A Case of Generalized Pustular Psoriasis with Organizing Pneumonia During Treatment for Rheumatoid Arthritis.

Generalized pustular psoriasis (GPP) is a disease that presents with fever and multiple sterile pustules on flushed skin all over the body. GPP should be considered as systemic inflammatory response syndrome (SIRS), and is occasionally associated with respiratory failure. We encountered a case of GPP with organizing pneumonia (OP) during treatment for rheumatoid arthritis (RA). A 74-year-old Japanese woman with RA developed fever and erythema with small pustules on the trunk and extremities. She was diagnosed as GPP and admitted to our hospital. During the clinical course, she suffered hypoxia from OP. Although RA and OP are known to coexist, GPP and OP share the involvement of cytokines such as interleukin 8 in the pathogenesis. These cytokines are therefore also involved in the complications of GPP and OP.

Summary of certolizumab pegol in psoriasis including structural features, pharmacokinetics and treatment.

Psoriasis pathogenesis involves TNF-α, IL-23 and IL17, against which biologics have been highly effective. Among the five TNF-α inhibitors available for psoriasis, namely infliximab, adalimumab, etanercept, golimumab and certolizumab pegol (CZP), CZP has a unique mechanism of action due to its structure. As CZP lacks the Fc region, it does not cross the placenta and can be safely used in pregnant women. Its PEGylated nature allows for longer distribution time in tissues, potentially leading to a longer-lasting effect compared with other TNF-α inhibitors. In clinical trials, the efficacy of CZP on psoriasis skin symptoms and joint symptoms was comparable to other TNF-α inhibitors, with no discernible differences in safety profiles.

Psoriasis is a skin condition that affects the skin and causes joint problems. There are some medicines called TNF-α inhibitors that work well, especially for the joint issues. There are currently five TNF-α inhibitors available for treating psoriasis. One of these, certolizumab pegol, is different from the others. It lacks a specific part, which makes it less likely to pass through the placenta. This means it's safer for pregnant and breastfeeding women. Clinical trials have shown that certolizumab pegol is just as effective as other TNF-α inhibitors for treating the skin and joint symptoms of psoriasis. It's also equally safe.

Epidemiological analysis of the patients with psoriasis in Asian countries and region using the same clinical case cards between 2020 and 2022.

Although many epidemiological surveys for patients with psoriasis have been reported based on individual countries or facilities, there has been no study encompassing the major countries or the region in Asia. The Asian Society for Psoriasis (ASP) has been conducting an epidemiological study across various Asian countries and regions to elucidate the and compare the epidemiology of psoriasis. A total of 1948 cases were analyzed, with 938 cases from Japan, 530 cases from China, 325 cases from Korea, 141 cases from Chinese Taipei, and 14 cases from Thailand, all of which were enrolled between 2020 and 2022. In the Asian region total, the male-female ratio was 1.87:1 and the peak age at disease onset was 20-29 years. The proportion of psoriasis vulgaris (PsV), psoriatic arthritis (PsA), and pustular psoriasis (PP) was 80.1%, 17.7%, and 2.2%, respectively, and PsA was more commonly associated with nail symptoms than psoriasis vulgaris (PsV). Of the patients, 13% had a familial history of psoriasis and the most frequently affected family member was the father. Regarding treatment, 78.3% of the patients received topical medications, 9.0% underwent phototherapy, 34.0% received oral medications, and 36.1% were treated with biological agents. This study provided valuable information on the epidemiology and treatment of psoriasis using the registry data collected with the common reporting form in the same period in major Asian countries and regions. Male predominance is a distinctive feature of psoriasis in Asia. This epidemiological data registry in the ASP will continue afterwards.

Case of Exacerbation of Psoriasis Following COVID-19 Vaccination During Treatment with Brodalumab, Which Resulted in Secondary Failure.

A 43-year-old Japanese man who had suffered psoriasis vulgaris for eight years visited our hospital. His comorbidities were dyslipidemia, hyperuricemia, and obesity. He received phototherapy for six months, which did not result in improvement. Following treatment with brodalumab, his skin symptoms improved. However, seven months after brodalumab treatment, he received two doses of the mRNA-1273 COVID-19 vaccine, with a one-month interval between doses. One month following the second vaccination, his skin symptoms were exacerbated. He received additional NB-UVB therapy, but his skin symptoms did not improve. Nine months after the addition of NB-UVB therapy, treatment was switched to bimekizumab, and his skin became almost clear. Psoriasis is often associated with comorbidities like metabolic syndrome. Currently, additional COVID-19 vaccination is recommended for high-risk cases such as those with metabolic syndrome. Therefore, it is essential to remain vigilant regarding the potential exacerbation of psoriasis following COVID-19 vaccination even during treatment with highly effective biologic therapy.

A Case of Disseminated Cutaneous Sporotrichosis Mimicking Sarcoidosis, that Required Four Biopsies to Diagnose.

A 69-year-old Japanese woman visited Tokai University Oiso hospital with cutaneous ulcers on her left upper arm that appeared in January 2013, and on her right nose that appeared in December of 2013. Neither the two biopsies and tissue culture from the arm lesion nor the biopsy and tissue culture from the nose lesion detected any organism. In December of 2013, she was diagnosed as cutaneous sarcoidosis at Oiso hospital and treated with oral prednisolone for six months, however, did not show improvement. In June of 2014, third skin biopsy and culture from her left upper arm was done at our hospital, and also could not detect any organism. After six months of continuing treatment with oral steroids and steroid injections, the cutaneous ulcers became enlarged, with purulent exudate, requiring a fourth skin biopsy and culture from left upper arm, which finally detected Sporotrichosis. After one-month administration of itraconazole, in January of 2015, cutaneous ulcers of both the arm and nose shrunk. Sporotrichosis mimics sarcoidosis as well as other skin conditions clinically and histologically, therefore recognizing the importance of carrying out multiple skin biopsies and cultures are imperative to prevent misdiagnosis and improper treatments and possible dissemination.

Zinc Deficiency with Cheilitis: A Report of Five Cases.

Zinc deficiency has long been known as acrodermatitis enteric dermatitis (congenital zinc deficiency). On the other hand, acquired zinc deficiency has attracted attention as a familiar disease in recent years. Epidemiological studies in Japan have shown that acquired zinc deficiency is more common than expected. It is also known that serum zinc levels fall markedly with age. In this report, several cases of acquired zinc deficiency that caused cheilitis are described. In all cases, the only symptom was cheilitis, the serum zinc level was low, and all cases were relieved by zinc supplementation. Zinc deficiency is associated with a range of pathological conditions, including mucocutaneous symptoms, delayed wound healing, dysgeusia, anemia, impaired immunity, and retarded growth development disorders. However, zinc deficiency may be overlooked even in cases of cheilitis alone. Especially in intractable cases, it is important to suspect zinc deficiency as one at the differential diagnoses.

Case of Wound Myiasis in a Squamous Cell Carcinoma Lesion of the Scalp.

Myiasis refers to the infestation of living humans and vertebrate animals by dipterous larvae. Many organs can be infested by fly larvae, but cutaneous and wound myiases are the most frequently encountered clinical forms. Persistent ulcer or non-healing wound is one of the symptoms of squamous cell carcinoma which is the second most common skin cancer in the world. Here we report a case of an elderly man with a severe wound myiasis in a squamous cell carcinoma lesion of the scalp. The maggots were confirmed to be Lucilia sericata which are widespread flies in Japan. Human myiasis is rarely reported in Japan, but patients with necrotic, hemorrhaging, or pus-filled wounds are susceptible to infestation. It is necessary for doctors and nurses to ensure that their patients change their dressings daily and keep their wounds clean.

Biological Retention Rates, the Reasons of Switching, and Prognostic Factors in Patients with Psoriasis Treated Biologics.

OBJECTIVE: To review patients who were treated at Tokai University Hospital with biologic agents for psoriasis vulgaris and psoriatic arthritis and analyze the biological retention rate, reasons for switching biologics, and investigate possible clinical prognostic factor which may affect whether a patient preferred one biologic to another. METHODS: Clinical courses of 63 patients who received biologic agents between Sep of 2010 to June of 2019 were investigated. Biological retention rate of each biologic agents, reasons of switching to another biologic agent, and prognostic factors, if any, between switched and non-switched patients were examined. RESULTS: The biological retention rate of ustekinumab (UST) was significantly longer than that of infliximab (IFX) or adalimumab (ADA). The major reason of switching was due to secondary loss of efficacy. Patients being treated with UST were more likely to switch to another biologic when they exhibited nail lesions. CONCLUSION: These results suggested that biological retention rate of UST was superior than that of IFX or ADA. Furthermore, with patients administered UST, nail symptom suggested possible clinical prognostic factor for switching to other biologic agents.

New Treatment Addressing the Pathogenesis of Psoriasis.

Psoriasis is an immune cell-mediated inflammatory skin disease. The interleukin (IL)23/IL17 axis plays an important role in the development of psoriasis. The effectiveness of biologic treatments such as tumor necrosis factor (TNF)α inhibitors (infliximab, adalimumab, certolizumab pegol), IL23 inhibitors (ustekinumab, guselkumab, tildrakizumab, risankizumab), and IL17 inhibitors (secukinumab, ixekizumab, brodalumab) have verified these findings. Immune-related cells such as dendritic cells (DCs) and macrophages, in addition to Toll-like receptors and cytokines such as interferon (IFN)α, TNFα, IFNɤ, IL12, IL22, IL23, and IL17, are related to the pathogenesis of psoriasis. Here, we first review new insights regarding the pathogenesis of psoriasis, as it relates to DCs, Langerhans cells, macrophages, the signal transducer and activator of transcription 3 pathway, and aryl hydrocarbon receptor in cutaneous vascular endothelial cells. Based on these findings, we summarize currently available oral treatments and biologics. Furthermore, we describe a new treatment option including Janus kinase inhibitor, tyrosine kinase 2 inhibitor, modulator of sphingosine 1-phosphate receptor 1, and Rho-associated kinase 2 inhibitor.

Analyses of kinetic glass transition in short-range attractive colloids based on time-convolutionless mode-coupling theory.

For short-range attractive colloids, the phase diagram of the kinetic glass transition is studied by time-convolutionless mode-coupling theory (TMCT). Using numerical calculations, TMCT is shown to recover all the remarkable features predicted by the mode-coupling theory for attractive colloids: the glass-liquid-glass reentrant, the glass-glass transition, and the higher-order singularities. It is also demonstrated through the comparisons with the results of molecular dynamics for the binary attractive colloids that TMCT improves the critical values of the volume fraction. In addition, a schematic model of three control parameters is investigated analytically. It is thus confirmed that TMCT can describe the glass-glass transition and higher-order singularities even in such a schematic model.

Pediatric case of anaplastic lymphoma kinase-positive anaplastic large cell lymphoma forming a solitary skin tumor on the forearm.

A 5-year-old girl noticed a rapidly growing reddish nodule on her right forearm. Although oral antibiotics had been administrated for 2 weeks, the tumor enlarged. Skin biopsy revealed excessive infiltration of atypical neoplastic cells expressing CD4, CD30 and anaplastic lymphoma kinase (ALK). These histological and immunohistochemical findings were consistent with anaplastic large cell lymphoma (ALCL). Computed tomography showed multiple lymphadenopathy, but lymph node biopsy and bone marrow examination did not show any evidence of systemic dissemination. However, due to the positive results for ALK and multiple lymphadenopathy, we diagnosed ALK-positive ALCL forming a solitary skin tumor on the forearm. The patient received chemotherapy and presented marked improvement. This paper discusses the difficulty of diagnosing pediatric ALK-positive ALCL limited to the skin and reviews the medical published work.

Comparison of mode-coupling theory with molecular dynamics simulations from a unified point of view.

We study the tagged-particle dynamics by solving equations of the mode-coupling theory (MCT). The numerical solutions are compared with results obtained by the molecular dynamics (MD) simulations from a unified point of view proposed by Tokuyama [Phys. Rev. E 80, 031503 (2009)]. We propose a way of comparison in which the reduced long-time self-diffusion coefficient is used to characterize states of the system. The comparison reveals that the tagged-particle dynamics calculated from MCT qualitatively deviates from that obtained by MD. Our results suggest that the deviation originates from the starting equation of MCT.

Universality in self-diffusion of atoms among distinctly different glass-forming liquids.

The long-time self-diffusion coefficients D(S)(L) in distinctly different glass-forming liquids are analyzed from a unified point of view recently proposed by the present author. It is shown that as long as the systems are in equilibrium, they are all described by the following two types of master curves, depending on whether the control parameter is intensive or extensive: D(S)(L)(x) = d(0)x(-1)(1 - x)(2+η) exp[cx(3+η)(1 - x)(2+η)] for a reduced intensive control parameter x, such as a reduced inverse temperature, and D(S)(L)(x) = d(0)x(-1)(1 - x)(2) for a reduced extensive control parameter x, such as a reduced volume fraction, where d(0) and c are constant. Here, the exponent η (≠0) results from many-body correlations in a supercooled liquid state. The constants η and c depend on the systems and are given by (η,c) = (4/3,62) for fragile liquids, (5/3, 62) for strong liquids, and (0,0) for other glass-forming systems in which the peak heights of their non-Gaussian parameters are always much less than 1.0. It is also shown that all of the data for the diffusion coefficient start to deviate from the master curves at lower temperatures (or higher volume fraction), where the systems become out of equilibrium, leading to a glass state.

Self-diffusion of biomolecules in solution.

A simple soft-core model potential is proposed to discuss the self-diffusion of biomolecules in solution. Extensive Brownian-dynamics simulations are performed to obtain the long-time self-diffusion coefficient. Then the simulation results are compared with the experimental data from a unified point of view recently obtained for suspensions of hard spheres. Thus, it is shown that the proposed potential can qualitatively well describe the experimental data.

Dynamics of a single atom in ternary metallic glass-forming Cu60Ti(x)Zr(40-x) melts by molecular-dynamics simulations.

The recently proposed universality near the glass transition [M. Tokuyama, Phys. Rev. E 80, 031503 (2009)] is tested for the dynamics of a single atom in ternary metallic glass-forming Cu60Ti(x)Zr(40-x) melts by using molecular-dynamics simulations for different compositions, x = 10, 20, and 30. First, a master curve for the dynamics of the atom, such as the mean-square and mean-fourth displacements, is shown to exist independently of x if the long-time self-diffusion coefficient D(S)(L) has the same value. Second, a master curve for the temperature dependence of D(S)(L) is shown to exist independently of x. Finally, master curves for characteristic length and time scales of the atom are also shown to exist independently of x.

Single master curve for self-diffusion coefficients in distinctly different glass-forming liquids.

An existence of a single master curve for the long-time self-diffusion coefficients D(S)(L)(T) in diversely different glass-forming liquids is predicted over wide temperature T ranges above the glass transition point T(g) by analyzing various experimental and simulation data consistently from a unified point of view based on the mean-field theory recently developed. In order to scale those data appropriately, the power-law dependence of the α- and the ß-relaxation times on D(S)(L) is used. Then, it is shown that any equilibrium data for self-diffusion of atom in different systems are all collapsed onto a singular function f(T(f)((α))/T) , where T(f)((α)) is a fictive singular temperature of atom α. Thus, we emphasize that any equilibrium self-diffusion data can be described by a single master curve f(x) above T(g)(>T(f)), while the data out of equilibrium start to deviate from f(x) around T(g).

Universality in multicomponent glass-forming liquids near the glass transition.

The slow dynamics of a single particle in multicomponent glass-forming systems including fragile and strong glasses is studied from a unified point of view. The simulation results on two different systems, bulk glass-forming Cu60Ti20Zr20 melt and network-forming SiO2 , melt are analyzed by the mean-field theory (MFT) recently proposed and are compared with other systems near the glass transition. It is shown that the simulation results for the mean-square displacement are all collapsed into a master curve given by MFT if a long-time self-diffusion coefficient has the same value in each system. It is also shown that each long-time self-diffusion coefficient is described well by a singular function predicted recently from first principles. Thus, we conclude that there exists a simple universal mechanism near the glass transition even among any diversely different glass-forming systems.

Slow dynamics and re-entrant melting in a polydisperse hard-sphere fluid.

Extensive molecular dynamics simulations are performed at 6% polydispersity to investigate the phase diagram of a polydisperse hard-sphere fluid and the dynamical behavior in each phase. As the volume fraction phi is increased, the existence of a supercooled liquid is suggested above phi = 0.5524 by the mean-field analysis proposed recently. The first-order phase transition from supercooled liquid to crystal is then shown to occur around phi = 0.5630. The occurrence of re-entrant melting, a first-order phase transition from crystal to supercooled liquid, is also found around phi = 0.5715. The existence of the glass transition is thus suggested, even in the hard-sphere fluid with small polydispersity.