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].

• 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]

  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]

  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]

• 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]

  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]

  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]

  Can Med Assoc J 146: 1927–1934 Google Scholar Köylü R, Tozkoparan E et al (1997) Unusual miliary tuberculosis presenting with generalized lymphadenopathy and abdominal involvement. [link.springer.com]

• Recurrent Vomiting

  A 40-year-old manual labourer presented with easy fatiguability, recurrent vomiting and loss of weight of 3 months, duration. Upon examination, there was significant axillary and cervical lymphadenopathy. No pallor, icterus or clubbing was evident. [ncbi.nlm.nih.gov]

• Oral Ulcers

  There was generalised hyperpigmentation and multiple oral ulcers. The blood pressure 90/60 mm Hg in the right upper limb in the supine position. Investigations showed a low serum cortisol. [ncbi.nlm.nih.gov]

• 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]

  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]

  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]

  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]

  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]

  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]

• Hyperpigmentation

  There was generalised hyperpigmentation and multiple oral ulcers. The blood pressure 90/60 mm Hg in the right upper limb in the supine position. Investigations showed a low serum cortisol. [ncbi.nlm.nih.gov]

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]

• 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]

  Lymphopenia stands for one of the most common laboratory abnormalities in TB-infected patients, in addition to anemia, leucopenia, thrombocytopenia, erythrocyte sedimentation rate, C-reactive protein, hyponatremia or hypocalcaemia, and it constitutes [sciforschenonline.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.