Undiagnosed tuberculosis associated with hemophagocytic lymphohistiocytosis due to improper use of corticosteroid.

INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening hematologic disease segregated into familial (primary) and acquired (secondary) subtypes. Hyperinflammation and HLH occur when the immune system fails to clear activated macrophages and histiocytes. Infections, malignancies, and rheumatologic disorders are the major triggers leading to HLH. Miliary tuberculosis is a serious disease with a lymphohematogenous spread of Mycobacterium tuberculosis, which is known to be one of the causative agents of HLH. Miliary tuberculosis and HLH have atypical presentations which are similar to routine diseases. Hence, physicians may face challenges to diagnose and treat these complications. CASE REPORT: We report the case of a 60-year-old man with a history of prolonged fever, shortness of breath, jaundice, altered mental status, undiagnosed lower back pain, and overuse of parenteral betamethasone. Miliary tuberculosis was diagnosed by diffuse, vague random micronodules in both lungs and positive acid-fast bacilli in bronchoalveolar lavage and bone marrow aspiration and biopsy. Moreover, compatible presentation and pancytopenia, hypertriglyceridemia, high serum level of ferritin and fibrinogen-derived products, and evidence of hemophagocytosis on bone marrow aspirate led to the diagnosis of HLH. Unfortunately, despite nearly two months of an anti-tuberculosis regimen (standard and salvage) and eight doses of etoposide, he eventually passed away after clinical improvement. CONCLUSIONS: Irrational and indiscriminate use of glucocorticoids can be a devastating cause of the spread of tuberculosis and its rare complications, such as HLH.

A study of analysis on prevalence, serological marker and prognosis of tuberculosis in tertiary care hospital.

BACKGROUND: Tuberculosis is an infectious disease responsible for a significant cause of ill health. According to the WHO global tuberculosis report 2021. 9.9 million cases fell sick with TB in 2020. Significantly, the prevalence of tuberculosis in India is 25%. OBJECTIVE: To analyze the prevalence of tuberculosis in the suburban areas of the metropolitan city in South India. To analyze the serological marker and prognosis of tuberculosis among males and females. To determine the importance of molecular testing - PCR confirmation on TB after AFB smear. METHODS: A retrospective study to analyze 462 patients enrolled by the respiratory medicine department on suspecting pulmonary- 356 (M-264 & F-92) and extra-pulmonary-106 (M-73&F-33) patients and diagnosed Zhiel-Neelsen staining, Mantoux test, Chip-based RT-PCR test, Erythrocyte sedimentation rate, and analyzed serological test such as C-Reactive Protein, Chemiluminescence immune assay. RESULTS: 23 patients were positive in Ziehl-Neelsen staining, 65 were positive in molecular True-Nat PCR test, Mantoux skin test induration in 10 patients, 98 TB Positive patients examined in the serological analysis, 1 & 3 patients reacted in HIV/HBsAg, and HBsAg test respectively, by chemiluminescence immunoassay, 8 PTB and 4 EPTB and 47 non-TB patients were positive in C-reactive protein, 46 TB and 94 non-TB patients detected abnormal values out of these 160 patients in ESR test. CONCLUSION: The Prevalence of tuberculosis is significantly rising, especially in the middle-aged population. The rapid molecular diagnostics to detect TB are highly sensitive and specific. Serological markers are essential for the analysis of disease prognosis and need to focus on the guidance of DOTS and RNTCP to End TB.

Arteriovenous thrombosis in a patient with miliary tuberculosis complicated by a left ventricular mass and its treatment.

INTRODUCTION: Tuberculosis (TB) is considered one of the two greater long-term global public health threats than the coronavirus disease 2019 (COVID-19) pandemic. Although venous thromboembolism has a low prevalence of 3.5% among patients with active TB, miliary TB complicated by arteriovenous thrombosis is a rare and potentially life-threatening condition. CASE STUDY: We present here an unusual case of a 32-year-old man with a two-month history of shortness of breath and painful swelling in the right lower extremity. In addition, elevated plasma levels of platelets, white blood cells, neutrophils, and D-dimer were observed upon his admission to the hospital. The patient was diagnosed with miliary TB complicated by arteriovenous thrombosis in the right lower extremity and a left ventricular mass measuring 3.5 × 1.7 cm. He was successfully treated with anti-TB drugs and low molecular weight heparin followed by warfarin, aspirin and clopidogrel. CONCLUSIONS: This case study demonstrates that a patient with miliary TB complicated by arteriovenous thrombosis and a left ventricular mass can be cured with timely diagnosis and appropriate treatment. The implications of this report are to raise awareness about miliary TB and arteriovenous thrombosis, to improve diagnosis and treatment, and to reduce patient mortality through sharing our successful experience with clinicians and healthcare providers in the developing countries of the world.

Extracorporeal blood purification benefits in post-caesarean patient with severe acute respiratory distress syndrome due to miliary tuberculosis: a case report.

BACKGROUND: Miliary tuberculosis is a life-threatening disease caused by the hematogenous spread of Mycobacterium tuberculosis. It is uncommon in pregnancy. Mortality rates for patients with miliary tuberculosis who require mechanical ventilation are high (60-70%). CASE PRESENTATION: We reported a rare and challenging case, a 35-year-old Asian woman with 34 weeks of pregnancy, and miliary tuberculosis with acute respiratory distress syndrome and septic shock. The patient presented with severe acute respiratory distress syndrome, necessitating mechanical ventilation, vasopressor, and pregnancy termination with caesarean section. The patient underwent blood purification with continuous veno-venous hemofiltration using an oXiris filter for 24 hours. After continuous veno-venous hemofiltration, the patient's condition was greatly improved, and the patient was successfully extubated and was able to breathe spontaneously without vasopressor on the third day. High levels of interleukin-6, interleukin-10, procalcitonin, C-reactive protein, interferon-γ, and tumor necrosis factor-α were found postoperatively. CONCLUSION: The bacterial infection of tuberculosis, acute respiratory distress syndrome, and the stress response from the caesarean section contributed to the high levels of cytokines, which correlated with the patient's severe inflammatory condition. The cytokine levels were greatly reduced after the blood purification procedure and this might be associated with the patient's clinical improvement. Extracorporeal blood purification could help to disrupt the vicious cycle of inflammation.

The role of early blood purification for miliary tuberculosis presenting as acute respiratory distress syndrome in pregnancy: A case report.

RATIONALE: Acute respiratory distress syndrome (ARDS) in miliary tuberculosis (TB) remains rare, especially in pregnant women. The role of blood purification is potential in managing ARDS due to miliary TB. PATIENT CONCERNS: A 36-year-old woman presenting with difficulty breathing 6 hours before admission. She never had any constitutional symptoms due to TB. DIAGNOSES: ARDS in TB was diagnosed based on the deterioration of PaO2/FiO2, increased acute phase reactants, positive gene-Xpert, and typical chest x-ray of miliary TB. INTERVENTIONS: A C-section was performed and followed by continuous venovenous hemofiltration to tackle her inflammatory condition. antituberculosis drugs were given after the transaminases showed declining trends. OUTCOMES: No major complications associated with continuous venovenous hemofiltration occurred. After 14 days of hospitalization, the patient's clinical condition improved and was finally discharged. LESSONS: This case underscores the potential role of blood purification in ARDS due to miliary TB in pregnancy.

Concurrent cerebral infarction and intracranial tuberculoma induced by the carotid plaque complicated with miliary tuberculosis.

Cerebrovascular complications of central nervous system tuberculosis (TB) are predictors of poor prognosis and adverse outcomes. These complications are mainly intracranial arterial involvement, with occasional venous involvement. Here, we present a 67-year-old woman with concurrent cerebral infarction and intracranial tuberculoma induced by the carotid plaque complicated by miliary tuberculosis. Mycobacterium tuberculosis was observed on the luminal side of the carotid plaques in pathological specimens. Treatment with anti-TB drugs alone would likely not cure the patient, as M. tuberculosis would continue to disseminate. Endarterectomy could directly remove the embolic source, and a complete cure was achieved.

Miliary tuberculosis-associated hemophagocytic lymphohistiocytosis with a high level of soluble interleukin-2 receptor successfully treated with concomitant recombinant thrombomodulin: A case report.

Hemophagocytic lymphohistiocytosis (HLH) is a fatal disease characterized by a highly inflammatory state due to the abnormal activation of T lymphocytes and macrophages. Miliary tuberculosis (MTB) is a rare cause of HLH and its clinical appearances occasionally resembles that of intravascular lymphoma (IVL). A 76-year-old woman presented with persistent fever and fatigue. Abnormal laboratory findings showing thrombocytopenia (13,000/µL), hypofibrinogenemia (101 mg/dL), hyperferritinemia (2,312 ng/mL), and markedly elevated soluble interleukin-2 receptor (sIL-2R) level (32,200 U/mL), in addition, hemophagocytosis in the bone marrow (BM) smear, were suggestive of IVL-associated HLH. The pathology of the BM biopsy specimen showed granuloma with non-caseous necrosis, and culture tests using sputum, gastric fluid, urine, and peripheral and bone marrow blood revealed the presence of Mycobacterium tuberculosis, leading to the final diagnosis of MTB-associated HLH. Anti-TB medications and corticosteroids were administered, but thrombocytopenia, hypofibrinogenemia, and hyperferritinemia persisted. Concomitant use of recombinant thrombomodulin (rTM) enabled regression of clinical status. In this case, BM biopsy served as the diagnosis of MTB-associated HLH, although IVL-associated HLH is initially suspected by an extremely high level of sIL-2R. Furthermore, this case report informs that using rTM could improve the outcomes of MTB-associated HLH.

Massive gastrointestinal bleeding as a clinical manifestation of miliary tuberculosis

Tuberculosis is still a public health problem today and can have acute and chronic manifestations challenging clinics for various medical specialties. Because it's a disease of multisystem potential, it is often overlooked when outside the respiratory clinical context. As a result, a clinical case report was carried out at the Hospital de Clínicas de Porto Alegre, in 2020, of a patient with voluminous gastrointestinal bleeding as severe acute clinical manifestation of Miliary and Intestinal Tuberculosis. Due to the potential severity of undiagnosed and untreated tuberculosis, high suspicion is suggested at all levels of health systems (whether public or private) with a view to early diagnosis, treatment and prevention of complications resulting from the disease.

A rare case of miliary tuberculosis in a patient with NSCLC receiving PD1 inhibitor therapy, mimicking autoimmune pneumonitis.

ABSTRACT: Immune checkpoint inhibitors (ICIs) are widely used for the treatment of various types of cancer. One of the possible immune-related adverse effects of ICI is pneumonitis, which is a life-threatening condition that can present as a variety of radiographic patterns, so it can be difficult to differentiate from infectious cases of pneumonia based on radiological findings alone. We present a rare case of miliary tuberculosis (M. tuberculosis) in a patient receiving programmed death-1 (PD-1) inhibitor therapy mimicking autoimmune pneumonitis and possible pathophysiological mechanisms of this unexpected event. We presented a 52-year-old patient with stage IV non-small-cell lung carcinoma (NSCLC) who was admitted to the hospital with radiological and clinical signs of pneumonitis caused by immunotherapy-Pembrolizumab. During hospitalization, she was clinically, laboratory, and microbiologically processed and her diagnosis of M. tuberculosis was confirmed. Initial treatment started with corticosteroids as a pneumonitis treatment, and because there was no adequate response, and the diagnosis of tuberculosis was confirmed, treatment with a four-regimen antituberculotic drug started. On a control, CT scan regression in distribution and number of changes in lungs occurred. After a while, patient died due to hepatic failure. There are not many reported cases of pulmonary tuberculosis in patients receiving immunotherapy; to our knowledge, no cases of M. tuberculosis in a patient with lung cancer were described. Since there is a different approach to the treatment of tuberculosis and pneumonitis, we presented our dilemmas and literature review in this article. A multidisciplinary approach (oncologist, radiologist, microbiologist, etc.) is essential in a case like this.

Multifocal cutaneous tuberculosis coexisting with pulmonary tuberculosis.

Tuberculosis (TB) is caused by Mycobacterium tuberculosis and it can affect multiple organ systems. Cutaneous TB, a less common type of extrapulmonary TB can coexist with TB of other organs. Here, we describe a case of multifocal cutaneous TB suggestive of two different morphological types with concomitant miliary pulmonary TB.

Rapidly Evolving and Fatal Miliary Tuberculosis and COVID-19 Infection in an Infant.

Tuberculosis (TB) and SARS-CoV-2 (COVID-19) are two important infectious diseases causing morbidity and mortality worldwide. Active TB infection can stimulate host immune responses and together with COVID-19, may lead to cytokine storm and immune dysregulation leading to multi-organ failure. We present a rare case of both miliary tuberculosis and SARS-CoV-2 co-infection in an infant who was a 6-month-old previously healthy term boy. He had persistent cough and congestion, became severely ill, and was brought to the emergency department. He was found to be COVID-19 positive by PCR test. Laboratory studies showed pancytopenia, elevated inflammatory markers, and an abnormal coagulation profile with coagulopathy. He developed strokes, severe sepsis, and electrolyte abnormalities, and declined rapidly within 6 days. Autopsy examination showed multifocal micro-abscesses in multiple organs, which on microscopic examination showed necrotic foci teeming with Mycobacteria and were culture positive for M. tuberculosis Neuropathological examination showed infarction in the right middle and posterior cerebral artery territories. This patient helps illuminate some immunological and pathological aspects of two co-occurring infectious diseases and the susceptibility for the development of fatal complications with SARS-CoV-2 infection in the pediatric population.

Intestinal perforation due to miliary tuberculosis in a patient with myasthenia gravis.

A man in his early 70s presented to the emergency department with a fall, following a history of fatigue and malodorous urine. On presentation, he was feverish, tachycardic and confused and was treated for presumed urinary sepsis. A chest radiograph showed increased opacification in the left upper lobe with calcification. CT imaging and bronchoalveolar lavage demonstrated miliary tuberculosis infection. His background included myasthenia gravis, which led to challenges in selecting appropriate antituberculosis treatment. During his stay, he developed sudden-onset abdominal pain due to intestinal perforation. He subsequently deteriorated and underwent multiple interventions, including a Hartmann's procedure and ileocaecal resection. Histological examination of his sigmoid colon revealed abundant acid-fast bacilli. Unfortunately, the patient died due to multiorgan failure in the context of several complications. This case highlights intestinal perforation as a rare complication of miliary tuberculosis and emphasises the importance of being vigilant for this potential complication.

'Miliary metastasis' in a child with papillary thyroid cancer.

Lung disease with diffuse nodules has a broad differential diagnosis. We present a case of childhood papillary thyroid carcinoma with diffuse lung metastases in which the diagnosis was delayed due to fact that the diffuse nodules were considered to be pathognomonic of miliary tuberculosis. Diffuse nodular lung disease in children requires a careful diagnostic approach. The role of multidisciplinary involvement in these rare cases is invaluable.

Ruxolitinib and tuberculosis: A case report with brief review.

JAK 2 inhibitors are widely used for the treatment of primary myelofibrosis. Ruxolitinib is the most commonly used JAK inhibitor in clinical practice. We report two cases of Primary Myelofibrosis who developed tuberculosis on active treatment with ruxolitinib. Our first case was a 48 year male who developed disseminated tuberculosis during fourth month of treatment and second case was a 50 year male developing tubercular lymphadenitis during second month of treatment respectively. These case reports indicate reactivation of underling tubercular infection as a very dreaded complication of this treatment. The prevalence of tuberculosis is much higher in India compared to the west. A thorough pretreatment evaluation should ideally be done using Mantoux test or interferon gamma release assay (IGRA) to rule out latent tuberculosis. Furthermore, the patients should be counselled regarding the possibility of reactivation of infections including tuberculosis. Also, proper follow up is the need of hour in all patients on any kind of immunomodulators.

Esophageal tuberculosis as an unusual cause of dysphagia: a case report.

Esophageal tuberculosis is a rare cause of infectious esophagitis, even in countries with endemic tuberculosis. This impairment is often secondary. We report a case of secondary esophageal tuberculosis in an immunocompetent patient, clinically revealed by dysphagia. Esophagogastroduodenoscopy showed a large ulcer in the middle third of the esophagus with a fistula opening in the center of the ulcer. Histopathological examination of multiple esophageal tissue biopsies revealed epithelioid cell granulomas without caseous necrosis. We completed with Computed Tomography (CT) scan of the chest which revealed a fistula of the middle third of the esophagus, multiple mediastinal necrotic adenopathies and diffuse pulmonary micronodules suggesting miliary tuberculosis. Sputum examination for acid-fast-bacilli was positive. Anti-tuberculosis treatment resulted in a good response with complete remission. It is therefore important to recognize and include this entity in the differential diagnosis of patients with dysphagia particularly in countries with a high incidence of tuberculosis.

An infant of 26 weeks gestation with congenital miliary tuberculosis complicated by chronic lung disease requiring CPAP was diagnosed on Day 104 of life: congenital tuberculosis was confirmed by detection of calcified ovaries in his mother.

INTRODUCTION: Early diagnosis of tuberculosis (TB) in infants is important but is commonly missed because the symptoms are often non-specific. CASE PRESENTATION: A Nepalese male infant born at 26 weeks gestation and weighing 1227 g (97th centile) was admitted to the neonatal intensive care unit (NICU) immediately after birth for the management of his prematurity. After extubation on Day 8, his oxygen saturation became unstable and he required nasal continuous positive airway pressure with oxygen for 3 months. On Day 104, further detailed evaluation was required because there was no improvement in his respiratory condition. A computed tomography (CT) scan demonstrated scattered miliary nodules in both lung fields. Acid-fast staining for the mycobacteria and TB polymerase chain reaction (PCR) of the sputum obtained directly by laryngeal aspiration confirmed Mycobacterium tuberculosis. On Day 105, he was therefore transferred to a tertiary care hospital for further intensive care. Pathology findings suggested placental involvement with TB owing to chronic endometrial infection. In addition, a maternal abdominal CT scan demonstrated bilateral calcified lesions in the ovaries. He completed antituberculous chemotherapy and was discharged 3 months later. At 18 months of age there are no sequelae and his development is almost normal. None of the infants or medical personnel who were exposed in the NICU developed secondary TB. CONCLUSION: In neonates with persistent respiratory distress, neonatologists should consider TB infection as a differential diagnosis. ABBREVIATIONS: CLD: chronic lung disease; CRP: C-reactive protein; CT: computed tomography; IGRA: interferon-γ release assay; IVF-ET: in vitro fertilisation-embryo transfer; N-CPAP: nasal continuous positive airway pressure; NICU: neonatal intensive care unit; PCR: polymerase chain reaction; PROM: premature rupture of membranes; TB: tuberculosis; WBC: white blood cells.

Extremely high levels of central nervous system involvement in miliary tuberculosis.

BACKGROUND: Miliary tuberculosis (TB) is one of the severest manifestations of TB that can be lethal when concomitant with the central nervous system (CNS) involvement. Bacteriological, biochemical and radiological methods for find CNS comorbidity in miliary TB was evaluated in this study. METHODS: Consecutive miliary TB adults were retrospectively enrolled from two designated TB hospitals in China. The capacities of examinations of cerebrospinal fluid (CSF), cerebral computed tomography (CT) and magnetic resonance imaging (MRI) for diagnosis of CNS involvement were assessed. RESULTS: Assessment of CNS involvement with a lumbar puncture and/or neuroimaging was undertaken in 282 out of 392 of acute miliary TB. Of these 282 patients, 87.59% (247/282) had CNS involvement. Cerebral contrast-enhanced MRI (96.05%, 170/177) and MRI (93.15%, 204/219) yielded significantly higher sensitivities over CSF examination (71.92%, 146/203, P < 0.001) and CT (34.69%, 17/49, P < 0.001). The sensitivity of CSF examination was superior to CT scan (P < 0.001). Although 59.65% (134/225) miliary TB patients acquired bacteriological evidence with sputum examination, the positivity was only 8.82% (21/238) for CSF examination by conventional and molecular tests. CONCLUSION: Almost all miliary TB had CNS involvement and MRI demonstrated outstanding potential over other methods. Therefore, a routinely screening of CNS TB should be strongly suggested in miliary TB and MRI could be used as the initial approach in resources rich settings.

Disseminated tuberculosis associated with autoimmune haemolytic anaemia and adrenal deficiency: a rare association.

Tuberculosis (TB) is one of the greatest masqueraders in medical practice and can have manifestations involving any organ or organ systems of the body. The presentation of disseminated TB can range from typical features like fever, weight loss and fatigue to protean manifestations. We share the case of an elderly man who presented to us with weight loss, anaemia, weakness and lymphadenopathy involving thoracic and intraabdominal locations. Work up of anaemia revealed features of Coombs-positive autoimmune haemolytic anaemia (AIHA) and evaluation of weakness showed laboratory results consistent with adrenal insufficiency. Biopsy of the abdominal lymphnode yielded caseating granulomas with CB-NAAT positivity for Mycobacterium tuberculosis Anti-TB chemotherapy with short-term replacement dose of systemic steroids corrected the haemolysis, anaemia and addisonian crisis. The case alerts clinicians regarding the uncommon association of TB with Coombs positive AIHA and adds one more aetiology to the pathogenesis of anaemia in TB. Furthermore, the occurrence of AIHA and hypoadrenalism in the same patient with TB is exceedingly rare and has not been reported.