ≥10 years), presence of psoriatic arthritis, involvement of scalp lesions, involvement of palmoplantar lesion, involvement of nail lesions, having cardiometabolic comorbidities, and a history of prior systemic treatment did not have any significant impact on drug survival. The most common reason for apremilast discontinuation was inadequate efficacy (27%), followed by adverse events (12%). Approximately 49% of the patients experienced one or more adverse events. Diarrhea was the most common adverse event (24%), followed by nausea (19%) and headache (11%).

Epidemiological survey of patients with psoriatic arthritis in the Japanese Society for Psoriasis Research from 2017 to 2020.

The Japanese Society for Psoriasis Research (JSPR) conducted annual epidemiological surveys of patients with psoriatic arthritis (PsA). This study aimed to analyze a recent epidemiological survey of enrolled PsA patients in the JSPR from 2017 to 2020. A total of 1641 patients (1032 men [62.9%] and 609 women [37.1%]) were enrolled from 131 medical institutions. The mean ± standard deviation age of the patients was 51.4 ± 13.6 years and those at the onset of skin lesions and joint symptoms were 39.2 ± 15.8 and 47.9 ± 14.0 years, respectively. According to the Moll and Wright criteria, distal, oligoarticular, polyarticular, arthritis mutilans, and axial or spondyloarthritis types were 27.2%, 29.9%, 18.6%, 0.4%, and 6.6%, respectively. Approximately 56.3% of the patients had past history and comorbidities, such as hypertension (35.9%), dyslipidemia (20.7%), diabetes mellitus (19.2%), hyperuricemia (13.5%), cardiovascular disease (4.1%), and cerebrovascular disease (3.9%). Regarding systemic therapy, 55.9% and 45.5% of the patients were treated with oral medications and biologics, respectively. The most common oral medication was methotrexate (39.1%), followed by apremilast (27.4%). Non-steroidal anti-inflammatory drugs were also used in many patients (40.3%). Among the biologics, the most common was adalimumab (30.1%), followed by secukinumab (20.9%) and ixekizumab (17.0%). This survey shows the recent perspective of PsA in the Japanese society, which will lead to a better understanding of this disease, including patient characteristics, comorbidities, and treatment trends.

Epidemiological survey of patients with pustular psoriasis in the Japanese Society for Psoriasis Research from 2017 to 2020.

The Japanese Society for Psoriasis Research (JSPR) has been conducting annual epidemiological surveys of patients with pustular psoriasis in Japan since 2017. This study aimed to conduct a recent epidemiological analysis of patients with pustular psoriasis who were enrolled in the JSPR from 2017 to 2020. A total of 291 patients from 131 medical institutions were enrolled, of which 47.4% (138 cases) were males and 52.6% (153 cases) were females. The mean ± standard deviation (SD) age of the patients was 57.4 ± 20.3 years (males, 61.2 ± 17.3 years; females, 54.1 ± 22.1 years). The mean ± SD age of the patients at disease onset was 48.5 ± 22.5 years (males, 50.8 ± 20.6 years; females, 46.4 ± 24.0 years). The types of pustular psoriasis observed included the von Zumbusch type (59.8%), annular pustular psoriasis (8.2%), impetigo herpetiformis (6.5%), and acrodermatitis continua of Hallopeau (4.8%), of which, the majority of the patients with impetigo herpetiformis were female. Among the patients, 58.4% were treated with oral medications and 44.0% were treated with biologics. The most common oral medication prescribed was etretinate (52.4%), followed by corticosteroids (24.7%) and cyclosporin (22.9%). The most common biologics used were IL-17 inhibitors (ixekizumab [28.1%] and secukinumab [22.7%]), followed by tumor necrosis factor (TNF) inhibitors (infliximab [15.6%]) and IL-23 inhibitors (guselkumab [14.8%] and risankizumab [10.2%]). This survey thus provides new and significant information regarding the recent perspective of pustular psoriasis, such as patient characteristics and treatment trends, in Japan.

Proactive versus Rank-Down Topical Corticosteroid Therapy for Maintenance of Remission in Pediatric Atopic Dermatitis: A Randomized, Open-Label, Active-Controlled, Parallel-Group Study (Anticipate Study).

Topical corticosteroids are used as first-line treatment for atopic dermatitis (AD). Regarding the maintenance of remission achieved by topical corticosteroids, no previous studies have compared proactive therapy with rank-down therapy. We compared their efficacy and safety in Japanese children with moderate to severe AD. Patients who had achieved remission with a very strong topical corticosteroid were randomized to 4-week maintenance treatment with either intermittent use of the same drug (proactive therapy) or daily use of a strong topical corticosteroid for 1 week followed by daily use of a medium-potency topical corticosteroid for 3 weeks (rank-down therapy); 49 patients were randomized (proactive therapy, n = 24; rank-down therapy, n = 25). During maintenance treatment, the relapse rate was 8.33% in the proactive therapy group and 20.0% in the rank-down therapy group (p = 0.0859). The mean (±standard deviation) itching score on a numerical rating scale in the rank-down therapy group increased significantly from 2.5 ± 1.9 to 3.6 ± 2.6 (p = 0.0438). Adverse events occurred in 2 patients receiving proactive therapy and 3 patients receiving rank-down therapy. Proactive therapy appears to be as safe as rank-down therapy and may be more effective for itch in pediatric AD in remission.

Inflammation Causes Exacerbation of COVID-19: How about Skin Inflammation?

COVID-19 is a recently emerged viral infection worldwide. SARS-CoV-2, the causative virus, is believed to have emerged from bat coronaviruses, probably through host conversion. The bat coronavirus which has the highest gene homology to SARS-CoV-2 specifically infects deep forest bats in China whose habitat extends through the Middle East to Southern Europe. Host conversion might have occurred due to the deforestation by humans exposing wild bats to the environment they had never encountered before. SARS-CoV-2 infects cells through two mechanisms: through its receptor ACE2 with the help of enzyme TMPRSS and through membrane fusion with the help of elastases in the inflammatory condition. Obesity, hypertension, diabetes mellitus, and pulmonary diseases cause poor prognosis of COVID-19. Aging is another factor promoting poor prognosis. These diseases and aging cause low-level and persistent inflammation in humans, which can promote poor prognosis of COVID-19. Psoriasis and atopic dermatitis are the major inflammatory skin diseases. These inflammatory skin conditions, however, do not seem to cause poor prognosis for COVID-19 based on the epidemiological data accumulated so far. These mechanisms need to be elucidated.