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Alpha-1 Antitrypsin Deficiency (AATD)-associated panniculitis is a rare inflammatory condition characterized by painful subcutaneous plaques or nodules, often accompanied by ulceration or oily discharge. Despite its clinical and emotional burden, limited data exist on the lived experiences of individuals with this condition. An international online survey was conducted between April and July 2024, targeting individuals with AATD-associated panniculitis. The survey, co-designed with an affected individual and multi-disciplinary specialists, included 32 questions on demographics, diagnostic journey, life impact, and treatments. Responses were analysed using descriptive statistics and thematic analysis. 41 responses were included in the analysis (68% female; mean age 52.3 years). Participants reported lesions at diverse sites, affecting the lower and upper limbs, followed by the trunk, buttocks, and genitalia. 41.5% experienced both ulceration and oily discharge. 61% of participants reported being misdiagnosed which negatively affected their mental health. More than half of respondents 'strongly agreed' or 'agreed' that living with alpha-1 panniculitis had made them anxious. Access to specialist care was a major concern, with 69% finding it difficult to obtain specialist advice. Treatments varied, and augmentation therapy was identified as the subjectively the most effective. Open-ended responses revealed gaps in healthcare professionals' awareness and highlighted the need for better mental health support and specialist access. AATD-associated panniculitis significantly impacts physical, emotional, and social well-being. Addressing gaps in diagnosis and treatment, increasing healthcare providers awareness, and adopting multidisciplinary approaches are essential to improve individuals' outcomes and quality of life.

Background Melioidosis, caused by the gram-negative bacterium Burkholderia pseudomallei , is a heterogeneous disease with diverse clinical manifestations, including cutaneous involvement in 10–20% of cases. Case presentation We report the first documented case of infection-induced panniculitis caused by direct inoculation of B. pseudomallei . A 32-year-old woman from Mukdahan, Thailand, with chronic myeloid leukemia treated with a tyrosine kinase inhibitor, was hospitalized for allogenic stem cell transplantation. Three days before admission, she developed a solitary erythematous papule on her left forearm, which rapidly progressed to a tender subcutaneous nodule following chemotherapy. Her hobby of caring for cacti exposed her to soil and caused repeated cactus pricks on her upper extremities. Incisional biopsy of the lesion revealed mixed lobular and septal neutrophilic panniculitis with ischemic fat necrosis, without evidence of vascular occlusion or vasculitis. B. pseudomallei was isolated from a tissue aerobic culture, while blood cultures were negative. She was diagnosed with cutaneous melioidosis. After intensive treatment, the lesion healed, leaving a hyperpigmented patch and a biopsy scar. Conclusion This case highlights the importance of considering melioidosis in patients presenting with panniculitis, particularly those with immunosuppression, minor trauma, and exposure in endemic regions.

Persistent, unresolved inflammation in adipose tissue is a major contributor to obesity-associated metabolic complications. However, the molecular links between lipid-overloaded adipocytes and inflammatory immune cells in obese adipose tissues remain elusive. Here we identified adipocyte-secreted microRNA-34a (miR-34a) as a key mediator through its paracrine actions on adipose-resident macrophages. The expression of miR-34a in adipose tissues was progressively increased with the development of dietary obesity. Adipose-selective or adipocyte-specific miR-34a-KO mice were resistant to obesity-induced glucose intolerance, insulin resistance, and systemic inflammation, and this was accompanied by a significant shift in polarization of adipose-resident macrophages from proinflammatory M1 to antiinflammatory M2 phenotype. Mechanistically, mature adipocyte-secreted exosomes transported miR-34a into macrophages, thereby suppressing M2 polarization by repressing the expression of Krüppel-like factor 4 (Klf4). The suppressive effects of miR-34a on M2 polarization and its stimulation of inflammatory responses were reversed by ectopic expression of Klf4 in both bone marrow-derived macrophages and adipose depots of obese mice. Furthermore, increased miR-34a expression in visceral fat of overweight/obese subjects correlated negatively with reduced Klf4 expression, but positively with the parameters of insulin resistance and metabolic inflammation. In summary, miR-34a was a key component of adipocyte-secreted exosomal vesicles that transmitted the signal of nutrient overload to the adipose-resident macrophages for exacerbation of obesity-induced systemic inflammation and metabolic dysregulation.

Two of the crucial aspects of human immunodeficiency virus (HIV) infection are (i) viral persistence in reservoirs (precluding viral eradication) and (ii) chronic inflammation (directly associated with all-cause morbidities in antiretroviral therapy (ART)-controlled HIV-infected patients). The objective of the present study was to assess the potential involvement of adipose tissue in these two aspects. Adipose tissue is composed of adipocytes and the stromal vascular fraction (SVF); the latter comprises immune cells such as CD4+ T cells and macrophages (both of which are important target cells for HIV). The inflammatory potential of adipose tissue has been extensively described in the context of obesity. During HIV infection, the inflammatory profile of adipose tissue has been revealed by the occurrence of lipodystrophies (primarily related to ART). Data on the impact of HIV on the SVF (especially in individuals not receiving ART) are scarce. We first analyzed the impact of simian immunodeficiency virus (SIV) infection on abdominal subcutaneous and visceral adipose tissues in SIVmac251 infected macaques and found that both adipocytes and adipose tissue immune cells were affected. The adipocyte density was elevated, and adipose tissue immune cells presented enhanced immune activation and/or inflammatory profiles. We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue. We demonstrated that SVF cells (including CD4+ T cells) are infected in ART-controlled HIV-infected patients. Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue. We thus identified adipose tissue as a crucial cofactor in both viral persistence and chronic immune activation/inflammation during HIV infection. These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low-grade chronic inflammation via the modulation of adipose tissue-related pathways.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of cutaneous lymphoma, and the standard of care for SPTCL has not been well-defined. This retrospective study analyzed the efficacy of the CHOP-regimen in newly-diagnosed SPTCL patients in China. The study reviewed 32 SPTCL patients treated at Peking Union Medical College Hospital over the last two decades. The median age of these patients was 27 years. Among them, 56.3% were female. Sixteen patients had a PIT score ≥ 2, and 28.1% patients had concurrent hemophagocytic lymphohistiocytosis. Histopathology typically showed a lobular panniculitis with individual adipocytes surrounded by atypical lymphocytes, usually with a CD3 + , CD4 − , CD8 + , CD56 − phenotype. Twenty-eight patients (87.5%) received CHOP-like regimen as the first-line treatment. The ORR and CR rate of induction therapy were only 42.9% and 35.7%, respectively. The median PFS and OS were 3.2 months and 147.5 months. Factors, concurrent HLH and PIT ≥ 2, were indicators of shorter PFS in univariate analysis. This study showed that CHOP-like regimen was inadequate as a first-line treatment for SPTCL, emphasizing the need for alternative therapeutic strategies.

Type 2 diabetes (T2D) is a complex, polygenic disease affecting nearly 300 million people worldwide. T2D is primarily characterized by insulin resistance, and growing evidence has indicated the causative link between adipose tissue inflammation and the development of insulin resistance. Genetic association studies have successfully revealed a number of important genes consistently associated with T2D to date. However, these robust T2D-associated genes do not fully elucidate the mechanisms underlying the development and progression of the disease. Here, we report an alternative approach, gene expression-based genome-wide association study (eGWAS): searching for genes repeatedly implicated in functional microarray experiments (often publicly available). We performed an eGWAS across 130 independent experiments (totally 1,175 T2D case-control microarrays) to find additional genes implicated in the molecular pathogenesis of T2D and identified the immune-cell receptor CD44 as our top candidate (P = 8.5 x 10–20). We found CD44 deficiency in a diabetic mouse model ameliorates insulin resistance and adipose tissue inflammation and also found that anti-CD44 antibody treatment decreases blood glucose levels and adipose tissue macrophage accumulation in a high-fat, diet-fed mouse model. Further, in humans, we observed CD44 is expressed in inflammatory cells in obese adipose tissue and discovered serum CD44 levels were positively correlated with insulin resistance and glycemic control. CD44 likely plays a causative role in the development of adipose tissue inflammation and insulin resistance in rodents and humans. Genes repeatedly implicated in publicly available experimental data may have unique functionally important roles in T2D and other complex diseases.

Subcutaneous panniculitis-like T cell lymphoma (SPTCL), a non-Hodgkin lymphoma, can be associated with hemophagocytic lymphohistiocytosis (HLH), a life-threatening immune activation that adversely affects survival 1 , 2 . T cell immunoglobulin mucin 3 (TIM-3) is a modulator of immune responses expressed on subgroups of T and innate immune cells. We identify in ~60% of SPTCL cases germline, loss-of-function, missense variants altering highly conserved residues of TIM-3, c.245A>G (p.Tyr82Cys) and c.291A>G (p.Ile97Met), each with specific geographic distribution. The variant encoding p.Tyr82Cys TIM-3 occurs on a potential founder chromosome in patients with East Asian and Polynesian ancestry, while p.Ile97Met TIM-3 occurs in patients with European ancestry. Both variants induce protein misfolding and abrogate TIM-3’s plasma membrane expression, leading to persistent immune activation and increased production of inflammatory cytokines, including tumor necrosis factor-α and interleukin-1β, promoting HLH and SPTCL. Our findings highlight HLH–SPTCL as a new genetic entity and identify mutations causing TIM-3 alterations as a causative genetic defect in SPTCL. While HLH–SPTCL patients with mutant TIM-3 benefit from immunomodulation, therapeutic repression of the TIM-3 checkpoint may have adverse consequences. This study finds germline loss-of-function mutations in HAVCR2 , which encodes the immune modulator TIM-3, in individuals with subcutaneous panniculitis-like T cell lymphomas and hemophagocytic lymphohistiocytosis, a life-threatening inflammatory condition.

Panniculitis is associated with a variety of disease processes that can be challenging to distinguish clinically. While diagnosis often relies on histopathology, sometimes this is not sufficiently diagnostic, which requires careful consideration of clinical features. We sought to provide an overview of the most common adult noninfectious panniculitis by reviewing not only the histological distinguishing features but also the clinical characteristics of various types of panniculitis including patient history, distribution, morphology, and other clues. A narrative review of both common and rare panniculitis primarily affecting the adult patient population was performed, with focus on recent English language publications. Additionally, both traditional and emerging therapeutic options are discussed. This article focused on diseases affecting predominantly adult populations and does not detail pediatric panniculitis or infectious etiologies. Overall, histopathology remains a key component in the diagnosis of panniculitis, but clinical characteristics provide substantial aid.

Background Sclerosing mesenteritis (SM) is sometimes used as an umbrella-term for idiopathic inflammatory conditions in the mesentery. Mesenteric panniculitis (MP) is a radiological finding and its relation to clinical SM is not fully understood. The aims of this study were to determine whether any correlation could be found between the radiological findings and the clinical disease course. Methods Patients observed due to idiopathic inflammation of the mesentery were identified. If SM could be verified histologically or MP radiologically, the patients were included in this descriptive retro perspective study. Results Typical radiological changes were observed in 27 patients. A majority (23/27) of these patients had mild to moderate symptoms. This group with typical radiology was labelled MP. Four patients were included due to histologically verified disease but had uncharacteristic radiology involving multiple compartments of the abdomen. All four had marked systemic inflammation, fever and fluctuating radiologic findings. Three had severe disease with multiple hospitalisations and complications but responded promptly to corticosteroids. This group was denoted SM. Conclusions We have identified two subgroups of patients; firstly, MP with stable and characteristic radiologic changes and secondly SM with atypical radiology and a more aggressive clinical course. We propose that the term SM should be reserved for this latter condition.

Mycolicibacterium hassiacum (homotypic synonym: Mycobacterium hassiacum) represents an ungrouped thermotolerant rapidly growing mycobacteria (RGM) species occasionally associated with infections and disease in humans. In this report, we describe a case of pyogranulomatous dermatitis and panniculitis due to M. hassiacum in an immunocompetent adult cat. To the best of our knowledge, this represents the first report of M. hassiacum infection in animals. We also report the results of the in-depth genome characterization of the isolate using a combined short- and long-read whole-genome sequencing (WGS) approach. We observed the lack of acquired-resistance genes and no evidence of mutations in housekeeping genes associated with resistance to rifampicin and isoniazid. We detected some virulence factors in our isolate, such as some associated with the interaction of mycobacteria with host cells, and the presence of multiple copies of heavy metal resistance genes (arsB, arsR, and arsL/cadL). In conclusion, M. hassiacum should be included among the RGM species associated with feline subcutaneous atypical mycobacteriosis (SAM). A reliable and fast RGM laboratory identification and characterization is important not only for an accurate etiological diagnosis but also for a correct approach to SAM treatment options.