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Reumatologia Clinica Jan 2024VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is an adult-onset autoinflammatory syndrome characterized by somatic mutations in the UBA1 gene... (Review)
Review
VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is an adult-onset autoinflammatory syndrome characterized by somatic mutations in the UBA1 gene and is considered the prototype of hematoinflammatory diseases. Patients with VEXAS syndrome exhibit inflammatory and hematological manifestations that can lead to clinical diagnoses such as relapsing polychondritis, polyarteritis nodosa, Sweet syndrome, and myelodysplastic syndrome. Diagnosis requires bone marrow evaluation to identify cytoplasmic vacuoles in myeloid and erythroid precursors. However, genetic confirmation of mutations in UBA1 is necessary. Treatment is challenging and often involves glucocorticoids and immunosuppressants with variable responses. Hypomethylating agents and allogenic haemopoietic stem cell transplant are considered promising therapies. Prognosis is influenced by genetic and clinical factors. The aim of this review is to provide an overview of the pathogenesis, clinical presentation, treatment, and prognosis of VEXAS syndrome for the Latin American medical community.
Topics: Adult; Humans; Myelodysplastic Syndromes; Glucocorticoids; Immunosuppressive Agents; Mutation; Skin Diseases, Genetic
PubMed: 38160120
DOI: 10.1016/j.reumae.2023.12.004 -
Cureus Nov 2023Rare and sometimes fatal, spontaneous hepatic rupture (SHR) is frequently documented in conjunction with various benign and malignant hepatic tumors, peliosis hepatis...
Rare and sometimes fatal, spontaneous hepatic rupture (SHR) is frequently documented in conjunction with various benign and malignant hepatic tumors, peliosis hepatis (PH), amyloidosis, and polyarteritis nodosa. PH is a rare disease characterized by the presence of sinusoidal dilation and blood-filled cysts throughout the hepatic parenchyma. Handling and identifying this condition can be challenging, particularly in the absence of a history of liver cirrhosis or a tumor. The present case involves a 61-year-old male with a SHR and PH, accompanied by a significant history of end-stage renal disease (ESRD) over the past year. The patient presented to the emergency department with a three-week history of right flank pain. Hemoglobin levels were found to be low; the Glasgow Coma Scale (GCS) score was progressively decreasing. A computed tomography (CT) scan revealed a rupture of the right liver capsule, hemoperitoneum, PH, and an edematous gall bladder. The current case illustrates the diagnosis and management of PH and hemoperitoneum. This case emphasizes the challenging diagnosis of this potentially fatal liver complication in an outwardly healthy male, highlighting the connection between PH and ESRD.
PubMed: 38156167
DOI: 10.7759/cureus.49567 -
Zhurnal Nevrologii I Psikhiatrii Imeni... 2023The review considers the clinical picture, key aspects of the diagnosis and treatment of vasculitis that are the causes of strokes (giant cell arteritis, polyarteritis...
The review considers the clinical picture, key aspects of the diagnosis and treatment of vasculitis that are the causes of strokes (giant cell arteritis, polyarteritis nodosa, varicella zoster virus vasculopathy, cerebrovascular pathology caused by herpes simplex virus types 1 and 2, primary CNS angiitis, adenosine deaminase-2 deficiency).
Topics: Humans; Vasculitis; Stroke; Herpesvirus 3, Human
PubMed: 38148691
DOI: 10.17116/jnevro20231231225 -
Rheumatology (Oxford, England) Dec 2023Granulomatosis with polyangiitis (GPA) is an antineutrophil cytoplasmic antibody-associated vasculitis. The 2022 American College of Rheumatology/European Alliance of...
OBJECTIVE
Granulomatosis with polyangiitis (GPA) is an antineutrophil cytoplasmic antibody-associated vasculitis. The 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR)-endorsed classification criteria for GPA was derived using data only from adult patients. We aimed to assess the performance of the ACR/EULAR classification criteria for GPA in pediatric patients and compare it with the EULAR/Pediatric Rheumatology International Trials Organization (PRINTO)/Pediatric Rheumatology European Society (PReS)-endorsed Ankara 2008 criteria for GPA.
METHODS
Retrospective data of pediatric patients with GPA in 20 centers from 9 countries were evaluated. The diagnosis of GPA was made according to the expert opinion. The sensitivity, specificity, positive predictive value, and negative predictive value of the criteria sets were evaluated.
RESULTS
The study included 77 patients with GPA and 108 controls (immunoglobulin A vasculitis (n = 44), Takayasu's arteritis (n = 20), microscopic polyangiitis (n = 16), polyarteritis nodosa (n = 14), Behçet's disease (n = 12), eosinophilic granulomatosis with polyangiitis (n = 1), and Cogan's syndrome (n = 1)) with a median age of 17.8 and 15.2 years, respectively. Of patients with GPA, constitutional symptoms (85.7%) and ear-nose-throat involvement (79.2%) were the most common presentations. In the GPA group, 73 patients fulfilled the Ankara 2008 criteria and 69 the ACR/EULAR classification criteria. Sensitivities of the Ankara 2008 criteria and the ACR/EULAR classification criteria were 94.8% and 89.6%, while specificities were 95.3% and 96.3%, respectively. No significant difference was found between sensitivities and specificities of both classification criteria (p= 0.229 and p= 0.733, respectively).
CONCLUSION
In children, both the ACR/EULAR and EULAR/PRINTO/PReS Ankara 2008 classification criteria for GPA perform well and similarly.
PubMed: 38135503
DOI: 10.1093/rheumatology/kead693 -
Rheumatology International Jul 2024VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly discovered autoinflammatory condition characterised by somatic mutation of the UBA1... (Review)
Review Meta-Analysis
BACKGROUND
VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly discovered autoinflammatory condition characterised by somatic mutation of the UBA1 gene. The syndrome leads to multi-system inflammation affecting predominantly the skin, lungs and bone marrow.
METHODS
We undertook a systematic review of the multisystem features and genotypes observed in VEXAS syndrome. Articles discussing VEXAS syndrome were included. Medline, Embase and Cochrane databases were searched. Information was extracted on: demographics, type and prevalence of clinical manifestations, genetic mutations and treatment. Meta-analysis using a random effects model was used to determine pooled estimates of serum markers.
RESULTS
From 303 articles, 90 were included, comprising 394 patients with VEXAS. 99.2% were male, with a mean age of 67.1 years (SD 8.5) at disease onset. The most frequent diagnoses made prior to VEXAS were: relapsing polychondritis (n = 59); Sweet's syndrome (n = 24); polyarteritis nodosa (n = 11); and myelodysplastic syndrome (n = 10). Fever was reported in 270 cases (68.5%) and weight loss in 79 (20.1%). Most patients had haematological (n = 342; 86.8%), dermatological (n = 321; 81.5%), pulmonary (n = 297; 75.4%%) and musculoskeletal (n = 172; 43.7%) involvement, although other organ manifestations of varying prevalence were also recorded. The most commonly reported mutations were "c.122T > C pMET41Thr" (n = 124), "c.121A > G pMET41Val" (n = 62) and "c.121A > C pMet41Leu" (n = 52). Most patients received glucocorticoids (n = 240; 60.9%) followed by methotrexate (n = 82; 20.8%) and IL-6 inhibitors (n = 61, 15.4%). One patient underwent splenectomy; 24 received bone marrow transplants.
CONCLUSION
VEXAS syndrome is a rare disorder affecting predominantly middle-aged men. This is the first systematic review to capture clinical manifestations, genetics and treatment of reported cases. Further studies are needed to optimise treatment and subsequently reduce morbidity and mortality.
Topics: Humans; Male; Ubiquitin-Activating Enzymes; Female; Mutation; Syndrome; Aged; Middle Aged; Myelodysplastic Syndromes; Sweet Syndrome; Polyarteritis Nodosa; Hereditary Autoinflammatory Diseases
PubMed: 38129348
DOI: 10.1007/s00296-023-05513-0 -
Medicine Dec 2023Cutaneous polyarteritis nodosa (cPAN) is a form of medium-sized vessel necrotizing vasculitis. It is a rare, skin-limited variant of polyarteritis nodosa, characterized...
BACKGROUND
Cutaneous polyarteritis nodosa (cPAN) is a form of medium-sized vessel necrotizing vasculitis. It is a rare, skin-limited variant of polyarteritis nodosa, characterized by dermal and subcutaneous tissue involvement. The most common findings in cPAN include digital gangrene, livedo reticularis, and tender subcutaneous nodules. However, while limited to the skin, cPAN results in significant morbidity and mortality due to the accompanying skin ischemia and necrosis, such that patients are vulnerable to superinfection. Here, we describe a unique presentation of cPAN associated with pulmonary arterial hypertension (PAH).
METHODS
A 78-year-old female presented with digital ischemia and leg ulcers associated with PAH. Skin biopsy showed necrotizing fibrinoid necrosis of the small- and middle-sized vessels of the dermis. A diagnosis of cPAN and PAH was made. The patient was treated with glucocorticoids, vasodilators, and cyclophosphamide.
RESULTS
She died due to severe sepsis complications.
CONCLUSION
To date, this is the first case report describing the association between cPAN and PAH. In this case, PAH is a complication of the cutaneous vasculitides suggesting that vasculopathy could play a role in the pathophysiology of PAH. However, the underlying pathophysiological mechanisms still have to be firmly established.
Topics: Female; Humans; Aged; Polyarteritis Nodosa; Pulmonary Arterial Hypertension; Skin Diseases, Vascular; Vasculitis; Necrosis; Familial Primary Pulmonary Hypertension; Ischemia
PubMed: 38115264
DOI: 10.1097/MD.0000000000036563 -
Journal of Vascular Surgery Cases and... Dec 2023Polyarteritis nodosa (PAN) is a rare form of vasculitis. Acute limb ischemia is a rare presentation and complication of PAN. Plain old balloon angioplasty (POBA) is one...
Polyarteritis nodosa (PAN) is a rare form of vasculitis. Acute limb ischemia is a rare presentation and complication of PAN. Plain old balloon angioplasty (POBA) is one of the treatment strategies for addressing PAN-related critical limb threatening ischemia (CLTI). However, recurrence of stenosis and occlusion is frequent, making POBA a poor treatment choice, as evidenced in our described clinical case. Consequently, with consideration of sirolimus's anti-inflammatory and immunosuppressive properties, we used a sirolimus-coated balloon in the treatment of PAN-induced CLTI. A 37-year-old woman first presented with acute limb ischemia as her initial symptom. Diagnostic angiography demonstrated occlusion of her tibial vessels, and POBA was performed to restore perfusion. Later in the course of her illness, she developed foot gangrene despite multiple courses of immunosuppressive drugs and several attempts with POBA to achieve limb salvage. Because of her disease trajectory, a MagicTouch (Concept Medical) sirolimus-coated balloon was deployed to her anterior tibial artery during her third angioplasty. At 17 months after her last angioplasty, she remained ulcer free, and surveillance scans demonstrated occlusion-free tibial vessels. The use of sirolimus-coated balloon angioplasty is a promising treatment approach for successful limb salvage in patients with PAN vasculitis and CLTI.
PubMed: 38106351
DOI: 10.1016/j.jvscit.2023.101266 -
Rinsho Shinkeigaku = Clinical Neurology Jan 2024A 33-year-old female was admitted to our department complaining of multifocal paresthesia and weakness of the upper and lower extremities that had developed over the...
[Mononeuropathy multiplex caused by cutaneous arteritis diagnosed by skin biopsies for emerging atypical erythema on upper limbs following neurological symptoms: a case report].
A 33-year-old female was admitted to our department complaining of multifocal paresthesia and weakness of the upper and lower extremities that had developed over the previous three months. She had also been undergoing treatment for atopic dermatitis with dupilumab, an anti-interleukin 4/13 receptor antibody. A nerve conduction study revealed multifocal axonal sensorimotor neuropathy of bilateral limbs. On admission, a small erythema appeared on her right forearm, but it was atypical for vasculitic skin lesions due to its location and time course. Nonetheless, a biopsy revealed medium-sized vessel vasculitis. The patient was therefore diagnosed with vasculitic neuropathy caused by cutaneous arteritis. Methylprednisolone pulse therapy with prednisolone and azathioprine markedly improved her symptoms. A skin biopsy is useful when mononeuropathy multiplex is suspected, even if the skin findings are atypical for vasculitic rash.
Topics: Humans; Female; Adult; Arteritis; Mononeuropathies; Erythema; Upper Extremity; Biopsy
PubMed: 38092413
DOI: 10.5692/clinicalneurol.cn-001912 -
Cardiovascular Pathology : the Official... 2024A 28-year-old male was found dead in his bedroom. There were no anomalies in his birth and medical history, and there was no family history of sudden unexpected death... (Review)
Review
A 28-year-old male was found dead in his bedroom. There were no anomalies in his birth and medical history, and there was no family history of sudden unexpected death (SUD). Autopsy showed subarachnoid hemorrhage (SAH) with basilar top inflammatory pseudoaneurysm rupture accompanied by fibrinoid necrosis in the aneurysm wall. Active and healed arteritides in small- to medium-sized arteries were identified in the brain, heart, and systemic connective tissue, which was consistent with polyarteritis nodosa (PAN). Furthermore, pneumatosis cystoides intestinalis was observed in the ascending colon. Hepatitis B virus infection and antineutrophil nuclear antibodies were negative. Genetic investigation using whole-exome sequencing showed no mutations among autoinflammatory-related genes, including UBA1, MEFV, and ADA2. SAH due to rupture of a pseudoaneurysm formed by PAN was considered as the cause of death in the present case. Although myocardial ischemia linked to coronary arteritis is a recognized trigger for SUD in PAN, our study showed that rupture of inflammatory pseudoaneurysm in the cerebral artery can also cause SUD in younger subjects with PAN, even if prodromal symptoms are not evident before death.
Topics: Male; Humans; Young Adult; Adult; Subarachnoid Hemorrhage; Polyarteritis Nodosa; Aneurysm, False; Arteries; Aneurysm; Death, Sudden; Pyrin
PubMed: 38072093
DOI: 10.1016/j.carpath.2023.107602 -
International Journal of Molecular... Nov 2023Polyarteritis nodosa (PAN), also known as panarteritis nodosa, represents a form of necrotizing vasculitis that predominantly affects medium-sized vessels, although it... (Review)
Review
Polyarteritis nodosa (PAN), also known as panarteritis nodosa, represents a form of necrotizing vasculitis that predominantly affects medium-sized vessels, although it is not restricted to them and can also involve smaller vessels. The clinical presentation is heterogeneous and characterized by a significant number of patients exhibiting general symptoms, including asthenia, fever, and unintended weight loss. Although PAN can involve virtually any organ, it preferentially affects the skin, nervous system, and the gastrointestinal tract. Orchitis is a rare but specific manifestation of PAN. The absence of granulomas, glomerulonephritis, and anti-neutrophil cytoplasmic antibodies serves to distinguish PAN from other types of vasculitis. Major complications consist of hemorrhagic and thrombotic events occurring in mesenteric, cardiac, cerebral, and renal systems. Historically, PAN was frequently linked to hepatitis B virus (HBV) infection, but this association has dramatically changed in recent years due to declining HBV prevalence. Current epidemiological research often identifies a connection between PAN and genetic syndromes as well as neoplasia. This article provides a comprehensive review of PAN, specifically focusing on the progression of its clinical manifestations over time.
Topics: Male; Humans; Polyarteritis Nodosa; Vasculitis; Hepatitis B; Hepatitis B virus; Gastrointestinal Tract
PubMed: 38068989
DOI: 10.3390/ijms242316668