Background: Direct immunofluorescence (DIF) is a histochemical technique used to detect tissue-bound autoantibodies and diagnose various immune-mediated skin diseases. Objective: This study aimed to evaluate the sensitivity of DIF for each disorder, and the consistency between clinical, histopathological, and DIF results. Methods: A retrospective study was conducted in 194 patients who underwent skin biopsy and DIF testing at our hospital between January 2011 and December 2021. An antibody panel against immunoglobulin G (IgG), IgA, IgM, C3, C1q, and fibrinogen was used. The concordance rate and κ-coefficient between the clinical, histopathological, and DIF results were evaluated. Results: DIF was observed to be positive in 87 cases; 51 cases of immune-mediated bullous diseases, seven cases of connective tissue diseases (CTDs), 25 cases of vasculitis, and four cases of other diseases. The overall sensitivity of DIF for immune-mediated bullous diseases was 71.8%, which was higher than that of histopathology (64.8%). In CTDs and vasculitis, the overall sensitivities of DIF were 30.4% and 65.8%, respectively, which were lower than those of histopathology (73.9% and 84.2%, respectively). In addition, good concordance among the clinical, histological, and DIF results was observed. Conclusion DIF is a useful diagnostic method, especially for immune-mediated bullous diseases, lupus erythematosus, and Henoch-Schonlein purpura. However, in other CTDs and vasculitis cases, the sensitivity of DIF is relatively low. Therefore, the diagnostic value of DIF along with clinical and histopathological findings will be maximized only when the DIF test is performed for appropriate diseases.

Eosinophilic dermatosis of hematological malignancy (EDHM) is a rare condition associated with various hematologic malignancies, characterized by pruritic skin eruptions. We present a case of a 66-year-old woman with follicular lymphoma who developed urticarial and vesicular lesions indicative of EDHM following chemotherapy.The diagnosis was confirmed through histological analysis, revealing eosinophilic infiltration. Treatment included additional chemotherapy sessions and topical corticosteroids, resulting in complete resolution of skin lesions and lymphoma. EDHM requires careful differentiation based on clinical and histological findings. The pathogenesis remains unclear, but addressing underlying hematologic malignancies appears crucial in management. Early recognition of EDHM is essential for appropriate intervention due to its limited therapeutic options.

BACKGROUND/OBJECTIVES: Atherosclerosis is associated with increased inflammation in the visceral adipose tissue (VAT). Vitamin D has been reported to modulate the inflammatory responses of stromal vascular cells (SVCs) and adipocytes in adipose tissue, but the role of vitamin D in atherosclerosis biology is unclear. This study examined the effects of in vitro 1,25-dihydroxyvitamin D 3 (1,25[OH] 2 D 3 ) treatment on the inflammatory responses of SVCs and adipocytes from atherosclerotic mice.MATERIALS/METHODS: C57BL/6J (B6) mice were divided randomly into 2 groups and fed a 10% kcal fat control diet (control group, CON) or 41% kcal fat, 0.21% cholesterol (high fat+ cholesterol, HFC) diet (obese group, OB), and B6.129S7-Ldlr tm1Her /J (Ldlr −/− ) mice were fed a HFC diet (obese with atherosclerosis group, OBA) for 16 weeks. SVCs and adipocytes isolated from VAT were pre-incubated with 1,25(OH) 2 D 3 for 24 h and stimulated with lipopolysaccarides for the next 24 h. Proinflammatory cytokine production by adipocytes and SVCs, the immune cell population in SVCs, and the expression of the genes involved in the inflammatory signaling pathway in SVCs were determined. RESULTS: The numbers of total macrophages and SVCs per mouse were higher in OB and OBA groups than the CON group. The in vitro 1,25(OH) 2 D 3 treatment significantly reduced macrophages/SVCs (%) in the OBA group. Consistent with this change, the production of interleukin-6 and monocyte chemoattractant protein 1 (MCP-1) by SVCs from the OBA group was decreased by 1,25(OH) 2 D 3 treatment. The 1,25(OH) 2 D 3 treatment significantly reduced the toll-like receptor 4 and dual-specificity protein phosphatase 1 (also known as mitogenactivated protein kinase phosphatase 1) mRNA levels in SVCs and MCP-1 production by adipocytes from all 3 groups. CONCLUSIONS These findings suggest that vitamin D can attribute to the inhibition of the inflammatory response in VAT from atherosclerotic mice by reducing proinflammatory cytokine production.

Background/Aims: The prognostic significance of 18F-fluorodeoxyglucose (FDG)-positron emission tomography-computed tomography (PET/CT) in peripheral T-cell lymphomas (PTCLs) are controversial. We explored the prognostic impact of sequential 18F-FDG PET/CT during frontline chemotherapy of patients with PTCLs. Methods: In total, 143 patients with newly diagnosed PTCLs were included. Sequential 18F-FDG PET/CTs were performed at the time of diagnosis, during chemotherapy, and at the end of chemotherapy. The baseline total metabolic tumor volume (TMTV) was calculated using the the standard uptake value with a threshold method of 2.5. Results: A baseline TMTV of 457.0 cm3 was used to categorize patients into high and low TMTV groups. Patients with a requirehigh TMTV had shorter progression-free survival (PFS) and overall survival (OS) than those with a low TMTV (PFS, 9.8 vs. 26.5 mo, p = 0.043; OS, 18.9 vs. 71.2 mo, p = 0.004). The interim 18F-FDG PET/CT response score was recorded as 1, 2–3, and 4–5 according to the Deauville criteria. The PFS and OS showed significant differences according to the interim 18F-FDG PET/CT response score (PFS, 120.7 vs. 34.1 vs. 5.1 mo, p < 0.001; OS, not reached vs. 61.1 mo vs. 12.1 mo, p < 0.001). Conclusions The interim PET/CT response based on visual assessment predicts disease progression and survival outcome in PTCLs. A high baseline TMTV is associated with a poor response to anthracycline-based chemotherapy in PTCLs. However, TMTV was not an independent predictor for PFS in the multivariate analysis.

Background: The quality-of-life of patients with irritable bowel syndrome is low; incorrect diagnosis/treatment causes economic burden and inappropriate consumption of medical resources. This survey-based study aimed to analyze the current status of irritable bowel syndrome treatment to examine differences in doctors’ perceptions of the disease, and treatment patterns. Methods: From October 2019 to February 2020, the irritable bowel syndrome and Intestinal Function Research Study Group of the Korean Society of Neurogastroenterology and Motility conducted a survey on doctors working in primary, secondary, and tertiary healthcare institutions. The questionnaire included 37 items and was completed anonymously using the NAVER platform (a web-based platform), e-mails, and written forms. Results: A total of 272 doctors responded; respondents reported using the Rome IV diagnostic criteria (amended in 2016) for diagnosing and treating irritable bowel syndrome.Several differences were noted between the primary, secondary, and tertiary physicians’ groups. The rate of colonoscopy was high in tertiary healthcare institutions. During a colonoscopy, the necessity of random biopsy was higher among physicians who worked at tertiary institutions. ‘The patient did not adhere to the diet’ as a reason for ineffectiveness using low-fermentable oligo-, di-, and mono-saccharides, and polyols diet treatment was higher among physicians in primary/secondary institutions, and ‘There are individual differences in terms of effectiveness’ was higher among physicians in tertiary institutions. In irritable bowel syndrome constipation predominant subtype, the use of serotonin type 3 receptor antagonist (ramosetron) and probiotics was higher in primary/secondary institutions, while serotonin type 4 receptor agonist was used more in tertiary institutions. In irritable bowel syndrome diarrhea predominant subtype, the use of antispasmodics was higher in primary/secondary institutions, while the use of serotonin type 3 receptor antagonist (ramosetron) was higher in tertiary institutions. Conclusion Notable differences were observed between physicians in primary/secondary and tertiary institiutions regarding the rate of colonoscopy, necessity of random biopsy, the reason for the ineffectiveness of low-fermentable oligo-, di-, and mono-saccharides, and polyols diet, and use of drug therapy in irritable bowel syndrome. In South Korea, irritable bowel syndrome is diagnosed and treated according to the Rome IV diagnostic criteria, revised in 2016.

Background: Fibroblasts produce collagen molecules that support the structure of the skin.The decrease and hypersynthesis of collagen causes skin problems such as skin atrophy, wrinkles and scars. Objective: The purpose of this study is to investigate the mechanism of mitoxantrone on collagen synthesis in fibroblasts. Methods: Cultured fibroblasts were treated with mitoxantrone, and then collagen synthesis was confirmed by reverse transcription-polymerase chain reaction and Western blot. Results: Mitoxantrone inhibited the expression of type I collagen in fibroblasts at both the mRNA and protein levels. In the collagen gel contraction assay, mitoxantrone significantly inhibited gel contraction compared to the control group. Mitoxantrone inhibited transforming growth factor (TGF)-β-induced phosphorylation of SMAD3. Finally, mitoxantrone inhibited the expression of LARP6, an RNA-binding protein that regulates collagen mRNA stability. Conclusion These results suggest that mitoxantrone reduces collagen synthesis by inhibiting TGF-β/SMAD signaling and LARP6 expression in fibroblasts, which can be developed as a therapeutic agent for diseases caused by collagen hypersynthesis.

Background and Objectives: Identifying patients with high bleeding risk (HBR) is important when making decisions for antiplatelet therapy strategy. This study evaluated the impact of ticagrelor monotherapy after 3-month dual antiplatelet therapy (DAPT) according to HBR in acute coronary syndrome (ACS) patients treated with drug eluting stents (DESs). Methods: In this post-hoc analysis of the TICO trial, HBR was defined by 2 approaches: meeting Academic Research Consortium for HBR (ARC-HBR) criteria or Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent DAPT (PRECISEDAPT) score ≥25. The primary outcome was a 3–12 months net adverse clinical event (composite of major bleeding and adverse cardiac and cerebrovascular events). Results: Of the 2,980 patients without adverse events during the first 3 months after DES implantation, 453 (15.2%) were HBR by ARC-HBR criteria and 504 (16.9%) were HBR by PRECISE-DAPT score. The primary outcome rate was higher in HBR versus non-HBR patients (by ARC-HBR criteria: hazard ratio [HR], 2.87; 95% confidence interval [CI], 1.76– 4.69; p<0.001; by PRECISE-DAPT score: HR, 3.09; 95% CI, 1.92–4.98; p<0.001). Ticagrelor monotherapy after 3-month DAPT was associated with lower primary outcome rate than ticagrelor-based 12-month DAPT regardless of HBR by ARC-HBR criteria, with similar magnitudes of therapy effect for HBR and non-HBR patients (p-interaction=0.400). Results were consistent by PRECISE-DAPT score (p-interaction=0.178). Conclusions In ACS patients treated with DESs, ticagrelor monotherapy after 3-month DAPT was associated with lower rate of adverse clinical outcomes regardless of HBR, with similar magnitudes of therapy effect between HBR and non-HBR.Trial Registration: ClinicalTrials.gov Identifier: NCT02494895

Background/Aims: Dietary factors can aggravate the symptoms of irritable bowel syndrome (IBS). Many IBS patients try restrictive diets to relieve their symptoms, but the types of diets with an exacerbating factor are unknown. Therefore, this paper reports the results of a systematic review and network meta-analysis of randomized-controlled trials (RCTs) reviewing the efficacy of food restriction diets in IBS. Methods: The MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov databases were searched until July 21, 2021, to retrieve RCTs assessing the efficacy of restriction diets in adults with IBS. Two independent reviewers performed the eligibility assessment and data abstraction. RCTs that evaluated a restriction diet versus a control diet and assessed the improvement in global IBS symptoms were included. These trials reported a dichotomous assessment of the overall response to therapy. Results: A total of 1,949 citations were identified. After full-text screening, 14 RCTs were considered eligible for the systematic review and network meta-analysis. A starch- and sucrose-reduced diet and a diet with low-fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) showed significantly better results than a usual diet. Symptom flare-ups in patients on a gluten-free diet were also significantly lower than in those on high-gluten diets. Conclusions These findings showed that the starch- and sucrose-reduced, low FODMAP, and gluten-free diets had superior effects in reducing IBS symptoms. Further studies, including head-to-head trials will be needed to establish the effectiveness of dietary restrictions on IBS symptoms.

BACKGROUND: Alopecia areata (AA), a chronic, relapsing hair-loss disorder, is considered to be a T-cell-mediated autoimmune disease. Cold-inducible RNA-binding protein (CIRP) belongs to a family of cold-shock proteins that respond to cold stress, and has been identified as a damage-associated molecular pattern (DAMP) molecule that triggers the inflammatory response. Recent studies have shown that high-mobility group box 1, another DAMP molecule, is elevated in serum and scalp tissue of AA patients, suggesting a relationship between DAMP molecules and the pathogenesis of AA. OBJECTIVE: To investigate the clinical significance of serum CIRP levels in AA. METHODS: The serum levels of CIRP were compared between 68 patients with AA and 20 healthy controls. Additionally, the correlation between CIRP level and various clinical parameters was evaluated. RESULTS: The serum CIRP levels were significantly higher in AA patients compared to healthy subjects. Moreover, there was an association between the serum CIRP level and clinical characteristics, such as disease duration and disease activity. However, there was no significant difference in the serum CIRP level among the clinical types of AA (AA multiplex, alopecia totalis, and alopecia universalis). CONCLUSION: These results suggest that CIRP may play a significant role in the pathogenesis of AA and could be a potential biologic marker for monitoring the disease activity of AA.
Alopecia Areata ; Alopecia ; Autoimmune Diseases ; Biomarkers ; Healthy Volunteers ; Humans ; Inflammation ; RNA-Binding Proteins ; Scalp

BACKGROUND: Alopecia areata (AA) is an autoimmune skin disease difficult to manage and treat. The pathogenesis of AA features a T-cell-associated autoimmune process, and systemic immunosuppressive therapy is prescribed widely for AA. OBJECTIVE: To evaluate the efficacy and tolerance of systemic low-dose methotrexate (LD-MTX) therapy in treatment of recalcitrant AA multiplex. METHODS: In a retrospective, non-controlled study, we evaluated 29 patients with recalcitrant AA treated with LD-MTX and assessed the therapeutic response according to severity of disease, disease duration, cumulative dose of MTX, and drug safety. RESULTS: MTX was administered twice weekly, and the mean maximum weekly dose was 14.48 mg. The response was A5 (regrowth=100.0%) in 14 (48.3%) patients and A4 (regrowth of 75%~90%) in 12 (41.4%) patients. Three patients had poor response to LD-MTX treatment (A2: n=2 [6.9%], A1: n=1 [3.4%]). All three of the patients showing a poor response had disease durations exceeding 24 months. Relapse was observed in 31% of patients with more than 75% regrowth. Common side-effects were elevated liver enzyme levels and gastrointestinal discomfort. CONCLUSION: LD-MTX appears to be an effective and well-tolerated treatment for recalcitrant AA multiplex.
Alopecia Areata* ; Alopecia* ; Humans ; Liver ; Methotrexate* ; Recurrence ; Retrospective Studies ; Skin Diseases