Paniculitis mesentérica / Mesenteric panniculitis

Introducción: La paniculitis mesentérica es una afección infrecuente. Aparece en la adultez tardía, con manifestaciones clínicas inespecíficas, puede cursar asintomática o caracterizarse por dolor, hinchazón y distensión abdominal, masa palpable a nivel del abdomen. Esto puede ser un hallazgo casual al realizar exploraciones radiológicas. Objetivo: Describir las características clínico-imagenológicas, así como terapéutica empleada en el tratamiento de un paciente con paniculitis mesentérica. Presentación de caso: Se presenta el caso de un paciente blanco, masculino de 59 años. Con antecedentes de hiperlipidemia, con cuadros doloroso abdominal inespecífico, de 6 meses de evolución. Se le realiza tomografía axial computarizada de abdomen simple y E/V donde se observó engrosamiento de la grasa mesentérica y múltiples imágenes nodulares a nivel del mesenterio compatible con paniculitis mesentérica. Desarrollo: La paniculitis mesentérica es una enfermedad de baja prevalencia, con mayor predominio en la sexta década de la vida, es habitualmente un hallazgo incidental en laparotomía exploratoria o tomografía computarizada de abdomen. Conclusiones: Deben conocerse las manifestaciones clínicas y hallazgos imagenológicos de la paniculitis mesentérica, así como las variantes terapéuticas en su tratamiento para evitar las intervenciones quirúrgicas innecesarias(AU)

Introduction: Mesenteric panniculitis is a rare condition. It appears in late adulthood, with nonspecific clinical manifestations, it can be asymptomatic or characterized by pain, swelling and abdominal distension, a palpable mass in the abdomen. This can be a chance finding when performing radiological examinations. Objective: To describe the clinical-imaging characteristics, as well as the therapy used in the treatment of a patient with mesenteric panniculitis. Case report: We report the case of a 59-year-old white male patient, with history of hyperlipidemia, nonspecific abdominal pain and 6 months of evolution. A simple abdominal computed tomography and E / V were performed, showing thickening of the mesenteric fat and multiple nodular images at the level of the mesentery compatible with mesenteric panniculitis. Findings: Mesenteric panniculitis is a low prevalence disease, with greater prevalence in the sixth decade of life, which is usually found incidentally in exploratory laparotomy or abdominal computed tomography. Conclusions: The clinical manifestations and imaging findings of mesenteric panniculitis must be known, as well as the therapeutic variants in its treatment to avoid unnecessary surgical interventions(AU)

Values of ultrasound for diagnosis and management of insulin-induced lipohypertrophy: A prospective cohort study in China.

ABSTRACT: The aim of this study was to explore the values of ultrasound for diagnosis and management of insulin-induced lipohypertrophy and further analyzing the impact of body mass index and subcutaneous fat thickness on ultrasound manifestations of lipohypertrophy.In this 3-month, prospective cohort study, a total of 162 patients with diabetes who used insulin therapy more than 1 year with unknown lipohypertrophy status were enrolled into this study. Demographic information, assessment of glycemic control and insulin injection technique were evaluated. Physical and ultrasound examination were separately performed to detect lipohypertrophy by a team of diabetes educator nurses or ultrasonographer in a blinded fashion. Patients with lipohypertrophy received insulin injection technique education based on ultrasound examination and Chinese guideline.Ultrasound examination detected 41.1% more patients (74.1% vs 52.5%; P < .001) with lipohypertrophy and 61.2% more lesions (216 vs 134; P < .001) than physical examination. Glycosylated hemoglobin A1c and fasting blood glucose were significantly decreased in patients with lipohypertrophy or subclinical lipohypertrophy (lipohypertrophy without visual and palpation changes) after receiving insulin injection technique education based on ultrasound examination and Chinese guideline than baseline at 3 months (P < .001). The proportion of lesions with ultrasound manifestation 2 (distortion of surrounding connective tissue) in obese and STF (>15 mm) groups were no more than 50% and showed a decreased trend with increased subcutaneous fat thickness and body mass index (P < .001).Lipohypertrophy has characteristic ultrasound manifestations which can detect more accurate results than palpation alone and provide detailed information to promote effective education on lipohypertrophy management, thereby improving glycemic control.

Adipose tissue is a critical regulator of osteoarthritis.

Osteoarthritis (OA), the leading cause of pain and disability worldwide, disproportionally affects individuals with obesity. The mechanisms by which obesity leads to the onset and progression of OA are unclear due to the complex interactions among the metabolic, biomechanical, and inflammatory factors that accompany increased adiposity. We used a murine preclinical model of lipodystrophy (LD) to examine the direct contribution of adipose tissue to OA. Knee joints of LD mice were protected from spontaneous or posttraumatic OA, on either a chow or high-fat diet, despite similar body weight and the presence of systemic inflammation. These findings indicate that adipose tissue itself plays a critical role in the pathophysiology of OA. Susceptibility to posttraumatic OA was reintroduced into LD mice using implantation of a small adipose tissue depot derived from wild-type animals or mouse embryonic fibroblasts that undergo spontaneous adipogenesis, implicating paracrine signaling from fat, rather than body weight, as a mediator of joint degeneration.

Exercise Increases Bone in SEIPIN Deficient Lipodystrophy, Despite Low Marrow Adiposity.

Exercise, typically beneficial for skeletal health, has not yet been studied in lipodystrophy, a condition characterized by paucity of white adipose tissue, with eventual diabetes, and steatosis. We applied a mouse model of global deficiency of Bscl2 (SEIPIN), required for lipid droplet formation. Male twelve-week-old B6 knockouts (KO) and wild type (WT) littermates were assigned six-weeks of voluntary, running exercise (E) versus non-exercise (N=5-8). KO weighed 14% less than WT (p=0.01) and exhibited an absence of epididymal adipose tissue; KO liver Plin1 via qPCR was 9-fold that of WT (p=0.04), consistent with steatosis. Bone marrow adipose tissue (BMAT), unlike white adipose, was measurable, although 40.5% lower in KO vs WT (p=0.0003) via 9.4T MRI/advanced image analysis. SEIPIN ablation's most notable effect marrow adiposity was in the proximal femoral diaphysis (-56% KO vs WT, p=0.005), with relative preservation in KO-distal-femur. Bone via µCT was preserved in SEIPIN KO, though some quality parameters were attenuated. Running distance, speed, and time were comparable in KO and WT. Exercise reduced weight (-24% WT-E vs WT p<0.001) but not in KO. Notably, exercise increased trabecular BV/TV in both (+31%, KO-E vs KO, p=0.004; +14%, WT-E vs WT, p=0.006). The presence and distribution of BMAT in SEIPIN KO, though lower than WT, is unexpected and points to a uniqueness of this depot. That trabecular bone increases were achievable in both KO and WT, despite a difference in BMAT quantity/distribution, points to potential metabolic flexibility during exercise-induced skeletal anabolism.

Neuropathological Alzheimer's Disease Lesions in Nasu-Hakola Disease with TREM2 Mutation: Atypical Distribution of Neurofibrillary Changes.

Nasu-Hakola disease is a rare autosomal recessive disorder associated to mutations in TREM2 and DAP12 genes, neuropathologically characterized by leukoencephalopathy with axonal spheroids. We report the neuropathologic findings of a 51-year-old female with a homozygous mutation (Q33X) of TREM2 gene. Beside severe cerebral atrophy and hallmarks of Nasu-Hakola disease, significant Alzheimer's disease lesions were present. Neurofibrillary changes showed an atypical topographic distribution being severe at spots in the neocortex while sparing the mesial temporal structures. Our finding suggests that TREM2 genetic defects may favor Alzheimer's disease pathology with neurofibrillary changes not following the hierarchical staging of cortical involvement identified by Braak.

Loss of MTX2 causes mandibuloacral dysplasia and links mitochondrial dysfunction to altered nuclear morphology.

Mandibuloacral dysplasia syndromes are mainly due to recessive LMNA or ZMPSTE24 mutations, with cardinal nuclear morphological abnormalities and dysfunction. We report five homozygous null mutations in MTX2, encoding Metaxin-2 (MTX2), an outer mitochondrial membrane protein, in patients presenting with a severe laminopathy-like mandibuloacral dysplasia characterized by growth retardation, bone resorption, arterial calcification, renal glomerulosclerosis and severe hypertension. Loss of MTX2 in patients' primary fibroblasts leads to loss of Metaxin-1 (MTX1) and mitochondrial dysfunction, including network fragmentation and oxidative phosphorylation impairment. Furthermore, patients' fibroblasts are resistant to induced apoptosis, leading to increased cell senescence and mitophagy and reduced proliferation. Interestingly, secondary nuclear morphological defects are observed in both MTX2-mutant fibroblasts and mtx-2-depleted C. elegans. We thus report the identification of a severe premature aging syndrome revealing an unsuspected link between mitochondrial composition and function and nuclear morphology, establishing a pathophysiological link with premature aging laminopathies and likely explaining common clinical features.

Non-invasive monitoring of chronic liver disease via near-infrared and shortwave-infrared imaging of endogenous lipofuscin.

Monitoring the progression of non-alcoholic fatty liver disease is hindered by a lack of suitable non-invasive imaging methods. Here, we show that the endogenous pigment lipofuscin displays strong near-infrared and shortwave-infrared fluorescence when excited at 808 nm, enabling label-free imaging of liver injury in mice and the discrimination of pathological processes from normal liver processes with high specificity and sensitivity. We also show that the near-infrared and shortwave-infrared fluorescence of lipofuscin can be used to monitor the progression and regression of liver necroinflammation and fibrosis in mouse models of non-alcoholic fatty liver disease and advanced fibrosis, as well as to detect non-alcoholic steatohepatitis and cirrhosis in biopsied samples of human liver tissue.

Looking at New Unexpected Disease Targets in LMNA-Linked Lipodystrophies in the Light of Complex Cardiovascular Phenotypes: Implications for Clinical Practice.

Variants in LMNA, encoding A-type lamins, are responsible for laminopathies including muscular dystrophies, lipodystrophies, and progeroid syndromes. Cardiovascular laminopathic involvement is classically described as cardiomyopathy in striated muscle laminopathies, and arterial wall dysfunction and/or valvulopathy in lipodystrophic and/or progeroid laminopathies. We report unexpected cardiovascular phenotypes in patients with LMNA-associated lipodystrophies, illustrating the complex multitissular pathophysiology of the disease and the need for specific cardiovascular investigations in affected patients. A 33-year-old woman was diagnosed with generalized lipodystrophy and atypical progeroid syndrome due to the newly identified heterozygous LMNA p.(Asp136Val) variant. Her complex cardiovascular phenotype was associated with atherosclerosis, aortic valvular disease and left ventricular hypertrophy with rhythm and conduction defects. A 29-year-old woman presented with a partial lipodystrophy syndrome and a severe coronary atherosclerosis which required a triple coronary artery bypass grafting. She carried the novel heterozygous p.(Arg60Pro) LMNA variant inherited from her mother, affected with partial lipodystrophy and dilated cardiomyopathy. Different lipodystrophy-associated LMNA pathogenic variants could target cardiac vasculature and/or muscle, leading to complex overlapping phenotypes. Unifying pathophysiological hypotheses should be explored in several cell models including adipocytes, cardiomyocytes and vascular cells. Patients with LMNA-associated lipodystrophy should be systematically investigated with 24-h ECG monitoring, echocardiography and non-invasive coronary function testing.

The influence of hypertensive environment on adipose tissue remodeling measured by fluorescence lifetime imaging in spontaneously hypertensive rats.

There is a lack of information correlating low adiposity with hypertension experienced by Spontaneous Hypertensive Rats (SHR) or overweight and normotension in Wistar-Kyoto (WKY). We aimed to investigate this lipodystrophy phenomenon by measuring fluorescence lifetime (FLIM), optical redox ratio (ORR), serum levels of hypothalamic-pituitary-adrenal (HPA) and/or hypothalamic-pituitary-thyroid (HPT) hormones axes between Wistar, WKY and SHR before and after establishment of hypertension. Under high blood pressure, we evaluated serum adipokines. Brown adipose tissue was characterized as lower ORR and shorter FLIM compared to white adipose tissue. HPT axis showed a crucial role in the SHR adipose tissue configuration by attenuating whitening. The increased adiposity in WKY may act as a preventive agent for hypertension, since SHR, with low adiposity, establishes the disease. The hypertensive environment can highlight key adipokines that may result in new therapeutic approaches to the treatment of adiposity dysfunctions and hypertension.

Lower serum adiponectin level is associated with lipodystrophy among HIV-infected men in the Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN) study.

OBJECTIVES: Adiponectin levels are inversely related to cardiovascular risk and are low in diabetics and obese persons. We examined the association between adiponectin concentration and HIV-associated lipodystrophy, which remains unclear. METHODS: The Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN) was a prospective cohort study of HIV-infected adults conducted in four US cities. Lean body and fat masses were assessed using dual-energy X-ray absorptiometry scans. Using baseline data from 2004 to 2006, we defined lipodystrophy using a sex-specific fat mass ratio and performed cross-sectional analyses of associated risks using multivariable logistic regression. RESULTS: Among 440 male participants (median age 42 years; 68% non-Hispanic white; 88% prescribed combination antiretroviral therapy; median CD4 lymphocyte count 468 cells/µL; 76% with viral load < 400 HIV-1 RNA copies/mL; 5% diabetic; median body mass index 25 kg/m2 ), median concentrations of leptin and adiponectin were 3.04 ng/L [interquartile range (IQR) 1.77-5.43 ng/L] and 8005 µg/mL (IQR 4950-11 935 µg/mL), respectively. The prevalence of lipodystrophy was 14%. Lipodystrophy was significantly associated with increasing age [prevalence ratio (PR) 1.50; 95% confidence interval (CI) 1.10-2.06, per 10 years], adiponectin < 8005 µg/mL (PR 5.02; 95% CI 2.53-9.95), ever stavudine use (PR 2.26; 95% CI 1.36-3.75), CD4 cell count > 500 cells/µL (PR 2.59; 95% CI 1.46-4.61), viral load < 400 copies/mL (PR 3.98; 95% CI 1.25-12.6), highly sensitive C-reactive protein < 1.61 mg/L (PR 1.91; 95% CI 1.11-3.28) and smoking (PR 0.42; 95% CI 0.22-0.78). CONCLUSIONS: Among men in this HIV-infected cohort, the prevalence of lipodystrophy was similar to previous estimates for persons living with HIV, and was associated with lower adiponectin levels, potentially indicating increased cardiovascular disease risk.

Early-onset dementia, leukoencephalopathy and brain calcifications: a clinical, imaging and pathological comparison of ALSP and PLOSL/Nasu Hakola disease.

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia, and Nasu Hakola disease or polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy are both underrecognized progressive degenerative white matter diseases that can present with young dementia, leukoencephalopathy and brain calcifications. We report and compare three cases in terms of clinical phenotype, imaging and neuropathological findings. Both cases have led to the identification of two novel causal mutations.

"Fat Shadows" From DXA for the Qualitative Assessment of Lipodystrophy: When a Picture Is Worth a Thousand Numbers.

OBJECTIVE: Lipodystrophy syndromes are a heterogeneous group of disorders associated with selective absence of fat. Currently, the diagnosis is established only clinically. RESEARCH DESIGN AND METHODS: We developed a new method from DXA scans called a "fat shadow," which is a color-coded representation highlighting only the fat tissue. We conducted a blinded retrospective validation study to assess its usefulness for the diagnosis of lipodystrophy syndromes. RESULTS: We evaluated the fat shadows from 16 patients (11 female and 5 male) with generalized lipodystrophy (GL), 57 (50 female and 7 male) with familial partial lipodystrophy (FPLD), 2 (1 female and 1 male) with acquired partial lipodystrophy, and 126 (90 female and 36 male) control subjects. FPLD was differentiated from control subjects with 85% sensitivity and 96% specificity (95% CIs 72-93 and 91-99, respectively). GL was differentiated from nonobese control subjects with 100% sensitivity and specificity (95% CIs 79-100 and 92-100, respectively). CONCLUSIONS: Fat shadows provided sufficient qualitative information to infer clinical phenotype and differentiate these patients from appropriate control subjects. We propose that this method could be used to support the diagnosis.

Mandibuloacral dysplasia: A premature ageing disease with aspects of physiological ageing.

Mandibuloacral dysplasia (MAD) is a rare genetic condition characterized by bone abnormalities including localized osteolysis and generalized osteoporosis, skin pigmentation, lipodystrophic signs and mildly accelerated ageing. The molecular defects associated with MAD are mutations in LMNA or ZMPSTE24 (FACE1) gene, causing type A or type B MAD, respectively. Downstream of LMNA or ZMPSTE24 mutations, the lamin A precursor, prelamin A, is accumulated in cells and affects chromatin dynamics and stress response. A new form of mandibuloacral dysplasia has been recently associated with mutations in POLD1 gene, encoding DNA polymerase delta, a major player in DNA replication. Of note, involvement of prelamin A in chromatin dynamics and recruitment of DNA repair factors has been also determined under physiological conditions, at the border between stress response and cellular senescence. Here, we review current knowledge on MAD clinical and pathogenetic aspects and highlight aspects typical of physiological ageing.

Centrifugal lipodystrophy of the scalp manifesting as centrifugal lipodystrophic alopecia.

Centrifugal lipodystrophy (CLD), characterized by a depressed lesion in the abdominal skin, is a chronic disease occurring more often among younger patients of East Asian descent. We present an extremely unusual case of CLD of the scalp associated with reversible hair loss. The patient demonstrated alopecia in the frontal, temporal and occipital areas of the scalp, which connected to form a ring-shaped area of hair loss. Curiously, the area of hair loss gradually expanded outwards while the central region showed normal hair regrowth. Immunohistochemical analysis demonstrated reduced expression of leptin, an adipokine capable of inducing the anagen phase of the hair cycle, in the adipose tissue, associated with active inflammation. By contrast, recovery of leptin expression was observed at sites of healed inflammatory lesions, suggesting that reversible hair loss might be caused by a change in leptin expression in adipose tissue.