Hidradenitis suppurativa (HS) is a chronic inflammatory disorder characterized by painful nodules, abscesses, and sinus tracts, leading to significant quality-of-life impairment. Biologic therapies, including adalimumab, secukinumab, and bimekizumab, are approved for HS, yet reporting of patient-reported outcomes, such as the Dermatology Life Quality Index (DLQI), remains inconsistent. This PRISMA-compliant systematic review (PROSPERO ID: CRD42025633081) synthesized DLQI data from phase II and III randomized controlled trials (RCTs) of these agents. PubMed, Embase, and ClinicalTrials.gov were searched through January 13, 2025. Only multi-armed phase II or III RCTs on secukinumab, adalimumab, and bimekizumab for adult patients with HS, regardless of severity. Texts were excluded if the full text was unavailable in either English or Spanish. Studies were independently screened by two authors and adjudicated by a third author. The risk of bias assessments using the Cochrane Collaboration tool were independently performed by two authors and adjudicated by a third author. Data were collected simultaneously by two authors and qualitatively synthesized. Meta-analysis was not performed due to underlying heterogeneity in the data. Six studies comprising nine RCTs and 2,994 patients (1,203 male, 1,791 female) were included. Baseline mean DLQI was reported in 8 RCTs (n = 1,905), ranging from 8.3 to 16.4, with lower scores observed in bimekizumab trials. Mean DLQI change from baseline at weeks 12–16 was available for six RCTs (n = 1,822), ranging from − 6.0 to – 2.8 with adalimumab and − 5.5 to -4.1 with bimekizumab. Secukinumab trials reported the proportion of patients achieving ≥ 5-point DLQI improvement (37.3–48.4

The association between hidradenitis suppurativa (HS) and endometriosis was explored using the US National Institutes of Health All of Us database. The odds of having endometriosis were 1.67-fold [95% confidence interval (CI) 1.36–2.02] in those with HS compared with those without the condition, after controlling for demographics, smoking status, body mass index, polycystic ovarian syndrome and type 2 diabetes mellitus. After stratifying by age range, we found that participants with HS aged 18–45 years had an odds ratio (OR) of 1.59 (95% CI 1.18–2.10), those 46–60 years had an OR of 1.53 (95% CI 1.08–2.10) and those over 60 years had an OR of 2.63 (95% CI 1.58–4.12).

In dermatology, the art and skill of morphologic assessment is key to generating logical differential diagnoses and understanding disease pathogenesis. Dr. Irwin M. Braverman, Professor Emeritus of Dermatology at the Yale School of Medicine, is a master morphologist and his book, Skin Signs of Systemic Disease, provided key insights into the relationships between cutaneous lesions and internal disease. In an interview with Dr. Braverman, he stressed the importance morphology plays in how dermatologists diagnosis skin disorders. From Dr. Braverman, we learned an approach to the study of morphology through the lens of an art connoisseur, in addition to how to appreciate subtle clues that suggest a diagnosis and how examination of the skin brings us closer to understanding our patient, what ails them, and how we can heal them.

Sepsis is a condition marked by physiologic dysregulation secondary to infection and is influenced by the nutritional state. Despite several preclinical studies and clinical trials examining nutrition and supplements in sepsis, there are no clear guidelines. Omega-3 fatty acids are polyunsaturated fatty acids with anti-inflammatory properties, represented mainly by alpha-linolenic (ALA, C18:3), eicosapentaenoic (EPA, C20:5), and docosahexaenoic (DHA, C22:6). Since sepsis is characterized with high levels of inflammation and subsequent organ dysfunction, we hypothesized that omega-3 ingestion would improve sepsis survival by attenuating inflammation via activation of GPR120 in immune cells. Here, we aimed to experimentally explore the role of omega-3 and the receptor that mediates their anti-inflammatory functions, GPR120, during sepsis. To evaluate GPR120 functionality, acute inflammation was induced via lipopolysaccharide (LPS) treatment in Raw 264.7 cells, 3T3-L1 cells, bone marrow-derived macrophages, and primary adipocytes. To evaluate the impact of omega-3 in sepsis, C57BL/6J mice were supplemented with omega-3 before LPS administration or cecal ligation and puncture (CLP) surgery. GPR120 mRNA expression decreased during inflammation. Unexpectedly, omega-3 supplementation preceding CLP worsened sepsis survival in mice. In addition, omega-3 did not affect inflammatory markers such as TNFα, IL1β, IL10, and IL6. Overall, our findings that omega-3 do not influence inflammation or improve survival in sepsis are surprising, given that omega-3 supplementation is recommended for the prevention of cardiovascular diseases due to its anti-inflammatory properties. The negative impact of omega-3 supplementation on survival in the CLP model raises caution for future clinical studies involving sepsis.NEW & NOTEWORTHY This study uncovers worsening in survival in mice models pretreated with omega-3 supplementation. We demonstrated decreased Ffar4 receptor expression in macrophages and adipocytes when challenged with acute and chronic sepsis models in vitro and in vivo. This study offers insight into the role of omega-3 supplementation in the context of sepsis, highlighting concerns and underscoring the need for further investigation.

Our current understanding of immunity to pathogens suggests that anatomic coupling of antigens with danger signals is a required feature for the formation of immune memory. However, in the context of pathogen-independent inflammation, the stringency of this anatomical coupling is unclear. Here, we demonstrate that multiple modes of skin injury were sufficient to induce a humoral response to antigens introduced in the gut. Skin damage induced a narrow subset of endocrine cytokines that were necessary and sufficient for the priming of antigens introduced at various distal tissues. Thus, in addition to "local priming" of antigen entering through damaged skin, there also exists another paradigm of "remote priming" where anatomical coupling is not essential because of the dissemination of damage-associated intermediaries. Our findings have implications for understanding the fundamental mechanisms of the formation of humoral memory with wide implications for diseases such as food allergy and in vaccinology.

Food insecurity (FI) presents unique challenges for individuals with food allergies (FA) and atopic dermatitis (AD), conditions that often encompass tailored dietary management and medical care. Limited access to safe, nutritious foods exacerbates symptoms and complicates disease management, leading to poorer health outcomes and increased healthcare costs. This review explores the complex relationship between FI, FA, and AD, focusing on the challenges faced by affected individuals and identifying potential strategies for reducing disparities. The intersection of FI, FA, and AD creates barriers to disease management, increasing the risk of allergic reactions and disease flares due to limited access to allergen-free foods and over-the-counter topical emollients. Financial strain forces individuals to consume cheaper, less nutritious foods and limit emollient use, worsening health outcomes. Nutritional deficiencies and psychological stress from managing multiple conditions further exacerbate both FA and AD, underscoring the need for multi-level solutions. Public health policies should address these issues by improving access to allergen-free foods and reducing associated financial burdens. This review highlights the bidirectional relationship between FI, FA, and AD and calls for integrated interventions to address both immediate nutritional needs and long-term disease management. Further research is needed to understand the mechanisms linking FI to allergic diseases and to develop strategies to mitigate these risks.

International Journal of DermatologyVolume 63, Issue 3 p. e74-e75 Clinical Correspondence Associations between hidradenitis suppurativa and asthma and allergic rhinitis: a case–control study in the All of Us research program Gloria F. Chen BA, Gloria F. Chen BA orcid.org/0000-0002-5643-2676 Yale School of Medicine, New Haven, CT, USASearch for more papers by this authorJeffrey M. Cohen MD, Corresponding Author Jeffrey M. Cohen MD [email protected] Department of Dermatology, Yale School of Medicine, New Haven, CT, USA Section of Biomedical Informatics and Data Science, Yale School of Medicine, New Haven, CT, USASearch for more papers by this authorAnna Eisenstein MD, PhD, Anna Eisenstein MD, PhD Department of Dermatology, Yale School of Medicine, New Haven, CT, USASearch for more papers by this author Gloria F. Chen BA, Gloria F. Chen BA orcid.org/0000-0002-5643-2676 Yale School of Medicine, New Haven, CT, USASearch for more papers by this authorJeffrey M. Cohen MD, Corresponding Author Jeffrey M. Cohen MD [email protected] Department of Dermatology, Yale School of Medicine, New Haven, CT, USA Section of Biomedical Informatics and Data Science, Yale School of Medicine, New Haven, CT, USASearch for more papers by this authorAnna Eisenstein MD, PhD, Anna Eisenstein MD, PhD Department of Dermatology, Yale School of Medicine, New Haven, CT, USASearch for more papers by this author First published: 18 December 2023 https://doi.org/10.1111/ijd.16994 †These authors contributed equally (co-senior authors). Conflict of interest: JMC serves on a data and safety monitoring board (DSMB) for Advarra. The remainder of the authors have no conflicts of interest to declare. Funding source: GFC received research support from the Richard K. Gershon, M.D., Endowed Medical Student Research Fellowship. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1Petrasca A, Hambly R, Molloy O, Kearns S, Moran B, Smith CM, et al. Innate lymphoid cell (ILC) subsets are enriched in the skin of patients with hidradenitis suppurativa. PloS One. 2023; 18(2):e0281688. 10.1371/journal.pone.0281688 CASPubMedWeb of Science®Google Scholar 2Hofmann MA, Fluhr JW, Ruwwe-Glösenkamp C, Stevanovic K, Bergmann KC, Zuberbier T. Role of IL-17 in atopy-a systematic review. Clin Transl Allergy. 2021; 11(6):e12047. 10.1002/clt2.12047 CASPubMedWeb of Science®Google Scholar 3Gau SY, Chan WL, Tsai JD. Risk of atopic diseases in patients with hidradenitis suppurativa: a systematic review and meta-analysis of observational studies. Dermatology. 2023; 239(2): 314–322. 10.1159/000528920 PubMedWeb of Science®Google Scholar 4Cho MK, Shin JU, Kim DH, Lee HJ. Severe atopic dermatitis and concurrent severe hidradenitis suppurativa successfully treated with dupilumab. Clin Exp Dermatol. 2022; 47(12): 2303–2305. 10.1111/ced.15387 PubMedWeb of Science®Google Scholar 5Drucker AM, Li WQ, Savitz DA, Weinstock MA, Han J, Li T, et al. Association between health maintenance practices and skin cancer risk as a possible source of detection bias. JAMA Dermatol. 2019; 155(3): 353–357. 10.1001/jamadermatol.2018.4216 PubMedWeb of Science®Google Scholar Volume63, Issue3March 2024Pages e74-e75 ReferencesRelatedInformation

Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX) enzymes and are ubiquitously used for their anti-inflammatory properties. However, COX inhibition alone fails to explain numerous clinical outcomes of NSAID usage. Screening commonly used NSAIDs in primary human and murine myeloid cells demonstrated that NSAIDs could be differentiated by their ability to induce growth/differentiation factor 15 (GDF15), independent of COX specificity. Using genetic and pharmacologic approaches, NSAID-mediated GDF15 induction was dependent on the activation of nuclear factor erythroid 2-related factor 2 (NRF2) in myeloid cells. Sensing by Cysteine 151 of the NRF2 chaperone, Kelch-like ECH-associated protein 1 (KEAP1) was required for NSAID activation of NRF2 and subsequent anti-inflammatory effects both in vitro and in vivo. Myeloid-specific deletion of NRF2 abolished NSAID-mediated tissue protection in murine models of gout and endotoxemia. This highlights a noncanonical NRF2-dependent mechanism of action for the anti-inflammatory activity of a subset of commonly used NSAIDs.

Langerhans cell histiocytosis (LCH) is an inflammatory, neoplastic disease, most commonly of toddlers and young children, that can present as a skin-limited disease or as a systemic disease with or without cutaneous manifestations.1 The pathogenetic basis of LCH is the accumulation of S100, CD1a, and langerin-positive (CD207+) dendritic cells. BRAF V600E mutations are found in 60% of the cases.1,2 In both the skin-limited and systemic forms, LCH has a vast range of possible presentations.3 Particularly with skin-limited LCH, the disease may spontaneously resolve, leading to underdiagnosis.

Adenosine is an extracellular signaling molecule that is particularly relevant in times of cellular stress, inflammation and metabolic disturbances when the levels of the purine increase. Adenosine acts on two G-protein-coupled stimulatory and on two G-protein-coupled inhibitory receptors, which have varying expression profiles in different tissues and conditions, and have different affinities for the endogenous ligand. Studies point to significant roles of adenosine and its receptors in metabolic disease and bone health, implicating the receptors as potential therapeutic targets. This review will highlight our current understanding of the dichotomous effects of adenosine and its receptors on adipogenesis versus osteogenesis within the bone marrow to maintain bone health, as well as its relationship to obesity. Therapeutic implications will also be reviewed.

Food allergy is a modern disease. Its exponential increase in prevalence in the last 70 years cannot be explained by genetic factors alone. In this review we discuss the hypotheses that have been suggested previously, and the evidence that supports them, to explain this rise in prevalence as well as the medical treatments that have developed as a result of basic exploration within these paradigms. We argue that one major area of fruitful exploration that would help generate new ideas may be systematic analyses of the unknown factors of the modern environment that may contribute to the formation of food allergy. Through this lens, we review the current understanding of food allergy pathogenesis and propose novel research directions, with implications for the current strategies for managing food allergy.

Earlier identification of aggressive melanoma remains a goal in the field of melanoma research. With new targeted and immune therapies that have revolutionized the care of patients with melanoma, the ability to predict progression and monitor or predict response to therapy has become the new focus of research into biomarkers in melanoma. In this review, promising biomarkers are highlighted. These biomarkers have been used to diagnose melanoma as well as predict progression to advanced disease and response to therapy. The biomarkers take various forms, including protein expression at the level of tissue, genetic mutations of cancer cells, and detection of circulating DNA. First, a brief description is provided about the conventional tissue markers used to stage melanoma, including tumor depth. Next, protein biomarkers, which provide both diagnostic and prognostic information, are described. This is followed by a discussion of important genetic mutations, microRNA, and epigenetic modifications that can provide therapeutic and prognostic material. Finally, emerging serologic biomarkers are reviewed, including circulating melanoma cells and exosomes. Overall the goal is to identify biomarkers that aid in the earlier identification and improved treatment of aggressive melanoma.

There is a significant need for the development of diagnostic tools that can precisely distinguish Spitz nevi and spitzoid melanomas. Here, we report the development of a PCR-based quantitative diagnostic assay for spitzoid melanocytic lesions utilizing the expression ratio of neuropilin-2 and melan-A genes in primary tumor specimens. We find that the expression ratio of neuropilin-2/melan-A is significantly increased in spitzoid melanomas compared with Spitz nevi. The diagnostic potential of this quantitative assay was validated in two independent sets of patient samples as demonstrated in a receiver operating characteristic curve analysis showing an area under the curve value of 91.8%. Furthermore, the assay was found to quantitatively distinguish the clinical nature of atypical spitzoid melanocytic lesions that were diagnostically undetermined using histopathologic criteria alone. Our data indicate that this quantitative assay may be used as a tool in determining the diagnostic classification of histologically challenging spitzoid tumors.

Modulation of the low affinity adenosine receptor subtype, the A2b adenosine receptor (A2bAR), has gained interest as a therapeutic target in various pathologic areas associated with cardiovascular disease. The actions of the A2bAR are diverse and at times conflicting depending on cell and tissue type and the timing of activation or inhibition of the receptor. The A2bAR is a promising and exciting pharmacologic target, however, a thorough understanding of A2bAR action is necessary to reach the therapeutic potential of this receptor. This review will focus on the role of the A2bAR in various cardiovascular and metabolic pathologies in which the receptor is currently being studied. We will illustrate the complexities of A2bAR signaling and highlight areas of research with potential for therapeutic development. J. Cell. Physiol. 230: 2891–2897, 2015. © 2015 Wiley Periodicals, Inc.

High fat diet (HFD)-induced type 2 diabetes continues to be an epidemic with significant risk for various pathologies. Previously, we identified the A2b adenosine receptor (A2bAR), an established regulator of inflammation, as a regulator of HFD-induced insulin resistance. In particular, HFD was associated with vast upregulation of liver A2bAR in control mice, and while mice lacking this receptor showed augmented liver inflammation and tissue insulin resistance. As the A2bAR is expressed in different tissues, here, we provide the first lead to cellular mechanism by demonstrating that the receptor's influence on tissue insulin sensitivity is mediated via its expression in macrophages. This was shown using a newly generated transgenic mouse model expressing the A2bAR gene in the macrophage lineage on an otherwise A2bAR null background. Reinstatement of macrophage A2bAR expression in A2bAR null mice fed HFD restored insulin tolerance and tissue insulin signaling to the level of control mice. The molecular mechanism for this effect involves A2bAR-mediated changes in cyclic adenosine monophosphate in macrophages, reducing the expression and release of inflammatory cytokines, which downregulate insulin receptor-2. Thus, our results illustrate that macrophage A2bAR signaling is needed and sufficient for relaying the protective effect of the A2bAR against HFD-induced tissue inflammation and insulin resistance in mice.

PROBLEM:Curricular integration has emerged as a consistent theme in medical education reform. Vertical integration of topics such as pathology offers the potential to bring basic science content into the clinical arena, but faculty/student acceptance and curricular design pose challenges for such integration.APPROACH:The authors describe the Cadaver Biopsy Project (CBP) at Boston University School of Medicine as a sustainable model of vertical integration. Faculty and select senior medical students obtained biopsies of cadavers during the first-year gross anatomy course (fall 2009) and used these to develop clinical cases for courses in histology (spring 2010), pathology (fall 2010-spring 2011), and radiology (fall 2011 or spring 2012), thereby linking students' first experiences in basic sciences with other basic science courses and later clinical courses. Project goals included engaging medical stu dents in applying basic science princi ples in all aspects of patient care as they acquire skills. The educational intervention used a patient (cadaver)-centered approach and small-group, collaborative, case-based learning.OUTCOMES:Through this project, the authors involved clinical and basic science faculty-plus senior medical students-in a collaborative project to design and implement an integrated curriculum through which students revisited, at several different points, the microscopic structure and pathophysiology of common diseases.NEXT STEPS:Developing appropriate, measurable out comes for medical education initiatives, including the CBP, is challenging. Accumu lation of qualitative feedback from surveys will guide continuous improvement of the CBP. Documenting longer-term impact of the curricular innovation on test scores and other competency-based outcomes is an ultimate goal.

Curricular integration has emerged as a consistent theme in medical education reform. Vertical integration of topics such as pathology offers the potential to bring basic science content into the clinical arena, but faculty/student acceptance and curricular design pose challenges for such integration.The authors describe the Cadaver Biopsy Project (CBP) at Boston University School of Medicine as a sustainable model of vertical integration. Faculty and select senior medical students obtained biopsies of cadavers during the first-year gross anatomy course (fall 2009) and used these to develop clinical cases for courses in histology (spring 2010), pathology (fall 2010-spring 2011), and radiology (fall 2011 or spring 2012), thereby linking students' first experiences in basic sciences with other basic science courses and later clinical courses. Project goals included engaging medical stu dents in applying basic science princi ples in all aspects of patient care as they acquire skills. The educational intervention used a patient (cadaver)-centered approach and small-group, collaborative, case-based learning.Through this project, the authors involved clinical and basic science faculty-plus senior medical students-in a collaborative project to design and implement an integrated curriculum through which students revisited, at several different points, the microscopic structure and pathophysiology of common diseases.Developing appropriate, measurable out comes for medical education initiatives, including the CBP, is challenging. Accumu lation of qualitative feedback from surveys will guide continuous improvement of the CBP. Documenting longer-term impact of the curricular innovation on test scores and other competency-based outcomes is an ultimate goal.