ALOK SINHA Department of Medicine Manipal College of Medical Sciences Pokhara, 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

Mechanism 1. 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 – Occasionally may 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

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 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)

DIFFERENTIALS Acute Respiratory Distress Syndrome Addison Disease Alcoholism Ascites Bone Marrow Failure Leukemia Disseminated Intravascular Coagulation various pneumonias - Bacterial, Community-Acquired, Fungal,Viral eosinophilic Pneumonia Hypersensitivity Histoplasmosis Hyponatremia Influenza Pneumocystis Carinii Pneumonia Sarcoidosis Silicosis

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

Milary Tuberculosis Miliary shadows around 1mm. Smaller than the other causes Present 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 mononuclear cells/μL with lymphocytic predominance 2. 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 months. ○ daily medications for the entire length of therapy recommended

ComplicationsComplications

 Paradoxical enlargement of the lymph nodes or intracerebral tuberculomas during adequate treatment ○ may require steroids