A Case of Polyarteritis Nodosa with Positive Anti-Phospholipid Antibodies Presenting with Multifocal Myositis

A Case of Polyarteritis Nodosa with Positive Anti-Phospholipid Antibodies Presenting with Multifocal Myositis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report A Case of Polyarteritis Nodosa with Positive Anti-Phospholipid Antibodies Presenting with Multifocal Myositis Ha Nguyen Thi Thu, Chi Quynh Le, Thach Ngoc Hoang, Giang Dinh Nguyen, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4108739/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Polyarteritis nodosa (PAN) is a rarely necrotizing vasculitis in childhood and is characterized by the inflammation of small and medium vessels affecting multiple organs. Although the presence of antiphospholipid (aPL) antibodies in PAN has been documented, there is limited data on the prevalence and understanding of pathogenesis and management for such co-incidence. Case presentation: We herein reported that a 7-year-old boy without significant past medical history presented initially with high-grade fever, painful subcutaneous nodules, and ankle arthritis for 14 days prior to hospitalization. Biological findings revealed increased acute inflammatory biomarkers and no evidence of infection. The deep skin biopsy taken from the subcutaneous nodule proved leukocytoclastic medium-sized vasculitis suggestive of the PAN diagnosis. He eventually achieved a complete response with the use of intravenous corticosteroids (2 mg/kg/day) and subcutaneous methotrexate (15 mg/m2 body surface area (BSA)/week). However, the patient developed painfulness of bilateral proximal muscles and new-onset subcutaneous nodules of lower limbs after 1-week maintenance. Though the creatine phosphokinase (CPK) level was normal, the magnetic resonant imaging (MRI) showed multiple foci myositis of bilateral gluteal and femur regions. The serum level of D-dimer was remarkably elevated, and the lupus anticoagulant was positive. A combination of subcutaneous enoxaparin and pulsed cyclophosphamide (500 mg/m2 BSA) and three-day methylprednisolone (30 mg/kg/day) have contributed to a favorable outcome in this case. She further sustained remission on maintenance of gradually tapering doses of oral prednisolone and methotrexate. Conclusions: We describe a case of PAN with the presence of aPL antibody manifesting with multifocal myositis. It is recommended that general testing for aPL antibodies should be undergone in patients with PAN, as well as other systemic vasculitis. Despite unusual co-incidence, aPL antibodies might worsen systemic vasculitis through thrombotic events, which clinicians should consider adequate coagulant therapeutics besides immunosuppressors. antiphospholipid polyarteritis nodosa vasculitis myositis Figures Figure 1 Figure 2 Figure 3 Introduction Polyarteritis nodosa (PAN) is a necrotizing, focal segmental vasculitis predominantly affecting medium-sized arteries without glomerulonephritis or vasculitis in arterioles, venules, or capillaries [ 1 ]. The incidence of PAN is around 0.9-8.0 cases per million in European countries and peaks at the ages of 40 to 50, with a male-to-female ratio of 2:1 [ 2 ] [ 3 ] [ 4 ]. Although epidemiological data on childhood-onset PAN is scarce, the disease is known to be comparatively rare and related to a newly discovered monogenic disease, deficiency of adenosine deaminase 2 (DADA2) in children [ 5 ] [ 6 ]. PAN can present a broad spectrum of manifestations with multiple organ systems, including the skin, gastrointestinal tract, kidney, nervous system, and muscles…[ 7 ] [ 8 ]. With spare lesions of the lung, the disease most commonly targets the peripheral nervous system and the skin and is distinctive to the antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis [ 9 ] [ 10 ]. Musculoskeletal involvement in PAN may present in a limited form or a component of a systemic entity, including myalgia, arthralgia, polymyositis-like syndrome, asymmetric nondeforming polyarthritis, acute leg ischemia, or myopathy [ 11 ]. The pathophysiology of muscular manifestations in PAN might be ischemia due to compromised intramuscular arteries, neuropathy of the peripheral nervous system, or, more rarely, myositis [ 12 ] [ 13 ]. Myositis in PAN has been described as a diffuse or focal form, which might suggest the underlying mechanisms of the lesion [ 7 ] [ 8 ] [ 14 ]. Antiphospholipid syndrome (APS) is an autoimmune disease characterized by the presence of antiphospholipid antibodies, including lupus anticoagulant, anticardiolipin antibodies, and anti-β2-glycoprotein-1 antibodies [ 15 ]. The hallmark pathophysiology of APS is thrombosis, inducing a variety of clinical phenotypes, including occlusion in the veins, arteries, and microvasculature, as well as obstetrical complications [ 15 ] [ 16 ]. The rare coexistence of the antiphospholipid syndrome and systemic vasculitis, such as polyarteritis nodosa (PAN), giant cell arteritis, Takayasu's arteritis, and Behcet's syndrome, have been documented in the literature [ 17 ]. The presence of aPL antibodies in vasculitis might be hypothesized as the endothelial cell disruption occurring in vasculitis, which presents immunologically hidden antigens and stimulates anti-endothelial antibodies [ 17 ]. The coincidence of PAN and APS has also been described mainly just case by case. The severity of illness with both conditions might be more acute and organ-threatening, suggesting the resonant risk of occlusive vasculopathy associated with aPL antibodies [ 17 ] [ 18 ]. Besides the mainstay of immunosuppressors, therapeutic dilemmas with prophylactic anticoagulation for preventing thrombosis should be considered in such cases. Here, we describe a case of PAN with the presence of aPL antibody manifesting with multifocal myositis. This report contributes to the current pediatric literature on the existence of aPL antibodies in PAN and highlights the need for further investigations into this issue. It is recommended that general testing for aPL antibodies should be undergone in patients with PAN, as well as other systemic vasculitis. Despite unusual co-incidence, aPL antibodies might worsen systemic vasculitis through thrombotic events, which clinicians should consider adequate coagulant therapeutics besides immunosuppressors. Case presentation A previously healthy 7-year-old boy suffered from a high-grade fever (39°C), painful subcutaneous nodules, and bilateral ankle arthritis for 14 days prior to hospitalization. His parents denied any history of purpura, Raynaud's phenomenon, oral ulcers, and hair loss. With suspected cutaneous infection, he was put on a seven-day-course oral oxacillin, but the symptoms were not resolved. On initial examination at admission, the patient appeared to have normal vital signs, with a blood pressure of 115/65 mmHg and a heart rate of 95 beats per minute. He had good air entry to both lungs and no crackle on respiratory examination. Multiple palpable subcutaneous nodules are predominantly positioned over both the lower limbs. Hepatosplenomegaly sign or lymph node enlargement and livedo reticularis were absent. Initial blood tests revealed a remarkable elevation in inflammatory markers, including erythrocyte sedimentation rate (ESR), 93 mm/1st hour and 101 mm/2nd hour (ref. 3–13); white blood cells (WBC), 29,000 cells/µl (ref. 4–10); neutrophil cells (NEU), 24,000 cells/µl (ref. 4–10); lymphocyte (LYM) 3260 cells/µl (ref. 4–10); C-reactive protein (CRP), 120 mg/L (ref. <6); lactate dehydrogenase (LDH), 300 U/L (ref. <266 U/L); and ferritin, 214 ng/mL (ref. <140). The cogulation profile presented as following: prothrombin time/international normalized ratio (PT/INR), 1.19 (ref. 0.87–1.2); fibrinogen, 4.79 g/L (ref. 1.89–4.75); activated partial thromboplastin time (aPTT), 38 seconds, (ref. 25.1–36.5); D-dimer, 788 ng/mL (ref. <500); protein C, 100.5 UI/mL (ref. 45.9-153.5); protein S, 110 UI/mL (ref. 66.5-161.5); and antithrombin III, 97 UI/mL (ref. 64.2-136.4). Other laboratory investigations were insignificant, as described in Table 1 . Table 1 Laboratory results Parameters Admission 1 Day 3 Day 7 Admission 2 Day 5 Discharge ESR (mm/h) 93/101 54/82 61/101 88/102 40/70 45/78 WBC (cells/µ) 29,000 13,600 12,000 20,500 21,000 15,410 NEU (cells/µ) 24,000 8,900 7,774 15,700 16,400 11,600 LYM (cells/µ) 3,260 3,200 3,600 3,400 3,800 3,450 PLT (x 10 3 cells/µ) 565 651 455 468 600 556 Ferritin (ng/mL) 214 194 205 245 213 196 LDH (UI/mL) 300 302 312 280 272 267 IL-6 (pg/mL) 5.34 14.5 N.A N.A N.A N.A D-dimer (ngFEU/mL) 788 650 675 2450 902 602 CRP (mg/L) 120 22.8 34.7 92 38 2.8 CK (UI/mL) 15 N.A N.A 31.2 9.4 13.3 ESR: erythrocyte sedimentation rate, WBC: white blood cell, NEU: neutrophils, LYM: lymphocyte, PLT: platelets, LDH: lactate dehydrogenase, IL-6: interleukin-6, CRP: C-reactive protein, CK: creatine kinase, N.A: not applicable The immunology profile taken on admission was unremarkable, with anti-nuclear antibody (ANA), double-stranded deoxyribonucleic acid (dsDNA), rheumatoid factor (RF), anti-streptolysin O, and anti-neutrophil cytoplasmic antibody (ANCA) were all negative. Complement C3 (1.7 g/L; ref. 0.9–1.8) and C4 (0.4 g/L; ref. 0.1–0.4) and IgG-4 (83 mg/dL; ref. 0.4–99.2) were in the normal range, while serum gammaglobulinemia (19 g/L; ref. 5.5–11.5) was increased. His microbiology investigations failed to detect mycoplasma pneumonia, tuberculosis, B hepatitis virus, Epstein-Barr virus, cytomegalovirus, human herpesvirus-6, human immunodeficiency virus, adenovirus, influenza virus, and coronavirus. The nasopharyngeal and blood cultures showed no growth of bacteria. Because of persistent leukocytosis, the bone marrow aspiration was obtained to exclude the malignant condition. With the clinical suspicion of PAN, the deep incisional skin biopsy taken from the subcutaneous nodule revealed leukocytoclastic and necrotizing vasculitis of the medium-sized arteries, particularly at the branch points. No malignant characteristics were seen (see Fig. 1 ). The Doppler ultrasonography and Computed Tomography Angiography (CTA) performed on general vessels showed normal structure and no thrombosis. The urinary analysis and peripheral electromyography of both upper and lower limbs confirmed spare lesions of kidney and nervous system. The child was diagnosed with cutaneous polyarteritis nodosa (cPAN) and was initially managed by intravenous corticosteroids (2 mg/kg/day) and subcutaneous methotrexate (15 mg/m 2 BSA/week). He eventually achieved a complete response regarding clinical signs and inflammatory markers and was switched to oral corticosteroid and methotrexate on day 7 for discharge. However, the patient presented to us again after 1-week maintenance with complaints of bilateral muscular painfulness and new-onset subcutaneous nodules of lower limbs. No other organ was involved by clinical examination, but the laboratory findings showed elevated inflammatory markers (see Table 1 ). Though CPK level and repeated electromyography were normal, MRI with the contrast agent showed multiple foci myositis of bilateral gluteal and femur regions (Fig. 2 ). Histological image of muscular biopsy presented neutrophil infiltration, debris, and endothelial swelling within a muscular artery wall. Occlusion and fibrinoid necrosis within damaged small-sized blood vessels were noted (Fig. 3 ). We checked the panel of the 18 myositis-specific antibodies that showed negative. Along with focal lesions of myositis and blocking of blood vessels as described, an increase in fibrinogen (6.79 g/L; ref. 1.89–4.75), D-dimer (2450 ng/mL; ref. <500), and aPTT (42 seconds, ref. 25.1–36.5) were found. Assessing the aPL antibodies profile exposed that the lupus anticoagulant was positive. This test was performed by an activated partial thromboplastin time assay, a dilute Russell Venom Viper Test (dRVVT), and confirmatory testing. In conjunction with pulsed cyclophosphamide (500 mg/m 2 BSA) and intravenous corticosteroid of 30 mg/kg/day for 3-consecutive days, the patient received subcutaneous enoxaparin doses of 1 mg/kg every 12 hours. His symptoms and laboratory findings completely resolved after the end of the therapy course (Table 1 ). Switching to aspirin, gradually tapering oral corticosteroid doses, and maintenance on methotrexate were given based on the above result. After 15 days of admission, he was discharged home and required regular follow-up in our outpatient clinic. Discussion Polyarteritis nodosa (PAN) is a rarely necrotizing vasculitis in childhood and is marked by the predominant inflammation of medium vessels affecting multiple organs. Antiphospholipid syndrome (APS) is an autoimmune disease characterized by the presence of aPL antibodies in the bloodstream, showing the risk of multi-organ involvement-induced thrombosis [ 15 ] [ 16 ]. The previous papers have described the co-incidence of aPL antibodies and PAN with worse outcomes; however, there is only a limited number of case reports [ 18 ] [ 19 ]. Here, we describe a case of PAN with the presence of aPL antibody manifesting with multifocal myositis. This report contributes to the current pediatric literature on the existence of aPL antibodies in PAN. It highlights the need for further investigations into pathophysiology insights and disease management. Any organ containing small or medium arteries can be involved in PAN [ 20 ]. According to the literature, the most commonly affected organs are the skin, gastrointestinal tract, kidneys, peripheral nerves, and muscles…[ 5 ] [ 9 ] [ 12 ]. Skeletal muscle manifestations are not uncommon in PAN, with a rate varying from 30–70% [ 20 ]. Musculoskeletal involvement in PAN may present in a limited form or a component of a systemic entity, including myalgia, arthralgia, polymyositis-like syndrome, asymmetric nondeforming polyarthritis, acute leg ischemia, or myopathy [ 11 ]. Among them, myalgia has been well documented in about 51% of PAN cases, while myositis is a rare form of scenario [ 12 ]. The high incidence of myalgia is in line with the common involvement of intramuscular arteries and the peripheral nervous system in PAN [ 7 ] [ 12 ]. Patients with myositis-associated PAN usually present with symmetrical, proximal muscle weakness prominently in the lower extremities [ 7 ] [ 13 ] [ 14 ] [ 20 ] [ 21 ]. The probable underlying pathophysiology of myositis in PAN can be explained by an overwhelming immune-inflammatory infiltration and ischemia due to the occlusion of blood vessels supplying the muscles [ 13 ] [ 14 ]. In the presenting case, muscular fiber necrosis, mixed leuko-infiltration, and occlusion of small-sized blood vessels were presented histologically, in line with the suspected theory. The normal CKP level presents one peculiarity in our report. Elevated CPK levels account for only 2–5% of cases, while elevated LDH and aldolase have been reported in some cases [ 22 ] [ 13 ]. The popularity of a normal CPK level can overshadow a suspicion of myositis, for which we suggested the pivotal role of muscular MRI or biopsy in evaluating the lesion. Myositis in PAN has been described as a diffuse or focal form, which might suggest the underlying mechanisms of the lesion [ 7 ] [ 8 ] [ 14 ]. Antiphospholipid syndrome (APS) is an autoimmune disease characterized by the presence of antiphospholipid antibodies, including lupus anticoagulant, anticardiolipin antibodies, and anti-β2-glycoprotein-1 antibodies [ 15 ]. The literature mentions the rare coexistence of the antiphospholipid syndrome and systemic vasculitis, such as polyarteritis nodosa (PAN), giant cell arteritis (GCA), Takayasu's arteritis, and Behcet's syndrome [ 17 ]. The presence of aPL antibodies in vasculitis might be hypothesized as the endothelial cell disruption occurring in vasculitis, which presents immunologically hidden antigens and stimulates anti-endothelial antibodies [ 17 ]. Therefore, we emphasize that general testing for aPL antibodies should be undergone in patients with PAN, as well as other systemic vasculitis. The severity of illness with both conditions might be more acute and organ-threatening, suggesting the resonant risk of occlusive vasculopathy associated with the presence of aPL antibodies [ 17 ] [ 18 ]. In our case, the existence of aPL may account for the occlusion of small-sized blood vessels in the muscular biopsy, in line with focal rather than diffuse myositis in the illustrated MRI. Nung-Hoang et al. reported a PAN case with aPL positivity that presented as acute deterioration of renal function and then responded well to immunosuppression and anticoagulation combination [ 23 ]. Similarly, some case reports described central nervous system damage in PAN with the high anticardiolipin antibody [ 24 ] [ 25 ]. While many reports reinforce the critical role of aPL in worsening thrombosis events [ 2 ] [ 18 ] [ 26 ] [ 27 ], the intriguing question is whether clinical outcomes are favorable if anticoagulation therapy is administered. This point underlines the difficulties in clinical decision-making regarding the anticoagulation options and duration in managing this complex situation. According to the pathophysiology, we accentuated the need for integrative therapy in PAN cases with aPL antibodies coexistence, including immunosuppression to limit muscular damage in the inflammatory response and anticoagulation therapy to reduce further lesions due to thrombosis events. However, there remains not enough evidence-based data on treatment and outcome of this picture; further well-designed investigations on this issue are necessary. Conclusions We describe a case of PAN with the presence of aPL antibody manifesting with multifocal myositis. It is recommended that general testing for aPL antibodies should be undergone in patients with PAN, as well as other systemic vasculitis. Despite unusual co-incidence, aPL antibodies might worsen systemic vasculitis through thrombotic events, which clinicians should consider adequate coagulant therapeutics besides immunosuppressors. Abbreviations PAN Polyarteritis nodosa aPL Antiphospholipid CPK Creatine phosphokinase BSA Body surface area MRI Magnetic resonant imaging DADA2 Deficiency of adenosine deaminase 2 ANCA Antineutrophilic cytoplasmic antibody APS Antiphospholipid syndrome ESR Erythrocyte sedimentation rate WBC white blood cells NEU Neutrophil cells LYM Lymphocyte CRP C-reactive protein LDH Lactate dehydrogenase PT/INR Prothrombin time/international normalized ratio ANA Anti-nuclear antibody dsDNA double-stranded deoxyribonucleic acid RF Rheumatoid factor C3 Complement 3 C4 Complement 4 CTA Computed Tomography Angiography cPAN Cutaneous polyarteritis nodosa aPTT Activated partial thromboplastin time dRVV Dilute Russell Venom Viper Test Declarations Acknowledgments The authors thank all medical and nursing staff of the Immunology, Allergy, and Rheumatology Department of the Vietnam National Children’s Hospital. Author Contributions HTTN, AVTN, and CQL provided the concept for the study and were major contributors to the manuscript revision. GDN and HTTN were involved in the patient care and collected the data regarding the patient’s history, clinical course, and the trends in vital parameters. TNH collected, prepared, and researched the biopsy samples. HTTN reviewed the literature and drafted the manuscript. All authors read and approved the final manuscript. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Availability of data and materials The datasets used during the current study are available from the corresponding author upon reasonable request. Ethics approval and consent to participate The study complied with the Declaration of Helsinki and was approved by the Institutional Review Board of Vietnam National Children's Hospital. Written informed consent to participate in this study was provided by the participant’s legal guardian/next of kin. Consent for publication Informed written consent for patient information and images to be published was obtained from the participant's legal guardian/next of kin. Competing interests The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. References De Virgilio A, Greco A, Magliulo G, Gallo A, Ruoppolo G, Conte M, et al. Polyarteritis nodosa: A contemporary overview. Autoimmunity Reviews. 2016;15:564–70. Watts RA, Hatemi G, Burns JC, Mohammad AJ. Global epidemiology of vasculitis. Nat Rev Rheumatol. 2022;18:22–34. Navab R, Yeragudi Jangamareddy VR, Midthala NV, Kamalakannan T. A Young Female Case of Polyarteritis Nodosa Presenting With Multisystem Involvement and Acute Abdomen: A Case Report. Cureus. 13:e20778. Hočevar A, Tomšič M, Perdan Pirkmajer K. Clinical Approach to Diagnosis and Therapy of Polyarteritis Nodosa. Curr Rheumatol Rep. 2021;23:14. Tekgöz N, Aydın F, Kurt T, Sezer M, Tekin Z, Karagöl C, et al. Clinical features and outcomes of childhood polyarteritis nodosa: A single referral center experience. Modern Rheumatology. 2021;31:1142–7. Ozaltin F, Ozen S. Childhood Polyarteritis Nodosa. In: Elzouki AY, Harfi HA, Nazer HM, Stapleton FB, Oh W, Whitley RJ, editors. Textbook of Clinical Pediatrics. Berlin, Heidelberg: Springer; 2012. p. 1685–7. Kang Y, Hong SH, Yoo HJ, Choi J-Y, Park JK, Park J, et al. Muscle Involvement in Polyarteritis Nodosa: Report of Eight Cases With Characteristic Contrast Enhancement Pattern on MRI. American Journal of Roentgenology. 2016;206:378–84. Calvo R, Negri M, Ortiz A, Roverano S, Paira S. Myositis as the Initial Presentation of Panarteritis Nodosa. Reumatol Clin. 2019;15:e24–6. Erden A, Batu ED, Sönmez HE, Sarı A, Armagan B, Arıcı ZS, et al. 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S, De Silva PUT, Weerarathna TP. Severe Disabling Myalgia as an Initial Presentation of Polyarteritis Nodosa. Case Reports in Rheumatology. 2019;2019:e4364289. Huang M-N, Wu C-H. Polyarteritis Nodosa and Antiphospholipid Syndrome Causing Bilateral Renal Infarction. J Rheumatol. 2009;36:197–197. de la Fuente Fernandez R, Graña Gil J. Anticardiolipin antibodies and polyarteritis nodosa. Lupus. 1994;3:523–4. Han BK, Inaganti K, Fahmi S, Reimold A. Polyarteritis nodosa complicated by catastrophic antiphospholipid syndrome. J Clin Rheumatol. 2004;10:210–3. Caldas CAM, de Carvalho JF. Antiphospholipid syndrome and polyarteritis nodosa: a diagnostic and therapeutic challenge. Rheumatol Int. 2013;33:2697–8. Miller S, Miller E, Khalidi N. Catastrophic Antiphospholipid Syndrome and Polyarteritis Nodosa. The Journal of Rheumatology. 2009;36:2619–21. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4108739","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":283170212,"identity":"315970d3-e1df-41c8-84df-588c82a139f0","order_by":0,"name":"Ha Nguyen Thi Thu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzUlEQVRIiWNgGAWjYFACHjYgcYCBgb0BSBtYEKGDDaaF5wBIiwQpWiQSQFwitJjL9x578IPhTrTBzedXN/wokGDgb+9OwKvFso0v3bCH4Vnuhts5ZTd7gA6TOHN2A14tBsd4zCR4GA6DtKTd4AFqMZDIJaxF8g9Iy80zaTf/EKtFGmzLDfZjt4m0JcdMWsbgcO7MMzlst2UMJHgI++XwGTPJNxWHc/uOH392880fGzn+9l78WqAaQQQPhCRCORywPyBF9SgYBaNgFIwgAADIlklS4f7AYQAAAABJRU5ErkJggg==","orcid":"","institution":"Vietnam National Children’s Hospital","correspondingAuthor":true,"prefix":"","firstName":"Ha","middleName":"Nguyen Thi","lastName":"Thu","suffix":""},{"id":283170213,"identity":"76135d8f-e8b8-4bc6-a18c-3359858cdeca","order_by":1,"name":"Chi Quynh Le","email":"","orcid":"","institution":"Vietnam National Children’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Chi","middleName":"Quynh","lastName":"Le","suffix":""},{"id":283170214,"identity":"7eee3d93-1294-4faa-bdc3-d45bea992524","order_by":2,"name":"Thach Ngoc Hoang","email":"","orcid":"","institution":"Vietnam National Children’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Thach","middleName":"Ngoc","lastName":"Hoang","suffix":""},{"id":283170215,"identity":"71cecda6-99e1-4622-8701-0d08e2549bbe","order_by":3,"name":"Giang Dinh Nguyen","email":"","orcid":"","institution":"Vietnam National Children’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Giang","middleName":"Dinh","lastName":"Nguyen","suffix":""},{"id":283170216,"identity":"ddc72724-da2d-4ef4-b914-6fe54de1bd6d","order_by":4,"name":"Anh Nguyen Thi Van","email":"","orcid":"","institution":"Vietnam National Children’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Anh","middleName":"Nguyen Thi","lastName":"Van","suffix":""}],"badges":[],"createdAt":"2024-03-15 14:46:51","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4108739/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4108739/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":53678812,"identity":"de5c3f03-388b-4b1e-b328-294e70d62f82","added_by":"auto","created_at":"2024-03-28 19:50:55","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1183914,"visible":true,"origin":"","legend":"\u003cp\u003eThe deep dermis and subcutaneous tissue showed neutrophilic infiltration with prominent debris around medium-sized vessels and branch points of vessels. Fibrinoid necrosis within vessel walls, endothelial swelling, and thrombi are present. Granulomatous inflammation and neoplastic lesions were absent (40x).\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4108739/v1/18fcb3025d41fe6e0f8fb074.png"},{"id":53678810,"identity":"0818c078-cd05-408e-8300-39b573248caf","added_by":"auto","created_at":"2024-03-28 19:50:55","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":382426,"visible":true,"origin":"","legend":"\u003cp\u003eMRI with the contrast agent showed multiple foci myositis of bilateral gluteal and femur regions.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4108739/v1/468b24f11b2f1c4d165ba1ec.png"},{"id":53678814,"identity":"39cbe74a-966d-4552-8aae-d3ffbd6146ae","added_by":"auto","created_at":"2024-03-28 19:50:58","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1317564,"visible":true,"origin":"","legend":"\u003cp\u003eHistological image of muscular biopsy presented neutrophil infiltration, debris, and endothelial swelling within a muscular artery wall. Occlusion and fibrinoid necrosis within damaged small-sized blood vessels were noted (40x).\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-4108739/v1/f1baa1c024c039548814b426.png"},{"id":62850915,"identity":"b6054a58-546a-4e6a-998d-b3928df99fc2","added_by":"auto","created_at":"2024-08-20 08:31:13","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3692116,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4108739/v1/6fbb2805-079d-4a7a-891f-cb30f087b12c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A Case of Polyarteritis Nodosa with Positive Anti-Phospholipid Antibodies Presenting with Multifocal Myositis","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePolyarteritis nodosa (PAN) is a necrotizing, focal segmental vasculitis predominantly affecting medium-sized arteries without glomerulonephritis or vasculitis in arterioles, venules, or capillaries [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The incidence of PAN is around 0.9-8.0 cases per million in European countries and peaks at the ages of 40 to 50, with a male-to-female ratio of 2:1 [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Although epidemiological data on childhood-onset PAN is scarce, the disease is known to be comparatively rare and related to a newly discovered monogenic disease, deficiency of adenosine deaminase 2 (DADA2) in children [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePAN can present a broad spectrum of manifestations with multiple organ systems, including the skin, gastrointestinal tract, kidney, nervous system, and muscles\u0026hellip;[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. With spare lesions of the lung, the disease most commonly targets the peripheral nervous system and the skin and is distinctive to the antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Musculoskeletal involvement in PAN may present in a limited form or a component of a systemic entity, including myalgia, arthralgia, polymyositis-like syndrome, asymmetric nondeforming polyarthritis, acute leg ischemia, or myopathy [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The pathophysiology of muscular manifestations in PAN might be ischemia due to compromised intramuscular arteries, neuropathy of the peripheral nervous system, or, more rarely, myositis [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Myositis in PAN has been described as a diffuse or focal form, which might suggest the underlying mechanisms of the lesion [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAntiphospholipid syndrome (APS) is an autoimmune disease characterized by the presence of antiphospholipid antibodies, including lupus anticoagulant, anticardiolipin antibodies, and anti-β2-glycoprotein-1 antibodies [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The hallmark pathophysiology of APS is thrombosis, inducing a variety of clinical phenotypes, including occlusion in the veins, arteries, and microvasculature, as well as obstetrical complications [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The rare coexistence of the antiphospholipid syndrome and systemic vasculitis, such as polyarteritis nodosa (PAN), giant cell arteritis, Takayasu's arteritis, and Behcet's syndrome, have been documented in the literature [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The presence of aPL antibodies in vasculitis might be hypothesized as the endothelial cell disruption occurring in vasculitis, which presents immunologically hidden antigens and stimulates anti-endothelial antibodies [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The coincidence of PAN and APS has also been described mainly just case by case. The severity of illness with both conditions might be more acute and organ-threatening, suggesting the resonant risk of occlusive vasculopathy associated with aPL antibodies [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Besides the mainstay of immunosuppressors, therapeutic dilemmas with prophylactic anticoagulation for preventing thrombosis should be considered in such cases.\u003c/p\u003e \u003cp\u003eHere, we describe a case of PAN with the presence of aPL antibody manifesting with multifocal myositis. This report contributes to the current pediatric literature on the existence of aPL antibodies in PAN and highlights the need for further investigations into this issue. It is recommended that general testing for aPL antibodies should be undergone in patients with PAN, as well as other systemic vasculitis. Despite unusual co-incidence, aPL antibodies might worsen systemic vasculitis through thrombotic events, which clinicians should consider adequate coagulant therapeutics besides immunosuppressors.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA previously healthy 7-year-old boy suffered from a high-grade fever (39\u0026deg;C), painful subcutaneous nodules, and bilateral ankle arthritis for 14 days prior to hospitalization. His parents denied any history of purpura, Raynaud\u0026apos;s phenomenon, oral ulcers, and hair loss. With suspected cutaneous infection, he was put on a seven-day-course oral oxacillin, but the symptoms were not resolved.\u003c/p\u003e\n\u003cp\u003eOn initial examination at admission, the patient appeared to have normal vital signs, with a blood pressure of 115/65 mmHg and a heart rate of 95 beats per minute. He had good air entry to both lungs and no crackle on respiratory examination. Multiple palpable subcutaneous nodules are predominantly positioned over both the lower limbs. Hepatosplenomegaly sign or lymph node enlargement and livedo reticularis were absent.\u003c/p\u003e\n\u003cp\u003eInitial blood tests revealed a remarkable elevation in inflammatory markers, including erythrocyte sedimentation rate (ESR), 93 mm/1st hour and 101 mm/2nd hour (ref. 3\u0026ndash;13); white blood cells (WBC), 29,000 cells/\u0026micro;l (ref. 4\u0026ndash;10); neutrophil cells (NEU), 24,000 cells/\u0026micro;l (ref. 4\u0026ndash;10); lymphocyte (LYM) 3260 cells/\u0026micro;l (ref. 4\u0026ndash;10); C-reactive protein (CRP), 120 mg/L (ref. \u0026lt;6); lactate dehydrogenase (LDH), 300 U/L (ref. \u0026lt;266 U/L); and ferritin, 214 ng/mL (ref. \u0026lt;140). The cogulation profile presented as following: prothrombin time/international normalized ratio (PT/INR), 1.19 (ref. 0.87\u0026ndash;1.2); fibrinogen, 4.79 g/L (ref. 1.89\u0026ndash;4.75); activated partial thromboplastin time (aPTT), 38 seconds, (ref. 25.1\u0026ndash;36.5); D-dimer, 788 ng/mL (ref. \u0026lt;500); protein C, 100.5 UI/mL (ref. 45.9-153.5); protein S, 110 UI/mL (ref. 66.5-161.5); and antithrombin III, 97 UI/mL (ref. 64.2-136.4). Other laboratory investigations were insignificant, as described in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eLaboratory results\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"7\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eParameters\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAdmission 1\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDay 3\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDay 7\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAdmission 2\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDay 5\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDischarge\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eESR \u003cem\u003e(mm/h)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e93/101\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e54/82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e61/101\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e88/102\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40/70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e45/78\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWBC \u003cem\u003e(cells/\u0026micro;)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29,000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13,600\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12,000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20,500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21,000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15,410\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNEU \u003cem\u003e(cells/\u0026micro;)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24,000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8,900\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7,774\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15,700\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16,400\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11,600\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLYM \u003cem\u003e(cells/\u0026micro;)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3,260\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3,200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3,600\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3,400\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3,800\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3,450\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePLT \u003cem\u003e(x\u003c/em\u003e 10\u003csup\u003e3\u003c/sup\u003e \u003cem\u003ecells/\u0026micro;)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e565\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e651\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e455\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e468\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e600\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e556\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFerritin \u003cem\u003e(ng/mL)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e214\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e194\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e205\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e245\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e213\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e196\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLDH \u003cem\u003e(UI/mL)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e300\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e302\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e312\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e280\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e272\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e267\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIL-6 \u003cem\u003e(pg/mL)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN.A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN.A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN.A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN.A\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eD-dimer \u003cem\u003e(ngFEU/mL)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e788\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e650\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e675\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2450\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e902\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e602\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCRP \u003cem\u003e(mg/L)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e120\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCK \u003cem\u003e(UI/mL)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN.A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN.A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\"\u003e\u003cem\u003eESR: erythrocyte sedimentation rate, WBC: white blood cell, NEU: neutrophils, LYM: lymphocyte, PLT: platelets, LDH: lactate dehydrogenase, IL-6: interleukin-6, CRP: C-reactive protein, CK: creatine kinase, N.A: not applicable\u003c/em\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eThe immunology profile taken on admission was unremarkable, with anti-nuclear antibody (ANA), double-stranded deoxyribonucleic acid (dsDNA), rheumatoid factor (RF), anti-streptolysin O, and anti-neutrophil cytoplasmic antibody (ANCA) were all negative. Complement C3 (1.7 g/L; ref. 0.9\u0026ndash;1.8) and C4 (0.4 g/L; ref. 0.1\u0026ndash;0.4) and IgG-4 (83 mg/dL; ref. 0.4\u0026ndash;99.2) were in the normal range, while serum gammaglobulinemia (19 g/L; ref. 5.5\u0026ndash;11.5) was increased. His microbiology investigations failed to detect mycoplasma pneumonia, tuberculosis, B hepatitis virus, Epstein-Barr virus, cytomegalovirus, human herpesvirus-6, human immunodeficiency virus, adenovirus, influenza virus, and coronavirus. The nasopharyngeal and blood cultures showed no growth of bacteria. Because of persistent leukocytosis, the bone marrow aspiration was obtained to exclude the malignant condition.\u003c/p\u003e\n\u003cp\u003eWith the clinical suspicion of PAN, the deep incisional skin biopsy taken from the subcutaneous nodule revealed leukocytoclastic and necrotizing vasculitis of the medium-sized arteries, particularly at the branch points. No malignant characteristics were seen (see Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eThe Doppler ultrasonography and Computed Tomography Angiography (CTA) performed on general vessels showed normal structure and no thrombosis. The urinary analysis and peripheral electromyography of both upper and lower limbs confirmed spare lesions of kidney and nervous system. The child was diagnosed with cutaneous polyarteritis nodosa (cPAN) and was initially managed by intravenous corticosteroids (2 mg/kg/day) and subcutaneous methotrexate (15 mg/m\u003csup\u003e2\u003c/sup\u003e BSA/week). He eventually achieved a complete response regarding clinical signs and inflammatory markers and was switched to oral corticosteroid and methotrexate on day 7 for discharge.\u003c/p\u003e\n\u003cp\u003eHowever, the patient presented to us again after 1-week maintenance with complaints of bilateral muscular painfulness and new-onset subcutaneous nodules of lower limbs. No other organ was involved by clinical examination, but the laboratory findings showed elevated inflammatory markers (see Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Though CPK level and repeated electromyography were normal, MRI with the contrast agent showed multiple foci myositis of bilateral gluteal and femur regions (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eHistological image of muscular biopsy presented neutrophil infiltration, debris, and endothelial swelling within a muscular artery wall. Occlusion and fibrinoid necrosis within damaged small-sized blood vessels were noted (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eWe checked the panel of the 18 myositis-specific antibodies that showed negative. Along with focal lesions of myositis and blocking of blood vessels as described, an increase in fibrinogen (6.79 g/L; ref. 1.89\u0026ndash;4.75), D-dimer (2450 ng/mL; ref. \u0026lt;500), and aPTT (42 seconds, ref. 25.1\u0026ndash;36.5) were found. Assessing the aPL antibodies profile exposed that the lupus anticoagulant was positive. This test was performed by an activated partial thromboplastin time assay, a dilute Russell Venom Viper Test (dRVVT), and confirmatory testing.\u003c/p\u003e\n\u003cp\u003eIn conjunction with pulsed cyclophosphamide (500 mg/m\u003csup\u003e2\u003c/sup\u003e BSA) and intravenous corticosteroid of 30 mg/kg/day for 3-consecutive days, the patient received subcutaneous enoxaparin doses of 1 mg/kg every 12 hours. His symptoms and laboratory findings completely resolved after the end of the therapy course (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Switching to aspirin, gradually tapering oral corticosteroid doses, and maintenance on methotrexate were given based on the above result. After 15 days of admission, he was discharged home and required regular follow-up in our outpatient clinic.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003ePolyarteritis nodosa (PAN) is a rarely necrotizing vasculitis in childhood and is marked by the predominant inflammation of medium vessels affecting multiple organs. Antiphospholipid syndrome (APS) is an autoimmune disease characterized by the presence of aPL antibodies in the bloodstream, showing the risk of multi-organ involvement-induced thrombosis [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The previous papers have described the co-incidence of aPL antibodies and PAN with worse outcomes; however, there is only a limited number of case reports [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Here, we describe a case of PAN with the presence of aPL antibody manifesting with multifocal myositis. This report contributes to the current pediatric literature on the existence of aPL antibodies in PAN. It highlights the need for further investigations into pathophysiology insights and disease management.\u003c/p\u003e \u003cp\u003eAny organ containing small or medium arteries can be involved in PAN [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. According to the literature, the most commonly affected organs are the skin, gastrointestinal tract, kidneys, peripheral nerves, and muscles\u0026hellip;[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Skeletal muscle manifestations are not uncommon in PAN, with a rate varying from 30\u0026ndash;70% [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Musculoskeletal involvement in PAN may present in a limited form or a component of a systemic entity, including myalgia, arthralgia, polymyositis-like syndrome, asymmetric nondeforming polyarthritis, acute leg ischemia, or myopathy [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Among them, myalgia has been well documented in about 51% of PAN cases, while myositis is a rare form of scenario [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The high incidence of myalgia is in line with the common involvement of intramuscular arteries and the peripheral nervous system in PAN [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Patients with myositis-associated PAN usually present with symmetrical, proximal muscle weakness prominently in the lower extremities [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe probable underlying pathophysiology of myositis in PAN can be explained by an overwhelming immune-inflammatory infiltration and ischemia due to the occlusion of blood vessels supplying the muscles [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. In the presenting case, muscular fiber necrosis, mixed leuko-infiltration, and occlusion of small-sized blood vessels were presented histologically, in line with the suspected theory. The normal CKP level presents one peculiarity in our report. Elevated CPK levels account for only 2\u0026ndash;5% of cases, while elevated LDH and aldolase have been reported in some cases [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The popularity of a normal CPK level can overshadow a suspicion of myositis, for which we suggested the pivotal role of muscular MRI or biopsy in evaluating the lesion. Myositis in PAN has been described as a diffuse or focal form, which might suggest the underlying mechanisms of the lesion [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAntiphospholipid syndrome (APS) is an autoimmune disease characterized by the presence of antiphospholipid antibodies, including lupus anticoagulant, anticardiolipin antibodies, and anti-β2-glycoprotein-1 antibodies [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The literature mentions the rare coexistence of the antiphospholipid syndrome and systemic vasculitis, such as polyarteritis nodosa (PAN), giant cell arteritis (GCA), Takayasu's arteritis, and Behcet's syndrome [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The presence of aPL antibodies in vasculitis might be hypothesized as the endothelial cell disruption occurring in vasculitis, which presents immunologically hidden antigens and stimulates anti-endothelial antibodies [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Therefore, we emphasize that general testing for aPL antibodies should be undergone in patients with PAN, as well as other systemic vasculitis. The severity of illness with both conditions might be more acute and organ-threatening, suggesting the resonant risk of occlusive vasculopathy associated with the presence of aPL antibodies [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. In our case, the existence of aPL may account for the occlusion of small-sized blood vessels in the muscular biopsy, in line with focal rather than diffuse myositis in the illustrated MRI. Nung-Hoang et al. reported a PAN case with aPL positivity that presented as acute deterioration of renal function and then responded well to immunosuppression and anticoagulation combination [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Similarly, some case reports described central nervous system damage in PAN with the high anticardiolipin antibody [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. While many reports reinforce the critical role of aPL in worsening thrombosis events [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e], the intriguing question is whether clinical outcomes are favorable if anticoagulation therapy is administered. This point underlines the difficulties in clinical decision-making regarding the anticoagulation options and duration in managing this complex situation.\u003c/p\u003e \u003cp\u003eAccording to the pathophysiology, we accentuated the need for integrative therapy in PAN cases with aPL antibodies coexistence, including immunosuppression to limit muscular damage in the inflammatory response and anticoagulation therapy to reduce further lesions due to thrombosis events. However, there remains not enough evidence-based data on treatment and outcome of this picture; further well-designed investigations on this issue are necessary.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eWe describe a case of PAN with the presence of aPL antibody manifesting with multifocal myositis. It is recommended that general testing for aPL antibodies should be undergone in patients with PAN, as well as other systemic vasculitis. Despite unusual co-incidence, aPL antibodies might worsen systemic vasculitis through thrombotic events, which clinicians should consider adequate coagulant therapeutics besides immunosuppressors.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePAN\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePolyarteritis nodosa\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eaPL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAntiphospholipid\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCPK\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCreatine phosphokinase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBSA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBody surface area\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMRI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMagnetic resonant imaging\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eDADA2\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eDeficiency of adenosine deaminase 2\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eANCA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAntineutrophilic cytoplasmic antibody\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAPS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAntiphospholipid syndrome\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eESR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eErythrocyte sedimentation rate\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eWBC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ewhite blood cells\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNEU\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNeutrophil cells\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLYM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLymphocyte\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCRP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eC-reactive protein\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLDH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLactate dehydrogenase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePT/INR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eProthrombin time/international normalized ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eANA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAnti-nuclear antibody\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003edsDNA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003edouble-stranded deoxyribonucleic acid\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eRheumatoid factor\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eC3\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eComplement 3\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eC4\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eComplement 4\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCTA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eComputed Tomography Angiography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ecPAN\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCutaneous polyarteritis nodosa\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eaPTT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eActivated partial thromboplastin time\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003edRVV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eDilute Russell Venom Viper Test\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank all medical and nursing staff of the Immunology, Allergy, and Rheumatology Department of the Vietnam National Children\u0026rsquo;s Hospital.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHTTN, AVTN, and CQL provided the concept for the study and were major contributors to the manuscript revision. GDN and HTTN were involved in the patient care and collected the data regarding the patient\u0026rsquo;s history, clinical course, and the trends in vital parameters. TNH collected, prepared, and researched the biopsy samples. HTTN reviewed the literature and drafted the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study complied with the Declaration of Helsinki and was approved by the Institutional Review Board of Vietnam National Children\u0026apos;s Hospital. Written informed consent to participate in this study was provided by the participant\u0026rsquo;s legal guardian/next of kin.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed written consent for patient information and images to be published was obtained from the participant\u0026apos;s legal guardian/next of kin.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eDe Virgilio A, Greco A, Magliulo G, Gallo A, Ruoppolo G, Conte M, et al. Polyarteritis nodosa: A contemporary overview. Autoimmunity Reviews. 2016;15:564\u0026ndash;70.\u003c/li\u003e\n\u003cli\u003eWatts RA, Hatemi G, Burns JC, Mohammad AJ. Global epidemiology of vasculitis. Nat Rev Rheumatol. 2022;18:22\u0026ndash;34.\u003c/li\u003e\n\u003cli\u003eNavab R, Yeragudi Jangamareddy VR, Midthala NV, Kamalakannan T. A Young Female Case of Polyarteritis Nodosa Presenting With Multisystem Involvement and Acute Abdomen: A Case Report. Cureus. 13:e20778.\u003c/li\u003e\n\u003cli\u003eHočevar A, Tom\u0026scaron;ič M, Perdan Pirkmajer K. Clinical Approach to Diagnosis and Therapy of Polyarteritis Nodosa. Curr Rheumatol Rep. 2021;23:14.\u003c/li\u003e\n\u003cli\u003eTekg\u0026ouml;z N, Aydın F, Kurt T, Sezer M, Tekin Z, Karag\u0026ouml;l C, et al. Clinical features and outcomes of childhood polyarteritis nodosa: A single referral center experience. Modern Rheumatology. 2021;31:1142\u0026ndash;7.\u003c/li\u003e\n\u003cli\u003eOzaltin F, Ozen S. Childhood Polyarteritis Nodosa. In: Elzouki AY, Harfi HA, Nazer HM, Stapleton FB, Oh W, Whitley RJ, editors. Textbook of Clinical Pediatrics. Berlin, Heidelberg: Springer; 2012. p. 1685\u0026ndash;7.\u003c/li\u003e\n\u003cli\u003eKang Y, Hong SH, Yoo HJ, Choi J-Y, Park JK, Park J, et al. Muscle Involvement in Polyarteritis Nodosa: Report of Eight Cases With Characteristic Contrast Enhancement Pattern on MRI. American Journal of Roentgenology. 2016;206:378\u0026ndash;84.\u003c/li\u003e\n\u003cli\u003eCalvo R, Negri M, Ortiz A, Roverano S, Paira S. Myositis as the Initial Presentation of Panarteritis Nodosa. Reumatol Clin. 2019;15:e24\u0026ndash;6.\u003c/li\u003e\n\u003cli\u003eErden A, Batu ED, S\u0026ouml;nmez HE, Sarı A, Armagan B, Arıcı ZS, et al. Comparing polyarteritis nodosa in children and adults: a single center study. Int J of Rheum Dis. 2017;20:1016\u0026ndash;22.\u003c/li\u003e\n\u003cli\u003eLee J-S, Kim J-G, Lee S. Clinical presentations and long term prognosis of childhood onset polyarteritis nodosa in single centre of Korea. Sci Rep. 2021;11:8393.\u003c/li\u003e\n\u003cli\u003eSong SO, Lee RW, Lim MJ, Kwon SR, Park W. A Rare Case of Limited Muscle Involvement in Polyarteritis Nodosa. Investigative Magnetic Resonance Imaging. 2021;25:53\u0026ndash;8.\u003c/li\u003e\n\u003cli\u003eCam\u0026otilde;es S. Polyarteritis Nodosa: A Rare Form of Presentation. BJSTR. 2018;6.\u003c/li\u003e\n\u003cli\u003eHan IJ, Jeong CH, Choi H. Polyarteritis nodosa initially presenting as concomitant peripheral neuropathy and myositis in unilateral limb: A case report. Medicine (Baltimore). 2023;102:e34335.\u003c/li\u003e\n\u003cli\u003ePrada LP, Garc\u0026iacute;a FA, P\u0026aacute;ez HD, M\u0026eacute;ndez PA, Quintana G, Coral PX. Multifocal myopathy in a patient with polyarteritis nodosa; usefulness of magnetic nuclear resonance as a diagnostic test. Rev Colomb Reumatol. 2019;26:63\u0026ndash;7.\u003c/li\u003e\n\u003cli\u003eSchreiber K, Sciascia S, de Groot PG, Devreese K, Jacobsen S, Ruiz-Irastorza G, et al. Antiphospholipid syndrome. Nat Rev Dis Primers. 2018;4:1\u0026ndash;20.\u003c/li\u003e\n\u003cli\u003eLim W. Antiphospholipid syndrome. Hematology. 2013;2013:675\u0026ndash;80.\u003c/li\u003e\n\u003cli\u003eNorden DK, Ostrov BE, Shafritz AB, Von Feldt JM. Vasculitis associated with antiphospholipid syndrome. Seminars in Arthritis and Rheumatism. 1995;24:273\u0026ndash;81.\u003c/li\u003e\n\u003cli\u003eDe La Fuente Fernandez R, Gil JG. Anticardiolipin Antibodies and Polyarteritis Nodosa. Lupus. 1994;3:523\u0026ndash;4.\u003c/li\u003e\n\u003cli\u003eMusuruana JL, Cavallasca JA. Polyarteritis nodosa complicated by antiphospholipid syndrome. South Med J. 2008;101:419\u0026ndash;21.\u003c/li\u003e\n\u003cli\u003ePlumley SG, Rubio R, Alasfar S, Jasin HE. Polyarteritis nodosa presenting as polymyositis. Seminars in Arthritis and Rheumatism. 2002;31:377\u0026ndash;83.\u003c/li\u003e\n\u003cli\u003eGaneshanandan LR, Brusch AM, Dyke JM, McLean-Tooke APC. Polyarteritis nodosa isolated to muscles-A case series with a review of the literature. Seminars in Arthritis and Rheumatism. 2020;50:503\u0026ndash;8.\u003c/li\u003e\n\u003cli\u003eSenarathna HM, Fonseka CL, Perera H a. S, De Silva PUT, Weerarathna TP. Severe Disabling Myalgia as an Initial Presentation of Polyarteritis Nodosa. Case Reports in Rheumatology. 2019;2019:e4364289.\u003c/li\u003e\n\u003cli\u003eHuang M-N, Wu C-H. Polyarteritis Nodosa and Antiphospholipid Syndrome Causing Bilateral Renal Infarction. J Rheumatol. 2009;36:197\u0026ndash;197.\u003c/li\u003e\n\u003cli\u003ede la Fuente Fernandez R, Gra\u0026ntilde;a Gil J. Anticardiolipin antibodies and polyarteritis nodosa. Lupus. 1994;3:523\u0026ndash;4.\u003c/li\u003e\n\u003cli\u003eHan BK, Inaganti K, Fahmi S, Reimold A. Polyarteritis nodosa complicated by catastrophic antiphospholipid syndrome. J Clin Rheumatol. 2004;10:210\u0026ndash;3.\u003c/li\u003e\n\u003cli\u003eCaldas CAM, de Carvalho JF. Antiphospholipid syndrome and polyarteritis nodosa: a diagnostic and therapeutic challenge. Rheumatol Int. 2013;33:2697\u0026ndash;8.\u003c/li\u003e\n\u003cli\u003eMiller S, Miller E, Khalidi N. Catastrophic Antiphospholipid Syndrome and Polyarteritis Nodosa. The Journal of Rheumatology. 2009;36:2619\u0026ndash;21.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"antiphospholipid, polyarteritis nodosa, vasculitis, myositis","lastPublishedDoi":"10.21203/rs.3.rs-4108739/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4108739/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003ePolyarteritis nodosa (PAN) is a rarely necrotizing vasculitis in childhood and is characterized by the inflammation of small and medium vessels affecting multiple organs. Although the presence of antiphospholipid (aPL) antibodies in PAN has been documented, there is limited data on the prevalence and understanding of pathogenesis and management for such co-incidence.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation: \u003c/strong\u003eWe herein reported that a 7-year-old boy without significant past medical history presented initially with high-grade fever, painful subcutaneous nodules, and ankle arthritis for 14 days prior to hospitalization. Biological findings revealed increased acute inflammatory biomarkers and no evidence of infection. The deep skin biopsy taken from the subcutaneous nodule proved leukocytoclastic medium-sized vasculitis suggestive of the PAN diagnosis. He eventually achieved a complete response with the use of intravenous corticosteroids (2 mg/kg/day) and subcutaneous methotrexate (15 mg/m2 body surface area (BSA)/week). However, the patient developed painfulness of bilateral proximal muscles and new-onset subcutaneous nodules of lower limbs after 1-week maintenance. Though the creatine phosphokinase (CPK) level was normal, the magnetic resonant imaging (MRI) showed multiple foci myositis of bilateral gluteal and femur regions. The serum level of D-dimer was remarkably elevated, and the lupus anticoagulant was positive. A combination of subcutaneous enoxaparin and pulsed cyclophosphamide (500 mg/m2 BSA) and three-day methylprednisolone (30 mg/kg/day) have contributed to a favorable outcome in this case. She further sustained remission on maintenance of gradually tapering doses of oral prednisolone and methotrexate.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eWe describe a case of PAN with the presence of aPL antibody manifesting with multifocal myositis. It is recommended that general testing for aPL antibodies should be undergone in patients with PAN, as well as other systemic vasculitis. Despite unusual co-incidence, aPL antibodies might worsen systemic vasculitis through thrombotic events, which clinicians should consider adequate coagulant therapeutics besides immunosuppressors.\u003c/p\u003e","manuscriptTitle":"A Case of Polyarteritis Nodosa with Positive Anti-Phospholipid Antibodies Presenting with Multifocal Myositis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-28 19:50:32","doi":"10.21203/rs.3.rs-4108739/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"68f39b1e-627e-4c04-bfb3-7a8f512c912d","owner":[],"postedDate":"March 28th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-08-20T08:23:05+00:00","versionOfRecord":[],"versionCreatedAt":"2024-03-28 19:50:32","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4108739","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4108739","identity":"rs-4108739","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}