A case description of multisystem tuberculosis complicated with diabetes mellitus and pulmonary embolism

Introduction

Tuberculosis (TB) is a chronic respiratory infectious disease caused by Mycobacterium tuberculosis (MTB) infection, whereas pulmonary thromboembolism (PTE) is a clinical syndrome resulting from thrombus obstruction of the pulmonary artery and its branches. Diabetes mellitus (DM) is a metabolic disease characterized by chronic hyperglycemia. There is a close association among these three conditions. DM can reduce the body’s cellular immune function, and the elevated blood glucose level creates a favorable environment for the growth of MTB, thereby increasing the risk of TB. At the same time, DM can also cause vascular endothelial damage, abnormal platelet function, and a hypercoagulable state of the blood, among other effects, increasing the risk of PTE. TB usually affects the lungs, but it can also invade organs outside the lungs through the lymphatic or blood systems, leading to extrapulmonary TB and complicating the condition (1). Beyond its impact on the respiratory system, TB also disrupts multiple systemic physiological functions, particularly involving the coagulation pathway and resulting in a hypercoagulable state in the body (2), increasing the risk of PTE through multiple pathways. When TB and DM coexist, they may interact with each other, further aggravating the body’s hypercoagulable state, thereby significantly increasing the incidence of PTE.

Case presentation

A 24-year-old male patient with a history of type 2 DM was admitted to the hospital due to “cough, expectoration accompanied by fatigue and fever for 15 days”. The patient had developed cough and expectoration 15 days prior, without obvious inducement. The sputum was mostly yellow and purulent, accompanied by intermittent fever, with a self-measured body temperature fluctuating between 38 and 40 ℃. During this period, he took cold medicine by himself, but his body temperature was not effectively controlled. Gradually, he also experienced symptoms such as fatigue, loss of appetite, shortness of breath after activity, and edema of both lower limbs, and he felt that his condition was deteriorating. He then attended Yining Second People’s Hospital for treatment. A chest computed tomography (CT) scan (Figure 1) showed the following: multiple patchy, nodular and cord-like hyperdense shadows in both lungs, considered as infectious lesions, with pulmonary tuberculosis (PT) to be excluded; partial destruction of the right upper lung tissue, multiple thick-walled cavities in both lungs; patchy hyperdense shadows in the dorsal segment of the right lower lobe and the posterior basal segment of the left lower lobe, suggesting that further enhanced CT examination be conducted; bronchiectasis in the upper lobes of both lungs, slightly enlarged lymph nodes in the mediastinum with partial calcification; and right encapsulated pleural effusion. The patient was admitted to the hospital because PT could not be ruled out. The results of the examinations after admission were as follows: blood routine showed that the percentage of neutrophils was 84.5% (normal reference range 50–70%); C-reactive protein (CRP) was 111.1 mg/L (normal reference range 0.0–8.0 mg/L); biochemical examination showed that total protein was 51.7 g/L (normal reference range 65.0–85.0 g/L); albumin was 26.8 g/L (normal reference range 40.0–55.0 g/L); and D-dimer was 7.63 mg/L (normal reference range ≤0.50 mg/L). Sputum smear for TB bacteria was 4+, sputum Gene Xpert MTB/RIF (referred to as “Xpert”) was positive and sensitive to rifampicin, and Xpert tests of pleural effusion and feces were also positive with rifampicin sensitivity. Coagulation function and the four infectious disease items were normal. Blood gas analysis results were as follows: pH 7.546, partial pressure of oxygen (PO₂) 63 mmHg, partial pressure of carbon dioxide (PCO₂) 30.6 mmHg. Three days later, the re-examined D-dimer had risen to 10.0 mg/L (normal reference range ≤0.50 mg/L). Emergency CT pulmonary angiography (CTPA) (Figure 2) showed a filling defect in the dorsal branch of the left lower pulmonary artery. Based on the above examination results, the diagnoses were secondary PT, tuberculous pleurisy, intestinal TB, and type 2 DM complicated with pulmonary embolism (PE). The treatment plan was as follows: anti-TB treatment with oral isoniazid 0.3 g (once a day), ethambutol 1 g (once a day), pyrazinamide 1.5 g (once a day), and levofloxacin 0.5 g (once a day); meanwhile, oral rivaroxaban 15 mg (twice a day) was administered for anticoagulation, which was adjusted to 20 mg (once a day) after 21 days. Two months after treatment, a re-examination of CTPA (Figure 3) showed that the filling defect in the dorsal branch of the left lower pulmonary artery had disappeared. The patient continued to receive anti-TB and anticoagulant treatment, with a good prognosis.

Figure 1 Chest computed tomography examination image. (A,B) There are multiple nodular, patchy and striated areas of increased density in both lungs. Some lung tissues show destruction with the formation of cavities. (C) There is encapsulated pleural effusion in the right thoracic cavity.

Figure 2 Computed tomography angiography of pulmonary artery. The red arrow indicated that a filling defect is noted within the branches of the dorsal segment of the left lower pulmonary artery.

Figure 3 A follow-up computed tomography angiography of pulmonary artery. (A,B) No filling defect is observed within the branches of the dorsal segment of the left lower pulmonary artery.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s). This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. Written informed consent was provided by the patient for publication of this study and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

China is among the countries with a high burden of DM combined with TB (3). Poor glycemic control represents a potential risk factor for the development of active PT and PE (4). Research has shown that the average blood glucose level of patients with DM complicated by acute PE upon admission is 175.4±78.94 mg/dL (5). The blood glucose level of this patient at admission was 270 mg/dL, higher than the reported average blood glucose level. Hyperglycemia drives passive glucose diffusion into endothelial cells, activating secondary metabolism and mimicking hypoxic effects, which leads to cytotoxicity and reduced nitric oxide availability, causing endothelial dysfunction (6). Concurrently, diabetes alters fibrin network structure and impairs fibrinolysis (7). These promote procoagulant and proinflammatory states, ultimately resulting in a prothrombotic state in diabetes (8).

TB can induce a hypercoagulable state characterized by systemic inflammation, endothelial dysfunction, and alterations in coagulation and fibrinolysis pathways (9). Dentan et al. (10) suggested that MTB can directly cause vascular endothelial damage and release chemotactic factors such as complement C3a, C5a, plasma enzyme activators, and kinin-releasing enzymes, which further promote thrombus formation (11). Chung et al. (12) have revealed that the incidence of PE in TB patients is 2.9 times that of non-TB patients, indicating that active TB increases the risk of venous thromboembolism (VTE). In patients with active PT, there is a certain correlation between nutritional status and PTE. If a patient presents with anemia or hypoproteinemia, vigilance against the occurrence of PE is warranted (13). Studies have shown that although anemia is a rare pathogenic factor for PTE (14), it is associated with increased incidence and risk of VTE (15); other studies have indicated that albumin levels are related to the severity of PE (16). The patient in this case also had intestinal TB, with a body mass index (BMI) of only 18, moderate anemia, hypoproteinemia, and poor nutritional status, all of which are risk factors for PTE. Therefore, active correction of anemia and hypoproteinemia should be carried out during treatment. Tuberculous pleurisy is an important cause of pleural effusion in areas endemic for TB. Studies have shown that the incidence of pleural effusion is relatively high in patients with PE, mostly presenting as unilateral and small-volume effusions (17). Although the mechanism linking pleural effusion to the occurrence of PE remains unclear, when pleural effusion occurs in PE, the risk of short-term death is relatively high, and pleural effusion is regarded as one of the independent risk factors for poor prognosis in PE patients (18). Thus, when PTE patients develop pleural effusion, the risk of death should be recognized.

In this case, the patient was clearly diagnosed with PT, intestinal TB, tuberculous pleurisy, and DM. Chest CT showed partial destruction of the right upper lung and multiple thick-walled cavitations in both lungs. Due to the long course of the disease, MTB infection can cause chronic granulomatous inflammation. Chronic TB infection may regulate thrombus formation by upregulating activated procoagulants, downregulating anticoagulants, and inhibiting fibrinolysis (19), eventually leading to the development of deep vein thrombosis (DVT) in the right lower extremity. When the embolus detaches and circulates to the pulmonary artery, it further results in acute PTE. In terms of clinical manifestations, PTE has poor specificity and is prone to misdiagnosis or missed diagnosis (20). Upon admission, the patient mainly presented with tuberculous toxic symptoms such as cough, expectoration, chest tightness, shortness of breath, fever, night sweats, and fatigue, without typical PTE symptoms such as chest pain or hemoptysis. According to the Pulmonary Embolism Severity Index (PESI) (21), the patient was classified as PESI Class I, indicating a very low risk of PTE. However, after admission, it was noted that the patient’s D-dimer level was significantly higher than normal, and a re-examination 3 days later showed a progressive increase in D-dimer. A CTPA was immediately performed, which confirmed the diagnosis of PTE.

For high-risk PTE characterized by hemodynamic impairment, the key to treatment lies in the rapid recanalization of the pulmonary artery (11). In such patients, if there is no improvement within 2–4 hours after full-dose thrombolysis, catheter-based thrombectomy should be considered. For patients with hemodynamic stability, anticoagulant therapy is the main treatment; for those with absolute contraindications to anticoagulation, alternative therapies such as inferior vena cava filter placement can be chosen (22). However, anticoagulant therapy for TB patients faces unique challenges. The core issue lies in the significant interactions between anticoagulants such as warfarin and rivaroxaban, and anti-TB drugs such as rifampicin; among these, rifampicin directly reduces the plasma concentration of anticoagulants, impairing therapeutic efficacy (23). Rivaroxaban is mainly metabolized via the CYP450 enzyme system, particularly through three enzymes: CYP3A4, CYP3A5, and CYP2J2. Meanwhile, rivaroxaban is also a substrate of P-glycoprotein (P-gp). This means any drug that inhibits or induces the aforementioned CYP450 enzyme system and P-gp may interfere with the normal metabolism of rivaroxaban, thereby altering its anticoagulant effect (24). Therefore, the patient in this case was treated with isoniazid, ethambutol, pyrazinamide, and levofloxacin for anti-TB, administered lispro insulin and glargine insulin to control blood glucose, along with rivaroxaban for anticoagulation. Due to the timely diagnosis and proper management of PTE during the treatment process, blood glucose was well controlled, and the patient had a good prognosis.

Malnutrition can accelerate the progression and poor prognosis of TB, and can also increase the risk of complications such as thromboembolism by damaging the host’s defense function. Implementing nutritional intervention, through a balanced diet to enhance immunity and reduce inflammation, is a crucial non-pharmacological support measure in the management of this disease (25). In addition, actively controlling blood glucose plays a crucial role in improving the CD8⁺ T cell immunity of diabetic patients, and this cell assumes a key function in the body’s defense against MTB infection. CD8⁺ T cells are capable of releasing perforin, granzyme, and cytokines to combat pathogens. More specifically, perforin can destroy MTB-infected macrophages, and granzyme B can penetrate these damaged cells and induce their death (26). Actively controlling blood glucose can prevent vascular endothelial dysfunction and the exposure of subendothelial collagen fibers, both of which would impair the function of the fibrinolytic system, and thus inhibit thrombus formation. It also avoids inducing increased platelet activity and blood viscosity, which is equally vital for reducing the risk of thrombus formation (27).

Acknowledgments

None.

Footnote

Funding: This study was funded by Jiangsu Commission of Health under Grant No. M2021073.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1664/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s). This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for publication of this study and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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