Increased Circulating CD14+ Monocytes in Patients with Psoriatic Arthritis Presenting Impaired Apoptosis Activity.

Psoriatic arthritis (PsA) is a chronic inflammatory arthritis primarily affecting peripheral and axial joints. The osteolytic effect in the damaged joint is mediated by osteoclast activation. We aimed to investigate differential gene expression in peripheral CD14+ monocytes between patients with psoriatic arthritis (n = 15) and healthy controls (HCs; n = 15). Circulating CD14+ monocytes were isolated from peripheral blood mononuclear cells using CD14+ magnetic beads. Cell apoptosis was measured via Annexin V using flow cytometry. The gene expression profiling was analyzed via microarray (available in the NCBI GEO database; accession number GSE261765), and the candidate genes were validated using PCR. The results showed a higher number of peripheral CD14+ monocytes in patients with PsA than in the HCs. By analyzing the microarray data, identifying the differentially expressed genes, and conducting pathway enrichment analysis, we found that the apoptosis signaling pathway in CD14+ cells was significantly impaired in patients with PsA compared to the HCs. Among the candidate genes in the apoptotic signaling pathway, the relative expression level of cathepsin L was confirmed to be significantly lower in the PsAs than in the HCs. We concluded that the numbers of peripheral CD14+ monocytes increased, and their apoptosis activity was impaired in patients with PsA, which could lead to enhanced macrophage maturation and osteoclast activation. The resistance of apoptotic death in peripheral CD14+ monocytes may contribute to active joint inflammation in PsA.

Onychopapilloma: a single medical center experience in Southern Taiwan.

Background: Onychopapilloma is an uncommon benign tumor of the nail bed and the distal matrix. Objectives: We aimed to investigate the clinical and pathological features of onychopapilloma in Taiwan.Materials and methods: We conducted a retrospective analysis of 12 patients with histopathologically proven onychopapilloma in a medical center in southern Taiwan from 2017 to 2023. Results: This case series consisted of 5 men and 7 women aged 29 to 38, with a mean age of 41.25 years. The clinical features were as follows: distal subungual hyperkeratosis (100%), longitudinal erythronychia (50%), longitudinal leukonychia (50 %), distal onycholysis (41%), and distal nail plate fissuring (41%). The duration of the disease varied greatly, ranging from 1 month to several years. Most patients were asymptomatic (58%), while some presented tenderness (41%). Fingernail involvement was more prevalent than toe involvement, with the thumb being the most commonly affected site. Most of the patients presented with a solitary onychopapilloma. None of the seven patients who underwent surgery and were available for follow-up experienced recurrence.Conclusions: This study highlights that longitudinal erythronychia and leukonychia emerged as the predominant clinical presentations of onychopapilloma. Furthermore, our findings suggest that surgical excision appears to be an effective method for onychopapilloma.

Real-world efficacy of adjunctive calcipotriene/betamethasone dipropionate foam for recalcitrant psoriatic lesions on the scalp or lower legs with biologic therapy.

Many patients with moderate-to-severe psoriasis may not achieve complete skin clearance with recalcitrant lesions despite being on biologics. We aimed to evaluate the real-world effectiveness and safety of combining topical calcipotriene/betamethasone dipropionate (Cal/BD) foam with biologic therapy for the treatment of recalcitrant psoriatic lesions over the scalp or lower legs. We retrospectively reviewed the medical charts of psoriasis patients receiving adjunctive topical Cal/BD foam with biologics for at least 16 weeks on recalcitrant psoriatic lesions of the scalp or lower legs between 2020 and 2021 at a tertiary referral medical center in southern Taiwan. Among the 18 recruited patients, the severity outcomes of body surface area (BSA), Physician's Global Assessment (PGA), and BSA × PGA of the recalcitrant areas decreased by approximately 31%, 48%, and 50%, respectively, after 4 weeks of once-daily adjunctive Cal/BD foam use. Thereafter, the effect remained nearly constant after dose reduction to twice weekly until week 16. The Dermatology Life Quality Index and the nine-item Treatment Satisfaction Questionnaire for Medication questionnaire revealed improved life quality and a high level of satisfaction, with only a few mild adverse effects reported. In conclusion, adjunctive topical Cal/BD foam might be an effective and safe option for patients with recalcitrant lesions on the scalp and lower legs despite biologics use.

2022 Taiwanese Dermatological Association (TDA), Taiwanese Association for Psoriasis and Skin Immunology (TAPSI), and Taiwan Society of cardiology (TSOC) joint consensus recommendations for the management of psoriatic disease with attention to cardiovascular comorbidities.

Psoriatic disease is a chronic inflammatory disorder with skin and joint manifestations. Due to the persistent inflammatory state exhibited by patients with psoriasis, multiple systemic comorbidities occur more frequently in patients with psoriasis than in the general population, and the risk of cardiovascular (CV) diseases is significantly increased. As the pathophysiology of psoriatic disease is becoming better understood, the sharing of underlying pathogenic mechanisms between psoriatic and CV diseases is becoming increasingly apparent. Consequently, careful attention to CV comorbidities that already exist or may potentially develop is needed in the management of patients with psoriasis, particularly in the screening and primary prevention of CV disease and in treatment selection due to potential drug-drug and drug-disease interactions. Furthermore, as the use of effective biologic therapy and more aggressive oral systemic treatment for psoriatic disease is increasing, consideration of the potential positive and negative effects of oral and biologic treatment on CV disease is warranted. To improve outcomes and quality of care for patients with psoriasis, the Taiwanese Dermatological Association, the Taiwanese Association for Psoriasis and Skin Immunology, and the Taiwan Society of Cardiology established a Task Force of 20 clinicians from the fields of dermatology, cardiology, and rheumatology to jointly develop consensus expert recommendations for the management of patients with psoriatic disease with attention to CV comorbidities.

Efficacy of Dupilumab on Different Phenotypes of Adult with Moderate-to-Severe Atopic Dermatitis in Taiwan: A Real-World Study.

To determine phenotype-related dupilumab response in adult patients with atopic dermatitis (AD), this multicenter, retrospective study included 111 adults with moderate-to-severe AD in Taiwan, with median age of 31.5 years (18-87) and 71 (64.0%) males. Patients received dupilumab 300 mg per two to three weeks up to 12 months. We found a significant improvement after 4 and 16 weeks of treatment in all patients for all the assessed scores, including eczema area and severity index (EASI) improvement ≥50% (EASI-50) and 75% (EASI-75), EASI reaching minimal clinically important difference (MCID), and Investigator's Global Assessment (IGA) improvement ≥2. Importantly, prior to asthma, early AD onset and 3-week drug intervals were significantly associated with a high proportion of EASI-75 at month 12, while prurigo and lichenoid phenotypes were associated with a lower proportion of EASI-75 at month 12. However, the majority of adverse events were mild in severity. In conclusion, our study results identify phenotype-related dupilumab response at month 12 in adults with moderate-to-severe AD, and we suggest that treatment should not be discontinued until reaching a satisfactory clinical response.

Gut microbiota differences between psoriatic arthritis and other undifferentiated arthritis: A pilot study.

BACKGROUND: Psoriatic arthritis (PSA) is a form of immune-mediated inflammatory arthritis that predominantly begins with enthesitis. Studying the gut microbiota of PSA patients may offer new insights into the pathogenesis of enthesitis, compared to other arthritis. We designed a prospective study to examine gut microbiome of patients with PSA, primarily with enthesitis and dactylitis, and compared the data with other undifferentiated types of arthritis (NO PSA) patients, without enthesitis or dactylitis. METHODS: We enrolled 9 PSA patients and 10 NO PSA patients in this study. We excluded rheumatoid arthritis, systemic lupus erythematosus, Sjogren syndrome, systemic sclerosis, mixed connective tissue disease, polymyositis, dermatomyositis, ANCA-associated vasculitis, and gouty arthritis patients. The fecal samples were investigated using 16S rRNA amplicon sequencing, followed by bioinformatics and statistical analyses. RESULTS: None of the available objective clinical laboratory data could differentiate PSA group from the NO PSA subgroup. The microbiota result shows that Family: XIII_AD3011 is significantly higher in NO PSA patients' than in PSA patients' stool samples (P = .039). Megasphaera elsdenii in the PSA group was 10,000 times higher than in the NO PSA group.Our results demonstrated high intragroup homogeneous and high intergroup heterogeneous microbiota. The clinical symptoms of either enthesitis or dactylitis are associated with higher presence of specific microbiota in the current study. The PSA and other undifferentiated arthritis could be differentiated with microbiota analysis. In the future, a larger cohort and thorough biochemical study are needed for confirmation.The microbiota is different between PSA and NO PSA patients, and the species could be used as a differential diagnostic tool between these 2 diseases. The clinically available serum markers may not be enough to reflect the details of patients with different patterns of arthritis. Megasphaera elsdenii species could be a link between gut flora and enthesitis and/or dactylitis clinically in PSA. We confirm the fact that the Bifidobacterium longum correlates negatively with eosinophils.

TNF-α Activating Osteoclasts in Patients with Psoriatic Arthritis Enhances the Recruitment of Osteoclast Precursors: A Plausible Role of WNT5A-MCP-1 in Osteoclast Engagement in Psoriatic Arthritis.

Psoriatic arthritis (PsA) results from joint destruction by osteoclasts. The promising efficacy of TNF-α blockage indicates its important role in osteoclastogenesis of PsA. WNT ligands actively regulate osteoclastogenesis. We investigated how WNT ligands activate osteoclasts amid the TNF-α milieu in PsA. We first profiled the expression of WNT ligands in CD14+ monocyte-derived osteoclasts (MDOC) from five PsA patients and five healthy controls (HC) and then validated the candidate WNT ligands in 32 PsA patients and 16 HC. Through RNA interference against WNT ligands in MDOC, we determined the mechanisms by which TNF-α exerts its effects on osteclastogenesis or chemotaxis. WNT5A was selectively upregulated by TNF-α in MDOC from PsA patients. The number of CD68+WNT5A+ osteoclasts increased in PsA joints. CXCL1, CXCL16, and MCP-1 was selectively increased in supernatants of MDOC from PsA patients. RNA interference against WNT5A abolished the increased MCP-1 from MDOC and THP-1-cell-derived osteoclasts. The increased migration of osteoclast precursors (OCP) induced by supernatant from PsA MDOC was abolished by the MCP-1 neutralizing antibody. WNT5A and MCP-1 expressions were decreased in MDOC from PsA patients treated by biologics against TNF-α but not IL-17. We conclude that TNF-α recruits OCP by increased MCP-1 production but does not directly activate osteoclastogenesis in PsA.

Minimally Invasive Transungual Tumors Enucleation With Nail Preservation for Subungual Glomus Tumors.

BACKGROUND: Glomus tumors are benign neurovascular neoplasms, most commonly located in the subungual region. These subcutaneous nodules are characterized by intense pain and temperature sensitivity. Although surgical excision is the curative treatment, permanent nail deformity and recurrence are not uncommon after conventional surgery. OBJECTIVE: This study evaluated the long-term efficacy of a modified transungual approach with nail preservation for removing subungual glomus tumors. MATERIAL AND METHODS: Thirty-nine patients with clinically diagnosed and histopathologically proven glomus tumors treated at a medical center over a 13-year period (2007-2019) were retrospectively evaluated. RESULTS: The 39 patients included 28 women and 11 men (ratio, 2.5:1), with a mean age of 48.9 years. Thirty-four tumors were located in the fingers and 5 in the toes. All patients returned to normal activity soon after the surgery. At a mean follow-up of 28.8 months, all were pain free or experienced minimal pain and were satisfied with treatment outcomes. One patient (2.6%) experienced recurrence. No nail deformity was observed. CONCLUSION: The transungual approach with nail plate preservation is a novel and effective method for removing subungual glomus tumors with reduced postoperative pain and rapid healing, while preserving or improving the configuration of the nail.

Whole genome sequencing identifies genetic variants associated with co-trimoxazole hypersensitivity in Asians.

BACKGROUND: Co-trimoxazole, a sulfonamide antibiotic, is used to treat a variety of infections worldwide, and it remains a common first-line medicine for prophylaxis against Pneumocystis jiroveci pneumonia. However, it can cause severe cutaneous adverse reaction (SCAR), including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms. The pathomechanism of co-trimoxazole-induced SCAR remains unclear. OBJECTIVE: We aimed to investigate the genetic predisposition of co-trimoxazole-induced SCAR. METHODS: We conducted a multicountry case-control association study that included 151 patients with of co-trimoxazole-induced SCAR and 4631 population controls from Taiwan, Thailand, and Malaysia, as well as 138 tolerant controls from Taiwan. Whole-genome sequencing was performed for the patients and population controls from Taiwan; it further validated the results from Thailand and Malaysia. RESULTS: The whole-genome sequencing study (43 case patients vs 507 controls) discovered that the single-nucleotide polymorphism rs41554616, which is located between the HLA-B and MICA loci, had the strongest association with co-trimoxazole-induced SCAR (P = 8.2 × 10-9; odds ratio [OR] = 7.7). There were weak associations of variants in co-trimoxazole-related metabolizing enzymes (CYP2D6, GSTP1, GCLC, N-acetyltransferase [NAT2], and CYP2C8). A replication study using HLA genotyping revealed that HLA-B∗13:01 was strongly associated with co-trimoxazole-induced SCAR (the combined sample comprised 91 case patients vs 2545 controls [P = 7.2 × 10-21; OR = 8.7]). A strong HLA association was also observed in the case patients from Thailand (P = 3.2 × 10-5; OR = 3.6) and Malaysia (P = .002; OR = 12.8), respectively. A meta-analysis and phenotype stratification study further indicated a strong association between HLA-B∗13:01 and co-trimoxazole-induced drug reaction with eosinophilia and systemic symptoms (P = 4.2 × 10-23; OR = 40.1). CONCLUSION: This study identified HLA-B∗13:01 as an important genetic factor associated with co-trimoxazole-induced SCAR in Asians.

The Clinical Trend of Leprosy from 2000 to 2016 in Kaohsiung, a Major International Harbor City in Taiwan, Where Leprosy is Almost Eradicated.

Leprosy is a socially stigmatized granulomatous skin disease caused by Mycobacterium leprae. Due to improvements in medicine and hygiene in Taiwan, the incidence is very low, up to one dozen per year; however, leprosy has never been eradicated due to the increased numbers of immigrants from Southeast Asia. This study aimed to characterize the clinical and histopathological features of patients with leprosy in the context of near elimination. Fifteen cases of pathologically proven leprosy were identified from 2000 to 2016 in Kaohsiung Chang Gung Memorial Hospital. The clinical presentations, demographic details, treatment responses, and disease outcomes were reviewed. The mean age was 46 years (range: 26-73 years). Eight cases were native Taiwanese, while 6 cases and 1 case involved foreign workers from Indonesia and Thailand, respectively. The diagnosis was made 3-6 months on average after skin lesions appeared. The most common clinical subtype was lepromatous leprosy (n = 7). Ten patients were multibacillus microscopically. Three cases were deported. The remaining 12 patients received dapsone and rifampicin for 12 months without recurrence to date. In the near leprosy-eradicated country, early diagnosis and physician vigilance are critical in disease control. Immigrants from endemic countries require strict and professional dermatological examinations and regular follow-up.

Recommendations for psoriatic arthritis management: A joint position paper of the Taiwan Rheumatology Association and the Taiwanese Association for Psoriasis and Skin Immunology.

In Taiwan, the incidence and prevalence of psoriatic arthritis (PsA) have risen significantly in recent years. Moreover, data from the Taiwan National Health Insurance Research Database (NHIRD) show that more than 85% of PsA patients are treated with just non-steroidal anti-inflammatory drugs (NSAIDs) and/or conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). Taiwanese clinicians have also expressed concerns regarding uncertainties in the diagnosis of PsA and the delayed, interrupted, and/or tapered use of biologics, as well as differences in therapeutic preferences between and within dermatologists and rheumatologists. To address these issues, the Taiwan Rheumatology Association and the Taiwanese Association for Psoriasis and Skin Immunology jointly convened a committee of 28 clinicians from the fields of rheumatology, dermatology, orthopedics, and rehabilitation, to develop evidence-based consensus recommendations for the practical management of PsA in Taiwan. A total of six overarching principles and 13 recommendations were developed and approved, as well as a treatment algorithm with four separate tracks for axial PsA, peripheral PsA, enthesitis, and dactylitis. Psoriasis (PsO) management was not discussed here, as the Taiwanese Dermatological Association has recently published a comprehensive consensus statement on the management of PsO. Together, these recommendations provide an up-to-date, evidence-based framework for PsA care in Taiwan.

Upregulation of miR-941 in Circulating CD14+ Monocytes Enhances Osteoclast Activation via WNT16 Inhibition in Patients with Psoriatic Arthritis.

Psoriatic arthritis (PsA) is a destructive joint disease mediated by osteoclasts. MicroRNAs (miRNAs) regulate several important pathways in osteoclastogenesis. We profiled the expression of miRNAs in CD14+ monocytes from PsA patients and investigated how candidate microRNAs regulate the pathophysiology in osteoclastogenesis. The RNA from circulatory CD14+ monocytes was isolated from PsA patients, psoriasis patients without arthritis (PsO), and healthy controls (HCs). The miRNAs were initially profiled by next-generation sequencing (NGS). The candidate miRNAs revealed by NGS were validated by PCR in 40 PsA patients, 40 PsO patients, and 40 HCs. The osteoclast differentiation and its functional resorption activity were measured with or without RNA interference against the candidate miRNA. The microRNA-941 was selectively upregulated in CD14+ monocytes from PsA patients. Osteoclast development and resorption ability were increased in CD14+ monocytes from PsA patients. Inhibition of miR-941 abrogated the osteoclast development and function while increased the expression of WNT16. After successful treatment, the increased miR-941 expression in CD14+ monocytes from PsA patients was revoked. The expression of miR-941 in CD14+ monocytes is associated with PsA disease activity. MiR-941 enhances osteoclastogenesis in PsA via WNT16 repression. The miR-941 could be a potential biomarker and treatment target for PsA.

Selective AhR knockout in langerin-expressing cells abates Langerhans cells and polarizes Th2/Tr1 in epicutaneous protein sensitization.

The aryl hydrocarbon receptor (AhR) represents an environmental sensor regulating immune responses. In the skin, AhR is expressed in several cell types, including keratinocytes, epidermal Langerhans cells (LC), and dermal dendritic cells (DC). The mechanisms how AhR activates or inhibits cutaneous immune responses remain controversial, owing to differences in the cell-specific functions of AhR and the different activating ligands. Therefore, we sought to investigate the role of AhR in LC and langerin+ and negative DC in the skin. To this aim, we generated Langerin-specific and CD11c-specific knockout (-/-) mice lacking AhR, respectively, in LC and Langerin+ dermal DC and in all CD11c+ cells. These were then tested in an epicutaneous protein (ovalbumin, Ova) sensitization model. Immunofluorescence microscopy and flow cytometry revealed that Langerin-AhR-/- but not CD11c-AhR-/- mice harbored a decreased number of LC with fewer and stunted dendrites in the epidermis as well as a decreased number of LC in skin-draining lymph nodes (LN). Moreover, in the absence of AhR, we detected an enhanced T helper type-2 (Th2) [increased interleukin 5 (IL-5) and interleukin 13 (IL-13)] and T regulatory type-1 (Tr1) (IL-10) response when LN cells were challenged with Ova in vitro, though the number of regulatory T cells (Treg) in the LN remained comparable. Langerin-AhR-/- mice also exhibited increased blood levels of Ova-specific immunoglobulin E (IgE). In conclusion, deletion of AhR in langerin-expressing cells diminishes the number and activation of LC, while enhancing Th2 and Tr1 responses upon epicutaneous protein sensitization.

Modified Suction-Assisted Cartilage Shaver for Axillary Osmidrosis.

Apocrine osmidrosis (AO) is a chronic, recurrent, and disturbing disease characterized by malodorous secretion from apocrine glands. Despite various conservative and nonsurgical treatments, surgical removal of apocrine glands remains the cornerstone for AO treatment. Conventional suction-assisted cartilage shaver is effective; however, there are several risks and complications. Hence, we modified the conventional method to achieve better effectiveness and reduce complications. This paper aims to evaluate the clinical effectiveness and the complications arising from the modified suction-assisted cartilage shaver for AO. Thirty-nine patients (M/F=11/28, average age 26.3 years) received this surgical treatment for AO from 2013 to 2017 in the Department of Dermatology at Kaohsiung Chang Gung Memorial Hospital, Taiwan. A suction-assisted cartilage shaver was introduced for the ultimate removal of the subcutaneous tissue containing the apocrine glands. A 0.5 cm incision was made in the center of the identified elliptical surgical area at each axilla. After defatting, the incision was closed primarily. The defatting skin was anchored to the axillary fascia by using 4-0 sutures without drains. We then evaluated the clinical efficacy and complications. The mean duration of follow-up was 31.8 months (12-68 months). Among patients receiving the modified cartilage shaving for AO, 92.3% achieved excellent-to-good results, 5.1% had acceptable results, and 2.6% had fair results. None of them experienced poor clinical efficacy. There was no skin necrosis, hematoma, nor wound infection after the surgery. There were no recurrences in all these patients 2 years after the surgery. This modified suction-assisted cartilage shaver for AO results in good efficacy, a low complication rate, and a low recurrence rate. The method is superior to the conventional one due to tissue glue-free procedure, greater comfort in postoperative care, minimal wounds, less hematoma, and less skin necrosis. The clinical study registration number of this study is NCT03793374.

CCL21 Induces mTOR-dependent MALAT1 Expression, Leading to Cell Migration in Cutaneous T-Cell Lymphoma.

BACKGROUND: Mycosis fungoides (MF) is indolent, but may disseminate to leukemia. We reported that C-C motif chemokine ligand 21 (CCL21) is associated with MF invasion and progression. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long noncoding RNA, is associated with several cancer types, however, how it interacts with CCL21 to regulate MF progression, remains unclear. MATERIALS AND METHODS: Expression of long noncoding RNAs MALAT1, antisense noncoding RNA in the INK4 locus (ANRIL), Hox antisense intergenic RNA (HOTAIR), highly up-regulated in liver cancer RNA (HULC), and leukemia-associated non-coding insulin-like growth factor 1 receptor activator RNA 1 (LUNAR1) in tissues from MF was studied using polymerase chain reaction and RNA interference in MF cell line MyLa were used to address this question. RESULTS: Expression of MALAT1 was selectively increased in MF tissues. C-C Chemokine receptor type 7 (CCR7) expression was found to be increased in MyLa cells. CCL21 was found not only to mediate migration, but also to enhance MALAT1 and mammalian target of rapamycin (mTOR) activation in MyLa cells. Knockdown of MALAT1 abrogated CCL21-mediated migration, but not mTOR activation. In contrast, mTOR inhibition reduced CCL21-mediated migration and MALAT1 expression. CONCLUSION: CCL21 induced mTOR activation in MyLa cells, followed by expression of MALAT1, causing cell migration. MALAT1 and mTOR are potential therapeutic targets for MF.

MiR-146a-5p Expression in Peripheral CD14⁺ Monocytes from Patients with Psoriatic Arthritis Induces Osteoclast Activation, Bone Resorption, and Correlates with Clinical Response.

In psoriatic arthritis (PsA), progressive bone destruction is mediated by monocyte-derived osteoclasts. MicroRNAs (miRNAs) regulate many pathophysiological processes; however, their function in PsA patient monocytes has not been examined. This study aims to address whether specific miRNAs in CD14⁺ monocytes and monocyte-derived osteoclasts cause active osteoclastogenesis in PsA patients. Candidate miRNAs related to monocyte activation (miR-146a-5p, miR-146b-5p and miR-155-5p) were measured in circulatory CD14⁺ monocytes collected from 34 PsA patients, 17 psoriasis without arthritis (PsO) patients, and 34 normal controls (NCs). CD14⁺ monocytes were cultured with media containing TNF-α and RANKL to differentiate into osteoclasts. Osteoclast differentiation and bone resorption were measured by TRAP immunostaining and dentin slice resorption, respectively. The results showed that the miR-146a-5p expression was higher in PsA patient-derived CD14⁺ monocytes compared to PsO and NCs. Activation and bone resorption were selectively enhanced in osteoclasts from PsA patients, but both were abrogated by RNA interference against miR-146a-5p. More importantly, after clinical improvement using biologics, the increased miR-146a-5p expression in CD14⁺ monocytes from PsA patients was selectively abolished, and associated with blood CRP level. Our findings indicate that miR-146a-5p expression in CD14⁺ monocytes derived from PsA patients correlates with clinical efficacy, and induction of osteoclast activation and bone resorption.

Treatment with TNF-α inhibitor rectifies M1 macrophage polarization from blood CD14+ monocytes in patients with psoriasis independent of STAT1 and IRF-1 activation.

BACKGROUND: Psoriasis is a systemic inflammatory disease with dramatic responses to TNF-α inhibitors. TNF-α is mainly produced by macrophages. However, how macrophage polarization contributes to psoriasis remains unknown. OBJECTIVE: We aimed to investigate the molecular mechanisms of macrophage polarization in psoriasis. METHODS: 8 patients with moderate to severe psoriasis (Male/Female: 4/4, average age: 47.9 years old) and 8 healthy controls (Male/Female: 4/4, average age: 49.3 years old) were recruited. Their peripheral CD14+ monocytes were isolated with magnetic beads and then were differentiated into macrophages. The differential macrophage polarization was compared among normal controls, psoriatic patients before and after TNF-α inhibitors. The U937 cells were used to investigate the mechanisms by which TNF-α altered the macrophage polarization. RESULTS: The ratio of M1 to M2a macrophage polarization was higher in psoriatic patients comparing with that in controls. The decreasing M1/M2a ratio was parallel to decreasing PASI severity score after adalimumab treatment. Consistently, TNF-α blockage decreased M1/M2a ratio in U937 cells. The induction of STAT1 and IRF-1 in polarized U937 M1 cells was inhibited by TNF-α inhibitor. However, STAT1 and/or IRF-1 interference could not resume M1 polarization. In skin, the increased M1 and M2 infiltration in lesions returned to baseline after successful treatment with TNF-α inhibitor. CONCLUSIONS: Increased M1 polarization is associated with higher disease severity in psoriasis, resuming to baseline after successful treatment by TNF-α inhibitors. TNF-α blockage inhibits M1 polarization through STAT1- and IRF-1-independent pathways. Macrophage polarization may contribute to disease progression in psoriasis.

Efficacy and safety of topical SR-T100 gel in treating actinic keratosis in Taiwan: A Phase III randomized double-blind vehicle-controlled parallel trial.

BACKGROUND: Currently available topical treatments for actinic keratosis (AK) are associated with substantial side-effects. OBJECTIVES: To evaluate the efficacy and safety of topical SR-T100 gel in treating AK. METHODS: A multicenter, randomized, double-blinded phase III trial was conducted. Patients with at least two clinically visible AK were enrolled and a punch biopsy was performed on one of the AK to confirm the diagnosis. This study consisted of up to 16-week treatment and 8-week post-treatment periods. Medication was applied daily with occlusive dressing. RESULTS: 123 subjects were recruited and 113 were randomized. 76 subjects were in the SR-T100 and 37 in the vehicle arms. In SR-T100 and vehicle groups, 32.39% and 17.14% of subjects achieved complete clearance, respectively. For 75% partial clearance of lesions, 71.83% and 37.1% of subjects achieved this goal in SR-T100 and vehicle group, respectively. When comparing SR-T100 to vehicle, the odds ratio of complete clearance was 2.14 (p = 0.111), and odds ratio of partial clearance was 4.36 (p < 0.001). Severe local reactions were reported by only one subject using SR-T100. CONCLUSION: The imitation of the study was that not all the treated AK lesions were confirmed by histopathology. The diagnostic uncertainty may contribute to the high partial clearance rate in the vehicle group since the clinical-diagnosed AK showed higher clearance rate compared to histopathology-confirmed AK. The use of occlusive dressing was another possible explanation for high placebo effects. The results suggested that topical SR-T100 gel may be an effective and safe treatment for field therapy of AK.