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Background@#Psoriasis is a complex and heterogeneous disease that widely affects a patient’s life. Biological therapy is usually prescribed in patients with severe psoriasis that do not respond to conventional treatment. However, data on the specific patient characteristics receiving biologics are still unavailable. @*Objective@#To classify patients with psoriasis into subgroups with distinct phenotypes through cluster analysis, and to evaluate the differences between the clusters to predict disease prognosis by examining the response to biological therapy. @*Methods@#The clinical characteristics of the patients with psoriasis were investigated and categorized using hierarchical cluster analysis. After clustering, the clinical characteristics of the patients were compared and the initiation of treatment with biologics according to the clusters were evaluated. @*Results@#A total of 361 patients with psoriasis were classified into two clusters using 16 distinct clinical phenotypes. Group 1 (n=202) consisted of male smokers and alcohol users with higher psoriasis area and severity index (PASI), older age of onset, higher body mass index, and comorbidities including psoriatic arthritis, hypertension, and diabetes when compared to group 2 (n=159). Group 1 had a significantly higher probability of biological treatment initiation than group 2 (p=0.039). The measured risk factors for the initiation of biologics compared were PASI (p<0.001) and nail involvement (p=0.022). @*Conclusion@#Cluster analysis classified patients with psoriasis into two subgroups according to their clinical characteristics. Predicting the disease prognosis using a combination of specific clinical parameters may aid in the management of the disease.
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Background@#Psoriasis imposes a significant treatment burden on patients, particularly impacting well-being and quality of life (QoL). The psychosocial impact of psoriasis treatments remains unexplored in most patient populations. @*Objective@#To assess the impact of adalimumab on health-related QoL (HRQoL) in Korean patients with psoriasis. @*Methods@#This 24-week, multicenter, observational study, assessed HRQoL in Korean patients treated with adalimumab in a real-world setting. Patient-reported outcomes (PROs) including European Quality of Life-5 Dimension scale (EQ-5D), EQ-5D VAS, SF-36, and DLQI were evaluated at week 16 and 24, versus baseline. Patient satisfaction was assessed using TSQM. @*Results@#Among 97 enrolled patients, 77 were assessed for treatment effectiveness. Most patients were male (52, 67.5%) and mean age was 45.4 years. Median baseline body surface area and Psoriasis Area and Severity Index (PASI) scores were 15.00 (range 4.00~80.00) and 12.40 (range 2.70~39.40), respectively. Statistically significant improvements in all PROs were observed between baseline and week 24. Mean EQ-5D score improved from 0.88 (standard deviation [SD], 0.14) at baseline to 0.91 (SD, 0.17) at week 24 (p=0.0067). The number of patients with changes in PASI 75, 90, or 100 from baseline to week 16 and 24 were 65 (84.4%), 17 (22.1%), and 1 (1.3%); and 64 (83.1%), 21 (27.3%), and 2 (2.6%), respectively. Overall treatment satisfaction was reported, including effectiveness and convenience. No unexpected safety findings were noted. @*Conclusion@#Adalimumab improved QoL and was well-tolerated in Korean patients with moderate to severe psoriasis, as demonstrated in a real-world setting. Clinical trial registration number (clinicaltrials.gov: NCT03099083).
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Background@#Currently, there is no consensus on the treatment of psoriasis in Korean patients. @*Objective@#This study aimed to establish a consensus on the basic therapeutic principles for Korean patients with plaque psoriasis. @*Methods@#Using the modified Delphi method, a steering committee proposed 53 statements for the first Delphi round, which covered five subjects: (1) the goal of treatment and evaluation of disease severity, (2) topical therapy, (3) phototherapy, (4) conventional systemic therapy, and (5) biologic therapy. The panel of dermatologists scored the level of agreement for each statement on a ten-point scale with scores ranging from 1 (strongly disagree) to 10 (strongly agree). After discussing the results of the first round, the committee reformulated 41 statements. Finally, consensus was defined as more than 70% of the second round scores being ≥7. @*Results@#The panel participants strongly agreed that the ideal treatment goals for Korean patients with plaque psoriasis should include complete skin clearance and high dermatological quality of life. A strong consensus was also reached on the use of topical agents for psoriasis of any severity, the consideration of phototherapy before biologics therapy, the conventional systemic agents for moderate-to-severe psoriasis, and the recommendation of biologic for retractable psoriasis to conventional systemic therapy and phototherapy. @*Conclusion@#This modified Delphi panel established an expert consensus on the therapeutic approach for Korean patients with plaque psoriasis. This consensus may improve the treatment outcomes for psoriasis in Korea.
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Vitiligo has been considered an unexplained paradoxical phenomenon during biologics use.Herein, we report an adult case of progression of pre-existing vitiligo during secukinumab treatment for psoriasis, and we also examined the immunohistochemical changes in relation to biologics use. He was being administered monthly secukinumab of 300 mg dose for 2 years, and all psoriatic lesions were cleared, but pre-existing hypopigmented lesions became more distinct and larger than before unlike when using adalimumab. A skin biopsy of the hypopigmented lesion showed loss of epidermal melanocytes and absence of gp100 immune activities, and he was finally diagnosed with progression of pre-existing vitiligo.Immunohistochemical staining of vitiligo lesion showed decrease in interleukin-17 and tumor necrosis factor-α and increase in CD8+ T cells, interferon-γ, and CXCL10 after the use of secukinumab. In this study, we suggest that biologics-induced cytokine imbalance play a critical role in vitiligo progression in patients with chronic inflammatory diseases, including psoriasis.
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Background@#Interleukin (IL)-17 and IL-23 inhibitors have helped achieve clear skin in many patients with psoriasis. However, real-world data to compare short- and long-term efficacy of these biologics in Korean patients are lacking. @*Objective@#To compare short- and long-term efficacy of IL-17A and IL-23 inhibitors in patients with moderateto-severe psoriasis. @*Methods@#We retrospectively evaluated efficacy of IL-17A and IL-23 inhibitors among patients treated at Ajou University Hospital from 2017 to 2022. The specific agents studied were as follows: secukinumab, 32 patients; ixekizumab, four patients; guselkumab, 13 patients; and risankizumab, 31 patients. Patients who were followed up for less than a year or changed biologics were excluded. @*Results@#The rates of psoriasis area and severity index (PASI) 90 achievement of secukinumab were 62.5%, 86.7%, 89.3%, 80.8%, and 70.8% at weeks 16, 40, 88, 112, and 136, respectively. For ixekizumab, the PASI90 achievement rates were 75%, 100%, 75%, and 100% at weeks 16, 40, 64, and 88, respectively. The PASI90 achievement rates of guselkumab were 53.8%, 76.9%, 72.7%, and 77.8% at weeks 20, 44, 68, and 92, respectively. For risankizumab, PASI90 achievement rates were 69.7%, 90.0%, 93.7%, and 100% at weeks 28, 52, 76, and 100, respectively. Before 52 weeks, PASI90 achievement was significantly lower with guselkumab than with secukinumab (hazardratio=0.22). After 52 weeks, PASI90 achievement was significantly higher with risankizumab than with secukinumab (hazard ratio=2.00). @*Conclusion@#PASI90 was achieved faster with IL-17A inhibitors than with IL-23 inhibitors. However, IL-23 inhibitors afforded the maintenance of a higher PASI score after 52 weeks.
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Background@#Psoriasis is a multifactorial, chronic immunological disease, in which a specific allele HLA-Cw6 is associated with various clinical manifestations. However, information regarding this genetic factor in Korean patients with psoriasis remains limited. @*Objective@#We aimed to explore the differences in clinical patterns and treatment responsiveness, depending on the expression of HLA-Cw6, in Korean patients with psoriasis. @*Methods@#We divided patients into two groups, namely HLA-Cw6-positive and HLACw6-negative, based on the HLA-Cw6 allelic analysis using the single specific primerpolymerase chain reaction method. All clinical information regarding these patients was collected in a retrospective manner. Next, we evaluated the levels of serum Th17-related cytokines in 34 patients diagnosed with psoriasis using a multiplex immunoassay. Finally, we performed immunohistochemical staining of interleukin (IL)-22 and IL-31, as these cytokines showed the maximum differential expression between the HLA-Cw6 positive and negative groups. @*Results@#HLA-Cw6 positive and negative groups comprised of 13 and 21 patients, respectively. HLA-Cw6-positive group had more chance of having metabolic comorbidities (76.9% for HLA-Cw6-positive group; 28.6% for HLA-Cw6-negative group; p=0.002). Also, HLA-Cw6-positive group showed significantly higher treatment response (38.5% in positive group showed Psoriasis Area and Severity Index 90% improvement compared to 4.8% in the negative group; p=0.012). However, all Th17-related cytokines were not significantly different across the two groups. Furthermore, IL-22 and IL-31 immunohistochemical staining did not correlate with the serum cytokines levels. @*Conclusion@#HLA-Cw6 types can be associated with disease severity, comorbidities, and treatment responsiveness in Korean patients with psoriasis.
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Background@#Palmoplantar pustulosis (PPP) is initiated from the acrosyringium. However, it is unclear whether PPP should be considered a distinct entity or should be classified into the spectrum of pustular psoriasis, also known as palmoplantar pustular psoriasis (PPPP). @*Objective@#We evaluated the differences in immunohistochemical staining in patients with PPP to determine whether they can be classified into two groups based on psoriatic properties or acrosyringeal properties. @*Methods@#Nineteen punch biopsy specimens diagnosed with PPP were collected. Antibodies were chosen for identifying the acrosyringeal properties of α-3-nicotine acetylcholine receptors (α-3-nAChR), psoriatic properties of interleukin (IL)-23 and IL-36R, inflammatory cell properties of human cathelicidin antimicrobial peptide 18/LL-37, IL-8, lipocalin-2 (LCN2), and CD3. The degree of staining of the epidermis was evaluated using the ordinal scale (0~3). The principal component analysis was used to derive principal components (PCs) of common variation between the stains, and the two groups were divided using PCs and cluster analysis. @*Results@#Three main PCs explained 64% of the total variance in PPP. PC1 (pustular psoriasis properties) showed a higher correlation with IL-36R. PC2 (acrosyringeal/inflammatory properties) showed a higher correlation with α-3-nAChR, IL-8, LCN2, and CD3. PC3 (psoriasis properties) showed a higher correlation with IL-23. PC1 showed a statistically significant difference (p=0.0284) between the two groups. We identified three PCs associated with the pathomechanisms of PPP. @*Conclusion@#Although PC1 showed a statistically significant difference between the two groups, we did not identify differential protein expression related to the pathogenesis between PPP and PPPP.
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Background@#Since the advent of biologics, they have been an efficient treatment for severe psoriasis vulgaris. Psoriasis that is refractory to biologics is associated with factors, such as old age, a high initial psoriasis area and severity index, a high body mass index (BMI), and nail involvement. @*Objective@#We evaluated the clinical characteristics and differences in laboratory parameters in patients with severe psoriasis who switched biologics at least once. @*Methods@#We analyzed the demographics, medical records, and laboratory data of 29 Korean patients who had switched biologics. Patients were classified into two groups based on the number of times they switched to biologics. @*Results@#The reasons for switching biologics in the 29 patients were primary failure (37.9%), secondary failure (58.6%), and occurrence of adverse events (3.5%). The multiple switching group showed higher mean values than the single switching group for the factors associated with low efficacy of biologics, such as age at initial presentation (43.4±9.6 years vs. 42.1±12.1 years), an initial psoriasis area severity index (15.3±6.3 vs. 12.9±4.4), and a BMI (27.4±4.0 kg/m2 and 26.3±3.4 kg/m2 ), respectively. @*Conclusion@#In this single-centered study, secondary failure was the most common reason for switching biologics. Higher mean values for factors affecting the efficacy of biologics were noted in the multiple switching group; however, the difference was not statistically significant. When choosing biologics for patients, dermatologists should be mindful of this as they select the second-line biologics.
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Background@#Psoriasis is a chronic relapsing inflammatory disease, with several cytokines related to its pathophysiology and clinical manifestations, such as disease activity, severity, and clinical subtype. However, there is limited information regarding Korean psoriasis patients.Objective We investigated the association between serum inflammatory cytokines and clinical characteristics of psoriasis, including treatment modalities. @*Methods@#We evaluated the serum Th17-related cytokine levels of 70 patients diagnosed with psoriasis using a multiplex immunoassay. All clinical information of patients was collected by reviewing electronic medical records and photo documentation in a retrospective manner. @*Results@#The serum IL-23 level was significantly higher in the young age group (<40 years), and the IL-6, TNFβ, and IL-28A levels were significantly higher in the early onset group (<40 years). In addition, patients with moderate-to-severe psoriasis (PASI≥10 and body surface area ≥10%) exhibited significantly lower serum IL-28A levels. We observed high serum TNF-α and CCL20 levels in patients with metabolic comorbidities and those with psoriatic arthritis, respectively, and biologics use and systemic treatment modality were also significantly associated with the serum levels of some cytokines. @*Conclusion@#Disease severity, comorbidities, presence of psoriatic arthritis, and treatment responsiveness might affect the inflammatory cytokine levels in psoriasis patients. Therefore, the serum cytokine levels can be used to predict the severity or treatment responsiveness of psoriasis patients.
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Henoch-Schönlein purpura (HSP) is a systemic vasculitis characterized by purpura, arthritis, abdominal pain, and nephritis. Gastrointestinal involvement can manifest as pain, intussusception, intestinal bleeding, and intestinal perforation. We report a case of fulminant HSP at an age of eight in 1994, with multiple complications of intra-thoracic bleeding, massive intestinal perforation, nephritis, and various skin rashes. The brisk bleeding findings of intestinal on Technetium-99m-labeled red blood cell scan (99mTc RBC scan) were well matched to those of the emergency laparotomy and the resected intestine. The patient's abdominal conditions improved gradually but nodular skin eruptions developed newly apart from improving preexisting lower limb rashes and the urine findings continued abnormal, so skin and kidney biopsy were done for the diagnosis. After cyclosporine therapy, skin eruptions and urine findings returned to normal gradually. On a follow-up after 25 years in 2019, the patient is 33-year-old, healthy without any abnormality on blood chemistries and urine examination.
Subject(s)
Adult , Humans , Abdominal Pain , Arthritis , Biopsy , Cyclosporine , Diagnosis , Emergencies , Erythrocytes , Exanthema , Follow-Up Studies , Hemorrhage , Intestinal Perforation , Intestines , Intussusception , Kidney , Laparotomy , Lower Extremity , Nephritis , Purpura , Skin , Systemic VasculitisABSTRACT
BACKGROUND: Controlling inflammation is a therapeutic goal of various autoimmune/autoinflammatory diseases including Behçet's disease (BD). The immunomodulatory effect of metabolites or metabolic analogs such as butyrate and 3-bromopyruvate has been observed in animal disease models. OBJECTIVE: We attempted to evaluate the effect of butyrate and 3-bromopyruvate on the inflammatory cytokine production by peripheral blood mononuclear cells (PBMCs) isolated from patients with mucocutaneous involvement of BD. METHODS: PBMCs isolated from 11 patients with BD and 10 healthy controls were stimulated with lipopolysaccharide in the presence of butyrate or 3-bromopyruvate. Butyrate receptor and cytokine messenger ribonucleic acid (mRNA) expression was analyzed by real-time reverse transcription polymerase chain reaction. Cytokine secretion was assessed by enzyme-linked immunosorbent assay. PBMCs survival was analyzed by flow cytometry. RESULTS: Bromopyruvate or butyrate treatment suppressed inflammatory cytokine production in PBMCs from all our subjects. Bromopyruvate also reduced PBMCs survival while butyrate did not. As the effect of butyrate was slightly greater in BD patients than in healthy controls, we analyzed butyrate receptor expression and found that lipopolysaccharide-induced free fatty acid receptor 2 mRNA level in PBMCs was higher in BD patients than in controls. CONCLUSION: We propose bromopyruvate and butyrate as supplementary therapeutic candidates to control inflammation in patients with BD.
Subject(s)
Humans , Autoimmune Diseases , Butyrates , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Glycolysis , Inflammation , Polymerase Chain Reaction , Reverse Transcription , RNA , RNA, MessengerABSTRACT
PURPOSE: To investigate whether subfoveal choroidal thickness, measured using enhanced depth imaging optical coherence tomography (EDI-OCT), is an indicator of subclinical ocular or systemic inflammation in eyes with Behçet disease (BD) without active ocular inflammation. METHODS: A retrospective analysis was used to examine clinical features of non-uveitic patients with BD (NUBD group), patients with a previous history of Behçet uveitis in an inactive state (IUBD group), and healthy controls were evaluated from October 2014 to September 2015. Subfoveal choroidal thickness was measured using EDI-OCT. RESULTS: The NUBD group included 46 eyes in 24 patients; the IUBD group included 16 eyes in 11 patients; and the control group included 35 eyes in 23 individuals. The mean subfoveal choroidal thicknesses differed significantly among these groups. Choroidal thickness was significantly greater in the NUBD (310.5 ± 81.0 µm) than in the IUBD (263.1 ± 56.6 µm, p = 0.013) and control (256.9 ± 67.9 µm, p = 0.002) groups. The disease activity score was significantly higher in the NUBD than in the IUBD group (p < 0.001), while the use of cyclosporine was significantly associated with choroidal thickness in eyes with NUBD (p = 0.039). CONCLUSIONS: Subfoveal choroidal thickness, as measured by EDI-OCT, may be a clinical indicator of subclinical ocular inflammation and systemic inflammation in BD patients without active ocular inflammation.
Subject(s)
Humans , Behcet Syndrome , Choroid , Cyclosporine , Inflammation , Retrospective Studies , Tomography, Optical Coherence , UveitisABSTRACT
BACKGROUND: Psoriasis is a chronic inflammatory skin disorder histopathologically characterized by epidermal hyperplasia, vascular proliferation, and inflammatory infiltrates. It runs a less severe course in women than in men. The role of estrogen in the pathogenesis of psoriasis remains unclear. OBJECTIVE: We investigated the clinicohistopathological differences between men and women with psoriasis and examined whether serum estrogen levels and immunohistochemical findings correlate with gender and disease severity. METHODS: We retrospectively reviewed the medical records of 500 patients with psoriasis. Among these patients, 60 who consented to participate in the study were classified into four groups as follows: 10 men showing psoriasis on < 10% of their body surface area (BSA) with psoriasis area severity index (PASI) < 10; 20 men showing psoriasis on ≥10% of their BSA with PASI≥10; 10 women showing psoriasis on < 10% of their BSA with PASI < 10; and 20 women showing psoriasis on ≥10% of their BSA with PASI ≥10. Serum estrogen levels were measured using radioimmunoassay. Immunohistochemical staining of skin biopsy tissues was performed using ERα, ERβ, and CCL5. RESULTS: Men diagnosed with psoriasis showed higher BSA and PASI scores than women. Women aged ≥60 years showed higher BSA and PASI scores than women aged < 60 years. There were no histological differences between the four groups. Serum estrogen levels were higher in the patients presenting with mild psoriasis, as well as in women. ERα, ERβ, and CCL5 showed a stronger staining tendency in patients with more severe psoriasis. CONCLUSION: Gender influences the severity of psoriasis, and estrogen plays an important role. This finding is explained by the fact that estrogen decreases inflammation in psoriasis possibly via its action on estrogen receptors in epidermal keratinocytes.
Subject(s)
Female , Humans , Male , Biopsy , Body Surface Area , Estrogens , Hyperplasia , Immunohistochemistry , Inflammation , Keratinocytes , Medical Records , Psoriasis , Radioimmunoassay , Receptors, Estrogen , Retrospective Studies , SkinABSTRACT
No abstract available.
Subject(s)
Adolescent , Female , Humans , Herpesvirus 4, Human , UlcerABSTRACT
BACKGROUND: Behçet disease (BD) is a relapsing inflammatory disease with increased production of inflammatory cytokines in peripheral blood mononuclear cells (PBMCs); however, the underlying molecular mechanisms are not well known. OBJECTIVE: To analyze whether the differential expression of transcription factors is involved in the increased tumor necrosis factor (TNF)-α and interleukin (IL)-6 production by PBMCs of BD patients compared to healthy controls (HCs). METHODS: Expression of transcription factors was examined by real-time reverse transcriptase-polymerase chain reaction and western blotting. Cytokine production by CD11b+ cells transfected with siRNAs against transcription factors was measured by enzyme-linked immunosorbent assay. RESULTS: In the absence of lipopolysaccharide stimulation, the transcript level of CCAAT-enhancer-binding proteins (C/EBP) β was increased in PBMCs from patients with active BD compared to that in PBMCs from patients with stable BD. The C/EBPδ transcript level was higher in PBMCs from patients with active BD than in those from HCs. The activating transcription factor 3 (ATF3) transcript level was increased in PBMCs from patients with stable BD compared to that in PBMCs from HCs. siRNAs targeting C/EBPβ and C/EBPδ significantly reduced the production of IL-6 and TNF-α in lipopolysaccharide-stimulated CD11b+ cells from patients with BD as well as from HCs. CONCLUSION: We found differential expression of C/EBPβ, C/EBPδ, and ATF3 in PBMCs from patients with BD depending on disease activity, indicating the involvement of these molecules in BD pathogenesis.
Subject(s)
Humans , Activating Transcription Factor 3 , Behcet Syndrome , Blotting, Western , CCAAT-Enhancer-Binding Proteins , Cytokines , Enzyme-Linked Immunosorbent Assay , Gene Expression , Interleukin-6 , Interleukins , RNA, Small Interfering , Transcription Factors , Tumor Necrosis Factor-alphaABSTRACT
BACKGROUND: Cutaneous pustular disorders include generalized pustular psoriasis (GPP) and acute generalized exanthematous pustulosis (AGEP). OBJECTIVE: To identify differences between GPP and AGEP, here we immunohistochemically evaluated interleukin (IL)-36 and the IL-23/Th17 axis. METHODS: This retrospective comparative immunohistochemical study was completed using 11 biopsies of 11 cases of GPP and 11 biopsies of 11 cases of AGEP. Through staining with the anti-IL-36-alpha (IL-36α), anti-IL-36 receptor antagonist (IL-36Ra), anti-nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), anti-IL-23, anti-IL-17, and anti-IL-8 antibodies, main expression location and intensity were visualized in the epidermis and dermis. RESULTS: In both diseases, diffuse IL-36α expression was observed in the epidermis. IL-36Ra expression was observed in the dermal perivascular area as well as in the epidermis. NF-κB expression was observed in the epidermis and perivascular dermal area. Diffuse IL-23 and IL-17 expression was seen in the whole epidermis and the perivascular dermal area. IL-8 was expressed in the subcorneal pustules and parakeratotic area. Contrary to other cytokines, IL-23 expression in the epidermis of patients with GPP was more intense than only that in patients with AGEP. CONCLUSION: Common pathomechanisms might exist in the development of GPP and AGEP based on these immunohistochemical results, but further studies are needed.
Subject(s)
Humans , Acute Generalized Exanthematous Pustulosis , Antibodies , B-Lymphocytes , Biopsy , Cytokines , Dermis , Epidermis , Immunohistochemistry , Interleukin-17 , Interleukin-23 , Interleukin-8 , Interleukins , Psoriasis , Retrospective StudiesABSTRACT
BACKGROUND: The differential diagnosis of psoriasis and seborrheic dermatitis can be difficult when both conditions are localized to the scalp without the involvement of other skin sites. OBJECTIVE: We aimed to evaluate the histopathological differences between psoriasis and seborrheic dermatitis on the scalp and identify favorable criteria for their differential diagnosis. METHODS: We evaluated 15 cases of psoriasis and 20 cases of seborrheic dermatitis of the scalp that had been clinicopathologically diagnosed. Skin biopsy sections stained with H&E were examined. Additional immunohistochemistry was performed, including Ki-67, keratin 10, caspase-5, and GLUT-1. RESULTS: On histopathological examination, mounds of parakeratosis with neutrophils, spongiform micropustules of Kogoj, and clubbed and evenly elongated rete ridges were significantly more frequently observed in psoriasis. Follicular plugging, shoulder parakeratosis and prominent lymphocytic exocytosis were significantly more common in seborrheic dermatitis. Moreover, significantly higher mitotic figures were observed in psoriatic lesions than in seborrheic dermatitis. Immunohistochemistry did not show any difference between psoriasis and seborrheic dermatitis. CONCLUSION: Histopathological features favoring psoriasis include mounds of parakeratosis with neutrophils, spongiform micropustules of Kogoj, clubbed and evenly elongated rete ridges, and increased mitotic figures (≥6/high-powered field). Features indicating seborrheic dermatitis are follicular plugging, shoulder parakeratosis and prominent lymphocytic exocytosis. Immunohistochemistry was not helpful in differentiating psoriasis from seborrheic dermatitis.