Kikuchi-Fujimoto Disease Masquerading as Dysphagia with an Isolated Pulmonary Nodule: A Clinical Conundrum

Kikuchi-Fujimoto Disease Masquerading as Dysphagia with an Isolated Pulmonary Nodule: A Clinical Conundrum | 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 Kikuchi-Fujimoto Disease Masquerading as Dysphagia with an Isolated Pulmonary Nodule: A Clinical Conundrum Ahmed Jalwa, Mohit Singh Chauhan, Rakshith Uthappa, Ravishankara S, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7526812/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract INTRODUCTION Kikuchi-Fujimoto Disease (KFD), also known as Histiocytic Nectrotizing Lymphadenitis is a rare disease, more commonly seen in young Asian women. Though the exact cause is unknown but several Autoimmune and Infectious etiologies have been postulated. It is characterized by cervical lymphadenopathy, low-grade fever, night sweats and leucopenia. It clinically mimics several diseases, leading to misdiagnosis and inappropriate treatment. Diagnosis is confirmed by Histopathological Examination of the Lymph node. CASE REPORT A 40 year old Male with no comorbidities, presented with complaints of multiple Neck swellings, Dysphagia and odynophagia for both solids and liquids for 2 months, associated with low-grade fever and significant weight loss. On examination, multiple bilateral cervical lymph nodes were palpable. Hematological study showed raised ESR (Erythrocyte Sedimentation Rate) and CRP (C-Reactive Protein). Ultrasonography and Contrast-Enhanced CT (CECT) Neck showed multiple bilateral Cervical and Preauricular lymphadenopathy . CECT Chest revealed Hilar and Mediastinal lymphadenopathy with calcifications and a solitary pleural-based solid pulmonary nodule in the anterior segment of the lower lobe of the right lung. Excision biopsy and Histopathology confirmed the diagnosis of Kikuchi-Fujimoto disease. The patient completely recovered with a short course of oral Methylprednisolone (tapering dose) and antibiotics. CONCLUSION Atypical presentations of Kikuchi-Fujimoto disease pose a diagnostic challenge and may lead to inappropriate treatment and complications. It should be considered in patients presenting with persistent low-grade fever, cervical lymphadenopathy and leukopenia. A multidisciplinary approach is crucial for timely and accurate diagnosis. Greater clinical awareness of this rare entity is essential to prevent misdiagnosis and inappropriate management. Kikuchi-Fujimoto disease Dysphagia Cervical Lymphadenopathy Fever Pulmonary nodule Figures Figure 1 Figure 2 Figure 3 INTRODUCTION Kikuchi–Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis is a rare disease that was first reported in Japan by Kikuchi and Fujimoto (1972), respectively (Hossain et al. 2008). It has been more commonly reported in Asia, but has been identified in various ethnic groups around the world (Manasra et al. 2022 ). It mainly affects young women (Jung et al. 2017 ). The exact cause of this disease is unknown, but several autoimmune and infective etiologies have been postulated. Many support the immunological theory of response to an infectious etiology (Anini et al. 2024 ). A few cases of KFD are suggested to be associated with patients with a pacemaker, breast and other implants, suggesting that they may trigger an autoimmune reaction. The silicone implants can induce autoimmunity in genetically predisposed individuals (José et al. 2020). It is usually characterized by cervical lymphadenopathy, low-grade fever, night sweats and leucopenia (Deb et al. 2024 ). It mainly involves the cervical lymph nodes and rarely other lymph nodes (Anini et al. 2024 ; José et al. 2020 and Deb et al. 2024 ). Pulmonary system involvement is extremely rare (Huang et al. 2024). Impaired liver functions, elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are common (Kedar et al. 2024 and Sandakly et al. 2024 ). Diagnosis is confirmed by Histopathological Examination of the lymph nodes. The disease is classified into 3 stages or subtypes: Early proliferative: presence of predominant immunoblastic paracortical infiltrate mixed with histiocytes. Necrotizing (most common): non-neutrophilic necrotizing foci are present with mononuclear cells and abundant karyorrhectic debris. Xanthomatous: presence of foamy histiocytes, also known as Kikuchi histiocytes, which are the hallmark cells of KFD. The mainstay of treatment is a short course of oral corticosteroids. NSAIDs are used for symptomatic relief (Sandakly et al. 2024 ). Hydroxychloroquine and intravenous immunoglobulin have also been successfully used in the treatment of a few cases (Manasra et al. 2022 ; Sandakly et al. 2024 and Youssef 2017 ). KFD mimics several conditions (Hossain et al. 2008). Significant morbidity is due to frequent hospitalization because of mistaken diagnoses and co-morbidities leading to potentially fatal complications (Manasra et al. 2022 and Jung et al. 2017 ). KFD is said to be highly associated with Systemic Lupus Erythematosus (SLE); it may sometimes precede, coexist with, or follow SLE (Youssef et al. 2017). CASE REPORT A 40 year old Male presented with complaints of multiple bilateral neck swellings for 2 months. The largest swelling was over the right side of the neck, which was insidious in onset, initially small and gradually progressive. Dysphagia and odynophagia for both solids and liquids were present for 2 months and were gradually progressive, associated with low-grade fever (99.8°F) and significant weight loss (6% weight loss in the past 3 months). The patient had no significant past medical history. Clinical Examination: The patient was moderately built and moderately nourished. General physical examination was unremarkable except for cervical Lymphadenopathy. Lymph node examination- Multiple bilateral cervical lymph nodes palpable in Right Level II, III, & V and Left Level II, III, & IV, which were firm in consistency, non-tender, non-reducible, no localized rise of temperature and mobile. The largest lymph node was Right Level-V, size 3x2cm extending 2cm below the mastoid tip superiorly and 3cm above the clavicle inferiorly. The skin over the swelling was normal and pinchable. Nose and Ear examination was Normal. Hematological study reported Leucopenia (2550 cells/µL) was present with raised ESR (35 mm/hr) and CRP (6.51mg/L). LDH level was normal. Mantoux test, dengue serology, HIV, HBsAg, HCV serology, and ANA (Antinuclear Antibody) profile were Negative. Ultrasonography (USG) and Contrast-Enhanced CT (CECT) Neck showed multiple bilateral Cervical and Preauricular lymphadenopathy (Fig. 1 a). CECT Chest revealed Hilar and Mediastinal lymphadenopathy with calcifications within a few nodes (Fig. 1 b) and a solitary pleural-based solid pulmonary nodule in the anterior segment of the lower lobe of the right lung (Fig. 1 c). Based on clinical examination and radiological findings, differential diagnosis of tuberculous lymphadenitis, Lymphoma or sarcoidosis was considered. FNAC revealed chronic granulomatous lymphadenitis. USG abdomen and pelvis, spirometry and serum angiotensin converting enzyme (ACE) levels were normal. Excision biopsy of the largest lymph node (right level V) was performed under local anesthesia and the specimen was sent for histopathological examination. Post lymph node excision scar (circled) present on the lateral aspect of the neck, as shown in Fig. 2 . Intravenous antibiotics and analgesics were given postoperatively. Histopathological examination showed partial effacement of nodal architecture with residual follicles having reactive germinal centers (Fig. 3 a). The paracortical area had patchy areas of necrosis consisting of brightly eosinophilic fibrinoid deposits, surrounded by large aggregates of pale-stained Kikuchi histiocytes , admixed with scattered apoptotic cells, cellular debris and nuclear dust. The intervening areas showed small lymphocytes, plasmacytoid dendritic cells and immunoblasts (Fig. 3 b). The excised lymph node was negative for CBNAAT (Cartridge Based Nucleic Acid Amplification Test), ruling out Tuberculosis. The histopathology report confirmed the diagnosis of Kikuchi-Fujimoto disease. Oral Methylprednisolone 60 mg was started initially and gradually tapered and stopped after 3 weeks. The patient completely recovered within 2 months, and regular follow-up was advised. Regular follow-up was done at 2 months, 6 months, 1 year, and 2 years, showed no recurrence and complete recovery. DISCUSSION Kikuchi-Fujimoto disease (KFD) is an extremely rare disease (Hossain et al. 2008). It is more common in young Asian women of the age group 20–50 years (Manasra et al. 2022 ), with a female predominance of 4:1 to 16:1 (Jung et al. 2017 ), but our case showed an elderly male. Though the exact cause is unknown, several autoimmune and infectious etiologies have been postulated, such as SLE and silicone implants, and Epstein Barr virus, Herpes virus 6 & 8, immunodeficiency virus (HIV), cytomegalovirus (CMV), Parvovirus B19 and Torque tenovirus (TTV), respectively. The acute duration, febrile benign nature, as well as the histological changes present in this disease, support the immunological theory of response to an infectious etiology (Anini et al. 2024 ). After a detailed history, no known etiology could be traced in our case. Dysphagia and odynophagia are extremely rare complaints with only a few cases reported so far (Hossain et al. 2008). It may be due to laryngeal submucosal micro-lymphadenopathy, which is usually not picked up even on CECT. Cervical lymphadenopathy, low grade fever and night sweats are the classical hallmark features of the disease (Manasra et al. 2022 ), as reported in our case. Rarely axillary, supraclavicular, hilar, mediastinal, retroperitoneal and inguinal lymph nodes are involved (Anini et al. 2024 ; José et al. 2020 and Deb et al. 2024 ), whereas our case reported unusual involvement of hilar and mediastinal lymph nodes with calcification. KFD can have a diverse range of cutaneous presentations (Deb et al. 2024 ), but no skin involvement was reported in our case. Pulmonary involvement with a pleural-based solid pulmonary nodule in the anterior segment of the lower lobe of the right lung, as reported in this case is another extremely rare finding, with only a few cases reported (Huang et al. 2024). Leucopenia with elevated ESR and CRP levels is common, as reported in our case. Elevated liver enzymes and Lactate Dehydrogenase (LDH) levels are common but were absent in our case (Kedar et al. 2024 ). Histopathology is the most accurate way to diagnose KFD (Sandakly et al. 2024 ). Out of the three subtypes of KFD, the Early proliferative, Necrotizing and Xanthomatous, the most common subtype, which is the necrotizing variety, was reported in our case which consists of non-neutrophilic necrotizing foci with mononuclear cells and abundant karyorrhectic debris. Treatment commonly includes a short course of oral corticosteroids with antibiotics and NSAIDs, few studies also suggest the use of Hydroxychloroquine and intravenous immunoglobulin (Hossain et al. 2008 and Sandakly et al. 2024 ). The timely diagnosis and treatment of our patient with a tapering dose of oral corticosteroids and antibiotics helped in early recovery and reduced morbidity, preventing relapse of the disease. Overlapping clinical features often lead to misdiagnoses such as lymphoma, tuberculous lymphadenitis, sarcoidosis or metastatic malignancies, leading to misdiagnosis and inappropriate treatment, overall increasing morbidity and fatality significantly (Hossain et al. 2008 and Manasra et al. 2022 ). Multiple reports suggest that patients with KFD are often initially misdiagnosed as lymphoma (Jung et al. 2017 and Sandakly et al. 2024 ). Our case did not have any of the co-morbidities or complications such as Systemic Lupus Erythematosus (SLE), disseminated intravascular coagulation (DIC), KFD-triggered hemophagocytic syndrome and abrupt heart failure because of the timely Diagnosis and treatment. KFD has a recurrence rate of 4–15% usually after 8 years, and a fatality rate of 0.5–2.1% (Youssef et al. 2017). Our case showed no recurrence and complete recovery. CONCLUSION Atypical presentations of Kikuchi-Fujimoto disease pose a diagnostic challenge and may lead to inappropriate treatment and complications. It should be considered in patients presenting with persistent low-grade fever, cervical lymphadenopathy and leukopenia. A multidisciplinary approach is crucial for timely and accurate diagnosis. Greater clinical awareness of this rare entity is essential to prevent misdiagnosis and inappropriate management. Declarations Competing interests: • The author(s) declared no potential competing interest with respect to the research, authorship, and/or publication of this article. Ethics approval • of the Institutional IRB: The study was approved by the Institutional IRB. Consent to participate: • Written informed consent was obtained from the participant. Consent to publication: • The participant has consented to the submission of the case report to the journal. Funding: No funding was received to assist with the preparation of this manuscript. • Availability of the data and materials: All of the material is owned by the authors and/or no permissions are required. This manuscript does not report data generation or analysis. Author Contribution Conceptualization: [Ahmed Jalwa, Rakshith Uthappa]; Methodology: [Ahmed Jalwa, Rakshith Uthappa]; Formal analysis and investigation: [Ahmed Jalwa, Rakshith Uthappa]; Writing - original draft preparation: [Mohit Singh Chauhan, Rakshith Uthappa, Swetha Shankar]; Writing - review and editing: [Ahmed Jalwa, Mohit Singh Chauhan, Ravishankar A S, Swetha Shankar]; Supervision: [Ravishankar A S] Acknowledgement: • None References Anini EM, AlBaik TM, Ibrahim AT and AbuKaresh NA (2024). Kikuchi-Fujimoto Disease: A Case Report of Prolonged Fever and Lymphadenopathy in a Young Girl. Journal of Investigative Medicine High Impact Case Reports , 12(doi: 10.1177/23247096241246618 ). doi:https://doi.org/10.1177/23247096241246618. Deb A, Fernandez V, Kilinc E and Bahmad FH (2024). Kikuchi–Fujimoto Disease: A Case Series and Review of the Literature. Diseases , 12(11), pp.271–271. doi: https://doi.org/10.3390/diseases12110271 . Heffernan JAJ, Hernández PM and Bárcena C (2020). Kikuchi-Fujimoto Disease-Like Inflammatory Reaction in a Silicone Breast Implant Seroma. Acta Cytologica , 64(4), pp.386–389. doi: https://doi.org/10.1159/000505253 . Huang HY and Ko KH (2024). Pulmonary Involvement of Kikuchi-Fujimoto Disease in Rheumatoid Arthritis. JCR Journal of Clinical Rheumatology , 30(4), pp.e122–e122. doi: https://doi.org/10.1097/rhu.0000000000002077 . Jung, I.Y., Ann, H.W., Kim, J.J. and Lee, S.J. (2017). The incidence and clinical characteristics by gender differences in patients with Kikuchi–Fujimoto disease. Medicine , 96(11), p.e6332. doi: https://doi.org/10.1097/md.0000000000006332 . Kedar A K, Ghewade B, Jadhav U, et al. (March 06, 2024) Kikuchi-Fujimoto Disease: A Rare Presentation in a Young Male. Cureus 16(3): e55615. doi: 10.7759/cureus.55615 . (n.d.). Manasra ARA, Domaidat HA, Aideh MA and Qaoud DA (2022). Kikuchi–Fujimoto disease in the Eastern Mediterranean zone. Scientific Reports , 12(1). doi: https://doi.org/10.1038/s41598-022-06757-9 . Mosharraf-Hossain, A.K.M., Datta, P.G., Amin, A.S.A. and Uddin, M.J. (2008). Kikuchi-Fujimoto Disease presenting with fever, lymphadenopathy and dysphagia. JPMA. The Journal of the Pakistan Medical Association , 58(11), pp.647–9. Sandakly, N., Georgio El Koubayati, Sarkis, J. and Naderi, S. (2024). Kikuchi-Fujimoto disease associated with a flare-up of a leukocytoclastic vasculitis: A rare case report and review of literature. Medicine , 103(13), pp.e37626–e37626. doi: https://doi.org/10.1097/md.0000000000037626 . Youssef, A. and Ali, R. (2017). Kikuchi–Fujimoto disease: a case report of a multi-drug resistant, grueling disease. Oxford Medical Case Reports , 2017(6). doi: https://doi.org/10.1093/omcr/omx024 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 07 Oct, 2025 Reviews received at journal 05 Oct, 2025 Reviewers agreed at journal 22 Sep, 2025 Reviews received at journal 22 Sep, 2025 Reviewers agreed at journal 22 Sep, 2025 Reviewers invited by journal 22 Sep, 2025 Submission checks completed at journal 22 Sep, 2025 First submitted to journal 15 Sep, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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1","display":"","copyAsset":false,"role":"figure","size":377052,"visible":true,"origin":"","legend":"\u003cp\u003e(a) Ultrasonography (USG) neck showing bilateral cervical and Preauricular lymphadenopathy. (b) Contrast-Enhanced CT (CECT) Chest showing hilar and mediastinal lymphadenopathy. (c) Contrast-Enhanced CT (CECT) Chest showing solid pulmonary nodule in the anterior segment of the lower lobe of the right lung\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7526812/v1/f6d232dae0163e52746ce466.png"},{"id":93007305,"identity":"eab6a768-6b67-481e-8ee2-99d6fed13555","added_by":"auto","created_at":"2025-10-08 06:53:16","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":149396,"visible":true,"origin":"","legend":"\u003cp\u003ePost lymph node excision scar (circled) on the lateral aspect of the neck\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7526812/v1/e7e8c1dffc174ff7fc363307.png"},{"id":93007304,"identity":"edf7b07c-28c0-41f0-abda-1d12e797e822","added_by":"auto","created_at":"2025-10-08 06:53:16","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":401153,"visible":true,"origin":"","legend":"\u003cp\u003e(a) Histopathological slide of lymph node showing effacement of nodal architecture with areas of confluent necrosis (H\u0026amp;E stain, 10×). (b) Higher magnification slides showing karyorrhectic debris within necrotic foci, surrounded by mononuclear cells including histiocytes and immunoblasts is (H\u0026amp;E stain, 40×)\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7526812/v1/16f56c3e9a048bb6229f5c68.png"},{"id":93007386,"identity":"cbe710e0-0afd-4efe-b9fb-92c1f948e0b4","added_by":"auto","created_at":"2025-10-08 06:53:25","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1206272,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7526812/v1/e83c8347-fbb0-43dd-8e71-834f033c3c4c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Kikuchi-Fujimoto Disease Masquerading as Dysphagia with an Isolated Pulmonary Nodule: A Clinical Conundrum","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eKikuchi\u0026ndash;Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis is a rare disease that was first reported in Japan by Kikuchi and Fujimoto (1972), respectively (Hossain et al. 2008). It has been more commonly reported in Asia, but has been identified in various ethnic groups around the world (Manasra et al. \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). It mainly affects young women (Jung et al. \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2017\u003c/span\u003e). The exact cause of this disease is unknown, but several autoimmune and infective etiologies have been postulated. Many support the immunological theory of response to an infectious etiology (Anini et al. \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). A few cases of KFD are suggested to be associated with patients with a pacemaker, breast and other implants, suggesting that they may trigger an autoimmune reaction. The silicone implants can induce autoimmunity in genetically predisposed individuals (Jos\u0026eacute; et al. 2020). It is usually characterized by cervical lymphadenopathy, low-grade fever, night sweats and leucopenia (Deb et al. \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). It mainly involves the cervical lymph nodes and rarely other lymph nodes (Anini et al. \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2024\u003c/span\u003e; Jos\u0026eacute; et al. 2020 and Deb et al. \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). Pulmonary system involvement is extremely rare (Huang et al. 2024). Impaired liver functions, elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are common (Kedar et al. \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2024\u003c/span\u003e and Sandakly et al. \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2024\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eDiagnosis is confirmed by Histopathological Examination of the lymph nodes. The disease is classified into 3 stages or subtypes:\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eEarly proliferative: presence of predominant immunoblastic paracortical infiltrate mixed with histiocytes.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eNecrotizing (most common): non-neutrophilic necrotizing foci are present with mononuclear cells and abundant karyorrhectic debris.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eXanthomatous: presence of foamy histiocytes, also known as Kikuchi histiocytes, which are the hallmark cells of KFD.\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003cp\u003eThe mainstay of treatment is a short course of oral corticosteroids. NSAIDs are used for symptomatic relief (Sandakly et al. \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). Hydroxychloroquine and intravenous immunoglobulin have also been successfully used in the treatment of a few cases (Manasra et al. \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Sandakly et al. \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2024\u003c/span\u003e and Youssef \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2017\u003c/span\u003e). KFD mimics several conditions (Hossain et al. 2008). Significant morbidity is due to frequent hospitalization because of mistaken diagnoses and co-morbidities leading to potentially fatal complications (Manasra et al. \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2022\u003c/span\u003e and Jung et al. \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2017\u003c/span\u003e). KFD is said to be highly associated with Systemic Lupus Erythematosus (SLE); it may sometimes precede, coexist with, or follow SLE (Youssef et al. 2017).\u003c/p\u003e"},{"header":"CASE REPORT","content":"\u003cp\u003eA 40 year old Male presented with complaints of multiple bilateral neck swellings for 2 months. The largest swelling was over the right side of the neck, which was insidious in onset, initially small and gradually progressive. \u003cem\u003eDysphagia\u003c/em\u003e and \u003cem\u003eodynophagia\u003c/em\u003e for both solids and liquids were present for 2 months and were gradually progressive, associated with low-grade fever (99.8\u0026deg;F) and significant weight loss (6% weight loss in the past 3 months). The patient had no significant past medical history. Clinical Examination: The patient was moderately built and moderately nourished. General physical examination was unremarkable except for cervical Lymphadenopathy. Lymph node examination- Multiple bilateral cervical lymph nodes palpable in Right Level II, III, \u0026amp; V and Left Level II, III, \u0026amp; IV, which were firm in consistency, non-tender, non-reducible, no localized rise of temperature and mobile. The largest lymph node was Right Level-V, size 3x2cm extending 2cm below the mastoid tip superiorly and 3cm above the clavicle inferiorly. The skin over the swelling was normal and pinchable. Nose and Ear examination was Normal. Hematological study reported Leucopenia (2550 cells/\u0026micro;L) was present with raised ESR (35 mm/hr) and CRP (6.51mg/L). LDH level was normal. Mantoux test, dengue serology, HIV, HBsAg, HCV serology, and ANA (Antinuclear Antibody) profile were Negative. Ultrasonography (USG) and Contrast-Enhanced CT (CECT) Neck showed multiple bilateral \u003cem\u003eCervical\u003c/em\u003e and \u003cem\u003ePreauricular lymphadenopathy\u003c/em\u003e (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eCECT Chest revealed \u003cem\u003eHilar and Mediastinal lymphadenopathy\u003c/em\u003e with calcifications within a few nodes (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb) and a solitary pleural-based \u003cem\u003esolid pulmonary nodule\u003c/em\u003e in the anterior segment of the lower lobe of the right lung (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ec).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eBased on clinical examination and radiological findings, differential diagnosis of tuberculous lymphadenitis, Lymphoma or sarcoidosis was considered. FNAC revealed chronic granulomatous lymphadenitis. USG abdomen and pelvis, spirometry and serum angiotensin converting enzyme (ACE) levels were normal. Excision biopsy of the largest lymph node (right level V) was performed under local anesthesia and the specimen was sent for histopathological examination. Post lymph node excision scar (circled) present on the lateral aspect of the neck, as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eIntravenous antibiotics and analgesics were given postoperatively. Histopathological examination showed partial effacement of nodal architecture with residual follicles having reactive germinal centers (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea). \u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe paracortical area had patchy areas of necrosis consisting of brightly eosinophilic fibrinoid deposits, surrounded by large aggregates of pale-stained \u003cem\u003eKikuchi histiocytes\u003c/em\u003e, admixed with scattered apoptotic cells, cellular debris and nuclear dust. The intervening areas showed small lymphocytes, plasmacytoid dendritic cells and immunoblasts (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eb). \u003c/p\u003e\u003cp\u003eThe excised lymph node was negative for CBNAAT (Cartridge Based Nucleic Acid Amplification Test), ruling out Tuberculosis. The histopathology report confirmed the diagnosis of Kikuchi-Fujimoto disease. Oral Methylprednisolone 60 mg was started initially and gradually tapered and stopped after 3 weeks. The patient completely recovered within 2 months, and regular follow-up was advised. Regular follow-up was done at 2 months, 6 months, 1 year, and 2 years, showed no recurrence and complete recovery.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eKikuchi-Fujimoto disease (KFD) is an extremely rare disease (Hossain et al. 2008). It is more common in young Asian women of the age group 20\u0026ndash;50 years (Manasra et al. \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2022\u003c/span\u003e), with a female predominance of 4:1 to 16:1 (Jung et al. \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2017\u003c/span\u003e), but our case showed an elderly male. Though the exact cause is unknown, several autoimmune and infectious etiologies have been postulated, such as SLE and silicone implants, and Epstein Barr virus, Herpes virus 6 \u0026amp; 8, immunodeficiency virus (HIV), cytomegalovirus (CMV), Parvovirus B19 and Torque tenovirus (TTV), respectively. The acute duration, febrile benign nature, as well as the histological changes present in this disease, support the immunological theory of response to an infectious etiology (Anini et al. \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). After a detailed history, no known etiology could be traced in our case. Dysphagia and odynophagia are extremely rare complaints with only a few cases reported so far (Hossain et al. 2008). It may be due to laryngeal submucosal micro-lymphadenopathy, which is usually not picked up even on CECT. Cervical lymphadenopathy, low grade fever and night sweats are the classical hallmark features of the disease (Manasra et al. \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2022\u003c/span\u003e), as reported in our case. Rarely axillary, supraclavicular, hilar, mediastinal, retroperitoneal and inguinal lymph nodes are involved (Anini et al. \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2024\u003c/span\u003e; Jos\u0026eacute; et al. 2020 and Deb et al. \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2024\u003c/span\u003e), whereas our case reported unusual involvement of hilar and mediastinal lymph nodes with calcification. KFD can have a diverse range of cutaneous presentations (Deb et al. \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2024\u003c/span\u003e), but no skin involvement was reported in our case. Pulmonary involvement with a pleural-based solid pulmonary nodule in the anterior segment of the lower lobe of the right lung, as reported in this case is another extremely rare finding, with only a few cases reported (Huang et al. 2024). Leucopenia with elevated ESR and CRP levels is common, as reported in our case. Elevated liver enzymes and Lactate Dehydrogenase (LDH) levels are common but were absent in our case (Kedar et al. \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). Histopathology is the most accurate way to diagnose KFD (Sandakly et al. \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). Out of the three subtypes of KFD, the Early proliferative, Necrotizing and Xanthomatous, the most common subtype, which is the necrotizing variety, was reported in our case which consists of non-neutrophilic necrotizing foci with mononuclear cells and abundant karyorrhectic debris. Treatment commonly includes a short course of oral corticosteroids with antibiotics and NSAIDs, few studies also suggest the use of Hydroxychloroquine and intravenous immunoglobulin (Hossain et al. 2008 and Sandakly et al. \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). The timely diagnosis and treatment of our patient with a tapering dose of oral corticosteroids and antibiotics helped in early recovery and reduced morbidity, preventing relapse of the disease. Overlapping clinical features often lead to misdiagnoses such as lymphoma, tuberculous lymphadenitis, sarcoidosis or metastatic malignancies, leading to misdiagnosis and inappropriate treatment, overall increasing morbidity and fatality significantly (Hossain et al. 2008 and Manasra et al. \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). Multiple reports suggest that patients with KFD are often initially misdiagnosed as lymphoma (Jung et al. \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2017\u003c/span\u003e and Sandakly et al. \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). Our case did not have any of the co-morbidities or complications such as Systemic Lupus Erythematosus (SLE), disseminated intravascular coagulation (DIC), KFD-triggered hemophagocytic syndrome and abrupt heart failure because of the timely Diagnosis and treatment. KFD has a recurrence rate of 4\u0026ndash;15% usually after 8 years, and a fatality rate of 0.5\u0026ndash;2.1% (Youssef et al. 2017). Our case showed no recurrence and complete recovery.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eAtypical presentations of Kikuchi-Fujimoto disease pose a diagnostic challenge and may lead to inappropriate treatment and complications. It should be considered in patients presenting with persistent low-grade fever, cervical lymphadenopathy and leukopenia. A multidisciplinary approach is crucial for timely and accurate diagnosis. Greater clinical awareness of this rare entity is essential to prevent misdiagnosis and inappropriate management.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e\u003cp\u003e\u0026bull; The author(s) declared no potential competing interest with respect to the research, authorship, and/or publication of this article.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003cp\u003e\u0026bull; of the Institutional IRB: The study was approved by the Institutional IRB.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConsent to participate:\u003c/strong\u003e\u003cp\u003e\u0026bull; Written informed consent was obtained from the participant.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConsent to publication:\u003c/strong\u003e\u003cp\u003e\u0026bull; The participant has consented to the submission of the case report to the journal.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e\u003cp\u003eNo funding was received to assist with the preparation of this manuscript.\u003c/p\u003e\u003cp\u003e\u0026bull; Availability of the data and materials: All of the material is owned by the authors and/or no permissions are required. This manuscript does not report data generation or analysis.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eConceptualization: [Ahmed Jalwa, Rakshith Uthappa]; Methodology: [Ahmed Jalwa, Rakshith Uthappa]; Formal analysis and investigation: [Ahmed Jalwa, Rakshith Uthappa]; Writing - original draft preparation: [Mohit Singh Chauhan, Rakshith Uthappa, Swetha Shankar]; Writing - review and editing: [Ahmed Jalwa, Mohit Singh Chauhan, Ravishankar A S, Swetha Shankar]; Supervision: [Ravishankar A S]\u003c/p\u003e\u003ch2\u003eAcknowledgement:\u003c/h2\u003e\u003cp\u003e\u0026bull; None\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAnini EM, AlBaik TM, Ibrahim AT and AbuKaresh NA (2024). Kikuchi-Fujimoto Disease: A Case Report of Prolonged Fever and Lymphadenopathy in a Young Girl. \u003cem\u003eJournal of Investigative Medicine High Impact Case Reports\u003c/em\u003e, 12(doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1177/23247096241246618\u003c/span\u003e\u003cspan address=\"10.1177/23247096241246618\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). doi:https://doi.org/10.1177/23247096241246618.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDeb A, Fernandez V, Kilinc E and Bahmad FH (2024). Kikuchi\u0026ndash;Fujimoto Disease: A Case Series and Review of the Literature. \u003cem\u003eDiseases\u003c/em\u003e, 12(11), pp.271\u0026ndash;271. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/diseases12110271\u003c/span\u003e\u003cspan address=\"10.3390/diseases12110271\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHeffernan JAJ, Hern\u0026aacute;ndez PM and B\u0026aacute;rcena C (2020). Kikuchi-Fujimoto Disease-Like Inflammatory Reaction in a Silicone Breast Implant Seroma. \u003cem\u003eActa Cytologica\u003c/em\u003e, 64(4), pp.386\u0026ndash;389. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1159/000505253\u003c/span\u003e\u003cspan address=\"10.1159/000505253\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHuang HY and Ko KH (2024). Pulmonary Involvement of Kikuchi-Fujimoto Disease in Rheumatoid Arthritis. \u003cem\u003eJCR Journal of Clinical Rheumatology\u003c/em\u003e, 30(4), pp.e122\u0026ndash;e122. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/rhu.0000000000002077\u003c/span\u003e\u003cspan address=\"10.1097/rhu.0000000000002077\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJung, I.Y., Ann, H.W., Kim, J.J. and Lee, S.J. (2017). The incidence and clinical characteristics by gender differences in patients with Kikuchi\u0026ndash;Fujimoto disease. \u003cem\u003eMedicine\u003c/em\u003e, 96(11), p.e6332. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/md.0000000000006332\u003c/span\u003e\u003cspan address=\"10.1097/md.0000000000006332\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKedar A K, Ghewade B, Jadhav U, et al. (March 06, 2024) Kikuchi-Fujimoto Disease: A Rare Presentation in a Young Male. Cureus 16(3): e55615. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.7759/cureus.55615\u003c/span\u003e\u003cspan address=\"10.7759/cureus.55615\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (n.d.).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eManasra ARA, Domaidat HA, Aideh MA and Qaoud DA (2022). Kikuchi\u0026ndash;Fujimoto disease in the Eastern Mediterranean zone. \u003cem\u003eScientific Reports\u003c/em\u003e, 12(1). doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41598-022-06757-9\u003c/span\u003e\u003cspan address=\"10.1038/s41598-022-06757-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMosharraf-Hossain, A.K.M., Datta, P.G., Amin, A.S.A. and Uddin, M.J. (2008). Kikuchi-Fujimoto Disease presenting with fever, lymphadenopathy and dysphagia. \u003cem\u003eJPMA. The Journal of the Pakistan Medical Association\u003c/em\u003e, 58(11), pp.647\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSandakly, N., Georgio El Koubayati, Sarkis, J. and Naderi, S. (2024). Kikuchi-Fujimoto disease associated with a flare-up of a leukocytoclastic vasculitis: A rare case report and review of literature. \u003cem\u003eMedicine\u003c/em\u003e, 103(13), pp.e37626\u0026ndash;e37626. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/md.0000000000037626\u003c/span\u003e\u003cspan address=\"10.1097/md.0000000000037626\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYoussef, A. and Ali, R. (2017). Kikuchi\u0026ndash;Fujimoto disease: a case report of a multi-drug resistant, grueling disease. \u003cem\u003eOxford Medical Case Reports\u003c/em\u003e, 2017(6). doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/omcr/omx024\u003c/span\u003e\u003cspan address=\"10.1093/omcr/omx024\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-rare-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Journal of Rare Diseases](https://link.springer.com/journal/44162)","snPcode":"44162","submissionUrl":"https://submission.nature.com/new-submission/44162/3","title":"Journal of Rare Diseases","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Kikuchi-Fujimoto disease, Dysphagia, Cervical Lymphadenopathy, Fever, Pulmonary nodule","lastPublishedDoi":"10.21203/rs.3.rs-7526812/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7526812/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eINTRODUCTION\u003c/p\u003e\u003cp\u003eKikuchi-Fujimoto Disease (KFD), also known as Histiocytic Nectrotizing Lymphadenitis is a rare disease, more commonly seen in young Asian women. Though the exact cause is unknown but several Autoimmune and Infectious etiologies have been postulated. It is characterized by cervical lymphadenopathy, low-grade fever, night sweats and leucopenia. It clinically mimics several diseases, leading to misdiagnosis and inappropriate treatment. Diagnosis is confirmed by Histopathological Examination of the Lymph node.\u003c/p\u003e\u003cp\u003eCASE REPORT\u003c/p\u003e\u003cp\u003eA 40 year old Male with no comorbidities, presented with complaints of multiple Neck swellings, \u003cem\u003eDysphagia\u003c/em\u003e and \u003cem\u003eodynophagia\u003c/em\u003e for both solids and liquids for 2 months, associated with low-grade fever and significant weight loss. On examination, multiple bilateral cervical lymph nodes were palpable. Hematological study showed raised ESR (Erythrocyte Sedimentation Rate) and CRP (C-Reactive Protein). Ultrasonography and Contrast-Enhanced CT (CECT) Neck showed multiple bilateral \u003cem\u003eCervical and Preauricular lymphadenopathy\u003c/em\u003e. CECT Chest revealed \u003cem\u003eHilar and Mediastinal lymphadenopathy\u003c/em\u003e with calcifications and a solitary pleural-based solid pulmonary nodule in the anterior segment of the lower lobe of the right lung. Excision biopsy and Histopathology confirmed the diagnosis of Kikuchi-Fujimoto disease. The patient completely recovered with a short course of oral Methylprednisolone (tapering dose) and antibiotics.\u003c/p\u003e\u003cp\u003eCONCLUSION\u003c/p\u003e\u003cp\u003eAtypical presentations of Kikuchi-Fujimoto disease pose a diagnostic challenge and may lead to inappropriate treatment and complications. It should be considered in patients presenting with persistent low-grade fever, cervical lymphadenopathy and leukopenia. A multidisciplinary approach is crucial for timely and accurate diagnosis. Greater clinical awareness of this rare entity is essential to prevent misdiagnosis and inappropriate management.\u003c/p\u003e","manuscriptTitle":"Kikuchi-Fujimoto Disease Masquerading as Dysphagia with an Isolated Pulmonary Nodule: A Clinical Conundrum","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-08 06:45:11","doi":"10.21203/rs.3.rs-7526812/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-07T10:32:11+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-06T02:12:45+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"318137385920249362241498559126234657038","date":"2025-09-22T22:31:45+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-22T19:11:33+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"206164564454331397833036102903844679050","date":"2025-09-22T18:55:57+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-22T17:44:36+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-22T13:10:33+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Rare Diseases","date":"2025-09-15T07:35:10+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-rare-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Journal of Rare Diseases](https://link.springer.com/journal/44162)","snPcode":"44162","submissionUrl":"https://submission.nature.com/new-submission/44162/3","title":"Journal of Rare Diseases","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"06911829-5c35-4058-b5a5-91bb5b9c3bb1","owner":[],"postedDate":"October 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-02-13T10:55:17+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-08 06:45:11","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7526812","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7526812","identity":"rs-7526812","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}