Fever with Eosinophilia and Bone Marrow Granulomas in an Elderly Female: A Rare Case Report and Literature Review

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When FUO is accompanied by marked eosinophilia and progressive cytopenia, the differential diagnosis expands considerably and becomes more complex. Bone marrow granulomas represent an uncommon pathological finding and may arise from a wide range of etiologies, including infectious diseases, malignancies, and autoimmune disorders. Case presentation We report the case of a 79-year-old woman who was admitted with a six-day history of high-grade fever. Laboratory evaluation revealed peripheral blood eosinophilia, thrombocytopenia, and markedly elevated inflammatory markers. Comprehensive microbiological investigations, including blood cultures and respiratory pathogen screening, failed to identify a causative organism. Empirical anti-infective therapy was initially ineffective, and the patient’s condition progressed to pancytopenia, with neutropenia as the predominant feature. Bone marrow aspiration and biopsy demonstrated a hypocellular marrow with grade 3 fibrosis and non-caseating granuloma formation, accompanied by CD3⁺ T-cell infiltration. Based on the clinical course and pathological findings, a diagnosis of infection-related myelosuppression associated with granulomatous bone marrow involvement was established. Treatment with mezlocillin in combination with dexamethasone resulted in rapid defervescence and gradual recovery of peripheral blood counts. The patient was subsequently discharged in clinical remission. At one-month follow-up, there was no evidence of disease recurrence, and complete blood count parameters had returned to normal. Conclusions This case underscores the importance of considering bone marrow granulomas in elderly patients presenting with FUO accompanied by eosinophilia and hematologic abnormalities. Bone marrow biopsy plays a pivotal role in establishing a definitive diagnosis in such complex clinical scenarios. Furthermore, even in the absence of an identifiable pathogen, empirical treatment with broad-spectrum antibiotics in combination with corticosteroids may represent an effective therapeutic approach for mitigating excessive inflammatory responses and reversing infection-associated myelosuppression. Fever of Unknown Origin Eosinophilia Bone Marrow Granulomas Myelosuppression Elderly Patient Figures Figure 1 Background Fever of unknown origin (FUO) is defined by persistent febrile episodes that exceed the expected duration of self-limiting infections, despite comprehensive diagnostic evaluation in either inpatient or outpatient settings [1] . FUO constitutes a heterogeneous clinical syndrome encompassing a broad spectrum of underlying pathophysiological mechanisms, including infectious diseases, neoplastic processes, autoimmune disorders, and rare metabolic abnormalities [ 2 ] . The diagnosis of FUO is fundamentally one of exclusion, requiring systematic elimination of identifiable causes through an extensive workup. Consequently, diagnostic strategies often necessitate individualized adjustment of investigative algorithms and observation periods, taking into account factors such as host immune status, availability of healthcare resources, and variability in clinical context [1] . Eosinophilia, defined as an absolute eosinophil count greater than 0.5 × 10 9 /L, represents a clinically significant hematologic abnormality [ 3 ] . Its differential diagnosis is broad, ranging from relatively benign conditions, including allergic disorders and parasitic infections [ 4 ] , to severe drug-induced hypersensitivity reactions, such as drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome [ 5 ] , as well as hematologic malignancies [ 6 ] . Bone marrow granulomas are an uncommon pathological finding in bone marrow biopsy specimens, with a reported incidence ranging from 0.3% to 2.2% [ 7 ] . Their presence reflects a cell-mediated immune response and is associated with a broad spectrum of underlying etiologies. The most frequently reported causes include infectious diseases, particularly mycobacterial infections [ 8 ] malignancies, most notably lymphomas [ 9 ] , sarcoidosis [ 10 ] , and drug-induced reactions [ 7 ] . The simultaneous occurrence of fever of unknown origin (FUO), eosinophilia, and bone marrow granulomas therefore represents a significant diagnostic challenge in clinical practice. In this report, we describe the case of an elderly woman who initially presented with persistent fever and marked eosinophilia, followed by rapid progression to severe bone marrow suppression. A definitive diagnosis of infection-related bone marrow granulomatous involvement was established through bone marrow biopsy. The patient achieved complete clinical and hematologic recovery after treatment with broad-spectrum antibiotics in combination with glucocorticoids. This case highlights the diagnostic approach, differential considerations, and therapeutic strategies relevant to this rare and complex clinical presentation. Case Report A 79-year-old woman was admitted to the Department of Infectious Diseases at Songjiang Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, on November 9,2025,with a chief complaint of fever persisting for six days. History of Present Illness Six days prior to admission, the patient developed fever of unknown origin, with a maximum recorded temperature of 39.0°C. The fever was accompanied by chills, generalized fatigue, and anorexia. She denied respiratory symptoms, including cough or sputum production, as well as gastrointestinal complaints such as abdominal pain or diarrhea. There were no reports of chest tightness or chest pain. Self-administration of ibuprofen resulted in only transient symptomatic relief, with persistent febrile episodes thereafter. The patient subsequently presented to the hospital’s fever clinic, where initial laboratory investigations revealed a white blood cell (WBC) count of 6.22 × 10 9 /L, red blood cell (RBC) count of 4.04 × 10 12 /L, hemoglobin (HGB) level of 123 g/L, and platelet (PLT) count of 78 × 10 9 /L. The eosinophil percentage was markedly elevated at 20.6%, corresponding to an absolute eosinophil count of 1.28 × 10 9 /L. Inflammatory markers were significantly increased, with a C-reactive protein (CRP) level of 111.88 mg/L. Nasopharyngeal swab testing for influenza A/B viruses and SARS-CoV-2 antigens yielded negative results. Non-contrast chest computed tomography (CT) demonstrated changes consistent with chronic bronchitis. Given the unclear etiology of the fever, the patient was admitted for further diagnostic evaluation. Past Medical History The patient had a history of gallstones without prior surgical or medical intervention. She also had long-standing hypertension, which was well controlled with a combination of losartan and hydrochlorothiazide. She denied any known drug or food allergies. Epidemiological and Family History The patient reported no recent travel, no exposure to animals, and no known contact with individuals with infectious diseases. Her children were healthy and had not experienced similar symptoms. Physical Examination On admission, the patient’s temperature was 38.2°C, blood pressure was 146/82 mmHg, pulse rate was 98 beats/min, and respiratory rate was 20 breaths/min. She was alert and oriented, with a fair general condition. Pulmonary auscultation revealed clear breath sounds bilaterally, without rales or wheezes. Cardiac examination showed a regular rhythm at 98 beats/min, with no audible murmurs. The abdomen was soft and non-tender, without guarding or rebound tenderness. No superficial lymphadenopathy was detected. There were no signs of jaundice, skin rash, or petechiae. Laboratory and Imaging Investigations Further laboratory testing demonstrated normal liver and renal function, cardiac enzyme levels, serum electrolytes, coagulation parameters, antinuclear antibody profile, and tumor markers. Procalcitonin (PCT) was elevated at 1.82 ng/mL (reference range: 0–0.5 ng/mL). Immunoglobulin E (IgE) was markedly increased at 1007.04 IU/mL (reference range: 0–100 IU/mL). Cytokine analysis revealed significantly elevated levels of soluble interleukin-2 receptor (sIL-2R) at 6159.00 U/mL (reference range: 228–724 U/mL), interleukin-6 (IL-6) at 21.93 pg/mL (reference range: 0–7 pg/mL), and interleukin-10 (IL-10) at 18.66 pg/mL (reference range: 0–9.5 pg/mL). Serum ferritin was elevated at 449.07 µg/L (reference range: 0–160 µg/L). CD4⁺ and CD8⁺ T-lymphocyte counts were within normal limits. Fungal biomarkers, including (1,3)-β-D-glucan (G test) and galactomannan (GM test), were negative. Serological testing for Epstein–Barr virus (EBV), cytomegalovirus (CMV), and human immunodeficiency virus (HIV) was negative. Targeted next-generation sequencing (tNGS) of a nasopharyngeal swab did not identify any clinically significant pathogens. Two sets of blood cultures yielded no growth, and the Mycobacterium tuberculosis T-cell spot test (T-SPOT.TB) was negative. Serological tests for Toxoplasma gondii, echinococcus, and schistosomiasis were also negative. Transthoracic echocardiography revealed no abnormalities. Ultrasonography of the cervical, axillary, and inguinal regions showed no evidence of masses or lymphadenopathy. Abdominal ultrasonography confirmed the presence of gallstones. The initial working diagnosis was infectious fever, and the patient was treated empirically with intravenous ceftazidime (2.0 g every 12 h). However, after three days of therapy, the fever persisted. Repeat laboratory investigations revealed rapid hematologic deterioration, with a white blood cell (WBC) count of 1.89 × 10 9 /L, an absolute neutrophil count (ANC) of 0.03 × 10 9 /L, hemoglobin (HGB) level of 119 g/L, and platelet (PLT) count of 128 × 10 9 /L. The eosinophil proportion increased to 37.61%, corresponding to an absolute eosinophil count of 0.71 × 10 9 /L. Serum ferritin levels further increased to 617.16 µg/L. Pro-inflammatory cytokines remained markedly elevated, including interleukin-6 (IL-6) at 15.71 pg/mL, interleukin-10 (IL-10) at 14.36 pg/mL, and soluble interleukin-2 receptor (sIL-2R) at 4214 U/mL. Although procalcitonin (PCT) decreased to 0.38 ng/mL, C-reactive protein (CRP) remained significantly elevated at 63.00 mg/L. Given the development of severe bone marrow suppression, a hematology consultation was obtained, and urgent bone marrow aspiration and biopsy were recommended. Treatment was adjusted to include granulocyte colony-stimulating factor (G-CSF) at 150 µg administered subcutaneously once daily, along with intravenous methylprednisolone at a dose of 40 mg daily to suppress excessive inflammation. Despite these interventions, the patient’s fever persisted, and WBC and ANC levels declined further (Table 1 ). Bone marrow examination revealed marked hypocellularity, with approximately 10% nucleated cells and severely reduced trilineage hematopoiesis. Reticulin staining demonstrated grade 3 fibrosis (WF = 3). Prominent eosinophilic infiltration was observed (Fig. 1 A), along with granulomatous nodules composed of multinucleated giant cells without evidence of caseous necrosis (Fig. 1 B). Acid-fast staining was negative. Immunohistochemical analysis showed enrichment of CD3⁺ T lymphocytes within and surrounding the granulomas, while CD20⁺ B lymphocytes were absent (Fig. 1 C). Myeloperoxidase (MPO), CD61, and E-cadherin staining demonstrated scattered myeloid, megakaryocytic, and erythroid elements. CD34 and CD117 staining were negative, effectively excluding significant blast proliferation. Fluorescence in situ hybridization (FISH) analysis showed no rearrangements involving PDGFRA or PDGFRB. Conventional cytogenetic analysis revealed a normal female karyotype (46,XX[4]), and BCR::ABL1 fusion testing was negative. Flow cytometric analysis demonstrated a predominance of lymphocytes (54.39%) and eosinophils (20.02%) without aberrant immunophenotypic features. Based on the integrated clinical, laboratory, and pathological findings, infection-related granulomatous involvement of the bone marrow was strongly suspected. Antimicrobial therapy was therefore escalated to intravenous meropenem (1.0 g every 8 h), and corticosteroid therapy was adjusted to intravenous dexamethasone at a dose of 5 mg daily. The patient’s fever gradually resolved, and WBC and ANC levels progressively recovered with continued G-CSF support. By hospital day 14, she was afebrile, with stable vital signs and improving hematologic parameters. She was subsequently discharged with the final diagnoses of infection-related granulomatous bone marrow involvement and severe bone marrow suppression. At one-month outpatient follow-up, the patient reported no recurrence of fever or fatigue. Repeat laboratory testing demonstrated normalization of peripheral blood counts, including a WBC count of 8.5 × 10 9 /L, neutrophils comprising 64%, eosinophils 3%, HGB level of 118 g/L, and PLT count of 127 × 10 9 /L. Table 1 Summary of Key Hematological Parameters During Hospitalization Time Point White Blood Cell Count (×10 9 /L) Hemoglobin (g/L) Platelet Count (×10 9 /L) Neutrophil Count (×10 9 /L) Eosinophil Count (×10 9 /L) Day1 6.22 123 78 2.52 1.28 Day3 1.89 119 128 0.03 0.71 Day4 1.33 110 123 0.07 0.48 Day5 1.05 100 125 0.01 0.04 Day6 1.34 96 111 0.01 0.09 Day7 1.94 101 120 0.01 0.06 Day8 1.77 96 125 0.03 0.03 Day9 2.98 106 164 0.48 0.07 Day10 30.4 104 161 22.39 0.04 Day11 22.1 101 130 16.35 0.04 discharge 16.8 100 117 12.56 0.03 Discussion This case report describes a critically ill elderly patient with complex and evolving clinical manifestations, which posed substantial challenges in both diagnostic evaluation and therapeutic decision-making. The initial presentation with fever of unknown origin (FUO) accompanied by marked eosinophilia required a broad and systematic differential diagnostic approach. Differential Diagnosis of Eosinophilia Eosinophils are key effector cells of the immune system and typically increase in response to allergic disorders, parasitic infections, and certain malignancies [ 11 ] . In the present case, the patient’s marked eosinophilia, reaching a peak of 37.61%, together with a markedly elevated serum IgE level initially prompted consideration of allergic and parasitic etiologies. However, the absence of a history of allergic disease, lack of cutaneous manifestations, and negative serological testing for parasitic infections rendered these diagnoses unlikely. Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, characterized by drug exposure–related eosinophilia, cutaneous eruptions, and multiorgan involvement [ 12 , 13 ] was also considered. Although the patient had a history of long-term use of losartan/hydrochlorothiazide, this medication is infrequently associated with DRESS syndrome, and the absence of a characteristic rash or organ-specific injury further argued against this diagnosis. Eosinophilic granulomatosis with polyangiitis (EGPA), a rare antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis characterized by asthma, marked eosinophilia in peripheral blood and tissues, and necrotizing vasculitis affecting small- to medium-sized vessels across multiple organ systems [ 14 ] , was likewise evaluated. However, the lack of respiratory symptoms, absence of clinical features suggestive of systemic vasculitis, and negative ANCA testing made EGPA highly improbable. Hematologic malignancies, particularly myeloproliferative neoplasms associated with eosinophilia [ 15 ] , were also considered. These were effectively excluded by bone marrow examination, which demonstrated marked hypocellularity rather than hypercellularity, as well as the absence of clonal hematopoietic proliferation or cytogenetic abnormalities. Notably, eosinophil counts declined in parallel with the development of profound neutropenia, a finding more consistent with global bone marrow failure than with true resolution of eosinophilic pathology. Diagnostic Significance and Etiology of Granulomatous Marrow Granulomatous involvement of the bone marrow represented a pivotal diagnostic finding in this case. Infectious etiologies, particularly Mycobacterium tuberculosis in regions where it is endemic, are the most frequently reported causes of bone marrow granulomas [ 16 ] . In the present patient, however, the presence of non-caseating granulomas, together with negative acid-fast staining and a negative T-SPOT.TB assay, argued strongly against mycobacterial infection. Other infectious causes, including brucellosis, Q fever, and invasive fungal infections, remained potential considerations despite negative blood cultures and respiratory pathogen sequencing [ 17 , 18 ] . These diagnostic modalities are known to have limited sensitivity for fastidious or intracellular pathogens. In support of an infectious etiology, the patient exhibited persistent high-grade fever, markedly elevated inflammatory markers (including procalcitonin and C-reactive protein), and a pronounced clinical response to escalation of antimicrobial therapy with meropenem. Malignancy-associated granulomatous marrow involvement, particularly in Hodgkin and non-Hodgkin lymphomas, was also carefully considered [ 9 ] . However, immunohistochemical findings demonstrating predominance of CD3⁺ T lymphocytes with absence of CD20⁺ B cells effectively excluded B-cell lymphoma. Furthermore, the rapid clinical improvement following antimicrobial and corticosteroid therapy, along with the absence of clonal proliferation on flow cytometry and cytogenetic analysis, made T-cell lymphoma highly unlikely. Sarcoidosis, a classic non-infectious cause of non-caseating granulomas, was deemed improbable due to the absence of characteristic multi-organ involvement, including pulmonary, lymphatic, or cutaneous manifestations. Notably, prior studies have reported that approximately 20% of cases of granulomatous bone marrow involvement remain etiologically undefined despite extensive diagnostic evaluation [ 8 ] , underscoring the inherent complexity of establishing a definitive cause in such presentations. Pathophysiological Mechanisms The pathophysiology in this case likely involved an aberrant and exaggerated host immune response to an unidentified pathogen. The initial eosinophilia and elevated serum IgE suggested a predominance of Th2-polarized immunity [ 19 ] . As the disease progressed, immune dysregulation appeared to shift toward T-cell–mediated granuloma formation, as evidenced by the CD3⁺ T-cell infiltration observed on bone marrow biopsy. The coexistence of granulomas and grade 3 reticulin fibrosis indicated secondary , rather than primary, myelofibrosis. Severe bone marrow suppression and fibrosis may have resulted from a localized "cytokine storm" within the marrow microenvironment [ 20 ] . Markedly elevated serum levels of soluble interleukin-2 receptor (sIL-2R), interleukin-6 (IL-6), and interleukin-10 (IL-10) implicated cytokine-mediated injury to hematopoietic progenitors via multiple mechanisms, including: (1) direct inhibition of hematopoietic stem cell (HSC) self-renewal and differentiation, and (2) fibroblast activation through JAK-STAT signaling pathways, promoting secretion of transforming growth factor-beta (TGF-β) and other profibrotic mediators [ 21 , 22 ] . Persistently elevated eosinophil counts likely contributed to marrow fibrosis through TGF-β secretion, which drives fibroblast proliferation and extracellular matrix deposition [ 23 , 24 ] . Progressive replacement of hematopoietic tissue by fibrotic stroma ultimately culminated in bone marrow failure, explaining the clinical transition from initial eosinophilia to subsequent pancytopenia. Therapeutic Implications Initial treatment with narrow-spectrum antibiotics (ceftazidime) proved ineffective, suggesting the involvement of atypical or resistant pathogens. Upon identification of granulomatous bone marrow involvement, a dual therapeutic approach was implemented: (1) broad-spectrum antibiotics (meropenem) to target a wide range of potential infectious agents, and (2) corticosteroids (dexamethasone) to suppress cytokine-mediated inflammation and alleviate bone marrow suppression. This combined strategy effectively disrupted the cycle of inflammation and marrow dysfunction, thereby facilitating hematopoietic recovery. Corticosteroids likely attenuated T-cell activation and cytokine overproduction, creating a more favorable microenvironment for bone marrow regeneration. Limitations This study acknowledges several methodological constraints that merit critical consideration. Primarily, the diagnostic paradigm was constrained by the temporal limitations of molecular diagnostic technologies at the time of clinical management, precluding the implementation of advanced pathogen detection modalities such as targeted next-generation sequencing (tNGS) and metagenomic next-generation sequencing (mNGS) on peripheral blood specimens. Consequently, microbial identification relied exclusively on conventional culture-based microbiological techniques, with infectious etiology determination contingent upon clinical phenotype extrapolation and therapeutic response to empirical antimicrobial regimens, thereby introducing inherent limitations in diagnostic specificity and etiological certainty.Secondly, the implementation of a longitudinal pathological monitoring framework was impeded by geriatric frailty indices and procedural risk stratification for invasive interventions, resulting in a single baseline bone marrow biopsy. This methodology engendered epistemological limitations in characterizing granulomatous lesion resolution kinetics, fibrotic progression dynamics, and long-term therapeutic efficacy assessment.Furthermore, the glucocorticoid therapeutic regimen lacked standardized dosing algorithms and evidence-based treatment duration parameters. The interpretation of therapeutic outcomes may have been influenced by multiple confounding variables including baseline immune competence profiles, comorbid disease heterogeneity, and interindividual pharmacokinetic variability, which collectively challenge the generalizability of treatment paradigms.Lastly, as a singular case report, this investigation is inherently limited by methodological constraints inherent to single-case designs, including restricted statistical power and external validity. The elucidation of pathogenic mechanisms and formulation of diagnostic-therapeutic frameworks for granulomatous bone marrow lesions complicated by pancytopenia necessitate multicenter prospective cohort investigations with standardized data acquisition protocols to establish robust clinical evidence. Conclusion This case highlights a rare clinical course of fever of unknown origin (FUO) accompanied by eosinophilia, which rapidly progressed to granulomatous bone marrow involvement and severe marrow suppression. It underscores three key points: (1) early bone marrow evaluation is essential in FUO patients presenting with complex hematologic abnormalities, such as eosinophilia evolving into pancytopenia; (2)granulomatous bone marrow warrants a thorough etiological investigation encompassing infectious, malignant, and autoimmune causes; and (3) in cases of suspected infection without definitive microbiological confirmation, combined treatment with broad-spectrum antibiotics and corticosteroids can be life-saving, particularly when excessive inflammation drives organ dysfunction, such as bone marrow failure. Clinicians managing such complex presentations must maintain broad diagnostic vigilance and dynamically adjust therapeutic strategies to optimize outcomes. Abbreviations DRESS Drug Reaction with Eosinophilia and Systemic Symptoms FUO Fever of Unknown Origin Declarations Ethical approval and consent to participate Not applicable. Consent for publication Written informed consent was obtained from the patient, and ethical approval was obtained from the hospital ethics committee for publication of their clinical details and clinical images. Availability of data and materials Not applicable. Clinical trial number Not applicable. Competing interests The authors declare that they have no competing interests. Funding National Natural Science Foundation of China (81770612, 81070357, 30660066). Authors’ contributions Ping Xie contributed to the study’s conception and design and wrote the first draft of the manuscript. Yuting Zhang data curation, visualization, Jinli Jiang,Caiping Chen, Yingying Wang and Liang ming Liu revised and edited the manuscript. All authors read and approved the final manuscript. Acknowledgments Not applicable. 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Bone marrow fibrosis in primary myelofibrosis: pathogenic mechanisms and the role of TGF-β. Stem Cell Investig. 2016;3:5. Additional Declarations No competing interests reported. Supplementary Files Supplementary1.pdf Supplementary2.pdf Supplementary6.pdf Supplementary4.pdf Supplementary7.pdf Supplementary5.pdf Supplementary3.pdf Cite Share Download PDF Status: Posted Version 1 posted 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-8397064","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":597023753,"identity":"d86d17a5-b8ee-44cf-b943-e2db4abad046","order_by":0,"name":"Ping Xie","email":"","orcid":"","institution":"Shanghai Jiao Tong University","correspondingAuthor":false,"prefix":"","firstName":"Ping","middleName":"","lastName":"Xie","suffix":""},{"id":597023754,"identity":"3b5fa168-adeb-4762-a4d5-83e514f9430e","order_by":1,"name":"Yuting Zhang","email":"","orcid":"","institution":"Nanjing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yuting","middleName":"","lastName":"Zhang","suffix":""},{"id":597023755,"identity":"92238fc4-c4a6-4800-bb7e-a7a5b0837e0b","order_by":2,"name":"Jinli Jiang","email":"","orcid":"","institution":"Shanghai Jiao Tong University","correspondingAuthor":false,"prefix":"","firstName":"Jinli","middleName":"","lastName":"Jiang","suffix":""},{"id":597023756,"identity":"f419c73f-bf0c-4214-82f9-710b1ef70d46","order_by":3,"name":"Caiping Chen","email":"","orcid":"","institution":"Shanghai Jiao Tong University","correspondingAuthor":false,"prefix":"","firstName":"Caiping","middleName":"","lastName":"Chen","suffix":""},{"id":597023757,"identity":"543834d0-14ab-40cf-a97c-5efc5019b81f","order_by":4,"name":"Yingying Wang","email":"","orcid":"","institution":"Shanghai Jiao Tong University","correspondingAuthor":false,"prefix":"","firstName":"Yingying","middleName":"","lastName":"Wang","suffix":""},{"id":597023758,"identity":"544c4c5e-69ff-4a52-a90b-4129c5b8a2dd","order_by":5,"name":"Liangming Liu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABBElEQVRIiWNgGAWjYBACPmYGxgMJIBYzEH9gOAAR5sGjhQ2oEq6FcQZRWoD4AIzDzEOUFnYegwMPau7YrW3nPfza5s8de90ZCYwP3rYxyJvjdBhQS8KxZ8nbDvOlWee2PUvcdiOB2XBuG4PhzgZ8WtgOJ5sd5jEzzm04nGB2I4FNmreNIcHgAD4t/6BaLP4ctgdqYf9NUEti22E7oBbjxwxshxmBDmNjxq+FreBAYh/QPUBbGHvbDiduO/OwWXLOOQnDDTi08PMf3vjwxzege86fMf7wA+Sw48kHP7wps5HHZQsMJDYAbZSAsBmBbAYJ/OqBwB6ImT8QVDYKRsEoGAUjEgAAwg5fofJCrO4AAAAASUVORK5CYII=","orcid":"","institution":"Shanghai Jiao Tong University","correspondingAuthor":true,"prefix":"","firstName":"Liangming","middleName":"","lastName":"Liu","suffix":""}],"badges":[],"createdAt":"2025-12-18 16:08:23","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8397064/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8397064/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":103590399,"identity":"bc9c6a5d-3ac3-450c-93be-952a6d9748b7","added_by":"auto","created_at":"2026-02-27 12:03:01","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":761313,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eBone Marrow Pathological Findings. A:\u003c/strong\u003e Aggregates of eosinophils in bone marrow biopsy smear (H\u0026amp;E staining, ×40; black arrows). \u003cstrong\u003eB:\u003c/strong\u003eClassic granulomatous nodules composed of multinucleated giant cells (H\u0026amp;E staining, ×10; green arrows). \u003cstrong\u003eC:\u003c/strong\u003e Dense infiltration of CD3⁺T lymphocytes within and surrounding granulomas (Immunohistochemistry, ×10; red arrows).\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8397064/v1/9bb253896da0e269fe790526.png"},{"id":104399365,"identity":"eac1e5e7-2064-4a7b-9ac8-c48cd8682241","added_by":"auto","created_at":"2026-03-11 12:05:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1293488,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8397064/v1/fc1e3950-d7b3-4efa-93dd-e8a76bdd8939.pdf"},{"id":103590403,"identity":"cc6441ee-17c8-4fb4-8dde-80692f33fea6","added_by":"auto","created_at":"2026-02-27 12:03:01","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":509637,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementary1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8397064/v1/2103c21cc25dfbcfe09ed8c5.pdf"},{"id":103590405,"identity":"a0bcc40c-cd24-4d41-b255-ae3795d93441","added_by":"auto","created_at":"2026-02-27 12:03:01","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":560641,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementary2.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8397064/v1/11c1bbbf7bff4e59b1f73c8c.pdf"},{"id":103590400,"identity":"99e57df7-8de4-41ac-afa2-ff21bd51f50d","added_by":"auto","created_at":"2026-02-27 12:03:01","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":452718,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementary6.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8397064/v1/e3473a6c82710b5f67fc8b4c.pdf"},{"id":103590404,"identity":"75b08723-5f1e-4c97-bd20-4238eaa25140","added_by":"auto","created_at":"2026-02-27 12:03:01","extension":"pdf","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":547630,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementary4.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8397064/v1/4173c9faf94001c141df8c7b.pdf"},{"id":103590401,"identity":"feee6e29-645a-4ee1-9936-d6f922a98639","added_by":"auto","created_at":"2026-02-27 12:03:01","extension":"pdf","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":477438,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementary7.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8397064/v1/9e4ecd3673b683aeb2ecbc65.pdf"},{"id":103590406,"identity":"bedf766a-bc88-48c6-b4b3-3f2c129906d3","added_by":"auto","created_at":"2026-02-27 12:03:01","extension":"pdf","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":1042090,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementary5.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8397064/v1/1d1a066d16af7d14cd976b16.pdf"},{"id":103590408,"identity":"27a3cc8c-9256-4fc0-a4c5-4c6f1e461c2c","added_by":"auto","created_at":"2026-02-27 12:03:02","extension":"pdf","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":3414964,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementary3.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8397064/v1/1f332a68f5cc82f1d6bf2930.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Fever with Eosinophilia and Bone Marrow Granulomas in an Elderly Female: A Rare Case Report and Literature Review","fulltext":[{"header":"Background","content":"\u003cp\u003eFever of unknown origin (FUO) is defined by persistent febrile episodes that exceed the expected duration of self-limiting infections, despite comprehensive diagnostic evaluation in either inpatient or outpatient settings \u003csup\u003e[1]\u003c/sup\u003e. FUO constitutes a heterogeneous clinical syndrome encompassing a broad spectrum of underlying pathophysiological mechanisms, including infectious diseases, neoplastic processes, autoimmune disorders, and rare metabolic abnormalities \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. The diagnosis of FUO is fundamentally one of exclusion, requiring systematic elimination of identifiable causes through an extensive workup. Consequently, diagnostic strategies often necessitate individualized adjustment of investigative algorithms and observation periods, taking into account factors such as host immune status, availability of healthcare resources, and variability in clinical context \u003csup\u003e[1]\u003c/sup\u003e. Eosinophilia, defined as an absolute eosinophil count greater than 0.5 \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L, represents a clinically significant hematologic abnormality \u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. Its differential diagnosis is broad, ranging from relatively benign conditions, including allergic disorders and parasitic infections\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e, to severe drug-induced hypersensitivity reactions, such as drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome \u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e, as well as hematologic malignancies \u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eBone marrow granulomas are an uncommon pathological finding in bone marrow biopsy specimens, with a reported incidence ranging from 0.3% to 2.2% \u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. Their presence reflects a cell-mediated immune response and is associated with a broad spectrum of underlying etiologies. The most frequently reported causes include infectious diseases, particularly mycobacterial infections\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e malignancies, most notably lymphomas \u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e, sarcoidosis \u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e, and drug-induced reactions \u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. The simultaneous occurrence of fever of unknown origin (FUO), eosinophilia, and bone marrow granulomas therefore represents a significant diagnostic challenge in clinical practice.\u003c/p\u003e \u003cp\u003eIn this report, we describe the case of an elderly woman who initially presented with persistent fever and marked eosinophilia, followed by rapid progression to severe bone marrow suppression. A definitive diagnosis of infection-related bone marrow granulomatous involvement was established through bone marrow biopsy. The patient achieved complete clinical and hematologic recovery after treatment with broad-spectrum antibiotics in combination with glucocorticoids. This case highlights the diagnostic approach, differential considerations, and therapeutic strategies relevant to this rare and complex clinical presentation.\u003c/p\u003e "},{"header":"Case Report","content":"\u003cp\u003eA 79-year-old woman was admitted to the Department of Infectious Diseases at Songjiang Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, on November 9,2025,with a chief complaint of fever persisting for six days. History of Present Illness Six days prior to admission, the patient developed fever of unknown origin, with a maximum recorded temperature of 39.0\u0026deg;C. The fever was accompanied by chills, generalized fatigue, and anorexia. She denied respiratory symptoms, including cough or sputum production, as well as gastrointestinal complaints such as abdominal pain or diarrhea. There were no reports of chest tightness or chest pain. Self-administration of ibuprofen resulted in only transient symptomatic relief, with persistent febrile episodes thereafter. The patient subsequently presented to the hospital\u0026rsquo;s fever clinic, where initial laboratory investigations revealed a white blood cell (WBC) count of 6.22 \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L, red blood cell (RBC) count of 4.04 \u0026times; 10\u003csup\u003e12\u003c/sup\u003e/L, hemoglobin (HGB) level of 123 g/L, and platelet (PLT) count of 78 \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L. The eosinophil percentage was markedly elevated at 20.6%, corresponding to an absolute eosinophil count of 1.28 \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L. Inflammatory markers were significantly increased, with a C-reactive protein (CRP) level of 111.88 mg/L. Nasopharyngeal swab testing for influenza A/B viruses and SARS-CoV-2 antigens yielded negative results. Non-contrast chest computed tomography (CT) demonstrated changes consistent with chronic bronchitis. Given the unclear etiology of the fever, the patient was admitted for further diagnostic evaluation. Past Medical History The patient had a history of gallstones without prior surgical or medical intervention. She also had long-standing hypertension, which was well controlled with a combination of losartan and hydrochlorothiazide. She denied any known drug or food allergies. Epidemiological and Family History The patient reported no recent travel, no exposure to animals, and no known contact with individuals with infectious diseases. Her children were healthy and had not experienced similar symptoms. Physical Examination On admission, the patient\u0026rsquo;s temperature was 38.2\u0026deg;C, blood pressure was 146/82 mmHg, pulse rate was 98 beats/min, and respiratory rate was 20 breaths/min. She was alert and oriented, with a fair general condition. Pulmonary auscultation revealed clear breath sounds bilaterally, without rales or wheezes. Cardiac examination showed a regular rhythm at 98 beats/min, with no audible murmurs. The abdomen was soft and non-tender, without guarding or rebound tenderness. No superficial lymphadenopathy was detected. There were no signs of jaundice, skin rash, or petechiae. Laboratory and Imaging Investigations Further laboratory testing demonstrated normal liver and renal function, cardiac enzyme levels, serum electrolytes, coagulation parameters, antinuclear antibody profile, and tumor markers. Procalcitonin (PCT) was elevated at 1.82 ng/mL (reference range: 0\u0026ndash;0.5 ng/mL). Immunoglobulin E (IgE) was markedly increased at 1007.04 IU/mL (reference range: 0\u0026ndash;100 IU/mL). Cytokine analysis revealed significantly elevated levels of soluble interleukin-2 receptor (sIL-2R) at 6159.00 U/mL (reference range: 228\u0026ndash;724 U/mL), interleukin-6 (IL-6) at 21.93 pg/mL (reference range: 0\u0026ndash;7 pg/mL), and interleukin-10 (IL-10) at 18.66 pg/mL (reference range: 0\u0026ndash;9.5 pg/mL). Serum ferritin was elevated at 449.07 \u0026micro;g/L (reference range: 0\u0026ndash;160 \u0026micro;g/L). CD4⁺ and CD8⁺ T-lymphocyte counts were within normal limits. Fungal biomarkers, including (1,3)-β-D-glucan (G test) and galactomannan (GM test), were negative. Serological testing for Epstein\u0026ndash;Barr virus (EBV), cytomegalovirus (CMV), and human immunodeficiency virus (HIV) was negative. Targeted next-generation sequencing (tNGS) of a nasopharyngeal swab did not identify any clinically significant pathogens. Two sets of blood cultures yielded no growth, and the Mycobacterium tuberculosis T-cell spot test (T-SPOT.TB) was negative. Serological tests for Toxoplasma gondii, echinococcus, and schistosomiasis were also negative. Transthoracic echocardiography revealed no abnormalities. Ultrasonography of the cervical, axillary, and inguinal regions showed no evidence of masses or lymphadenopathy. Abdominal ultrasonography confirmed the presence of gallstones.\u003c/p\u003e \u003cp\u003eThe initial working diagnosis was infectious fever, and the patient was treated empirically with intravenous ceftazidime (2.0 g every 12 h). However, after three days of therapy, the fever persisted. Repeat laboratory investigations revealed rapid hematologic deterioration, with a white blood cell (WBC) count of 1.89 \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L, an absolute neutrophil count (ANC) of 0.03 \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L, hemoglobin (HGB) level of 119 g/L, and platelet (PLT) count of 128 \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L. The eosinophil proportion increased to 37.61%, corresponding to an absolute eosinophil count of 0.71 \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L. Serum ferritin levels further increased to 617.16 \u0026micro;g/L. Pro-inflammatory cytokines remained markedly elevated, including interleukin-6 (IL-6) at 15.71 pg/mL, interleukin-10 (IL-10) at 14.36 pg/mL, and soluble interleukin-2 receptor (sIL-2R) at 4214 U/mL. Although procalcitonin (PCT) decreased to 0.38 ng/mL, C-reactive protein (CRP) remained significantly elevated at 63.00 mg/L. Given the development of severe bone marrow suppression, a hematology consultation was obtained, and urgent bone marrow aspiration and biopsy were recommended. Treatment was adjusted to include granulocyte colony-stimulating factor (G-CSF) at 150 \u0026micro;g administered subcutaneously once daily, along with intravenous methylprednisolone at a dose of 40 mg daily to suppress excessive inflammation. Despite these interventions, the patient\u0026rsquo;s fever persisted, and WBC and ANC levels declined further (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eBone marrow examination revealed marked hypocellularity, with approximately 10% nucleated cells and severely reduced trilineage hematopoiesis. Reticulin staining demonstrated grade 3 fibrosis (WF\u0026thinsp;=\u0026thinsp;3). Prominent eosinophilic infiltration was observed (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA), along with granulomatous nodules composed of multinucleated giant cells without evidence of caseous necrosis (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB). Acid-fast staining was negative. Immunohistochemical analysis showed enrichment of CD3⁺ T lymphocytes within and surrounding the granulomas, while CD20⁺ B lymphocytes were absent (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC). Myeloperoxidase (MPO), CD61, and E-cadherin staining demonstrated scattered myeloid, megakaryocytic, and erythroid elements. CD34 and CD117 staining were negative, effectively excluding significant blast proliferation. Fluorescence in situ hybridization (FISH) analysis showed no rearrangements involving PDGFRA or PDGFRB. Conventional cytogenetic analysis revealed a normal female karyotype (46,XX[4]), and BCR::ABL1 fusion testing was negative. Flow cytometric analysis demonstrated a predominance of lymphocytes (54.39%) and eosinophils (20.02%) without aberrant immunophenotypic features. Based on the integrated clinical, laboratory, and pathological findings, infection-related granulomatous involvement of the bone marrow was strongly suspected. Antimicrobial therapy was therefore escalated to intravenous meropenem (1.0 g every 8 h), and corticosteroid therapy was adjusted to intravenous dexamethasone at a dose of 5 mg daily. The patient\u0026rsquo;s fever gradually resolved, and WBC and ANC levels progressively recovered with continued G-CSF support. By hospital day 14, she was afebrile, with stable vital signs and improving hematologic parameters. She was subsequently discharged with the final diagnoses of infection-related granulomatous bone marrow involvement and severe bone marrow suppression. At one-month outpatient follow-up, the patient reported no recurrence of fever or fatigue. Repeat laboratory testing demonstrated normalization of peripheral blood counts, including a WBC count of 8.5 \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L, neutrophils comprising 64%, eosinophils 3%, HGB level of 118 g/L, and PLT count of 127 \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSummary of Key Hematological Parameters During Hospitalization\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime Point\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWhite Blood Cell Count (\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHemoglobin (g/L)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlatelet Count (\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNeutrophil Count (\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eEosinophil Count (\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDay1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e123\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDay3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e119\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e128\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.71\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDay4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e123\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.48\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDay5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e125\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDay6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e111\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.09\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDay7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e101\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e120\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDay8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e125\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDay9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e106\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e164\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDay10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e30.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e104\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e161\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e22.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDay11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e22.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e101\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e130\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e16.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003edischarge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e117\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e12.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis case report describes a critically ill elderly patient with complex and evolving clinical manifestations, which posed substantial challenges in both diagnostic evaluation and therapeutic decision-making. The initial presentation with fever of unknown origin (FUO) accompanied by marked eosinophilia required a broad and systematic differential diagnostic approach.\u003c/p\u003e \u003cp\u003eDifferential Diagnosis of Eosinophilia\u003c/p\u003e \u003cp\u003eEosinophils are key effector cells of the immune system and typically increase in response to allergic disorders, parasitic infections, and certain malignancies \u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. In the present case, the patient\u0026rsquo;s marked eosinophilia, reaching a peak of 37.61%, together with a markedly elevated serum IgE level initially prompted consideration of allergic and parasitic etiologies. However, the absence of a history of allergic disease, lack of cutaneous manifestations, and negative serological testing for parasitic infections rendered these diagnoses unlikely. Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, characterized by drug exposure\u0026ndash;related eosinophilia, cutaneous eruptions, and multiorgan involvement \u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e was also considered. Although the patient had a history of long-term use of losartan/hydrochlorothiazide, this medication is infrequently associated with DRESS syndrome, and the absence of a characteristic rash or organ-specific injury further argued against this diagnosis. Eosinophilic granulomatosis with polyangiitis (EGPA), a rare antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis characterized by asthma, marked eosinophilia in peripheral blood and tissues, and necrotizing vasculitis affecting small- to medium-sized vessels across multiple organ systems \u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e, was likewise evaluated. However, the lack of respiratory symptoms, absence of clinical features suggestive of systemic vasculitis, and negative ANCA testing made EGPA highly improbable. Hematologic malignancies, particularly myeloproliferative neoplasms associated with eosinophilia \u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e, were also considered. These were effectively excluded by bone marrow examination, which demonstrated marked hypocellularity rather than hypercellularity, as well as the absence of clonal hematopoietic proliferation or cytogenetic abnormalities. Notably, eosinophil counts declined in parallel with the development of profound neutropenia, a finding more consistent with \u003cem\u003eglobal bone marrow failure\u003c/em\u003e than with true resolution of eosinophilic pathology.\u003c/p\u003e \u003cp\u003eDiagnostic Significance and Etiology of Granulomatous Marrow\u003c/p\u003e \u003cp\u003eGranulomatous involvement of the bone marrow represented a pivotal diagnostic finding in this case. Infectious etiologies, particularly Mycobacterium tuberculosis in regions where it is endemic, are the most frequently reported causes of bone marrow granulomas \u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e. In the present patient, however, the presence of non-caseating granulomas, together with negative acid-fast staining and a negative T-SPOT.TB assay, argued strongly against mycobacterial infection. Other infectious causes, including brucellosis, Q fever, and invasive fungal infections, remained potential considerations despite negative blood cultures and respiratory pathogen sequencing \u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e. These diagnostic modalities are known to have limited sensitivity for fastidious or intracellular pathogens. In support of an infectious etiology, the patient exhibited persistent high-grade fever, markedly elevated inflammatory markers (including procalcitonin and C-reactive protein), and a pronounced clinical response to escalation of antimicrobial therapy with meropenem. Malignancy-associated granulomatous marrow involvement, particularly in Hodgkin and non-Hodgkin lymphomas, was also carefully considered \u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. However, immunohistochemical findings demonstrating predominance of CD3⁺ T lymphocytes with absence of CD20⁺ B cells effectively excluded B-cell lymphoma. Furthermore, the rapid clinical improvement following antimicrobial and corticosteroid therapy, along with the absence of clonal proliferation on flow cytometry and cytogenetic analysis, made T-cell lymphoma highly unlikely. Sarcoidosis, a classic non-infectious cause of non-caseating granulomas, was deemed improbable due to the absence of characteristic multi-organ involvement, including pulmonary, lymphatic, or cutaneous manifestations. Notably, prior studies have reported that approximately 20% of cases of granulomatous bone marrow involvement remain etiologically undefined despite extensive diagnostic evaluation \u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e, underscoring the inherent complexity of establishing a definitive cause in such presentations.\u003c/p\u003e \u003cp\u003ePathophysiological Mechanisms\u003c/p\u003e \u003cp\u003eThe pathophysiology in this case likely involved an aberrant and exaggerated host immune response to an unidentified pathogen. The initial eosinophilia and elevated serum IgE suggested a predominance of Th2-polarized immunity \u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e. As the disease progressed, immune dysregulation appeared to shift toward T-cell\u0026ndash;mediated granuloma formation, as evidenced by the CD3⁺ T-cell infiltration observed on bone marrow biopsy. The coexistence of granulomas and grade 3 reticulin fibrosis indicated \u003cem\u003esecondary\u003c/em\u003e, rather than primary, myelofibrosis. Severe bone marrow suppression and fibrosis may have resulted from a localized \"cytokine storm\" within the marrow microenvironment \u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. Markedly elevated serum levels of soluble interleukin-2 receptor (sIL-2R), interleukin-6 (IL-6), and interleukin-10 (IL-10) implicated cytokine-mediated injury to hematopoietic progenitors via multiple mechanisms, including: (1) direct inhibition of hematopoietic stem cell (HSC) self-renewal and differentiation, and (2) fibroblast activation through JAK-STAT signaling pathways, promoting secretion of transforming growth factor-beta (TGF-β) and other profibrotic mediators \u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003ePersistently elevated eosinophil counts likely contributed to marrow fibrosis through TGF-β secretion, which drives fibroblast proliferation and extracellular matrix deposition \u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e. Progressive replacement of hematopoietic tissue by fibrotic stroma ultimately culminated in bone marrow failure, explaining the clinical transition from initial eosinophilia to subsequent pancytopenia.\u003c/p\u003e \u003cp\u003eTherapeutic Implications\u003c/p\u003e \u003cp\u003eInitial treatment with narrow-spectrum antibiotics (ceftazidime) proved ineffective, suggesting the involvement of atypical or resistant pathogens. Upon identification of granulomatous bone marrow involvement, a dual therapeutic approach was implemented: (1) broad-spectrum antibiotics (meropenem) to target a wide range of potential infectious agents, and (2) corticosteroids (dexamethasone) to suppress cytokine-mediated inflammation and alleviate bone marrow suppression. This combined strategy effectively disrupted the cycle of inflammation and marrow dysfunction, thereby facilitating hematopoietic recovery. Corticosteroids likely attenuated T-cell activation and cytokine overproduction, creating a more favorable microenvironment for bone marrow regeneration.\u003c/p\u003e \u003cp\u003eLimitations\u003c/p\u003e \u003cp\u003eThis study acknowledges several methodological constraints that merit critical consideration. Primarily, the diagnostic paradigm was constrained by the temporal limitations of molecular diagnostic technologies at the time of clinical management, precluding the implementation of advanced pathogen detection modalities such as targeted next-generation sequencing (tNGS) and metagenomic next-generation sequencing (mNGS) on peripheral blood specimens. Consequently, microbial identification relied exclusively on conventional culture-based microbiological techniques, with infectious etiology determination contingent upon clinical phenotype extrapolation and therapeutic response to empirical antimicrobial regimens, thereby introducing inherent limitations in diagnostic specificity and etiological certainty.Secondly, the implementation of a longitudinal pathological monitoring framework was impeded by geriatric frailty indices and procedural risk stratification for invasive interventions, resulting in a single baseline bone marrow biopsy. This methodology engendered epistemological limitations in characterizing granulomatous lesion resolution kinetics, fibrotic progression dynamics, and long-term therapeutic efficacy assessment.Furthermore, the glucocorticoid therapeutic regimen lacked standardized dosing algorithms and evidence-based treatment duration parameters. The interpretation of therapeutic outcomes may have been influenced by multiple confounding variables including baseline immune competence profiles, comorbid disease heterogeneity, and interindividual pharmacokinetic variability, which collectively challenge the generalizability of treatment paradigms.Lastly, as a singular case report, this investigation is inherently limited by methodological constraints inherent to single-case designs, including restricted statistical power and external validity. The elucidation of pathogenic mechanisms and formulation of diagnostic-therapeutic frameworks for granulomatous bone marrow lesions complicated by pancytopenia necessitate multicenter prospective cohort investigations with standardized data acquisition protocols to establish robust clinical evidence.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis case highlights a rare clinical course of fever of unknown origin (FUO) accompanied by eosinophilia, which rapidly progressed to granulomatous bone marrow involvement and severe marrow suppression. It underscores three key points: (1) early bone marrow evaluation is essential in FUO patients presenting with complex hematologic abnormalities, such as eosinophilia evolving into pancytopenia; (2)granulomatous bone marrow warrants a thorough etiological investigation encompassing infectious, malignant, and autoimmune causes; and (3) in cases of suspected infection without definitive microbiological confirmation, combined treatment with broad-spectrum antibiotics and corticosteroids can be life-saving, particularly when excessive inflammation drives organ dysfunction, such as bone marrow failure. Clinicians managing such complex presentations must maintain broad diagnostic vigilance and dynamically adjust therapeutic strategies to optimize outcomes.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eDRESS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eDrug Reaction with Eosinophilia and Systemic Symptoms\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFUO\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eFever of Unknown Origin\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthical approval and consent to participate\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient, and ethical approval was obtained from the hospital ethics committee for publication of their clinical details and\u0026nbsp;clinical images.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003eClinical trial number\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eNational Natural Science Foundation of China (81770612,\u0026nbsp;81070357,\u0026nbsp;30660066).\u003c/p\u003e\n\u003cp\u003eAuthors\u0026rsquo; contributions\u003c/p\u003e\n\u003cp\u003ePing Xie contributed to the study\u0026rsquo;s conception and design and wrote the first draft of the manuscript. Yuting Zhang data curation, visualization, Jinli Jiang,Caiping Chen, Yingying Wang and Liang ming Liu revised and edited the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003eAcknowledgments\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHaidar G, Singh N. Fever of unknown origin. N Engl J Med. 2022;386(5):463\u0026ndash;77.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShuchismita, Jamal I, Raman RB, et al. Clinico-hematological portrait of bone marrow infections: unusual visitors unveiled. Niger Med J. 2025;66(3):1027\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShomali W, Gotlib J. World Health Organization and International Consensus Classification of eosinophilic disorders: 2024 update on diagnosis, risk stratification, and management. Am J Hematol. 2024;99(5):946\u0026ndash;68.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSanchez-Vegas C, Villavicencio KLH. Helminth infections in children. Pediatr Rev. 2022;43(5):243\u0026ndash;55.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKroshinsky D, Cardones ARG, Blumenthal KG. Drug reaction with eosinophilia and systemic symptoms. N Engl J Med. 2024;391(23):2242\u0026ndash;54.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAndersen CL, Siersma VD, Hasselbalch HC, et al. Eosinophilia in routine blood samples and the subsequent risk of hematological malignancies and death. Am J Hematol. 2013;88(10):843\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAhsan E, Singh S, Kumar Gautam S, et al. Granulomas in bone marrow: is it always tuberculosis? J Hematopathol. 2025;18(1):32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDe Brackers L, Ffrench M, Broussolle C, et al. Granulomatous lesions in bone marrow: clinicopathologic findings and significance in a study of 48 cases. Eur J Intern Med. 2013;24(5):468\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSacks EL, Donaldson SS, Gordon J, et al. Epithelioid granulomas associated with Hodgkin's disease: clinical correlations in 55 previously untreated patients. Cancer. 1978;41(2):562\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLame D, Pianelli M, Kordasti S, et al. Uncommon presentation of sarcoidosis with severe thrombocytopenia and hemorrhagic diathesis. Hematol Rep. 2024;16(1):125\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGupta K, Falta NA, Spencer LA. Innate immune pairing: eosinophils as hidden architects of T cell immunity. Cells. 2025;14(22):1\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWei BM, Fox LP, Kaffenberger BH, et al. Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms. Part I. Epidemiology, pathogenesis, clinicopathological features, and prognosis. J Am Acad Dermatol. 2024;90(5):885\u0026ndash;908.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi M, Li F, Dai Y, et al. Sulfasalazine-induced drug reaction with eosinophilia and systemic symptoms (DRESS) coinfected with COVID-19 complicated by hemophagocytic lymphohistiocytosis: a case report. Front Immunol. 2024;15:1371490.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKamide Y, Taniguchi M. Eosinophilic granulomatosis with polyangiitis: current status and future perspectives. Respir Investig. 2025;63(4):639\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMorales-Camacho RM, Caballero-Vel\u0026aacute;zquez T, Borrero JJ, et al. Hematological neoplasms with eosinophilia. 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Curr Allergy Asthma Rep. 2022;22(11):141\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMitamura Y, Schulz D, Oro S, et al. Cutaneous and systemic hyperinflammation drives maculopapular drug exanthema in severely ill COVID-19 patients. Allergy. 2022;77(2):595\u0026ndash;608.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eValletta S, Thomas A, Meng Y, et al. Micro-environmental sensing by bone marrow stroma identifies IL-6 and TGFβ1 as regulators of hematopoietic ageing. Nat Commun. 2020;11(1):4075.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCruz NM, Gergis U, Silver RT. Myelofibrosis: best practices, controversies and 2019 update. Expert Rev Hematol. 2020;13(1):71\u0026ndash;84.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGomes I, Mathur SK, Espenshade BM, et al. Eosinophil\u0026ndash;fibroblast interactions induce fibroblast IL-6 secretion and extracellular matrix gene expression: implications in fibrogenesis. J Allergy Clin Immunol. 2005;116(4):796\u0026ndash;804.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAgarwal A, Morrone K, Bartenstein M, et al. Bone marrow fibrosis in primary myelofibrosis: pathogenic mechanisms and the role of TGF-β. Stem Cell Investig. 2016;3:5.\u003c/span\u003e\u003c/li\u003e\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":"Fever of Unknown Origin, Eosinophilia, Bone Marrow Granulomas, Myelosuppression, Elderly Patient","lastPublishedDoi":"10.21203/rs.3.rs-8397064/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8397064/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e \u003cp\u003eDiagnosing fever of unknown origin (FUO) in elderly patients remains particularly challenging. When FUO is accompanied by marked eosinophilia and progressive cytopenia, the differential diagnosis expands considerably and becomes more complex. Bone marrow granulomas represent an uncommon pathological finding and may arise from a wide range of etiologies, including infectious diseases, malignancies, and autoimmune disorders.\u003c/p\u003e\u003cp\u003e\u003cb\u003eCase presentation\u003c/b\u003e\u003c/p\u003e \u003cp\u003eWe report the case of a 79-year-old woman who was admitted with a six-day history of high-grade fever. Laboratory evaluation revealed peripheral blood eosinophilia, thrombocytopenia, and markedly elevated inflammatory markers. Comprehensive microbiological investigations, including blood cultures and respiratory pathogen screening, failed to identify a causative organism. Empirical anti-infective therapy was initially ineffective, and the patient\u0026rsquo;s condition progressed to pancytopenia, with neutropenia as the predominant feature. Bone marrow aspiration and biopsy demonstrated a hypocellular marrow with grade 3 fibrosis and non-caseating granuloma formation, accompanied by CD3⁺ T-cell infiltration. Based on the clinical course and pathological findings, a diagnosis of infection-related myelosuppression associated with granulomatous bone marrow involvement was established. Treatment with mezlocillin in combination with dexamethasone resulted in rapid defervescence and gradual recovery of peripheral blood counts. The patient was subsequently discharged in clinical remission. At one-month follow-up, there was no evidence of disease recurrence, and complete blood count parameters had returned to normal.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThis case underscores the importance of considering bone marrow granulomas in elderly patients presenting with FUO accompanied by eosinophilia and hematologic abnormalities. Bone marrow biopsy plays a pivotal role in establishing a definitive diagnosis in such complex clinical scenarios. Furthermore, even in the absence of an identifiable pathogen, empirical treatment with broad-spectrum antibiotics in combination with corticosteroids may represent an effective therapeutic approach for mitigating excessive inflammatory responses and reversing infection-associated myelosuppression.\u003c/p\u003e","manuscriptTitle":"Fever with Eosinophilia and Bone Marrow Granulomas in an Elderly Female: A Rare Case Report and Literature Review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-27 12:02:56","doi":"10.21203/rs.3.rs-8397064/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":"95b70802-0ed0-47c3-8e32-6a5e9e282290","owner":[],"postedDate":"February 27th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-10T15:10:09+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-27 12:02:56","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8397064","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8397064","identity":"rs-8397064","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}