Prominent Diffuse Ground-Glass Opacities: A Challenging Case of CTD-ILD, IPH, and Secondary PAP Coexistence

Prominent Diffuse Ground-Glass Opacities: A Challenging Case of CTD-ILD, IPH, and Secondary PAP Coexistence | 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 Prominent Diffuse Ground-Glass Opacities: A Challenging Case of CTD-ILD, IPH, and Secondary PAP Coexistence Xingyi Zhao, Jie Xia, Qiongjie Hu, Liyan Zhu, Guifen Shen This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9128043/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 24 You are reading this latest preprint version Abstract Background: Diffuse ground-glass opacities (GGOs) are a commonly observed radiographic finding in pulmonary imaging, frequently associated with various pulmonary pathologies. The etiology of ground-glass opacities is multifactorial, with connective tissue disease-associated interstitial lung disease (CTD-ILD), pulmonary haemosiderosis (PH), and pulmonary alveolar proteinosis (PAP) being potential underlying causes. Since the radiographic presentations of PH and PAP may overlap with those of CTD-ILD, a comprehensive differential diagnosis is crucial. Case presentation: This paper presents the case of a 24-year-old female patient who initially presented with thrombocytopenia and pulmonary opacities, accompanied by exertional dyspnoea, and was diagnosed with CTD-ILD. After treatment with glucocorticoids and mycophenolic acid (MPA), her symptoms improved. However, chest imaging over 8 months revealed recurrent fluctuations in pulmonary ground-glass opacities. Nine months after treatment, fibreoptic bronchoscopy revealed greyish-white gelatinous material in the bronchoalveolar lavage fluid. Anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies were found to be <1 IU/ml, leading to the diagnosis of CTD-ILD with SPAP. Atorvastatin was then added to the treatment regimen. Despite ten months of statin therapy, Chest CT findings show that the condition remains recurrent. After 12 months of statin therapy, re-examination of the lung biopsy specimen revealed alveolar hemosiderin deposition, confirming the diagnosis of CTD-ILD with idiopathic pulmonary hemosiderosis (IPH). Conclusion: This case report describes the rare occurrence of SPAP in a patient with CTD-ILD complicated by IPH. This case highlights the importance of vigilance for IPH and SPAP in patients with CTD who present with persistent or fluctuating pulmonary imaging abnormalities that do not adequately respond to conventional therapy. Prompt alveolar lavage and lung biopsy are essential for establishing a definitive diagnosis. Connective tissue disease Interstitial lung disease Pulmonary alveolar proteinosis Idiopathic pulmonary haemosiderosis Lung biopsy Figures Figure 1 Figure 2 Introduction Diffuse ground-glass opacities (GGOs) are a common radiological finding in pulmonary imaging, frequently observed in various pulmonary conditions, including interstitial lung disease, infections, and tumours. 1,2 In patients with connective tissue disorders (CTDs), diffuse GGOs often constitute one of the radiological hallmarks of CTD-associated interstitial lung disease (CTD-ILD). 3 Idiopathic pulmonary hemosiderosis (IPH) is a rare cause of diffuse alveolar hemorrhage (DAH) and can occasionally precede the clinical manifestation of connective tissue disorders (CTD) by several years. 4–6 Secondary pulmonary alveolar proteinosis (SPAP) represents a small subset (5–10%) of PAP, a rare diffuse lung disorder caused by impaired surfactant clearance or abnormal production leading to intra-alveolar accumulation. 7–9 This paper reports a case of CTD-ILD with IPH and SPAP, in which the patient achieved temporary control through a combination of corticosteroids, mycophenolate mofetil (MMF), and statin therapy. Case Study We present the case of a 24-year-old female who was admitted with a six-month history of thrombocytopenia and pulmonary shadows. The patient has no history of smoking, no known family history of hereditary diseases, and has not been exposed to any identifiable occupational or environmental risk factors. In February 2023, initial blood tests showed a platelet count (PLT) of 45.0 ×10^9/L, a plateletcrit (PCT) of 0.06%, and an activated partial thromboplastin time (APTT) of 44.8 seconds. At that time, the patient exhibited no significant clinical symptoms, and physical examination revealed no notable abnormalities. Chest computed tomography (CT) revealed GGOs in both lungs, a ground-glass nodular shadow in the left upper lobe, and bilateral pleural thickening (Fig. 1a) . Pulmonary function tests demonstrated normal ventilation capacity but moderate impairment in diffusion capacity. Immunological tests showed positive antinuclear antibodies (ANA) at a titre of 1:160, with negative results for antineutrophil cytoplasmic antibodies (ANCA) and extractable nuclear antigens (ENA). Bronchoscopy excluded infection and malignancy. Based on the available findings, the previous hospital suspected interstitial lung disease (ILD) complicated by infection and initiated antimicrobial and symptomatic treatment, which provided temporary relief. Over the subsequent five months, the patient's symptoms and imaging findings showed no significant improvement. Immunological abnormalities progressively worsened, with the ANA titre increasing to a nuclear granular pattern of 1:320 and a cytoplasmic granular pattern of 1:100, though all myositis-specific antibodies remained negative. In August 2023, the patient presented with an acute onset of symptoms following the consumption of cold beverages, including fever with a peak temperature of 38.2°C, cough with sputum production, and wheezing. The patient was referred to the Rheumatology and Immunology Department of our hospital. Physical examination revealed cutaneous findings, including bilateral facial erythema and papules, notably characterized by purplish-red rashes on the upper eyelids, without significant pruritus. Laboratory investigations revealed extensive multisystem involvement: platelet count of 76 × 10⁹/L, direct antiglobulin test (Coombs) positive at 3+, erythrocyte sedimentation rate (ESR) of 59 mm/h, C-reactive protein (CRP) of 26.12 g/L, and immunoglobulin E (IgE) of 788.6 IU/ml. The autoantibody profile showed positive lupus anticoagulant, anti-cardiolipin antibody IgG of 30.0 CU, anti-β2-glycoprotein I (Anti-β2GP1) antibody IgG of 20.6 CU, and positive anti-endothelial cell antibodies (Table 1) . CT revealed GGOs in both lungs, with areas of consolidation predominantly in the right lung, and thickening of the right pulmonary interlobular septa (Fig. 1b) . Pulmonary function tests indicated a moderate reduction in total diffusion capacity, decreased specific diffusion capacity, and small airway dysfunction (Table 2) . Bone marrow cytology revealed granulocyte system hyperplasia and megakaryocyte system maturation impairment. Based on the aforementioned laboratory findings, a diagnosis of CTD-ILD was considered. Treatment was initiated with prednisolone 25 mg/day combined with mycophenolic acid (MPA) 0.36 g/day. The patient's subjective symptoms improved, with significant resolution of fever and rash. Despite improvement in subjective symptoms, the patient's pulmonary imaging demonstrated fluctuating changes over eight months of corticosteroid and immunosuppressive therapy (Fig. 1c-e) . Given the persistent fluctuations in imaging and the unclear nature of the lesions, the patient was transferred to the respiratory department of our hospital at nine months post-treatment for a cryopreserved lung biopsy via fibreoptic bronchoscopy to establish a definitive diagnosis. At this stage, immunosuppressive therapy had elicited a marked systemic response (Table 1) : anti-CCP and anti-β2GP1 antibodies had seroconverted to negative, lupus anticoagulants remained present in low quantities, the Coombs test had changed from strongly positive to positive, and IgE levels had decreased. Chest CT revealed diffuse GGOs in both lungs with focal interlobular septal thickening, showing marked resolution and reduction compared to previous imaging (Fig. 1f) . Pulmonary function tests demonstrated mildly decreased lung diffusion capacity, reduced specific diffusion capacity, and decreased end-expiratory flow rate, all showing improvement compared to previous measurements (Table 2) . Additionally, fibreoptic bronchoscopy provided key diagnostic pathological evidence. Bronchoalveolar lavage fluid (BALF) revealed greyish-white gelatinous tissue measuring 0.5 cm × 0.5 cm × 0.2 cm, with mucus-like material containing numerous histiocytes and neutrophils. Microscopic examination of BALF revealed abundant macrophages, scattered ciliated columnar epithelial cells, superficial squamous epithelial cells, and neutrophils. Histopathological examination of haematoxylin and eosin (HE)-stained lung biopsy specimens revealed chronic inflammatory changes in the mucosal tissue of the posterior basal segment of the right lower lobe. The interstitium showed lymphocytic infiltration and hemosiderin deposition, with scattered histiocytes within the alveolar spaces. The same material tested positive for periodic acid-schiff (PAS) staining. To differentiate between APAP and SPAP, the patient underwent anti-GM-CSF antibody testing, which yielded a result of <1 IU/ml (Table 1) . Based on these findings, the patient was diagnosed with CTD-ILD complicated by SPAP. Treatment was initiated with an additional atorvastatin dose of 10 mg/day. Between 13 and 20 months post-treatment, the patient's CT imaging findings fluctuated between improvement and exacerbation. Consequently, at the 22nd month post-treatment, the patient underwent a re-examination of the histopathological sections from the previous lung biopsy. The findings revealed hemosiderin-laden macrophages were observed in the peri-bronchial and within some alveolar spaces (Fig. 2) . Further detailed history-taking revealed a 16-year history of haematemesis. Episodes were typically minor, involving bright red blood, and frequently coincided with respiratory tract infections. The blood was usually expectorated with sputum, leading the patient to pay little attention to this symptom. Integrating the comprehensive clinical history, the final diagnosis was CTD-ILD complicated by IPH, with superimposed SPAP during the disease course. Following this new diagnosis, the treatment regimen was adjusted: statin therapy was discontinued and replaced with prednisolone 40 mg/day combined with mycophenolate mofetil (MMF) 1.5 g/day. CT scans conducted within six months of initiating prednisolone and MMF therapy showed no progression of the pulmonary disease. Discussion IPH often presents with the classic triad of iron deficiency anemia (IDA), recurrent hemoptysis, and diffuse pulmonary infiltrates on imaging. 10 However, this triad may be incomplete or absent in adults, which can lead to significant diagnostic delays. 11 A statistical analysis of Medline and Embase databases from their inception to 2021 revealed that the classic triad was present in 61 out of 84 (79%) patients. 11 In this case, the patient had a 16-year history of hemoptysis, but its intermittent nature delayed the recognition of IPH, resulting in a prolonged diagnostic period. The absence of typical manifestations of iron deficiency anemia further complicated the diagnosis. The patient’s prolonged hemoptysis, however, lacked immunologically related clinical signs, which substantially excluded autoimmune causes of diffuse alveolar hemorrhage (DAH) in this case. IPH is one of the causes of DAH, and its diagnosis relies on excluding all known causes of DAH, particularly vasculitis-associated DAH. After systematically ruling out other potential causes, including infections, ANCA-associated vasculitis, anti-glomerular basement membrane disease, systemic lupus erythematosus (SLE), and drug-induced conditions, IPH was deemed the most likely diagnosis. The aetiology of IPH involves multiple factors, including genetics, environmental factors, and autoimmune mechanisms. 4,10 Substantial evidence indicates immune involvement in the pathogenesis of IPH. A cohort study tracking 15 pediatric IPH patients found that approximately 25% of those surviving beyond 10 years subsequently developed autoimmune diseases. 6 A French cohort study indicated that over 90% of IPH patients tested positive for autoantibodies during follow-up, with these antibodies either persisting, gradually diminishing, or disappearing over time. 13 Another study reported that 26.4% of 288 IPH patients tested positive for autoantibodies. 14 IPH may not merely represent an isolated alveolar capillary disorder but could involve immune system abnormalities, potentially signaling or co-occurring with autoimmune diseases in certain patients. 15,16 The clinical course in this case demonstrated an initial predominance of pulmonary immune manifestations, followed by the later emergence of systemic features, including cutaneous involvement and autoantibody positivity, suggesting a transition toward more generalized immune activation. There have been reports of PAP being misdiagnosed as CTD-ILD or worsening despite immunosuppressive therapy. 17–19 During immunosuppressive therapy for anti-MDA5 antibody-positive dermatomyositis complicated by ILD, worsening infection in a patient with PAP was misinterpreted as an ILD flare. 20 Patients with both SLE and systemic sclerosis (SSc) experienced exacerbation of PAP following immunosuppressive therapy. 21,22 In this case, SPAP was initially missed at the time of CTD-ILD diagnosis. Besides, although GGOs were common in both APAP and SPAP, SPAP predominantly showed diffuse, evenly distributed GGOs, whereas APAP was characterized by patchy geographic GGOs with frequent crazy-paving and subpleural sparing, preferentially involving the lower lung fields. 23 Therefore, this case actually aligns more with the imaging characteristics of SPAP rather than APAP. The etiology of SPAP is diverse, encompassing inhalation exposures, hematological disorders, immune-mediated diseases, and chemotherapy agents. 24 SPAP is rarely associated with immunodeficiency and has only sporadically been reported in patients with CTD, including dermatomyositis, 25 rheumatoid arthritis (RA), 26 and Behçet’s disease. 27 Patients with autoimmune diseases may develop SPAP after receiving immunosuppressive therapy for several months to years, indicating that immunosuppressive agents may induce or exacerbate SPAP. 2829 This patient concurrently presented with CTD-ILD, IPH, and SPAP. Immunosuppressive therapy may have improved the first two conditions by controlling systemic inflammation and reducing alveolar haemorrhage. In contrast, SPAP may progress slowly, with early symptoms masked by the marked improvement in CTD-ILD and IPH, creating a lag in the therapeutic response. Immunosuppressive therapy is crucial for controlling CTD-ILD 30,31 and IPH, with the majority of IPH patients responding favorably to such treatment in clinical practice. 32 Although no standardized IPH management protocol currently exists, clinical evidence suggests that glucocorticoid therapy is the treatment of choice, with some patients achieving favorable outcomes upon the addition of a second immunosuppressive agent. 32 In this case, the immunosuppressive regimen combining glucocorticoids with MMF resulted in decreased levels of autoimmune-related antibodies and partial improvement in pulmonary imaging, indicating effective control of immune dysregulation. The treatment principles for SPAP focus on actively managing the underlying disease. 28,33 Depending on the severity of the condition, whole lung lavage (WLL) is employed as the primary intervention, alongside symptomatic supportive care, including oxygen therapy and infection management when necessary. 33 Given the relatively mild symptoms, the efficacy of immunosuppressive therapy, and the increased risk of WLL associated with coagulation abnormalities, the decision to forgo whole lung lavage is considered reasonable. This case underscores the importance of distinguishing between ILD, IPH, and PAP when diagnosing pulmonary lesions in patients with CTD. For individuals with a history of haemoptysis, recurrent imaging changes, or new pulmonary opacities emerging during immunosuppressive therapy, early lung biopsy and comprehensive histopathological examination are essential for a definitive diagnosis. In chronic cases, histopathological examination may provide greater diagnostic value than bronchoalveolar lavage fluid cytology for IPH. Furthermore, when managing pulmonary disease associated with CTD, appropriate doses of immunosuppressive agents may be employed, with ongoing monitoring of imaging changes and timely adjustments to treatment regimens as needed. Declarations Ethics approval and consent to participate This study was approved by the Ethics Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. Consent for publication Written informed consent was obtained from the patient for participation in the study and for the publication of any identifying information or images. Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding Not applicable Authors' contributions XZ analyzed and interpreted the patient data and was a major contributor in writing the manuscript. JX followed up with patients and participated in the revision of the manuscript. QH conducted a detailed review of lung imaging and contributed to the revision of the manuscript. LZ performed the histological examination of the lung. GS contributed to the conception and design of the work and substantively revised it. All authors read and approved the final manuscript. Acknowledgements Not applicable. References Cozzi D, Cavigli E, Moroni C, et al. Ground-glass opacity (GGO): a review of the differential diagnosis in the era of COVID-19. Jpn J Radiol . 2021;39(8):721-732. doi:10.1007/s11604-021-01120-w Parekh M, Donuru A, Balasubramanya R, Kapur S. Review of the Chest CT Differential Diagnosis of Ground-Glass Opacities in the COVID Era. Radiology . 2020;297(3):E289-E302. doi:10.1148/radiol.2020202504 Fischer A, du Bois R. 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BMJ . 2016;352:h6819. doi:10.1136/bmj.h6819 Antoniou KM, Distler O, Gheorghiu AM, et al. ERS/EULAR clinical practice guidelines for connective tissue disease-associated interstitial lung disease. Eur Respir J . 2026;67(1):2402533. doi:10.1183/13993003.02533-2024 Saha BK, Milman NT. Idiopathic pulmonary hemosiderosis: a review of the treatments used during the past 30 years and future directions. Clin Rheumatol . 2021;40(7):2547-2557. doi:10.1007/s10067-020-05507-4 Lim J, Boyle N, McCarthy C. Secondary Pulmonary Alveolar Proteinosis. Semin Respir Crit Care Med . Published online November 24, 2025. doi:10.1055/a-2741-2079 Tables Table 1. The patient's laboratory test results Variables Admission Follow-up Reference Range (10 months) Hematology WBC (/µL) 9050 6910 3500-9500 RBC (M/µL) 3.97 4.3 3.80-5.10 Hgb (g/dL) 12.1 12.4 11.5-15.0 PLT (/µL) 76000 121000 125000-350000 Neutrophils (%) 77.5 70.9 40.0-75.0 Lymphocytes (%) 16 16.9 20.0-50.0 Monocytes (%) 5.7 11.7 3.0-10.0 Eosinophils (%) 0.7 0.4 0.4-8.0 Basophils (%) 0.1 0.1 0.0-1.0 Neutrophils (/µL) 7010 4890 1800-6300 Lymphocytes (/µL) 1450 1170 1100-3200 Monocytes (/µL) 520 810 100-600 Eosinophils (/µL) 60 30 20-52 Basophils (/µL) 10 10 0-100 Direct Coombs Test +++ + - Biochemistry ALT (U/L) 10 7 7-40 AST (U/L) 23 20 13-35 TB (µmol/L) 22.9 10.9 ≤23.0 DB(µmol/L) 7.4 4 ≤6.89 IB (µmol/L) 15.5 6.9 ≤12.9 LDH(U/L) 199 303 120-250 ESR (mm/H) 59 6 0-20 CRP(g/L) 26.1 3.8 0-10 Coagulation function PT (s) 13.7 13.6 11.5-14.5 PT Activity (%) 89 94 80.0-135.0 Fibrinogen (g/L) 4.1 2.62 2.00-4.00 APTT (s) 48.9 40.2 29.0-42.0 Thrombin Time (s) 16.2 17.8 ＜21.0 D-Dimer (µg/mL) 0.34 <0.22 <0.50 Autoimmune and Antibody Profile ANA (1:100) Cytoplasmic Granular 1:320 ↑ Cytoplasmic Granular 1:100 ↑ - Total IgE (IU/mL) 788.6 198.3 ≤100 Anti-Cardiolipin Ab IgA (CU) 8.4 6.8 ＜20.0 Anti-Cardiolipin Ab IgG (CU) 30 19.5 ＜20.0 Anti-Cardiolipin Ab IgM (CU) 2.2 1.8 ＜20.0 Anti-β2GP1 Ab IgA (CU) <4.0 <4.0 ＜20.0 Anti-β2GP1 Ab IgG (CU) 20.6 13.2 ＜20.0 Anti-β2GP1 Ab IgM (CU) <1.1 <1.1 ＜20.0 Anti-Endothelial Cell Ab testing - - - Lupus Anticoagulant SCT Screening Ratio 1.48 1.47 <1.2 Perinuclear Anti-Neutrophil Cytoplasmic Ab - - - Classic Anti-Neutrophil Cytoplasmic Ab - - - Anti-MPO Ab IgG (RU/mL) 5.8 3.9 0-20.0 Anti-PR3 Ab IgG (RU/mL) <2.00 <2.00 0-20.0 Anti-GBM Ab - - - Anti-GM-CSF Ab (IU/ml) <1 <1 <1 Abbreviations: WBC , White Blood Cell; RBC , Red Blood Cell; Hgb , Hemoglobin; PLT, Platelet; ALT, Alanine Aminotransferase; AST , Aspartate Aminotransferase; TB , Total Bilirubin; DB , Direct Bilirubin; IB , Indirect Bilirubin; ESR , Erythrocyte Sedimentation Rate; CRP , C-Reactive Protein. PT , Prothrombin Time; PT Activity, Prothrombin Activity; APTT , Activated Partial Thromboplastin Time; D-Dimer , D-Dimer Quantification; ANA , Antinuclear Antibody; IgA , Immunoglobulin A; IgG , Immunoglobulin G; IgM , Immunoglobulin M; Ab , Antibody; β2GP1 , Beta-2 Glycoprotein 1; MPO , Myeloperoxidase; PR3 , Proteinase 3; GBM , Glomerular Basement Membrane; GM-CSF , Granulocyte-Macrophage Colony-Stimulating Factor. Table 2. Pulmonary function test Tests Admission Follow-up (10 months) Result Predicted value Result Predicted value FVC (L) 3.13 3.37 3.11 3.28 FVC%pred (%) 92.9 94.8 FEV 1(L) 2.52 2.94 2.53 2.86 FEV 1 %pred (%) 85.8 88.6 FEV 1 /FVC (%) 80.48 86.89 81.38 87.41 FEV1/FVC %pred (%) 92.6 93.1 TLC (L) 4.17 4.51 4.61 4.37 TLC%pred (%) 92.6 105.4 DLCO (mmol/min/kPa) 4.59 8.8 5.95 8.63 DLCO%pred (%) 52.2 68.9 Abbreviations: FVC, forced vital capacity; FEV1, forced expiratory volume in 1 second; TLC, total lung volume; DLCO , diffusion capacity of carbon monoxide; %pred , percentage of the predicted value. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9128043","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":623144313,"identity":"8775321c-ae99-4eed-bce3-009dfb3c5175","order_by":0,"name":"Xingyi Zhao","email":"","orcid":"","institution":"Huazhong University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Xingyi","middleName":"","lastName":"Zhao","suffix":""},{"id":623144314,"identity":"b543fc03-ae51-4f65-be58-684c386af127","order_by":1,"name":"Jie Xia","email":"","orcid":"","institution":"Huazhong University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Jie","middleName":"","lastName":"Xia","suffix":""},{"id":623144316,"identity":"30081067-cc49-4011-a715-2ec266e4c75f","order_by":2,"name":"Qiongjie Hu","email":"","orcid":"","institution":"Huazhong University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Qiongjie","middleName":"","lastName":"Hu","suffix":""},{"id":623144317,"identity":"8a3b5734-3791-4e2d-b85c-325e8be3d129","order_by":3,"name":"Liyan Zhu","email":"","orcid":"","institution":"Huazhong University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Liyan","middleName":"","lastName":"Zhu","suffix":""},{"id":623144319,"identity":"e925eea6-1bfa-4392-8005-e3a0c14358cb","order_by":4,"name":"Guifen Shen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2ElEQVRIiWNgGAWjYFACxoYPQDKBgYH5wIEPP4jT0jgDooUt8eDMHiKtgWrhMT7MwUaEevmI5MaGjzvq8vilez4cZuBhkOcXO4Bfi+GNxMbGmWcOF0vOObvhcIEFg+HM2QkEtMxIbH/M23YgccON3A2HZ/AwJBjcJqylsflvW13i/hs5Dw7zsBGhRV4CqIWxjTlxg0QOA3FaDHgeNjb2th1OnHEjzQAYyBKE/SLfnv6w4SfQYf0zkh9/+PDDRp5fmpAtB1D5EviVg21pIKxmFIyCUTAKRjoAAJvPTqhRPxNnAAAAAElFTkSuQmCC","orcid":"","institution":"Huazhong University of Science and Technology","correspondingAuthor":true,"prefix":"","firstName":"Guifen","middleName":"","lastName":"Shen","suffix":""}],"badges":[],"createdAt":"2026-03-15 10:53:47","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9128043/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9128043/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107481131,"identity":"5b2a23a0-03fd-4c89-92db-e52ec75961db","added_by":"auto","created_at":"2026-04-22 02:15:59","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":484721,"visible":true,"origin":"","legend":"\u003cp\u003eCourse of interstitial pneumonia on chest computed tomography (CT) scans: \u003cstrong\u003e(a) Initial CT:\u003c/strong\u003e diffuse ground-glass opacities in both lungs; \u003cstrong\u003e(b) At the first admission (acute exacerbation phase): \u003c/strong\u003ediffuse ground-glass opacities with partial consolidation were present in both lungs, more pronounced in the right lung, with thickened interlobular septa and progression from previous findings; \u003cstrong\u003e(c) Four months post-treatment:\u003c/strong\u003e diffuse bilateral ground-glass opacities with improvement over baseline; \u003cstrong\u003e(d) Seven months post-treatment:\u003c/strong\u003ebilateral ground-glass opacities with minor consolidation in the right upper lobe, thickened interlobular septa, and progression compared to previous findings; \u003cstrong\u003e(e) Eight months post-treatment (prior to lung lavage and biopsy):\u003c/strong\u003ebilateral ground-glass opacities with minor consolidation in the right upper lobe, showing improvement over baseline; \u003cstrong\u003e(f) Ten months post-treatment (with statin therapy added):\u003c/strong\u003e diffuse ground-glass opacities in both lungs with localised interlobular septal thickening, showing marked absorption and reduction compared to previous findings.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9128043/v1/3644ae26e00544846f5d8820.jpg"},{"id":107042903,"identity":"707d2dfe-69f1-43fb-8af5-e96c6c267c3b","added_by":"auto","created_at":"2026-04-16 06:44:04","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":694275,"visible":true,"origin":"","legend":"\u003cp\u003eHistopathological examination: Haematoxylin and eosin (HE) staining revealed hemosiderin-laden macrophages (as indicated by the arrows) was observed in the peribronchial and within some alveolar spaces. \u003cstrong\u003e(a)\u003c/strong\u003e Magnification, x10; \u003cstrong\u003e(b)\u003c/strong\u003eMagnification, x20.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-9128043/v1/8d789d51afdd9523fd9ceca2.jpeg"},{"id":107483689,"identity":"6af2f545-2085-4609-a2b9-9dc38d8e29d7","added_by":"auto","created_at":"2026-04-22 02:28:49","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1742592,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9128043/v1/8b26fc32-808b-435d-81ac-672db5ccc797.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Prominent Diffuse Ground-Glass Opacities: A Challenging Case of CTD-ILD, IPH, and Secondary PAP Coexistence","fulltext":[{"header":"Introduction","content":"\u003cp\u003eDiffuse ground-glass opacities (GGOs) are a common radiological finding in pulmonary imaging, frequently observed in various pulmonary conditions, including interstitial lung disease, infections, and tumours.\u003csup\u003e1,2\u003c/sup\u003e In patients with connective tissue disorders (CTDs), diffuse GGOs often constitute one of the radiological hallmarks of CTD-associated interstitial lung disease (CTD-ILD).\u003csup\u003e3\u003c/sup\u003e Idiopathic pulmonary hemosiderosis (IPH) is a rare cause of diffuse alveolar hemorrhage (DAH) and can occasionally precede the clinical manifestation of connective tissue disorders (CTD) by several years.\u003csup\u003e4\u0026ndash;6\u003c/sup\u003e Secondary pulmonary alveolar proteinosis (SPAP) represents a small subset (5\u0026ndash;10%) of PAP, a rare diffuse lung disorder caused by impaired surfactant clearance or abnormal production leading to intra-alveolar accumulation.\u003csup\u003e7\u0026ndash;9\u003c/sup\u003e This paper reports a case of CTD-ILD with IPH and SPAP, in which the patient achieved temporary control through a combination of corticosteroids, mycophenolate mofetil (MMF), and statin therapy.\u003c/p\u003e"},{"header":"Case Study","content":"\u003cp\u003eWe present the case of a 24-year-old female who was admitted with a six-month history of thrombocytopenia and pulmonary shadows. The patient has no history of smoking, no known family history of hereditary diseases, and has not been exposed to any identifiable occupational or environmental risk factors. In February 2023, initial blood tests showed a platelet count (PLT) of 45.0\u0026nbsp;×10^9/L, a plateletcrit (PCT) of 0.06%, and an activated partial thromboplastin time (APTT) of 44.8 seconds. At that time, the patient exhibited no significant clinical symptoms, and physical examination revealed no notable abnormalities. Chest computed tomography (CT) revealed GGOs in both lungs, a ground-glass nodular shadow in the left upper lobe, and bilateral pleural thickening \u003cstrong\u003e(Fig. 1a)\u003c/strong\u003e. Pulmonary function tests demonstrated normal ventilation capacity but moderate impairment in diffusion capacity. Immunological tests showed positive antinuclear antibodies (ANA) at a titre of 1:160, with negative results for antineutrophil cytoplasmic antibodies (ANCA) and extractable nuclear antigens (ENA). Bronchoscopy excluded infection and malignancy. Based on the available findings, the previous hospital suspected interstitial lung disease (ILD) complicated by infection and initiated antimicrobial and symptomatic treatment, which provided temporary relief. Over the subsequent five months, the patient's symptoms and imaging findings showed no significant improvement. Immunological abnormalities progressively worsened, with the ANA titre increasing to a nuclear granular pattern of 1:320 and a cytoplasmic granular pattern of 1:100, though all myositis-specific antibodies remained negative.\u003c/p\u003e\n\u003cp\u003eIn August 2023, the patient presented with an acute onset of symptoms following the consumption of cold beverages, including fever with a peak temperature of 38.2°C, cough with sputum production, and wheezing. The patient was referred to the Rheumatology and Immunology Department of our hospital. Physical examination revealed cutaneous findings, including bilateral facial erythema and papules, notably characterized by purplish-red rashes on the upper eyelids, without significant pruritus. Laboratory investigations revealed extensive multisystem involvement: platelet count of 76 × 10⁹/L, direct antiglobulin test (Coombs) positive at 3+, erythrocyte sedimentation rate (ESR) of 59 mm/h, C-reactive protein (CRP) of 26.12 g/L, and immunoglobulin E (IgE) of 788.6 IU/ml. The autoantibody profile showed positive lupus anticoagulant, anti-cardiolipin antibody IgG of 30.0 CU, anti-β2-glycoprotein I (Anti-β2GP1) antibody IgG of 20.6 CU, and positive anti-endothelial cell antibodies\u003cstrong\u003e\u0026nbsp;(Table 1)\u003c/strong\u003e. CT revealed GGOs in both lungs, with areas of consolidation predominantly in the right lung, and thickening of the right pulmonary interlobular septa \u003cstrong\u003e(Fig. 1b)\u003c/strong\u003e. Pulmonary function tests indicated a moderate reduction in total diffusion capacity, decreased specific diffusion capacity, and small airway dysfunction \u003cstrong\u003e(Table 2)\u003c/strong\u003e. Bone marrow cytology revealed granulocyte system hyperplasia and megakaryocyte system maturation impairment. Based on the aforementioned laboratory findings, a diagnosis of CTD-ILD was considered. Treatment was initiated with prednisolone 25 mg/day combined with mycophenolic acid (MPA) 0.36 g/day. The patient's subjective symptoms improved, with significant resolution of fever and rash.\u003c/p\u003e\n\u003cp\u003eDespite improvement in subjective symptoms, the patient's pulmonary imaging demonstrated fluctuating changes over eight months of corticosteroid and immunosuppressive therapy \u003cstrong\u003e(Fig. 1c-e)\u003c/strong\u003e. Given the persistent fluctuations in imaging and the unclear nature of the lesions, the patient was transferred to the respiratory department of our hospital at nine months post-treatment for a cryopreserved lung biopsy via fibreoptic bronchoscopy to establish a definitive diagnosis. At this stage, immunosuppressive therapy had elicited a marked systemic response \u003cstrong\u003e(Table 1)\u003c/strong\u003e: anti-CCP and anti-β2GP1 antibodies had seroconverted to negative, lupus anticoagulants remained present in low quantities, the Coombs test had changed from strongly positive to positive, and IgE levels had decreased. Chest CT revealed diffuse GGOs in both lungs with focal interlobular septal thickening, showing marked resolution and reduction compared to previous imaging \u003cstrong\u003e(Fig. 1f)\u003c/strong\u003e. Pulmonary function tests demonstrated mildly decreased lung diffusion capacity, reduced specific diffusion capacity, and decreased end-expiratory flow rate, all showing improvement compared to previous measurements\u003cstrong\u003e\u0026nbsp;(Table 2)\u003c/strong\u003e. Additionally, fibreoptic bronchoscopy provided key diagnostic pathological evidence. Bronchoalveolar lavage fluid (BALF) revealed greyish-white gelatinous tissue measuring 0.5 cm × 0.5 cm × 0.2 cm, with mucus-like material containing numerous histiocytes and neutrophils. Microscopic examination of BALF revealed abundant macrophages, scattered ciliated columnar epithelial cells, superficial squamous epithelial cells, and neutrophils. Histopathological examination of haematoxylin and eosin (HE)-stained lung biopsy specimens revealed chronic inflammatory changes in the mucosal tissue of the posterior basal segment of the right lower lobe. The interstitium showed lymphocytic infiltration and hemosiderin deposition, with scattered histiocytes within the alveolar spaces. The same material tested positive for periodic acid-schiff (PAS) staining. To differentiate between APAP and SPAP, the patient underwent anti-GM-CSF antibody testing, which yielded a result of \u0026lt;1 IU/ml \u003cstrong\u003e(Table 1)\u003c/strong\u003e. Based on these findings, the patient was diagnosed with CTD-ILD complicated by SPAP. Treatment was initiated with an additional atorvastatin dose of 10 mg/day.\u003c/p\u003e\n\u003cp\u003eBetween 13 and 20 months post-treatment, the patient's CT imaging findings fluctuated between improvement and exacerbation. Consequently, at the 22nd month post-treatment, the patient underwent a re-examination of the histopathological sections from the previous lung biopsy. The findings revealed hemosiderin-laden macrophages were observed in the peri-bronchial and within some alveolar spaces\u003cstrong\u003e\u0026nbsp;(Fig. 2)\u003c/strong\u003e. Further detailed history-taking revealed a 16-year history of haematemesis. Episodes were typically minor, involving bright red blood, and frequently coincided with respiratory tract infections. The blood was usually expectorated with sputum, leading the patient to pay little attention to this symptom. Integrating the comprehensive clinical history, the final diagnosis was CTD-ILD complicated by IPH, with superimposed SPAP during the disease course. Following this new diagnosis, the treatment regimen was adjusted: statin therapy was discontinued and replaced with prednisolone 40 mg/day combined with mycophenolate mofetil (MMF) 1.5 g/day. CT scans conducted within six months of initiating prednisolone and MMF therapy showed no progression of the pulmonary disease.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIPH often presents with the classic triad of iron deficiency anemia (IDA), recurrent hemoptysis, and diffuse pulmonary infiltrates on imaging.\u003csup\u003e10\u003c/sup\u003e However, this triad may be incomplete or absent in adults, which can lead to significant diagnostic delays.\u003csup\u003e11\u003c/sup\u003e A statistical analysis of Medline and Embase databases from their inception to 2021 revealed that the classic triad was present in 61 out of 84 (79%) patients.\u003csup\u003e11\u003c/sup\u003e In this case, the patient had a 16-year history of hemoptysis, but its intermittent nature delayed the recognition of IPH, resulting in a prolonged diagnostic period. The absence of typical manifestations of iron deficiency anemia further complicated the diagnosis. The patient\u0026rsquo;s prolonged hemoptysis, however, lacked immunologically related clinical signs, which substantially excluded autoimmune causes of diffuse alveolar hemorrhage (DAH) in this case. IPH is one of the causes of DAH, and its diagnosis relies on excluding all known causes of DAH, particularly vasculitis-associated DAH. After systematically ruling out other potential causes, including infections, ANCA-associated vasculitis, anti-glomerular basement membrane disease, systemic lupus erythematosus (SLE), and drug-induced conditions, IPH was deemed the most likely diagnosis.\u003c/p\u003e\n\u003cp\u003eThe aetiology of IPH involves multiple factors, including genetics, environmental factors, and autoimmune mechanisms.\u003csup\u003e4,10\u003c/sup\u003e Substantial evidence indicates immune involvement in the pathogenesis of IPH. A cohort study tracking 15 pediatric IPH patients found that approximately 25% of those surviving beyond 10 years subsequently developed autoimmune diseases.\u003csup\u003e6\u003c/sup\u003e A French cohort study indicated that over 90% of IPH patients tested positive for autoantibodies during follow-up, with these antibodies either persisting, gradually diminishing, or disappearing over time.\u003csup\u003e13\u003c/sup\u003e Another study reported that 26.4% of 288 IPH patients tested positive for autoantibodies.\u003csup\u003e14\u003c/sup\u003e IPH may not merely represent an isolated alveolar capillary disorder but could involve immune system abnormalities, potentially signaling or co-occurring with autoimmune diseases in certain patients.\u003csup\u003e15,16\u003c/sup\u003e The clinical course in this case demonstrated an initial predominance of pulmonary immune manifestations, followed by the later emergence of systemic features, including cutaneous involvement and autoantibody positivity, suggesting a transition toward more generalized immune activation.\u003c/p\u003e\n\u003cp\u003eThere have been reports of PAP being misdiagnosed as CTD-ILD or worsening despite immunosuppressive therapy.\u003csup\u003e17\u0026ndash;19\u003c/sup\u003e During immunosuppressive therapy for anti-MDA5 antibody-positive dermatomyositis complicated by ILD, worsening infection in a patient with PAP was misinterpreted as an ILD flare.\u003csup\u003e20\u003c/sup\u003e Patients with both SLE and systemic sclerosis (SSc) experienced exacerbation of PAP following immunosuppressive therapy.\u003csup\u003e21,22\u003c/sup\u003e In this case, SPAP was initially missed at the time of CTD-ILD diagnosis. Besides, although GGOs were common in both APAP and SPAP, SPAP predominantly showed diffuse, evenly distributed GGOs, whereas APAP was characterized by patchy geographic GGOs with frequent crazy-paving and subpleural sparing, preferentially involving the lower lung fields.\u003csup\u003e23\u003c/sup\u003e Therefore, this case actually aligns more with the imaging characteristics of SPAP rather than APAP. The etiology of SPAP is diverse, encompassing inhalation exposures, hematological disorders, immune-mediated diseases, and chemotherapy agents.\u003csup\u003e24\u003c/sup\u003e SPAP is rarely associated with immunodeficiency and has only sporadically been reported in patients with CTD, including dermatomyositis,\u003csup\u003e25\u003c/sup\u003e rheumatoid arthritis (RA),\u003csup\u003e26\u003c/sup\u003e and Beh\u0026ccedil;et\u0026rsquo;s disease.\u003csup\u003e27\u003c/sup\u003e Patients with autoimmune diseases may develop SPAP after receiving immunosuppressive therapy for several months to years, indicating that immunosuppressive agents may induce or exacerbate SPAP.\u003csup\u003e2829\u003c/sup\u003e This patient concurrently presented with CTD-ILD, IPH, and SPAP. Immunosuppressive therapy may have improved the first two conditions by controlling systemic inflammation and reducing alveolar haemorrhage. In contrast, SPAP may progress slowly, with early symptoms masked by the marked improvement in CTD-ILD and IPH, creating a lag in the therapeutic response.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eImmunosuppressive therapy is crucial for controlling CTD-ILD\u003csup\u003e30,31\u003c/sup\u003e and IPH, with the majority of IPH patients responding favorably to such treatment in clinical practice.\u003csup\u003e32\u003c/sup\u003e Although no standardized IPH management protocol currently exists, clinical evidence suggests that glucocorticoid therapy is the treatment of choice, with some patients achieving favorable outcomes upon the addition of a second immunosuppressive agent.\u003csup\u003e32\u003c/sup\u003e In this case, the immunosuppressive regimen combining glucocorticoids with MMF resulted in decreased levels of autoimmune-related antibodies and partial improvement in pulmonary imaging, indicating effective control of immune dysregulation. The treatment principles for SPAP focus on actively managing the underlying disease.\u003csup\u003e28,33\u003c/sup\u003e Depending on the severity of the condition, whole lung lavage (WLL) is employed as the primary intervention, alongside symptomatic supportive care, including oxygen therapy and infection management when necessary.\u003csup\u003e33\u003c/sup\u003e Given the relatively mild symptoms, the efficacy of immunosuppressive therapy, and the increased risk of WLL associated with coagulation abnormalities, the decision to forgo whole lung lavage is considered reasonable.\u003c/p\u003e\n\u003cp\u003eThis case underscores the importance of distinguishing between ILD, IPH, and PAP when diagnosing pulmonary lesions in patients with CTD. For individuals with a history of haemoptysis, recurrent imaging changes, or new pulmonary opacities emerging during immunosuppressive therapy, early lung biopsy and comprehensive histopathological examination are essential for a definitive diagnosis. In chronic cases, histopathological examination may provide greater diagnostic value than bronchoalveolar lavage fluid cytology for IPH. Furthermore, when managing pulmonary disease associated with CTD, appropriate doses of immunosuppressive agents may be employed, with ongoing monitoring of imaging changes and timely adjustments to treatment regimens as needed.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eEthics approval and consent to participate\u003c/h2\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eConsent for publication\u003c/h2\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for participation in the study and for the publication of any identifying information or images.\u003c/p\u003e\n\u003ch2\u003eAvailability of data and materials\u003c/h2\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003ch2\u003eCompeting interests\u003c/h2\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003ch2\u003eFunding\u003c/h2\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003ch2\u003eAuthors' contributions\u003c/h2\u003e\n\u003cp\u003eXZ analyzed and interpreted the patient data and was a major contributor in writing the manuscript. JX followed up with patients and participated in the revision of the manuscript. QH conducted a detailed review of lung imaging and contributed to the revision of the manuscript. LZ performed the histological examination of the lung. GS contributed to the conception and design of the work and substantively revised it. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003ch2\u003eAcknowledgements\u003c/h2\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eCozzi D, Cavigli E, Moroni C, et al. Ground-glass opacity (GGO): a review of the differential diagnosis in the era of COVID-19. \u003cem\u003eJpn J Radiol\u003c/em\u003e. 2021;39(8):721-732. doi:10.1007/s11604-021-01120-w\u003c/li\u003e\n\u003cli\u003eParekh M, Donuru A, Balasubramanya R, Kapur S. Review of the Chest CT Differential Diagnosis of Ground-Glass Opacities in the COVID Era. \u003cem\u003eRadiology\u003c/em\u003e. 2020;297(3):E289-E302. doi:10.1148/radiol.2020202504\u003c/li\u003e\n\u003cli\u003eFischer A, du Bois R. Interstitial lung disease in connective tissue disorders. \u003cem\u003eLancet\u003c/em\u003e. 2012;380(9842):689-698. doi:10.1016/S0140-6736(12)61079-4\u003c/li\u003e\n\u003cli\u003eSaha BK, Aiman A, Chong WH, Saha S, Song J, Bonnier A. Updates in idiopathic pulmonary hemosiderosis in 2022: A state of the art review. \u003cem\u003ePediatr Pulmonol\u003c/em\u003e. 2023;58(2):382-391. doi:10.1002/ppul.26230\u003c/li\u003e\n\u003cli\u003eYanagihara T, Yamamoto Y, Hamada N, et al. 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Pulmonary Alveolar Proteinosis. \u003cem\u003eClin Chest Med\u003c/em\u003e. 2025;46(4):633-647. doi:10.1016/j.ccm.2025.07.005\u003c/li\u003e\n\u003cli\u003eTrapnell BC, Nakata K, Bonella F, et al. Pulmonary alveolar proteinosis. \u003cem\u003eNat Rev Dis Primers\u003c/em\u003e. 2019;5(1):16. doi:10.1038/s41572-019-0066-3\u003c/li\u003e\n\u003cli\u003eSaha BK. Idiopathic pulmonary hemosiderosis: A state of the art review. \u003cem\u003eRespir Med\u003c/em\u003e. 2021;176:106234. doi:10.1016/j.rmed.2020.106234\u003c/li\u003e\n\u003cli\u003eSaha BK, Bonnier A, Saha S, Saha BN, Shkolnik B. Adult patients with idiopathic pulmonary hemosiderosis: a comprehensive review of the literature. \u003cem\u003eClin Rheumatol\u003c/em\u003e. 2022;41(6):1627-1640. doi:10.1007/s10067-022-06104-3\u003c/li\u003e\n\u003cli\u003eSaha BK, Chong WH, Milman NT. Differentiation of idiopathic pulmonary hemosiderosis from rheumatologic and autoimmune diseases causing diffuse alveolar hemorrhage: establishing a diagnostic approach. \u003cem\u003eClin Rheumatol\u003c/em\u003e. 2022;41(2):325-336. doi:10.1007/s10067-021-05895-1\u003c/li\u003e\n\u003cli\u003eTaytard J, Nathan N, de Blic J, et al. New insights into pediatric idiopathic pulmonary hemosiderosis: the French RespiRare(\u0026reg;) cohort. \u003cem\u003eOrphanet J Rare Dis\u003c/em\u003e. 2013;8:161. doi:10.1186/1750-1172-8-161\u003c/li\u003e\n\u003cli\u003eSaha BK, Bonnier A, Chenna P, Milman NT. Prevalence of autoantibodies in pediatric patients with idiopathic pulmonary hemosiderosis: a scoping review of the literature in the period 1980-2021. \u003cem\u003eClin Rheumatol\u003c/em\u003e. 2022;41(4):977-990. doi:10.1007/s10067-021-06029-3\u003c/li\u003e\n\u003cli\u003eBuckley M, Van Mater H. Idiopathic Pulmonary Hemosiderosis as a Mimic of Pulmonary Vasculitis: A Case Report and Review of the Literature. \u003cem\u003eCurr Allergy Asthma Rep\u003c/em\u003e. 2020;20(5):13. doi:10.1007/s11882-020-00907-7\u003c/li\u003e\n\u003cli\u003eRen X, Yang T, Li J, Zhang J, Geng J, Dai H. Possible association of idiopathic pulmonary hemosiderosis with rheumatoid arthritis: A case report. \u003cem\u003eExp Ther Med\u003c/em\u003e. 2020;20(3):2291-2297. doi:10.3892/etm.2020.8938\u003c/li\u003e\n\u003cli\u003eKozono T, Tanaka K, Yagi T, et al. Autoimmune pulmonary alveolar proteinosis developed during treatment for systemic sclerosis: a case report. \u003cem\u003eBMC Pulm Med\u003c/em\u003e. 2025;25(1):32. doi:10.1186/s12890-025-03489-0\u003c/li\u003e\n\u003cli\u003eIshimoto H, Sakamoto N, Yura H, et al. Autoimmune pulmonary alveolar proteinosis exacerbated by steroid therapy due to misdiagnosis as anti-aminoacyl-tRNA synthetase (ARS) antibody positive- interstitial pneumonia: a case report. \u003cem\u003eBMC Pulm Med\u003c/em\u003e. 2022;22(1):120. doi:10.1186/s12890-022-01909-z\u003c/li\u003e\n\u003cli\u003eYanagisawa A, Konaka H, Tanaka M, Ihara S, Tachibana I. Pulmonary Alveolar Proteinosis During Intensive Immunosuppressive Treatment for Acute Exacerbation of Interstitial Pneumonia: A Case Report and Literature Review. \u003cem\u003eCureus\u003c/em\u003e. 2024;16(11):e74669. doi:10.7759/cureus.74669\u003c/li\u003e\n\u003cli\u003eYatomi M, Akasaka K, Sato S, et al. A case of autoimmune pulmonary alveolar proteinosis during the course of treatment of rapidly progressive interstitial pneumonia associated with anti-MDA5 antibody-positive dermatomyositis. \u003cem\u003eBMC Pulm Med\u003c/em\u003e. 2024;24(1):170. doi:10.1186/s12890-024-02989-9\u003c/li\u003e\n\u003cli\u003eNagasawa J, Kurasawa K, Maezawa R, Owada T, Hanaoka R, Fukuda T. Systemic lupus erythematosus complicating autoimmune pulmonary alveolar proteinosis that was worsened by immunosuppressive therapy. \u003cem\u003eLupus\u003c/em\u003e. 2013;22(10):1060-1063. doi:10.1177/0961203313498798\u003c/li\u003e\n\u003cli\u003eKozono T, Tanaka K, Yagi T, et al. Autoimmune pulmonary alveolar proteinosis developed during treatment for systemic sclerosis: a case report. \u003cem\u003eBMC Pulm Med\u003c/em\u003e. 2025;25(1):32. doi:10.1186/s12890-025-03489-0\u003c/li\u003e\n\u003cli\u003eIshii H, Trapnell BC, Tazawa R, et al. Comparative study of high-resolution CT findings between autoimmune and secondary pulmonary alveolar proteinosis. \u003cem\u003eChest\u003c/em\u003e. 2009;136(5):1348-1355. doi:10.1378/chest.09-0097\u003c/li\u003e\n\u003cli\u003eZhang D, Tian X, Feng R, et al. Secondary pulmonary alveolar proteinosis: a single-center retrospective study (a case series and literature review). \u003cem\u003eBMC Pulm Med\u003c/em\u003e. 2018;18(1):15. doi:10.1186/s12890-018-0590-z\u003c/li\u003e\n\u003cli\u003eSamuels MP, Warner JO. Pulmonary alveolar lipoproteinosis complicating juvenile dermatomyositis. \u003cem\u003eThorax\u003c/em\u003e. 1988;43(11):939-940. doi:10.1136/thx.43.11.939\u003c/li\u003e\n\u003cli\u003eWardwell NR, Miller R, Ware LB. Pulmonary alveolar proteinosis associated with a disease-modifying antirheumatoid arthritis drug. \u003cem\u003eRespirology\u003c/em\u003e. 2006;11(5):663-665. doi:10.1111/j.1440-1843.2006.00905.x\u003c/li\u003e\n\u003cli\u003eUchiyama M, Nagao T, Hattori A, et al. Pulmonary alveolar proteinosis in a patient with Behcet\u0026rsquo;s disease. \u003cem\u003eRespirology\u003c/em\u003e. 2009;14(2):305-308. doi:10.1111/j.1440-1843.2008.01450.x\u003c/li\u003e\n\u003cli\u003eKatakura T, Shirai T, Ishii Y, et al. Secondary Pulmonary Alveolar Proteinosis Complicated by Hemophagocytic Syndrome in a Patient with Adult-onset Still\u0026rsquo;s disease: A Case-based Review. \u003cem\u003eIntern Med\u003c/em\u003e. 2026;65(2):331-336. doi:10.2169/internalmedicine.5421-25\u003c/li\u003e\n\u003cli\u003eImura Y, Yukawa N, Handa T, et al. Two cases of autoimmune and secondary pulmonary alveolar proteinosis during immunosuppressive therapy in dermatomyositis with interstitial lung disease. \u003cem\u003eMod Rheumatol\u003c/em\u003e. 2018;28(4):724-729. doi:10.3109/14397595.2016.1153443\u003c/li\u003e\n\u003cli\u003eMathai SC, Danoff SK. Management of interstitial lung disease associated with connective tissue disease. \u003cem\u003eBMJ\u003c/em\u003e. 2016;352:h6819. doi:10.1136/bmj.h6819\u003c/li\u003e\n\u003cli\u003eAntoniou KM, Distler O, Gheorghiu AM, et al. ERS/EULAR clinical practice guidelines for connective tissue disease-associated interstitial lung disease. \u003cem\u003eEur Respir J\u003c/em\u003e. 2026;67(1):2402533. doi:10.1183/13993003.02533-2024\u003c/li\u003e\n\u003cli\u003eSaha BK, Milman NT. Idiopathic pulmonary hemosiderosis: a review of the treatments used during the past 30 years and future directions. \u003cem\u003eClin Rheumatol\u003c/em\u003e. 2021;40(7):2547-2557. doi:10.1007/s10067-020-05507-4\u003c/li\u003e\n\u003cli\u003eLim J, Boyle N, McCarthy C. Secondary Pulmonary Alveolar Proteinosis. \u003cem\u003eSemin Respir Crit Care Med\u003c/em\u003e. Published online November 24, 2025. doi:10.1055/a-2741-2079\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"98%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 1. The patient\u0026apos;s laboratory test results\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdmission\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eFollow-up\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eReference Range\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e(10 months)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eHematology\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eWBC (/\u0026micro;L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e9050\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e6910\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3500-9500\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eRBC (M/\u0026micro;L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.80-5.10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eHgb (g/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e12.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e12.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e11.5-15.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ePLT (/\u0026micro;L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e76000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e121000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e125000-350000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNeutrophils (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e77.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e70.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e40.0-75.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eLymphocytes (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e16.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e20.0-50.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eMonocytes (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e5.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e11.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.0-10.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eEosinophils (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.4-8.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eBasophils (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.0-1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNeutrophils (/\u0026micro;L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4890\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1800-6300\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eLymphocytes (/\u0026micro;L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1450\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1170\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1100-3200\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eMonocytes (/\u0026micro;L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e520\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e810\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e100-600\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eEosinophils (/\u0026micro;L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e20-52\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eBasophils (/\u0026micro;L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0-100\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eDirect Coombs Test\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e+++\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eBiochemistry\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eALT (U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7-40\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAST (U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e13-35\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eTB (\u0026micro;mol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e22.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e10.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026le;23.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eDB(\u0026micro;mol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026le;6.89\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eIB (\u0026micro;mol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e15.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e6.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026le;12.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eLDH(U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e199\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e303\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e120-250\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eESR (mm/H)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0-20\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eCRP(g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e26.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0-10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eCoagulation function\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ePT (s)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e13.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e13.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e11.5-14.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ePT Activity (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e80.0-135.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eFibrinogen (g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.00-4.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAPTT (s)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e48.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e40.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e29.0-42.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eThrombin Time (s)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e16.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e17.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e＜21.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eD-Dimer (\u0026micro;g/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt;0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt;0.50\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eAutoimmune and Antibody Profile\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eANA (1:100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eCytoplasmic Granular 1:320 \u0026uarr;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eCytoplasmic Granular 1:100 \u0026uarr;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eTotal IgE (IU/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e788.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e198.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026le;100\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAnti-Cardiolipin Ab IgA (CU)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e8.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e6.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e＜20.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAnti-Cardiolipin Ab IgG (CU)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e19.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e＜20.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAnti-Cardiolipin Ab IgM (CU)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e＜20.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAnti-\u0026beta;2GP1 Ab IgA (CU)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt;4.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt;4.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e＜20.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAnti-\u0026beta;2GP1 Ab IgG (CU)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e20.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e13.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e＜20.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAnti-\u0026beta;2GP1 Ab IgM (CU)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt;1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt;1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e＜20.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAnti-Endothelial Cell Ab testing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eLupus Anticoagulant SCT Screening Ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt;1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ePerinuclear Anti-Neutrophil Cytoplasmic Ab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eClassic Anti-Neutrophil Cytoplasmic Ab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAnti-MPO Ab IgG (RU/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e5.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0-20.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAnti-PR3 Ab IgG (RU/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt;2.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt;2.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0-20.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAnti-GBM Ab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAnti-GM-CSF Ab (IU/ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt;1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt;1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt;1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e \u003cstrong\u003eWBC\u003c/strong\u003e, White Blood Cell; \u003cstrong\u003eRBC\u003c/strong\u003e, Red Blood Cell; \u003cstrong\u003eHgb\u003c/strong\u003e, Hemoglobin; \u003cstrong\u003ePLT,\u003c/strong\u003e Platelet; \u003cstrong\u003eALT,\u003c/strong\u003e Alanine Aminotransferase; \u003cstrong\u003eAST\u003c/strong\u003e, Aspartate Aminotransferase; \u003cstrong\u003eTB\u003c/strong\u003e, Total Bilirubin;\u003cstrong\u003e\u0026nbsp;DB\u003c/strong\u003e, Direct Bilirubin;\u003cstrong\u003e\u0026nbsp;IB\u003c/strong\u003e, Indirect Bilirubin; \u003cstrong\u003eESR\u003c/strong\u003e, Erythrocyte Sedimentation Rate; \u003cstrong\u003eCRP\u003c/strong\u003e, C-Reactive Protein.\u003cstrong\u003ePT\u003c/strong\u003e, Prothrombin Time; \u003cstrong\u003ePT\u003c/strong\u003e Activity, Prothrombin Activity; \u003cstrong\u003eAPTT\u003c/strong\u003e, Activated Partial Thromboplastin Time;\u003cstrong\u003e\u0026nbsp;D-Dimer\u003c/strong\u003e, D-Dimer Quantification; \u003cstrong\u003eANA\u003c/strong\u003e, Antinuclear Antibody; \u003cstrong\u003eIgA\u003c/strong\u003e, Immunoglobulin A; \u003cstrong\u003eIgG\u003c/strong\u003e, Immunoglobulin G; \u003cstrong\u003eIgM\u003c/strong\u003e, Immunoglobulin M; \u003cstrong\u003eAb\u003c/strong\u003e, Antibody; \u003cstrong\u003e\u0026beta;2GP1\u003c/strong\u003e, Beta-2 Glycoprotein 1; \u003cstrong\u003eMPO\u003c/strong\u003e, Myeloperoxidase; \u003cstrong\u003ePR3\u003c/strong\u003e, Proteinase 3; \u003cstrong\u003eGBM\u003c/strong\u003e, Glomerular Basement Membrane; \u003cstrong\u003eGM-CSF\u003c/strong\u003e, Granulocyte-Macrophage Colony-Stimulating Factor.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 2. Pulmonary function test\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\"\u003e\n \u003cp\u003e\u003cstrong\u003eTests\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdmission\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eFollow-up\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e(10 months)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eResult\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ePredicted value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eResult\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ePredicted value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eFVC (L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.28\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eFVC%pred (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e92.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e94.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eFEV\u003csub\u003e1(L)\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.86\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eFEV\u003csub\u003e1\u003c/sub\u003e%pred (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e85.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e88.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eFEV\u003csub\u003e1\u003c/sub\u003e/FVC (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e80.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e86.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e81.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e87.41\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eFEV1/FVC %pred (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e92.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e93.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eTLC (L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4.37\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eTLC%pred (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e92.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e105.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eDLCO (mmol/min/kPa)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e8.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e5.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e8.63\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eDLCO%pred (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e52.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e68.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbbreviations: FVC,\u003c/strong\u003e forced vital capacity; \u003cstrong\u003eFEV1,\u003c/strong\u003e forced expiratory volume in 1 second; \u003cstrong\u003eTLC,\u003c/strong\u003e total lung volume; \u003cstrong\u003eDLCO\u003c/strong\u003e, diffusion capacity of carbon monoxide; \u003cstrong\u003e%pred\u003c/strong\u003e, percentage of the predicted value.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"bmc-pulmonary-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pulm","sideBox":"Learn more about [BMC Pulmonary Medicine](http://bmcpulmmed.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/pulm/default.aspx","title":"BMC Pulmonary Medicine","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Connective tissue disease, Interstitial lung disease, Pulmonary alveolar proteinosis, Idiopathic pulmonary haemosiderosis, Lung biopsy","lastPublishedDoi":"10.21203/rs.3.rs-9128043/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9128043/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eDiffuse ground-glass opacities (GGOs) are a commonly observed radiographic finding in pulmonary imaging, frequently associated with various pulmonary pathologies. The etiology of ground-glass opacities is multifactorial, with connective tissue disease-associated interstitial lung disease (CTD-ILD), pulmonary haemosiderosis (PH), and pulmonary alveolar proteinosis (PAP) being potential underlying causes. Since the radiographic presentations of PH and PAP may overlap with those of CTD-ILD, a comprehensive differential diagnosis is crucial.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation:\u003c/strong\u003e This paper presents the case of a 24-year-old female patient who initially presented with thrombocytopenia and pulmonary opacities, accompanied by exertional dyspnoea, and was diagnosed with CTD-ILD. After treatment with glucocorticoids and mycophenolic acid (MPA), her symptoms improved. However, chest imaging over 8 months revealed recurrent fluctuations in pulmonary ground-glass opacities. Nine months after treatment, fibreoptic bronchoscopy revealed greyish-white gelatinous material in the bronchoalveolar lavage fluid. Anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies were found to be \u0026lt;1 IU/ml, leading to the diagnosis of CTD-ILD with SPAP. Atorvastatin was then added to the treatment regimen. Despite ten months of statin therapy, Chest CT findings show that the condition remains recurrent. After 12 months of statin therapy, re-examination of the lung biopsy specimen revealed alveolar hemosiderin deposition, confirming the diagnosis of CTD-ILD with idiopathic pulmonary hemosiderosis (IPH).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e This case report describes the rare occurrence of SPAP in a patient with CTD-ILD complicated by IPH. This case highlights the importance of vigilance for IPH and SPAP in patients with CTD who present with persistent or fluctuating pulmonary imaging abnormalities that do not adequately respond to conventional therapy. Prompt alveolar lavage and lung biopsy are essential for establishing a definitive diagnosis.\u003c/p\u003e","manuscriptTitle":"Prominent Diffuse Ground-Glass Opacities: A Challenging Case of CTD-ILD, IPH, and Secondary PAP Coexistence","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-16 06:44:00","doi":"10.21203/rs.3.rs-9128043/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-05-06T13:52:01+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-28T08:48:38+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-23T13:19:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"222341774663548545526272576053500797590","date":"2026-04-23T06:53:25+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-22T11:37:43+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-20T11:01:08+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"253929102238553631777506720267629813911","date":"2026-04-20T04:34:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"172921703535457719762910548803170935105","date":"2026-04-19T18:07:38+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-17T11:28:10+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-17T08:53:13+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"288870192361304072979339653428426077319","date":"2026-04-17T08:39:18+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"157998457587357736714840302701355438651","date":"2026-04-16T10:32:09+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-14T17:38:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"99706547144492448686739951382581230540","date":"2026-04-14T17:22:37+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"227763013961878344035779665789367238043","date":"2026-04-14T13:09:54+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"322750761398811002591300171556024202367","date":"2026-04-14T12:50:51+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-08T11:52:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"252560061648259671752462549152571043283","date":"2026-04-08T11:41:24+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"256988502642095025066881047976972395073","date":"2026-04-08T02:03:55+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-07T19:20:01+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-03-17T09:05:46+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-17T05:51:45+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-17T05:51:38+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pulmonary Medicine","date":"2026-03-15T10:41:10+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pulmonary-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pulm","sideBox":"Learn more about [BMC Pulmonary Medicine](http://bmcpulmmed.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/pulm/default.aspx","title":"BMC Pulmonary Medicine","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3ed980de-1eca-4a76-be48-dbcd9ac61015","owner":[],"postedDate":"April 16th, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-05-06T13:52:01+00:00","index":78,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-16T06:44:00+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-16 06:44:00","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9128043","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9128043","identity":"rs-9128043","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}