Clinical and laboratory features between anti-TIF1γ dermatomyositis with and without malignancy: 37 case series and a review.

We aimed to analyze the clinical profile and malignancy indicators in dermatomyositis (DM) with anti-transcriptional intermediary factor 1 antibody (anti-TIF1γ-Ab). A comparison was made between clinical information of anti-TIF1γ DM patients with and without malignancy. Additionally, a review of the literature on anti-TIF1γ DM and malignancy was conducted by searching PubMed and EMBASE databases. In our cohort of 37 patients, 27.0% (10/37) developed malignancy. The timeframe during which these 10 patients developed malignancy ranged from 21 months prior to the diagnosis of DM to 36 months following the diagnosis of DM. Specifically, one patient was diagnosed with breast cancer at the age of 36. Comparing the groups with and without malignancy, we found that age over 65 years (40% vs 7.4%, P = 0.035), a shorter duration from the onset of symptoms to the diagnosis of DM (2.5 vs 10 months, P = 0.003), and higher erythrocyte sedimentation rate (ESR) levels (23 vs 10 mm/h, P = 0.048) were found to be associated with an increased risk of malignancy. Conversely, the presence of Gottron's papules (63% vs 20%, P = 0.029) may suggest a lower likelihood of malignancy. The literature review revealed that the prevalence of myositis-associated malignancy was 40.7% (340/836), with variations ranging from 19% to 82.9% across different series. In summary, factors such as age over 65 years, a shorter duration between symptom onset and diagnosis of DM, and elevated ESR levels may indicate an increased risk of malignancy in anti-TIF1γ DM patients.

Isolation and analysis of the exosomal membrane proteins in bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is a severe autoimmune sub-epidermal bullous disease. Exosomes are small extracellular vesicles secreted by most cell types. The exosomal membrane proteins are implicated in various biological and pathological pathways. This study aims to explore the potential roles of exosomes in BP pathomechanism. RESEARCH DESIGN: We collected plasma samples from 30 BP patients and 31 healthy controls. Nanoparticle tracking analysis (NTA) was used to analyze the size and concentration of exosomes. The immunogold labelling experiment and extracellular vesicle (EV) array were performed to detect the content and distribution of exosomes. RESULTS: The exosomes from both the BP and control groups' plasma were successfully extracted. EV Array showed that CD63 and CD9 levels were significantly higher in the BP group than in the control group (p < 0.05). Expression levels of the BP180 NC16A and intracellular domain (ICD) were higher in the anti-BP180 positive group versus the controls (p < 0.05). The active BP group exhibits higher CD63 and BP180 ICD protein concentrations than the control or inactive BP groups (p < 0.05). CONCLUSION: BP180 autoantigen fragments were expressed on the exosomal membrane in BP patients. The BP180 ICD and CD63 on exosomes could potentially be novel biomarkers for monitoring disease activity.

Tumor necrosis factor inhibitors enhance corticosteroid therapy for Stevens-Johnson syndrome and toxic epidermal necrolysis linked to immune checkpoint inhibitors: a prospective study.

Introduction: Immune-related epidermal necrolysis (irEN), including Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN), represents a potentially lethal reaction to immune checkpoint inhibitors. An optimal treatment strategy remains undefined. This study evaluates the effectiveness and safety of combination therapy with corticosteroids and tumor necrosis factor inhibitors (TNFi) in treating irEN patients. Methods: In this single-center, prospective, observational study, patients with irEN received either corticosteroid monotherapy or a combination therapy of corticosteroids and TNFi (etanercept for SJS, infliximab for TEN). The primary endpoint was re-epithelization time, with secondary endpoints including corticosteroid exposure, major adverse event incidence, acute mortality rates, and biomarkers indicating disease activity and prognosis. The study was registered at the Chinese Clinical Trial Registry (ChiCTR2100051052). Results: Thirty-two patients were enrolled (21 SJS, 11 TEN); 14 received combination therapy and 18 received corticosteroid monotherapy. IrEN typically occurred after 1 cycle of ICI administration, with a median latency of 16 days. Despite higher SCORTEN scores in the combination group (3 vs. 2, p = 0.008), these patients experienced faster re-epithelization (14 vs. 21 days; p < 0.001), shorter corticosteroid treatment duration (22 vs. 32 days; p = 0.005), and lower prednisone cumulative dose (1177 mg vs. 1594 mg; p = 0.073). Major adverse event rates were similar between groups. Three deaths occurred due to lung infection or disseminated intravascular coagulation, with mortality rates for both groups lower than predicted. Potential risk factors for increased mortality included continuous reduction in lymphocyte subset counts (CD4+ T cells, CD8+ T cells, natural killer cells) and consistent rises in inflammatory markers (serum ferritin, interleukin-6, TNF-α). Re-epithelization time negatively correlated with body mass index and positively correlated with epidermal detachment area and serum levels of interleukin-6 and TNF-α. Conclusions: Corticosteroids combined with TNFi markedly promote re-epithelization, reduce corticosteroid use, and decrease acute mortality in irEN patients without increasing major adverse events, offering a superior alternative to corticosteroid monotherapy. Inflammatory markers and lymphocyte subsets are valuable for assessing disease activity and prognosis.

Ixekizumab Improved Refractory Erythrodermic Psoriasis with Comorbid Diffuse Alopecia: A Case Report with 52-Week Follow-Up.

Erythrodermic psoriasis (EP) is a severe and rare variant of psoriasis, accounting for less than 3% of cases. It is characterized by widespread scaling and erythema that affects more than 90% of the body surface area. Alopecia can manifest as a symptom associated with the disease, further exacerbating the impact on the patient's quality of life. We present the case of a patient with severe EP and diffuse alopecia who did not respond to conventional therapies. The patient was subsequently treated with ixekizumab as per labeled usage, resulting in complete resolution of both psoriatic skin lesions (Psoriasis area and severity index/PASI 100) and alopecia (The Severity of Alopecia Tool/SALT 0).

Identification of Challenging Diagnostic Factors in Livedoid Vasculopathy: A Retrospective Study.

Background: Livedoid vasculopathy is an uncommon cutaneous ulcerative dermatosis that is challenging to diagnose. Diagnostic delay brought both pain and uncurable atrophied scar to patients. Purpose: We conducted this study to identify the factors responsible for the initial misdiagnosis of livedoid vasculopathy and to identify possible methods to increase the diagnostic accuracy of livedoid vasculopathy. Patients and Methods: We conducted a retrospective medical record review to confirm the diagnosis of livedoid vasculopathy in patients who visited the Department of Peking Union Medical College Hospital for the first time. We used the Diagnosis Error Evaluation and Research taxonomy to evaluate missed cases. Results: Twenty-three patients (85.18%) had an alternate diagnosis, including 10 (43.4%) with two or more diagnoses. The average time from disease onset to the final diagnosis of livedoid vasculopathy was 4.61 ± 0.69 years. The major diagnostic errors were clinician assessment failures and failures in the timely follow-up and rechecking of patients. Allergic vasculitis was the most common misdiagnosis. Other alternate diagnoses include Henoch-Schoenlein purpura, pigmented purpuric dermatosis, eczema, erythema nodosum, and reactive perforating collagenases. Twenty-three patients (65.21%) received systemic corticosteroid therapy before the final diagnosis of livedoid vasculopathy. Conclusion: It is critical to raise the awareness of clinicians about livedoid vasculopathy, especially when patient present with extensive livedo racemosa or long-lasting purpuric lesions on the lower limbs. Long-term follow-up is necessary, especially for younger patients. Skin biopsy is recommended before systematic therapy.

The systemic treatments for drug reaction with eosinophilia and systemic symptoms (DRESS) beyond corticosteroids.

Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome (DiHS), is a severe type of cutaneous adverse reaction. The gold standard therapy for DRESS involves the discontinuation of the culprit drug, supportive therapies, and administration of corticosteroids. However, in cases of primary treatment failure or suboptimal response, there arises an urgent need for alternative interventions. This review focuses on exploring alternative systemic therapies for patients with steroid-resistant DRESS, steroid-dependent DRESS, or refractory DRESS, encompassing immunosuppressive agents, intravenous immunoglobulin, plasmapheresis, biologics, and small molecule drugs, with an emphasis on their clinical efficacy and the underlying mechanisms in the treatment of DRESS. Furthermore, this review provides a summary of potential management strategies and laboratory workup during the treatment of DRESS.

A retrospective study of prognostic factors and treatment outcome in advanced-stage Mycosis Fungoides and Sezary Syndrome.

Background: Mycosis fungoides (MF) and Sezary Syndrome (SS) comprise over half of all Cutaneous T-cell lymphoma diagnoses. Current risk stratification is largely based on TNMB staging, few research investigated the prognostic value of clinical exams. Current systemic therapy for advanced disease includes immunomodulatory drugs, chemotherapy, and HADC inhibitors. Few clinical trials or retrospective research compared the efficacy of different drugs.Method: Here, we performed a retrospective analysis of prognostic factors and treatment outcomes of 92 patients diagnosed with MF/SS at the Peking Union Medical College Hospital from 2013-2023.Results: Cox regression analysis identified that age ≥ 50 years, WBC ≥ 8 × 109/L, serum LDH ≥ 250U/L, ß2-MG ≥ 4.50 mg/L, and stage IV were associated with reduced overall survival, age ≥ 50 years, serum LDH ≥ 250U/L and stage IV were associated with reduced progression free survival. Kaplan-Meier analysis established that immunomodulatory therapy was associated with longer progression free survival.Conclusion: These results suggested new factors in predicting prognosis and selecting appropriate treatments in patients with advanced MF/SS.

Comparative Proteomics Analysis Reveals Distinct Molecular Phenotype and Biomarkers in Patients with Erythrodermic Atopic Dermatitis and Erythrodermic Psoriasis.

Erythrodermic atopic dermatitis (EAD) and erythrodermic psoriasis (EP) are rare yet debilitating inflammatory skin disorders that propose challenges in diagnosis and discovering effective therapeutic targets. Despite their clinical and histological similarities, the underlying molecular mechanisms and systemic biomarkers of these diseases are substantially unclear. In this study, we sought to investigate the differential serum proteome of EP and EAD patients and identify biomarkers for these two subtypes of erythroderma. We recruited 14 EAD patients, 14 EP patients and 14 healthy controls. Serum samples were collected and analyzed using the Olink high-throughput platform to assess the levels of 269 inflammation-/immune response-/cardiovascular-related biomarkers. Both EAD and EP patients exhibited enhanced immune activation and dysregulated cardiovascular profiles compared to healthy controls. EAD demonstrated a more pronounced inflammation tone, characterized by Th1/Th2/Th22/IL-1-dominant patterns, as well as increased TNF superfamily, Th17, and apoptosis markers. Conversely, EP displayed inflammation with Th1/Th17/TNF-skewing and mild Th2 upregulation, along with notable increases in epidermal-development markers. Disease severity in EAD was strongly correlated with apoptosis/Th2 markers, while correlated with Th17 markers in EP. Furthermore, a panel of eight markers (IL-17A/IL-17C/PI3/CCL20/SH2D1A/SIRT2/DFFA/IL-13) was identified that effectively discriminated between EP and EAD, with an Area Under the Curve greater than 0.8. Our study comprehensively characterizes the circulating molecular profiles in EAD and EP patients, providing insights into the similarities and complexities of their inflammation phenotypes. The identified serum biomarkers have the potential to differentiate between EP and EAD, which could aid in the diagnosis and guiding tailored therapeutics.

Exploration of circulating metabolic signature of erythrodermic psoriasis based on LC-MS metabolomics.

Erythrodermic psoriasis (EP) is a rare and life-threatening disease, the pathogenesis of which remains to be largely unknown. Metabolomics analysis can provide global information on disease pathophysiology, candidate biomarkers, and potential intervention strategies. To gain a better understanding of the mechanisms of EP and explore the serum metabolic signature of EP, we conducted an untargeted metabolomics analysis from 20 EP patients and 20 healthy controls. Furthermore, targeted metabolomics for focused metabolites were identified in the serum samples of 30 EP patients and 30 psoriasis vulgaris (PsV) patients. In the untargeted analysis, a total of 2992 molecular features were extracted from each sample, and the peak intensity of each feature was obtained. Principal component analysis (PCA), orthogonal partial least squares-discriminant analysis (OPLS-DA) revealed significant difference between groups. After screening, 98 metabolites were found to be significantly dysregulated in EP, including 67 down-regulated and 31 up-regulated. EP patients had lower levels of L-tryptophan, L-isoleucine, retinol, lysophosphatidylcholine (LPC), and higher levels of betaine and uric acid. KEGG analysis showed differential metabolites were enriched in amino acid metabolism and glycerophospholipid metabolism. The targeted metabolomics showed lower L-tryptophan in EP than PsV with significant difference and L-tryptophan levels were negatively correlated with the PASI scores. The serum metabolic signature of EP was discovered. Amino acid and glycerophospholipid metabolism were dysregulated in EP. The metabolite differences provide clues for pathogenesis of EP and they may provide insights for therapeutic interventions.

Anti-Interleukin 17A Biologic Therapy Attempts on Livedoid Vasculopathy: A Report of Case Series.

The application of biologics such as anti-tumor necrosis factor (TNF) has shown great efficacy in livedoid vasculopathy (LV). However, new biological options need to be identified for those with a high tuberculosis reactivation risk. In this study, we evaluated the efficacy of anti-17A biologics for LV therapy. Two patients with LV who were irresponsive to traditional anticoagulation therapy were studied at the outpatient dermatology clinic of Peking Union Medical College Hospital. All patients received anti-17A biological therapy for at least two-four weeks. Both patients reported an exacerbation of the skin lesions, which might indicate that the IL-17 pathway plays a critical role in LV pathogenesis.

Evaluation of hematological inflammatory parameters in patients with palmoplantar pustulosis.

BACKGROUND: Palmoplantar pustulosis (PPP) is a chronic inflammatory disease of ill-defined etiopathology. Recent studies have proposed complete blood count-based hematological parameters, such as neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR), as biomarkers to monitor disease status in many inflammatory diseases. This study aimed to analyze for the first time the clinical significance of hematological parameters, including NLR, monocyte/lymphocyte ratio (MLR), PLR, mean platelet volume (MPV), plateletcrit (PCT), and pan-immune-inflammation value (PIV) in PPP patients. METHODS: We retrospectively investigated the clinical and laboratory data of 237 patients with PPP and 250 sex-age-matched healthy controls (HCs). Hematological parameters were compared between patients with PPP and HCs. The correlations between these parameters and disease severity, as well as treatment response, were analyzed. RESULTS: NLR, MLR, MPV, PCT, and PIV values were significantly higher in PPP patients than in HCs. But in receiver-operating characteristic analyses, only monocyte count (Youden Index = 0.53), PCT (Youden Index = 0.65), and PIV (Youden Index = 0.52) performed relatively accurate distinguishment between moderate-to-severe cases and mild cases. PCT and PIV values were significantly correlated with disease severity. After treatment, both PIV and PCT values decreased significantly in the responder group but not in the non-responder group. CONCLUSIONS: Hematological parameters altered significantly in PPP patients. PCT and PIV can be used as simple and inexpensive biomarkers for systemic inflammation in PPP patients.

2% supramolecular salicylic acid hydrogel vs. adapaline gel in mild to moderate acne vulgaris treatment: A multicenter, randomized, evaluator-blind, parallel-controlled trial.

OBJECTIVE: Salicylic acid (SA) has been used for treatment of acne of different severity levels. However, there are few researches about the safety and efficacy for treatment of mild to moderate acne, and the improvement of the skin condition by using 2% supramolecular salicylic acid (SSA) compared to Davuwen Adapaline gel. METHODS: A multicenter, randomized, assessor-blind and parallel-controlled study was conducted. A total of 500 patients (trial group: 249, control group: 251) with mild to moderate (grade I-II) facial acne vulgaris were recruited in this study over a 16-week trial period. Patients in the trial group were treated with Broda 2% SSA hydrogel, while control group treated with Davuwen Adapaline gel once a day. The number of inflammatory papules, comedones, and pustules were counted and the rate of lesion reduction was calculated pre- and post-treatment. Then, the skin physiological indicators, including L*a*b*, TEWL, skin sebum and hydration were measured. Statistical analysis was conducted using SAS 9.4. Significance was set at p = 0.05. RESULTS: At the end of 12 weeks' therapy, the regression and markedly improvement rate of the trail group and the control group were 51.01% and 43.10% respectively, and there was no significant difference in the improvement rate between two groups (p = 0.0831). Although, there was no difference in adverse events rate between two groups, the adverse events rate of the trail group was 0.40%, a little lower than the control group (0.80%). Moreover, there was a significant difference in the numbers of pores at T1 between two groups. CONCLUSION: Both 2% SSA and Adapaline gel were equally effective in the treatment of mild to moderate acne vulgaris. 2% SSA is worth the clinical promotion and application in mild to moderate acne vulgaris.

Abrocitinib Improved Dupilumab-Resistant Severe Atopic Dermatitis with Comorbid Mild Alopecia Areata in a 12-Year-Old Boy: A Case Report with 1-Year Follow-Up.

Atopic dermatitis (AD) may sometimes be comorbid with alopecia areata (AA). However, traditional treatments for AA show limited efficacy. New treatment options, such as dupilumab and Janus kinase inhibitors, have proven efficacy in addressing both AD and AA. This article highlights the challenging case of a 12-year-old boy experiencing severe refractory AD and comorbid AA treated with oral abrocitinib after dupilumab failure with 1-year follow-up. After 3 months of treatment, his skin manifestations improved and the hair completely regenerated. No adverse reactions were observed during the 1-year follow-up period. This case provides evidence of the efficacy and safety of using abrocitinib to treat pediatric patients with both AD and AA.

Human-multimodal deep learning collaboration in 'precise' diagnosis of lupus erythematosus subtypes and similar skin diseases.

BACKGROUND: Lupus erythematosus (LE) is a spectrum of autoimmune diseases. Due to the complexity of cutaneous LE (CLE), clinical skin image-based artificial intelligence is still experiencing difficulties in distinguishing subtypes of LE. OBJECTIVES: We aim to develop a multimodal deep learning system (MMDLS) for human-AI collaboration in diagnosis of LE subtypes. METHODS: This is a multi-centre study based on 25 institutions across China to assist in diagnosis of LE subtypes, other eight similar skin diseases and healthy subjects. In total, 446 cases with 800 clinical skin images, 3786 multicolor-immunohistochemistry (multi-IHC) images and clinical data were collected, and EfficientNet-B3 and ResNet-18 were utilized in this study. RESULTS: In the multi-classification task, the overall performance of MMDLS on 13 skin conditions is much higher than single or dual modals (Sen = 0.8288, Spe = 0.9852, Pre = 0.8518, AUC = 0.9844). Further, the MMDLS-based diagnostic-support help improves the accuracy of dermatologists from 66.88% ± 6.94% to 81.25% ± 4.23% (p = 0.0004). CONCLUSIONS: These results highlight the benefit of human-MMDLS collaborated framework in telemedicine by assisting dermatologists and rheumatologists in the differential diagnosis of LE subtypes and similar skin diseases.

Interleukin-17A Inhibitors in Patients with Psoriasis and Tuberculosis Infection: A 2-Year Prospective Study on Safety Without Preventive Treatment.

INTRODUCTION: The necessity for tuberculosis preventive treatment (TPT) and routine T-SPOT.TB monitoring in patients with psoriasis and tuberculosis infection (TBI) undergoing interleukin (IL)-17A inhibitor therapy remains uncertain. This study aims to evaluate the long-term safety of IL-17A inhibitors administered without TPT and analyze changes in T-SPOT.TB among these patients. It also identifies risk factors for TBI in patients with psoriasis. METHODS: This single-center prospective study enrolled adult patients with plaque psoriasis and TBI receiving IL-17A inhibitors. TBI was defined as positive T-SPOT.TB results (≥ 6 spots) without symptoms or evidence of active tuberculosis (ATB). TPT administration was based on contraindications, tuberculosis risk factors, and patient preferences. The primary endpoint was the incidence of ATB over 2 years. Secondary outcomes included T-SPOT.TB changes and TBI risk factors. RESULTS: Of the 129 patients with psoriasis and TBI enrolled in the study, 97 (75.2%) did not receive TPT, while 32 (24.8%) did. Among them, 109 patients (84.5%) completed the 2-year follow-up. During the 235 person-years of observation, no ATB cases were identified. Median T-SPOT.TB values showed no significant changes from baseline to year 2 in both the non-TPT (20 vs. 17 spots, p = 0.975) and TPT groups (55 vs. 58 spots, p = 0.830). T-SPOT.TB reversed in 14 patients (12.8%), mostly in the non-TPT group. Moreover, for TBI risk factor analysis, a cohort of 212 patients with psoriasis with negative baseline T-SPOT.TB was evaluated, revealing a TBI prevalence of 37.8%. Logistic regression analysis highlighted age ≥ 45 years (odds ratio [OR] 2.44, 95% confidence interval [CI] 1.50-3.99, p < 0.001) and body mass index (BMI) < 24.0 kg/m2 (OR 2.12, 95% CI 1.27-3.54, p = 0.004) as independent risk factors for TBI. CONCLUSION: IL-17A inhibitors do not appear to reactivate tuberculosis in patients with psoriasis and TBI, potentially reducing the need for routine TBI screening and preventive treatment. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100045823.

Pregnancy in pemphigus vulgaris: A systematic review.

PROBLEM: Pemphigus vulgaris may worsen during pregnancy, leading to both maternal and fetal complications. The relationship between pemphigus vulgaris and pregnancy remains unclear, and the outcomes and treatments of pemphigus vulgaris during pregnancy have not been extensively discussed. METHOD OF STUDY: This article systematically reviews the literature, focusing on the relationship between pemphigus vulgaris and pregnancy. We conducted comprehensive searches in PubMed, Embase, Cochrane Library, and Web of Science databases, identifying 42 studies reporting the disease course, pregnancy outcomes, and management of both pregnancy and pemphigus vulgaris. RESULTS: A total of 57 cases were included in the analysis, categorized into three distinct forms: pemphigus vulgaris onset before pregnancy (n = 33), onset during pregnancy (n = 20), and onset during the postpartum period (n = 4). Fifty four cases reported treatment strategies, among them, 44 cases (81.5%) initially received systemic corticosteroid therapy during pregnancy. Out of these cases, 7 (15.9%) did not achieve successful remission and required alternative treatment approaches. In terms of pregnancy outcomes, 23 out of 62 neonates (37.1%) exhibited skin lesions or tested positive for anti-dsg IgG in their serum, while 16 neonates (25.8%) experienced other complications. CONCLUSIONS: These findings highlight the importance of effectively managing pemphigus vulgaris during pregnancy to ensure optimal outcomes.

Extracellular vesicles from keratinocytes and other skin-related cells in psoriasis: A review.

Psoriasis is a highly prevalent chronic inflammatory skin condition involving abnormal proliferation and differentiation of keratinocytes, together with substantial infiltration of immune cells. Extracellular vesicles (EVs), which are released spontaneously into the extracellular space by virtually all cell types, play a crucial role in cell-to-cell communication by delivering bioactive cargos such as mRNA nucleic acids and proteins to recipient cells. Numerous studies have highlighted the significant contributions of EVs to both the pathogenesis and treatment of psoriasis. This review provides a concise overview of skin-derived EVs and their involvement in the pathogenesis of psoriasis.