Abdominal aortic mural thrombus in association with active ulcerative colitis.

Aortic mural thrombus (AMT) in the absence of aneurysm or atherosclerosis is a rare clinical finding and an uncommon cause of peripheral arterial embolization. AMT in a normal artery is usually attributed to systemic hypercoagulability. We describe a case of subacute lower limb ischemia due to AMT associated with active ulcerative colitis (UC). A 46-year-old man with active UC was referred to our hospital for the evaluation and treatment of left leg pain. Ultrasound and contrast computed tomography showed occlusion of the left popliteal artery, and an AMT in the abdominal aorta between the inferior mesenteric artery and the aortic bifurcation. We started anticoagulant therapy, intravenous infliximab, and cytapheresis. Four weeks after initiating anticoagulation therapy, we were able to successfully treat the AMT with anticoagulation therapy without surgical thrombectomy. The inflammatory status of ulcerative colitis was also under control, and AMT had not recurred at 1 year after treatment. Invasive therapies are often selected to treat AMT. However, if a patient's hypercoagulable state is controlled, AMT can safely be treated with anticoagulation therapy alone without recurrence. Learning objective: Aortic mural thrombus (AMT) in the absence of aneurysm or atherosclerosis is a rare clinical finding and an uncommon cause of peripheral arterial embolization. AMT in a normal artery is usually attributed to systemic hypercoagulability. We describe a case of subacute lower limb ischemia due to AMT associated with active ulcerative colitis. We controlled the ulcerative colitis condition and successfully treated the AMT with anticoagulation therapy alone.

A Comprehensive Study of the Immunophenotype and its Clinicopathologic Significance in Adult T-Cell Leukemia/Lymphoma.

Adult T-cell leukemia/lymphoma (ATLL) is a mature T-cell tumor caused by human T-lymphotropic virus type 1 (HTLV-1). The typical ATLL immunophenotypes are described in the 2017 World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues (positive: CD2, CD3, CD5, CD4, and CD25; negative: CD7, CD8, and cytotoxic markers; and partially positive: CD30, CCR4, and FOXP3). However, limited studies are available on the expression of these markers, and their mutual relationship remains unknown. Furthermore, the expression status of novel markers associated with T-cell lymphomas, including Th1 markers (T-bet and CXCR3), Th2 markers (GATA3 and CCR4), T follicular helper markers (BCL6, PD1, and ICOS), and T-cell receptor (TCR) markers, and their clinicopathologic significance is unclear. In this study, we performed >20 immunohistochemical stains in 117 ATLL cases to determine the comprehensive immunophenotypic profile of ATLL, which were compared on the basis of clinicopathologic factors, including morphologic variants (pleomorphic vs anaplastic), biopsy locations, treatments, Shimoyama classification-based clinical subtype, and overall survival. CD3+/CD4+/CD25+/CCR4+ was considered a typical immunophenotype of ATLL, but approximately 20% of cases did not conform to this pattern. Simultaneously, the following new findings were obtained: (1) most cases were negative for TCR-ß and TCR-δ (104 cases, 88.9%), indicating the usefulness of negative conversion of TCR expression to provide differentiation from other T-cell tumors; (2) the positivity of CD30 and CD15 and the negativity of FOXP3 and CD3 were significantly associated with anaplastic morphology; and (3) atypical cases, such as T follicular helper marker-positive (12 cases, 10.3%) and cytotoxic molecule-positive cases (3 cases, 2.6%), were identified. No single markers could predict the overall survival among patients with acute/lymphoma subtypes of ATLL. The results of this study illustrate the diversity of ATLL phenotypes. In T-cell tumors occurring in HTLV-1 carriers, the possibility of ATLL should not be eliminated even when the tumor exhibits an atypical phenotype, and the confirmation of HTLV-1 in the tissue is recommended.

Survival rates of systemic interventions for psoriasis in the Western Japan Psoriasis Registry: A multicenter retrospective study.

Psoriasis affects approximately 0.3% of the Japanese population. Recently, various effective systemic drugs have become available, and the continuation of a given treatment has become critical because of the chronic nature of psoriasis. Factors affecting drug survival (the time until treatment discontinuation) in psoriasis treatment include efficacy, safety, ease of use, and patient preference. In the present study, the authors retrospectively surveyed a multifacility patient registry to determine the real-world evidence of the survival rate of systemic interventions for psoriasis treatment. Patients with psoriasis who visited 20 facilities in the Western Japan area between January 2019 and May 2020 and gave written consent were registered as study participants, and their medical history of systemic interventions for psoriasis (starting from 2010) was retrospectively collected and analyzed. The drugs investigated were adalimumab, infliximab, ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, risankizumab, cyclosporine, and apremilast. When drugs were discontinued, the reasons were also recorded. A total of 1003 patients with psoriasis including 268 with psoriatic arthritis (PsA) were enrolled. In biologics, more recently released drugs such as interleukin 17 inhibitors showed a numerically higher survival rate in the overall (post-2010) analysis. However, in the subset of patients who began treatment after 2017, the difference in the survival rate among the drugs was smaller. The reasons for discontinuing drugs varied, but a loss of efficacy against dermatological or joint symptoms were relatively frequently seen with some biologics and cyclosporine. The stratification of drug survival rates based on patient characteristics such as bio-naive or experienced, normal weight or obese, and with or without PsA, revealed that bio-experienced, obese, and PsA groups had poorer survival rates for most drugs. No notable safety issues were identified in this study. Overall, the present study revealed that the biologics show differences in their tendency to develop a loss of efficacy, and the factors that negatively impact the survival rate of biologics include the previous use of biologics, obesity, and PsA.

Clinical characteristics of patients with psoriasis with family history: A multicenter observational study.

Previous studies on family history of psoriasis showed that patients with a family history have an earlier onset of the disease, but such studies in Japan are still limited. To elucidate the characteristics of patients with familial psoriasis, we studied the family history of patients with psoriasis using the West Japan Psoriasis Registry, a multi-institutional registry operated by 26 facilities in the western part of Japan, including university hospitals, community hospitals, and clinics. This study enrolled 1847 patients registered between September 2019 and December 2021, with 199 (10.8%) having a family history of psoriasis. Patients with a family history of psoriasis had significantly earlier onset of the disease than those without a family history. Furthermore, patients with a family history of psoriasis had significantly longer disease duration. Psoriatic arthritis (PsA) was significantly more common in patients with a family history (69/199, 34.7%) than in those without a family history (439/1648, 26.6%) (adjusted P = 0.023). A subanalysis of patients with PsA revealed a significant difference in the patient global assessment (PaGA) score in Fisher's exact test and adjusted test. The numbers of patients with PaGA 0/1 were 29 (43.3%) and 172 (39.9%) in patients with PsA with and without family history of psoriasis, respectively, whereas the numbers of patients with PaGA 3/4 were 13 (19.4%) and 145 (33.6%) in patients with PsA with and without family history of psoriasis, respectively. Other disease severity variables did not show a difference between the two groups. Our findings suggest that genetics play a larger role in the development of PsA than in the development of psoriasis vulgaris. Most cases of PsA occur in patients who already have psoriasis, therefore dermatologists should pay attention to joint symptoms, especially in patients with psoriasis who have a family history of psoriasis.

Itch as a critical factor in impaired health-related quality of life in patients with plaque psoriasis achieving clear or almost-clear skin: Analysis of the single-arm, open-label, multicenter, prospective ProLOGUE study.

Background: Patients with psoriasis report impaired health-related quality of life (HRQoL; Dermatology Life Quality Index score ≥ 2) even after achieving clear or almost-clear skin with biologic treatment. Objective: To assess the effectiveness of brodalumab in HRQoL improvement and the factors associated with incomplete HRQoL improvement in Japanese patients with psoriasis. Methods: As a part of the single-arm, open-label, multicenter, prospective ProLOGUE study (Japan Registry of Clinical Trials identifier: jRCTs031180037), patients were treated with 210 mg of subcutaneous brodalumab in daily clinical practice until week 48. The absolute Psoriasis Area and Severity Index scores and patient-reported outcomes were assessed at baseline and weeks 12 and 48. Results: Seventy-three patients (male, 82.2%; median age, 54.0 years) were enrolled. The Dermatology Life Quality Index and European Quality of Life 5-Dimension 5-Level Utility Index scores significantly improved from baseline to weeks 12 and 48. At week 48, all 13 patients with a Dermatology Life Quality Index score of ≥2 and an absolute Psoriasis Area and Severity Index score of 0 to ≤2 reported itching. Limitations: Unclear generalizability of the results to other biologics. Conclusion: Treatment with brodalumab improved HRQoL in patients with psoriasis. Itching may contribute to incomplete HRQoL improvement in patients who have achieved clear or almost-clear skin.

Work productivity in real-life employed patients with plaque psoriasis: Results from the ProLOGUE study.

Psoriasis poses a substantial economic burden by reducing the work productivity of affected patients. We aimed to evaluate the negative impact of plaque psoriasis on work productivity and effectiveness of brodalumab in improving work productivity impairment in real-life employed patients. This analysis was conducted in employed patients from ProLOGUE, an open-label, multicenter, prospective cohort study (Japan Registry of Clinical Trials identifier: jRCTs031180037). Outcomes included association of Work Productivity and Activity Impairment-Psoriasis (WPAI-PSO) domain scores with scores from various patient-reported outcome measures or Psoriasis Area and Severity Index (PASI) scores at baseline. Change from baseline in WPAI-PSO domain scores following brodalumab treatment was also evaluated. Of the 73 patients enrolled, 51, 48, and 40 patients were considered employed at baseline, Week 12, and Week 48 of brodalumab treatment, respectively. In the model adjusted by age and sex, the work productivity loss score correlated with the Dermatology Life Quality Index (DLQI), itch Numeric Rating Scale (NRS), Patient Health Questionnaire-8 (PHQ-8), and skin pain NRS scores (partial Spearman correlation coefficient [ρ] = 0.608, 0.510, 0.461, and 0.424, respectively); presenteeism score correlated with the DLQI, itch NRS, and skin pain NRS scores (ρ = 0.568, 0.500, and 0.403, respectively); and activity impairment score correlated with the DLQI and PHQ-8 scores (ρ = 0.530 and 0.414, respectively). None of the WPAI-PSO domain scores correlated with the PASI score. All WPAI-PSO domain scores (except absenteeism) significantly reduced from baseline to Weeks 12 (p < 0.0001) and 48 (p < 0.001) with brodalumab treatment. In conclusion, work productivity impairment in psoriasis was associated with various subjective symptoms that can be captured using patient-reported outcome measures. Brodalumab treatment improved work productivity in real-life employed patients with plaque psoriasis.

Efficacy and safety of a dimethicone lotion in patients with pyrethroid-resistant head lice in an epidemic area, Okinawa, Japan.

Pyrethroid insecticides are the only pesticides approved for the treatment of head lice (pediculosis capitis) infestations in Japan. However, in Okinawa Prefecture, 96% of head lice are resistant to pyrethroids. Here, we conducted a clinical trial to assess the safety and efficacy of a dimethicone preparation against head lice infestations in Okinawa Prefecture. Dimethicone-containing lotion was applied over the entire scalp three times over a 7-day period. Lice bodies (nymphs/adults) and eggs (nits) were counted before (day 0) and after treatment (day 8); a subset of eggs was collected to estimate viability based on hatch rate. Efficacy was evaluated based on improvement (reduction) in head lice counts post-treatment with respect to baseline. Safety was evaluated based on subjects' scalp condition and adverse event incidence. Utility was a composite end-point combining efficacy and safety. In total, 35 subjects were enrolled. Efficacy and safety were evaluated in 23 and 35 subjects, respectively. No side-effects of note were reported during the treatment period. The dimethicone lotion resulted in a utility rating of "marginally useful" or higher in over 80% of the study population, signifying the formulation to be both safe and effective. The dimethicone lotion was also a potent ovicide; 99.4% of eggs collected after treatment failed to hatch when incubated. Eradication of head lice remained successful for at least 4 weeks after the final topical dimethicone application in 25 of the 28 subjects reached by telephone survey. Lice bodies and eggs were genotyped to analyze the prevalence of three knockdown resistance (kdr)-type mutations within the voltage-sensitive sodium channel known to confer pyrethroid resistance. One or more kdr mutations were confirmed in 30 of the 32 subjects from whom specimens were collected (93.8%). Dimethicone was confirmed to be both safe and effective in treating pyrethroid-resistant head lice.

Utility of the Dermatology Life Quality Index at initiation or switching of biologics in real-life Japanese patients with plaque psoriasis: Results from the ProLOGUE study.

BACKGROUND: Plaque psoriasis significantly affects patients' health-related quality of life. To aid treatment decisions, not only objective assessment by physicians but also subjective assessment by patients is important. OBJECTIVE: To assess the significance of Dermatology Life Quality Index (DLQI) evaluation at the time of biologics introduction in clinical practice in Japanese patients with plaque psoriasis. METHODS: This was a single-arm, open-label, multicenter study. At baseline, Psoriasis Area and Severity Index (PASI) and DLQI scores were measured and stratified based on DLQI scores ≥6/≤5 and PASI scores ≤10/>10. Other patient-reported outcomes assessed included EQ-5D-5L, itch numerical rating scale (NRS), skin pain NRS, Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-8 (PHQ-8), Sleep Problem Index-II (SPI-II), and Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9). RESULTS: Of the 73 enrolled patients, 23 had PASI scores ≤10. Those with PASI/DLQI scores >10/≥6 had a significantly higher median PASI score than those with PASI/DLQI scores >10/≤5 (p = 0.0125). Regardless of PASI scores (>10/≤10), median itch NRS and GAD-7 scores were significantly higher in patients with DLQI scores ≥6 than in those with DLQI scores ≤5 (itch NRS, p = 0.0361 and p = 0.0086, respectively; GAD-7, p = 0.0167 and p = 0.0273, respectively). Patients with PASI/DLQI scores ≤10/≥6 had significantly higher skin pain NRS (p = 0.0292) and PHQ-8 (p = 0.0255) scores and significantly lower median SPI-II scores (p = 0.0137) and TSQM-9 Effectiveness domain scores (p = 0.0178) than those with PASI/DLQI scores ≤10/≤5. CONCLUSION: DLQI may be useful for assessing patients' concerns that cannot be identified by PASI alone while initiating biologics or switching from other biologics in clinical practice.

Effects of synchronised engine sound and vibration presentation on visually induced motion sickness.

Driving simulator usage is often accompanied by motion sickness, and techniques for its prevention are not yet established. To reduce visually induced motion sickness (VIMS), we investigated the effects of synchronised presentation of engine sounds and motorcycle vibration on VIMS. A total of 80 participants experienced a driving scene with a head-mounted display for 5 minutes with or without synchronised presentation of engine sound and vibration. The results showed that VIMS scores, as measured by the Fast Motion Sickness scale, were significantly lower in participants who experienced the driving scene with sounds and vibration than in those who experienced the scene with sounds only, vibration only, or neither. Multiple regression analyses revealed that susceptibility to VIMS consistently explained the severity of VIMS to some extent but not with perceived realism of the virtual reality (VR) scene, sex, and experiences about VR devices and vehicles. This study demonstrated that simultaneous presentation of engine sounds and vibration, which were synchronous to each other and tightly coupled with the visual flow speed, effectively reduces VIMS while experiencing motorcycling simulators. The findings not only improve practical knowledge for reducing VIMS in driving simulators but also provide evidence for understanding the mechanisms of VIMS.

Clinical characteristics of hidradenitis suppurativa patients in Okinawa, Japan: Differences between East Asia and Western countries.

Hidradenitis suppurativa (HS) is a long-term inflammatory follicular disease. In Western countries, the prevalence of HS has been estimated to be 0.1-4% in the general population. In Okinawa Prefecture, the southernmost area of Japan, HS is more frequent than in other parts of Japan. The aim of this study is to elucidate the epidemiological features of HS patients in Okinawa, Japan, to determine the factors correlated with severity and to compare characteristics of HS patients in East Asia and Western countries. This study was a retrospective, single-center, case series study. Data of patients with HS diagnosed at the University of the Ryukyus Hospital from April 2010 to March 2019 were collected and compared with data of previous studies performed in Japan, Korea, France and the USA. There were 42 male and 16 female HS patients (age range, 15-76 years). The median modified Sartorius score was 49 (interquartile range, 87.3). A multivariate analysis indicated that disease duration was associated with the modified Sartorius score. The ratio of serum C-reactive protein to albumin was significantly correlated with disease severity (rs  = 0.64, P < 0.001). Overall, in East Asia, HS was more common in males, and very few patients had a family history of HS (1.7% vs 29.1%, P < 0.001) compared with Western countries. This study revealed the characteristics of HS patients in Okinawa and elucidated the differences between the epidemiology of HS in Western countries and East Asia. In addition, we found out factors that correlated with disease severity such as disease duration and serum C-reactive protein to albumin ratio.

Dermatopathic reaction of lymph nodes in HTLV-1 carriers: a spectrum of reactive and neoplastic lesions.

AIMS: Dermatopathic reaction is a histopathological finding of lymph nodes that usually occurs in patients with inflammatory pruritic cutaneous lesions. However, it is sometimes seen in patients with cutaneous T cell lymphoma. Adult T cell leukaemia/lymphoma (ATLL) is a T cell malignancy caused by infection with human T cell leukaemia virus type I (HTLV-1), which is frequently accompanied by cutaneous lesions. However, the detailed clinicopathological characteristics of the dermatopathic reaction of lymph nodes in ATLL patients and HTLV-1 carriers, addressed in this study, remains to be clarified. METHODS AND RESULTS: We retrospectively analysed 18 nodal lesions with dermatopathic reaction in HTLV-1 carriers. Axillary and inguinal lymph nodes were the primary affected tissues. Three cases with atypical lymphoid cell infiltration were defined as ATLL with dermatopathic reaction (ATLL-D), showing an abnormal T cell immunophenotype and T cell monoclonality. Two of the three ATLL-D patients died 14 and 7 months after diagnosis (the third case had a very short follow-up). The other 15 patients were indistinguishable from reactive lesions and were defined as HTLV-1-associated lymphadenitis with dermatopathic reaction (HAL-D). They showed an indolent clinical course, with only one case eventually transforming to aggressive disease. CONCLUSIONS: Lymph node lesions accompanied by dermatopathic reaction in HTLV1 carriers represent a spectrum that includes reactive and neoplastic conditions. HAL-D should be distinguished from ATLL-D, especially to avoid overtreatment.

Mycobacterium tuberculosis infection in psoriatic patients treated with biologics: Real-world data from 18 Japanese facilities.

Although rare, tuberculosis has been reported with biologic treatment against psoriasis in Japan, a tuberculosis medium-burden country. Mycobacterial infection often develops after a long incubation period and might not have been adequately identified in clinical trials or post-marketing surveillance. To determine the real-world incidence of tuberculosis in psoriatic patients treated with biologics, we conducted a retrospective, multicenter, observational study in 18 facilities in Western Japan. Psoriatic patients who visited a participating facility between 2010 and March 2017 and received biologic reagents were enrolled. Information on sex, age at first biologic treatment, results of interferon-γ release assay (IGRA) for Mycobacterium tuberculosis, treatment history with isoniazid, and onset of active and/or latent tuberculosis was collected. A total of 1117 patients (830 men and 287 women) were enrolled. The mean duration of biologic treatment was 3.54 years. Sixty-five patients (5.8%) showed positive IGRA results at screening. Active tuberculosis developed in two patients after the administration of tumor necrosis factor inhibitors (both involved miliary tuberculosis). Latent tuberculosis was observed in two patients treated with anti-interleukin-12/23p40 antibody. The incidence rate of tuberculosis, including latent tuberculosis, in this survey was 0.36%. Although the incidence rate of tuberculosis was low considering the observation period of biologic treatment, active tuberculosis was found in both the screening-negative group and a screening-positive subject after isoniazid prophylaxis (both miliary tuberculosis), concluding that negative screening or isoniazid treatment does not always assure that an individual has no tuberculosis. Hence, dermatologists still need to pay careful attention to tuberculosis at every patient visit.

Efficacy and Safety of Vonoprazan in Patients With Nonerosive Gastroesophageal Reflux Disease: A Randomized, Placebo-Controlled, Phase 3 Study.

OBJECTIVES: To assess the efficacy and safety of vonoprazan on heartburn symptoms in patients with nonerosive reflux disease (NERD) (ClinicalTrials.gov: NCT02954848). METHODS: This phase 3, double-blind, placebo-controlled study included Japanese patients aged 20 years and older with grade N/M NERD and recurrent heartburn. Patients received placebo (n = 245) or vonoprazan 10 mg (n = 238) for 4 weeks. The primary efficacy outcome was frequency of heartburn experienced by patients during the treatment period (proportion of days without heartburn). Other outcomes included cumulative improvement rates of heartburn, proportion of patients with complete heartburn resolution in the fourth week of treatment, and safety. RESULTS: Compared with placebo, the proportion of days without heartburn was not significantly higher in the vonoprazan group in the full analysis (primary end point, 72.55% vs 61.50%, vonoprazan vs placebo, P = 0.0643) but was significantly higher in the per-protocol-set sensitivity analysis (P = 0.0341). Early onset of response and significantly greater cumulative improvement rates of heartburn were observed in the vonoprazan group (P = 0.0003). In a post hoc analysis, a greater proportion of patients with complete heartburn resolution in the fourth week of treatment were reported in the vonoprazan group (P = 0.0023). Incidence of treatment-emergent adverse events was similar between treatment groups (23.5% vs 23.3%); most treatment-emergent adverse events were mild in severity. DISCUSSION: Although vonoprazan 10 mg was not superior to placebo with respect to proportion of days without heartburn in Japanese patients with NERD, vonoprazan had a significantly higher cumulative rate of heartburn resolution and was well tolerated.

Extracellular signal-regulated kinase activation of self-healing Langerhans cell histiocytosis: A case report.

A 3-month-old boy developed small papules on his trunk. After the papules increased in number, the patient was diagnosed with Langerhans cell histiocytosis based on the pathological findings. He was referred to our department for further examination. Upon initial examination, the papules and nodules were scattered on his back, abdomen and lumbar region. Because he did not present with any organ involvement except the skin, he was diagnosed with single-system and skin-limited Langerhans cell histiocytosis. Skin rashes were treated with a topical steroid and started regressing 3 months after onset. All papules disappeared 6 months after onset. In this boy, the Langerhans cell histiocytosis tumor cells expressed phosphorylated extracellular signal-regulated kinases. In Langerhans cell histiocytosis, BRAF V600E and other genes are known to mutate to act as driver mutations in stem cells of the myeloid dendritic cell lineage. Consequently, extracellular signal-regulated kinases are continuously activated, which contributes to Langerhans cell histiocytosis carcinogenesis.