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.

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.

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.

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.

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.

'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.

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.

Haemophagocytic lymphohistiocytosis in a patient with familial Mediterranean fever and miliary tuberculosis: a case report.

Haemophagocytic lymphohistiocytosis (HLH) is a lethal complication of several infections, especially viral origin. Mycobacterium tuberculosis infection can also lead to HLH, yet it is an uncommon trigger. Considering the role of increased cytokines in HLH, autoinflammatory conditions, such as familial Mediterranean fever (FMF), might contribute to its development. Nevertheless, the possible relationship between FMF and HLH has been suggested only in some case reports. We present a case of FMF who admitted to the hospital with consitutional symptoms and chest pain regarding to recurrent pericarditis. On a blood test, pancytopenia and elevated acute phase reactants were seen. Fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography demonstrated positive FDG uptake sites on both the right and left surrenal glands, the visceral layer of pericard, and reactive lymphadenomegalies at multiple mediastinal regions. Bone marrow biopsy revealed haemophagocytosis. Methylprednisolone treatment was initiated. Despite immunosuppressive treatment, clinical and biochemical parameters deteriorated; thus, a thorax computed tomography was executed. Findings were consistent with miliary tuberculosis infection. M. tuberculosis was detected in blood culture and bronchoalveolar lavage culture material. Also, bone marrow and surrenal biopsy material revealed necrotising caseating granuloma.

Haematological profiles after Intensive phase of Anti Koch Treatment with special emphasis on bone marrow changes.

BACKGROUND: Tuberculosis remains a major public health problem in various parts of the world. It leads to various haematological changes. Study of these haematological changes will help better patient management. OBJECTIVE & METHODS: It is to evaluate haematological changes in tuberculosis patients and compare the result with special emphasis to bone marrow changes as active case search is sharply decreasing the miliary tuberculosis. It is also to evaluate the patients with before and after the Intensive Phase of Anti Koch Treatment. Sputum positive and sputum negative tuberculosis patients confirmed by other ancillary techniques were included into this study. It is conducted at a tertiary level hospital in rural area. RESULT: In this study bone marrow hypercellularity was of erythroid series with only 1.92% patients showed granuloma in bone marrow aspiration. In addition to bone marrow changes, significant changes were evident in haemoglobin level, Erythrocyte Sedimentation Rate (ESR) Total White Blood Cell count and RBC count. DISCUSSION: In majority cases this study showed Erythroid Hyperplasia. It is sharp contrast with other study where myeloid hyperplasia was evident. This study also differs from other study where high number of bone marrow granuloma was reported. In this study only 1.92% cases showed bone marrow granuloma. This study also documented higher number of anaemic cases mostly because of the institute serves poor and tribal population. CONCLUSION: In our study the cases showing granuloma and hyperplasia of myeloid series were limited. With introduction of Directly Observed Treatment and house to house active case search helped to sharply decrease bone marrow granuloma by limiting multi-organ spread. This study showed, ESR level may be considered as prognostic parameters of tuberculosis.

Hemophagocytic lymphohistiocytosis and miliary tuberculosis in a previously healthy individual: a case report.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare heterogenous genetic or acquired hyperinflammatory syndrome associated with a high degree of morbidity and mortality. HLH has clinical manifestations related to abnormal prolonged activation of T lymphocytes and macrophages with an excess of proinflammatory cytokines. The main causes of secondary HLH are malignancies and infectious diseases. CASE PRESENTATION: The patient was a 54-year-old man, originally from Eastern Africa, who had lived in Northern Europe for 30 years. Here we describe the clinical features, laboratory parameters, diagnostic workup, management and outcome data of a previously healthy 54-year-old man diagnosed with HLH secondary to tuberculosis. The patient was initially treated for a community-acquired pneumonia. He developed multiorgan failure with acute respiratory distress syndrome, hypertransaminasemia, and kidney and bone marrow dysfunction. The clinical course together with a simultaneous increase in serum ferritin raised the suspicion of HLH. The patient fulfilled seven out of eight diagnostic criteria for HLH. A thorough diagnostic workup with respect to HLH and a potential underlying disease was initiated. Cultivation of bronchoalveolar lavage fluid, stool and urine, and polymerase chain reaction of epithelioid cell granulomas in the bone marrow were all positive for Mycobacterium tuberculosis. He was treated for both HLH and tuberculosis, and he survived without any sequelae. CONCLUSIONS: We present one of few published cases of a patient who survived HLH triggered by miliary tuberculosis. The current case illustrates the need for awareness of these two diagnoses, and the timely initiation of specific and supportive treatment to reduce mortality.

Haemophagocytic lymphohistiocytosis (HLH) secondary to miliary tuberculosis.

HLH is a rare, life-threatening, hematologic disorder resulting from prolonged and excessive activation of antigen presenting cells (macrophages, histiocytes) and CD8+ T cells. It is characterized by fever, pancytopenia,splenomegaly and haemophagocytosis in bone marrow,liver or lymph node. This hyperinflammatory condition is often triggered by a variety of agents or events, mostly genetic or infectious. HLH secondary to TB, have 100 % mortality in absence of anti-tubercular treatment .Since it mimics other disorders, its timely diagnosis remains a challenge. We report a case of hemophagocytic syndrome associated with disseminated tuberculosis in an immunocompetent man managed with anti-tubercular treatment and corticosteroid as immune modulator.

Disseminated Histoplasmosis and Miliary Tuberculosis Imitating Colon Cancer in Patient with HIV Who Refuses to Antirretroviral Treatment.

Simultaneous infection with histoplasmosis and miliary tuberculosis is rare and mainly affects people with severe immunosuppression, they can present very diverse clinical forms, similar to other infectious and neoplastic pathologies. We present the case of a 27-year-old woman diagnosed with HIV infection for 08 years who refuses to receive antiretroviral treatment (ART) and conceals her diagnosis, comes to the Hospital for pain, abdominal distension and ulcer in the oral cavity. The patient was diagnosed with likely cancer by presenting irregular intestinal thickening with homogeneous gray pattern in colon tomography and signs of intestinal obstruction, that after hemicolectomy was evidenced histoplasmosis in the pathological study, during the treatment with amphotericin B deoxycholate and improvement of the oral ulcer, the patient presented dyspnea, micronodular pattern on the chest radiograph that had not previously existed and the lipoarabinomanan antigen in the urine was positive for tuberculosis. In immunosuppressed patients, intestinal histoplasma infection may have clinical and tomographic characteristics similar to colon cáncer.

Kaposi-like manifestations in a newly diagnosed AIDS transgendered patient with silicone embolism syndrome and disseminated tuberculosis.

The use of liquid silicone for cosmetic procedures can yield serious sequelae including embolization and pneumonia. We describe a recent case of silicone embolism syndrome occurring together with systemic tuberculosis in a transgendered patient newly diagnosed with AIDS. She presented with fever, hematochezia, lymphadenopathies, purple nodular lesions and lower limb edema. HIV test was positive. A chest X-Ray showed interstitial infiltrates and a tomography showed necrotic lymph nodes and pulmonary nodules with blurred borders, suggesting Kaposi sarcoma. Psychomotor impairment then occurred in the absence of tomographic signs of acute neurological events. The Mycobacterium tuberculosis genome was isolated from stool and bronchial washing samples. Histological examination of a necrotic lymph node showed lymphoadenopathy due to silicone accumulation. Moreover, the patient presented fever and swelling of lower limbs; a tomography showed multiple foreign body granulomas. After starting antitubercular, antiretroviral and antibiotic treatment she reported symptomatic improvement including a mild recovery of motor-slowing. There are few reports about silicone-induced pulmonary disease in HIV-1 infected patients and, as far as we know, none of them describes an overlapping pulmonary involvement due to Mycobacterium tuberculosis infection. Even if extensive clinical and radiologic evidence is suggestive of Kaposi sarcoma (fever, severe immunodeficiency, multiple cutaneous nodules, hematochezia, diffuse lymphoadenopathies), it is possible to see Kaposi-like manifestations in patients with systemic silicone embolization. With this article we wish to stress the attention on the possible overlap of more than one concurrent disease in an immunocompromised host.