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Diabetes Jan 2023Acquired lipodystrophy is often characterized as an idiopathic subtype of lipodystrophy. Despite suspicion of an immune-mediated pathology, biomarkers such as...
Acquired lipodystrophy is often characterized as an idiopathic subtype of lipodystrophy. Despite suspicion of an immune-mediated pathology, biomarkers such as autoantibodies are generally lacking. Here, we used an unbiased proteome-wide screening approach to identify autoantibodies to the adipocyte-specific lipid droplet protein perilipin 1 (PLIN1) in a murine model of autoimmune polyendocrine syndrome type 1 (APS1). We then tested for PLIN1 autoantibodies in human subjects with acquired lipodystrophy with two independent severe breaks in immune tolerance (including APS1) along with control subjects using a specific radioligand binding assay and indirect immunofluorescence on fat tissue. We identified autoantibodies to PLIN1 in these two cases, including the first reported case of APS1 with acquired lipodystrophy and a second patient who acquired lipodystrophy as an immune-related adverse event following cancer immunotherapy. Lastly, we also found PLIN1 autoantibodies to be specifically enriched in a subset of patients with acquired generalized lipodystrophy (17 of 46 [37%]), particularly those with panniculitis and other features of autoimmunity. These data lend additional support to new literature that suggests that PLIN1 autoantibodies represent a marker of acquired autoimmune lipodystrophies and further link them to a break in immune tolerance.
Topics: Humans; Animals; Mice; Perilipin-1; Autoantibodies; Lipodystrophy, Congenital Generalized; Lipodystrophy; Adipose Tissue
PubMed: 35709010
DOI: 10.2337/db21-1172 -
Cureus Jan 2022Coronavirus disease 2019 (COVID-19) typically involves the respiratory system, but gastrointestinal involvement is common. Further, patients with severe COVID-19 are at...
Coronavirus disease 2019 (COVID-19) typically involves the respiratory system, but gastrointestinal involvement is common. Further, patients with severe COVID-19 are at high risk to develop gastrointestinal complications, including bowel ischemia, ileus, and deranged liver enzymes. We present the case of a 44-year-old woman with mild COVID-19 pneumonia who was in home isolation. Ten days after the isolation, the patient presented to the emergency department complaining of generalized abdominal pain that was sharp in nature and associated with nausea and recurrent episodes of vomiting. The patient did not complain of any respiratory symptoms. Physical examination showed diffuse tenderness with no clinical signs to suggest generalized peritonitis. The laboratory parameters showed normal hematological, renal, and hepatic profiles. No elevation in the inflammatory markers was observed. The amylase level was within the normal range. Abdominal computed tomography scan demonstrated the presence of misty mesentery with increased density of the mesentery with fat stranding encasing the mesenteric vessels along with mesenteric adenopathy. Such radiological features suggested the diagnosis of mesenteric panniculitis. Subsequently, intravenous corticosteroid therapy was initiated and the patient exhibited significant improvement after 24 hours. The patient was discharged after nine days of hospitalization. She was followed up after one month and she had no complaints. Mesenteric panniculitis is a rare idiopathic inflammatory condition involving the mesenteric adipose tissue. The case shed a light on the possible association of COVID-19 with mesenteric panniculitis. The clinical manifestations of mesenteric panniculitis are non-specific and imaging studies are essential to suggest the diagnosis.
PubMed: 35186573
DOI: 10.7759/cureus.21314 -
Indian Journal of Dermatology,... 2020
Review
Topics: Adult; Anti-Inflammatory Agents; Antimetabolites, Antineoplastic; Humans; Lymphoma, T-Cell; Male; Methotrexate; Panniculitis; Prednisolone; Skin Neoplasms
PubMed: 31975700
DOI: 10.4103/ijdvl.IJDVL_635_18 -
Clinical, Cosmetic and Investigational... 2021Giant cell arteritis (GCA) is characterized by granulomatous inflammation of large and medium-sized vessels. It is the most common vasculitis among elderly people in... (Review)
Review
Giant cell arteritis (GCA) is characterized by granulomatous inflammation of large and medium-sized vessels. It is the most common vasculitis among elderly people in Europe and North America. GCA usually presents with ischemic cranial manifestations such as headache, scalp tenderness, visual manifestations, and claudication of the tongue and jaw. Thickness and tenderness of temporal arteries are the most recognizable signs of GCA on physical examination. Laboratory tests usually show raised acute phase reactants. Skin manifestations are uncommon in GCA and are rarely found as a presenting symptom of GCA. Necrosis of the scalp and tongue is the most common ischemic cutaneous manifestation of GCA. Although infrequent, when present it reflects severe affection and poor prognosis of GCA. Panniculitis-like lesions have been reported in the setting of GCA, with nodules being the most common finding. Other entities, such as generalized granuloma annulare or basal cell carcinoma have been occasionally described in GCA patients. Prompt recognition and initiation of therapy are crucial to prevent serious complications of GCA. When high suspicion of GCA exists, immediate administration of glucocorticoids is recommended. It is advisable to refer the patient to a specialist GCA team for further multidisciplinary assessment.
PubMed: 33790612
DOI: 10.2147/CCID.S284795 -
Arteriosclerosis, Thrombosis, and... Feb 2021Infiltrated macrophages actively promote perivascular adipose tissue remodeling and represent a dominant population in the perivascular adipose tissue microenvironment...
OBJECTIVE
Infiltrated macrophages actively promote perivascular adipose tissue remodeling and represent a dominant population in the perivascular adipose tissue microenvironment of hypertensive mice. However, the role of macrophages in initiating metabolic inflammation remains uncertain. SIRT3 (sirtuin-3), a NAD-dependent deacetylase, is sensitive to metabolic status and mediates adaptation responses. In this study, we investigated the role of SIRT3-mediated metabolic shift in regulating NLRP3 (Nod-like receptor family pyrin domain-containing 3) inflammasome activation. Approach and Results: Here, we report that Ang II (angiotensin II) accelerates perivascular adipose tissue inflammation and fibrosis, accompanied by NLRP3 inflammasome activation and IL (interleukin)-1β secretion in myeloid SIRT3 knockout (SIRT3) mice. This effect is associated with adipose tissue mitochondrial dysfunction. In vitro studies indicate that the deletion of SIRT3 in bone marrow-derived macrophages induces IL-1β production by shifting the metabolic phenotype from oxidative phosphorylation to glycolysis. Mechanistically, SIRT3 deacetylates and activates PDHA1 (pyruvate dehydrogenase E1 alpha) at lysine 83, and the loss of SIRT3 leads to PDH activity decrease and lactate accumulation. Knocking down LDHA (lactate dehydrogenase A) or using carnosine, a buffer against lactic acid, attenuates IL-1β secretion. Furthermore, the blockade of IL-1β from macrophages into brown adipocytes restores thermogenic markers and mitochondrial oxygen consumption. Moreover, NLRP3 knockout (NLRP3) mice exhibited reduced IL-1β production while rescuing the mitochondrial function of brown adipocytes and alleviating perivascular adipose tissue fibrosis.
CONCLUSIONS
SIRT3 represents a potential therapeutic target to attenuate NLRP3-related inflammation. Pharmacological targeting of glycolytic metabolism may represent an effective therapeutic approach.
Topics: Acetylation; Adipose Tissue, Brown; Angiotensin II; Animals; Cell Plasticity; Disease Models, Animal; Energy Metabolism; Fibrosis; HEK293 Cells; Humans; Hypertension; Inflammasomes; Interleukin-1beta; Lactic Acid; Macrophages; Male; Mice, Inbred C57BL; Mice, Knockout; NLR Family, Pyrin Domain-Containing 3 Protein; Panniculitis; Phenotype; Pyruvate Dehydrogenase (Lipoamide); Signal Transduction; Sirtuin 3; Mice
PubMed: 33327751
DOI: 10.1161/ATVBAHA.120.315337 -
Haematologica Dec 2023While all peripheral T-cell lymphomas are uncommon, certain subtypes are truly rare, with less than a few hundred cases per year in the USA. There are often no dedicated... (Review)
Review
While all peripheral T-cell lymphomas are uncommon, certain subtypes are truly rare, with less than a few hundred cases per year in the USA. There are often no dedicated clinical trials in these rare subtypes, and data are generally limited to case reports and retrospective case series. Therefore, clinical management is often based on this limited literature and extrapolation of data from the more common, nodal T-cell lymphomas in conjunction with personal experience. Nevertheless, thanks to tremendous pre-clinical efforts to understand these rare diseases, an increasing appreciation of the biological changes that underlie these entities is forming. In this review, we attempt to summarize the relevant literature regarding the initial management of certain rare subtypes, specifically subcutaneous panniculitis-like T-cell lymphoma, hepatosplenic T-cell lymphoma, intestinal T-cell lymphomas, and extranodal NK/T-cell lymphoma. While unequivocally established approaches in these diseases do not exist, we make cautious efforts to provide our approaches to clinical management when possible.
Topics: Humans; T-Lymphocytes; Retrospective Studies; Killer Cells, Natural; Lymphoma, T-Cell, Peripheral; Lymphoma, Extranodal NK-T-Cell
PubMed: 38037801
DOI: 10.3324/haematol.2023.282717 -
Clinical, Cosmetic and Investigational... 2024Cytophagic histiocytic panniculitis (CHP) is a rare panniculitis associated with systemic features characterized by the infiltration of subcutaneous adipose tissue by...
BACKGROUND
Cytophagic histiocytic panniculitis (CHP) is a rare panniculitis associated with systemic features characterized by the infiltration of subcutaneous adipose tissue by benign-appearing T lymphocytes and phagocytic histiocytes, mimicking hemophagocytic lymphohistiocytosis (HLH) and subcutaneous panniculitis-like T-cell lymphoma (SPTCL).
PURPOSE
To establish the clinicopathological features and response to treatment of CHP and evaluate the prognosis of patients and guide therapy based on the current state of knowledge.
MATERIAL AND METHODS
Clinical, laboratory, histopathological, and outcome data of 12 patients with CHP were retrospectively collected between 2009 and 2022.
RESULTS
All the patients presented with plaques or nodules, mostly located in the lower extremities (11/12). Fewer cases involved systemic symptoms (9/12) and laboratory abnormalities (6/12), and none were positive for serum Epstein-Barr virus (EBV)-DNA. Histopathological examination revealed mixed septal and lobular inflammatory infiltration of histiocytes and lymphocytes. Large or atypical lymphocytes were rarely present (2/12). In some patients, varying proportions of plasma cells, neutrophils, and eosinophils were observed. The extent of histocytophagy was mild (9/12), moderate (2/12), and severe (1/12). HLH was not observed in any of our cases, none of which were fatal.
CONCLUSION
The uniqueness of our study lies in the presence of neutrophil-rich dermal and subcutaneous infiltrates, associated with connective tissue disorders (CTD) and streptococcal infections. Our study reveals that EBV-negative CHP tends to a better prognosis than previously research, filling the gap in the much-needed details of CHP in the Chinese population. Moreover, CHP may present as a reactive process in combined primary diseases; further studies are required to validate these findings.
PubMed: 38831784
DOI: 10.2147/CCID.S460784 -
Clinical Case Reports Dec 2022Since patients with mesenteric panniculitis (MP) present non-specific symptoms, diagnosing MP is challenging. We describe a 45-year-old man who developed MP with...
Since patients with mesenteric panniculitis (MP) present non-specific symptoms, diagnosing MP is challenging. We describe a 45-year-old man who developed MP with radiologic findings of a "fat ring sign" and a "tumoral pseudocapsule sign." These signs shown in the present case are crucial for a precise diagnosis of MP.
PubMed: 36514474
DOI: 10.1002/ccr3.6654 -
Lupus Science & Medicine Dec 2023To assess the efficacy of anifrolumab, a type-1 interferon receptor subunit-1 monoclonal antibody, in treating refractory cutaneous lupus erythematosus (CLE) and lupus...
OBJECTIVE
To assess the efficacy of anifrolumab, a type-1 interferon receptor subunit-1 monoclonal antibody, in treating refractory cutaneous lupus erythematosus (CLE) and lupus non-specific mucocutaneous manifestations in patients with systemic lupus erythematosus (SLE).
METHODS
A case series comprising four SLE patients with refractory CLE received anifrolumab (300mg) as add-on therapy. Medical history, serological markers and images were collected. Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity (CLASI-A) was assessed at baseline and post-treatment visits.
RESULTS
Anifrolumab effectively treated refractory chronic cutaneous lupus erythematosus with lupus panniculitis and calcinosis cutis. Anifrolumab demonstrated rapid improvement in generalised discoid lupus, achieving a substantial reduction in CLASI-A from 40 to 8. Switching from belimumab to anifrolumab led to notable improvement in photosensitivity and tumid lupus. Anifrolumab effectively managed refractory subacute cutaneous lupus erythematosus, resulting in remarkable cutaneous improvement and successful tapering of prednisone and mycophenolate mofetil.
CONCLUSION
Anifrolumab demonstrates efficacy in treating refractory CLE subtypes and lupus non-specific mucocutaneous manifestations in SLE patients. Further studies are needed to establish response rates, optimal dosing, and long-term outcomes.
Topics: Humans; Lupus Erythematosus, Systemic; Lupus Erythematosus, Cutaneous; Antibodies, Monoclonal; Prednisone
PubMed: 38114267
DOI: 10.1136/lupus-2023-001007 -
Annals of Hepato-biliary-pancreatic... Feb 2021Pancreaticoduodenectomy (PD) is the gold standard for the treatment of periampullary tumors. Many specialized centers have adopted the totally laparoscopic or hybrid...
BACKGROUNDS/AIMS
Pancreaticoduodenectomy (PD) is the gold standard for the treatment of periampullary tumors. Many specialized centers have adopted the totally laparoscopic or hybrid laparoscopic PD (LPD). However, this procedure has not yet been standardized and serious debate is taking place towards its safety and feasibility. Herein, we report our recent experience whit hybrid-LPD.
METHODS
During 2019 in our department 56 PD were performed and 21 (37.5%) underwent hybrid-LPD. We have retrospectively reviewed the short-term outcomes of these patients.
RESULTS
Main indication was pancreatic adenocarcinoma (71,4%). The median operative time and intraoperative blood loss were respectively 425 min (range, 226 to 576) and 317 ml (range 60 to 800 ml). Conversion to an open procedure was required in 4 patients (19%): 2 with suspected vein involvement, 1 for mesenteric panniculitis and 1 for biliary injury. The post-operative complication rate was 42.8% (9/21). Regarding post-operative pancreatic fistula, three patients (14.2%) had grade B and 1 grade C (4.7%). Median length of hospital stay was 14 days (range 9-23) and 90- days mortality was 4.7%. The mean number of harvested lymph nodes was 17.7 (range 12 to 26). The rate of margins R0 was 80%; R1 >0<1 mm was 10.5% and R1 0 mm was 9.5%.
CONCLUSIONS
Hydrid-LPD is safe and feasible. Careful patient selection and increasing experience can reduce the risk of post-operative complications.
PubMed: 33649262
DOI: 10.14701/ahbps.2021.25.1.102