-
Nature Jun 2024Increasing rates of autoimmune and inflammatory disease present a burgeoning threat to human health. This is compounded by the limited efficacy of available treatments...
Increasing rates of autoimmune and inflammatory disease present a burgeoning threat to human health. This is compounded by the limited efficacy of available treatments and high failure rates during drug development, highlighting an urgent need to better understand disease mechanisms. Here we show how functional genomics could address this challenge. By investigating an intergenic haplotype on chr21q22-which has been independently linked to inflammatory bowel disease, ankylosing spondylitis, primary sclerosing cholangitis and Takayasu's arteritis-we identify that the causal gene, ETS2, is a central regulator of human inflammatory macrophages and delineate the shared disease mechanism that amplifies ETS2 expression. Genes regulated by ETS2 were prominently expressed in diseased tissues and more enriched for inflammatory bowel disease GWAS hits than most previously described pathways. Overexpressing ETS2 in resting macrophages reproduced the inflammatory state observed in chr21q22-associated diseases, with upregulation of multiple drug targets, including TNF and IL-23. Using a database of cellular signatures, we identified drugs that might modulate this pathway and validated the potent anti-inflammatory activity of one class of small molecules in vitro and ex vivo. Together, this illustrates the power of functional genomics, applied directly in primary human cells, to identify immune-mediated disease mechanisms and potential therapeutic opportunities.
Topics: Female; Humans; Male; Anti-Inflammatory Agents; Cells, Cultured; Chromosomes, Human, Pair 21; Databases, Factual; Gene Expression Regulation; Genome-Wide Association Study; Genomics; Haplotypes; Inflammation; Inflammatory Bowel Diseases; Macrophages; Proto-Oncogene Protein c-ets-2; Reproducibility of Results; Tumor Necrosis Factors; Interleukin-23
PubMed: 38839969
DOI: 10.1038/s41586-024-07501-1 -
Cureus May 2024Giant-cell arteritis (GCA) is a type of vasculitis characterised by the presence of granulomas. It is the predominant form of systemic vasculitis in adults and primarily...
Giant-cell arteritis (GCA) is a type of vasculitis characterised by the presence of granulomas. It is the predominant form of systemic vasculitis in adults and primarily affects the larger arteries in individuals aged ≥ 50 years. GCA affects the major arteries, such as the aorta and its branches, particularly the outer branches of the external carotid artery. Signs and symptoms can be categorised into cranial, extracranial, and systemic manifestations. Patients with headaches, jaw claudication, and vision disturbances usually have extracranial branches of the external carotid artery. Aside from being the prevailing manifestation of GCA, our primary concern regarding this variant is the potential for irreversible vision loss if not properly identified and addressed. Conversely, the GCA can also affect other major blood vessels such as the aorta. Here, we present the case of a 70-year-old Caucasian female patient with cranial GCA who had experienced a temporal headache three years prior. The patient was successfully treated with prednisolone, which was gradually reduced to a very low level with the assistance of methotrexate. Recently, the patient presented with a dry cough that lasted for two months and elevated inflammatory markers. After thorough research, it was determined that there was no evidence of infection, including atypical infections, and that no abnormalities were found in the lungs. Ultimately, via an 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) scan, the patient was diagnosed with large vessel giant cell arteritis (LV-GCA). This impacted the aorta, carotid arteries, and subclavian arteries. The patient experienced notable improvement in her cough and a reduction in inflammatory markers after receiving a high dosage of oral prednisolone. This case exemplifies the unusual manifestation of LV-GCA and verifies that recurring symptoms may differ from the original presentation. While dry cough is not commonly listed as a symptom of LV-GCA, it can be present as a manifestation or the sole presentation in certain patients, particularly when inflammatory markers are consistently high and there is no pulmonary disease.
PubMed: 38836133
DOI: 10.7759/cureus.59686 -
Clinical Case Reports Jun 2024Timely recognition of atypical Takayasu arteritis is crucial. Unusual presentations, such as pericardial effusion, can complicate diagnosis. CT angiogram aids in precise...
KEY CLINICAL MESSAGE
Timely recognition of atypical Takayasu arteritis is crucial. Unusual presentations, such as pericardial effusion, can complicate diagnosis. CT angiogram aids in precise diagnosis, guiding targeted immunosuppressive therapy. Multidisciplinary collaboration is vital for comprehensive management, improving patient outcomes in this challenging condition.
ABSTRACT
This case study highlights the diagnostic challenges posed by atypical presentations of Takayasu arteritis (TA), focusing on a 42-year-old male presenting with pericardial effusion. Despite inconclusive initial investigations, a CT angiogram revealed large vessel vasculitis, confirming TA. Management with immunosuppressive therapy led to clinical improvement. This case emphasize the importance of recognizing unusual manifestations of TA for timely diagnosis and appropriate treatment, emphasizing the role of multidisciplinary collaboration in optimizing patient outcomes.
PubMed: 38836110
DOI: 10.1002/ccr3.9051 -
JTCVS Techniques Apr 2024Mid-aortic syndrome is a rare condition characterized by severe aortic narrowing, leading to high upper body blood pressure and organ hypoperfusion, necessitating...
OBJECTIVES
Mid-aortic syndrome is a rare condition characterized by severe aortic narrowing, leading to high upper body blood pressure and organ hypoperfusion, necessitating surgical intervention. Although central bypassing is considered ideal, it involves extensive incisions. To overcome these limitations, less-invasive approaches have been developed. This study aims to introduce a mini-access approach using video-endoscopy and to evaluate the feasibility and outcomes of mini-access ascending aorto-bifemoral bypass surgery.
METHODS
From November 2020 to May 2022, we performed ascending aorta to bifemoral artery bypass operations on 7 patients to treat steno-occlusive diseases in the downstream aorta. A Y-graft was created, and procedures were conducted under general anesthesia using video-endoscopy with limited skin incisions.
RESULTS
Intraoperatively, there were no major complications, and none of the patients required cardiopulmonary bypass support. Furthermore, there were no postoperative mortalities or major complications. Postoperatively, the mean ankle-brachial index significantly improved from 0.59/0.59 to 0.96/0.92 ( = .004), and the mean glomerular filtration rate increased from 61.1 to 85.3 mL/min/1.73 mm ( = .012). Additionally, symptoms of claudication resolved in all patients.
CONCLUSIONS
Videoscope-assisted mini-access aortic bypass surgery not only provides favorable early postoperative outcomes but also represents a technically feasible alternative to traditional surgical approaches for the treatment of steno-occlusive aortic diseases.
PubMed: 38835566
DOI: 10.1016/j.xjtc.2024.01.006 -
Zeitschrift Fur Rheumatologie Jun 2024A German expert committee recommends defining fast-track clinics (FTC) for the acute diagnosis of giant cell arteritis (GCA) as follows: easy and prompt reachability at...
A German expert committee recommends defining fast-track clinics (FTC) for the acute diagnosis of giant cell arteritis (GCA) as follows: easy and prompt reachability at least on weekdays, scheduling appointments ideally within 24 h, examination by a specialist with GCA expertise, ≥ 2 experts per FTC, ≥ 50 patients with suspected GCA per year, sonologists with ≥ 300 (≥ 50) temporal and axillary artery examinations, adherence to standard operating procedures, availability of an ≥ 18 (≥ 15) MHz and a lower frequency linear ultrasound probe, and collaboration with partners for neurology and ophthalmology consultations, magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT, possibly CT), and for temporal artery biopsy.
PubMed: 38832967
DOI: 10.1007/s00393-024-01532-9 -
Radiology Case Reports Aug 2024This case describes a rare and complex presentation of Takayasu arteritis, a large vessel vasculitis primarily affecting young females. Unlike typical Takayasu arteritis...
This case describes a rare and complex presentation of Takayasu arteritis, a large vessel vasculitis primarily affecting young females. Unlike typical Takayasu arteritis cases characterized by arterial stenosis, this 34-year-old male presented with an unusually high number of aneurysms affecting the aorta, subclavian arteries, and other segments. This unique abundance of aneurysms complicates diagnosis and management. This disease typically manifests as arterial stenosis, with aneurysms occurring in a minority of cases. The most common site for aneurysms is the ascending aorta, making multifocal aneurysms, as seen in this case, exceptionally rare. Managing multiple aneurysms in Takayasu arteritis is complex, necessitating careful consideration of factors like aneurysm size, morphology, and risk of complications. This case underscores the unique challenges posed by multifocal aneurysms in this condition, highlighting the need for a comprehensive approach to treatment.
PubMed: 38832341
DOI: 10.1016/j.radcr.2024.04.056 -
The Canadian Veterinary Journal = La... Jun 2024is one of the most pathogenic nematodes affecting equids. Larval migration through the cranial mesenteric artery (CMA) with attendant arteritis and thromboembolism can...
BACKGROUND
is one of the most pathogenic nematodes affecting equids. Larval migration through the cranial mesenteric artery (CMA) with attendant arteritis and thromboembolism can result in fatal non-strangulating intestinal infarction. Once considered a historical disease, recent studies have described the reemergence of this pathogen in several European countries; however, little is known of the current prevalence of in the Canadian horse population.
OBJECTIVE
To determine the prevalence of active cranial mesenteric arteritis in horses submitted for postmortem examination to the Diagnostic Services Unit (DSU) at the University of Calgary Faculty of Veterinary Medicine.
ANIMALS AND PROCEDURE
We conducted a retrospective review of all equine postmortem cases submitted to the DSU between July 1, 2010 and June 30, 2022. Over 12 y, 510 horses > 2 mo of age from Alberta were submitted to the DSU for necropsy. Active cases were defined as those with endarteritis and thrombosis in the CMA or its branches. Those cases with only intimal scarring of the CMA were classified as historical.
RESULTS
The prevalence of all CMA lesions (both historical and active) over the study period was 17.3% (88/510). Active cranial mesenteric arteritis was documented in 6.1% (31/510) of equine postmortems and the sequelae of verminous arteritis were the cause of euthanasia or death in 1.5% (8/510) of the cases submitted.
CONCLUSION AND CLINICAL RELEVANCE
Even after historically intense efforts to eradicate this parasite, the continued effects of are demonstrated by the results of this study. should not be regarded as a parasite of the past and verminous arteritis remains an important differential diagnosis for horses in western Canada presenting with mild colic or dull demeanor and anorexia of duration > 24 h. Furthermore, should be taken into careful consideration when implementing antiparasitic control strategies. Practitioners should remain current on prevention, diagnosis, and treatment of this potentially reemerging and fatal equine disease.
Topics: Animals; Horses; Retrospective Studies; Prevalence; Female; Male; Alberta; Horse Diseases; Arteritis; Strongylus; Mesenteric Arteries; Strongyle Infections, Equine
PubMed: 38827589
DOI: No ID Found -
Cureus May 2024This case report describes a complicated case of giant cell arteritis (GCA) with tongue necrosis and bilateral central retinal artery occlusion (CRAO). An 81-year-old...
This case report describes a complicated case of giant cell arteritis (GCA) with tongue necrosis and bilateral central retinal artery occlusion (CRAO). An 81-year-old male patient with a history of recent retinal artery occlusion, ischemic stroke, and hypertensive emergency was evaluated. Clinical examination, including a visual acuity assessment, fundus evaluation, and oral examination, was performed. Laboratory investigations, such as erythrocyte sedimentation rate (ESR), were conducted. A temporal artery biopsy was performed to confirm the diagnosis of GCA. The patient presented with sudden vision loss in the left eye following a prior episode of retinal artery occlusion in the right eye. Ophthalmoscopic examination revealed CRAO in the left eye. Additionally, tongue necrosis, a rare manifestation of GCA, was observed. The ESR was significantly elevated. A temporal artery biopsy supported the diagnosis of GCA. The patient was promptly referred for immunologist consultation and initiated on intravenous methylprednisolone therapy. This case highlights the diverse and potentially devastating nature of GCA, involving ocular and systemic manifestations. Bilateral CRAO and tongue necrosis are rare but significant complications of GCA. Prompt diagnosis and early initiation of corticosteroid therapy are crucial to prevent irreversible visual loss and further complications. A multidisciplinary approach involving ophthalmologists and other specialists is essential for the comprehensive management of GCA.
PubMed: 38826883
DOI: 10.7759/cureus.59554 -
The Journal of Rheumatology Jun 2024This study explored the reproductive journeys of women with vasculitis, including their conversations with healthcare providers, disease activity, medication changes,...
OBJECTIVE
This study explored the reproductive journeys of women with vasculitis, including their conversations with healthcare providers, disease activity, medication changes, and delivery experiences.
METHODS
Interviews were conducted with women registered in the Vasculitis Pregnancy Registry (VPREG), an online patient-reported registry of pregnant women with vasculitis. A team of physicians, patients, and qualitative researchers developed a qualitative interview guide. Participant responses were evaluated using thematic analysis.
RESULTS
Eighteen patients with vasculitis who had experienced pregnancy were interviewed (10 antineutrophil cytoplasmic antibody-associated vasculitis, 4 Takayasu arteritis, 2 Behçet disease, 1 IgA vasculitis, 1 relapsing polychondritis). Thematic analysis revealed common experiences in the decision-making process during pregnancy planning, including accessing information from multiple sources, communicating with medical professionals, and changing treatment for vasculitis. Women sought information about vasculitis and pregnancy from various sources, including social media; however, opinions from their physicians and family members were most influential. Patients were more likely than providers to initiate conversations regarding family planning. Balancing differing opinions from subspecialists was challenging as many patients recalled acting as a liaison between multiple physicians during pregnancy. The need for self-advocacy was a common experience among patients. Most women had pregnancies that resulted in live births with delivery at term.
CONCLUSION
When making decisions about pregnancy, women of reproductive age with vasculitis used multiple resources. Patients consistently valued their medical provider's opinion over alternative sources of information. To ensure comprehensive medical care, half of women relied on self-advocacy to coordinate communication among subspecialists. Most women had pregnancies that resulted in live births with delivery at term.
PubMed: 38825350
DOI: 10.3899/jrheum.2023-1055 -
Reumatologia Clinica May 2024Infections in patients with systemic vasculitis represent one of the main causes of mortality. Corticosteroid use, immunosuppressive therapy, age, associated organic...
UNLABELLED
Infections in patients with systemic vasculitis represent one of the main causes of mortality. Corticosteroid use, immunosuppressive therapy, age, associated organic involvement and dialysis dependence are risk factors of infection.
OBJECTIVES
To determine the prevalence of severe infection and associated factors in patients diagnosed with ANCA-associated vasculitis (AAV) and Polyarteritis Nodosa (PAN).
METHODS
retrospective study was conduced in a single rheumatology center (2000-2018). We included patients diagnosed with AAV (Granulomatosis with Polyangiitis (GPA), Eosinophilic Granulomatosis with Polyangiitis (EGPA) and Microscopic Polyangiitis (PAM) and Polyarteritis nodosa (PAN). Serious infectious events requiring hospitalisation or prolonged antibiotic/antiviral treatment, recurrent infection of Herpes Zoster Virus or opportunistic infections were evaluated. Sites of infection, isolated microorganisms and mortality related were analyzed.
RESULTS
105 patients were analyzed, follow-up time median 18 m, 58.7% were women and median age was 52 years. Types of vasculitis: 41.9% PAM, 16.2% EPGA, 40% GPA, 1.9% PAN. Constitutional, pulmonary, renal and otorhinolaryngology manifestations were the most frequent.
PREVALENCE OF INFECTION
34.2%, with a median of 3 months from diagnosis of vasculitis to the infectious event. Low respiratory tract (42.8%), sepsis (31.4%), and urinary tract (14.3%) were the most common sites of infections. Bacterial aetiology was the most prevalent (67.7%). Mortality at the first event was 14.3% and a 72.2% of patients were in the induction phase of treatment. Infectious events were significantly associated with age > 65 years (p = 0.030), presence of lung (p = 0.016) and renal involvement (p = 0.001), BVASv3 > 15, mortality (p = 0.0002).
CONCLUSIONS
The prevalence of infection was 34.2%. Lower airway infections, septicemia and urinary tract infections were the most prevalent. Infections were associated with renal and pulmonary involvement, age older than 65 years and score BVAS > 15. Severe infections were associated with mortality, especially in elderly patients.
Topics: Humans; Female; Male; Middle Aged; Retrospective Studies; Adult; Aged; Prevalence; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Polyarteritis Nodosa; Risk Factors; Infections; Opportunistic Infections
PubMed: 38821740
DOI: 10.1016/j.reumae.2024.05.004