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 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]

  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]

• Generalized Lymphadenopathy

  Physical examination reveals cough, splenomegaly, hepatomegaly, generalized lymphadenopathy and signs of multiorgan dysfunction. Genitourinary involvement is common. [symptoma.com]

  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]

• Cervical Lymphadenopathy

  Upon examination, there was significant axillary and cervical lymphadenopathy. No pallor, icterus or clubbing was evident. There was generalised hyperpigmentation and multiple oral ulcers. [ncbi.nlm.nih.gov]

  She had pink palpebral conjunctiva, anicteric sclera, no tonsillopharyngeal congestion, no anterior neck mass, no cervical lymphadenopathies. [medcraveonline.com]

• 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]

• Weight Loss

  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]

• Malnutrition

  Our patient had multiple of these major risk factors, including immigration from an endemic area, malnutrition, overcrowding and alcohol abuse. [oxfordjournals.org]

  There are important risk factors such as socioeconomic, malnutrition and immunological disorders. [elsevier.es]

  […] 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]

• 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]

  […] meningitis Risk Factors Immunosuppression Cancer 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 [learningradiology.com]

  They include weight loss, fever, chills, weakness, general discomfort, and difficulty breathing. Infection of the bone marrow may cause severe anemia and other blood abnormalities, suggesting leukemia. [merckmanuals.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]

• Aspiration

  Mantoux test was strongly positive (20 mm).A fine needle aspiration biopsy of the cervical lymph node revealed reactive changes. Bone marrow aspiration and biopsy were normal. [ncbi.nlm.nih.gov]

  The bone marrow aspirate, however carries a comparatively low risk. In a small pilot study (not published) in 1997 we investigated the incidence of TB-culture-positive bone marrow aspirates obtained from 30 unselected patients. [tbonline.info]

  Another route of infection is by direct ingestion or aspiration of infected amniotic fluid if the placental caseous lesion ruptures directly into the amniotic cavity. [2] Transplacental infection occurs late in pregnancy and aspiration from amniotic fluid [jfmpc.com]

• Tachycardia

  Initial physical exam revealed vital signs that were within normal limits aside from mild tachycardia and tachypnea with a temperature of 36.7°C, heart rate of 112/min, blood pressure of 110/79 mmHg and respiratory rate of 22 breaths per minute with oxygen [oxfordjournals.org]

  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]

  Systemic inflammatory response syndrome: due to the presence of hypothermia, tachycardia, tachypnea and leukopenia. With the support of the syndromatic diagnoses and patient evolution, the following nosological diagnoses were made: 1. [elsevier.es]

• 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]

  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]

  Symptoms of TB in the lungs may include A bad cough that lasts 3 weeks or longer Weight loss Loss of appetite Coughing up blood or mucus Weakness or fatigue Fever Night sweats Skin tests, blood tests, x-rays, and other tests can tell if you have TB. [icdlist.com]

  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]

• Dysuria

  We present a 55-year-old male who presented with painful non-healing ulcers on the lower lip and scrotum associated with productive cough, fever, anorexia and dysuria. [ncbi.nlm.nih.gov]

  Noninfectious are more frequently encountered and include abacterial cystitis and dysuria occurring in 80% patients, followed by hematuria in 40%, and low grade fever in 30%. [8] These are usually benign and self-limiting, but cystitis may facilitate [cancerjournal.net]

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.

• Anergy

  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. [karger.com]

  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]

  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]

  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]

  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]

  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]

• Bicytopenia

  Patients and Methods 312 bone marrow aspirates from patients with the diagnosis of anaemia, severe granulocytopenia, thrombocytopenia, bicytopenia or pancytopenia, referred to Mpilo Hospital, Department of Haematology during the period from 1st May 2010 [tbonline.info]

  Working impression was bicytopenia, multi factorial, secondary to chronic inflammation, rule out tuberculous infiltration of the marrow. They agreed with restarting anti-tuberculosis meds as soon as possible to address overwhelming infection. [medcraveonline.com]

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]

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]

Factors associated with poor prognosis included albumin 1.0 mg/dL, creatinine >1.5 mg/dL, and delayed antituberculosis treatment. [journals.lww.com]

Treatment may continue for 6-9 months 9-12 months with meningeal involvement Complications Dissemination via bloodstream to Lymph nodes Liver Spleen Skeleton Kidneys Adrenals Prostate Seminal vesicles Epididymis Fallopian tubes Endometrium Meninges Prognosis [learningradiology.com]

The diagnosis of peliosis hepatis was based on liver biopsy results which were suggestive of tuberculous etiology. [ncbi.nlm.nih.gov]

Certain conditions have both an underlying etiology and multiple body system manifestations due to the underlying etiology. [icd10coded.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]

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]

The epidemiology of miliary TB has been altered by the emergence of the human immunodeficiency virus (HIV) infection and widespread use of immunosuppressive drugs. [doi.org]

In the epidemiological study of his contacts no further cases were detected. [archbronconeumol.org]

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]

The concomitant high serum phosphate and low parathyroid hormone suggested a vitamin D-dependent pathophysiology rather than malignancy or hyperparathyroidism. [journals.lww.com]

[…] and Prevention) Tuberculosis Facts - Testing for TB (Centers for Disease Control and Prevention) Tuberculosis Facts - You Can Prevent TB (Centers for Disease Control and Prevention) Tuberculosis: General Information (Centers for Disease Control and Prevention [icdlist.com]

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]

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]

Centers for Disease Control and Prevention: Essential components of a tuberculosis prevention and control program. MMWR Morb Mortal Wkly Rep 1995;44:1–16. [doi.org]

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.