Visualization of intradermal blood vessel structures by dual-wavelength photoacoustic microscopy and characterization of three-dimensional construction of livedo-racemosa in cutaneous polyarteritis nodosa.

BACKGROUND: Photoacoustic microscopy is expected to have clinical applications as a noninvasive and three-dimensional (3D) method of observing intradermal structures. OBJECTIVE: Investigate the applicability of a photoacoustic microscope equipped with two types of pulsed lasers that can simultaneously recognize hemoglobin and melanin. METHODS: 16 skin lesions including erythema, pigmented lesions, vitiligo and purpura, were analyzed to visualize 3D structure of melanin granule distribution and dermal blood vessels. 13 cases of livedo racemosa in cutaneous polyarteritis nodosa (cPN) were further analyzed to visualize the 3D structure of dermal blood vessels in detail. Vascular structure was also analyzed in the biopsy specimens obtained from tender indurated erythema of cPN by CD34 immunostaining. RESULTS: Hemoglobin-recognition signal clearly visualized the 3D structure of dermal blood vessels and melanin-recognition signal was consistently reduced in vitiligo. In livedo racemosa, the hemoglobin-recognition signal revealed a relatively thick and large reticular structure in the deeper layers that became denser and finer toward the upper layers. The numerical analysis revealed that the number of dermal blood vessels was 1.29-fold higher (p<0.05) in the deeper region of the lesion than that of normal skin. The CD34 immunohistochemical analysis in tender indurated erythema revealed an increased number of dermal vessels compared with normal skin in 88.9% (8/9) of the cases, suggesting that vascular network remodeling had occurred in cPN. CONCLUSION: The photoacoustic system has an advantage in noninvasively detecting dermal blood vessel structures that are difficult to recognize by two-dimensional histopathology specimen examination and is worth evaluating in various skin diseases.

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.

Polyarteritis Nodosa.

Online supplemental material is available for this article.

Hypertrophic pachymeningitis in polyarteritis nodosa: a case-based review.

Hypertrophic pachymeningitis (HP) is a rare neurological disorder with focal or diffuse thickening of the dura mater, which usually causes headache, cranial neuropathies, seizures, and motor or sensory impairments. The development of HP is attributed to an immune-mediated mechanism, and some autoimmune diseases have been implicated in the development of HP. Herein, we describe the case of a 73-year-old woman with persistent headache ascribable to HP, which developed approximately 3 years after a diagnosis of polyarteritis nodosa (PAN). She was treated with high-dose corticosteroid and cyclophosphamide that resulted in immediate disappearance of headache and improved radiological findings of thickened dura mater. In addition, she was subsequently administered methotrexate, ultimately resulting in maintenance of remission and regular reduction of prednisolone. In our review of published English articles, only two cases of HP in patients with PAN have been reported to date, suggesting that HP is a rare complication in PAN. However, it should be recognized that HP may develop as a neurological involvement related to PAN.

Fluorodeoxyglucose positron emission tomography-computed tomography findings in a first series of 10 patients with polyarteritis nodosa.

OBJECTIVE: 18F-fluorodeoxyglucose PET/CT (FDG-PET/CT) is widely used in patients with large vessel vasculitis. The benefits of FDG-PET/CT in PAN has only ever been assessed in three case reports. Our aim was to describe FDG-PET/CT findings in 10 patients with newly diagnosed PAN. METHODS: This was a retrospective study of patients with PAN who underwent FDG-PET/CT at diagnosis between 2017 and 2020. The FDG-PET/CT data were analysed retrospectively. RESULTS: Ten patients were included: nine men and one woman with a median age of 67 years (range 43-78). PAN was diagnosed according to ACR criteria in nine patients and histologically in one. All patients had high CRP levels (median 223 mg/l). The main FDG-PET/CT abnormality was increased tracer uptake in the muscles, particularly in the connective tissue (perimysium, epimysium) (n = 7), and in linear (n = 5) or focal (n = 2) patterns. Increased FDG uptake in large-diameter vessels was observed in four patients, in the humeral (n = 4), femoral (n = 1) and common interosseous arteries (n = 1). Nine patients had bone marrow FDG uptake and six had splenic FDG uptake. Three had synovitis and three had lymph node uptake. One patient had subcutaneous FDG uptake with a 'leopard skin' appearance. CONCLUSIONS: FDG-PET/CT seems to be a useful non-invasive imaging technique for diagnosing PAN, particularly in patients with non-specific systemic features. Tracer uptake in muscular connective tissue seems to be a recurrent sign in patients with PAN and may be pathognomonic.

Value of second opinion subspecialty radiology consultation in suspected abdominal medium vessel vasculitis.

PURPOSE: To perform a descriptive analysis of individuals with suspected Polyarteritis nodosa (PAN) referred for second opinion imaging consultation. METHODS: A retrospective observational cohort study was performed at a single institution. A consecutive sample was performed of individuals who underwent a second opinion CT or MR angiography subspecialty radiologist consultation between January 2008 and September 2019 for suspected abdominal medium vessel vasculitis. Demographic, clinical, and imaging data were collected. Clinical and imaging findings were reported for PAN, small vessel vasculitis, and "non-vasculitis" groups. Agreement and diagnostic accuracy between final clinical and second opinion imaging diagnoses for PAN were determined. Two-tailed t-tests with a significant p-value < 0.05 were utilized. RESULTS: Of the 58 participants, 9 were clinically diagnosed with PAN, 11 with small vessel vasculitis (including lupus, IgA, and ANCA-associated vasculitis), and 38 with non-vasculitis diagnoses. The non-vasculitis group included 15 SAM, 3 FMD, and 1 SAM-FMD spectrum diagnoses. Higher C-reactive protein level (51 vs 17, p = 0.04) and superior mesenteric artery involvement (56% vs 21%, p = 0.04) were more common in PAN than non-vasculitis diagnoses, while arterial dissection (40% vs 0%, p = 0.02) and celiac vasculature involvement (53% vs 0%, p = 0.003) were more common in the non-vasculitis group. There was 88% agreement (51/58; Cohen's kappa 0.56); sensitivity was 67% [95%-confidence interval (CI) 30-93%] and specificity was 92% (95%-CI 80-98%). CONCLUSION: Isolated celiac artery involvement and arterial dissection were more common in non-inflammatory vasculopathies than PAN. Our findings highlight the need for multidisciplinary collaboration and awareness of the diverse findings of abdominal vasculopathies.

2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Polyarteritis Nodosa.

OBJECTIVE: To provide evidence-based recommendations and expert guidance for the management of systemic polyarteritis nodosa (PAN). METHODS: Twenty-one clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for systemic, non-hepatitis B-related PAN. Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the quality of evidence and formulate recommendations. Each recommendation required ≥70% consensus among the Voting Panel. RESULTS: We present 16 recommendations and 1 ungraded position statement for PAN. Most recommendations were graded as conditional due to the paucity of evidence. These recommendations support early treatment of severe PAN with cyclophosphamide and glucocorticoids, limiting toxicity through minimizing long-term exposure to both treatments, and the use of imaging and tissue biopsy for disease diagnosis. These recommendations endorse minimizing risk to the patient by using established therapy at disease onset and identify new areas where adjunctive therapy may be warranted. CONCLUSION: These recommendations provide guidance regarding diagnostic strategies, use of pharmacologic agents, and imaging for patients with PAN.

Sudden death complicating a coronary arteritis: polyarteritis nodosa (case report).

Coronary artery aneurysms are uncommon, are usually associated with atherosclerosis, and rarely involve all three major coronary arteries. Data on the optimal choice of acute myocardial infarction (AMI)´s revascularization in the context of polyarteritis nodosa (PAN) is limited to case reports and is still an open question. The present report describes a rare case of a young male patient followed for PAN presenting with acute myocardial infarction (AMI). Coronary angiography revealed multiple severe aneurysmal and stenotic changes. Based on clinical feature and angiographic findings, it was strongly suspected that the AMI was a complication of his vasculitis. This case indicates that coronary artery involvement should be carefully monitored during the chronic phase of PAN. The pathophysiology of AMI in PAN patients should be kept in mind and the interventional approach must be performed according to the angiographic findings to avoid complications.

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.

Radiologic Imaging in Large and Medium Vessel Vasculitis.

Vasculitides are a complex group of diseases sharing the defining feature of inflamed vessel walls. Vasculitides can be classified depending on the size of the predominantly affected vessels. Modern cross-sectional imaging methods have become a cornerstone in the diagnosis of vasculitis and may help in narrowing down differential diagnoses. This review presents the most important imaging modalities and typical findings in large and medium size vasculitis, implementing current imaging recommendations.

Choroidal vascularity index as a biomarker of systemic inflammation in childhood Polyarteritis Nodosa and adenosine deaminase-2 deficiency.

BACKGROUND/PURPOSE: To assess EDI-OCT (enhanced depth imaging optical coherence tomography) of choroid for inflammatory signs in children with polyarteritis nodosa (PAN) and adenosine deaminase-2 deficiency (DADA-2). METHODS: In this cross-sectional study conducted between June 2017 and September 2018, we evaluated children diagnosed with PAN (n = 11) and DADA-2 (n = 4) and an age- and sex-matched control group (n = 15). Demographic and laboratory data were retrospectively analyzed from patient charts. Disease activity was assessed using the pediatric vasculitis activity score (PVAS). Choroidal images were obtained with spectral domain-OCT to measure choroidal thickness (ChT) at 5 points (750 and 1500 µm from the foveal center in the temporal and nasal quadrants and beneath the fovea), and to calculate the total subfoveal choroidal area (TCA), luminal area (LA), stromal area (SA), and the choroidal vascularity index (CVI). RESULTS: The median (min-max) age was 8 (4-16) years in PAN patients, 6 (5-16) years in DADA-2 patients and 8 (8-10) years in control group at the OCT visit (p = 0.214). The ChT at 3 points and the TCA, LA, and SA were higher in children with both PAN and DADA-2 patients compared to those of the control group (p < 0.0001, p = 0.049, p = 0.007, p = 0.007, p = 0.006, p = 0.033, respectively). The CVI was similar in both groups. No association was observed between the OCT findings, PVAS, and the erythrocyte sedimentation rate, and serum leukocyte and C-reactive protein levels. CONCLUSION: Similar CVI scores were obtained from PAN and DADA2 patients under treatment and from healthy controls. Increased subfoveal ChT without any other signs of ocular involvement may suggest choroidal thickening as a sign of mild subclinical inflammation.