OBJECTIVE: To assess the impact of long-term biologic therapy on metabolic biochemical parameters in moderate to severe plaque psoriasis patients. METHODS: The study included patients over 18 years old who had been treated by biological agents for at least 24 weeks for moderate to severe plaque psoriasis from Novermber 2015 to January 2024. According to the biological agents the patients used, they were divided into three groups: interleukin-17 (IL-17) inhibitor group, IL-23 and IL-12/23 inhibitor group and tumor necrosis factor-α (TNF-α) inhibitor group. The metabolic biochemical parameters of each group were evaluated and compared before and after the administration of the biologic therapies. RESULTS: A total of 174 patients with moderate to severe plaque psoriasis were included in the long-term treatment with biologics, including 127 males (73.00%), 47 females (27.00%), with a median age of 38.00 (31.50, 49.00) years and a median duration of psoriasis of 12.00 (10.00, 20.00) years. The median duration of biologic treatment was 61.00 (49.00, 96.25) weeks, ranging from 26 to 301 weeks. There were 101 patients in the IL-17 inhibitor group, 38 patients in the IL-23 and IL-12/23 inhibitor group, and 35 patients in the TNF-α inhibitor group. After long-term treatment with IL-17 inhibitors, no statistically significant changes were observed in body weight, body mass index (BMI), alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting glucose (GLU), total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) compared with baseline measurements (P>0.05). However, low-density lipoprotein cholesterol (LDL-C) levels were significantly reduced [(2.90±0.75) mmol/L vs. (3.05±0.79) mmol/L, t=－2.100, P=0.038], while uric acid (UA) levels showed a significant increase [(401.13±99.13) μmol/L vs. (364.94±91.11) μmol/L, t=5.215, P < 0.001]. The group with normal UA levels before treatment showed a significant increase after long-term application of biological agents compared with before treatment [(370.69± 89.59) μmol/L vs. (324.66±64.50) μmol/L, t=5.856, P < 0.001]. Following long-term application of IL-23 and IL-12/23 inhibitors, no statistically significant differences were observed in body weight, BMI, ALT, AST, GLU, TC, TG, HDL-C and UA levels when compared with baseline measurements (P> 0.05). However, LDL-C levels exhibited a significant reduction from baseline [(2.85±0.74) mmol/L vs. (3.12±0.68) mmol/L, t=－2.082, P=0.045]. After long-term treatment with TNF-α inhibitor, there were no significant differences in body weight, BMI, ALT, AST, GLU, TC, TG, HDL-C, LDL-C and UA compared with baseline measurements (P>0.05). CONCLUSION Long-term application of IL-17 inhibitors in moderate to severe plaque psoriasis patients may result in elevated uric acid levels, particularly in patients with normal uric acid levels before treatment. The long-term use of IL-17 inhibitors, IL-23 inhibitors or IL-12/23 inhibitors might reduce LDL-C levels.
Humans ; Psoriasis/blood* ; Male ; Female ; Adult ; Middle Aged ; Interleukin-17/antagonists & inhibitors* ; Interleukin-23/antagonists & inhibitors* ; Tumor Necrosis Factor-alpha/antagonists & inhibitors* ; Interleukin-12/antagonists & inhibitors* ; Biological Therapy ; Biological Products/therapeutic use* ; Triglycerides/blood* ; Cholesterol, LDL/blood* ; Cholesterol, HDL/blood*

OBJECTIVES: Psoriasis is associated with lipid metabolism disorders, but the underlying mechanisms remain unclear. This study aims to investigate the role of trimethylamine N-oxide (TMAO) in lipid metabolism dysregulation in psoriasis. METHODS: An imiquimod (IMQ)-induced psoriasis-like mouse model was used to assess lipid metabolism parameters, TMAO levels, and liver flavin monooxygenase 3 (FMO3) mRNA expression. Blood samples from healthy individuals and psoriatic patients were collected to measure serum TMAO levels and lipid profiles. To clarify the role of TMAO in the lipid metabolism disorder of mice with psoriasis model, exogenous TMAO, choline, or 3,3-dimethyl-1-butanol (DMB) were administered via intraperitoneal injections or diet in IMQ-treated mice. Liver tissues from the mouse models were subjected to RNA sequencing to identify TMAO-regulated signaling pathways. RESULTS: IMQ-induced psoriatic mice exhibited abnormal glucose, insulin, and lipid levels. IMQ treatment also downregulated the hepatic mRNA expression of glucose transporter 2 (Glut2) and silence information regulator 1 (Sirt1), while upregulating glucose transporter 4 (Glut4) and peroxisome proliferator-activated receptor gamma (PPARγ). Elevated serum TMAO levels were observed in both psoriatic patients and IMQ-treated mice. Additionally, liver FMO3 mRNA expression was increased in the psoriatic mouse model. In patients, TMAO levels positively correlated with Psoriasis Area and Severity Index (PASI) scores, serum triglyceride (TG), and total cholesterol (TC) levels. The intraperitoneal injection of TMAO exacerbated lipid dysregulation in IMQ-treated mice. A choline-rich diet further aggravated lipid abnormalities and liver injury in psoriatic mice, whereas DMB treatment alleviated these effects. RNA-Seq analysis demonstrated that TMAO upregulated hepatic microRNA-122 (miR-122), which may suppress the expression of gremlin 2 (GREM2), thus contributing to lipid metabolism disorder. CONCLUSIONS TMAO may promote lipid metabolism dysregulation in psoriasis by modulating the hepatic miR-122/GREM2 pathway.
Animals ; Methylamines/blood* ; Mice ; Psoriasis/chemically induced* ; Lipid Metabolism/drug effects* ; Humans ; Male ; Liver/metabolism* ; Female ; Oxygenases/genetics* ; Disease Models, Animal ; Lipid Metabolism Disorders/etiology* ; Adult ; Mice, Inbred C57BL

Psoriasis is a chronic inflammatory skin disease, and its pathogenesis is largely modulated by abnormal angiogenesis. Previous research has indicated that AlkB homolog 5 (ALKBH5), an important demethylase affecting N⁶-methyladenosine (m⁶A) modification, plays a role in regulating angiogenesis in cardiovascular and eye diseases. Our present study found that ALKBH5 was upregulated and co-localized with cluster of differentiation 31 (CD31) in the skin of IMQ group compared with control group. ALKBH5-deficient mice decreased IMQ-induced psoriatic dermatitis and exhibited histological improvements, including decreased epidermal thickness, hyperkeratosis, numbers of dermal capillary vessels and inflammatory cell infiltration. ALKBH5-KO mice alleviated angiogenesis in psoriatic lesions by downregulating the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. Additionally, the expression of ALKBH5 was significantly upregulated in IL-17A-induced human umbilical vein endothelial cells (HUVECs), which further promoted the expression of angiogenesis-related cytokines and endothelial cell proliferation. Cell proliferation and angiogenesis were suppressed in ALKBH5 knockdown group, whereas ALKBH5 overexpression promoted these processes. The regulation of angiogenesis in HUVECs by ALKBH5 was facilitated through the AKT-mTOR pathway. Collectively, ALKBH5 plays a pivotal role in psoriatic dermatitis and angiogenesis, which may offer a new potential targets for treating psoriasis.
Animals ; Psoriasis/chemically induced* ; Mice ; Humans ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; AlkB Homolog 5, RNA Demethylase/genetics* ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Cell Proliferation ; Mice, Knockout ; Disease Models, Animal ; Signal Transduction ; Male ; Skin/blood supply* ; Mice, Inbred C57BL ; Angiogenesis

OBJECTIVE: To observe the clinical efficacy of moxibustion combined with coptis chinensis ointment sealing on plaque psoriasis complicated with obesity. METHODS: A total of 52 patients of plaque psoriasis complicated with obesity were randomized into an observation group (26 cases) and a control group (26 cases, 2 cases dropped off). Coptis chinensis ointment sealing was adopted in the control group. On the basis of the treatment in the control group, moxibustion was applied at ashi point (area of local target lesions), Zhongwan (CV 12) and bilateral Zusanli (ST 36), Fenglong (ST 40), Quchi (LI 11), Tianshu (ST 25), Shangjuxu (ST 37) in the observation group. The treatment was given 30 min each time, once a day for 4 weeks in both groups. The psoriasis area and severity index (PASI) score, obesity related indexes (body mass, waist circumference, body mass index [BMI]), triglyceride, cholesterol, uric acid and plasma glucose were compared before and after treatment, and the clinical efficacy was evaluated in the two groups. RESULTS: After treatment, the PASI scores were decreased compared with those before treatment in the two groups (P<0.01), and the PASI score in the observation group was lower than that in the control group (P<0.05); the body mass, waist circumference, BMI, triglyceride, cholesterol, uric acid and plasma glucose were decreased compared with those before treatment in the observation group (P<0.01, P<0.05), the triglyceride and cholesterol in the observation group were lower than those in the control group (P<0.05). The total effective rate was 53.8% (14/26) in the observation group, which was superior to 20.8% (5/24) in the control group (P<0.05). CONCLUSION Moxibustion combined with coptis chinensis ointment sealing can effectively improve the clinical symptoms in patients of plaque psoriasis complicated with obesity.
Humans ; Moxibustion ; Blood Glucose ; Ointments ; Uric Acid ; Psoriasis/therapy* ; Triglycerides ; Obesity/therapy*

BACKGROUND: Psoriasis is an immune-mediated, chronic inflammatory disease affecting multiple aspects of patients' lives. Its epidemiology varies regionally; however, nationwide epidemiologic data on psoriasis depicting profile of Korean patients has not been available to date. OBJECTIVE: To understand nationwide epidemiologic characteristics and clinical features of adult patients with psoriasis visited university hospitals in Korea. METHODS: This multicenter, non-interventional, cross-sectional study recruited 1,278 adult patients with psoriasis across 25 centers in Korea in 2013. Various clinical data including PASI, BSA, DLQI, SF-36 and PASE were collected. RESULTS: A total of 1,260 patients completed the study (male:female=1.47:1). The mean age was 47.0 years with a distribution mostly in the 50s (24.9%). Early onset (<40 years) of psoriasis accounted for 53.9% of patients. The mean disease duration was 109.2 months; mean body mass index was 23.9 kg/m²; and 12.7% of patients had a family history of psoriasis. Plaque and guttate types of psoriasis accounted for 85.8% and 8.4%, respectively. Patients with PASI ≥10 accounted for 24.9%; patients with body surface area ≥10 were 45.9%. Patients with DLQI ≥6 accounted for 78.8%. Between PASI <10 and PASI ≥10 groups, significant difference was noted in age at diagnosis, disease duration, blood pressure, waist circumference of female, and treatment experiences with phototherapy, systemic agents, and biologics. CONCLUSION: This was the first nationwide epidemiologic study of patients with psoriasis in Korea and provides an overview of the epidemiologic characteristics and clinical profiles of this patient population.
Adult ; Biological Products ; Blood Pressure ; Body Mass Index ; Body Surface Area ; Cross-Sectional Studies* ; Diagnosis ; Epidemiologic Studies ; Epidemiology ; Female ; Hospitals, University ; Humans ; Korea* ; Phototherapy ; Psoriasis* ; Waist Circumference

BACKGROUND: Psoriasis is a chronic recurrent disease requiring long-term treatment; therefore, special attention is warranted when prescribing cyclosporine A (CsA) for patients diagnosed with psoriasis. Various forms of maintenance therapy have been suggested to reduce the incidence of adverse events associated with CsA use. OBJECTIVE: We aimed to compare the efficacy and safety of the three aforementioned CsA therapies for management of patients with psoriasis. METHODS: Patients fulfilling our selection criteria were selected for the study. CsA therapy (2.5∼5 mg/kg/day) was administered for 12 weeks, and patients who showed remission following this treatment were administered maintenance therapy. Patients with successful induction of response were randomly assigned to three treatment groups. Group A was the continuous regimen group (2∼3 mg/kg/day). Group B was the pulsed regimen group (4 mg/kg/day for 4 days, 3 days of discontinuation). Group C was the weekend regimen group (5 mg/kg/day for 2 days, 5 days of discontinuation). Patients were followed up on an outpatient basis at 4-week intervals to monitor treatment effects. RESULTS: In each group, the Psoriasis Area and Severity Index (PASI) and body surface area (BSA) values decreased in a similar fashion from visit 1 to visit 4 and at the time of the final visit 7. In each group, dermatology life quality index (DLQI) values showed statistically significant differences between pre- and post-treatment states; however, no inter-group differences were observed. Although adverse events such as elevated blood pressure and serum creatinine levels were slightly higher in the intermittent group, there was no significant inter-group difference. CONCLUSION: The pulsed regimen did not show a major difference in treatment effects compared to the everyday use group. We propose that the patient's age, presence of underlying diseases, lifestyle patterns, and convenience of use should be considered while determining the type of regimen administered to a patient.
Blood Pressure ; Body Surface Area ; Creatinine ; Cyclosporine* ; Dermatology ; Humans ; Incidence ; Life Style ; Outpatients ; Patient Selection ; Psoriasis* ; Quality of Life

BACKGROUND: Psoriatic arthritis (PsA) is one of the inflammatory arthritis associated with psoriasis. Several studies have described the clinical difference between psoriatic patients with PsA and those without PsA. OBJECTIVE: The purpose of this study was to examine the difference in clinical features and prevalence of comorbidities between psoriatic patients with and without PsA in Korea. METHODS: We retrospectively evaluated 173 patients diagnosed with psoriasis. Patients were subdivided based on the presence or absence of PsA. We analyzed clinical manifestations including comorbidities and laboratory tests such as total cholesterol, triglyceride, C-reactive protein, erythrocyte sedimentation rate (ESR), and fasting glucose. RESULTS: Among 173 patients with psoriasis, 29 patients (16.8%) were diagnosed with PsA. The mean age of psoriasis onset for patients with PsA was 7.6 years earlier (p=0.017) than for those without PsA. The duration of psoriasis was 4.6 years longer (p<0.001) in patients with PsA than in patients without PsA. Nail involvement was more common in patients with PsA (p<0.001). There were statistically significant differences between the two groups regarding ESR levels (p=0.003) and the prevalence of diabetes mellitus (p=0.032). CONCLUSION: We found several differences in the prevalence of comorbidities, levels of inflammatory markers, and epidemiologic characteristics between psoriatic patients with and without PsA. This study may help improve strategies for the clinical approach for treating psoriasis in dermatology.
Arthritis ; Arthritis, Psoriatic* ; Blood Sedimentation ; C-Reactive Protein ; Cholesterol ; Comorbidity* ; Dermatology ; Diabetes Mellitus ; Fasting ; Glucose ; Humans ; Korea ; Prevalence ; Psoriasis* ; Retrospective Studies* ; Triglycerides

BACKGROUND: Systemic inflammation in psoriasis causes insulin resistance and cardiovascular diseases. Adipokines are adipose-tissue-derived factors that are involved in metabolic processes. It is thought that these adipokines are associated with the development of psoriasis. OBJECTIVE: The purpose of this study was to determine the changes in adipokine levels, insulin resistance, hypertension, and dyslipidemia over a 12-week period. METHODS: The study comprised 35 psoriasis patients and 50 controls. Blood samples were obtained twice from the patients, one sample at the start and one at the end of a 12-week follow-up period. The following parameters were assessed in both groups: serum fasting glucose, fasting insulin, homeostasis model assessment-estimated insulin resistance (HOMA-IR) index, serum lipids, adiponectin, leptin, resistin, chemerin, omentin, vaspin, visfatin, retinol-binding protein 4, and high-sensitivity C-reactive protein (hs-CRP) levels; blood pressure; body mass index; and the psoriasis area severity index (PASI) scores. RESULTS: The patients showed an improvement in the PASI score and a significant decrease in serum hs-CRP, omentin, and chemerin values. Moreover, at the start of the follow-up, the psoriasis patients had significantly lower levels of adiponectin and visfatin and significantly higher levels of vaspin and resistin than those of the control group. Visfatin levels correlated negatively with low-density lipoprotein (LDL) and cholesterol, while vaspin and omentin levels correlated positively with diastolic blood pressure. Decreased adiponectin levels correlated negatively with diastolic blood pressure and LDL. CONCLUSION: Plasma levels of adipokines might be useful for evaluating the disease activity of psoriasis and its comorbidities.
Adipokines* ; Adiponectin ; Blood Pressure ; Body Mass Index ; C-Reactive Protein ; Cardiovascular Diseases ; Cholesterol ; Comorbidity ; Dyslipidemias* ; Fasting ; Follow-Up Studies ; Glucose ; Homeostasis ; Humans ; Hypertension* ; Inflammation ; Insulin Resistance* ; Insulin* ; Leptin ; Lipoproteins ; Metabolism ; Nicotinamide Phosphoribosyltransferase ; Plasma ; Psoriasis* ; Resistin

Drug-induced pancreatitis accounts for 0.1~2.0% of all pancreatitis cases. Generally, the mechanism of drug-induced pancreatitis is an immune reaction, accumulation of toxic material, and/or ischemia. However, how dapsone causes pancreatitis remains unclear. A 61-year-old man presented with a 2-week history of epigastric discomfort. He had taken dapsone for 2 months to treat psoriasis. Laboratory findings showed high blood glucose levels and metabolic acidosis; however, hemoglobin A1c was low. Serum amylase and lipase levels were elevated to 125/4,479 U/L. Abdominal computed tomography was indicative of pancreatitis. There was no causative history of pancreatitis and no other medication history except dapsone. Thus, we reached a diagnosis of diabetic ketoacidosis (DKA) followed by dapsone-induced pancreatitis. The patient fasted and was treated with insulin administration and fluid hydration in accordance with treatment guidelines. After treatment, amylase and lipase decreased and symptoms subsided, but insulin injection was required to control blood glucose levels. Drug-induced pancreatitis is a very rare adverse effect of dapsone. Only four cases of pancreatitis related to dapsone could be found in a PubMed search. Moreover, diabetes caused by dapsone-induced pancreatitis has not been reported previously. Here, we report a case of DKA caused by dapsoneinduced acute pancreatitis.
Acidosis ; Amylases ; Blood Glucose ; Dapsone ; Diabetic Ketoacidosis* ; Diagnosis ; Humans ; Insulin ; Ischemia ; Lipase ; Middle Aged ; Pancreatitis* ; Psoriasis

OBJECTIVETo investigate whether the serum levels of inflammation-related cytokines might be different between the healthy individuals and the psoriatic patients diagnosed of three varied Chinese medicine (CM) syndromes [blood-stasis syndrome (BSS), blood-dryness syndrome (BDS) and wind-heat syndrome (WHS)].

METHODSA total of 62 psoriatic patients were recruited and assigned to 3 groups according to their CM syndromes, including 27 patients of BSS, 21 of BDS and 14 of WHS. Another 20 sex- and age-matched healthy subjects were enrolled into the control group. Serum concentrations of multiple cytokines, including monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), soluble CD4O ligand (SCD40L), tumor necrosis factor-α (TNF-α), epidermal growth factor (EGF), interleukin-8 (IL-8), interleukin-17 (IL-17), interferon γ inducible protein-10 (IP-10) and vascular endothelial growth factor (VEGF), were measured by a multiplexed flow cytometric assay.

RESULTSThe circulating levels of MIP-1α, TNF-α, IL-8, and IP-10 were significantly increased in the psoriatic patients compared with the healthy controls (P<0.01). Male and female patients tended to have higher serum levels of MCP-1 and IP-10, respectively (P<0.05). Interestingly, compared with the control group, 6 out of the 9 cytokines (MCP-1, MIP-1α, TNF-α, EGF, IL-8 and IP-10) were substantially increased in the BSS group (P<0.05 or P<0.01), whereas only MIP-1α and IL-8 levels were elevated in the BDS group (P<0.05 or P<0.01) concurrent with lowered concentrations of SCD40L and IL-17 (P<0.05). In the WHS group, MIP-1α was the only cytokine whose level was evidently increased (P<0.01), in contrast to IL-17 which was decreased as compared with the control (P<0.05). The psoriatic patients overall owned higher levels of MIP-1α and IL-8 in the circulation which were comparable among the 3 groups of CM syndromes (P<0.01). In contrast, TNF-α level of the BSS group was the highest among the three (P<0.01), followed by the BDS and the WHS groups.

CONCLUSIONSThe expression profiles of cytokines in the circulation might not be necessarily identical for psoriatic patients with different CM syndromes. Accordingly, the serum concentrations of certain cytokines could potentially be used as the ancillary indices for the clinical classification of psoriatic CM syndromes.

Adult ; Aged ; Case-Control Studies ; Cytokines ; blood ; Female ; Humans ; Inflammation Mediators ; blood ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Psoriasis ; blood ; Severity of Illness Index ; Statistics, Nonparametric ; Syndrome ; Young Adult