Shifting perspectives in coronary involvement of polyarteritis nodosa: case of 3-vessel occlusion treated with 4-vessel CABG and review of literature.

BACKGROUND: Polyarteritis Nodosa (PAN) is a systemic vasculitis (SV) historically thought to spare the coronary arteries. Coronary angiography and contemporary imaging reveal coronary stenosis and dilation, which are associated with significant morbidity and mortality. Coronary arteries in PAN are burdened with accelerated atherosclerosis from generalized inflammation adding to an inherent arteritic process. Traditional atherosclerotic risk factors fail to approximate risk. Few reports document coronary pathology and optimal therapy has been guarded. METHODS: Database publication query of English literature from 1990-2022. RESULTS: Severity of coronary involvement eludes laboratory monitoring, but coronary disease associates with several clinical symptoms. Framingham risk factors inadequately approximate disease burden. Separating atherosclerosis from arteritis requires advanced angiographic methods. Therapy includes anticoagulation, immunosuppression and revascularization. PCI has been the mainstay, though stenting is confounded by vagarious alteration in luminal diameter and reports of neointimization soon after placement. CONCLUSIONS: When graft selection avoids the vascular territory of SV's, CABG offers definitive therapy. We have contributed report of a novel CABG configuration in addition to reviewing, updating and discussing the literature. Accumulating evidence suggests discrete clinical symptoms warrant suspicion for coronary involvement.

Clinical characteristics, disease trajectories and management of vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome: a systematic review.

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.

Wunderlich syndrome as a rare complication of polyarteritis nodosa: a case report.

Spontaneous subcapsular and perirenal hemorrhage, known as Wunderlich syndrome (WS), is a rare clinical manifestation of polyarteritis nodosa (PAN). We report a case of a 48-year-old male with a history of recurrent episodes of leg muscle tenderness and dysesthesia, bilateral flank pain, painful nodular skin lesions in the lower limbs, weight loss, and difficult-to-control arterial hypertension. The abdominopelvic computed tomography angiography showed a large left perirenal hematoma, leading to the patient's admission to the intensive care unit. After the exclusion of infectious or neoplastic foci, the patient was diagnosed with PAN and started intravenous methylprednisolone pulses with a good response. Since WS is a rare initial clinical manifestation of PAN, an early diagnosis and aggressive treatment will significantly improve clinical outcomes.

Medium- and Large-Vessel Vasculitis.

Systemic vasculitides are multisystem blood vessel disorders, which are defined by the size of the vessel predominantly affected, namely small, medium, or large vessels. The term "large vessel" relates to the aorta and its major branches; "medium vessel" refers to the main visceral arteries and veins and their initial branches. The most common causes of large-vessel vasculitis are giant cell arteritis and Takayasu arteritis, and those of medium-vessel arteritis are polyarteritis nodosa and Kawasaki disease. However, there is some overlap, and arteries of any size can potentially be involved in any of the 3 main categories of dominant vessel involvement. In addition to multisystem vasculitides, other forms of vasculitis have been defined, including single-organ vasculitis (eg, isolated aortitis). Prompt identification of vasculitides is important because they are associated with an increased risk of mortality. Left undiagnosed or mismanaged, these conditions may result in serious adverse outcomes that might otherwise have been avoided or minimized. The ethnic and regional differences in the incidence, prevalence, and clinical characteristics of patients with vasculitis should be recognized. Because the clinical presentation of vasculitis is highly variable, the cardiovascular clinician must have a high index of suspicion to establish a reliable and prompt diagnosis. This article reviews the pathophysiology, epidemiology, diagnostic strategies, and management of vasculitis.

Polyarteritis nodosa.

PURPOSE OF REVIEW: The aim is to review recent reports on childhood polyarteritis nodosa, including recent reports on treatment and outcome. Recently deficiency of adenosine deaminase-2 (ADA2), which may present as a polyarteritis nodosa-mimic, is becoming an important part of our practice. We also aim to highlight differences of childhood polyarteritis nodosa with deficiency of ADA2 as well as adult-onset disease. RECENT FINDINGS: The few recent childhood series confirm the systemic nature of this vasculitis with predominantly medium-vessel involvement. American College of Rheumatology Vasculitis foundation has suggested recommendations for the management of this vasculitis. Unfortunately, we lack large patient numbers to provide us high evidence for the treatment of these patients. However, for induction mycophenolate mofetil or shorter courses of cyclophosphamide can be considered.Deficiency of ADA2 is now in the differential diagnosis of polyarteritis nodosa patients presenting with a family history and/or stroke with hematological and/or immunological abnormalities. SUMMARY: We need collaborative work to define management and treatment strategies for childhood polyarteritis nodosa. Distinguishing deficiency of ADA2 is important because the treatment is different.

[Recommendations of diagnosis and treatment of polyarteritis nodosa].

Polyarteritis nodosa (PAN) is a rare vasculitis that mainly involves small and medium arteries. It often occurs at the points where the vessels bifurcate, leading to microaneurysm formation, thrombosis, aneurysm rupture and bleeding, and infarction of organs.About a third of cases are associated with hepatitis B virus (HBV) infection.All tissues and organs of the body can be affected, with skin, joints and peripheral nerves being the most common.The pathological changes were fibrinoid necrosis, inflammatory cell infiltration and luminal thrombosis in the acute stage, and fibrous hyperplasia in the chronic stage.Overall outcomes for the disease have improved in recent decades, mainly reflecting early diagnosis and more effective treatments.The main treatments for PAN are glucocorticoid and cyclophosphamide.Patients with HBV-associated PAN should receive antiviral therapy and plasma exchange.

Clinical Approach to Diagnosis and Therapy of Polyarteritis Nodosa.

PURPOSE OF THE REVIEW: Polyarteritis nodosa is a rare disease characterized by the necrotizing inflammation of medium-sized arteries. Different etiopathogenetic and clinical variants of the disease have been recognized over the past decades. In the present paper, we review the clinical features, diagnosis, and treatment of the different subtypes of the disease. RECENT FINDINGS: The diagnosis of polyarteritis nodosa is primarily based on clinical findings, imaging, and histopathological investigations. Microbiological and genetic investigations complement the diagnostic work-up. Idiopathic and hereditary variants of polyarteritis nodosa are treated with immunomodulatory medications such as glucocorticoids, conventional immunomodulatory drugs (e.g., cyclophosphamide) and biologic agents (e.g., tumor necrosis factor inhibitors, interleukin 6 inhibitor), while hepatitis B virus-associated polyarteritis nodosa primarily requires antiviral therapy combined with plasma exchange. PAN is a disease with heterogeneous presentations, severity, and therapeutic approaches. The overall prognosis of this disease is improving, mainly due to early diagnosis and more effective treatments. Treatment choices are guided mainly by the disease subtype and severity. In this review, we have presented the current knowledge on PAN clinical variants, their classification, diagnosis, and treatment approaches.

Coronary artery vasculitis: a review of current literature.

Cardiac vasculitis is recognized as a heterogeneous disease process with a wide spectrum of manifestations including pericarditis, myocarditis, valvular heart disease and less frequently, coronary artery vasculitis (CAV). CAV encompasses an emerging field of diseases which differ from conventional atherosclerotic disease and have a proclivity for the younger population groups. CAV portends multiple complications including the development of coronary artery aneurysms, coronary stenotic lesions, and thrombosis, all which may result in acute coronary syndromes. There are several aetiologies for CAV; with Kawasaki's disease, Takayasu's arteritis, Polyarteritis Nodosa, and Giant-Cell Arteritis more frequently described clinically, and in literature. There is a growing role for multi-modality imaging in assisting the diagnostic process; including transthoracic echocardiography, cardiac magnetic resonance imaging, computed tomography coronary angiography, fluorodeoxyglucose-positron emission tomography and conventional coronary angiogram with intravascular ultrasound. Whilst the treatment paradigms fundamentally vary between different aetiologies, there are overlaps with pharmacological regimes in immunosuppressive agents and anti-platelet therapies. Interventional and surgical management are is a consideration in select populations groups, within a multi-disciplinary context. Further large-scale studies are required to better appropriately outline management protocols in this niche population.

[Update: polyarteritis nodosa]. / Update: Polyarteriitis nodosa.

Polyarteritis nodosa (PAN) is a necrotizing arteritis of medium-sized vessels, which is often fatal if untreated. It frequently affects the skin (nodules and ulcers), the peripheral nervous system (mononeuritis multiplex) and the visceral vessels (stenoses and microaneurysms). The complex diagnostic work-up requires discriminating PAN from infectious, malignant, drug-induced and other inflammatory conditions. It can be subclassified into further variants (idiopathic, associated with hepatitis B, associated with hereditary inflammatory diseases or isolated cutaneous disease). While idiopathic and hereditary inflammatory variants require immunosuppressive treatment, the hepatitis B-associated variant is treated with virustatic agents and plasmapheresis. The isolated cutaneous variant has a good prognosis and rarely requires highly potent immunosuppressives.

[The changing face of medium-sized vasculitis].

Polyarteritis nodosa is a systemic necrotizing vasculitis which predominantly affects medium-sized arteries. It is a rare disease nowadays. Both the nomenclature and the classification of polyarteritis nodosa was amended several times in the past. Currently, there is a distinction between the primary form described as classical polyarteritis nodosa and other forms that are associated with their probable cause e.g. with viral hepatitis B, C or HIV infection. Moreover, polyarteritis-like necrotizing vasculitis can appear in the course of genetic diseases caused by mutations in single genes. The pathogenesis of idiopathic polyarteritis nodosa is still unclear, but a dominant role of the adaptive immune system disorders is suggested. Interestingly, in the hepatitis B virus-related vasculitis development, immune complexes are believed to play a crucial role. The spectrum of clinical manifestations of polyarteritis nodosa is wide, from involving a single organ to the polyvisceral failure. In the course of polyarteritis nodosa nearly each organ can be involved, however the disease never affects the lungs. Special forms of polyarteritis nodosa include a single-organ disease and a cutaneous form. The diagnosis of polyarteritis nodosa requires integration of clinical, angiographic and biopsy findings. Recognizing the form of polyarteritis nodosa, determining affected organs and the progression of the disease is very important since those are deciding factors when choosing treatment strategies.

Plasma exchanges for the treatment of severe systemic necrotizing vasculitides in clinical daily practice: Data from the French Vasculitis Study Group.

The use of plasma exchanges (PLEX) in systemic necrotizing vasculitides (SNV) still need to be codified. To describe indications, efficacy and safety of PLEX for the treatment of SNV, we conducted a multicenter retrospective study on patients with ANCA-associated vasculitis (AAV) or non-viral polyarteritis nodosa (PAN) treated with PLEX. One hundred and fifty-two patients were included: GPA (n = 87), MPA (n = 56), EGPA (n = 4) and PAN (n = 5). PLEX were used for rapidly progressive glomerulonephritis (RPGN) in 126 cases (86%), alveolar hemorrhage in 64 cases (42%), and severe mononeuritis multiplex in 23 cases (15%). In patients with RPGN, there was a significant improvement in renal function compared to baseline value (P < 0.0001), the plateau being reached at month 3 after PLEX initiation, and estimated glomerular filtration rate improved especially as the number of PLEX increased. In patients with alveolar hemorrhage, mechanical ventilation was discontinued in all patients after a median time of 15 days. Patients treated for mononeuritis multiplex showed improvement of severe motor weakness. After a median follow of 22 months, 18 deaths (12%) were recorded, mainly in patients with RPGN and within the first 6 months. Incidence of end-stage renal disease and/or death was similar between groups of different baseline renal function, but was increased in MPO-ANCA compared to PR3-ANCA. Adverse events attributable to PLEX were recorded in 63%. No death occurred during PLEX. This large series describes indications, efficacy and safety of PLEX in daily practice. Randomized controlled studies are ongoing to define optimal indications, PLEX regimen and concomitant medications.

Systemic polyarteritis nodosa in the young: a single-center experience over thirty-two years.

OBJECTIVE: Polyarteritis nodosa (PAN) is a rare disease of childhood. The aims of this study were to describe the clinical features, treatment, and outcome of systemic childhood PAN and to identify predictors of relapse. METHODS: A single-center retrospective medical records review of children with PAN fulfilling the European League Against Rheumatism (EULAR)/Paediatric Rheumatology European Society (PRES)/Paediatric Rheumatology International Trials Organisation (PRINTO) classification criteria who were seen over a 32-year period was performed. Data on demographic and clinical features, treatments, relapses (recurrence of clinical signs/symptoms or occurrence of new symptoms after initial remission requiring escalation or resumption of immunosuppressive therapy), and deaths were recorded. A disease activity score was retrospectively assigned using the Paediatric Vasculitis Activity Score (PVAS) instrument. Cox regression analysis was used to identify significant predictors of relapse. RESULTS: Sixty-nine children with PAN were identified; 55% were male, and their median age was 8.5 years (range 0.9-15.8 years). Their clinical features at presentation were fever (87%), myalgia (83%), skin (88%), renal (19%), severe gastrointestinal (GI) (10%), and neurologic (10%) involvement. The PVAS at presentation was 9 of 63 (range 4-24). Histopathologic analysis of the skin showed necrotizing vasculitis in biopsy samples from 40 of 50 children. Results of selective visceral arteriography suggested the presence of PAN in 96% of patients. Treatment included cyclophosphamide and corticosteroids (83%), plasma exchange (9%), and biologic agents (after 2002; 13%). The relapse rate was 35%, and the mortality rate was 4%. Severe GI involvement was associated with increased risk of relapse (P = 0.031), while longer time to induce remission (P = 0.022) and increased cumulative dose of cyclophosphamide (P = 0.005) were associated with lower relapse risk. CONCLUSION: Childhood PAN is a severe inflammatory disease of insidious onset and variable clinical presentation. Relapses occurred more frequently in those with severe GI involvement. A higher cumulative dose of cyclophosphamide was associated with a lower risk of relapse.

Atypical ulcers.

Atypical ulcers of the skin challenge the dermatologist with respect to recognition, diagnosis, management, and treatment. The entire gamut of pathogenic categories including vascular, inflammatory, neoplastic, genetic, medication-related, and infectious processes may give rise to atypical ulcers. By definition, these ulcers are unusual, and accurate diagnosis may ultimately require the clinician to violate the dictum that "common things are common." Atypical ulcers may present with features that the clinician has not previously encountered, or may present with seemingly typical features that actually mislead due to phenotypic mimicry. Because skin ulcers are inherently tissue-destructive, and may reflect an underlying systemic disease process, there is heightened urgency to achieving an accurate diagnosis and initiating appropriate therapy.

Deficiency of adenosine deaminase 2 (DADA2): Review.

The deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive disease caused by loss-of-function (LOF) mutations in the ADA2 gene and was first described in 2014. Initially, it was described as vasculopathy/vasculitis that mostly affected infants and young children and closely resembled polyarteritis nodosa (PAN). Skin rash and ischemic/hemorrhagic stroke are predominant symptoms. However, the clinical spectrum of DADA2 has continued to expand since then. It has now been reported in adults as well. Besides vasculitis-related manifestations, hematological, immunological, and autoinflammatory manifestations are now well recognized. More than 100 disease-causing mutations have been described. The decrease in ADA2 enzyme leads to an increased extracellular adenosine level that, in turn, triggers a proinflammatory cascade. The disease is highly variable, and patients carrying same mutation may have different ages of presentation and clinical features. Anti-tumor necrosis factor (TNF) agents are mainstay of treatment of the vasculitis/vasculopathy phenotype. Hematopoietic stem cell transplant (HSCT) has been performed in patients with severe hematological manifestations. Recombinant ADA2 protein and gene therapy hold a promise for future.

Thiabendazole-induced acute liver failure requiring transplantation and subsequent diagnosis of polyarteritis nodosa.

Polyarteritis nodosa (PAN), a systemic necrotising vasculitis that affects medium- and small-sized arteries, has visceral involvement in 40-60% of the patients. According to the Five-Factor Score (FFS), it is associated with poor outcome. We describe a patient who underwent orthotopic liver transplantation (OLT) for severe ductopenia induced by thiabendazole that was empirically prescribed for chronic hypereosinophilia. Eleven years later, despite immunosuppressive treatment to prevent graft rejection, he developed mononeuritis multiplex; PAN was diagnosed. He also had severe recurrent ischaemic cholangitides because of post-OLT hepatic artery ligation to treat a postoperative severe haematemesis. His outcome was favourable after second OLT, under steroids, cyclophosphamide pulses and tacrolimus. In retrospect, his initial symptoms and hypereosinophilia were probably attributable to PAN.

Recent understanding on diagnosis and management of central nervous system vasculitis in children.

Central nervous system vasculitides in children may develop as a primary condition or secondary to an underlying systemic disease. Many vasculitides affect both adults and children, while some others occur almost exclusively in childhood. Patients usually present with systemic symptoms with single or multiorgan dysfunction. The involvement of central nervous system in childhood is not frequent and it occurs more often as a feature of subtypes like childhood polyarteritis nodosa, Kawasaki disease, Henoch Schönlein purpura, and Bechet disease. Primary angiitis of the central nervous system of childhood is a reversible cause of severe neurological impairment, including acute ischemic stroke, intractable seizures, and cognitive decline. The first line therapy of CNS vasculitides is mainly based on corticosteroids and immunosuppressor drugs. Other strategies include plasmapheresis, immunoglobulins, and biologic drugs. This paper discusses on current understanding of most frequent primary and secondary central nervous system vasculitides in children including a tailored-diagnostic approach and new evidence regarding treatment.

Polyarteritis nodosa: a case presenting with renal mass.

An adolescent girl was hospitalized due to fever and abdominal flank pain. A left renal haematoma was detected on magnetic resonance imaging. Renal angiography demonstrated multiple microaneurysms at both hepatic arteries, intrarenal segments of the bilateral renal arteries, and inferior lobar segment of the left pulmonary artery, which is consistent with the diagnosis of polyarteritis nodosa. Vasculitic syndromes should be considered in patients with visceral haemorrhage.