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Disseminated Tuberculosis

Tuberculosis Miliaris Disseminata

Disseminated tuberculosis represents the multi-site disease caused by Mycobacterium tuberculosis after it has migrated from the primary site of infection to multiple locations. Thus, this stage of the infection is defined after the pathogen is isolated from at least two noncontiguous organs like bone marrow, liver, blood, kidney, brain, scrotum or lungs. This condition is now more frequent in developed countries, as it occurs more frequently in human immunodeficiency virus-infected individuals.


Presentation

Disseminated tuberculosis presents in a non-specific manner [1] because usually several organs are involved at the same time and produce symptoms, therefore the diagnosis can be easily missed, with fatal consequences [2]. Systemic symptoms include fever, fatigability and weight loss and progress for weeks or months [3]. Physical examination reveals cough, splenomegaly, hepatomegaly, generalized lymphadenopathy [4] and signs of multiorgan dysfunction [5]. Genitourinary involvement is common. Kidneys, prostate, testes, epididymis and seminal vesicles may be affected, leading to sterile pyuria and hematuria [6]. Epididymis tuberculosis presents with pain, swelling or a palpable mass in the scrotum. Splenic tuberculosis leads to splenomegaly, nausea, vomiting and abdominal pain [7].

Due to the high degree of non-specificity of the presentation, allopathic medicine relies on the typical finding on a chest radiograph for diagnosis, but this can be absent, leading to the conclusion that a high degree of suspicion must be maintained when facing a patient with prolonged hyperpyrexia of unknown etiology and other often encountered signs [8].

Splenomegaly
  • Splenic tuberculosis leads to splenomegaly, nausea, vomiting and abdominal pain.[symptoma.com]
  • Splenomegaly showed multiple hypermetabolic nodules, and hypermetabolic focal lesions in the C3, C4, and D8 vertebral bodies, and the fourth costal arch.[revistanefrologia.com]
  • The onset of acute respiratory distress syndrome (ARDS) may be acute or subacute the clinical signs include tachypnea bilateral crepitations in lung fields hepatomegaly, splenomegaly.[jacpjournal.org]
  • Computed tomography scan of the chest revealed multiple pulmonary nodules [figure 3 ], necrotic lymph nodes, and splenomegaly. The patient underwent incision, drainage, and biopsy of the affected finger.[ann-clinmicrob.biomedcentral.com]
  • The features were reported to be consistent with tropical splenomegaly syndrome. Two weeks post-splenectomy he developed high grade fever. On examination his chest was clear.[jpma.org.pk]
Generalized Lymphadenopathy
  • Physical examination reveals cough, splenomegaly, hepatomegaly, generalized lymphadenopathy and signs of multiorgan dysfunction. Genitourinary involvement is common.[symptoma.com]
  • lymphadenopathy (40%) Hepatomegaly (40%) Splenomegaly (15%) Pancreatitis ( 5%) Multiorgan dysfunction, adrenal insufficiency Differential Diagnosis of Miliary TB The differential diagnosis of miliary tuberculosis includes the following: Acute respiratory[emedicine.medscape.com]
  • lymphadenopathy B232 HIV disease resulting in haematological and immunological abnormalities ,not elsewhere classified B238 HIV disease resulting in other specified conditions B24 Unspecified human immunodeficie virus (HIV) disease B250 Cytomegaloviral[dent.nu.ac.th]
Fever
  • Although ruxolitinib rapidly induced relief, he developed a high-grade fever. A comprehensive fever work-up found no apparent cause of the fever, except for PMF.[ncbi.nlm.nih.gov]
  • A 62-year-old woman with rheumatoid arthritis presented with fever (T-103.9 F). Vital signs and physical examination were normal. She was taking adalimumab, methotrexate, and prednisone for the past 9 months.[ncbi.nlm.nih.gov]
  • We hereby report a case who presented with short history of fever, associated with vomiting and altered sensorium. He also had evidence of meningitis on neuroimaging with equivocal CSF finding.[ncbi.nlm.nih.gov]
  • At the time of diagnosis, fever 2 weeks plus 5 kg weight loss was reported in 16 (80%) patients, abnormal chest X-rays in 7/17 (41%), and positive sputum cultures in 10 (50%); median CD4 count was 30 cells/μl (range 1-122).[ncbi.nlm.nih.gov]
  • Empiric TB therapy is warranted for HIV-infected patients from TB-endemic countries with prolonged cough or fever.[ncbi.nlm.nih.gov]
Weight Loss
  • We describe the case of a 61-year-old man from the Dominican Republic admitted with diarrhoea, fevers and weight loss who was found to have lab studies and imaging (including radiolabeled somatostatin positron emission tomography/CT scan) initially consistent[ncbi.nlm.nih.gov]
  • A 48-year-old man of Indian descent and chronic untreated HIV infection presented with a 3-week history of persistent fever, jaundice and a subacute 10-pound weight loss. His presentation was notable for a painless cholestatic jaundice.[ncbi.nlm.nih.gov]
  • A 48-year-old man with a 4 months history of asthenia, anorexia, 10 kg weight loss and 1 month of hematuria and dysuria was admitted to another hospital for sudden muscular weakness.[ncbi.nlm.nih.gov]
  • At the time of diagnosis, fever 2 weeks plus 5 kg weight loss was reported in 16 (80%) patients, abnormal chest X-rays in 7/17 (41%), and positive sputum cultures in 10 (50%); median CD4 count was 30 cells/μl (range 1-122).[ncbi.nlm.nih.gov]
  • Dry cough, low-grade fever, decreased appetite, drenching night sweats, global throbbing headache, and a significant amount of weight loss were also reported.[ncbi.nlm.nih.gov]
Chills
  • Case Presentation: A 58 year-old man presented with a 3-month history of night sweats, chills and a 30 pound weight loss. His temperature was 102 F with decreased breath sounds and dullness to percussion at the left lung base.[shmabstracts.com]
  • Symptoms depend on the affected areas of the body and can include: Abdominal pain or swelling Chills Cough and shortness of breath Fatigue Fever General discomfort, uneasiness, or ill feeling ( malaise ) Joint pain Pale skin due to anemia (pallor) Sweating[nlm.nih.gov]
  • Common general symptoms of tuberculosis include: Fever Chills Night sweats Malaise, i.e. feeling generally unwell Joint pain Weight loss Fatigue Pale skin due to anemia Swollen glands A cough and shortness of breath Skin rashes Less common symptoms that[ada.com]
Malaise
  • The commonest symptoms were cough, loss of weight and appetite, fever and general malaise. Headache, when present, was highly specific for meningeal involvement.[ncbi.nlm.nih.gov]
  • Symptoms depend on the affected areas of the body and can include: Abdominal pain or swelling Chills Cough and shortness of breath Fatigue Fever General discomfort, uneasiness, or ill feeling ( malaise ) Joint pain Pale skin due to anemia (pallor) Sweating[nlm.nih.gov]
  • Common general symptoms of tuberculosis include: Fever Chills Night sweats Malaise, i.e. feeling generally unwell Joint pain Weight loss Fatigue Pale skin due to anemia Swollen glands A cough and shortness of breath Skin rashes Less common symptoms that[ada.com]
Malnutrition
  • […] occur for many years after initial infection When treated, clearing is frequently rapid Miliary TB seldom, if ever, produces calcification Under age 5, there is an increased risk of meningitis Risk Factors Immunosuppression Cancer Transplantation HIV Malnutrition[learningradiology.com]
  • Many patients with miliary TB are debilitated by the disease, and malnutrition can contribute to a weakened immune system.[emedicine.medscape.com]
  • […] reported in only 2.7%. [4] [5] Miliary TB usually occurs in the presence of immunocompromising conditions such as advanced age, cancer, organ transplantation, immunosuppresive and cytotoxic therapy (including biologic agents antitumor necrosis factor), malnutrition[ijcasereportsandimages.com]
Tachycardia
  • On examination, he was alert and febrile (38.4 C) and had a sinus tachycardia (127 beats/min), with blood pressure of 83/45 mmHg and oxygen saturation of 98% on ambient air.[jmedscindmc.com]
  • Vital signs were normal except mild tachycardia of 101/minute. Physical examination was unremarkable including respiratory system examination.[ijcasereportsandimages.com]
Hepatomegaly
  • Physical examination reveals cough, splenomegaly, hepatomegaly, generalized lymphadenopathy and signs of multiorgan dysfunction. Genitourinary involvement is common.[symptoma.com]
  • Pyrexia, hepatomegaly, evidence of weight loss and adventitious chest sounds were the commonest physical signs. Hyponatraemia, hypo-albuminaemia and abnormal liver function were common.[ncbi.nlm.nih.gov]
  • The onset of acute respiratory distress syndrome (ARDS) may be acute or subacute the clinical signs include tachypnea bilateral crepitations in lung fields hepatomegaly, splenomegaly.[jacpjournal.org]
  • Transplantation HIV Malnutrition Diabetes Silicosis End-stage renal disease Clinical Findings Onset is insidious Patients may not be acutely ill Symptoms include Fever and weight loss Weakness and fatigue Chills, night sweats are common Cough Hemoptysis Anorexia Hepatomegaly[learningradiology.com]
  • Ultrasonography Ultrasonography may reveal diffuse liver disease, hepatomegaly, splenomegaly, or para-aortic lymph nodes. Head CT scanning with contrast and/or MRI of the brain Use this to assess for suspected TB lesions.[emedicine.medscape.com]
Night Sweats
  • Dry cough, low-grade fever, decreased appetite, drenching night sweats, global throbbing headache, and a significant amount of weight loss were also reported.[ncbi.nlm.nih.gov]
  • The most common presenting symptoms were: weight loss (100%), night sweats (85%) and fever (66.6%). Extrathoracic symptoms suggestive of the organs involved were hemiplegia (n 1), lameness (n 1) and chronic diarrhea (n 2).[erj.ersjournals.com]
  • Case Presentation: A 58 year-old man presented with a 3-month history of night sweats, chills and a 30 pound weight loss. His temperature was 102 F with decreased breath sounds and dullness to percussion at the left lung base.[shmabstracts.com]
  • Common general symptoms of tuberculosis include: Fever Chills Night sweats Malaise, i.e. feeling generally unwell Joint pain Weight loss Fatigue Pale skin due to anemia Swollen glands A cough and shortness of breath Skin rashes Less common symptoms that[ada.com]
  • He was admitted with week-long fever and night sweats without apparent source. The case history of the patient and physical examination were not specific, only revealing asthenia and weight loss in the last few months.[revistanefrologia.com]
Limb Weakness
  • On examination, the patient had positive Kernig's sign, right third cranial nerve palsy and bilateral sixth cranial nerve palsy, bilateral lower limb weakness and crepititions on lung auscultation bilaterally.[ncbi.nlm.nih.gov]

Workup

Blood workup should include a complete cell blood count, that may show either leukopenia or leukocytosis, pancytopenia, agranulocytosis, aplastic anemia, leukoerythroblastic anemia, thrombocytopenia or, in rare cases, thrombocytosis. Sodium level may be decreased due to the syndrome of inappropriate secretion of antidiuretic hormone. Alkaline phosphatase level may be increased. High transaminase levels may be caused by hepatic involvement or drug toxicity [9]. Inflammation markers, such as the erythrocyte sedimentation rate are high. Hypoalbuminemia, hypercalcemia and high ferritin levels [10] have also been described.

Mycobacterium tuberculosis is sometimes not found in the cultured sputum of disseminated tuberculosis patients. In such instances, the diagnosis is even more difficult [11] and cultures should be obtained from other sites (blood, cerebral spinal fluid, urine). If the bacteria is isolated, sensitivity testing should be performed. Acid fast bacilli staining should also be performed.

If cerebral symptoms are present, a lumbar puncture should be performed. Analysis may reveal increased leukocyte and lymphocyte counts, elevated protein and low glucose levels.

The tuberculin skin prick test is often negative in disseminated tuberculosis but does not exclude the diagnosis.

Thoracic radiography may show miliary shadowing in some patients, but sensibility and specificity of this finding are considered low [12] [13]. Pleural effusion may also be noticed, while pericardial effusion is better observed with echocardiography and electrocardiography.

Abdominal ultrasound detects hepatomegaly, splenomegaly, abscesses and enlarged lymph nodes, if present. Computer tomography evaluation is even more reliable in this case. The cranium can also be scanned or head magnetic resonance imaging may be performed in cases of suspected lesions and in order to exclude hydrocephalus and tuberculoma. Retinal tubercles may be observed if fundoscopy is performed.

More invasive procedures include fiberoptic bronchoscopy, liver and bone marrow biopsy. They are only recommended in selected cases, as they induce significant discomfort [14]. Liver bleeding after biopsy is potentially life-threatening.

Mediastinal Mass
  • We describe a case of a patient with end-stage renal failure, who presented with disseminated tuberculosis over the course of five months, manifesting with a self-resolving mediastinal mass, progressive lymphadenopathy, genitourinary, and musculoskeletal[ncbi.nlm.nih.gov]
  • The authors emphasise that an active search for tuberculosis should be made routinely in patients with IJV thrombosis with an underlying mediastinal mass and/or generalised lymphadenopathy.[ncbi.nlm.nih.gov]
Anergy
  • Tuberculin anergy is more common in miliary tuberculosis than in other forms of tuberculosis. The characteristic finding in chest X-ray is bilateral nodular opacities 1-3 mm in diameter (seen in 90% of patients).[jacpjournal.org]
  • These false negatives may occur because of higher rates of tuberculin anergy compared to other forms of tuberculosis.A case of miliary tuberculosis in an 82-year-old woman: The standard treatment recommended by the WHO is with isoniazid and rifampicin[en.wikipedia.org]
  • Pesanti EP: The negative tuberculin test: Tuberculin, HIV, and anergy panels. Am J Respir Crit Care Med 1994;149:1699–1709.[doi.org]
  • Anergy, or absence of PPD reactivity in persons infected with TB, can occur in immunocompromised persons, or it may even occur in persons newly infected with TB, or in persons with miliary TB. Injecting PPD intracutaneously, gross.[library.med.utah.edu]
Hyponatremia
  • Laboratory results showed metabolic acidemia, severe hyperkalemia and hyponatremia, acute renal dysfunction and sterile pyuria.[ncbi.nlm.nih.gov]
  • Miliary tuberculosis presenting with hyponatremia and thrombocytopenia. Can Med Assoc J 1976;115:871-3. [ PUBMED ] [ FULLTEXT ] 14. Akyildiz B, Uzel N, Yanni D, Citak A, Karaböcüoðlu M, Uçsel R.[lungindia.com]
  • Laboratory results revealed anemia (10.8 g/dL), hyponatremia (125 mmol/L), and elevated C-reactive protein (18.48 mg/dL). White blood cell count was elevated (19330/μL), of which neutrophils was accounted for 79.7% and lymphocytes for 12.4%.[jmedscindmc.com]
  • As in the first case, hyponatremia in tuberculosis was first described in 1930 10 and is thought to be due to SJADH 11 but may also be due to adrenal hypofunction.[jpma.org.pk]
  • Other lab abnormalities may include elevated ESR and C-reactive protein, hyponatremia, hypercalcemia and sterile pyuria. [13] Advanced age ( 60 years), lymphopenia, thrombocytopenia, pancytopenia, hypoalbuminemia, elevated transaminase levels and delayed[ijcasereportsandimages.com]

Treatment

  • Paradoxical response (PR) during antituberculosis treatment also arises via recovery from immunosuppression. However, no study focused on PR during antituberculosis treatment in a postpartum patient has been reported.[ncbi.nlm.nih.gov]
  • Possible implications for screening, diagnosis, and treatment of tuberculosis in children and adolescents receiving anti-TNF treatment are discussed.[ncbi.nlm.nih.gov]
  • The authors conclude that patients undergoing biological therapy require thorough evaluation prior to initiating treatment, followed by continuous and rigorous monitoring by a multidisciplinary team during biological treatment, particularly in countries[ncbi.nlm.nih.gov]
  • All forms of TB and exposure need prompt evaluation and treatment. TB is a preventable disease, even in those who have been exposed to an infected person.[nlm.nih.gov]
  • Treatment with tumor necrosis factor α inhibitors is a risk factor for tuberculosis (TB).[ncbi.nlm.nih.gov]

Prognosis

  • When a patient presents with TB of the bone marrow, the clinical condition is more perplexing and the prognosis is typically poor.[ncbi.nlm.nih.gov]
  • Extrathoracic locations are usually deceptive, causing delays in diagnosis and treatment of DTB and therefore a worse prognosis. Tuberculosis - management Extrapulmonary impact 2013 ERS[erj.ersjournals.com]
  • Since prognosis was worse in patients with delayed treatment, a high index of suspicion is required, especially in those with clinical findings suggestive of disseminated tuberculosis.[ncbi.nlm.nih.gov]
  • Evaluation of clinical presentation and prognosis of tuberculosis in patients undergoing hemodiálisis. Acta Med Croatica 2008;62(1):65-8. [Pubmed] [3] Aladrén MJ, Vives PJ, Celorrio JM.[revistanefrologia.com]
  • The prognosis is good if the patient is operated on in the early stages of the illness This patient underwent ileostomy regarding his rectovesical fistula and was initially treated with four antituberculous agents: Rifabutin, Isoniazid, Ethambutol, and[path.upmc.edu]

Etiology

  • The diagnosis of peliosis hepatis was based on liver biopsy results which were suggestive of tuberculous etiology.[ncbi.nlm.nih.gov]
  • It results from the formation of lymphaticorenal fistulae due to various etiologies. The most common implicated cause is filariasis especially in endemic areas.[ncbi.nlm.nih.gov]
  • CONCLUSIONS: In an adult patient with hemophagocytic lymphohistiocytosis, it is pivotal to understand the underlying etiology, as it needs extensive immunosuppression.[ncbi.nlm.nih.gov]
  • […] allopathic medicine relies on the typical finding on a chest radiograph for diagnosis, but this can be absent, leading to the conclusion that a high degree of suspicion must be maintained when facing a patient with prolonged hyperpyrexia of unknown etiology[symptoma.com]
  • We are highlighting a case of disseminated tuberculosis which presented as acute lung injury, the etiologic diagnosis of which could only be established postmortem.[jacpjournal.org]

Epidemiology

  • We discuss the epidemiology of tuberculosis in the Australian paediatric population and highlight the sentinel role of childhood infection in public health surveillance.[ncbi.nlm.nih.gov]
  • : dheidenpea@yahoo.com. 2 Southern Africa Medical Unit, Operational Centre Brussels, Médecins Sans Frontières, Cape Town, South Africa. 3 Francis I Proctor Foundation, University of California, San Francisco, CA, USA. 4 Centre for Infectious Disease Epidemiology[ncbi.nlm.nih.gov]
  • In the epidemiological study of his contacts no further cases were detected.[archbronconeumol.org]
  • Epidemiology of extrapulmonary tuberculosis in the United States, 1993-2006. Clin Infect Dis. 2009; 49 (9): 1350-7[ DOI ][ PubMed ] 5. Kuo PH, Yang PC, Kuo SS, Luh KT.[archcid.com]
  • ORIGINAL ARTICLE Year : 2017 Volume : 6 Issue : 2 Page : 162-166 Epidemiology of extrapulmonary and disseminated tuberculosis in a tertiary care center in Oman Department of Medicine, Sultan Qaboos University Hospital, Sultanate of Oman, Oman Correspondence[ijmyco.org]
Sex distribution
Age distribution

Pathophysiology

  • Pathophysiology of Miliary TB Following exposure and inhalation of TB bacilli in the lung, a primary pulmonary complex is established, followed by development of pulmonary lymphangitis and hilar lymphadenopathy.[emedicine.medscape.com]

Prevention

  • Histopathologic diagnosis should be considered to rule out other skin pathologies and also to prevent delay in treatment. Better tuberculosis prevention strategies, including vaccination scale-up, are warranted.[ncbi.nlm.nih.gov]
  • Tuberculosis screening and eventually preventive chemotherapy should become the standard of care for individual undergoing tumor necrosis factor α antagonist therapies.[ncbi.nlm.nih.gov]
  • TB is a preventable disease, even in those who have been exposed to an infected person. Skin testing for TB is used in high-risk populations or in people who may have been exposed to TB, such as health care workers.[nlm.nih.gov]
  • Control will require effective prevention of both remotely and recently acquired infection, and wider use of empiric therapy in patients with advanced AIDS and prolonged fever. TRIAL REGISTRATION: ClinicalTrials.gov NCT00052195 .[ncbi.nlm.nih.gov]
  • The purpose of this study is to evaluate the safety and effectiveness of a vaccine designed to prevent disseminated tuberculosis.[clinicaltrials.gov]

References

Article

  1. Wang JY, Hsueh PR, Wang SK, et al. Disseminated tuberculosis: a 10-year experience in a medical center. Medicine. 2007; 86: 39-46.
  2. Kishore PV, Palaian S, Paudel R, et al. Diagnostic delay in a multi-organ tuberculosis immunocompetent patient: a case report. Southeast Asian J Trop Med Public Health. 2007;38:507-511.
  3. Maartens G, Willcox PA, Benatar SR. Miliary tuberculosis: rapid diagnosis, hematologic abnormalities, and outcome in 109 treated adults. Am J Med. 1990;89(3):291-296.
  4. Ilgazli A, Boyaci H, Basyigit I, et al. Extrapulmonary tuberculosis: clinical and epidemiologic spectrum of 636 cases. Arch Med Res. 2004;35:435-441.
  5. Hussain SF, Irfan M, Abbasi M, et al. Clinical characteristics of 110 miliary tuberculosis patients from a low HIV prevalence country. Int J Tuberc Lung Dis. 2004;8(4):493-499.
  6. Bhargava P: Epididymal tuberculosis: presentations and diagnosis. ANZ J Surg. 2007;77:495-496.
  7. Pérez-Solís D, Luyando LH, Callejo-Ortea A, et al. Case 90: disseminated tuberculosis. Radiology. 2006;238:366-370.
  8. Hussain SF, Irfan M, Abbasi M, et al. Clinical characteristics of 110 miliary tuberculosis patients from a low HIV prevalence country. Int J Tuberc Lung Dis. 2004;8:493–499.
  9. Shafer RW, Kim DS, Weiss JP, et al. Extrapulmonary tuberculosis in patients with human immunodeficiency virus infection. Medicine. 1991;70:384–397.
  10. Arranz Caso JA, Garcia Tena J, Llorens MM, et al. High serum ferritin concentration in an AIDS patient with miliary tuberculosis. Clin Infect Dis. 1997;25:1263–1264.
  11. Harries AD. Unrecognized Mycobacterium tuberculosis. Lancet. 2000;355:142.
  12. McGuinness G, Naidich DP, Jagirdar J, et al. High resolution CT findings in miliary lung disease. J Comput Assist Tomogr. 1992; 16:384-390.
  13. American Thoracic Society, US Centers for Disease Control and Prevention. Diagnostic Standards and Classification of Tuberculosis in Adults and Children. Am J Respir Crit Care Med. 2000;161(4):1376-1395.
  14. Kilby JM, Marques MB, Jaye DL, et al. The yield of bone marrow biopsy and culture compared with blood culture in the evaluation of HIV-infected patients for mycobacterial and fungal infections. Am J Med. 1998;104:123–128.

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Last updated: 2019-07-11 20:29