Miliary Tuberculosis: Understanding the Disseminated Form of Tuberculosis

Introduction

Miliary tuberculosis is one of the serious infections affecting the lungs which is characterized by the hematogenous spread of bacteria throughout the body. Initially, the lesion starts with a formation of one to two millimeters of tuberculous foci. This may occur as a result of progressive primary infection or through reactivation of focus with further spread through the bloodstream.

What Are the Signs and Symptoms of Miliary Tuberculosis?

The common symptoms of miliary tuberculosis include:

• Fever.

• Weight loss.

• Weakness.

• Generalized discomfort.

• Difficulty breathing.

• Chills.

• Severe anemia and blood-related abnormalities.

• Night sweats.

• Rigors.

• Headache.

• Cough.

• Generalized lymphadenopathy.

• Hepatomegaly.

• Pancreatitis.

• Splenomegaly.

• Multiorgan dysfunction, adrenal insufficiency.

What Are the Risk Factors of Miliary Tuberculosis?

Various medical conditions are considered as a risk factors in causing miliary tuberculosis and these include:

• Diabetes.

• Silicosis.

• Cancer.

• Transplantation.

• Acquired human immunodeficiency.

• End-stage renal disease.

• Malnutrition.

• Surgical procedures may trigger dissemination.

How to Diagnose Miliary Tuberculosis?

Several tests are performed to confirm the diagnosis of miliary tuberculosis. These include-

1. Laboratory Test:

• In 30 % of cases, alkaline phosphatase levels are elevated.

• A decrease in the level of sodium is the marker of disease severity, the syndrome of inappropriate secretion of antidiuretic hormone or hypoadrenalism results in the complication of tuberculosis.

• There are elevated levels of transaminases that suggest liver involvement.

2. Complete Blood Count:

• The erythrocyte sedimentation rate is elevated in about 50 percent of patients.

• Leukocytosis or leukopenia may be present.

• Patients may present with anemia and thrombocytopenia.

• Rare cases of thrombocytosis can also be observed.

3. Culture Test:

• Sputum, blood, cerebrospinal fluid, or urine samples are collected for the evaluation of mycobacteria in the culture test.

• Lumbar puncture should be performed mandatorily, with magnetic resonance imaging findings may reveal the following details-

• The predominance of lymphocytes.

• Leukocytes- White blood cell counts with 100 to 500 mononuclear cells per microliter are observed in about 65 % of patients.

• Elevations in the level of cerebrospinal fluid lactic acid levels.

• Low glucose levels are observed in 90 percent of patients.

• Red blood cells are common.

• Protein levels are elevated in about 90 percent of patients.

• Acid-fast bacilli are observed in greater than 40 percent with serial spinal taps.

4. Tuberculin Skin Test:

• The tuberculin skin test with purified protein derivative (PPD) shows negative test results in patients with miliary tuberculosis.

• This negative test result does not exclude the probability of tuberculosis.

5. Nucleic Acid Probes:

• Positive results are obtained from polymerase chain reaction testing of the blood in patients with human immunodeficiency virus-related disseminated tuberculosis, whereas the value is low in patients with non-human immunodeficiency virus miliary tuberculosis.

• The specificity for culture-negative and smear-negative specimens is less than 100 %. The accuracy or false-negative results are due to laboratory contamination.

Imaging Techniques for Miliary Tuberculosis-

1. Chest Radiography:

• In about 50 % of cases, the chest radiography findings are typical.

• Bilateral pleural effusions demonstrate dissemination versus localized and unilateral pleural tuberculosis.

• Lateral chest radiography reveals clear visualization of the nodules which is the characteristic feature of miliary tuberculosis.

2. Chest Computed Tomography (CT) Scan:

• Randomly distributed nodules are revealed with well-defined borders more accurately in computed tomography scans than in chest radiography.

• High-resolution computed tomography scan findings provide the best results with more accuracy and help to conclude the diagnosis in a shorter period.

3. Ultrasonography:

• Ultrasonography reveals findings of diffuse liver disease, hepatomegaly, para-aortic lymph nodes, and splenomegaly.

4. Fiberoptic Bronchoscopy:

Fiberoptic bronchoscopy is indicated for obtaining cultures. It is the most effective method.

5. Bone marrow Biopsy:

The yield of bone marrow biopsy is 50 % without serious adverse effects.

6. Laparoscopy:

In case of abdominal involvement, this method is used to get the tissue and material for culture.

7. Liver Biopsy:

In the case of liver biopsy, around 10 percent of cases experience liver bleeding which is a serious and life-threatening complication.

How Is Miliary Tuberculosis Treated?

• Early treatment reduces the risk of mortality and increases outcomes.

• Surgery is recommended only if necessary.

• In the case of hydrocephalus, a ventriculoatrial shunt and neurosurgical decompression are indicated.

• Since malnutrition can result in a weakened immune system, adequate nutrition is important.

• Various treatment approaches are followed in the management of miliary tuberculosis.

Pharmacological Therapy:

• Steroids are prescribed for hypotension due to adrenal insufficiency after the examination of the adrenocorticotropic hormone stimulation test.

• Generally, the treatment is around 6 to 9 months. In the case of meningitis, the overall treatment duration takes around 9 to 12 months.

• In military tuberculosis, patients associated with meningeal involvement, regular medications for the entire treatment are recommended.

• Rifampin is the primary choice of drug for treating miliary tuberculosis.

• Ethambutol is useful to prevent rifampin resistance if the mycobacteria organism is resistant to Isoniazid. The administration of Ethambutol can be discontinued as the organism starts to respond to Rifampin and Isoniazid.

• Pyrazinamide is initially administered for the first two months of treatment to decrease the duration from 9 months to 6 months if the organism is non-resistant to Rifampin and Isoniazid.

• In the case of pregnant patients affected with miliary tuberculosis, this can be treated safely with the administration of Rifampin, Isoniazid, and Ethambutol. However, the presence of miliary tuberculosis in a newborn mother associated with tuberculosis is hard to diagnose.

• The gastric aspirates of newborns taken thrice are more specific and useful.

• Due to the limited immune response of the newborn, a tuberculin skin test during the first six months is rarely useful, lumbar puncture is indicated.

• Patients with miliary tuberculosis, are not allowed to stay with immunocompromised patients prior to the confirmation of negative sputum culture. They are maintained in a negative pressure room or inadequate respiratory isolation.

• Patients showing clinical improvement and negative smear results for three consecutive tests are removed from isolation.

Conclusion

A proper examination and timely management aid in a better prognosis and positive outcome. If left untreated, the delayed treatment results in the mortality associated with miliary tuberculosis being close to 100 percent. However with early treatment, the mortality rate is reduced to less than 10 percent. Most relapse cases occur during the first 24 months after completion of the treatment.