Effects of IL-17 on Epidermal Development

Immunotherapies targeting interleukin 17 (IL-17) have a strong effect on plaque psoriasis. However, many previous studies on IL-17 focused only on the T-helper 17 (Th17) immune response, and a few studies have reported that IL-17A may affect psoriatic epidermal structure. IL-17 includes six family members, namely IL-17A–F, which are involved in a wide variety of biological responses. IL-17A is produced mainly by Th17 cells or group 3 innate lymphoid cells (ILC3), while IL-17C is locally produced by epithelial cells, such as keratinocytes. In contrast to IL-17C, which is locally produced in various cells such as keratinocytes, it is predicted that IL-17A, which is produced by limited cells and has systemic effects, has different roles in epidermal development. For example, several research studies have shown that IL-17A affects terminal differentiation of epidermis by suppressing the expression of filaggrin or loricrin in keratinocytes. On the other hand, IL-17C, which is produced by keratinocytes themselves, does not have as strong as an effect on epidermal development as IL-17A. In this chapter, we summarized the effects of IL-17A and other IL-17 members on epidermal development and their comprehensive roles based on previously reported papers

Distribution of diffuse plexiform neurofibroma on the body surface in patients with neurofibromatosis 1

Neurofibromatosis 1 (NF1) is a genetic disease characterized by cutaneous, neurological and osseous abnormalities. Approximately 20% of patients develop plexiform neurofibroma (PN), resulting in impaired quality of life. To evaluate distribution of diffuse PN on the body surface, a retrospective study was conducted for 354 patients with NF1 from 2007 to 2018 in Japan. We investigated a total of 40 patients with clinically apparent superficial diffuse PN. In the cases evaluated, 57.4% of the diffuse PN were located on the trunk, 19.2% the head and neck, 12.8% the lower limbs and 10.6% the upper limbs. Remarkably, 75.0% of the diffuse PN were located on the dorsal side. The frequency was significantly higher on the trunk than on the head and neck (P = 0.026). Our findings provide useful information for giving attention to the high possibility of diffuse PN on the dorsal side before progression in childhood and for future treatment in NF1

Epidemiological Analysis of Major Complications Requiring Medical Intervention in Patients with Neurofibromatosis 1

Neurofibromatosis 1 has various complications. To elucidate the frequency of neurofibromatosis 1-related major complications requiring medical intervention, a nationwide retrospective study was conducted of 3,530 patients with neurofibromatosis 1 registered from 2001 to 2014 in Japan. The ratio of certified patients requiring medical intervention (>stage 3) was 82%. Patients classified in the most severe grade experienced dermatological complications (71.8% of patients), neurological complications (38.1%) and bone complications (33.3%). In patients with dermatological manifestations, medical treatment was needed for cutaneous neurofibromas (58%), diffuse plexiform neurofibromas (31%) and malignant peripheral nerve sheath tumours (10%). Patients with neurological manifestations needed medical treatment mainly for brain tumours (53%) and intellectual disability (26%). Patients with bone manifestations needed medical treatment for pseudoarthrosis (9%), scoliosis (55%) and bone defects (16%). It is necessary for physicians to be aware of neurofibromatosis 1-related complications requiring medical intervention in order to provide appropriate care for patients with neurofibromatosis 1

Activation Pattern of Langerhans Cells in the Afferent and Efferent Phases of Contact Hypersensitivity

Langerhans cells are MHC class II (Ia) positive antigen- presenting cells that play a crucial role in the induction of contact hypersensitivity (CHS). The topical application of a hapten modifies the cell surface moieties of Langerhans cells, and activates Langerhans cells to increase their size and Ia intensity. The haptenated and activated Langerhans cells emigrate from the epidermis and thus the in situ density of Langerhans cells usually decreases during 24-48h after the hapten application in CHS. To determine whether the early activation pattern of Langerhans cells is different between the afferent phase and the efferent phase of CHS, we compared the density and morphologic changes of Langerhans cells in CHS to trinitrochlorobenzene using nonsensitized and sensitized mice. We found that the application of a hapten induces more significant enlargement of Langerhans cell size in the afferent phase than in the efferent phase, whereas the reduction of Langerhans cell density is more marked in the efferent than in the afferent phase of CHS. Moreover, topical immunosuppressive drugs inhibit the in situ activation of Langerhans cells

Subcutaneous Nodule on the Right Palm of a Young Boy : A Quiz

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Transient improvement of urticaria induces poor adherence as assessed by Morisky Medication Adherence Scale-8.

Poor adherence to medication is a major public health challenge. Here, we aimed to determine the adherence to oral and topical medications and to analyze underlying associated factors using the translated Japanese version of Morisky Medication Adherence Scale-8 regarding urticaria treatment. Web-based questionnaires were performed for 3096 registered dermatological patients, along with a subanalysis of 751 registered urticaria patients in this study. The adherence to oral medication was significantly associated with the frequency of hospital visits. Variables that affected the adherence to topical medication included age and experience of drug effectiveness. The rate of responses that "It felt like the symptoms had improved" varied significantly among the dermatological diseases treated with oral medications. Dermatologists should be aware that adherence to the treatment of urticaria is quite low. Regular visits and active education for patients with urticaria are mandatory in order to achieve a good therapeutic outcome by increasing the adherence

Rapid and sustained improvements in Generalized Pustular Psoriasis Physician Global Assessment scores with spesolimab for treatment of generalized pustular psoriasis flares in the randomized, placebo-controlled Effisayil 1 study

BACKGROUND: Effisayil 1 was a randomized, placebo-controlled study of spesolimab, which is an anti-IL-36 receptor antibody, in patients presenting with a generalized pustular psoriasis flare. OBJECTIVE: To assess the effects of spesolimab over the 12-week study. METHODS: The primary endpoint of the study was Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 at week 1. Patients (N = 53) were randomized (2:1) to receive a single intravenous dose of 900 mg spesolimab or placebo on day 1. Patients could receive open-label spesolimab for persistent flare symptoms on day 8. RESULTS: Most patients receiving spesolimab achieved a GPPGA pustulation subscore of 0 (60.0%) and GPPGA total score of 0 or 1 (60.0%) by week 12. In patients randomized to placebo who received open-label spesolimab on day 8, the proportion with GPPGA pustulation subscore of 0 increased from 5.6% at day 8 to 83.3% at week 2. No factors predictive of spesolimab response were identified in patient demographics or clinical characteristics. LIMITATIONS: The effect of initial randomization was not determined conventionally beyond week 1 due to patients receiving open-label spesolimab. CONCLUSION: Rapid control of generalized pustular psoriasis flare symptoms with spesolimab was sustained over 12 weeks, further supporting its potential use as a therapeutic option for patients

Poor adherence to medication as assessed by the Morisky Medication Adherence Scale-8 and low satisfaction with treatment in 237 psoriasis patients

Previously we assessed the medication adherence for oral and topical remedies by a translated Japanese version of the Morisky Medication Adherence Scale-8 (MMAS-8) together with socioeconomic backgrounds in 3096 Japanese dermatological patients, and found the medication adherence, especially to topical drugs, was poor in these patients. In order to elucidate the disease-specific sociomedical factors, we further sub-analyzed the medication adherence in 237 psoriasis patients and compared it with that in other dermatological diseases such as atopic dermatitis, urticaria or tinea. This study was conducted among patients registered in monitoring system and 3096 eligible patients were enrolled. Our web-based questionnaire included the following items such as age, sex, annual income, main health-care institution, experience of effectiveness by oral or topical medication, overall satisfaction with treatment, and MMAS-8 for oral or topical medication. Mean adherence score by MMAS-8 was 5.2 for oral and 4.3 for topical medication. More patients with psoriasis used a university hospital and fewer used a private clinic compared with those with the other skin disease patients. Experience of drug effectiveness by oral medication and overall satisfaction with treatment was lower in psoriasis patients than in other patients. In oral medication, significantly better adherence was observed in those of higher age and with higher annual income. The adherence to medication, especially to topical drugs, was poor in 237 psoriasis patients. We speculated that some severe psoriasis patients were not sufficiently treated systemically and were resistant to topical therapy, leading to poor adherence

Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis

BACKGROUND Two phase 3 trials (UNCOVER-2 and UNCOVER-3) showed that at 12 weeks of treatment, ixekizumab, a monoclonal antibody against interleukin-17A, was superior to placebo and etanercept in the treatment of moderate-to-severe psoriasis. We report the 60-week data from the UNCOVER-2 and UNCOVER-3 trials, as well as 12-week and 60-week data from a third phase 3 trial, UNCOVER-1. METHODS We randomly assigned 1296 patients in the UNCOVER-1 trial, 1224 patients in the UNCOVER-2 trial, and 1346 patients in the UNCOVER-3 trial to receive subcutaneous injections of placebo (placebo group), 80 mg of ixekizumab every 2 weeks after a starting dose of 160 mg (2-wk dosing group), or 80 mg of ixekizumab every 4 weeks after a starting dose of 160 mg (4-wk dosing group). Additional cohorts in the UNCOVER-2 and UNCOVER-3 trials were randomly assigned to receive 50 mg of etanercept twice weekly. At week 12 in the UNCOVER-3 trial, the patients entered a long-term extension period during which they received 80 mg of ixekizumab every 4 weeks through week 60; at week 12 in the UNCOVER-1 and UNCOVER-2 trials, the patients who had a response to ixekizumab (defined as a static Physicians Global Assessment [sPGA] score of 0 [clear] or 1 [minimal psoriasis]) were randomly reassigned to receive placebo, 80 mg of ixekizumab every 4 weeks, or 80 mg of ixekizumab every 12 weeks through week 60. Coprimary end points were the percentage of patients who had a score on the sPGA of 0 or 1 and a 75% or greater reduction from baseline in Psoriasis Area and Severity Index (PASI 75) at week 12. RESULTS In the UNCOVER-1 trial, at week 12, the patients had better responses to ixekizumab than to placebo; in the 2-wk dosing group, 81.8% had an sPGA score of 0 or 1 and 89.1% had a PASI 75 response; in the 4-wk dosing group, the respective rates were 76.4% and 82.6%; and in the placebo group, the rates were 3.2% and 3.9% (P<0.001 for all comparisons of ixekizumab with placebo). In the UNCOVER-1 and UNCOVER-2 trials, among the patients who were randomly reassigned at week 12 to receive 80 mg of ixekizumab every 4 weeks, 80 mg of ixekizumab every 12 weeks, or placebo, an sPGA score of 0 or 1 was maintained by 73.8%, 39.0%, and 7.0% of the patients, respectively. Patients in the UNCOVER-3 trial received continuous treatment of ixekizumab from weeks 0 through 60, and at week 60, at least 73% had an sPGA score of 0 or 1 and at least 80% had a PASI 75 response. Adverse events reported during ixekizumab use included neutropenia, candidal infections, and inflammatory bowel disease. CONCLUSIONS In three phase 3 trials involving patients with psoriasis, ixekizumab was effective through 60 weeks of treatment. As with any treatment, the benefits need to be weighed against the risks of adverse events. The efficacy and safety of ixekizumab beyond 60 weeks of treatment are not yet known