Coffea arabica Extract Attenuates Atopic Dermatitis-like Skin Lesions by Regulating NLRP3 Inflammasome Expression and Skin Barrier Functions.

Atopic dermatitis (AD) is a common skin disease worldwide. The major causes of AD are skin barrier defects, immune dysfunction, and oxidative stress. In this study, we investigated the anti-oxidation and anti-inflammation effects of Coffea arabica extract (CAE) and its regulation of the skin barrier and immune functions in AD. In vitro experiments revealed that CAE decreased the reactive oxygen species levels and inhibited the translocation of nuclear factor-κB (NF-κB), further reducing the secretion of interleukin (IL)-1ß and IL-6 induced by interferon-γ (IFN-γ)/tumor necrosis factor-α (TNF-α). Moreover, CAE decreased IFN-γ/TNF-α-induced NLR family pyrin domain-containing 3 (NLRP3), caspase-1, high-mobility group box 1 (HMGB1), and receptor for advanced glycation end products (RAGE) expression levels. It also restored the protein levels of skin barrier function-related markers including filaggrin and claudin-1. In vivo experiments revealed that CAE not only reduced the redness of the backs of mice caused by 2,4-dinitrochlorobenzene (DNCB) but also reduced the levels of pro-inflammatory factors in their skin. CAE also reduced transepidermal water loss (TEWL) and immune cell infiltration in DNCB-treated mice. Overall, CAE exerted anti-oxidation and anti-inflammation effects and ameliorated skin barrier dysfunction, suggesting its potential as an active ingredient for AD treatment.

Taiwanese dermatological association consensus for the definition, classification, diagnosis, and management of urticaria: A 2021 update.

Urticaria is a prevalent disease with substantial physical, psychological, and economic impacts. With the advent of understandings of the disease and the emerging evidence of treatments, the international guidelines for treating urticaria have been updated in recent years. In order to update the 2014 edition of the Taiwanese Dermatological Association (TDA) consensus of urticaria, a total of 17 dermatologists with extensive experience in urticaria management were invited to and attended the TDA consensus meetings. All the specific aspects of the content were approved by at least 75% of the experts in attendance. Comparing to the former edition, several substantial modifications were made. For diagnosis, D-dimer was added as the recommended routine test in patients with chronic spontaneous urticaria. For pharmacological management, treatment suggestions were simplified. The approved-dosed, the up-dosed second-generation antihistamines, omalizumab, and cyclosporine were listed as the first-line to the fourth-line treatment, respectively. In addition, the management for patients of special considerations, such as the elderly, children, and pregnant women, were all discussed and mentioned in the consensus. We hope the updated TDA consensus can serve as a reference for all physicians and can help the physicians providing up-to-dated managements for these patients.

Fermented Taiwanofungus camphoratus Extract Ameliorates Psoriasis-Associated Response in HaCaT Cells via Modulating NF-𝜠B and mTOR Pathways.

Psoriasis is a chronic autoimmune disease, and until now, it remains an incurable disease. Therefore, the development of new drugs or agents that ameliorate the disease will have marketing potential. Taiwanofungus camphoratus (TC) is a specific fungus in Taiwan. It is demonstrated to have anticancer, anti-inflammation, and hepatoprotective effects. However, the effects of TC fermented extract on psoriasis are under investigation. In this research, we studied the ability of TC on antioxidative activity and the efficacy of TC on interleukin-17 (IL-17A)-induced intracellular oxidative stress, inflammation-relative, and proliferation-relative protein expression in human keratinocytes. The results of a DPPH radical scavenging assay, reducing power assay, and hydroxyl peroxide inhibition assay indicated that TC has a potent antioxidant ability. Furthermore, TC could reduce IL-17A-induced intracellular ROS generation and restore the NADPH level. In the investigation of pathogenesis, we discovered TC could regulate inflammatory and cell proliferation pathways via p-IKKα/p-p65 and p-mTOR/p-p70S6k signaling pathways in human keratinocytes. In conclusion, TC showed characteristics such as antioxidant, anti-inflammatory, and anti-psoriatic-associated responses. It is expected to be developed as a candidate for oxidative-stress-induced skin disorders or psoriasis treatment.

Co-existence of Langerhans cell histiocytosis and reticulohistiocytosis with initial presentation of skull lesions: A case report.

Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder resulting from dysregulated clonal proliferation of Langerhans cells. Reticulohistiocytosis (RH) is another rare histiocytosis caused by the proliferation of histiocytes other than Langerhans cells. Co-existence of LCH and RH in different organs and in the same skin area has not been reported. We present the case of a 20-year-old woman who initially had co-existing bone LCH and cutaneous RH. After 1 year of chemotherapy with cytarabine, bone LCH significantly improved but cutaneous LCH developed in the same area where cutaneous RH was, resulting in hybrid LCH and RH of the skin. This unique history provides some evidence to support the theory that LCH and RH originate from the same stem cells and subsequently develop into hybrid LCH and RH of the skin in a cytokine environment influenced by chemotherapy. Repeat skin biopsies may be considered for adjusting treatment regimens in LCH patients whenever pre-existing skin lesions progress.

Protective Effects and Mechanisms of N-Phenethyl Caffeamide from UVA-Induced Skin Damage in Human Epidermal Keratinocytes through Nrf2/HO-1 Regulation.

The skin provides an effective barrier against physical, chemical, and microbial invasion; however, overexposure to ultraviolet (UV) radiation causes excessive cellular oxidative stress, which leads to skin damage, DNA damage, mutations, and skin cancer. This study investigated the protective effects of N-phenethyl caffeamide (K36) from UVA damage on human epidermal keratinocytes. We found that K36 reduced UVA-induced intracellular reactive oxygen species (ROS) production and induced the expression of the intrinsic antioxidant enzyme heme oxygenase-1 (HO-1) by increasing the translocation of nuclear factor erythroid 2⁻related factor 2 (Nrf2). K36 could inhibit the phosphorylation of extracellular-signal-regulated kinase (ERK) and c-Jun N-terminal kinases (JNK) and reduce UVA-induced matrix metalloproteinase (MMP)-1 and MMP-2 overexpression; it could also elevate the expression of tissue inhibitors of metalloproteinases (TIMP). In addition, K36 ameliorated 8-hydroxy-2'-deoxyguanosine (8-OHdG) induced by UVA irradiation. Furthermore, K36 could downregulate the expression of inducible nitric oxide synthase (iNOS) and interleukin-6 (IL-6) and the subsequent production of nitric oxide (NO) and prostaglandin E2 (PGE2). Based on our findings, K36 possessed potent antioxidant, anti-inflammatory, antiphotodamage, and even antiphotocarcinogenesis activities. Thus, K36 has the potential to be used to multifunctional skin care products and drugs.

Protective effects and mechanisms of Terminalia catappa L. methenolic extract on hydrogen-peroxide-induced oxidative stress in human skin fibroblasts.

BACKGROUND: Oxidative stress plays a crucial role in aging-related phenomenon, including skin aging and photoaging. This study investigated the protective role and possible mechanism of Terminalia catappa L. methanolic extract (TCE) in human fibroblasts (Hs68) against hydrogen peroxide (H2O2)-induced oxidative damage. METHODS: Various in vitro antioxidant assays were performed in this study. The effect and mechanisms of TCE on oxidative stress-induced oxidative damage were studied by using western blotting. RESULTS: The IC50 of TCE was 8.2 µg/mL for 1,1-diphenyl-2-picrylhydrazyl radical scavenging, 20.7 µg/mL for superoxide anion radical scavenging, 173.0 µg/mL for H2O2 scavenging, 44.8 µg/mL for hydroxyl radical scavenging, and 427.6 µg/mL for ferrous chelation activities. Moreover, TCE inhibited the H2O2-induced mitogen-activated protein kinase signaling pathway, resulting in the inhibition of c-Jun, c-Fos, matrix metalloproteinase (MMP)-1, MMP-3, MMP-9, and cyclooxygenase-2 expression. TCE also increased hemeoxygenase-1 expression inhibited by H2O2. Finally, TCE was demonstrated reverse type I procollagen expression in fibroblasts after H2O2 treatment. CONCLUSIONS: According to our findings, TCE is a potent antioxidant and protective agent that can be used in antioxidative stress-induced skin aging.

Sesamol Inhibited Melanogenesis by Regulating Melanin-Related Signal Transduction in B16F10 Cells.

Melanin is synthesized through a series of interactions catalyzed by melanogenic enzymes such as tyrosinase, dopachrome tautomerase (tyrosinase-related protein-2; TRP-2), and tyrosinase-related protein-1 (TRP-1). Tyrosinase plays a key role in catalysing the initial and limiting steps of melanogenesis. The melanin that results from melanogenesis has the protective effect of absorbing ultraviolet radiation. However, overproduction of melanin, in addition to altering the appearance of skin, may lead to skin disorders such as melasma, solar lentigo, and postinflammatory hyperpigmentation. Previous studies have revealed that sesamol is a strong antioxidant and a free radical scavenger. In this study, we investigated the effects of sesamol on the regulation of melanogenesis and related mechanisms in B16F10 cells. The results indicated that sesamol inhibited tyrosinase activity and melanogenesis induced by α-melanocyte-stimulating hormone (α-MSH) in B16F10 melanoma cells. Sesamol decreased the protein level of melanocortin 1 receptor (MC1R), microphthalmia-associated transcription factor (MITF), tyrosinase, and TRP-1 by downregulating cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathways that had been activated by α-MSH. Sesamol increased glycogen synthase kinase 3 beta (GSK3ß), protein kinase B (AKT), and extracellular signal-related kinase (ERK) phosphorylation, thus inhibiting the transcription of MITF. Sesamol also inhibited melanin synthesis and tyrosinase expression by modulating ERK, phosphoinositide 3-kinase (PI3K)/AKT, p38, and c-Jun amino-terminal kinase (JNK) signalling pathways. These results indicate that sesamol acted as a potent depigmenting agent.

N-(4-methoxyphenyl) caffeamide-induced melanogenesis inhibition mechanisms.

BACKGROUND: The derivative of caffeamide exhibits antioxidant and antityrosinase activity. The activity and mechanism of N-(4-methoxyphenyl) caffeamide (K36E) on melanogenesis was investigated. METHODS: B16F0 cells were treated with various concentrations of K36E; the melanin contents and related signal transduction were studied. Western blotting assay was applied to determine the protein expression, and spectrophotometry was performed to identify the tyrosinase activity and melanin content. RESULTS: Our results indicated that K36E reduced α-melanocyte-stimulating hormone (α-MSH)-induced melanin content and tyrosinase activity in B16F0 cells. In addition, K36E inhibited the expression of phospho-cyclic adenosine monophosphate (cAMP)-response element-binding protein, microphthalmia-associated transcription factor (MITF), tyrosinase, and tyrosinase-related protein-1 (TRP-1). K36E activated the phosphorylation of protein kinase B (AKT) and glycogen synthase kinase 3 beta (GSK3ß), leading to the inhibition of MITF transcription activity. K36E attenuated α-MSH induced cAMP pathways, contributing to hypopigmentation. CONCLUSIONS: K36E regulated melanin synthesis through reducing the expression of downstream proteins including p-CREB, p-AKT, p-GSK3ß, tyrosinase, and TRP-1, and activated the transcription factor, MITF. K36E may have the potential to be developed as a skin whitening agent.

Fisetin Regulates Nrf2 Expression and the Inflammation-Related Signaling Pathway to Prevent UVB-Induced Skin Damage in Hairless Mice.

Chronic ultraviolet (UV) exposure may cause skin damage, disrupt skin barrier function, and promote wrinkle formation. UV induces oxidative stress and inflammation, which results in extracellular matrix degradation in the dermis and epidermal hyperplasia. Our previous study demonstrated that fisetin exerts photoprotective activity by inhibiting mitogen-activated protein kinase/activator protein-1/matrix metalloproteinases (MMPs) activation. In this study, fisetin was applied topically to investigate its antiphotodamage effects in hairless mice. The erythema index (a* values) and transepidermal water loss were evaluated to assess skin damage, and immunohistochemical staining was conducted to elucidate the photoprotective mechanism of fisetin. The results revealed that the topical application of fisetin reduced UVB-induced increase in the a* value and wrinkle formation. In addition, fisetin inhibited epidermal hyperplasia and increased the collagen content in the dermis. Fisetin exerted photoprotective activity by inhibiting the expression of MMP-1, MMP-2, and cyclooxygenase-2 and increasing the expression of nuclear factor erythroid 2-related factor. Furthermore, fisetin increased the expression of filaggrin to prevent UVB-induced barrier function disruption. Altogether, the present results provide evidence of the effects and mechanisms of fisetin's antiphotodamage and antiphotoinflammation activities.

Alleviation of Ultraviolet B-Induced Photodamage by Coffea arabica Extract in Human Skin Fibroblasts and Hairless Mouse Skin.

Coffea arabica extract (CAE) containing 48.3 ± 0.4 mg/g of chlorogenic acid and a trace amount of caffeic acid was found to alleviate photoaging activity in human skin fibroblasts. In this study, polyphenol-rich CAE was investigated for its antioxidant and antiinflammatory properties, as well as for its capability to alleviate ultraviolet B (UVB)-induced photodamage in BALB/c hairless mice. The results indicated that 500 µg/mL of CAE exhibited a reducing power of 94.7%, ferrous ion chelating activity of 46.4%, and hydroxyl radical scavenging activity of 20.3%. The CAE dose dependently reduced UVB-induced reactive oxygen species (ROS) generation in fibroblasts. Furthermore, CAE inhibited the UVB-induced expression of cyclooxygenase-2 and p-inhibitor κB, and the translocation of nuclear factor-kappa B (NF-κB) to the nucleus of fibroblasts. In addition, CAE alleviated UVB-induced photoaging and photodamage in BALB/c hairless mice by restoring the collagen content and reduced UVB-induced epidermal hyperplasia. CAE also inhibited UVB-induced NF-κB, interleukin-6, and matrix metalloproteinase-1 expression in the hairless mouse skin. The results indicated that CAE exhibits antiphotodamage activity by inhibiting UV-induced oxidative stress and inflammation. Therefore, CAE is a candidate for use in antioxidant, antiinflammatory, and antiphotodamage products.

N-(4-bromophenethyl) Caffeamide Protects Skin from UVB-Induced Inflammation Through MAPK/IL-6/NF-κB-Dependent Signaling in Human Skin Fibroblasts and Hairless Mouse Skin.

Long-term exposure to ultraviolet (UV) irradiation causes skin inflammation and aging. N-(4-bromophenethyl) caffeamide (K36H) possesses antioxidant and antimelanogenic properties. The present study investigated the effects of K36H on UVB-induced skin inflammation in human skin fibroblasts and hairless mice and evaluated the underlying mechanisms. The in vitro results indicated that K36H reduced UVB-induced mitogen-activated protein kinase (MAP kinase) expression. Furthermore, K36H treatment reduced cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) protein expression in UVB-irradiated fibroblasts by regulating IκB and nuclear factor-kappa B (NF-κB) expression. In the animal study, topically applied K36H markedly reduced inflammation and skin thickness and prevented photodamage to the skin of hairless mice. In addition, K36H inhibited the levels of UV-upregulated inflammation-related proteins levels such as IL-1, iNOS, and NF-κB in the dermis of hairless mice. Our findings demonstrated the antioxidant and anti-inflammatory properties of K36H in human skin fibroblasts and hairless mice. Therefore, K36H can be developed as an antiphotodamage and antiphotoinflammation agent.

Increased risk of cardiovascular events in patients with herpes zoster: a population-based study.

The association between herpes zoster and cardiovascular complications remains vague with limited study on the association between these two disorders. This study evaluated the risk of cardiovascular diseases in patients with herpes zoster. From insurance claims data of Taiwan, 19,483 patients with herpes zoster diagnosed in 1998-2008 and 77,932 subjects without herpes zoster were identified in this study. Both cohorts were followed up until the end of 2010 to measure the incidence of arrhythmia and coronary artery disease. The incidence rate ratio and adjusted hazard ratio (HR) of the cardiovascular complications with 95% confidence interval (CI) were estimated. The incidence of arrhythmia was 1.17-fold greater in the herpes zoster cohort than in the non-herpes zoster cohort (13.2 vs. 11.3 per 1,000 person-years), with an adjusted HR of 1.16 (P < 0.01). The coronary artery disease incidence in the herpes zoster cohort was 1.16-fold higher than that in the non-herpes zoster cohort (9.02 vs. 7.83 per 1,000 person-years), with an adjusted HR of 1.11 (P < 0.01). Over the stratified follow-up years, adjusted HRs were 1.22 (95% CI = 1.12-1.34) for arrhythmia and 1.14 (95% CI = 1.02-1.28) for coronary artery disease within 2 years after herpes zoster diagnosis. The risk measured for these disorders declined over time. Comorbidities of hypertension, diabetes, and hyperlipidemia also contributed to these cardiovascular disorders with greater extent. It is concluded that the contribution of herpes zoster to the risk of arrhythmia and cardiovascular diseases is less strong than that of hypertension, diabetes, and hyperlipidemia.

Tranexamic acid improves psoriasis-like skin inflammation: Evidence from in vivo and in vitro studies.

The chronic disease psoriasis is associated with severe inflammation and abnormal keratinocyte propagation in the skin. Tranexamic acid (TXA), a plasmin inhibitor, is used to cure serious bleeding. We investigated whether TXA ointment mitigated Imiquimod (IMQ)-induced psoriasis-like inflammation. Furthermore, this study investigated the effect of noncytotoxic concentrations of TXA on IL-17-induced human keratinocyte (HaCaT) cells to determine the status of proliferative psoriatic keratinocytes. We found that TXA reduced IMQ-induced psoriasis-like erythema, thickness, scaling, and cumulative scores (erythema plus thickness plus scaling) on the back skin of BALB/c mice. Additionally, TXA decreased ear thickness and suppressed hyperkeratosis, hyperplasia, and inflammation of the ear epidermis in IMQ-induced BALB/c mice. Furthermore, TXA inhibited IMQ-induced splenomegaly in BALB/c mouse models. In IL-17-induced HaCaT cells, TXA inhibited ROS production and IL-8 secretion. Interestingly, TXA suppressed the IL-17-induced NFκB signaling pathway via IKK-mediated IκB degradation. TXA inhibited IL-17-induced activation of the NLRP3 inflammasome through caspase-1 and IL1ß expression. TXA inhibited IL-17-induced NLRP3 inflammasome activation by enhancing autophagy, as indicated by LC3-II accumulation, p62/SQSTM1 expression, ATG4B inhibition, and Beclin-1/Bcl-2 dysregulation. Notably, TXA suppressed IL-17-induced Nrf2-mediated keratin 17 expression. N-acetylcysteine pretreatment reversed the effects of TXA on NFκB, NLRP3 inflammasomes, and the Nrf2-mediated keratin 17 pathway in IL-17-induced HaCaT cells. Results further confirmed that in the ear skin of IMQ-induced mice, psoriasis biomarkers such as NLRP3, IL1ß, Nrf2, and keratin 17 expression were downregulated by TXA treatment. TXA improves IMQ-induced psoriasis-like inflammation in vivo and psoriatic keratinocytes in vitro. Tranexamic acid is a promising future treatment for psoriasis.

Targeting Nrf2 with 3 H-1,2-dithiole-3-thione to moderate OXPHOS-driven oxidative stress attenuates IL-17A-induced psoriasis.

Psoriasis, a chronic autoimmune disease characterized by the hyperproliferation of keratinocytes in the epidermis and parakeratosis, significantly impacts quality of life. Interleukin (IL)- 17A dominates the pathogenesis of psoriasis and facilitates reactive oxygen species (ROS) accumulation, which exacerbates local psoriatic lesions. Biologic treatment provides remarkable clinical efficacy, but its high cost and unignorable side effects limit its applications. 3 H-1,2-Dithiole-3-thione (D3T) possesses compelling antioxidative capacities against several diseases through the nuclear factor erythroid 2-related factor 2 (Nrf2) cascade. Hence, we aimed to evaluate the effect and mechanism of D3T in psoriasis. We found that D3T attenuates skin thickening and scaling by inhibiting IL-17A-secreting γδT cells in imiquimod (IMQ)-induced psoriatic mice. Interleukin-17A markedly enhanced IL-6 and IL-8 expression, lipid peroxidation, the contents of nitric oxide and hydrogen peroxide, oxidative phosphorylation and the MAPK/NF-κB pathways in keratinocytes. IL-17A also inhibited the Nrf2-NQO1-HO-1 axis and the activities of superoxide dismutase and glutathione peroxidase. D3T significantly reversed these parameters in IL-17A-treated keratinocytes. ML-385, a Nrf2 neutralizer, failed to improve D3T-induced anti-inflammatory and antioxidative effects in IL-17A-treated keratinocytes. We conclude that targeting Nrf2 with D3T to diminish oxidative and inflammatory damage in keratinocytes may attenuate psoriasis.

Risk of All-Cause Mortality, Cardiovascular Disease Mortality, and Cancer Mortality in Patients With Bullous Pemphigoid.

IMPORTANCE: The role of bullous pemphigoid (BP) in cardiovascular disease (CVD) mortality remains controversial, and analyses of causes of death among patients with BP based on individual data remain lacking. OBJECTIVE: To evaluate the risk of all-cause mortality, CVD mortality, and cancer mortality in patients with BP. DESIGN, SETTING, AND PARTICIPANTS: This cohort study identified patients who received a diagnosis of and treatment for BP during their dermatology clinic visits at a tertiary medical center in central Taiwan between January 1, 2007, and December 31, 2017. Controls were patients without BP and were individually matched to cases (4:1) according to age, sex, and date of the dermatology clinic visit. Data were analyzed from March 6, 2019, to April 2, 2021. EXPOSURES: Bullous pemphigoid was confirmed pathologically with typical direct immunofluorescence findings or clinically with typical clinical presentation, positive findings of an anti-basement membrane zone antibody test, and corticosteroid use for at least 28 cumulative days. MAIN OUTCOMES AND MEASURES: Mortality outcomes confirmed by the National Death Registry. RESULTS: Of 252 patients with BP and 1008 matched control patients (N = 1260), 685 (54.4%) were men and the median age was 78.0 (IQR, 70.3-84.8) years. Patients with BP had higher CVD mortality at 1 year (20 [7.9%] vs 13 [1.3%]), 3 years (28 [11.1%] vs 24 [2.4%]), and 5 years (31 [12.3%] vs 39 [3.9%]) compared with matched control patients. After adjusting for potential confounding variables, patients with BP had a 5-fold higher risk of CVD mortality at 1 year (hazard ratio [HR], 5.29 [95% CI, 2.40-11.68]), 3 years (HR, 5.79 [95% CI, 3.11-10.78]), and 5 years (HR, 4.95 [95% CI, 2.88-8.51]). Subgroup analyses revealed that the CVD mortality risk associated with BP was higher in patients without a history of hypertension (HR, 7.28 [95% CI, 3.87-13.69]) or CVD (HR, 6.59 [95% CI, 3.40-12.79]) and in patients without prior diuretic use (HR, 5.75 [95% CI, 3.15-10.50]) compared with matched control patients. In addition, all-cause mortality associated with BP was higher in patients without prior corticosteroid use than in control patients (HR 5.65 [95% CI, 4.19-7.61]). CONCLUSIONS AND RELEVANCE: The findings of this cohort study suggest that BP was associated with a 5-fold higher risk of CVD mortality, particularly in patients without underlying hypertension or CVD or those without prior corticosteroid or diuretic use. Future studies should investigate the benefits of routine monitoring and timely management of CVD symptoms and signs in patients with BP.

Image and Speech Recognition Technology in the Development of an Elderly Care Robot: Practical Issues Review and Improvement Strategies.

As the world's population is aging and there is a shortage of sufficient caring manpower, the development of intelligent care robots is a feasible solution. At present, plenty of care robots have been developed, but humanized care robots that can suitably respond to the individual behaviors of elderly people, such as pose, expression, gaze, and speech are generally lacking. To achieve the interaction, the main objectives of this study are: (1) conducting a literature review and analyzing the status quo on the following four core tasks of image and speech recognition technology: human pose recognition, human facial expression recognition, eye gazing recognition, and Chinese speech recognition; (2) proposing improvement strategies for these tasks based on the results of the literature review. The results of the study on these improvement strategies will provide the basis for using human facial expression robots in elderly care.

Topical Tirbanibulin, a Dual Src Kinase and Tubulin Polymerization Inhibitor, for the Treatment of Plaque-Type Psoriasis: Phase I Results.

Plaque-type psoriasis is a common skin disorder. Tirbanibulin (KX01) is a new Src kinase inhibitor with potent antiproliferative activity against keratinocytes and has been approved for treatment of actinic keratosis. This Phase I study investigates the safety and activity of KX01 ointment in patients with plaque-type psoriasis. We recruited 28 patients from two medical centers in Taiwan. This study was performed in four stages. Double-blind treatments were randomized in stages I (KX01 0.01% + placebo, two rounds of two-week treatment) and II (KX01 0.1% + placebo, four weeks) and open-labelled in stages III (KX01 1%, five days) and IV (KX01 1%, five days weekly for four weeks). The safety, tolerability, KX01 concentration, target area score, physician global assessment, and disease relapse were determined. Most treatment-emergent adverse events were mild-to-moderate application site reactions. Three (50.0%) subjects from the stage IV group showed ≥50% reduction in the target area score (TAS50), while two subjects (33.3%) showed a clinically meaningful improvement in the physician global assessment score. KX01 0.01%, 0.1%, and 1% were safe and well-tolerated. KX01 1% at four weeks showed a promising activity for the treatment of plaque-type psoriasis.

Brain abscess in a patient with psoriatic arthritis treated with adalimumab: A case report.

RATIONALE: In patients receiving biological therapies, serious infections are a major concern. Infections associated with anti-tumor necrosis factor antibody therapy include tuberculosis, viral, fungal, and bacterial infections. Likewise, severe infections of the upper and lower respiratory tract, lung, skin and soft tissue, urinary tract, gastrointestinal tract, joint, and bone have also been reported previously. However, infections involving the central nervous system are rare, especially an intracranial infection caused by odontogenic infection. To date, only few cases have been reported of this infection. This is the first case of a patient with psoriatic arthritis receiving adalimumab and developing brain abscess of odontogenic origin. PATIENT CONCERNS: A 39-year-old male with psoriatic arthritis receiving adalimumab treatment came to the emergency department with initial presentation of sudden onset convulsions. He had been receiving adalimumab treatment for 1 month. Two days after the third injection, the patient had an episode of sudden-onset general convulsion for nearly 5 min with the upgazing and general tonic presentation. Magnetic resonance imaging (MRI) showed left frontal lobe brain abscess. Pus culture from the brain abscess detected Streptococcus sanguinis (S. sanguinis), Fusobacterium nucleatum (F. nucleatum), and Parvimonas micra (P. micra). DIAGNOSIS: Brain abscess with odontogenic infection. INTERVENTIONS: The patient received left frontal craniotomy, abscess drainage and systemic empiric antibiotics treatment with vancomycin, cefepime, and metronidazole. Due to drug rash with eosinophilia and systemic symptoms during the treatment, vancomycin and metronidazole were discontinued, and systemic antibiotics were switched to teicoplanin and ceftriaxone. OUTCOMES: A brain MRI follow-up performed after 1 month of initial treatment revealed the reduced size of the abscess lesion and minimal oedema. The patient was discharged with stable condition. LESSONS: To the best of our knowledge, this is the first case of a patient with psoriatic arthritis receiving adalimumab and developing brain abscess of odontogenic origin. Such a rare diagnosis must be kept in mind when patients treated with adalimumab present with sudden-onset convulsions. Careful dental examination should be performed before administration of adalimumab.

The association of dipeptidyl peptidase IV inhibitors and other risk factors with bullous pemphigoid in patients with type 2 diabetes mellitus: A retrospective cohort study.

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune blistering skin disorder with unknown etiology. Evidence revealed that dipeptidyl peptidase IV inhibitors (DPP4i) may increase the associated risk. This study aimed to evaluate the relationship of BP with the administration of DPP4i and other risk factors in patients with type 2 diabetes mellitus (T2DM). METHODS: Using the Taiwan National Health Insurance Database (NHIRD) from 2009 to 2013, we identified patients with T2DM and the use of DPP4i 12 weeks or greater as a DPP4i cohort and patients with T2DM who never use DPP4i as a control cohort. They were frequency matched on gender and age within 5 years at a ratio of 1:2. The Cox proportional hazard regression model was used to estimate the hazard ratios (HRs) and confidence intervals (CIs) for the cohorts. RESULTS: A total of 14,187 individuals taking DPP4i and 28,374 matched cohorts without taking DPP4i were included. The incidence rate of BP was higher in DPP4i cohort than in control cohort (1.41 vs. 0.59 per 1000 person-years; adjusted HR 2.14, 95% CI = 1.02-4.50). The cumulative event rate of BP in DPP4i cohort was higher than in control cohort (log-rank test, p = .01). Patients with dementia and taking spironolactone had a higher associated risk to develop BP; lower associated risk in patients taking metformin. CONCLUSIONS: In patients with T2DM, subjects taking DPP4i, having dementia, and taking spironolactone were associated with an increased risk for the development of BP.