Cannabinoids for the treatment of autoimmune and inflammatory skin diseases: A systematic review.

In recent years, the medical use of cannabinoids has attracted growing attention worldwide. In particular, anti-inflammatory properties of cannabinoids led to their emergence as potential therapeutic options for autoimmune and inflammatory disorders. Recent studies have also shown that cannabinoid receptors are widely expressed and have endogenous ligands in the skin, suggesting that the skin has its own endocannabinoid system. The aim of this review is to discuss the potential therapeutic effects of cannabinoids in autoimmune and inflammatory skin diseases. Following an overview of cannabinoids and the endocannabinoid system, we describe the cellular and molecular mechanisms of cannabinoids in skin health and disease. We then review the clinical studies of cannabinoids in autoimmune and inflammatory skin diseases including systemic sclerosis (SSc), dermatomyositis (DM), psoriasis (Pso) and atopic dermatitis (AD). A primary literature search was conducted in July 2023, using PubMed and Web of Science. A total of 15 articles were included after excluding reviews, non-human studies and in vitro studies from 389 non-duplicated articles. Available evidence suggests that cannabinoids may be beneficial for SSc, DM, Pso and AD. However, further studies, ideally randomized controlled trials, are needed to further evaluate the use of cannabinoids in autoimmune and inflammatory skin diseases.

Marital Quality and Depressive Symptoms Among Older Hispanic Adults in the United States.

OBJECTIVES: Despite the cultural importance of marriage as a social support system and its well-established link to mental health, older Hispanic adult populations, which are the largest racial and ethnic minoritized groups, remain understudied. The current study examined how positive and negative dimensions of marital quality are associated with depressive symptoms. METHODS: Data from Hispanic adults aged 51 years and older (n = 1,012) were obtained from the 2016 and 2018 Health and Retirement Study waves. The Center for Epidemiological Studies-Depression scale (0-8 symptoms) was modeled as a function of positive and negative marital quality measures (1-4), as well as the relevant covariates. RESULTS: Results from a negative binomial regression model showed that a 1-unit change in positive and negative marital quality was associated with a 23.61% reduction and a 23.74% increase, respectively, in depressive symptoms. The interaction terms with marital quality and gender, as well as marital quality and religion, were not statistically significant. DISCUSSION: In the United States, a large percentage of older Hispanic adults are immigrants, and their extended family tends to reside in their countries of origin. As such, older Hispanic adults may have smaller social networks, and marital quality most likely represents a culturally important social support network in later life. Significant associations between depressive symptoms and marital quality among older Hispanic adults should receive more attention in family and public health policy discussions, particularly given the increasing diversity in U.S. society.

A Case of Thoracic Empyema Caused by Actinomyces naeslundii.

BACKGROUND Actinomycosis is a clinically significant but uncommon infectious disease caused by anaerobic commensals of Actinomyces species, and the incidence of thoracic empyema is rare. We report an extremely rare case of empyema caused by Actinomyces naeslundii (A. naeslundii). CASE REPORT A 39-year-old man presented to our hospital with fever and dyspnea. He had massive pleural effusion and was diagnosed with a left lower-lobe abscess and left thoracic empyema. Thoracic drainage was performed and Ampicillin/Sulbactam was administered for 3 weeks. Four years later, the patient presented with back pain, and chest X-ray showed increased left pleural effusion. After close examination, malignant pleural mesothelioma was suspected, and computed tomography-guided needle biopsy was performed, which yielded a viscous purulent pleural effusion with numerous greenish-yellow sulfur granules. A. naeslundii was identified through anaerobic culture. Thoracoscopic surgery of the empyema cavity was conducted, and Ampicillin/Sulbactam followed by Amoxicillin/Clavulanate was administered for approximately 6 months. No recurrence has been observed for 1 year since the surgical procedure. CONCLUSIONS Actinomyces empyema is a rare condition, and this case is the second reported occurrence of empyema caused by A. naeslundii. The visual identification of sulfur granules contributed to the diagnosis. Long-term antibiotic therapy plays a crucial role in treatment.

Traumatic tumor hemorrhage of inflammatory myofibroblastic tumor of the lung.

A 23-year-old female with a history of idiopathic epilepsy was found to have a right chest cavity shadow in a school health checkup 5 years before. CT revealed a thin-walled cavity lesion in the right middle lobe containing a ball-like mass, showing air crescent sign. After falling due to a seizure, she was transported by ambulance and admitted. CT revealed diffuse ground-glass opacities throughout the right lung field. Bronchoscopy revealed bloody bronchial alveolar lavage fluid. Due to the tumor hemorrhage, an elective simple right middle lobe resection was performed without complications. The initial immunohistochemical staining was negative for ALK using ALK1 clone; however, subsequent staining of ALK by D5F3 and 5A4 clone was positive. Immunostaining findings led to a diagnosis of inflammatory myofibroblastic tumor. The patient remains under regular observation and has experienced no recurrence over the 6-year postoperative period. This case contains two different points: the first is that a cavity lesion of inflammatory myofibroblastic tumor may cause traumatic bleeding and should be treated with caution; the second is that attention should be paid to differences in stainability among clones when diagnosing inflammatory myofibroblastic tumor.

Optimal treatments and outcome measures of palmoplantar pustulosis: A systematic review and network meta-analysis-based comparison of treatment efficacy.

Few studies have made direct comparisons between treatments for palmoplantar pustulosis (PPP); therefore, it is difficult to select the best treatment for each patient. To determine the best therapy and to compare reported measures of efficacy in clinical trials of systemic treatments for PPP in this systematic review and network meta-analysis. Six databases were used to perform database search on 10 July 2022. Randomized controlled trials (RCTs) were identified through a systematic literature search. The titles and abstracts of articles were initially screened for inclusion by two authors independently using our predetermined criteria. The full texts of selected articles were then independently assessed for inclusion in a blinded fashion. Disagreement between the authors was resolved by consensus. Data were abstracted in duplicate. Random-effects model was accepted to perform network meta-analysis. Assessed Grading of Recommendations Assessment, Development and Evaluation certainty of evidence were performed according to the PRISMA guidelines. The analysis was completed in July 2022. The primary outcome was the change of PPP Area and Severity Index (PPPASI) from baseline and the secondary outcome was the achievement of PPPASI-50 response. Seven RCTs with 567 patients were included. Guselkumab 100 mg was the one with the highest probability of reaching the proposed outcomes (mean difference [MD], -8.00; 95% confidence interval [CI], 4.88-11.11), while the achievement of PPPASI-50 response did not show a significant difference (odds ratio [OR], 3.79; 95% CI, 0.51-28.37). Guselkumab 200 mg was next to 100 mg of reaching the proposed outcomes (MD, -4.71; 95% CI, 2.12-7.30), while the achievement of PPPASI-50 response did not show a significant difference (OR, 2.34; 95% CI, 0.48-11.43). Network meta-analysis showed guselkumab 100 mg was the treatment with the highest probability of reaching both PPPASI and PPPASI-50 outcomes. Absolute PPPASI may be more appropriate as an outcome than PPPASI-50.

Delayed severe hemothorax caused by a staple line of a bullectomy performed 11 years earlier.

BACKGROUND: At present, relatively few lung surgeries are performed without endostaplers. Although there are few staple-related adverse events, severe events must be shared to improve safety. CASE PRESENTATION: A 74-year-old male suddenly collapsed and was transferred to the Emergency Rescue department. He had shock vitals and contrast-enhanced CT revealed extensive right hemothorax with contrast leakage. He lost consciousness and tension massive hemothorax was suspected. We performed emergency thoracotomy at two sites and were able to achieve hemostasis and save the patient. Upon examining the patient's medical history after his condition stabilized, it was revealed that he was a lung cancer patient who was taking ramucirumab and cilostazol. In addition, the CT scan taken one month before onset revealed the bleeding site of the fifth intercostal artery were almost contact with the staple line from a prior right spontaneous pneumothorax surgery that was performed 11 years previously, which was seemed to damage the intercostal artery. CONCLUSION: Despite the difficulty in achieving hemostasis due to drug administration history, we successfully treated a case of remote period massive hemothorax attributed to staples, thereby saving the patient. When using drugs that increase the risk of bleeding events, it may be important to consider the position of the staple line while assessing the risk. In the emergent or ICU setting, if the initial incision is not effective, the placement of a new second incision may be valuable.

The optimal use of tildrakizumab in the elderly via improvement of Treg function and its preventive effect of psoriatic arthritis.

Introduction: As a form of precision medicine, this study aimed to investigate the specific patient population that would derive the greatest benefit from tildrakizumab, as well as the mechanism of action and efficacy of tildrakizumab in reducing the occurrence of psoriatic arthritis (PsA). Methods: To achieve this, a multi-center, prospective cohort study was conducted, involving a population of 246 psoriasis patients who had not received any systemic therapy or topical finger therapy between January 2020 and April 2023. Two independent clinicians, who were blinded to the study, analyzed nailfold capillary (NFC) abnormalities, such as nailfold bleeding (NFB) and enlarged capillaries, as well as the incidence of new PsA. Additionally, the factors that determined the response of psoriasis after seven months of tildrakizumab treatment were examined. The study also examined the quantity and role of regulatory T cells (Tregs) and T helper 17 cells both pre- and post-treatment. Results: The severity of psoriasis, as measured by the Psoriasis Area and Severity Index (PASI), was found to be more pronounced in the tildrakizumab group (n=20) in comparison to the topical group (n=226). At 7 months after tildrakizumab treatment, multivariate analysis showed that those 65 years and older had a significantly better response to treatment in those achieved PASI clear or PASI 2 or less (Likelihood ratio (LR) 16.15, p<0.0001; LR 6. 16, p=0.01). Tildrakizumab improved the number and function of Tregs, which had been reduced by aging. Tildrakizumab demonstrated significant efficacy in improving various pathological factors associated with PsA. These factors include the reduction of NFB, enlargement of capillaries, and inhibition of PsA progression. The hazard ratio for progression to PsA was found to be 0.06 (95% confidence interval: 0.0007-0.46, p=0.007), indicating a substantial reduction in the risk of developing PsA. Discussion: Tildrakizumab's effectiveness in improving skin lesions can be attributed to its ability to enhance the number and function of Tregs, which are known to decline with age. Furthermore, the drug's positive impact on NFB activity and capillary enlargement, both of which are recognized as risk factors for PsA, further contribute to its inhibitory effect on PsA progression.

Reliance on Social Networks and Health Professionals for Health Information in the U.S. Adult Population.

The subpopulation of adults depends on non-online health information sources including their social networks and health professionals, to the exclusion of online sources. In view of the digital divide and health information disparities, the roles of race/ethnicity and digital skills are yet to be explored. A nationally representative sample of 6,830 adults from the Program for the International Assessment of Adult Competencies (PIAAC) was analyzed, using binary logistic regression. Black adults and adults with higher digital skills were less likely to be reliant on non-online health information sources, compared to White adults and those with lower digital skills, respectively. Differences in non-online health information source reliance by race/ethnicity and digital skills might be further nuanced by the relevant demographic and socioeconomic characteristics. Increasing digital skills may expand one's health information sources to include reliable online sources and empower adults to promote their health.

Comprehensive autoantibody profiling in systemic autoimmunity by a highly-sensitive multiplex protein array.

Comprehensive autoantibody evaluation is essential for the management of autoimmune disorders. However, conventional methods suffer from poor sensitivity, low throughput, or limited availability. Here, using a proteome-wide human cDNA library, we developed a novel multiplex protein assay (autoantibody array assay; A-Cube) covering 65 antigens of 43 autoantibodies that are associated with systemic sclerosis (SSc) and polymyositis/dermatomyositis (PM/DM). The performance of A-Cube was validated against immunoprecipitation and established enzyme-linked immunosorbent assay. Further, through an evaluation of serum samples from 357 SSc and 172 PM/DM patients, A-Cube meticulously illustrated a diverse autoantibody landscape in these diseases. The wide coverage and high sensitivity of A-Cube also allowed the overlap and correlation analysis between multiple autoantibodies. Lastly, reviewing the cases with distinct autoantibody profiles by A-Cube underscored the importance of thorough autoantibody detection. Together, these data highlighted the utility of A-Cube as well as the clinical relevance of autoantibody profiles in SSc and PM/DM.

An Intersectional Approach to Examining Breast Cancer Screening among Subpopulations of Black Women in the United States.

This study examines breast cancer screening behavior among subpopulations of Black women in the United States. Binary logistic regression was used to analyze breast cancer screening among a nationally-representative sample (n = 9,783) of Black women-US-born, non-US-born Caribbean, and non-US-born African-from the 2011-2017 National Health Interview Survey dataset. Non-US-born African Black women were less likely to have breast cancer screening, compared to US-born Black women. Among non-US-born Black women, non-US-born Caribbean Black women were more likely to have had breast cancer screening. Differential healthcare access associated with nativity differences among Black women can be informing their breast cancer screening behaviors. Efforts to improve breast cancer outcomes among Black women can benefit from interventions that account for differential access to healthcare and breast cancer screening behaviors among subgroups of Black women.

Development of Epoxy and Urethane Thermosetting Resin Using Chlorella sp. as Curing Agent for Materials with Low Environmental Impact.

In the current system, the disposal of plastic materials causes serious environmental pollution such as the generation of carbon dioxide and destruction of the ecosystem by micro-plastics. To solve this problem, bioplastics, biomass and biodegradable plastics have been developed. As part of our research, we have developed novel bioplastics called "cell-plastics", in which a unicellular green algal cell serves as a fundamental resource. The production of the cell-plastics would be expected to reduce environmental impact due to the usage of a natural product. Herein, to overcome the mechanical strength of cell-plastics, we used thermosetting epoxy and urethane resins containing Chlorella sp. as the green algae. We successfully fabricated thermosetting resins with a Chlorella sp. content of approximately 70 wt% or more. IR measurements revealed that the chemical structure of an epoxide or isocyanate monomer mixed with Chlorella sp. was modified, which suggests that the resins were hardened by the chemical reaction. In addition, we investigated the effect of thermosetting conditions such as temperature and compression for curing both resins. It was revealed that the Young's moduli and tensile strengths were controlled by thermosetting temperature and compression, whereas the elongation ratios of the resins were constant at low values regardless of the conditions.

Utility of nailfold capillary assessment for predicting pustulotic arthro-osteitis in palmoplantar pustulosis based on a prospective cohort study.

BACKGROUND: Pustulotic arthro-osteitis (PAO) is 1 of the most serious comorbidities associated with palmoplantar pustulosis (PPP). Risk factors of PAO development are not well-known. OBJECTIVE: To evaluate the clinical significance of nailfold capillary (NFC) changes in patients with PPP. METHODS: We conducted a prospective cohort study in a population of 102 PPP patients. Correlations of NFC abnormalities, including nailfold bleeding and enlarged capillaries, with the prevalence of PAO, the incidence of new PAO, and serum levels of cytokines were analyzed. RESULTS: Detailed examination revealed that of 102 PPP patients, 52 without PAO and 50 with PAO. Both nailfold bleeding and enlarged capillaries were significantly more frequent in patients with PAO (50.0% vs 92.0%, P < .0001; 50.0% vs 94.0%, P < .0001). In addition, PPP patients without PAO were prospectively observed before they developed PAO (mean 28 months [1-52 months]). Multivariate analysis suggested that these NFC abnormalities were predictors of PAO development (hazard ratio 3.37, 95% confidence interval 1.13-10.07; 3.37, 1.13-10.07) and guselkumab prevent PAO development (0.093, 0.012-0.76). The degree of NFC abnormalities correlated with the severity of PAO and serum cytokine levels. LIMITATIONS: All participants were Japanese. CONCLUSION: NFC abnormalities could be predictors of PAO in PPP patients, and their degree indicators of disease severity.

Lung adenocarcinoma and squamous cell carcinoma difficult for immunohistochemical diagnosis can be distinguished by lipid profile.

In patients with unresectable non-small cell lung cancer, histological diagnosis is frequently based on small biopsy specimens unsuitable for histological diagnosis when they are severely crushed and do not retain their morphology. Therefore, establishing a novel diagnostic method independent of tissue morphology or conventional immunohistochemistry (IHC) markers is required. We analyzed the lipid profiles of resected primary lung adenocarcinoma (ADC) and squamous cell carcinoma (SQCC) specimens using liquid chromatography-tandem mass spectrometry. The specimens of 26 ADC and 18 SQCC cases were evenly assigned to the discovery and validation cohorts. Non-target screening on the discovery cohort identified 96 and 13 lipid peaks abundant in ADC and SQCC, respectively. Among these 109 lipid peaks, six and six lipid peaks in ADC and SQCC showed reproducibility in target screening on the validation cohort. Finally, we selected three and four positive lipid markers for ADC and SQCC, demonstrating high discrimination abilities. In cases difficult to diagnose by IHC staining, [cardiolipin(18:2_18:2_18:2_18:2)-H]- and [triglyceride(18:1_17:1_18:1) + NH4]+ showed the excellent diagnostic ability for ADC (sensitivity: 1.00, specificity: 0.89, accuracy: 0.93) and SQCC (sensitivity: 0.89, specificity: 0.83, accuracy: 0.87), respectively. These novel candidate lipid markers may contribute to a more accurate diagnosis and subsequent treatment strategy for unresectable NSCLC.

Intrapleural findings of pulmonary light-chain deposition disease.

Light-chain deposition disease is accompanied not only by characteristic CT findings but also by characteristic gross findings of the visceral pleura. Medical thoracoscopy could diagnose LCDD by the findings of the thoracic cavity.

Impact of Pretreatment Systemic Inflammatory Markers on Treatment Persistence with Biologics and Conventional Systemic Therapy: A Retrospective Study of Patients with Psoriasis Vulgaris and Psoriatic Arthritis.

Systemic inflammation plays a central role in the pathophysiology of psoriasis. This study examined accessible systemic inflammatory markers in patients with psoriasis vulgaris and psoriatic arthritis. We aimed to evaluate their association with psoriasis severity, the presence of arthritis, and drug continuation rates. The findings revealed that neutrophil, monocyte, and platelet count, neutrophil/lymphocyte ratio, monocyte/lymphocyte ratio, systemic inflammation response index, systemic immune/inflammation index (SII), and CRP were positively correlated with Psoriasis Area and Severity Index scores. Patients presenting with higher platelet/lymphocyte ratio (PLR) or CRP values were more likely to be diagnosed with psoriatic arthritis than with psoriasis vulgaris in the multivariate regression analysis. Importantly, patients with higher pretreatment neutrophil or platelet count, PLR, and SII were associated with lower treatment continuation rates of conventional systemic agents. Higher pretreatment scores of systemic inflammatory markers did not affect treatment retention rates of biologics. These findings suggest that several accessible systemic inflammatory markers may effectively assess underlying systemic inflammation and may provide an indication for a therapeutic approach in patients with psoriasis vulgaris and psoriatic arthritis.

Native T1 mapping in early diffuse and limited systemic sclerosis, and its association with diastolic function.

BACKGROUND: Systemic sclerosis (SSc) is divided into diffuse and limited cutaneous SSc (dcSSc and lcSSc). The dcSSc subtype has more severe internal organ damage. This study aimed to assess whether cardiovascular magnetic resonance (CMR) parametric mapping could detect early cardiac involvement and evaluate differences between these two subtypes. METHODS: Eighty SSc patients (37 dcSSc and 43 lcSSc) underwent CMR at 3.0 T (Philips Healthcare, Best, The Netherlands) in our hospital between July 2018 and July 2021. We analyzed myocardial damage by CMR parametric mapping and compared it with clinical data. RESULTS: The median duration of the disease was 10.2 months. The left ventricular ejection fraction was preserved in both groups. DcSSc had significantly higher native T1 (1333.4 ±â€¯71.2 ms vs. 1295.0 ±â€¯42.7 ms, p = 0.006) and extracellular volume fraction (32.6 ±â€¯4.1 % vs. 30.3 ±â€¯4.0 %, p = 0.018) in the mid-ventricular septum as compared to lcSSc, although there were no differences in T2 values. Native T1 values were positively correlated with the E/e' ratio and left atrial volume indices evaluated by transthoracic echocardiography in overall SSc and dcSSc, but not in lcSSc. Logistic regression analysis revealed that native T1 was an independent predictor of left ventricular diastolic dysfunction in SSc patients (odds ratio, 1.194; 95 % confidence interval, 1.021-1.396; p = 0.026). Native T1 was higher in SSc patients with progressive skin lesions. Additionally, there were positive correlations between brain natriuretic peptide, New York Heart Association functional classification, and native T1. CONCLUSIONS: CMR parametric mapping is a useful tool for detecting myocardial changes. Native T1 was the most sensitive parameter for identifying diffuse myocardial changes in the early stages of SSc and was associated with left ventricular diastolic function. DcSSc had more severe myocardial involvement than lcSSc; therefore, the use of CMR parametric mapping may aid in its prediction.

A Case of Primary Epithelioid Sarcoma of the Pleura.

BACKGROUND Epithelioid sarcoma is a rare tumor and that is extremely rare as a primary pleural neoplasm. On imaging, it may appear similar to malignant pleural mesothelioma; thus, it can be difficult to diagnose. CASE REPORT A 64-year-old Asian woman, who had a treatment history of cervix adenocarcinoma, was admitted with dyspnea and right massive pleural effusion. Chest drainage was performed, and malignant cells were found in the pleural effusion. The malignant cells were thought to be metastasized from previous cervical cancer. We continued pleural drainage; however, the volume of the pleural effusion did not decrease. On the 5th hospital day, the chest tube became occluded. Computed tomography showed structures similar to empyema. Pleural irrigation and fibrinolytic therapy did not improve her condition. Empyema curettage was performed on the 14th hospital day. The resected pleura was submitted for pathological examination and showed tumor lesion but not metastatic adenocarcinoma of the cervix. The intrathoracic tumor grew extremely rapidly, and the patient died of respiratory failure on postoperative day 8 (22nd hospital day) before a diagnosis could be made. The final pathological diagnosis obtained on the 34th hospital day was epithelioid sarcoma. CONCLUSIONS For patients who appear to have empyema complicated by neoplastic lesions, a histopathological examination should also be performed to ensure accurate diagnosis. In addition, if a tumorous lesion is detected and it is neither metastatic nor malignant pleural mesothelioma, pleural epithelioid sarcoma should be added to the differential diagnosis in the presence of a rapidly growing and histologically difficult-to-diagnose pleural tumor.

Analysis of Health-Related Quality of Life and Clinical Evaluations in Patients with the Triad of Combined Knee Injuries.

Combined knee injuries of the anterior cruciate ligament (ACL), medial collateral ligament (MCL), and medial meniscus were called "the unhappy triad" in the past. With recent advances in diagnostic technology, combined ACL, MCL, and lateral meniscus injuries are now known to be the predominant triad. We examined and verified the treatment outcomes of the triad of combined knee injuries from both patient-based subjective evaluation and objective assessments. We studied 49 knees (49 patients) with combined injuries of the ACL, MCL, and lateral meniscus. These cases were divided into those who underwent simultaneous ACL and MCL reconstruction (group A, 18 cases) and those who underwent ACL reconstruction only because MCL injury could be treated conservatively (group B, 31 cases). Clinical evaluation was conducted preoperative and 24 months or longer after surgery. The methods included patient-reported outcomes using Short Form-36, and conventional assessments using Lysholm's score, visual analogue scale (VAS), and quantitative measurement of knee instability using Telos SE. Compared with presurgical scores, the postsurgical Short Form-36 scores showed improvements in all eight subscales, all reaching the national standard values. Significant improvements were observed in the five subscales in group A and seven subscales in group B. Furthermore, significant improvements in Lysholm's score, VAS pain score, and quantitative knee instability were achieved in both groups. This study demonstrated successful clinical outcomes in patients with a triad of knee injuries who were treated with lateral meniscus repair or partial meniscectomy and either combined MCL/ACL reconstruction or ACL reconstruction alone.

Fibroblast A20 governs fibrosis susceptibility and its repression by DREAM promotes fibrosis in multiple organs.

In addition to autoimmune and inflammatory diseases, variants of the TNFAIP3 gene encoding the ubiquitin-editing enzyme A20 are also associated with fibrosis in systemic sclerosis (SSc). However, it remains unclear how genetic factors contribute to SSc pathogenesis, and which cell types drive the disease due to SSc-specific genetic alterations. We therefore characterize the expression, function, and role of A20, and its negative transcriptional regulator DREAM, in patients with SSc and disease models. Levels of A20 are significantly reduced in SSc skin and lungs, while DREAM is elevated. In isolated fibroblasts, A20 mitigates ex vivo profibrotic responses. Mice haploinsufficient for A20, or harboring fibroblasts-specific A20 deletion, recapitulate major pathological features of SSc, whereas DREAM-null mice with elevated A20 expression are protected. In DREAM-null fibroblasts, TGF-ß induces the expression of A20, compared to wild-type fibroblasts. An anti-fibrotic small molecule targeting cellular adiponectin receptors stimulates A20 expression in vitro in wild-type but not A20-deficient fibroblasts and in bleomycin-treated mice. Thus, A20 has a novel cell-intrinsic function in restraining fibroblast activation, and together with DREAM, constitutes a critical regulatory network governing the fibrotic process in SSc. A20 and DREAM represent novel druggable targets for fibrosis therapy.