ALOK SINHADepartment of Medicine

Manipal College of Medical SciencesPokhara, Nepal

Disseminated (miliary) tuberculosis Widespread dissemination of

Mycobacterium tuberculosis from the lungs to other parts of the body through the blood or lymph system

Characterized by ○ tiny size of the lesions (1-5 mm)

Seen in 1-3% of all TB cases

May easily be missed & fatal if untreated

Miliary TB classically seen in Chest X ray but occur in

○an individual organ (very rare, <5%), ○ in several organs○ throughout the whole body (>90%),

including the brain

Organs and tissues affected

Bones and joints Bronchus Eye Intestines Larynx Urinary system

Peritoneum Meninges Pericardium Lymph nodes Organs of the male or female urinary and

reproductive systems Skin Stomach

Mechanism1. Miliary tuberculosis is result of erosion of the

infection into a pulmonary vein. bacteria reach the left side of the heart and enter the systemic circulation & seed organs - liver and spleen

2. bacteria may enter the lymph node(s), drain into a systemic vein and eventually reach the right side of the heart & to lungs causing "miliary" appearance

Pathophysiology Mycobacteremia and hematogenous seeding may

occur after the primary infection

Miliary TB may develop years after the initial infection – Post primary infection

Disseminated nodules consist of central caseating necrosis and peripheral epithelioid and fibrous tissue

Are not calcified (as opposed to the initial Ghon focus, which often is visible on chest radiographs as a small calcified nodule)

Age Children younger than 5 years

○present with acute onset○ follows primary infection, with no or only a

short latency period Adults older than 65 years

○have a higher risk of miliary TB ○Clinically, present subacute or may

masquerade as a malignancy ○ If undiagnosed, the disease is detected at

autopsy

Risk factors Immunosuppression due to any cause

○ Cancer ○ Transplantation ○ HIV infection ○ Malnutrition (including alcoholism) ○ Diabetes ○ Silicosis ○ End-stage renal disease ○ Major surgical procedures – Occasionallymay trigger dissemination

Mortality/Morbidity Untreated, the mortality rate close to 100%. With early and appropriate treatment, the mortality

rate is reduced to less than 10%.

Most deaths occur within the first 2 weeks of admission to the hospital. This may be related to delayed onset of treatment

Up to 50% of all cases of disseminated TB detected at autopsy are missed antemortem

.

Please

listen !

Patients may experience progressive symptoms over days to weeks or occasionally over several months. Symptoms include the following:

○Weakness, fatigue (90%)

○Weight loss (80%)

○Fever (80%) ○Cough (60%)

○Generalized lymphadenopathy (40%) ○Hepatomegaly (40%)

○Splenomegaly (15%)

○Headache (10%) Uncommon:

○Pancreatitis (<5%) ○Multiorgan dysfunction specially adrenal

insufficiency (Addison’s disease)

DIFFERENTIALSAcute Respiratory Distress SyndromeAddison DiseaseAlcoholismAscitesBone Marrow FailureLeukemiaDisseminated Intravascular Coagulationvarious pneumonias - Bacterial, Community-Acquired, Fungal,Viral eosinophilic Pneumonia Hypersensitivity

HistoplasmosisHyponatremiaInfluenzaPneumocystis Carinii PneumoniaSarcoidosisSilicosis

CBC count Leukopenia/leukocytosis may be present

Leukemoid reactions may occur(transient myeloproliferative disorder with

leukocytosis - a physiologic response to stress or infection)

Anemia may be present Thrombocytopenia usual

ESR elevated in approximately 50% of patients

Chemistry ○Hyponatremia: correlate with disease

severity. Syndrome of inappropriate secretion of antidiuretic hormone (SIADH)

○Alkaline phosphatase levels elevated in approximately 30% of cases.

○Elevated levels of transaminases suggest liver involvement if treatment has been initiated, drug toxicity

Sputum usually not positive for AFB Fiberoptic bronchoscopy - most effective procedure

for obtaining cultures (bronchoalveolar lavage). ○ The culture yield for transbronchial biopsies is 90%.

Cultures for mycobacteria ○ sputum ○ blood○ urine ○ CSF and other body fluids

Sensitivity testing essential for all positive isolates. Consider investigation for multidrug-resistant TB

(MDR-TB) in all cases.

• Tuberculin skin test with purified protein derivative (PPD)-

• often yields negative results in patients with miliary TB.

• This may be explained by the large number of TB antigens throughout the body

Mycobacterial blood cultures

Positive in approximately 5% of patients (who do not have HIV infection)

In patients who have HIV infection○ up to 85% positivity rate

Chest radiographyTypical findings in 50% of cases. Bilateral pleural effusions indicate

dissemination –useful clinical clue (provided pt is not having

CCF)

Nodules characteristic of miliary TB may be better visualized on lateral chest radiography (especially in the retrocardiac space)

Chest CT scanning Higher sensitivity and specificity than

chest radiography in displaying well-defined randomly distributed nodules. High-resolution CT scanning with 1-mm cuts may be even better

It is useful in the presence of suggestive and inconclusive chest radiography findings

Milary Tuberculosis

Miliary shadows around 1mm. Smaller than the other causesPresent through out but more In upper zone and less in the bases. Uniform in size. No calcification seen.

Other Tests

ECG & USG: to find out pericardial effussion

Funduscopy: This may reveal retinal tubercles

retinal tubercles

Lumbar puncture Should be strongly considered even with normal

brain MRI findings 1. Leukocytes: WBC counts with 100-500 mononuclear

cells/μL with lymphocytic predominance2. CSF lactic acid levels are mildly elevated 3. Elevated protein levels (90%) 4. Low glucose levels (90%) 5. RBCs are common 6. Acid-fast bacilli (≥40% with serial spinal taps)

TREATMENT Early treatment of patients with suspected

miliary tuberculosis (TB) decreases the likelihood of mortality and improves outcome

Adequate attention to nutrition essential For susceptible organisms, the treatment

period is 6-9 months. For meningitis - 9-12 months.

○ daily medications for the entire length of therapy recommended

Complications

Paradoxical enlargement of the lymph nodes or intracerebral tuberculomas during adequate treatment

○may require steroids