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Amyloid precursor protein expression is upregulated in adipocytes in obesity.

The aim of this study was to determine whether amyloid precursor protein (APP) is expressed in human adipose tissue, dysregulated in obesity, and related to insulin resistance and inflammation. APP expression was examined by microarray expression profiling of subcutaneous abdominal adipocytes (SAC) and cultured preadipocytes from obese and nonobese subjects. Quantitative real-time PCR (QPCR) was performed to confirm differences in APP expression in SAC and to compare APP expression levels in adipose tissue, adipocytes, and stromal vascular cells (SVCs) from subcutaneous adipose tissue (SAT) an

Role of Proteasomes in Inflammation.

The ubiquitin-proteasome system (UPS) is involved in multiple cellular functions including the regulation of protein homeostasis, major histocompatibility (MHC) class I antigen processing, cell cycle proliferation and signaling. In humans, proteasome loss-of-function mutations result in autoinflammation dominated by a prominent type I interferon (IFN) gene signature. These genomic alterations typically cause the development of proteasome-associated autoinflammatory syndromes (PRAAS) by impairing proteasome activity and perturbing protein homeostasis. However, an abnormal increased proteasomal

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… Consequently, this leads to increased secretion of pro-inflammatory cytokines due to unbalanced LUBAC-activity ( Figure 2 ).The resulting disease is named otulipenia or otulin-related autoinflammatory syndrome (ORAS) [ 103 ], whereby patients suffer from recurring fevers, sterile neutrophilia, lipodystrophy, panniculitis … PSMB8 Encoding the β5i Proteasome Subunit Is Mutated in Joint Contractures, Muscle Atrophy, Microcytic Anemia, and Panniculitis-Induced Lipodystrophy Syndrome Am. J. Hum. Genet. 2010 87 866 872 10.1016/j.ajhg.2010.10.031 21129723 PMC2997366 69. Arima K. Kinoshita A. Mishima H. Kanazawa N. …

Detection of clonally rearranged T-cell-receptor gamma chain genes from T-cell malignancies and acute inflammatory rheumatic disease using PCR amplification, PAGE, and automated analysis.

Clonal expansions of T cells carrying identical T-cell-receptor (TCR) genes are the hallmark of T-cell malignancies, but they can also result from a strong immune reaction to a dominant epitope. The basis for the molecular detection of clonal T cells is amplification of the V-(D)-N-J region of the TCR gene. We evaluated PCR amplification of the rearranged gamma TCR from genomic DNA extracted from peripheral blood and subsequent polyacrylamide gel electrophoresis (PAGE) in an automated DNA sequencer. We determined the sensitivity for the detection of clonal T cells and propose a standardized ev

Dermatologic conditions in women receiving systemic cancer therapy.

As advances in cancer therapies have improved cancer-related survival, novel therapeutics have also introduced a variety of dermatologic toxicities, and an increased number of patients are living with these sequalae. Women with cancer in particular experience a spectrum of dermatologic conditions that affect their skin, hair, nail, and mucosal surfaces. Studies have shown that these toxic effects can significantly affect quality of life and alter a woman's self-image, cultural identity, femininity, sexuality, and mental health. In severe instances, dermatologic toxicities may even disrupt canc

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… hemorrhage | MKIs, VEGFR Mucositis | Alkylating agents, anthracyclines, antimetabolites, antibiotics, taxanes, topoisomerase inhibitors mTOR anti-CTLA-4, PD-1/PD-L1 therapy Nail changes (onycholysis, pigmentary alteration, brittle nails) | Antimetabolites, anthracyclines, taxanes MKIs, EGFR, MEK, HER2 Panniculitis … BRAF inhibitors may also result in phototoxicity and panniculitis mimicking erythema nodosum, and other MKIs (e.g., imatinib) may result in periorbital edema and pigmentary changes ( McClelland et al., 2010 , Sollfrank et al., 2019 , Vance et al., 2017 , Zimmer et al., 2012 ). …

Central Nervous System Manifestations of Cutaneous Lymphomas.

PURPOSE OF REVIEW: Primary cutaneous lymphomas (PCL) are an uncommon malignancy of the lymphocytes, primarily presenting with dermatologic l … zary syndrome, CD30 + lymphoproliferative disorders, and other more rare entities like subcutaneous panniculitis- like T-cell lymphoma, extranodal NK/T cell lymphoma nasal type, primary cutaneous peripheral T-cell lymphoma not otherwise specified, and adult T-cell leukemia/lymphoma. Cutaneous B-cell lymphomas comprise approximately 25% of all cutaneous lymphom …

Unusual Case of Granulomatosis with Polyangiitis Complicated with Hormographilella aspergillata Skin Infection.

Granulomatosis with polyangiitis (GPA) is a rare ANCA-associated small-vessel vasculitis that predominantly affects the respiratory tract an … CA (anti-PR3). Initial microbiological cultures were sterile. Histopathology revealed granulomatous panniculitis with abscess formation. Fungal culture isolated H. aspergillata. Itraconazole therapy was ineffective; subsequent voriconazole treatment led to complete resolution of the cutaneous infection. Due to persistent systemic inflammation and c-ANCA positi …

Neutrophilic and eosinophilic dermatoses associated with hematological malignancy.

Cutaneous manifestations of hematologic malignancy represent both a clinical challenge for the treating physician and a pathophysiological model for advancing the knowledge on individual neoplasms. Indeed, a growing body of evidence supports the concept of recurrent molecular defects associating with specific clinical features, as best exemplified by VEXAS. Herein neutrophilic and eosinophilic dermatoses of potential interest for both hematologists and dermatologists will be reviewed, including subcorneal pustular dermatosis-type IgA pemphigus, neutrophilic eccrine hidradenitis, Sweet's syndro

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… In some rare instances, the infiltrates may also involve the subcutaneous tissue, with a clinicopathologic picture of eosinophilic panniculitis ( 98 ). … Eosinophilic panniculitis and insect bite-like eruption in a patient with chronic lymphocytic leukaemia: a spectrum of the same entity . Dermatol Res Pract . ( 2010 ) 2010 : 263827 . doi: 10.1155/2010/263827 , PMID: 20631833 PMC2901615 99. …

Livedoid vasculopathy: A multidisciplinary clinical approach to diagnosis and management.

Livedoid vasculopathy (LV) is a rare, chronic, and occlusive disease of the veins supplying the upper parts of the skin. The pathogenesis of the disease is not precisely understood, and its attacks are often unpredictable but tend to worsen during the summer. LV affects women more often. This increased risk for LV in women might be related to sex-specific physiological conditions, such as pregnancy, or a higher incidence of LV-associated conditions, such as connective tissue diseases, hypercoagulable states, and venous stasis in women. The typical clinical appearance of LV consists of three ma

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… vasculitis Recurrent and short-term hemorrhagic macules, hypergammaglobulinemia positive UV Normocomplementemic UV Hypocomplementemic UV Urticaria >24 h, postinflammatory pigmentation, ± hypocomplementemia Nodular vasculitis Dark red violet ± ulcerated nodules on the lateral/posterior tibia, lobular panniculitis … vasculitis | Recurrent and short-term hemorrhagic macules, hypergammaglobulinemia positive UV Normocomplementemic UV Hypocomplementemic UV | Urticaria >24 h, postinflammatory pigmentation, ± hypocomplementemia Nodular vasculitis | Dark red violet ± ulcerated nodules on the lateral/posterior tibia, lobular panniculitis …

A case of VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) with decreased oxidative stress levels after oral prednisone and tocilizumab treatment.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome has recently been described as an autoinflammatory disease associated with severe adult-onset inflammatory manifestations. The various clinical manifestations include recurrent high-grade fever, neutrophilic dermatoses, cutaneous vasculitis, chondritis of the ear and nose, pulmonary infiltrates, cytopenia, uveitis, gastrointestinal pain or inflammation, aortitis, hepatosplenomegaly, and hematological disorders. VEXAS syndrome is caused by somatic mutations of the ubiquitin-like modifier activating enzyme 1 (UBA1) gene in

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… In previous reports of VEXAS syndrome, the UBA1 variant was found only in neutrophilic dermatitis by skin biopsy, and not in leukocytoclastic vasculitis or septal panniculitis ( 10 – 14 ). …

Subcutaneous Granuloma Annulare.

Dear Editor, Subcutaneous granuloma annulare (SGA) is considered a rare clinical variant of granuloma annulare, a common self-healing chroni … al mechanism, possibly a delayed type hypersensitivity reaction mediated by T-cells that triggers a panniculitis-type inflammatory response (8,10). Correlations between SGA and systemic diseases such as diabetes mellitus, sarcoidosis, HIV infection, or autoimmune diseases have not been found (8). A positive diagnosis of pseudorheumatoid nodules relies on clini …

Treatment-free survival to bortezomib combined with dexamethasone in patients with refractory/relapsed pure red cell aplasia: a prospective clinical study.

BackgroundImmunosuppressive treatments induce and maintain remissions in a majority of patients with acquired pure red cell aplasia (aPRCA); however, salvage therapy for non-responders remains unsatisfactory.MethodsIn this prospective, open-label, clinical trial (NCT04423367), patients with refractory/relapsed aPRCA were recruited and received subcutaneous bortezomib at 1.3 mg/m2 in combination with dexamethasone 40 mg weekly(BD regimen) for 12 weeks. The primary endpoint was the overall response rate at 12 weeks.ResultsIn total, 18 patients were enrolled, including 10 (55.6%) with primary aPR

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… Successful treatment of refractory pure red cell aplasia with bortezomib after allogeneic haematopoietic cell transplantation in a patient with alpha-beta subcutaneous panniculitis-like T cell lymphoma . …

Short term outcome of patients attending a renal-immunology clinic in central India.

BACKGROUND: : Glomerular diseases (GDs) and other renal immunologic diseases are an important cause of morbidity and mortality. Providing a single point of service in collaboration with various specialists at a renal immunology clinic for such patients is not novel, but outcomes have not been reported. Here, we report the short-term outcome of Indian patients attending our clinic. METHODS: : This single-center prospective cohort study enrolled biopsy-proven immunologically-mediated adults with renal diseases between April 2018 and December 2019, and followed them for six months. The primary e

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… Table 7 Summary of patients with lupus nephritis Lupus nephritis ISN -class | Number of patients | Treatment received | Outcome | Complications Class-I | 1 | Prednisolone 1 mg/kg/day then tapering 0.25 mg/kg every 4 weeks started for skin manifestations (lupus panniculitis) | Complete remission | None …

Multicenter phase 2 study of romidepsin plus lenalidomide for previously untreated peripheral T-cell lymphoma.

Peripheral T-cell lymphomas (PTCLs) are associated with poor prognosis when treated with cytotoxic chemotherapy. We report the findings of a phase 2 study evaluating a chemotherapy-free combination of romidepsin plus lenalidomide as initial treatment for patients with PTCL who were aged >60 years or noncandidates for chemotherapy. Treatment was initiated with romidepsin 10 mg/m2 IV on days 1, 8, and 15 and lenalidomide 25 mg taken orally from days 1 to 21 of 28-day cycle for up to 1 year. The primary objective was overall response rate (ORR). Secondary objectives included safety and survival.

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… Methods Patient eligibility Patients with ALCL (ALK – ), AITL, EATL, hepatosplenic T-cell lymphoma, PTCL–not otherwise specified (PTCL-NOS), subcutaneous panniculitis-like T-cell lymphoma, transformed mycosis fungoides, or ATLL subtypes were eligible for the study. …

American College of Rheumatology Guidance Statement for Diagnosis and Management of VEXAS Developed by the International VEXAS Working Group Expert Panel.

OBJECTIVE: Vacuoles E1 enzyme X-linked autoinflammatory somatic syndrome (VEXAS) is a recently identified rare genetic disorder associated with somatic mutations in the UBA1 gene. VEXAS presents with a combination of inflammatory and hematologic manifestations, leading to increased morbidity and mortality. METHODS: Given the variability in disease presentation and the limited number of studies to date, no clinical documents currently exist to provide guidance to health care providers about the management of VEXAS. To address this gap, we formed an international multidisciplinary panel of VEXA

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… It is crucial for clinicians and other health providers to be familiar with the most common features present in confirmed patients with VEXAS, including recurrent noninfectious fever (75–100%); various skin involvements (erythema nodosum, maculopapular lesions, panniculitis, urticarial, and possibly …

Blastic plasmacytoid dendritic cell neoplasm: a short review and update.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic neoplasm (less than 1% of primary cutaneous lymphomas and acute leukemia) with a highly aggressive clinical course and frequent skin, bone marrow and central nervous system involvement. Even though there is often an early response to chemotherapy, leukemic dissemination relapses are very common and result in poor outcomes, with a median overall survival of 8 to 14 months in the first-line setting using standard combination chemotherapy regimens. Almost 90% of patients experience skin involvement as their initial site of

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… EORTC cutaneous lymphoma group. subcutaneous panniculitis-like T-cell lymphoma: definition, classification, and prognostic factors: an EORTC Cutaneous Lymphoma Group Study of 83 cases . Blood 2008 ; 111 : 838 - 45 . 17934071 10.1182/blood-2007-04-087288 19. Cota C Vale E Viana I . …

Severe cutaneous adverse reactions induced by targeted anticancer therapies and immunotherapies.

With the increasing use of targeted anticancer drugs and immunotherapies, there have been a substantial number of reports concerning life-threatening severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic symptoms, drug-induced hypersensitivity syndrome, and acute generalized exanthematous pustulosis. Although the potential risks and characteristics for targeted anticancer agent- and immunotherapy-induced SCAR were not well understood, these serious adverse reactions usually result in morb

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… emerged as a remarkable anticancer therapy and improved the survival of melanoma patients carrying BRAF V600E/K . 64 Cutaneous adverse events induced by BRAF inhibitors vary from skin eruptions with photosensitivity, folliculocentric morbilliform eruptions, hyperkeratotic hand–foot skin reactions, and panniculitis …

Immune-Mediated Dermatoses in Patients with Haematological Malignancies: A Comprehensive Review.

Haematological malignancies induce important alterations of the immune system, which account for the high frequency of autoimmune complications observed in patients. Cutaneous immune-mediated diseases associated with haematological malignancies encompass a heterogeneous group of dermatoses, including, among others, neutrophilic and eosinophilic dermatoses, autoantibody-mediated skin diseases, vasculitis and granulomatous dermatoses. Some of these diseases, such as paraneoplastic pemphigus, are associated with an increased risk of death; others, such as eosinophilic dermatoses of haematological

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… Beyond these entities, other NDs such as neutrophilic panniculitis and immunoglobulin A (IgA) pemphigus [ 42 – 44 ] have been more rarely reported to arise in the context of HMs. … Table 2 Classification of polymorphic eruption of haematological malignancy Eosinophilic | Lymphocytic Bullous (bullous pemphigoid-like) Panniculitis (Wells syndrome-like) Insect bite-like Eosinophilic pustular folliculitis (Ofuji disease-like) | T-cell papulosis associated with B-cell malignancies …

Single-cell sequencing technology to characterize stem T-cell subpopulations in acute T-lymphoblastic leukemia and the role of stem T-cells in the disease process.

BackgroundPrecursor T-cell acute lymphoblastic leukemia (Pre-T ALL) is a malignant neoplastic disease in which T-cells proliferate in the bone marrow. Single-cell sequencing technology could identify characteristic cell types, facilitating the study of the therapeutic mechanisms in Pre-T ALL.MethodsThe single-cell sequencing data (scRNA-seq) of Pre-T ALL were obtained from public databases. Key immune cell subpopulations involved in the progression of Pre-T ALL were identified by clustering and annotating the cellular data using AUCell. Next, pseudo-temporal analysis was performed to identify

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… Germline HAVCR2 mutations and their relation to the clinical spectrum of subcutaneous panniculitis-like T-cell lymphoma and hemophagocytic lymphohistiocytosis: results from a multicenter study and meta-analysis. Haematologica. 2023; 108:2743–52. 10.3324/haematol.2022.282419 56. …

Immunotherapy-Associated Pancreatic Adverse Events: Current Understanding of Their Mechanism, Diagnosis, and Management.

Immune checkpoint inhibitors (ICIs) such as anti-programmed death-1 (PD-1) and its ligand PD-L1 and anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) monoclonal antibodies, are involved in T cell-mediated immune response augmentation and promote anti-tumor immunity. Cancer patients treated with combination of immunotherapy, chemotherapy, radiotherapy, and targeted therapy exhibit superior clinical outcomes and tolerance compared with patients treated with monotherapies. However, immutherapy is associated with several concomitant immune-related adverse events (irAEs). For instance, IrAEs interfere

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… Histological analysis of the subcutaneous biopsy of the medial surface of the arm showed chronic lobular panniculitis with CD3+ lymphocytic infiltration and extensive fibroelastosis replacement. …

Targeting Proteasomes in Cancer and Infectious Disease: A Parallel Strategy to Treat Malignancies and Microbes.

Essential core pathways of cellular biology are preserved throughout evolution, highlighting the importance of these pathways for both bacteria and human cancer cells alike. Cell viability requires a proper balance between protein synthesis and degradation in order to maintain integrity of the proteome. Proteasomes are highly intricate, tightly regulated multisubunit complexes that are critical to achieve protein homeostasis (proteostasis) through the selective degradation of misfolded, redundant and damaged proteins. Proteasomes function as the catalytic core of the ubiquitin-proteasome pathw

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… PSMB8 Encoding the β5i Proteasome Subunit is Mutated in Joint Contractures, Muscle Atrophy, Microcytic Anemia, and Panniculitis-Induced Lipodystrophy Syndrome . Am. J. Hum. Genet. 87 ( 6 ): 866 – 872 . doi: 10.1016/j.ajhg.2010.10.031 21129723 PMC2997366 Al-Salama Z. T. Garnock-Jones K. P. Scott L. …