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.

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.

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.

[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.

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.

Polyarteritis Nodosa: State of the art.

Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis that preferentially affects medium-sized vessels. The idiopathic form has become rare. Its treatment relies on corticosteroid therapy and is combined with cyclophosphamide infusions for severe forms. Secondary PANs were mainly associated with hepatitis B virus infection; they were treated with plasma exchange and antivirals in combination with short-term corticosteroid therapy. Other secondary forms of PAN are now becoming more common, such as those due to blood disorders. More recently, a monogenic form linked to adenosine deaminase-2 mutations has been identified. It requires treatment with TNF inhibitors to decrease the occurrence of ischemic central nervous system complications, which make it serious. Once remission is obtained, relapses are typically rare during PAN and affect 28% of idiopathic PANs, within an average of 26 months from the diagnosis. The prognosis has improved considerably, with 5- and 10-year survival rates of 83% and 74%.

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.

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.

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.

Bacterial-Infection-Associated Polyarteritis Nodosa Presenting as Acute, Rapidly Progressive Multiple Hepatic Artery Aneurysms.

A 26-year-old male soldier was clinically characterized by transient fever, persistent right upper quadrant pain, hypertension, and elevated inflammatory biomarkers associated with bacterial infection. On the fifteenth day after the onset of symptoms, he had typical CT findings in polyarteritis nodosa involving only the hepatic arteries. Transcatheter arterial coil embolization of the right hepatic artery was performed due to ruptured hepatic aneurysms. Combination therapy with antibiotics and antihypertensives was administrated after embolization. The intrahepatic aneurysms completely vanished and inflammatory biomarkers returned to normal on the tenth day after embolization. The current case highlights the diagnosis and treatment of bacterial-infection-associated polyarteritis nodosa involving only the hepatic arteries, coexisting with hypertension.

Characteristics and Outcomes of Coronary Artery Involvement in Polyarteritis Nodosa.

BACKGROUND: Coronary artery involvement is a severe but uncommon manifestation of polyarteritis nodosa (PAN), so clinicians have little knowledge of it. Our aim was to investigate the clinical characteristics, risk factors and outcomes of patients with PAN complicated with coronary artery lesions. METHODS: Data from 145 patients with PAN who were admitted to Peking Union Medical College Hospital from January 2000 to September 2019 were retrospectively collected. RESULTS: Nineteen patients (13.1%) had coronary artery lesions due to PAN. The age at the onset of PAN was 32.3 ± 11.8 years. There were no significant differences in common risk factors for coronary arterial atherosclerosis between the patients with coronary artery involvement and those without. Affected branches of the coronary arteries were left anterior descending branch (15 patients), right coronary artery (14 patients), and left circumflex branch (9 patients). Eleven of the 19 patients exhibited multivessel lesions. Multivariate logistic regression analysis showed that celiac artery involvement (odds ratio [OR] 3.722, 95% confidence interval [CI] 1.115-12.427; P = 0.033) and new-onset hypertension (OR 6.668, 95% CI 1.936-22.961; P = 0.003) were risk factors for coronary artery involvement in patients with PAN. Stent placement was performed for 2 patients, and in-stent restenosis occurred in 1 of those patients a year later. CONCLUSIONS: PAN with coronary artery involvement exhibits more combined involvement of arteries of other organs and more severe diseases. PAN should be considered when treating young adults with an unknown origin of coronary artery lesions. In addition to systemic immunosuppressive treatment, other measures including antiplatelet and anticoagulation therapy should be initiated; however, determining the optimal time to perform procedures such as intervention or surgery is still challenging.

Treatment of systemic necrotizing vasculitides: The 40-year experience of the French Vasculitis Study Group.

Treatment of vasculitides has benefited from the results of several prospective clinical trials focusing on the evaluation of new drugs, therapeutic strategies and adjuvant treatments. In the field of autoimmunity, vasculitides are the group of diseases for which the most important medical progress has been made, combining advances in understanding the pathogenetic mechanisms, classification of the various entities and willingness to evaluate treatments. Several international groups have been actively involved in these tasks. The French Vasculitis Study Group was the first to design and organize prospective trials in the field and to contribute to these medical advances. In this review, we analyze the different treatments and therapeutic strategies evaluated over the last few decades and, more precisely, the last 39 years by the French Vasculitis Study Group.

Pulmonary manifestations of large, medium, and variable vessel vasculitis.

The hallmark of vasculitis is autoimmune inflammation of blood vessels and surrounding tissues, resulting in an array of constitutional symptoms and organ damage. The lung is commonly targeted in the more familiar ANCA-associated small vessel vasculitidies, but large and medium vessel vasculitides, including Takayasu arteritis, giant cell arteritis, polyarteritis nodosa, Behcet's disease, and necrotizing sarcoid granulomatosis, may also feature prominent pulmonary involvement. Pulmonary manifestations of these conditions include pulmonary arterial aneurysms, pulmonary hypertension, diffuse alveolar hemorrhage, pulmonary nodules, and parenchymal infiltrates. An understanding of the diverse manifestations of vasculitis and a high index of clinical suspicion are essential to avoid delays in disease recognition that may result in permanent or life threatening morbidity. In this review, we outline the general clinical manifestations, pulmonary manifestations, diagnostic workup, imaging findings, and treatment of medium, large, and variable vessel vasculitides.

Mortality in systemic necrotizing vasculitides: A retrospective analysis of the French Vasculitis Study Group registry.

OBJECTIVE: The aim of the study was to describe the evolution of mortality and cause-specific mortality over time in patients with systemic necrotizing vasculitides (SNV), including polyarteritis nodosa (PAN), granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). METHODS: Patients with SNV from the French Vasculitis Study Group registry were divided into 5 groups according to the date of diagnosis: <1980, 1980-1989, 1990-1999, 2000-2010, and ≥ 2010. The causes of death were classified as vasculitis, infection, cardiovascular, malignancy, miscellaneous, or unknown. RESULTS: Among the 2217 patients included (PAN 16.1%, GPA 41.7%, EGPA 22.6%, MPA 19.6%), overall incidence of death was 2.26 per 100 person-years. The overall survival improved during each period considered. The 5-year survival rate increased from 72.2% (95% confidence interval [CI] 59.7-87.2) for patients diagnosed before 1980 to 94.5% (95% CI 90.4-98.8) after 2010 (p < 0.001). Periods of diagnosis, age, and male gender were independently associated with a poor survival with a non-significant difference between vasculitis. The incidence of mortality between the 1980s and after 2010 significantly decreased for vasculitis-related (p = 0.03) and cardiovascular-related deaths (p = 0.04). Incidence of death by infection remained stable between the 1980s and the 2000s but no death by infection occurred after 2010. The incidence of death by malignancy remained stable over time. CONCLUSION: Overall survival of SNV patients has improved since the 1980s with the decrease of vasculitis- and cardiovascular-related deaths, but cancer-related mortality remained stable. These results highlight malignancy as the current target to improve the overall prognosis.

[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.

Poliarteritis nodosa cutánea / CUTANEOUS POLYARTERITIS NODOSA

La poliarteritis nodosa es una vasculitis de los vasos de mediano calibre que puede afectar solamente la piel o tener compromiso sistémico. Los signos cutáneos más frecuentes son livedo reticularis, nódulos y ulceras dolorosas. Se presenta un paciente masculino de 40 años de edad que consultó por nódulos eritematovioláceos dolorosos en miembros de un mes de evolución. Se realizó biopsia sugestiva de poliarteristis nodosa, se detectó serología para VIH positiva, cavitaciones pulmonares en TAC de tórax y lavado broncoalveolar con baciloscopía positiva para tuberculosis (TBC). Se inicia tratamiento antifímico y antiretroviral con mejoría de la clínica respiratoria y resolución a los 2 meses de las lesiones en piel

Polyarteritis nodosa is a vasculitis of medium sized vessels that can affect only skin or have systemic involvement. The most frequent cutaneous signs are livedo reticularis, nodules and painful ulcers. We present a 40 year-old male patient who consulted for painful erythematouspelvic nodules in a month of evolution. A biopsy suggestive of polyarteritis nodosa was detected, positive HIV serology, pulmonary cavitations in chest CT and bronchoalveolar lavage with tuberculosis-positive smear microscopy (TB). Antimicrobial and antiretroviral treatment with respiratory clinic improvement and resolution at 2 months of skin lesions are started